Silverstein f01.tex V3 - 07/24/2014 2:44 P.M.

Page 1

EIGHTH EDITION

SPECTROMETRIC
IDENTIFICATION OF
ORGANIC COMPOUNDS

ROBERT M. SILVERSTEIN
FRANCIS X. WEBSTER
DAVID J. KIEMLE
State University of New York College
of Environmental Science & Forestry

DAVID L. BRYCE
University of Ottawa
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Library of Congress Cataloging-in-Publication Data

Silverstein, Robert M. (Robert Milton), 1916-2007.

Spectrometric identification of organic compounds / Robert M. Silverstein, Francis X. Webster, David J.
Kiemle, State University of New York, College of Environmental Science & Forestry; David L. Bryce,
University of Ottawa. – Eighth edition.
pages cm
Includes index.
ISBN 978-0-470-61637-6 (pbk.)
1. Spectrum analysis–Textbooks. 2. Organic compounds–Spectra–Textbooks. I. Webster, Francis X. II.
Kiemle, David J. III. Bryce, David L. (David Lawson), 1975- IV. Title.
QD272.S6S55 2015
543’.5–dc23
2014018634

Printed in the United States of America

10 9 8 7 6 5 4 3 2 1
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PREFACE TO EIGHTH EDITION

This problem-solving textbook, known as “Silverstein” to and of more advanced data acquisition methods in mod-
many of its generations of readers, has been a popular and ern NMR research are also briefly highlighted in Chapter
very useful resource for students and instructors over the 5. Chapter 6, on multinuclear magnetic resonance, includes
past 50 years. The book presents a unified approach to the details on additional isotopes of interest to the chemist and
structural determination of organic compounds based largely several additional tables of chemical shifts and coupling con-
on mass spectrometry (MS), infrared (IR) spectroscopy, stants. Hopefully, this chapter will encourage the reader to
and multinuclear and multidimensional nuclear magnetic pursue studies of isotopes beyond 1 H and 13 C when present
resonance (NMR) spectroscopy. We are very pleased to in their molecules of interest. Chapters 7 and 8, which feature
present the newly revised eighth edition. The strengths for solved problems and assigned problems, have been revised
which Spectrometric Identification of Organic Compounds but the core content consisting of the problems themselves
is known are preserved and updated. Such strengths include has been maintained from the previous edition. Reviewers
the pragmatic approach to problem solving and the wealth of have consistently noted the values of the problems to students
useful NMR and mass spectrometric data available in tabular in these two chapters.
form. Some of the more important revisions to this edition of We would like to thank the Wiley staff, including
the book are briefly detailed below. Jennifer Yee, Ellen Keohane, and Mary O’Sullivan, for their
Throughout the text, wording has been updated for con- hard work and dedication to this project. We are also grateful
sistency and to be more reflective of modern usage. We to the following reviewers for their invaluable suggestions
have replaced the older terminologies “spectrometry” and that greatly improved the manuscript:
“spectrometric” in reference to IR and NMR with the more
widely used “spectroscopy” and “spectroscopic” throughout
the text, even though we are aware there are valid arguments Scott Burt, Brigham Young University, Provo, Utah
for keeping the former. The original familiar title of the book
Charles Garner, Baylor University, Waco, Texas
has been maintained. New information on polymers and
phosphorus functional groups has been added to Chapter 2 Kevin Gwaltney, Kennesaw State University, Kennesaw,
on IR spectroscopy. Chapter 3 on proton NMR spectroscopy Georgia
has been overhauled, some sections having been thoroughly
revised. The latest techniques in cutting-edge NMR signal Vera Kolb, University of Wisconsin-Parkside
enhancement methods are highlighted. We have attempted James Nowick, University of California, Irvine
to maintain an appropriate balance between theory and prac-
tice. The concepts of chemical and magnetic equivalence, Michael Wentzel, Augsburg College, Minneapolis,
central to understanding many NMR spectra, are explained Minnesota
with more clarity. Chapters 4 and 5 on 13 C NMR and two-
dimensional NMR feature clearer explanations and revised David L. Bryce, Ottawa, Ontario
sections, which more accurately convey how some of the Francis X. Webster, Syracuse, New York
experiments actually work. The important roles of gradients David J. Kiemle, Syracuse, New York

iii
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PREFACE TO FIRST EDITION

During the past several years, we have been engaged in wish to acknowledge also the cooperation at the management
isolating small amounts of organic compounds from complex level, Dr. C. M. Himel, chairman of the Organic Research
mixtures and identifying these compounds spectrometri- Department, and Dr. D. M. Coulson, chairman of the
cally. Analytical Research Department.
At the suggestion of Dr. A. J. Castro of San Jose Varian Associates contributed the time and talents of
State College, we developed a one unit course entitled its NMR Applications Laboratory. We are indebted to Mr.
“Spectrometric Identification of Organic Compounds,” and N. S. Bhacca, Mr. L. F. Johnson, and Dr. J. N. Shoolery for
presented it to a class of graduate students and industrial the NMR spectra and for their generous help with points of
chemists during the 1962 spring semester. This book has interpretation.
evolved largely from the material gathered for the course and The invitation to teach at San Jose State College was
bears the same title as the course.* extended to Dr. Bert M. Morris, head of the Department of
We should first like to acknowledge the financial support Chemistry, who kindly arranged the administrative details.
we received from two sources: The Perkin-Elmer Corpora- The bulk of the manuscript was read by Dr. R. H.
tion and Stanford Research Institute. Eastman of the Stanford University whose comments were
A large debt of gratitude is owed to our colleagues at most helpful and are deeply appreciated.
Stanford Research Institute. We have taken advantage of the Finally, we want to thank our wives. As a test of a wife’s
generosity of too many of them to list them individually, patience, there are few things to compare with an author in
but we should like to thank Dr. S. A. Fuqua, in particu- the throes of composition. Our wives not only endured, they
lar, for many helpful discussions of NMR spectrometry. We also encouraged, assisted, and inspired.
*A brief description of the methodology had been published: R. M. R. M. Silverstein Menlo Park, California
Silverstein and G. C. Bassler, J. Chem. Educ. 39, 546 (1962). G. C. Bassler April 1963

iv
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CONTENTS

CHAPTER 1 MASS SPECTROMETRY 1 1.6.6.2 Aromatic Acids 29

1.6.7 Carboxylic Esters 29
1.1 Introduction 1 1.6.7.1 Aliphatic Esters 29
1.6.7.2 Benzyl and Phenyl Esters 30
1.2 Instrumentation 2
1.6.7.3 Esters of Aromatic Acids 30
1.3 Ionization Methods 3 1.6.8 Lactones 31
1.3.1 Gas-Phase Ionization Methods 3 1.6.9 Amines 31
1.3.1.1 Electron Impact Ionization 3 1.6.9.1 Aliphatic Amines 31
1.3.1.2 Chemical Ionization 3 1.6.9.2 Cyclic Amines 32
1.3.2 Desorption Ionization Methods 4 1.6.9.3 Aromatic Amines (Anilines) 32
1.3.2.1 Field Desorption Ionization 4 1.6.10 Amides 32
1.3.2.2 Fast Atom Bombardment Ionization 4 1.6.10.1 Aliphatic Amides 32
1.3.2.3 Plasma Desorption Ionization 5 1.6.10.2 Aromatic Amides 32
1.3.2.4 Laser Desorption Ionization 6 1.6.11 Aliphatic Nitriles 32
1.3.3 Evaporative Ionization Methods 6 1.6.12 Nitro Compounds 33
1.3.3.1 Thermospray Mass Spectrometry 6 1.6.12.1 Aliphatic Nitro Compounds 33
1.3.3.2 Electrospray Mass Spectrometry 6 1.6.12.2 Aromatic Nitro Compounds 33
1.6.13 Aliphatic Nitrites 33
1.4 Mass Analyzers 8 1.6.14 Aliphatic Nitrates 33
1.4.1 Magnetic Sector Mass Spectrometers 8 1.6.15 Sulfur Compounds 33
1.4.2 Quadrupole Mass Spectrometers 9 1.6.15.1 Aliphatic Mercaptans (Thiols) 33
1.4.3 Ion Trap Mass Spectrometer 10 1.6.15.2 Aliphatic Sulfides 34
1.4.4 Time-of-Flight Mass Spectrometer 11 1.6.15.3 Aliphatic Disulfides 34
1.4.5 Fourier Transform Mass Spectrometer 12 1.6.16 Halogen Compounds 35
1.4.6 Tandem Mass Spectrometry 12 1.6.16.1 Aliphatic Chlorides 35
1.6.16.2 Aliphatic Bromides 35
1.5 Interpretation of EI Mass Spectra 12 1.6.16.3 Aliphatic Iodides 35
1.5.1 Recognition of the Molecular Ion Peak 13 1.6.16.4 Aliphatic Fluorides 36
1.5.2 Determination of a Molecular Formula 14 1.6.16.5 Benzyl Halides 37
1.5.2.1 Unit-Mass Molecular Ion and Isotope Peaks 14 1.6.16.6 Aromatic Halides 37
1.5.2.2 High-Resolution Molecular Ion 15 1.6.17 Heteroaromatic Compounds 37
1.5.3 Use of the Molecular Formula. Index of
Hydrogen Deficiency 15 References 37
1.5.4 Fragmentation 16 Student Exercises 37
1.5.5 Rearrangements 18
Appendices 46
1.6 Mass Spectra of Some Chemical Classes 18 A Formula Masses (FM) for Various Combinations
1.6.1 Hydrocarbons 18 of Carbon, Hydrogen, Nitrogen, and Oxygen 46
1.6.1.1 Saturated Hydrocarbons 18
B Common Fragment Ions 67
1.6.1.2 Alkenes (Olefins) 19
1.6.1.3 Aromatic and Aralkyl Hydrocarbons 21 C Common Fragments Lost 69
1.6.2 Hydroxy Compounds 22
1.6.2.1 Alcohols 22
1.6.2.2 Phenols 23 CHAPTER 2 INFRARED SPECTROSCOPY 71
1.6.3 Ethers 24 2.1 Introduction 71
1.6.3.1 Aliphatic Ethers (and Acetals) 24
1.6.3.2 Aromatic Ethers 25 2.2 Theory 71
1.6.4 Ketones 26 2.2.1 Coupled Interactions 74
1.6.4.1 Aliphatic Ketones 26 2.2.2 Hydrogen Bonding 75
1.6.4.2 Cyclic Ketones 26
1.6.4.3 Aromatic Ketones 26 2.3 Instrumentation 76
1.6.5 Aldehydes 28 2.3.1 Dispersion IR 76
1.6.5.1 Aliphatic Aldehydes 28 2.3.2 Fourier Transform Infrared Spectrometer
1.6.5.2 Aromatic Aldehydes 28 (Interferometer) 76
1.6.6 Carboxylic Acids 28
1.6.6.1 Aliphatic Acids 28 2.4 Sample Handling 77

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vi CONTENTS

2.5 Interpretation of Spectra 78 2.6.20.2 N⏤H Bending Vibrations 101

2.6.21 Amino Acids and Salts of Amino Acids 101
2.6 Characteristic Group Absorptions of Organic 2.6.22 Nitriles 101
Molecules 81 2.6.23 Isonitriles (R⏤N⏤⏤C), Cyanates
2.6.1 Normal Alkanes (Paraffins) 81 (R⏤O⏤C⏤ ⏤N), Isocyanates
2.6.1.1 C⏤H Stretching Vibrations 81 (R⏤N⏤C⏤O), Thiocyanates
C⏤H Bending Vibrations 81
(R⏤S⏤C⏤
2.6.1.2
Branched-Chain Alkanes 82
⏤N), and Isothiocyanates
(R⏤N⏤C⏤S) 102
2.6.2
2.6.2.1 C⏤H Stretching Vibrations: Tertiary C⏤H
Groups 82
2.6.24 Compounds Containing a ⏤N⏤N Group 102
2.6.2.2 C⏤H Bending Vibrations: gem-Dimethyl 2.6.25 Covalent Compounds Containing
Groups 82 Nitrogen⏤Oxygen Bonds 102
2.6.3 Cyclic Alkanes 83 2.6.25.1 N⏤O Stretching Vibrations 102
2.6.3.1 C⏤H Stretching Vibrations 83 2.6.26 Organic Sulfur Compounds 103
2.6.3.2 C⏤H Bending Vibrations 83 2.6.26.1 S⏤H Stretching Vibrations: Mercaptans 103
2.6.4 Alkenes 83 2.6.26.2 C⏤S and C⏤S Stretching Vibrations 103
2.6.4.1 C⏤C Stretching Vibrations Unconjugated 2.6.27 Compounds Containing Sulfur⏤Oxygen
Linear Alkenes 83 Bonds 104
2.6.4.2 Alkene C⏤H Stretching Vibrations 84 2.6.27.1 S⏤O Stretching Vibrations 104
2.6.4.3 Alkene C⏤H Bending Vibrations 84 2.6.28 Organic Halogen Compounds 105
2.6.5 Alkynes 84 2.6.29 Silicon Compounds 106
2.6.5.1 C⏤
⏤C Stretching Vibrations 84 2.6.29.1 Si⏤H Vibrations 106
2.6.5.2 C⏤H Stretching Vibrations 85 2.6.29.2 SiO⏤H and Si⏤O Vibrations 106
2.6.5.3 C⏤H Bending Vibrations 85 2.6.29.3 Silicon-Halogen Stretching Vibrations 106
2.6.6 Mononuclear Aromatic Hydrocarbons 85 2.6.30 Phosphorus Compounds 106
2.6.6.1 Out-of-Plane C⏤H Bending Vibrations 85 2.6.30.1 P⏤H, P⏤C, P⏤O, and P⏤O Stretching
2.6.7 Polynuclear Aromatic Hydrocarbons 86 Vibrations 106
2.6.8 Polymers 86 2.6.31 Heteroaromatic Compounds 107
2.6.9 Alcohols and Phenols 88 2.6.31.1 C⏤H Stretching Vibrations 107
2.6.9.1 O⏤H Stretching Vibrations 88 2.6.31.2 N⏤H Stretching Frequencies 107
2.6.9.2 C⏤O Stretching Vibrations 89 2.6.31.3 Ring Stretching Vibrations (Skeletal Bands) 108
2.6.9.3 O⏤H Bending Vibrations 89 2.6.31.4 C⏤H Out-of-Plane Bending 108
2.6.10 Ethers, Epoxides, and Peroxides 89
References 108
2.6.10.1 C⏤O Stretching Vibrations 89
2.6.11 Ketones 92 Student Exercises 108
2.6.11.1 C⏤O Stretching Vibrations 92
2.6.11.2 C⏤C(⏤O)⏤C Stretching and Bending Appendices 118
Vibrations 94 A Transparent Regions of Solvents and Mulling Oils 118
2.6.12 Aldehydes 94 B Characteristic Group Absorptions 119
2.6.12.1 C⏤O Stretching Vibrations 94 C Absorptions for Alkenes 124
2.6.12.2 C⏤H Stretching Vibrations 94 D Absorptions for Phosphorus Compounds 125
2.6.13 Carboxylic Acids 94 E Absorptions for Heteroaromatics 125
2.6.13.1 O⏤H Stretching Vibrations 94
2.6.13.2 C⏤O Stretching Vibrations 95
2.6.13.3 C⏤O Stretching and O⏤H Bending Vibrations 95
2.6.14 Carboxylate Anion 95
PROTON (1 H) MAGNETIC RESONANCE
CHAPTER 3

2.6.15 Esters and Lactones 96

SPECTROSCOPY 126
2.6.15.1 C⏤O Stretching Vibrations 96 3.1 Introduction 126
2.6.15.2 C⏤O Stretching Vibrations 97
2.6.16 Acid Halides 97 3.2 Theory 126
2.6.16.1 C⏤O Stretching Vibrations 97 3.2.1 Magnetic Properties of Nuclei 126
2.6.17 Carboxylic Acid Anhydrides 97 3.2.2 Excitation of Spin 12 Nuclei 127
2.6.17.1 C⏤O Stretching Vibrations 97 3.2.3 Relaxation 128
2.6.17.2 C⏤O Stretching Vibrations 97
2.6.18 Amides and Lactams 98 3.3 Instrumentation and Sample Handling 129
2.6.18.1 N⏤H Stretching Vibrations 98 3.3.1 Instrumentation 129
2.6.18.2 C⏤O Stretching Vibrations (Amide I Band) 99 3.3.2 Sensitivity of NMR Experiments 130
2.6.18.3 N⏤H Bending Vibrations (Amide II Band) 99 3.3.3 Solvent Selection and Sample Handling 131
2.6.18.4 Other Vibration Bands 99
2.6.18.5 C⏤O Stretching Vibrations of Lactams 100 3.4 Chemical Shift 132
2.6.19 Amines 100
2.6.19.1 N⏤H Stretching Vibrations 100 3.5 Spin-Spin Coupling, Multiplets, and Spin
2.6.19.2 N⏤H Bending Vibrations 100 Systems 137
2.6.19.3 C⏤N Stretching Vibrations 100 3.5.1 Simple and Complex First-Order Multiplets 137
2.6.20 Amine Salts 100 3.5.2 First-Order Spin Systems 140
2.6.20.1 N⏤H Stretching Vibrations 100 3.5.3 Pople Notation 140
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CONTENTS vii

3.5.4 Further Examples of Simple First-Order Spin Appendices 175

Systems 141 A Chart A.1: Chemical Shifts of Protons on a Carbon
3.5.5 Analysis of First-Order Multiplets 143 Atom Adjacent (𝛼 Position) to a Functional Group in
Aliphatic Compounds (M–Y) 175
3.6 Protons on Oxygen, Nitrogen, and Sulfur Atoms:
Chart A.2: Chemical Shifts of Protons on a Carbon
Exchangeable Protons 144
Atom Once Removed (𝛽 Position) from a Functional
3.6.1 Protons on an Oxygen Atom 144
Group in Aliphatic Compounds (M–C–Y) 177
3.6.1.1 Alcohols 144
3.6.1.2 Water 146
B Effect on Chemical Shifts by Two or Three Directly
3.6.1.3 Phenols 147 Attached Functional Groups 178
3.6.1.4 Enols 147 C Chemical Shifts in Alicyclic and Heterocyclic Rings 180
3.6.1.5 Carboxylic Acids 147 D Chemical Shifts in Unsaturated and Aromatic
3.6.2 Protons on Nitrogen 147 Systems 181
3.6.3 Protons on Sulfur 149 Chart D.1: Chemical Shifts of Protons on
3.6.4 Protons on or near Chlorine, Bromine, or Monosubstituted Benzene Rings 183
Iodine Nuclei 149 E Protons Subject to Hydrogen-Bonding Effects
(Protons on Heteroatoms) 184
3.7 Coupling of Protons to Other Important Nuclei F Proton Spin-Spin Coupling Constants 185
(19 F, D (2 H), 31 P, 29 Si, and 13 C) 149 G Chemical Shifts and Multiplicities of Residual Protons
3.7.1 Coupling of Protons to 19 F 149 in Commercially Available Deuterated Solvents 187
3.7.2 Coupling of Protons to D (2 H) 149 H Chemical Shifts of Common Laboratory Solvents as
3.7.3 Coupling of Protons to 31 P 150 Trace Impurities 188
3.7.4 Coupling of Protons to 29 Si 150 I Proton NMR Chemical Shifts of Amino Acids in
3.7.5 Coupling of Protons to 13 C 150 D2 O 190
3.8 Chemical Equivalence 150
3.8.1 Determination of Chemical Equivalence by
Interchange Through Symmetry Operations 150
3.8.2 Determination of Chemical Equivalence by CHAPTER 4 CARBON-13 NMR SPECTROSCOPY 191
Tagging (or Substitution) 151
3.8.3 Chemical Equivalence by Rapid 4.1 Introduction 191
Interconversion of Structures 151
3.8.3.1 Keto-Enol Interconversion 151 4.2 Theory 191
1
3.8.3.2 Interconversion Around a Partial Double Bond 4.2.1 H Decoupling Techniques 191
(Restricted Rotation) 152 4.2.2 Chemical Shift Scale and Range 192
3.8.3.3 Interconversion Around the Single Bonds of 4.2.3 T1 Relaxation 193
Rings 152 4.2.4 Nuclear Overhauser Effect (NOE) 193
3.8.3.4 Interconversion Around the Single Bonds of 13 ⏤1
4.2.5 C H Spin-Spin Coupling (J Coupling) 196
Chains 152 4.2.6 Sensitivity 197
3.9 Magnetic Equivalence 154 4.2.7 Solvents 197

3.10 AMX, ABX, and ABC Rigid Systems with Three 4.3 Interpretation of a Simple 13 C NMR Spectrum:
Coupling Constants 155 Diethyl Phthalate 198

3.11 Weakly and Strongly Coupled Systems: Virtual 4.4 Quantitative 13 C Analysis 198
Coupling 156
3.11.1 Weakly Coupled Systems 156 4.5 Chemical Equivalence 200
3.11.1.1 1-Nitropropane 156
4.6 DEPT 200
3.11.2 Strongly Coupled Systems 157
3.11.2.1 1-Hexanol 157 4.7 Chemical Classes and Chemical Shifts 203
3.11.2.2 3-Methylglutaric Acid 157 4.7.1 Alkanes 204
3.12 Chirality 158 4.7.1.1 Linear and Branched Alkanes 204
4.7.1.2 Effect of Substituents on Alkanes 205
3.13 Magnitude of Vicinal and Geminal Coupling 4.7.1.3 Cycloalkanes and Saturated Heterocyclics 205
Constants 160 4.7.2 Alkenes 206
4.7.3 Alkynes 208
3.14 Long-Range Coupling 162 4.7.4 Aromatic Compounds 208
4.7.5 Heteroaromatic Compounds 209
3.15 Selective Spin Decoupling: Double Resonance 162
4.7.6 Alcohols 209
3.16 Nuclear Overhauser Effect 162 4.7.7 Ethers, Acetals, and Epoxides 209
4.7.8 Halides 211
3.17 Conclusion 163 4.7.9 Amines 211
4.7.10 Thiols, Sulfides, and Disulfides 211
References 164
4.7.11 Functional Groups Containing Carbon 211
Student Exercises 164 4.7.11.1 Ketones and Aldehydes 212
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viii CONTENTS

4.7.11.2 Carboxylic Acids, Esters, Chlorides, Anhydrides, 5.11 VGSE 262

Amides, and Nitriles 214 5.11.1 COSY: VGSE 262
4.7.11.3 Oximes 214 5.11.2 TOCSY: VGSE 262
References 214 5.11.3 HMQC: VGSE 262
5.11.4 HMBC: VGSE 264
Student Exercises 214 5.11.5 ROESY: VGSE 265

Appendices 225 5.12 Pulsed Field Gradient NMR 265

A The 13 C Chemical Shifts, Coupling Constants, and
Peak Multiplicities of Common Deuterated NMR References 268
Solvents 225 Student Exercises 268
13
B C Chemical Shifts of Common Laboratory Solvents
as Trace Impurities in Selected Deuterated NMR
Solvents 226 MULTINUCLEAR MAGNETIC RESONANCE
CHAPTER 6
13
C C Chemical Shift Ranges for Chemical Classes 227 SPECTROSCOPY 298
13
D C Chemical Shifts (ppm) for Several Natural
Products 229 6.1 Introduction and General Considerations 298
15
6.2 N Nuclear Magnetic Resonance 299

TWO-DIMENSIONAL NMR SPECTROSCOPY 19

CHAPTER 5 230 6.3 F Nuclear Magnetic Resonance 306

5.1 Introduction 230 6.4 29

Si Nuclear Magnetic Resonance 309
5.2 Theory 231 6.5 31
P Nuclear Magnetic Resonance 312
5.3 Correlation Spectroscopy 233 6.6 Conclusions 315
1 ⏤1
5.3.1 H H Correlation: COSY 235
References 315
5.4 Ipsenol: 1 H⏤1 H COSY 235
5.4.1 Ipsenol: Double Quantum Filtered 1 H⏤1 H Student Exercises 315
COSY 238
Appendix 320
5.4.2 Carbon Detected 13 C⏤1 H COSY: HETCOR 238
A Properties of Magnetically Active Nuclei 320
5.4.3 Proton Detected 1 H⏤13 C COSY: HMQC 239
5.4.4 Ipsenol: HETCOR and HMQC 239
5.4.5 Ipsenol: Proton-Detected, Long-Range
1 ⏤13
CHAPTER 7 SOLVED PROBLEMS 325
H C Heteronuclear Correlation: HMBC 241
7.1 Introduction 325
5.5 Caryophyllene Oxide 243
5.5.1 Caryophyllene Oxide: DQF-COSY 243 Problem 7.1 Discussion 329
5.5.2 Caryophyllene Oxide: HMQC 243
5.5.3 Caryophyllene Oxide: HMBC 247 Problem 7.2 Discussion 333

5.6 13
C⏤13 C Correlations: INADEQUATE 249 Problem 7.3 Discussion 337
5.6.1 INADEQUATE: Caryophyllene Oxide 251 Problem 7.4 Discussion 344
5.7 Lactose 251 Problem 7.5 Discussion 350
5.7.1 DQF-COSY: Lactose 251
5.7.2 HMQC: Lactose 254 Problem 7.6 Discussion 356
5.7.3 HMBC: Lactose 254
Student Exercises 357
5.8 Relayed Coherence Transfer: TOCSY 254
5.8.1 2D TOCSY: Lactose 254
5.8.2 1D TOCSY: Lactose 257 CHAPTER 8 ASSIGNED PROBLEMS 364

5.9 HMQC-TOCSY 259 8.1 Introduction 364

5.9.1 HMQC-TOCSY: Lactose 259
INDEX 453
5.10 ROESY 259
5.10.1 ROESY: Lactose 259
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CHAPTER 1
MASS SPECTROMETRY

1.1 INTRODUCTION ion, M + . The energetic molecular ion produces a series of

•

fragment ions, some of which are rationalized in

The concept of mass spectrometry is relatively simple: Figure 1.1.
a compound is ionized (ionization method), the ions are It is routine to couple a mass spectrometer to some form
separated on the basis of their mass/charge ratio (ion sep- of chromatographic instrument, such as a gas chromatograph
aration method), and the number of ions representing each (GC-MS) or a liquid chromatograph (LC-MS). The mass
mass/charge unit is recorded as a spectrum. There are many spectrometer finds widespread use in the analysis of com-
ionization methods and many methods for separating the pounds whose mass spectrum is known and in the analysis
resulting ions (see Section 1.2). For instance, in the com- of completely unknown compounds. In the case of known
monly used electron impact (EI) mode, the mass spectrom- compounds, a computer search is conducted comparing the
eter bombards molecules in the vapor phase with a high- mass spectrum of the compound in question with a library of
energy electron beam and records the result as a spectrum mass spectra. Electron impact mass spectrometry is particu-
of positive ions, which have been separated on the basis of larly useful in this regard since EI mass spectrometry leads
mass/charge (m∕z).* to considerable fragmentation. Congruence of mass spectra
To illustrate, the EI mass spectrum of benzamide is is convincing evidence for identification and is often even
given in Figure 1.1 showing a plot of abundance (% of the admissible in court. In the case of an unknown compound,
base peak, the most intense peak in the spectrum) versus the molecular ion, the fragmentation pattern, and evidence
m∕z. The positive ion peak at m∕z 121 represents the intact from other forms of spectrometry (e.g., IR and NMR) can
molecule (M) less one electron, which was removed by the lead to the identification of a new compound. Our focus and
impacting electron beam; it is designated as the molecular goal in this chapter is to develop skill in the latter use,

O
Benzamide
C7H7NO C+
Mol. Wt.: 121
-CO
O NH2 O NH2 H
-N 2

- m/z 105 m/z 77

+ e- - 2e -C H
65
O NH2
M m/z 121 m/z 44
77
105
% of Base Peak

100 M+
121
51

50
44
18 28

0
20 30 40 50 60 m/z 70 80 90 100 110 120
FIGURE 1.1 The EI mass spectrum of benzamide, above which is a fragmentation pathway to explain some of the
important ions.

* The 1
unit of mass is the Dalton (Da), defined as 12 of the mass of an atom
of the isotope 12 C, which is arbitrarily 12.0000 … mass units.

1
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2 CHAPTER 1 MASS SPECTROMETRY

especially using the EI method. For other applications or for To determine the resolution* of an instrument, consider
more detail, mass spectrometry texts and spectral compila- two adjacent peaks of approximately equal intensity. These
tions are listed online at www.wiley.com/college/silverstein. peaks should be chosen so that the height of the valley
between the peaks is less than 10% of the intensity of the
peaks. The resolution (R) is R = Mn ∕(Mn − Mm ), where Mn
1.2 INSTRUMENTATION is the higher mass number of the two adjacent peaks, and
Mm is the lower mass number.
As with all modern analytical instrumentation, there has There are two important categories of mass spec-
been recent, rapid growth and change in instrumentation for trometers: low (unit) resolution and high resolution. Low-
mass spectrometry. Instead of discussing individual instru- resolution instruments can be defined arbitrarily as the
ments, the discussion will be broken down into (1) ionization instruments that separate unit masses up to m∕z 3000 [R =
methods and (2) ion separation methods. In general, the 3000∕(3000 − 2999) = 3000]. A high-resolution instrument
method of ionization is independent of the method of (e.g., R = 20,000) can distinguish between C16 H26 O2 and
ion separation and vice versa, although there are excep- C15 H24 NO2 [R = 250.1933∕(250.1933 − 250.1807)=19857].
tions. Some of the ionization methods depend on a spe- This important class of mass spectrometers, which can have
cific chromatographic front end (e.g., LC-MS), while still R as large as 100,000, can measure the mass of an ion
others are precluded from using chromatography for intro- with sufficient accuracy to determine its atomic composi-
duction of the sample (e.g., FAB and MALDI). Before tion (molecular formula). As a practical matter, the term
delving further into instrumentation, let us make a distinc- high-resolution mass spectrometry will be used to designate
tion between two types of mass spectrometers based on accurate mass measurement. The number of decimal places
resolution. needed for an unambiguous determination of elemental com-
The minimum requirement for the organic chemist is position is related to the mass of the ion. For instance, an
the ability to record the molecular weight of the compound accuracy of 0.0025 Da should be sufficient for ions with a
under examination to the nearest whole number. Thus, the mass of less than 500 Da.
spectrum should show a peak at, say, m∕z 400, which is All mass spectrometers share common features (see
distinguishable from a peak at m∕z 399 or at m∕z 401. In Figure 1.2). Introduction of the sample into the mass spec-
order to select possible molecular formulas by measuring trometer is an important consideration, but it often depends
isotope peak intensities (see Section 1.5.2.1), adjacent peaks on the type of ionization method (see below). All mass spec-
must be cleanly separated. Arbitrarily, the valley between trometers have methods for ionizing the sample and for sep-
two such peaks should not be more than 10% of the height arating the ions on the basis of m∕z. These methods are
of the larger peak. This degree of resolution is qualitatively discussed in detail below. Once separated, the ions must be
termed “unit” resolution and can be obtained up to a mass of detected and quantified. A typical ion collector consists of
approximately 3000 Da on readily available “unit resolution” collimating slits that direct only one set of ions at a time
instruments. into the collector, where they are detected and amplified by
an electron multiplier. Ion detectors are designed to balance
sensitivity, accuracy, and response time. Generally speaking,
Mm Mn
fast response times and high accuracy are mutually exclusive.
The method of ion detection is dependent to some extent on
H (Hh (100 ≤ 10% the method of ion separation.

h * This definition is the most common way to calculate resolution, but not the

only way.

Computer system

Sample Ionization Ion separation Detector

introduction method method
FIGURE 1.2 Block diagram of features of a typical mass spectrometer.
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1.3 IONIZATION METHODS 3

Nearly all mass spectrometers today are interfaced with accessible databases contain EI mass spectra of over 390000
a computer. Typically, the computer controls the operation of compounds and they are easily searched by efficient com-
the instrument, which includes any chromatography, collects puter algorithms. The uniqueness of the EI mass spectrum
and stores the data, and provides either graphical output for a given organic compound, even for diastereomers, is
(essentially a bar graph) or tabular lists of the data. an almost certainty. This uniqueness, coupled with the great
sensitivity of the method, is what makes GC-MS such a pow-
erful and popular analytical tool. We will discuss EI mass
1.3 IONIZATION METHODS spectra beginning in Section 1.5.

The large number of ionization methods, some of which 1.3.1.2 Chemical Ionization. Electron impact ionization
are highly specialized, precludes complete coverage. The often leads to such extensive fragmentation that no molec-
most common ones in the three general areas of gas-phase, ular ion is observed. One way to avoid this problem is to
desorption, and evaporative ionization are described below. use an indirect ionization method; chemical ionization (CI)
is popular and readily available on many commercial instru-
ments. In CI, sample molecules (in the vapor phase) are
1.3.1 Gas-Phase Ionization Methods not subjected to bombardment by high-energy electrons.
Gas-phase methods for generating ions for mass spectrom- Instead, a reagent gas (usually methane, isobutane, ammo-
etry are the oldest and most popular methods for organic nia, but others are also used) is introduced into the ion-
chemists. These methods are applicable to compounds that ization source and ionized. Sample molecules collide with
have a minimum vapor pressure of ca. 10−6 Torr at a tem- ionized reagent gas molecules (CH5 + , C4 H9 + , etc.) in the
perature at which the compound is stable; this criterion relatively high-pressure CI source and undergo secondary
applies to a large number of nonionic organic molecules with ionization (i.e., chemical ionization) by proton transfer pro-
MW<1000 Da. ducing an [M + 1]+ ion, by electrophilic addition produc-
ing [M + 15]+ , [M + 29]+ , [M + 41]+ , or [M + 18]+ (with
1.3.1.1 Electron Impact Ionization. Electron impact (EI) NH4 + ions), or by charge exchange (rare) producing a [M]+
has historically been the most widely used method for gener- ion. Chemical ionization spectra sometimes have prominent
ating ions for mass spectrometry. It is also the main focus in [M − 1]+ ion peaks because of hydride abstraction. The ions
this chapter for interpreting mass spectra for structure deter- thus produced are even electron species. The excess energy
mination. Vapor-phase sample molecules are bombarded transfered to the sample molecules during the ionization
with high-energy electrons (generally 70 eV), the purpose of phase is small, generally less than 5 eV, so that much less
which is to eject an electron from a sample molecule to pro- fragmentation takes place. There are several important con-
duce a radical cation, known as the molecular ion. Because sequences, the most valuable of which are an abundance of
the ionization potential of typical organic compounds is quasimolecular ions and greater sensitivity because the total
generally less than 15 eV, the bombarding electrons impart ion current is concentrated into a few ions. There is how-
50 eV (or more) of excess energy to the newly created molec- ever, less information on structure. The quasimolecular ions
ular ion, which is dissipated, in part, by the breaking of cova- are usually quite stable and they are readily detected. Often-
lent bonds, which have strengths between 3 and 10 eV. times, there are only one or two fragment ions produced and
Bond breaking is usually extensive and critically, highly sometimes there are none.
reproducible, and characteristic of the compound. Further- For example, the EI mass spectrum of 3, 4-dimethoxy-
more, this fragmentation process is also partly predictable acetophenone (Figure 1.3) shows, in addition to the molec-
and is the source of the powerful structure elucidation poten- ular ion at m∕z 180, numerous fragment peaks in the range
tial of mass spectrometry. Often, the excess energy imparted of m∕z 15 to 167; these include the base peak at m∕z 165
to the molecular ion is too great, which leads to a mass spec- and prominent peaks at m∕z 137 and m∕z 77. The CI mass
trum with no discernible molecular ion. Reduction of the spectrum (methane, CH4 , as reagent gas) shows the quasi-
ionization voltage is a commonly used strategy to obtain a molecular ion ([M + 1]+ , m∕z 181) as the base peak (100%),
molecular ion; the strategy is often successful because there and no fragment ion peaks. The only other peaks, each of
is greatly reduced fragmentation. The disadvantage of this just a few percent intensity, are the molecular ion peak,
strategy is that the spectrum changes and cannot be compared m∕z 180, m∕z 209 ([M + 29]+ or M + C2 H5 + ), and m∕z 221
to standard literature spectra. ([M + 41]+ or M + C3 H5 + ). These last two peaks are a result
To many organic chemists, mass spectrometry is of electrophilic addition of carbocations and are very useful
synonymous with EI mass spectrometry. This view is in identifying the molecular ion. The excess methane carrier
understandable for two reasons. First, historically, EI was gas is ionized by electron impact to the primary ions CH4 +
universally available before other ionization methods were and CH3 + . These react with the excess methane to give sec-
developed. Much of the early work was EI mass spectrom- ondary ions.
etry. Second, the major libraries and databases of mass
spectral data, which are relied upon so heavily and cited CH3 + + CH4 −→ C2 H5 + and H2
so often, are of EI mass spectra. Some of the readily CH4 + C2 H5 + −→ C3 H5 + and 2H2
 Silverstein c01.tex V3 - 07/10/2014 3:46 P.M. Page 4

4 CHAPTER 1 MASS SPECTROMETRY

EI O
H3CO 165
CH3
% of Base Peak

100
H3CO M+
3,4-Dimethoxyacetophenone 180
C10H12O3
50 Mol. Wt.: 180
43 77 137
15 51 94 109

0
50 100 m/z 150 200
CI reagent gas methane
181
% of Base Peak

100
[M+1]+ = M+H+
[M+29]+ = M+C2H5+
[M+41]+ = M+C3H5+
50
209
221

0
50 100 m/z 150 200

FIGURE 1.3 The EI and CI mass spectra of 3,4-dimethoxyacetophenone.

The energy content of the various secondary ions (from, molecular ion or the quasimolecular ion may not be evident.
respectively, methane, isobutane, and ammonia) decrease in The resulting spectra are often complicated by abundant
the order: C3 H5 + > t-C4 H9 + > NH4 + . Thus, by choice of matrix ions.
reagent gas, we can control the tendency of the CI produced
[M + 1]+ ion to fragment. For example, when methane is 1.3.2.1 Field Desorption Ionization. In the field desorp-
the reagent gas, dioctyl phthalate shows its [M + 1]+ peak tion (FD) method, the sample is applied to a metal emitter
(m∕z 391) as the base peak; more importantly, the fragment on the surface of which is found carbon microneedles. The
peaks (e.g., m∕z 113 and 149) are 30% to 60% of the intensity microneedles activate the surface, which is maintained at the
of the base beak. When isobutane is used, the [M + 1]+ peak accelerating voltage and functions as the anode. Very high
is still large, while the fragment peaks are only roughly 5% voltage gradients at the tips of the needles remove an electron
as intense as the [M + 1]+ peak. from the sample, and the resulting cation is repelled away
Chemical ionization mass spectrometry is neither useful from the emitter. The ions generated have little excess energy
for peak matching (either manually or by computer) nor is so there is minimal fragmentation, that is, the molecular ion
it particularly useful for structure elucidation; its main use is usually the only significant ion seen. For example, with
is for the detection of molecular ions and hence molecular cholest-5-ene-3,16,22,26-tetrol, the EI and CI mass spectra
weights. do not show a molecular ion peak. However, the FD mass
spectrum (Figure 1.4) shows predominately the molecular
ion with virtually no fragmentation.
1.3.2 Desorption Ionization Methods
Desorption ionization methods are those techniques in which 1.3.2.2 Fast Atom Bombardment Ionization. Fast atom
sample molecules are emitted directly from a condensed bombardment (FAB) uses high-energy xenon or argon atoms
phase into the vapor phase as ions. The primary use of (6 keV to 10 keV) to bombard samples dissolved in a liquid
these methods is for large, nonvolatile, or ionic compounds. of low vapor pressure (e.g., glycerol). The matrix protects the
There can be significant disadvantages. Desorption methods sample from excessive radiation damage. A related method,
generally do not use available sample efficiently. Often times, liquid secondary ionization mass spectrometry, LSIMS, is
the information content is limited. For unknown compounds, similar except that it uses somewhat more energetic cesium
the methods are used primarily to provide molecular weight, ions (10 keV to 30 keV).
and in some cases to obtain an exact mass. However, even In both methods, positive ions (by cation attachment
for this purpose, it should be used with caution because the ([M + 1]+ or [M + 23, Na]+ ) and negative ions (by
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1.3 IONIZATION METHODS 5

EI
99
% of Base Peak

100

55
44 82
50 117
145 159 271 300
318
416
0
50 100 150 200 250 300 350 400
m/z
CI reagent gas isobutane
99
% of Base Peak

100 399
283
271

417
50 255 381

0
50 100 150 200 250 300 350 400
m/z
FD (18 MA)
OH 434
CH3 CH3
% of Base Peak

100 CH3 M+
CH2
CH3 OH OH

50 Cholest-5-ene-3,16,22,26-tetrol
HO C27H46O4
Mol. Wt.: 434

0
50 100 150 200 250 300 350 400
m/z
FIGURE 1.4 The electron impact (EI), chemical ionization (CI), and field desorption (FD) mass spectra of cholest-5-ene-3,
16, 22, 26-tetrol.

deprotonation [M − 1]− ) are formed; both types of ions are resolution of about 0.3 m∕z over the entire mass range; FAB
usually singly charged and, depending on the instrument, can, however, be used with most types of mass analyzers. The
FAB can be used in high-resolution mode. FAB is used biggest drawback to using FAB is that the spectrum always
primarily with large nonvolatile molecules, particularly to shows a high level of matrix generated ions, which limit
determine molecular weight. For most classes of compounds, sensitivity and which may obscure important fragment ions.
the rest of the spectrum is less useful, partially because the
lower mass ranges may be composed of ions produced by the 1.3.2.3 Plasma Desorption Ionization. Plasma desorp-
matrix itself. However, for certain classes of compounds that tion ionization is a highly specialized technique used almost
are composed of “building blocks,” such as polysaccharides exclusively with a time-of-flight (TOF) mass analyzer
and peptides, some structural information may be obtained (Section 1.4.4). The fission products from californium-
because fragmentation usually occurs at the glycosidic and 252 (252 Cf), with energies in the range of 80 MeV to
peptide bonds, respectively, thereby affording a method of 100 MeV, are used to bombard and ionize the sample. Each
sequencing these classes of compounds. time a 252 Cf splits, two particles are produced moving in
The upper mass limit for FAB (and LSIMS) ionization opposite directions. One of the particles hits a triggering
is between 10 kDa and 20 kDa, and FAB is really most detector and signals a start time. The other particle strikes
useful up to about 6 kDa. FAB is seen most often with the sample matrix ejecting some sample ions into a time-
double focusing magnetic sector instruments where it has a of-flight mass spectrometer (TOF-MS). The sample ions
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6 CHAPTER 1 MASS SPECTROMETRY

are most often released as singly, doubly, or triply proto- further exacerbated by matrix adduction. Thus, the assign-
nated moieties. These ions are of fairly low energy so that ment of a molecular ion of an unknown compound can be
structurally useful fragmentation is rarely observed and, for uncertain.
polysaccharides and polypeptides, sequencing information is
not available. The mass accuracy of the method is limited
1.3.3 Evaporative Ionization Methods
by the TOF mass spectrometer. The technique is useful on
compounds with molecular weights up to at least 45 kDa. There are two important methods in which ions or, less
often, neutral compounds in solution (often containing
formic acid) have their solvent molecules stripped by evap-
1.3.2.4 Laser Desorption Ionization. A pulsed laser
oration, with simultaneous ionization leaving behind the
beam can be used to ionize samples for mass spectrometry.
ions for mass analysis. Coupled with liquid chromatogra-
Because this method of ionization is pulsed, it must be used
phy instrumentation, these methods have become immensely
with either a TOF or a Fourier transform mass spectrometer
popular.
(Section 1.4.5). Two types of lasers have found widespread
use: a CO2 laser, which emits radiation in the far infrared
1.3.3.1 Thermospray Mass Spectrometry. In the ther-
region, and a frequency-quadrupled neodymium/yttrium-
mospray method, a solution of the sample is introduced into
aluminum-garnet (Nd∕YAG) laser, which emits radiation
the mass spectrometer by means of a heated capillary tube.
in the UV region at 266 nm. Without matrix assistance,
The tube nebulizes and partially vaporizes the solvent, form-
the method is limited to low molecular weight molecules
ing a stream of fine droplets which enter the ion source. When
(<2 kDa).
the solvent completely evaporates, the sample ions can be
The power of the method is greatly enhanced by using
mass analyzed. This method can handle high flow rates and
matrix assistance (matrix-assisted laser desorption ioniza-
buffers; it was an early solution to interfacing mass spectrom-
tion, or MALDI). Two matrix materials, 2,5-dihydroxyben-
eters with aqueous liquid chromatography. The method has
zoic acid and sinapinic acid, which have absorption bands
largely been supplanted by electrospray.
coinciding with the laser employed, have found widespread
use and sample molecular weights of up to two to three hun- 1.3.3.2 Electrospray Mass Spectrometry. The electro-
dred thousand Da have been successfully analyzed. A few spray (ES) ion source (Figure 1.5) is operated at or near
picomoles of sample are mixed with the matrix compound atmospheric pressure and, thus is also called atmospheric
followed by pulsed irradiation, which causes sample ions pressure ionization or API. The sample in solution (usually a
(usually singly charged monomers but occasionally multiply polar, volatile solvent) enters the ion source through a stain-
charged ions and dimers have been observed) to be ejected less steel capillary, which is surrounded by a co-axial flow of
from the matrix into the mass spectrometer. nitrogen, called the nebulizing gas. The tip of the capillary
The ions have little excess energy and show little propen- is maintained at a high potential with respect to a counter-
sity to fragment. For this reason, the method is fairly useful electrode. The potential difference produces a field gradient
for mixtures. MALDI is used most often with a TOF-MS of up to 5 kV/cm. As the solution exits the capillary, an
or a Fourier transform mass spectrometer (FT-MS); both aerosol of charged droplets forms. The flow of nebulizing
mass analyzers are capable of accurate mass measurement. gas directs the effluent toward the mass spectrometer.
As with other matrix-assisted methods, MALDI suffers from Droplets in the aerosol shrink as the solvent evapo-
background interference from the matrix material, which is rates, thereby concentrating the charged sample ions. When

ESI spray droplets with Charged Plates

excess charge on surface
Mass
Nebulizer gas spectrometer
Nebulizer needle Solvent/sample
Nebulizer gas
Capillary entrance

2 kV to 5 kV
Power supply
FIGURE 1.5 A diagram showing the evaporation of solvent leading to individual ions in an electrospray instrument.
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1.3 IONIZATION METHODS 7

the electrostatic repulsion among the charged sample ions A simple computer program automates this calculation for
reaches a critical point, the droplet undergoes a so-called every peak in the spectrum and calculates the mass directly.
Coulombic explosion, which releases the sample ions into Many manufacturers have introduced inexpensive mass
the vapor phase. The vapor phase ions are focused with a spectrometers dedicated to electrospray for two reasons.
number of sampling orifices into the mass analyzer. First, the method has been very successful while remaining a
Electrospray MS has undergone an explosion of activity fairly simple method to employ. Second, the analysis of pro-
since about 1990, mainly for compounds that have multiple teins and smaller peptides has grown in importance, and they
charge-bearing sites. With proteins, for example, ions with are probably analyzed best by the electrospray method.
multiple charges are formed. Since the mass spectrometer Figure 1.6 compares the EI mass spectrum (lower por-
measures mass to charge ratio (m∕z) rather than mass tion of the figure) of lactose to its ES mass spectrum (upper
directly, these multiply charged ions are recorded at apparent portion of figure). Lactose is considered in more detail
mass values of 12 , 13 , … 1n of their actual masses, where n is in Chapter 5. The EI mass spectrum is completely useless
the number of charges (z). Large proteins can have 40 or because lactose has low vapor pressure, it is thermally labile,
more charges so that molecules of up to 100 kDa can be and the spectrum shows no characteristic peaks. The ES mass
detected in the range of conventional quadrupole, ion trap, spectrum shows a weak molecular ion peak at m∕z 342 and
or magnetic sector mass spectrometers. The appearance of a characteristic [M + 23]+ peak, the molecular ion peak plus
the spectrum is a series of peaks increasing in mass, which sodium. Because sodium ions are ubiquitous in aqueous solu-
correspond to pseudomolecular ions possessing sequentially tion, these sodium adducts are very common.
one less proton and therefore one less charge. The ES mass spectrum of a tetra peptide comprised
Determination of the actual mass of the ion requires of valine, glycine, serine, and glutamic acid (VGSE) is
that the charge of the ion be known. If two peaks, which given in Figure 1.7. VGSE is also an example compound in
differ by a single charge, can be identified, the calculation Chapter 5. The base beak is the [M + 1]+ ion at m∕z 391
is reduced to simple algebra. Recall that each ion of the and the sodium adduct, [M + 23]+ , is nearly 90% of the
sample molecule (Ms ) has the general form (Ms + zH)z+ base peak. In addition, there is some useful fragmentation
where H is the mass of a proton (1.0079 Da). For two information characteristic of each of the amino acids. For
ions differing by one charge, m1 = [Ms + (z + 1)H]∕(z + small peptides, it is not uncommon to find some helpful
1) and m2 = [(Ms + zH)∕z]. Solving the two simultaneous fragmentation, but for proteins it is less likely.
equations for the charge z, yields z = (m1 − H)∕(m2 − m1 ). Methods of ionization are summarized in Table 1.1.

ES HO OH H OH 365
HO
100 O
% of Base Peak

+
H H [M+23] (Na)
HO HO O
H OH
H H H H OH H
50 Lactose (C12H22O11) Mol. Wt.: 342 OH

M+
200 251 342

0
50 100 150 200 m/z 250 300 350
EI 73
100
% of Base Peak

57
60

85
50
103

131
163 191
0
50 100 150 200 m/z 250 300 350
FIGURE 1.6 The EI and ES mass spectra of lactose.
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8 CHAPTER 1 MASS SPECTROMETRY

OH
5C O
4 CH3 OH 4 CH2
5
3 CH CH3 3 CH2 3 CH2
2 1 1
H2N CH C N CH2 C N CH C N CH C OH
2 1 2 2 1
H H H
O O O O
Valine (V) Glycine (G) Serine (S) Glutamate (E) [M + 1]+
[M + H]+ [M + 23]+
C5H10ON C2H3ON C3H5O2N C5H8O4N
ES [M + Na]+
mw=100 mw=57 mw=87 mw=146 391
413
100
M-(V,G)
% of Base Peak

235
M-(V)
50 M-(E,S) M-(E) 292 M-17
157 244
373

150 200 250 300 350 400

m/z
FIGURE 1.7 The electrospray (ES) mass spectrum for the tetra peptide whose structure is given in the figure. See text for
explanation.

TABLE 1.1 Summary of Ionization Methods

Ionization Method Ions Formed Sensitivity Advantage Disadvantage

Electron impact M+ ng – pg Data base searchable M+ occasionally absent

Structural information
Chemical ionization M + 1, M + 18, etc. ng – pg M+ usually present Little structural information
Field desorption M+ μg − ng Nonvolatile compounds Specialized equipment
Fast atom M + 1, M + cation μg − ng Nonvolatile compounds Matrix interference
bombardment M + matrix Sequencing information Difficult to interpret
Plasma desorption M+ μg − ng Nonvolatile compounds Matrix interference
Laser desorption M + 1, M + matrix μg − ng Nonvolatile compounds Matrix interference
Burst of ions
Thermospray M+ μg − ng Nonvolatile compounds Outdated
Electrospray M+ , M++ , M+++ , ng – pg Nonvolatile compounds Limited classes of compounds
etc. interfaces w/LC
Forms multiply charged ions Little structural information

1.4 MASS ANALYZERS awarded partly for the development of the mass spectrograph.
All of the early instruments were of the magnetic sector
type. The magnetic sector mass spectrometer uses a magnetic
The mass analyzer, which separates the mixture of ions that is field to deflect moving ions around a curved path (see
generated during the ionization step by m∕z in order to obtain Figure 1.8). Even though magnetic sector mass spectrome-
a spectrum, is the heart of each mass spectrometer, and there ters were the first commercially available instruments, they
are several different types with different characteristics. Each remain important today. Separation of ions occurs based on
of the major types of mass analyzers is described below. This the mass/charge ratio, with lighter ions deflected to a greater
section concludes with a brief discussion of tandem MS and extent than the heavier ions. Resolution depends on each ion
related processes. entering the magnetic field (from the source) with the same
kinetic energy, accomplished by accelerating the ions (which
1.4.1 Magnetic Sector Mass have a charge z) with a voltage V. Each ion acquires kinetic
Spectrometers energy E = zV = mv2 ∕2. When an accelerated ion enters the
Mass spectrometers were originally developed in the early magnetic field (B), it experiences a deflecting force (Bzv),
twentieth century; the 1922 Nobel Prize in chemistry was which bends the path of the ion orthogonal to its original
 Silverstein c01.tex V3 - 07/10/2014 3:46 P.M. Page 9

1.4 MASS ANALYZERS 9

Lens stack

Sample Ionization
Introduction source

Magnet sector (B)

N
B0
Collector slits

Computer Detector

FIGURE 1.8 Schematic diagram of a single focusing, 180∘ sector mass analyzer. The magnetic field
is perpendicular to the page. The radius of curvature varies from one instrument to another.

Lens stack

Magnet sector (B)

Sample Ionization
Introduction source

r = 35 cm
m = 65
o Focusing slit
Focusing element
Electric sector

Collector slit

Computer Detector

FIGURE 1.9 Schematic of double-focusing mass spectrometer.

direction. The ion is now traveling in a circular path of radius The resolution of a double-focusing magnetic sec-
r, given by Bzv = mv2 ∕r. The two equations can be com- tor instrument (Figure 1.9) can be as high as 100000
bined to give the familiar magnetic sector equation: m∕z = through the use of extremely small slit widths. This very
B2 r2 ∕2V. Because the radius of the instrument is fixed, the high resolution allows the measurement of “exact masses,”
magnetic field is scanned to bring the ions of different m∕z which unequivocally provide molecular formulas and is
sequentially into focus. As these equations show, a magnetic enormously useful. By comparison, slits allowing an energy
sector instrument separates ions on the basis of momentum, distribution for about 5000 resolution give at least 0.5 m∕z
which is the product of mass and velocity, rather than mass accuracy across the entire mass range, that is, the “unit res-
alone; therefore, ions of the same mass but different energies olution” that is used in a standard mass spectrometer. The
will come into focus at different points. upper mass limit for commercial magnetic sector instruments
An electrostatic analyzer (ESA) can greatly reduce the is about m∕z 15000. Raising this upper limit is theoretically
energy distribution of an ion beam by forcing ions of the possible but impractical.
same charge (z) and kinetic energy (regardless of mass) to
follow the same path. A slit at the exit of the ESA further
1.4.2 Quadrupole Mass Spectrometers
focuses the ion beam before it enters the detector. The
combination of an ESA and a magnetic sector is known The quadrupole mass analyzer (sometimes abbreviated QMF
as double focusing because the two fields counteract the for quadrupole mass filter), also known as the transmission
dispersive effects each has on direction and velocity. quadrupole, is much smaller and cheaper than a magnetic
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10 CHAPTER 1 MASS SPECTROMETRY

Ion beam Quadrupole Resonant ions

Ion volume + +

Detector

Source lenses

DC and RF voltages
FIGURE 1.10 Schematic representation of a quadrupole “mass filter” or ion separator.

sector instrument. A quadrupole setup (seen schematically the quadrupole mass spectrometer is ideal for interfacing
in Figure 1.10) consists of four cylindrical (or of hyperbolic to LC systems and for atmospheric pressure ionization
cross-section) rods (100 mm to 200 mm long) mounted (API) techniques such as electrospray (see Section 1.3.3.2).
parallel to each other, at the corners of a square. A complete These techniques work best on ions of low energy so that
mathematical analysis of the quadrupole mass analyzer is fewer high-energy collisions will occur before they enter the
complex, but we can discuss how it works in a simplified quadrupole.
form. This nonmagnetic mass analyzer uses a constant DC
voltage, which is modified by a radiofrequency voltage,
applied to the rods. Ions are introduced to the “tunnel”
1.4.3 Ion Trap Mass Spectrometer
formed by the four rods of the quadrupole in the center of
the square at one end to the rods and travel down the axis. The ion trap, also known as the quadrupole ion trap, is
For any given combination of DC voltage and modified sometimes considered as a variant of the quadrupole, since
voltage applied at the appropriate frequency (always at a it resulted as a direct outgrowth of quadrupole research.
constant ratio), only ions with a certain m∕z value possess However, the ion trap is much more versatile and clearly
a stable trajectory and therefore are able to pass all the has greater potential for development. At one time the ion
way to the end of the quadrupole to the detector. All ions trap had a bad reputation because the earliest versions gave
with different m∕z values travel unstable or erratic paths and inferior results compared to quadrupoles. These problems
collide with one of the rods or pass outside the quadrupole. have been overcome and the EI spectra obtained with
An easy way to look at the quadrupole mass analyzer is as an ion trap are now fully searchable with commercial
a tunable mass filter. In other words, as the ions enter at databases. Furthermore, the ion trap is more sensitive than
one end, only one m∕z ion will pass through. In practice, the quadrupole arrangement, and the ion trap is routinely
the filtering can be carried out at a very fast rate so that the configured to carry out tandem experiments with no extra
entire mass range can be scanned in considerably less than hardware needed.
1 second. In one sense, an ion trap is aptly named because, unlike
The development of the QMF forever changed mass the quadrupole, which merely acts as a mass filter, the
spectrometry. Lower cost and ease-of-use led to “benchtop” ion trap literally “traps” ions for relatively long periods of
instruments, which in turn led to everyday use by chemists time, with important consequences. The simplest use of
and technicians. Also, the very fast scan times enabled the the trapped ions is to sequentially eject them to a detector,
coupling of the quadrupole mass spectrometer with the gas producing a conventional mass spectrum. Before other uses
chromatograph. of trapped ions are briefly described, a closer look at the ion
With respect to resolution and mass range, the quad- trap itself will be helpful.
rupole is generally inferior to the magnetic sector. For The ion trap generally consists of three electrodes
instance, the current upper mass range is generally less than (hence, it is often called a 3D quadrupole ion trap or 3D QIT):
5000 m∕z. On the other hand, sensitivity is generally high one ring electrode with a hyperbolic inner surface, and two
because there is no need for resolving slits, which would hyperbolic endcap electrodes at either end (a cross section
remove a portion of the ions. An important advantage of of an ion trap is found in Figure 1.11). The ring electrode
quadrupoles is that they operate most efficiently on ions is operated with a sinusoidal radiofrequency field while the
of low velocity, which means that their ion sources can endcap electrodes are operated in one of three modes. The
operate close to ground potential (i.e., low voltage). Since endcap may be operated at ground potential, or with either a
the entering ions generally have energies of less than 100 eV, DC or an AC voltage.
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1.4 MASS ANALYZERS 11

Einzel lens,
Central element Trap ring electrode

Ion volume

Source lenses
Einzel lens,
First element Trap end caps
FIGURE 1.11 Cross-sectional view of an ion trap.

The mathematics that describes the motion of ions with the nearly 100% tandem efficiency, the use of the ion
within the ion trap are given by the Mathieu equation. Details trap for the tandem MS experiment greatly outshines the so-
and discussions of three-dimensional ion stability diagrams called triple quad (see below).
can be found in either March and Hughes (1989) or Nourse Another way to use this kinetic energy addition mode is
and Cooks (1990). The beauty of the ion trap is that by to selectively reject unwanted ions from the ion trap. These
controlling the three parameters of RF voltage, AC voltage, could be ions derived from solvent or from the matrix in FAB
and DC voltage, a wide variety of experiments can be run or LSIMS experiments. A constant frequency field at high
quite easily (for details see March and Hughes, 1989). voltage during the ionization period will selectively reject a
There are three basic modes in which the ion trap can be single ion. Multiple ions can also be selected in this mode.
operated. First, when the ion trap is operated with a fixed
RF voltage and no DC bias between the endcap and ring
electrodes, all ions above a certain cutoff m∕z ratio will 1.4.4 Time-of-Flight Mass
be trapped. As the RF voltage is raised, the cutoff m∕z is Spectrometer
increased in a controlled manner and the ions are sequen-
The concept of time-of-flight (TOF) mass spectrometers is
tially ejected and detected. The result is the standard mass
simple. Ions are accelerated through a potential (V) and
spectrum and this procedure is called the “mass-selective
are then allowed to “drift” down a tube to a detector. If
instability” mode of operation. The maximum RF potential
the assumption is made that all of the ions arriving at the
that can be applied between the electrodes limits the upper
beginning of the drift tube have the same energy given by
mass range in this mode. Ions of mass contained beyond the
zeV = mv2 ∕2, then ions of different mass will have different
upper limit are removed after the RF potential is brought back 1
to zero. velocities: v = (2zeV∕m) 2 . If a spectrometer possesses a
The second mode of operation uses a DC potential drift tube of length L, the time of flight for an ion is given
1
across the endcaps; the general result is that there is now both by: t = (L2 m∕2zeV) 2 , from which the mass for a given ion
a low- and high-end cutoff (m∕z) of ions. The possibilities can be easily calculated.
of experiments in this mode of operation are tremendous, The critical aspect of this otherwise simple instrument
and most operations with the ion trap use this mode. As few is the need to produce the ions at an accurately known start
as one ion mass can be selected. Selective ion monitoring time and position. These constraints generally limit TOF
is an important use of this mode of operation. There is no spectrometers to use pulsed ionization techniques, which
practical limit on the number of ionic masses that can be include plasma and laser desorption (e.g., MALDI, matrix
selected. assisted laser desorption ionization).
The third mode of operation is similar to the second, The resolution of TOF instruments is usually less than
with the addition of an auxiliary oscillatory field between 20000 because some variation in ion energy is unavoidable.
the endcap electrodes, which results in adding kinetic energy Also, since the difference in arrival times at the detector can
selectively to a particular ion. With a small amplitude be less than 10−7 seconds, fast electronics are necessary for
auxiliary field, selected ions gain kinetic energy slowly, adequate resolution. On the positive side, the mass range of
during which time they usually undergo a fragmenting these instruments is unlimited, and, like quadrupoles, they
collision; the result can be a nearly 100% MS-MS efficiency. have excellent sensitivity due to lack of resolving slits. Thus,
If the inherent sensitivity of the ion trap is considered along the technique is most useful for large biomolecules.
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12 CHAPTER 1 MASS SPECTROMETRY

1.4.5 Fourier Transform Mass from other animals such as race horses) for the presence of
Spectrometer drugs or drug metabolites can be carried out routinely on
whole urine (i.e., no purification or separation) by MS-MS.
In a Fourier transform mass spectrometer (formerly called an For unknown compounds, these daughter ions can provide
ion cyclotron resonance mass spectrometer), ions are held structural information as well.
in a cell with an electric trapping potential within a strong One way to carry out MS-MS is to link two or more
magnetic field. Within the cell, each ion orbits in a direction mass analyzers in series to produce an instrument capa-
perpendicular to the magnetic field, with a frequency propor- ble of selecting a single ion, and examining how that ion
tional to the ion’s m∕z value. A radiofrequency pulse applied (either a parent or daughter ion) fragments. For instance,
to the cell brings all of the cycloidal frequencies into reso- three quadrupoles can be linked (a so-called triple quad) to
nance simultaneously to yield an interferogram, conceptually produce a tandem mass spectrometer. In this arrangement,
similar to the free induction decay (FID) signal in NMR or the first quadrupole selects a specific ion for further analysis,
the interferogram generated in FTIR experiments. The inter- the second quadrupole functions as a collision cell (collision
ferogram, which is a time domain spectrum, is Fourier trans- induced dissociation, CID) and is operated with radiofre-
formed into a frequency domain spectrum, which then yields quency only, and the third quadrupole separates the prod-
the conventional m∕z spectrum. Pulsed Fourier transform uct ions to produce a spectrum of daughter ions. The field
methods applied to nuclear magnetic resonance spectroscopy of tandem mass spectrometry is already rather mature with
are discussed in Chapters 3, 4, and 5. good books available (Benninghoven et al., 1987; Wilson
Because the instrument is operated at fixed mag- et al., 1989).
netic field strength, extremely high field superconducting In order for an instrument to carry out MS-MS, it must
magnets can be used. Also, because mass range is directly be able to do the three operations outlined above. As we
proportional to magnetic field strength, very high mass have seen, however, ion-trap systems capable of MS-MS and
detection is possible. Finally, since all of the ions from a MS(n) do not use a tandem arrangement of mass analyzers at
single ionization event can be trapped and analyzed, the all, but rather use a single ion trap for all three operations
method is very sensitive and works well with pulsed ion- simultaneously. As has already been stated, these ion-trap
ization methods. The most compelling aspect of the method tandem mass spectrometer experiments are very sensitive
is its high resolution, making FT mass spectrometers an and are now user friendly. The ion trap brings the capability
attractive alternative to other mass analyzers. The FT mass for carrying out MS-MS experiments to the benchtop at
spectrometer can be coupled to chromatographic instrumen- relatively low cost.
tation and various ionization methods, which means that it A summary of mass analyzers and ionization methods
can be easily used with small molecules. Further informa- is displayed in Table 1.2.
tion on FT mass spectrometers can be found in the book by
Gross (1990).
1.5 INTERPRETATION OF EI MASS
1.4.6 Tandem Mass Spectrometry SPECTRA
Tandem mass spectrometry or MS-MS (“MS squared”) is
useful in studies with both known and unknown compounds; Our discussion of interpreting mass spectra is limited to EI
with certain ion traps, MS to the nth (MS(n) ) is possible mass spectrometry. Fragmentation in EI mass spectra is rich
where n = 2 to 9. In practice, n rarely exceeds 2 or 3. With with structural information; mastery of EI mass spectra is
MS-MS, a “parent” ion from the initial fragmentation (the especially useful for the organic chemist.
initial fragmentation gives rise to the conventional mass EI mass spectra are routinely obtained at an electron
spectrum) is selected and allowed or induced to fragment beam energy of 70 eV. The desired and simplest event that
further thus giving rise to “daughter” ions. In complex occurs is the removal of a single electron from the molecule
mixtures, these daughter ions provide unequivocal evidence in the gas phase by an electron of the electron beam to form
for the presence of a known compound. For unknown or new the molecular ion, which is a radical cation. For example,
compounds, these daughter ions provide potential for further methanol forms a molecular ion in which the single dot
structural information. represents the remaining odd electron as seen in Scheme 1.1.
One popular use of MS-MS involves ionizing a crude When the charge can be localized on one particular atom, the
sample, selectively “fishing out” an ion characteristic for charge is shown on that atom:
the compound under study and obtaining the diagnostic
spectrum of the daughter ions produced from that ion. In this • +
CH3 OH
way, a compound can be unequivocally detected in a crude ••

sample, with no prior chromatographic (or other separation CH3 OH + e− → CH3 OH + (m∕z 32) + 2e−
•

steps) being required. Thus, MS-MS can be a very powerful

(Sch 1.1)
screening tool. This type of analysis alleviates the need for
complex separations of mixtures for many routine analyses. Many of these molecular ions rapidly disintegrate in
For instance, the analysis of urine samples from humans (or 10−10 seconds to 10−3 seconds to give, in the simplest
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1.5 INTERPRETATION OF EI MASS SPECTRA 13

TABLE 1.2 Summary of Mass Analyzers

Mass Analyzer Mass Range Resolution Sensitivity Advantage Disadvantage

Magnetic sector 1 – 15000 m∕z 0.0001 Low High resolution Low sensitivity
Very expensive
High technical expertise
Quadrupole 1 – 5000 m∕z Unit High Easy to use Low resolution
Inexpensive Low mass range
High sensitivity
Ion trap 1 – 5000 m∕z Unit High Easy to use Low resolution
Inexpensive Low mass range
High sensitivity
Tandem MS (MSn )
Time of flight Unlimited 0.0001 High High mass range Very high resolution
Simple design
Fourier transform Up to 70 kDa 0.0001 High Very high resolution and Very expensive
mass range High technical expertise

case, a positively charged fragment ion and a radical. Many very weak or it may not appear at all; how can we be sure
fragment ions are thus formed, and each of these can cleave that it is the molecular ion peak and not a fragment peak or
to yield smaller fragments; examples of possible cleavages an impurity? Often the best solution, if there is doubt, is to
for methanol are given in Scheme 1.2. obtain a chemical ionization spectrum (see Section 1.3.1.2).
The usual result is an intense peak at [M + 1]+ and little
CH3 OH + −→ CH2 OH+ (m∕z 31) + H
• •

fragmentation.
CH3 OH + −→ CH3 + (m∕z 15) + OH
• •

Many peaks can be ruled out as possible molecular

CH2 OH+ −→ CHO+ (m∕z 29) + H2 ions simply on grounds of reasonable structure requirements.
The nitrogen rule is often helpful. It states that a molecule
(Sch 1.2)
of even-numbered molecular weight must contain either no
If some of the molecular ions remain intact long enough nitrogen atoms or an even number of nitrogen atoms; an
to reach the detector, we see a molecular ion peak. It is impor- odd-numbered molecular weight requires an odd number
tant to recognize the molecular ion peak because this gives of nitrogen atoms.* This rule holds for all compounds
the molecular weight of the compound. With unit resolu- containing carbon, hydrogen, oxygen, nitrogen, sulfur, and
tion, this weight is the molecular weight to the nearest whole the halogens, as well as many of the less usual atoms such as
number. phosphorus, boron, silicon, arsenic, and the alkaline earths.
A mass spectrum is a presentation of the masses of the A useful corollary of the nitrogen rule states that
positively charged fragments (including the molecular ion) fragmentation at a single bond gives an odd-numbered
versus their relative abundances. The most intense peak in ion fragment from an even-numbered molecular ion, and
the spectrum, called the base peak, is assigned a value of an even-numbered ion fragment from an odd-numbered
100%, and the intensities (height × sensitivity factor) of the molecular ion. For this corollary to hold, the ion fragment
other peaks, including the molecular ion peak, are reported must contain all of the nitrogen (if any) of the molecular ion.
as percentages of the base peak. Of course, the molecular Consideration of the breakdown pattern coupled with
ion peak may sometimes be the base peak. In Figure 1.1, the other information will also assist in identifying molecular
molecular ion peak is m∕z 121, and the base peak is m∕z 77. ions. It should be kept in mind that Appendix A contains
A tabular or graphic presentation of a spectrum may fragment formulas as well as molecular formulas. Some of
be used. A graph has the advantage of presenting patterns the formulas may be discarded as trivial in attempts to solve
that, with experience, can be quickly recognized. However, a particular problem.
a graph must be drawn so that there is no difficulty in dis- The intensity of the molecular ion peak depends on the
tinguishing mass units. Mistaking a peak at, say, m∕z 79 for stability of the molecular ion. The most stable molecular ions
m∕z 80 can result in total confusion. The molecular ion peak are those of purely aromatic systems. If substituents that have
is usually the peak of highest mass number except for the favorable modes of cleavage are present, the molecular ion
isotope peaks. peak will be less intense, and the fragment peaks relatively
more intense. In general, the following group of compounds
will, in order of decreasing ability, give prominent molecu-
1.5.1 Recognition of the Molecular lar ion peaks: aromatic compounds > conjugated alkenes >
Ion Peak
Quite often, under electron impact (EI), recognition of the * Forthe nitrogen rule to hold, only unit atomic masses (i.e., integers) are
molecular ion peak (M)+ poses a problem. The peak may be used in calculating the formula masses.
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14 CHAPTER 1 MASS SPECTROMETRY

cyclic compounds > organic sulfides > short, normal al- The only contributor to the M + 2 peak of C7 H7 NO is 18 O,
kanes > mercaptans. Recognizable molecular ions are usu- whose relative abundance is very low (or a combination
ally produced for these compounds in order of decreasing of two of the isotopes that contribute to the M + 1, for
ability: ketones > amines > esters > ethers > carboxylic example, one 13 C and one 2 H); thus the M + 2 peak is
acids ∼ aldehydes ∼ amides ∼ halides. The molecular ion undetected. If only C, H, N, O, F, P, and I are present, the
is frequently not detectable in aliphatic alcohols, nitrites, approximate expected percentage (M + 1) and percentage
nitrates, nitro compounds, nitriles, and in highly branched (M + 2) intensities can be calculated by use of the following
compounds. equations for a compound of formula Cn Hm Nx Oy (note: F,
The presence of an M − 15 peak (loss of CH3 ), or P, and I are monoisotopic and do not contribute and can be
an M − 18 peak (loss of H2 O), or an M − 31 peak (loss ignored for the calculation):
of OCH3 from methyl esters), and so on, is taken as
confirmation of a molecular ion peak. An M − 1 peak is % (M + 1) ≈ (1.1 n) + (0.36 x) and % (M + 2) ≈
• •

common, and occasionally an M − 2 peak (loss of H2 by (1.1 n)2 ∕200 + (0.2 y)

• •

either fragmentation or thermolysis), or even a rare M −

3 peak (from alcohols) is reasonable. Peaks in the range If these isotope peaks are intense enough to be measured
of M − 3 to M − 14, however, indicate that contaminants accurately, the above calculations may be useful in determin-
may be present or that the presumed molecular ion peak ing the molecular formula.*
is actually a fragment ion peak. Losses of fragments of If sulfur or silicon is present, the M + 2 peak will
masses of 19 to 25 are also unlikely (except for loss of be more intense. In the case of a single sulfur atom, 34 S
F = 19 or HF = 20 from fluorinated compounds). Loss contributes approximately 4.40% to the M + 2 peak; for
of 16 (O), 17 (OH), or18 (H2 O) are likely only if an oxygen a single silicon in the molecule, 30 Si contributes about
atom is in the molecule. 3.35% to the M + 2 peak (see Section 1.6.15). A single
chlorine atom results in a contribution of 32.50% to the
M + 2 peak, while a single bromine atom contributes 98.00%
1.5.2 Determination of a Molecular to the M + 2 isotope peak. The effect of several bromine
Formula and chlorine atoms is described in Section 1.6.16. Note the
appearance of additional isotope peaks in the case of multiple
1.5.2.1 Unit-Mass Molecular Ion and Isotope Peaks. bromine and chlorine atoms. Obviously the mass spectrum
So far, we have discussed the mass spectrum in terms of should be routinely scanned for the relative intensities of
unit resolutions: The unit mass of the molecular ion of the M + 2, M + 4, and higher isotope peaks, and the relative
C7 H7 NO (Figure 1.1) is m∕z 121—that is, the sum of the unit intensities should be carefully measured. Since F, P, and I are
masses of the most abundant isotopes: (7 × 12 [for 12 C]) + monoisotopic, they can be difficult to spot.
(7 × 1 [for 1 H]) + (1 × 14 [for 14 N] + (1 × 16 [for 16 O]) = For most of the Problems in this text, the unit-resolution
121. molecular ion, used in conjunction with IR and NMR, will
In addition, molecular species exist that contain the suffice for determining the molecular formula by browsing
less abundant isotopes, and these give rise to the “isotope
peaks” at M + 1, M + 2, etc. In Figure 1.1, the M + 1 peak
* There are limitations beyond the difficulty of measuring small peaks: The
is approximately 8% of the intensity of the molecular ion
13 C∕12 C ratio differs with the source of the compound—synthetic compa-
peak, which for this purpose, is assigned an intensity of
red with a natural source. A natural product from different organisms or
100%. Contributing to the M + 1 peak are the isotopes, regions may show differences. Furthermore, isotope peaks may be more
13 C, 2 H, 15 N, and 17 O. Table 1.3 gives the abundances of
intense than the calculated value because of ion – molecule interactions that
these isotopes relative to those of the most abundant isotopes. vary with the sample concentration or with the class of compound involved.

TABLE 1.3 Relative Isotopic Abundances of Common Elements

Relative Relative Relative

Element Isotope Abundance Isotope Abundance Isotope Abundance
12 13
Carbon C 100 C 1.11
1 2
Hydrogen H 100 H 0.016
14 15
Nitrogen N 100 N 0.38
16 17 18
Oxygen O 100 O 0.04 O 0.2
19
Fluorine F 100
28 29 30
Silicon Si 100 Si 5.1 Si 3.35
31
Phosphorus P 100
32 33 34
Sulfur S 100 S 0.78 S 4.4
35 37
Chlorine Cl 100 Cl 32.5
79 81
Bromine Br 100 Br 98
127
Iodine I 100
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1.5 INTERPRETATION OF EI MASS SPECTRA 15

Appendix A. For several more difficult Problems, the high- Appendix A lists molecular and fragment formulas in
resolution formula masses—for use with Appendix A (see order of the unit masses. Under each unit mass, the formulas
Section 1.5.2.2)—have been supplied. are listed in order of the standard Chemical Abstract system.
Table 1.3 lists the principal stable isotopes of the com- The calculated formula mass (FM) to four decimal places is
mon elements and their relative abundance calculated on the given for each formula. Appendix A is designed for brows-
basis of 100 molecules containing the most common iso- ing, on the assumption that the student has a unit molecu-
tope. Note that this presentation differs from many isotopic lar mass from a unit-resolution mass spectrometer and clues
abundance tables, in which the sum of all the isotopes of an from other spectra. Note that the table includes only C, H, N,
element adds up to 100%. and O.

1.5.2.2 High-Resolution Molecular Ion. A unique molec-

1.5.3 Use of the Molecular Formula.
ular formula (or fragment formula) can often be derived Index of Hydrogen Deficiency
from a sufficiently accurate mass measurement alone (high-
resolution mass spectrometry). This is possible because If organic chemists had to choose a single item of information
the nuclide masses are not integers (see Table 1.4). For above all others that are usually available from spectra or
example, we can distinguish at a unit mass of 28 among from chemical manipulations, they would certainly choose
CO, N2 , CH2 N, and C2 H4 . The exact mass of CO is: 12.0000 the molecular formula.
(for 12 C) + 15.9949 (for 16 O) = 27.9949; the exact mass of In addition to the kinds and numbers of atoms, the
N2 is: 2 × 14.0031 (for 14 N) = 28.0062. Similar calculations molecular formula gives the index of hydrogen deficiency.
give an exact mass of 28.0187 for CH2 N and 28.0312 for The index of hydrogen deficiency is the number of pairs
C2 H4 . of hydrogen atoms that must be removed from the corre-
Thus, the mass observed for the molecular ion of CO, for sponding “saturated” formula to produce the molecular for-
example, is the sum of the exact formula masses of the most mula of the compound of interest. The index of hydrogen
abundant isotope of carbon and of oxygen. This differs from deficiency is also called the number of “sites (or degrees)
a molecular weight of CO based on atomic weights that are of unsaturation”; this description is incomplete since hydro-
the average of weights of all natural isotopes of an element gen deficiency can result from cyclic structures as well as
(e.g., C = 12.01, O = 15.999). from multiple bonds. The index is thus the sum of the num-
Table 1.4 gives the masses to four or five decimal ber of rings, the number of double bonds, and twice the
places for the common naturally occurring isotopes; it also number of triple bonds.
gives the familiar atomic weights (average weights for the The index of hydrogen deficiency can be calculated for
elements). compounds containing carbon, hydrogen, nitrogen, halogen,
oxygen, and sulfur having the generalized molecular for-
mula, Cn Hm Xx Ny Oz , from the equation
TABLE 1.4 Exact Masses of Isotopes
Index = (n) − (m∕2) − (x∕2) + (y∕2) + 1
Atomic
Element Weight Nuclide Mass Thus, the compound C7 H7 NO has an index of 7 − 3.5 +
0.5 + 1 = 5. Note that divalent atoms (oxygen and sulfur) are
1
Hydrogen 1.00794 H 1.00783 not counted in the formula.
D(2 H) 2.01410 For the generalized molecular formula 𝛼I 𝛽II 𝛾III 𝛿IV , the
12
Carbon 12.01115 C 12.00000 (std) index is given by (IV) − (I∕2) + (III∕2) + 1, where 𝛼 is H,
13
C 13.00336
14
D, or halogen (i.e., any monovalent atom), 𝛽 is O, S, or any
Nitrogen 14.0067 N 14.0031
15 other bivalent atom, 𝛾 is N, P, or any other trivalent atom, and
N 15.0001
Oxygen 15.9994 16
O 15.9949 𝛿 is C, Si, or any other tetravalent atom. The numerals I – IV
17
O 16.9991 designate the numbers of the mono-, di-, tri-, and tetravalent
18
O 17.9992 atoms, respectively.
Fluorine 18.9984 19
F 18.9984 For simple molecular formulas, we can arrive at the
Silicon 28.0855 28
Si 27.9769 index by comparison of the formula of interest with the
29
Si 28.9765 molecular formula of the corresponding saturated com-
30
Si 29.9738 pound. Compare C6 H6 and C6 H14 ; the index is 4 for the
31
Phosphorus 30.9738 P 30.9738 former and 0 for the latter.
32
Sulfur 32.0660 S 31.9721 The index for C7 H7 NO is 5, and a possible structure is
33
S 32.9715
34
benzamide (see Figure 1.1). Of course, other isomers (i.e.,
S 33.9679
35 compounds with the same molecular formula) are possible,
Chlorine 35.4527 Cl 34.9689
37
Cl 36.9659 such as
79
Bromine 79.9094 Br 78.9183 O
81
Br 80.9163 H2N
127
Iodine 126.9045 I 126.9045
H
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16 CHAPTER 1 MASS SPECTROMETRY

O O by the degree of hydrogen deficiency. Much of the potential

structural information is readily confirmed with information
S N from IR and NMR spectra (See Chapters 2, 3, and 4).
H 3C CH3 H 3C O (C 6H5) 3P O
Dimethyl Nitromethane Triphenylphosphine 1.5.4 Fragmentation
sulfoxide oxide
FIGURE 1.12 “Polar” Lewis structures of dimethyl
As a first impression, fragmenting a molecule with a huge
sulfoxide, nitromethane, and triphenylphosphine excess of energy would seem a brute-force approach to
oxide that correctly account for the index of hydrogen molecular structure. The rationalizations used to corre-
deficiency. late spectral patterns with structure, however, can only
be described as elegant, though sometimes arbitrary. The
insight of such pioneers as McLafferty, Beynon, Stenhagen,
Note that the benzene ring itself accounts for four sites of Ryhage, and Meyerson led to a number of rational mech-
unsaturation: three for the double bonds and one for the ring. anisms for fragmentation. These were masterfully summa-
“Polar” structures must be used for compounds con- rized and elaborated by Biemann (1962), Budzikiewicz et al.
taining an atom in a higher valence state, such as sulfur or (1967), and others.
phosphorus. Thus, if we treat sulfur in dimethyl sulfoxide Generally, the tendency is to represent the molecular ion
(DMSO) formally as a divalent atom, the calculated index, with a localized charge. The approach of Budzikiewicz et al.
0, is compatible with the structure in Figure 1.12. We must (1967) is to localize the positive charge on either a 𝜋 bond
use only formulas with filled valence shells; that is, the Lewis (except in conjugated systems), or on a heteroatom. Whether
octet rule must be obeyed. or not this concept is totally rigorous, it is, at the least, a
Similarly, if we treat the nitrogen in nitromethane as pedagogic tour de force. We shall use such locally charged
a trivalent atom, the index is 1, which is compatible with molecular ions in this book.
Figure 1.12. If we treat phosphorus in triphenylphosphine Structures A, B, and C in Figure 1.13, for example,
oxide as trivalent, the index is 12, which fits the Lewis represent the molecular ion of cyclohexadiene. Compound A
structure in Figure 1.12. As an example, let us consider the is a delocalized structure with one less electron than the
molecular formula C13 H9 N2 O4 BrS. The index of hydrogen original uncharged diene; both the electron and the positive
deficiency would be 13 − 10
+ 2
+ 1 = 10 and a consistent charge are delocalized over the 𝜋 system. Since the electron
2 2
structure would be removed to form the molecular ion is a 𝜋 electron, other
structures, such as B or C (resonance structures) can be
NO2 used. Structures such as B and C localize the electron
H and the positive charge and thus are useful for describing
fragmentation processes.
O2N S C Br Fragmentation is initiated by electron impact. Only a
H small part of the driving force for fragmentation is energy
transferred as the result of the impact. The major driving
(Index of hydrogen deficiency = 4 per benzene ring and 1 force is the cation-radical character that is imposed upon the
per NO2 group.) structure.
The formula above for the index can be applied to Fragmentation of the odd-electron molecular ion
fragment ions as well as to the molecular ion. When it is (radical-cation, M + ) may occur by homolytic or heterolytic
•

applied to even-electron (all electrons paired) ions, the result cleavage of a single bond. In homolytic cleavage (Scheme 1.3,
is always an odd multiple of 0.5. As an example, consider I) each electron moves independently as shown by a (single-
C7 H5 O+ with an index of 5.5. A reasonable structure is barbed) fishhook: the fragments are an even-electron cation
and a free radical (odd electron). To prevent clutter, only
one of each pair of fishhooks need to be shown (Scheme 1.3,
C O II). In heterolytic cleavage, a pair of electrons move together

since 5.5 pairs of hydrogen atoms would be necessary

to obtain the corresponding saturated formula C7 H16 O
(Cn H2n + 2 O). Odd-electron fragment ions will always give
integer values of the index.
Such simple considerations give the chemist very ready
information about structure. As another example, a com- A B C
pound containing a single oxygen atom might quickly be FIGURE 1.13 Different representations
determined to be an ether or a carbonyl compound simply of the radical cation of cyclohexadiene.
 Silverstein c01.tex V3 - 07/10/2014 3:46 P.M. Page 17

1.5 INTERPRETATION OF EI MASS SPECTRA 17

toward the charged site as shown by the conventional curved 3. Cleavage is favored at alkyl-substituted carbon atoms:
arrow; the fragments are again an even-electron cation and a the more substituted, the more likely is cleavage. This
radical, but here the final charge site is on the alkyl product is a consequence of the increased stability of a tertiary
(Scheme 1.3, III). carbocation over a secondary, which in turn is more
stable than a primary. Generally, the largest substituent
at a branch is eliminated most readily as a radical,
I C H3 CH2 O R C H3 H2C O R presumably because a long-chain radical can achieve
some stability by delocalization of the lone electron.
II C H3 CH2 O R C H3 H2C O R
Cation stability order:
III C H3 CH2 CH2 Br C H3 CH 2 CH 2 Br CH3 + < R2 CH2 + < R3 CH+ < R3 C+
4. Double bonds, cyclic structures, and especially aromatic
IV C H3 CH2 CH2 CH 3 H2C CH (or heteroaromatic) rings stabilize the molecular ion and
(Sch 1.3) thus increase the probability of its appearance.
5. Double bonds favor allylic cleavage and give the reso-
nance-stabilized allylic carbocation. This rule does not
In the absence of rings (whose fragmentation requires
hold for simple alkenes because of the ready migration
cleavage of two or more bonds), most of the prominent
of the double bond, but it does hold for cycloalkenes.
fragments in a mass spectrum are even-electron cations
formed as above by a single cleavage. Further fragmentation 6. Saturated rings tend to lose alkyl side chains at the 𝛼
of an even-electron cation usually results in another even- bond. This is merely a special case of branching (rule 3).
electron cation and an even-electron neutral molecule or The positive charge tends to stay with the ring fragment.
fragment (Scheme 1.3, IV). See Scheme 1.4. Unsaturated rings can undergo a retro-
Simultaneous or consecutive cleavage of several bonds Diels-Alder reaction (see Scheme 1.5).
may occur when energy benefits accrue from formation of a
highly stabilized cation and/or a stable radical, or a neutral R
molecule, often through a well-defined low-energy pathway. R
These are treated in Section 1.5.5 (rearrangements) and in
Section 1.6 under individual chemical classes.
The probability of cleavage of a particular bond is (Sch 1.4)
related to the bond strength, to the possibility of low energy
transitions, and to the stability of the fragments, both charged
and uncharged, formed in the fragmentation process. Our CH2
knowledge of pyrolytic cleavages can be used, to some CH2
extent, to predict likely modes of cleavage of the molecu-
lar ion. Because of the extremely low pressure in the mass (Sch 1.5)
spectrometer, there are very few fragment collisions; we
are dealing largely with unimolecular decompositions. This 7. In alkyl-substituted aromatic compounds, cleavage is
assumption, backed by a large collection of reference spec- very probable at the bond 𝛽 to the ring, giving the
tra, is the basis for the vast amount of information available resonance-stabilized benzyl ion or, more likely, the
from the fragmentation pattern of a molecule. Whereas con- tropylium ion (see Scheme 1.6).
ventional organic chemistry deals with reactions initiated by
chemical reagents, by thermal energy, or by light, mass spec- R
trometry is concerned with the consequences suffered by an CH2 CH2
organic molecule at a vapor pressure of about 10−6 mm Hg
struck by an ionizing electron beam. R
A number of general guidelines for predicting prominent
peaks in EI spectra can be written and rationalized by using
standard concepts of physical organic chemistry: H H
H H
1. The relative intensity of the molecular ion peak is H H H
greatest for the straight-chain compound and decreases H shift
H
as the degree of branching increases (see rule 3).
H H
2. The relative intensity of the molecular ion peak usually H H
decreases with increasing molecular weight in a homol- H H
ogous series. Fatty esters appear to be an exception. (Sch 1.6)
 Silverstein c01.tex V3 - 07/10/2014 3:46 P.M. Page 18

18 CHAPTER 1 MASS SPECTROMETRY

8. The C⏤C bonds next to a heteroatom are frequently cular ions. A simple (no rearrangement) cleavage of an even-
cleaved, leaving the charge on the fragment containing numbered molecular ion gives an odd-numbered fragment
the heteroatom whose nonbonding electrons provide ion and simple cleavage of an odd-numbered molecular
resonance stabilization. ion gives an even-numbered fragment. Observation of a
9. Cleavage is often associated with elimination of small, fragment ion mass different by 1 unit from that expected
stable, neutral molecules, such as carbon monoxide, for a fragment resulting from simple cleavage (e.g., an even-
alkenes, water, ammonia, hydrogen sulfide, hydrogen numbered fragment mass from an even-numbered molecular
cyanide, mercaptans, ketenes, or alcohols, often with ion mass) indicates rearrangement of a hydrogen atom has
rearrangement (Section 1.5.5). accompanied fragmentation. Rearrangement peaks may be
recognized by considering the corollary to the “nitrogen
It should be kept in mind that the fragmentation guide- rule” (Section 1.5.1). Thus, an even-numbered peak derived
lines above apply to EI mass spectrometry. Since other ion- from an even-numbered molecular ion is a result of two
izing techniques (CI, etc.) often produce molecular ions with cleavages, which may involve a rearrangement.
much lower energy or quasimolecular ions with very differ- Seemingly random rearrangements of hydrocarbons
ent fragmentation patterns, different rules govern the frag- were noted by the early mass spectrometrists in the petroleum
mentation of these molecular ions. industry. For example, the rearrangement of the neo-pentyl
radical-cation to the ethyl cation, shown in Scheme 1.8,
1.5.5 Rearrangements defies a straightforward explanation.

Rearrangement ions are fragments whose origin cannot be

described by simple cleavage of bonds in the molecular CH3
ion but are a result of intramolecular atomic rearrangement
during fragmentation. Rearrangements involving migration H3C C CH3 [C2H5]
of hydrogen atoms in molecules that contain a heteroatom are
CH3
especially common. One important example is the so-called
McLafferty rearrangement; it is illustrated in Scheme 1.7 for
(Sch 1.8)
the general case.

H R
where Y O RHC CH2 1.6 MASS SPECTRA OF SOME
H, R, OH, CHEMICAL CLASSES
OR, NH2
Y
R Mass spectra of a number of chemical classes are briefly
described in this section in terms of the most useful
H H H
O O O generalizations for identification. For more details, the refer-
ences cited should be consulted (in particular, the thorough
Y CH Y CH Y CH treatment by Budzikiewicz et al., 1967). Databases are avail-
able both from publishers and as part of instrument capabili-
R R R ties. The references are selective rather than comprehensive.
(Sch 1.7) A table of frequently encountered fragment ions is given
in Appendix B. A table of fragments (uncharged) that are
To undergo a McLafferty rearrangement, a molecule commonly eliminated and some structural inferences are pre-
must possess an appropriately located heteroatom (e.g., O), sented in Appendix C. More exhaustive listings of common
a 𝜋 system (usually a double bond), and an abstractable fragment ions have been compiled (see References).
hydrogen atom 𝛾 to the C⏤O system.
Such rearrangements often account for prominent char-
acteristic peaks and are consequently very useful for our 1.6.1 Hydrocarbons
purpose. They can frequently be rationalized on the basis
of low-energy transitions and increased stability of the prod- 1.6.1.1 Saturated Hydrocarbons. Most of the early work
ucts. Rearrangements resulting in elimination of a stable neu- in mass spectrometry was done on hydrocarbons of interest
tral molecule are common (e.g., the alkene product in the to the petroleum industry. Guidelines 1 – 3, (Section 1.5.4)
McLafferty rearrangement) and will be encountered in the apply quite generally; rearrangement peaks, though com-
discussion of mass spectra of chemical classes. mon, are not usually intense (random rearrangements), and
Rearrangement peaks, with loss of a neutral molecule, numerous reference spectra are available.
can be recognized by considering the unit mass number The molecular ion peak of a straight-chain, saturated
(m∕z) for fragment ions and for their corresponding mole- hydrocarbon is always present, though of low intensity for
 Silverstein c01.tex V3 - 07/10/2014 3:46 P.M. Page 19

1.6 MASS SPECTRA OF SOME CHEMICAL CLASSES 19

43 57
100 n-Hexadecane
% of Base Peak

C16H34
71 Mol. Wt.: 226

50
M+
99 113 141 155 183 197 226

0
50 100 m/z 150 200
169 141
43
% of Base Peak

100
57 85
5-Methylpentadecane
57 85 C16H34
50 Mol. Wt.: 226
71

99 168 M+
127 141 211 226
0
50 100 m/z 150 200
FIGURE 1.14 EI mass spectra of isomeric C16 hydrocarbons.

long-chain compounds. The fragmentation pattern is char- peak is prominent and sometimes more intense than the
acterized by clusters of peaks, and the corresponding peaks corresponding Cn H2n + 1 peak.
of each cluster are 14 mass units (⏤CH2 ⏤) apart. The A saturated ring in a hydrocarbon increases the rela-
largest peak in each cluster represents a Cn H2n + 1 fragment tive intensity of the molecular ion peak and favors cleavage
and thus occurs at m∕z = 14n + 1; this peak is accompanied at the bond connecting the ring to the rest of the molecule
by Cn H2n and Cn H2n − 1 fragments. The most abundant frag- (guideline 6, Section 1.5.4). Fragmentation of the ring is usu-
ments are at C3 and C4 , and the fragment abundances loga- ally characterized by the loss of two carbon atoms as C2 H4
rithmically decrease down to [M − C2 H5 ]+ ; the [M − CH3 ]+ (28) and C2 H5 (29). This tendency to lose even-numbered
peak is characteristically very weak or missing. Compounds fragments gives a spectrum that contains a greater propor-
containing more than eight carbon atoms show fairly simi- tion of even-numbered mass ions than the spectrum of an
lar spectra; identification then depends on the molecular ion acyclic hydrocarbon. As in branched hydrocarbons, C⏤C
peak. cleavage is accompanied by the loss of a hydrogen atom.
Spectra of branched saturated hydrocarbons are grossly The characteristic peaks are therefore in the Cn H2n−1 and
similar to those of straight-chain compounds, but the smooth Cn H2n−2 series.
curve of decreasing intensities is broken by preferred frag- The mass spectrum of cyclohexane (Figure 1.15) shows
mentation at each branch. The smooth curve for the a much more intense molecular ion than those of acyclic
n-alkane in Figure 1.14 (top) is in contrast to the discon- compounds, since fragmentation requires the cleavage of two
tinuity at C12 for the branched alkane (Figure 1.14, bot- carbon-carbon bonds. This spectrum has its base peak at m∕z
tom). This discontinuity indicates that the longest branch of 56 (because of a loss of C2 H4 ) and a large peak at m∕z 41,
5-methylpentadecane has 10 carbon atoms. which is a fragment in the Cn H2n − 1 series with n = 3.
In the bottom spectrum of Figure 1.14, the peaks at
m∕z 169 and 85 represent cleavage on either side of the 1.6.1.2 Alkenes (Olefins). The molecular ion peak of
branch with charge retention on the substituted carbon alkenes, especially polyalkenes, is usually distinct. Loca-
atom. Subtraction of the molecular weight from the sum tion of the double bond in acyclic alkenes is sometimes dif-
of these fragments accounts for the fragment ⏤CH⏤CH3 . ficult because of its facile migration in the fragments. In
Again, we appreciate the absence of a C11 unit, which cyclic (especially polycyclic) alkenes, location of the double
cannot form by a single cleavage. Finally, the presence bond is frequently evident as a result of a strong tendency
of a distinct M − 15 peak also indicates a methyl branch. for allylic cleavage without much double-bond migration
The fragment resulting from cleavage at a branch tends to (guideline 5, Section 1.5.4). Conjugation with a carbonyl
lose a single hydrogen atom so that the resulting Cn H2n group also fixes the position of the double bond. As with
 Silverstein c01.tex V3 - 07/10/2014 3:46 P.M. Page 20

20 CHAPTER 1 MASS SPECTROMETRY

56
C4H8 M+
100
% of Base Peak

C3H5 84
41 Cyclohexane
C6H12
50 Mol. Wt.: 84
27 69
57

0
30 35 40 45 50 55 60 65 70 75 80 85
m/z
FIGURE 1.15 EI mass spectrum of cyclohexane.

saturated hydrocarbons, acyclic alkenes are characterized by an exercise, the student is encouraged to draw them.
clusters of peaks at intervals of 14 units. In these clusters
the Cn H2n − 1 and Cn H2n peaks are more intense than the
Cn H2n + 1 peaks.
The mass spectrum of 𝛽-myrcene, a monoterpene, is
shown in Figure 1.16. The peaks at m∕z 41, 55, and 69
correspond to the formula Cn H2n − 1 with n = 3, 4, and 5,
respectively. Formation of the m∕z 41 peak must involve m/z 93
isomerization. The peaks at m∕z 67 and 69 are the fragments
from cleavage of a bi-allylic bond, which is shown in (Sch 1.10)
Scheme 1.9.
Cyclic alkenes usually show a distinct molecular ion
peak. A unique mode of cleavage is the retro-Diels-Alder
reaction. This reaction is illustrated with limonene in
Scheme 1.11 (see Figure 1.17). A retro-Diels-Alder reaction
in this example gives two isoprene molecules. Since the reac-
or
tion is an example of a rearrangement, one of the isoprene
moieties is a neutral molecule.
m/z 69 m/z 67

(Sch 1.9)

The peak at m∕z 93 is rationalized in Scheme 1.10

as a structure of formula C7 H9 + formed by double bond
isomerization (resulting in increased conjugation), followed
by allylic cleavage. The ion at m∕z 93 has at least two
important resonance forms that contribute to its stability. As (Sch 1.11)

41 C5H9+
C3H5+ 93
% of Base Peak

100 69 C7H9+ -Myrcene

C10H16
Mol. Wt.: 136
80
50 C4H7+ M+
121 136
55
117

0
40 50 60 70 80 m/z 90 100 110 120 130
FIGURE 1.16 EI mass spectrum of 𝛽-myrcene.
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1.6 MASS SPECTRA OF SOME CHEMICAL CLASSES 21

68
H3 C
100
CH3
% of Base Peak

75 93 H2 C

50
41 79 121 136
25 53 107
77
108

40 50 60 70 80 90 100 110 120 130

m/z
FIGURE 1.17 EI mass spectrum of limonene.
128
100
% of Base Peak

M+
Naphthalene 128 (M) 100.0%
C10H8 129 (M+1) 11.0%
50 Mol. Wt.: 128 130 (M+2) 0.4%

51 64 102
39 75

0
40 50 60 70 80 90 100 110 120 130
m/z
FIGURE 1.18 EI mass spectrum of naphthalene.

1.6.1.3 Aromatic and Aralkyl Hydrocarbons. An aro- It has been proposed that, in most cases, the ion of mass
matic ring in a molecule stabilizes the molecular ion peak 91 is a tropylium rather than a benzylic cation. This explains
(guideline 4, Section 1.5.4), which is usually sufficiently the ready loss of a methyl group, which seems to violate
large that accurate intensity measurements can be made on guideline 7, from xylenes (Scheme 1.12, see Figure 1.19).
the M + 1 and M + 2 peaks. By comparison, toluene does not easily lose a methyl group.
Shown in Figure 1.18 is the mass spectrum of naphtha- The incipient molecular radical ion of xylene rearranges to
lene. The molecular ion peak is also the base peak, and the the methylcycloheptatriene radical ion, which then cleaves
largest fragment peak, m∕z 51, is only 12.5% as intense as to the tropylium ion (C7 H+7 ). The frequently observed peak
the molecular ion peak. at m∕z 65 results from the elimination of a neutral acetylene
An alkyl-substituted benzene ring frequently gives a molecule from the tropylium ion.
prominent peak (often the base peak) at m∕z 91 (C6 H5 CH2 + ).
Branching at the 𝛼-carbon leads to masses higher than 91, H
by increments of 14, the largest substituent being eliminated CH3 H
most readily (guideline 3, Section 1.5.4). The mere presence CH3
of a peak at mass 91, however, does not preclude branching
at the 𝛼-carbon because this highly stabilized fragment may
result from rearrangements. A distinct and sometimes promi- CH3 CH3 m/z 91
nent M − 1 peak results from similar benzylic cleavage of a
(Sch 1.12)
C⏤H bond.

91
100
% of Base Peak

75 H3 C CH3 106

50
25 39 51 65
77
53

40 48 56 64 72 80 88 96 104
m/z
FIGURE 1.19 EI mass spectrum of p-xylene.
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22 CHAPTER 1 MASS SPECTROMETRY

Hydrogen migration with elimination of a neutral alkene spectrum in the vicinity of a very weak or missing molecular
molecule accounts for the peak at m∕z 92 observed when the ion peak of a primary alcohol is sometimes complicated by
alkyl group is longer than C2 . Scheme 1.13 illustrates with weak M − 2 and M − 3 peaks.
a general example. Note again that this is an example of a A distinct and sometimes prominent peak can usually
rearrangement. be found at M − 18 from loss of water. This peak is most
noticeable in spectra of primary alcohols. This elimination
by electron impact has been rationalized and a mechanism
H2C CHR
H in which a 𝛿-hydrogen is lost is shown in Scheme 1.14, I. A
similar mechanism can be drawn in which a 𝛾-hydrogen is
H R H
lost. The M − 18 peak is frequently exaggerated by thermal
m/z 92
decomposition of higher alcohols on hot inlet surfaces.
(Sch 1.13) Elimination of water, together with elimination of an alkene
from primary alcohols (see Scheme 1.14, II), accounts for
A characteristic cluster of ions resulting from an 𝛼
the presence of a peak at M − (alkene + H2 O), that is, a peak
cleavage and hydrogen migration in monoalkylbenzenes
at M − 46, M − 74, M − 102, …
appears at m∕z 77 (C6 H5 + ), 78 (C6 H6 + ), and 79 (C6 H7 + ).
Alkylated polyphenyls and alkylated polycyclic aro- R H H R H H R
matic hydrocarbons exhibit the same 𝛽 cleavage as alkylben- O O
zene compounds. I H2O

R H H
1.6.2 Hydroxy Compounds O H2C CH2
[H2C CHR ]
II H2O
1.6.2.1 Alcohols. The molecular ion peak of a primary
or secondary alcohol is usually quite small and for a (Sch 1.14)
tertiary alcohol is often undetectable. The molecular ion
of 1-pentanol is extremely weak compared with its near Alcohols containing branched methyl groups (e.g., ter-
homologs. Expedients such as CI, or derivatization, may be pene alcohols) frequently show a fairly strong peak at M − 33
used to obtain the molecular weight. resulting from loss of CH3 and H2 O.
Cleavage of the C⏤C bond next to the oxygen atom Cyclic alcohols undergo fragmentation by complicated
is of general occurrence (guideline 8, Section 1.5.4). Thus, pathways; for example, cyclohexanol (Figure 1.20) (M =
primary alcohols show a prominent peak resulting from m∕z 100) forms C6 H11 O+ by simple loss of the 𝛼-hydrogen,
+ CH ⏤OH (m∕z 31). Secondary and tertiary alcohols loses H2 O to form C6 H10 + (which appears to have more than
2
cleave analogously to give a prominent peak resulting from one possible bridged bicyclic structure), and forms C3 H5 O+
+ CHR⏤OH (m∕z 45, 59, 73, etc.) and + CRR′ ⏤OH (m∕z (m∕z 57) by a complex ring cleavage pathway.
59, 73, 87, etc.), respectively. The largest substituent is A peak at m∕z 31 (see above) is quite diagnostic
expelled most readily (guideline 3). It is not unusual that the for a primary alcohol provided it is more intense than
C⏤H bond next to the oxygen atom is cleaved; this less (or peaks at m∕z 45, 59, 73 …. However, the first-formed ion
least) favored pathway gives rise to an M − 1 peak. of a secondary alcohol can decompose further to give a
Primary alcohols, in addition to the principal C⏤C moderately intense m∕z 31 peak.
cleavage next to the oxygen atom, show a homologous series Figure 1.21 gives the characteristic spectra of isomeric
of peaks of progressively decreasing intensity resulting from primary, secondary, and tertiary C5 alcohols.
cleavage at C⏤C bonds successively removed from the oxy- Benzyl alcohols and their substituted homologs and
gen atom. In long-chain (>C6 ) alcohols, the fragmentation analogs constitute a distinct class. Generally, the parent peak
becomes dominated by the hydrocarbon pattern; in fact, the is strong. A moderate benzylic peak (M − OH) may be
spectrum resembles that of the corresponding alkene. The present as expected from cleavage 𝛽 to the ring.

57
OH
100
% of Base Peak

75
82
50
44 67
25 58 71
51 83 100

40 48 56 64 72 80 88 96
m/z
FIGURE 1.20 EI mass spectrum of cyclohexanol.
 Silverstein c01.tex V3 - 07/10/2014 3:46 P.M. Page 23

1.6 MASS SPECTRA OF SOME CHEMICAL CLASSES 23

M – (H2O + CH2=CH2)
42 31
M – (H2O + CH3) OH
% of Base Peak

100 CH2O+H
31 57
55 1-Pentanol
M – H 2O
C5H12O
70 Mol. Wt.: 88
50
57
M –1
45 87

0
20 30 40 50 m/z 60 70 80 90

45 45
% of Base Peak

100 43
OH
2-Pentanol
M – (H2O + CH2=CH2) M – (H2O + CH3) C5H12O
50 Mol. Wt.: 88
27 55 M – H2O M – CH3
39 46 73 M –187 M+ (88)

0
20 30 40 50 m/z 60 70 80 90
59 59
% of Base Peak

100
29 OH
M – (H2O + CH3) M – CH3
M – (H2O + CH2=CH2) 2-Methyl-2-butanol
73
C5H12O
31 43 Mol. Wt.: 88
50 55
29
39 45 M – H2O

0
20 30 40 50 m/z 60 70 80 90
FIGURE 1.21 EI mass spectra of isomeric pentanols.

A complicated sequence leads to prominent M − 1, M − 2, Loss of H2 O to give a distinct M − 18 peak is a

and M − 3 peaks. Benzyl alcohol itself (Figure 1.22) frag- common feature, especially pronounced and mechanistically
ments to give sequentially the M − 1 ion, the C6 H7 + ion straightforward in some ortho-substituted benzyl alcohols
by loss of CO, and the C6 H5 + ion by loss of H2 (see (see Figure 1.23). The loss of water shown in Scheme 1.16
Scheme 1.15). works equally well with an oxygen atom at the ortho-
position (a phenol). The aromatic cluster at m∕z 77, 78,
CH2OH OH
and 79 resulting from complex degradation is prominent
here also.
H CO
OH H2O
H
m/z 108 m/z 107
H (Sch 1.16)
H H
H H
H2
1.6.2.2 Phenols. A conspicuous molecular ion peak facil-
itates identification of phenols. In phenol itself, the molecu-
H H
lar ion peak is the base peak, and the M − 1 peak is small.
m/z 79 m/z 77 In cresols, the M − 1 peak is larger than that of the molec-
(Sch 1.15) ular ion as a result of a facile benzylic C⏤H cleavage.
 Silverstein c01.tex V3 - 07/10/2014 3:46 P.M. Page 24

24 CHAPTER 1 MASS SPECTROMETRY

79 108
100
% of Base Peak

75 HO
50
51 91
25 39 53 65

40 48 56 64 72 80 88 96 104
m/z
FIGURE 1.22 EI mass spectrum of benzyl alcohol.

H3 C 104
100 HO
% of Base Peak

75
50 79 91 107 122
65
25 39 51
63

40 48 56 64 72 80 88 96 104 112 120

m/z
FIGURE 1.23 EI mass spectrum of o-methylbenzyl alcohol.

A rearrangement peak at m∕z 77 and peaks resulting from the The presence of an oxygen atom can be deduced from
loss of CO (M − 28) and CHO (M − 29) are usually found in strong peaks at m∕z 31, 45, 59, 73, … These peaks repre-
the mass spectra of phenols. sent the RO+ and ROCH2 + fragments. A typical aliphatic
The mass spectrum of o-ethylphenol, a typical phenol, ether is shown in Figure 1.25. Fragmentation occurs in two
is shown in Figure 1.24. This spectrum shows that a methyl principal ways:
group is lost much more readily than an 𝛼-hydrogen. 1. Cleavage of the C⏤C bond next to the oxygen atom
(𝛼, 𝛽 bond, guideline 8, Section 1.5.4). One or the other
of these oxygen-containing ions may account for the
base peak. In the case shown in Figure 1.25, the first
1.6.3 Ethers
cleavage (i.e., at the branch position leading to loss of the
1.6.3.1 Aliphatic Ethers (and Acetals). The molecular larger fragment) is preferred. However, the first-formed
ion peak (two mass units larger than that of an analogous fragment decomposes further by loss of ethylene to give
hydrocarbon) is small, but larger sample size usually will the base peak; this decomposition is important when the
make the molecular ion peak or the M + 1 peak obvious (H •
𝛼-carbon is substituted (see McLafferty rearrangement,
transfer during ion-molecule collision). Section 1.5.5)

HO 107
[M – CH3]+
% of Base Peak

100

o-Ethylphenol 122
50 C8H10O C6H5+ [M – H2O]+ +
Mol. Wt.: 122 M
77
39 51 91 103

0
40 50 60 70 m/z 80 90 100 110 120
FIGURE 1.24 EI mass spectrum of o-ethylphenol.
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1.6 MASS SPECTRA OF SOME CHEMICAL CLASSES 25

O O O
–CH3CH2 –H2C C H2 H

Ethyl sec-butyl ether

C6H14O Mol. Wt.: 102
O O
H
45
m/z 45
% of Base Peak

100 m/z 73
H
73
CH3CH2+
50 29
M+
59 M – CH3
41
56 87 102

0
30 40 50 60 m/z 70 80 90 100
FIGURE 1.25 EI mass spectrum of ethyl sec-butyl ether.

2. C⏤O bond cleavage with the charge remaining on and alkene elimination. Ketals behave similarly.
the alkyl fragment. The spectrum of long-chain ethers H
becomes dominated by the hydrocarbon pattern.
R C OR
Acetals are a special class of ethers. Their mass spectra
OR
are characterized by an extremely weak molecular ion peak,
by the prominent peaks at M − R and M − OR (and/or 1.6.3.2 Aromatic Ethers. The molecular ion peak of aro-
M − OR′ ), and a weak peak at M − H. Each of these matic ethers is prominent. Primary cleavage occurs at the
cleavages is mediated by an oxygen atom and thus facile. bond 𝛽 to the ring, and the first-formed ion can decompose
As usual, elimination of the largest group is preferred. As further. Thus, anisole (Figure 1.26, MW 108) gives ions of
with aliphatic ethers, the first-formed oxygen-containing m∕z 93 and 65. The characteristic aromatic peaks at m∕z 78
fragments can decompose further with hydrogen migration and 77 may arise from anisole.

Anisole O O
CH3 –CH3 –CO
C7H8O
Mol. Wt.: 108

m/z 93 m/z 65

O
CH2 –CH2O –H M+
H H 108
100 H
% of Base Peak

m/z 78 m/z 77
65 78

50
39
51 93
57
0
30 40 50 60 m/z 70 80 90 100 110
FIGURE 1.26 EI mass spectrum of anisole.
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26 CHAPTER 1 MASS SPECTROMETRY

94
100
O
% of Base Peak

75
50 H3 C
150
25 29 41
66 77
57 107

30 40 50 60 70 80 90 100 110 120 130 140 150

m/z
FIGURE 1.27 EI mass spectrum of butyl phenyl ether.

When the alkyl portion of an aromatic alkyl ether is C2 stability because it would have two adjacent positive centers.
or larger, cleavage 𝛽 to the ring is accompanied by hydrogen
H R
migration (Scheme 1.17) as noted above for alkylbenzenes.
O RHC CH2
Clearly, cleavage is mediated by the ring rather than by the
oxygen atom; C⏤C cleavage next to the oxygen atom is R
insignificant. An example of this type is illustrated in the
spectrum of butyl phenyl ether, Figure 1.27. H H H
O O O
O
H2C CHR
R CH2 R CH2 R CH2
H R (Sch 1.19)
O OH Note that in long-chain ketones the hydrocarbon peaks
H are indistinguishable (without the aid of high-resolution
H
techniques) from the acyl peaks, since the mass of the C⏤O
m/z 94
unit (28) is the same as two methylene units. The multiple
cleavage modes in ketones sometimes make difficult the
(Sch 1.17)
determination of the carbon chain configuration. Reduction
Diphenyl ethers show peaks at M − H, M − CO, and of the carbonyl group to a methylene group yields the
M − CHO by complex rearrangements. corresponding hydrocarbon whose fragmentation pattern
leads to the carbon skeleton.

1.6.4 Ketones 1.6.4.2 Cyclic Ketones. The molecular ion peak in cyclic
ketones is prominent. As with acyclic ketones, the primary
1.6.4.1 Aliphatic Ketones. The molecular ion peak of
cleavage of cyclic ketones is adjacent to the C⏤O group, but
ketones is usually quite pronounced. Major fragmenta-
the ion thus formed must undergo further cleavage in order
tion peaks of aliphatic ketones result from cleavage at
to produce a fragment. The base peak in the spectrum of
one of the C⏤C bonds adjacent to the oxygen atom, the
cyclopentanone and of cyclohexanone (Figure 1.28) is m∕z
charge remaining with the resonance-stabilized acylium ion
55. The mechanisms are similar in both cases: hydrogen
(Scheme 1.18). Thus, as with alcohols and ethers, cleavage
shift to convert a primary radical to a conjugated secondary
is mediated by the oxygen atom. This cleavage gives rise to
radical followed by formation of the resonance-stabilized
a peak at m∕z 43 or 57 or 71…. The base peak very often
ion, m∕z 55. The other distinctive peaks at m∕z 83 and 42
results from loss of the larger alkyl group.
in the spectrum of cyclohexanone have been rationalized as
R depicted in Figure 1.28.
R
C O R C O R C O
R 1.6.4.3 Aromatic Ketones. The molecular ion peak of an
(Sch 1.18) aromatic ketone is prominent. Cleavage of aryl alkyl ketones
occurs at the bond 𝛽 to the ring, leaving a characteristic
When one of the alkyl chains attached to the C⏤O ArC⏤ +
⏤O fragment (m∕z 105 when Ar = phenyl), which
group is C3 or longer, cleavage of the C⏤C bond once usually accounts for the base peak. Loss of CO from this
removed (𝛼, 𝛽-bond) from the C⏤O group occurs with fragment gives the “aryl” ion (m∕z 77 in the case of
hydrogen migration to give a major peak (McLafferty rear- acetophenone). Cleavage of the bond adjacent to the ring
rangement, Scheme 1.19). Simple cleavage of the 𝛼, 𝛽-bond, to form a RC⏤ +
⏤O fragment (R = alkyl) is less important
which does not occur to any extent, would give an ion of low though somewhat enhanced by electron-withdrawing groups
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1.6 MASS SPECTRA OF SOME CHEMICAL CLASSES 27

O
O O O
O C
H C C C
H2C CH3 CH -C3H7 CH CH
CH2 CH2
Cyclohexanone
m/z 55
C6H10O O
Mol. Wt.: 98 C CH2
H2C - CH2=CH2
H2C or
- CO
CH2
55 m/z 42
% of Base Peak

100

42 M+
98
50 [M - H2O]+ [M – CH3]+

80 83

0
30 40 50 60 m/z 70 80 90 100
FIGURE 1.28 EI mass spectrum of cyclohexanone.

(and diminished by electron-donating groups) in the para- The mass spectrum of an unsymmetrical diaryl ketone,
position of the Ar group. p-chlorobenzophenone, is displayed in Figure 1.29. The
When the alkyl chain is C3 or longer, cleavage of the molecular ion peak (m∕z 216) is prominent and the intensity
C⏤C bond once removed from the C⏤O group occurs of the M + 2 peak (33.99%, relative to the molecular ion
with hydrogen migration. This is the same cleavage noted peak) demonstrates that chlorine is in the structure (see the
for aliphatic ketones that proceeds through a cyclic transition discussion of Table 1.5 and Figure 1.35 in Section 1.6.16).
state and results in elimination of an alkene and formation of Since the intensity of the m∕z 141 peak is about 13
a stable ion. the intensity of the m∕z 139 peak, these peaks, which are

C O O C Cl
m/z 105 m/z 139
C O p-Chlorobenzophenone
-CO -CO C13H9ClO
Mol. Wt.: 216

Cl
105 Cl
m/z 77 m/z 111 216 M
+
100.00%
% of Base Peak

100 217 M+1 19.28%

139 218 M+2 33.99%
219 M+3 6.21%
77 220 M+4 0.98%

50 216
51
181
94

0
50 100 m/z 150 200
FIGURE 1.29 EI mass spectrum of p-chlorobenzophenone.
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28 CHAPTER 1 MASS SPECTROMETRY

due to fragments which contain chlorine, correspond to the 57, 71, …) becomes dominant. These features are evident in
same fragment. The same can be said about the fragments the spectrum of nonanal (Figure 1.30).
producing the m∕z 111 and 113 peaks.
The fragmentation leading to the major peaks is sketched
1.6.5.2 Aromatic Aldehydes. Aromatic aldehydes are
in Figure 1.29. The Cl⏤ArC⏤ +
⏤O peak is larger than the
⏤ + ⏤ + characterized by a large molecular ion peak and by an M − 1
Cl Ar peak, and the ArC⏤O peak is larger than the Ar +
peak (Ar ⏤C⏤O+ ) that is always large and may be larger
peak (𝛽 cleavage favored). If the [f ragment + 2] peaks for the
than the molecular ion peak. The M − 1 ion, C6 H5 ⏤CO+
Cl-substituted moieties are taken into account however, there
when Ar = phenyl, eliminates CO to give the phenyl ion
is little difference in abundance between Cl⏤ArCO+ and
(m∕z 77), which in turn eliminates acetylene to give the
ArCO+ , or between Cl⏤Ar + and Ar + ; the inductive (elec-
C4 H3 + ion (m∕z 51).
tron withdrawing) and resonance (electron releasing) effects
of the para-substituted Cl are roughly balanced out as they
are in electrophilic aromatic substitution reactions.
1.6.6 Carboxylic Acids
1.6.6.1 Aliphatic Acids. The molecular ion peak of a
1.6.5 Aldehydes
straight-chain monocarboxylic acid is weak but usually
1.6.5.1 Aliphatic Aldehydes. The molecular ion peak of discernible. The most characteristic (sometimes the base)
aliphatic aldehydes is usually discernible. Cleavage of the peak is m∕z 60 resulting from the McLafferty rearrangement
C⏤H and C⏤C bonds next to the oxygen atom results in (Scheme 1.21). Branching at the 𝛼-carbon enhances this
an M − 1 peak and in an M − R peak (m∕z 29, CHO+ ). The cleavage.
M − 1 peak is a good diagnostic peak even for long-chain
aldehydes, but the m∕z 29 peak present in C4 and higher H R
O RHC CH2
aldehydes results from the hydrocarbon C2 H5 + ion.
In the C4 and higher aldehydes, McLafferty cleavage of
HO
the 𝛼, 𝛽 C⏤C bond occurs to give a major peak at m∕z 44,
R
58, or 72, …, depending on the 𝛼 substituents. This is the
resonance-stabilized ion (Scheme 1.20) formed through the H H
cyclic transition state as shown in Scheme 1.7, where Y⏤H. O O
H H HO CH HO CH
O O
H H R R
H H
(Sch 1.21)
R R
(Sch 1.20) In short-chain acids, peaks at M − OH and M − CO2 H
are prominent: these represent cleavage of bonds next to
In straight-chain aldehydes, other unique, diagnostic C⏤O. In long-chain acids, the spectrum consists of two
peaks are at M − 18 (loss of water), M − 28 (loss of ethy- series of peaks resulting from cleavage at each C⏤C bond
lene), M − 43 (loss of CH2 ⏤CH⏤O ), and M − 44 (loss
•
with retention of charge either on the oxygen-containing
of CH2 ⏤CH⏤OH). The rearrangements leading to these fragment (m∕z 45, 59, 73, 87, …) or on the alkyl fragment
peaks have been rationalized (see Budzikiewicz et al., 1967). (m∕z 29, 43, 57, 71, 85, …). As previously discussed, the
As the chain lengthens, the hydrocarbon pattern (m∕z 29, 43, hydrocarbon pattern also shows peaks at m∕z 27, 28; 41, 42;

41 57 O
100 29
% of Base Peak

Nonanal
OH C9H18O
Mol. Wt.: 142

50 69 98
M - 44 M - CH2=CH2
82 95
M - H 2O M+
114 124 M-1 142

0
30 40 50 60 70 80 90 100 110 120 130 140
m/z
FIGURE 1.30 EI mass spectrum of nonanal.
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1.6 MASS SPECTRA OF SOME CHEMICAL CLASSES 29

29 43 57 71 85 99 113 128 O

H
O CH3 CH2 CH2 CH2 CH2 CH2 CH2 CH2 CH2 C OH

HO CH2 143 129 115 101 87 73 59 45

60
73 Decanoic acid
100 C10H20O2
% of Base Peak

Mol. Wt.: 172

43
50 129
M+
112 143 172

0
50 100 150
m/z
FIGURE 1.31 EI mass spectrum of decanoic acid.

55, 56; 69, 70; …. In summary, besides the McLafferty rear- 74, which in fact, is the base peak in straight-chain methyl
rangement peak, the spectrum of a long-chain acid resem- esters from C6 to C26 . The alcohol moiety and/or the 𝛼
bles the series of hydrocarbon clusters at intervals of 14 substituent can often be deduced by the location of the peak
mass units. In each cluster, however, is a prominent peak at resulting from this cleavage.
Cn H2n − 1 O2 . Decanoic acid, (Figure 1.31), nicely illustrates H R
many of the points discussed above. O RHC CH2
Dibasic acids usually have low volatility and hence are
converted to esters to increase vapor pressure. Trimethylsilyl RO
esters are often successful.
R

1.6.6.2 Aromatic Acids. The molecular ion peak of aro- H H

matic acids is large. The other prominent peaks are formed O O
by loss of OH (M − 17) and of CO2 H (M − 45). Loss of
RO CH2 RO CH
H2 O (M − 18) is prominent if a hydrogen-bearing ortho
group is available as outlined in Scheme 1.22. This is one R R
example of the general “ortho effect” noted when the sub-
(Sch 1.23)
stituents can be in a six-membered transition state to facili-
tate loss of a neutral molecule of H2 O, ROH, or NH3 . For the general ester, four ions can result from bond
cleavage next to C⏤O.
O O
O
C R C OR
Z HZ
H The ion R+ is prominent for the short-chain esters but
Y Y diminishes rapidly with increasing chain length and is barely
Z = OH, OR, NH2; Y = CH2, O, NH perceptible in methyl hexanoate. The ion R⏤C⏤ +
⏤O gives
(Sch 1.22) an easily recognizable peak for esters. In methyl esters, it
occurs at M − 31. It is the base peak in methyl acetate and
is still 4% of the base peak in the C26 methyl ester. The ions
1.6.7 Carboxylic Esters [OR′ ] and [C(⏤O)OR′ ] are usually of little importance.
+ +

1.6.7.1 Aliphatic Esters. The molecular ion peak of a The latter is discernible when R′ ⏤CH3 (see m∕z 59 peak of
methyl ester of a straight-chain aliphatic acid is usually Figure 1.32).
distinct. Even waxes usually show a discernible molecular First, consider esters in which the acid portion is the
ion peak. The molecular ion peak is weak in the range m∕z predominant portion of the molecule. The fragmentation
130 to ∼200, but becomes somewhat more intense beyond pattern for methyl esters of straight-chain acids can be
this range. The most characteristic peak results from the described in the same terms used for the pattern of the
familiar McLafferty rearrangement (Scheme 1.23 gives the free acid. Cleavage at each C⏤C bond gives an alkyl
rearrangement for an ester) and cleavage one bond removed ion (m∕z 29, 43, 57, …) and an oxygen-containing ion,
from the C⏤O group. Thus, a methyl ester of an aliphatic Cn H2n − 1 O2 + (m∕z 59, 73, 87, …). Thus, there are hydrocar-
acid unbranched at the 𝛼-carbon gives a strong peak at m∕z bon clusters at intervals of 14 mass units; in each cluster is a
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30 CHAPTER 1 MASS SPECTROMETRY

H O
O
CH2 COCH3 74 × 20
% of Base Peak

O Methyl octanoate O
100 CH2CH2COC H3
C9H18O2
Mol. Wt.: 158
M+
29 87 H M – OCH3 158
50 43 H3COC O M – 31
55
101 127

0
50 100 150
m/z
FIGURE 1.32 EI mass spectrum of methyl octanoate.

prominent peak at Cn H2n − 1 O2 + . The peak (m∕z 87) formally acetate eliminate the neutral molecule ketene (Scheme 1.24);
represented by the ion [CH2 CH2 COOCH3 ]+ is always more frequently this gives rise to the base peak.
intense than its homologs, but the reason is not immediately
obvious. However, it seems clear that the Cn H2n − 1 O2 + ions O OH
do not at all arise from simple cleavage.
O H2C C O
The spectrum of methyl octanoate is presented as
Figure 1.32. This spectrum illustrates one difficulty in using
the M + 1 peak to arrive at a molecular formula (previ-
ously mentioned, Section 1.5.2.1). The measured value for m /z 108
the M + 1 peak is 12%. The calculated value is 10.0%. The
(Sch 1.24)
measured value is high because of an ion-molecule reaction
induced by the relatively large sample that was used to see Of course, the m∕z 43 peak (CH3 C⏤O)+ and m∕z
the weak molecular ion peak. 91 (C7 H7 )+ peaks are prominent for benzyl acetate.
Now let us consider esters in which the alcohol portion
is the predominant portion of the molecule. Esters of fatty 1.6.7.3 Esters of Aromatic Acids. The molecular ion
alcohols (except methyl esters) eliminate a molecule of acid peak of methyl esters of aromatic acids is prominent
in the same manner that alcohols eliminate water. A scheme (ArCOOR, R⏤CH3 ). As the size of the alcohol moiety
similar to that described earlier for alcohols, involving a sin- increases, the intensity of the molecular ion peak decreases
gle hydrogen transfer to the alcohol oxygen of the ester, rapidly to practically zero at C5 . The base peak results from
can be written. An alternative mechanism involves a hydride elimination of OR, and elimination of COOR accounts for
• •

transfer to the carbonyl oxygen (McLafferty rearrange- another prominent peak. In methyl esters, these peaks are at
ment). M − 31 and M − 59, respectively.
The loss of acetic acid by the mechanism described As the alkyl moiety increases in length, three modes of
above is so facile in steroidal acetates that they frequently cleavage become important: (1) McLafferty rearrangement,
show no detectable molecular ion peak. Steroidal systems (2) rearrangement of two hydrogen atoms with elimination
also seem unusual in that they often display significant of an allylic radical, and (3) retention of the positive charge
molecular ions as alcohols, even when the corresponding by the alkyl group.
acetates do not. The familiar McLafferty rearrangement pathway gives
Esters of long-chain alcohols show a diagnostic peak at rise to a peak for the aromatic acid, (ArCOOH)+ . The
m∕z 61, 75, or 89 … from elimination of the alkyl moiety second, similar pathway gives the protonated aromatic acid,
as an alkene and transfer of two hydrogen atoms to the (ArCOOH2 )+ . The third mode of cleavage gives the alkyl
fragment containing the oxygen atoms, which in essence is cation, R+ .
the protonated carboxylic acid. Appropriately, ortho-substituted benzoates eliminate
Esters of dibasic acids ROOC(CH2 )n COOR, in general, ROH through the general “ortho” effect described above
give recognizable molecular ion peaks. Intense peaks are under aromatic acids. Thus, the base peak in the spectrum
found at [ROOC(CH2 )n C⏤O]+ and at [ROOC(CH2 )n ]+ . of methyl salicylate is m∕z 120; this ion eliminates carbon
monoxide to give a strong peak at m∕z 92.
1.6.7.2 Benzyl and Phenyl Esters. Benzyl acetate (also A strong characteristic peak at mass 149 is found in the
furfuryl acetate and other similar acetates) and phenyl spectra of all esters of phthalic acid, starting with the diethyl
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1.6 MASS SPECTRA OF SOME CHEMICAL CLASSES 31

O
O
-Valerolactone
–CH3CH O
C5H8O2 O
56 Mol. Wt.: 100 H2C
28
% of Base Peak

100 m/z 56
41 85
29
43 M - 15
50
M+
100

0
30 40 50 60 m/z 70 80 90 100

FIGURE 1.33 EI mass spectrum of 𝛾-valerolactone.

ester. This peak is not significant in the dimethyl or methyl Scheme 1.25) from the 𝛼-C atom is preferred.
ethyl ester of phthalic acid, nor in esters of isophthalic or R R R
terephthalic acids, all of which give the expected peaks at R
M − R, M − 2R, M − CO2 R, and M − 2CO2 R. Since long- H2N C R H2N C H 2N C
chain phthalate esters are widely used as plasticizers, a strong R R R
peak at m∕z 149 may indicate contamination. The m∕z 149 (Sch 1.25)
fragment (essentially a protonated phthalic anhydride) is
probably formed by two ester cleavages involving the shift When branching at the 𝛼-carbon is absent, an M − 1
of two hydrogen atoms and then another hydrogen atom, peak is usually visible. This is the same type of cleavage
followed by elimination of H2 O. noted above for alcohols. The effect is more pronounced in
amines because of the better resonance stabilization of the
1.6.8 Lactones ion fragment by the less electronegative N atom compared
with the O atom.
The molecular ion peak of five-membered ring lactones is Primary straight-chain amines show a homologous
distinct but is weaker when an alkyl substituent is present at series of peaks of progressively decreasing intensity (the
C4 . Facile cleavage of the side chain at C4 (guidelines 3 and cleavage at the 𝜖-bond is slightly more important than at the
8, Section 1.5.4) gives a strong peak at M − alkyl. neighboring bonds) at m∕z 30, 44, 58,…resulting from cleav-
The base peak (m∕z 56) of 𝛾-valerolactone (Figure 1.33) age at C⏤C bonds successively removed from the nitro-
and the same strong peak of butyrolactone are rationalized, gen atom with retention of the charge on the N-containing
which shows the elimination of acetaldehyde. fragment. These peaks are accompanied by the hydrocar-
Labeling experiments indicate that some of the m∕z 56 bon pattern of Cn H2n + 1 , Cn H2n , and Cn H2n − 1 ions. Thus, we
peak in 𝛾-valerolactone arises from the C4 H8 + ion. The other note characteristic clusters at intervals of 14 mass units, each
intense peaks in 𝛾-valerolactone are at m∕z 27 (C2 H3 + ), cluster containing a peak resulting from a Cn H2n + 2 N ion.
28 (C2 H4 + ), 29 (C2 H5 + ), 41 (C3 H5 + ), and 43 (C3 H7 + ), and Because of the very facile cleavage to form the base peak,
85 (C4 H5 O2 + , loss of the methyl group). In butyrolactone, the fragmentation pattern in the high mass region becomes
there are strong peaks at m∕z 27, 28, 29, 41, and 42 (C3 H6 + ). extremely weak.
Cyclic fragments apparently occur during the frag-
1.6.9 Amines mentation of longer chain amines. The fragment shown
1.6.9.1 Aliphatic Amines. The molecular ion peak of an in Scheme 1.26 gives a six-membered ring; five-membered
aliphatic monoamine is an odd number, but it is usu- rings are also commonly formed.
ally quite weak and, in long-chain or highly branched
amines, undetectable. The base peak frequently results from R
C⏤C cleavage next to the nitrogen atom (𝛼, 𝛽 guideline
NH2 R NH2
8, Section 1.5.4); for primary amines unbranched at the 𝛼-
carbon, this is m∕z 30 (CH2 NH2 + ) shown in Scheme 1.25.
This cleavage accounts for the base peak in all primary m /z 86
amines and secondary and tertiary amines that are not
(Sch 1.26)
branched at the 𝛼-carbon. Loss of the largest branch ( R″ in •
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32 CHAPTER 1 MASS SPECTROMETRY

A peak at m∕z 30 is good though not conclusive evidence 1.6.10 Amides

for a straight-chain primary amine. Further decomposition of
1.6.10.1 Aliphatic Amides. The molecular ion peak of
the first-formed ion from a secondary or tertiary amine leads
to a peak at m∕z 30, 44, 58, 72, …. This is a process similar straight-chain monoamides is usually discernible. The dom-
to that described for aliphatic alcohols and ethers above and, inant modes of cleavage depend on the length of the acyl
similarly, is enhanced by branching at one of the 𝛼-carbon moiety and on the lengths and number of the alkyl groups
atoms. attached to the nitrogen atom.
The base peak (m∕z 59, H2 NC(⏤OH+ )CH2 ) in all
•

Cleavage of amino acid esters occurs at both C⏤C

bonds (dashed lines below) next to the nitrogen atom; loss of straight-chain primary amides higher than propionamide
the carbalkoxy group (⏤COOR′ ) is preferred. The aliphatic results from the familiar McLafferty rearrangement. Branch-
amine fragment (+ NH2 ⏤CHCH2 CH2 R) decomposes fur- ing at the 𝛼-carbon (CH3 , etc.) gives a homologous peak at
ther to give a peak at m∕z 30. m∕z 73 or 87, ….
Primary amides give a strong peak at m∕z 44 from cleav-
age of the R⏤CONH2 bond: (O⏤C⏤+ NH2 ); this is the
NH2 base peak in C1 ⏤C3 primary amides and in isobutyramide.
R OOC C CH2CH2R A moderate peak at m∕z 86 results from 𝛾,𝛿 C⏤C cleavage,
H possibly accompanied by cyclization (Scheme 1.28).
H2
NH2 R N
1.6.9.2 Cyclic Amines. In contrast to acyclic amines, the R
O O
molecular ion peaks of cyclic amines are usually intense
unless there is substitution at the 𝛼 position; for example, the m /z 86
molecular ion peak of pyrrolidine is strong. Primary cleavage (Sch 1.28)
at the bonds next to the N atom leads either to loss of an
𝛼-hydrogen atom to give a strong M − 1 peak or to opening Secondary and tertiary amides with an available hydro-
of the ring; the latter event is followed by elimination of gen on the 𝛾-carbon of the acyl moiety and methyl groups
ethylene to give CH2 ⏤+ NH⏤CH2 (m∕z 43, base peak),
•
on the N atom show the dominant peak resulting from the
hence by loss of a hydrogen atom to give CH2 ⏤N+ ⏤CH2 McLafferty rearrangement. When the N-alkyl groups are C2
(m∕z 42). N-methyl pyrrolidine also gives a C2 H4 N+ (m∕z or longer and the acyl moiety is shorter than C3 , another
42) peak, apparently by more than one pathway. mode of cleavage predominates. This is cleavage of the
Piperidine likewise shows a strong molecular ion and N-alkyl group 𝛽 to the nitrogen atom, and cleavage of the
M − 1 (base) peak. Ring opening followed by several avail- carbonyl C⏤N bond with migration of an 𝛼-hydrogen atom
able sequences leads to characteristic peaks at m∕z 70, 57, of the acyl moiety (expelling a neutral ketene molecule) and
56, 44, 43, 42, 30, 29, and 28. Substituents are cleaved from leaving + NH2 ⏤CH2 (m∕z 30).
the ring (guideline 6, Section 1.5.4).
1.6.10.2 Aromatic Amides. Benzamide (Figure 1.1) is a
typical example. Loss of NH2 from the molecular ion yields
1.6.9.3 Aromatic Amines (Anilines). The molecular ion a resonance-stabilized benzoyl cation that in turn undergoes
peak (odd number) of an aromatic monoamine is intense. cleavage to a phenyl cation. A separate fragmentation path-
Loss of one of the amino H atoms of aniline gives a way gives rise to a modest m∕z 44 peak.
moderately intense M − 1 peak; loss of a neutral molecule of
HCN followed by loss of a hydrogen atom gives prominent
peaks at m∕z 66 and 65, respectively. 1.6.11 Aliphatic Nitriles
It was noted above that cleavage of alkyl aryl ethers The molecular ion peaks of aliphatic nitriles (except for
occurs with rearrangement involving cleavage of the ArO⏤R acetonitrile and propionitrile) are weak or absent, but the
bond: that is, cleavage was controlled by the ring rather than M + 1 peak can usually be located by its behavior on
by the oxygen atom. In the case of alkyl aryl amines, cleav- increasing the sample size (Section 1.5.2.1). A weak but
age of the C⏤C bond next to the nitrogen atom is dominant diagnostically useful M − 1 peak is formed by loss of an
(Scheme 1.27): that is, the heteroatom controls cleavage. 𝛼-hydrogen to form the stable ion: RCH⏤C⏤N+ .
The base peak of straight-chain nitriles between C4 and
CH2 C9 is m∕z 41. This peak corresponds to the ion resulting
HN CH2R HN
from hydrogen rearrangement in a six-membered transition
state, similar to a McLafferty rearrangement giving a peak
CH2R
at m∕z 41 CH2 ⏤C⏤N+ ⏤H. However, this peak lacks
diagnostic value because of the presence of C3 H5 + (m∕z 41)
m/z 106 for all molecules containing a hydrocarbon chain.
A peak at m∕z 97 is characteristic and intense (some-
(Sch 1.27) times the base peak) in straight-chain nitriles C8 and higher.
 Silverstein c01.tex V3 - 07/10/2014 3:46 P.M. Page 33

1.6 MASS SPECTRA OF SOME CHEMICAL CLASSES 33

The mechanism depicted in Scheme 1.29 has been proposed 1.6.13 Aliphatic Nitrites
to account for this ion.
R The molecular ion peak (odd number) of aliphatic nitrites
H (one N present) is weak or absent. The peak at m∕z 30 (NO+ )
is always large and is often the base peak. There is a large
N peak at m∕z 60 (CH2 ⏤+ ONO) in all nitrites unbranched at
HN
H2C CHR
the 𝛼-carbon; this represents cleavage of the C⏤C bond next
to the ONO group. An 𝛼 branch can be identified by a peak
at m∕z 74, 88, or 102 …. Absence of a large peak at m∕z 46
m /z 97 permits differentiation from nitro compounds. Hydrocarbon
(Sch 1.29) peaks are prominent, and their distribution and intensities
describe the arrangement of the carbon chain.
Simple cleavage at each C⏤C bond (except the one
next to the N atom) gives a characteristic series of homol-
ogous peaks of even mass number down the entire length 1.6.14 Aliphatic Nitrates
of the chain (m∕z 40, 54, 68, 82, …) resulting from the
(CH2 )n C⏤ + The molecular ion peak (odd number) of aliphatic nitrates
⏤N ions. Accompanying these peaks are the
usual peaks of the hydrocarbon pattern. (one nitrogen present) is weak or absent. A prominent
(frequently the base) peak is formed by cleavage of the C⏤C
bond next to the ONO2 group with loss of the heaviest alkyl
1.6.12 Nitro Compounds group attached to the 𝛼-carbon. The NO2 + peak at m∕z 46
1.6.12.1 Aliphatic Nitro Compounds. The molecular ion is also prominent. As in the case of aliphatic nitrites, the
peak (odd number) of an aliphatic mononitro compound is hydrocarbon fragment ions are distinct.
weak or absent (except in the lower homologs). The main
peaks are attributable to the hydrocarbon fragments up to
1.6.15 Sulfur Compounds
M − NO2 . Presence of a nitro group is indicated by an appre-
ciable peak at m∕z 30 (NO+ ) and a smaller peak at mass The contribution (4.4%, see Table 1.3 and Figure 1.34) of the
46 (NO2 + ). 34 S isotope to the M + 2 peak, and often to a (f ragment + 2)

peak, affords ready recognition of sulfur-containing com-

1.6.12.2 Aromatic Nitro Compounds. The molecular ion pounds. A homologous series of sulfur containing frag-
peak of aromatic nitro compounds (odd number for one N ments is four mass units higher than the hydrocarbon
atom) is strong. Prominent peaks result from elimination of fragment series. The number of sulfur atoms can be deter-
an NO2 radical (M − 46, the base peak in nitrobenzene), and mined from the size of the contribution of the 34 S isotope
of a neutral NO molecule with rearrangement to form the to the M + 2 peak. The mass of the sulfur atom(s) present is
phenoxy cation (M − 30); both are good diagnostic peaks. subtracted from the molecular weight. In diisopentyl disul-
Loss of acetylene from the M − 46 ion accounts for a strong fide, for example, the molecular weight is 206, and the
peak at M − 72; loss of CO from the M − 30 ion gives a molecule contains two sulfur atoms. The formula for the rest
peak at M − 58. A diagnostic peak at m∕z 30 results from of the molecule is therefore found under mass 142, that is,
the NO+ ion. 206 − (2 × 32).
The isomeric o-, m-, and p-nitroanilines each give a
strong molecular ion (even number). They all give prominent 1.6.15.1 Aliphatic Mercaptans (Thiols). The molecular
peaks resulting from two sequences. The first pathway entails ion peak of aliphatic mercaptans, except for higher tertiary
a loss of an NO2 group (M − 46) to give an m∕z 92; this ion mercaptans, is usually strong enough so that the M + 2 peak
loses HCN to give an m∕z 65. The second sequence records can be accurately measured. In general, the cleavage modes
a loss of NO (M − 30) to give m∕z 108, which loses CO to resemble those of alcohols. Cleavage of the C⏤C bond
give m∕z 80. (𝛼,𝛽-bond) next to the SH group gives the characteristic ion
Aside from differences in intensities, the three isomers CH2 ⏤SH+ (m∕z 47). Sulfur is poorer than nitrogen, but
give very similar spectra. The meta and para compounds give better than oxygen, at stabilizing such a fragment. Cleavage
a small peak at m∕z 122 from loss of an O atom, whereas the at the 𝛽,𝛾 bond gives a peak at m∕z 61 of about one-half the
ortho compound eliminates OH as depicted in Scheme 1.30 intensity of the m∕z 47 peak. Cleavage at the 𝛾,𝛿-bond gives
to give a small peak at m∕z 121. a small peak at m∕z 75, and cleavage at the 𝛿,𝜖-bond gives a
O
O peak at m∕z 89 that is more intense than the peak at m∕z 73;
N N presumably the m∕z 89 ion is stabilized by cyclization:
O OH
H
N NH S H
H m/z 121
(Sch 1.30)
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34 CHAPTER 1 MASS SPECTROMETRY

H2
C 70 S +
C5H10 174 M 100.00%
100 H2 C SH Di-n-pentyl sulfide 175 M+1 11.33%
% of Base Peak

43 61 C10H22S 176 M+2 4.67%

Mol. Wt.: 174
C5H11S+
+ C5H11S+H
50 CH2=S H 103
C5H11S+=CH2
117 174
131

0
50 100 m/z 150

FIGURE 1.34 EI mass spectrum of di-n-pentyl sulfide.

Again analogous to alcohols, primary mercaptans frag- cleavage. Methyl primary sulfides cleave at the 𝛼, 𝛽-bond to
ment to give H2 S and a strong M − 34 peak, the resulting give the m∕z 61 ion, CH3 ⏤S+ ⏤CH2 .
ion then eliminating ethylene: thus the homologous series However, a strong m∕z 61 peak in the spectrum of
M − H2 S − (CH2 ⏤CH2 )n arises. a straight-chain sulfide calls for a different explanation.
Secondary and tertiary mercaptans cleave at the Scheme 1.32 offers a plausible explanation.
𝛼-carbon atom with loss of the largest group to give a promi- H
nent peak M − CH3 , M − C2 H5 , M − C3 H7 , …. However, a H
peak at m∕z 47 may also appear as a rearrangement peak of S S
H2C CHR CH2 RCH2 S
secondary and tertiary mercaptans. A peak at M − 33 (loss
H
of HS) is usually present for secondary mercaptans. m /z 61
In long-chain mercaptans, the hydrocarbon pattern is R R
superimposed on the mercaptan pattern. As for alcohols, the R
alkenyl peaks (i.e., m∕z 41, 55, 69, …) are as intense or even (Sch 1.32)
more so than the alkyl peaks (m∕z 43, 57, 71, …).
Sulfides give a characteristic ion by cleavage of the
1.6.15.2 Aliphatic Sulfides. The molecular ion peak of C⏤S bond with retention of charge on sulfur. The resulting
aliphatic sulfides is usually intense enough so that the RS+ ion gives a peak at m∕z 32 + CH3 , 32 + C2 H5 , 32 +
M + 2 peak can be accurately measured. The cleavage modes C3 H7 , … . The ion of m∕z 103 seems especially favored
generally resemble those of ethers. Cleavage of one or possibly because of formation of a rearranged cyclic ion
the other of the 𝛼, 𝛽 C⏤C bonds occurs, with loss of (Scheme 1.33). These features are illustrated by the spectrum
the largest group being favored. These first-formed ions of di-n-pentyl sulfide (Figure 1.34).
decompose further with hydrogen transfer and elimination H
of an alkene. The steps for aliphatic ethers also occur for
sulfides (Scheme 1.31); the end result is the ion RCH⏤SH+ S
(see Figure 1.34 for an example.) S

S S S S m /z 103
CH3 C2H4 H H
(Sch 1.33)
H m/z 61
As with long-chain ethers, the hydrocarbon pattern may
(Sch 1.31) dominate the spectrum of long-chain sulfides; the Cn H2n
For a sulfide unbranched at either 𝛿-carbon atom, this peaks seem especially prominent. In branched chain sulfides,
ion is CH2 ⏤SH+ (m∕z 47), and its intensity may lead to cleavage at the branch may reduce the relative intensity of the
confusion with the same ion derived from a mercaptan. characteristic sulfide peaks.
However, the absence of M − H2 S or M − SH peaks in
sulfide spectra makes the distinction. 1.6.15.3 Aliphatic Disulfides. The molecular ion peak for
A moderate to strong peak at m∕z 61 is present (see alkyl at least up to C10 disulfides is strong. A major peak found
sulfide cleavage, Figure 1.34) in the spectrum of all except in these spectra results from cleavage of one of the C⏤S
tertiary sulfides. When an 𝛼-methyl substituent is present, bonds with retention of the charge on the alkyl fragment.
m∕z 61 is the ion CH3 CH⏤SH+ , resulting from the double Another major peak results from the same cleavage along
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1.6 MASS SPECTRA OF SOME CHEMICAL CLASSES 35

with a shift of a hydrogen atom to form the RSSH fragment, mentioned earlier, the chlorine containing fragments (m∕z
which retains the charge. Other peaks apparently result from 141 and 113) show [f ragment + 2] peaks of the proper inten-
cleavage between the sulfur atoms without rearrangement, sity.
and with migration of one or two hydrogen atoms to give, Unfortunately, the application of isotope contributions,
respectively, RS+ , RS+ − 1, and RS+ − 2. though generally useful for aromatic halogen compounds, is
limited by the weak molecular ion peak of many aliphatic
halogen compounds of more than about six carbon atoms
1.6.16 Halogen Compounds for a straight chain, or fewer for a branched chain. How-
A compound that contains one chlorine atom will have an ever, the halogen-containing fragments are recognizable by
M + 2 peak approximately one-third the intensity of the the ratio of the (f ragment + 2) peaks to fragment peaks
molecular ion peak because of the presence of a molecular in monochlorides or monobromides. In polychloro or poly-
ion containing the 37 Cl isotope (see Table 1.4). A compound bromo compounds, these (f ragment + isotope) peaks form
that contains one bromine atom will have an M + 2 peak a distinctive series of multiplets (Figure 1.36). Coincidence
almost equal in intensity to the molecular ion because of of a fragment ion with one of the isotope fragments, with
the presence of a molecular ion containing the 81 Br isotope. another disruption of the characteristic ratios, must always
A compound that contains two chlorines, or two bromines, be kept in mind.
or one chlorine and one bromine will show a distinct M + 4
peak, in addition to the M + 2 peak, because of the presence 1.6.16.1 Aliphatic Chlorides. The molecular ion peak is
of a molecular ion containing two atoms of the heavy isotope. detectable only in the lower monochlorides. Fragmentation
In general, the number of chlorine and/or bromine atoms in a of the molecular ion is mediated by the chlorine atom but to a
molecule can be ascertained by the number of alternate peaks much lesser degree than is the case in oxygen-, nitrogen-, or
beyond the molecular ion peak. Thus, three chlorine atoms sulfur-containing compounds. Thus, cleavage of a straight-
in a molecule will give peaks at M + 2, M + 4, and M + 6; in chain monochloride at the C⏤C bond adjacent to the chlo-
polychloro compounds, the peak of highest mass may be so rine atom accounts for a small peak at m∕z 49, CH2 ⏤Cl+
weak as to escape notice. (and, of course, the isotope peak at m∕z 51).
The relative abundances of the peaks (molecular ion, Cleavage of the C⏤Cl bond leads to a small Cl+ peak
M + 2, M + 4, and so on) have been calculated by Beynon and to a R+ peak, which is prominent in the lower chlorides
et al. (1968) for compounds containing chlorine and bromine but quite small when the chain is longer than about C5 .
(atoms other than chlorine and bromine were ignored). Straight-chain chlorides longer than C6 give C3 H6 Cl+ ,
A portion of these results is presented here, somewhat C4 H8 Cl+ , and C5 H10 Cl+ ions. Of these, the C4 H8 Cl+ ion
modified, as Table 1.5. We can now tell what combination forms the most intense (sometimes the base) peak; a five-
of chlorine and bromine atoms is present. It should be noted membered cyclic structure (Scheme 1.34) may explain its
that Table 1.5 presents the isotope contributions in terms of stability.
R
percent of the molecular ion peak. Figure 1.35 provides the
corresponding bar graphs. R
As required by Table 1.5, the M + 2 peak in the spec- Cl Cl
trum of p-chlorobenzophenone (Figure 1.29) is about one-
(Sch 1.34)
third the intensity of the molecular ion peak (m∕z 218). As
Loss of HCl occurs, possibly by 1,3 elimination, to give
TABLE 1.5 Intensities of Isotope Peaks (Relative to the Molecular a peak (weak or moderate) at M − 36.
Ion) for Combinations of Chlorine and Bromine In general, the spectrum of an aliphatic monochloride
is dominated by the hydrocarbon pattern to a greater extent
Halogen % % % % % %
Present M+2 M+4 M+6 M+8 M + 10 M + 12
than that of a corresponding alcohol, amine, or mercaptan.

Cl 32.6 1.6.16.2 Aliphatic Bromides. The remarks under aliphatic

Cl2 65.3 10.6 chlorides apply quite generally to the corresponding bro-
Cl3 97.8 31.9 3.5 mides.
Cl4 131.0 63.9 14.0 1.2
Cl5 163.0 106.0 34.7 5.7 0.4 1.6.16.3 Aliphatic Iodides. Aliphatic iodides give the
Cl6 196.0 161.0 69.4 17.0 2.2 0.1 strongest molecular ion peak of the aliphatic halides. Since
Br 97.9 iodine is monoisotopic, there is no distinctive isotope peak.
Br 2 195.0 95.5 The presence of an iodine atom can sometimes be deduced
Br 3 293.0 286.0 93.4 from isotope peaks that are suspiciously low in relation to the
BrCl 130.0 31.9 molecular ion peaks, and from several distinctive peaks; in
BrCl2 163.0 74.4 10.4 polyiodo compounds, the large interval between major peaks
Br 2 Cl 228.0 159.0 31.2
is characteristic.
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36 CHAPTER 1 MASS SPECTROMETRY

200
% of Molecular Ion

150

100
Missing
M+2 M+4 M+6 M+8 M+10 M+12
50

Cl Cl2 Cl3 Cl4 Cl5 Cl6

300
% of Molecular Ion

250
M+4
200
M+2 M+4 M+6
150

100 M+4 M+6

50
0

Br Br2 Br3 BrCl BrCl2 Br2Cl

FIGURE 1.35 Predicted patterns of M, M + 2, M + 4, … for compounds with various combinations of chlorine and bromine.

CCl3
117 119
% of Base Peak

100
Cl
35 CCl
47 CCl2
50 82 121
84
37 49 59
86 123

0
40 50 60 70 80 90 100 110 120 130 140 150 160
m/z
FIGURE 1.36 EI mass spectrum of carbon tetrachloride (CCl4 ).

Iodides cleave much as do chlorides and bromides, compounds. In monofluorides, cleavage of the 𝛼, 𝛽 C⏤C
but the C4 H8 I+ ion is not as evident as the corresponding bond is less important than in the other monohalides,
chloride and bromide ions. but cleavage of a C⏤H bond on the 𝛼-carbon atom is
more important. This reversal is a consequence of the high
1.6.16.4 Aliphatic Fluorides. Aliphatic fluorides give the electronegativity of the F atom and is rationalized by placing
weakest molecular ion peak of the aliphatic halides. Fluorine the positive charge on the 𝛼-carbon atom. The secondary
is monoisotopic, and its detection in polyfluoro compounds carbonium ion thus depicted in Scheme 1.35 by a loss of a
depends on suspiciously small isotopic peaks relative to hydrogen atom is more stable than the primary carbonium
the molecular ion, on the intervals between peaks, and on ion resulting from loss of an alkyl radical.
characteristic peaks. Of these, the most characteristic is m∕z
R CH2 F H
69 resulting from the ion CF3 + , which is the base peak R CH F
in all perfluorocarbons. Prominent peaks are noted at m∕z
119, 169, 219…; these are increments of CF2 . The stable R
CH2 F
ions C3 F5 + and C4 F7 + give large peaks at m∕z 131 and
181. The M − F peak is frequently visible in perfluorinated (Sch 1.35)
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STUDENT EXERCISES 37

1.6.16.5 Benzyl Halides. The molecular ion peak of ben- acetylene molecule or by loss of radical fragments. Thus,
zyl halides is usually detectable. The benzyl (or tropylium) furan exhibits two principal peaks: C3 H3 + (m∕z 39) and
ion from loss of the halide (guideline 8, Section 1.5.4) is HC⏤ +
⏤O (m∕z 29). For thiophene, there are three peaks,
favored even over 𝛽-bond cleavage of an alkyl substituent. A C3 H3 (m∕z 39), HC⏤
+ + +
⏤S (m∕z 45), and C2 H2 S (m∕z 58).
substituted phenyl ion (𝛼-bond cleavage) is prominent when For pyrrole, there are three peaks: C3 H3 + (m∕z 39),
the ring is polysubstituted. HC⏤NH+ (m∕z 28) and C2 H2 NH+ (m∕z 41). Pyrrole also
eliminates a neutral molecule of HCN to give an intense
1.6.16.6 Aromatic Halides. The molecular ion peak of an peak at m∕z 40. The base peak of 2,5-dimethylfuran is
aryl halide is readily apparent. The M − X peak is large for m∕z 43 (CH3 C⏤ ⏤O+ ).
all compounds in which X is attached directly to the ring. Cleavage of the 𝛽 C⏤C bond in alkylpyridines
(Scheme 1.36) depends on the position of the ring substitu-
tion, being more pronounced when the alkyl group is in the
1.6.17 Heteroaromatic Compounds
3 position. An alkyl group of more than three carbon atoms
The molecular ion peak of heteroaromatics and alkylated het- in the 2 position can undergo migration of a hydrogen atom
eroaromatics is intense. Cleavage of the bond 𝛽 to the ring, as to the ring nitrogen.
in alkylbenzenes, is the general rule; in pyridine, the position
of substitution determines the ease of cleavage of the 𝛽-bond
RHC CH2
(see below).
Localizing the charge of the molecular ion on the N
N CH2 N CH2
heteroatom, rather than in the ring 𝜋 structure, provides H
a satisfactory rationale for the observed mode of cleav- H H
age. The present treatment follows that used by Djerassi R m/z 93
(Budzikiewicz et al., 1967). (Sch 1.36)
The five-membered ring heteroaromatics (furan, thio-
phene, and pyrrole) show very similar ring cleavage pat- A similar cleavage is found in pyrazines since all ring
terns. The first step in each case is cleavage of the substituents are necessarily ortho to one of the nitrogen
carbon-heteroatom bond, followed by loss of either a neutral atoms.

REFERENCES

For a list of Chapter References, please visit: www.wiley.com/college/silverstein.

STUDENT EXERCISES

1.1 Using Table 1.4, calculate the exact mass for the compounds (j) 113.0845, (k) 114.1043, (l) 116.0841, (m) 116.1206,
below (a – o). (n) 122.0733, (o) 122.0733, (p) 126.1041, (q) 138.0687,
1.2 Determine the index of hydrogen deficiency for the compounds (r) 150.0041, (s) 152.0476, (t) 156.9934, (u) 161.9637,
below. (v) 169.9735, (w) 208.0094.
1.3 Write the structure for the molecular ion for each compound 1.7 For each of the mass spectra (A–W), determine if there are any
(a – o) showing, when possible, the location of the radical of the following heteroatoms in the compound: S, Cl, Br.
cation. 1.8 For each exact mass corresponding to mass spectra A–W,
1.4 Predict three major fragmentation/rearrangement pathways for determine the molecular formula. Remember to look at the het-
the compounds below. For each pathway, cite the guideline eroatoms that were determined in exercise 1.7.
from Section 1.5.4 that supports your prediction. 1.9 Determine the index of hydrogen deficiency for each of the for-
1.5 For each fragmentation/rearrangement pathway from exercise mulas in exercise 1.6.
1.4, show a detailed mechanism using either single barbed or 1.10 List the base peak and molecular ion peak for each of the EI
double barbed arrows as appropriate. mass spectra (A – W).
1.6 Match each of the exact masses to the mass spectra shown on 1.11 Choose three ions (besides the molecular ion) from each EI
the following pages (labelled A – W). Note that two compounds mass spectrum (A – W, except for H), determine the molecular
have the same exact mass, and you will need to consider the formula for each fragment ion, and give the molecular formula
CI mass spectrum when given. The masses are: (a) 56.0264, for the portion that is lost from the molecular ion. Indicate
(b) 73.0896, (c) 74.0363, (d) 89.0479, (e) 94.0535, which ions result from a rearrangement.
(f) 96.0572, (g) 98.0736, (h) 100.0893, (i) 102.0678,
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38 CHAPTER 1 MASS SPECTROMETRY Exercise 1.1

a b c

OH

d e f

COOH OH
OH
g h i
O
OH
S
NO2
j k l

O O
OAc
H
Br
m n o
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Exercise 1.6 (A – C) STUDENT EXERCISES 39

A
71
43
100
% of Base Peak

50
114
58
86 99

40 50 60 70 80 90 100 110
m/z
B
59
69
100
% of Base Peak

87
41
50
43
45 98
115

40 50 60 70 80 90 100 110
m/z
B CI Reagent gas Methane
117
100
% of Base Peak

50
99

0
60 65 70 75 80 85 90 95 100 105 110 115
m/z
C
91
100
% of Base Peak

172
170
50
65
39 50 75

50 100 150
m/z
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40 CHAPTER 1 MASS SPECTROMETRY Exercise 1.6 (D – G)

× 10
71
% of Base Peak

100 43

50 55 152
107 109 121
123 150

40 50 60 70 80 90 100 110 120 130 140 150

m/z
E
43
100 58
% of Base Peak

50 100
71 85

40 50 60 70 80 90 100
F m/z

74
100
73
% of Base Peak

45
50 57
56
75

40 45 50 55 60 65 70 75
G m/z

73
100
% of Base Peak

50
41
44 56

40 45 50 55 60 65 70 75
m/z
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Exercise 1.6 (H – I) STUDENT EXERCISES 41

H
55
100
% of Base Peak

50 39

56 57

40 45 50 55
m/z
H CI Reagent gas Methane

57
100
% of Base Peak

50

85 97

0
55 60 65 70 75 m/z 80 85 90 95 100 105
I
43
100
% of Base Peak

50

72 90

40 45 50 55 60 65 70 75 80 85 90
m/z
I CI Reagent gas Methane
90
100
% of Base Peak

50
119
130

0
70 75 80 85 90 95 100 105 110 115 120 125 130 135
m/z
 Silverstein c01.tex V3 - 07/10/2014 3:46 P.M. Page 42

42 CHAPTER 1 MASS SPECTROMETRY Exercise 1.6 (J – M)

J
94
100
% of Base Peak

50 138
77
45 51 66
39 107

40 50 60 70 80 90 100 110 120 130 140

K m/z

94
100
% of Base Peak

122
50
66
39 51 77

40 50 60 70 80 90 100 110 120

L m/z

43
100 74
71
% of Base Peak

50
59
87
102

40 50 60 70 80 90 100
m/z
M
113
100 55
% of Base Peak

56 85
84
42
50
67

40 50 60 70 80 90 100 110
m/z
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Exercise 1.6 (N – Q) STUDENT EXERCISES 43

N
94
100
% of Base Peak

67
50
40 53
42

40 45 50 55 60 65 70 75 80 85 90 95
O m/z

152
100
% of Base Peak

135
50
77 107
39 63 92
53 122

40 50 60 70 80 90 100 110 120 130 140 150

m/z
P
75 111 157
100
% of Base Peak

101 127
99 113
159
50 50
129
141

40 50 60 70 80 90 100 110 120 130 140 150 160

m/z
Q

60
100
% of Base Peak

111
69
50 41 55 83
129
149 151 181
179 191 193
0
50 100 150 200
m/z
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44 CHAPTER 1 MASS SPECTROMETRY Exercise 1.6 (Q – T)

Q CI Reagent gas Methane

100
% of Base Peak

111 209 211

129
50
239
191 193 237

0
100 150 200
m/z
R
70
79
100 41
% of Base Peak

39
54 57

50 98
83 97

40 45 50 55 60 65 70 75 80 85 90 95
S m/z

43
100 108
% of Base Peak

69
55

50 111
58 93 126
83

40 50 60 70 80 90 100 110 120 130

m/z
T

60
100
% of Base Peak

73

50
41
45 56 87
116
0
40 50 60 70 80 90 100 110
m/z
 Silverstein c01.tex V3 - 07/10/2014 3:46 P.M. Page 45

Exercise 1.6 (T – W) STUDENT EXERCISES 45

T CI Reagent gas Methane

117
100
% of Base Peak

50 99

145
157

0
70 80 90 100 110 120 130 140 150 160
m/z
U
162
100
% of Base Peak

63
50 98 126
73 128

50 100 150
m/z
V
122
107
100
% of Base Peak

50 77
79 91
65

40 50 60 70 80 90 100 110 120

m/z
W

68
100
% of Base Peak

96
50
40 55
42
53

40 45 50 55 60 65 70 75 80 85 90 95
m/z
 Silverstein c01.tex V3 - 07/10/2014 3:46 P.M. Page 46

46 CHAPTER 1 MASS SPECTROMETRY

FORMULA MASSES (FM) FOR VARIOUS COMBINATIONS OF

APPENDIX A CARBON, HYDROGEN, NITROGEN, AND OXYGEN𝐚

FM FM FM FM

12 H4 N2 32.0375 C2 H6 O 46.0419 CH3 N2 O 59.0246

C 12.0000 CH4 O 32.0262 47 CH5 N3 59.0484
13 33 HNO2 47.0007 C2 H3 O2 59.0133
CH 13.0078 HO2 32.9976 CH3 O2 47.0133 C2 H5 NO 59.0371
14 H3 NO 33.0215 CH5 NO 47.0371 C2 H7 N2 59.0610
N 14.0031 34 48 C3 H7 O 59.0497
CH2 14.0157 H2 O2 34.0054 O3 47.9847 C3 H9 N 59.0736
15 38 H2 NO2 48.0085 60
HN 15.0109 C3 H2 38.0157 H4 N2 O 48.0324 CH2 NO2 60.0085
CH3 15.0235 39 CH4 O2 48.0211 CH4 N2 O 60.0324
16 C2 HN 39.0109 49 CH6 N3 60.0563
O 15.9949 C3 H3 39.0235 H3 NO2 49.0164 C2 H4 O2 60.0211
H2 N 16.0187 40 52 C2 H6 NO 60.0450
CH4 16.0313 C2 H2 N 40.0187 C4 H4 52.0313 C2 H8 N2 60.0688
17 C3 H4 40.0313 53 C3 H8 O 60.0575
HO 17.0027 41 C3 H3 N 53.0266 C5 60.0000
H3 N 17.0266 CHN2 41.0140 C4 H5 53.0391 61
18 C2 H3 N 41.0266 54 CH3 NO2 61.0164
H2 O 18.0106 C3 H5 41.0391 C2 H2 N2 54.0218 CH5 N2 O 61.0402
24 42 C3 H2 O 54.0106 CH7 N3 61.0641
C2 24.0000 N3 42.0093 C3 H4 N 54.0344 C2 H5 O2 61.0289
26 CNO 41.9980 C4 H6 54.0470 C2 H7 NO 61.0528
CN 26.0031 CH2 N2 42.0218 55 62
C2 H2 26.0157 C2 H2 O 42.0106 C2 H3 N2 55.0297 CH2 O3 62.0003
27 C2 H4 N 42.0344 C3 H3 O 55.0184 CH4 NO2 62.0242
CHN 27.0109 C3 H6 42.0470 C3 H5 N 55.0422 CH6 N2 O 62.0480
C2 H3 27.0235 43 C4 H7 55.0548 C2 H6 O2 62.0368
28 HN3 43.0170 56 63
N2 28.0062 CHNO 43.0058 C2 O2 55.9898 HNO3 62.9956
CO 27.9949 CH3 N2 43.0297 C2 H2 NO 56.0136 CH5 NO2 63.0320
CH2 N 28.0187 C2 H3 O 43.0184 C2 H4 N2 56.0375 64
C2 H4 28.0313 C2 H5 N 43.0422 C3 H4 O 56.0262 C5 H4 64.0313
29 C3 H7 43.0548 C3 H6 N 56.0501 65
HN2 29.0140 44 C4 H8 56.0626 C4 H3 N 65.0266
CHO 29.0027 N2 O 44.0011 57 C5 H5 65.0391
CH3 N 29.0266 CO2 43.9898 C2 H3 NO 57.0215 66
C2 H5 29.0391 CH2 NO 44.0136 C2 H5 N2 57.0453 C4 H4 N 66.0344
30 CH4 N2 44.0375 C3 H5 O 57.0340 C5 H6 66.0470
NO 29.9980 C2 H4 O 44.0262 C3 H7 N 57.0579 67
H2 N2 30.0218 C2 H6 N 44.0501 C4 H9 57.0705 C3 H3 N2 67.0297
CH2 O 30.0106 C3 H8 44.0626 58 C4 H3 O 67.0184
CH4 N 30.0344 45 CH2 N2 O 58.0167 C4 H5 N 67.0422
C2 H6 30.0470 CH3 NO 45.0215 CH4 N3 58.0406 C5 H7 67.0548
31 CH5 N2 45.0453 C2 H2 O2 58.0054 68
HNO 31.0058 C2 H5 O 45.0340 C2 H4 NO 58.0293 C3 H4 N2 68.0375
H3 N2 31.0297 C2 H7 N 45.0579 C2 H6 N2 58.0532 C4 H4 O 68.0262
CH3 O 31.0184 46 C3 H6 O 58.0419 C4 H6 N 68.0501
CH5 N 31.0422 NO2 45.9929 C3 H8 N 58.0657 C5 H8 68.0626
32 CH2 O2 46.0054 C4 H10 58.0783 69
O2 31.9898 CH4 NO 46.0293 59 C3 H3 NO 69.0215
H2 NO 32.0136 CH6 N2 46.0532 CHNO2 59.0007 C3 H5 N2 69.0453

a Withpermission from J.H. Beynon, Mass Spectrometry and its Application to Organic Chemistry, Amsterdam, 1960. The columns headed FM contain the formula masses based on
the exact mass of the most abundant isotope of each element; these masses are based on the most abundant isotope of carbon having a mass of 12.0000. Note that the table includes
only C, H, N, and O.
 Silverstein c01.tex V3 - 07/10/2014 3:46 P.M. Page 47

APPENDIX A 47

APPENDIX A (Continued)

FM FM FM FM

C4 H5 O 69.0340 C2 H6 NO2 76.0399 C4 H9 N2 85.0767 C3 H8 NO2 90.0555

C4 H7 N 69.0579 C2 H8 N2 O 76.0637 C5 H9 O 85.0653 C3 H10 N2 O 90.0794
C5 H9 69.0705 C3 H8 O2 76.0524 C5 H11 N 85.0892 C4 H10 O2 90.0681
70 C5 H2 N 76.0187 C6 H13 85.1018 C7 H6 90.0470
C2 H4 N3 70.0406 C6 H4 76.0313 86 91
C3 H2 O2 70.0054 77 C2 H2 N2 O2 86.0116 C2 H3 O4 91.0031
C3 H4 NO 70.0293 CH3 NO3 77.0113 C2 H4 N3 O 86.0355 C2 H5 NO3 91.0269
C3 H6 N2 70.0532 C2 H5 O3 77.0238 C2 H6 N4 86.0594 C2 H7 N2 O2 91.0508
C4 H6 O 70.0419 C2 H7 NO2 77.0477 C3 H4 NO2 86.0242 C2 H9 N3 O 91.0746
C4 H8 N 70.0657 C6 H5 77.0391 C3 H6 N2 O 86.0480 C3 H7 O3 91.0395
C5 H10 70.0783 78 C3 H8 N3 86.0719 C3 H9 NO2 91.0634
71 C2 H6 O3 78.0317 C4 H6 O2 86.0368 C6 H5 N 91.0422
C2 H3 N2 O 71.0246 C5 H4 N 78.0344 C4 H8 NO 86.0606 C7 H7 91.0548
C2 H5 N3 71.0484 C6 H6 78.0470 C4 H10 N2 86.0845 92
C3 H3 O2 71.0133 79 C5 H10 O 86.0732 C2 H4 O4 92.0109
C3 H5 NO 71.0371 C5 H5 N 79.0422 C5 H12 N 86.0970 C2 H6 NO3 92.0348
C3 H7 N2 71.0610 C6 H7 79.0548 C6 H14 86.1096 C2 H8 N2 O2 92.0586
C4 H7 O 71.0497 80 87 C3 H8 O3 92.0473
C4 H9 N 71.0736 C3 H2 N3 80.0249 C2 H7 N4 87.0672 C6 H4 O 92.0262
C5 H11 71.0861 C4 H4 N2 80.0375 C3 H3 O3 87.0082 C6 H6 N 92.0501
72 C5 H4 O 80.0262 C3 H5 NO2 87.0320 C7 H8 92.0626
C2 H2 NO2 72.0085 C5 H6 N 80.0501 C3 H7 N2 O 87.0559 93
C2 H4 N2 O 72.0324 C6 H8 80.0626 C3 H9 N3 87.0798 C2 H5 O4 93.0187
C2 H6 N3 72.0563 81 C4 H7 O2 87.0446 C2 H7 NO3 92.0426
C3 H4 O2 72.0211 C3 H3 N3 81.0328 C4 H9 NO 87.0684 C5 H5 N2 93.0453
C3 H6 NO 72.0449 C4 H5 N2 81.0453 C4 H11 N2 87.0923 C6 H5 O 93.0340
C3 H8 N2 72.0688 C5 H5 O 81.0340 C5 H11 O 87.0810 C6 H7 N 93.0579
C4 H8 O 72.0575 C5 H7 N 81.0579 C5 H13 N 87.1049 C7 H9 93.0705
C4 H10 N 72.0814 C6 H9 81.0705 88 94
C5 H12 72.0939 82 C2 H4 N2 O2 88.0273 C2 H6 O4 94.0266
73 C3 H4 N3 82.0406 C2 H6 N3 O 88.0511 C4 H4 N3 94.0406
C2 H3 NO2 73.0164 C4 H4 NO 82.0293 C2 H8 N4 88.0750 C5 H4 NO 94.0293
C2 H5 N2 O 73.0402 C4 H6 N2 82.0532 C3 H4 O3 88.0160 C5 H6 N2 94.0532
C2 H7 N3 73.0641 C5 H6 O 82.0419 C3 H6 NO2 88.0399 C6 H6 O 94.0419
C3 H5 O2 73.0289 C5 H8 N 82.0657 C3 H8 N2 O 88.0637 C6 H8 N 94.0657
C3 H7 NO 73.0528 C6 H10 82.0783 C3 H10 N3 88.0876 C7 H10 94.0783
C3 H9 N2 73.0767 83 C4 H8 O2 88.0524 95
C4 H9 O 73.0653 C3 H5 N3 83.0484 C4 H10 NO 88.0763 C4 H5 N3 95.0484
C4 H11 N 73.0892 C4 H3 O2 83.0133 C4 H12 N2 88.1001 C5 H5 NO 95.0371
74 C4 H5 NO 83.0371 C5 H12 O 88.0888 C5 H7 N2 95.0610
C2 H2 O3 74.0003 C4 H7 N2 83.0610 89 C6 H7 O 95.0497
C2 H4 NO2 74.0242 C5 H7 O 83.0497 C2 H5 N2 O2 89.0351 C6 H9 N 95.0736
C2 H6 N2 O 74.0480 C5 H9 N 83.0736 C2 H7 N3 O 89.0590 C7 H11 95.0861
C2 H8 N3 74.0719 C6 H11 83.0861 C2 H9 N4 89.0829 96
C3 H6 O2 74.0368 84 C3 H5 O3 89.0238 C4 H6 N3 96.0563
C3 H8 NO 74.0606 C3 H6 N3 84.0563 C3 H7 NO2 89.0477 C5 H4 O2 96.0211
C3 H10 N2 74.0845 C4 H4 O2 84.0211 C3 H9 N2 O 89.0715 C5 H6 NO 96.0449
C4 H10 O 74.0732 C4 H6 NO 84.0449 C3 H11 N3 89.0954 C5 H8 N2 96.0688
75 C4 H8 N2 84.0688 C4 H9 O2 89.0603 C6 H8 O 96.0575
C2 H3 O3 75.0082 C5 H8 O 84.0575 C4 H11 NO 89.0841 C6 H10 N 96.0814
C2 H5 NO2 75.0320 C5 H10 N 84.0814 C7 H5 89.0391 C7 H12 96.0939
C2 H7 N2 O 75.0559 C6 H12 84.0939 90 97
C2 H9 N3 75.0798 85 C2 H4 NO3 90.0191 C3 H5 N4 97.0515
C3 H7 O2 75.0446 C3 H5 N2 O 85.0402 C2 H6 N2 O2 90.0429 C4 H5 N2 O 97.0402
C3 H9 NO 75.0684 C3 H7 N3 85.0641 C2 H8 N3 O 90.0668 C5 H5 O2 97.0289
76 C4 H5 O2 85.0289 C2 H10 N4 90.0907 C5 H7 NO 97.0528
C2 H4 O3 76.0160 C4 H7 NO 85.0528 C3 H6 O3 90.0317 C5 H9 N2 97.0767
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48 CHAPTER 1 MASS SPECTROMETRY

APPENDIX A (Continued)

FM FM FM FM

C6 H9 O 97.0653 102 C4 H11 NO2 105.0790 C4 H6 N4 110.0594

C6 H11 N 97.0892 C2 H6 N4 O 102.0542 C6 H5 N2 105.0453 C5 H6 N2 O 110.0480
C7 H13 97.1018 C3 H4 NO3 102.0191 C7 H5 O 105.0340 C5 H8 N3 110.0719
98 C3 H6 N2 O2 102.0429 C7 H7 N 105.0579 C6 H6 O2 110.0368
C3 H4 N3 O 98.0355 C3 H8 N3 O 102.0668 C8 H9 105.0705 C6 H8 NO 110.0606
C3 H6 N4 98.0594 C3 H10 N4 102.0907 106 C6 H10 N2 110.0845
C4 H4 NO2 98.0242 C4 H6 O3 102.0317 C2 H4 NO4 106.0140 C7 H10 O 110.0732
C4 H6 N2 O 98.0480 C4 H8 NO2 102.0555 C2 H6 N2 O3 106.0379 C7 H12 N 110.0970
C4 H8 N3 98.0719 C4 H10 N2 O 102.0794 C2 H8 N3 O2 106.0617 C8 H14 110.1096
C5 H6 O2 98.0368 C4 H12 N3 102.1032 C2 H10 N4 O 106.0856 111
C5 H8 NO 98.0606 C5 H10 O2 102.0681 C3 H6 O4 106.0266 C4 H5 N3 O 111.0433
C5 H10 N2 98.0845 C5 H12 NO 102.0919 C3 H8 NO3 106.0504 C4 H7 N4 111.0672
C6 H10 O 98.0732 C5 H14 N2 102.1158 C3 H10 N2 O2 106.0743 C5 H5 NO2 111.0320
C6 H12 N 98.0970 C6 H14 O 102.1045 C4 H10 O3 106.0630 C5 H7 N2 O 111.0559
C7 H14 98.1096 C8 H6 102.0470 C6 H4 NO 106.0293 C5 H9 N3 111.0789
99 103 C6 H6 N2 106.0532 C6 H7 O2 111.0446
C3 H5 N3 O 99.0433 C2 H5 N3 O2 103.0382 C7 H6 O 106.0419 C6 H9 NO 111.0684
C3 H7 N4 99.0672 C2 H7 N4 O 103.0621 C7 H8 N 106.0657 C6 H11 N2 111.0923
C4 H3 O3 99.0082 C3 H3 O4 103.0031 C8 H10 106.0783 C7 H11 O 111.0810
C4 H5 NO2 99.0320 C3 H5 NO3 103.0269 107 C7 H13 N 111.1049
C4 H7 N2 O 99.0559 C3 H7 N2 O2 103.0508 C2 H5 NO4 107.0218 C8 H15 111.1174
C4 H9 N3 99.0798 C3 H9 N3 O 103.0746 C2 H7 N2 O3 107.0457 112
C5 H7 O2 99.0446 C3 H11 N4 103.0985 C2 H9 N3 O2 107.0695 C3 H4 N4 O 112.0386
C5 H9 NO 99.0685 C4 H7 O3 103.0395 C3 H7 O4 107.0344 C4 H4 N2 O2 112.0273
C5 H11 N2 99.0923 C4 H9 NO2 103.0634 C3 H9 NO3 107.0583 C4 H6 N3 O 112.0511
C6 H11 O 99.0810 C4 H11 N2 O 103.0872 C5 H5 N3 107.0484 C4 H8 N4 112.0750
C6 H13 N 99.1049 C4 H13 N3 103.1111 C6 H5 NO 107.0371 C5 H4 O3 112.0160
C7 H15 99.1174 C5 H11 O2 103.0759 C6 H7 N2 107.0610 C5 H6 NO2 112.0399
100 C5 H13 NO 103.0998 C7 H7 O 107.0497 C5 H8 N2 O 112.0637
C2 H4 N4 O 100.0386 C7 H5 N 103.0422 C7 H9 N 107.0736 C5 H10 N3 112.0876
C3 H4 N2 O2 100.0273 C8 H7 103.0548 C8 H11 107.0861 C6 H8 O2 112.0524
C3 H6 N3 O 100.0511 104 108 C6 H10 NO 112.0763
C3 H8 N4 100.0750 C2 H4 N2 O3 104.0222 C2 H6 NO4 108.0297 C6 H12 N2 112.1001
C4 H4 O3 100.0160 C2 H6 N3 O2 104.0460 C2 H8 N2 O3 108.0535 C7 H12 O 112.0888
C4 H6 NO2 100.0399 C2 H8 N4 O 104.0699 C3 H8 O4 108.0422 C7 H14 N 112.1127
C4 H8 N2 O 100.0637 C3 H4 O4 104.0109 C4 H4 N4 108.0437 C8 H16 112.1253
C4 H10 N3 100.0876 C3 H6 NO3 104.0348 C5 H4 N2 O 108.0324 113
C5 H8 O2 100.0524 C3 H8 N2 O2 104.0586 C5 H6 N3 108.0563 C3 H5 N4 O 113.0464
C5 H10 NO 100.0763 C3 H10 N3 O 104.0825 C6 H4 O2 108.0211 C4 H5 N2 O2 113.0351
C5 H12 N2 100.1001 C3 H12 N4 104.1063 C6 H6 NO 108.0449 C4 H7 N3 O 113.0590
C6 H12 O 100.0888 C4 H8 O3 104.0473 C6 H8 N2 108.0688 C4 H9 N4 113.0829
C6 H14 N 100.1127 C4 H10 NO2 104.0712 C7 H8 O 108.0575 C5 H5 O3 113.0238
C7 H16 100.1253 C4 H12 N2 O 104.0950 C7 H10 N 108.0814 C5 H7 NO2 113.0477
101 C5 H12 O2 104.0837 C8 H12 108.0939 C5 H9 N2 O 113.0715
C3 H3 NO3 101.0113 C6 H4 N2 104.0375 109 C5 H11 N3 113.0954
C3 H5 N2 O2 101.0351 C7 H4 O 104.0262 C2 H7 NO4 109.0375 C6 H9 O2 113.0603
C3 H7 N3 O 101.0590 C7 H6 N 104.0501 C4 H5 N4 109.0515 C6 H11 NO 113.0841
C3 H9 N4 101.0829 C8 H8 104.0626 C5 H5 N2 O 109.0402 C6 H13 N2 113.1080
C4 H5 O3 101.0238 105 C5 H7 N3 109.0641 C7 H13 O 113.0967
C4 H7 NO2 101.0477 C2 H5 N2 O3 105.0300 C6 H5 O2 109.0289 C7 H15 N 113.1205
C4 H9 N2 O 101.0715 C2 H7 N3 O2 105.0539 C6 H7 NO 109.0528 C8 H17 113.1331
C4 H11 N3 101.0954 C2 H9 N4 O 105.0777 C6 H9 N2 109.0767 114
C5 H9 O2 101.0603 C3 H5 O4 105.0187 C7 H9 O 109.0653 C3 H6 N4 O 114.0542
C5 H11 NO 101.0841 C3 H7 NO3 105.0426 C7 H11 N 109.0892 C4 H4 NO3 114.0191
C5 H13 N2 101.1080 C3 H9 N2 O2 105.0664 C8 H13 109.1018 C4 H6 N2 O2 114.0429
C6 H13 O 101.0967 C3 H11 N3 O 105.0903 110 C4 H8 N3 O 114.0668
C6 H15 N 101.1205 C4 H9 O3 105.0552 C4 H4 N3 O 110.0355 C4 H10 N4 114.0907
 Silverstein c01.tex V3 - 07/10/2014 3:46 P.M. Page 49

APPENDIX A 49

APPENDIX A (Continued)

FM FM FM FM

C5 H6 O3 114.0317 C4 H9 N2 O2 117.0664 C4 H8 O4 120.0422 C7 H9 NO 123.0684

C5 H8 NO2 114.0555 C4 H11 N3 O 117.0903 C4 H10 NO3 120.0661 C7 H11 N2 123.0923
C5 H10 N2 O 114.0794 C4 H13 N4 117.1142 C4 H12 N2 O2 120.0899 C8 H11 O 123.0810
C5 H12 N3 114.1032 C5 H9 O3 117.0552 C5 H4 N4 120.0437 C8 H13 N 123.1049
C6 H10 O2 114.0681 C5 H11 NO2 117.0790 C5 H12 O3 120.0786 C9 H15 123.1174
C6 H12 NO 114.0919 C5 H13 N2 O 117.1029 C6 H4 N2 O 120.0324 124
C6 H14 N2 114.1158 C5 H15 N3 117.1267 C6 H6 N3 120.0563 C2 H8 N2 O4 124.0484
C7 H14 O 114.1045 C6 H13 O2 117.0916 C7 H6 NO 120.0449 C4 H4 N4 O 124.0386
C7 H16 N 114.1284 C6 H15 NO 117.1154 C7 H8 N2 120.0688 C5 H4 N2 O2 124.0273
C8 H18 114.1409 C8 H7 N 117.0579 C8 H8 O 120.0575 C5 H6 N3 O 124.0511
C9 H6 114.0470 C9 H9 117.0705 C8 H10 N 120.0814 C5 H8 N4 124.0750
115 118 C9 H12 120.0939 C6 H4 O3 124.0160
C3 H5 N3 O2 115.0382 C2 H4 N3 O3 118.0253 121 C6 H6 NO2 124.0399
C3 H7 N4 O 115.0621 C2 H6 N4 O2 118.0491 C2 H5 N2 O4 121.0249 C6 H8 N2 O 124.0637
C4 H5 NO3 115.0269 C3 H4 NO4 118.0140 C2 H7 N3 O3 121.0488 C6 H10 N3 124.0876
C4 H7 N2 O2 115.0508 C3 H6 N2 O3 118.0379 C2 H9 N4 O2 121.0726 C7 H8 O2 124.0524
C4 H9 N3 O 115.0746 C3 H8 N3 O2 118.0617 C3 H7 NO4 121.0375 C7 H10 NO 124.0763
C4 H11 N4 115.0985 C3 H10 N4 O 118.0856 C3 H9 N2 O3 121.0614 C7 H12 N2 124.1001
C5 H7 O3 115.0395 C4 H6 O4 118.0266 C3 H11 N3 O2 121.0852 C8 N2 124.0062
C5 H9 NO2 115.0634 C4 H8 NO3 118.0504 C4 H9 O4 121.0501 C8 H12 O 124.0888
C5 H11 N2 O 115.0872 C4 H10 N2 O2 118.0743 C4 H11 NO3 121.0739 C8 H14 N 124.1127
C5 H13 N3 115.1111 C4 H12 N3 O 118.0981 C5 H5 N4 121.0515 C9 H16 124.1253
C6 H11 O2 115.0759 C4 H14 N4 118.1220 C6 H5 N2 O 121.0402 125
C6 H13 NO 115.0998 C5 H10 O3 118.0630 C6 H7 N3 121.0641 C4 H3 N3 O2 125.0226
C6 H15 N2 115.1236 C5 H12 NO2 118.0868 C7 H5 O2 121.0289 C4 H5 N4 O 125.0464
C7 H15 O 115.1123 C5 H14 N2 O 118.1107 C7 H7 NO 121.0528 C5 H5 N2 O2 125.0351
C7 H17 N 115.1362 C6 H14 O2 118.0994 C7 H9 N2 121.0767 C5 H7 N3 O 125.0590
C9 H7 115.0548 C7 H6 N2 118.0532 C8 H9 O 121.0653 C5 H9 N4 125.0829
116 C8 H6 O 118.0419 C8 H11 N 121.0892 C6 H5 O3 125.0238
C2 H4 N4 O2 116.0335 C8 H8 N 118.0657 C9 H13 121.1018 C6 H7 NO2 125.0477
C3 H4 N2 O3 116.0222 C9 H10 118.0783 122 C6 H9 N2 O 125.0715
C3 H6 N3 O2 116.0460 119 C2 H6 N2 O4 122.0328 C6 H11 N3 125.0954
C3 H8 N4 O 116.0699 C2 H5 N3 O3 119.0331 C2 H8 N3 O3 122.0566 C7 H9 O2 125.0603
C4 H4 O4 116.0109 C2 H7 N4 O2 119.0570 C2 H10 N4 O2 122.0805 C7 H11 NO 125.0841
C4 H6 NO3 116.0348 C3 H5 NO4 119.0218 C3 H8 NO4 122.0453 C7 H13 N2 125.1080
C4 H8 N2 O2 116.0586 C3 H7 N2 O3 119.0457 C3 H10 N2 O3 122.0692 C8 H13 O 125.0967
C4 H10 N3 O 116.0825 C3 H9 N3 O2 119.0695 C4 H10 O4 122.0579 C8 H15 N 125.1205
C4 H12 N4 116.1063 C3 H11 N4 O 119.0934 C5 H6 N4 122.0594 C9 H17 125.1331
C5 H8 O3 116.0473 C4 H7 O4 119.0344 C6 H4 NO2 122.0242 126
C5 H10 NO2 116.0712 C4 H9 NO3 119.0583 C6 H6 N2 O 122.0480 C3 H2 N4 O2 126.0178
C5 H12 N2 O 116.0950 C4 H11 N2 O2 119.0821 C6 H8 N3 122.0719 C4 H4 N3 O2 126.0304
C5 H14 N3 116.1189 C4 H13 N3 O 119.1060 C7 H6 O2 122.0368 C4 H6 N4 O 126.0542
C6 H12 O2 116.0837 C5 H11 O3 119.0708 C7 H8 NO 122.0606 C5 H4 NO3 126.0191
C6 H14 NO 116.1076 C5 H13 NO2 119.0947 C7 H10 N2 122.0845 C5 H6 N2 O2 126.0429
C6 H16 N2 116.1315 C6 H5 N3 119.0484 C8 H10 O 122.0732 C5 H8 N3 O 126.0668
C7 H4 N2 116.0375 C7 H5 NO 119.0371 C8 H12 N 122.0970 C5 H10 N4 126.0907
C7 H16 O 116.1202 C7 H7 N2 119.0610 C9 H14 122.1096 C6 H6 O3 126.0317
C8 H6 N 116.0501 C8 H7 O 119.0497 123 C6 H8 NO2 126.0555
C9 H8 116.0626 C8 H9 N 119.0736 C2 H7 N2 O4 123.0406 C6 H10 N2 O 126.0794
117 C9 H11 119.0861 C2 H9 N3 O3 123.0644 C6 H12 N3 126.1032
C2 H5 N4 O2 117.0413 120 C3 H9 NO4 123.0532 C7 H10 O2 126.0681
C3 H3 NO4 117.0062 C2 H6 N3 O3 120.0410 C5 H5 N3 O 123.0433 C7 H12 NO 126.0919
C3 H5 N2 O3 117.0300 C2 H8 N4 O2 120.0648 C5 H7 N4 123.0672 C7 H14 N2 126.1158
C3 H7 N3 O2 117.0539 C3 H6 NO4 120.0297 C6 H5 NO2 123.0320 C8 H14 O 126.1045
C3 H9 N4 O 117.0777 C3 H8 N2 O3 120.0535 C6 H7 N2 O 123.0559 C8 H16 N 126.1284
C4 H5 O4 117.0187 C3 H10 N3 O2 120.0774 C6 H9 N3 123.0798 C9 H18 126.1409
C4 H7 NO3 117.0426 C3 H12 N4 O 120.1012 C7 H7 O2 123.0446 127
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50 CHAPTER 1 MASS SPECTROMETRY

APPENDIX A (Continued)

FM FM FM FM

C3 H3 N4 O2 127.0257 C8 H19 N 129.1519 C4 H10 N3 O2 132.0774 C8 H8 NO 134.0606

C4 H5 N3 O2 127.0382 C9 H7 N 129.0579 C4 H12 N4 O 132.1012 C8 H10 N2 134.0845
C4 H7 N4 O 127.0621 C10 H9 129.0705 C5 H8 O4 132.0422 C9 H10 O 134.0732
C5 H5 NO3 127.0269 130 C5 H10 NO3 132.0661 C9 H12 N 134.0970
C5 H7 N2 O2 127.0508 C3 H4 N3 O3 130.0253 C5 H12 N2 O2 132.0899 C10 H14 134.1096
C5 H9 N3 O 127.0746 C3 H6 N4 O2 130.0491 C5 H14 N3 O 132.1138 135
C5 H11 N4 127.0985 C4 H4 NO4 130.0140 C5 H16 N4 132.1377 C3 H7 N2 O4 135.0406
C6 H7 O3 127.0395 C4 H6 N2 O3 130.0379 C6 H4 N4 132.0437 C3 H9 N3 O3 135.0644
C6 H9 NO2 127.0634 C4 H8 N3 O2 130.0617 C6 H12 O3 132.0786 C3 H11 N4 O2 135.0883
C6 H11 N2 O 127.0872 C4 H10 N4 O 130.0856 C6 H14 NO2 132.1025 C4 H9 NO4 135.0532
C6 H13 N3 127.1111 C5 H6 O4 130.0266 C6 H16 N2 O 132.1264 C4 H11 N2 O3 135.0770
C7 H11 O2 127.0759 C5 H8 NO3 130.0504 C7 H9 N3 132.0563 C4 H13 N3 O2 135.1009
C7 H13 NO 127.0998 C5 H10 N2 O2 130.0743 C7 H16 O2 132.1151 C5 H3 N4 O 135.0308
C7 H15 N2 127.1236 C5 H12 N3 O 130.0981 C8 H6 NO 132.0449 C5 H11 O4 135.0657
C8 H15 O 127.1123 C5 H14 N4 130.1220 C8 H8 N2 132.0688 C5 H13 NO3 135.0896
C8 H17 N 127.1362 C6 H10 O3 130.0630 C9 H8 O 132.0575 C6 H5 N3 O 135.0433
C9 H19 127.1488 C6 H12 NO2 130.0868 C9 H10 N 132.0814 C6 H7 N4 135.0672
128 C6 H14 N2 O 130.1107 C10 H12 132.0939 C7 H5 NO2 135.0320
C3 H4 N4 O2 128.0335 C6 H16 N3 130.1346 133 C7 H7 N2 O 135.0559
C4 H4 N2 O3 128.0222 C7 H4 N3 130.0406 C3 H5 N2 O4 133.0249 C7 H9 N3 135.0798
C4 H6 N3 O2 128.0460 C7 H14 O2 130.0994 C3 H7 N3 O3 133.0488 C8 H7 O2 135.0446
C4 H8 N4 O 128.0699 C7 H16 NO 130.1233 C3 H9 N4 O2 133.0726 C8 H9 NO 135.0684
C5 H4 O4 128.0109 C7 H18 N2 130.1471 C4 H7 NO4 133.0375 C8 H11 N2 135.0923
C5 H6 NO3 128.0348 C8 H6 N2 130.0532 C4 H9 N2 O3 133.0614 C9 H11 O 135.0810
C5 H8 N2 O2 128.0586 C8 H18 O 130.1358 C4 H11 N3 O2 133.0852 C9 H13 N 135.1049
C5 H10 N3 O 128.0825 C9 H8 N 130.0657 C4 H13 N4 O 133.1091 C10 H15 135.1174
C5 H12 N4 128.1063 C10 H10 130.0783 C5 H9 O4 133.0501 136
C6 H8 O3 128.0473 131 C5 H11 NO3 133.0739 C3 H8 N2 O4 136.0484
C6 H10 NO2 128.0712 C3 H3 N2 O4 131.0093 C5 H13 N2 O2 133.0978 C3 H10 N3 O3 136.0723
C6 H12 N2 O 128.0950 C3 H5 N3 O3 131.0331 C5 H15 N3 O 133.1216 C3 H12 N4 O2 136.0961
C6 H14 N3 128.1189 C3 H7 N4 O2 131.0570 C6 H5 N4 133.0515 C4 H10 NO4 136.0610
C7 H12 O2 128.0837 C4 H5 NO4 131.0218 C6 H13 O3 133.0865 C4 H12 N2 O3 136.0848
C7 H14 NO 128.1076 C4 H7 N2 O3 131.0457 C6 H15 NO2 133.1103 C5 H2 N3 O2 136.0147
C7 H16 N2 128.1315 C4 H9 N3 O2 131.0695 C7 H5 N2 O 133.0402 C5 H4 N4 O 136.0386
C8 H16 O 128.1202 C4 H11 N4 O 131.0934 C7 H7 N3 133.0641 C5 H12 O4 136.0735
C8 H18 N 128.1440 C5 H7 O4 131.0344 C8 H7 NO 133.0528 C6 H4 N2 O2 136.0273
C9 H20 128.1566 C5 H9 NO3 131.0583 C8 H9 N2 133.0767 C6 H6 N3 O 136.0511
C10 H8 128.0626 C5 H11 N2 O2 131.0821 C9 H9 O 133.0653 C6 H8 N4 136.0750
129 C5 H13 N3 O 131.1060 C9 H11 N 133.0892 C7 H4 O3 136.0160
C3 H3 N3 O3 129.0175 C5 H15 N4 131.1298 C10 H13 133.1018 C7 H6 NO2 136.0399
C3 H5 N4 O2 129.0413 C6 H11 O3 131.0708 134 C7 H8 N2 O 136.0637
C4 H5 N2 O3 129.0300 C6 H13 NO2 131.0947 C3 H6 N2 O4 134.0328 C7 H10 N3 136.0876
C4 H7 N3 O2 129.0539 C6 H15 N2 O 131.1185 C3 H8 N3 O3 134.0566 C8 H8 O2 136.0524
C4 H9 N4 O 129.0777 C6 H17 N3 131.1424 C3 H10 N4 O2 134.0805 C8 H10 NO 136.0763
C5 H5 O4 129.0187 C7 H5 N3 131.0484 C4 H8 NO4 134.0453 C8 H12 N2 136.1001
C5 H7 NO3 129.0426 C7 H15 O2 131.1072 C4 H10 N2 O3 134.0692 C9 H12 O 136.0888
C5 H9 N2 O2 129.0664 C7 H17 NO 131.1311 C4 H12 N3 O2 134.0930 C9 H14 N 136.1127
C5 H11 N3 O 129.0903 C8 H7 N2 131.0610 C4 H14 N4 O 134.1169 C10 H16 136.1253
C5 H13 N4 129.1142 C9 H7 O 131.0497 C5 H10 O4 134.0579 137
C6 H9 O3 129.0552 C9 H9 N 131.0736 C5 H12 NO3 134.0817 C3 H9 N2 O4 137.0563
C6 H11 NO2 129.0790 C10 H11 131.0861 C5 H14 N2 O2 134.1056 C3 H11 N3 O3 137.0801
C6 H13 N2 O 129.1029 132 C6 H4 N3 O 134.0355 C4 H11 NO4 137.0688
C6 H15 N3 129.1267 C3 H4 N2 O4 132.0171 C6 H6 N4 134.0594 C5 H3 N3 O2 137.0226
C7 H13 O2 129.0916 C3 H6 N3 O3 132.0410 C6 H14 O3 134.0943 C5 H5 N4 O 137.0464
C7 H15 NO 129.1154 C3 H8 N4 O2 132.0648 C7 H6 N2 O 134.0480 C6 H5 N2 O2 137.0351
C7 H17 N2 129.1393 C4 H6 NO4 132.0297 C7 H8 N3 134.0719 C6 H7 N3 O 137.0590
C8 H17 O 129.1280 C4 H8 N2 O3 132.0535 C8 H6 O2 134.0368 C6 H9 N4 137.0829
 Silverstein c01.tex V3 - 07/10/2014 3:46 P.M. Page 51

APPENDIX A 51

APPENDIX A (Continued)

FM FM FM FM

C7 H5 O3 137.0238 C6 H8 N2 O2 140.0586 C8 H16 NO 142.1233 C9 H8 N2 144.0688

C7 H7 NO2 137.0477 C6 H10 N3 O 140.0825 C8 H18 N2 142.1471 C9 H20 O 144.1515
C7 H9 N2 O 137.0715 C6 H12 N4 140.1063 C9 H6 N2 142.0532 C10 H8 O 144.0575
C7 H11 N3 137.0954 C7 H8 O3 140.0473 C9 H18 O 142.1358 C10 H10 N 144.0814
C8 H9 O2 137.0603 C7 H10 NO2 140.0712 C9 H20 N 142.1597 C11 H12 144.0939
C8 H11 NO 137.0841 C7 H12 N2 O 140.0950 C10 H8 N 142.0657 145
C8 H13 N2 137.1080 C7 H14 N3 140.1189 C10 H22 142.1722 C4 H5 N2 O4 145.0249
C9 H13 O 137.0967 C8 H12 O2 140.0837 C11 H10 142.0783 C4 H7 N3 O3 145.0488
C9 H15 N 137.1205 C8 H14 NO 140.1076 143 C4 H9 N4 O2 145.0726
C10 H17 137.1331 C8 H16 N2 140.1315 C4 H3 N2 O4 143.0093 C5 H7 NO4 145.0375
138 C9 H16 O 140.1202 C4 H5 N3 O3 143.0331 C5 H9 N2 O3 145.0614
C3 H10 N2 O4 138.0641 C9 H18 N 140.1440 C4 H7 N4 O2 143.0570 C5 H11 N3 O2 145.0852
C5 H4 N3 O2 138.0304 C10 H6 N 140.0501 C5 H5 NO4 143.0218 C5 H13 N4 O 145.1091
C5 H6 N4 O 138.0542 C10 H20 140.1566 C5 H7 N2 O3 143.0457 C6 H5 N4 145.0501
C6 H4 NO3 138.0191 C11 H8 140.0626 C5 H9 N3 O2 143.0695 C6 H11 NO3 145.0739
C6 H6 N2 O2 138.0429 141 C5 H11 N4 O 143.0934 C6 H13 N2 O2 145.0978
C6 H8 N3 O 138.0668 C4 H3 N3 O3 141.0175 C6 H7 O4 143.0344 C6 H15 N3 O 145.1216
C6 H10 N4 138.0907 C4 H5 N4 O2 141.0413 C6 H9 NO3 143.0583 C6 H17 N4 145.1455
C7 H6 O3 138.0317 C5 H3 NO4 141.0062 C6 H11 N2 O2 143.0821 C7 H5 N4 145.0515
C7 H8 NO2 138.0555 C5 H5 N2 O3 141.0300 C6 H13 N3 O 143.1060 C7 H13 O3 145.0865
C7 H10 N2 O 138.0794 C5 H7 N3 O2 141.0539 C6 H15 N4 143.1298 C7 H15 NO2 145.1103
C7 H12 N3 138.1032 C5 H9 N4 O 141.0777 C7 H11 O3 143.0708 C7 H17 N2 O 145.1342
C8 H10 O2 138.0681 C6 H5 O4 141.0187 C7 H13 NO2 143.0947 C7 H19 N3 145.1580
C8 H12 NO 138.0919 C6 H7 NO3 141.0426 C7 H15 N2 O 143.1185 C8 H5 N2 O 145.0402
C8 H14 N2 138.1158 C6 H9 N2 O2 141.0664 C7 H17 N3 143.1424 C8 H7 N3 145.0641
C9 H14 O 138.1045 C6 H11 N3 O 141.0903 C8 H15 O2 143.1072 C8 H17 O2 145.1229
C9 H16 N 138.1284 C6 H13 N4 141.1142 C8 H17 NO 143.1311 C8 H19 NO 145.1467
C10 H18 138.1409 C7 H9 O3 141.0552 C8 H19 N2 143.1549 C9 H7 NO 145.0528
139 C7 H11 NO2 141.0790 C9 H7 N2 143.0610 C9 H9 N2 145.0767
C4 H3 N4 O2 139.0257 C7 H13 N2 O 141.1029 C9 H19 O 143.1436 C10 H9 O 145.0653
C5 H3 N2 O3 139.0144 C7 H15 N3 141.1267 C9 H21 N 143.1675 C10 H11 N 145.0892
C5 H5 N3 O2 139.0382 C8 H13 O2 141.0916 C10 H7 O 143.0497 C11 H13 145.1018
C5 H7 N4 O 139.0621 C8 H15 NO 141.1154 C10 H9 N 143.0736 146
C6 H5 NO3 139.0269 C8 H17 N2 141.1393 C11 H11 143.0861 C4 H6 N2 O4 146.0328
C6 H7 N2 O2 139.0508 C9 H17 O 141.1280 144 C4 H8 N3 O3 146.0566
C6 H9 N3 O 139.0747 C9 H19 N 141.1519 C4 H4 N2 O4 144.0171 C4 H10 N4 O2 146.0805
C6 H11 N4 139.0985 C10 H7 N 141.0579 C4 H6 N3 O3 144.0410 C5 H8 NO4 146.0453
C7 H7 O3 139.0395 C10 H21 141.1644 C4 H8 N4 O2 144.0648 C5 H10 N2 O3 146.0692
C7 H9 NO2 139.0634 C11 H9 141.0705 C5 H6 NO4 144.0297 C5 H12 N3 O2 146.0930
C7 H11 N2 O 139.0872 142 C5 H8 N2 O3 144.0535 C5 H14 N4 O 146.1169
C7 H13 N3 139.1111 C4 H4 N3 O3 142.0253 C5 H10 N3 O2 144.0774 C6 H10 O4 146.0579
C8 H11 O2 139.0759 C4 H6 N4 O2 142.0491 C5 H12 N4 O 144.1012 C6 H12 NO3 146.0817
C8 H13 NO 139.0998 C5 H4 NO4 142.0140 C6 H8 O4 144.0422 C6 H14 N2 O2 146.1056
C8 H15 N2 139.1236 C5 H6 N2 O3 142.0379 C6 H10 NO3 144.0661 C6 H16 N3 O 146.1295
C9 H3 N2 139.0297 C5 H8 N3 O2 142.0617 C6 H12 N2 O2 144.0899 C7 H6 N4 146.0594
C9 H15 O 139.1123 C5 H10 N4 O 142.0856 C6 H14 N3 O 144.1138 C7 H14 O3 146.0943
C9 H17 N 139.1362 C6 H6 O4 142.0266 C6 H16 N4 144.1377 C7 H16 NO2 146.1182
C10 H19 139.1488 C6 H8 NO3 142.0504 C7 H12 O3 144.0786 C7 H18 N2 O 146.1420
C11 H7 139.0548 C6 H10 N2 O2 142.0743 C7 H14 NO2 144.1025 C8 H2 O3 146.0003
140 C6 H12 N3 O 142.0981 C7 H16 N2 O 144.1264 C8 H6 N2 O 146.0480
C4 H4 N4 O2 140.0335 C6 H14 N4 142.1220 C7 H18 N3 144.1502 C8 H8 N3 146.0719
C5 H4 N2 O3 140.0222 C7 H10 O3 142.0630 C8 H6 N3 144.0563 C8 H18 O2 146.1307
C5 H6 N3 O2 140.0460 C7 H12 NO2 142.0868 C8 H16 O2 144.1151 C9 H6 O2 146.0368
C5 H8 N4 O 140.0699 C7 H14 N2 O 142.1107 C8 H18 NO 144.1389 C9 H8 NO 146.0606
C6 H4 O4 140.0109 C7 H16 N3 142.1346 C8 H20 N2 144.1628 C9 H10 N2 146.0845
C6 H6 NO3 140.0348 C8 H14 O2 142.0994 C9 H6 NO 144.0449 C10 H10 O 146.0732
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52 CHAPTER 1 MASS SPECTROMETRY

APPENDIX A (Continued)

FM FM FM FM

C10 H12 N 146.0970 C5 H15 N3 O2 149.1165 C9 H13 NO 151.0998 C6 H10 N4 O 154.0856

C11 H14 146.1096 C6 H5 N4 O 149.0464 C9 H15 N2 151.1236 C7 H6 O4 154.0266
147 C6 H13 O4 149.0814 C10 H15 O 151.1123 C7 H8 NO3 154.0504
C4 H7 N2 O4 147.0406 C6 H15 NO3 149.1052 C10 H17 N 151.1362 C7 H10 N2 O2 154.0743
C4 H9 N3 O3 147.0644 C7 H5 N2 O2 149.0351 C11 H19 151.1488 C7 H12 N3 O 154.0981
C4 H11 N4 O2 147.0883 C7 H7 N3 O 149.0590 152 C7 H14 N4 154.1220
C5 H9 NO4 147.0532 C7 H9 N4 149.0829 C4 H12 N2 O4 152.0797 C8 H10 O3 154.0630
C5 H11 N2 O3 147.0770 C8 H5 O3 149.0238 C5 H4 N4 O2 152.0335 C8 H12 NO2 154.0868
C5 H13 N3 O2 147.1009 C8 H7 NO2 149.0477 C6 H4 N2 O3 152.0222 C8 H14 N2 O 154.1107
C5 H15 N4 O 147.1247 C8 H9 N2 O 149.0715 C6 H6 N3 O2 152.0460 C8 H16 N3 154.1346
C6 H11 O4 147.0657 C8 H11 N3 149.0954 C6 H8 N4 O 152.0699 C9 H14 O2 154.0994
C6 H13 NO3 147.0896 C9 H9 O2 149.0603 C7 H6 NO3 152.0348 C9 H16 NO 154.1233
C6 H15 N2 O2 147.1134 C9 H11 NO 149.0841 C7 H8 N2 O2 152.0586 C9 H18 N2 154.1471
C6 H17 N3 O 147.1373 C9 H13 N2 149.1080 C7 H10 N3 O 152.0825 C10 H18 O 154.1358
C7 H5 N3 O 147.0433 C10 H13 O 149.0967 C7 H12 N4 152.1063 C10 H20 N 154.1597
C7 H7 N4 147.0672 C10 H15 N 149.1205 C8 H8 O3 152.0473 C11 H8 N 154.0657
C7 H15 O3 147.1021 C11 H17 149.1331 C8 H10 NO2 152.0712 C11 H22 154.1722
C7 H17 NO2 147.1260 150 C8 H12 N2 O 152.0950 C12 H10 154.0783
C8 H5 NO2 147.0320 C4 H10 N2 O4 150.0641 C8 H14 N3 152.1189 155
C8 H7 N2 O 147.0559 C4 H12 N3 O3 150.0879 C9 H12 O2 152.0837 C5 H3 N2 O4 155.0093
C8 H9 N3 147.0798 C4 H14 N4 O2 150.1118 C9 H14 NO 152.1076 C5 H5 N3 O3 155.0331
C9 H7 O2 147.0446 C5 H12 NO4 150.0766 C9 H16 N2 152.1315 C5 H7 N4 O2 155.0570
C9 H9 NO 147.0684 C5 H14 N2 O3 150.1005 C10 H16 O 152.1202 C6 H5 NO4 155.0218
C9 H11 N2 147.0923 C6 H4 N3 O2 150.0304 C10 H18 N 152.1440 C6 H7 N2 O3 155.0457
C10 H11 O 147.0810 C6 H6 N4 O 150.0542 C11 H6 N 152.0501 C6 H9 N3 O2 155.0695
C10 H13 N 147.1049 C6 H14 O4 150.0892 C11 H20 152.1566 C6 H11 N4 O 155.0934
C11 H15 147.1174 C7 H6 N2 O2 150.0429 C12 H8 152.0626 C7 H7 O4 155.0344
148 C7 H8 N3 O 150.0668 153 C7 H9 NO3 155.0583
C4 H8 N2 O4 148.0484 C7 H10 N4 150.0907 C5 H3 N3 O3 153.0175 C7 H11 N2 O2 155.0821
C4 H10 N3 O3 148.0723 C8 H6 O3 150.0317 C5 H5 N4 O2 153.0413 C7 H13 N3 O 155.1060
C4 H12 N4 O2 148.0961 C8 H8 NO2 150.0555 C6 H5 N2 O3 153.0300 C8 H11 O3 155.0708
C5 H10 NO4 148.0610 C8 H10 N2 O 150.0794 C6 H7 N3 O2 153.0539 C8 H13 NO2 155.0947
C5 H12 N2 O3 148.0849 C8 H12 N3 150.1032 C6 H9 N4 O 153.0777 C8 H15 N2 O 155.1185
C5 H16 N4 O 148.1325 C9 H10 O2 150.0681 C7 H5 O4 153.0187 C8 H17 N3 155.1424
C6 H4 N4 O 148.0386 C9 H12 NO 150.0919 C7 H7 NO3 153.0426 C9 H15 O2 155.1072
C6 H12 O4 148.0735 C9 H14 N2 150.1158 C7 H9 N2 O2 153.0664 C9 H17 NO 155.1311
C6 H14 NO3 148.0974 C10 H14 O 150.1045 C7 H11 N3 O 153.0903 C9 H19 N2 155.1549
C6 H16 N2 O2 148.1213 C10 H16 N 150.1284 C7 H13 N4 153.1142 C10 H7 N2 155.0610
C7 H6 N3 O 148.0511 C11 H18 150.1409 C8 H9 O3 153.0552 C10 H19 O 155.1436
C7 H8 N4 148.0750 151 C8 H11 NO2 153.0790 C10 H21 N 155.1675
C7 H16 O3 148.1100 C4 H11 N2 O4 151.0719 C8 H13 N2 O 153.1029 C11 H7 O 155.0497
C8 H6 NO2 148.0399 C4 H13 N3 O3 151.0958 C8 H15 N3 153.1267 C11 H9 N 155.0736
C8 H8 N2 O 148.0637 C5 H3 N4 O2 151.0257 C9 H13 O2 153.0916 C11 H23 155.1801
C8 H10 N3 148.0876 C5 H13 NO4 151.0845 C9 H15 NO 153.1154 C12 H11 155.0861
C9 H8 O2 148.0524 C6 H3 N2 O3 151.0144 C9 H17 N2 153.1393 156
C9 H10 NO 148.0763 C6 H5 N3 O2 151.0382 C10 H17 O 153.1280 C5 H4 N2 O4 156.0171
C9 H12 N2 148.1001 C6 H7 N4 O 151.0621 C10 H19 N 153.1519 C5 H6 N3 O3 156.0410
C10 H12 O 148.0888 C7 H5 NO3 151.0269 C11 H7 N 153.0579 C5 H8 N4 O2 156.0648
C10 H14 N 148.1127 C7 H7 N2 O2 151.0508 C11 H21 153.1644 C6 H6 NO4 156.0297
C11 H16 148.1253 C7 H9 N3 O 151.0746 C12 H9 153.0705 C6 H8 N2 O3 156.0535
149 C7 H11 N4 151.0985 154 C6 H10 N3 O2 156.0774
C4 H9 N2 O4 149.0563 C8 H7 O3 151.0395 C5 H4 N3 O3 154.0253 C6 H12 N4 O 156.1012
C4 H11 N3 O3 149.0801 C8 H9 NO2 151.0634 C5 H6 N4 O2 154.0491 C7 H8 O4 156.0422
C4 H13 N4 O2 149.1040 C8 H11 N2 O 151.0872 C6 H4 NO4 154.0140 C7 H10 NO3 156.0661
C5 H11 NO4 149.0688 C8 H13 N3 151.1111 C6 H6 N2 O3 154.0379 C7 H12 N2 O2 156.0899
C5 H13 N2 O3 149.0927 C9 H11 O2 151.0759 C6 H8 N3 O2 154.0617 C7 H14 N3 O 156.1138
 Silverstein c01.tex V3 - 07/10/2014 3:46 P.M. Page 53

APPENDIX A 53

APPENDIX A (Continued)

FM FM FM FM

C7 H16 N4 156.1377 C7 H14 N2 O2 158.1056 C7 H14 NO3 160.0974 C8 H10 N4 162.0907

C8 H12 O3 156.0786 C7 H16 N3 O 158.1295 C7 H16 N2 O2 160.1213 C8 H18 O3 162.1256
C8 H14 NO2 156.1025 C7 H18 N4 158.1533 C7 H18 N3 O 160.1451 C9 H6 O3 162.0317
C8 H16 N2 O 156.1264 C8 H6 N4 158.0594 C7 H20 N4 160.1690 C9 H8 NO2 162.0555
C8 H18 N3 156.1502 C8 H14 O3 158.0943 C8 H6 N3 O 160.0511 C9 H10 N2 O 162.0794
C9 H6 N3 156.0563 C8 H16 NO2 158.1182 C8 H8 N4 160.0750 C9 H12 N3 162.1032
C9 H16 O2 156.1151 C8 H18 N2 O 158.1420 C8 H16 O3 160.1100 C10 H10 O2 162.0681
C9 H18 NO 156.1389 C8 H20 N3 158.1659 C8 H18 NO2 160.1338 C10 H12 NO 162.0919
C9 H20 N2 156.1628 C9 H6 N2 O 158.0480 C8 H20 N2 O 160.1577 C10 H14 N2 162.1158
C10 H6 NO 156.0449 C9 H8 N3 158.0719 C9 H6 NO2 160.0399 C11 H14 O 162.1045
C10 H8 N2 156.0688 C9 H18 O2 158.1307 C9 H8 N2 O 160.0637 C11 H16 N 162.1284
C10 H20 O 156.1515 C9 H20 NO 158.1546 C9 H10 N3 160.0876 C12 H18 162.1409
C10 H22 N 156.1753 C10 H6 O2 158.0368 C9 H20 O2 160.1464 163
C11 H8 O 156.0575 C10 H8 NO 158.0606 C10 H8 O2 160.0524 C5 H11 N2 O4 163.0719
C11 H10 N 156.0814 C10 H10 N2 158.0845 C10 H10 NO 160.0763 C5 H13 N3 O3 163.0958
C11 H24 156.1879 C10 H22 O 158.1672 C10 H12 N2 160.1001 C5 H15 N4 O2 163.1196
C12 H12 156.0939 C11 H10 O 158.0732 C11 H12 O 160.0888 C6 H13 NO4 163.0845
157 C11 H12 N 158.0970 C11 H14 N 160.1127 C6 H15 N2 O3 163.1083
C5 H5 N2 O4 157.0249 C12 H14 158.1096 C12 H16 160.1253 C6 H17 N3 O2 163.1322
C5 H7 N3 O3 157.0488 159 161 C7 H5 N3 O2 163.0382
C5 H9 N4 O2 157.0726 C5 H7 N2 O4 159.0406 C5 H9 N2 O4 161.0563 C7 H7 N4 O 163.0621
C6 H7 NO4 157.0375 C5 H9 N3 O3 159.0644 C5 H11 N3 O3 161.0801 C7 H15 O4 163.0970
C6 H9 N2 O3 157.0614 C5 H11 N4 O2 159.0883 C5 H13 N4 O2 161.1040 C7 H17 NO3 163.1209
C6 H11 N3 O2 157.0852 C6 H9 NO4 159.0532 C6 H11 NO4 161.0688 C8 H5 NO3 163.0269
C6 H13 N4 O 157.1091 C6 H11 N2 O3 159.0770 C6 H13 N2 O3 161.0927 C8 H7 N2 O2 163.0508
C7 H9 O4 157.0501 C6 H13 N3 O2 159.1009 C6 H15 N3 O2 161.1165 C8 H9 N3 O 163.0746
C7 H11 NO3 157.0739 C6 H15 N4 O 159.1247 C6 H17 N4 O 161.1404 C8 H11 N4 163.0985
C7 H13 N2 O2 157.0978 C7 H11 O4 159.0657 C7 H5 N4 O 161.0464 C9 H7 O3 163.0395
C7 H15 N3 O 157.1216 C7 H13 NO3 159.0896 C8 H5 N2 O2 161.0351 C9 H9 NO2 163.0634
C7 H17 N4 157.1455 C7 H15 N2 O2 159.1134 C8 H7 N3 O 161.0590 C9 H11 N2 O 163.0872
C8 H5 N4 157.0515 C7 H17 N3 O 159.1373 C8 H9 N4 161.0829 C9 H13 N3 163.1111
C8 H13 O3 157.0865 C8 H5 N3 O 159.0433 C8 H17 O3 161.1178 C10 H11 O2 163.0759
C8 H15 NO2 157.1103 C8 H7 N4 159.0672 C8 H19 NO2 161.1416 C10 H13 NO 163.0998
C8 H17 N2 O 157.1342 C8 H15 O3 159.1021 C9 H5 O3 161.0238 C10 H15 N2 163.1236
C8 H19 N3 157.1580 C8 H17 NO2 159.1260 C9 H7 NO2 161.0477 C11 H15 O 163.1123
C9 H5 N2 O 157.0402 C8 H19 N2 O 159.1498 C9 H9 N2 O 161.0715 C11 H17 N 163.1362
C9 H7 N3 157.0641 C8 H21 N3 159.1737 C9 H11 N3 161.0954 C12 H19 163.1488
C9 H17 O2 157.1229 C9 H5 NO2 159.0320 C10 H9 O2 161.0603 164
C9 H19 NO 157.1467 C9 H7 N2 O 159.0559 C10 H11 NO 161.0841 C5 H12 N2 O4 164.0797
C9 H21 N2 157.1706 C9 H9 N3 159.0798 C10 H13 N2 161.1080 C5 H14 N3 O3 164.1036
C10 H7 NO 157.0528 C9 H19 O2 159.1385 C11 H13 O 161.0967 C5 H16 N4 O2 164.1275
C10 H9 N2 157.0767 C9 H21 NO 159.1624 C11 H15 N 161.1205 C6 H4 N4 O2 164.0335
C10 H21 O 157.1593 C10 H7 O2 159.0446 C12 H17 161.1331 C6 H14 NO4 164.0923
C10 H23 N 157.1832 C10 H9 NO 159.0684 162 C6 H16 N2 O3 164.1162
C11 H9 O 157.0653 C10 H11 N2 159.0923 C5 H10 N2 O4 162.0641 C7 H6 N3 O2 164.0460
C11 H11 N 157.0892 C11 H11 O 159.0810 C5 H12 N3 O3 162.0879 C7 H8 N4 O 164.0699
C12 H13 157.1018 C11 H13 N 159.1049 C5 H14 N4 O2 162.1118 C7 H16 O4 164.1049
158 C12 H15 159.1174 C6 H12 NO4 162.0766 C8 H6 NO3 164.0348
C5 H6 N2 O4 158.0328 160 C6 H14 N2 O3 162.1005 C8 H8 N2 O2 164.0586
C5 H8 N3 O3 158.0566 C5 H8 N2 O4 160.0484 C6 H16 N3 O2 162.1244 C8 H10 N3 O 164.0825
C5 H10 N4 O2 158.0805 C5 H10 N3 O3 160.0723 C6 H18 N4 O 162.1482 C8 H12 N4 164.1063
C6 H8 NO4 158.0453 C5 H12 N4 O2 160.0961 C7 H6 N4 O 162.0542 C9 H8 O3 164.0473
C6 H10 N2 O3 158.0692 C6 H10 NO4 160.0610 C7 H14 O4 162.0892 C9 H10 NO2 164.0712
C6 H12 N3 O2 158.0930 C6 H12 N2 O3 160.0848 C7 H16 NO3 162.1131 C9 H12 N2 O 164.0950
C6 H14 N4 O 158.1169 C6 H14 N3 O2 160.1087 C7 H18 N2 O2 162.1369 C9 H14 N3 164.1189
C7 H10 O4 158.0579 C6 H16 N4 O 160.1325 C8 H6 N2 O2 162.0429 C10 H12 O2 164.0837
C7 H12 NO3 158.0817 C7 H12 O4 160.0735 C8 H8 N3 O 162.0668 C10 H14 NO 164.1076
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54 CHAPTER 1 MASS SPECTROMETRY

APPENDIX A (Continued)

FM FM FM FM

C10 H16 N2 164.1315 C7 H7 N2 O3 167.0457 C8 H11 NO3 169.0739 C7 H13 N3 O2 171.1009

C11 H16 O 164.1202 C7 H9 N3 O2 167.0695 C8 H13 N2 O2 169.0978 C7 H15 N4 O 171.1247
C11 H18 N 164.1440 C7 H11 N4 O 167.0934 C8 H15 N3 O 169.1216 C8 H11 O4 171.0657
C12 H20 164.1566 C8 H7 O4 167.0344 C8 H17 N4 169.1455 C8 H13 NO3 171.0896
165 C8 H9 NO3 167.0583 C9 H13 O3 169.0865 C8 H15 N2 O2 171.1134
C5 H13 N2 O4 165.0876 C8 H11 N2 O2 167.0821 C9 H15 NO2 169.1103 C8 H17 N3 O 171.1373
C5 H15 N3 O3 165.1114 C8 H13 N3 O 167.1060 C9 H17 N2 O 169.1342 C8 H19 N4 171.1611
C6 H5 N4 O2 165.0413 C8 H15 N4 167.1298 C9 H19 N3 169.1580 C9 H5 N3 O 171.0433
C6 H15 NO4 165.1001 C9 H11 O3 167.0708 C10 H7 N3 169.0641 C9 H7 N4 171.0672
C7 H5 N2 O3 165.0300 C9 H13 NO2 167.0947 C10 H17 O2 169.1229 C9 H15 O3 171.1021
C7 H7 N3 O2 165.0539 C9 H15 N2 O 167.1185 C10 H19 NO 169.1467 C9 H17 NO2 171.1260
C7 H9 N4 O 165.0777 C9 H17 N3 167.1424 C10 H21 N2 169.1706 C9 H19 N2 O 171.1498
C8 H5 O4 165.0187 C10 H15 O2 167.1072 C11 H7 NO 169.0528 C9 H21 N3 171.1737
C8 H7 NO3 165.0426 C10 H17 NO 167.1311 C11 H9 N2 169.0767 C10 H7 N2 O 171.0559
C8 H9 N2 O2 165.0664 C10 H19 N2 167.1549 C11 H21 O 169.1593 C10 H9 N3 171.0798
C8 H11 N3 O 165.0903 C11 H7 N2 167.0610 C11 H23 N 169.1832 C10 H19 O2 171.1385
C8 H13 N4 165.1142 C11 H19 O 167.1436 C12 H9 O 169.0653 C10 H21 NO 171.1624
C9 H9 O3 165.0552 C11 H21 N 167.1675 C12 H11 N 169.0892 C10 H23 N2 171.1863
C9 H11 NO2 165.0790 C12 H9 N 167.0736 C12 H25 169.1957 C11 H7 O2 171.0446
C9 H13 N2 O 165.1029 C12 H23 167.1801 C13 H13 169.1018 C11 H9 NO 171.0684
C9 H15 N3 165.1267 C13 H11 167.0861 170 C11 H11 N2 171.0923
C10 H13 O2 165.0916 168 C6 H6 N2 O4 170.0328 C11 H23 O 171.1750
C10 H15 NO 165.1154 C6 H4 N2 O4 168.0171 C6 H8 N3 O3 170.0566 C11 H25 N 171.1988
C10 H17 N2 165.1393 C6 H6 N3 O3 168.0410 C6 H10 N4 O2 170.0805 C12 H11 O 171.0810
C11 H17 O 165.1280 C6 H8 N4 O2 168.0648 C7 H8 NO4 170.0453 C12 H13 N 171.1049
C11 H19 N 165.1519 C7 H6 NO4 168.0297 C7 H10 N2 O3 170.0692 C13 H15 171.1174
C12 H7 N 165.0579 C7 H8 N2 O3 168.0535 C7 H12 N3 O2 170.0930 172
C12 H21 165.1644 C7 H10 N3 O2 168.0774 C7 H14 N4 O 170.1169 C6 H8 N2 O4 172.0484
C13 H9 165.0705 C7 H12 N4 O 168.1012 C8 H10 O4 170.0579 C6 H10 N3 O3 172.0723
166 C8 H8 O4 168.0422 C8 H12 NO3 170.0817 C6 H12 N4 O2 172.0961
C5 H14 N2 O4 166.0954 C8 H10 NO3 168.0661 C8 H14 N2 O2 170.1056 C7 H10 NO4 172.0610
C6 H4 N3 O3 166.0253 C8 H12 N2 O2 168.0899 C8 H16 N3 O 170.1295 C7 H12 H12 N2 O3 172.0848
C6 H6 N4 O2 166.0491 C8 H14 N3 O 168.1138 C8 H18 N4 170.1533 C7 H14 N3 O2 172.1087
C7 H6 N2 O3 166.0379 C8 H16 N4 168.1377 C9 H6 N4 170.0594 C7 H16 N4 O 172.1325
C7 H8 N3 O2 166.0617 C9 H12 O3 168.0786 C9 H14 O3 170.0943 C8 H12 O4 172.0735
C7 H10 N4 O 166.0856 C9 H14 NO2 168.1025 C9 H16 NO2 170.1182 C8 H14 NO3 172.0974
C8 H6 O4 166.0266 C9 H16 N2 O 168.1264 C9 H18 N2 O 170.1420 C8 H16 N2 O2 172.1213
C8 H8 NO3 166.0504 C9 H18 N3 168.1502 C9 H20 N3 170.1659 C8 H18 N3 O 172.1451
C8 H10 N2 O2 166.0743 C10 H16 O2 168.1151 C10 H6 N2 O 170.0480 C8 H20 N4 172.1690
C8 H12 N3 O 166.0981 C10 H18 NO 168.1389 C10 H8 N3 170.0719 C9 H6 N3 O 172.0511
C8 H14 N4 166.1220 C10 H20 N2 168.1628 C10 H18 O2 170.1307 C9 H8 N4 172.0750
C9 H10 O3 166.0630 C11 H8 N2 168.0688 C10 H20 NO 170.1546 C9 H16 O3 172.1100
C9 H12 NO2 166.0868 C11 H20 O 168.1515 C10 H22 N2 170.1784 C9 H18 NO2 172.1338
C9 H14 N2 O 166.1107 C11 H22 N 168.1753 C11 H8 NO 170.0606 C9 H20 N2 O 172.1577
C9 H16 N3 166.1346 C12 H8 O 168.0575 C11 H10 N2 170.0845 C9 H22 N3 172.1815
C10 H14 O2 166.0994 C12 H10 N 168.0814 C11 H22 O 170.1671 C10 H6 NO2 172.0399
C10 H16 NO 166.1233 C12 H24 168.1879 C11 H24 N 170.1910 C10 H8 N2 O 172.0637
C10 H18 N2 166.1471 C13 H12 168.0939 C12 H10 O 170.0732 C10 H10 N3 172.0876
C11 H18 O 166.1358 169 C12 H12 N 170.0970 C10 H20 O2 172.1464
C11 H20 N 166.1597 C6 H5 N2 O4 169.0249 C12 H26 170.2036 C10 H22 NO 172.1702
C12 H8 N 166.0657 C6 H7 N3 O3 169.0488 C13 H14 170.1096 C10 H24 N2 172.1941
C12 H22 166.1722 C6 H9 N4 O2 169.0726 171 C11 H8 O2 172.0524
C13 H10 166.0783 C7 H7 NO4 169.0375 C6 H7 N2 O4 171.0406 C11 H10 NO 172.0763
167 C7 H9 N2 O3 169.0614 C6 H9 N3 O3 171.0644 C11 H12 N2 172.1001
C6 H5 N3 O3 167.0331 C7 H11 N3 O2 169.0852 C6 H11 N4 O2 171.0883 C11 H24 O 172.1828
C6 H7 N4 O2 167.0570 C7 H13 N4 O 169.1091 C7 H9 NO4 171.0532 C12 H12 O 172.0888
C7 H5 NO4 167.0218 C8 H9 O4 169.0501 C7 H11 N2 O3 171.0770 C12 H14 N 172.1127
 Silverstein c01.tex V3 - 07/10/2014 3:46 P.M. Page 55

APPENDIX A 55

APPENDIX A (Continued)

FM FM FM FM

C13 H16 172.1253 C11 H12 NO 174.0919 C11 H12 O2 176.0837 C12 H20 N 178.1597
173 C11 H14 N2 174.1158 C11 H14 NO 176.1076 C13 H8 N 178.0657
C6 H9 N2 O4 173.0563 C12 H14 O 174.1045 C11 H16 N2 176.1315 C13 H22 178.1722
C6 H11 N3 O3 173.0801 C12 H16 N 174.1284 C12 H16 O 176.1202 C14 H10 178.0783
C6 H13 N4 O2 173.1040 C13 H18 174.1409 C12 H18 N 176.1440 179
C7 H11 NO4 173.0688 175 C13 H20 176.1566 C6 H15 N2 O4 179.1032
C7 H13 N2 O3 173.0927 C6 H11 N2 O4 175.0719 177 C6 H17 N3 O3 179.1271
C7 H15 N3 O2 173.1165 C6 H13 N3 O3 175.0958 C6 H13 N2 O4 177.0876 C7 H5 N3 O3 179.0331
C7 H17 N4 O 173.1404 C6 H15 N4 O2 175.1196 C6 H15 N3 O3 177.1114 C7 H7 N4 O2 179.0570
C8 H13 O4 173.0814 C7 H13 NO4 175.0845 C6 H17 N4 O2 177.1353 C7 H17 NO4 179.1158
C8 H15 NO3 173.1052 C7 H15 N2 O3 175.1083 C7 H5 N4 O2 177.0413 C8 H5 NO4 179.0218
C8 H17 N2 O2 173.1291 C7 H17 N3 O2 175.1322 C7 H15 NO4 177.1001 C8 H7 N2 O3 179.0457
C8 H19 N3 O 173.1529 C7 H19 N4 O 175.1560 C7 H17 N2 O3 177.1240 C8 H9 N3 O2 179.0695
C8 H21 N4 173.1768 C8 H7 N4 O 175.0621 C7 H19 N3 O2 177.1478 C8 H11 N4 O 179.0934
C9 H7 N3 O 173.0590 C8 H15 O4 175.0970 C8 H5 N2 O3 177.0300 C9 H7 O4 179.0344
C9 H9 N4 173.0829 C8 H17 NO3 175.1209 C8 H7 N3 O2 177.0539 C9 H9 NO3 179.0583
C9 H17 O3 173.1178 C8 H19 N2 O2 175.1447 C8 H9 N4 O 177.0777 C9 H11 N2 O2 179.0821
C9 H19 NO2 173.1416 C8 H21 N3 O 175.1686 C8 H17 O4 177.1127 C9 H13 N3 O 179.1060
C9 H21 N2 O 173.1655 C9 H5 NO3 175.0269 C8 H19 NO3 177.1365 C9 H15 N4 179.1298
C10 H5 O3 173.0238 C9 H7 N2 O2 175.0508 C9 H7 NO3 177.0426 C10 H11 O3 179.0708
C10 H7 NO2 173.0477 C9 H9 N3 O 175.0746 C9 H9 N2 O2 177.0664 C10 H13 NO2 179.0947
C10 H9 N2 O 173.0715 C9 H11 N4 175.0985 C9 H11 N3 O 177.0903 C10 H15 N2 O 179.1185
C10 H11 N3 173.0954 C9 H19 O3 175.1334 C9 H13 N4 177.1142 C10 H17 N3 179.1424
C10 H21 O2 173.1542 C9 H21 NO2 175.1573 C10 H9 O3 177.0552 C11 H15 O2 179.1072
C10 H23 NO 173.1781 C10 H7 O3 175.0395 C10 H11 NO2 177.0790 C11 H17 NO 179.1311
C11 H9 O2 173.0603 C10 H9 NO2 175.0634 C10 H13 N2 O 177.1029 C11 H19 N2 179.1549
C11 H11 NO 173.0841 C10 H11 N2 O 175.0872 C10 H15 N3 177.1267 C12 H19 O 179.1436
C11 H13 N2 173.1080 C10 H13 N3 175.1111 C11 H13 O2 177.0916 C12 H21 N 179.1675
C12 H13 O 173.0967 C11 H11 O2 175.0759 C11 H15 NO 177.1154 C13 H9 N 179.0736
C12 H15 N 173.1205 C11 H13 NO 175.0998 C11 H17 N2 177.1393 C13 H23 179.1801
C13 H17 173.1331 C11 H15 N2 175.1236 C12 H17 O 177.1280 C14 H11 179.0861
174 C12 H15 O 175.1123 C12 H19 N 177.1519 180
C6 H10 N2 O4 174.0641 C12 H17 N 175.1362 C13 H21 177.1644 C6 H16 N2 O4 180.1111
C6 H12 N3 O3 174.0879 C13 H3 O 175.0184 178 C7 H6 N3 O3 180.0410
C6 H14 N4 O2 174.1118 C13 H19 175.1488 C6 H14 N2 O4 178.0954 C7 H8 N4 O2 180.0648
C7 H12 NO4 174.0766 176 C6 H16 N3 O3 178.1193 C8 H6 NO4 180.0297
C7 H14 N2 O3 174.1005 C6 H12 N2 O4 176.0797 C6 H18 N4 O2 178.1431 C8 H8 N2 O3 180.0535
C7 H16 N3 O2 174.1244 C6 H14 N3 O3 176.1036 C7 H6 N4 O2 178.0491 C8 H10 N3 O2 180.0774
C7 H18 N4 O 174.1482 C6 H16 N4 O2 176.1275 C7 H16 NO4 178.1080 C8 H12 N4 O 180.1012
C7 H16 N4 O 174.1244 C7 H14 NO4 176.0923 C7 H18 N2 O3 178.1318 C9 H8 O4 180.0422
C8 H6 N4 O 174.0542 C7 H16 N2 O3 176.1162 C8 H6 N2 O3 178.0379 C9 H10 NO3 180.0661
C8 H14 O4 174.0892 C7 H18 N3 O2 176.1400 C8 H8 N3 O2 178.0617 C9 H12 N2 O2 180.0899
C8 H16 NO3 174.1131 C7 H20 N4 O 176.1639 C8 H10 N4 O 178.0856 C9 H14 N3 O 180.1138
C8 H18 N2 O2 174.1369 C8 H6 N3 O2 176.0460 C8 H18 O4 178.1205 C9 H16 N4 180.1377
C8 H20 N3 O 174.1608 C8 H8 N4 O 176.0699 C9 H6 O4 178.0266 C10 H12 O3 180.0786
C8 H22 N4 174.1846 C8 H16 O4 176.1049 C9 H8 NO3 178.0504 C10 H14 NO2 180.1025
C9 H6 N2 O2 174.0429 C8 H18 NO3 176.1287 C9 H10 N2 O2 178.0743 C10 H16 N2 O 180.1264
C9 H10 N4 174.0907 C8 H20 N2 O2 176.1526 C9 H12 N3 O 178.0981 C10 H18 N3 180.1502
C9 H18 O3 174.1256 C9 H6 NO3 176.0348 C9 H14 N4 178.1220 C11 H16 O2 180.1151
C9 H20 NO2 174.1495 C9 H8 N2 O2 176.0586 C10 H10 O3 178.0630 C11 H18 NO 180.1389
C9 H22 N2 O 174.1733 C9 H10 N3 O 176.0825 C10 H12 NO2 178.0868 C11 H20 N2 180.1628
C10 H6 O3 174.0317 C9 H12 N4 176.1063 C10 H14 N2 O 178.1107 C12 H8 N2 180.0688
C10 H8 NO2 174.0555 C9 H20 O3 176.1413 C10 H16 N3 178.1346 C12 H20 O 180.1515
C10 H10 N2 O 174.0794 C10 H8 O3 176.0473 C11 H14 O2 178.0994 C12 H22 N 180.1753
C10 H12 N3 174.1032 C10 H10 NO2 176.0712 C11 H16 NO 178.1233 C13 H8 O 180.0575
C10 H22 O2 174.1620 C10 H12 N2 O 176.0950 C11 H18 N2 178.1471 C13 H10 N 180.0814
C11 H10 O2 174.0681 C10 H14 N3 176.1189 C12 H18 O 178.1358 C13 H24 180.1879
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56 CHAPTER 1 MASS SPECTROMETRY

APPENDIX A (Continued)

FM FM FM FM

C14 H12 180.0939 C13 H12 N 182.0970 C11 H22 NO 184.1702 C10 H8 N3 O 186.0668
181 C13 H26 182.2036 C11 H24 N2 184.1941 C10 H10 N4 186.0907
C7 H5 N2 O4 181.0249 C14 H14 182.1096 C12 H8 O2 184.0524 C10 H18 O3 186.1256
C7 H7 N3 O3 181.0488 183 C12 H10 NO 184.0763 C10 H20 NO2 186.1495
C7 H9 N4 O2 181.0726 C7 H7 N2 O4 183.0406 C12 H12 N2 184.1001 C10 H22 N2 O 186.1733
C8 H7 NO4 181.0375 C7 H9 N3 O3 183.0644 C12 H24 O 184.1828 C10 H24 N3 186.1972
C8 H9 N2 O3 181.0614 C7 H11 N4 O2 183.0883 C12 H26 N 184.2067 C11 H8 NO2 186.0555
C8 H11 N3 O2 181.0852 C8 H9 NO4 183.0532 C13 H12 O 184.0888 C11 H10 N2 O 186.0794
C8 H13 N4 O 181.1091 C8 H11 N2 O3 183.0770 C13 H14 N 184.1127 C11 H12 N3 186.1032
C9 H9 O4 181.0501 C8 H13 N3 O2 183.1009 C13 H28 184.2192 C11 H22 O2 186.1620
C9 H11 NO3 181.0739 C8 H15 N4 O 183.1247 C14 H16 184.1253 C11 H24 NO 186.1859
C9 H13 N2 O2 181.0978 C9 H11 O4 183.0657 185 C11 H26 N2 186.2098
C9 H15 N3 O 181.1216 C9 H13 NO3 183.0896 C7 H9 N2 O4 185.0563 C12 H10 O2 186.0681
C9 H17 N4 181.1455 C9 H15 N2 O2 183.1134 C7 H11 N3 O3 185.0801 C12 H12 NO 186.0919
C10 H13 O3 181.0865 C9 H17 N3 O 183.1373 C7 H13 N4 O2 185.1040 C12 H14 N2 186.1158
C10 H15 NO2 181.1103 C9 H19 N4 183.1611 C8 H11 NO4 185.0688 C12 H26 O 186.1985
C10 H17 N2 O 181.1342 C10 H7 N4 183.0672 C8 H13 N2 O3 185.0927 C13 H14 O 186.1045
C10 H19 N3 181.1580 C10 H15 O3 183.1021 C8 H15 N3 O2 185.1165 C13 H16 N 186.1284
C11 H7 N3 181.0641 C10 H17 NO2 183.1260 C8 H17 N4 O 185.1404 C14 H18 186.1409
C11 H17 O2 181.1229 C10 H19 N2 O 183.1498 C9 H13 O4 185.0814 187
C11 H19 NO 181.1467 C10 H21 N3 183.1737 C9 H15 NO3 185.1052 C7 H11 N2 O4 187.0719
C11 H21 N2 181.1706 C11 H7 N2 O 183.0559 C9 H17 N2 O2 185.1291 C7 H13 N3 O3 187.0958
C12 H7 NO 181.0528 C11 H9 N3 183.0798 C9 H19 N3 O 185.1529 C7 H15 N4 O2 187.1196
C12 H9 N2 181.0767 C11 H19 O2 183.1385 C9 H21 N4 185.1768 C8 H13 NO4 187.0845
C12 H21 O 181.1593 C11 H21 NO 183.1624 C10 H7 N3 O 185.0590 C8 H15 N2 O3 187.1083
C12 H23 N 181.1832 C11 H23 N2 183.1863 C10 H9 N4 185.0829 C8 H17 N3 O2 187.1322
C13 H9 O 181.0653 C12 H7 O2 183.0446 C10 H17 O3 185.1178 C8 H19 N4 O 187.1560
C13 H11 N 181.0892 C12 H9 NO 183.0684 C10 H19 NO2 185.1416 C9 H7 N4 O 187.0621
C13 H25 181.1957 C12 H11 N2 183.0923 C10 H21 N2 O 185.1655 C9 H15 O4 187.0970
C14 H13 181.1018 C12 H23 O 183.1750 C10 H23 N3 185.1894 C9 H17 NO3 187.1209
182 C12 H25 N 183.1988 C11 H9 N2 O 185.0715 C9 H19 N2 O2 187.1447
C7 H6 N2 O4 182.0328 C13 H11 O 183.0810 C11 H11 N3 185.0954 C9 H21 N3 O 187.1686
C7 H8 N3 O3 182.0566 C13 H13 N 183.1049 C11 H21 O2 185.1542 C9 H23 N4 187.1925
C7 H10 N4 O2 182.0805 C13 H27 183.2114 C11 H23 NO 185.1781 C10 H7 N2 O2 187.0508
C8 H8 NO4 182.0453 C14 H15 183.1174 C11 H25 N2 185.2019 C10 H9 N3 O 187.0746
C8 H10 N2 O3 182.0692 184 C12 H9 O2 185.0603 C10 H11 N4 187.0985
C8 H12 N3 O2 182.0930 C7 H8 N2 O4 184.0484 C12 H11 NO 185.0841 C10 H19 O3 187.1334
C8 H14 N4 O 182.1169 C7 H10 N3 O3 184.0723 C12 H13 N2 185.1080 C10 H21 NO2 187.1573
C9 H10 O4 182.0579 C7 H12 N4 O2 184.0961 C12 H25 O 185.1906 C10 H23 N2 O 187.1811
C9 H12 NO3 182.0817 C8 H10 NO4 184.0610 C12 H27 N 185.2145 C10 H25 N3 187.2050
C9 H14 N2 O2 182.1056 C8 H12 N2 O3 184.0848 C13 H13 O 185.0967 C11 H7 O3 187.0395
C9 H16 N3 O 182.1295 C8 H14 N3 O2 184.1087 C13 H15 N 185.1205 C11 H9 NO2 187.0634
C9 H18 N4 182.1533 C8 H16 N4 O 184.1325 C14 H17 185.1331 C11 H11 N2 O 187.0872
C10 H6 N4 182.0594 C9 H12 O4 184.0735 186 C11 H13 N3 187.1111
C10 H14 O3 182.0943 C9 H14 NO3 184.0974 C7 H10 N2 O4 186.0641 C11 H23 O2 187.1699
C10 H16 NO2 182.1182 C9 H16 N2 O2 184.1213 C7 H12 N3 O3 186.0879 C11 H25 NO 187.1937
C10 H18 N2 O 182.1420 C9 H18 N3 O 184.1451 C7 H14 N4 O2 186.1118 C12 H11 O2 187.0759
C10 H20 N3 182.1659 C9 H20 N4 184.1690 C8 H12 NO4 186.0766 C12 H13 NO 187.0998
C11 H8 N3 182.0719 C10 H6 N3 O 184.0511 C8 H14 N2 O3 186.1005 C12 H15 N2 187.1236
C11 H18 O2 182.1307 C10 H8 N4 184.0750 C8 H16 N3 O2 186.1244 C13 H15 O 187.1123
C11 H20 NO 182.1546 C10 H16 O3 184.1100 C8 H18 N4 O 186.1482 C13 H17 N 187.1362
C11 H22 N2 182.1784 C10 H18 NO2 184.1338 C9 H6 N4 O 186.0542 C14 H19 187.1488
C12 H8 NO 182.0606 C10 H20 N2 O 184.1577 C9 H14 O4 186.0892 188
C12 H10 N2 182.0845 C10 H22 N3 184.1815 C9 H16 NO3 186.1131 C7 H12 N2 O4 188.0797
C12 H22 O 182.1671 C11 H8 N2 O 184.0637 C9 H18 N2 O2 186.1369 C7 H14 N3 O3 188.1036
C12 H24 N 182.1910 C11 H10 N3 184.0876 C9 H20 N3 O 186.1608 C7 H16 N4 O2 188.1275
C13 H10 O 182.0732 C11 H20 O2 184.1464 C10 H6 N2 O2 186.0429 C8 H14 NO4 188.0923
 Silverstein c01.tex V3 - 07/10/2014 3:46 P.M. Page 57

APPENDIX A 57

APPENDIX A (Continued)

FM FM FM FM

C8 H16 N2 O3 188.1162 190 C14 H9 N 191.0736 C13 H21 O 193.1593

C8 H18 N3 O2 188.1400 C7 H14 N2 O4 190.0954 C14 H23 N 191.1801 C13 H23 N 193.1832
C8 H20 N4 O 188.1639 C7 H16 N3 O3 190.1193 C15 H11 191.0861 C14 H9 O 193.0653
C9 H6 N3 O2 188.0460 C7 H18 N4 O2 190.1431 192 C14 H11 N 193.0892
C9 H8 N4 O 188.0699 C8 H6 N4 O2 190.0491 C7 H16 N2 O4 192.1111 C14 H25 193.1957
C9 H16 O4 188.1049 C8 H16 NO4 190.1080 C7 H18 N3 O3 192.1349 C15 H13 193.1018
C9 H18 NO3 188.1287 C8 H18 N2 O3 190.1318 C7 H20 N4 O2 192.1588 194
C9 H20 N2 O2 188.1526 C8 H20 N3 O2 190.1557 C8 H6 N3 O3 192.0410 C7 H18 N2 O4 194.1267
C9 H22 N3 O 188.1764 C8 H22 N4 O 190.1795 C8 H8 N4 O2 192.0648 C8 H6 N2 O4 194.0328
C9 H24 N4 188.2003 C9 H8 N3 O2 190.0617 C8 H18 NO4 192.1236 C8 H8 N3 O3 194.0566
C10 H8 N2 O2 188.0586 C9 H10 N4 O 190.0856 C8 H20 N2 O3 192.1475 C8 H10 N4 O2 194.0805
C10 H10 N3 O 188.0825 C9 H18 O4 190.1205 C9 H6 NO4 192.0297 C9 H8 NO4 194.0453
C10 H12 N4 188.1063 C9 H20 NO3 190.1444 C9 H8 N2 O3 192.0535 C9 H10 N2 O3 194.0692
C10 H20 O3 188.1413 C9 H22 N2 O2 190.1682 C9 H10 N3 O2 192.0774 C9 H12 N3 O2 194.0930
C10 H22 NO2 188.1651 C10 H8 NO3 190.0504 C9 H12 N4 O 192.1012 C9 H14 N4 O 194.1169
C10 H24 N2 O 188.1890 C10 H10 N2 O2 190.0743 C9 H20 O4 192.1362 C10 H10 O4 194.0579
C11 H8 O3 188.0473 C10 H12 N3 O 190.0981 C10 H8 O4 192.0422 C10 H12 NO3 194.0817
C11 H10 NO2 188.0712 C10 H14 N4 190.1220 C10 H10 NO3 192.0661 C10 H14 N2 O2 194.1056
C11 H12 N2 O 188.0950 C10 H22 O3 190.1569 C10 H12 N2 O2 192.0899 C10 H16 N3 O 194.1295
C11 H14 N3 188.1189 C11 H10 O3 190.0630 C10 H14 N3 O 192.1138 C10 H18 N4 194.1533
C11 H24 O2 188.1777 C11 H12 NO2 190.0868 C10 H16 N4 192.1377 C11 H14 O3 194.0943
C12 H12 O2 188.0837 C11 H14 N2 O 190.1107 C11 H12 O3 192.0786 C11 H16 NO2 194.1182
C12 H14 NO 188.1076 C11 H16 N3 190.1346 C11 H14 NO2 192.1025 C11 H18 N2 O 194.1420
C12 H16 N2 188.1315 C12 H14 O2 190.0994 C11 H16 N2 O 192.1264 C11 H20 N3 194.1659
C13 H16 O 188.1202 C12 H16 NO 190.1233 C11 H18 N3 192.1502 C12 H8 N3 194.0719
C13 H18 N 188.1440 C12 H18 N2 190.1471 C12 H16 O2 192.1151 C12 H18 O2 194.1307
C14 H20 188.1566 C13 H18 O 190.1358 C12 H18 NO 192.1389 C12 H20 NO 194.1546
189 C13 H20 N 190.1597 C12 H20 N2 192.1628 C12 H22 N2 194.1784
C7 H13 N2 O4 189.0876 C14 H22 190.1722 C13 H8 N2 192.0688 C13 H8 NO 194.0606
C7 H15 N3 O3 189.1114 C15 H10 190.0783 C13 H20 O 192.1515 C13 H10 N2 194.0845
C7 H17 N4 O2 189.1353 191 C13 H22 N 192.1753 C13 H22 O 194.1671
C8 H15 NO4 189.1001 C7 H15 N2 O4 191.1032 C14 H10 N 192.0814 C13 H24 N 194.1910
C8 H17 N2 O3 189.1240 C7 H17 N3 O3 191.1271 C14 H24 192.1879 C14 H10 O 194.0732
C8 H19 N3 O2 189.1478 C7 H19 N4 O2 191.1509 C15 H12 192.0939 C14 H12 N 194.0970
C8 H21 N4 O 189.1717 C8 H7 N4 O2 191.0570 193 C14 H26 194.2036
C9 H7 N3 O2 189.0539 C8 H17 NO4 191.1158 C7 H17 N2 O4 193.1189 C15 H14 194.1096
C9 H9 N4 O 189.0777 C8 H19 N2 O3 191.1396 C7 H19 N3 O3 193.1427 195
C9 H17 O4 189.1127 C8 H21 N3 O2 191.1635 C8 H7 N3 O3 193.0488 C8 H7 N2 O4 195.0406
C9 H19 NO3 189.1365 C9 H7 N2 O3 191.0457 C8 H9 N4 O2 193.0726 C8 H9 N3 O3 195.0644
C9 H21 N2 O2 189.1604 C9 H9 N3 O2 191.0695 C8 H19 NO4 193.1315 C8 H11 N4 O2 195.0883
C9 H23 N3 O 189.1842 C9 H11 N4 O 191.0934 C9 H7 NO4 193.0375 C9 H9 NO4 195.0532
C10 H7 NO3 189.0426 C9 H19 O4 191.1284 C9 H9 N2 O3 193.0614 C9 H11 N2 O3 195.0770
C10 H9 N2 O2 189.0664 C9 H21 NO3 191.1522 C9 H11 N3 O2 193.0852 C9 H13 N3 O2 195.1009
C10 H11 N3 O 189.0903 C10 H7 O4 191.0344 C9 H13 N4 O 193.1091 C9 H15 N4 O 195.1247
C10 H13 N4 189.1142 C10 H9 NO3 191.0583 C10 H9 O4 193.0501 C10 H11 O4 195.0657
C10 H21 O3 189.1491 C10 H11 N2 O2 191.0821 C10 H11 NO3 193.0739 C10 H13 NO3 195.0896
C10 H23 NO2 189.1730 C10 H13 N3 O 191.1060 C10 H13 N2 O2 193.0978 C10 H15 N2 O2 195.1134
C11 H9 O3 189.0552 C10 H15 N4 191.1298 C10 H15 N3 O 193.1216 C10 H17 N3 O 195.1373
C11 H11 NO2 189.0790 C11 H11 O3 191.0708 C10 H17 N4 193.1455 C10 H19 N4 195.1611
C11 H13 N2 O 189.1029 C11 H13 NO2 191.0947 C11 H13 O3 193.0865 C11 H7 N4 195.0672
C11 H15 N3 189.1267 C11 H15 N2 O 191.1185 C11 H15 NO2 193.1103 C11 H15 O3 195.1021
C12 H13 O2 189.0916 C11 H17 N3 191.1424 C11 H17 N2 O 193.1342 C11 H17 NO2 195.1260
C12 H15 NO 189.1154 C12 H15 O2 191.1072 C11 H19 N3 193.1580 C11 H19 N2 O 195.1498
C12 H17 N2 189.1393 C12 H17 NO 191.1311 C12 H17 O2 193.1229 C11 H21 N3 195.1737
C13 H17 O 189.1280 C12 H19 N2 191.1549 C12 H19 NO 193.1467 C12 H7 N2 O 195.0559
C13 H19 N 189.1519 C13 H19 O 191.1436 C12 H21 N2 193.1706 C12 H9 N3 195.0798
C14 H21 189.1644 C13 H21 N 191.1675 C13 H9 N2 193.0767 C12 H19 O2 195.1385
 Silverstein c01.tex V3 - 07/10/2014 3:46 P.M. Page 58

58 CHAPTER 1 MASS SPECTROMETRY

APPENDIX A (Continued)

FM FM FM FM

C12 H21 NO 195.1624 C11 H17 O3 197.1178 C9 H15 N2 O3 199.1083 C12 H28 N2 200.2254
C12 H23 N2 195.1863 C11 H19 NO2 197.1416 C9 H17 N3 O2 199.1322 C13 H12 O2 200.0837
C13 H9 NO 195.0684 C11 H21 N2 O 197.1655 C9 H19 N4 O 199.1560 C13 H14 NO 200.1076
C13 H11 N2 195.0923 C11 H23 N3 197.1894 C10 H7 N4 O 199.0621 C13 H16 N2 200.1315
C13 H23 O 195.1750 C12 H9 N2 O 197.0715 C10 H15 O4 199.0970 C13 H28 O 200.2141
C13 H25 N 195.1988 C12 H11 N3 197.0954 C10 H17 NO3 199.1209 C14 H16 O 200.1202
C14 H11 O 195.0810 C12 H21 O2 197.1542 C10 H19 N2 O2 199.1447 C14 H18 N 200.1440
C14 H13 N 195.1049 C12 H23 NO 197.1781 C10 H21 N3 O 199.1686 C15 H20 200.1566
C14 H27 195.2114 C12 H25 N2 197.2019 C10 H23 N4 199.1925 201
C15 H15 195.1174 C13 H9 O2 197.0603 C11 H7 N2 O2 199.0508 C8 H13 N2 O4 201.0876
196 C13 H11 NO 197.0841 C11 H9 N3 O 199.0746 C8 H15 N3 O3 201.1114
C8 H8 N2 O4 196.0484 C13 H13 N2 197.1080 C11 H11 N4 199.0985 C8 H17 N4 O2 201.1353
C8 H10 N3 O3 196.0723 C13 H25 O 197.1906 C11 H19 O3 199.1334 C9 H15 NO4 201.1001
C8 H12 N4 O2 196.0961 C13 H27 N 197.2145 C11 H21 NO2 199.1573 C9 H17 N2 O3 201.1240
C9 H10 NO4 196.0610 C14 H13 O 197.0967 C11 H23 N2 O 199.1811 C9 H19 N3 O2 201.1478
C9 H12 N2 O3 196.0848 C14 H15 N 197.1205 C11 H25 N3 199.2050 C9 H21 N4 O 201.1717
C9 H14 N3 O2 196.1087 C14 H29 197.2270 C12 H9 NO2 199.0634 C10 H7 N3 O2 201.0539
C9 H16 N4 O 196.1325 C15 H17 197.1331 C12 H11 N2 O 199.0872 C10 H9 N4 O 201.0777
C10 H12 O4 196.0735 198 C12 H13 N3 199.1111 C10 H17 O4 201.1127
C10 H14 NO3 196.0974 C8 H10 N2 O4 198.0641 C12 H23 O2 199.1699 C10 H19 NO3 201.1365
C10 H16 N2 O2 196.1213 C8 H12 N3 O3 198.0879 C12 H25 NO 199.1937 C10 H21 N2 O2 201.1604
C10 H18 N3 O 196.1451 C8 H14 N4 O2 198.1118 C12 H27 N2 199.2176 C10 H23 N3 O 201.1842
C10 H20 N4 196.1690 C9 H12 NO4 198.0766 C13 H11 O2 199.0759 C10 H25 N4 201.2081
C11 H8 N4 196.0750 C9 H14 N2 O3 198.1005 C13 H13 NO 199.0998 C11 H7 NO3 201.0426
C11 H16 O3 196.1100 C9 H16 N3 O2 198.1244 C13 H15 N2 199.1236 C11 H9 N2 O2 201.0664
C11 H18 NO2 196.1338 C9 H18 N4 O 198.1482 C13 H27 O 199.2063 C11 H11 N3 O 201.0903
C11 H20 N2 O 196.1577 C10 H14 O4 198.0892 C13 H29 N 199.2301 C11 H13 N4 201.1142
C11 H22 N3 196.1815 C10 H16 NO3 198.1131 C14 H15 O 199.1123 C11 H21 O3 201.1491
C12 H8 N2 O 196.0637 C10 H18 N2 O2 198.1369 C14 H17 N 199.1362 C11 H23 NO2 201.1730
C12 H10 N3 196.0876 C10 H20 N3 O 198.1608 C15 H19 199.1488 C11 H25 N2 O 201.1968
C12 H20 O2 196.1464 C10 H22 N4 198.1846 200 C11 H27 N3 201.2207
C12 H22 NO 196.1702 C11 H8 N3 O 198.0668 C8 H12 N2 O4 200.0797 C12 H9 O3 201.0552
C12 H24 N2 196.1941 C11 H10 N4 198.0907 C8 H14 N3 O3 200.1036 C12 H11 NO2 201.0790
C13 H8 O2 196.0524 C11 H18 O3 198.1256 C8 H16 N4 O2 200.1275 C12 H13 N2 O 201.1029
C13 H10 NO 196.0763 C11 H20 NO2 198.1495 C9 H14 NO4 200.0923 C12 H15 N3 201.1267
C13 H12 N2 196.1001 C11 H22 N2 O 198.1733 C9 H16 N2 O3 200.1162 C12 H25 O2 201.1855
C13 H24 O 196.1828 C11 H24 N3 198.1972 C9 H18 N3 O2 200.1400 C12 H27 NO 201.2094
C13 H26 N 196.2067 C12 H8 NO2 198.0555 C9 H20 N4 O 200.1639 C13 H13 O2 201.0916
C14 H12 O 196.0888 C12 H10 N2 O 198.0794 C10 H8 N4 O 200.0699 C13 H15 NO 201.1154
C14 H14 N 196.1127 C12 H12 N3 198.1032 C10 H16 O4 200.1049 C13 H17 N2 201.1393
C14 H28 196.2192 C12 H22 O2 198.1620 C10 H18 NO3 200.1287 C14 H17 O 201.1280
C15 H16 196.1253 C12 H24 NO 198.1859 C10 H20 N2 O2 200.1526 C14 H19 N 201.1519
197 C12 H26 N2 198.2098 C10 H22 N3 O 200.1764 C15 H21 201.1644
C8 H9 N2 O4 197.0563 C13 H10 O2 198.0681 C10 H24 N4 200.2003 202
C8 H11 N3 O3 197.0801 C13 H12 NO 198.0919 C11 H8 N2 O2 200.0586 C8 H14 N2 O4 202.0954
C8 H13 N4 O2 197.1040 C13 H14 N2 198.1158 C11 H10 N3 O 200.0825 C8 H16 N3 O3 202.1193
C9 H11 NO4 197.0688 C13 H26 O 198.1985 C11 H12 N4 200.1063 C8 H18 N4 O2 202.1431
C9 H13 N2 O3 197.0927 C13 H28 N 198.2223 C11 H20 O3 200.1413 C9 H6 N4 O2 202.0491
C9 H15 N3 O2 197.1165 C14 H14 O 198.1045 C11 H22 NO2 200.1651 C9 H16 NO4 202.1080
C9 H17 N4 O 197.1404 C14 H16 N 198.1284 C11 H24 N2 O 200.1890 C9 H18 N2 O3 202.1318
C10 H13 O4 197.0814 C14 H30 198.2349 C11 N26 N3 200.2129 C9 H20 N3 O2 202.1557
C10 H15 NO3 197.1052 C15 H18 198.1409 C12 H8 O3 200.0473 C9 H22 N4 O 202.1795
C10 H17 N2 O2 197.1291 199 C12 H10 NO2 200.0712 C10 H8 N3 O2 202.0617
C10 H19 N3 O 197.1529 C8 H11 N2 O4 199.0719 C12 H12 N2 O 200.0950 C10 H10 N4 O 202.0856
C10 H21 N4 197.1768 C8 H13 N3 O3 199.0958 C12 H14 N3 200.1189 C10 H18 O4 202.1205
C11 H7 N3 O 197.0590 C8 H15 N4 O2 199.1196 C12 H24 O2 200.1777 C10 H20 NO3 202.1444
C11 H9 N4 197.0829 C9 H13 NO4 199.0845 C12 H26 NO 200.2015 C10 H22 N2 O2 202.1682
 Silverstein c01.tex V3 - 07/10/2014 3:46 P.M. Page 59

APPENDIX A 59

APPENDIX A (Continued)

FM FM FM FM

C10 H24 N3 O 202.1921 C8 H20 N4 O2 204.1588 C13 H21 N2 205.1706 C11 H19 N4 207.1611
C10 H26 N4 202.2160 C9 H6 N3 O3 204.0410 C14 H9 N2 205.0767 C12 H15 O3 207.1021
C11 H8 NO3 202.0504 C9 H8 N4 O2 204.0648 C14 H21 O 205.1593 C12 H17 NO2 207.1260
C11 H10 N2 O2 202.0743 C9 H18 NO4 204.1236 C14 H23 N 205.1832 C12 H19 N2 O 207.1498
C11 H12 N3 O 202.0981 C9 H20 N2 O3 204.1475 C15 H9 O 205.0653 C12 H21 N3 207.1737
C11 H14 N4 202.1220 C9 H22 N3 O2 204.1713 C15 H11 N 205.0892 C13 H9 N3 207.0798
C11 H22 O3 202.1569 C9 H24 N4 O 204.1952 C15 H25 205.1957 C13 H19 O2 207.1385
C11 H24 NO2 202.1808 C10 H8 N2 O3 204.0535 C16 H13 205.1018 C13 H21 NO 207.1624
C11 H26 N2 O 202.2046 C10 H10 N3 O2 204.0774 206 C13 H23 N2 207.1863
C12 H10 O3 202.0630 C10 H12 N4 O 204.1012 C8 H18 N2 O4 206.1267 C14 H9 NO 207.0684
C12 H12 NO2 202.0868 C10 H20 O4 204.1362 C8 H20 N3 O3 206.1506 C14 H11 N2 207.0923
C12 H14 N2 O 202.1107 C10 H22 NO3 204.1600 C8 H22 N4 O2 206.1744 C14 H23 O 207.1750
C12 H16 N3 202.1346 C10 H24 N2 O2 204.1839 C9 H6 N2 O4 206.0328 C14 H25 N 207.1988
C12 H26 O2 202.1934 C11 H8 O4 204.0422 C9 H8 N3 O3 206.0566 C15 H11 O 207.0810
C13 H14 O2 202.0994 C11 H10 NO3 204.0661 C9 H10 N4 O2 206.0805 C15 H13 N 207.1049
C13 H16 NO 202.1233 C11 H12 N2 O2 204.0899 C9 H20 NO4 206.1393 C15 H27 207.2114
C13 H18 N2 202.1471 C11 H14 N3 O 204.1138 C9 H22 N2 O3 206.1631 C16 H15 207.1174
C14 H18 O 202.1358 C11 H16 N4 204.1377 C10 H8 NO4 206.0453 208
C14 H20 N 202.1597 C11 H24 O3 204.1726 C10 H10 N2 O3 206.0692 C8 H20 N2 O4 208.1424
C15 H22 202.1722 C12 H12 O3 204.0786 C10 H12 N3 O2 206.0930 C9 H8 N2 O4 208.0484
203 C12 H14 NO2 204.1025 C10 H14 N4 O 206.1169 C9 H10 N3 O3 208.0723
C8 H15 N2 O4 203.1032 C12 H16 N2 O 204.1264 C10 H22 O4 206.1518 C9 H12 N4 O2 208.0961
C8 H17 N3 O3 203.1271 C12 H18 N3 204.1502 C11 H10 O4 206.0579 C10 H10 NO4 208.0610
C8 H19 N4 O2 203.1509 C13 H16 O2 204.1151 C11 H12 NO3 206.0817 C10 H12 N2 O3 208.0848
C9 H7 N4 O2 203.0570 C13 H18 NO 204.1389 C11 H14 N2 O2 206.1056 C10 H14 N3 O2 208.1087
C9 H17 NO4 203.1158 C13 H20 N2 204.1628 C11 H16 N3 O 206.1295 C10 H16 N4 O 208.1325
C9 H19 N2 O3 203.1396 C14 H20 O 204.1515 C11 H18 N4 206.1533 C11 H12 O4 208.0735
C9 H21 N3 O2 203.1635 C14 H22 N 204.1753 C12 H14 O3 206.0943 C11 H14 NO3 208.0974
C9 H23 N4 O 203.1873 C15 H10 N 204.0814 C12 H16 NO2 206.1182 C11 H16 N2 O2 208.1213
C10 H7 N2 O3 203.0457 C15 H24 204.1879 C12 H18 N2 O 206.1420 C11 H18 N3 O 208.1451
C10 H9 N3 O2 203.0695 C16 H12 204.0939 C12 H20 N3 206.1659 C11 H20 N4 208.1690
C10 H11 N4 O 203.0934 205 C13 H8 N3 206.0719 C12 H8 N4 208.0750
C10 H19 O4 203.1284 C8 H17 N2 O4 205.1189 C13 H18 O2 206.1307 C12 H16 O3 208.1100
C10 H21 NO3 203.1522 C8 H19 N3 O3 205.1427 C13 H20 NO 206.1546 C12 H18 NO2 208.1338
C10 H23 N2 O2 203.1761 C8 H21 N4 O2 205.1666 C13 H22 N2 206.1784 C12 H20 N2 O 208.1577
C10 H25 N3 O 203.1999 C9 H7 N3 O3 205.0488 C14 H10 N2 206.0845 C12 H22 N3 208.1815
C11 H7 O4 203.0344 C9 H9 N4 O2 205.0726 C14 H22 O 206.1671 C13 H8 N2 O 208.0637
C11 H9 NO3 203.0583 C9 H19 NO4 205.1315 C14 H24 N 206.1910 C13 H10 N3 208.0876
C11 H11 N2 O2 203.0821 C9 H21 N2 O3 205.1553 C15 H10 O 206.0732 C13 H20 O2 208.1464
C11 H13 N3 O 203.1060 C9 H23 N3 O2 205.1791 C15 H12 N 206.0970 C13 H22 NO 208.1702
C11 H15 N4 203.1298 C10 H7 NO4 205.0375 C15 H26 206.2036 C13 H24 N2 208.1941
C11 H23 O3 203.1648 C10 H9 N2 O3 205.0614 C16 H14 206.1096 C14 H10 NO 208.0763
C11 H25 NO2 203.1886 C10 H11 N3 O2 205.0852 207 C14 H12 N2 208.1001
C12 H11 O3 203.0708 C10 H13 N4 O 205.1091 C8 H19 N2 O4 207.1345 C14 H24 O 208.1828
C12 H13 NO2 203.0947 C10 H21 O4 205.1440 C8 H21 N3 O3 207.1584 C14 H26 N 208.2067
C12 H15 N2 O 203.1185 C10 H23 NO3 205.1679 C9 H7 N2 O4 207.0406 C15 H12 O 208.0888
C12 H17 N3 203.1424 C11 H9 O4 205.0501 C9 H9 N3 O3 207.0644 C15 H14 N 208.1127
C13 H15 O2 203.1072 C11 H11 NO3 205.0739 C9 H11 N4 O2 207.0883 C15 H28 208.2192
C13 H17 NO 203.1311 C11 H13 N2 O2 205.0978 C9 H21 NO4 207.1471 C16 H16 208.1253
C13 H19 N2 203.1549 C11 H15 N3 O 205.1216 C10 H9 NO4 207.0532 209
C14 H19 O 203.1436 C11 H17 N4 205.1455 C10 H11 N2 O3 207.0770 C9 H9 N2 O4 209.0563
C14 H21 N 203.1675 C12 H13 O3 205.0865 C10 H13 N3 O2 207.1009 C9 H11 N3 O3 209.0801
C15 H9 N 203.0736 C12 H15 N 205.1103 C10 H15 N4 O 207.1247 C9 H13 N4 O2 209.1040
C15 H23 203.1801 C12 H17 N2 O 205.1342 C11 H11 O4 207.0657 C10 H11 NO4 209.0688
204 C12 H19 N3 205.1580 C11 H13 NO3 207.0896 C10 H13 N2 O3 209.0927
C8 H16 N2 O4 204.1111 C13 H17 O2 205.1229 C11 H15 N2 O2 207.1134 C10 H15 N3 O2 209.1165
C8 H18 N3 O3 204.1349 C13 H19 NO 205.1467 C11 H17 N3 O 207.1373 C10 H17 N4 O 209.1404
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60 CHAPTER 1 MASS SPECTROMETRY

APPENDIX A (Continued)

FM FM FM FM

C11 H13 O4 209.0814 C16 H18 210.1409 C13 H8 O3 212.0473 C10 H18 N2 O3 214.1318
C11 H15 NO3 209.1052 211 C13 H10 NO2 212.0712 C10 H20 N3 O2 214.1557
C11 H17 N2 O2 209.1291 C9 H11 N2 O4 211.0719 C13 H12 N2 O 212.0950 C10 H22 N4 O 214.1795
C11 H19 N3 O 209.1529 C9 H13 N3 O3 211.0958 C13 H14 N3 212.1189 C11 H8 N3 O2 214.0617
C11 H21 N4 209.1768 C9 H15 N4 O2 211.1196 C13 H24 O2 212.1777 C11 H10 N4 O 214.0856
C12 H9 N4 209.0829 C10 H13 NO4 211.0845 C13 H26 NO 212.2015 C11 H18 O4 214.1205
C12 H17 O3 209.1178 C10 H15 N2 O3 211.1083 C13 H28 N2 212.2254 C11 H20 NO3 214.1444
C12 H19 NO2 209.1416 C10 H17 N3 O2 211.1322 C14 H12 O2 212.0837 C11 H22 N2 O2 214.1682
C12 H21 N2 O 209.1655 C10 H19 N4 O 211.1560 C14 H14 NO 212.1076 C11 H24 N3 O 214.1921
C12 H23 N3 209.1894 C11 H7 N4 O 211.0621 C14 H16 N2 212.1315 C11 H26 N4 214.2160
C13 H9 N2 O 209.0715 C11 H15 O4 211.0970 C14 H28 O 212.2141 C12 H8 NO3 214.0504
C13 H11 N3 209.0954 C11 H17 NO3 211.1209 C14 H30 N 212.2380 C12 H10 N2 O2 214.0743
C13 H21 O2 209.1542 C11 H19 N2 O2 211.1447 C15 H16 O 212.1202 C12 H12 N3 O 214.0981
C13 H23 NO 209.1781 C11 H21 N3 O 211.1686 C15 H18 N 212.1440 C12 H14 N4 214.1220
C13 H25 N2 209.2019 C11 H23 N4 211.1925 C15 H32 212.2505 C12 H22 O3 214.1569
C14 H9 O2 209.0603 C12 H9 N3 O 211.0746 C16 H20 212.1566 C12 H24 NO2 214.1808
C14 H11 NO 209.0841 C12 H11 N4 211.0985 213 C12 H26 N2 O 214.2046
C14 H13 N2 209.1080 C12 H19 O3 211.1334 C9 H13 N2 O4 213.0876 C12 H28 N3 214.2285
C14 H25 O 209.1906 C12 H21 NO2 211.1573 C9 H15 N3 O3 213.1114 C13 H10 O3 214.0630
C14 H27 N 209.2145 C12 H23 N2 O 211.1811 C9 H17 N4 O2 213.1353 C13 H12 NO2 214.0869
C15 H13 O 209.0967 C12 H25 N3 211.2050 C10 H15 NO4 213.1001 C13 H14 N2 O 214.1107
C15 H15 N 209.1205 C13 H9 NO2 211.0634 C10 H17 N2 O3 213.1240 C13 H16 N3 214.1346
C15 H29 209.2270 C13 H11 N2 O 211.0872 C10 H19 N3 O2 213.1478 C13 H26 O2 214.1934
C16 H17 209.1331 C13 H13 N3 211.1111 C10 H21 N4 O 213.1717 C13 H28 NO 214.2172
210 C13 H23 O2 211.1699 C11 H7 N3 O2 213.0539 C13 H30 N2 214.2411
C9 H10 N2 O4 210.0641 C13 H25 NO 211.1937 C11 H9 N4 O 213.0777 C14 H14 O2 214.0994
C9 H12 N3 O3 210.0879 C13 H27 N2 211.2176 C11 H17 O4 213.1127 C14 H16 NO 214.1233
C9 H14 N4 O2 210.1118 C14 H11 O2 211.0759 C11 H19 NO3 213.1365 C14 H18 N2 214.1471
C10 H12 NO4 210.0766 C14 H13 NO 211.0998 C11 H21 N2 O2 213.1604 C15 H18 O 214.1358
C10 H14 N2 O3 210.1005 C14 H15 N2 211.1236 C11 H23 N3 O 213.1842 C15 H20 N 214.1597
C10 H16 N3 O2 210.1244 C14 H27 O 211.2063 C11 H25 N4 213.2081 C16 H22 214.1722
C10 H18 N4 O 210.1482 C14 H29 N 211.2301 C12 H9 N2 O2 213.0664 215
C11 H14 O4 210.0892 C15 H15 O 211.1123 C12 H11 N3 O 213.0903 C9 H15 N2 O4 215.1032
C11 H16 NO3 210.1131 C15 H17 N 211.1362 C12 H13 N4 213.1142 C9 H17 N3 O3 215.1271
C11 H18 N2 O2 210.1369 C15 H31 211.2427 C12 H21 O3 213.1491 C9 H19 N4 O2 215.1509
C11 H20 N3 O 210.1608 C16 H19 211.1488 C12 H23 NO2 213.1730 C10 H7 N4 O2 215.0570
C11 H22 N4 210.1846 212 C12 H25 N2 O 213.1968 C10 H17 NO4 215.1158
C12 H8 N3 O 210.0668 C9 H12 N2 O4 212.0797 C12 H27 N3 213.2207 C10 H19 N2 O3 215.1396
C12 H10 N4 210.0907 C9 H14 N3 O3 212.1036 C13 H9 O3 213.0552 C10 H21 N3 O2 215.1635
C12 H18 O3 210.1256 C9 H16 N4 O2 212.1275 C13 H11 NO2 213.0790 C10 H23 N4 O 215.1873
C12 H20 NO2 210.1495 C10 H14 NO4 212.0923 C13 H13 N2 O 213.1029 C11 H7 N2 O3 215.0457
C12 H22 N2 O 210.1733 C10 H16 N2 O3 212.1162 C13 H15 N3 213.1267 C11 H9 N3 O2 215.0695
C12 H24 N3 210.1972 C10 H18 N3 O2 212.1400 C13 H25 O2 213.1855 C11 H11 N4 O 215.0934
C13 H8 NO2 210.0555 C10 H20 N4 O 212.1639 C13 H27 NO 213.2094 C11 H19 O4 215.1284
C13 H10 N2 O 210.0794 C11 H8 N4 O 212.0699 C13 H29 N2 213.2332 C11 H21 NO3 215.1522
C13 H12 N3 210.1032 C11 H16 O4 212.1049 C14 H13 O2 213.0916 C11 H23 N2 O2 215.1761
C13 H22 O2 210.1620 C11 H18 NO3 212.1287 C14 H15 NO 213.1154 C11 H25 N3 O 215.1999
C13 H24 NO 210.1859 C11 H20 N2 O2 212.1526 C14 H17 N2 213.1393 C11 H27 N4 215.2238
C13 H26 N2 210.2098 C11 H22 N3 O 212.1764 C14 H29 O 213.2219 C12 H9 NO3 215.0583
C14 H10 O2 210.0681 C11 H24 N4 212.2003 C15 H17 O 213.1280 C12 H11 N2 O2 215.0821
C14 H12 NO 210.0919 C12 H8 N2 O2 212.0586 C15 H19 N 213.1519 C12 H13 N3 O 215.1060
C14 H14 N2 210.1158 C12 H10 N3 O 212.0825 C16 H21 213.1644 C12 H15 N4 215.1298
C14 H26 O 210.1985 C12 H12 N4 212.1063 214 C12 H23 O3 215.1648
C14 H28 N 210.2223 C12 H20 O3 212.1413 C9 H14 N2 O4 214.0954 C12 H25 NO2 215.1886
C15 H14 O 210.1045 C12 H22 NO2 212.1651 C9 H16 N3 O3 214.1193 C12 H27 N2 O 215.2125
C15 H16 N 210.1284 C12 H24 N2 O 212.1890 C9 H18 N4 O2 214.1431 C12 H29 N3 215.2363
C15 H30 210.2349 C12 H26 N3 212.2129 C10 H16 NO4 214.1080 C13 H11 O3 215.0708
 Silverstein c01.tex V3 - 07/10/2014 3:46 P.M. Page 61

APPENDIX A 61

APPENDIX A (Continued)

FM FM FM FM

C13 H13 NO2 215.0947 C11 H7 NO4 217.0375 C14 H22 N2 218.1784 C11 H16 N4 O 220.1325
C13 H15 N2 O 215.1185 C11 H9 N2 O3 217.0614 C15 H10 N2 218.0845 C12 H12 O4 220.0735
C13 H17 N3 215.1424 C11 H11 N3 O2 217.0852 C15 H22 O 218.1671 C12 H14 NO3 220.0974
C14 H15 O2 215.1072 C11 H13 N4 O 217.1091 C15 H24 N 218.1910 C12 H16 N2 O2 220.1213
C14 H17 NO 215.1311 C11 H21 O4 217.1440 C16 H10 O 218.0732 C12 H18 N3 O 220.1451
C14 H19 N2 215.1549 C11 H23 NO3 217.1679 C16 H12 N 218.0970 C12 H20 N4 220.1690
C15 H19 O 215.1436 C11 H25 N2 O2 217.1917 C16 H26 218.2036 C13 H8 N4 220.0750
C15 H21 N 215.1675 C11 H27 N3 O 217.2156 C17 H14 218.1096 C13 H16 O3 220.1100
C16 H23 215.1801 C12 H9 O4 217.0501 219 C13 H18 NO2 220.1338
216 C12 H11 NO3 217.0739 C9 H19 N2 O4 219.1345 C13 H20 N2 O 220.1577
C9 H16 N2 O4 216.1111 C12 H13 N2 O2 217.0978 C9 H21 N3 O3 219.1584 C13 H22 N3 220.1815
C9 H18 N3 O3 216.1349 C12 H15 N3 O 217.1216 C9 H23 N4 O2 219.1822 C14 H10 N3 220.0876
C9 H20 N4 O2 216.1588 C12 H17 N4 217.1455 C10 H7 N2 O4 219.0406 C14 H20 O2 220.1464
C10 H8 N4 O2 216.0648 C12 H25 O3 217.1804 C10 H9 N3 O3 219.0644 C14 H22 NO 220.1702
C10 H18 NO4 216.1236 C12 H27 NO2 217.2043 C10 H11 N4 O2 219.0883 C14 H24 N2 220.1941
C10 H20 N2 O3 216.1475 C13 H13 O3 217.0865 C10 H21 NO4 219.1471 C15 H10 NO 220.0763
C10 H22 N3 O2 216.1713 C13 H15 NO2 217.1103 C10 H23 N2 O3 219.1710 C15 H12 N2 220.1001
C10 H24 N4 O 216.1952 C13 H17 N2 O 217.1342 C10 H25 N3 O2 219.1948 C15 H24 O 220.1828
C11 H8 N2 O3 216.0535 C13 H19 N3 217.1580 C11 H9 NO4 219.0532 C15 H26 N 220.2067
C11 H10 N3 O2 216.0774 C14 H17 O2 217.1229 C11 H11 N2 O3 219.0770 C16 H12 O 220.0888
C11 H12 N4 O 216.1012 C14 H19 NO 217.1467 C11 H13 N3 O2 219.1009 C16 H14 N 220.1127
C11 H20 O4 216.1362 C14 H21 N2 217.1706 C11 H15 N4 O 219.1247 C16 H28 220.2192
C11 H22 NO3 216.1600 C15 H9 N2 217.0767 C11 H23 O4 219.1597 C17 H16 220.1253
C11 H24 N2 O2 216.1839 C15 H21 O 217.1593 C11 H25 NO3 219.1835 221
C11 H26 N3 O 216.2077 C15 H23 N 217.1832 C12 H11 O4 219.0657 C9 H21 N2 O4 221.1502
C11 H28 N4 216.2316 C16 H11 N 217.0892 C12 H13 NO3 219.0896 C9 H23 N3 O3 221.1741
C12 H8 O4 216.0422 C16 H25 217.1957 C12 H15 N2 O2 219.1134 C10 H9 N2 O4 221.0563
C12 H10 NO3 216.0661 C17 H13 217.1018 C12 H17 N3 O 219.1373 C10 H11 N3 O3 221.0801
C12 H12 N2 O2 216.0899 218 C12 H19 N4 219.1611 C10 H13 N4 O2 221.1040
C12 H14 N3 O 216.1138 C9 H18 N2 O4 218.1267 C13 H15 O3 219.1021 C10 H23 NO4 221.1628
C12 H16 N4 216.1377 C9 H20 N3 O3 218.1506 C13 H17 NO2 219.1260 C11 H11 NO4 221.0688
C12 H24 O3 216.1726 C9 H22 N4 O2 218.1744 C13 H19 N2 O 219.1498 C11 H13 N2 O3 221.0927
C12 H26 NO2 216.1965 C10 H8 N3 O3 218.0566 C13 H21 N3 219.1737 C11 H15 N3 O2 221.1165
C12 H28 N2 O 216.2203 C10 H10 N4 O2 218.0805 C14 H9 N3 219.0798 C11 H17 N4 O 221.1404
C13 H12 O3 216.0786 C10 H20 NO4 218.1393 C14 H19 O2 219.1385 C12 H13 O4 221.0814
C13 H14 NO2 216.1025 C10 H22 N2 O3 218.1631 C14 H21 NO 219.1624 C12 H15 NO3 221.1052
C13 H16 N2 O 216.1264 C10 H24 N3 O2 218.1870 C14 H23 N2 219.1863 C12 H17 N2 O2 221.1291
C13 H18 N3 216.1502 C10 H26 N4 O 218.2108 C15 H9 NO 219.0684 C12 H19 N3 O 221.1529
C13 H28 O2 216.2090 C11 H8 NO4 218.0453 C15 H11 N2 219.0923 C12 H21 N4 221.1768
C14 H16 O2 216.1151 C11 H10 N2 O3 218.0692 C15 H23 O 219.1750 C13 H9 N4 221.0829
C14 H18 NO 216.1389 C11 H12 N3 O2 218.0930 C15 H25 N 219.1988 C13 H17 O3 221.1178
C14 H20 N2 216.1628 C11 H14 N4 O 218.1169 C16 H11 O 219.0810 C13 H19 NO2 221.1416
C15 H20 O 216.1515 C11 H22 O4 218.1518 C16 H13 N 219.1049 C13 H21 N2 O 221.1655
C15 H22 N 216.1753 C11 H24 NO3 218.1757 C16 H27 219.2114 C13 H23 N3 221.1894
C16 H10 N 216.0814 C11 H26 N2 O2 218.1996 C17 H15 219.1174 C14 H9 N2 O 221.0715
C16 H24 216.1879 C12 H10 O4 218.0579 220 C14 H11 N3 221.0954
C17 H12 216.0939 C12 H12 NO3 218.0817 C9 H20 N2 O4 220.1424 C14 H21 O2 221.1542
217 C12 H14 N2 O2 218.1056 C9 H22 N3 O3 220.1662 C14 H23 NO 221.1781
C9 H17 N2 O4 217.1189 C12 H16 N3 O 218.1295 C9 H24 N4 O2 220.1901 C14 H25 N2 221.2019
C9 H19 N3 O3 217.1427 C12 H18 N4 218.1533 C10 H8 N2 O4 220.0484 C15 H9 O2 221.0603
C9 H21 N4 O2 217.1666 C12 H26 O3 218.1883 C10 H10 N3 O3 220.0723 C15 H11 NO 221.0841
C10 H7 N3 O3 217.0488 C13 H14 O3 218.0943 C10 H12 N4 O2 220.0961 C15 H13 N2 221.1080
C10 H9 N4 O2 217.0726 C13 H16 NO2 218.1182 C10 H22 NO4 220.1549 C15 H25 O 221.1906
C10 H19 NO4 217.1315 C13 H18 N2 O 218.1420 C10 H24 N2 O3 220.1788 C15 H27 N 221.2145
C10 H21 N2 O3 217.1553 C13 H20 N3 218.1659 C11 H10 NO4 220.0610 C16 H13 O 221.0967
C10 H23 N3 O2 217.1791 C14 H18 O2 218.1307 C11 H12 N2 O3 220.0848 C16 H15 N 221.1205
C10 H25 N4 O 217.2030 C14 H20 NO 218.1546 C11 H14 N3 O2 220.1087 C16 H29 221.2270
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62 CHAPTER 1 MASS SPECTROMETRY

APPENDIX A (Continued)

FM FM FM FM

C17 H17 221.1331 C14 H9 NO2 223.0634 C11 H21 N4 O 225.1717 C14 H28 NO 226.2172
222 C14 H11 N2 O 223.0872 C12 H9 N4 O 225.0777 C14 H30 N2 226.2411
C9 H22 N2 O4 222.1580 C14 H13 N3 223.1111 C12 H17 O4 225.1127 C15 H14 O2 226.0994
C10 H10 N2 O4 222.0641 C14 H23 O2 223.1699 C12 H19 NO3 225.1365 C15 H16 NO 226.1233
C10 H12 N3 O3 222.0879 C14 H25 NO 223.1937 C12 H21 N2 O2 225.1604 C15 H18 N2 226.1471
C10 H14 N4 O2 222.1118 C14 H27 N2 223.2176 C12 H23 N3 O 225.1842 C15 H30 O 226.2298
C11 H12 NO4 222.0766 C15 H11 O2 223.0759 C12 H25 N4 225.2081 C15 H32 N 226.2536
C11 H14 N2 O3 222.1005 C15 H13 NO 223.0998 C13 H9 N2 O2 225.0664 C16 H18 O 226.1358
C11 H16 N3 O2 222.1244 C15 H27 O 223.2063 C13 H11 N3 O 225.0903 C16 H20 N 226.1597
C11 H18 N4 O 222.1482 C15 H29 N 223.2301 C13 H13 N4 225.1142 C16 H34 226.2662
C11 N3 O3 221.9940 C16 H15 O 223.1123 C13 H21 O3 225.1491 C17 H22 226.1722
C12 H14 O4 222.0892 C16 H17 N 223.1362 C13 H23 NO2 225.1730 227
C12 H16 NO3 222.1131 C16 H31 223.2427 C13 H25 N2 O 225.1968 C10 H15 N2 O4 227.1032
C12 H18 N2 O2 222.1369 C17 H19 223.1488 C13 H27 N3 225.2207 C10 H17 N3 O3 227.1271
C12 H20 N3 O 222.1608 224 C14 H9 O3 225.0552 C10 H19 N4 O2 227.1509
C12 H22 N4 222.1846 C10 H12 N2 O4 224.0797 C14 H11 NO2 225.0790 C11 H17 NO4 227.1158
C13 H8 N3 O 222.0668 C10 H14 N3 O3 224.1036 C14 H13 N2 O 225.1029 C11 H21 N3 O2 227.1635
C13 H10 N4 222.0907 C10 H16 N4 O2 224.1275 C14 H15 N3 225.1267 C11 H23 N4 O 227.1873
C13 H18 O3 222.1256 C11 H14 NO4 224.0923 C14 H25 O2 225.1855 C12 H7 N2 O3 227.0457
C13 H20 NO2 222.1495 C11 H16 N2 O3 224.1162 C14 H27 NO 225.2094 C12 H9 N3 O2 227.0695
C13 H22 N2 O 222.1733 C11 H18 N3 O2 224.1400 C14 H29 N2 225.2332 C12 H11 N4 O 227.0934
C13 H24 N3 222.1972 C11 H20 N4 O 224.1639 C15 H13 O2 225.0916 C12 H19 O4 227.1284
C14 H10 N2 O 222.0794 C12 H8 N4 O 224.0699 C15 H15 NO 225.1154 C12 H21 NO3 227.1522
C14 H12 N3 222.1032 C12 H16 O4 224.1049 C15 H17 N2 225.1393 C12 H23 N2 O2 227.1761
C14 H22 O2 222.1620 C12 H18 NO3 224.1287 C15 H29 O 225.2219 C12 H25 N3 O 227.1999
C14 H24 NO 222.1859 C12 H20 N2 O2 224.1526 C15 H31 N 225.2458 C12 H27 N4 227.2238
C14 H26 N2 222.2098 C12 H22 N3 O 224.1764 C16 H17 O 225.1280 C13 H9 NO3 227.0583
C15 H10 O2 222.0681 C12 H24 N4 224.2003 C16 H19 N 225.1519 C13 H11 N2 O2 227.0821
C15 H12 NO 222.0919 C13 H8 N2 O2 224.0586 C16 H33 225.2584 C13 H13 N3 O 227.1060
C15 H14 N2 222.1158 C13 H10 N3 O 224.0825 C17 H21 225.1644 C13 H15 N4 227.1298
C15 H26 O 222.1985 C13 H12 N4 224.1063 226 C13 H25 NO2 227.1886
C15 H28 N 222.2223 C13 H20 O3 224.1413 C10 H14 N2 O4 226.0954 C13 H27 N2 O 227.2125
C16 H14 O 222.1045 C13 H22 NO2 224.1651 C10 H16 N3 O3 226.1193 C13 H29 N3 227.2363
C16 H16 N 222.1284 C13 H24 N2 O 224.1890 C10 H18 N4 O2 226.1431 C14 H11 O3 227.0708
C16 H30 222.2349 C13 H26 N3 224.2129 C11 H16 NO4 226.1080 C14 H13 NO2 227.0947
C16 NO 221.9980 C14 H10 NO2 224.0712 C11 H18 N2 O3 226.1318 C14 H15 N2 O 227.1185
C17 H18 222.1409 C14 H12 N2 O 224.0950 C11 H20 N3 O2 226.1557 C14 H17 N3 227.1424
223 C14 H14 N3 224.1189 C11 H22 N4 O 226.1795 C14 H27 O2 227.2012
C10 H11 N2 O4 223.0719 C14 H24 O2 224.1777 C12 H8 N3 O2 226.0617 C14 H29 NO 227.2250
C10 H13 N3 O3 223.0958 C14 H26 NO 224.2015 C12 H10 N4 O 226.0856 C15 H15 O2 227.1072
C10 H15 N4 O2 223.1196 C14 H28 N2 224.2254 C12 H18 O4 226.1205 C15 H17 NO 227.1311
C11 H13 NO4 223.0845 C15 H12 O2 224.0837 C12 H20 NO3 226.1444 C15 H19 N2 227.1549
C11 H15 N2 O3 223.1083 C15 H14 NO 224.1076 C12 H22 N2 O2 226.1682 C15 H31 O 227.2376
C11 H17 N3 O2 223.1322 C15 H16 N2 224.1315 C12 H24 N3 O 226.1929 C15 H33 N 227.2615
C11 H19 N4 O 223.1560 C15 H28 O 224.2141 C12 H26 N4 226.2160 C16 H19 O 227.1436
C12 H7 N4 O 223.0621 C15 H30 N 224.2380 C13 H10 N2 O2 226.0743 C16 H21 N 227.1675
C12 H15 O4 223.0970 C16 H16 O 224.1202 C13 H12 N3 O 226.0981 C17 H23 227.1801
C12 H17 NO3 223.1209 C16 H18 N 224.1440 C13 H14 N4 226.1220 228
C12 H19 N2 O2 223.1447 C16 H32 224.2505 C13 H22 O3 226.1569 C10 H16 N2 O2 228.1111
C12 H21 N3 O 223.1686 C17 H20 224.1566 C13 H24 NO2 226.1808 C10 H18 N3 O3 228.1349
C12 H23 N4 223.1925 225 C13 H26 N2 O 226.2046 C10 H20 N4 O2 228.1588
C13 H9 N3 O 223.0746 C10 H13 N2 O4 225.0876 C13 H28 N3 226.2285 C11 H8 N4 O2 228.0648
C13 H11 N4 223.0985 C10 H15 N3 O3 225.1114 C14 H10 O3 226.0630 C11 H18 NO4 228.1236
C13 H19 O3 223.1334 C10 H17 N4 O2 225.1353 C14 H12 NO2 226.0868 C11 H20 N2 O3 228.1475
C13 H21 NO2 223.1573 C11 H15 NO4 225.1001 C14 H14 N2 O 226.1107 C11 H22 N3 O2 228.1713
C13 H23 N2 O 223.1811 C11 H17 N2 O3 225.1240 C14 H16 N3 226.1346 C11 H24 N4 O 228.1952
C13 H25 N3 223.2050 C11 H19 N3 O2 225.1478 C14 H26 O2 226.1934 C12 H8 N2 O3 228.0535
 Silverstein c01.tex V3 - 07/10/2014 3:46 P.M. Page 63

APPENDIX A 63

APPENDIX A (Continued)

FM FM FM FM

C12 H12 N4 O 228.1012 C14 H15 NO2 229.1103 C10 H23 N4 O2 231.1822 C13 H20 N4 232.1690
C12 H20 O4 228.1362 C14 H17 N2 O 229.1342 C11 H7 N2 O4 231.0406 C13 H28 O3 232.2039
C12 H22 NO3 228.1600 C14 H19 N3 229.1580 C11 H9 N3 O3 231.0644 C14 H16 O3 232.1100
C12 H24 N2 O2 228.1839 C14 H29 O2 229.2168 C11 H11 N4 O2 231.0883 C14 H18 NO2 232.1338
C12 H26 N3 O 228.2077 C14 H31 NO 229.2407 C11 H21 NO4 231.1471 C14 H20 N2 O 232.1577
C12 H28 N4 228.2316 C15 H17 O2 229.1229 C11 H23 N2 O3 231.1710 C14 H22 N3 232.1815
C13 H8 O4 228.0422 C15 H19 NO 229.1467 C11 H25 N3 O2 231.1948 C15 H10 N3 232.0876
C13 H10 NO3 228.0661 C15 H21 N2 229.1706 C11 H27 N4 O 231.2187 C15 H20 O2 232.1464
C13 H12 N2 O2 228.0899 C16 H21 O 229.1593 C12 H9 NO4 231.0532 C15 H22 NO 232.1702
C13 H14 N3 O 228.1138 C16 H23 N 229.1832 C12 H11 N2 O3 231.0770 C15 H24 N2 232.1941
C13 H24 O3 228.1726 C17 H9 O 229.0653 C12 H13 N3 O2 231.1009 C16 H10 NO 232.0768
C13 H26 NO2 228.1965 C17 H11 N 229.0892 C12 H15 N4 O 231.1247 C16 H12 N2 232.1001
C13 H28 N2 O 228.2203 C18 H13 229.1018 C12 H23 O4 231.1597 C16 H24 O 232.1828
C13 H30 N3 228.2442 230 C12 H25 NO3 231.1835 C16 H26 N 232.2067
C14 H12 O3 228.0786 C10 H18 N2 O4 230.1267 C12 H27 N2 O2 231.2074 C17 H12 O 232.0888
C14 H14 NO2 228.1025 C10 H20 N3 O3 230.1506 C12 H29 N3 O 231.2312 C17 H14 N 232.1127
C14 H16 N2 O 228.1264 C10 H22 N4 O2 230.1744 C13 H11 O4 231.0657 C17 H28 232.2192
C14 H18 N3 228.1502 C11 H8 N3 O3 230.0566 C13 H13 NO3 231.0896 C18 H16 232.1253
C14 H28 O2 228.2090 C11 H10 N4 O2 230.0805 C13 H15 N2 O2 231.1134 233
C14 H30 NO 228.2329 C11 H20 NO4 230.1393 C13 H17 N3 O 231.1373 C10 H23 N3 O3 233.1741
C14 H32 N2 228.2567 C11 H22 N2 O3 230.1631 C13 H19 N4 231.1611 C10 H25 N4 O2 233.1979
C15 H16 O2 228.1151 C11 H24 N3 O2 230.1870 C14 H15 O3 231.1021 C11 H9 N2 O4 233.0563
C15 H18 NO 228.1389 C11 H26 N4 O 230.2108 C14 H17 NO2 231.1260 C11 H11 N3 O3 233.0801
C15 H20 N2 228.1628 C12 H8 NO4 230.0453 C14 H19 N2 O 231.1498 C11 H23 NO4 233.1628
C15 H32 O 228.2454 C12 H10 N2 O3 230.0692 C14 H21 N3 231.1737 C11 H25 N2 O3 233.1866
C16 H20 O 228.1515 C12 H12 N3 O2 230.0930 C15 H9 N3 231.0798 C11 H27 N3 O2 233.2105
C16 H22 N 228.1753 C12 H14 N4 O 230.1169 C15 H19 O2 231.1385 C12 H11 NO4 233.0688
C17 H10 N 228.0814 C12 H22 O4 230.1518 C15 H21 NO 231.1624 C12 H13 N2 O3 233.0927
C17 H24 228.1879 C12 H24 NO3 230.1757 C15 H23 N2 231.1863 C12 H15 N3 O2 233.1165
C18 H12 228.0939 C12 H26 N2 O2 230.1996 C16 H9 NO 231.0684 C12 H17 N4 O 233.1404
229 C12 H28 N3 O 230.2234 C16 H11 N2 231.0923 C12 H25 O4 233.1753
C10 H17 N2 O4 229.1189 C12 H30 N4 230.2473 C16 H23 O 231.1750 C12 H27 NO3 233.1992
C10 H19 N3 O3 229.1427 C13 H10 O4 230.0579 C17 H11 O 231.0810 C13 H13 O4 233.0814
C10 H21 N4 O2 229.1666 C13 H12 NO3 230.0817 C17 H13 N 231.1049 C13 H15 NO3 233.1052
C11 H7 N3 O3 229.0488 C13 H14 N2 O2 230.1056 C17 H27 231.2114 C13 H17 N2 O2 233.1291
C11 H9 N4 O2 229.0726 C13 H16 N3 O 230.1295 C18 H15 231.1174 C13 H19 N3 O 233.1529
C11 H19 NO4 229.1315 C13 H18 N4 230.1533 232 C13 H21 N4 233.1768
C11 H21 N2 O3 229.1553 C13 H26 O3 230.1883 C10 H20 N2 O4 232.1424 C14 H9 N4 233.0829
C11 H23 N3 O2 229.1791 C13 H28 NO2 230.2121 C10 H22 N3 O3 232.1662 C14 H17 O3 233.1178
C11 H25 N4 O 229.2030 C13 H30 N2 O 230.2360 C10 H24 N4 O2 232.1901 C14 H19 NO2 233.1416
C12 H9 N2 O3 229.0614 C14 H14 O3 230.0943 C11 H8 N2 O4 232.0484 C14 H21 N2 O 233.1655
C12 H11 N3 O2 229.0852 C14 H16 NO2 230.1182 C11 H10 N3 O3 232.0723 C15 H9 N2 O 233.0715
C12 H13 N4 O 229.1091 C14 H18 N2 O 230.1420 C11 H12 N4 O2 232.0961 C15 H11 N3 233.0954
C12 H21 O4 229.1440 C14 H20 N3 230.1659 C11 H22 NO4 232.1549 C15 H21 O2 233.1542
C12 H23 NO3 229.1679 C14 H30 O2 230.2247 C11 H24 N2 O3 232.1788 C15 H23 NO 233.1781
C12 H25 N2 O2 229.1917 C15 H18 O2 230.1307 C11 H26 N3 O2 232.2026 C15 H25 N2 233.2019
C12 H27 N3 O 229.2156 C15 H20 NO 230.1546 C11 H28 N4 O 232.2265 C16 H9 O2 233.0603
C12 H29 N4 229.2394 C15 H22 N2 230.1784 C12 H10 NO4 232.0610 C16 H11 NO 233.0841
C13 H9 O4 229.0501 C16 H10 N2 230.0845 C12 H12 N2 O3 232.0848 C16 H13 N2 233.1080
C13 H11 NO3 229.0739 C16 H22 O 230.1671 C12 H14 N3 O2 232.1087 C16 H25 O 233.1906
C13 H13 N2 O2 229.0978 C16 H24 N 230.1910 C12 H16 N4 O 232.1325 C16 H27 N 233.2145
C13 H15 N3 O 229.1216 C17 H10 O 230.0732 C12 H24 O4 232.1675 C17 H13 O 233.0967
C13 H17 N4 229.1455 C17 H12 N 230.0970 C12 H26 NO3 232.1914 C17 H15 N 233.1205
C13 H25 O3 229.1804 C17 H26 230.2036 C12 H28 N2 O2 232.2152 C17 H29 233.2270
C13 H27 NO2 229.2043 C18 H14 230.1096 C13 H12 O4 232.0735 C18 H17 233.1331
C13 H29 N2 O 229.2281 231 C13 H14 NO3 232.0974 234
C13 H31 N3 229.2520 C10 H19 N2 O4 231.1345 C13 H16 N2 O2 232.1213 C10 H22 N2 O4 234.1580
C14 H13 O3 229.0865 C10 H21 N3 O3 231.1584 C13 H18 N3 O 232.1451 C10 H24 N3 O3 234.1819
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64 CHAPTER 1 MASS SPECTROMETRY

APPENDIX A (Continued)

FM FM FM FM

C10 H26 N4 O2 234.2057 C15 H13 N3 235.1111 C12 H21 N4 O 237.1717 C15 H30 N2 238.2411
C11 H10 N2 O4 234.0641 C15 H23 O2 235.1699 C13 H9 N4 O 237.0777 C16 H14 O2 238.0994
C11 H12 N3 O3 234.0879 C15 H25 NO 235.1937 C13 H17 O4 237.1127 C16 H16 NO 238.1233
C11 H14 N4 O2 234.1118 C15 H27 N2 235.2176 C13 H19 NO3 237.1365 C16 H18 N2 238.1471
C11 H24 NO4 234.1706 C16 H11 O2 235.0759 C13 H21 N2 O2 237.1604 C16 H30 O 238.2298
C11 H26 N2 O3 234.1945 C16 H13 NO 235.0998 C13 H23 N3 O 237.1842 C16 H32 N 238.2536
C12 H12 NO4 234.0766 C16 H15 N2 235.1236 C13 H25 N 237.2081 C17 H18 O 238.1358
C12 H14 N2 O3 234.1005 C16 H27 O 235.2063 C14 H9 N2 O2 237.0664 C17 H20 N 238.1597
C12 H16 N3 O2 234.1244 C16 H29 N 235.2301 C14 H11 N3 O 237.0903 C17 H34 238.2662
C12 H18 N4 O 234.1482 C17 H15 O 235.1123 C14 H13 N4 237.1142 C18 H22 238.1722
C12 H26 O4 234.1832 C17 H17 N 235.1362 C14 H21 O3 237.1491 239
C13 H14 O4 234.0892 C17 H31 235.2427 C14 H23 NO2 237.1730 C11 H15 N2 O4 239.1032
C13 H16 NO3 234.1131 C18 H19 235.1488 C14 H25 N2 O 237.1968 C11 H17 N3 O3 239.1271
C13 H18 N2 O2 234.1369 236 C14 H27 N3 237.2207 C11 H19 N4 O2 239.1509
C13 H20 N3 O 234.1608 C10 H24 N2 O4 236.1737 C15 H9 O3 237.0552 C12 H17 NO4 239.1158
C13 H22 N4 234.1846 C11 H12 N2 O4 236.0797 C15 H11 NO2 237.0790 C12 H19 N2 O3 239.1396
C14 H10 N4 234.0907 C11 H14 N3 O3 236.1036 C15 H13 N2 O 237.1029 C12 H21 N3 O2 239.1635
C14 H18 O3 234.1256 C11 H16 N4 O2 236.1275 C15 H15 N3 237.1267 C12 H23 N4 O 239.1873
C14 H20 NO2 234.1495 C12 H2 N3 O3 236.0096 C15 H25 O2 237.1855 C13 H9 N3 O2 239.0695
C14 H22 N2 O 234.1733 C12 H4 N4 O2 236.0335 C15 H27 NO 237.2094 C13 H11 N4 O 239.0934
C14 H24 N3 234.1972 C12 H14 NO4 236.0923 C15 H29 N2 237.2332 C13 H19 O4 239.1284
C15 H10 N2 O 234.0794 C12 H16 N2 O3 236.1162 C16 H13 O2 237.0916 C13 H21 NO3 239.1522
C15 H12 N3 234.1032 C12 H18 N3 O2 236.1400 C16 H15 NO 237.1154 C13 H23 N2 O2 239.1761
C15 H22 O2 234.1620 C12 H20 N4 O 236.1639 C16 H17 N2 237.1393 C13 H25 N3 O 239.1999
C15 H24 NO 234.1859 C13 H8 N4 O 236.0699 C16 H29 O 237.2219 C13 H27 N4 239.2238
C15 H26 N2 234.2098 C13 H16 O4 236.1049 C16 H31 N 237.2458 C14 H9 NO3 239.0583
C16 H10 O2 234.0681 C13 H18 NO3 236.1287 C17 H17 O 237.1280 C14 H11 N2 O2 239.0821
C16 H12 NO 234.0919 C13 H20 N2 O2 236.1526 C17 H19 N 237.1519 C14 H13 N3 O 239.1060
C16 H14 N2 234.1158 C13 H22 N3 O 236.1764 C17 H33 237.2584 C14 H15 N4 239.1298
C16 H26 O 234.1985 C13 H24 N4 236.2003 C18 H21 237.1644 C14 H23 O3 239.1648
C16 H28 N 234.2223 C14 H10 N3 O 236.0825 238 C14 H25 NO2 239.1886
C17 H16 N 234.1284 C14 H12 N4 236.1063 C11 H14 N2 O4 238.0954 C14 H27 N2 O 239.2125
C17 H30 234.2349 C14 H20 O3 236.1413 C11 H16 N3 O3 238.1193 C14 H29 N3 239.2363
C18 H18 234.1409 C14 H22 NO2 236.1651 C11 H18 N4 O2 238.1431 C15 H11 O3 239.0708
235 C14 H24 N2 O 236.1890 C12 H16 NO4 238.1080 C15 H13 NO2 239.0947
C10 H23 N2 O4 235.1659 C14 H26 N3 236.2129 C12 H18 N2 O3 238.1318 C15 H15 N2 O 239.1185
C10 H25 N3 O3 235.1897 C15 H10 NO2 236.0712 C12 H20 N3 O2 238.1557 C15 H17 N3 239.1424
C11 H11 N2 O4 235.0719 C15 H12 N2 O 236.0950 C12 H22 N4 O 238.1795 C15 H27 O2 239.2012
C11 H13 N3 O3 235.0958 C15 H14 N3 236.1189 C13 H8 N3 O2 238.0617 C15 H29 NO 239.2250
C11 H15 N4 O2 235.1196 C15 H24 O2 236.1777 C13 H10 N4 O 238.0856 C15 H31 N2 239.2489
C11 H25 NO4 235.1784 C15 H26 NO 236.2015 C13 H18 O4 238.1205 C16 H15 O2 239.1072
C12 H13 NO4 235.0845 C15 H28 N2 236.2254 C13 H20 NO3 238.1444 C16 H17 NO 239.1311
C12 H15 N2 O3 235.1083 C16 H12 O2 236.0837 C13 H22 N2 O2 238.1682 C16 H19 N2 239.1549
C12 H17 N3 O2 235.1322 C16 H14 NO 236.1076 C13 H24 N3 O 238.1921 C16 H31 O 239.2376
C12 H19 N4 O 235.1560 C16 H16 N2 236.1315 C13 H26 N4 238.2160 C16 H33 N 239.2615
C13 H15 O4 235.0970 C16 H28 O 236.2141 C14 H10 N2 O2 238.0743 C17 H19 O 239.1436
C13 H17 NO3 235.1209 C16 H30 N 236.2380 C14 H12 N3 O 238.0981 C17 H21 N 239.1675
C13 H19 N2 O2 235.1447 C17 H16 O 236.1202 C14 H14 N4 238.1220 C17 H35 239.2740
C13 H21 N3 O 235.1686 C17 H18 N 236.1440 C14 H22 O3 238.1569 C18 H23 239.1801
C13 H23 N4 235.1925 C17 H32 236.2505 C14 H24 NO2 238.1808 240
C14 H9 N3 O 235.0746 C18 H20 236.1566 C14 H26 N2 O 238.2046 C11 H16 N2 O4 240.1111
C14 H11 N4 235.0985 237 C14 H28 N3 238.2285 C11 H18 N3 O3 240.1349
C14 H19 O3 235.1334 C11 H13 N2 O4 237.0876 C15 H10 O3 238.0630 C11 H20 N4 O2 240.1588
C14 H21 NO2 235.1573 C11 H15 N3 O3 237.1114 C15 H12 NO2 238.0868 C12 H8 N4 O2 240.0648
C14 H23 N2 O 235.1811 C11 H17 N4 O2 237.1353 C15 H14 N2 O 238.1107 C12 H18 NO4 240.1236
C14 H25 N3 235.2050 C12 H15 NO4 237.1001 C15 H16 N3 238.1346 C12 H20 N2 O3 240.1475
C15 H9 NO2 235.0634 C12 H17 N2 O3 237.1240 C15 H26 O2 238.1934 C12 H22 N3 O2 240.1713
C15 H11 N2 O 235.0872 C12 H19 N3 O2 237.1478 C15 H28 NO 238.2172 C12 H24 N4 O 240.1952
 Silverstein c01.tex V3 - 07/10/2014 3:46 P.M. Page 65

APPENDIX A 65

APPENDIX A (Continued)

FM FM FM FM

C13 H8 N2 O3 240.0535 C15 H17 N2 O 241.1342 C17 H24 N 242.1910 C12 H24 N2 O3 244.1788
C13 H10 N3 O2 240.0774 C15 H19 N3 241.1580 C18 H10 O 242.0732 C12 H26 N3 O2 244.2026
C13 H12 N4 O 240.1012 C15 H29 O2 241.2168 C18 H12 N 242.0970 C12 H28 N4 O 244.2265
C13 H20 O4 240.1362 C15 H31 NO 241.2407 C18 H26 242.2036 C13 H10 NO4 244.0610
C13 H22 NO3 240.1600 C15 H33 N2 241.2646 C19 H14 242.1096 C13 H12 N2 O3 244.0848
C13 H24 N2 O2 240.1839 C16 H17 O2 241.1229 243 C13 H14 N3 O2 244.1087
C13 H28 N4 240.2316 C16 H19 NO 241.1467 C11 H19 N2 O4 243.1345 C13 H16 N4 O 244.1325
C14 H8 O4 240.0422 C16 H21 N2 241.1706 C11 H21 N3 O3 243.1584 C13 H24 O4 244.1675
C14 H10 NO3 240.0661 C16 H33 O 241.2533 C11 H23 N4 O2 243.1822 C13 H26 NO3 244.1914
C14 H12 N2 O2 240.0899 C16 H35 N 241.2771 C12 H7 N2 O4 243.0406 C13 H28 N2 O2 244.2152
C14 H14 N3 O 240.1138 C17 H21 O 241.1593 C12 H9 N3 O3 243.0644 C13 H30 N3 O 244.2391
C14 H16 N4 240.1377 C17 H23 N 241.1832 C12 H11 N4 O2 243.0883 C13 H32 N4 244.2629
C14 H24 O3 240.1726 C18 H25 241.1957 C12 H21 NO4 243.1471 C14 H12 O4 244.0735
C14 H26 NO2 240.1965 242 C12 H23 N2 O3 243.1710 C14 H14 NO3 244.0974
C14 H28 N2 O 240.2203 C11 H18 N2 O4 242.1267 C12 H25 N3 O2 243.1948 C14 H16 N2 O2 244.1213
C14 H30 N3 240.2442 C11 H20 N3 O3 242.1506 C12 H27 N4 O 243.2187 C14 H18 N3 O 244.1451
C15 H12 O3 240.0786 C11 H22 N4 O2 242.1744 C13 H9 NO4 243.0532 C14 H20 N4 244.1690
C15 H14 NO2 240.1025 C12 H8 N3 O3 242.0566 C13 H11 N2 O3 243.0770 C14 H28 O3 244.2039
C15 H16 N2 O 240.1264 C12 H10 N4 O2 242.0805 C13 H13 N3 O2 243.1009 C14 H30 NO2 244.2278
C15 H18 N3 240.1502 C12 H20 NO4 242.1393 C13 H15 N4 O 243.1247 C14 H32 N2 O 244.2516
C15 H28 O2 240.2090 C12 H22 N2 O3 242.1631 C13 H23 O4 243.1597 C15 H16 O3 244.1100
C15 H30 NO 240.2329 C12 H24 N3 O2 242.1870 C13 H25 NO3 243.1835 C15 H18 NO2 244.1338
C15 H32 N2 240.2567 C12 H26 N4 O 242.2108 C13 H27 N2 O2 243.2074 C15 H20 N2 O 244.1577
C16 H16 O2 240.1151 C13 H8 NO4 242.0453 C13 H29 N3 O 243.2312 C15 H22 N3 244.1815
C16 H20 N2 240.1628 C13 H10 N2 O3 242.0692 C13 H31 N4 243.2551 C15 H32 O2 244.2403
C16 H18 NO 240.1389 C13 H12 N3 O2 242.0930 C14 H11 O4 243.0657 C16 H10 N3 244.0876
C16 H32 O 240.2454 C13 H14 N4 O 242.1169 C14 H13 NO3 243.0896 C16 H20 O2 244.1464
C16 H34 N 240.2693 C13 H22 O4 242.1518 C14 H15 N2 O2 243.1134 C16 H22 NO 244.1702
C17 H20 O 240.1515 C13 H24 NO3 242.1757 C14 H17 N3 O 243.1373 C16 H24 N2 244.1941
C17 H22 N 240.1753 C13 H26 N2 O2 242.1996 C14 H19 N4 243.1611 C17 H10 NO 244.0763
C17 H36 240.2819 C13 H28 N3 O 242.2234 C14 H27 O3 243.1961 C17 H12 N2 244.1001
C18 H24 240.1879 C13 H30 N4 242.2473 C14 H29 NO2 243.2199 C17 H24 O 244.1828
241 C14 H10 O4 242.0579 C14 H31 N2 O 243.2438 C17 H26 N 244.2067
C11 H17 N2 O4 241.1189 C14 H12 NO3 242.0817 C14 H33 N3 243.2677 C18 H12 O 244.0888
C11 H19 N3 O3 241.1427 C14 H14 N2 O2 242.1056 C15 H15 O3 243.1021 C18 H14 N 244.1127
C11 H21 N4 O2 241.1666 C14 H16 N3 O 242.1295 C15 H17 NO2 243.1260 C18 H28 244.2192
C12 H19 NO4 241.1315 C14 H18 N4 242.1533 C15 H19 N2 O 243.1498 C19 H16 244.1253
C12 H21 N2 O3 241.1553 C14 H26 O3 242.1883 C15 H21 N3 243.1737 245
C12 H23 N3 O2 241.1791 C14 H28 NO2 242.2121 C15 H31 O2 243.2325 C11 H21 N2 O4 245.1502
C12 H25 N4 O 241.2030 C14 H30 N2 O 242.2360 C15 H33 NO 243.2564 C11 H23 N3 O3 245.1741
C13 H11 N3 O2 241.0852 C14 H32 N3 242.2598 C16 H19 O2 243.1385 C11 H25 N4 O2 245.1979
C13 H13 N4 O 241.1091 C15 H14 O3 242.0943 C16 H21 NO 243.1624 C12 H9 N2 O4 245.0563
C13 H21 O4 241.1440 C15 H16 NO2 242.1182 C16 H23 N2 243.1863 C12 H11 N3 O3 245.0801
C13 H25 N2 O2 241.1679 C15 H18 N2 O 242.1420 C17 H23 O 243.1750 C12 H13 N4 O2 245.1040
C13 H25 N2 O2 241.1917 C15 H20 N3 242.1659 C17 H25 N 243.1988 C12 H23 NO4 245.1628
C13 H27 N3 O 241.2156 C15 H30 O2 242.2247 C18 H11 O 243.0810 C12 H25 N2 O3 245.1866
C13 H29 N4 241.2394 C15 H32 NO 242.2485 C18 H13 N 243.1049 C12 H27 N3 O2 245.2105
C14 H11 NO3 241.0739 C15 H34 N2 242.2724 C18 H27 243.2114 C12 H29 N4 O 245.2343
C14 H13 N2 O2 241.0978 C16 H18 O2 242.1307 C19 H15 243.1174 C13 H11 NO4 245.0688
C14 H15 N3 O 241.1216 C16 H20 NO 242.1546 244 C13 H13 N2 O3 245.0927
C14 H17 N4 241.1445 C16 H22 N2 242.1784 C11 H20 N2 O4 244.1424 C13 H15 N3 O2 245.1165
C14 H25 O3 241.1804 C16 H34 O 242.2611 C11 H22 N3 O3 244.1662 C13 H17 N4 O 245.1404
C14 H27 NO2 241.2043 C16 H18 O2 242.1307 C11 H24 N4 O2 244.1901 C13 H25 O4 245.1753
C14 H29 N2 O 241.2281 C16 H20 NO 242.1546 C12 H8 N2 O4 244.0484 C13 H27 NO3 245.1992
C14 H31 N3 241.2520 C16 H22 N2 242.1784 C12 H10 N3 O3 244.0723 C13 H29 N2 O2 245.2230
C15 H13 O3 241.0865 C16 H34 O 242.2611 C12 H12 N4 O2 244.0961 C13 H31 N3 O 245.2469
C15 H15 NO2 241.1103 C17 H22 O 242.1871 C12 H22 NO4 244.1549 C14 H13 O4 245.0814
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66 CHAPTER 1 MASS SPECTROMETRY

APPENDIX A (Continued)

FM FM FM FM

C14 H15 NO3 245.1052 C16 H26 N2 246.2098 C12 H14 N3 O3 248.1036 C15 H25 N2 O 249.1968
C14 H17 N2 O2 245.1291 C17 H10 O2 246.0681 C12 H16 N4 O2 248.1275 C15 H27 N3 249.2207
C14 H19 N3 O 245.1529 C17 H12 NO 246.0919 C12 H26 NO4 248.1863 C16 H11 NO2 249.0790
C14 H21 N4 245.1768 C17 H14 N2 246.1158 C12 H28 N2 O3 248.2101 C16 H13 N2 O 249.1029
C14 H29 O3 245.2117 C17 H26 O 246.1985 C13 H14 NO4 248.0923 C16 H15 N3 249.1267
C14 H31 NO2 245.2356 C17 H28 N 246.2223 C13 H16 N2 O3 248.1162 C16 H25 O2 249.1855
C15 H17 O3 245.1178 C18 H14 O 246.1045 C13 H18 N3 O2 248.1400 C16 H27 NO 249.2094
C15 H19 NO2 245.1416 C18 H16 N 246.1284 C13 H20 N4 O 248.1639 C16 H29 N2 249.2332
C15 H21 N2 O 245.1655 C18 H30 246.2349 C13 H28 O4 248.1988 C17 H13 O2 249.0916
C15 H23 N3 245.1894 C19 H18 246.1409 C14 H16 O4 248.1049 C17 H15 NO 249.1154
C16 H9 N2 O 245.0715 247 C14 H20 N2 O2 248.1526 C17 H17 N2 249.1393
C16 H11 N3 245.0954 C11 H23 N2 O4 247.1659 C14 H22 N3 O 248.1764 C17 H29 O 249.2219
C16 H21 O2 245.1542 C11 H25 N3 O3 247.1897 C14 H24 N4 248.2003 C17 H31 N 249.2458
C16 H23 NO 245.1781 C11 H27 N4 O2 247.2136 C15 H10 N3 O 248.0825 C18 H17 O 249.1280
C16 H25 N2 245.2019 C12 H11 N2 O4 247.0719 C15 H12 N4 248.1063 C18 H19 N 249.1519
C17 H11 NO 245.0841 C12 H13 N3 O3 247.0958 C15 H20 O3 248.1413 C18 H33 249.2584
C17 H13 N2 245.1080 C12 H15 N4 O2 247.1196 C15 H22 NO2 248.1651 C19 H21 249.1644
C17 H25 O 245.1906 C12 H25 NO4 247.1784 C15 H24 N2 O 248.1890 250
C17 H27 N 245.2145 C12 H27 N2 O3 247.2023 C15 H26 N3 248.2129 C11 H26 N2 O4 250.1894
C18 H13 O 245.0967 C12 H29 N3 O2 247.2261 C16 H10 NO2 248.0712 C12 H14 N2 O4 250.0954
C18 H15 N 245.1205 C13 H13 NO4 247.0845 C16 H12 N2 O 248.0950 C12 H16 N3 O3 250.1193
C18 H29 245.2270 C13 H15 N2 O3 247.1083 C16 H14 N3 248.1189 C12 H18 N4 O2 250.1431
C19 H17 245.1331 C13 H17 N3 O2 247.1322 C16 H24 O2 248.1777 C13 H16 NO4 250.1080
246 C13 H19 N4 O 247.1560 C16 H26 NO 248.2015 C13 H18 N2 O3 250.1318
C11 H22 N2 O4 246.1580 C13 H27 O4 247.1910 C16 H28 N2 248.2254 C13 H20 N3 O2 250.1557
C11 H24 N3 O3 246.1819 C13 H29 NO3 247.2148 C17 H12 O2 248.0837 C13 H22 N4 O 250.1795
C11 H26 N4 O2 246.2057 C14 H15 O4 247.0970 C17 H14 NO 248.1076 C14 H10 N4 O 250.0856
C12 H10 N2 O4 246.0641 C14 H17 NO3 247.1209 C17 H16 N2 248.1315 C14 H20 NO3 250.1444
C12 H12 N3 O3 246.0879 C14 H19 N2 O2 247.1448 C17 H28 O 248.2141 C14 H22 N2 O2 250.1682
C12 H14 N4 O2 246.1118 C14 H21 N3 O 247.1686 C17 H30 N 248.2380 C14 H24 N3 O 250.1921
C12 H24 NO4 246.1706 C14 H23 N4 247.1925 C18 H16 O 248.1202 C14 H26 N4 250.2160
C12 H26 N2 O3 246.1945 C15 H9 N3 O 247.0746 C18 H18 N 248.1440 C15 H10 N2 O2 250.0743
C12 H28 N3 O2 246.2183 C15 H11 N4 247.0985 C18 H32 248.2505 C15 H12 N3 O 250.0981
C12 H30 N4 O 246.2422 C15 H19 O3 247.1334 C19 H20 248.1566 C15 H14 N4 250.1220
C13 H12 NO4 246.0766 C15 H21 NO2 247.1573 249 C15 H22 O3 250.1569
C13 H14 N2 O3 246.1005 C15 H23 N2 O 247.1811 C11 H25 N2 O4 249.1815 C15 H24 NO2 250.1808
C13 H16 N3 O2 246.1244 C15 H25 N3 247.2050 C11 H27 N3 O3 249.2054 C15 H26 N2 O 250.2046
C13 H18 N4 O 246.1482 C16 H11 N2 O 247.0872 C12 H13 N2 O4 249.0876 C15 H28 N3 250.2285
C13 H26 O4 246.1832 C16 H13 N3 247.1111 C12 H15 N3 O3 249.1114 C16 H10 O3 250.0630
C13 H28 NO3 246.2070 C16 H23 O2 247.1699 C12 H17 N4 O2 249.1353 C16 H12 NO2 250.0868
C13 H30 N2 O2 246.2309 C16 H25 NO 247.1937 C12 H27 NO4 249.1941 C16 H14 N2 O 250.1107
C14 H14 O4 246.0892 C16 H27 N2 247.2176 C13 H15 NO4 249.1001 C16 H16 N3 250.1346
C14 H16 NO3 246.1131 C17 H11 O2 247.0759 C13 H17 N2 O3 249.1240 C16 H26 O2 250.1934
C14 H18 N2 O2 246.1369 C17 H13 NO 247.0998 C13 H19 N3 O2 249.1478 C16 H28 NO 250.2172
C14 H20 N3 O 246.1608 C17 H15 N2 247.1236 C13 H21 N4 O 249.1717 C16 H30 N2 250.2411
C14 H22 N4 246.1846 C17 H27 O 247.2063 C14 H9 N4 O 249.0777 C17 H14 O2 250.0994
Cl4 H30 O3 246.2196 C17 H29 N 247.2301 C14 H17 O4 249.1127 C17 H16 NO 250.1233
C15 H10 N4 246.0907 C18 H15 O 247.1123 C14 H19 NO3 249.1365 C17 H18 N2 250.1471
C15 H18 O3 246.1256 C18 H17 N 247.1362 C14 H21 N2 O2 249.1604 C17 H30 O 250.2298
C15 H20 NO2 246.1495 C18 H31 247.2427 C14 H23 N3 O 249.1842 C17 H32 N 250.2536
C15 H22 N2 O 246.1733 C19 H19 247.1488 C14 H25 N4 249.2081 C18 H18 O 250.1358
C15 H24 N3 246.1972 248 C15 H9 N2 O2 249.0664 C18 H20 N 250.1597
C16 H10 N2 O 246.0794 C11 H24 N2 O4 248.1737 C15 H11 N3 O 249.0903 C18 H34 250.2662
C16 H12 N3 246.1032 C11 H26 N3 O3 248.1976 C15 H13 N4 249.1142 C19 H22 250.1722
C16 H22 O2 246.1620 C11 H28 N4 O2 248.2214 C15 H21 O3 249.1491
C16 H24 NO 246.1859 C12 H12 N2 O4 248.0797 C15 H23 NO2 249.1730
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APPENDIX B 67

APPENDIX B COMMON FRAGMENT IONS

All fragments listed bear +1 charges. To be used in conjunction with McLafferty and Turecek’s (1993) interpretative book, and the
Appendix C. Not all members of homologous and isomeric series high-resolution ion data of McLafferty and Venkataraghavan
are given. The list is meant to be suggestive rather than exhaus- (1982) are recommended as supplements.
tive. Appendix II of Hamming and Foster (1972), Table A-7 of

m/z Ions a
14 CH2 70 C 5H10
15 CH3 71 C 5H11, C 3H 7C O
16 O 72 C 2H5C( O)CH2 H, C 3H 7CHNH2,
17 OH (CH3) 2N C O, C 2H 5NHCHCH3
18 H2O, NH4 and isomers
19 F, H3O 73 Homologs of 59, (CH3) 3Si
26 C N, C 2H 2 74 CH2CO2CH3 H
27 C 2H 3 75 CO2C 2H5 2H, C 2H5CO2 2H,
28 C 2H 4, CO, N 2 (air), CH NH CH2SC2H5, (CH3)2CSH, (CH3O)2CH,
29 C 2H 5, CHO (CH3)2SiOH
30 CH2NH2, N O 76 C 6H 4 (C 6H 4XY)
31 CH2OH, OCH3 77 C 6H 5 (C 6H 5X)
32 O2 (air) 78 C 6H 5 H
33 SH, CH2F 79 C 6H 5 2H, 79Br b
34 H2S 80 CH3SS H, H79Brb,
35
35 Cl b CH2
36 H35Cl b
39 C 3H 3 N , N
40 CH2C N, Ar (air)
41 C 3H5, CH2C N H, C 2H 2NH H CH2
42 C 3H 6, C 2H2O
43 C 3H 7, CH 3C O, C 2H 5N
81
44 CH2C( O)H H, CH3CHNH2, C O2 (air), O CH2 , C 6H 9
NH2C O, (CH 3) 2N
45 CH3CH(OH), CH2CH2OH, CH2OCH3, 82 (CH2) 4C N, C 6H 10, C 35Cl 2b
C( O)OH
46 NO2 83 C 6H11,CH35Cl 2b ,
47 CH2SH, CH3S S
48 CH3S H
49 CH235Cl b 85
51 CH2F2, C4H3 , , C 6H13, C 4H9C O, Cl35ClF2b
O O O
53 C 4H 5
54 CH2CH2C N 86 C 3H 7C( O)CH2 H, C 4H 9CHNH2
55 C 4H 7, CH2 CHC O and isomers
56 C 4H 8 87 C3H7CO2, Homologs of 73,
57 C 4H 9, C 2H 5C O CH2CH2CO2CH3
58 CH3C( O)CH2 H, C2H5CHNH2, 88 CH2CO2C 2H 5 H
(CH3)2NCH2, C2H5NHCH2, C2H5S
59 (CH3)2COH, CH2OC2H5, CO2CH3, C
NH2C( O)CH2 H, CH3OCHCH3, 89 CO2C 3H 7 2H,
CH3CHCH2OH, C2H5CHOH
60 CH2CO2H H, CH2ONO
61 CH3CO2 2H, CH2CH2SH, CH2SCH3 CH
90
65 C 5H 5 , CH3CHONO2

66 H 2S2, C 5H 6 91 (C 6H 5)CH2, (C 6H 5)CH H, (C 6H 5)C 2H,

(CH2) 435Cl b , (C 6H 5)N
67 C 5H 7
68 CH2CH2CH2C N 92
CH2, (C 6H 5)CH 2 H
69 C 5H9, CF3, CH3CH CHC O,
CH2 C(CH3)C O N
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68 CHAPTER 1 MASS SPECTROMETRY

APPENDIX B (Continued)

m/z Ionsa

C O
93 CH279Br b , C 7H9, (C 6H 5)O, 111
N C S
O
119 CF3CF2, (C6H5)C(CH3)2,
C O CH3CH(C6H4)CH3, CO(C6H4)CH3
94 (C 6H5)O H,
C O
N
H 120
C O O
95
O C O O CH3 O
N
96 (CH2)5C N
CH2 121 C 9H13, OH, CH2,
97 C 7H13, NH
S
122 C 6H 5CO2 H
CH2O 123 F(C6H4)C O, C 6H5CO2 2H
98 125 C 6H 5SO
O H
127 I
128 HI
99 C7H15, C6H11O, CH2
O O 130
100 C4H 9C( O)CH2 H, C5H11CHNH2 N
101 CO2C4H9 H
102 CH 2CO 2C 2H 7 H 131 C3F5, C6H5CH CHC O
103 CO2C 4H 9 2H, C 5H11S, CH(OCH2CH3)2 135 (CH2)479Brb
104 C2H5CHONO2 138 CO2(C6H 4)OH H
35
105 C6H 5C O, C6H5CH2CH2, C6H5CHCH3 139 Cl(C6H 4)C O b
106 C6H5NHCH2 141 CH2I
107 C 6H5CH2O, HO(C6H4)CH 2, C 2H 479Brb 147 (CH3) 2Si O Si(CH3)3
C O O
108 C 6H 5CH2O H,
N 149 O H
CH3
O
154 (C6H5)2
109
C O

a
Ions indicated as a fragment nH (n 1,2,3, . . .) are ions that arise via rearrangement involving hydrogen transfer.
b
Only the more abundant isotope is indicated.
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APPENDIX C 69

APPENDIX C COMMON FRAGMENTS LOST

This list is suggestive rather than comprehensive. It should be (1993) are recommended as supplements. All of these frag-
used in conjunction with Appendix B. Table 5-19 of Hamming ments are lost as neutral species.
and Foster (1972) and Table A-5 of McLafferty and Turecek
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70 CHAPTER 1 MASS SPECTROMETRY

APPENDIX C (Continued)
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CHAPTER 2
INFRARED SPECTROSCOPY

2.1 INTRODUCTION of molecular rotation. This absorption is quantized; thus, a

molecular rotational spectrum consists of discrete lines.
Infrared (IR) radiation refers broadly to that part of the elec- Infrared radiation in the range from about 10000 cm−1 to
tromagnetic spectrum between the visible and microwave 100 cm−1 is absorbed and converted by an organic molecule
regions. Of greatest practical use to the organic chemist is into energy of molecular vibration. This absorption is also
the limited portion between 4000 cm−1 and 400 cm−1 . There quantized, but vibrational spectra appear as bands rather
has been some interest in the near-IR (14290 cm−1 to 4000 than as lines because a single vibrational energy change is
cm−1 ) and the far-IR (700 cm−1 to 200 cm−1 ) regions. accompanied by a number of rotational energy changes. It
From the brief theoretical discussion that follows, it is is with these vibrational–rotational bands, particularly those
clear that even a very simple molecule can give an extremely occurring between 4000 cm−1 and 400 cm−1 , that we shall
complex spectrum. The organic chemist takes advantage of be concerned. The frequency or wavelength of absorption
this complexity when matching the spectrum of an unknown depends on the relative masses of the atoms, the force
compound against that of an authentic sample. A peak-by- constants of the bonds, and the geometrical arrangement of
peak correlation is excellent evidence for identity. Any two the atoms (i.e., the molecular structure).
compounds, except enantiomers, are unlikely to give exactly Band positions in IR spectra are presented here as
the same IR spectrum. wavenumbers ( 𝜈̃ ) whose unit is the reciprocal centimeter
Although the IR spectrum is characteristic of the entire (cm−1 ); this unit is proportional to the energy of vibra-
molecule, it is true that certain groups of atoms give rise tion and modern instruments are linear in reciprocal cen-
to bands at or near the same frequency regardless of the timeters. Wavelength (𝜆) was used in the older literature in
structure of the rest of the molecule. It is the persistence units of micrometers (μm = 10−6 m; earlier called microns).
of these characteristic bands that permits the chemist to Wavenumbers are reciprocally related to wavelength:
obtain useful structural information by simple inspection
and reference to generalized charts of characteristic group 𝜈̃ = 1∕𝜆
frequencies. We shall rely heavily on these characteristic
group frequencies. The IR spectra in this text are generally shown with units as
Since we are not solely dependent on IR spectra for a linear function of cm−1 unless otherwise indicated. Note
identification, a detailed analysis of the spectrum will not be that spectra that are plotted as a function of wavelength are
required. Following our general plan, we shall present only quite different in appearance from those plotted in wavenum-
sufficient theory to accomplish our purpose: utilization of IR bers, but the information content is the same (see Figure 2.5).
spectra in conjunction with other spectral data in order to Wavenumbers (in cm−1 ) are directly proportional to fre-
determine or confirm molecular structure. quency (in Hertz), and the two are related by the speed of
The importance of IR spectroscopy as a tool of the 𝜈 = 𝜈∕c); therefore, higher frequency vibrations cor-
light (̃
practicing organic chemist is readily apparent from the respond to higher wavenumbers.
number of books devoted wholly or in part to discus- Band intensities can be expressed either as transmit-
sions of applications of this method (see the references at tance (T) or absorbance (A). Transmittance is the ratio
www.wiley.com/college/silverstein). There are many com- of the radiant power transmitted by a sample to the radi-
pilations of spectra as well as indexes to spectral collec- ant power incident on the sample. Absorbance is the loga-
tions and to the literature. Among the more commonly rithm, to the base 10, of the reciprocal of the transmittance;
used compilations are those published by Sadtler (1994) A = log10 (1∕T). Organic chemists usually report intensity in
and by Aldrich (1989). There are also numerous special- qualitative terms (s = strong, m = medium, and w = weak).
ized texts dealing with specific classes of materials such Two of the most important types of molecular vibra-
as polymers and plastics. Examples include Haslam et al. tions are stretching and bending. A stretching vibration is a
(1979), Hummel (1980), Koenig (1992), and Everall (2007). rhythmical movement along the bond axis such that the inter-
atomic distance is increasing or decreasing. A bending vibra-
tion may consist of a change in angle between bonds with a
2.2 THEORY common atom or the movement of a group of atoms with
respect to the remainder of the molecule without movement
Radiation of wavenumbers less than about 100 cm−1 is of the atoms in the group with respect to one another. For
absorbed and converted by an organic molecule into energy example, twisting, rocking, and torsional vibrations involve
71
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72 CHAPTER 2 INFRARED SPECTROSCOPY

a change in bond angles with reference to a set of coordinates 5. The failure of certain fundamental vibrations to appear
arbitrarily set up within the molecule. in the IR because of the lack of change in molecular
Only those vibrations that result in a change in the net dipole.
dipole moment of the molecule are observed in the IR spec-
Assignments for stretching frequencies can be approxi-
trum. The alternating electric field, produced by the changing
mated by the application of Hooke’s law. In the application
charge distribution accompanying a vibration, couples the
of the law, two atoms and their connecting bond are treated as
molecular vibration with the oscillating electric field of the
a simple harmonic oscillator composed of two masses joined
electromagnetic radiation.
by a spring. The following equation, derived from Hooke’s
A molecule has as many degrees of freedom as the total
law, states the relationship between wavenumber of oscilla-
degrees of freedom of its individual atoms. Each atom has
tion, atomic masses, and the force constant of the bond:
three degrees of freedom corresponding to the Cartesian
coordinates (x, y, z) necessary to describe its position relative √
1 f
to other atoms in the molecule. A molecule of n atoms there- 𝜈̃ =
fore has 3n degrees of freedom. For nonlinear molecules, 2𝜋c (Mx My )∕(Mx + My )
three degrees of freedom describe rotation and three describe
where
translation; the remaining 3n − 6 degrees of freedom are
𝜈̃ = the vibrational wavenumber (cm−1 )
vibrational degrees of freedom that correspond to funda-
c = speed of light (cm/s)
mental vibrations. Linear molecules have 3n − 5 vibrational
f = force constant of bond (dyne/cm)
degrees of freedom, since only two independent degrees of
Mx and My = mass (g) of atom x and atom y,
freedom are required to describe rotation.
respectively.
Fundamental vibrations involve no change in the center
of gravity of the molecule. The three fundamental vibrations The value of f is approximately 5 × 105 dyne/cm
of the nonlinear triatomic water molecule are depicted in the for single bonds and approximately two and three times
top portion of Figure 2.1. Note the very close energetic spac- this value for double and triple bonds, respectively (see
ing of the interacting or coupled asymmetric and symmetric Table 2.1). The force constant, f , can be thought of as a
stretching compared with the far-removed scissoring mode. measure of bond “stiffness.” This force constant can be cor-
The CO2 molecule is linear and contains three atoms; related with properties such as bond order and bond strength.
therefore, it has four fundamental vibrations [(3 × 3) − 5] as Because the wavenumber is directly related to the square
shown in the middle section of Figure 2.1. The symmetrical root of the force constant, we know that the frequency
stretching vibration in (1) is inactive in the IR since it pro- of bond vibrations should decrease as bonds decrease in
duces no net change in the dipole moment of the molecule. strength.
The bending vibrations in (3) and (4) of Figure 2.1 are equiv- Application of the formula to C⏤H stretching using
alent and are the resolved components of bending motion 2.10 × 10−23 g and 1.67 × 10−24 g as mass values for C
oriented at any angle to the internuclear axis; they have the and H, respectively, places the frequency of the C⏤H bond
same frequency and are said to be doubly degenerate. vibration at 3032 cm−1 . Actually, C⏤H stretching vibra-
The various stretching and bending modes for an AX2 tions, associated with methyl and methylene groups, are
group appearing as a portion of a molecule, for example, generally observed in the region between 2960 cm−1 and
the CH2 group in a hydrocarbon molecule, are shown in 2850 cm−1 . The calculation is not highly accurate because
Figure 2.1. The 3n − 6 rule does not apply since the CH2 effects arising from the environment of the C⏤H group
group represents only a portion of a molecule. within a molecule have been ignored. The observed fre-
The theoretical number of fundamental vibrations (ab- quency of IR absorption is commonly used to calculate the
sorption frequencies) will seldom be observed because over- force constants of bonds.
tones (multiples of a given frequency) and combination tones The shift in absorption frequency following deutera-
(sum of two other vibrations) increase the number of bands, tion is often employed in the assignment of C⏤H stretching
whereas other phenomena reduce the number of bands. The frequencies. The above equation can be used to
following will reduce the number of observed bands: estimate the change in stretching frequency as a result
1. Fundamental wavenumbers that fall outside of the of deuteration. The term Mx My ∕(Mx + My ) will be equal
4000 cm−1 to 400 cm−1 region. to MC MH ∕(MC + MH ) for the C⏤H compound. Since
MC ≫ MH , this term is approximately equal to MC MH ∕MC
2. Fundamental bands that are too weak to be observed. or to MH . Thus, for the C⏤D compound, the term is equal
3. Fundamental vibrational wavenumbers that are so close to MD ; the frequency by Hooke’s law application is inversely
that the bands coalesce. proportional to the square root of the mass of the isotope
4. The occurrence of a degenerate band from several of hydrogen. The ratio of the C⏤H √ to C⏤D stretching
absorptions of the same frequency in highly symmet- frequencies should, therefore, equal 2. If the ratio of√the
rical molecules. frequencies, following deuteration, is much less than 2,
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2.2 THEORY 73

H 2O

Symmetrical Asymmetrical Scissoring

stretching (vs OH) stretching (vas OH) ( s OH)
3652 cm–1 3756 cm–1 1596 cm–1

CO2

(2) Asymmetrical (4) Scissoring (bending)

stretching (vas CO2) ( s CO2)
(1) Symmetrical 2350 cm–1 (3) Scissoring (bending) 665 cm–1
stretching (vs CO2) ( s CO2)
1340 cm–1 665 cm–1

CH2

Symmetrical Asymmetrical In-plane bending

stretching (vs CH2) stretching (vas CH2) or scissoring ( s CH2)
~2853 cm–1 ~2926 cm–1 ~1465 cm–1

Out-of-plane bending Out-of-plane bending In-plane bending

or wagging ( CH2) or twisting ( CH2) or rocking ( CH2)
1350 cm–1 to 1150 cm–1 1350 cm–1 to 1150 cm–1 ~720 cm–1

FIGURE 2.1 (Top) Vibrational modes for H2 O. (Middle) Vibrational modes for linear CO2 . (Bottom) Vibrational modes for a
CH2 group (+ and − indicate movement perpendicular to the plane of the page).
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74 CHAPTER 2 INFRARED SPECTROSCOPY

TABLE 2.1 IR Absorption Regions Using Hooke’s Law out of phase; one C⏤O bond stretches as the other con-
tracts. The asymmetrical stretching mode, since it produces
Bond Force Constant Absorption Region (cm−1 )
a change in the dipole moment, is IR active; the absorption
Type f in (dyne/cm) Calculated Observed
(2350 cm−1 ) is at a higher frequency (shorter wavelength)
C⏤O 5.0 × 105 1113 1300 – 800 than observed for a carbonyl group in aliphatic ketones.
C⏤C 4.5 × 105 1128 1300 – 800
C⏤N 4.9 × 105 1135 1250 – 1000 O C O O C O
C⏤C 9.7 × 105 1657 1900 – 1500 Symmetrical Asymmetrical
C⏤O 12.1 × 105 1731 1850 – 1600 μ 0 μ 0
C⏤
⏤C 15.6 × 105 2101 2150 – 2100
C⏤D 5.0 × 105 2225 2250 – 2080 This difference in carbonyl absorption frequencies dis-
C⏤H 5.0 × 105 3032 3000 – 2850 played by the carbon dioxide molecule results from strong
O⏤H 7.01 × 105 3553 3800 – 2700 mechanical coupling or interaction. In contrast, two ketonic
carbonyl groups separated by one or more carbon atoms
show normal carbonyl absorption near 1715 cm−1 because
appreciable coupling is prevented by the intervening carbon
we can assume that the vibration is not simply a C⏤H
atom(s).
stretching vibration but instead a mixed vibration involving
Coupling accounts for the two N⏤H stretching bands
interaction (coupling) with another vibration.
in the 3497 cm−1 to 3077 cm−1 region in the spectra of
Crude approximations based on Hooke’s law can be
primary amines and primary amides, for the two C⏤O
made by calculating the stretching frequencies for certain
stretching bands in the 1818 cm−1 to 1720 cm−1 region
bond types as indicated in Table 2.1.
in carboxylic anhydride and imide spectra, and for the two
To approximate the vibrational frequencies of bond
C⏤H stretching bands in the 3000 cm−1 to 2760 cm−1
stretching by Hooke’s law, the relative contributions of
region for both methylene and methyl groups.
bond strengths and atomic masses must be considered. For
Useful characteristic group frequency bands often in-
example, a superficial comparison of the C⏤H group with
volve coupled vibrations. The spectra of alcohols have a
the F⏤H group, on the basis of atomic masses, might lead
strong band in the region between 1260 cm−1 and 1000
to the conclusion that the stretching frequency of the F⏤H
cm−1 , which is usually designated as the C⏤O stretching
bond should occur at a lower frequency than that for the
band. In the spectrum of methanol, this band is at 1034
C⏤H bond. However, the increase in the force constant from
cm−1 ; in the spectrum of ethanol it occurs at 1053 cm−1 .
left to right across the first two rows of the periodic table has
Branching and unsaturation produce absorptions character-
a greater effect than the mass increase. Thus, the F⏤H group
istic of these structures (see Section 2.6.9). It is evident that
absorbs at a higher wavenumber (4138 cm−1 ) than the C⏤H
we are dealing not with an isolated C⏤O stretching vibra-
group (3040 cm−1 ).
tion but rather a coupled asymmetric vibration involving
In general, functional groups that have a strong dipole
C⏤C⏤O stretching.
give rise to strong absorptions in the IR.
Vibrations resulting from bond angle changes frequently
couple in a manner similar to stretching vibrations. Thus,
2.2.1 Coupled Interactions the ring C⏤H out-of-plane bending frequencies of aromatic
molecules depend on the number of adjacent hydrogen atoms
When two bond oscillators share a common atom, they on the ring; coupling between the hydrogen atoms is affected
seldom behave as individual oscillators unless the indi- by the bending of the C⏤C bond in the ring to which the
vidual oscillation frequencies are widely different. This is hydrogen atoms are attached.
because there is mechanical coupling interaction between Interaction arising from coupling of stretching and bend-
the oscillators. For example, the carbon dioxide molecule ing vibrations is illustrated by the absorption of secondary
(see Figure 2.1), which consists of two C⏤O bonds with a acyclic amides. Secondary acyclic amides, which exist pre-
common carbon atom, has two fundamental stretching vibra- dominantly in the trans conformation, show strong absorp-
tions: an asymmetrical and a symmetrical stretching mode. tion in the 1563 cm−1 to 1515 cm−1 region; this absorption
The symmetrical stretching mode consists of an in-phase involves coupling of the N⏤H bending and C⏤N stretching
stretching or contracting of the C⏤O bonds, and absorption vibrations.
occurs at a wavelength longer than that observed for the car- The requirements for effective coupling interaction may
bonyl group in an aliphatic ketone. The symmetrical stretch- be summarized as follows:
ing mode produces no change in the dipole moment (𝜇) of
the molecule and is therefore inactive in the IR, but it is eas- 1. The vibrations must be of the same symmetry species if
ily observed in the Raman spectrum* near 1340 cm−1 . In the interaction is to occur.
asymmetrical stretching mode, the two C⏤O bonds stretch 2. Strong coupling between stretching vibrations requires
a common atom between the groups.
* Band intensity in Raman spectra depends on bond polarizability rather than 3. Interaction is greatest when the coupled groups absorb,
molecular dipole changes. individually, near the same frequency.
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2.2 THEORY 75

100

861
946
O

1169
1347
%Transmittance

1455
2859
50

2936

1709
4000 3000 2000 1000
Wavenumber (cm–1)
FIGURE 2.2 IR spectrum of cycloheptanone, neat.

4. Coupling between bending and stretching vibrations

can occur if the stretching bond forms one side of the
changing angle.
5. A common bond is required for coupling of bending
vibrations.
6. Coupling is negligible when groups are separated by one
or more carbon atoms and the vibrations are mutually
perpendicular.
As we have seen in our discussion of interaction, cou-
pling of two fundamental vibrational modes will produce
two new modes of vibration, with frequencies higher and FIGURE 2.3 Infrared spectrum of cyclopentanone in various
lower than that observed when interaction is absent. Inter- media. A. Carbon tetrachloride solution (0.15 M). B. Carbon
action can also occur between fundamental vibrations and disulfide solution (0.023 M). C. Chloroform solution (0.025 M).
overtones or combination-tone vibrations. Such interaction is D. Liquid state (thin film). (Computed spectral slit width 2 cm−1 .)
known as Fermi resonance. One example of Fermi resonance
is afforded by the absorption pattern of carbon dioxide. In
our discussion of interaction, we indicated that the symmet-
2.2.2 Hydrogen Bonding
rical stretching band of CO2 appears in the Raman spectrum
near 1340 cm−1 . Actually two bands are observed: one at Hydrogen bonding can occur in any system containing a
1286 cm−1 and one at 1388 cm−1 . The splitting results from proton donor group (X⏤H) and a proton acceptor (Y) ̈ if
coupling between the fundamental C⏤O stretching vibra- the s orbital of the proton can effectively overlap with the
tion, near 1340 cm−1 , and the first overtone of the bending p or 𝜋 orbital of the acceptor group. Atoms X and Y
vibration. The fundamental bending vibration occurs near are electronegative, with Y ̈ possessing lone pair electrons.
666 cm−1 , and the first overtone near 1334 cm−1 . The common proton donor groups in organic molecules are
Fermi resonance is a common phenomenon in IR and carboxyl, hydroxyl, amine, or amide groups. Common proton
Raman spectra. It requires that the vibrational levels be of acceptor atoms are oxygen, nitrogen, and the halogens.
the same symmetry species and that the interacting groups Unsaturated groups, such as the C⏤C linkage, can also act
be located in the molecule so that mechanical coupling is as proton acceptors.
appreciable. The strength of the hydrogen bond is at a maximum
An example of Fermi resonance in an organic struc- when the proton donor group and the axis of the lone pair
ture is the doublet appearance of the C⏤O stretch of cer- orbital are collinear. The strength of the bond decreases as
tain cyclic ketones under sufficient resolution conditions. the distance between X and Y increases.
Figure 2.2 shows the appearance of the spectrum of cyclo- Hydrogen bonding alters the force constant of both
heptanone under the usual conditions of resolution; the groups; thus, the frequencies of both stretching and
carbonyl peak at 1709 cm−1 is a singlet. With adequate reso- bending vibrations are altered. The X⏤H stretching bands
lution however, the IR spectra of cyclopentanone’s carbonyl move to lower frequencies (longer wavelengths) usually with
region, which are given in Figure 2.3 for four different condi- increased intensity and band widening. The stretching fre-
tions, show a doublet for the carbonyl group. These doublets quency of the acceptor group, for example, C⏤O, is also
are due to Fermi resonance of the carbonyl group with an reduced but to a lesser degree than the proton donor group.
overtone or combination band of an 𝛼-methylene group. The H⏤X bending vibration usually shifts to a shorter
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76 CHAPTER 2 INFRARED SPECTROSCOPY

wavelength when bonding occurs; this shift is less pro- 2.3 INSTRUMENTATION
nounced than that of the stretching frequency.
Intermolecular hydrogen bonding involves association 2.3.1 Dispersion IR
of two or more molecules of the same or different com-
pounds. Intermolecular bonding may result in dimer mole- For many years, an infrared spectrum was obtained by pass-
cules (as observed for carboxylic acids) or in polymeric ing an infrared beam though the sample and scanning the
molecular chains, which exist in neat samples or concen- spectrum with a dispersion device (the familiar diffraction
trated solutions of monohydroxy alcohols. Intramolecular grating). The spectrum was scanned by rotating the diffrac-
hydrogen bonds are formed when the proton donor and tion grating; the absorption areas (peaks) were detected
acceptor are present in a single molecule under spatial and plotted as frequencies versus intensities. Because FT-IR
conditions that allow the required overlap of orbitals; for methods have largely replaced dispersion methods, there is
example, the formation of a five- or six-membered ring. no need to discuss this further.
The extent of both intermolecular and intramolecular
bonding is temperature dependent. The effect of concentra-
tion on intermolecular and intramolecular hydrogen bond- 2.3.2 Fourier Transform Infrared
ing is markedly different. The bands that result from inter- Spectrometer (Interferometer)
molecular bonding generally disappear at low concentrations
(less than about 0.01 M in nonpolar solvents). Intramolecu- Fourier transform infrared (FT-IR) spectroscopy has been
lar hydrogen bonding is an internal effect and persists at very extensively developed over the past 25 years. FT-IR provides
low concentrations. a number of advantages over the old dispersive method,
The change in frequency between free OH absorption including better sensitivity, resolution, and speed; therefore,
and bonded OH absorption is a measure of the strength of FT-IR has become the only method of IR spectroscopy
the hydrogen bond. Ring strain, molecular geometry, and commonly performed today. In FT-IR, radiation containing
the relative acidity and basicity of the proton donor and all IR wavenumbers (e.g., 4000 cm−1 ) to 400 cm−1 ) is split
acceptor groups affect the strength of bonding. Intramolec- into two beams (Figure 2.4). One beam is of fixed length, and
ular bonding involving the same bonding groups is stronger the other is of variable length (movable mirror).
when a six-membered ring is formed than when a smaller The varying distances between two path lengths result
ring results from bonding. Hydrogen bonding is strongest in a sequence of constructive and destructive interferences
when the bonded structure is stabilized by resonance. and hence variations in intensities: an interferogram. Fourier
The effects of hydrogen bonding on the stretching transformation converts this interferogram from the time
frequencies of hydroxyl and carbonyl groups are summarized domain into one spectral point on the more familiar form
in Table 2.2. Figure 2.18 (spectrum of cyclohexylcarbinol in of the frequency domain. Smooth and continuous variation
the O⏤H stretch region) clearly illustrates this effect. of the length of the piston adjusts the position of mirror B
An important aspect of hydrogen bonding involves and varies the length of beam B; Fourier transformation at
interaction between functional groups of solvent and solute. successive points throughout this variation gives rise to the
If the solute is polar, then it is important to note the solvent complete IR spectrum. Passage of this radiation through a
used and the solute concentration. sample subjects the compound to a broadband of energies.

TABLE 2.2 Impact of Hydrogen Bonding on IR Stretching Wavenumbers

Intermolecular Bonding Intramolecular Bonding

X⏤H · · · Y Wavenumber Reduction Wavenumber Reduction
𝛎 𝛎 𝛎 𝛎 ⏤
Strength 𝐎𝐇 𝐂⏤𝐎 Compound Class 𝐎𝐇 𝐂 𝐎 Compound Class

Weak 300a 15b Alcohols, phenols, and <100a 10 1,2-Diols, 𝛼- and most
intermolecular hydroxyl 𝛽-hydroxy ketones;
to carbonyl bonding o-chloro and o-alkoxy
phenols
Medium 100 to 300a 50 1,3-Diols; some
𝛽-hydroxy ketones;
𝛽-hydroxy amino
compounds; nitro
compounds
Strong 500a 50b RCO2 H dimers >300a 100 o-Hydroxy aryl ketones;
o-hydroxyaryl acids;
𝛽-diketones; tropolones
a Shift relative to “free” stretching wavenumbers.
b Carbonyl stretching only where applicable.
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2.4 SAMPLE HANDLING 77

characterization of production defects down to micron area

dimensions, and the study of chain order and chain packing.
FT-IR microscopy allows the study of cells at the molecu-
lar level to obtain information that is rich in structural and
functional information (Sasic, 2010).

2.4 SAMPLE HANDLING

Infrared spectra may be obtained for gases, liquids, or solids.

The spectra of gases or low-boiling liquids may be obtained
by expansion of the sample into an evacuated cell. Gas
cells are available in lengths of a few centimeters to 40 m.
The sampling area of a standard IR spectrometer will not
accommodate cells much longer than 10 cm; long paths are
achieved by multiple reflection optics.
Liquids may be examined neat or in solution. Neat
liquids are examined between salt plates, usually without a
spacer. Pressing a liquid sample between flat plates produces
a film 0.01 mm or less in thickness, the plates being held
together by capillary action. Samples of 1 mg to 10 mg are
required. Thick samples of neat liquids usually absorb too
strongly to produce a satisfactory spectrum. Volatile liquids
are examined in sealed cells with very thin spacers. Silver
chloride plates may be used for samples that dissolve sodium
FIGURE 2.4 Schematic of an FT-IR spectrometer. chloride plates.
Solutions are handled in cells of 0.1 mm to 1 mm in
In principle, the analysis of one broadbanded pass of radi- thickness. Volumes of 0.1 mL to 1 mL of 0.05% to 10%
ation through the sample will give rise to a complete IR solutions are required for readily available cells. A compen-
spectrum. sating cell, containing pure solvent, is placed in the refer-
There are a number of advantages to FT-IR methods. ence beam. The spectrum thus obtained is that of the solute
Since a monochromator is not used, the entire radiation range except in those regions in which the solvent absorbs strongly.
is passed through the sample simultaneously and much time For example, thick samples of carbon tetrachloride absorb
is saved (Felgett’s advantage). FT-IR instruments can have strongly near 800 cm−1 ; compensation for this band is inef-
very high resolution (≤ 0.001 cm−1 ). Moreover, since the fective since strong absorption prevents any radiation from
data undergo analog-to-digital conversion, IR results are eas- reaching the detector.
ily manipulated: results of several scans are combined to The solvent selected must be dry and transparent in the
average out random absorption artifacts, and excellent spec- region of interest. When the entire spectrum is of interest,
tra from very small samples can be obtained. Another advan- several solvents must be used. A common pair of solvents
tage of FT-IR is that accurate analysis can be done on mix- is carbon tetrachloride (CCl4 ) and carbon disulfide (CS2 ).
tures by computerized spectral subtraction. This technique Carbon tetrachloride is relatively free of absorption at fre-
depends on having a standard spectrum of the one component quencies above 1333 cm−1 , whereas CS2 shows little absorp-
whose peaks are then subtracted from those of the mixture. tion below 1333 cm−1 . Solvent and solute combinations that
FT-IR can be interfaced with chromatographic instru- react must be avoided. For example, CS2 cannot be used
mentation. The techniques of gas chromatographic FT-IR as a solvent for primary or secondary amines. Amino alco-
(GC-FT-IR) and liquid chromatographic FT-IR (LC-FT-IR) hols react slowly with CS2 and CCl4 . The absorption pat-
are particularly useful in identifying compounds in mix- terns of selected solvents and mulling oils are presented in
tures. GC-FT-IR instruments are capable of providing a Appendix A.
vapor-phase spectrum on nanogram amounts of a com- Solids can be examined as a mull, a pressed disk, a
pound eluted from a capillary GC column. Vapor-phase deposited glassy film, or as powders using a method called
spectra resemble those run at high dilution in a nonpo- diffuse reflectance. Mulls are prepared by thoroughly grind-
lar solvent; concentration-dependent peaks are shifted to ing 2 mg to 5 mg of a solid in a smooth agate mortar. Grind-
higher frequency compared with those obtained from con- ing is continued after the addition of one or two drops of
centrated solutions, thin films, or the solid state [see Aldrich the mulling oil. The suspended particles must be < 2 μm to
(1989)]. The combination of FT-IR spectroscopy with visible avoid excessive scattering of radiation. The mull is examined
microscopy also has been used in a wide range of appli- as a thin film between flat salt plates. Nujol® (a high-boiling
cations including the identification of trace contaminants, petroleum oil) is commonly used as a mulling agent. When
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78 CHAPTER 2 INFRARED SPECTROSCOPY

hydrocarbon bands interfere with the spectrum, Fluorolube® surface of the sample (down to a few micrometers). These
(a completely halogenated polymer containing F and Cl) or spectroscopic methods of analysis were initially developed
hexachlorobutadiene may be used. The use of both Nujol® for specimens that cannot be analyzed by conventional trans-
and Fluorolube® mulls makes possible a scan, essentially mission techniques. With minimal sample preparation, IR
free of interfering bands, over the 4000 cm−1 to 250 cm−1 spectra can be effectively obtained for highly absorbing sam-
region. ples (such as aqueous solutions and biological specimens)
The pellet (pressed-disk) technique depends on the fact and opaque materials such as polymers, coatings, powders,
that dry, powdered potassium bromide (or other alkali metal and liquids.
halides) can be compacted under pressure to form transpar- ATR FT-IR is based on the principle of internal reflec-
ent disks. The sample (0.5 mg to 1.0 mg) is intimately mixed tion spectroscopy. Thus, when a beam of light passes through
with approximately 100 mg of dry, powdered KBr. Mixing an optically clear, dense material (e.g., a crystal having a
can be effected by thorough grinding in a smooth agate mor- high refractive index), it is internally reflected from the
tar or, more efficiently, with a small vibrating ball mill, or by interface of an adjoining medium of lower optical den-
lyophilization. The mixture is pressed with special dies under sity and lower refractive index. Qualitatively, ATR works
a pressure of 70000 kPa to 100000 kPa into a transparent as follows: the reflected radiation waves (called standing
disk. The quality of the spectrum depends on the intimacy waves) lose a minute fraction of their intensity via absorption
of mixing and the reduction of the suspended particles to to the functional groups of the material at the interface where
≤ 2 μm. Microdisks, 0.5 mm to 1.5 mm in diameter, can be the vanishing wave (evanescent wave) is formed, and hence
used with a beam condenser. The microdisk technique per- an absorption spectrum is produced. Particular attention is
mits examination of samples as small as 1 μg. Bands near required to establish good optical contact of the sample and
3448 cm−1 and 1639 cm−1 , resulting from moisture, fre- the crystal. This can be done in various ways, for example,
quently appear in spectra obtained by the pressed-disk tech- by casting from solution, or by pressing the sample on the
nique. surface of the crystal. However, it is important to note that
The use of KBr disks or pellets has often been avoided pressure can have an effect on the quality and intensity of
in the past because of the demanding task of making good the recorded spectra, and therefore should be uniform for the
pellets. Such KBr techniques can be made less daunting entire measurement.
by using the Mini-Press, which affords a simple procedure. The DRIFTS method is based on the concept of dif-
The KBr-sample mixture is placed in the nut portion of fusion reflectance spectroscopy. It enables one to study the
the assembly with one bolt in place. The second bolt is surface chemistry of materials that can reflect light, such as
introduced, and pressure is applied by tightening the bolts. heterogeneous catalysts, composites, powders, organic crys-
Removal of the bolts leaves a pellet in the nut that now serves tals, and pharmaceutical substances. In the DRIFTS acces-
as a cell. sory, the IR light reflects off the surface (a powdered sample
Deposited films are useful only when the material can is preferable) at all angles, and a parabolic mirror collector
be deposited from solution or cooled from a melt as micro- refocuses the diffusely reflected light to an IR detector.
crystals or as a glassy film. Crystalline films generally lead FT-IR-ATR and DRIFTS spectra are similar to conven-
to excessive light scattering. Specific crystal orientation may tional IR spectra. The absorption band positions are identi-
lead to spectra differing from those observed for randomly cal; however, the relative intensities of corresponding bands
oriented particles which exist in a mull or halide disk. The are often different.
deposited film technique is particularly useful for obtain-
ing spectra of resins and plastics. Care must be taken to
free the sample of solvent by vacuum treatment or gentle
2.5 INTERPRETATION OF SPECTRA
heating.
In general, a dilute solution in a nonpolar solvent fur-
nishes the best (i.e., least distorted) spectrum. Nonpolar com- There are no rigid rules for interpreting an IR spectrum.
pounds give essentially the same spectra in the condensed Certain requirements, however, must be met before an
phase (i.e., neat liquid, a mull, a KBr disk, or a thin film) attempt is made to interpret a spectrum:
as they give in nonpolar solvents. Polar compounds, how- 1. The spectrum must be adequately resolved and of
ever, often show hydrogen bonding effects in the condensed adequate intensity.
phase. Unfortunately, polar compounds are frequently insol-
2. The spectrum should be that of a reasonably pure
uble in nonpolar solvents, and the spectrum must be obtained
compound.
either in a condensed phase or in a polar solvent; the lat-
ter introduces the possibility of solute–solvent hydrogen 3. The spectrometer should be calibrated so that the bands
bonding. are observed at their proper frequencies or wavelengths.
In recent years, the development of IR measurements Proper calibration can be made with reliable standards,
has been focused on reflectance methods. Two common such as polystyrene film.
reflectance methods are attenuated total reflectance (ATR) 4. The method of sample handling must be specified. If a
and diffuse reflectance infrared Fourier transform solvent is employed, the solvent, concentration, and the
spectroscopy (DRIFTS). Both methods probe primarily the cell thickness should be indicated.
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2.5 INTERPRETATION OF SPECTRA 79

A precise treatment of the vibrations of a complex out-of-plane bending in this region. If the region is extended
molecule is not feasible; thus, the IR spectrum must be to 1000 cm−1 , absorption band characteristics of alkene
interpreted from empirical comparison of spectra and extrap- structures are included.
olation of studies of simpler molecules. Many questions aris- The intermediate portion of the spectrum, 1300 cm−1
ing in the interpretation of an IR spectrum can be answered to 900 cm−1 , is usually referred to as the fingerprint region.
by data obtained from the mass (Chapter 1) and NMR spectra The absorption pattern in this region is frequently complex,
(Chapters 3 to 6). with the bands originating in interacting vibrational modes.
Infrared absorption of organic molecules is summa- This portion of the spectrum is extremely valuable when
rized in the chart of characteristic group absorptions in examined in reference to the other regions. For example, if
Appendix B. Many of the group absorptions vary over a alcoholic or phenolic O⏤H stretching absorption appears
wide range because the bands arise from complex interact- in the high-frequency region of the spectrum, the position
ing vibrations within the molecule. Absorption bands may, of the C⏤C⏤O absorption band in the 1260 cm−1 to
however, represent predominantly a single vibrational mode. 1000 cm−1 region frequently makes it possible to assign
Certain absorption bands, for example, those arising from the the O⏤H absorption to alcohols and phenols with highly
C⏤H, O⏤H, and C⏤O stretching modes, remain within specific structures. Absorption in this intermediate region is
fairly narrow regions of the spectrum. Important details of probably unique for every molecular species.
structure may be revealed by the exact position of an absorp- Any conclusions reached after examination of a partic-
tion band within these narrow regions. Shifts in absorp- ular band should be confirmed where possible by exami-
tion position and changes in band contours, accompanying nation of other portions of the spectrum. For example, the
changes in molecular environment, may also suggest impor- assignment of a carbonyl band to an aldehyde should be con-
tant structural details. firmed by the appearance of a band or a pair of bands in
The two important areas for a preliminary examina- the 2900 cm−1 to 2695 cm−1 region of the spectrum, arising
tion of a spectrum are the regions 4000 cm−1 to 1300 cm−1 from C⏤H stretching vibrations of the aldehyde group. Sim-
and 900 cm−1 to 650 cm−1 . The high-frequency portion of ilarly, the assignment of a carbonyl band to an ester should
the spectrum is called the functional group region. The be confirmed by observation of a strong band in the C⏤O
characteristic stretching frequencies for important functional stretching region, 1300 cm−1 to 1100 cm−1 .
groups such as OH, NH, and C⏤O occur in this portion Similar compounds may give virtually identical spectra
of the spectrum. The absence of absorption in the assigned under normal conditions, but fingerprint differences can be
ranges for the various functional groups can usually be used detected with an expanded vertical scale or with a very
as evidence for the absence of such groups in the molecule. large sample (major bands off scale). For example, pentane
Care must be exercised, however, in such interpretations and hexane are essentially indistinguishable under normal
since certain structural characteristics may cause a band conditions and can be differentiated only with very high
to become extremely broad so that it may go unnoticed. sensitivity experiments.
For example, intramolecular hydrogen bonding in the enolic Finally, in a fingerprint comparison of spectra, or any
form of acetylacetone results in a broad OH band, which may other situation in which the shapes of peaks are important, we
be overlooked. The absence of absorption in the 1850 cm−1 should be aware of the substantial differences in the appear-
to 1540 cm−1 region excludes a structure containing a car- ance of the spectrum in changing from a presentation that
bonyl group. is linear in wavenumber to one that is linear in wavelength
Weak bands in the high-frequency region, resulting from (Figure 2.5).
the fundamental absorption of functional groups, such as Admittedly, the full chart of characteristic absorption
S⏤H and C⏤C, are extremely valuable in the determina- groups (Appendix B) is intimidating. The following state-
tion of structure. Such weak bands would be of little value ments and a simplified chart may help (Figure 2.6).
in the more complicated regions of the spectrum. Overtones The first bit of advice is negative: do not attempt a
and combination tones of lower frequency bands frequently frontal, systematic assault on an infrared spectrum. Rather,
appear in the high-frequency region of the spectrum. Over- look for evidence of the presence or absence of a few com-
tone and combination-tone bands are characteristically weak mon functional groups with very characteristic absorptions.
except when Fermi resonance occurs. Strong skeletal bands Start with OH, C⏤O, and NH groups in Figure 2.6 since
for aromatics and heteroaromatics fall in the 1600 cm−1 to a “yes/no” answer is usually available. A “yes” answer for
1300 cm−1 region of the spectrum. any of these groups sharpens the focus considerably. Cer-
The lack of strong absorption bands in the 900 cm−1 to tainly, the answer will contribute to development of a molec-
650 cm−1 region generally indicates a nonaromatic structure. ular formula from the mass spectrum (Chapter 1) and to an
Aromatic and heteroaromatic compounds display strong out- entry point for the NMR spectra (Chapters 3 to 6). These
of-plane C⏤H bending and ring bending absorption bands other spectra, in turn, will suggest further leads in the IR
in this region that can frequently be correlated with the spectrum.
substitution pattern. Broad, moderately intense absorption Figure 2.6 lists the common groups that provide distinc-
in the low-frequency region suggests the presence of car- tive, characteristic absorptions. Section 2.6 furnishes more
boxylic acid dimers, amines, or amides, all of which show detailed information, including a number of caveats.
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80 CHAPTER 2 INFRARED SPECTROSCOPY

100

CH2 CH n
%Transmittance

50
C6H5

1601
2859

1493

545
3067

1455
3028
0

707
761
2928
4000 3000 2000 1000
Wavenumber (cm–1 )
(a)

100
%Transmittance

50
6.2
3.5

6.7

18.4
3.3

6.9
3.3

0
14.2
13.1
3.4

5 10 15 20
Wavelength (micrometers)
(b)
FIGURE 2.5 Polystyrene, same sample for both (a) and (b). Spectrum (a) linear in wavenumber (cm−1 ); spectrum (b) linear
in wavelength (μm).

cm –1 4000 3600 3200 2800 2400 2000 1800 1600 1400 1200 1000 800 600

3800 3400 3000 2600 2200

m m/w m sw
Alkenes
s w w s
Alkynes
w m m s
Aromatics
m/sh s/br s
OH*
s
C O
mw
NH2 NH
mw
C N
s s/m
NO2
w
SH
s
S O
s s
O S O

3800 3400 3000 2600 2200

cm –1 4000 3600 3200 2800 2400 2000 1800 1600 1400 1200 1000 800 600

*Free OH, medium and sharp; bonded OH, strong and broad

FIGURE 2.6 Simplified chart of several common functional groups with very characteristic absorptions. s = strong,
m = medium, w = weak, sh = sharp, and br = broad.
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2.6 CHARACTERISTIC GROUP ABSORPTIONS OF ORGANIC MOLECULES 81

100

724
1379
1464
%Transmittance

CH3(CH2)10CH3

2870
50

2953
2853
In-plane bending In-plane bending
or scissoring ( s CH2) or rocking ( CH2)

2922
~1465 cm–1 ~720 cm–1

4000 3000 2000 1000

Wavenumber (cm–1)
FIGURE 2.7 Dodecane. C⏤H stretch: 2953 cm−1 𝜈as CH3 , 2870 cm−1 𝜈vs CH3 , 2922 cm−1 𝜈as CH2 , 2853 cm−1 𝜈s CH2 . C⏤H
bend: 1464 cm−1 𝛿s CH2 , 1450 cm−1 𝛿as CH3 , 1379 cm−1 𝛿s CH3 . CH2 rock: 724 cm−1 𝜌CH2 .

2.6 CHARACTERISTIC GROUP The vibrational modes of alkanes are common to many
ABSORPTIONS OF ORGANIC organic molecules. Although the positions of C⏤H stretch-
ing and bending frequencies of methyl and methylene groups
MOLECULES
remain nearly constant in hydrocarbons, the attachment of
CH3 or CH2 groups to atoms other than carbon, or to a car-
A table of characteristic group absorptions is presented in bonyl group or aromatic ring, may result in appreciable shifts
Appendix B. The ranges presented for group absorptions of the C⏤H stretching and bending frequencies.
have been assigned following the examination of many The spectrum of dodecane (Figure 2.7) is that of a
compounds in which the groups occur. Although the ranges typical straight-chain hydrocarbon.
are quite well defined, the precise frequency or wavelength
at which a specific group absorbs is dependent on its 2.6.1.1 C⏤H Stretching Vibrations. Absorption arising
environment within the molecule and on its physical state. from C⏤H stretching in the alkanes occurs in the general
This section is concerned with a comprehensive look at region of 3000 cm−1 to 2840 cm−1 . The positions of the
these characteristic group absorptions and their relationship C⏤H stretching vibrations are among the most stable in the
to molecular structure. As a major type or class of molecule spectrum.
or functional group is introduced in the following sections,
an example of an IR spectrum with the important peak Methyl Groups An examination of a large number
assignments will be given for most. of saturated hydrocarbons containing methyl groups showed,
in all cases, two distinct bands occurring at approximately
2.6.1 Normal Alkanes (Paraffins) 2962 cm−1 and 2872 cm−1 . The first of these results from
the asymmetrical (as) stretching mode in which two C⏤H
The spectra of normal alkanes (paraffins) can be interpreted bonds of the methyl group are extending while the third one
in terms of four vibrations, namely, the stretching and is contracting (vas CH3 ). The second arises from symmetrical
bending of C⏤H and C⏤C bonds. Detailed analysis of the (s) stretching (vs CH3 ) in which all three of the C⏤H bonds
spectra of the lower members of the alkane series has made extend and contract in phase. The presence of several methyl
detailed assignments of the spectral positions of specific groups in a molecule results in strong absorption at these
vibrational modes possible. positions.
Not all of the possible absorption frequencies of alkanes
are of equal value in the assignment of structure. The C⏤C Methylene Groups The asymmetrical stretching
bending vibrations occur at very low frequencies (below (vas CH2 ) and symmetrical stretching (vs CH2 ) occur, respec-
500 cm−1 ) and therefore do not appear in our spectra. The tively, near 2926 cm−1 and 2853 cm−1 . The positions of these
bands assigned to C⏤C stretching vibrations are weak and bands do not vary more than ±10 cm−1 in the aliphatic and
appear in the broad region of 1200 cm−1 to 800 cm−1 ; they unstrained cyclic hydrocarbons. The frequency of methylene
are generally of little value for identification. stretching is increased when the methylene group is part of a
The most characteristic vibrations are those arising from strained ring.
C⏤H stretching and bending. Of these vibrations, those
arising from methylene twisting and wagging are usually 2.6.1.2 C⏤H Bending Vibrations.
of limited diagnostic value because of their weakness and
instability. This instability is a result of strong coupling to Methyl Groups Two bending vibrations can occur
the remainder of the molecule. within a methyl group. The first of these, the symmetrical
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82 CHAPTER 2 INFRARED SPECTROSCOPY

bending vibration, involves the in-phase bending of the in the spectra of solid samples. In the lower members of
C⏤H bonds (I). The second, the asymmetrical bending the n-alkane series, the band appears at somewhat higher
vibration, involves out-of-phase bending of the C⏤H bonds frequencies.
(II). For hydrocarbons, because of methylene twisting and
wagging vibrations, absorption is observed in the 1350 cm−1
H H
H H to 1150 cm−1 region. These bands are generally appreciably
H H weaker than those resulting from methylene scissoring. A
series of bands in this region, arising from the methylene
I II group, is characteristic of the spectra of solid samples of
long-chain acids, amides, and esters.
In I, the C⏤H bonds are moving like the closing petals
of a flower; in II, one petal opens as two petals close. 2.6.2 Branched-Chain Alkanes
The symmetrical bending vibration (𝛿s CH3 ) occurs
near 1375 cm−1 , and the asymmetrical bending vibration In general, the changes brought about in the spectrum
(𝛿as CH3 ) near 1450 cm−1 . of a hydrocarbon by branching result from changes in
The asymmetrical vibration generally overlaps the scis- skeletal stretching vibrations and methyl bending vibrations;
soring vibration of the methylene groups (see below). Two these occur below 1500 cm−1 . The spectrum of 2,2,4-
distinct bands are observed, however, in compounds such as trimethylpentane in Figure 2.8 is that of a typical branched
diethyl ketone, in which the methylene scissoring band has alkane.
been shifted to a lower frequency, 1439 to 1399 cm−1 , and
increased in intensity because of its proximity to the carbonyl 2.6.2.1 C⏤H Stretching Vibrations: Tertiary C⏤H
group. Groups. Absorption resulting from this vibrational mode is
The absorption band near 1375 cm−1 , arising from the very weak and is usually lost in other aliphatic C⏤H absorp-
symmetrical bending of the methyl C⏤H bonds, is very tions. Absorption in hydrocarbons occurs near 2890 cm−1 .
stable in position when the methyl group is attached to
another carbon atom. The intensity of this band is greater 2.6.2.2 C⏤H Bending Vibrations: gem-Dimethyl
for each methyl group in the compound than that for the Groups. Configurations in which two methyl groups are
asymmetrical methyl bending vibration or the methylene attached to the same carbon atom exhibit distinctive absorp-
scissoring vibration. tion in the C⏤H bending region. The isopropyl group shows
a strong doublet, with peaks of almost equal intensity at
Methylene Groups The bending vibrations of the 1385 cm−1 to 1380 cm−1 and 1370 cm−1 to 1365 cm−1 .
C⏤H bonds in the methylene group have been shown The tertiary butyl group gives rise to two C⏤H bending
schematically in Figure 2.1. The four bending vibrations are bands, one in the 1395 cm−1 to 1385 cm−1 region and one
referred to as scissoring, rocking, wagging, and twisting. near 1370 cm−1 . In the t-butyl doublet, the long wavelength
The scissoring band (𝛿s CH2 ) in the spectra of hydrocar- band is more intense. When the gem-dimethyl group occurs
bons occurs at a nearly constant position near 1465 cm−1 (see at an internal position, a doublet is observed in essentially
Figure 2.7). the same region where absorption occurs for the isopropyl
The band resulting from the methylene rocking vibration and t-butyl groups. Doublets are observed for gem-dimethyl
(𝜌CH2 ), in which all of the methylene groups rock in phase, groups because of interaction between the in-phase and out-
appears near 720 cm−1 for straight-chain alkanes of seven of-phase CH3 bending of the two methyl groups attached to
or more carbon atoms. This band may appear as a doublet a common carbon atom.

100

CH3 CH3
CH3 CH CH2 C CH3
%Transmittance

50
CH3
1370
1478

0
2882
2905
2959

4000 3000 2000 1000

Wavenumber (cm–1)
FIGURE 2.8 2,2,4-Trimethylpentane. C⏤H stretch (see Figure 2.7). C⏤H bend (see Figure 2.7). There are overlapping
doublets for the t-butyl and the isopropyl groups at 1400 – 1340 cm−1 . Compare the absence of a methylene rocking band(s)
1000 cm−1 to 800 cm−1 to Figure 2.7.
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2.6 CHARACTERISTIC GROUP ABSORPTIONS OF ORGANIC MOLECULES 83

Weak bands result from methyl rocking vibrations in substituted alkenes absorb at or near 1670 cm−1 ; disubsti-
isopropyl and t-butyl groups. These vibrations are sensitive tuted cis-alkenes and vinylidene alkenes absorb near 1650
to mass and interaction with skeletal stretching modes and cm−1 .
are generally less reliable than the C⏤H bending vibrations. The absorption of symmetrical disubstituted trans-
The following assignments have been made: isopropyl group, alkenes or tetrasubstituted alkenes may be extremely weak or
922 cm−1 to 919 cm−1 , and t-butyl group, 932 cm−1 to 926 absent. The cis-alkenes, which lack the symmetry of the trans
cm−1 . structure, absorb more strongly than trans-alkenes. Internal
double bonds generally absorb more weakly than terminal
double bonds because of pseudosymmetry.
2.6.3 Cyclic Alkanes Abnormally high absorption frequencies are observed
2.6.3.1 C⏤H Stretching Vibrations. The methylene for ⏤CH⏤CF2 and ⏤CF⏤CF2 groups. The former
stretching vibrations of unstrained cyclic poly(methylene) absorbs near 1754 cm−1 , and the latter near 1786 cm−1 . In
structures are much the same as those observed for acyclic contrast, the absorption frequency is reduced by the attach-
alkanes. Increasing ring strain moves the C⏤H stretching ment of chlorine, bromine, or iodine.
bands progressively to higher frequencies. The ring CH2 and
CH groups in a monoalkylcyclopropane ring absorb in the Cycloalkenes Absorption due to the internal double
region of 3100 cm−1 to 2990 cm−1 . bond in the unstrained cyclohexene system is essentially the
same as that of a cis-isomer in an acyclic system. The C⏤C
stretch vibration is coupled with the C⏤C stretching of the
2.6.3.2 C⏤H Bending Vibrations. Cyclization decreases
adjacent bonds. As the angle 𝛼
the frequency of the CH2 scissoring vibration. Cyclohex-
ane absorbs at 1452 cm−1 , whereas n-hexane absorbs at C
1468 cm−1 . Cyclopentane absorbs at 1455 cm−1 and cyclo-
C C
propane absorbs at 1442 cm−1 . This shift frequently makes it
possible to observe distinct bands for methylene and methyl
absorption in this region. becomes smaller, the interaction becomes less until it is at a
minimum of 90∘ in cyclobutene (1566 cm−1 ). In the cyclo-
propene structure, interaction again becomes appreciable,
2.6.4 Alkenes and the absorption wavenumber increases (1641 cm−1 ).
The substitution of alkyl groups for a hydrogen atom
Alkene (olefinic) structures introduce several new modes of
in strained ring systems serves to increase the frequency of
vibration into a hydrocarbon molecule: a C⏤C stretching
C⏤C absorption. Cyclobutene absorbs at 1566 cm−1 and
vibration, C⏤H stretching vibrations in which the carbon
1-methylcyclobutene absorbs at 1641 cm−1 .
atom is present in the alkene linkage, and in-plane and out-
The absorption frequency of external exocyclic bonds
of-plane bending of the alkene C⏤H bond. The spectrum in
increases with decreasing ring size. Methylenecyclohexane
Figure 2.9 is that of a typical terminal alkene.
absorbs at 1650 cm−1 and methylenecyclopropane absorbs
at 1781 cm−1 .
2.6.4.1 C⏤C Stretching Vibrations Unconjugated
Linear Alkenes. The C⏤C stretching mode of unconju- Conjugated Systems The alkene bond stretching
gated alkenes usually shows moderate to weak absorption vibrations in conjugated dienes without a center of sym-
at 1667 cm−1 to 1640 cm−1 . Monosubstituted alkenes, that metry interact to produce two C⏤C stretching bands. The
is, vinyl groups, absorb near 1640 cm−1 , with moderate spectrum of an unsymmetrical conjugated diene, such as
intensity. Disubstituted trans-alkenes, tri- and tetraalkyl- 1,3-pentadiene, shows absorption near 1650 cm−1 and

100
637
730
3082

1648

1000
1470

915
%Transmittance

50
H2C CH (CH2)9CH3
2859
2928

4000 3000 2000 1000

Wavenumber (cm–1)
FIGURE 2.9 1-Dodecene. C⏤H stretch (see Figure 2.7). Note alkene C⏤H stretch at 3082 cm−1 . C⏤C stretch,
1648 cm−1 , see Appendix Table C.1. Out-of-plane C⏤H bend: 1000 cm−1 , (alkene) 915 cm−1 . Methylene rock:
730 cm−1 .
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84 CHAPTER 2 INFRARED SPECTROSCOPY

100

1640
1794

1378
1439
%Transmittance

CH2

2951
3090

992
H3C C CH CH2

2982
50

1601

899
4000 3000 2000 1000
Wavenumber (cm–1)
FIGURE 2.10 Isoprene. C⏤H stretch: ⏤C⏤H 3090 cm−1 . Coupled C⏤C⏤C⏤C stretch: symmetric 1640 cm−1
(weak), asymmetric 1601 cm−1 (strong). C⏤H bend (saturated, alkene in-plane). C⏤H out-of-plane bend: 992 cm−1 ,
899 cm−1 (see vinyl, Appendix Table C.1).

1600 cm−1 . The symmetrical molecule 1,3-butadiene shows Assignments have been made for a few of the more
only one band near 1600 cm−1 , resulting from asymmet- prominent and reliable in-plane bending vibrations. The
ric stretching; the symmetrical stretching band is inactive in vinyl group absorbs near 1416 cm−1 because of a scissoring
the IR. The IR spectrum of isoprene (Figure 2.10) illustrates vibration of the terminal methylene. The C⏤H rocking
many of these features. vibration of a cis-disubstituted alkene occurs in the same
Conjugation of an alkene double bond with an aromatic general region.
ring produces enhanced alkene absorption near 1625 cm−1 . The most characteristic vibrational modes of alkenes
The absorption frequency of the alkene bond in conju- are the out-of-plane C⏤H bending vibrations between 1000
gation with a carbonyl group is lowered by about 30 cm−1 ; cm−1 and 650 cm−1 . These bands are usually the strongest
the intensity of absorption is increased. In s-cis structures, in the spectra of alkenes. The most reliable bands are those
the alkene absorption may be as intense as that of the car- of the vinyl group, the vinylidene group, and the trans-
bonyl group. s-Trans structures absorb more weakly than disubstituted alkene. Alkene absorptions are summarized in
s-cis structures. the Appendix (Tables C.1 and C.2).
In allene structures, strong absorption is observed near
Cumulated Alkenes A cumulated double-bond sys- 850 cm−1 , arising from ⏤CH2 wagging. The first overtone
tem, as occurs in the allenes of this band may also be seen.
C C CH2 absorbs near
2000 cm−1 to 1900 cm−1 . The absorption results from asym-
metric C⏤C⏤C stretching. The absorption may be consid- 2.6.5 Alkynes
ered an extreme case of exocyclic C⏤C absorption.
The two stretching vibrations in alkynes (acetylenes) involve
2.6.4.2 Alkene C⏤H Stretching Vibrations. In general, C⏤⏤C and C⏤H stretching. Absorption due to C⏤H
any C⏤H stretching bands above 3000 cm−1 result from bending is characteristic of acetylene and monosubstituted
aromatic, heteroaromatic, alkyne, or alkene C⏤H stretch- alkynes. The spectrum shown in Figure 2.11 is that of a typ-
ing. Also found in the same region are the C⏤H stretching ical terminal alkyne.
bands for small rings, such as cyclopropane, and the C⏤H
bands for halogenated alkyl groups. The frequency and inten- 2.6.5.1 C⏤
⏤C Stretching Vibrations. The weak C⏤
⏤C
sity of alkene C⏤H stretching absorptions are influenced by stretching band of alkyne molecules occurs in the region of
the pattern of substitution. With proper resolution, multiple 2260 cm−1 to 2100 cm−1 . Because of symmetry, no C⏤ ⏤C
bands are observed for structures in which stretching interac- band is observed in the IR for symmetrically substituted
tion may occur. For example, the vinyl group produces three alkynes. In the IR spectra of monosubstituted alkynes, the
closely spaced C⏤H stretching bands. Two of these result band appears at 2140 cm−1 to 2100 cm−1 . Disubstituted
from symmetrical and asymmetrical stretching of the termi- alkynes, in which the substituents are different, absorb
nal C⏤H groups, and the third from the stretching of the near 2260 cm−1 to 2190 cm−1 . When the substituents are
remaining single C⏤H. similar in mass, or produce similar inductive and resonance
effects, the band may be so weak as to be unobserved
2.6.4.3 Alkene C⏤H Bending Vibrations. Alkene C⏤H in the IR spectrum. For reasons of symmetry, a terminal
bonds can undergo bending either in the same plane as the C⏤⏤C bond produces a stronger band than an internal C⏤ ⏤C
C⏤C bond or perpendicular to it; the bending vibrations bond (pseudosymmetry). The intensity of the C⏤ ⏤ C bond
can be either in phase or out of phase with respect to each stretching band is increased by conjugation with a carbonyl
other. group.
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2.6 CHARACTERISTIC GROUP ABSORPTIONS OF ORGANIC MOLECULES 85

100

2126
%Transmittance

1247
50

HC C (CH2)4CH3

1463
2866
3314
0

637
2959
4000 3000 2000 1000
Wavenumber (cm–1)
FIGURE 2.11 1-Heptyne. ⏤ ⏤C⏤H stretch, 3314 cm−1 . Alkyl C⏤H stretch 1450 – 1360 cm−1 , 2960 – 2860 cm−1 . C⏤
⏤C
stretch, 2126 cm−1 . C⏤H bend: 1463 cm−1 𝛿s CH2 , 1450 cm−1 𝛿as CH3 . ⏤
⏤C⏤H bend overtone, 1247 cm−1 ; ⏤
⏤C⏤H bend
fundamental, 637 cm−1 .

2.6.5.2 C⏤H Stretching Vibrations. The C⏤H stretch- The skeletal bands frequently appear as doublets, depending
ing band of monosubstituted alkynes occurs in the general on the nature of the ring substituents.
region of 3333 cm−1 to 3267 cm−1 . This is a strong band Aromatic C⏤H stretching bands occur between 3100
and is narrower than the hydrogen-bonded OH and NH bands cm−1 and 3000 cm−1 .
occurring in the same region. Weak combination and overtone bands appear in the
2000 cm−1 to 1650 cm−1 region. The pattern of the overtone
2.6.5.3 C⏤H Bending Vibrations. The C⏤H bending bands is not a reliable guide to the substitution pattern of the
vibration of alkynes or monosubstituted alkynes leads to ring. Because they are weak, the overtone and combination
strong, broad absorption in the 700 cm−1 to 610 cm−1 region. bands are most readily observed in spectra obtained from
The first overtone of the C⏤H bending vibration appears as thick samples. The spectrum shown in Figure 2.12 is that of
a weak, broadband in the 1370 cm−1 to 1220 cm−1 region. a typical aromatic (benzenoid) compound.

2.6.6.1 Out-of-Plane C⏤H Bending Vibrations. The

2.6.6 Mononuclear Aromatic
in-phase, out-of-plane bending of a ring hydrogen atom is
Hydrocarbons
strongly coupled to adjacent hydrogen atoms. The position
The most prominent and most informative bands in the of absorption of the out-of-plane bending bands is therefore
spectra of aromatic compounds occur in the low-frequency characteristic of the number of adjacent hydrogen atoms on
range from 900 cm−1 to 675 cm−1 . These strong absorption the ring. The bands are frequently intense and appear at 900
bands result from the out-of-plane (“oop”) bending of the cm−1 to 675 cm−1 .
ring C⏤H bonds. In-plane bending bands appear in the 1300 Assignments for C⏤H out-of-plane bending bands in
cm−1 to 1000 cm−1 region. Skeletal vibrations, involving the spectra of substituted benzenes appear in the chart
carbon–carbon stretching within the ring, absorb in the 1600 of characteristic group absorptions (Appendix B). These
cm−1 to 1585 cm−1 and 1500 cm−1 to 1400 cm−1 regions. assignments are usually reliable for alkyl-substituted

100

Overtone or combination bands

1605

CH3
1050
%Transmittance

1381

1019

50
2878

CH3
2970

1497
3017

1466
2940

741

0
4000 3000 2000 1000
Wavenumber (cm–1)
FIGURE 2.12 o-Xylene. Aromatic C⏤H stretch, 3017 cm−1 . Methyl bands, C⏤H stretch 3970, 2940, 2875 cm−1 . Overtone
or combination bands, 2000 cm−1 to 1667 cm−1 . C⏤C ring stretch, 1605, 1497, 1466 cm−1 . In-plane C⏤H bend, 1050, 1019
cm−1 . Out-of-plane ⏤C⏤H bend, 741 cm−1 .
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86 CHAPTER 2 INFRARED SPECTROSCOPY

TABLE 2.3 C⏤H Out-of-Plane Bending Vibrations of a and other polynuclear aromatics are summarized by Colthup
𝛽-Substituted Naphthalene et al. (1990).
Substitution Pattern Absorption Range (cm−1 )

Isolated hydrogen 862 to 835

2.6.8 Polymers
Two adjacent hydrogen atoms 835 to 805 In this section, we limit the discussion to a particular class
Four adjacent hydrogen atoms 760 to 735 of synthetic macromolecules that consist of a set of regu-
larly repeated chemical units (i.e., a monomer). A macro-
molecule with only one type of chemical repeat unit in the
benzenes, but caution must be observed in the interpretation polymer chain is called a homopolymer. A copolymer con-
of spectra when polar groups are attached directly to the ring, sists of a very limited number of different types of monomers
for example, in nitrobenzenes, aromatic acids, and esters or joined end to end to form a chain molecule. Polymers may
amides of aromatic acids. be linear, branched, or crosslinked and they may exist in
The absorption band that frequently appears in the crystalline, semicrystalline, or amorphous states. A molecule
spectra of substituted benzenes near 600 cm−1 to 420 cm−1 consisting of N atoms has 3N-6 normal modes of vibra-
is attributed to out-of-plane ring bending. tion (Section 2.2); a polymer molecule may contain tens of
thousands of atoms, and thus, can have tens to hundreds of
thousands of normal modes. This situation could conceiv-
2.6.7 Polynuclear Aromatic
ably lead to extremely complicated IR spectra. However,
Hydrocarbons
homopolymers consist of a large number of chemically iden-
Polynuclear aromatic compounds, like the mononuclear tical repeat units, each of which contains a limited number
aromatics, show characteristic absorption in three regions of of atoms. This leads to a considerable reduction in the com-
the spectrum. plexity of the IR spectrum. Therefore, the IR spectrum of a
The aromatic C⏤H stretching and the skeletal vibra- polymer usually contains a number of peaks usually on the
tions absorb in the same regions as observed for the order of ≤3n, where n is the number of atoms in an individ-
mononuclear aromatics. The most characteristic absorption ual repeat unit, rather than 3N, where N is the number of
of polynuclear aromatics results from C⏤H out-of-plane atoms in the whole molecule. The bands in the spectrum of a
bending in the 900 cm−1 to 675 cm−1 region. These bands polymer may then be assigned largely on the basis of charac-
can be correlated with the number of adjacent hydrogen teristic stretching and deformation vibrations of the specific
atoms on the rings. Most 𝛽-substituted naphthalenes, for groups in the repeat units that comprise the polymer chain.
example, show three absorption bands resulting from out-of- Identification of an unknown polymer thus involves
plane C⏤H bending; these correspond to an isolated hydro- detection of characteristic absorption bands due to a par-
gen atom and two adjacent hydrogen atoms on one ring and ticular chemical group in the repeat unit. By using a func-
four adjacent hydrogen atoms on the other ring. tional group frequency correlation table for small molecules
In the spectra of 𝛼-substituted naphthalenes, the bands (Appendix B), it is then a relatively simple task, for example,
for the isolated hydrogen and the two adjacent hydrogen to ascertain whether the spectrum is that of an aliphatic or
atoms of 𝛽-naphthalenes are replaced by a band for three aromatic hydrocarbon polymer, a polyester, a polyamide, and
adjacent hydrogen atoms. This band is near 810 cm−1 so forth.
to 785 cm−1 . Additional bands may appear because of FT-IR spectra of the simplest polymer, polyethylene
ring bending vibrations (see Table 2.3). The positions of (⏤CH2 ⏤CH2 ⏤)n , are shown in Figures 2.13 and 2.14.
absorption bands for more highly substituted naphthalenes The spectrum of high-density polyethylene (HDPE)

100
1378

H H
Transmittance %

C C n
H H
50
720
731
1471
1462
2848
2915

0
4000 3500 3000 2500 2000 1500 1000 500
Wavenumber (cm–1)
FIGURE 2.13 IR spectrum of high-density polyethylene.
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2.6 CHARACTERISTIC GROUP ABSORPTIONS OF ORGANIC MOLECULES 87

100

1080
H H

1303
Transmittance %

C C n

1378
H H
50

0
4000 3500 3000 2500 2000 1500 1000 500
Wavenumber (cm–1)
FIGURE 2.14 IR spectrum of low-density polyethylene.

(Figure 2.13) shows a strong CH2 symmetric stretch at Figure 2.15 shows the spectrum of polypropylene where
2848 cm−1 , a CH2 asymmetric stretch at 2915 cm−1 , a dou- a methyl group substitutes for one of the hydrogen atoms in
blet at 1461 cm−1 and 1471 cm−1 due to a CH2 bend, an the units of polyethylene. The spectrum not only shows all
out-of-phase CH2 rock of the two chains in the unit cell at the characteristics of a saturated aliphatic hydrocarbon but
720 cm−1 , and an in-phase CH2 rock of the two chains in the also has a number of sharp bands in the C⏤C stretching
unit cell at 730 cm−1 . HDPE is a linear, highly crystalline and C⏤H deformation regions, suggesting a well-defined
polymer with a low CH3 group content, found almost entirely carbon–carbon backbone. Polypropylene, like vinyl or the
as chain end-groups of the polymer. Thus, the 𝜈as CH3 at vinylidene class of polymer, can form stereochemical con-
2950 cm−1 , 𝜈s CH3 at 2870 cm−1 , and 𝛿s CH3 at 1378 cm−1 figurational isomers.
are absent or have very low intensity. In contrast, LDPE (low- Polypropylene has three types as illustrated in
density polyethylene produced at high pressure and temper- Figure 2.16. The isotactic type, where all the R groups lie
ature, 82 MPa to 276 MPa and 405∘ C to 605∘ C, respec- on the same side of the extended chain; the syndiotactic
tively) contains some chain branches, and consequently, an type, where the R groups have alternating positions along the
elevated content of ⏤CH3 groups. Hence, the CH3 symmet- chain; and the atactic type, where the placement of R group
rical bending at 1378 cm−1 of LDPE has a relatively high along the polymer units is random. These different tacticities
intensity compared to HDPE (Figure 2.14). have a considerable effect on the ordering and packing of the
By measuring the relative intensity of the CH3 vibration polymer in the solid state, which consequentially affects the
band, the degree of short chain branching in polyethylene can IR spectrum of the material. The configuration of atactic-
be determined. A band near 1303 cm−1 (CH2 wag) and a PP exhibits no overall regularity of successive repeat units.
bend at 1080 cm−1 (skeletal C⏤C stretch) are associated Isotactic-PP coils up into a 31 helix, and also packs regu-
with the amorphous character of the polymer; thus, these larly to form crystalline arrangements. In general, increasing
bands can be used to verify the degree of crystallinity of crystallinity and order leads to a sharpening and increase in
polyethylene sample. the intensity of some bands in the IR spectra. Accordingly,

100
840

H H
1165
997
Transmittance %

C C n
CH3 H
50
2838

1456
1376
2970
2918
2948

0
4000 3500 3000 2500 2000 1500 1000 500
Wavenumber (cm–1)
FIGURE 2.15 IR spectrum of isotactic polypropylene.
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88 CHAPTER 2 INFRARED SPECTROSCOPY

CH3 CH3 CH3 CH3 CH3 or for hindered OH groups. Intermolecular hydrogen bond-
Isotactic ing increases as the concentration of the solution increases,
and additional bands start to appear at lower wavenum-
bers, 3550 cm−1 to 3200 cm−1 , at the expense of the free
CH3 CH3 CH3 CH3 CH3 CH3 hydroxyl band. This effect is illustrated in Figure 2.18, in
Syndiotactic which the absorption bands in the O⏤H stretching region
are shown for two different concentrations of cyclohexyl-
carbinol in carbon tetrachloride. For comparisons of this
CH3 CH3 CH3 CH3 CH3
type, the path length of the cell must be altered with chang-
Atactic ing concentration, so that the same number of absorbing
molecules will be present in the IR beam at each concen-
FIGURE 2.16 Stereochemical configurations of polypropylene. tration. The band at 3623 cm−1 results from the monomer,
whereas the broad absorption near 3333 cm−1 arises from
“polymeric” structures.
the IR spectra of atactic polymers are similar to those of
the amorphous polymer. However, isotactic PP has more H R R
pronounced intensity at 1170 cm−1 , 998 cm−1 , and 841 cm−1 O O O
compared to atactic forms.
Figure 2.17 shows the IR spectrum of polybutadiene R H H etc.
where a ⏤CH⏤CH2 group substitutes for one of the
Strong intramolecular hydrogen bonding occurs in
hydrogen atoms of the units of polyethylene. Character-
o-hydroxyacetophenone. The resulting absorption at
istic bands of the out-of-plane deformation modes of the
3077 cm−1 is broad, shallow, and independent of concentra-
hydrogen atoms that are attached to the carbon atoms
tion (Figure 2.19).
adjacent to the double bonds appear at different positions
in the IR spectra. For 1,4-cis-polybutadiene, this band is O
observed at 740 cm−1 , but for 1,4 trans-polybutadiene it is at H
966 cm−1 . O

2.6.9 Alcohols and Phenols CH3

The characteristic bands observed in the spectra of alcohols In contrast, p-hydroxyacetophenone

and phenols result from O⏤H stretching and C⏤O stretch-
ing. These vibrations are sensitive to hydrogen bonding. The Ar O etc.
C⏤O stretching and O⏤H bending modes are not indepen- C O HO
dent vibrational modes because they couple with the vibra- H 3C CH3
tions of adjacent groups.
shows a sharp free hydroxy peak at 3600 cm−1 in dilute
2.6.9.1 O⏤H Stretching Vibrations. The non-hydrogen- CCl4 solution as well as a broad, strong intermolecular
bonded or “free” hydroxyl group of alcohols and phe- peak at 3100 cm−1 in the spectrum of a neat sample.
nols absorbs strongly in the 3700 cm−1 to 3584 cm−1 In structures such as 2,6-di-t-butylphenol, in which steric
region. These sharp, free hydroxyl bands are observed in hindrance prevents hydrogen bonding, no bonded hydroxyl
the vapor phase, in very dilute solution in nonpolar solvents, band is observed, not even in spectra of neat samples.
1120
Transmittance %

908

H
H 2C C
CH CH2
1210
1659

1262

740
1020
1424

4000 3000 2500 2000 1500 1400 1250 1100 1000 900 800 700 600
Wavenumber (cm–1)
FIGURE 2.17 IR spectrum of 1,4-cis-polybutadiene.
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2.6 CHARACTERISTIC GROUP ABSORPTIONS OF ORGANIC MOLECULES 89

the vibration might better be described as an asymmetric

C⏤C⏤O stretching vibration. The vibrational mode is fur-
ther complicated by branching and 𝛼,𝛽-unsaturation. These
effects are summarized in Table 2.4 for a series of secondary
alcohols (neat samples).
The absorption ranges of the various types of alcohols
are provided in Table 2.5. These values are for neat samples
of the alcohols.
Mulls, pellets, or melts of phenols absorb at 1390 cm−1
to 1330 cm−1 and 1260 cm−1 to 1180 cm−1 . These bands
apparently result from an interaction between O⏤H bending
and C⏤O stretching. The long-wavelength band is the
stronger one and both bands appear at longer wavelengths
in spectra observed in solution. The spectrum of phenol in
Figure 2.21 was determined on a melt to show a high degree
of association.

2.6.9.3 O⏤H Bending Vibrations. The O⏤H in-plane

bending vibration occurs in the general region of 1420 cm−1
to 1330 cm−1 . In primary and secondary alcohols, the O⏤H
in-plane bending couples with the C⏤H wagging vibrations
FIGURE 2.18 Infrared spectrum of the OH stretching region of to produce two bands: the first near 1420 cm−1 and the second
cyclohexylcarbinol in CCl4 . Peak A at 0.03 M (0.406 mm cell); near 1330 cm−1 . These bands are of little diagnostic value.
Peak B at 1.00 M (0.014 mm cell). Tertiary alcohols, in which no coupling can occur, show a
single band in this region, the position depending on the
degree of hydrogen bonding (Figure 2.22).
The spectra of alcohols and phenols determined in the
liquid state show a broad absorption band in the 769 cm−1
to 650 cm−1 region because of out-of-plane bending of the
bonded O⏤H group.

2.6.10 Ethers, Epoxides, and Peroxides

2.6.10.1 C⏤O Stretching Vibrations. The characteris-
tic response of ethers in the IR is associated with the stretch-
ing vibration of the C⏤O⏤C system. Since the vibrational
characteristics of this system would not be expected to dif-
fer greatly from the C⏤C⏤C system, it is not surprising to
find the response to C⏤O⏤C stretching in the same general
region. However, since vibrations involving oxygen atoms
result in greater dipole moment changes than those involving
carbon atoms, more intense IR bands are observed for ethers.
The C⏤O⏤C stretching bands of ethers, as is the case
with the C⏤O stretching bands of alcohols, involve coupling
with other vibrations within the molecule. The spectrum of
anisole in Figure 2.23 is that of a typical aryl alkyl ether.
In the spectra of aliphatic ethers, the most characteristic
absorption is a strong band in the 1150 cm−1 to 1085
FIGURE 2.19 A portion of the IR spectra of cm−1 region because of asymmetrical C⏤O⏤C stretching;
o-hydroxyacetophenone. Peak A at 0.03 M, cell thickness: this band usually occurs near 1125 cm−1 . The symmetrical
0.41 mm. Peak B at 1.0 M, cell thickness: 0.015 mm. stretching band is usually weak and is more readily observed
in the Raman spectrum.
The C⏤O⏤C group in a six-membered ring absorbs
2.6.9.2 C⏤O Stretching Vibrations. The C⏤O stretch- at the same frequency as in an acyclic ether. As the ring
ing vibrations in alcohols (Figures 2.20 and 2.22) and becomes smaller, the asymmetrical C⏤O⏤C stretching
phenols (Figure 2.21) produce a strong band in the vibration moves progressively to lower wavenumbers (longer
1260 cm−1 –1000 cm−1 region of the spectrum. wavelengths), whereas the symmetrical C⏤O⏤C stretch-
The C⏤O stretching mode is coupled with the adja- ing vibration (ring breathing frequency) moves to higher
cent C⏤C stretching vibration; thus, in primary alcohols, wavenumbers.
 Silverstein c02.tex V3 - 07/30/2014 1:37 P.M. Page 90

90 CHAPTER 2 INFRARED SPECTROSCOPY

100

90

80
CH2OH

1501
%Transmittance

70

2936
3067

1208
2882
3036
60

1455
50

707
40

1023

745
3329

4000 3000 2000 1000

Wavenumber (cm–1)
FIGURE 2.20 Benzyl alcohol. O⏤H stretch: intermolecular hydrogen bonded, 3329 cm−1 . C⏤H stretch: aromatic
3100 cm to 3000 cm−1 . C⏤H stretch: methylene, 2940 cm−1 to 2860 cm−1 . Overtone or combination bands, 2000 cm−1 to
−1

---O ring stretch, 1501 cm−1 , 1455 cm−1 , overlapped by CH2 scissoring, about 1471 cm−1 . O⏤H bend, possibly
1667 cm−1 . C⏤
augmented by C⏤H in-plane bend, 1209 cm−1 . C⏤O stretch, primary alcohol (see Table 2.5) 1023 cm−1 . Out-of-plane
aromatic C⏤H bend, 745 cm−1 . Ring C⏤C bend, 707 cm−1 .

100

95
%Transmittance

OH

815
90
3052

1378

699
1501
1601

85
1478

753
3244

1231

80
4000 3000 2000 1000
Wavenumber (cm–1)
FIGURE 2.21 Phenol (melt). Broad intermolecular hydrogen bonded, O⏤H stretch, 3244 cm−1 . Aromatic C⏤H stretch,
3052 cm . Overtone or combination bands, 2000 cm−1 to 1667 cm−1 . C⏤C ring stretch, 1601, 1501, 1478 cm−1 . In-plane
−1

O⏤H bend, 1378 cm−1 . C⏤O stretch, 1231 cm−1 . Out-of-plane C⏤H bend, 815, 753 cm−1 . Out-of-plane ring C⏤C bend,
699 cm−1 . (Broad) hydrogen-bonded, out-of-plane O⏤H bend, about 650 cm−1 .

100
660
1385
%Transmittance

HO CH2 CH CH2 CH3

1015

CH3
1463

50
1054
3337

2882
2928
2967

4000 3000 2000 1000

Wavenumber (cm–1)
FIGURE 2.22 2-Methyl-1-butanol. O⏤H stretch, intermolecular hydrogen bonding 3337 cm−1 . C⏤H stretch
(3000 – 2800 cm−1 ). C⏤H bend (see Figure 2.8). C⏤O stretch 1054 cm−1 .
 Silverstein c02.tex V3 - 07/30/2014 1:37 P.M. Page 91

2.6 CHARACTERISTIC GROUP ABSORPTIONS OF ORGANIC MOLECULES 91

TABLE 2.4 C⏤C⏤O Stretching Vibrations of Resonance structures can account for the shift in the asym-
Secondary Alcohols metric absorption band of arylalkyl and vinyl ethers.
The C⏤C stretching band of vinyl ethers occurs in
Secondary Alcohol Absorption (cm−1 )
the 1660 cm−1 to 1610 cm−1 region. This alkene band
2-Butanol 1105 is characterized by its higher intensity compared with the
3-Methyl-2-butanol 1091 C⏤C stretching band in alkenes. This band frequently
1-Phenylethanol 1073 appears as a doublet resulting from absorption of rotational
3-Buten-2-ol 1058 isomers.
Diphenylmethanol 1014
H H
1
C C trans 1620 cm
TABLE 2.5 Alcoholic C⏤O Stretch Absorptions
H O
Absorption Range H H C
Alcohol Type (cm−1 ) C C
(1) Saturated tertiary H O C
H H
(2) Secondary, highly symmetrical 1205 – 1124
(1) Saturated secondary C C
1
cis 1640 cm
(2) 𝛼-Unsaturated or cyclic tertiary 1124 – 1087 H O
(1) Secondary, 𝛼-unsaturated C
(2) Secondary, alicyclic five- or 1085 – 1050
six-membered ring
Coplanarity in the trans-isomer allows maximum res-
(3) Saturated primary
(1) Tertiary, highly 𝛼-unsaturated
onance, thus more effectively reducing the double-bond
(2) Secondary, di-𝛼-unsaturated character of the alkene linkage. Steric hindrance reduces res-
(3) Secondary, 𝛼-unsaturated and 𝛼-branched onance in the cis-isomer.
(4) Secondary, alicyclic seven- or <1050 The two bands arising from ⏤C⏤H wagging in ter-
eight-membered ring minal alkenes occur near 1000 cm−1 and 909 cm−1 . In the
(5) Primary, 𝛼-unsaturated and/or spectra of vinyl ethers, these bands are shifted to longer
𝛼-branched wavelengths because of resonance.

H H
Branching on the carbon atoms adjacent to the oxygen
usually leads to splitting of the C⏤O⏤C band. Isopropyl R O C C
ether shows a triplet structure in the 1170 cm−1 to 1114 cm−1 H
region with the principal band occurring at 1114 cm−1 . terminal CH2 wag, 813 cm–1
Spectra of aryl alkyl ethers display an asymmetrical trans CH wag, 960 cm–1
C⏤O⏤C stretching band at 1275 cm−1 to 1200 cm−1 with
symmetrical stretching near 1075 cm−1 to 1020 cm−1 . Strong Alkyl and aryl peroxides display C⏤C⏤O absorption
absorption caused by asymmetrical C⏤O⏤C stretching in in the 1198 cm−1 to 1176 cm−1 region. Acyl and aroyl
vinyl ethers occurs in the 1225 cm−1 to 1200 cm−1 region peroxides display two carbonyl absorption bands in the 1818
with a strong symmetrical band at 1075 cm−1 to 1020 cm−1 . cm−1 to 1754 cm−1 region. Two bands are observed because

100
3067
3005

2843
2959

OCH3
%Transmittance

1177
1301

699
1046
1601

761

50
1501

1254

4000 3000 2000 1000

Wavenumber (cm–1)
FIGURE 2.23 Anisole. Aromatic C⏤H stretch, 3067, 3030, 3005 cm−1 . Methyl C⏤H stretch, 2950, 2843 cm−1 . Overtone-
combination region, 2000 cm−1 to 1650 cm−1 . C⏤C ring stretch, 1601, 1501 cm−1 . Asymmetric C⏤O⏤C stretch, 1254
cm−1 . Symmetric C⏤O⏤C stretch, 1046 cm−1 . Out-of-plane C⏤H bend, 784, 761 cm−1 . Out-of-plane ring C⏤
---O bend,
699 cm−1 .
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92 CHAPTER 2 INFRARED SPECTROSCOPY

of mechanical interaction between the stretching modes of Replacement of an alkyl group of a saturated aliphatic
the two carbonyl groups. ketone by a heteroatom (G) shifts the carbonyl absorption.
The symmetrical stretching, or ring breathing frequency, The direction of the shift depends on whether the inductive
of the epoxy ring, with all ring bonds stretching and contract- effect (a) or resonance effect (b) predominates.
ing in phase, occurs near 1250 cm−1 . Another band appears
G G
in the 950 cm−1 to 810 cm−1 region and is attributed to asym-
metrical ring stretching in which the C⏤C bond is stretching C O C O
during contraction of the C⏤O bond. A third band, referred R R
to as the “12 micron band,” appears in the 840 cm−1 to 750 (a) (b)
cm−1 region. The C⏤H stretching vibrations of epoxy rings
occur in the 3050 cm−1 to 2990 cm−1 region of the spectrum. The inductive effect reduces the length of the C⏤O
bond and thus increases its force constant and the frequency
of absorption. The resonance effect increases the C⏤O bond
2.6.11 Ketones length and reduces the frequency of absorption.
The absorptions of several carbonyl compound classes
2.6.11.1 C⏤O Stretching Vibrations. Ketones, aldehy- are summarized in Table 2.6.
des, carboxylic acids, carboxylic esters, lactones, acid Conjugation with a C⏤C bond results in delocaliza-
halides, anhydrides, amides, and lactams show a strong tion of the 𝜋 electrons of both unsaturated groups. Delocal-
C⏤O stretching absorption band in the region of 1870 cm−1 ization of the 𝜋 electrons of the C⏤O group reduces the
to 1540 cm−1 . Its relatively constant position, high intensity, double-bond character of the C⏤O bond, causing absorp-
and relative freedom from interfering bands make this one of tion at lower wavenumbers (longer wavelengths). Conjuga-
the easiest bands to recognize in IR spectra. tion with an alkene or phenyl group causes absorption in the
Within its given range, the position of the C⏤O stretch-
ing band is determined by the following factors: (i) the phys-
The Carbonyl Absorption of Various
TABLE 2.6
ical state, (ii) electronic and mass effects of neighboring RC(⏤O)G Compounds
substituents, (iii) conjugation, (iv) hydrogen bonding (inter-
molecular and intramolecular), and (v) ring strain. Consid- G Effect Predominantly Inductive
eration of these factors leads to a considerable amount of
G 𝜈𝐂⏤𝐎 (cm−𝟏 )
information about the environment of the C⏤O group.
In a discussion of these effects, it is customary to refer Cl 1815 to 1785
to the absorption wavenumber of a neat sample of a saturated F ∼1869
aliphatic ketone, 1715 cm−1 , as “normal.” For example, Br 1812
acetone and cyclohexanone absorb at 1715 cm−1 . Changes in OH (monomer) 1760
the environment of the carbonyl can either lower or raise the OR 1750 to 1735
absorption wavenumber from this “normal” value. A typical G Effect Predominantly Resonance
ketone spectrum is displayed in Figure 2.24.
The absorption wavenumber observed for a neat sample G 𝜈𝐂⏤𝐎 (cm−𝟏 )
is increased when absorption is observed in nonpolar sol-
NH2 1695 – 1650
vents. Polar solvents reduce the wavenumber of absorption.
SR 1720 – 1690
The overall range of solvent effects does not exceed 25 cm−1 .

100
%Transmittance

897

50
2918

O
2964

1090

C
2995

H3 C CH3
527

0
1422

1213
1715

1360

4000 3000 2000 1000

Wavenumber (cm–1)
FIGURE 2.24 Acetone. 𝜈as , Methyl, 2995 cm−1 . 𝜈as , Methylene, 2964 cm−1 . 𝜈s , Methyl, 2918 cm−1 . Normal C⏤O stretch,
1715 cm . 𝛿as , CH3 1422 cm−1 . 𝛿s , CH3 1360 cm−1 . C⏤CO⏤C stretch and bend, 1213 cm−1 .
−1
 Silverstein c02.tex V3 - 07/30/2014 1:37 P.M. Page 93

2.6 CHARACTERISTIC GROUP ABSORPTIONS OF ORGANIC MOLECULES 93

1685 cm−1 to 1666 cm−1 region. Additional conjugation may H H

cause a slight further reduction in wavenumber. This conju- O O O O
gation effect is illustrated in Figure 2.25.
Steric effects that reduce the coplanarity of the conju- C C C C
R C R R C R
gated system reduce the effect of conjugation. In the absence
of steric hindrance, a conjugated system will tend toward R R
a planar conformation. Thus, 𝛼,𝛽-unsaturated ketones may
exist in s-cis and s-trans conformations. When both forms Acetylacetone as a liquid at 40∘ C exists about 64% in the
are present, absorption for each of the forms is observed. The enolic form that absorbs at 1613 cm−1 . The keto form and a
absorption of benzalacetone in CS2 serves as an example; small amount of unbonded enolic form may be responsible
both the s-cis and s-trans forms are present at room temper- for two bands centered near 1725 cm−1 . Interaction between
ature. the two carbonyl groups in the keto form was suggested
as a cause for this doublet. The enolic O⏤H stretching
H O H absorption is seen as a broad shallow band at 3000 cm−1 to
2700 cm−1 .
O 𝛼-Diketones, in which carbonyl groups exist in for-
mal conjugation, show a single absorption band near the
H H
1 1
frequency observed for the corresponding monoketone.
s-trans 1674 cm s-cis 1699 cm
Biacetyl absorbs at 1718 cm−1 and benzil absorbs at
1681 cm−1 . Conjugation is ineffective for 𝛼-diketones and
The absorption of the alkene bond in conjugation with the C⏤O groups of these diketones do not couple as do, for
the carbonyl group occurs at a lower wavenumber than that example, the corresponding groups in acid anhydrides (see
of an isolated C⏤C bond; the intensity of the conjugated Section 2.6.17).
double bond absorption, when in an s-cis system, is greater Quinones, which have both carbonyl groups in the same
than that of an isolated double bond. ring, absorb in the 1690 cm−1 to 1655 cm−1 region. With
Intermolecular hydrogen bonding between a ketone extended conjugation, in which the carbonyl groups appear
and a hydroxylic solvent such as methanol causes a slight in different rings, the absorption shifts to the 1655 cm−1 to
decrease in the wavenumber of the carbonyl group. For 1635 cm−1 region.
example, a neat sample of ethyl methyl ketone absorbs at Acyclic 𝛼-chloroketones absorb at two frequencies
1715 cm−1 , whereas a 10% solution of the ketone in methanol because of rotational isomerism. When the chlorine atom
absorbs at 1706 cm−1 . is near the oxygen, its negative field repels the nonbond-
𝛽-Diketones usually exist as mixtures of tautomeric keto ing electrons of the oxygen atom, thus increasing the force
and enol forms. The enolic form does not show the nor- constant of the C⏤O bond. This conformation absorbs
mal absorption of conjugated ketones. Instead, a broadband at a higher wavenumber (1745 cm−1 ) than that in which
appears in the 1640 cm−1 to 1580 cm−1 region, many times the carbonyl oxygen and chlorine atom are widely sepa-
more intense than a normal carbonyl absorption. The intense rated (1725 cm−1 ). In rigid molecules such as the monoketo
and displaced absorption results from intramolecular hydro- steroids, 𝛼-halogenation results in equatorial or axial substi-
gen bonding, with the bonded structure being stabilized by tution. In the equatorial orientation, the halogen atom is near
resonance. the carbonyl group and the “field effect” causes an increase

100
3352

3013
3067
%Transmittance

961
1601

1455

O
591
699

C
768
1362

CH3
50
1270
1686

4000 3000 2000 1000

Wavenumber (cm–1)
FIGURE 2.25 Acetophenone. Overtone of C⏤O stretch 3352 cm−1 ; frequency about twice that of C⏤O stretch. C⏤O
stretch, 1686 cm−1 , lower frequency than observed in Figure 2.24 because of the conjugation with the phenyl group.
 Silverstein c02.tex V3 - 07/30/2014 1:37 P.M. Page 94

94 CHAPTER 2 INFRARED SPECTROSCOPY

in the C⏤O stretching frequency. In the isomer in which the to 1685 cm−1 . Internal hydrogen bonding, such as occurs
halogen atom is axial to the ring, and distant from the C⏤O, in salicylaldehyde, shifts the absorption to lower wavenum-
no shift is observed. bers (1666 cm−1 for salicylaldehyde). Glyoxal, like the
In cyclic ketones, the C⏤C⏤C bond angle of the 𝛼-diketones, shows only one carbonyl absorption peak with
C (C⏤O)⏤C group influences the absorption frequency
⏤ no shift from the normal absorption position of monoalde-
of the carbonyl group. The C⏤O stretching undoubtedly hydic absorption.
is affected by adjacent C⏤C stretching. In acyclic ketones
and in ketones with a six-membered ring, the angle is near 2.6.12.2 C⏤H Stretching Vibrations. The majority of
120∘ . In strained rings in which the angle is <120∘ , interac- aldehydes show aldehydic C⏤H stretching absorption in the
tion with C⏤C bond stretching increases the energy required 2830 cm−1 to 2695 cm−1 region. Two moderately intense
to produce C⏤O stretching and thus increases the stretch- bands are frequently observed in this region. The appearance
ing frequency. Cycloheptanone absorbs at 1709 cm−1 , cyclo- of two bands is attributed to Fermi resonance between the
hexanone absorbs at 1715 cm−1 , cyclopentanone absorbs at fundamental aldehydic C⏤H stretch and the first overtone of
1751 cm−1 , and cyclobutanone absorbs at 1775 cm−1 . the aldehydic C⏤H bending vibration that usually appears
near 1390 cm−1 . Only one C⏤H stretching band is observed
2.6.11.2 C⏤C(⏤O)⏤C Stretching and Bending
for aldehydes, whose C⏤H bending band has been shifted
Vibrations. Ketones show moderate absorption in the 1300
appreciably from 1390 cm−1 .
cm−1 to 1100 cm−1 region as a result of C⏤C⏤C stretching
Some aromatic aldehydes with strongly electronega-
and C⏤C(⏤O)⏤C bending in the C⏤C⏤C group. The
tive groups in the ortho position may absorb as high as
absorption may consist of multiple bands. Aliphatic ketones
2900 cm−1 .
absorb in the 1230 cm−1 to 1100 cm−1 region; aromatic
The absorption of medium intensity near 2720 cm−1 ,
ketones absorb at the higher frequency end of the general
accompanied by a carbonyl absorption band, is good evi-
absorption region.
dence for the presence of an aldehyde group.

2.6.12 Aldehydes
2.6.13 Carboxylic Acids
The spectrum of octanal, illustrating typical aldehydic
absorption characteristics, is shown in Figure 2.26. 2.6.13.1 O⏤H Stretching Vibrations. In the liquid or
solid state, and in CCl4 solution at concentrations much
2.6.12.1 C⏤O Stretching Vibrations. The carbonyl over 0.01 M, carboxylic acids exist as dimers due to strong
groups of aldehydes absorb at slightly higher frequencies hydrogen bonding.
than those of the corresponding methyl ketones. Aliphatic
aldehydes absorb near 1740 cm−1 to 1720 cm−1 . Aldehy- O H O O H O
dic carbonyl absorption responds to structural changes in R C R R C R
the same manner as ketones. Electronegative substitution on
the 𝛼-carbon increases the frequency of carbonyl absorption. O H O O H O
Acetaldehyde absorbs at 1730 cm−1 and trichloroacetalde-
hyde absorbs at 1768 cm−1 . Conjugate unsaturation, as in The exceptional strength of the hydrogen bonding is
𝛼,𝛽-unsaturated aldehydes and benzaldehydes, reduces the explained on the basis of the large contribution of the ionic
frequency of carbonyl absorption. 𝛼,𝛽-Unsaturated aldehy- resonance structure. Because of the strong bonding, a free
des and benzaldehydes absorb in the region of 1710 cm−1 hydroxyl stretching vibration (near 3520 cm−1 ) is observed

100
725
2715

1381
%Transmittance

964

50
1142
1458

O
H C (CH2)6CH3
1728
2862

0
2924

4000 3000 2000 1000

Wavenumber (cm–1)
FIGURE 2.26 Octanal. Aliphatic, 2980 cm−1 to 2860 cm−1 (see Figure 2.8). Aldehydic, C⏤H stretch, 2715 cm−1 . Normal
aldehydic C⏤O stretch, 1728 cm−1 . Aldehydic C⏤H bend, 1381 cm−1 .
 Silverstein c02.tex V3 - 07/30/2014 1:37 P.M. Page 95

2.6 CHARACTERISTIC GROUP ABSORPTIONS OF ORGANIC MOLECULES 95

only in very dilute solution in nonpolar solvents or in the forms only slightly. In general, 𝛼,𝛽-unsaturated and aryl con-
vapor phase. jugated acids show absorption for the dimer in the 1710 cm−1
Carboxylic acid dimers display very broad, intense to 1680 cm−1 region. Extension of conjugation beyond the
O⏤H stretching absorptions in the region of 3300 cm−1 to 𝛼,𝛽-position results in very little additional shifting of the
2500 cm−1 . The band is usually centered near 3000 cm−1 . C⏤O absorption.
The weaker C⏤H stretching bands are generally seen super- Substitution in the 𝛼-position with electronegative
imposed upon the broad O⏤H band. Fine structure observed groups, such as the halogens, brings about a slight increase
on the long-wavelength side of the broad O⏤H band repre- in the C⏤O absorption wavenumber (10 cm−1 to 20 cm−1 ).
sents overtones and combination tones of fundamental bands The spectra of acids with halogens in the 𝛼-position, deter-
occurring at longer wavelengths. The spectrum of a typical mined in the liquid state or in solution, show dual carbonyl
aliphatic carboxylic acid is displayed in Figure 2.27. bands resulting from rotational isomerism (field effect). The
Other structures with strong hydrogen bonding, such as higher frequency band corresponds to the conformation in
𝛽-diketones, also absorb in the 3300 cm−1 to 2500 cm−1 which the halogen is in proximity to the carbonyl group.
region, but the absorption is usually less intense. Also, the
C⏤O stretching vibrations of structures such as 𝛽-diketones 2.6.13.3 C⏤O Stretching and O⏤H Bending Vibra-
are shifted to lower frequencies than those observed for tions. Two bands arising from C⏤O stretching and O⏤H
carboxylic acids. bending appear in the spectra of carboxylic acids near 1320
Carboxylic acids can bond intermolecularly with ethers, cm−1 to 1210 cm−1 and 1440 cm−1 to 1395 cm−1 , respec-
such as dioxane and tetrahydrofuran, or with other solvents tively. Both of these bands involve some interaction between
that can act as proton acceptors. Spectra determined in such C⏤O stretching and in-plane C⏤O⏤H bending. The more
solvents show bonded O⏤H absorption near 3100 cm−1 . intense band, near 1315 cm−1 to 1280 cm−1 for dimers, is
generally referred to as the C⏤O stretching band and usu-
2.6.13.2 C⏤O Stretching Vibrations. The C⏤O stretch- ally appears as a doublet in the spectra of long-chain fatty
ing bands of acids are considerably more intense than ketonic acids. The C⏤O⏤H bending band at 1440 cm−1 to 1395
C⏤O stretching bands. The monomers of saturated aliphatic cm−1 is of moderate intensity and occurs in the same region
acids absorb near 1760 cm−1 . as the CH2 scissoring vibration of the CH2 group adjacent to
The carboxylic dimer has a center of symmetry; only the carbonyl.
the asymmetrical C⏤O stretching mode absorbs in the One of the characteristic bands in the spectra of dimeric
IR. Hydrogen bonding and resonance weaken the C⏤O carboxylic acids results from the out-of-plane bending of
bond, resulting in absorption at a lower frequency than the the bonded O⏤H. The band appears near 920 cm−1 and is
monomer. The C⏤O group in dimerized saturated aliphatic characteristically broad with medium intensity.
acids absorbs in the region of 1720 cm−1 to 1706 cm−1 .
Internal hydrogen bonding reduces the frequency of the 2.6.14 Carboxylate Anion
carbonyl stretching absorption to a greater degree than does - --O bonds
The carboxylate anion has two strongly coupled C⏤
intermolecular hydrogen bonding. For example, salicylic
with bond strengths intermediate between C⏤O and C⏤O.
acid absorbs at 1665 cm−1 , whereas p-hydroxybenzoic acid
absorbs at 1680 cm−1 . O
Unsaturation in conjugation with the carboxylic car-
C
bonyl group decreases the frequency (increases the
wavelength) of absorption of both the monomer and dimer O

100
1108
1216
%Transmittance

2674

946

50
1301
1424
3044

O
2874

HO C (CH2)4CH3
2967

1717

4000 3000 2000 1000

Wavenumber (cm–1)
FIGURE 2.27 Hexanoic acid. Broad O⏤H stretch, 3300 cm−1 to 2500 cm−1 . C⏤H stretch (see Figure 2.8), 2967, 2874,
2855 cm . Superimposed upon O⏤H stretch. Normal, dimeric carboxylic C⏤O stretch, 1717 cm−1 . C⏤O⏤H in-plane
−1

bend, 1424 cm−1 . C⏤O stretch, dimer, 1301 cm−1 . O⏤H out-of-plane bend, 946 cm−1 .
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96 CHAPTER 2 INFRARED SPECTROSCOPY

The carboxylate ion gives rise to two bands: a strong The force constant of the carbonyl bond is increased by
asymmetrical stretching band near 1650 cm−1 to 1550 cm−1 the electron-attracting nature of the adjacent oxygen atom
and a weaker, symmetrical stretching band near 1400 cm−1 . (inductive effect). Overlapping occurs between esters in
The conversion of a carboxylic acid to a salt can serve as which the carbonyl frequency is lowered, and ketones in
confirmation of the acid structure. This is conveniently done which the normal ketone frequency is raised. A distin-
by the addition of a tertiary aliphatic amine, such as triethy- guishing feature of esters and lactones, however, is the
lamine, to a solution of the carboxylic acid in chloroform (no strong C⏤O stretching band in the region where a weaker
reaction occurs in CCl4 ). The carboxylate ion thus formed band occurs for ketones. There is overlapping in the C⏤O
shows the two characteristic carbonyl absorption bands in frequencies of esters or lactones and acids, but the OH
addition to an ammonium band in the 2700 cm−1 to 2200 stretching and bending vibrations and the possibility of salt
cm−1 region. The O⏤H stretching band, of course, disap- formation distinguish the acids.
pears. The spectrum of ammonium benzoate (Figure 2.28) The frequency of the ester carbonyl responds to environ-
demonstrates most of these features. mental changes in the vicinity of the carbonyl group in much
the same manner as ketones. The spectrum of phenyl acetate
illustrates most of the important absorption characteristics
2.6.15 Esters and Lactones for esters (Figure 2.29).
Esters and lactones have two characteristically strong absorp-
tion bands arising from C⏤O and C⏤O stretching. The 2.6.15.1 C⏤O Stretching Vibrations. The C⏤O absorp-
intense C⏤O stretching vibration occurs at higher fre- tion band of saturated aliphatic esters (except formates) is in
quencies (shorter wavelength) than that of normal ketones. the 1750 cm−1 to 1735 cm−1 region. The C⏤O absorption

–1
Wavenumber (cm )

FIGURE 2.28 Benzoic acid, ammonium salt. A. N⏤H and C⏤H stretch, 3600 cm−1 to 2500 cm−1 . B. Ring C⏤O stretch, 1600 cm−1 .
C. Asymmetric carboxylate anion C(−O)−2 stretch, 1550 cm−1 . D. Symmetric carboxylate C(−O)−2 stretch, 1385 cm−1 .

100
3075
3052

1023
%Transmittance

1601

O
930

699
753

50
1493
1378

O CH3
1771

1223
1200

4000 3000 2000 1000

Wavenumber (cm–1)
FIGURE 2.29 Phenyl acetate. Aromatic C⏤H stretch, 3075, 3052 cm−1 . C⏤O stretch, 1771 cm−1 : this is higher frequency
than that from a normal ester C⏤O stretch (1740 cm−1 : see Table 2.6) because of phenyl conjugation with alcohol oxygen;
conjugation of an aryl group or other unsaturation with the carbonyl group causes this C⏤O stretch to be at lower than
normal frequency (e.g., benzoates absorb at about 1724 cm−1 ). Ring C⏤C stretch, 1601 cm−1 . 𝛿as CH3 , 1493 cm−1 , 𝛿s CH3 ,
1378 cm−1 . Acetate C(⏤O)⏤O stretch, 1223 cm−1 O⏤C⏤C asymmetrical stretch, 1200 cm−1 .
 Silverstein c02.tex V3 - 07/30/2014 1:37 P.M. Page 97

2.6 CHARACTERISTIC GROUP ABSORPTIONS OF ORGANIC MOLECULES 97

bands of formates and of 𝛼,𝛽-unsaturated and benzoate esters band at 1240 cm−1 . Vinyl and phenyl acetates absorb at a
are in the region of 1730 cm−1 to 1715 cm−1 . Further con- somewhat lower wavenumber, 1190 cm−1 to 1140 cm−1 ; for
jugation has little or no additional effect on the frequency of example, see Figure 2.29. The C⏤C(⏤O)⏤O stretch of
the carbonyl absorption. esters of 𝛼,𝛽-unsaturated acids results in multiple bands in
In the spectra of vinyl or phenyl esters, with unsaturation the 1300 cm−1 to 1160 cm−1 region. Esters of aromatic acids
adjacent to the C⏤O⏤ group, a marked rise in the carbonyl absorb strongly in the 1310 cm−1 to 1250 cm−1 region. The
frequency is observed along with a lowering of the C⏤O analogous type of stretch in lactones is observed in the 1250
frequency. Vinyl acetate has a carbonyl band at 1776 cm−1 ; cm−1 to 1111 cm−1 region.
phenyl acetate absorbs at 1771 cm−1 . The O⏤C⏤C band of esters (alcohol carbon–oxygen
𝛼-Halogen substitution results in a rise in the C⏤O stretch) of primary alcohols occurs at about 1164 cm−1 to
stretching frequency. Ethyl trichloroacetate absorbs at 1031 cm−1 and that of esters of secondary alcohols occurs at
1770 cm−1 . about 1100 cm−1 . Aromatic esters of primary alcohols show
In oxalates and 𝛼-keto esters, as in 𝛼-diketones, there this absorption near 1111 cm−1 .
appears to be little or no interaction between the two carbonyl Methyl esters of long-chain fatty acids present a three-
groups so that normal absorption occurs in the region of 1755 band pattern with bands near 1250, 1205, and 1175 cm−1 .
cm−1 to 1740 cm−1 . In the spectra of 𝛽-keto esters, however, The band near 1175 cm−1 is the strongest.
where enolization can occur, a band is observed near 1650
cm−1 that results from hydrogen bonding between the ester
C⏤O and the enolic hydroxyl group. 2.6.16 Acid Halides
The carbonyl absorption of saturated 𝛿-lactones (six-
2.6.16.1 C⏤O Stretching Vibrations. Acid halides show
membered ring) occurs in the same region as straight-chain,
strong absorption in the C⏤O stretching region. Unconju-
unconjugated esters. Unsaturation 𝛼 to the C⏤O group
gated acid chlorides absorb in the 1815 cm−1 to 1785 cm−1
O O region. Acetyl fluoride in the gas phase absorbs near 1869
O O cm−1 . Conjugated acid halides absorb at a slightly lower fre-
quency because resonance reduces the force constant of the
1720 cm 1
1760 cm 1 C⏤O bond; aromatic acid chlorides absorb strongly at 1800
cm−1 to 1770 cm−1 . A weak band near 1750 cm−1 to 1735
reduces the C⏤O absorption frequency. Unsaturation 𝛼 to cm−1 appearing in the spectra of aroyl chlorides probably
the ⏤O⏤ group increases it. results from Fermi resonance between the C⏤O band and
𝛼-Pyrones frequently display two carbonyl absorption the overtone of a lower wavenumber band near 875 cm−1 .
bands in the 1775 cm−1 to 1715 cm−1 region, probably The spectrum of a typical aromatic acid chloride is given in
because of Fermi resonance. Figure 2.30.
Saturated 𝛾-lactones (five-membered ring) absorb at
shorter wavelengths than esters or 𝛿-lactones: 1795 cm−1 to
1760 cm−1 ; 𝛿-valerolactone absorbs at 1770 cm−1 . Unsatura- 2.6.17 Carboxylic Acid Anhydrides
tion in the 𝛾-lactone molecule affects the carbonyl absorption 2.6.17.1 C⏤O Stretching Vibrations. Anhydrides dis-
in the same manner as unsaturation in 𝛿-lactones. play two stretching bands in the carbonyl region. The two
O O bands result from asymmetrical and symmetrical C⏤O
O O stretching modes. Saturated acyclic anhydrides absorb near
1818 cm−1 and 1750 cm−1 . Conjugated acyclic anhydrides
1800 cm 1
1750 cm 1 show absorption near 1775 cm−1 and 1720 cm−1 ; the
decrease in the frequency of absorption may be explained by
In unsaturated lactones, when the double bond is adja- resonance structures. The higher frequency band is the more
cent to the ⏤O⏤, a strong C⏤C absorption is observed in intense.
the 1685 cm−1 to 1660 cm−1 region. Cyclic anhydrides with five-membered rings show
absorption at higher frequencies than acyclic anhydrides
2.6.15.2 C⏤O Stretching Vibrations. The C⏤O stretch- because of ring strain; succinic anhydride absorbs at 1865
ing vibrations of esters actually consist of two asymmetrical cm−1 and 1782 cm−1 . The lower frequency C⏤O band is
coupled vibrations: C⏤C(⏤O)⏤O and O⏤C⏤C, the for- the stronger of the two carbonyl bands in five-membered ring
mer being more important. These bands occur in the region cyclic anhydrides.
of 1300 cm−1 to 1000 cm−1 . The corresponding symmetric
vibrations are of little importance. The C⏤O stretch corre-
2.6.17.2 C⏤O Stretching Vibrations. Other strong
lations are less reliable than the C⏤O stretch correlations.
bands appear in the spectra of anhydrides as a result of
The C⏤C(⏤O)⏤O band of saturated esters, except
for acetates, is shown strongly in the 1210 cm−1 to 1163 O O
cm−1 region. It is often broader and stronger than the C⏤O
stretch absorption. Acetates of saturated alcohols display this C C O C C
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98 CHAPTER 2 INFRARED SPECTROSCOPY

100

90
(CH2)5CH3

3036
%Transmittance

80

1470

660
70

1216
1177
1748
1609
2866
60

884
1779
C
O Cl

2936
50

4000 3000 2000 1000

Wavenumber (cm–1)
FIGURE 2.30 IR spectrum of 4-hexylbenzoyl chloride. Aromatic C⏤H stretch, 3036 cm−1 . C⏤H stretch, 2936 cm−1 and
2866 cm−1 . C⏤O stretch, 1779 cm−1 . Acid chloride C⏤O stretch wavenumbers show a small dependence on conjugation.
Aroyl chlorides can be identified by a Fermi resonance band such as that seen at 1748 cm−1 (due to the C⏤O stretch and the
overtone of the 884 cm−1 band).

stretching vibrations. Unconjugated straight-chain anhy- Primary amides and secondary amides, and a few
drides absorb near 1047 cm−1 . Cyclic anhydrides display lactams, display a band or bands in the region of 1650 cm−1
bands near 952 cm−1 to 909 cm−1 and 1299 cm−1 to to 1515 cm−1 caused primarily by NH2 or NH bending. This
1176 cm−1 . The C⏤O stretching band for acetic anhydride is called the amide II band. This absorption involves coupling
is at 1125 cm−1 . between N⏤H bending and other fundamental vibrations
The spectrum of benzoic anhydride in Figure 2.31 is that and requires a trans geometry.
of a typical aromatic anhydride. Out-of-plane N⏤H wagging is responsible for a broad-
band of medium intensity in the 800 cm−1 to 666 cm−1 region.
The spectrum of acrylamide in Figure 2.32 is that of a
2.6.18 Amides and Lactams typical primary amide of an unsaturated acid.
All amides show a carbonyl absorption band known as the
amide I band. Its position depends on the degree of hydrogen 2.6.18.1 N⏤H Stretching Vibrations. In dilute solution
bonding and, thus, on the physical state of the compound. in nonpolar solvents, primary amides show two moder-
Primary amides show two N⏤H stretching bands ately intense N⏤H stretching frequencies corresponding to
resulting from symmetrical and asymmetrical N⏤H stretch- the asymmetrical and symmetrical N⏤H stretching vibra-
ing. Secondary amides and lactams show only one N⏤H tions. These bands occur near 3520 cm−1 and 3400 cm−1 ,
stretching band. As in the case of O⏤H stretching, the fre- respectively. In the spectra of solid samples, these bands are
quency of the N⏤H stretching is reduced by hydrogen bond- observed near 3350 cm−1 and 3180 cm−1 because of hydro-
ing, though to a lesser degree. Overlapping occurs in the gen bonding.
observed position of N⏤H and O⏤H stretching frequencies In IR spectra of secondary amides, which exist mainly
so that an unequivocal differentiation in structure is some- in the trans conformation, the free N⏤H stretching vibration
times impossible. observed in dilute solutions occurs near 3500 cm−1 to 3400

100
3013
3067

622
1601
%Transmittance

1455

1285

784
1717

50 O
714
1216

O O
1779

1046

4000 3000 2000 1000

Wavenumber (cm–1)
FIGURE 2.31 Benzoic anhydride. Aromatic C⏤H stretch, 3067, 3013 cm−1 . Asymmetric and symmetric C⏤O coupled
stretching, respectively: 1779, 1717 cm−1 . See Table 2.6. C⏤CO⏤O⏤CO⏤C stretch, 1046 cm−1 .
 Silverstein c02.tex V3 - 07/30/2014 1:37 P.M. Page 99

2.6 CHARACTERISTIC GROUP ABSORPTIONS OF ORGANIC MOLECULES 99

100

2820
%Transmittance

984
50 O

1139

660
1285
C
H2C CH NH2

1355
1432
1679
1617
0 3198
3352

4000 3000 2000 1000

Wavenumber (cm–1)
FIGURE 2.32 Acrylamide. N⏤H stretch, coupled, primary amide, hydrogen bonded; asymmetric, 3352 cm−1 ; symmetric,
3198 cm−1 . Overlap C⏤O stretch, amide I band, 1679 cm−1 ; see Table 2.6. N⏤H bend, amide II band, 1617 cm−1 . C⏤N
stretch, 1432 cm−1 . Broad N⏤H out-of-plane bend 700 – 600 cm−1 .

cm−1 . In more concentrated solutions and in solid samples, N, N-diethylacetamide absorbs at 1647 cm−1 in dioxane and
the free N⏤H band is replaced by multiple bands in the 3330 at 1615 cm−1 in methanol.
cm−1 to 3060 cm−1 region. Multiple bands are observed Electron-attracting groups attached to the nitrogen
since the amide group can bond to produce dimers with an s- increase the frequency of absorption since they effectively
cis conformation and polymers with an s-trans conformation. compete with the carbonyl oxygen for the electrons of
the nitrogen, thus increasing the force constant of the
R O H R R R C⏤O bond.
C C N H O C
C C O C N H 2.6.18.3 N⏤H Bending Vibrations (Amide II Band).
R H O R R R All primary amides show a sharp absorption band in dilute
s-cis s-trans solution (amide II band) resulting from N⏤H bending at
a somewhat lower frequency than the C⏤O band. This
2.6.18.2 C⏤O Stretching Vibrations (Amide I Band). band has an intensity of one-half to one-third of the C⏤O
The C⏤O absorption of amides occurs at lower frequencies absorption band. In mulls and pellets, the band occurs near
than “normal” carbonyl absorption due to the resonance 1655 cm−1 to 1620 cm−1 and is usually under the envelope
effect (see Section 2.6.10.1). The position of absorption of the amide I band. In dilute solutions, the band appears at
depends on the same environmental factors as the carbonyl lower wavenumbers, 1620 cm−1 to 1590 cm−1 , and normally
absorption of other compounds. is separated from the amide I band. Multiple bands may
Primary amides (except acetamide, whose C⏤O bond appear in the spectra of concentrated solutions, arising from
absorbs at 1694 cm−1 ) have a strong amide I band in the the free and associated states. The nature of the R group in
region of 1650 cm−1 when examined in the solid phase. R⏤C(⏤O) ⏤NH2 has little effect on the amide II band.
When the amide is examined in dilute solution, the absorp- Secondary acyclic amides in the solid-state display
tion is observed at a higher wavenumber, near 1690 cm−1 . an amide II band in the region of 1570 cm−1 to 1515
In more concentrated solutions, the C⏤O wavenumber is cm−1 . In dilute solution, the band occurs in the 1550 cm−1
observed at some intermediate value, depending on the to 1510 cm−1 region. This band results from interaction
degree of hydrogen bonding. between the N⏤H bending and the C⏤N stretching of the
Simple, open-chain, secondary amides absorb near C⏤N⏤H group. A second, weaker band near 1250 cm−1
1640 cm−1 when examined in the solid state. In dilute solu- also results from interaction between N⏤H bending and
tion, the wavenumber of the amide I band may be raised to C⏤N stretching.
1680 cm−1 and even to 1700 cm−1 in the case of the anilides.
In the anilide structure there is competition between the ring 2.6.18.4 Other Vibration Bands. The C⏤N stretching
and the C⏤O for the nonbonded electron pair of the nitrogen band of primary amides occurs near 1400 cm−1 . A broad,
atom. medium band in the 800 cm−1 to 666 cm−1 region in the
The carbonyl frequency of tertiary amides is indepen- spectra of primary and secondary amides results from out-
dent of the physical state since hydrogen bonding with of-plane N⏤H wagging.
another tertiary amide group is impossible. The C⏤O In lactams of medium ring size, the amide group is
absorption occurs in the range of 1680 cm−1 to 1630 forced into the s-cis conformation. Solid lactams absorb
cm−1 . The absorption range of tertiary amides in solu- strongly near 3200 cm−1 because of the N⏤H stretching
tion is influenced by hydrogen bonding with the solvent: vibration. This band does not shift appreciably with dilution
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100 CHAPTER 2 INFRARED SPECTROSCOPY

since the s-cis form remains associated at relatively low 1650 cm−1 to 1580 cm−1 region of the spectrum. The band
concentrations. is medium to strong in intensity and is moved to slightly
higher frequencies when the compound is associated. The
2.6.18.5 C⏤O Stretching Vibrations of Lactams. The N⏤H bending band is seldom detectable in the spectra
C⏤O absorption of lactams with six-membered rings or of aliphatic secondary amines, whereas secondary aromatic
larger is near 1650 cm−1 . Five-membered ring (𝛾) lactams amines absorb near 1515 cm−1 .
absorb in the 1750 cm−1 to 1700 cm−1 region. Unfused four- Liquid samples of primary and secondary amines dis-
membered ring (𝛽) lactams absorb at 1760 cm−1 to 1730 play medium-to-strong broad absorption in the 909 cm−1 to
cm−1 . Fusion of the lactam ring to another ring generally 666 cm−1 region of the spectrum arising from NH wagging.
increases the frequency by 20 cm−1 to 50 cm−1 . The position of this band depends on the degree of hydrogen
Most lactams do not show a band near 1550 cm−1 that bonding.
is a characteristic of s-trans noncyclic secondary amides.
The N⏤H out-of-plane wagging in lactams causes broad
absorption in the 800 cm−1 to 700 cm−1 region. 2.6.19.3 C⏤N Stretching Vibrations. Medium-to-weak
absorption bands for the unconjugated C⏤N linkage in
2.6.19 Amines primary, secondary, and tertiary aliphatic amines appear
in the region of 1250 cm−1 to 1020 cm−1 . The vibrations
The spectrum of a typical primary aliphatic diamine appears responsible for these bands involve C⏤N stretching coupled
in Figure 2.33. with the stretching of adjacent bonds in the molecule. The
position of absorption in this region depends on the class of
2.6.19.1 N⏤H Stretching Vibrations. Primary amines,
the amine and the pattern of substitution on the 𝛼-carbon.
examined in dilute solution, display two weak absorption Aromatic amines display strong C⏤N stretching
bands: one near 3500 cm−1 and the other near 3400 cm−1 . absorption in the 1342 cm−1 to 1266 cm−1 region. The
These bands represent, respectively, the “free” asymmetrical absorption appears at higher frequencies than the corre-
and symmetrical N⏤H stretching modes. Secondary amines sponding absorption of aliphatic amines because the force
show a single weak band in the 3350 cm−1 to 3310 cm−1 constant of the C⏤N bond is increased by resonance with
region. These bands are shifted to longer wavelengths by the ring.
hydrogen bonding. The associated N⏤H bands are weaker Characteristic strong C⏤N stretching bands in the
and frequently sharper than the corresponding O⏤H bands. spectra of aromatic amines have been assigned as shown in
Aliphatic primary amines (neat) absorb at 3400 cm−1 to Table 2.7.
3300 cm−1 and 3330 cm−1 to 3250 cm−1 . Aromatic primary
amines absorb at slightly higher wavenumbers. In the spectra
of liquid primary and secondary amines, a shoulder usually
appears on the low-frequency side of the N⏤H stretching
2.6.20 Amine Salts
band, arising from the overtone of the NH bending band
intensified by Fermi resonance. Tertiary amines do not 2.6.20.1 N⏤H Stretching Vibrations. The ammonium
absorb in this region. ion gives a strong, broad absorption in the 3300 cm−1 to
3030 cm−1 region because of N⏤H stretching vibrations
2.6.19.2 N⏤H Bending Vibrations. The N⏤H bending (see Figure 2.28). There is also a combination band in the
(scissoring) vibration of primary amines is observed in the 2000 cm−1 to 1709 cm−1 region.

100
1316

1069
1385
%Transmittance

CH3
1470
1601
3368
3291

838
876

H2N CH2 CH (CH2)3 NH2

50
2859
2928

4000 3000 2000 1000

Wavenumber (cm–1)
FIGURE 2.33 2-Methyl-1,5-pentanediamine. N⏤H stretch, hydrogen-bonded, primary amine coupled doublet:
asymmetric, 3368 cm−1 . Symmetric, 3291 cm−1 . (Shoulder at about 3200 cm−1 , Fermi resonance band with overtone of band
at 1601 cm−1 . Aliphatic C⏤H stretch, 2928, 2859 cm−1 . N⏤H bend (scissoring) 1601 cm−1 . 𝛿s CH2 (scissoring), 1470 cm−1 .
C⏤N stretch, 1069 cm−1 . N⏤H wag (neat sample), ∼900 cm−1 to 700 cm−1 .
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2.6 CHARACTERISTIC GROUP ABSORPTIONS OF ORGANIC MOLECULES 101

TABLE 2.7 C⏤N Stretch of Aromatic Amines Free primary amino acids are characterized by the
following absorptions (most of the work was done with
Aromatic Amine Absorption Region (cm−1 )
𝛼-amino acids, but the relative positions of the amino and
Primary 1340 to 1250 carboxyl groups seem to have little effect):
Secondary 1350 to 1280
1. A broad, strong NH+3 stretching band in the 3100 cm−1
Tertiary 1360 to 1310
to 2600 cm−1 region. Multiple combination and over-
tone bands extend the absorption to about 2000 cm−1 .
This overtone region usually contains a prominent band
Salts of primary amines show strong, broad absorption near 2222 cm−1 to 2000 cm−1 assigned to a combina-
between 3000 cm−1 and 2800 cm−1 arising from asymmet- tion of the asymmetrical NH+3 bending vibration and
rical and symmetrical stretching in the NH+3 group. In addi- the torsional oscillation of the NH+3 group. The torsional
tion, multiple combination bands of medium intensity occur oscillation occurs near 500 cm−1 . The 2000 cm−1 band
in the 2800 cm−1 to 2000 cm−1 region, the most prominent is absent if the nitrogen atom of the amino acid is sub-
being the band near 2000 cm−1 . Salts of secondary amines stituted.
absorb strongly in the 3000 cm−1 to 2700 cm−1 region with
multiple bands extending to 2273 cm−1 . A medium intensity 2. A weak asymmetrical NH+3 bending band near 1660
band near 2000 cm−1 may be observed. Tertiary amine salts cm−1 to 1610 cm−1 and a fairly strong symmetrical
absorb at longer wavelengths than do the salts of primary bending band near 1550 cm−1 to 1485 cm−1 .
and secondary amines (2700 cm−1 to 2250 cm−1 ). Quater- O
nary ammonium salts have no N⏤H stretching vibrations. 3. The carboxylate ion group C absorbs strongly
O
near 1600 cm−1 to 1590 cm−1 and more weakly near
2.6.20.2 N⏤H Bending Vibrations. The ammonium ion 1400 cm−1 . These bands result, respectively, from asym-
displays a strong, broad NH+4 bending band near 1429 cm−1 . metrical and symmetrical C(⏤O)2 stretching.
The NH+3 group of the salt of a primary amine absorbs near
The spectrum of the amino acid leucine, including
1600 cm−1 to 1575 cm−1 and 1550 cm−1 to 1504 cm−1 .
assignments corresponding to the preceding three categories,
These bands originate in asymmetrical and symmetrical
is shown in Figure 2.34.
NH+3 bending, analogous to the corresponding bands of the
Hydrochlorides of amino acids present the following
CH3 group. Salts of secondary amines absorb near 1620
patterns:
cm−1 to 1560 cm−1 . The N⏤H bending band of the salts
of tertiary amines is weak and of no practical value. 1. Broad, strong absorption in the 3333 cm−1 to 2380
cm−1 region resulting from superimposed O⏤H and
NH+3 stretching bands. Absorption in this region is
2.6.21 Amino Acids and Salts characterized by fine structure on the low-wavenumber
of Amino Acids side of the band.
Amino acids are encountered in three forms: 2. A weak, asymmetrical NH+3 bending band near 1610
1. The free amino acid (zwitterion).* cm−1 to 1590 cm−1 and a relatively strong, symmetrical
NH+3 bending band at 1550 cm−1 to 1481 cm−1 .
C CO2 3. A strong band at 1220 cm−1 to 1190 cm−1 arising from
C⏤C(⏤O)⏤O stretching.
NH 3 4. Strong carbonyl absorption at 1755 cm−1 to 1730 cm−1
for 𝛼-amino acid hydrochlorides, and at 1730 cm−1 to
2. The hydrochloride (or other salt).
1700 cm−1 for other amino acid hydrochlorides.

C CO2H Sodium salts of amino acids show the normal N⏤H

stretching vibrations at 3400 cm−1 to 3200 cm−1 common
NH 3 Cl to other amines. The characteristic carboxylate ion bands
appear near 1600 cm−1 to 1590 cm−1 and near 1400 cm−1 .
3. The sodium (or other cation) salt.
2.6.22 Nitriles
C CO2 Na
The spectra of nitriles (R⏤C⏤ ⏤N) are characterized by
NH2 weak-to-medium absorption in the triple-bond stretching
region of the spectrum. Aliphatic nitriles absorb at 2260
* Aromatic amino acids are not zwitterions. Thus p-aminobenzoic acid is cm−1 to 2240 cm−1 . Electron-attracting atoms, such as
oxygen or chlorine, attached to the carbon atom 𝛼 to the
H 2N COOH C⏤⏤N group reduce the intensity of absorption. Conjugation,
such as occurs in aromatic nitriles, reduces the wavenumber
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102 CHAPTER 2 INFRARED SPECTROSCOPY

Wavenumber (cm–1)

FIGURE 2.34 (±)-Leucine. A. Broad (−NH+ 3

) N⏤H stretch, 3100 – 2000 cm−1 , extended by combination band at 2140 cm−1 , and
other combination-overtone bands. B. Aliphatic C⏤H stretch (superimposed on N⏤H stretch), 2967 cm−1 . C. Asymmetric (−NH+3 )
N⏤H bend, 1610 cm−1 . D. Asymmetric carboxylate (C⏤O)2 stretch, 1580 cm−1 . E. Symmetric (−NH+3 ) N⏤H bend, 1505 cm−1 .
F. Symmetric carboxylate (C⏤O)2 stretch, 1405 cm−1 . G. Torsional (−NH+3 ) N⏤H oscillation, 525 cm−1 .

of absorption to 2240 cm−1 to 2222 cm−1 and enhances electron-donating group absorb near 1429 cm−1 . The bands
the intensity. The spectrum of a typical nitrile is shown in are weak because of the nonpolar nature of the bond.
Figure 2.35.
2.6.25 Covalent Compounds
Containing Nitrogen⏤Oxygen Bonds
2.6.23 Isonitriles (R⏤N⏤
⏤C),
Cyanates (R⏤O⏤C⏤ ⏤N), Nitro compounds, nitrates, and nitramines contain an NO2
Isocyanates (R⏤N⏤C⏤O), group. Each of these classes shows absorption caused by
Thiocyanates (R⏤S⏤C⏤ ⏤N), and asymmetrical and symmetrical stretching of the NO2 group.
Isothiocyanates (R⏤N⏤C⏤S) Asymmetrical absorption results in a strong band in the
1661 cm−1 to 1499 cm−1 region; symmetrical absorption
These groups show the triple bond or cumulative bond stretch
occurs in the region between 1389 cm−1 and 1259 cm−1 . The
in the 2280 cm−1 to 2000 cm−1 region.
exact position of the bands is dependent on substitution and
unsaturation in the vicinity of the NO2 group.
2.6.24 Compounds Containing
2.6.25.1 N⏤O Stretching Vibrations.
a ⏤N⏤N Group
The N⏤N stretching vibration of a symmetrical trans- Nitro Compounds In nitroalkanes, the bands occur
azo compound is forbidden in the IR but absorbs around near 1550 cm−1 and 1372 cm−1 . Conjugation lowers the
1576 cm−1 in the Raman spectrum. Unsymmetrical para- wavenumbers of both bands, resulting in absorption near
substituted azobenzenes in which the substituent is an 1550 cm−1 to 1500 cm−1 and 1360 cm−1 to 1290 cm−1 .

100

H
90
1601
%Transmittance

3067
2944

CH3 C C N
1686
2249

1270

1085
2990

80
1501
1455

761

70
707

4000 3000 2000 1000

Wavenumber (cm–1)
FIGURE 2.35 𝛼-Methylbenzyl cyanide. Aromatic C⏤H stretch, 3067, 3030 cm−1 . Aliphatic C⏤H stretch, 2990,
⏤
2944 cm . C⏤N stretch, 2249 cm−1 . Out-of-plane C⏤H bend (aromatic ring), 761 cm−1 .
−1
 Silverstein c02.tex V3 - 07/30/2014 1:37 P.M. Page 103

2.6 CHARACTERISTIC GROUP ABSORPTIONS OF ORGANIC MOLECULES 103

Attachment of electronegative groups to the 𝛼-carbon of a to 1610 cm−1 region. The N⏤O stretching band appears
nitro compound causes an increase in the frequency of the in the region between 850 cm−1 and 750 cm−1 . The nitrite
asymmetrical NO2 band and a reduction in the frequency absorption bands are among the strongest observed in IR
of the symmetrical band; chloropicrin, Cl3 CNO2 , absorbs at spectra.
1610 cm−1 and 1307 cm−1 .
Aromatic nitro groups absorb near the same frequen- Nitroso Compounds Primary and secondary ali-
cies as observed for conjugated aliphatic nitro compounds. phatic C-nitroso compounds are usually unstable and rear-
Interaction between the NO2 out-of-plane bending and ring range to oximes or dimerize. Tertiary and aromatic nitroso
C⏤H out-of-plane bending frequencies destroys the relia- compounds are reasonably stable, existing as monomers in
bility of the substitution pattern observed for nitroaromatics the gaseous phase or in dilute solution and as dimers in neat
in the long-wavelength region of the spectrum. Nitroaro- samples. Monomeric, tertiary, aliphatic nitroso compounds
matic compounds show a C⏤N stretching vibration near show N⏤O absorption in the 1585 cm−1 to 1539 cm−1
870 cm−1 . The spectrum of nitrobenzene, with assignments region; aromatic monomers absorb between 1511 cm−1 and
corresponding to the preceding discussion, is shown in 1495 cm−1 .
Figure 2.36. The N→O stretching absorptions of dimeric nitroso
Because of strong resonance in aromatic systems con- compounds are categorized in Appendix B as to cis versus
taining NO2 groups and electron-donating groups such as the trans and aliphatic versus aromatic. Nitrosoamine absorp-
amino group, ortho or para to one another, the symmetrical tions are given in Appendix B.
NO2 vibration is shifted to lower frequencies and increases
in intensity. p-Nitroaniline absorbs at 1475 cm−1 and 1310 2.6.26 Organic Sulfur Compounds
cm−1 . 2.6.26.1 S⏤H Stretching Vibrations: Mercaptans.
The positions of asymmetric and symmetric NO2 Aliphatic mercaptans and thiophenols, as liquids or in solu-
stretching bands of nitramines N NO2 and the NO stretch tion, show S⏤H stretching absorption in the range of 2600
cm−1 to 2550 cm−1 . The S⏤H stretching band is character-
of nitrosoamines are given in Appendix B. istically weak and may go undetected in the spectra of dilute
solutions or thin films. However, since few other groups
Nitrates Organic nitrates show absorption for N⏤O show absorption in this region, it is useful in detecting S⏤H
stretching vibrations of the NO2 group and for the O⏤N groups. The spectrum of 1,6-hexanedithiol in Figure 2.37 is
linkage. Asymmetrical stretching in the NO2 group results that of a mercaptan with a detectable S⏤H stretch band. The
in strong absorption in the 1660 cm−1 to 1625 cm−1 region; band may be obscured by strong carboxyl absorption in the
the symmetrical vibration absorbs strongly near 1300 cm−1 same region. Hydrogen bonding is much weaker for S⏤H
to 1255 cm−1 . Stretching of the 𝜋 bonds of the N⏤O linkage groups than for O⏤H and N⏤H groups.
produces absorption near 870 cm−1 to 833 cm−1 . Absorption The S⏤H group of thiol acids absorbs in the same
observed at longer wavelengths, near 763 cm−1 to 690 cm−1 , region as mercaptans and thiophenols.
likely results from NO2 bending vibrations.
2.6.26.2 C⏤S and C⏤S Stretching Vibrations.
Nitrites Nitrites display two strong N⏤O stretching
bands. The band near 1680 cm−1 to 1650 cm−1 is attributed Sulfides The stretching vibrations assigned to the
to the trans isomer; the cis isomer absorbs in the 1625 cm−1 C⏤S linkage occur in the region of 700 cm−1 to 600 cm−1 .

100
3113
3082

1108
1609

1486

NO2
%Transmittance

50
799
853

707
1355
1532

4000 3000 2000 1000

Wavenumber (cm–1)
FIGURE 2.36 Nitrobenzene. Aromatic C⏤H stretch, 3113, 3082 cm−1 . Asymmetric (ArNO2 )(N⏤O)2 stretch, 1532 cm−1 .
Symmetric (ArNO2 )(N⏤O)2 stretch 1355 cm−1 . C⏤N stretch for ArNO2 , 853 cm−1 . Low-frequency bands are of little use
in determining the nature of ring substitution since these absorption patterns result from interaction of NO2 and C⏤H out-of-
plane bending frequencies. The inability of the “oop” region to reveal structural information is typical of aromatic compounds
with highly polar substituents.
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104 CHAPTER 2 INFRARED SPECTROSCOPY

100

2558

730
1277
1463
%Transmittance

SH

2859
HS
50

2936
4000 3000 2000 1000
Wavenumber (cm–1)
FIGURE 2.37 IR spectrum of 1,6-hexanedithiol. Aliphatic C⏤H stretch, 2936 cm−1 , 259 cm−1 . Moderately weak S⏤H
stretch, 2558 cm−1 . C⏤S stretch, 730 cm−1 .

The weakness of absorption and variability of position make absorbs broadly at 2415 cm−1 because of hydrogen-bonded
this band of little value in structural determination. S⏤H stretching absorption.

Disulfides The S⏤S stretching vibration is very 2.6.27 Compounds Containing

weak and falls between 500 and 400 cm−1 . Sulfur⏤Oxygen Bonds
Thiocarbonyl Compounds Aliphatic thials or 2.6.27.1 S⏤O Stretching Vibrations.
thiones exist as trimeric, cyclic sulfides. Aralkyl thiones may
exist either as monomers or trimers, whereas diaryl thiones, Sulfoxides Alkyl and aryl sulfoxides as liquids or
such as thiobenzophenone, exist only as monomers. The in solution show strong absorption in the 1070 cm−1 to
C⏤S group is less polar than the C⏤O group and has a con- 1030 cm−1 region. This absorption occurs at 1050 cm−1
siderably weaker bond. As a consequence, the band is not for dimethyl sulfoxide (DMSO). Conjugation brings about
intense, and it falls at lower frequencies, where it is much a small change in the observed frequency, in contrast to
more susceptible to coupling effects. Identification is there- the marked reduction in frequency of the analogous C⏤O
fore difficult and uncertain. bond absorption accompanying conjugation. Diallyl sulfox-
Compounds that contain a thiocarbonyl group show ide absorbs at 1047 cm−1 . Phenyl methyl sulfoxide and
absorption in the 1250 cm−1 to 1020 cm−1 region. Thioben- cyclohexyl methyl sulfoxide absorb at 1055 cm−1 in dilute
zophenone and its derivatives absorb moderately in the 1224 solution in carbon tetrachloride. The sulfoxide group is sus-
cm−1 to 1207 cm−1 region. Since the absorption occurs in the ceptible to hydrogen bonding, with the absorption shifting
same general region as C⏤O and C⏤N stretching, consid- to slightly lower frequencies from dilute solution to the liq-
erable interaction can occur between these vibrations within uid phase. The frequency of S⏤O absorption is increased by
a single molecule. electronegative substitution.
Spectra of compounds in which the C⏤S group is
attached to a nitrogen atom show an absorption band in the Sulfones Spectra of sulfones show strong absorption
general C⏤S stretching region. In addition, several other bands at 1350 cm−1 to 1300 cm−1 and 1160 cm−1 to 1120
bands in the broad region of 1563 cm−1 to 700 cm−1 can be cm−1 . These bands arise from asymmetric and symmetric
attributed to vibrations involving interaction between C⏤S SO2 stretching, respectively. Hydrogen bonding results in
stretching and C⏤N stretching. absorption near 1300 cm−1 and 1125 cm−1 . Splitting of the
Thioketo compounds that can undergo enolization exist high-frequency band often occurs in CCl4 solution or in the
as thioketo–thioenol tautomeric systems; such systems show solid state.
S⏤H stretching absorption. The thioenol tautomer of ethyl
thiobenzoylacetate Sulfonyl Chlorides Sulfonyl chlorides absorb strong-
ly in the regions of 1410 cm−1 to 1380 cm−1 and 1204 cm−1
H to 1177 cm−1 . This increase in frequency, compared with the
sulfones, results from the electronegativity of the chlorine
OC2H5
C6H5 C atom.

S O Sulfonamides Solutions of sulfonamides absorb

H strongly at 1370 cm−1 to 1335 cm−1 and 1170 cm−1 to 1155
cm−1 . In the solid phase, these wavenumbers are lowered by
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2.6 CHARACTERISTIC GROUP ABSORPTIONS OF ORGANIC MOLECULES 105

TABLE 2.8 Stretching Wavenumber of Sulfonates, Sulfates, Sulfonic acids are listed in narrow ranges above; these
Sulfonic acids, and Sulfonate salts apply only to anhydrous forms. Such acids hydrate readily
to give bands that are probably a result of the formation of
Class Stretching Wavenumber (cm−1 )
hydronium sulfonate salts, in the 1230 cm−1 to 1120 cm−1
Sulfonates (covalent) 1372 to 1335, 1195 to 1168 range.
Sulfates (organic) 1415 to 1380, 1200 to 1185
Sulfonic acids 1350 to 1342, 1165 to 1150
Sulfonate salts 1175, 1055 2.6.28 Organic Halogen Compounds
The strong absorption of halogenated hydrocarbons arises
from the stretching vibrations of the carbon–halogen bond
(Table 2.9).
10 cm−1 to 20 cm−1 , the high-wavenumber band is broad- Aliphatic C⏤Cl absorption is observed in the broad
ened, and several submaxima usually appear. region between 850 cm−1 and 550 cm−1 . When several chlo-
Primary sulfonamides show strong N⏤H stretching rine atoms are attached to one carbon atom, the band is
bands at 3390 cm−1 to 3330 cm−1 and 3300 cm−1 to 3247 usually more intense and at the high-frequency end of the
cm−1 in the solid state; secondary sulfonamides absorb near assigned limits. Carbon tetrachloride shows an intense band
3265 cm−1 . at 797 cm−1 . The first overtones of the intense fundamen-
tal bands are frequently observed. Brominated compounds
Sulfonates, Sulfates, and Sulfonic Acids The asym- absorb in the 690 cm−1 to 515 cm−1 region and iodo com-
metric (higher frequency and shorter wavelength) and pounds in the 600 cm−1 to 500 cm−1 region. A strong CH2
symmetric S⏤O stretching frequency ranges for these com- wagging band is observed for the CH2 X (X = Cl, Br, and I)
pounds are provided in Table 2.8. group in the 1300 cm−1 to 1150 cm−1 region.
The spectrum of a typical alkyl arenesulfonate is given Fluorine-containing compounds absorb strongly over a
in Figure 2.38. In virtually all sulfonates, the asymmet- wide range from 1400 cm−1 to 1000 cm−1 because of C⏤F
ric stretch occurs as a doublet. Alkyl and aryl sulfonates stretching modes. A monofluoroalkane shows a strong band
show negligible differences; electron-donating groups in the in the 1100 cm−1 to 1000 cm−1 region. As the number of
para position of arenesulfonates cause higher frequency fluorine atoms in an aliphatic molecule increases, the band
absorption. pattern becomes more complex, with multiple strong bands

100 0.0
90 .05
80 0.1
%
70
T
R
60 A 0.2
N
S
50 O
M
I CH2CH3 0.3
T H 3C S O
40 T 0.4
A
30 N O 0.5
C
E 0.6
20 0.7
NEAT 0.8
10 A B 0.9
1.0
0
C 2.0
4600 4400 4200 4000 3800 3600 3400 3200 3000 2800 2600 2400 2200 2000 1800 1600 1400 1200 1000 800 600 400
NICOLET 20SX FT-IR
Wavenumber (cm–1)

FIGURE 2.38 Ethyl p-toluenesulfonate. A. Asymmetric S(⏤O)2 stretch, 1355 cm−1 . B. Symmetric S(⏤O)2 stretch, 1177 cm−1 .
C. Various strong S⏤O⏤C stretches, 1000 cm−1 to 769 cm−1 .

TABLE 2.9 Aliphatic Organohalogen Compound IR Wavenumbers

Functional Group Wavenumber (cm−1 ) Assignment

C⏤F 1100 to 1000 Monofluoroalkane C⏤F stretch

1350 to 1120 CF3 and CF2
C⏤Cl 850 to 550 Aliphatic chloro compounds, C⏤Cl stretch
C⏤Br 690 to 515 Aliphatic bromo compounds, C⏤Br stretch
C⏤I 600 to 500 Aliphatic iodo compounds, C⏤I stretch
CH2 X (X = Cl, Br, and I) 1300 to 1500 CH2 wagging
 Silverstein c02.tex V3 - 07/30/2014 1:37 P.M. Page 106

106 CHAPTER 2 INFRARED SPECTROSCOPY

appearing over the broad region of C⏤F absorption. The Bands resulting from Si⏤Cl stretching occur at wavenum-
CF3 and CF2 groups absorb strongly in the 1350 cm−1 to bers below 666 cm−1 .
1120 cm−1 region.
Chlorobenzenes absorb in the 1096 cm−1 to 1089 cm−1 2.6.30 Phosphorus Compounds
region. The position within this region depends on the
substitution pattern. Aryl fluorides absorb in the 1250 cm−1 2.6.30.1 P⏤H, P⏤C, P⏤O, and P⏤O Stretching
to 1100 cm−1 region of the spectrum. A monofluorinated Vibrations. The P⏤H bond, which occurs in many organo-
benzene ring displays a strong, narrow absorption band near phosphorus compounds, has stretching vibrations in the
1230 cm−1 . region of 2350 cm−1 to 2440 cm−1 and bending vibrations at
Since halogen atoms have high electronegativity, halo- 1120 cm−1 to 950 cm−1 . The latter may be overshadowed by
gen substitution has a noticeable impact on the spectrum of other intense bands not related to the P⏤H bond. Replace-
neighboring group frequencies, including adjacent hydrogen ment of hydrogen by deuterium produces a significant iso-
atoms. Significant shifting of C⏤H frequencies can occur. tope shift of ∼650 cm−1 , resulting in P⏤D stretching bands
The direction of the shift is dependent on the location of at ∼1750 cm−1 .
the C⏤H group, and whether the halogen adds (higher fre- The stretching vibrations of P⏤C bonds in aliphatic
quency) or subtracts (lower frequency) electron density from phosphine oxides appear in the range of 650 cm−1 to 750
the C⏤H bond. cm−1 , although the size and structure of alkyl groups and
the identity of other substituents on the phosphorus atom
are expected to have some effect. When an aromatic ring
2.6.29 Silicon Compounds is bonded directly to phosphorus, it shows the characteristic
aromatic frequencies corresponding to the respective struc-
2.6.29.1 Si⏤H Vibrations. Vibrations for the Si⏤H tures and positions of the substituents the same as the aro-
bond include the Si⏤H stretch (∼2200 cm−1 ) and the Si⏤H matic ring in hydrocarbons (Section 2.6.6). There are two
bend (800 cm−1 to 950 cm−1 ). The Si⏤H stretching frequen- additional bands near 1000 cm−1 and 1440 cm−1 for com-
cies are increased by the attachment of an electronegative pounds containing an aromatic ring directly attached to phos-
group to the silicon. phorus. The band at 1000 cm−1 is usually stronger than that
at 1440 cm−1 .
2.6.29.2 SiO⏤H and Si⏤O Vibrations. The OH stretch- In the phosphoryl group (P⏤O), unlike for C⏤O, the
ing vibrations of the SiOH group absorb in the same region oxygen atom bonds with the phosphorus in a highly polar
+ −
as the alcohols, 3700 cm−1 to 3200 cm−1 , and strong Si⏤O bond that is frequently designated as a (P − O) group. The
bands are at 830 cm−1 to 1110 cm−1 . As in alcohols, the latter suggests that the IR spectra of the P⏤O group may
absorption characteristics depend on the degree of hydrogen be largely interpreted in the context of a 𝜎 bond. The phos-
bonding. phoryl stretching absorption occurs over a rather wide range,
extending from 1150 cm−1 to 1310 cm−1 (Figure 2.39). The
2.6.29.3 Silicon–Halogen Stretching Vibrations. Absorp- frequency of this band is extremely sensitive to other sub-
tion caused by Si⏤F stretching is in the 800 cm−1 to stituents on the phosphorus atom, and there is a correlation
1000 cm−1 region. between the phosphoryl frequency and the electronegativity

100
3467

2440
Transmittance %

1740

50
1166

H O CH2 CH3
P
O O CH2 CH3
1082
1052

980
1259

0
4000 3000 2000 1500 1000 500
Wavenumber (cm–1)
FIGURE 2.39 IR spectrum of diethyl phosphite. Broad P⏤O⏤H band, 3467 cm−1 . P⏤H
band, 2440 cm−1 . P⏤O stretch, 1259 cm−1 . P⏤O⏤C band, 1166(w), 1062(m), 1052(m),
980(s) cm−1 .
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2.6 CHARACTERISTIC GROUP ABSORPTIONS OF ORGANIC MOLECULES 107

TABLE 2.10 Effect of Electronegativity of Substituents on IR of the other substituents on the phosphorus atom. Table 2.10
Wavenumber of the Phosphoryl Group lists the effects of some substituents on the phosphoryl IR
frequency.
No. Electronegative Wavenumber The phosphoryl group can interact through its oxygen
Compound Substituents in IR (cm−1 ) atom with hydroxyl groups to form hydrogen bonds, or form
O complexes with heavy metal compounds, which can signifi-
OC2H5 cantly shift the stretching bands of the P⏤O group to lower
F P 3 1305
frequency. The metal ions bonding to a phosphoryl group can
OC2H5
reduce the P⏤O absorption by more than 100 cm−1 . Accord-
Dimethylfluorophosphate ingly, in complexes formed between tributylphosphate and
thorium, cerium(IV), or uranyl nitrates, the P⏤O stretching
O band shifts from 1280 cm−1 to ∼1180 cm−1 .
OCH3
CH3O P 3 1275 Organic esters have a characteristic band at about
OCH3 1110 cm−1 , which has been ascribed to the C⏤O⏤C link-
Trimethylphosphate age. Substitution of phosphorus for carbon in an aliphatic
ester group will normally shift the absorption band toward
O lower frequencies. The absorption of the P⏤O⏤C group
OC2 H5
ClC6H4 P of the aliphatic phosphates appears as a strong-to-moderate
OC2 H5 2 1265 broadband near 1050 cm−1 ; an exception is P⏤O⏤CH3 , in
Diethyl p-chloro- which the absorption appears as a single, well-defined, strong
phenylphosphonic acid band, with an additional weak sharp band at 1190 cm−1 . Also
associated with the P⏤O⏤C group is a medium-intensity
O band between 835 cm−1 and 715 cm−1 which becomes quite
OC2H5
C6H5 P weak for an aliphatic group larger than methyl or ethyl. For
2 1257
OC2H5 an aromatic phosphate, this absorption shifts to a higher
wavenumber of 1260 cm−1 to 1160 cm−1 .
Diethylphenylphosphonate

O 2.6.31 Heteroaromatic Compounds

(C6H5)2 P Cl 1 1236 The spectra of heteroaromatic compounds result primarily
from the same vibrational modes as observed for aromatic
Diphenylchlorophosphine oxide
compounds.

2.6.31.1 C⏤H Stretching Vibrations. Heteroaromatics,

CH3

CH3 P O 0 1190 such as pyridines, pyrazines, pyrroles, furans, and thio-

CH3 phenes, show C⏤H stretching bands in the 3077 cm−1 to
Trimethylphosphine oxide 3003 cm−1 region.

2.6.31.2 N⏤H Stretching Frequencies. Heteroaromat-

ics containing an N⏤H group show an N⏤H stretching

100
%Transmittance

1154
1223

50
606
1069
1486
3005

N
1000
1038
3082
3028

753
1439
1586

0
707

4000 3000 2000 1000

Wavenumber (cm–1)
FIGURE 2.40 Pyridine. Aromatic C⏤H stretch, 3090 – 3000 cm−1 . C⏤C, C⏤N ring stretching (skeletal bands),
1600 cm−1 to 1430 cm−1 . C⏤H out-of-plane bending, 753, 707 cm−1 . See Appendix E, Table E.1 for patterns in region C
for substituted pyridines.
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108 CHAPTER 2 INFRARED SPECTROSCOPY

absorption in the region of 3500 cm−1 to 3220 cm−1 . The The IR spectrum of pyridine (Figure 2.40) shows four
position of the absorption within this general region depends bands in this region and, in this respect, closely resembles the
on the degree of hydrogen bonding, and hence upon the phys- spectrum of a monosubstituted benzene. Furans, pyrroles,
ical state of the sample or the polarity of the solvent. Pyrrole and thiophenes display two to four bands in this region.
and indole in dilute solution in nonpolar solvents show a
sharp band near 3495 cm−1 ; concentrated solutions show a 2.6.31.4 C⏤H Out-of-Plane Bending. The C⏤H out-
widened band near 3400 cm−1 . Both bands may be seen at of-plane bending (𝛾-CH) absorption pattern of the heteroaro-
intermediate concentrations. matics is determined by the number of adjacent hydrogen
atoms bending in phase. The C⏤H out-of-plane and ring
2.6.31.3 Ring Stretching Vibrations (Skeletal Bands). bending (𝛽 ring) absorptions of the alkylpyridines are sum-
Ring stretching vibrations occur in the general region marized in Appendix E, Table E.1.
between 1600 cm−1 and 1300 cm−1 . The absorption involves Absorption data for the out-of-phase C⏤H bending
stretching and contraction of all of the bonds in the ring and (𝛾-CH) and ring bending (𝛽 ring) modes of three common
interaction between these stretching modes. The band pattern five-membered heteroaromatic rings are presented in
and the relative intensities depend on the substitution pattern Appendix E, Table E.2. The ranges in Table E.2 include
and the nature of the substituents. polar and nonpolar substituents on the ring.

REFERENCES

For a list of Chapter References, please visit: www.wiley.com/college/silverstein.

STUDENT EXERCISES

2.1 The hydrogen halides have the following stretching wavenum- 100
bers: 4148.3 cm−1 (HF); 2988.9 cm−1 (HCl); 2649.7 cm−1
(HBr); 2309.5 cm−1 (HI). Use Hooke’s law to calculate the 80
force constants of the hydrogen–halogen bonds. Based on your
%Transmittance

60
calculations, predict the corresponding frequencies for the deu-
terium halides. 40
2.2 Which of the following molecules may show infrared absorption
spectra? Why? 20
(a) CH3 CH3 , (b) CH4 , (c) CH3 Cl, (d) N2 . 0
2.3 How many normal modes of vibration are there for each of the
00
00
00
00
00
00
00
00
00
00
00

0
80
40
36
32
28
24
20
18
16
14
12
10
following molecules:
Wavenumber (cm–1)
(a) C6 H6 , (b) C6 H5 CH3 , (c) HC⏤
⏤C⏤C⏤
⏤CH. (b)
2.4 The ATR IR spectra of three xylene isomers (m-, o-, p-xylene)
are shown below. Examine these spectra and label each with the 100
appropriate structure.
80
%Transmittance

60

100 40

80 20
%Transmittance

60 0
00
00
00
00
00
00
00
00
00
00
00

0
80

40
40
36
32
28
24
20
18
16
14
12
10

Wavenumber (cm–1)
20 (c)

0
00
00
00
00
00
00
00
00
00
00
00

0
80
40
36
32
28
24
20
18
16
14
12
10

Wavenumber (cm–1)
(a)
 Silverstein c02.tex V3 - 07/30/2014 1:37 P.M. Page 109

STUDENT EXERCISES 109

2.5 Select a compound that best fits each of the following sets of a broad, sharp doublet at 1750 cm−1 and 1825 cm−1 . Why are
IR bands (in cm−1 ). Each set corresponds to a list of just a few these so different?
important bands for each compound. 2.7 What are “combination bands”? What are “overtones”? How do
Benzamide Diphenyl sulfone each of these contribute to the interpretation of an IR spectrum?
Benzoic acid Formic acid Can you give an example?
Benzonitrile Isobutylamine 2.8 Rank the following phosphorus compounds in order of
Biphenyl 1-Nitropropane dioxane increasing P⏤O IR stretching frequencies.
1,4-Dioxane
a. 3080 (w), nothing 3000 to 2800, 2230 (s), 1450 (s), 760 (s), OCH3 F CH3 OCH3
688 (s) O P OCH3 O P OCH3 O P CH3 O P OCH3
b. 3380 (m), 3300 (m), nothing 3200 to 3000, 2980 (s), 2870 CH3 OCH3 CH3 OCH3
(m), 1610 (m), ∼900 to 700 (b)
c. 3080 (w), nothing 3000 to 2800, 1315 (s), 1300 (s), 1155 (s)
d. 2955 (s), 2850 (5), 1120 (s)
e. 2946 (s), 2930 (m), 1550 (s), 1386 (m) OC6H5 OCH2CH3 CH3
f. 2900 (b, s), 1720 (b, s)
O P OCH3 O P OCH2CH3 O P OCH2CH3
g. 3030 (m), 730 (s), 690 (s)
h. 3200 to 2400 (5), 1685 (b, s), 705 (s) OCH3 OCH2CH3 OCH2CH3
i. 3350 (s), 3060 (m), 1635 (s)
s = strong, m = medium, w = weak, b = broad
2.6 The IR spectra of butyric acid and ethyl butyrate show sharp 2.9 For each of the following IR spectra (A–W) list functional
strong singlet absorption at 1725 cm−1 and 1740 cm−1 , respec- groups that (a) are present and (b) are absent. The mass spectra
tively. By contrast, the IR spectrum of butyric anhydride shows of these compounds are in Chapter 1 (Exercise 1.6).
 Silverstein c02.tex V3 - 07/30/2014 1:37 P.M. Page 110

110 CHAPTER 2 INFRARED SPECTROSCOPY Exercise 2.9

Problem 2.9 Spectrum A

100

95

1030
1134
90

1462
1373
%Transmittance

85

2877
80

75

2962
70

1712
4000 3000 2000 1000
Wavenumber (cm–1)

Problem 2.9 Spectrum B

100

1377

1115
%Transmittance

968
1462
50
3344

2873
2958
2931

4000 3000 2000 1000

Wavenumber (cm–1 )

Problem 2.9 Spectrum C

100
1890
2862
3032
2924
%Transmittance

1072
1011

95
1489

802

4000 3000 2000 1000

Wavenumber (cm–1)
 Silverstein c02.tex V3 - 07/30/2014 1:37 P.M. Page 111

Exercise 2.9 STUDENT EXERCISES 111

Problem 2.9 Spectrum D

100

99

748
1381
1250

1149
98

1203
1458
%Transmittance

97

2877
96

2931
95

94

2962
4000 3000 2000 1000
Wavenumber (cm–1)

Problem 2.9 Spectrum E

100

1458
1412
90

1165
2870
%Transmittance

1365
80
2939
2962

70
1720

4000 3000 2000 1000

Wavenumber (cm–1)

Problem 2.9 Spectrum F

100
1076
2665

933
1466

1288
%Transmittance

1419

50
3035
2985

1238
1716

4000 3000 2000 1000

Wavenumber (cm–1)
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112 CHAPTER 2 INFRARED SPECTROSCOPY Exercise 2.9

Problem 2.9 Spectrum G

100

1088
3309

1381
95

1311

779
%Transmittance

1574
1466
2870
90

2931
2954

4000 3000 2000 1000

Wavenumber (cm–1)

Problem 2.9 Spectrum H

100

2121

1230
2927
2873

90

1419

914
%Transmittance

648
80

70
3294

1030
4000 3000 2000 1000
Wavenumber (cm–1)

Problem 2.9 Spectrum I

100
1134

609
795
2885

1227
2947

1435
2978
%Transmittance

1381

50
1558

4000 3000 2000 1000

Wavenumber (cm–1)
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Exercise 2.9 STUDENT EXERCISES 113

Problem 2.9 Spectrum J

100

3062
%Transmittance

2873
2935
50

3363

918
1458

690
1049
1084
1601

756
1496

1246
4000 3000 2000 1000
Wavenumber (cm–1)

Problem 2.9 Spectrum K

100
3062

2877
2931

1388
%Transmittance

2981

690
1477

1049
50
1601

752
1496

1246

4000 3000 2000 1000

Wavenumber (cm–1)

Problem 2.9 Spectrum L

100
1011
1365

1103
1442

95
1265
%Transmittance

2970

90
1188
1759

4000 3000 2000 1000

Wavenumber (cm–1)
 Silverstein c02.tex V3 - 07/30/2014 1:37 P.M. Page 114

114 CHAPTER 2 INFRARED SPECTROSCOPY Exercise 2.9

Problem 2.9 Spectrum M

100

582
984
%Transmittance

1122
1200
50

822
3078
3294

2858
2966

1365
1485

1419
3209

1439
2927

1662
4000 3000 2000 1000
Wavenumber (cm–1)

Problem 2.9 Spectrum N

100
2862

1581
2924

95
%Transmittance

3008

1304
1527
3055

1057
90

1157
1473

833
1018
1396

4000 3000 2000 1000

Wavenumber (cm–1)

Problem 2.9 Spectrum O

100

95
555
2843

926
2974

675
1415

90
%Transmittance

85
1049

748
1234
1585

80
1304
1281

75
1682

4000 3000 2000 1000

Wavenumber (cm–1)
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Exercise 2.9 STUDENT EXERCISES 115

Problem 2.9 Spectrum P

100

3066
3101

1107
1604

1092
%Transmittance

1577
1477
95

741
849
90

1342
1516
4000 3000 2000 1000
Wavenumber (cm–1)

Problem 2.9 Spectrum Q

100

563
729
644
90
2677

937
80

1219
1423

1254
1284
%Transmittance

70
2862

60
2935

50

40
1709

4000 3000 2000 1000

Wavenumber (cm–1)

Problem 2.9 Spectrum R

100
2117

90
937
1331

991

80
1454
1435
%Transmittance

70
2870

60
1065

636

50
2943

40
3298

4000 3000 2000 1000

Wavenumber (cm–1)
 Silverstein c02.tex V3 - 07/30/2014 1:37 P.M. Page 116

116 CHAPTER 2 INFRARED SPECTROSCOPY Exercise 2.9

Problem 2.9 Spectrum S

100

90

2866

1157
80

1442
%Transmittance

2970

1361
2920
70

60

50

1716
4000 3000 2000 1000
Wavenumber (cm–1)

Problem 2.9 Spectrum T

100

1107
2669

937
1215
1462

1254
1292
%Transmittance

1415
3035

50
2873 2935
2958

1712

4000 3000 2000 1000

Wavenumber (cm–1)

Problem 2.9 Spectrum U

100
3074

548
%Transmittance

714
1705

50
1338

1176
1577
1466

1242

771
1450
3437

4000 3000 2000 1000

Wavenumber (cm–1)
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Exercise 2.9 STUDENT EXERCISES 117

Problem 2.9 Spectrum V

100

3047
90

1593
2943

1446

910
%Transmittance

1334
80

70
3394

1477

1196

756
4000 3000 2000 1000
Wavenumber (cm–1)

Problem 2.9 Spectrum W

100
2827
3032

2870

1254
1427

1122
1211

876

733
%Transmittance

2947

50

1388
1685

4000 3000 2000 1000

Wavenumber (cm–1)
 Silverstein c02.tex V3 - 07/30/2014 1:37 P.M. Page 118

118 CHAPTER 2 INFRARED SPECTROSCOPY

CHART AND SPECTRAL PRESENTATIONS OF ORGANIC SOLVENTS, MULLING OILS,

AND OTHER COMMON LABORATORY SUBSTANCES

APPENDIX A TRANSPARENT REGIONS OF SOLVENTS AND MULLING OILS

Wavelength (cm–1)
3600 3200 2800 2400 2000 1800 1600 1400 1200 1000 800 600

Solvents a 3400 3000 2600 2200

Carbon disulfide

Methylene dichloride

Chloroform

Carbon tetrachloride

Tetrachloroethylene

Methylene dibromide

Bromoform

Mulling Oils b
Nujol

Hexachlorobutadiene

Fluorolube

a
The open regions are those in which the solvent transmits more than 25% of the incident light at 1 mm thickness.
b
The open regions for mulling oils indicate transparency of thin films.
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APPENDIX B 119

APPENDIX B CHARACTERISTIC GROUP ABSORPTIONS𝐚

cm –1 3600 3200 2800 2400 2000 1800 1600 1400 1200 1000 800 600

3400 3000 2600 2200

m m m m w
ALKANES
ALKENES
m m m s s
VINYL
m w s
TRANS
m m s
CIS
m m m s
VINYLIDENE
m w m
TRISUBSTITUTED
w
TETRASUBSTITUTED
m w
CONJUGATED
m s w
CUMULATED C C CH2
m m
CYCLIC
ALKYNES s w w s
MONOSUBSTITUTED
w
DISUBSTITUTED
MONONUCLEAR AROMATICS w w s m sd
BENZENE
m m m m ss
MONOSUBSTITUTED
m m s
1,2-DISUBSTITUTED
m m s sd
1,3-DISUBSTITUTED
m m s
1,4-DISUBSTITUTED
m s
1,2,4-TRISUBSTITUTED
s md
1,2,3-TRISUBSTITUTED
s md
1,3,5-TRISUBSTITUTED
ALCOHOLS AND PHENOLS m 3700-3450 sharp
FREE OH
m 3704-3509 sharp
INTRAMOLECULAR BONDED (WEAK)
br
INTRAMOLECULAR BONDED (STRONG)
s br
INTERMOLECULAR BONDED

SATURATED TERT. s
HIGHLY SYMMETRICAL SEC.
SATURATED SEC. s
α-UNSATURATED OR CYCLIC TERT.

α-UNSATURATED SEC.
ALICYCLIC SEC. (5 OR 6- s
MEMBERED RING)
SATURATED PRIMARY

α-UNSATURATED TERT.
α-UNSATURATED AND
α-BRANCHED SEC.
Di-α-UNSATURATED SEC. s
ALICYCLIC SEC. (7 OR 8-
MEMBERED RING)
α-BRANCHED AND/OR
α-UNSATURATED PRIM.
3400 3000 2600 2200

cm –1 3600 3200 2800 2400 2000 1800 1600 1400 1200 1000 800 600

a
Absorptions are shown by heavy bars. s strong, m medium, w weak, sh sharp, br broad. Two intensity designations over a single bar
indicate that two peaks may be present.
b
May be absent.
c
Frequently a doublet.
d
Ring bending bands.
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120 CHAPTER 2 INFRARED SPECTROSCOPY

APPENDIX B (continued)

cm –1 3600 3200 2800 2400 2000 1800 1600 1400 1200 1000 800 600

ACETALSa 3400 3000 2600 2200

s
“KETALS” s

ETHERS
s
ALIPHATIC
s m
AROMATIC (ARYL —O—CH2)
s s m
VINYL
m m m
OXIRANE RING
m
PEROXIDES (ALKYL AND ARYL)
m
PEROXIDES (ACYL AND AROYL)

CARBONYL COMPOUNDS
KETONESb s m
DIALKYL (—CH2COCH2—)
s m
AROMATIC (CONJ)
m br s
ENOL OF 1,3-DIKETONE
m br s
σ-HYDROXY ARYL KETONE

ALDEHYDESb
m (doublet) s m
ALKYL
s m
AROMATIC (CONJ)

CARBOXYLIC ACIDSc
s s m m m
DIMERc
s m
CARBOXYLATE ION

ESTERS
s s
FORMATES
s s
ACETATES
s s
OTHER UNCONJ ESTERS
s s s
CONJUGATED ESTERS
s s m
AROMATIC ESTERS

3400 3000 2600 2200

cm –1 3600 3200 2800 2400 2000 1800 1600 1400 1200 1000 800 600

a
Three bands, sometimes a fourth for ketals, and a fifth band for acetals.
b
Conjugated aliphatic examples show C O stretch at virtually the same position as aromatic structures.
c
Conjugated examples show C O stretch at lower wavenumbers (1710 cm–1 to 1680 cm–1). The O H stretch (3300 cm–1 to 2600 cm–1) is very broad.
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APPENDIX B 121

cm –1 3600 3200 2800 2400 2000 1800 1600 1400 1200 1000 800 600

LACTONES 3400 3000 2600 2200

s s s
BETA
s s
GAMMA
s s
DELTA

ACID CHLORIDES
s m
ALIPHATIC
s w m
AROMATIC

ANHYDRIDES
s s s
NON-CYCLIC (UNCONJ)
s s s
NON-CYCLIC (CONJ)
s s s s
CYCLIC (UNCONJ)
s s s s
CYCLIC (CONJ)

AMIDES
PRIMARY
mm sm m br
SOLUTION
mm s m br
SOLID
SECONDARY
m s
SOLUTION
m m s
SOLID
s
TERTIARY
LACTAMS
m
SOLUTION
mw
SOLID
s
5-MEMBERED RING
s
6 OR 7-MEMBERED RING

AMINES
PRIMARY
mw m m s br
ALIPHATIC
mw m m br
AROMATIC
SECONDARY
w m m
ALIPHATIC
w s
AROMATIC
TERTIARY
m
ALIPHATIC
s
AROMATIC
AMINE SALTS
s m m m
PRIMARY
s m
SECONDARY
m
TERTIARY
s m s
AMMONIUM ION
3400 3000 2600 2200

cm –1 3600 3200 2800 2400 2000 1800 1600 1400 1200 1000 800 600
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122 CHAPTER 2 INFRARED SPECTROSCOPY

APPENDIX B (continued)

cm –1 3600 3200 2800 2400 2000 1800 1600 1400 1200 1000 800 600

NITRILES (RCN) 3400 3000 2600 2200

ALIPHATIC
m
m
AROMATIC
s s
CARBODIIMIDES
ISONITRILES (RCN) s
ALIPHATIC
s
AROMATIC
s br w
ISOCYANATES (RNCO)
s
THIOCYANATES (RSCN)

ISOTHIOCYANATES (RNCS) s m
ALKYL
s m
AROMATIC

NITRO COMPOUNDS s m
ALIPHATIC
s m
AROMATIC
s m
CONJ.
NITRAMINE s s

NITROSOAMINES s
VAPOR
s
LIQUID
s s s
NITRATES (RONO2)
s s
NITRITES (RONO)
NITROSO COMPOUNDS (RNO)
s
ALIPHATIC DIMER (TRANS)
s s
ALIPHATIC DIMER (CIS)
AROMATIC DIMER (TRANS) s
ss
AROMATIC DIMER (CIS )
s
ALIPHATIC MONOMER
s
AROMATIC MONOMER
SULFUR COMPOUNDS w
MERCAPTANS, THIOPHENOLS
& THIO ACIDS
THIOCARBONYL GROUP
m
C S (NOT LINKED TO N)
m m
C S (LINKED TO N)

s
SULFOXIDES
s s
SULFONES
s s
SULFONYL CHLORIDES
ss s s
PRIM. SULFONAMIDE (SOLID)
s s
SEC. SULFONAMIDE (SOLID)
s s
SULFONATES

3400 3000 2600 2200

cm –1 3600 3200 2800 2400 2000 1800 1600 1400 1200 1000 800 600
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APPENDIX B 123

cm –1 3600 3200 2800 2400 2000 1800 1600 1400 1200 1000 800 600

HALOGEN COMPOUNDS 3400 3000 2600 2200

s s
—CH2Cl
s s
—CH2Br
s s
—CH2I
s
—CF2—
s s
—CF3
s s
—C CF2
s s
—CF CF2
s
Aryl Fluorides
s
Aryl Chlorides
SILICON COMPOUNDS
s
SiH
SiH2
SiH3
w s
SiCH3
m
SiCH2
m m s
SiC6H5
s
SiO Aliphatic
SiOCH3 m s
SiOCH2CH3 m s
SiOC6H5
SiOSi
m s
SiOH
s
SiF
sm
SiF2
s m
SiF3

PHOSPHORUS COMPOUNDS
m
PH
m m s
PH2
m s
PCH3
m
PCH2—
m m w
PC6H5
s
(Aliphatic)3P O
s
(Aromatic)3P O
s
(RO)3P O
m m s s
P—O—CH3
mm mm m s s
P—O—CH2CH3
s s
P—OC6H5
P—O—P s w
s s s
P—O—H
s s br s
O
P—OH (SINGLE OH)
s = strong m = medium w = weak v = variable
3400 3000 2600 2200

cm –1 3600 3200 2800 2400 2000 1800 1600 1400 1200 1000 800 600
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124 CHAPTER 2 INFRARED SPECTROSCOPY

APPENDIX C ABSORPTIONS FOR ALKENES

TABLE C-1 Alkene Absorptiona

H H H H R H
C C C C C C
R H R R H R
Vinyl cis trans
1648 cm–1 to 1638 cm–1 1662 cm–1 to 1626 cm–1 (v) 1678 cm–1 to 1668 cm–1 (v)
995 cm–1 to 985 cm–1 (s)b 730 cm–1 to 665 cm–1 (s) 980 cm–1 to 960 cm–1 (s)c
915 cm–1 to 905 cm–1 (s)

R H R R R R
C C C C C C
R H H R R R
Vinylidene Trisubstituted Tetrasubstituted
1658 cm–1 to 1648 cm–1 (m) 1675 cm–1 to 1665 cm–1 (w) 1675 cm–1 to 1665 cm–1 very weak
895 cm–1 to 885 cm–1 (s) 840 cm–1 to 790 cm–1 (m) or absent

a
s strong, m medium, w weak, v variable.
b
This band also shows a strong overtone band.
c
This band occurs near 1000 cm 1 in conjugated trans – trans systems such as the esters of sorbic acid.

TABLE C-2 C⏤C Stretching Frequencies in Cyclic and Acyclic Systems (cm−1 )

H H H CH 3 CH 3 CH 3 C
C C C C C C C CH 2
Ring a or Chain C C C C C C C

Chain cis 1661 1681 1672 1661

Chain trans 1676
Th r e e -m e m b e r e d r in g 1641 1890 1780
Fo u r-m e m b e r e d r in g 1566 1685 1678
Five-membered ring 1611 1658 1686 1657
Six-membered ring 1649 1678 1685 1651
Seven-membered ring 1651 1673
Eight-membered ring 1653

a
All rings have cis double bonds.
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APPENDIX E 125

APPENDIX D ABSORPTIONS FOR PHOSPHORUS COMPOUNDS

TABLE D-1 P⏤O and P⏤O Stretching Vibrations

Group Wavenumber (cm−1 )𝐚 𝝂𝐏−𝐎 Bands𝐚 (cm−1 )

P⏤O stretch
Phosphine oxides
Aliphatic ∼1150
Aromatic ∼1190
Phosphate estersb 1299 to 1250
P⏤OH 1040 to 910 (s)
P⏤O⏤P 1000 to 870 (s) ∼700 (w)
P⏤O⏤C (aliph) 1050 to 970 (s)c 830 to 740 (s)d
P⏤O⏤C (arom) 1260 to 1160 (s) 994 to 855 (s)
as = strong; w = weak.
b The increase in P⏤O stretching frequency of the ester, relative to the oxides, results from the
electronegativity of the attached alkoxy groups.
c May be a doublet.
d May be absent.

APPENDIX E ABSORPTIONS FOR HETEROAROMATICS

TABLE E-1 𝛾-CH and Ring Bending (𝛽-Ring) Bands of Pyridinesa

Number
Substitution Adjacent H Atoms 𝜸-CH (cm−1 ) 𝜷-Ring

2- 4 781 to 740 752 to 746

3- 3 810 to 789 715 to 712
4- 2 820 to 794 775 to 709
a The 𝛾 and 𝛽 notations are explained in the text and in the book by Katritzky (1963).

TABLE E-2 Characteristic 𝛾-CH or 𝛽-Ring Bands of Furans, Thiophenes, and Pyrroles

𝜸-CH or 𝜷-Ring Modes𝐚

Position of
Ring Substitution Phase cm−𝟏 cm−𝟏 cm−𝟏 cm−𝟏

Furan 2- CHCl3 ∼925 ∼884 835 to 780

2- Liquid 960 to 915 890 to 875 780 to 725
2- Solid 955 to 906 887 to 860 821 to 793 750 to 723
3- Liquid 885 to 870 741
Thiophene 2- CHCl3 ∼925 ∼853 843 to 803
3- Liquid 755
Pyrrole 2-Acyl Solid 774 to 740 ∼755
a The 𝛾 and 𝛽 notations are explained in the text and in the book by Katritzky (1963).
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CHAPTER 3
PROTON (1H) MAGNETIC RESONANCE
SPECTROSCOPY

3.1 INTRODUCTION like mass. Let us remember that nuclear spin is a quantum
mechanical phenomenon; our treatment will rely on familiar
Nuclear magnetic resonance (NMR) spectroscopy is the classical mechanical models. While this approach has an
single-most important analytical tool for the organic chemist. obvious visual appeal, it also has limitations that should be
It is impossible to overstate the impact that NMR, in all acknowledged from the start.
of its forms, has had on advancing organic chemistry and The nuclear spin angular momentum is described in
in advancing related fields such as biochemistry and poly- terms of its nuclear spin quantum number I; these numbers
mer chemistry. In a simple way, NMR spectroscopy can have values of 0, 12 , 1, 32 , and so on (I = 0 denotes no spin).
be thought of as another form of absorption spectroscopy, The intrinsic magnitude of the magnetic dipole is expressed
akin to IR or UV spectrometry in that, under appropriate in terms of the nuclear magnetic moment, 𝜇.
conditions in a magnetic field, a sample can absorb elec- Relevant properties, including the spin number I, of
tromagnetic radiation in the radiofrequency (rf) region at several nuclei are given in Chapter 6, Appendix A. While
frequencies governed by the characteristics of the sample. we cannot generally predict the exact value of I for every
However, due to the way in which the NMR experiment is isotope, useful restrictions on their possible values can be
performed, we will not discuss the concept of absorption fur- determined from the atomic mass and the atomic number as
ther. We will refer to NMR “peaks” or “resonances.” A plot shown in Table 3.1. It is best to simply memorize the values
of the peak intensity versus frequency constitutes an NMR of I for common isotopes such as 1 H and 13 C (I = 12 ). In
spectrum. Our approach will be relatively light on theory quantum mechanical terms, the spin number I determines the
and, instead, focus on interpretation. The reader is referred number of quantum mechanical states an isolated spin may
to Levitt (2008) for a more theoretical approach to the basics assume in an external uniform magnetic field in accordance
of NMR. This chapter covers proton nuclear magnetic res- with the formula 2I + 1. The possible states may be denoted
onance (1 H NMR) spectroscopy as well as some general by a second quantum number, m.
aspects of NMR. Spectra of several nuclei can be readily obtained (e.g.,
1 H, 13 C, 15 N, 19 F, and 31 P) since they have spin numbers
With some mastery of basic theory, interpretation of 1 6 7 9 15
NMR spectra merely by inspection is usually feasible in I of 12 and a uniform spherical nuclear charge distribution
greater detail than is the case for IR or mass spectra. The (Figure 3.1). Of these, the most widely used in NMR spec-
present account will allow for an in-depth interpretation troscopy are 1 H (this chapter) and 13 C (Chapter 4). Nuclei
of proton NMR spectra, which, in conjunction with other with a spin number, I, of one or higher have a nonspher-
spectroscopic information, will enable us to readily identify ical charge distribution. This is described by an electric
even moderately complex organic compounds. References quadrupole moment, which, as we shall see later, affects the
are given at the end of this chapter. nuclear spin relaxation time and, consequently, the line width

3.2 THEORY

3.2.1 Magnetic Properties of Nuclei

We begin by describing the magnetic properties of nuclei that
lead to NMR. All nuclei carry a charge. A sometimes useful,
though technically inaccurate, picture of spinning charge
leads to a magnetic dipole associated with certain nuclei
(Figure 3.1). In fact, the nuclei are not spinning. The concept
of nuclear spin describes the intrinsic angular momentum
associated with the magnetic nucleus. Some nuclei have FIGURE 3.1 Several nuclides, including 1 H, have intrinsic
intrinsic spin just as they have other intrinsic properties angular momentum called “spin.”

126
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3.2 THEORY 127

TABLE 3.1 Type of Nuclear Spin Number, I, with Various A transition from the lower energy state to the higher
Combinations of Atomic Mass and Atomic Number energy state can be brought about by applying radiation of
exactly the required frequency (in the radiofrequency range)
Atomic Atomic
for a given stationary magnetic field of strength B0 . The
I Mass Number Example of Nuclei
fundamental NMR equation correlates a particular value of
( ) ( ) ( )
Half-integer Odd Odd 1
1
H 12 , 31 H 12 , 157 N 12 , the applied radiofrequency known as the Larmor frequency,
( ) ( ) v, with the magnetic field strength:
19
9
F 12 , 31
15
P 12
( ) ( ) ( )
Half-integer Odd Even 13
6
C 12 , 178 O 52 , 29
14
Si 12 v = (𝛾∕2𝜋) B0
Integer Even Odd 2
1
H(1), 147 N(1), 105 B(3) since
Zero Even Even 12
6
C(0), 168 O(0), 34
16
S(0) ΔE = hv
The radiofrequency v is typically on the order of mega-
hertz (MHz). A frequency of 300 MHz is needed at a mag-
of the signal and coupling with neighboring nuclei. We are netic field strength B0 of 7.05 T for the proton (1 H) (or any
largely concerned in this chapter with the proton (1 H), whose other desired combination of v and B0 such that their ratio is
spin number I is 12 . equal to 𝛾∕2𝜋; see Chapter 6, Appendix A). At this ratio, the
system is in resonance. Hence, the name nuclear magnetic
3.2.2 Excitation of Spin 1
Nuclei resonance spectroscopy is applied. The constant, 𝛾, called
2 the magnetogyric ratio, is a fundamental constant specific to
For spin 12 nuclei in an external magnetic field (Figure 3.2), each nuclide; it is the proportionality constant between the
there are two energy levels and a slight excess of proton magnetic moment, 𝜇, and the spin number, I.
population in the lower energy state (N𝛼 > N𝛽 ) in accordance
𝛾 = 2𝜋𝜇∕hI
with the Boltzmann distribution. The states are labeled 𝛼
and 𝛽, or m = 12 and m = − 12 (m is a quantum number); the The fundamental NMR equation allows us the choice
energy gap between them, ΔE, is given by between two methods when describing a given instrument:
we could use (i) the magnetic field strength or (ii) the Larmor
ΔE = (h𝛾∕2𝜋) B0 frequency. Since modern instruments use superconducting
where h is Planck’s constant. The equation simply states magnets whose magnetic fields are extremely constant, it
that ΔE is proportional to B0 (as shown in Figure 3.2) since would make sense to refer to an instrument by its field
h, 𝛾, and 𝜋 are constants. B0 represents the magnetic field strength in tesla units. This common sense approach is
strength.* There is a subtle but important difference here (generally) not used. Instead, the resonance frequency of 1 H
compared to many other forms of spectroscopy such as IR: is used. Thus, an instrument that has a 7.05 T magnet is
the energy levels and, therefore, frequencies of peaks in the referred to as a 300 MHz NMR spectrometer.†
spectra, depend not only on the molecule itself but also on The standard method of recording NMR spectra is
the strength of the applied magnetic field. the pulsed-Fourier transform (FT) method. The sample is
placed in an NMR probe in the magnetic field and irradiated
with a short pulse (on the order of microseconds) of high-
Spin = – 12 , 𝛽
power radiofrequency energy. This pulse simultaneously
𝛽
excites all of the nuclei of a given type (e.g., 1 H) in the
E
sample. Immediately following the pulse, the excited spins
I = 12 precess around the external magnetic field together, creating
E a current in the receiver coil of the NMR probe. The resulting
signal, known as the free induction decay (FID), is recorded
and digitized by a computer. The information in the FID, a
Spin = + 1
,𝛼 function of time, is converted to a readable spectrum in the
2
𝛼
frequency domain using a mathematical operation known as
Field Strength (B0) the Fourier transform (see Figure 3.9).
Let us consider a large group of identical nuclei (1 H,
FIGURE 3.2 Two proton energy levels in a magnetic field of protons) in a strong, stationary magnetic field. The magnetic
magnitude B0 . N is the population of spins in the upper (N𝛽 ) and
axis of any single proton precesses about the stationary
lower (N𝛼 ) energy states. The direction of the magnetic field (B0 ) is
magnetic field, B0 (along the z-axis), in the same manner in
up, parallel to the ordinate, and field strength increases to the right.
Larger magnetic fields increase ΔE. which a spinning top (or a gyroscope) precesses under the
influence of gravity (Figure 3.3). The precessional frequency
* The designation B (magnetic induction or flux density) supercedes H

(magnetic intensity). The SI term tesla (T), the unit of measurement for B, † Use of the frequency instead of the magnetic field also harkens back to a
supercedes the term gauss (G); 1 T = 104 G. The frequency term hertz (Hz) previous “continuous wave” implementation of NMR where the frequency
supercedes cycles per second (cps). MHz is megahertz (106 Hz). was held constant and the magnetic field was varied during the experiment.
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128 CHAPTER 3 PROTON (1 H) MAGNETIC RESONANCE SPECTROSCOPY

Precession Figure 3.5 shows the fate of the net magnetization vector
during a simple pulsed NMR experiment. When a short
radiofrequency pulse is applied, a torque is exerted on the
net magnetization vector, M0 , and it will be tipped away
Nuclear magnetic from the z-axis and toward the xy plane (Figure 3.5a). The
dipole μ
magnetic component generated in the xy plane (the FID)
can be detected as a function of time by a receiver coil
mounted in the xy plane (this may be the same coil which
Proton spin generates the initial rf pulse). The torque experienced by
the net magnetization vector is more precisely explained
as arising from the fact that the oscillating magnetic field
B0 associated with the applied radiation is rotating with exactly
the same frequency as the individual nuclear spins. This
FIGURE 3.3 Classical representation of a proton spin precessing is one way of explaining the concept of resonance; further
in a magnetic field of magnitude B0 in analogy with a precessing technical details are beyond the scope of this book.
spinning top.

3.2.3 Relaxation
of the nuclear magnetic dipole, 𝜇, about the z-axis is equal
to the Larmor frequency, 𝜈. Relaxation refers to the establishment or re-establishment
Before a radiofrequency pulse, the individual members of the equilibrium state of the nuclear spin magnetization.
of a large group of nuclear spins will be precessing around Equilibrium is achieved when M0 returns to the z-axis after
the z-axis in a random fashion or in random phase. In a pulse. Relaxation is not the process which gives rise to
Figure 3.4, we see the precessing nuclei represented by their an FID. Relaxation is a complex subject, but it is important
individual spin vectors. Notice that some of the vectors have to have a basic grasp of the fundamentals in order to better
positive z components (pointing up) and some of them have understand NMR experiments and NMR spectra.
negative z components (pointing down). These two types There are two main types of relaxation which we will
of spins represent those in the low-energy (𝛼) and high- briefly discuss here. The first is longitudinal spin relaxation,
energy (𝛽) states, respectively. Notice also that there is a also known as spin–lattice relaxation, and it is quantified by
slight excess of spins in the low-energy state (pointing up). a time constant T1 . The second is transverse spin relaxation,
In Figure 3.4, there are eight vectors pointing up and six also known as spin–spin relaxation, and it is quantified by
vectors pointing down. If we sum all of these vectors, we a time constant T2 . The values of these time constants can
obtain a single total vector whose direction is on the positive vary quite a bit depending on the nature of the sample and
z-axis and whose magnitude depends on the Boltzmann the type of nucleus studied. For 1 H solution NMR studies of
distribution of spins. Notice that any components in the xy small molecules, these values are typically on the order of
plane cancel out as a result of this summation (see the right- seconds. For small organic molecules, 1 H T1 and T2 values
hand side of Figure 3.4). The resulting vector is called the are approximately equal to one another. More generally,
net magnetization vector, M0 . T1 ≥ T2 .

z z

M0

x
B0 y x y

FIGURE 3.4 Assemblage of precessing nuclei with net macroscopic magnetization M 0 in the direction of the stationary
magnetic field B0 along the z-axis.
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3.3 INSTRUMENTATION AND SAMPLE HANDLING 129

z
M0 M0
Rotational M M
component of B1

y
y component of M

x
Oscillator coil of B1

B0
(a) (b) (c)

FIGURE 3.5 (a and b) Oscillator generates rotating component of applied magnetic field B1 . The net magnetization M0 is tipped toward
the y-axis to give M, which precesses about the z-axis generating a component of magnetization in the horizontal plane. (c) Relaxation
of M to M0 follows a spiral of decreasing amplitude. The Cartesian frame is stationary.

T1 relaxation is what allows the z-components of the Faster spin–spin relaxation leads to shorter FIDs and broader
nuclear spin magnetization vectors to re-establish equilib- NMR peaks; slower spin–spin relaxation results in longer
rium according to the Boltzmann distribution. The value of FIDs and sharper NMR peaks.
T1 , therefore, typically determines how long the experimen-
talist must wait after an FID before repeating the process of
applying an rf pulse and acquiring another FID. A long T1
value means that it takes a relatively long time for magnetiza- 3.3 INSTRUMENTATION
tion along the z-axis to be established upon initially placing AND SAMPLE HANDLING
the sample in the magnet or after pulsing and acquiring a
single FID. The role of T1 relaxation in acquiring and inter-
3.3.1 Instrumentation
preting 13 C NMR spectra is discussed in Chapter 4.
T2 relaxation enables the net magnetization in the xy Beginning in 1953 with the first commercial NMR spec-
plane to decay to zero, that is, to the equilibrium state, after a trometer, the early instruments used permanent magnets or
radiofrequency pulse. One can see the effects of T2 relaxation electromagnets with fields of 1.41 T, 1.87 T, 2.20 T, or
on an FID; the relaxation causes the signal to decay exponen- 2.35 T corresponding to 60 MHz, 80 MHz, 90 MHz, or 100
tially to zero as it is being acquired (see Figure 3.9). Actually, MHz, respectively, for proton magnetic resonance.
due to magnetic field inhomogeneities associated with the The “horsepower race,” driven by the need for higher
spectrometer magnet rather than the molecule itself, the typ- resolution and sensitivity, has resulted in the widespread use
ically observed relaxation time constant is smaller than the of 300 MHz to 800 MHz instruments. Resolution, in gen-
true T2 and is denoted T2∗ . The value of T2∗ plays a very prac- eral terms, refers to the ability to resolve or differentiate
tical role in the appearance of NMR spectra (Figure 3.6): it is between different spectral peaks along the frequency axis.
inversely related to the width of the NMR peak at half-height The most powerful commercial NMR spectrometer is cur-
(Δ𝜈 1 ): rently 1000 MHz, or 1 GHz, and the development of 1.1 GHz
2
/ and 1.2 GHz spectrometers is in progress. All of the instru-
Δ𝜈 1 = 1 (𝜋T2∗ ) ments above 100 MHz are based on helium-cooled supercon-
2
ducting magnets (solenoids) and operate in the pulsed FT
mode. The other basic requirements besides high field are
frequency-field stability, field homogeneity, and a computer
interface (see Figure 3.7). The computer is used to acquire
the data, carry out the FT, and further process and analyze
the resulting spectra.
h The sample (routinely a solution in a deuterated solvent
in a 5 mm o.d. glass tube) is placed in the probe, which
1/2= ( T2* )–1 contains the transmitter and receiver coils and a spinner to
Relaxation rate (R) =1/T2* spin the tube about its vertical axis in order to average out
h/2 magnetic field inhomogeneities.
The proton NMR spectrum is shown as a series of
peaks whose areas are proportional to the number of protons
FIGURE 3.6 The peak width at half-height (h∕2) is inversely they represent. Peak areas are determined digitally and are
related to the transverse relaxation time constant. often shown as a series of steps with heights proportional
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130 CHAPTER 3 PROTON (1 H) MAGNETIC RESONANCE SPECTROSCOPY

Output and
Computer storage
Magnet bore
devices
Liquid nitrogen

Liquid helium
A/D Converter
Two or more rf
Magnet coils pulse generators,
one for high
Bandpass filter
frequency, that is,
1H, others for X
Shim control
module nuclei, that is,
Amplifier 13C
Shim coils

Field Quadrature
stabilizer detector
Probe

Receiver/
transmitter

FIGURE 3.7 Schematic diagram of a Fourier transform NMR spectrometer with a superconducting
magnet. The probe is parallel with the z-axis of the magnet, which is cooled with liquid helium
surrounded by liquid nitrogen in a large Dewar flask.

to the peak areas (see Figure 3.8).* A proton count from the 3.3.2 Sensitivity of NMR Experiments
integration (area under the peak) is useful to determine or
Sensitivity refers in this context to the signal to noise of the
confirm molecular formulas, detect hidden peaks, determine
NMR experiment. The signal-to-noise ratio (S/N) of an FID
sample purity, and do quantitative analysis. Peak positions
or NMR spectrum depends on many factors, and explicit
(chemical shifts, Section 3.4) are measured in frequency
expressions depend on approximations used and details of
units from a reference peak.
the experimental setup. One useful expression is given:
3 3
* Chemically different protons resonate at very slightly different frequen- ∗1 −3 1
S∕N ∝ NQ𝛾exc 𝛾det
2
B02 T2 2 T 2 ns 2
cies–differences up to around 5000 Hz at a Larmor frequency of 300 MHz.
The utility of NMR spectroscopy for the organic chemist dates from the
where N is the number of spins in the sample; Q is the quality
experiment at Varian Associates that obtained three peaks from the chemi-
cally different protons in CH3 CH2 OH; the peak areas were in the ratio 3:2:1. factor of the probe; 𝛾exc and 𝛾det are the magnetogyric ratios
[Arnold, J.T., Dharmatti, S.S., and Packard, M.E. (1951) J. Chem. Phys., 19, of the excited and detected nuclei, respectively; B0 is the
507.] external applied magnetic field; T2∗ is the effective spin–spin

CH2 CH3
O
O

7.4 ppm

7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 ppm
1
FIGURE 3.8 H NMR spectrum of benzyl acetate in CDCl3 , 300 MHz.
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3.3 INSTRUMENTATION AND SAMPLE HANDLING 131

relaxation time constant; T is the temperature of the sample, Deuterated solvents are typically, but not absolutely, nec-
and ns is the number of scans. For the 1 H NMR spectra essary for modern instruments because they depend on a
discussed in this chapter, 𝛾exc and 𝛾det are the same. deuterium signal to “lock” or stabilize the B0 field of the
It is important to be aware of the most important factors magnet. Modern instruments have a deuterium channel that
within the experimentalist’s control to increase the signal- constantly monitors and adjusts (locks) the B0 field to the fre-
to-noise ratio. The conceptually simplest and most effective quency of the deuterated solvent (see Figure 3.7). Typically,
way for the organic chemist to increase S/N is to increase the 1 H NMR signals are on the order of 0.1 to several Hz wide

number of spins in their sample; that is, to increase the sam- out of 300000000 Hz (for a 300 MHz system), so the B0 field
ple concentration. S/N increases linearly with the number of needs to be very stable and homogeneous.
spins in the sample. Conversely, acquiring more scans (sig- The deuterium signal is also typically used to shim
nal averaging of the FID) will result in an increase in S/N the B0 field. Instruments use small electromagnets (called
only proportional to the square root of the number of scans. shims) to adjust the main magnetic field (B0 ) so that the
Decreasing the temperature often affords an increase in S/N homogeneity of the field is high at the center of the magnet
due to the reduction of thermal noise in the electronics of where the sample resides. Most modern instruments have
the probe, and more obviously due to the greater polariza- approximately 20 to 40 electromagnetic shims; they are
tion of the nuclear spins according to the Boltzmann distri- computer controlled and can be adjusted in an automated
bution. The Boltzmann distribution may also be altered by manner. Good shimming will increase the value of T2∗ and is
increasing the applied magnetic field, B0 . It turns out that essential to obtaining sharp NMR peaks. Shimming is done
3
manually, or with computer automation, each time a new
the overall S/N typically increases with B02 . Nuclei with
sample is placed in the magnet. Bad shimming will result
higher magnetogyric ratios also give spectra with higher S/N.
in short T2∗ values, broad line shapes, and unusable spectra.
Note that the natural abundance of the isotope of interest
Deuterated chloroform (CDCl3 ) is used as the solvent
plays an important role in determining the value of N.
most of the time for organic compounds. The small sharp
We make brief mention here of three of the more
proton peak at 7.26 ppm from the CHCl3 impurity present
cutting-edge methods in NMR spectroscopy for improving
rarely interferes seriously. For very dilute samples, CDCl3
sensitivity. The first two of these work by exploiting an
can be obtained in close to 100% isotope purity, thereby
unnatural, large, non-Boltzmann distribution of nuclear spins
reducing even further the intensity of the CHCl3 peak. A
across their energy levels. For example, dynamic nuclear
list of common, commercially available solvents with the
polarization (DNP) exploits the greater spin polarization of
chemical shifts of protonated impurities (e.g., CHCl3 in
unpaired electrons to enhance the NMR spectrum. The elec-
CDCl3 ) is given in Appendix G.
tron spin polarization is transferred to the nuclei, like 1 H,
A routine sample for 1 H NMR on a 300 MHz instrument
giving the latter a large non-Boltzmann nuclear spin polar-
consists of about 5 mg to 10 mg of the compound in about
ization and the resulting NMR spectrum is characterized by
0.5 mL of solvent in a 5 mm o.d. glass tube. Microprobes
a concomitantly large S/N. DNP NMR enables the experi-
that accept a 1.0 mm, 1.7 mm, 2.5 mm, or 3 mm o.d. tube are
mentalist to examine chemical species present in very low
available and provide higher sensitivity per unit mass. Under
concentrations and/or in a very short time. Enhancement
favorable conditions, it is possible to obtain a spectrum on
of 1 H NMR can also be achieved using para-hydrogen, a
100 nmol (or less) of a compound of modest molecular
nuclear spin isomer of H2 gas. Reactions of para-H2 with
weight in a 1.0 mm microtube (volume 5 μL) on a 600 MHz
compounds of interest can generate products carrying large
instrument. Of course, one must be aware that it is the
non-Boltzmann distributions at particular 1 H sites, providing
concentration of spins which is important, and so the masses
spectra with large S/N. Cryogenically cooled NMR probes
required for good spectra will vary depending on the molar
can also increase S/N by reducing the noise associated with
mass of the compound.
the electronics in the probe. For further reading on this topic,
Traces of ferromagnetic impurities cause severe broad-
see Ardenkjær-Larsen (2003) and Duckett (2011).
ening of NMR peaks because of reduction of relaxation
times. Common sources are rust particles from tap water,
3.3.3 Solvent Selection and Sample steel wool, Raney nickel, and particles from metal spatulas
Handling or fittings (Figure 3.9). These impurities can be removed by
The sample must be soluble in order to perform NMR filtration. Dissolved oxygen gas can also broaden NMR lines.
measurements in solution.* The ideal solvent should con- The use of freeze–pump–thaw techniques and air-tight NMR
tain no protons and be inert, low boiling, and inexpensive. tubes (using special caps or by flame sealing) can alleviate
this problem.
* Ifthe sample is not soluble, solid-state NMR experiments can be carried Traces of common laboratory solvents can be annoying.
out, although there are particular challenges associated with 1 H NMR of See Appendix H or Fulmer et al. (2010) for an extensive list
solids. Solid-state NMR experiments generally require somewhat different
of common solvent impurities. Other offenders are greases
spectrometer hardware and sample preparation. See Fyfe, C. A. Solid State
NMR for Chemists, CFC Press, Guelph, 1983 and Bryce et al., (2001) Can. and plasticizers (phthalates in particular). NMR solvents
J. Anal. Sci. Spectrosc., 46, 46–82. should be kept in a dessicator.
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132 CHAPTER 3 PROTON (1 H) MAGNETIC RESONANCE SPECTROSCOPY

O
O
O O O
O
O
O O
O
O O O
O
O O
O
O O

Cellobiose octaacetate

0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 seconds 7 6 5 4 3 2 ppm

0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 seconds 7 6 5 4 3 2 ppm
FIGURE 3.9 The effect of a trace amount of ferromagnetic particles on the proton FID and spectrum of cellobiose octaacetate
is to speed up T2 relaxation and give broad spectra (top). The FID and spectrum of a pure sample without ferromagnetic
contaminants are shown at the bottom.

3.4 CHEMICAL SHIFT structure in the molecule. At a given value of B0 , the effective
frequency at resonance is less than the resonance frequency,
Our fundamental NMR equation seems insufficient since it v, of a hypothetical “naked” proton, H+ . Note that 𝜎 is not
states that there is a single resonance frequency (v) for all a constant in the sense of other fundamental constants; it is
protons at a given magnetic field strength (B0 ): a constant only for the particular nucleus we are observing
in a particular molecule. Its value varies with the chemical
v = (𝛾∕2𝜋) B0 environment.
Fortunately, and not surprisingly, the situation is not so sim- To visualize this shielding, consider that a pair of elec-
ple. A covalently bonded hydrogen atom in a molecule is trons under the influence of a magnetic field circulate and, in
shielded to a very small extent (on the order of parts per circulating, generate their own magnetic field opposing the
million (10−6 ), or ppm) by the local electronic structure of applied field; hence, the shielding effect (Figure 3.10). This
the molecule; the amount of shielding varies with the chem- effect accounts for the diamagnetism exhibited by organic
ical environment. This variation gives rise to differences in materials. It should be noted that this description is an
resonance frequencies, which are commonly called chemical approximation and that more detailed theories are required
shifts. The ability to discriminate among the individual spec- to properly describe and understand shielding constants. In
tral resonances (or peaks) describes high-resolution NMR the case of materials with an unpaired electron, the param-
spectroscopy. agnetism associated with the net electron spin far overrides
The basic NMR equation for all protons is now modified the diamagnetism of the circulating, paired electrons. We do
for an ensemble of equivalent protons in the molecule: not consider paramagnetic compounds in our discussion.
The degree of shielding depends on the details of the
vef f = (𝛾∕2𝜋) B0 (1 − 𝜎) electronic structure of the molecule and is well described
The symbol 𝜎 is the magnetic shielding constant whose using Ramsey’s theory (see References section). However,
value describes the shielding effect of the local electronic for the empirical interpretation of 1 H NMR spectra, the
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3.4 CHEMICAL SHIFT 133

Nucleus chemical shift. For the present, we shall deal with obvious
Circulating electrons cases and postpone a more rigorous treatment of chemical
equivalence to Section 3.8.
Tetramethylsilane (TMS), (CH3 )4 Si, is the universally
accepted reference compound for 1 H NMR and 13 C NMR
(Chapter 4). As proton NMR developed, this material quickly
Magnetic lines gained in popularity as a chemical shift reference because
B0 of force it has several desirable properties: it is chemically inert,
symmetrical, volatile (b.p. 27 ∘ C), and soluble in most
FIGURE 3.10 Diamagnetic shielding of a nucleus by circulating
organic solvents; it gives a single, intense, sharp, NMR
electrons. The arrows, ↑↑↑, represent the direction of the stationary
peak, and its protons are more shielded than almost all
magnetic field of magnitude B0 . The circulating electrons
comprise the electrical current, but the current direction is shown other protons in organic compounds. When water or deu-
conventionally as flow of positive charge. terium oxide is the solvent, TMS can be used as an external
reference in a concentric capillary tube, or the methyl pro-
tons of water-soluble sodium 2,2-dimethyl-2-silapentane-5-
sulfonate (DSS), (CH3 )3 SiCH2 CH2 CH2 SO3 Na, are used as
degree of shielding of a hydrogen atom can be roughly ratio- an internal reference (𝛿 = 0.015 ppm). Harris et al. (2008)
nalized by considering the density of the circulating electrons describe the IUPAC conventions for chemical shift
around the proton. For a proton bonded to a carbon atom, this referencing.
density will in turn depend on the inductive effect of other Historically, and now by convention, the TMS reference
groups attached to the carbon atom. At this stage, it is impor- peak is placed at the right-hand edge of the spectrum and
tant to understand that magnetic shielding is a fundamental designated zero on both the frequency (Hz) and chemical
physical property, whereas it is the chemical shift that one shift (𝛿) scales (defined below). Positive frequencies and
observes in an NMR experiment. The relationship between chemical shifts are to the left of TMS, negative values are
the two quantities is as follows: found on the right.* The term “shielded” is a relative one
𝛿 = (𝜎ref − 𝜎)∕(1 − 𝜎ref ) and means toward the right; “deshielded” means toward
the left. The strongly deshielded protons of dimethyl ether,
where 𝜎ref is the magnetic shielding constant of a refer- for example, are effectively more exposed than those of
ence compound specific to each nuclide under study. Since TMS to the applied field; hence, resonance occurs at higher
magnetic shielding constants are on the order of ppm, the frequency—that is, to the left—relative to the TMS proton
above equation is well approximated as 𝛿 = 𝜎ref − 𝜎 for light peak.
nuclides such as 1 H and 13 C. Let us look at the frequency and chemical shift scales in
We now have the concept that protons in different chem- Figure 3.11 and conventionally set the TMS peak at zero at
ical environments have different chemical shifts. Conversely, the right-hand edge. The chemical shifts are dimensionless;
protons in the same chemical environment have the same they are simply numbers on the order of 10−6 ; thus, a
chemical shift. But what do we mean by “different” and chemical shift of 2 × 10−6 is reported as 2 ppm. What is the
“same”? It is intuitively obvious that the chemically different purpose of using chemical shifts instead of simply reporting
methylene groups of ClCH2 CH2 OH have different chemi- frequencies in Hz? The chemical shift scale is useful because
cal shifts and that the protons in either one of the methy-
lene groups have the same chemical shift. But it may not be * The terms “upfield” and “downfield” are now obsolete and have been
so obvious, for example, that the individual protons of the replaced, respectively, by shielded (lower 𝛿, or to the right) and deshielded
methylene group of C6 H5 CH2 CHBrCl do not have the same (higher 𝛿, or to the left).

300 MHz
3000 2700 2400 2100 1800 1500 1200 900 600 300 0 v (Hz)
10 9 8 7 6 5 4 3 2 1 0 δ (ppm)

Higher frequency Lower frequency

less shielding more shielding
deshielded shielded

600 MHz
6000 5400 4800 4200 3600 3000 2400 1800 1200 600 0 v (Hz)
10 9 8 7 6 5 4 3 2 1 0 δ (ppm)

FIGURE 3.11 NMR scale at 300 MHz and 600 MHz 1 H Larmor frequency. Relatively few organic compounds show NMR peaks
to the right of the TMS peak. These lower frequency signals are designated by negative chemical shifts (not shown in the figure).
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134 CHAPTER 3 PROTON (1 H) MAGNETIC RESONANCE SPECTROSCOPY

chemical shifts are independent of the value of the Larmor resolution is made clear in Figure 3.11 and in Figure 3.12
frequency (and magnetic field strength) of the spectrometer (see also Figure 3.23) in which increased applied magnetic
in use. The frequencies (in Hz) of the various peaks are not field in the NMR spectrum of acrylonitrile means increased
independent of these values. Chemical shifts and frequencies separation of signals.
are interconverted as follows: The concept of electronegativity (see Table 3.2) of
substituents near the proton in question is a dependable
𝛿 = 𝜈 − 𝜈ref ∕𝜈ref
guide, up to a point, to chemical shifts. It tells us that the
where 𝜈 is the frequency of the peak of interest in the electron density around the protons of TMS is high (silicon
compound under study, and 𝜈ref is the frequency of the is electropositive relative to carbon), and these protons will
resonance of the reference compound (TMS in the case of be shielded (see Table 3.3). C is more electronegative than
1 H). Note that chemical shifts can be positive or negative; H, and the sequence of proton NMR peaks in the alkyl series
however, the reference compound is usually chosen such that CH4 , RCH3 , R2 CH2 , and R3 CH is from right to left in the
the vast majority of chemical shifts of other compounds are
positive.
In Figure 3.11, for example, a proton NMR peak at, say, TABLE 3.2 Electronegativity of Selected Elements According to
1200 Hz on the 300 MHz scale gives the following chemical Pauling
shift relative to TMS (whose frequency, 𝜈ref , is 300 MHz in H (2.1)
this example): Li (1.0) Be (1.5) B (2.0) C (2.5) N (3.0) O (3.5) F (4.0)
(300 MHz + 1200 Hz) − (300 MHz) Na (0.9) Mg (1.2) A1 (1.5) Si (1.8) P (2.1) S (2.5) Cl (3.0)
= 4 × 10−6 = 4 ppm Br (2.8)
300 MHz
I (2.5)
If the same peak is now observed in a spectrum recorded
on a 600 MHz spectrometer, its frequency changes but its
chemical shift does not. This is one of the advantages of using
TABLE 3.3 Chemical Shift Trends Guided by
chemical shifts rather than frequencies. The frequency of the
Electronegativity
peak relative to TMS (𝜈 − 𝜈ref ) would now be 2400 Hz:
Compound 𝜹 Compound 𝜹
𝜈 − 𝜈ref = (𝛿)(𝜈ref ) = (4 × 10−6 )(600 MHz) = 2400 Hz
(CH3 )4 Si 0.00 CH3 F 4.30
The strongest magnetic field necessary and/or available
(CH3 )2 O 3.27 RCO2 H ∼ 10.80
helps to spread out the various peaks. This increase in

60 MHz
simulated
HB HX
C C
HA CN 100 MHz
simulated
20 Hz

300 MHz
simulated

300 MHz
experimental

A B X
6.4 6.3 6.2 6.1 6.0 5.9 5.8 5.7 5.6 5.5 5.4 5.3 ppm
1
FIGURE 3.12 Simulated 60 MHz, 100 MHz, and 300 MHz H NMR spectra of acrylonitrile; 300 MHz experimental
spectrum (in CDCl3 ) for comparison.
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3.4 CHEMICAL SHIFT 135

spectrum (Appendix A, Chart A.1). Again, it is important to us visualize this effect. It also indicates that a proton
remember that these are empirical arguments. held directly above or below the aromatic ring should
We could make a number of good estimates as to be shielded. For example, the methylene protons in 1,4-
chemical shifts, using concepts of electronegativity and polymethylenebenzenes (cyclophanes) are about 2.2 ppm
proton acidity. For example, the values found in Table 3.3 more shielded than those of ethylbenzene.
are reasonable solely on the basis of electronegativity. All of the ring protons of acetophenone are deshielded
However, finding the protons of acetylene at 1.80 ppm, because of the ring-current effect. Moreover, the ortho
that is, more shielded than ethylene protons (5.25 ppm), is protons are further deshielded (meta, para ∼7.40 ppm; ortho
perhaps counterintuitive, and finding the aldehydic proton ∼7.85 ppm) because of the additional deshielding effect of
of acetaldehyde at 9.97 ppm demonstrates the caution which the carbonyl group. The carbonyl bond and the benzene
must be used in oversimplifying the interpretation of chemi- ring are coplanar. If the molecule is oriented so that the
cal shifts solely in terms of concepts such as electron density applied magnetic field B0 is perpendicular to the plane of
or electronegativity. We shall use diamagnetic anisotropy the molecule, the circulating 𝜋 electrons of the C⏤O bond
to explain some of these apparent anomalies, such as the shield the conical zones above and below them and deshield
unexpectedly large deshielding effect of the benzene ring the lateral zones in which the ortho protons are located.
(7.27 ppm). Both ortho protons are equally deshielded since another,
Let us begin with acetylene. The molecule is linear, and equally populated, conformation can be written in which
the triple bond is symmetrical about the axis. If this axis the other ortho proton is deshielded by the anisotropy cone.
is aligned with the applied magnetic field, the electrons in Nitrobenzene shows a stronger effect.
the triple bond 𝜋 orbitals can circulate at right angles to A spectacular example of shielding and deshielding by
the applied field, thus inducing their own magnetic field ring currents is furnished by some of the annulenes. At about
opposing the applied field. Since the protons lie along the −60 ∘ C, the protons outside the ring of [18]-annulene are
magnetic axis, the magnetic lines of force induced by the strongly deshielded (9.3 ppm) and those inside are strongly
circulating electrons act to shield the protons (Figure 3.13), shielded (−3.0 ppm, i.e., more shielded than TMS).
and the NMR peak is found at lower frequency than elec-
tronegativity would predict. Of course, only a small number
of the rapidly tumbling molecules are aligned at any given
moment with the magnetic field, but the overall average shift
is affected by these transiently aligned molecules. Circulating electrons
This effect is an example of diamagnetic anisotropy,
which means that shielding and deshielding depend on the
instantaneous orientation of the molecule with respect to the C O
applied magnetic field. Similar arguments can be adduced
to rationalize the unexpected deshielded position of the Induced magnetic
aldehydic proton resonance. In this case, the effect of the
H lines of force
applied magnetic field is the greatest along the transverse
axis of the C⏤O bond (i.e., in the plane of the page in
Figure 3.14). The geometry is such that the aldehydic proton,
which lies in front of the page, is in the deshielding portion of B0
the induced magnetic field. The same argument can be used
to account for at least part of the rather large deshielding of FIGURE 3.14 Deshielding of aldehydic protons.
alkene protons.
The so-called ring-current effect is another example of
diamagnetic anisotropy and accounts for the large
deshielding of benzene ring protons. Figure 3.15 helps Induced magnetic
lines of force

Induced magnetic lines of force

H H
B0 H C C H Circulating
electrons

Circulating 𝜋 electrons B0
FIGURE 3.13 Shielding of alkyne protons. FIGURE 3.15 Ring-current effects in benzene.
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136 CHAPTER 3 PROTON (1 H) MAGNETIC RESONANCE SPECTROSCOPY

H H rather than an apparent singlet. The expanded inset shows

partially resolved peaks.
H H
We point out again that an appreciation of the con-
cepts of electronegativity (inductive effects) and of electron
H H H delocalization—combined with an understanding of diamag-
H H
netic anisotropy—permits both rationalization and predic-
H H tion of approximate chemical shift. Several examples make
H H H
the point:
H H 1. In an 𝛼,𝛽-unsaturated ketone, deshielding of the 𝛽-
H H proton can be empirically rationalized using resonance:
[18]-Annulene H H
𝛽
Demonstration of such a ring current is good evidence H3C C CH3 H3C C CH3
for planarity and aromaticity, at least at low temperature. As
the temperature is raised, the signals broaden because of slow C C C C
𝛼
interchanges in ring conformations. At about 110 ∘ C, a single H O H O
averaged peak appears at approximately 5.3 ppm because of 𝛼-proton 𝛿 6.2
rapid interchanges in ring conformations to give an averaged 𝛽 -proton 𝛿 6.8
chemical shift. This hints at the powerful capability of NMR
2. In a substituted vinyl ether, the oxygen atom deshields
for studying molecular dynamics.
the 𝛼-proton by an inductive effect and shields the
In contrast with the striking anisotropic effects of elec-
𝛽-proton by resonance.
trons in 𝜋 orbitals, those in the 𝜎 orbitals of a C⏤C bond
produce a small effect. To a first approximation, one can con- H
sider cyclohexane as roughly of the same anisotropic disk 𝛼

shape as an aromatic ring, giving rise to similar effects as H3C C C O CH3

𝛽
observed for aromatic systems. The observation that an equa- H
torial proton is consistently found at higher chemical shifts
(by 0.1 ppm to 0.7 ppm) than the axial proton on the same H H
𝛽
carbon atom in a rigid six-membered ring can thus be ratio- H3C C H3C C
nalized.
Extensive tables and charts of chemical shifts in the C𝛼 O C O
Appendices give the useful impression that chemical shifts of H CH3 H CH3
protons in organic compounds fall roughly into eight regions 𝛼 -proton 𝛿 6.2
as shown in Figure 3.16. 𝛽 -proton 𝛿 4.6
To demonstrate the use of some of the material in the
Appendices, we predict the chemical shifts of the protons The above approximate chemical shift values were
in benzyl acetate. In Appendix A, Chart A.1, we see that calculated from Appendix D. In comparison, the alkenyl
the chemical shift of the CH3 group is ∼2.0 ppm. From protons of trans-3-hexene are at 5.40 ppm.
Table B.1, we find that the CH2 group is at ∼5.07 ppm. Since chemical shift increments are approximately addi-
In Appendix D, Chart D.1, the aromatic protons are at tive, it is possible to calculate the ring proton shifts in poly-
∼7.2 ppm. In the spectrum of benzyl acetate (Figure 3.8), we substituted benzene rings from the monosubstituted values
see three sharp peaks from right to left at 1.96 ppm, 5.00 in Appendix Chart D.1. The chemical shift increments for
ppm, and 7.22 ppm; the integrations shown are in the ratio the ring protons of m-diacetylbenzene,
3:2:5, corresponding to CH3 , CH2 , and five ring protons.* O O
The peaks are all singlets, that is, they are simple individual o o
peaks with no additional fine structure or splittings. This C C
means that the CH3 and CH2 groups are insulated, that H3C CH3
is, there are no protons on the adjacent carbon atoms for o p o p
coupling (see Section 3.5). However, there is a problem with m m
the apparent singlet representing the ring protons, which are
not chemically equivalent (Section 3.8.1) and do couple with for example, are calculated as follows.
one another. At higher resolution, we would see a multiplet Chemical shift increments are the shifts from that of
the protons of benzene (7.27 ppm). Thus for a CH3 C⏤O
* The “integration step,” that is, the vertical distance between the horizontal
substituent (line 26, Appendix Chart D.1), the ortho incre-
lines of the integration trace, is proportional to the number of protons
represented by the particular peak or multiplet of peaks. These steps give
ment is +0.63 ppm, and the meta and para increments are
ratios, not absolute numbers of protons. The ratios actually represent areas both +0.28 ppm. The C-2 proton has two ortho substituents;
under the peaks. the C-4 and C-6 protons are equivalent and have ortho and
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3.5 SPIN–SPIN COUPLING, MULTIPLETS, AND SPIN SYSTEMS 137

Aliphatic alicyclic

β-Substituted aliphatic

Alkyne

α-Monosubstituted aliphatic

α-Disubstituted aliphatic

Alkene

Aromatic and heteroaromatic

Aldehydic

10 9 8 7 6 5 4 3 2 1 0
ppm
FIGURE 3.16 General regions of proton chemical shifts in organic molecules. Several aldehydes, several enols, and most carboxylic
acids resonate at higher chemical shifts than 10 ppm. Metal hydrides can have chemical shifts as low as −50 ppm.

para substituents; the C-5 proton has two meta substituents. individual spin within the pair depends on the state (e.g.,
Thus, the calculated increment for C-2 is +1.26 ppm, for 𝛼 or 𝛽) of the other spin. According to the Pauli principle,
C-4 and C-6 is +0.91 ppm, and for C-5 is +0.56 ppm. The the bonding electrons between two nuclei are paired so that
spectrum shows increments of +1.13 ppm, +0.81 ppm, and the electron spins are antiparallel. In a magnetic field, there
+0.20 ppm, respectively. This agreement is adequate.* It is some tendency for each nucleus to pair its spin with one
must be emphasized that these calculations are empirical of the bonding electrons so that most electron–nuclear spin
and that improved understanding of chemical shifts may be pairs are aligned in an antiparallel fashion, this being the
obtained using quantum chemical computations. stable state. Coupling is ordinarily not important beyond
Obviously, proton NMR spectroscopy is a powerful three bonds unless there is ring strain as in small rings or
tool for elucidating aromatic substitution patterns—as is 13 C bridged systems, delocalization as in aromatic or unsaturated
NMR (see Chapter 4). Two-dimensional NMR spectroscopy systems, or four connecting bonds in a “W” configuration
offers another powerful tool (see Chapter 5). (Section 3.14). Two-bond coupling is termed geminal, three-
bond coupling, vicinal, and beyond three bonds, long range.

3.5 SPIN–SPIN COUPLING, H C H H C C H

MULTIPLETS, AND SPIN SYSTEMS Geminal coupling Vicinal coupling
2 bonds (2J) 3 bonds (3J)

3.5.1 Simple and Complex First-Order Suppose that two vicinal protons are in very different
Multiplets chemical environments. Each proton will have its own
We have obtained a series of NMR peaks representing chemical shift, and the corresponding peaks in the NMR
protons in different chemical environments, with the area spectrum will be widely separated. However, if the two
under each peak (from integration) being proportional to the proton spins are coupled, the resonance frequency of each
number of equivalent protons it represents. We have now of them is affected slightly by the two possible states
to consider one further phenomenon, spin–spin coupling. (𝛼, 𝛽) of the other proton through the intervening electrons,
This can be described as the coupling of proton spins so that each peak appears as a doublet (Figure 3.17) with
through the intervening bonding electrons. In a general one peak associated with each of the two states of the
sense, “coupling” between a pair of spins means that the other spin. The frequency difference, in Hz, between the
energy (and therefore NMR frequency) associated with an two peaks of a doublet is proportional to the strength of
the coupling and is denoted by a coupling constant, J.
* Calculations for ortho-disubstituted compounds are less satisfactory Although J is called a coupling “constant,” its value varies
because of steric or other interactions between the ortho substituents. depending on the molecule being studied. It is a constant with
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138 CHAPTER 3 PROTON (1 H) MAGNETIC RESONANCE SPECTROSCOPY

v/J
J J

(a) 5.0

(b) 4.0

v1 v2
v
FIGURE 3.17 NMR spectrum of two protons with very
different chemical shifts (the frequencies of which are
denoted by the tick marks at 𝜈1 and 𝜈2 ) relative to their J (c) 3.0
coupling constant (an AX spin system).

respect to the strength of the external magnetic field, B0 .*

Whereas chemical shifts usually range over about 3750 Hz at
300 MHz, coupling constants between protons rarely exceed (d) 2.0
20 Hz (see Appendix F). Notice that J coupling constants are
reported in frequency units (Hz) whereas chemical shifts are
unitless (on the order of ppm). In Figure 3.17, note that while
there are four peaks, there are still only two chemical shifts;
their positions are at the centers of each of the two doublets.
(e) 1.0
So long as the chemical shift difference in hertz (Δv)
is much larger than the coupling constant (arbitrarily Δv∕J
is greater than about 8), the simple pattern of two doublets
20 0 –20 Hz
appears. The value of Δ𝜈 may be calculated explicitly from
the chemical shifts as follows: FIGURE 3.18 Spectra for a coupled two-proton system with
a decreasing difference in chemical shifts and a large J value
Δ𝜈 = |(𝛿1 − 𝛿2 )|(𝜈ref ) (10 Hz); the difference between AB and AX notation is explained
where 𝛿1 and 𝛿2 are the chemical shifts of interest and 𝜈ref in the text.
is the frequency of the chemical shift reference (TMS for
1 H NMR).

As the ratio Δv∕J becomes smaller, however, the dou-

blets approach one another, the inner two peaks increase in
intensity, and the outer two peaks decrease (Figure 3.18).
The shift position of each proton is no longer midway
between its two peaks as in Figure 3.17 but is at the center of J J
gravity (Figure 3.19); it can be estimated with fair accuracy
by inspection.
The spectrum in Figure 3.18d (and reproduced in
Figure 3.19), which consists of two distorted doublets, can
readily be mistaken for a quartet. Increasing the applied mag-
netic field (and therefore the Larmor frequency) would not
pull a true quartet apart into two doublets. As the intensities
of the outer peaks of spectrum (e) continue to decrease, fail-
ure to notice the small outer peaks may lead to mistaking the
inner peaks for a doublet. Eventually, as Δ𝜈∕J approaches
zero,

* The
v2 v1
number of bonds between coupled nuclei (protons in this chapter)
is designated by J and a left superscript. For example, H⏤C⏤H is 2 J, FIGURE 3.19 The horizontal positions of the short vertical lines
H⏤C⏤C⏤H is 3 J, H⏤C⏤C⏤C⏤H is 4 J. Double or triple bonds at the top of the figure denote the centers of gravity, instead of
are counted as single bonds. linear midpoints, for shift location in the case of a low Δ𝜈∕J ratio.
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3.5 SPIN–SPIN COUPLING, MULTIPLETS, AND SPIN SYSTEMS 139

the outer peaks disappear and the inner peaks merge, produc-
ing a two-proton singlet; this is observed for two completely
equivalent protons.
The next level of complexity involves three protons.
Consider the methylene and methine groups in the hypothet-
ical compound
OR

RO C CH 2 Ph
H
in which the single methine proton is in a very different
chemical environment compared with the two methylene
protons. Both CH2 protons couple equally with the methine
proton. In Figure 3.20, we see a triplet and a doublet widely
separated with an integration ratio of 1:2. The doublet is a
result of splitting of the CH2 resonance by the CH proton. ab
The triplet can be explained as a result of consecutive
splitting of the CH resonance by each of the two CH2
protons; the peaks overlap since the coupling constants are ab ab
identical (see Figure 3.21).
In a simple first-order multiplet, the number of peaks ab
is determined by the number of coupled, neighboring pro- FIGURE 3.21 The appearance of a triplet may be
tons with the same (or negligibly different) coupling con- understood by considering, from top to bottom in
stants. Neighboring protons are geminal or vicinal, that is, the diagram, two consecutive splittings of peaks
involving two or three bonds; long-range coupling constants into doublets with equal coupling constants.
are usually much smaller (see Section 3.14). As we have
seen, one neighboring proton induces a doublet, and two (x + 1)n , where n is the number of neighboring protons. Pas-
equally coupled neighboring protons induce a triplet. The cal’s triangle (see Figure 3.22) gives both the multiplicity
multiplicity (the number of peaks within a multiplet) then and the intensities of a multiplet.
is n + 1, n being the number of neighboring, equally coupled The requirements and appearance for a simple first-
protons. This is known as the “n + 1 rule.” The general for- order multiplet involving spin 12 nuclei such as 1 H can be
mula that covers all nuclei is 2nI + 1, I being the quantum summarized as follows:
spin number of the nuclei which are coupling to the one being
observed (see Section 3.2.1). The relative intensities of the • The ratio Δv∕J must be larger than about 8; Δ𝜈 is the
peaks of a simple first-order multiplet also depend on n. For difference in Hz between the midpoints of the coupled
spin 12 nuclei, doublet peaks (n = 1) are in the ratio 1:1; multiplets (or the difference in chemical shifts expressed
triplets (n = 2) are 1:2:1; quartets (n = 3) are 1:3:3:1; and in frequency units). J is the coupling constant.
so forth. The intensities of the peaks in the multiplets are • The number of peaks in the multiplet is n + 1, where n is
given by the coefficients of the expanded form of the equation the number of neighboring protons with the same coupling
constant.
• The separation in Hz between the individual peaks of a
simple first-order multiplet gives the coupling constant, J.
• A simple first-order multiplet is centrosymmetric, with
the most intense peak(s) central (see Pascal’s triangle,
Figure 3.22).
A complex first-order multiplet differs from a simple
first-order multiplet in that several different coupling con-
stants are involved in the complex multiplet. The require-
ment that Δv∕J be greater than about 8 still holds, but
Pascal’s triangle (at least not a single Pascal’s triangle) does
not hold for the complex multiplet. It should become obvi-
ous, with some experience, that the ratio Δv∕J = 8 is not
CH CH2 rigorous, but as the ratio decreases the interpretation gets
FIGURE 3.20 Proton NMR spectrum showing rougher. The “horsepower race,” mentioned in Section 3.3
the effects of spin–spin coupling between CH and was (and is) immensely successful in increasing the value of
CH2 groups with different chemical shifts. this ratio since Δ𝜈 depends directly on the Larmor frequency.
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140 CHAPTER 3 PROTON (1 H) MAGNETIC RESONANCE SPECTROSCOPY

n Multiplicity Relative intensity Spins Coupling pattern

0 Singlet (s) 1 J

1 Doublet (d) 1 1 n=1

2 Triplet (t) 1 2 1 J J

3 Quartet (q) 1 3 3 1
n=2

4 Quintet 1 4 6 4 1
5 Sextet 1 5 10 10 5 1 J J J

6 Septet n=3
1 6 15 20 15 6 1
7 Octet 1 7 21 35 35 21 7 1
8 Nonet 1 8 28 56 70 56 28 8 1
FIGURE 3.22 Relative intensities of the peaks comprising first-order multiplets; n denotes the number of equivalent
1
coupling nuclei of spin 2
(e.g., protons) and the n + 1 rule applies. The relative intensities follow the pattern of Pascal’s
triangle.

The result has been to simplify spectra and thereby per- The 600 MHz spectrum in Figure 3.23 consists of a
mit spectral interpretation for more difficult molecules. It simple first-order multiplet. The 60 MHz spectrum consists
will be useful to get some feeling for this effect at 60 MHz, of a complex multiplet characteristic of a higher order
300 MHz, and 600 MHz in Figure 3.23. The compound is spin system. Importantly, one can realize here that the
way we describe and analyze a spin system can change
Cl⏤CH2 ⏤CH2 ⏤O⏤CH2 ⏤CH2 ⏤Cl
with the strength of the applied magnetic field, and is not
At 600 MHz, the spectrum consists of two simple first- always solely related to the structure of the molecule. A
order triplets. At 300 MHz, the spectrum is slightly distorted, spin system may give rise to one or more higher order
and there are splittings which cannot be explained using multiplets, in which case it is difficult to determine all of
first-order rules. At 60 MHz, there is obvious overlap and the chemical shifts, coupling constants,* and multiplicities
extraneous peaks. (The expanded multiplets are the result of by inspection. It is notable that 1 H chemical shifts are usually
using the same 𝛿 scale for all the spectra.) The Δv∕J ratios are reported to two decimal places. But are these numbers always
12 at 600 MHz (certainly first-order) and 6 at 300 MHz (still valid? Certainly they are for the almost perfect first-order
easily recognized if the additional splitting is ignored). The triplets at 600 MHz in Figure 3.23. At 60 MHz, however,
60 MHz overlapping multiplets with extraneous peaks are chemical shifts of the overlapping higher order multiplets
described as “higher order.” A glance at Appendix A shows cannot be measured accurately by inspection. Somewhere
that substituents Cl and OR are almost equally deshielding between 300 MHz and 60 MHz, attempts to measure the
and suggests that attempting to interpret a 60 MHz spectrum chemical shifts of similar compounds would only yield
using a simple first-order multiplet analysis would fail. approximations, but not values accurate to two decimal
Return to Figure 3.12 for a more complex example. places.

3.5.2 First-Order Spin Systems 3.5.3 Pople Notation

A spin system consists of those spins in a molecule that Pople notation provides a means for describing spin sys-
couple to one another. By definition, it therefore excludes tems.† Spectral multiplets arise due to various sets of nuclei,
other spins in the molecule. It is not necessary for every and each set is designated by a capital letter. A set refers
spin within the spin system to be directly coupled to every to a group of equivalent nuclei. Sets may be described as
other spin. A spin system is insulated from other spin systems strongly or weakly coupled to each other depending on the
by an absence of coupling due to, for example, heteroatoms ratio Δ𝜈∕J; the larger this value, the more weakly coupled the
or quaternary carbons (atoms without attached hydrogen spins are relative to their chemical shift difference, and vice
atoms). The coupling of spins may be described as simple
* Coupling constants may be positive or negative. However, the sign of these
first-order, complex first-order, or higher order. In a given
have no effect in a first-order system, in which we can measure J values by
spin system, there may be long-range coupling through the inspection but cannot determine the sign by inspection. Thus, we disregard
insulating atom, but this usually involves small coupling the sign.
constants, resulting in peak broadening in a multiplet rather † Pople, J.A., Schneider, W.G., and Bernstein, H.J. (1959). High Resolution

than additional resolved splittings. NMR. McGraw-Hill: New York.

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3.5 SPIN–SPIN COUPLING, MULTIPLETS, AND SPIN SYSTEMS 141

ClCH2CH2OCH2CH2Cl

(a)

(b)

(c)

3.95 3.90 3.85 3.80 3.75 3.70 3.65 3.60 3.55 3.50 3.45 ppm
FIGURE 3.23 Proton NMR spectra of chloroethyl ether at Larmor frequencies of (a) 60 MHz, (b) 300 MHz, and (c) 600 MHz, all
in CDCl3 .

versa. If the Δ𝜈∕J ratio is larger than about 8, the coupled with slightly different coupling constants, and a sextet with
sets are considered to weakly coupled, and the resulting spin slightly broadened peaks.
systems are designated by well-separated letters of the alpha- In the styrene molecule,
bet such as AX. This is because the corresponding chemical
HX
shifts of such a system are also well separated. If the ratio
is less than 8, letters such as AB are used. If there are three HA
weakly coupled sets, they are designated AMX. If the first
two sets are strongly coupled and the last two weakly, ABX HM
is used. The number of magnetically equivalent protons in a
set (Section 3.9) is designated by a subscript number; if there all of the alkenyl protons are weakly coupled with each
is only one proton in a set, no subscript is used. other at 600 MHz and form an AMX spin system (see
Any such collection of sets, insulated from all other Section 3.10).
sets, is a spin system. The following are examples of As mentioned above, letters close together in the alpha-
first-order spin systems: AX (two doublets), A2 X (doublet, bet are used to describe spin systems that are not first order:
triplet), A2 X2 (two triplets), and A3 X2 (triplet, quartet). The AB, A2 B, ABC, A3 B2 C2 , and so on. These strongly cou-
reasoning is as follows: in A2 X for example, the A2 set is pled spin systems cannot be easily interpreted by inspection.
split into a doublet by the n + 1 neighboring protons; in this The spectra can, however, be rendered first-order (e.g., AB
case there is one proton in the X set; the two protons in the becomes AX) if a suitably powerful magnetic field is avail-
A2 set account for the triplet. able.
With two or more sets, there is the complication of sev- Beyond these spin systems are those containing mag-
eral coupling constants; more importantly, one must under- netically nonequivalent but chemically equivalent protons,
stand how the various sets are coupled among themselves. which are quite common and have an unpleasant aspect: they
Thus, nitropropane can be described as follows since the cannot become first-order systems by increasing the mag-
effect of the NO2 group is to impart significantly different netic field. Pople notation for a pair of chemically equivalent
chemical shifts to each of the three sets of protons: (but magnetically inequivalent) spins is AA′ . These spin sys-
tems are discussed further in subsequent sections.
CH3 CH2 CH2 NO2
A3 M2 X2
3.5.4 Further Examples of Simple
First-Order Spin Systems
The A3 and X2 groups couple with the M2 group, but
the A3 group does not couple with the X2 group. At this With an understanding of simple first-order spin systems and
point, we note only that the spectrum consists of two triplets of Pople notation, we can consider the following example.
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142 CHAPTER 3 PROTON (1 H) MAGNETIC RESONANCE SPECTROSCOPY

CH2 CH3
TMS

1600 1590 1580 Hz 760 750 740 Hz

7 6 5 4 3 2 1 0 ppm
FIGURE 3.24 Proton NMR spectrum of ethylbenzene in CDCl3 at 600 MHz. The ethyl moiety is recognized by the CH3 triplet and
the CH2 quartet.

The spectrum in Figure 3.24 arises from two spin sys- interchangeable meta protons, and one para proton, all in the
tems insulated from each other by a carbon atom that has no characteristic region for ring protons. The alert student, hav-
attached proton. The CH3 ⏤CH2 spin system consists of a ing absorbed the concept of Pople notation (Section 3.5.3),
well-resolved triplet and quartet—that is, an A3 X2 system as would probably write A2 B2 C. The student might go even fur-
suggested by the peak multiplicities and by the 5:2:3 (left to ther and predict that a larger magnet might give a first-order
right) ratios of integration. ring system, A2 M2 X. While a larger magnet would sepa-
The ring system, which has a plane of symmetry, rate the chemical shifts of the ring system, we will see in
consists of two interchangeable ortho protons, two Section 3.9 that a first-order system would not be achieved.

H
H3C CH3

2200 2180 Hz 900 890 880 870 Hz 420 410 400 390 380 Hz

7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 ppm
FIGURE 3.25 Proton NMR spectrum of cumene (isopropylbenzene) in CDCl3 at 300 MHz. The isopropyl moiety is recognized
by the characteristic six-proton doublet and the one-proton septet.
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3.5 SPIN–SPIN COUPLING, MULTIPLETS, AND SPIN SYSTEMS 143

Briefly, the problem is that neither the ortho protons nor the (1995)]. First, remember that the spectrum we are looking
meta protons are “magnetically equivalent.” They are only at is only the part of the total 1 H NMR spectrum due to one
chemically equivalent. spin (or a set of equivalent spins).
One minor but common feature may be pointed out.
Note the slight broadening of each of the peaks in the CH2 1. Determine the integration of each peak and normalize
quartet. This is the result of a small long-range coupling to the values so that the integrals of the outermost peaks
the ortho protons through the insulating ipso carbon atom; (on each end of the spectra) are equal to 1. Write
as presented here, splittings due to this coupling are not the integral values under each of the peaks. (If the
resolved, but instead result in broadening. integration values are not given on the spectrum, a good
The spectrum of isopropylbenzene in Figure 3.25 pres- first approximation is simply to measure the heights of
ents two simple first-order multiplets. The methine proton the peaks with a ruler.) As a check, the spectrum and
gives a septet because of coupling with six neighboring the integral values should be centrosymmetric (i.e., the
identical protons of the two CH3 groups, all with the same on the left side of the spectrum as on the right).
same coupling constant. The two chemically equivalent CH3 2. Check that the sum of the integral values is 2n , where
groups (because of free rotation) show a six-proton doublet n is an integer. The value of n is the total number of
because of coupling with the single methine proton. The spins which are coupled to the one(s) giving rise to the
ring protons present the same difficulties as those of the ring multiplet in Figure 3.26 (e.g., a simple doublet would
protons of ethylbenzene (Figure 3.24). have intensities of 1:1 and so 2n = 1 + 1 = 2 and n = 1.
This means that one spin (n = 1) is coupled to the one
3.5.5 Analysis of First-Order we are observing, giving a doublet).
Multiplets 3. Draw a vertical line under each of the peaks in the NMR
spectrum (see line b in Figure 3.26). Ensure that these
The multiplet arising from one spin (or a set of equivalent
lines are labeled with the integral values you identified
spins) coupled to another spin (or a set of equivalent spins)
in step 1.
is straightforward and has been explained in Section 3.5.1.
There, we saw the familiar doublets, triplets, and quartets. 4. Look at the integral values associated with the two left-
In this section, we explain how to analyze, or deconvolute, most lines to determine a multiplicity. Their relative
spectra arising from a spin (or a set of equivalent spins) values tell you what type of multiplet is contributing to
coupled to two or more nonequivalent spins (or sets) with the spectrum. For example, if the values are 1 and 3,
two or more different J-coupling constants. As an example, Pascal’s triangle (Figure 3.22) tells us we have a quartet.
let us consider the spectrum shown in Figure 3.26. It should In Figure 3.26, the values are 1 and 1 (line a) and so we
be noted that NMR software can readily carry out this have a doublet. Using the n + 1 rule, we can conclude
type of analysis, but for educational purposes it is useful to that one spin led to the splitting.
understand the origins of this type of spectrum. 5. Measure, along the horizontal frequency axis, the sep-
The following are the general steps to be taken to analyze aration between the two peaks you identified in step 4.
such a spectrum [see also Hoye et al. (1994) and Mann The value you obtain, in Hz, is the J-coupling constant

20 15 10 5 0 –5 –10 –15 –20 Hz

a 1 1 3 3 1 3 1 3 3 1 3 1 3 3 1 1
b
c 1 3 1 3 3 1 3 1

d 1 1

e
FIGURE 3.26 Analysis of a first-order multiplet. The multiplets and coupling constants are as follows: doublets of 4 Hz and
12 Hz, and two quartets of 7 Hz. The numbers associated with the lines in the stick diagram are relative integration values.
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144 CHAPTER 3 PROTON (1 H) MAGNETIC RESONANCE SPECTROSCOPY

associated with the multiplet you found in step 4. Refer- It should be noted that accidental overlap of peaks can
ring again to line “a” of Figure 3.26, careful measure- lead to unexpected integral values. For example, to analyze
ment of the separation between the two left-most peaks the spectrum shown in Figure 3.27, one should realize that
gives a value of J = 18.5 –14.5 Hz = 4 Hz. there is a fortuitous overlap of triplets and extra care must
6. Combine the various vertical lines associated with the be taken in assigning the integral values and analyzing the
multiplet you identified in steps 4 and 5 into one multiplet.
single vertical line. In Figure 3.26, this means in line c
we are collapsing all doublets (two lines with equal
integrals) with separations of 4 Hz into single lines. In 3.6 PROTONS ON OXYGEN,
this example, 16 lines are collapsed into 8 lines; we NITROGEN, AND SULFUR ATOMS:
have removed the effect of the 4 Hz J-coupling from the EXCHANGEABLE PROTONS
spectrum. The integral values associated with the new
lines are those from the left-most peak of the original
Protons directly bonded to an oxygen, nitrogen, or sulfur
multiplet (line a).
atom differ from protons on a carbon atom in that:
7. Return to step 4 and repeat the analysis until you are left
with only a single line. Each time you repeat the process, 1. they are exchangeable;
you get the following information: the multiplicity 2. they are subject to hydrogen bonding; and
(which, because of the n + 1 rule, tells you the number 3. those on a nitrogen atom are subject to partial or com-
of coupled spins) and the J-coupling constant. plete decoupling due to the electric quadrupole moment
of the 14 N nucleus, whose spin quantum number is one.
The example in Figure 3.26 shows that the multiplet
observed is due to (i) coupling to one spin with a J value of Chemical shift ranges for such protons are given in
4 Hz, (ii) coupling to three equivalent spins with a J value of Appendix E. Variations in shift depend on concentration,
7 Hz, and (iii) coupling to one spin with a J value of 12 Hz. temperature, and solvent effects.
Note that all coupling happens at the same time, even if we
analyze their effects on the spectrum sequentially. In this
3.6.1 Protons on an Oxygen Atom
example, one could propose that the proton we are observing
is coupled simultaneously to a CH proton, a CH3 group, 3.6.1.1 Alcohols. Depending on concentration, the hydrox-
and a second nonequivalent CH proton. This combination ylic peak in alcohols is found between ∼0.5 ppm and
of functional groups is consistent with the multiplicities ∼4.0 ppm in CDCl3 . A change in temperature or solvent will
determined from the observed spectrum (n + 1 rule). also shift the peak position.
You can help to verify the correctness of your analysis Intermolecular hydrogen bonding explains why the shift
by ensuring that the stick patterns you draw are always depends on concentration, temperature, and polarity of
centrosymmetric, in terms of both the positions of the lines solvent. Hydrogen bonding decreases the electron density
and their intensities (see Figure 3.26). Remember also that around the hydroxylic proton (deshielding), thus moving the
the peaks which you combine into a single peak in step 6 proton peak to higher frequency. Decrease in concentration
must each be separated from the next by the same amount, in a nonpolar solvent disrupts such hydrogen bonding, and
that is, the value of J. the peak appears at lower frequency (shielding), that is, the

20 15 10 5 0 –5 –10 –15 –20 Hz

a 1 2 3 4 3 2 1
b 1 2 12 21 2 1

c 1 2 1

d
FIGURE 3.27 Peak coincidence arising from a triplet of triplets with coupling constants of 5 Hz and 10 Hz.
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3.6 PROTONS ON OXYGEN, NITROGEN, AND SULFUR ATOMS: EXCHANGEABLE PROTONS 145

H3C CH2 OH
in CDCl3

1110 1100 1090 1080 Hz 370 360 350 340 Hz

4.5 4.0 3.5 3.0 2.5 2.0 1.5 ppm

FIGURE 3.28 Proton NMR spectrum of CH3 CH2 OH in CDCl3 at 300 MHz, allowed to stand at room temperature, overnight
exposed to air. The CH2 peaks are broadened by residual coupling to OH, which also shows slight broadening. Absorbed moisture
has increased the intensity of the OH signal.

alcohol molecules become less polymeric. Increased temper- proton is not on the oxygen atom of an individual molecule
ature has a similar effect. long enough for it to be affected by the methylene protons;
therefore, there is no coupling. The OH proton shows a sin-
O H O H O H glet, the CH2 a quartet, and the CH3 a triplet.
R R R The rate of exchange can be decreased by lowering
the temperature, by using a dilute solution, or by treating
the solvent with anhydrous sodium carbonate or anhydrous
Intramolecular hydrogen bonds are less affected by their
alumina, then filtering through a pad of dry glass wool in a
environment than are intermolecular hydrogen bonds. In
Pasteur pipette immediately before obtaining the spectrum.
fact, the enolic hydroxylic NMR peak of 𝛽-diketones, for
Under these conditions, the OH proton is coupled with the
example, is hardly affected by change of concentration or
CH2 protons, and useful information is available: an OH
solvent, although it can be shifted to a lower frequency by
singlet indicates a tertiary alcohol, a doublet a secondary
warming. NMR spectroscopy is a powerful tool for studying
alcohol, and a triplet a primary alcohol.
hydrogen bonding.
The use of dry, deuterated dimethyl sulfoxide
H (DMSO-d6 ) or deuterated acetone has the same effect as the
O O above treatments. In addition, the OH proton peak is moved
to higher frequency by hydrogen bonding between the solute
C C
R C R and the solvent, thus providing a useful separation from over-
H lapping peaks of other protons (see Figure 3.29).
In Figure 3.29 and in the following stick diagram, the
Rapid exchangeability explains why the hydroxylic CH2 protons of ethanol are coupled to both the hydroxyl
peak of ethanol is usually seen as a singlet (Figure 3.28). proton and the CH3 protons. The diagram shows a somewhat
Under ordinary conditions—exposure to air, light, and water overlapping quartet of doublets. The OH coupling is 5 Hz,
vapor—acidic impurities develop in CDCl3 solution and whereas the CH3 coupling is 7 Hz. It is usually better to start
catalyze rapid exchange of the hydroxylic proton.* The a coupling diagram with the largest coupling constant.

* CDCl in small vials from Aldrich is pure enough so that a spectrum of the OH peak as a singlet (Figure 3.28). The high dilution used with
3
CH3 CH2 OH taken within several hours showed the OH peak as a triplet. On modern instruments also accounts for the persistence of the vicinal cou-
standing for about 24 hours exposed to air, the sample gave a spectrum with pling of the OH proton.
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146 CHAPTER 3 PROTON (1 H) MAGNETIC RESONANCE SPECTROSCOPY

H3C CH2 OH
in DMSO-d6

1310 1300 1290 Hz 1050 1040 1030 1020 Hz 330 320 310 Hz

DMSO-d6

4.5 4.0 3.5 3.0 2.5 2.0 1.5 ppm

FIGURE 3.29 Proton NMR spectrum of CH3 CH2 OH run in dry deuterated DMSO at 300 MHz. From left to right, the peaks
represent OH, CH2 , and CH3 . The small peak at 2.5 ppm represents the protonated impurity in DMSO-d6 (see Appendix G).

becomes sharper. The relative position of each peak depends

on the extent of hydrogen bonding of each hydroxylic proton.
The spectrum of a compound containing rapidly
exchangeable protons can be simplified, and the exchange-
1 3 3 1 able proton peak removed, simply by shaking the solution
with excess deuterium oxide or by obtaining a spectrum in
1 1 3 3 3 3 1 1 deuterium oxide solution if the compound is soluble. A peak
resulting from HOD will appear, generally between 5 ppm
and 4.5 ppm in nonpolar solvents and near 3.3 ppm in DMSO
(see Appendix E). A CDCl3 or CCl4 solution in a stoppered
NMR tube may be shaken vigorously for several seconds
with one or two drops of D2 O, and the mixture allowed to
stand (or centrifuged) until the layers are clearly separated.
The top aqueous layer does not interfere.
Acetylation or benzoylation of a hydroxyl group moves
the peak of the CH2 OH protons of a primary alcohol to
higher frequency by about 0.5 ppm, and the CHOH proton
1050 1040 1030 1020 Hz of a secondary alcohol about 1.0 ppm to 1.2 ppm. Such
shifts provide a confirmation of the presence of a primary
At intermediate rates of exchange, the hydroxylic multi-
or secondary alcohol.
plet merges into a broad band, which progresses to a singlet
at higher exchange rates (Figure 3.28).†
A diol may show separate peaks for each hydroxylic 3.6.1.2 Water. Aside from the problems of exchangeabil-
proton; in this case, the rate of exchange, in hertz, is much ity, as just discussed, water is a ubiquitous impurity that
less than the difference in hertz between the separate peaks. faithfully obeys Murphy’s law by interfering with critically
As the rate increases (due to addition of a trace of acid important peaks. Bulk water as suspended droplets or wall
catalyst), the two peaks broaden and then merge to form a films gives a peak at ∼4.7 ppm in CDCl3 (HOD occurs in the
single broad peak; at this point, the exchange rate (k), in D2 O exchange experiment mentioned in Section 3.6.1.1).
hertz, is approximately equal to twice the original signal Dissolved water appears at ∼1.55 ppm in CDCl3 and
separation in hertz. As the rate increases, the single peak can be a serious interference in a critical region of the
spectrum in dilute solutions.* Use of C6 D6 (dissolved H2 O
† H O as an impurity may exchange protons with other exchangeable protons
2 * Webster,
to form a single peak at an averaged position between the proton peaks F.X. and Silverstein, R.M. (1985) Aldrichimica Acta, 18 (3), 58.
involved. Webster and Silverstein (1985).
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3.6 PROTONS ON OXYGEN, NITROGEN, AND SULFUR ATOMS: EXCHANGEABLE PROTONS 147

at 0.4 ppm) avoids this interference. A table of water peaks with protons of water and alcohols (or hydroxyl groups of
in the common deuterated solvents appears in Appendix H. hydroxy acids) to give a single peak whose averaged posi-
tion depends on concentration. Sulfhydryl or enolic protons
3.6.1.3 Phenols. The behavior of a phenolic proton resem- do not exchange rapidly with carboxylic protons, and indi-
bles that of an alcoholic proton. The phenolic proton peak is vidual peaks are observed.
usually a sharp singlet (rapid exchange, no coupling), and
its range, depending on concentration, solvent, and tempera-
ture, is generally to higher frequency (∼7.5 ppm to 4.0 ppm) 3.6.2 Protons on Nitrogen
compared with the alcoholic proton. A carbonyl group in the The common 14 N nucleus* has a spin quantum number I
ortho position shifts the phenolic proton peak to the range of 1 and, in accordance with the formula 2nI + 1, should
of about 12.0 ppm to 10.0 ppm because of intramolecular cause a proton attached to it and a proton on an adjacent
hydrogen bonding. Thus, o-hydroxyacetophenone shows a carbon atom to show three equally spaced, equally intense
peak at about 12.05 ppm almost completely invariant with peaks. There are two factors, however, that complicate the
concentration. The much weaker intramolecular hydrogen picture: the rate of exchange of the proton on the nitrogen
bonding in o-chlorophenol explains its shift range (∼6.3 ppm atom and the electric quadrupole moment of the 14 N nucleus
at 1 M concentration to ∼5.6 ppm at infinite dilution), which (see Section 3.2.1).
is broad compared with that of o-hydroxyacetophenone but The 1 H bonded to the nitrogen nucleus may undergo
narrow compared with that of phenol. rapid, intermediate, or slow exchange. If the exchange is
3.6.1.4 Enols. The familiar tautomeric equilibrium of keto
rapid, the NH proton is decoupled from the N nucleus and
and enol forms of acetylacetone is described in from protons on adjacent carbon atoms. The NH proton peak
Section 3.8.3.1. The enol form predominates over the keto is therefore a sharp singlet, and the adjacent CH protons are
form under the conditions described. not split by the NH proton. Such is the case for most aliphatic
Ordinarily, we do not write the enol form of acetone amines.†
or the keto form of phenol, although minuscule amounts At an intermediate rate of exchange, the NH proton
do exist at equilibrium. But both forms of acetylacetone are is partially decoupled, and a broad NH peak results. The
seen in the NMR spectrum because equilibration is slow adjacent CH protons are not split by the NH proton. Such
enough on the NMR scale and the enol form is stabilized is the case for N-methyl-p-nitroaniline.
by intramolecular hydrogen bonding. The enol form of If the NH exchange rate is slow, the NH peak is
acetone and the keto form of phenol are not thus stabilized; still broad because the electric quadrupole interaction at
furthermore, the aromatic resonance stabilization of phenol the nitrogen nucleus induces a moderately efficient spin
strongly favors the enol form. relaxation and, thus, an intermediate lifetime for the spin
In 𝛼-diketones such as 2,3-butanedione, only the keto states of the nitrogen nucleus. The proton thus interacts with
form is seen in NMR spectra. However, if the enol form of three spin states of the nitrogen nucleus which are changing
an 𝛼-diketone is stabilized by hydrogen bonding—as in the at a moderate rate, and the proton NMR spectrum is a broad
following cyclic 𝛼-diketones—only the stabilized enol form peak that may disappear in the baseline. In this case, coupling
appears in the NMR spectra. of the NH proton to the adjacent protons is observed. Such is
the case for pyrroles, indoles, secondary and primary amides,
7.43 ppm 6.53 ppm and carbamates (Figure 3.30).
H H Note that H⏤N⏤C⏤H coupling takes place through
O O O O the C⏤H, C⏤N, and N⏤H bonds, but coupling between
nitrogen and protons on adjacent carbon atoms is negligible.
The proton–proton coupling is observed in the signal caused
O by hydrogen on carbon; the N⏤H proton signal is severely
broadened by the 14 N quadrupolar interaction.
In the spectrum of ethyl N-methylcarbamate
3.6.1.5 Carboxylic Acids. Carboxylic acids exist as stable (Figure 3.30), the NH proton shows a broad peak centered
hydrogen-bonded dimers in nonpolar solvents even at high about 4.70 ppm, and the N⏤CH3 peak at 2.78 ppm is split
dilution. The NMR peaks of carboxylic protons therefore into a doublet (J ∼ 5 Hz) by the NH proton. The ethoxy
appear in a characteristic range of ∼13.2 ppm to ∼10.0 ppm protons are represented by the triplet at 1.23 ppm and the
and are affected only slightly by concentration. Polar solvents quartet at 4.14 ppm.
partially disrupt the dimer and shift the peak accordingly. Aliphatic and cyclic amine NH protons have chemical
shifts from ∼3.0 ppm to 0.5 ppm; aromatic amines from
O H O ∼5.0 ppm to 3.0 ppm in CDCl3 (see Appendix E). Because
R R
O H O *15 N spectra are discussed in Chapter 6.
†H ⏤C⏤N⏤H coupling in several amines was observed following
The peak width at room temperature ranges from sharp rigorous removal (with Na⏤K alloy) of traces of water. This effectively
to broad, depending on the exchange rate of the partic- stops proton exchange on the NMR time scale. See Henold, K. L. (1970) J.
ular acid. The carboxylic proton exchanges quite rapidly Chem. Soc. D., Chem. Commun., 1340.
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148 CHAPTER 3 PROTON (1 H) MAGNETIC RESONANCE SPECTROSCOPY

1250 Hz 1210 840 Hz 800 380 Hz 340

O
H3C NH C O CH2 CH3

6 5 4 3 2 1 ppm
FIGURE 3.30 Proton NMR spectrum of ethyl N-methylcarbamate, at 300 MHz in CDCl3 .

amines are subject to hydrogen bonding, the shift depends the salt (Figure 3.31). Sometimes the broad + NH, + NH2 , or
on concentration, solvent, and temperature. Amide, pyrrole, + NH peak can be seen to consist of three broad humps.
3
and indole NH groups have chemical shifts from ∼8.5 ppm These humps are due to J-coupling with the 14 N nucleus
to 5.0 ppm; the effect on the chemical shift of concentration, (J ∼ 50 Hz). The reason that these splittings are observable
solvent, and temperature is generally smaller than in the case is due to the high (near tetrahedral) symmetry at the nitrogen
of amines. atom, which reduces the 14 N nuclear quadrupolar interaction.
The nonequivalence of the protons on the nitrogen With good resolution, it is sometimes possible to observe
atom of a primary amide and of the methyl groups of splitting of each of the humps by the protons on adjacent
N, N-dimethylamides is caused by slow rotation around the carbons (J ∼ 7 Hz), but it is easier to observe the splitting
CN bond, as can be rationalized by the contribution of the on the sharper 𝛼-CH signals. The behavior of the protons in
C N the H⏤C⏤N⏤H sequence may be summarized as follows
in Table 3.5.*
resonance form O (Section 3.8.3.2).
Protons on the nitrogen atom of an amine salt exchange
at a moderate rate; they are seen as a broad peak
(∼8.5 ppm to 6.0 ppm), and they are coupled to protons on C6H5CH2NH3+
adjacent carbon atoms (J ∼ 7 Hz).
The use of trifluoroacetic acid as both a protonating
agent and a solvent frequently allows classification of
amines as primary, secondary, or tertiary. This is illus-
trated in Table 3.4, where the number of protons on nitro-
gen determines the multiplicity of the methylene unit in

TABLE 3.4 Classification of Amines by NMR of their Ammonium

Salts in Trifluoroacetic Acid

Amine δ 4.4
Precursor Ammonium Multiplicity of
20 Hz
Class Salt Structure Methylene unit
FIGURE 3.31 Proton NMR spectrum of the 𝛼-methylene unit of
Primary C6 H5 CH2 NH+3 Quartet (Figure 3.31) a primary amine at a Larmor frequency of 100 MHz in CF3 CO2 H;
Secondary C6 H5 CH2 NH2 R+ Triplet corresponds to Table 3.4, first line.
Tertiary C6 H5 CH2 NHR+2 Doublet
Source: Anderson, W.R. Jr., and Silverstein R.M. (1965) Anal. Chem., 37, 1417. * Courtesy of Dr. Donald C. Dittmer (Syracuse University).
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3.7 COUPLING OF PROTONS TO OTHER IMPORTANT NUCLEI (19 F, D (2 H), 31 P, 29 Si, AND 13 C) 149

TABLE 3.5 Effect of NH Exchange Rate on Coupling 3.7 COUPLING OF PROTONS TO

Rate of NH Exchange OTHER IMPORTANT NUCLEI
Fast Intermediate Slow (19 F, D (2 H), 31 P, 29 Si, AND 13 C)
Effect on Singlet, sharp Singlet, broad Singlet, broad
N⏤H 3.7.1 Coupling of Protons to 19 F
Effect on No coupling No coupling Coupling Since 19 F has a nuclear spin quantum number of 12 and 100%
C⏤H
natural abundance, H⏤F coupling and H⏤H coupling obey
the same multiplicity rules; in general, the coupling constants
for H⏤F cover a somewhat larger range than those for H⏤H
Chemical shifts of several classes of protons bonded to (Appendix F), and there is more long-range coupling for
nitrogen atoms are available in Appendix E. H⏤F pairs.
The spectrum of fluoroacetone, CH3 ⏤(C⏤O)⏤CH2 F,
3.6.3 Protons on Sulfur in CDCl3 at 300 MHz (Figure 3.32), shows the CH3 group
as a doublet at 2.2 ppm (J = 4.3 Hz) resulting from long-
Sulfhydryl protons usually exchange at a low rate so that range coupling to the 19 F nucleus. The doublet at 4.75 ppm
at room temperature they are coupled to protons on adja- (J = 48 Hz) represents the protons of the CH2 group coupled
cent carbon atoms (J ∼ 8 Hz). They do not exchange rapidly to the geminal 19 F nucleus. The 19 F nucleus is about 80% as
with hydroxyl, carboxylic, or enolic protons on the same sensitive as the proton and can be readily observed at the
or on other molecules; thus, separate peaks are seen. How- appropriate Larmor frequency for a specific magnetic field
ever, exchange is rapid enough that shaking the solution for (see Chapter 6).
a few minutes with deuterium oxide replaces sulfhydryl pro-
tons with deuterium. The chemical shift range for aliphatic 3.7.2 Coupling of Protons to D (2 H)
sulfhydryl protons is 2.5 ppm to 0.9 ppm; for aromatic
sulfhydryl protons, 3.6 ppm to 2.8 ppm. Concentration, sol- For the purposes of NMR spectroscopy, deuterium (D or 2 H)
vent, and temperature affect the position within these ranges. usually is introduced into a molecule to detect a particular
functional group or to simplify a spectrum. Deuterium has a
nuclear spin quantum number of 1, small coupling constants
3.6.4 Protons on or near Chlorine, with protons, and a small electrical quadrupole moment. The
Bromine, or Iodine Nuclei ratio of the J values for H⏤H pairs to those of H⏤D pairs
In principle, protons may be weakly coupled to chlorine, is about 6.5.
bromine, or iodine nuclei, but the effects of such coupling Suppose the protons on the 𝛼-carbon atom of a ketone
are not observed because of the strong electric quadrupolar O
γ β α
relaxation of these halogen nuclei. For example, the proton
X CH 2 CH 2 CH 2 C Y
NMR spectrum of CH3 CH2 Cl is unaffected by the presence
of the chlorine nucleus; the triplet and quartet are sharp. were replaced by deuterium to give

48 Hz H3C CH2F 4.3 Hz

660 658 656 654 652 Hz

5.0 4.5 4.0 3.5 3.0 2.5 2.0 ppm

1
FIGURE 3.32 H NMR spectrum of fluoroacetone in CDCl3 at 300 MHz.
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150 CHAPTER 3 PROTON (1 H) MAGNETIC RESONANCE SPECTROSCOPY

O peak of the doublet is split into a triplet by the 12 CH2 protons

γ β α (J ∼ 7 Hz) as shown below. These 13 C satellite peaks are
X CH 2 CH 2 CD2 C Y of low intensity because of the small number of molecules
containing the 13 CH3 group and can usually be seen on
The spectrum of the undeuterated compound consists both sides of an intense 12 CH3 peak (e.g., the large 12 CH3
of a triplet for the 𝛼 protons, a quintet for the 𝛽 protons— triplet shown below). The dominant peaks in a 1 H NMR
assuming equal coupling for all protons—and a triplet for spectrum therefore do not show the effects of coupling to 13 C.
the 𝛾 protons. For the deuterated compound, the 𝛼-proton For 13 C-labeled compounds, multiplets are of higher inten-
peak would be absent, the 𝛽-proton peak would appear, at sity depending on the level of isotopic substitution.
modest resolution, as a slightly broadened triplet, and the
13
𝛾-proton peak would be unaffected. Actually, at very high CH3

resolution, each peak of the 𝛽-proton triplet would appear

as a very closely spaced quintet (JH−C−C−D ∼ 1 Hz) since
2nI + 1 = 2 × 2 × 1 + 1 = 5, where n is the number of D J 13CH3 ~ 120Hz
nuclei coupled to the 𝛽 protons.
Most deuterated solvents have residual proton impu-
rities in an otherwise completely deuterated sample; thus,
deuterated dimethyl sulfoxide, (CD3 )2 S⏤O, contains a few 12
CH3
molecules of CD2 H⏤(S⏤O)⏤CD3 , which show a closely
spaced quintet (J ∼ 2 Hz, intensities 1:2:3:2:1) in accordance J 13CH3 12
CH2 ~ 7Hz J 13CH3 12
CH2 ~ 7Hz

with 2nI + 1 (see Appendix G).

Since deuterium has an electric quadrupole moment,
relatively broad peaks are observed in 2 H NMR spectra. 3.8 CHEMICAL EQUIVALENCE

3.7.3 Coupling of Protons to 31 P The concept of chemical equivalence is central to NMR

spectroscopy. Chemically equivalent nuclei comprise a set
The 31 P nucleus has a natural abundance of 100% and a spin
within a spin system (Pople notation, Section 3.5.3). Correct
number of 12 . The multiplicity rules for proton–phosphorus
usage of Pople notation, and spectral interpretation, requires
splitting are the same as those for proton–proton splitting.
one to be able to identify sets of chemically equivalent nuclei.
The coupling constants are large (JH⏤P ∼ 200 to 700 Hz,
Nuclei are chemically equivalent if they are interchange-
and JHC⏤P is 0.5 to 20 Hz) (Appendix F) and are observable
able through any symmetry operation or by a rapid process.
through at least four bonds. The 31 P nucleus can be observed
(This broad definition assumes an achiral environment (sol-
at the appropriate Larmor frequency for a specific magnetic
vent or reagent) in the NMR experiment; the common sol-
field (Chapter 6).
vents are achiral.)

3.7.4 Coupling of Protons to 29 Si 3.8.1 Determination of Chemical

The NMR-active 29 Si isotope has a natural abundance of Equivalence by Interchange Through
4.70% and a nuclear spin quantum number of 12 . The value of Symmetry Operations
J29 Si⏤CH is about 6 Hz. The low-intensity doublet caused by There are three symmetry operations of interest, each
29 Si⏤CH coupling can often be seen straddling (±3 Hz)
3 involving a symmetry element: rotation about a simple axis
the dominant central TMS peak in a 1 H NMR spectrum; of symmetry (Cn ), reflection through a plane of symmetry
the low-intensity 13 CH3 satellite doublet can also be seen at (𝜎), and inversion through a center of symmetry (i).* More
±59 Hz (Section 3.7.5). 29 Si NMR spectra can be obtained rigorously, symmetry operations may be described under two
at the appropriate Larmor frequency for a specific magnetic headings: Cn and Sn . The latter is rotation around an alternat-
field (Chapter 6). ing axis of symmetry. It turns out that S1 is the same as 𝜎, S2
is the same as i, and higher subscripts for Sn are rare. The
subscripts denote the number of such rotations required to
3.7.5 Coupling of Protons to 13 C
make a full 360∘ rotation. Thus, C1 is a 360∘ rotation, C2
The 13 C isotope has a natural abundance of 1.1% and is a 180∘ rotation, and so on. The designation S1 requires a
a nuclear spin quantum number of 12 . The peaks due 360∘ rotation followed by a reflection through the plane at a
to protons directly bonded to 13 C are split into doublets right angle to the axis. S2 requires a 180∘ rotation followed
with large coupling constants, about 115 Hz to 270 Hz for by a reflection, and so forth. Students well versed in the use
13 C⏤H. The CH ⏤CH group, for example, is predom- of symmetry operations can use these methods to determine
3 2
inantly 12 CH3 ⏤12 CH2 but contains a small amount of chemical equivalence. A detailed discussion of symmetry
13 CH ⏤12 CH and of 12 CH ⏤13 CH . Thus, the 13 CH pro-
3 2 3 2 3
ton peak is split into a doublet by 13 C (J ∼ 120 Hz), and each * The symmetry operation must relate to the entire molecule.
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3.8 CHEMICAL EQUIVALENCE 151

operations is beyond the scope of this text, but briefly, if the of atoms. Alternatively, one proton in each structure may
nuclei are related or exchangeable through a symmetry oper- be replaced by Z, representing any nucleus not present in
ation, then they are chemically equivalent. Consider the sim- the molecule. From an analysis of symmetry operations,
ple example of the two hydrogen atoms in a water molecule. homotopic atoms or groups are chemically equivalent in all
The positions of these two hydrogen atoms can be chemical environments; enantiotopic atoms or groups are
exchanged through a C2 operation (rotation about an axis chemically equivalent in an achiral solvent; diastereotopic
∘
which passes through the oxygen atom by 360 2
= 180∘ ) or atoms or groups are not chemically equivalent in any chem-
by reflection through a plane of symmetry (𝜎) which passes ical environment; and likewise, heterotopic atoms or groups
through the oxygen atom and which is perpendicular to the are not chemically equivalent (usually obvious).
plane of the molecule. As a result, the two hydrogen nuclei If geminal protons (CH2 ) in a molecule cannot be
in water are chemically equivalent. interchanged through a symmetry operation, they are dia-
stereotopic to one another; each has a different chemical
shift – except for coincidental overlap (Figure 3.33c). This
3.8.2 Determination of Chemical compound has a stereogenic center, shown by an asterisk.
Equivalence by Tagging (or Note, however, that a stereogenic center is not necessary for
Substitution) the occurrence of nonequivalent methylene protons; in this
An alternative, equivalent, means of visualizing whether case the term “diastereotopic” is not technically correct but
nuclei are chemically equivalent is through a “tagging” or still sometimes used to describe the pair of protons.
substitution operation* in which two identical drawings of
the same compound are made: one hydrogen atom (or group
3.8.3 Chemical Equivalence by Rapid
of hydrogen atoms, e.g., a methyl group) in one of the
Interconversion of Structures
drawings is tagged (or substituted by a different atom
or isotope), and the other hydrogen atom (or group of If chemical structures can interconvert, the rate of intercon-
hydrogen atoms) in the second drawing is also tagged (or version depends on temperature, catalyst, solvent, and con-
substituted) in the same manner. The resulting drawings centration. We assume a given concentration and absence of
(or models) are related to each other using the follow- catalyst, and we treat four systems.
ing terms to describe stereochemical and isomeric relation-
ships between molecules: homomers, enantiomers, diastere- 3.8.3.1 Keto–Enol Interconversion. The tautomeric inter-
omers, or constitutional isomers. The H atoms (or groups conversion of acetylacetone (Figure 3.34) at room tempera-
of atoms) are called, respectively, homotopic, enantiotopic, ture is slow enough that the NMR peaks of both forms can
diastereotopic, or heterotopic. The examples in Figure 3.33 be observed. The equilibrium keto/enol ratio can be deter-
illustrate the process. mined from the relative areas of the keto and enol CH3 peaks,
In the first example, the models are superimposable as shown. At higher temperatures, the interconversion rate
(i.e., homomers); in the second, nonsuperimposable mirror will be increased so that a single averaged resonance will
images (i.e., enantiomers); and in the third, nonsuperimpos- be obtained. Chemical equivalence for all of the intercon-
able nonmirror images (i.e., diastereomers). Note that the verting protons has now been achieved. Note that the NMR
○
tags are permanent; that is, H and H are different kinds time scale is of the same order of magnitude as the chemical
shift separation of interchanging signals expressed in hertz,
* Ault, A. (1974) J. Chem. Educ., 51, 729. that is, about 101 Hz to 103 Hz. Processes occurring faster

H H H H Homomeric models
Homotopic atoms
(a) Cl Cl Cl Cl

H H H H Enantiomeric models
Enantiotopic atoms
(b) H3C COOH H3 C COOH

H H H H
Diastereomeric models
H3C * H3 C *
C COOH C COOH Diastereotopic atoms
(c) HO H HO H
FIGURE 3.33 Tagged molecules: (a) equivalent molecules, (b) enantiomers, and (c) diastereomers.
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152 CHAPTER 3 PROTON (1 H) MAGNETIC RESONANCE SPECTROSCOPY

15% ketone
O O
CH3 enol
H3C CH2 CH3

OH
× 64
85% enol
H
O O

H3C C CH3
16 ppm 15 H CH3 ketone
=CH enol
CH2 ketone

5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 ppm
FIGURE 3.34 Proton NMR spectrum of acetylacetone in CDCl3 at 300 MHz and 32 ∘ C. The enol–keto ratio was measured
by integration of the CH3 peaks.

than this will lead to averaged signals. Note also that the eno- and one for the equatorial protons. In other words, at room
lic OH proton peak is deshielded relative to the OH proton temperature, the axial and equatorial protons are chemically
of alcohols because the enolic form is strongly stabilized by equivalent by rapid interchange. At very low temperatures,
intramolecular hydrogen bonding. they are not chemically equivalent; in fact, in each “frozen”
chair form, the protons of each CH2 group are nonequivalent
3.8.3.2 Interconversion Around a Partial Double Bond pairs, but at room temperature, the rate of chair interconver-
(Restricted Rotation). At room temperature, a neat sam- sion is sufficiently high to average the chemical shifts of these
ple of dimethylformamide shows two CH3 peaks because geminal protons.
the rate of rotation around the hindered partial C⏤N dou- Methylcyclohexane exists at room temperature as a
ble bond is slow. At ∼123 ∘ C, the rate of exchange of the two rapidly interconverting mixture of axial and equatorial con-
CH3 groups is rapid enough so that the two peaks coalesce. formers. These conformers are not superimposable, and at
low temperatures, a spectrum of each conformer exists.
𝛿 2.85
In a fused cyclohexane ring, such as those of steroids,
O CH3 O CH 3 the rings are “frozen” at room temperature and the axial and
N N equatorial protons of each CH2 group are not chemically
H CH 3 H CH 3 equivalent.
𝛿 2.94

3.8.3.4 Interconversion Around the Single Bonds of

3.8.3.3 Interconversion Around the Single Bonds of
Chains. Chemical equivalence of protons on a CH3 group
Rings. Cyclohexane at room temperature exists in rapidly
results from rapid rotation around a carbon–carbon sin-
interconverting, superimposable chair forms.
gle bond even in the absence of a symmetry element.
Ha Figure 3.35a shows Newman projections of the three stag-
gered rotamers of a molecule containing a methyl group
Hb Ha attached to another sp3 carbon atom having four differ-
ent substituents, that is, a stereogenic center. In any sin-
Hb gle rotamer, none of the CH3 protons can be interchanged
by a symmetry operation. However, the protons are rapidly
An axial proton becomes an equatorial proton and changing positions. The time spent in any one rotamer is
vice versa in the interconverting structures, and the spec- short (∼10−6 seconds), because the energy barrier for rota-
trum consists of a single averaged peak. As the tem- tion around a C⏤C single bond is small. The observed
perature is lowered, the peak broadens and, at a sufficiently chemical shift of the protons in the methyl group is an aver-
low temperature, two peaks appear: one for the axial protons age of the shifts of the three protons. In other words, each
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3.8 CHEMICAL EQUIVALENCE 153

FIGURE 3.35 (a) Newman projection of the staggered rotamers of a molecule with a methyl group attached to a stereogenic
sp3 carbon atom. (b) 1-Bromo-2-chloroethane. (c) 1-Bromo-1, 2-dichloroethane.

proton can be interchanged with the others by a rapid rota- Pople notation (see Section 3.9). In general, if protons can be
tional operation. Thus, without the labels on the protons, the interchanged by a symmetry operation (through a plane of
rotamers are indistinguishable. symmetry) in one of the rotamers, they are also chemically
In the same way, the nine protons of the three rotating equivalent (enantiotopic) by rapid rotational interchange.*
methyl groups of a t-butyl group are all chemically equivalent Consider a methylene group next to a stereogenic center,
except in rare cases of steric hindrance. Both the methyl as in 1-bromo-1,2-dichloroethane (Figure 3.35c). Protons Ha
group and the t-butyl group are described as symmetrical and Hb are not chemically equivalent since they cannot be
tops. interchanged by a symmetry operation in any conformation;
The staggered rotamers of 1-bromo-2-chloroethane the molecule has no simple axis, plane, center, or alternat-
(Figure 3.35b) are distinguishable. However, in the anti ing axis of symmetry. Although there is a rapid rotation
rotamer, Ha and Hb are chemically equivalent (enantiotopic) around the carbon–carbon single bond, the CH2 protons are
by interchange through a plane of symmetry, as are Hc and not interchangeable by a rotational operation; the averaged
Hd ; thus, there are two sets of enantiotopic protons. In nei- chemical shifts of Ha and Hb are not identical. An observer
ther of the gauche rotamers is there a symmetry element, can detect the difference before and after rotating the methy-
but Ha and Hb , and Hc and Hd , are chemically equivalent lene group. The protons in this compound are diastereotopic:
by rapid rotational interchange between two enantiomeric each has its own chemical shift and they are coupled to each
rotamers. Now we have one chemical shift for Ha and Hb other. The spin system in this molecule is described with the
in the anti rotamer, and a different chemical shift for Ha and Pople notation ABX. It is useful to remember that any pair
Hb in the gauche rotamers. By rapid averaging of these two of methylene protons in a molecule with a stereogenic center
chemical shifts, we obtain a single chemical shift (i.e., chem- are diastereotopic; if the center is far-enough removed from
ical equivalence) for Ha and Hb , and of course for Hc and the CH2 group (e.g., several bonds away in a different spin
Hd . The Pople notation is AA′ XX′ ; it is useful to remem-
ber that for any compound of the form X⏤CH2 CH2 ⏤Y * The
discussion of rotamers is taken in part from Silverstein, R.M. and
(X ≠ Y), the four methylene protons will be described by this LaLonde, R.T. (1980). J. Chem. Educ., 57, 343.
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154 CHAPTER 3 PROTON (1 H) MAGNETIC RESONANCE SPECTROSCOPY

system), the protons may, however, appear to behave as if protons, AA′ XX′ . Neither the two A protons nor the two
they were chemically equivalent. X protons are magnetically equivalent; this is apparent by
realizing that the through-bond coupling path traced from
proton A to proton X (three bonds) is not the same as the
3.9 MAGNETIC EQUIVALENCE path traced from proton A to proton X′ (five bonds) (impor-
tant: it is not relevant that the path from A to X is equivalent
In addition to the above requirements for a first-order spin to the path from A′ to X′ ). This is not a first-order spin system
system, we now consider the concept of magnetic equiva- and the resulting multiplet patterns do not conform to first-
lence by comparison with the concept of chemical equiva- order intensity patterns in the Pascal triangle (Figure 3.22)
lence. In order to consider testing for magnetic equivalence nor do the separations (in Hz) between the peaks corre-
between a set of spins, those spins must have been already spond to coupling constants. Spectra such as these do not
identified as being chemically equivalent; that is, chemical become first-order spectra regardless of the strength of the
equivalence is a prerequisite for magnetic equivalence. magnetic field: the experimentalist cannot change the sym-
If two chemically equivalent protons each have the same metry relationships between the spins in the molecule by
coupling to every other proton in the spin system, then increasing the magnetic field. The choice of designating the
they are also magnetically equivalent, and the following spectrum as AA′ XX′ or AA′ BB′ , however, does depend on
Pople notations apply: A2 , B2 , X2 , and so on. This does the strength of the applied magnetic field. At lower mag-
not mean that a proton must couple equally to all other netic field, these spectra become deceptively simple. In the
protons in the spin system; it means that for any (and 60 MHz era, students learned to recognize two tight clus-
all) third proton chosen as a test spin, the two chemically ters in aromatic region as indicative of para disubstitution.
equivalent protons must couple equally to that third proton. The pattern of o-dichlorobenzene shows a pattern somewhat
As mentioned above, if two protons in a set are only resembling that of p-chloronitrobenzene for the same reasons
chemically equivalent and not magnetically equivalent, the (see Figure 3.37). Heteroaromatic rings behave similarly.
following notations apply: AA′ , BB′ , XX′ , and so on. Three isomeric difluoroethylenes furnish additional
To rephrase: two chemically equivalent protons are also examples of chemically equivalent nuclei that are not mag-
magnetically equivalent if they are symmetrically disposed netically equivalent. The systems are AA′ XX′ .
with respect to each and every other proton in the spin system
(excluding those in the chemically equivalent set to which H F F F F H
they belong). For example, to test whether a AA′ XX′ system
also has magnetic equivalences so that it could be described H F H H H F
as A2 X2 , we have to show that the coupling paths from A to
X and from A to X′ are equivalent (and also that the coupling
path from A′ to X is equivalent to the coupling path from A′ In each system, the protons comprise a set (AA′ ) and the
to X′ ). fluorine nuclei comprise a set (XX′ ) of chemically equivalent
The common occurrence of magnetic nonequivalence in nuclei, but since the nuclei in each set are not magnetically
aromatic rings depends on the number, kind, and distribution equivalent, the spectra are not first order. One way to quickly
of the substituents. see that there cannot be magnetic equivalence is by realizing
Consider the protons in p-chloronitrobenzene (see that each of the two protons do not couple equivalently to a
Figure 3.36). There is an axis of symmetry (through the particular fluorine; the cis and trans coupling constants are
substituents) that provides two sets of chemically equivalent not the same.

NO2

A A′

X X′

Cl

8.20 8.18 8.16 8.14 8.12 ppm 7.56 7.54 7.52 7.50 7.48 ppm
FIGURE 3.36 Proton NMR spectrum of p-chloronitrobenzene in CDCl3 at 300 MHz.
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3.10 AMX, ABX, AND ABC RIGID SYSTEMS WITH THREE COUPLING CONSTANTS 155

Cl
Cl

7.55 7.50 7.45 7.40 7.35 7.30 ppm

FIGURE 3.37 Proton NMR spectrum of o-dichlorobenzene in CDCl3 at 300 MHz.

The open-chain, conformationally mobile compounds of an A2 B system, additional peaks do appear, and the system
the type: presents a higher order spectrum; the J values no longer
coincide with the measured differences between peaks [see
H H simulated spectra in Bovey (1988)].
Y Having considered these systems, we can now examine
Z the systems AMX, ABX, and ABC, starting with a rigid
H H system. Styrene, whose rigid vinylic group furnishes an
AMX first-order spectrum at 600 MHz, is a good starting
consist of two different sets of proton coupled to each point (see Figure 3.38).
other. The groups Z and Y contain no chiral element and Correlation of the structure of a compound with its spec-
no protons that couple to the two sets shown; Z and Y trum is indeed a gentle approach compared with interpreting
polarities determine the difference between shifts of the sets the spectrum of an unknown compound, but it is instructive.
(i.e., Δv). Strictly, the protons are described as an AA′ XX′ Since in styrene there is free rotation around the sub-
or AA′ BB′ system depending on the magnitude of Δv∕J stituent bond, there are two symmetry planes through the
(as described in Section 3.8.3.4). However, in practice for molecule. In one conformation, the vinyl group and the ring
such a molecule undergoing rapid conformational changes are coplanar in the plane of the page with all of the pro-
(rotation about bonds) at room temperature – barring large tons in the symmetry plane, hence not interchangeable. In
conformational preferences – the relevant averaged J values the other conformation, the vinyl group and the benzene ring
are quite similar, and, in practice, spectra resembling those are perpendicular to one another, and the symmetry plane is
representative of A2 X2 or A2 B2 spin systems result. The perpendicular to the plane of the page. Again, the vinyl pro-
“weakly coupled” A2 X2 system would show two triplets, and tons are in the symmetry plane. The following data for the
a “strongly coupled” A2 B2 system would show a complex, vinyl group are relevant:
higher order spectrum.
There are three sets in the vinyl system, AMX, each set
consisting of one proton.
3.10 AMX, ABX, AND ABC Chemical shifts: X = 6.73 ppm, M = 5.75 ppm,
RIGID SYSTEMS WITH THREE A = 5.25 ppm.
COUPLING CONSTANTS ΔvXM = 588 Hz, ΔvXA = 888 Hz, ΔvAM = 300 Hz.
JXM = 17 Hz, JXA = 11 Hz, JAM = 1.0 Hz.
In Section 3.5, we discussed the simple first-order system The Δv∕J ratios: XM = 35, XA = 88, MA = 300.
AX. As the ratio Δv∕J decreases, the two doublets approach
each other with a characteristic distortion of peak heights to Each set gives a doublet of doublets (note the stick
give an AB system, but no additional peaks appear. However, diagrams in Figure 3.38). The X proton is the most strongly
as an A2 X system – a triplet and a doublet – develops into deshielded by the aromatic ring, and the A proton least so.
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156 CHAPTER 3 PROTON (1 H) MAGNETIC RESONANCE SPECTROSCOPY

AA′ BB′ C
CDCl3

4460 4450 4440 4430 4420 4410 4400 4390 4380 4370 4360 4350 Hz

X M A

4050 4040 4030 4020 Hz 3470 3460 3450 3440 Hz 3170 3160 3150 3140 Hz

HX HA
A
B C C
HM
C A′
B′

7.4 7.2 7.0 6.8 6.6 6.4 6.2 6.0 5.8 5.6 5.4 5.2 ppm
FIGURE 3.38 Proton NMR spectrum of styrene in CDCl3 at 600 MHz.

The X proton is coupled trans across the double bond to higher order system. At 600 MHz, it is possible to assign
the M proton with the largest coupling constant, and cis approximate chemical shifts (from left to right): ∼7.42 ppm,
across the double bond to the A proton with a slightly smaller ∼7.33 ppm, and ∼7.26 ppm.
coupling constant. The result is the doublet of doublets The ratio of the integrals (2:2:1:1:1:1 from left to right)
centered at 6.73 ppm with two large coupling constants. identifies the proton at 7.26 ppm as para. The ortho protons
The M proton is, of course, coupled to the X proton are the most deshielded because of the diamagnetic effect of
and is coupled geminally to the A proton with a very the vinyl double bond.
small coupling constant. The result is a doublet of doublets
centered at 5.75 ppm with one large and one very small
coupling constant. 3.11 WEAKLY AND STRONGLY
The A proton is coupled cis across the double bond
COUPLED SYSTEMS: VIRTUAL
to the X proton with the slightly smaller coupling constant
(as compared with the trans coupling). The A proton is COUPLING
coupled geminally to the M proton with the very small
coupling constant mentioned above. The result is a doublet This section compares weakly coupled systems, which are
of doublets centered at 5.25 ppm with the large coupling relatively easy to interpret, and strongly coupled systems,
constant (smaller than the trans coupling) and the very small which are more complicated.
geminal coupling constant.
In the conformation of the molecule with the perpendic-
ular plane of symmetry, the ortho protons of the ring system
3.11.1 Weakly Coupled Systems
are interchangeable with each other as are the meta protons. 3.11.1.1 1-Nitropropane. As mentioned in Section 3.9,
However, since the protons in neither set are magnetically most open-chain compounds – barring severe steric hin-
equivalent, the aromatic spin system is AA′ BB′ C. It is a drance – are conformationally mobile at room temperature;
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3.11 WEAKLY AND STRONGLY COUPLED SYSTEMS: VIRTUAL COUPLING 157

slightly different coupling constants in each set average out but the M2 multiplet is deshielded enough by the OH group
and spins become practically magnetically equivalent. Thus, at 300 MHz so that a somewhat distorted quintet (splitting
a 300 MHz, room-temperature spectrum of 1-nitropropane by the D and X protons) is apparent, as are incipient extra
is described as A3 M2 X2 rather than A3 MM′ XX′ , and first- peaks; at 600 MHz, we clearly see a first-order quintet. In
order rules apply (see Figure 3.39). both spectra, the strongly deshielded triplet represents the X2
The X2 protons are strongly deshielded by the NO2 methylene protons split by M2 methylene protons. The one-
group, the M2 protons less so, and the A3 protons very proton singlet represents the OH proton. In order to prevent
slightly. There are two coupling constants, JAM and JMX , hydrogen bonding of the OH proton to the X proton, a trace of
which are very similar but not exactly equal. In fact, at p-toluenesulfonic acid was added to the CDCl3 solution. This
300 MHz, the M2 resonance is a deceptively simple, slightly was necessary because of the high purity of the CDCl3 (see
broadened sextet (nA + nX + 1 = 6). At sufficient resolution, Section 3.6.1.1) and because of the low-solute concentration
12 peaks are possible: (nA + 1) (nX + 1) = 12. The A3 and used when working at high magnetic fields.
X2 resonances are triplets with slightly different coupling
constants. 3.11.2.2 3-Methylglutaric Acid. Another example of vir-
tual coupling is encountered in 3-methylglutaric acid.
3.11.2 Strongly Coupled Systems Because of the 3-substituent, there is no plane of symmetry
through the chain in the plane of the paper, and, as described
3.11.2.1 1-Hexanol. In contrast, consider the 300 MHz in Section 3.8, the protons in each methylene group are not
and 600 MHz spectra of 1-hexanol (Figure 3.40). In the interchangeable and are thus diastereotopic.
300 MHz spectrum, the three-proton triplet at 0.87 ppm We can be led astray by a structure that might be
seems odd for the CH3 group since the peak intensities devi- expected to give a first-order spectrum, at least at 300 MHz
ate from the first-order ratios of 1:2:1. Furthermore, the (see Figure 3.41a).
unusual appearance of the multiplets is obvious despite a rea- In other words, the Δv∕J ratios for
sonable Δv∕J value of 13 for the CH3 ⏤CH2 (A3 B2 ) groups.
The problem is that the B2 , C2 , and D2 methylene CH 2
groups are strongly coupled to one another; they appear H 3C CH
in the spectrum as a partially resolved band and act as a
conglomerate of spins in coupling to the methyl group, which CH 2
is formally coupled only to the adjoining CH2 group. This
phenomenon is termed “virtual coupling.” seem adequate, and our expectations of a clean doublet for
At 600 MHz, the CH2 ⏤CH3 Δv∕J value is 26, and the the CH3 group seem reasonable.
CH3 multiplet is now a first-order triplet. The B2 , C2 , and The difficulty is that the COOH groups deshield the CH2
D2 multiplets remain as a tight conglomerate at 300 MHz groups, thereby decreasing the Δv∕J ratio for CH2 ⏤CH; the

1320 1300 1280 Hz 630 620 610 600 590 Hz 330 320 310 300 290 Hz

A3 M2 X2
CH3 CH2 CH2 NO2

4.0 3.5 3.0 2.5 2.0 1.5 1.0 ppm

FIGURE 3.39 Proton NMR spectrum of 1-nitropropane in CDCl3 at 300 MHz.
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158 CHAPTER 3 PROTON (1 H) MAGNETIC RESONANCE SPECTROSCOPY

X2 M2 D2 C2 B2 A3

HO CH2 CH2 CH2 CH2 CH2 CH3

960 940 920 900 Hz 560 540 520 500 Hz

(a)

3.5 3.0 2.5 2.0 1.5 1.0 ppm

480 470 460 450 Hz 280 270 260 250 Hz

(b)

3.5 3.0 2.5 2.0 1.5 1.0 ppm

FIGURE 3.40 Proton NMR spectrum of hexanol in CDCl3 at (a) 600 MHz and (b) 300 MHz.

virtual coupling results in a broadened, distorted “doublet” example is found in the terpene alcohol, 2-methyl-6-
for the CH3 at 300 MHz. With some experience, such methylen-7-octen-4-ol (ipsenol, Figure 3.42). The first thing
distortions are tolerable. But the overlapping peaks of the that we note is that the two methyl groups (part of an iso-
CH2 ⏤CH⏤CH2 moiety are still beyond interpretation by propyl group) are diastereotopic. Compare this result with
inspection at 300 MHz. isopropylbenzene (Figure 3.25) in which the two methyl
At 600 MHz (see Figure 3.41b), the CH3 group is a groups of the isopropyl group are enantiotopic, and hence,
clean doublet resulting from coupling with the CH proton, chemically equivalent.
which is no longer complicated by the virtual coupling to Since the nonequivalent methyl groups are each split
CH2 multiplets. The CH proton is coupled, quite equally, to by the vicinal CH proton, we expect to see two separate
seven neighboring protons; this means that the CH multiplet doublets. At 300 MHz, unfortunately, the pattern appears to
should consist of eight peaks. And in fact it does, but be a classical triplet, usually an indication of a CH3 −CH2
the eighth peak is buried under the edge of one of the moiety—impossible to reconcile with the structural formula
CH2 multiplets, each of which is a doublet of somewhat and the integration. Higher resolution would pull apart the
distorted doublets. As mentioned above, the protons of middle peak to show two doublets.
each CH2 group are diastereotopic—meaning that they have To remove the coincidence of the inner peaks that
two different chemical shifts. The protons of each CH2 caused the apparent triplet, we used the very effective tech-
group couple with each other (geminal coupling) and with nique of adding deuterated benzene,* which gave
the CH proton (vicinal coupling); the geminal coupling is convincing evidence of two doublets at 20% C6 D6 ∕80%
larger—hence the two doublets of doublets. CDCl3 and optimal results at about a 50:50 mixture
(Figure 3.42). At 600 MHz, two individual doublets are seen.

3.12 CHIRALITY

The organic chemist—in particular, the natural products

chemist—must always be conscious of chirality when inter- * Sanders, J.K.M. and Hunter, B.K. (1993). Modern NMR Spectroscopy, 2nd

preting NMR spectra. An interesting and challenging ed. Oxford: Oxford University Press, p. 289.
 Silverstein c02.tex V3 - 07/10/2014 3:50 P.M. Page 159

3.12 CHIRALITY 159

HA HB HA HB
1 3
HOOC 2 4 COOH
5
HC CH3
X3

270 260 250 240 230 Hz

(a)

2.4 2.3 2.2 2.1 2.0 1.9 1.8 1.7 1.6 1.5 1.4 1.3 1.2 1.1 1.0 0.9 0.8 0.7 ppm

1350 1300 Hz 540 520 500 480 460 Hz

(b)

2.4 2.3 2.2 2.1 2.0 1.9 1.8 1.7 1.6 1.5 1.4 1.3 1.2 1.1 1.0 0.9 0.8 0.7 ppm
FIGURE 3.41 Proton NMR spectrum of 3-methylglutaric acid in D2 O (a) at 300 MHz and (b) at 600 MHz. The COOH proton
exchanges with the D2 O and the corresponding NMR peak is not shown.

10 CH2

C
6
H 2C 5 7 CH

CH4 8 CH2
HO 3 CH2
CH 100% d6-Benzene
1950 Hz 1550 Hz H 3C 2 CH3 1150 Hz 750 Hz
9 1

50% d6-Benzene / 50% CDCl 3

700 Hz 550 Hz 450 Hz 400 Hz 300 Hz

20% d6-Benzene / 80% CDCl 3

CDCl3

100% CDCl3
7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 ppm
FIGURE 3.42 Proton NMR spectrum of 2-methyl-6-methylen-7-octen-4-ol (ipsenol) in CDCl3 at 300 MHz and effect of titration with
benzene. The sample was a gift from Phero Tech, Inc., Vancouver, BC, Canada.
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160 CHAPTER 3 PROTON (1 H) MAGNETIC RESONANCE SPECTROSCOPY

superimposed on the OH peak, which could be confirmed by

600 MHz heating, by a solvent change, or by shaking the solution with
D2 O to remove it (see Section 3.6.1.1). Dilution moves it to
a lower frequency. The very small peak at about 2.05 ppm is
an impurity.
Predictably, the H-7 alkene proton is at the high fre-
quency end of the spectrum. It couples trans (J = 18 Hz) and
cis (J = 10.5 Hz) across the double bond to the H-8 protons
to give a doublet of doublets (see Appendix F).
The peaks between about 1585 Hz and 1525 Hz are due
to both the H-8 and H-10 protons. At the left side, there is an
18 Hz doublet representing one of the H-8 protons coupled
0.95 0.90 ppm trans across the double bond to H-7. These doublet peaks are
at 1585 Hz and 1567 Hz.
At 1546 Hz and 1525 Hz are the two individual peaks
Note that the stereogenic center accounts for the fact that
(not a doublet) of the H-10 protons. The very small geminal
the protons of each of the two aliphatic methylene groups are
coupling results in slight broadening; the jagged edges are
also diastereotopic. As a result, the rather simple structure
evidence of some long-range coupling. Note that the height
presents a challenge in assigning the spectrum.
of the right-hand peak is suspicious.
The proton integration ratios from left to right are
Having determined the trans coupling of one of the
1:4:1:1:1:2:1:1:6, which accounts for 18 protons in accord
H-8 protons, we search for the corresponding doublet of the
with the molecular formula C10 H18 O, but there are puzzling
cis coupling. Unfortunately, we seem to be left with only a
discrepancies. The six-proton step at 0.92 ppm in the integra-
singlet at about 1538 Hz but quickly assume that the missing
tion represents the diastereotopic methyl protons described
peak is buried under the suspiciously large peak at the right
above, and the one-proton integration step at 3.82 ppm with
edge. Examination at 600 MHz of these diene spin systems
several different coupling constants is a good choice for the
clearly shows the (H-8) 10.5 Hz doublet, appropriate for the
CHOH proton (see Appendix A, Chart A.1). So far, so good.
cis coupling, and justifies the above conclusions. The proton
But there are four CH2 groups in the structure and appar-
NMR spectrum of ipsenol is difficult (though not impossible)
ently only one in the integration ratios — and even this one
to fully understand and assign for us at this point. It is
is misleading.
heartening to know that the interpretation becomes much
It will help at this point to realize that the molecule
easier with correlation methods that are explained in detail
consists of three spin systems with the insulation point at
in Chapter 5.
C-6 (see Section 3.5.2). The alkyl system consists of H-1,
H-2, H-3, H-4, H-5, and H-9; an alkene system consists of
H-7 and H-8; and another alkene system consists of H-10. H-8 trans
The alkyl system accounts for the multiplets at the right of
the spectrum, and the alkenes account for the multiplets at H-8 cis
the left side. It will also help to reiterate that the protons of
an alkyl CH2 group will be diastereotopic in the presence of
a stereogenic center. The protons of the alkene ⏤CH2 group
will also be nonequivalent.
It should now be apparent that the diastereotopic protons
of each alkyl CH2 group occur as a pair. One pair (H-3) is at
1.28 ppm and 1.42 ppm; the other pair (H-5) is at 2.21 ppm
and 2.48 ppm. The two-proton multiplet at 1.80 ppm will be 5.25 5.20 5.15 ppm
discussed later.
Furthermore, the H-5 protons are at higher frequency
because they are deshielded by both the OH group and the
C⏤CH2 group, whereas the H-3 protons are deshielded only 3.13 MAGNITUDE OF VICINAL AND
by the OH group. The H-5 protons couple geminally and GEMINAL COUPLING CONSTANTS
each proton couples once vicinally; thus there is a doublet of
doublets (first order) for each C-5 proton. The H-3 protons Coupling between protons on vicinal carbon atoms depends
couple geminally and vicinally to two protons; the result for primarily on the dihedral angle 𝜙 between the H⏤C⏤C′
the H-3 protons (at 300 MHz) is two complex multiplets. and the C⏤C′ ⏤H′ planes. This angle can be visual-
Also in favor of the first-order status for the H-5 protons is a ized by an end-on view (Newman projection) of the bond
larger Δv value (in Hz) between the two H-5 multiplets. between the vicinal carbon atoms and by the perspective in
The mysterious multiplet at 1.80 ppm may now be Figure 3.43 in which the relationship between dihedral angle
identified by default as the highly coupled H-2 proton and vicinal coupling constant is graphed.
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3.13 MAGNITUDE OF VICINAL AND GEMINAL COUPLING CONSTANTS 161

TABLE 3.6 Calculated and Observed Coupling Constants, J, in

Cyclohexanes Based on Dihedral Angle

Dihedral Calculated Observed

Angle J (Hz) J (Hz)

Axial–axial 180∘ 9 8 – 14 (usually 8 – 10)

Axial– 60∘ 1.8 1 – 7 (usually 2 – 3)
equatorial
Equatorial– 60∘ 1.8 1 – 7 (usually 2 – 3)
equatorial

to 7.0 Hz, cyclobutenes 3 J = 2.5 Hz to 4.0 Hz, and cyclo-

propenes 3 J = 0.5 Hz to 2.0 Hz.
Two-bond geminal CH2 coupling depends on the
FIGURE 3.43 The vicinal Karplus correlation. Relationship H⏤C⏤H bond angle 𝜃 as shown in Figure 3.44. This
between dihedral angle (𝜙) and coupling constant for vicinal relationship is quite susceptible to other influences and
protons. should be used with due caution. However, it is useful for
characterizing methylene groups in a fused cyclohexane ring
(approximately tetrahedral, 2 J ∼ 12 Hz to 18 Hz), methy-
lene groups of a cyclopropane ring (2 J ∼ 5 Hz), or a termi-
H nal methylene group, that is, ⏤CH2 , (2 J ∼ 0 Hz to 3 Hz).
𝜙
Electronegative substituents reduce the geminal coupling
H constant, whereas sp2 or sp hybridized carbon atoms increase
it.
Geminal coupling constants are usually negative in sign,
but this can be ignored except for calculations. Note that
geminal couplings are seen in routine spectra only when the
methylene protons are diastereotopic.
In view of the many factors other than angle dependence
that influence coupling constants, it is not surprising that
Karplus* emphasized that his calculations are approxi- there have been abuses of the Karplus correlation. Attempts
mations and do not take into account factors such as elec- to precisely determine angles directly from the magnitude of
tronegative substituents, the bond angles 𝜃 (<H⏤C⏤C′ and the 2 J value are risky.
the <C⏤C′ ⏤H′ ), and bond lengths. Deductions of dihedral
angles from measured coupling constants are safely made
only by comparison with closely related compounds. The
correlation has been very useful in cyclopentanes, cyclohex-
anes, carbohydrates, and polycyclic systems. In cyclopen-
tanes, the observed values of about 8 Hz for vicinal cis
protons and about 0 Hz for vicinal trans protons are in accord
with the corresponding angles of about 0∘ and about 90 ∘ ,
respectively. In substituted cyclohexane or pyranose rings,
the chair is the preferred conformation; the following rela-
tions in Table 3.6 hold and dihedral angles of substituents
follow from these 3 J proton couplings.
Note the near-zero coupling at the 90∘ dihedral angle.
This has been a source of frustration in attempts at fitting
proposed structures to the NMR spectra.
A modified Karplus correlation can be applied to vic-
inal coupling in alkenes. The prediction of a larger trans
coupling (𝜙 = 180 ∘ ) than cis coupling (𝜙 = 0 ∘ ) is borne
out. The cis coupling in unsaturated rings decreases with
decreasing ring size (increasing bond angle) as follows:
cyclohexenes 3 J = 8.8 to 10.5 Hz, cyclopentenes 3 J = 5.1
FIGURE 3.44 The geminal Karplus correlation.
JHH for CH2 groups as a function of the H⏤C⏤H
* Karplus, M. (1959) J. Chem. Phys., 30, 11. angle. Note the zero coupling at about 125∘ .
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162 CHAPTER 3 PROTON (1 H) MAGNETIC RESONANCE SPECTROSCOPY

3.14 LONG-RANGE COUPLING Here, we have a powerful tool for determining the
connectivity of protons through bonds and assigning proton
Proton–proton coupling beyond three bonds (3 J) is usu- peaks. Furthermore, overlapping peaks can be simplified by
ally less than 1 Hz, but appreciable long-range coupling removing one of the couplings.
may occur in such rigid structures as alkenes, alkynes, Figure 3.45 displays the effect of selective spin decou-
aromatics, and heteroaromatics, and in strained ring systems pling on the neighboring protons of 3-butyne-l-ol.
(small or bridged). Allylic (H⏤C⏤C⏤C⏤H) couplings In spectrum 3.45a from left to right, the H-1 multiplet is
are typically about 1.6 Hz. The coupling through five bonds a triplet (J = 6 Hz); the H-2 multiplet is a triplet of doublets
in the conjugated system of butadiene is 1.3 Hz. Coupling (J = 6 Hz and 3 Hz); and the H-4 multiplet is a triplet (J =
through conjugated polyalkyne chains may occur through 3 Hz). The OH singlet is at 2.03 ppm. Again from left to
as many as nine bonds. Meta coupling in a benzene ring is right, the integration ratios of the multiplets are 2:2:1:1 (not
1 Hz to 3 Hz, and para, 0 Hz to 1 Hz. In five-membered het- shown).
eroaromatic rings, coupling between the two and four protons In spectrum (b), the H-1 protons are irradiated, and the
is 0 Hz to 2 Hz. 4 JAB in the bicyclo[2.1.1]hexane system is H-2 triplet of doublets is collapsed to a doublet (J = 3 Hz).
about 7 Hz. This doublet results from long-range coupling with H-4. In
spectrum (c), the H-2 triplet of doublets is irradiated, and the
HA H H-1 triplet is collapsed to a singlet, and the H-4 is collapsed
to a singlet.
In spectrum (d), the H-4 triplet is irradiated, and the H-2
H
triplet of doublets is collapsed to a triplet (J = 6 Hz).
The overall information obtained from selective spin
HB
decoupling is “connectivity” – that is, progressing through
the protons of the carbon chain.
This unusually high long-range coupling constant is It is also possible to simplify two overlapping multi-
attributed to the “W” conformation of the four 𝜎 bonds plets by selectively irradiating a neighboring proton, thus
between HA and HB . disclosing multiplicity and coupling constants in the residual
multiplet.
HA C HB Other methods for establishing 1 H⏤1 H relationships
C C are described in Chapter 5 and have certain advantages,
Long-range W coupling although selective spin decoupling methods remain useful.

3.15 SELECTIVE SPIN DECOUPLING: 3.16 NUCLEAR OVERHAUSER EFFECT

DOUBLE RESONANCE
The nuclear Overhauser effect (NOE) results from a type
Intense irradiation of a proton (or equivalent protons) at of nuclear spin relaxation, involving pairs of spins, called
its resonance frequency in a spin-coupled system removes cross-relaxation. The technical details of how the NOE works
the proton’s coupling effect on the neighboring protons to are beyond the scope of our discussion, but we will see
which it has been coupled. Thus, successive irradiation of briefly here and in Chapter 4 various applications of the NOE
the protons of 1-propanol, for example, yields the following to solving structural problems with NMR. We focus here
results: on the 1 H⏤1 H NOE: this is a through-space effect which
decreases with the sixth power of the distance between the
Irradiate
spins. No intervening chemical bonds or J-coupling between
the protons are required; instead, the NOE relies on a dipolar
H3C CH 2 CH 2OH H3C CH 2 CH 2OH interaction between the spins. One of the useful applications
Triplet Sextet Triplet Triplet Quartet of the NOE is therefore to determine which protons are close
in space to which other protons (typically up to ∼4 Å). The
Irradiate NOE can be observed by irradiating a peak corresponding to
a particular proton in the sample with lower power radiation
than is used for decoupling. The NMR peak of a proton
H 3C CH 2 CH 2OH H3C CH 2 CH 2OH
that is close in space to the irradiated proton is increased
Singlet Singlet
in intensity; this is one manifestation of the NOE. (This is
Irradiate generally true for small molecules; for large molecules such
as proteins, the signal may decrease instead of increase.) The
usual observable enhancement is less than 20%. To increase
H 3C CH 2 CH 2OH H3C CH 2 CH 2OH sensitivity, we use the NOE difference experiment, in which a
Triplet Triplet conventional 1 H NMR spectrum is subtracted from a specific
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3.17 CONCLUSION 163

Irradiated
HO CH2 CH2 C CH
(d) 1 2 3 4

Irradiated

(c)

Irradiated
(b)

(a)

1 2 OH 4
3.7 3.6 3.5 3.4 3.3 3.2 3.1 3.0 2.9 2.8 2.7 2.6 2.5 2.4 2.3 2.2 2.1 2.0 ppm
1
FIGURE 3.45 (a) 300 MHz H NMR spectrum of 3-butyn-l-ol in CDCl3 . (b) Irradiated protons on C-1. (c) Irradiated protons on C-2.
(d) Irradiated protons on C-4. Irradiation may cause a small change in chemical shift of nearby peaks.

proton-irradiated spectrum. The result is a spectrum which 5-methyl group results in enhancement of the resonances for
only contains the peaks which have been enhanced due to the both H-4 and H-6, whereas irradiation of the 3-methyl group
NOE, that is, it will only show peaks due to protons which enhances only the peak for H-4. The 5-methyl group is close
are close in space to the protons which have been irradiated. to both H-4 and H-6 whereas the 3-methyl group is only close
Consider the example given in Figure 3.46 [see also to H-4.
Charlton et al. (1993)]. The compound is an analog of a sex
pheromone natural product of the brownbanded cockroach.
O 3.17 CONCLUSION
H3C
2
3 1O 1H NMR spectroscopy is the foundation upon which we will
4 6
5 build an understanding of the magnetic resonance of other
H H
nuclei, especially 13 C, which leads to the important advanced
CH3 correlation experiments. We began by describing the mag-
netic properties of nuclei, noting the special importance of
Note that in Figure 3.46, the regular 1 H NMR spectrum spin 12 nuclei. For practical reasons, the historical investiga-
is shown in (c). Figure 3.46b shows the NOE difference tions into the 1 H nucleus led to high-resolution NMR and the
spectrum obtained upon irradiating the peak corresponding manufacture of commercial instruments.
to the 3-methyl protons, and Figure 3.46c shows the NOE Interpretation of 1 H NMR spectra is based on consid-
difference spectrum obtained upon irradiating the peak eration of three types of information: integration of sig-
corresponding to the 5-methyl protons. Recall that peaks nal peaks, chemical shifts, and spin–spin coupling con-
which remain in the difference spectra indicate that the stants. Integration of the signal peaks provides the ratios
corresponding protons are close in space to the protons which between the numbers of hydrogen atoms in different equiv-
have been irradiated. Thus, we see that irradiation of the alent sets in the compound. The concept of chemical shift
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164 CHAPTER 3 PROTON (1 H) MAGNETIC RESONANCE SPECTROSCOPY

3-CH3 5-CH3
H-6 H-4
O
×4 H3C 3
2
1
(c) O
4 6
Irradiated
5

×128 CH3
(b)
Irradiated
×128
(a)
6.6 6.2 1.8 1.4 ppm
FIGURE 3.46 NOE difference spectroscopy for the compound shown. (a) Enhancement of both protons on irradiation of the 5-
methyl group. (b) Enhancement of the H-4 proton on irradiation of the 3-methyl group. (c) The full 1 H NMR spectrum. 300 MHz
in CDCl3 .

relates the frequency of the signal in the spectrum with neighboring nuclei, giving crucial structural insights. The
the chemical environment. Spin–spin coupling explains the remaining chapters all deal with NMR either entirely
interaction of magnetic nuclei within a spin system. Among (Chapters 4, 5, and 6) or in major part (Chapters 7 and 8).
other things, spin–spin coupling provides information about

REFERENCES

For a list of Chapter References, please visit: www.wiley.com/college/silverstein.

STUDENT EXERCISES

3.1 For each compound given below (a–o), describe all spin sys- 3.6 For each structure determined in exercise 3.4, describe all
tems (using Pople notation where appropriate) Label chem- spin systems (using Pople notation where appropriate). Label
ically equivalent protons, magnetically equivalent protons, chemically equivalent protons, magnetically equivalent pro-
enantiotopic protons, and diastereotopic protons. tons, enantiotopic protons, and diastereotopic protons.
3.2 For each compound above, predict the chemical shifts for each 3.7 Sketch spectra for the following spin systems (stick diagrams
proton set. Give the source (table or appendix) that you use for are sufficient): AX, A2 X, A3 X, A2 X2 , A3 X2 .
your prediction. 3.8 Sketch spectra for the following spin systems (stick dia-
3.3 Sketch the 1 H NMR spectrum for each of the com- grams are sufficient): AMX, A2 MX, A3 MX, A2 MX2 , A2 MX3 ,
pounds in question 3.1. Assume first-order multiplets where A3 MX3 . Assume that A does not couple to X and that
possible. JAM = JMX .
3.4 Determine the structural formula for the compounds whose 1 H 3.9 Sketch spectra for the following spin systems (stick dia-
NMR spectra are given (A – W). They were all run at 300 MHz grams are sufficient): AMX, A2 MX, A3 MX, A2 MX2 , A2 MX3 ,
in CDCl3 . The mass spectra were given in Chapter 1 (Question A3 MX3 . Assume that A does not couple to X, and that
1.6) and the IR spectra were given in Chapter 2 (Question 2.9). JAM = 10 Hz and JMX = 5 Hz.
3.5 After determining the structures in exercise 3.4, calculate Δ𝜈∕J 3.10 For the following three simulated spin systems (at 300 MHz;
for appropriately coupled multiplets where possible in the fol- see pages 172–174), draw a stick diagram for each first-order
lowing spectra: A, E, F, G, H, I, K, L, Q, and U. Use a ruler to multiplet in each spin system. After determining one multiplet
measure or estimate J-coupling constants. in each spin system, the other two multiplets will be useful
checks.
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Exercise 3.1 STUDENT EXERCISES 165

OH
Br
OAc
a b c

O
O
H
d e f

N O O O
H OH
g h i

O O

N
S
S
OH
j k l

H H OAc
Cl H
O H
F
m n o
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166 CHAPTER 3 PROTON (1 H) MAGNETIC RESONANCE SPECTROSCOPY Exercise 3.4 (A–D)

Problem 3.4 A

2.5 2.4 2.3 2.2 2.1 2.0 1.9 1.8 1.7 1.6 1.5 1.4 1.3 1.2 1.1 1.0 0.9 0.8 ppm

Problem 3.4 B OH

3.5 3.0 2.5 2.0 1.5 1.0 ppm

Problem 3.4 C

7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 ppm

Problem 3.4 D

4.0 3.5 3.0 2.5 2.0 1.5 1.0 ppm

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Exercise 3.4 (E–H) STUDENT EXERCISES 167

Problem 3.4 E

2.5 2.4 2.3 2.2 2.1 2.0 1.9 1.8 1.7 1.6 1.5 1.4 1.3 1.2 1.1 1.0 0.9 0.8 ppm

Problem 3.4 F
×4

12.0 11.5 ppm

3.5 3.0 2.5 2.0 1.5 ppm

Problem 3.4 G

2.7 2.6 2.5 2.4 2.3 2.2 2.1 2.0 1.9 1.8 1.7 1.6 1.5 1.4 1.3 1.2 1.1 1.0 0.9 0.8 ppm

Problem 33.4 H

4.4 4.2 4.0 3.8 3.6 3.4 3.2 3.0 2.8 2.6 2.4 2.2 2.0 ppm
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168 CHAPTER 3 PROTON (1 H) MAGNETIC RESONANCE SPECTROSCOPY Exercise 3.4 (I–L)

Problem 3.4 I

4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 ppm

Problem 3.4 J

2200 2150 2100 Hz 1250 1200 1150 Hz

7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 ppm
Problem 3.4 K

7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 ppm
Problem 3.4 L

3.5 3.0 2.5 2.0 1.5 1.0 ppm

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Exercise 3.4 (M–P) STUDENT EXERCISES 169

Problem 3.4 M

7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 ppm

Problem 3.4 N a pyrazine

2520 2510 2500 2490 Hz

8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 ppm
Problem 3.4 O
1 proton (×32)

13 12 ppm
2300 2250 2200 2150 Hz

7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 ppm

Problem 3.4 P

8.2 8.1 8.0 7.9 7.8 7.7 7.6 7.5 7.4 7.3 ppm
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170 CHAPTER 3 PROTON (1 H) MAGNETIC RESONANCE SPECTROSCOPY Exercise 3.4 (Q–T)

Problem 3.4 Q

1 proton (×32)

12 11 ppm

4.5 4.0 3.5 3.0 2.5 2.0 1.5 ppm

Problem 3.4 R

3.6 3.4 3.2 3.0 2.8 2.6 2.4 2.2 2.0 1.8 1.6 ppm

Problem 3.4 S Unsaturated ketone

1520 1510 1500 Hz

5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 ppm

Problem 3.4 T

13 12 ppm

2.8 2.6 2.4 2.2 2.0 1.8 1.6 1.4 1.2 1.0 ppm
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Exercise 3.4 (U–W) STUDENT EXERCISES 171

Problem 3.4 U

7.5 7.4 7.3 7.2 7.1 7.0 6.9 6.8 6.7 6.6 6.5 6.4 6.3 6.2 6.1 6.0 5.9 5.8 5.7 ppm

Problem 3.4 V

2120 2100 2080 2060 Hz

7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 ppm
Problem 3.4 W Unsaturated ketone

7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 ppm
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172 CHAPTER 3 PROTON (1 H) MAGNETIC RESONANCE SPECTROSCOPY Exercise 3.10A

(c)

385 380 375 370 365 360 355 350 345 340 335 Hz

(b)

1120 1115 1110 1105 1100 1095 1090 1085 1080 Hz

(a)

1605 1600 1595 1590 1585 1580 1575 1570 1565 Hz

a b c

5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 ppm
 Silverstein c02.tex V3 - 07/10/2014 3:50 P.M. Page 173

Exercise 3.10B STUDENT EXERCISES 173

(c)

385 380 375 370 365 360 355 350 345 340 335 Hz

(b)

1120 1115 1110 1105 1100 1095 1090 1085 1080 Hz

(a)

1605 1600 1595 1590 1585 1580 1575 1570 1565 Hz

a b c

5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 ppm
 Silverstein c02.tex V3 - 07/10/2014 3:50 P.M. Page 174

174 CHAPTER 3 PROTON (1 H) MAGNETIC RESONANCE SPECTROSCOPY Exercise 3.10C

(c)

385 380 375 370 365 360 355 350 345 340 335 Hz

(b)

1120 1115 1110 1105 1100 1095 1090 1085 1080 Hz

(a)

1605 1600 1595 1590 1585 1580 1575 1570 1565 Hz

a b c

5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 ppm
 Silverstein c02.tex V3 - 07/10/2014 3:50 P.M. Page 175

APPENDIX A 175

CHART A.1: CHEMICAL SHIFTS OF PROTONS ON A CARBON ATOM

ADJACENT (𝜶 POSITION) TO A FUNCTIONAL GROUP IN
APPENDIX A ALIPHATIC COMPOUNDS (M⏤Y)
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176 CHAPTER 3 PROTON (1 H) MAGNETIC RESONANCE SPECTROSCOPY

APPENDIX A (Continued)

O
*OTS is O S CH3
O
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APPENDIX A 177

CHART A.2: CHEMICAL SHIFTS OF PROTONS ON A CARBON ATOM

ONCE REMOVED (𝜷 POSITION) FROM A FUNCTIONAL GROUP IN
APPENDIX A ALIPHATIC COMPOUNDS (M⏤C⏤Y)
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178 CHAPTER 3 PROTON (1 H) MAGNETIC RESONANCE SPECTROSCOPY

EFFECT ON CHEMICAL SHIFTS OF TWO OR THREE DIRECTLY

APPENDIX B ATTACHED FUNCTIONAL GROUPS

Y CH 2 Z and Y CH Z Tables B.2a, B.2b, and B.2c: Chemical

W
Shift Correlations for Methine Protons
Table B.2a gives the substituent constants‡ to be used with
The chemical shift of a methylene group attached to two the formulation
functional groups can be calculated by means of the sub-
stituent constants (𝜎 values) in Table B.1. Shoolery’s rule* 𝛿CHXYZ = 2.50 + 𝜎x + 𝜎Y + 𝜎Z
states that the sum of the constants for the attached functional
which is satisfactory if at least two of the substituents are
groups is added to 0.23 ppm, the chemical shift for CH4 :
electron-withdrawing groups. In other words, only a single
𝛿(Y ⏤CH2 ⏤Z) = 0.23 + 𝜎Y + 𝜎Z substituent may be an alkyl group (R). Within these limits,
the standard error of estimate is 0.20 ppm. For example, the
The chemical shift for the methylene protons, of
chemical shift of the methine proton in
C6 H5 CH2 Br, for example, is calculated from the 𝜎 values
in Table B.1. OEt
0.23 CH3 CH OEt
𝜎Ph = 1.85
𝜎Br = 2.33
𝛿 = 4.41 Found, 4.43 ppm is calculated from Table B.2a as follows:

Shoolery’s original constants have been revised and 𝛿 = 2.50 + 1.14 + 1.14 + 0.00 = 4.78 ppm
extended in Table B.1. The observed and calculated chem- The found value is 4.72 ppm.
ical shifts for 62% of the samples tested were within Tables B.2b and B.2c are used jointly for methine
±0.2 ppm, 92% within ±0.3 ppm, 96% within 0.4 ppm, and protons that are substituted by at least two alkyl groups (or
99% within ±0.5 ppm.† Table B.1 contains substituent con-
stants (Friedrich and Runkle, 1984) for the more common
functional groups. Note that chemical shifts of methyl pro- TABLE B.2a Substituent Constants for Methine Protons
tons can be calculated by using the constant for H (0.34). For
example H⏤CH2 ⏤Br is equivalent to CH3 Br. Group (𝝈)

⏤F 1.59
TABLE B.1 Substituent Constants for Alkyl Methylene (and ⏤Cl 1.56
Methyl) Protons ⏤Br 1.53
⏤NO2 1.84
Substituent Substituent ⏤NH2 0.64
Constants Constants ⏤NH+3 1.34
Y or Z (𝝈) Y or Z (𝝈) ⏤NHCOR 1.80
⏤OH, ⏤OR 1.14
⏤H 0.34 ⏤OC(⏤O)R 3.01 ⏤OAr 1.79
⏤CH3 0.68 ⏤OC(⏤O)Ph 3.27 ⏤OCOR 2.07
⏤C⏤C 1.32 ⏤C(⏤O)R 1.50 ⏤Ar 0.99
⏤C⏤⏤C 1.44 ⏤C(⏤O)Ph 1.90 ⏤C⏤C 0.46
⏤Ph 1.83 ⏤C(⏤O)OR 1.46 ⏤C⏤⏤C 0.79
⏤CF2 1.12 ⏤C(⏤O)NR2 (H2 ) 1.47 ⏤C⏤⏤N 0.66
⏤CF3 1.14 ⏤C⏤
⏤N 1.59 ⏤COR, ⏤COOR, ⏤COOH 0.47
⏤F 3.30 ⏤NR2 (H2 ) 1.57 ⏤CONH2 0.60
⏤Cl 2.53 ⏤NHPh 2.04 ⏤COAr 1.22
⏤Br 2.33 ⏤NHC(⏤O)R 2.27 ⏤SH, ⏤SR 0.61
⏤I 2.19 ⏤N3 1.97 ⏤SO2 R 0.94
⏤OH 2.56 ⏤NO2 3.36 ⏤R 0
⏤OR 2.36 ⏤SR(H) 1.64
⏤OPh 2.94 ⏤OSO2 R 3.13

* Shoolery,J.N. (1959). Varian Technical Information Bulletin, Vol 2,

No. 3. Palo Alto, CA: Varian Associates. ‡ Bell,
H.M., Bowles, D.B. and Senese, F. (1981). Org. Magn. Reson.,
† Data from Friedrich, E.C. and Runkle, K.G. (1984). J. Chem. Educ. 61 (now changed to Magnetic Resonance in Chemistry) 16, 285. With
830; (1986) 63, 127. permission.
 Silverstein c02.tex V3 - 07/10/2014 3:50 P.M. Page 179

APPENDIX B 179

TABLE B.2b Observed Methine Proton Chemical Shifts of TABLE B.2c Correction Factors for Methine Substituents of Low
Isopropyl Derivatives Polarity

(𝐂𝐇3 )2 𝐂𝐇𝐙 (𝐂𝐇3 )2 𝐂𝐇𝐙 Cyclic

Open-Chain Methine
𝜹 (ppm) 𝜹 (ppm) Methine Proton Proton
Z obs Z obs Systems xy Systems xy

H 1.33 HO 3.94 Z
H3 C 1.56 RO 3.55 Z
R 1.50 C6 H5 O 4.51 CH 3 CH CH 3 0.00 1.0
H
XCH2 1.85 R(H)C(⏤O)O 4.94 Z Z
R(H)C(⏤O) 2.54 C6 H5 C(⏤O)O 5.22 H
C6 H5 C(⏤O) 3.58 F3 CC(⏤O)O 5.20 CH 3 CH R 0.20 0.40
R(H)OC(⏤O) 2.52 ArSO2 O 4.70 Z
R2 (H2 )NC(⏤O) 2.44 Z
C6 H5 2.89 R(H)S 3.16 R CH R 0.40 0.20
R2 (H2 )C⏤CR(H) 2.62 RSS 2.63 H
R(H)C⏤ ⏤C 2.59 Z
Z
N⏤⏤C 2.67 F 4.50
CH 3 CH CH 2X 0.20 monosub. 0.20
Cl 4.14
R2 (H2 )N 3.07 Br 4.21 H
axial H 0.45
R(H)C(⏤O)NH 4.01 I 4.24
Z
O2 N 4.67
CH 3 CH CH CH 2 0.40 equat. H 0.25
Z
Z

other groups of low polarity). Friedrich and Runkle proposed CH 3 CH C 6H5 1.15 0.00
the relationship H
Z Z
𝛿CHXYZ = 𝛿(CH3 )2 CHZ = Δxy
R CH C 6H5 0.90 H 0.00
in which the X and Y substituents are alkyl groups or other
groups of low polarity. The Z substituent covers a range of
polarities. Δxy is a correction factor. The relationship states
that the chemical shift of a methine proton with at least two
low-polarity groups is equivalent to the chemical shift of an C 6H 5
isopropyl methine proton plus a correction factor.
The substituent constants for a Z substituent on an From Table B.2b, 𝛿 = 2.89 for CH 3 CH CH 3.
isopropyl methine proton are given in Table B.2b. The Δxy From Table B.2c, Δxy = 0.00 for CH3 Δxy = 0.40 for
correction factors are given in Table B.2c. CH = CH2 .
The following examples illustrate the joint use of Tables C 6H 5
B.2b and B.2c, with CH3 , CH⏤CH2 , and C6 H5 as sub-
Therefore, 𝛿 CH 3 CH CH CH 2 = 2.89 + 0.00 + 0.40
stituents. The most polar substituent is always designated Z.
= 3.29 (Found: 𝛿 = 3.44).

Z Z C 6H 5
𝛿X CH Y 𝛿 CH3 CH CH CH 2 𝛿 CH 3 CH CH 3 xy
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180 CHAPTER 3 PROTON (1 H) MAGNETIC RESONANCE SPECTROSCOPY

APPENDIX C CHEMICAL SHIFTS IN ALICYCLIC AND HETEROCYCLIC RINGS

TABLE C.1 Chemicals Shifts in Alicyclic Rings

0.22 1.96 1.51 1.44 1.54 1.78

O O O
O
O O
2.22 2.38 2.30
2.06
1.96 3.03 –1.8 –1.94
1.65 2.02
–1.8 –1.52 –1.52

TABLE C.2 Chemical Shifts in Heterocyclic Rings

2.54 O 1.85 1.51

O 2.72 4.73 3.75 3.52
O O

H 2.38 1.50
1.62 N 1.59 1.50
N 2.23 3.54 2.75 2.74
H 0.03 N N
H 2.01 H 1.84

2.27 CH 3 1.90
S 1.93 2.23
S 3.17 3.43 2.82 3.00 3.70
S S S
O2 O2

O O O
R O 4.70
3.9–4.1 5.90 3.55
H O 1.68 O
O O
4.75–4.90 3.80

O 1.62
2.08 4.38 1.62 4.06
3.01 O
2.31 O 2.27 O
O
O O
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APPENDIX D 181

APPENDIX D CHEMICAL SHIFTS IN UNSATURATED AND AROMATIC SYSTEMS

(see Table D.1) are calculated

R cis H Ha C6 H5 gem 1.35 5.25

C C ORtrans −1.28 0.07
0.07 𝛿 5.32
R trans R gem 𝛿H = 5.25 + Zgem + Zcis + Ztrans
Hb ORgem 1.18 5.25
For example, the chemical shifts of the alkene protons C6 H5 trans −0.10 1.08
in 1.08 𝛿 6.33
C 6H 5 OC 2H 5
C C
Ha Hb

TABLE D.1 Substituent Constants (Z) for Chemical Shifts of Substituted Ethylenes

Z Z
Substituent R gem cis trans Substituent R gem cis trans

⏤H 0 0 0 H
⏤Alkyl 0.44 −0.26 −0.29 C O 1.03 0.97 1.21
⏤Alkyl-ringa 0.71 −0.33 −0.30
⏤CH2 O, ⏤CH2 I 0.67 −0.02 −0.07 N
⏤CH2 S 0.53 −0.15 −0.15 C O 1.37 0.93 0.35
⏤CH2 Cl, ⏤CH2 Br 0.72 0.12 0.07
⏤CH2 N 0.66 −0.05 −0.23 Cl 1.10 1.41 0.99
⏤C⏤
⏤C 0.50 0.35 0.10 C O
⏤C⏤
⏤N 0.23 0.78 0.58 ⏤OR, R:aliph 1.18 −1.06 −1.28
⏤C⏤C 0.98 −0.04 −0.21 ⏤OR, R:conjb 1.14 −0.65 −1.05
⏤C⏤C conjb 1.26 0.08 −0.01 ⏤OCOR 2.09 −0.40 −0.67
⏤C⏤O 1.10 1.13 0.81 ⏤Aromatic 1.35 0.37 −0.10
⏤C⏤O conjb 1.06 1.01 0.95 ⏤Cl 1.00 0.19 0.03
⏤COOH 1.00 1.35 0.74 ⏤Br 1.04 0.40 0.55
R
⏤COOH conjb 0.69 0.97 0.39 N R:aliph 0.69 −1.19 −1.31
R
R
⏤COOR 0.84 1.15 0.56 N R:conjb 2.30 −0.73 −0.81
R
⏤COOR conjb 0.68 1.02 0.33 ⏤SR 1.00 −0.24 −0.04
⏤SO2 1.58 1.15 0.95

C
a Alkyl ring indicates that the double bond is part of the ring R .
C
b TheZ factor for the conjugated substituent is used when either the substituent or the double bond is further conjugated with other groups.
Source: Pascual C., Meier, J., and Simon, W. (1966) Helv. Chim. Acta, 49, 164.
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182 CHAPTER 3 PROTON (1 H) MAGNETIC RESONANCE SPECTROSCOPY

TABLE D.2 Chemical Shifts of Miscellaneous Alkenes

R C( O)OCH3 R C( O)CH3 R OC( O)CH3

6.73 1.97 2.12 2.06 1.65

H R H3C R H3C R H3C R H3C R

H3C CH3 H CH3 H3C H H3C H H3 C H

1.73 1.95 5.98 1.93 1.84 5.62 1.86 5.97 1.65 6.67

OSi(CH3)3
CH2 3.92 H5C2 H 6.19 4.35 H H 5.97
2.00
H
H3C 5.65
1.06 CH2 OSiMe3
H 4.90 OSi(CH3)3 H5C2 OSi(CH3)3

R 6.01 7.16 O H 2.57 5.60

5.02 H H 4.55
R CH2 C C 7.05
1.90
H3C C C OC2H5 N
1.71 H H 0.92 5.95 2.28
5.70 H H 6.50 6.08 5.62

2.20 7.71
5.80 2.02 6.40 6.88
6.50
1.65 2.15 5.92 3.61
2.66 6.10
6.42 5.93
1.96 O CH3
2.90 6.79 2.13
5.59 7.36 O O

O O
2.53 4.82 1.90 2.66 3.34
5.78 6.15 7.63
6.05 4.65 4.63 4.83
4.43 6.22
6.72
4.20 3.97 6.16 6.83 O 4.92
6.75 O O O
6.37
O O
O
CH2Ph O
OH
O 5.90 5.90
6.94 7.53 7.72 5.60
2.40 5.89 7.28 6.42 5.05, 5.25
1.41 O
7.10 O 5.11
O O 7.50 O O
H 7.32
4.53 O piperitone linalool 𝛼-terpinene

TABLE D.3 Chemical Shifts of Alkyne Protons

HC⏤
⏤CR 1.73 – 1.88 HC⏤
⏤C⏤COH 2.23
HC⏤
⏤C⏤C⏤
⏤CR 1.95 HC⏤
⏤CH 1.80
HC⏤
⏤C⏤Ph 2.71 – 3.37 HC⏤
⏤C⏤CH⏤CR2 2.60 – 3.10

TABLE D.4 Chemical Shifts of Protons on Fused Aromatic Rings

7.81 7.60 8.00 7.61 8.64

7.89 7.65 7.88 7.64
7.67
7.46
8.69 7.81
7.74 9.13 8.79
8.31 7.91
8.73
7.39 7.75
8.02
7.65 8.01
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APPENDIX D 183

CHEMICAL SHIFTS OF PROTONS ON MONOSUBSTITUTED

CHART D.1 BENZENE RINGS

a
The benzene ring proton is at 𝛿 7.27, from which the shift increments are calculated as shown at the end of Section 3.4.
b
OTS p-toluenesulfonyloxy group.
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184 CHAPTER 3 PROTON (1 H) MAGNETIC RESONANCE SPECTROSCOPY

TABLE D.5 Chemical Shifts of Protons on Heteroaromatic Rings

H O O O O H O O O O
9.70 3.88 9.92 3.92
6.30 7.10
3.90 O 3.88 O
7.32 7.55 6.63 7.68 7.66 7.43
7.40 O O 7.30
S S
O 7.83
S 7.98
7.24 7.15
6.67 7.78 6.45 7.10 O 7.22 7.78 6.91 7.40 S
O O 7.05
H O O 2.55 6.52 –8.0
6.22 7.62 7.54 8.77
9.45 3.86 NH 8.59 N
7.15 9.24
6.68 7.32 6.57 7.44 3.92 N
6.77
N NH N 8.59 N
–11.0 7.64 7.27 7.37 9.26 N
H –8.0 NH N N N
6.67 7.78 6.76 6.10 6.92
–10.0 7.12 7.18

TABLE D.6 Chemical Shifts of HC⏤O, HC⏤N, and HC(O)3 Protons

RCH⏤O 9.70 HC(⏤O)OR 8.05 RCH⏤NOH cis 7.25

PhCH⏤O 9.98 HC(⏤O)NR2 8.05 RCH⏤NOH trans 6.65
NO2

RCH⏤CHCH⏤O 9.78 HC(OR)3 5.00 R N 6.05

N
H
H NO2

PROTONS SUBJECT TO HYDROGEN-BONDING EFFECTS (PROTONS

APPENDIX E ON HETEROATOMS)𝐚

17 16 15 14 13 12 11 10 9 8 7 6 5 4 3 2 1 0

Proton Class

OH Carboxylic acids
Sulfonic acids
Phenols
Phenols (intramolecular H bond)
in DMSO
Alcohols
Enols (cyclic -diketones)
Enols ( -diketones)
Enols ( -ketoesters) in DMSO in acetone

Water b
Oximes
NH2 and NHR Alkyl and cyclic amines
Aryl amines
Amides
Urethanes
Amines in trifluoroacetic acid
SH Aliphatic mercaptans
Thiophenols

17 16 15 14 13 12 11 10 9 8 7 6 5 4 3 2 1 0

a
Solvent CDCl3. Chemical shifts within a range are a function of concentration.
b
See Section 3.6.1.2.
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APPENDIX F 185

APPENDIX F PROTON SPIN-SPIN COUPLING CONSTANTS

Type Jab (Hz) Jab Typical Type Jab (Hz) Jab Typical

Ha Ha Hb
C 0 – 30 12 – 15 C C 6 – 12 10
Hb
CHa CHb
CHa CHb (free rotation) 6–8 7 C C 0–3 1–2

CHa
CHa C CH b 0–1 0
C C 4 – 10 7
Ha Hb

CHb
C C 0–3 1.5
Hb Ha

ax–ax 6 – 14 8 – 10 Ha CH b 0–3 2
C C
ax–eq 0–5 2–3
eq–eq 0–5 2–3 C CHa CHb C 9 – 13 10
3 member 0.5 – 2.0
Ha Ha Hb
4 member 2.5 – 4.0
cis 5 – 10 C C 5 member 5.1 – 7.0
trans 5 – 10 (ring)
Hb 6 member 8.8 – 11.0
(cis or trans) 7 member 9 – 13
8 member 10 – 13
Ha CHa C CHb 2–3
cis 4 – 12 CHa C C CHb
trans 2 – 10 2–3
Hb
(cis or trans) Ha
Hb 6
Ha O
cis 7 – 13
trans 4 – 9 Ha Hb 4
Hb O
(cis or trans)
Hb
2.5
Ha O
CHa OHb (no exchange) 4 – 10 5
Ha J (ortho) 6 – 10 9
O J (meta) 1–3 3
CHa CHb 1–3 2–3 J ( para) 0–1 ~0
Hb
O

C CHa CHb 5–8 6 J (2 – 3) 5–6 5

J (3 – 4) 7–9 8
4
J (2 – 4) 1–2 1.5
Ha 5 3
J (3 – 5) 1–2 1.5
C C 12 – 18 17 6 2 J (2 – 5) 0–1 1
Hb N J (2 – 6) 0–1 ~0

Ha J (2 – 3) 1.3 – 2.0 1.8

4 3
J (3 – 4) 3.1 – 3.8 3.6
C C 0–3 0–2 5 2 J (2 – 4) 0–1 ~0
Hb O J (2 – 5) 1–2 1.5
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186 CHAPTER 3 PROTON (1 H) MAGNETIC RESONANCE SPECTROSCOPY

APPENDIX F (Continued)

Type Jab (Hz) Jab Typical Type Jab (Hz) Jab Typical

J (2 – 3) 4.9 – 6.2 5.4

4 3
J (3 – 4) 3.4 – 5.0 4.0
5 2 J (2 – 4) 1.2 – 1.7 1.5 Proton – Fluorine
S J (2 – 5) 3.2 – 3.7 3.4
Ha 44 – 81
4 3 J (1 – 3) 2–3
C
5 2
J (2 – 3) 2–3
N J (3 – 4) 3–4 Fb
J (2 – 4) 1–2
H J (2 – 5) 1.5 – 2.5 CH a CF b
4
J (4 – 5) 4–6 3 – 25
5 N J (2 – 5) 1–2 0–4
6 2 J (2 – 4) 0–1 CH a C CFb
N J (4 – 6) 2–3
4 N J (4 – 5) 3–4 C C
5 2 J (2 – 4) 0 Ha Fb
S 1–8
J (2 – 5) 1–2
Ha
C C
Fb 12 – 40

o 6 – 10
Ha m 5–6
p2
O
4.3
H 3C C CH 2 F 48

Proton – Phosphorus
O
630 – 707
PH
(CH 3) 3 P 2.7
(CH 3) 3 P 0 13.4
(CH 3 CH 2) 3P 0.5 (HCCP) 13.7 (HCP)
(CH 3 CH 2) 3 P 0 11.9 (HCCP) 16.3 (HCP)
O
CH3P (OR)2 10 – 13
O
CH3C P (OR) 2 15 – 20

CH3OP (OR) 2 10.5 – 12

P[N(CH 3) 2]3 8.8
O P[N(CH 3) 2]3 9.5

Source: Compiled by Varian Associates. Absolute values. Reproduced with permission.

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APPENDIX G 187

CHEMICAL SHIFTS AND MULTIPLICITIES OF RESIDUAL PROTONS

IN COMMERCIALLY AVAILABLE DEUTERATED SOLVENTS (MERCK
APPENDIX G & CO., INC.)

Compound𝐚 Molecular Weight 𝜹H (multiplet) Compound𝐚 Molecular Weight 𝜹H (multiplet)

Acetic acid-d4 b 11.53 (1) Nitromethane-d3 4.33 (5)

64.078 2.03 (5) 64.059
Acetone-d6 2.04 (5) Isopropyl alcohol-d8 5.12 (1)
64.117 68.146 3.89 (br)
Acetonitrile-d3 1.93 (5) 1.10 (br)
44.071 8.71 (br)
Benzene-d6 7.15 (br) Pyridine-d5 7.55 (br)
84.152 84.133 7.19 (br)
Chloroform-d 7.26 (1) Tetrahydrofuran-d8 3.58 (br)
120.384 80.157 1.73 (br)
Cyclohexane-d12 1.38 (br) Toluene-d8 7.09 (m)
96.236 100.191 7.00 (br)
Deuterium oxide 4.63 (ref. DSS)c 6.98 (m)
20.028 4.67 (ref. TSP)c 2.09 (5)
1,2-Dichloroethane-d4 3.72 (br) Trifluoroacetic acid-d 11.50 (1)
102.985 115.030
Diethyl-d10 ether 3.34 (m) 2,2,2-Trifluoroethyl alcohol-d3 5.02 (1)
84.185 1.07 (m) 103.059 3.88 (4 × 3)
Diglyme-d14 3.49 (br)
148.263 3.40 (br)
3.22 (5)
N, N-Dimethylformamide-d7 8.01 (br)
80.138 2.91 (5)
2.74 (5)
Dimethyl-d6 sulphoxide 2.49 (5)
84.170
p-Dioxane-d8 3.53 (m)
96.156
Ethyl alcohol-d6 (anh) 5.19 (1)
52.106 3.55 (br)
1.11 (m)
Glyme-d10 3.40 (m)
100.184 3.22 (5)
Hexafluroacetone deuterate 5.26 (1)
198.067
HMPT-d18 2.53 (2 × 5)
197.314
Methyl alcohol-d4 4.78 (1)
36.067 3.30 (5)
Methylene chloride-d2 5.32 (3)
86.945
Nitrobenzene-d5 8.11 (br)
128.143 7.67 (br)
7.50 (br)
a Purity(Atom % D) up to 99.96% (“100%”) for several solvents.
b Theresidual proton consists of one proton of each kind in an otherwise completely deuterated molecule. For example, deuterated acetic acid has two different kinds of residual
protons: CD2 H − COOD and CD3 − COOH. The CD2 H proton, coupled to two D nuclei is at 2.03 ppm with a multiplicity of 5 (i.e., 2nI + 1 = 2 × 2 × 1 + 1 = 5). The carboxylic
proton is a singlet at 11.53 ppm.
c DSS is 3-(trimethylsilyl)-1-propane sulfonic acid, sodium salt. TSP is sodium-3-trimethylpropionate-2,2,3,3-d . Both are reference standards used in aqueous solutions.
4
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188 CHAPTER 3 PROTON (1 H) MAGNETIC RESONANCE SPECTROSCOPY

CHEMICAL SHIFTS OF COMMON LABORATORY SOLVENTS AS

APPENDIX H TRACE IMPURITIES

Proton Mult 𝐂𝐃𝐂𝐥3 (𝐂𝐃3 )2 𝐂𝐎 (𝐂𝐃3 )2 𝐒𝐎 𝐂6 𝐃6 𝐂𝐃3 𝐂𝐍 𝐂𝐃3 𝐎𝐃 𝐃2 𝐎

Solvent residual peak 7.26 2.05 2.50 7.16 1.94 3.31 4.79
H2 O s 1.56 2.84a 3.33a 0.40 2.13 4.87
Acetic acid CH3 s 2.10 1.96 1.91 1.55 1.96 1.99 2.08
Acetone CH3 s 2.17 2.09 2.09 1.55 2.08 2.15 2.22
Acetonitrile CH3 s 2.10 2.05 2.07 1.55 1.96 2.03 2.06
Benzene CH s 7.36 7.36 7.37 7.15 7.37 7.33
Tert-Butyl alcohol CH3 s 1.28 1.18 1.11 1.05 1.16 1.40 1.24
OHc s 4.19 1.55 2.18
tert-Butyl methyl ether CCH3 s 1.19 1.13 1.11 1.07 1.14 1.15 1.21
OCH3 s 3.22 3.13 3.08 3.04 3.13 3.20 3.22
BHTb ArH s 6.98 6.96 6.87 7.05 6.97 6.92
OHc s 5.01 6.65 4.79 5.20
ArCH3 s 2.27 2.22 2.18 2.24 2.22 2.21
ArC(CH3 )3 s 1.43 1.41 1.36 1.38 1.39 1.40
Chloroform CH s 7.26 8.02 8.32 6.15 7.58 7.90
Cyclohexane CH2 s 1.43 1.43 1.40 1.40 1.44 1.45
1,2-Dichloroethane CH2 s 3.73 3.87 3.90 2.90 3.81 3.78
Dichloromethane CH2 s 5.30 5.63 5.76 4.27 5.44 5.49
Diethyl ether CH3 t, 7 1.21 1.11 1.09 1.11 1.12 1.18 1.17
CH2 q, 7 3.48 3.41 3.38 3.26 3.42 3.49 3.56
Diglyme CH2 m 3.65 3.56 3.51 3.46 3.53 3.61 3.67
CH2 m 3.57 3.47 3.38 3.34 3.45 3.58 3.61
OCH3 s 3.39 3.28 3.24 3.11 3.29 3.35 3.37
1,2-Dimethoxyethane CH3 s 3.40 3.28 3.24 3.12 3.28 3.35 3.37
CH2 s 3.55 3.46 3.43 3.33 3.45 3.52 3.60
Dimethylacetamide CH3 CO s 2.09 1.97 1.96 1.60 1.97 2.07 2.08
NCH3 s 3.02 3.00 2.94 2.57 2.96 3.31 3.06
NCH3 s 2.94 2.83 2.78 2.05 2.83 2.92 2.90
Dimethylformamide CH s 8.02 7.96 7.95 7.63 7.92 7.97 7.92
CH3 s 2.96 2.94 2.89 2.36 2.89 2.99 3.01
CH3 s 2.88 2.78 2.73 1.86 2.77 2.86 2.85
Dimethyl sulfoxide CH3 s 2.62 2.52 2.54 1.68 2.50 2.65 2.71
Dioxane CH2 s 3.71 3.59 3.57 3.35 3.60 3.66 3.75
Ethanol CH3 t, 7 1.25 1.12 1.06 0.96 1.12 1.19 1.17
CH2 q, 7d 3.72 3.57 3.44 3.34 3.54 3.60 3.65
OH sc,d 1.32 3.39 4.63 2.47
Ethyl acetate CH3 CO s 2.05 1.97 1.99 1.65 1.97 2.01 2.07
CH2 CH3 q, 7 4.12 4.05 4.03 3.89 4.06 4.09 4.14
CH2 CH3 t, 7 1.26 1.20 1.17 0.92 1.20 1.24 1.24
Ethyl methyl ketone CH3 CO s 2.14 2.07 2.07 1.58 2.06 2.12 2.19
CH2 CH3 q, 7 2.46 2.45 2.43 1.81 2.43 2.50 3.18
CH2 CH3 t, 7 1.06 0.96 0.91 0.85 0.96 1.01 1.26
Ethylene glycol CH se 3.76 3.28 3.34 3.41 3.51 3.59 3.65
“Grease”f CH3 m 0.86 0.87 0.92 0.86 0.88
CH2 br s 1.26 1.29 1.36 1.27 1.29
n-Hexane CH3 t 0.88 0.88 0.86 0.89 0.89 0.90
CH2 m 1.26 1.28 1.25 1.24 1.28 1.29
HMPAg CH3 d, 9.5 2.85 2.59 2.53 2.40 2.57 2.64 2.61
Methanol CH3 sh 3.49 3.31 3.16 3.07 3.28 3.34 3.34
OH sg,h 1.09 3.12 4.01 2.16
Nitromethane CH3 s 4.33 4.43 4.42 2.94 4.31 4.34 4.40
n-Pentane CH3 t, 7 0.88 0.88 0.86 0.87 0.89 0.90
CH2 m 1.27 1.27 1.27 1.23 1.29 1.29
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APPENDIX H 189

APPENDIX H (Continued)

Proton Mult 𝐂𝐃𝐂𝐥3 (𝐂𝐃3 )2 𝐂𝐎 (𝐂𝐃3 )2 𝐒𝐎 𝐂6 𝐃6 𝐂𝐃3 𝐂𝐍 𝐂𝐃3 𝐎𝐃 𝐃2 𝐎

2-Propanol CH3 d, 6 1.22 1.10 1.04 0.95 1.09 1.50 1.17

CH sep, 6 4.04 3.90 3.78 3.67 3.87 3.92 4.02
Pyridine CH(2) m 8.62 8.58 8.58 8.53 8.57 8.53 8.52
CH(3) m 7.29 7.35 7.39 6.66 7.33 7.44 7.45
CH(4) m 7.68 7.76 7.79 6.98 7.73 7.85 7.87
Silicone greasei CH3 s 0.07 0.13 0.29 0.08 0.10
Tetrahydrofuran CH2 m 1.85 1.79 1.76 1.40 1.80 1.87 1.88
CH2 O m 3.76 3.63 3.60 3.57 3.64 3.71 3.74
Toluene CH3 s 2.36 2.32 2.30 2.11 2.33 2.32
CH (o∕p) m 7.17 7.1 – 7.2 7.18 7.02 7.1 – 7.3 7.16
CH (m) m 7.25 7.1 – 7.2 7.25 7.13 7.1 – 7.3 7.16
Triethylamine CH3 t, 7 1.03 0.96 0.93 0.96 0.96 1.05 0.99
CH2 q, 7 2.53 2.45 2.43 2.40 2.45 2.58 2.57
a In these solvents the intermolecular rate of exchange is slow enough that a peak due to HDO is usually also observed; it appears at 2.81 and 3.30 ppm in acetone and DMSO,

respectively. In the former solvent, it is often seen as a 1:1:1 triplet, with 2 JH,D = 1 Hz.
b 2,6-Dimethyl-4-tert-butylphenol.
c The signals from exchangeable protons were not always identified.
d In some cases (see note a), the coupling interaction between the CH and the OH protons may be observed (J = 5 Hz).
2
e In CD CN, the OH proton was seen as a multiplet at 2.69 ppm, and extra coupling was also apparent on the methylene peak.
3
f Long-chain, linear aliphatic hydrocarbons. Their solubility in DMSO was too low to give visible peaks.
g Hexamethylphosphoramide.
h In some cases (see notes a, d), the coupling interaction between the CH and the OH protons may be observed (J = 5.5 Hz).
3
i Poly(dimethylsiloxane). Its solubility in DMSO was too low to give visible peaks.
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190 CHAPTER 3 PROTON (1 H) MAGNETIC RESONANCE SPECTROSCOPY

APPENDIX I PROTON NMR CHEMICAL SHIFTS OF AMINO ACIDS IN D2 O

O NH 2 O O O
O 1.67 3.74 H 2N 3.97 O 3.85
1.46 3.76 H 2N N 3.22 1.87 O 2.91 O 2.70 O
H
NH 3 NH 3 O NH 3 O NH 3
Alanine (Ala) (A) Arginine (Arg) (R) Asparagine (Asn) (N) Aspartic Acid (Asp) (D)

O O O O O O
O 2.33 3.72 2.43 3.73 H 3N 3.52
H 3N 3.95 O 2.06 O H 2N 2.10 O O
SH NH 3 NH 3
3.05
Cysteine (Cys) (C) Glutamic Acid (Glu) (E) Glutamine (Gln) (Q) Glycine (Gly) (G)

O 0.92 O
3.18 O 1.70 H 3N H 3N O
3.98 0.96 3.70 1.46
N O 1.24, 1.45 3.64 O
1.70 3.02 3.73
7.84 1.95 O
NH 3 O
7.08 0.96 1.70 1.87
HN NH 3 0.99
NH 3

Histidine (His) (H) Isoleucine (Ilue) (I) Leucine (Leu) (L) Lysine (Lys) (K)

O 3.11, 3.27 O
2.12 H2 O
S 3.83
N O O
O 3.34
2.12 2.64 3.98 H 3N 3.93
NH 3 2.01 4.11
O 7.40 H 3N O OH
3.85
2.07, 2.32
Methionine (Met) (M) Proline (Pro) (P) Phenylalanine (Phe) (F) Serine (Ser) (S)

7.20 7.54 O 0.97

3.38 H 3N O
NH 3 4.24 1.02
7.28 O 2.25
4.28
HO O HO O 3.59 NH 3
4.22 3.51
7.68
NH 3
7.32 2.97, 3.13 O
O N 6.88 7.20
1.31 H O
Threonine (Thr) (T) Tryptophan (Trp) (W) Tyrosine (Tyr) (Y) Valine (Val) (V)
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CHAPTER 4
CARBON-13 NMR SPECTROSCOPY∗

4.1 INTRODUCTION At first glance, some of the above summary would

seem to discourage the use of 13 C spectra. However, the
Faced with a choice during the early development of nuclear ingenious remedies for these difficulties have made 13 C
magnetic resonance spectroscopy, most organic chemists NMR spectroscopy a powerful tool, as this chapter will
would certainly have selected the carbon nucleus over the confirm. In fact, side-by-side interpretation of 13 C and 1 H
hydrogen nucleus for immediate investigation. After all, the spectra provides complementary information.
carbon skeletons of rings and chains are central to organic
chemistry. The problem, of course, is that the carbon skeleton
consists almost completely of the 12 C nucleus, which is not
4.2.1 1 H Decoupling Techniques
accessible to NMR spectroscopy. The spectroscopist is left
to cope with the very small amount of the 13 C nucleus. In 1 H NMR spectra, the main peaks do not show the effects of
There are enough differences between 13 C and 1 H NMR J coupling with carbon because 98.9% of the carbon atoms
to justify separate chapters on pedagogical grounds. With an are the 12 C isotope (I = 0). Protons that are coupled to the
understanding of the basic concepts of NMR in Chapter 3, 1.1% of carbon atoms, which are 13 C isotopes, do show J
mastery of 13 C spectroscopy will be rapid. coupling multiplets in the 1 H NMR spectra, but these weak
The 12 C nucleus is not magnetically active (spin number, “satellites” of the main peaks only account for 1.1% of the
I, is zero), but the 13 C nucleus, like the 1 H nucleus, has a spin total spectral intensity. Conversely, because the 1 H isotope
number of 12 . However, since the natural abundance of 13 C is is nearly 100% abundant, 13 C NMR peaks clearly show the
only 1.1% and its magnetogyric ratio is only about a quarter effects of J coupling with 1 H. Because of the large 1 JCH
that of 1 H, the overall sensitivity of 13 C compared with 1 H values for 13 C⏤1 H (∼110−320 Hz) and appreciable 2 JCH ,
1 3J 13 C⏤C⏤1 H and 13 C⏤C⏤C⏤1 H
is about 5870 . Because of the low natural abundance of 13 C, CH values for
the occurrence of adjacent 13 C atoms has a low probability; (∼0−60 Hz) couplings, proton-coupled 13 C spectra usually
thus, we are free of the complication of 13 C⏤13 C coupling. show complex overlapping multiplets that are difficult to
interpret (Figure 4.1a); the proton-coupled 13 C NMR spec-
trum of cholesterol is hopelessly overlapped and difficult to
4.2 THEORY decipher.
To alleviate this problem, an important development
The theoretical background for NMR has already been was the simultaneous use of proton broadband decou-
presented in Chapter 3. Some of the principal aspects of 13 C pling—irradiation and saturation of the attached protons—
NMR to consider that differ from 1 H NMR are as follows: and detection of 13 C signals. Irradiation of the protons over
a broad frequency range with composite pulse decoupling†
• In the commonly used proton-decoupled 13 C spectrum (CPD) removes these couplings. In Figure 4.1b, the proton-
(see Section 4.2.1), the peaks are singlets unless the decoupled 13 C spectrum of cholesterol shows 27 single
molecule contains other magnetically active nuclei such peaks, each representing one of the carbon atoms. Before
as 2 H, 31 P, or 19 F. we get too far ahead of ourselves, we defer our discus-
• The 13 C peaks are distributed over a larger chemical shift sions of actual interpretation of 13 C spectra until Sections 4.3
range in comparison with the proton range. and 4.7.
• 13 C peak intensities do not correlate with the number The standard pulse program for acquiring a proton-
of carbon atoms associated with a given peak in routine decoupled 13 C NMR spectrum is shown in Figure 4.2a.
spectra, due to variable T1 values and the NOE. The sequence consists of a relaxation delay (Rd ) (see
Section 4.2.3), rf pulse of tip angle 𝜃, and signal acquisi-
• The 13 C nuclei are much less abundant and much less
tion (t). The proton channel has the decoupler on to remove
sensitive than protons. More concentrated samples and
the 1 H⏤13 C coupling, while a short, powerful rf pulse (of
longer times are needed.
the order of a few microseconds) excites all the 13 C nuclei
• For a given deuterated solvent, the 13 C and 1 H solvent simultaneously. Since the transmitter frequency is slightly off
peaks differ in multiplicities.
† Composite pulse decoupling relies on a continuous sequence of individual
∗ Familiarity with Chapter 3 is assumed. rf pulses. See Claridge (1999) in references for details.

191
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192 CHAPTER 4 CARBON-13 NMR SPECTROSCOPY

HO
(a)

CH CH3

(b)

140 130 120 110 100 90 80 70 60 50 40 30 20 10 ppm

FIGURE 4.1 (a) Proton-coupled 13 C NMR spectrum of cholesterol. (b) Proton-decoupled 13 C NMR spectrum of cholesterol. Both
were acquired using CDCl3 as the solvent at a 13 C Larmor frequency of 150.9 MHz.

resonance for all the 13 C frequencies, each 13 C nucleus shows 4.2.2 Chemical Shift Scale and Range
a FID, which is an exponentially decaying sine wave. The
frequencies of the sine waves lead directly to the various fre- As with 1 H NMR, the 13 C NMR frequency axis is converted
quencies of the peaks in the NMR spectrum. to a unitless scale; this is the familiar chemical shift (δ) scale.
Figure 4.2b is a presentation of the FID of the proton- The chemical shifts in routine 13 C NMR spectra range over
decoupled 13 C NMR spectrum of cholesterol. Figure 4.2c about 220 ppm from TMS—about 20 times that of routine 1 H
is an expanded, small section of the beginning of the FID NMR spectra (∼10 ppm). As a result of the large range and
from Figure 4.2b. The complex FID is the result of a number the sharpness of the decoupled peaks, coincidences of 13 C
of overlapping sine waves and interfering (beat) patterns. A chemical shifts are uncommon, and impurities are readily
series of repetitive pulses, signal acquisitions, and relaxation detected. Often, even mixtures provide useful information.
delays builds the signal through a process known as signal (See Appendix B for an extensive list of common impurities.)
averaging. Fourier transform by the computer converts the For example, diastereomers that are difficult to analyze by
accumulated FID (a time domain signal) to the decoupled, means of 1 H spectroscopy usually show distinct 13 C NMR
frequency-domain spectrum of cholesterol (at 150.9 MHz in spectra.
CDCl3 ). See Figure 4.1b. The fundamental NMR equation [𝜈 = (𝛾∕2𝜋)B0 ] is used
The result, in the absence of other nuclei such as 2 H, 31 P, to calculate the resonance frequency for the 13 C nucleus at
19
or F, is a sharp peak for each chemically nonequivalent car- a given magnetic field strength. For example, a 600 MHz
bon in the compound, except for the infrequent coincidence instrument (for 1 H) is used at 150.9 MHz to produce a 13 C
of 13 C chemical shifts. See Figure 4.1b for the 1 H-decoupled spectrum—that is, the ratio is about 4:1. The ratio of fre-
13 C spectrum of cholesterol and compare its simplicity with quencies is directly related to the ratio of 𝛾’s, the magneto-
the 1 H-coupled spectrum in Figure 4.1a. Note that, when 13 C gyric ratios, which are (in units of 107 rad T−1 s−1 ) 26.753
is decoupled from 1 H, useful information on the multiplicity and 6.728 for 1 H and 13 C, respectively (see Appendix A
of the carbon resonances is lost (n + 1 rule). For example, in Chapter 6). As a quirk of history, an instrument is often
in Figure 4.1a, a methyl group is a quartet (3 + 1) and a referred to by its proton resonance frequency regardless of
methine group is a doublet (1 + 1). A more complete dis- the nucleus under investigation.
cussion of multiplets can be found in Sections 4.2.5 and 4.3. Figure 4.3 gives credence to the statement that 13 C
There are techniques, however, such as the DEPT sequence chemical shifts somewhat parallel to those of 1 H, but we
(Section 4.6) that supplies this information in a much note some divergences that are not readily explainable and
simpler way. require development of another set of interpretive skills
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4.2 THEORY 193

(see Section 4.7). In general, in comparison with 1 H NMR The overall pulse sequence in Figure 4.4a consists
spectra, it is less advisable to attempt to correlate 13 C shifts of the following: Relaxation—180∘ pulse—variable time
with substituent electronegativity. interval—90∘ pulse—acquire while decoupling.
In Figure 4.4b, the net magnetization M0 is represented
4.2.3 T1 Relaxation by the upright, boldface vector. The first pulse inverts the
vector clockwise 180∘ to the −z axis. After a short time
Unlike 1 H NMR spectra, the integration of which provides (Δ𝜏), during which the arrow shows a slight recovery toward
information on the relative numbers of protons in different its original, upright position, a 90∘ pulse rotates the vector
chemical environments, integrations of 13 C peaks do not cor- clockwise and places it along the −y axis, which is toward
relate with the relative number of each type of carbon atom the left at 270∘ . At this point, the receiver along the y axis
in routine spectra. There are two major factors that account reads the signal as slightly diminished and negative—that is,
for the problem of peak intensities in 13 C NMR spectra: pointed down in the spectrum. The receiver accepts the usual
• The spin-lattice relaxation process, quantified by a time 90∘ signal along the +y axis as positive, hence pointing up
constant, T1 (also termed longitudinal relaxation), varies in the phased spectrum.
widely for carbon atoms in different functional groups and In Figure 4.4c, Δ𝜏 has been increased so that the
chemical environments. inverted vector was allowed to proceed further toward
• The strongest NOEs are observed for carbons with directly recovery—in fact past the null point; it is again slightly
bonded protons (Section 4.2.4). diminished and pointing up. The 90∘ pulse rotates it clock-
wise and it is recorded as a positive signal.
As discussed in Section 3.2.3, T1 and T2 relaxation times In Figure 4.4d, the inversion-recovery sequence is
are short for protons resulting in intensities that are propor- repeated eight times on diethyl phthalate (see Section 4.4 for
tional to the number of protons involved and sharp peaks. In a complete assignment of diethyl phthalate) with increas-
proton-decoupled 13 C NMR spectra, large T1 values for qua- ingly longer Δ𝜏 time increments. It is apparent that most
ternary carbons, caused by an absence of dipole-dipole inter- signals have different null points indicating that they have
action with directly attached protons, may result in detection different T1 values. As implied above, the C⏤O signal
of only a part of the possible signal, which can be overcome at ∼167 ppm has the slowest recovery in the inversion-
by inserting a longer delay interval Rd between the individ- recovery experiment. Its signal inverts between the seventh
ual pulses (see Figure 4.2a). The relaxation delay needs to be and eighth spectra, whereas the methyl signal at ∼13 ppm
carefully considered when acquiring 13 C data because sig- inverts between the fourth and fifth spectra. T1 values can
nals can be missed completely if this delay is too short. For be calculated with the following formula: T1 = tnull ∕ln(2),
most samples, we strike a compromise between instrument which yields approximate values that suffice for most
time and sensitivity. Typically, a 45∘ pulse angle (𝜃) and a purposes.
delay of a few seconds may be used for small molecules. For
larger molecules, which usually have much shorter T1 values,
shorter relaxation delays can be used.
4.2.4 Nuclear Overhauser Effect (NOE)
It may sometimes be of interest to measure T1 values
so that weak signals are not lost in the noise or in order to We described the nuclear Overhauser effect (NOE) involving
obtain quantitative results. The inversion-recovery method protons in Section 3.16; we now discuss the heteronuclear
to determine T1 is demonstrated in Figure 4.4. Generally, T1 NOE, which results from broadband proton decoupling in
13 C NMR spectra (see Figure 4.1b). The net effect of NOE
values decrease as the number of protons directly bonded
to the 13 C nucleus increases. In other words, a quaternary on 13 C NMR spectra is the enhancement of peaks whose
13 C nucleus gives a peak of lowest intensity as shown carbon atoms have directly bonded protons. This enhance-
in Figure 4.4d; it also gives the slowest recovery in the ment is due to the reversal of spin populations from the
inversion-recovery method. However, it is often difficult to normal Boltzmann distribution. The total amount of enhance-
differentiate between CH3 , CH2 , and CH functional groups ment depends on the theoretical maximum and the mode
on the basis of T1 values alone since other factors are of relaxation. The maximum possible enhancement is equal
involved. T1 values cover a range of several seconds for a to one-half the ratio of the nuclei’s magnetogyric ratios
CH3 group to well over a minute for some quaternary 13 C (𝛾), while the actual enhancement is also proportional to
nuclei. As a point of reference, T1 values measured for the the extent of 13 C⏤1 H dipolar relaxation. For a proton-
various carbon functional groups in 3,5-dimethyl-cyclohex- decoupled 13 C experiment, the maximum NOE enhance-
2-ene-1-one are 2 to 6 seconds for the methyls, about 3 ment is 𝛾H ∕(2)𝛾C or 26.753/(2)6.728 which equals 1.98. The
seconds for the methylenes, 5 seconds for the methines, and total sensitivity increase is therefore nearly threefold because
30 to 40 seconds for the quaternary carbons (Freeman and the NOE enhancement is added to the original intensity.
Hill, 1970). A delay between pulses of approximately 5T1 is The actual enhancement for the 13 C⏤1 H system can
recommended for a 13 C nucleus without an attached proton, be anywhere from 0 to 1.98 depending on the mechanism
and this appreciable delay must be tolerated (for quantitative of relaxation for each individual nucleus. In practice, for
purposes). carbons with no directly bonded protons, the enhancement is
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194 CHAPTER 4 CARBON-13 NMR SPECTROSCOPY

1 Decouple on
H:
(a)
Relaxation Acquire (t )
13
delay (R d )
C:

(b)

0.2 0.4 0.6 0.8 1.0 1.2 1.4 1.6 1.8 2.0 2.2 2.4 2.6 2.8 seconds

(c)

0.028 0.030 0.032 0.034 0.036 0.038 0.040 seconds

FIGURE 4.2 (a) Standard C rf pulse sequence with proton decoupling. Rd is the relaxation delay, 𝜃 is a variable pulse angle, and t is the
13

acquisition time. (b) FID resulting from the pulse sequence shown in (a), for cholesterol at 150.9 MHz in CDCl3 . (c) Expanded small section
of the FID.

FIGURE 4.3 Comparison of 1 H and 13 C chemical shift scales.

 Silverstein c04.tex V3 - 07/25/2014 6:26 P.M. Page 195

4.2 THEORY 195

180°x 90°x
Relaxation
(a) 1 delay (Rd) Decoupler on
H:
Acquire (t)
13
C: 𝛥τ

(b) z z z z
M0

y y y y

x x x x

(c) z z z z
M0

y y y y

x x x x

Relaxation 180°x 𝛥τ 90°x Acquire (t)

delay (Rd) & FT

Increasing
𝛥τ
time
(d)

240 220 200 180 160 140 120 100 80 60 40 20

(ppm)
FIGURE 4.4 (a) Inversion-recovery pulse sequence with inverse-gated proton decoupling for T1 measurement. (b) Short Δ𝜏 time.
(c) Long Δ𝜏 time. (d) Example of a 13 C T1 data set for diethyl phthalate at 75.5 MHz. See Section 4.3 for complete assignment of
diethyl phthalate.

essentially zero since there is practically no 13 C⏤1 H dipolar coupled spectrum. Furthermore, this contribution to inten-
relaxation. For small- to medium-sized organic molecules, sity increase is a nonlinear function of the number of pro-
13 C⏤1 H dipolar relaxation for carbons with directly bonded tons directly bonded to the particular 13 C nucleus. 13 C nuclei
protons is very efficient, yielding close to the full threefold without directly bonded protons – are characterized by peaks
increase in signal. of distinctly low intensities (see Figure 4.1b). These erratic
The net effect is a large reduction in the time needed to contributions make peak intensities unrelated to the number
obtain a decoupled spectrum as compared with a of 13 C nuclei that they should represent.
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196 CHAPTER 4 CARBON-13 NMR SPECTROSCOPY

4.2.5 13 C⏤1 H Spin-Spin Coupling TABLE 4.1 Some 1 JCH Values

( J Coupling) Compound J(Hz)
Spin-spin (J) coupling constants—at least as an initial
sp3
consideration—are less important in 13 C NMR than in 1 H
CH4 125.0
NMR. Since routine 13 C NMR spectra are usually proton- CH3 CH3 124.9
decoupled, 13 C⏤1 H coupling values are discarded in the CH3 𝐂H2 CH3 119.2
interest of obtaining a spectrum in a short time or on (CH3 )3 CH 114.2
small samples—a spectrum, furthermore, free of complex,
overlapping multiplets. H
For the spectrum of cholesterol in Figure 4.1a, the 123
J couplings were retained using the gated proton-decoupling H
technique rather than the usual, continuous, broadband
128
decoupling. The gated proton-decoupling technique allows
us to retain part of the NOE (Section 4.2.3) and still main- PhCH3 129
tain C⏤H coupling (Figure 4.5). Briefly, the broadband CH3 NH2 133
proton decoupler is gated (switched) “on” during the relax-
ation delay period, then gated “off” during the brief acquisi-
tion period. The NOE (a slow process) builds up during the H 134
lengthy delay period (on the order of seconds). Coupling is in ROCH3 140
effect throughout the acquisition period. The result is a cou- CH3 OH 141
pled spectrum, in which part of the NOE has been retained; CH3 Cl 150
thus time has been saved compared to the direct acquisition CH3 Br 151
of a proton-coupled 13 C spectrum acquired without gated H
decoupling. 161
We demonstrated the utility of spin-spin coupling in (CH3 O)2 CH2 162
Figure 4.1a in which the 1 JCH coupling values are of interest. CH2 Cl2 178
Table 4.1 gives some representative 1 JCH values. O
One-bond 13 C⏤1 H coupling (1 JCH ) ranges from about H 180
110 Hz to 320 Hz, increasing with increased s character of H
the 13 C⏤1 H bond, with substitution on the carbon atom of
electron-withdrawing groups, and with angular distortion. 205
Appreciable 13 C⏤1 H coupling also extends over two or
CHCl3 209
more (n) bonds (n JCH ). Table 4.2 gives some representative
2J sp2
CH values, which range from about 5 Hz to 60 Hz. CH3 𝐂H⏤C(CH3 )2 148
The 3 JCH values are roughly comparable to 2 JCH val- CH2 ⏤CH2 156
ues for sp3 carbon atoms. In aromatic rings, however, the C6 H6 159
3J 2
CH values are characteristically larger than JCH values.
H
In benzene itself, 3 JCH = 7.6 Hz and 2 JCH = 1.0 Hz (see
Table 4.2). 160
Coupling of 13 C to several other nuclei, the most C⏤C⏤C⏤H 168
important of which are 31 P, 19 F, and 2 D, may be observed in
proton-decoupled spectra. Representative coupling constants
are given in Table 4.3. H 170
CH3 𝐂H⏤O 172
N
1 Decoupling on Decoupling off H
H: 178
NH2 𝐂H⏤O 188
(Rd) Acquire (t) ⏤COH(OR) 195
13
CH3 𝐂HX, X = halogen 198
C:
H 238
sp
FIGURE 4.5 Gated proton-decoupling pulse CH⏤⏤CH 249
sequence. R𝐝 is the relaxation delay, 𝜃 is a C6 H5 C⏤
⏤CH 251
variable pulse angle, and t is the acquisition time. HC⏤⏤ N 269
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4.2 THEORY 197

TABLE 4.2 Some 2 JCH Values which it describes an experiment that takes advantage of
the higher sensitivity of one nucleus (1 H) and transfers the
Compound J(Hz) magnetization to another less sensitive nucleus (13 C).
sp3 A routine 13 C NMR spectrum at a Larmor frequency
CH3 CH3 −4.5 of 75.5 MHz normally requires about 10 mg of sample in
CH3 CCl3 5.9 0.5 mL of deuterated solvent in a 5 mm o.d. tube. Samples
RC(⏤O)CH3 6.0 on the order of 100 𝜇g can be handled in a probe that
CH3 CH⏤O 26.7 accepts a 2.5-mm o.d. tube, which gives higher sensitivity
sp2 (see Section 3.3).
∗
C6 H6 1.0
CH2 ⏤CH2 2.4 4.2.7 Solvents
C⏤C(CH3 )H 5.0
(CH3 )2 C⏤O 5.5 Organic compounds are typically dissolved in CDCl3 for 13 C
CH2 ⏤CHCH⏤O 26.9 NMR experiments, and the 13 C peak of the solvent is used as
sp an internal secondary reference (77.0 ppm relative to TMS).
CH⏤ ⏤CH 49.3 Internal TMS may also be set to 0 ppm, if present in the
C6 H5 OC⏤⏤CH 61.0 solvent. A list of the common deuterated solvents is given
∗ 3J = 7.6 Hz (> 2 J). in Appendix A.
For a given deuterated solvent, the 13 C and 1 H solvent
TABLE 4.3 Coupling Constants for 19 F, 31 P, and 2 D Coupled to 13 C peaks differ in multiplicities. It is worth noting the difference
in appearance between the solvent peaks in a proton spectrum
1 2 3 4
Compound J(Hz) J(Hz) J(Hz) J(Hz) and a 13 C spectrum. For example, the familiar singlet at
CH3 CF3 271 7.26 ppm in a proton spectrum is the result of a small amount
CF2 H2 235 of CHCl3 in the solvent CDCl3 . The 1 H peak is not split
CF3 CO2 H 284 43.7 since 12 C is magnetically inactive, and the 35∕37Cl nuclei
C6 H5 F 245 21.0 7.7 3.3
(C4 H9 )3 P 10.9 11.7 12.5
have strong electric quadrupole moments. The small amount
(CH3 CH2 )4 P+ Br − 49.0 4.3 of 13 C present is insufficient to produce a visible doublet
(C6 H5 )3 P+ CH3 I− 88.0 10.9 (see Section 3.7). In the case of another useful solvent,
1
J(Hz) of CH3 = 52 dimethyl-d6 sulfoxide, the quintet at 2.49 ppm in a proton
C2 H5 (P⏤O)(OC2 H5 )2 143 7.1 (JCOP ) 6.9 (JCCOP )
(C6 H5 )3 P 12.4 19.6 6.7 spectrum is a result of the proton in the impurity split by
CDCl3 31.5 D2∶ 𝐇CD2 ⏤S(⏤O)⏤CD3 . The proton peak is split by two
CD3 (C⏤O)CD3 19.5 deuterium nuclei with nuclear spin quantum numbers (I)
(CD3 )2 SO 22.0
of one. The multiplicity can be calculated by the familiar
C6 D6 25.5
formula 2nI + 1; thus 2 × 2 × 1 + 1 = 5. The ⏤CD3 group
does not interfere because it comprises a different spin
4.2.6 Sensitivity system.
In a typical 13 C NMR spectrum, CDCl3 gives a triplet
13 C nuclei are much less abundant and much less sensitive centered at 77.0 ppm. But now the presence of small amount
than protons. More concentrated samples and longer times of CHCl3 is irrelevant since all protons are decoupled by
are needed to acquire spectra with sufficient signal-to-noise the usual broadband decoupling and because the signal from
ratios. Let us turn once again to the sensitivity of pulsed FT CDCl3 is much stronger. The triplet results from splitting of
NMR experiments in which the signal-to-noise ratio (S∕N) the 13 C peak by the D nucleus. The formula 2nI + 1 gives
is proportional to various factors within the control of the 2 × 1 × 1 + 1 = 3. The intensity ratios are 1:1:1. In the case
experimentalist (see the equation given√ in Section 3.3.2). of 𝐂D3 S(⏤O)CD3 , the formula gives 2 × 3 × 1 + 1 = 7.
S∕N grows proportionately to ns, where ns is the The multiplet at 39.7 ppm is a septet with a coupling con-
number of scans or repetitions of the pulse program. This stant of 21 Hz; the intensity ratios are 1:3:6:7:6:3:1 (see
relationship is not typically a problem with 1 H experiments, Appendix A). The following diagram is the deuterium ana-
where only a few 𝜇g to a mg of material is enough to get logue of Pascal’s triangle for protons (see Figure 3.22 for 1 H
good S∕N in a few scans. As mentioned previously, 13 C is equivalent).
∼6000 times less sensitive than 1 H, and therefore requires
either more sample (N), higher field strengths B0 (or better 1 Example
probe technology, i.e., a cryo-probe), or an increase in the
number of scans (ns). 1 1 1 CDCl3
In most labs, the only alternative is to increase ns, but
to double the S∕N you need to take four times the number 1 2 3 2 1 CD2Cl2
of scans, which rapidly escalates into long experiment times
due to 1, 4, 16, 64, 256, 1024(1k), 2k, 4k, 16k, 64k,…
scans. Another solution is presented in Section 5.4.2, in 1 3 6 7 6 3 1 (CD3)2SO
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198 CHAPTER 4 CARBON-13 NMR SPECTROSCOPY

Substitution of D for H on a carbon atom results in similarities with 1 H chemical shifts (see Figure 4.3 and
a dramatic diminution of the height of the 13 C signal in a Appendix C). For example, we can place the alkyl groups
proton-decoupled spectrum for the following reasons. Since on the right-hand side of the 13 C NMR spectrum with the
deuterium has a spin number of 1 and a magnetogyric ratio deshielded CH2 group to the left of the CH3 group. It seems
1
6.5
that of 1 H, it will split the 13 C peak into three lines safe to designate the strongly deshielded cluster of three
(ratio 1:1:1) with a J value equal to 0.154 × JCH . Further- peaks as aromatic. The C⏤O group is on the far left. We
more, T1 for 13 C⏤D is longer than that for 13 C⏤1 H because also note that the 13 C aromatic nucleus (labeled 1) without
of decreased dipole-dipole relaxation. Finally, the NOE is an attached proton gives a peak that is distinctly decreased in
lost, since there is no irradiation of deuterium.* A separate height relative to the protonated aromatic carbon atoms. The
peak may also be seen for any residual 13 C⏤1 H since the same applies to the C⏤O group.
isotope effect usually results in a slight shift to lower fre- The 1 J coupling in Figure 4.6b provides the multiplici-
quency of the 13 C⏤D peak (∼0.2 ppm per D atom). The ties; that is, the number of protons that are directly bonded
isotope effect may also slightly shift the 13 C peak positions to each carbon atom. These couplings confirm our chemical
relative to those in the same nondeuterated solvent. As an shift assignments. Thus, from right to left, we see the quar-
example, pure deuterated benzene, a common NMR solvent, tet of the CH3 group (the n + 1 rule) and triplet of the CH2
gives a 1:1:1 triplet centered at 128.0 ppm in a decoupled group. Then there is a cluster of the two doublets of the two
spectrum; J is 25 Hz. Under the same conditions, pure ben- aromatic CH groups and the singlet of the carbon atom to
zene (C6 H6 ) gives a singlet at 128.5 ppm (see Table 4.12 and which no proton is directly bonded (labeled 1). Finally, there
Appendix A). is the C⏤O singlet at higher frequency.
In Figure 4.6c, we see the expansion of the quartet
shown in Figure 4.6b, each peak of which is a triplet resulting
4.3 INTERPRETATION OF A SIMPLE from 2 J coupling of the methyl 13 C nucleus with the protons
13
C NMR SPECTRUM: DIETHYL of the adjacent CH2 group. These 2 J couplings are much
smaller than the 1 J couplings.
PHTHALATE In Figure 4.6d, we see the expansion of the CH2
triplet shown in Figure 4.6b, each peak of which is a
Even though we have not discussed the chemical shifts of quartet resulting from 2 J coupling with the CH3 protons. In
the different functional groups (Section 4.7), it is possible Figure 4.6e, we see the expansion of the right-hand doublet
to discuss the peak assignments of diethyl phthalate from of the aromatic cluster labeled 2 in Figure 4.6b. Each peak of
what we do know: peak intensities, 13 C⏤1 H coupling, and this doublet is split by 2 J and 3 J coupling of the neighboring
an expectation of chemical shifts relative to what we know protons.
for 1 H. The T1 and NOE affect the peak intensities and The expansion shown in Figure 4.6f is the other aromatic
the latter are therefore not representative of the relative doublet shown in Figure 4.6b labeled 3. Each peak of the
number of different types of carbon atoms: this, however, doublet is split by either 2 J or 3 J coupling. Also in the
results in an advantage. It is usually possible by inspection same panel is the expansion of the singlet remaining in the
of the 13 C spectrum to recognize the nuclei that do not aromatic cluster of Figure 4.6b. The singlet is not split by a
bear protons by their low intensity (Figure 4.6a, C⏤O and large coupling since there is no attached proton. It is split
the peak labeled 1). The common spin-lattice relaxation only by the small 2 J and 3 J couplings and is readily assigned
mechanism for 13 C results from dipole-dipole interaction to the carbon nucleus labeled 1.
with directly bonded protons. Thus, nonprotonated carbon Carbon atom 2 is ortho and meta to the substituents,
atoms have longer T1 relaxation times, which together with and carbon atom 3 is meta and para. Use of Table 4.12
little or no NOE, results in low-intensity peaks. It is therefore (Section 4.7.4) gives 129.6 ppm for peak 2 and 133.2 ppm
often possible to recognize carbonyl groups (except formyl), for peak 3. Measurements of peaks in Figure 4.6 give
nitriles, nonprotonated alkene and alkyne carbon atoms, and 128.5 ppm for peak 2 and 131.2 ppm for peak 3. Reasonable,
other quaternary carbon atoms readily. but perhaps unexpected to some who recall from Chapter 3
Since diethyl phthalate (C12 H14 O4 ) has an axis of that a carbonyl substituent deshields the ortho position
symmetry (and a plane of symmetry), the proton-decoupled of protons more so than the para position. Chart D.1 in
13 C NMR spectrum in Figure 4.6a consists of six peaks.
Chapter 3 confirms this impression, at least for a single
Since there is no coupling, the peaks are singlets, and there carbonyl substituent. And the result of comparing ortho and
is no overlap. We examine the chemical shifts and observe meta with meta and para gives the expected results for the 1 H
chemical shifts: 8.0 ppm for peak 2 and 7.60 ppm for peak 3.
* The same explanation also accounts for the relatively weak 13 C signal
shown by deuterated solvents. In addition, small solvent molecules tumble
rapidly; this rapid movement makes for a longer T1 , hence for less intense
peaks in the absence of complete 13 C relaxation. Deuterated chloroform, 4.4 QUANTITATIVE 13 C ANALYSIS
CDCl3 , shows a 1:1:1 triplet, deuterated p-dioxane a 1:2:3:2:1 quintet, and
deuterated DMSO a 1:3:6:7:6:3:1 septet in accordance with the 2nI + 1
rule (Chapter 3). The chemical shifts, coupling constants, and multiplicities
Quantitative 13 C NMR is desirable in two situations. First, in
associated with the 13 C atoms of common NMR solvents are given in structure determinations, it is clearly useful to know whether
Appendix A. a signal results from more than one chemically equivalent
 Silverstein c04.tex V3 - 07/25/2014 6:26 P.M. Page 199

4.4 QUANTITATIVE 13 C ANALYSIS 199

O
2
3 1 CH2CH3
O
O
32 CH2CH3
O CH2 CH3
(a) 1

C O
CDCl3

170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 ppm

CH3
3
2 CH2
1
(b)
C O

170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 ppm

CH3 CH2

(c) (d)

2200 2100 2000 Hz 9400 9300 9200 9100 Hz

2 3
1

(e) (f)

19500 19400 19300 Hz 19900 19800 19700 Hz

FIGURE 4.6 (a) Proton-decoupled 13 C NMR spectrum of diethyl phthalate at a Larmor frequency of 150.9 MHz in CDCl3 ,
(b) proton-coupled 13 C NMR spectrum, and (c–f) expansions of the proton-coupled 13 C NMR spectrum.
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200 CHAPTER 4 CARBON-13 NMR SPECTROSCOPY

carbon. Second, quantitative analysis of a mixture of two illustrates that, by using long relaxation delays (Rd > 5T1 )
or more components requires that the area of the peaks be and by minimizing the NOE by using the inverse-gated
proportional to the number of carbons atoms causing that proton-decoupling technique, 13 C data can be quantitative.
signal. The drawback is that it takes a long time to acquire the data
There are two reasons that broadband-decoupled 13 C because the relaxation delay has to be set to at least five
NMR spectra are usually not susceptible to quantitative times the expected T1 and the loss of the NOE means many
analysis: more repetitions are needed to build up the signal intensity.
13 C The time required can be reduced by addition of a param-
• nuclei with long T1 relaxation times may not return
agnetic relaxation reagent. A common procedure is to add a
to the equilibrium Boltzmann distribution between pulses.
trace amount of chromium (III) acetylacetonate (Cr(acac)3 ),
Thus, the signals do not achieve full amplitude (see
a paramagnetic substance, whose unpaired electrons effi-
Section 4.2.3).
ciently reduce the T1 and T2 relaxation times.
• The enhancement due to the NOE (see Section 4.2.4)
varies among 13 C nuclei, and the signal intensities vary
accordingly.
4.5 CHEMICAL EQUIVALENCE
In Section 4.2.5, we discussed the gated proton-
decoupling technique. The purpose was to develop a high The definition of chemical equivalence given for protons also
level of the nuclear Overhauser effect so that a coupled spec- applies to carbon atoms: interchangeability by a symmetry
trum could be achieved in the least time. In the present operation or by a rapid mechanism. The presence of equiv-
section, we deal with the inverse-gated proton-decoupling alent carbon atoms (or coincidence of shift) in a molecule
technique. The proton decoupler is gated off at the beginning results in a discrepancy between the apparent number of
of the relaxation delay and gated on at the beginning of the peaks and the actual number of carbon atoms in the molecule.
acquisition period (see Figure 4.7). The purpose is to main- Thus the three 13 C nuclei of the methyl groups in
tain a low, constant level of NOE (ideally zero). This is fea- t-butyl alcohol (Figure 4.9) are chemically equivalent by
sible because the NOE builds up slowly during the relatively rapid rotation in the same sense in which the protons of
brief time of the signal-acquisition period (t). The overall a methyl group are chemically equivalent. The 13 C NMR
result is a spectrum consisting of singlets whose intensities spectrum of t-butyl alcohol shows two peaks, one much more
correspond to the number of 13 C nuclei they represent. Lest intense than the other; the carbinyl carbon peak (quaternary)
we forget, we must still allow for the T1 relaxation delay (Rd ). is much less intense than the peak representing the carbon
Figure 4.8 demonstrates the effects of T1 and NOE atoms of the methyl groups.
on the peak intensities. Figure 4.8a is a standard proton- In the chiral molecule 2,2,4-trimethyl-1,3-pentanediol
decoupled 13 C NMR spectrum with Rd set to <T1 ; notice (Figure 4.10) at 75.5 MHz, we note that CH3 (a) and CH3 (b)
that the integrated intensity of the peak due to the methyl are not chemically equivalent and two peaks are seen.
carbon is set to one and the rest of the integrals are labeled Even though the two methyl groups labeled c and c′ are
above the peaks. The spectrum is not quantitative due to not chemically equivalent, they coincidently show only
NOE and T1 effects. In Figure 4.4d (Section 4.2.3), the pro- one peak. Two peaks are seen at higher field strength
tonated aromatic carbons showed the shortest T1 values, (150.9 MHz). Note that the lowercase letters used to label
which explains the larger integrals of those peaks. The spec- the atoms are not related to their Pople notation.
trum in Figure 4.8b was obtained using the inverse-gated In Section 3.8.3.2, we noted that the CH3 protons of
proton-decoupling technique. Notice that by removing the (CH3 )2 NCH⏤O gave separate peaks at room temperature,
NOE, the intensities of the peaks due to carbon atoms with but became chemically equivalent at about 123∘ . Of course,
directly bonded hydrogens are more quantitative than the the 13 C peaks show similar behavior.
ones that are quaternary. Rd is still less than T1 . Figure 4.8c

4.6 DEPT
1 Decoupling off Decoupling on
H: Broadband proton decoupling of 13 C NMR spectra is a mixed
blessing. On the one hand, the simplicity of a spectrum with
(Rd) Acquire (t) a single peak for each unique carbon atom in the molecule is
extremely attractive. On the other hand, 1 H⏤13 C coupling
13
C: information is valuable and clearly useful in determining
structure. There have been many experiments developed over
the years attempting to usefully tap this information and
FIGURE 4.7 Inverse-gated proton-decoupling still maintain the simplicity of the completely decoupled
pulse sequence. Rd is relaxation delay, 𝜃 is a spectrum. Two are worth mentioning because both were
variable pulse angle, and t is the acquisition time. popular at one time and both are common in older literature.
 Silverstein c04.tex V3 - 07/25/2014 6:26 P.M. Page 201

4.6 DEPT 201

0.99 0.98 0.99 0.99 1.00

0.98

(c)

1.01 0.98 0.99 1.00

0.35 0.41

(b)
1.37 1.31 0.92 1.00

0.12 0.17
(a)

170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 ppm

FIGURE 4.8 (a) Standard H-decoupled C NMR spectrum of diethyl phthalate with relaxation delay (Rd ) < T1 ,
1 13

(b) inverse-gated proton-decoupling technique with Rd < T1 and (c) Rd > 5T1 and inverse-gated decoupling to compensate
for NOE. The number above each peak represents its integrated value. Spectra recorded at 150.9 MHz in CDCl3 .

Also, some of the terminology that we use today grew from the apparent value of the one-bond JCH coupling constant is
one of these experiments. reduced from its true value as a result of this off-resonance
The first of these now obsolete experiments is called the decoupling. Thus, each carbon resonance gives a singlet (no
off-resonance 1 H-decoupled spectrum. In this experiment, attached protons), a doublet (one attached proton), a triplet
the 1 H⏤13 C coupling is restricted to one bond (i.e., each (two attached protons), or a quartet (three attached protons).
carbon only shows coupling to its directly bonded protons) Note that these patterns are an application of first-order
by moving the broadband decoupler “off-resonance” or away coupling rules and the n + 1 rule. This experiment also gave
from the middle of the proton chemical shift range. Note that rise to the common practice (still used today) of referring to a

(CH3)3C OH

180 160 140 120 100 80 60 40 20 ppm

1
FIGURE 4.9 H-decoupled 13 C NMR spectrum of t-butanol at 75.5 MHz, in CDCl3 .
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202 CHAPTER 4 CARBON-13 NMR SPECTROSCOPY

c a c,c'
H3C OH CH3
f d e f
g CH CH C CH2OH d b
g a
(a) H3C CH3
c' b e

23.5 ppm

85 80 75 70 65 60 55 50 45 40 35 30 25 20 15 10 ppm
c,c'

(b)

23.5 ppm

85 80 75 70 65 60 55 50 45 40 35 30 25 20 15 10 ppm
1 13
FIGURE 4.10 (a) H-decoupled C NMR spectrum of 2,2,4-trimethyl-1-3-pentanediol in CDCl3 at a Larmor frequency of
75.5 MHz. (b) Same as (a) but at a Larmor frequency of 150.9 MHz.

carbon resonance by its “multiplicity” (“s,” “d,” “t,” or “q”). phased up, whereas the peaks due to CH2 groups are phased
We use these descriptions of multiplicity whether or not we down. The top spectrum, Figure 4.12c, is a DEPT 90, where
use this experiment. only CH carbons are detected. Quaternary 13 C atoms are
The other experiment worth mentioning, which, by the not detected in the DEPT subspectra. We can now interpret
way, is also obsolete, is the attached proton test or APT. the 13 C peaks in the main spectrum as CH3 , CH2 , CH, or C
This experiment is based on the different values of the by examining the two subspectra peaks along with the main
1 H⏤13 C J coupling constant for methine, methylene, and
spectrum. The easiest way to approach the interpretation of
methyl groups. By adjusting certain delays in the pulse the 13 C-DEPT spectra is to first look for peaks that are in
sequence (not shown), quaternary and methylene carbons the 1 H-decoupled 13 C spectrum and not in either of the other
could be phased up, and methine and methyl carbons could two DEPT spectra. These are identified as being quaternary
be phased down. Since phase is arbitrary, this order could be (no protons attached). Next, look at the DEPT 135 and label
reversed. This ability to distinguish of carbon types by the all the CH2 peaks; they are easily identified because they
magnitude of their respective coupling constants led to the are phased down. Finally, identifying CH3 peaks versus CH
now popular DEPT experiment. peaks is accomplished by inspection of the DEPT 135 versus
The DEPT (distortionless enhancement by polarization
transfer) sequence has developed into the preferred proce-
dure for determining the number of protons directly bonded 90° 1 180°
to various 13 C nuclei. The DEPT experiment can be done in (Rd) 2J Decouple on
1
a reasonable time and on small samples; in fact, it is several H:
times more sensitive than the usual 13 C procedure. DEPT 90° 1 180° 1 Acquire (t)
is now routine in many laboratories and is widely used in
the Student Exercises in this textbook. The novel feature in 13
2J 2J
the DEPT sequence is a variable proton pulse angle 𝜃 (see C:
Figure 4.11) that is set at 90∘ for one subspectrum, and 135∘
for a second, separate experiment.
The DEPT spectra of ipsenol are shown in Figure 4.12. FIGURE 4.11 DEPT pulse sequence. Based on an
1
We see in Figure 4.12a a standard 1 H-decoupled 13 C spec- approximate average JCH value of 145 Hz, (2J) is 3.45 ms.
trum; the middle spectrum, Figure 4.12b, is a DEPT 135 Rd is the relaxation delay, 𝜃 is a variable pulse angle, and t is
where the peaks associated with CH3 and CH groups are the acquisition time.
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4.7 CHEMICAL CLASSES AND CHEMICAL SHIFTS 203

10
(c)
5 6 7

4 8
HO 3
(b) 2

9 1

(a)

140 130 120 110 100 90 80 70 60 50 40 30 20 10 ppm

FIGURE 4.12 (a) Standard proton-decoupled 13 C NMR spectrum of ipsenol in CDCl3 at 75.5 MHz. DEPT subspectra: (b) DEPT
135∘ (CH and CH3 up, CH2 down); (c) DEPT 90∘ (CH only).

the DEPT 90. The DEPT 90 has only CH carbons, so by dif- have the number of carbon and hydrogen atoms, but now we
ference the rest that are phased up in the DEPT 135 are due have the chemical shifts of the carbon atoms and the number
to CH3 groups. of hydrogen atoms attached to each carbon. However, there
To illustrate the simplicity of interpreting 13 C-DEPT is a discrepancy between the proton count (see Figure 3.42
spectra, we return to ipsenol in Figure 4.12, starting at the for 1 H spectrum for confirmation) in the proton spectrum
high-frequency peak at the left end of the main spectrum. and in the DEPT spectrum, since the OH is not accounted
We note that there are no peaks directly aligned above in for in the DEPT spectrum nor are protons that are attached to
the subspectra; therefore, this peak in the main spectrum is other atoms such as nitrogen, sulfur, silicon, or phosphorus.
due to a quaternary carbon atom, that is, no directly bonded It is not difficult to correlate the DEPT spectrum with the 1 H
protons. The next peak to the right in the main spectrum is a spectrum. In fact, it is striking to observe how resonances
CH peak, since the peak aligned in the lower subspectrum is due to the alkenyl and alkyl groups are widely separated in
pointed up, as is the aligned peak in the upper subspectrum. both spectra.
The next two peaks in the main spectrum are CH2 peaks,
since the aligned peaks in the lower subspectrum are pointed
down. The next peak to the right of the solvent peak (a triplet 4.7 CHEMICAL CLASSES
for CDCl3 ) is another CH peak. The next two peaks are CH2 AND CHEMICAL SHIFTS
peaks. The next peak is again associated with a CH group.
The next two are due to CH3 groups since the aligned peaks
In this section, chemical shifts will be discussed under
in the lower subspectrum are pointed up, and there are no
the headings of the common chemical classes of organic
aligned peaks in the upper subspectrum. Summing up, we
compounds. As noted earlier, the range of shifts generally
have (in order of decreasing frequency)
encountered in routine 13 C NMR studies is about 220 ppm.
Trends in 13 C chemical shifts somewhat parallel those of
6 7 8 10 4 5 3 2 1 9 1 H, so some of the empirical rules developed for assigning
C, CH, CH2 , CH2 , solvent, CH, CH2 , CH2 , CH, CH3 , CH3 1 H NMR spectra may carry over to 13 C NMR spectra.

Furthermore, the concept of additivity of substituent effects

Interpretation of the various DEPT spectra takes a bit of (see Sections 4.7.1 and 4.7.6) is useful for both nuclides. In
practice, but the results are most instructive. Not only do we some case, the 13 C shifts may be rationalized by considering
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204 CHAPTER 4 CARBON-13 NMR SPECTROSCOPY

hybridization, substituent electronegativity, and diamagnetic 4.7.1 Alkanes

anisotropy (to a lesser extent); solvent effects are important
in both spectra. As for 1 H chemical shifts, it is important 4.7.1.1 Linear and Branched Alkanes. We know from
to remember that such rationalizations are empirical and the general correlation chart (Appendix C) that alkane
will not work in every case. Chemical shifts for 13 C are groups unsubstituted by heteroatoms have 13 C chemical
affected by substitutions as far removed as the 𝛿 position; shifts of about 60 ppm. (Methane has a 13 C chemical shift
in the benzene ring, pronounced shifts for 13 C are caused of −2.5 ppm.) Within this range, we can predict the chemical
by substituents at the point of attachment and at the ortho, shifts of individual 13 C atoms in a straight-chain or branched-
meta, and para positions. The 13 C chemical shifts are chain hydrocarbon from the data in Table 4.4 and the empir-
also decreased significantly by the 𝛾-gauche effect (see ical formula given below.
Section 4.7.1). Decreases in the chemical shift by as much This table shows the additive shift parameters (A) in
as several ppm may occur on dilution. Hydrogen bonding hydrocarbons: the 𝛼 effect of +9.1, the 𝛽 effect of +9.4 ppm,
effects with polar solvents may result in increased chemical the 𝛾 effect of −2.5, the 𝛿 effect of +0.3, the 𝜖 effect of +0.1,
shifts. and the corrections for branching effects. The empirical (and
As with other types of spectroscopy, peak assignments observed) shifts for the carbon atoms of 3-methylpentane are
are facilitated by comparison with those of reference com- 19.3 (18.6)
pounds. Reference material for many classes of compounds
has accumulated in the literature. The starting point is a gen- 6
CH 3
eral correlation chart for 13 C chemical shifts of the major 1 2 3 4 5
chemical classes (see Figure 4.3 and Appendix C); then, CH 3 CH 2 CH CH 2 CH 3
minor changes within these regions are correlated with struc-
ture variations in the particular chemical class. The chem-
11.3 29.5 36.2
ical shift values in the following tables must not be taken ( 11.3) ( 29.3) ( 36.7)
too literally because of their variation with solvent and con-
centration. For example, the C⏤O peak of acetophenone in Calculations of the chemical shifts are made from the
CDCl3 appears 2.4 ppm higher than that in CCl4 ; the effect formula: 𝛿 = −2.5 + ΣnA, where 𝛿 is the predicted shift for
on the other carbon atoms of acetophenone ranges from 0.0 a carbon atom, A is the additive shift parameter, and n is the
to 1.1 ppm. Furthermore, much of the early work used vari- number of carbon atoms for each shift parameter (−2.5 is
ous reference compounds, and the values were corrected to the shift of the 13 C of methane). Thus, for carbon atom 1, we
give parts per million from TMS. have 1𝛼-, 1𝛽-, 2𝛾-, and 1𝛿-carbon atoms.
A 13 C NMR spectrum will often distinguish substitution
patterns on an aromatic ring. If, for example, there are two 𝛿1 = −2.5 + (9.1 × 1) + (9.4 × 1)
identical (achiral) substituents, the symmetry elements alone + (−2.5 × 2) + (0.3 × 1) = 11.3
will distinguish among the para, ortho, and meta isomers if Carbon atom 2 has 2𝛼-, 2𝛽-, and 1𝛾-carbon atoms. Car-
the chemical shifts of the ring carbon atoms are sufficiently bon atom 2 is a 2∘ carbon with a 3∘ carbon attached [2∘ (3∘ ) =
different. The para isomer has two rotational symmetry axes −2.5].
and two mirror planes. The ortho and meta isomers have
one rotational axis and one mirror plane, but in the meta
isomer the elements pass through two atoms. There is also TABLE 4.4 Empirical 13 C Chemical Shift Parameters in Some
a symmetry plane in the plane of the ring in each compound, Linear and Branched Hydrocarbons
which does not affect the ring carbon atoms.
13
C Atoms Shift (ppm) (A)

OCH3 𝛼 9.1
H3CO OCH3 𝛽 9.4
H3CO OCH3
𝛾 −2.5
𝛿 0.3
𝜖 0.1
1∘ (3∘ )a −1.1
OCH3
1∘ (4∘ )a −3.4
2∘ (3∘ )a −2.5
2∘ (4∘ ) −7.2
The aromatic region of the 13 C NMR spectrum for the 3∘ (2∘ ) −3.7
para isomer shows two peaks; for the ortho isomer, three 3∘ (3∘ ) −9.5
peaks; and for the meta isomer, four peaks. The quaternary 4∘ (1∘ ) −1.5
carbon peaks are much less intense than the unsubstituted 4∘ (2∘ ) −8.4
carbon peaks. a The notations 1∘ (3∘ ) and 1∘ (4∘ ) denote a CH3 group bonded to a R2 CH group and
The additivity of shift increments is demonstrated in the to a R3 C group, respectively. The notation 2∘ (3∘ ) denotes a RCH2 group bonded to a
following sections. R2 CH group, and so on.
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4.7 CHEMICAL CLASSES AND CHEMICAL SHIFTS 205

𝛿2 = −2.5 + (9.1 × 2) + (9.4 × 2) constant for all the substituents except for the carbonyl,
+ (−2.5 × 1) + (−2.5 × 1) = 29.5 cyano, and nitro groups. The decreased chemical shift at
the 𝛾 carbon results (as above) from steric compression of a
Carbon atom 3 has 3𝛼- and 2𝛽-carbon atoms, and it is a gauche interaction. For Y = N, O, and F, there is a decrease
3∘ atom with two 2∘ atoms attached [3∘ (2∘ ) = −3.7]. Thus, in chemical shift with Y in the anti conformation, attributed
𝛿3 = −2.5 + (9.1 × 3) + (9.4 × 2) + (−3.7 × 2) = 36.2. to hyperconjugation.

Carbon atom 6 has 1𝛼-, 2𝛽-, and 2𝛾-carbon atoms, and it Y Y

is a 1∘ atom with a 3∘ atom attached [1∘ (3∘ ) = −1.1]. Thus,
C
𝛿6 = −2.5 + (9.1 × 1) + (9.4 × 2)
+ (−2.5 × 2) + (−1.1 × 1) = 19.3
The agreement with the determined values for such cal-
culations is very good. Another useful calculation has been C
given.* The 13 C 𝛾 shift to lower frequency resulting from gauche anti
the 𝛾 carbon has been attributed to the steric compression
of a 𝛾 gauche interaction but has no counterpart in 1 H spec- Table 4.6 provides the functional group increments that
tra. It accounts, for example, for the decreased chemical shift must be added to the appropriate shift values for alkanes
of an axial methyl substituent on a conformationally rigid given in Table 4.5. For example, we can calculate the 13 C
cyclohexane ring, relative to an equatorial methyl, and for shifts for 3-pentanol.
the decreased chemical shift of the 𝛾 carbon atoms of the
    
ring. Table 4.5 lists the shifts in some linear and branched CH3 CH2 CH CH2 CH3
alkanes.
OH
TABLE 4-5 The 13 C Chemical Shifts for Some Linear and
Branched-Chain Alkanes (ppm from TMS) The OH substituent is attached “internally” (rather than
Compound C-1 C-2 C-3 C-4 C-5 “terminally”) to the linear alkane chain of pentane; the
point of attachment is labeled 𝛼, which corresponds to C-
Methane −2.5 3 of pentane, for which the shift value of 34.7 is given in
Ethane 5.7 Table 4.6. To this value is added the increment +41, this
Propane 15.8 16.3 being the increment for an OH group attached internally
Butane 13.4 25.2
to the 𝛼-carbon of 3-pentanol (see line 12, 2nd column of
Pentane 13.9 22.8 34.7
numbers). The shift, therefore, for the point of attachment
Hexane 14.1 23.1 32.2
Heptane 14.1 23.2 32.6 29.7 (the 𝛼-carbon) is calculated as 75.7. The 𝛽 and 𝛾 shifts
Octane 14.2 23.2 32.6 29.9 are calculated as shown below. All of the calculated shifts
Nonane 14.2 23.3 32.6 30.0 30.3 are in reasonable agreement with the experimental values
Decane 14.2 23.2 32.6 31.1 30.5 (Table 4.14).
Isobutane 24.5 25.4
Isopentane 22.2 31.1 32.0 11.7
Isohexane 22.7 28.0 42.0 20.9 14.3 Experimental
Neopentane 31.7 28.1
Calculated (See Table 4.14)
2,2-Dimethylbutane 29.1 30.6 36.9 8.9
3-Methylpentane 11.5 29.5 36.9 (18.8, 3-CH3 ) C𝛼 34.7 + 41 = 75.7 73.8
2,3-Dimethylbutane 19.5 34.3 C𝛽 22.8 + 8 = 30.8 29.7
2,2,3-Trimethylbutane 27.4 33.1 38.3 16.1
C𝛾 13.9 − 5 = 8.9 9.8
2,3-Dimethylpentane 7.0 25.3 36.3 (14.6, 3-CH3 )

1-Pentanol would be treated similarly but as a “terminal”

4.7.1.2 Effect of Substituents on Alkanes. Table 4.6 alcohol, and the carbon atom to which the OH group is
shows the effects of a substituent on linear and branched attached would again be labeled 𝛼.
alkanes. The effect on the 𝛼-carbon parallels the electroneg-
ativity of the substituent except for bromine and iodine.† 4.7.1.3 Cycloalkanes and Saturated Heterocyclics. The
This demonstrates again that these empirical computa- chemical shifts of the CH2 groups in monocyclic alkanes
tions will not always provide numbers in agreement with are given in Table 4.7. The striking feature here is the nega-
experimental shifts. The effect at the 𝛽-carbon seems fairly tive 13 C chemical shift of cyclopropane, analogous to its 1 H
chemical shift.
* Lindeman, L.P., and Adams, J.Q. (1971). Anal. Chem., 43, 1245. Each ring skeleton has its own set of empirical shift
† See Section 3.4, Table 3.2 (Pauling table of electronegativity). parameters, but a detailed listing of these is beyond the scope
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206 CHAPTER 4 CARBON-13 NMR SPECTROSCOPY

TABLE 4.6 Incremental Substituent Effects (ppm) on Replacement TABLE 4.8 13

C Chemical Shifts for Saturated Heterocyclics
of H by Y in Alkanes. Y is Terminal or Internala (ppm from TMS, neat)

Unsubstituted
Y
H
… O S N
Y
40.6 18.1 18.2
Terminal Internal
H
O S N
𝜶 𝜷 22.9 72.6 28.1 26.1 19.0 48.1

Y Terminal Internal Terminal Internal 𝛾 25.8 31.2 25.7

CH3 9 6 10 8 −2 67.9 31.7 47.1

CH⏤CH2 20 6 −0.5 O S N
H
C⏤⏤CH 4.5 5.5 −3.5
COOH 21 16 3 2 −2 24.9 26.6 25.9
COO− 25 20 5 3 −2 27.7 27.8 27.8
COOR 20 17 3 2 −2
COCl 33 28 2 69.5 29.1 47.9
O S N
CONH2 22 2.5 −0.5
COR 30 24 1 1 −2 H
CHO 31 −2 Substituted
Phenyl 23 17 9 7 −2 O 21.8 24.4
OH 48 41 10 8 −5 47.6 56.7
OR 58 51 8 5 −4 47.3 32.4
18.1 N
OCOR 51 45 6 5 −3 36.5
NH2 29 24 11 10 S 48.0
NH+3 26 24 8 6 −5
NHR 37 31 8 6 −4
NR2 42 6 −3
NR+3 31 5 −7 4.7.2 Alkenes
NO2 63 57 4 4 The sp2 carbon atoms of alkenes substituted only by alkyl
CN 4 1 3 3 −3 groups resonate in the range of about 110 ppm to 150 ppm.
SH 11 11 12 11 −4
The double bond has a rather small effect on the shifts of the
SR 20 7 −3
sp3 carbons in the molecule as the following comparisons
F 68 63 9 6 −4
Cl 31 32 11 10 −4 demonstrate:
Br 20 25 11 10 −3 25.4
I −6 4 11 12 −1 CH 3 CH 3
a Add these increments to the shift values of the appropriate carbon atom in Table 4.5 H3C C CH 2 C CH 2
or to the shift value calculated from Table 4.4. 30.4 52.2 143.7 114.4
Source: Wehrli et al. (1983).
CH 3
31.6
24.7
of this text. Rough estimates for substituted rings can be CH 3 CH 3
made with the substitution increments in Table 4.6. One of H3C C CH 2 CH CH 3
the striking effects in rigid cyclohexane rings is the shielding 29.9 53.5 25.3
caused by the 𝛾-gauche steric compression. Thus, an axial CH 3
30.4
methyl group at C-1 causes a decrease of several ppm of the
chemical shifts of C-3 and C-5. The methyl signal of propene is at 18.7 ppm and that of
Table 4.8 presents chemical shifts for several saturated propane is at 15.8 ppm. In (Z)-2-butene, the methyl signals
heterocyclics. are at 12.1 ppm, compared with 17.6 ppm in (E)-2-butene,
because of the 𝛾 effect. (For comparison, the methyl signals
TABLE 4.7 13
C Chemical Shifts of Cycloalkanes (ppm from of butane are at 13.4 ppm.) Note the 𝛾 effect on one of the
TMS) geminal methyl groups in 2-methyl-2-butene (Table 4.9).
In general, the terminal ⏤CH2 group has a lower
C3 H6 −2.9 C7 H14 28.4 13 C chemical shift than an internal ⏤CH⏤ group, and
C4 H8 22.4 C8 H16 26.9
(Z)⏤CH⏤CH⏤ 13 C chemical shifts are lower than those
C5 H10 25.6 C9 H18 26.1
of corresponding E groups. Calculations of approximate
C6 H12 26.9 C10 H20 25.3
shifts can be made from the following parameters, where
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4.7 CHEMICAL CLASSES AND CHEMICAL SHIFTS 207

TABLE 4.9 Alkene and Cycloalkene 13 C Chemical Shifts (ppm from TMS)

18.7 136.2 12.1

27.4 113.3 126.0
H 2C CH 2
123.2 115.9 13.4 140.2 124.6 17.6

13.7
132.7 123.2
13.7 36.1 114.3 14.0 133.3 17.9 14.0 31.4 138.7
29.4 12.6
22.6
22.3 138.5 14.0 20.5 12.3 25.8 123.7 22.4 33.7 114.5
137.2 124.0

13.7 35.3 125.1 131.2 14.4 131.3

CH 2 C CH 2
23.2 131.7 17.7 14.5 20.6 20.5 74.8 213.5

18.0
117.5 115.9 38.0 114.4 129.5 17.2 130.9 126.4
116.5 130.2 13.0

137.2 137.3 137.8 133.2 128.3

132.5 12.8
127.4 123.1

109.3 16.9 12.4 109.8 21.2 19.6 19.7

14.6
30.8 41.8 112.9
131.4 144.5 11.7 131.6
149.3 118.7 126.6
42.1
14.5 144.9 31.2
22.5 12.4 25.3 23.6 20.5 25.6

107.1
130.8 149.7 26.0 126.1 126.4 137.1
127.3 128.7
36.2 124.5 124.6 135.2 113.3
30.2 137.2 32.6
24.5 28.9 22.3 126.4
128.0
22.1 22.1 26.9 128.7

𝛼, 𝛽, and 𝛾 represent substituents on the same end of the Carbon atoms directly attached to a (Z) C⏤C group
double bond as the alkene carbon of interest, and 𝛼 ′ , 𝛽 ′ , and are more shielded than those attached to the stereoisomeric
𝛾 ′ represent substituents on the far side. (E) group by 4 to 6 ppm (Table 4.9). Alkene carbon atoms
in polyenes are treated as though they were alkane carbon
substituents on one of the double bonds. Thus, in calculating
𝛼 10.6 the shift of C-2 in 1,4-pentadiene, C-4 is treated like a 𝛽-sp3
𝛽 7.2 carbon atom.
𝛾 −1.5 Representative alkenes are presented in Table 4.9. There
𝛼′ −7.9 are no simple rules to handle polar substituents on an alkene
𝛽′ −1.8 carbon. The shifts for vinyl ethers can be rationalized using
𝛾′ −1.5 the following resonance structures
Z(cis) correction −1.1
H 2C C O CH 3 H 2C C O CH 3
H H
These parameters are added to 123.3 ppm, the shift for 84.2 153.2
ethylene. We can calculate the values of C-3 and C-2 for
as can the shifts for 𝛼, 𝛽-unsaturated ketones.
(Z)-3-methyl-2-pentene as follows:
O O
CH 3 H CH 3 H
H 3C CH 2 C C CH 3 H 3C CH 2 C C CH 3 129.3
5 4 3 2 1 5 4 3 2 1
150.7
𝛿3 = 123.3 + (10.6 × 2) + (7.2 × 1)
+ (−7.9 × 1) − 1.1 = 142.7 ppm The same rationalization applies to the proton shifts in
𝛿2 = 123.3 + (10.6 × 1) + (−7.9 × 2) these compounds. Shifts for several substituted alkenes are
presented in Table 4.10.
+ (−1.8 × 1) − 1.1 = 115.2 ppm
The chemical shift of the central carbon atom (⏤C⏤)
of alkyl-substituted allenes is about 200 ppm to 215 ppm,
The measured values are 137.2 ppm for C-3 and 116.8 whereas those of the terminal atoms (C⏤C⏤C) are about
ppm for C-2. The agreement is fair. 75 ppm to 97 ppm.
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208 CHAPTER 4 CARBON-13 NMR SPECTROSCOPY

13
TABLE 4.10 C Chemical Shifts of Substituted Alkenes (ppm from TMS)

126.1 122.0 84.8 176.0 153.2 136.4 O 107.7

Cl Br I OH O 55.1 CN
117.4 115.0 129.9 88.8 84.2 136.0 192.1 137.8 117.5

133.7 137.5 128.0 128.7 138.5

Cl OH 51.6 196.9
COOH COOCH3 C
117.5 45.1 114.9 63.4 131.9 173.2 129.9 166.7 129.3 26.3
O
166.5 20.2
15.3 17.9 12.6
Br H Br H COOCH3
104.7 132.7 108.9 129.4 144.1 122.3 142.9 124.4
52.0 141.7 C 167.6
O O
H CH3 H H H COOCH3 H H 96.4
18.2 167.0 51.3

O O O O
210.4 199.7 152.5
207.1 208.0 128.6
34.0 134.4 38.1 129.8 134.1
193.4
27.0 9.3 46.6 129.1 128.5 131.2
25.7 150.9 O
29.0 165.2
22.8

4.7.3 Alkynes Phenanthrene: C-1, 128.3; C-2, 126.3; C-3, 126.3; C-4,
122.2; C-4a, 131.9∗ ; C-9, 126.6; C-10a, 130.1 ppm.*
The 13 C chemical shifts of alkynes substituted only by
alkyl groups range from approximately 65 ppm to 90 ppm Shifts of the aromatic carbon atom directly attached to
(Table 4.11). The triple bond shields the directly attached the substituent have been correlated with substituent elec-
sp3 carbon atoms by about 5 ppm to 15 ppm relative to the tronegativity after correcting for magnetic anisotropy effects;
corresponding alkane. The 13 C chemical shifts of terminal shifts at the para aromatic carbon have been correlated with
⏤
⏤CH are lower than those of internal ⏤ ⏤CR groups. Alkyne the Hammett 𝜎 constant. Ortho shifts are not readily pre-
carbon atoms to which a polar group is directly bonded have dictable and range over about 15 ppm. Meta shifts are gener-
chemical shifts of about 20 ppm to 95 ppm. ally up to several ppm for a single substituent.
Polar resonance structures may be used to rationalize The resonances due to substituted aromatic carbon
these shifts for alkynyl ethers, which are analogous to the atoms can be distinguished from those due to protonated
shifts for vinyl ethers (Section 3.4). aromatic carbon atoms by the lower integrated intensities of
the former; that is, they lack directly bonded protons and thus
23.2 89.4 28.0 88.4
HC C O H 3C C C O
suffer from a longer T1 and a diminished NOE.
Incremental shifts from the carbon atoms of benzene
H 2C CH 3 CH 3
for the aromatic carbon atoms of representative monosub-
stituted benzene rings (and shifts from TMS of carbon-
4.7.4 Aromatic Compounds containing substituents) are given in Table 4.12. Shifts from
benzene for polysubstituted benzene ring carbon atoms
Benzene carbon atoms resonate at 128.5 ppm, neat or as a can be approximated by applying the principle of incre-
solution in CDCl3 . Substituents shift the attached aromatic ment additivity. For example, the shift from benzene for
carbon atom as much as ±35 ppm. Fused-ring chemical C-2 of the disubstituted compound 4-chlorobenzonitrile is
shifts are as follows:
CN CN
1 1 4
TABLE 4-11 Alkyne 13 C Chemical Shifts (ppm) 3
2 2
Compound C-1 C-2 C-3 C-4 C-5 C-6
+
3 3 2
4 1
1-Butyne 71.9 86.0 12.3 13.8
2-Butyne 3.3 73.6 Cl Cl
1-Hexyne 68.1 84.5 18.1 30.7 21.9 13.5 I II III
2-Hexyne 2.7 73.7 76.9 19.6 21.6 12.1 C# Cal Obs C # Obs C # Obs
3-Hexyne 15.4 13.0 80.9 1 –18.0 –16.6 1 –16.0 4 –2.0
2 4.6 5.1 2 3.6 3 1.0
3 0.8 1.3 3 0.6 2 0.2
Naphthalene: C-1, 128.1; C-2, 125.9; C-4a, 133.7 ppm. 4 10.7 10.8 4 4.3 1 6.4
Anthracene: C-1, 130.1; C-2, 125.4; C-4a, 132.2;
* Assignment uncertain.
C-9, 132.6 ppm.
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4.7 CHEMICAL CLASSES AND CHEMICAL SHIFTS 209

TABLE 4.12 Incremental Shifts for the Aromatic Carbon Atoms of Monosubstituted Benzenes (ppm from benzene at 128.5 ppm). 13 C
Chemical Shifts of Substituents in ppm from TMSa

C-1 C of Substituent
Substituent (Attachment) C-2 C-3 C-4 (ppm from TMS)

H 0.0 0.0 0.0 0.0

CH3 9.3 0.7 −0.1 −2.9 21.3
CH2 CH3 15.6 −0.5 0.0 −2.6 29.2 (CH2 ), 15.8 (CH3 )
CH(CH3 )2 20.1 −2.0 0.0 −2.5 34.4 (CH), 24.1 (CH3 )
C(CH3 )3 22.2 −3.4 −0.4 −3.1 34.5 (C), 31.4 (CH3 )
CH⏤CH2 9.1 −2.4 0.2 −0.5 137.1 (CH), 113.3 (CH2 )
C⏤⏤CH −5.8 6.9 0.1 0.4 84.0 (C), 77.8 (CH)
C6 H5 12.1 −1.8 −0.1 −1.6
CH2 OH 13.3 −0.8 −0.6 −0.4 64.5
CH2 O(C⏤O)CH3 7.7 ∼0.0 ∼0.0 ∼0.0 20.7 (CH3 ), 66.1 (CH2 ), 170.5 (C⏤O)
OH 26.6 −12.7 1.6 −7.3
OCH3 31.4 −14.4 1.0 −7.7 54.1
OC6 H5 29.0 −9.4 1.6 −5.3
O(C⏤O)CH3 22.4 −7.1 −0.4 −3.2 23.9 (CH3 ), 169.7 (C⏤O)
(C⏤O)H 8.2 1.2 0.6 5.8 192
(C⏤O)CH3 7.8 −0.4 −0.4 2.8 24.6 (CH3 ), 195.7 (C⏤O)
(C⏤O)C6 H5 9.1 1.5 −0.2 3.8 196.4 (C⏤O)
(C⏤O)F3 −5.6 1.8 0.7 6.7
(C⏤O)OH 2.9 1.3 0.4 4.3 168
(C⏤O)OCH3 2.0 1.2 −0.1 4.8 51.0 (CH3 ), 166.8 (C⏤O)
(C⏤O)Cl 4.6 2.9 0.6 7.0 168.5
(C⏤O)NH2 5.0 −1.2 0.0 3.4
C⏤⏤N −16 3.6 0.6 4.3 119.5
NH2 19.2 −12.4 1.3 −9.5
N(CH3 )2 22.4 −15.7 0.8 −11.8 40.3
NH(C⏤O)CH3 11.1 −9.9 0.2 −5.6
NO2 19.6 −5.3 0.9 6.0
N⏤C⏤O 5.7 −3.6 1.2 −2.8 129.5
F 35.1 −14.3 0.9 −4.5
Cl 6.4 0.2 1.0 −2.0
Br −5.4 3.4 2.2 −1.0
I −32.2 9.9 2.6 −7.3
CF3 2.6 −3.1 0.4 3.4
SH 2.3 0.6 0.2 −3.3
SCH3 10.2 −1.8 0.4 −3.6 15.9
SO2 NH2 15.3 −2.9 0.4 3.3
Si(CH3 )3 13.4 4.4 −1.1 −1.1
a See Ewing, D.E. (1979). Org. Magn. Reson., 12, 499, for 709 chemical shifts of monosubstituted benzenes.

calculated by adding the effect for an ortho CN group (+3.6) ppm to 52 ppm for C-1, 5 ppm to 12 ppm for C-2, and up
to that for a meta Cl group (+1.0): 128.5 + 3.6 + 1.0 = to −6 ppm for C-3. Shifts for several acyclic and alicyclic
133.1 ppm. alcohols are given in Table 4.14. Acetylation provides a
useful diagnostic test for an alcohol. The C-1 chemical
4.7.5 Heteroaromatic Compounds shift increases by about 2.5 ppm to 4.5 ppm, and the C-2
Complex empirical rationalizations have been offered for chemical shift decreases by a similar amount; a 1,3-diaxial
the shifts of carbon atoms in heteroaromatic compounds. interaction may cause a slight (∼1 ppm) increase in shift for
As a general rule, the chemical shift of C-2 of oxygen- and C-3. Table 4.14 may be used to empirically predict shifts for
nitrogen-containing rings is higher than that for C-3. Large alcohols as described earlier.
solvent and pH effects have been recorded. Table 4.13 gives
values for neat samples of several five- and six-membered 4.7.7 Ethers, Acetals, and Epoxides
heterocyclic compounds.
An alkoxy substituent causes a somewhat larger shift at C-1
(∼11 ppm larger) than that of a hydroxy substituent. This is
4.7.6 Alcohols
attributed to the C-1′ of the alkoxy group having the same
Substitution of H in an alkane by an OH group changes the effect as a 𝛽-C relative to C-1. The O atom is regarded here
chemical shift of the directly bonded carbon atom by 35 as an “𝛼-C” to C-1.
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210 CHAPTER 4 CARBON-13 NMR SPECTROSCOPY

13
TABLE 4.13 C Chemical Shifts of Heteroaromatics (ppm from neat TMS)

Compound C-2 C-3 C-4 C-5 C-6 Substituent

Furan 142.7 109.6

2-Methylfuran 152.2 106.2 110.9 141.2 13.4
Furan-2-carboxaldehyde 153.3 121.7 112.9 148.5 178.2
Methyl 2-furoate 144.8 117.9 111.9 146.4 159.1 (C⏤O),
51.8 (CH3 )
Pyrrole 118.4 108.0
2-Methylpyrrole 127.2 105.9 108.1 116.7 12.4
Pyrrole-2-carboxaldehyde 134.0 123.0 112.0 129.0 178.9
Thiophene 124.4 126.2
2-Methylthiophene 139.0 124.7 126.4 122.6 14.8
Thiophene-2-carboxaldehyde 143.3 136.4 128.1 134.6 182.8
Thiazole 152.2 142.4 118.5
Imidazole 136.2 122.3 122.3
Pyridine 150.2 123.9 135.9
Pyrimidine 159.5 157.4 122.1 157.4
Pyrazine 145.6
2-Methylpyrazine 154.0 141.8a 143.8a 144.7a 21.6
a Assignment not certain.

The dioxygenated carbon of acetals resonates in the

2 1 1 range of about 88 ppm to 112 ppm. Oxirane (an epoxide) has
CH 3 CH 2 OH CH 3 CH 2 O CH 3 a 13 C chemical shift of 40.6 ppm.
17.6 57.0 14.7 67.9 57.6
The alkyl carbon atoms of arylalkyl ethers have shifts
similar to those of dialkyl ethers. Note the large shielding of
Note also that the “𝛾 effect” (decreased shift) on the ring ortho carbon.
C-2 is explainable by similar reasoning. Conversely, the 129.5 159.9
ethoxy group affects the OCH3 group (compare CH3 OH). 120.8 OCH 3
Table 4.15 gives 13 C chemical shifts of several ethers. 54.1
114.1

13
TABLE 4.14 C Chemical Shifts of Alcohols (ppm from TMS)

OH 10.0 63.6 13.6 35.0 OH

CH3OH 17.6 25.1
49.0 57.0 25.8 OH 63.4 19.1 61.4

OH
OH OH
68.7 13.8 28.2 61.8 14.0 41.6 23.3
9.9 9.8
OH 73.8
32.0 22.6 22.6 32.5 19.1 67.0 29.7

OH
OH
14.2 32.0 32.8 OH 13.9 28.3 67.2 39.4 30.3 18.9 68.9
14.0 72.3
22.8 25.8 61.9 22.9 39.2 23.3 19.4 9.9 30.8 OH
OH
31.1 26.3 72.6 22.5 OH 22.8 48.9 24.0
68.4 32.6
OH 41.8 72.0 24.8
OH 24.8 18.1 65.2
60.2
OH 35.1 19.7 OH

23.4 25.9 22.8

OH OH 37.1
33.7 35.0 24.4 29.3
42.2 67.9 OH
73.3 35.5 71.3
7.3 15.4 OH 69.5
OH
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4.7 CHEMICAL CLASSES AND CHEMICAL SHIFTS 211

13
TABLE 4.15 C Chemical Shifts of Ethers, Acetals, and Epoxides (ppm from TMS)
59.7 14.7 17.1 73.2 11.1 153.2
O O 52.5
O O O 84.2
67.9 57.6 67.4 24.0

24.9
O 26.5
33.1 14.6
O 27.7
O
68.4
71.2 20.3 40.6 22.9 72.6 69.5
O O

95.0 92.8
O O O
O O
O O 109.9 19.9 99.6
60.7
66.5 65.9
64.5 O O O 15.4
26.2
53.7

13
4.7.8 Halides TABLE 4.16 C Chemical Shifts of Alkyl Halides (neat, ppm
from TMS)
The effect of halide substitution is complex. A single flu-
orine atom (in CH3 F) causes a large increase in the 13 C Compound C-1 C-2 C-3
chemical shift relative to CH4 as electronegativity con-
CH4 −2.5
siderations would suggest. Successive geminal substitution CH3 F 75.4
by Cl (CH3 Cl, CH2 Cl2 , CHCl3 , CCl4 ) results in increasing CH3 Cl 24.9
shifts, again expected on the basis of electronegativity. CH2 Cl2 54.0
But with Br and I, the heavy atom effect prevails. The CHCl3 77.5
carbon resonances of CH3 Br and CH2 Br 2 become pro- CCl4 96.5
gressively more shielded. A strong deshielding of the 13 C CH3 Br 10.0
peaks due to directly bonded iodine commences with CH3 I, CH2 Br 2 21.4
which is shielded relative to CH4 . There is a progres- CHBr 3 12.1
sive deshielding of C-2 in the order I > Br > F. Cl and CBr 4 −28.5
Br show 𝛾-gauche shielding at C-3, but I does not, pre- CH3 I −20.7
CH2 I2 −54.0
sumably because of the low population of the hindered
CHI3 −139.9
gauche rotamer. Relativistic effects can also play a role in CI4 −292.5
determining the 13 C chemical shift when carbon is bonded CH3 CH2 F 79.3 14.6
to a heavy atom such as iodine. Table 4.16 shows these CH3 CH2 Cl 39.9 18.7
trends. These examples demonstrate clearly that simple elec- CH3 CH2 Br 28.3 20.3
tronegativity or electron density interpretations of chemical CH3 CH2 I −0.2 21.6
shifts can fail spectacularly and that caution must always CH3 CH2 CH2 Cl 46.7 26.5 11.5
be exercised when attempting to interpret shifts in this CH3 CH2 CH2 Br 35.7 26.8 13.2
manner. CH3 CH2 CH2 I 10.0 27.6 16.2
I I
H CH3 H H increases the shift at C-1. Chemical shifts for selected acyclic
and alicyclic amines are given in Table 4.17 (see Table 4.8
for heterocyclic amines).
H H H H
H CH3 4.7.10 Thiols, Sulfides, and Disulfides
gauche anti
Substitution with sulfur generally has less of an effect on
13 C chemical shifts than does substitution with oxygen.
Halides may show large solvent effects, for example,
C-1 for iodoethane is at −6.6 ppm in cyclohexane and at Examples of thiols, sulfides, and disulfides are given in
−0.4 ppm in DMF. Table 4.18.

4.7.9 Amines 4.7.11 Functional Groups

Containing Carbon
A terminal NH2 group attached to an alkyl chain causes a
deshielding of about 30 ppm at C-1, a deshielding of about Carbon-13 NMR spectroscopy permits direct observation
11 ppm at C-2, and a shielding of about 4.0 ppm at C-3. The of carbon-containing functional groups; the shift ranges
NH3 + group shows a somewhat smaller effect. N-alkylation for these are given in Appendix C. With the exception of
 Silverstein c04.tex V3 - 07/25/2014 6:26 P.M. Page 212

212 CHAPTER 4 CARBON-13 NMR SPECTROSCOPY

13
TABLE 4.17 C Chemical Shifts of Acyclic and Alicyclic Amines (in CDCl3 , ppm from TMS)
26.2
36.7 27.1 20.1 42.0
H3C NH2 NH2 47.5
NH2 42.8 NH2 N NH2
26.9 18.8 11.4 44.4 13.9 36.1

20.0 45.1 33.0 44.1

NH2 NH2 47.4
53.6 48.6 NH2 N
31.6 N 10.7 15.5
H
50.2
23.5 32.6
13.0
NH2
22.7 33.8 H 32.2 14.1 44.3 52.0 15.5 24.1
NH2 N
14.1 29.3 42.4 36.6 52.0 20.6 11.9
N 23.5 14.2 42.7
46.8
19.7
H
17.1 NH2
10.5
11.4 43.2 25.8 H 36.8 41.8 48.8
NH2 54.3 N
38.2 30.3 N
26.9 48.2
H2 N 40.3 22.7 28.3 60.6 20.7 15.7 23.1
H
18.6 29.9
NH2 NH2
32.1 54.7 8.7 41.0
35.3 52.3 49.5 55.0 N N
26.9 NH2 18.1 20.6
37.5
18.5 41.2 51.1 12.4

11.8 11.0
45.5 23.6
22.8 31.9 42.4 H 23.4
N N NH2
14.1 26.7 34.1 NH2 52.0 11.8
44.4
44.1

NH2
NH2 33.6 NH2 41.6 N 52.8
NH2 NH2
50.6 58.6 63.8 38.6
48.9 53.4
37.0 33.3 29.0
36.4 28.2
34.3 25.3 25.1 25.8
14.0 24.0 25.8 26.3 26.4 24.2

NH2 22.6 21.3 45.2

51.5 63.0 56.4
35.6 32.0 H 26.7 NH2 N N
117.3 116.9
46.0 50.7 42.4 46.0
23.8 NH2 H 136.0 136.2 46.7 11.8
34.5 25.1 33.8 20.0
27.6 36.7 34.7
25.6

CH⏤O, the presence of these groups could not be directly 4.7.11.1 Ketones and Aldehydes. The R2 C⏤O and the
ascertained by 1 H NMR. RCH⏤O carbon nuclei resonate in a characteristic region.
Acetone resonates at 203.3 ppm, and acetaldehyde at
TABLE 4.18 13 C Chemical Shifts of Thiols, Sulfides, and 199.3 ppm. Alkyl substitution on the 𝛼-carbon causes an
Disulfides (ppm from TMS) increase in the C⏤O chemical shift of 2 ppm to 3 ppm,
although steric effects can reverse this trend. Replacement
Compound C-1 C-2 C-3
of the CH3 of acetone or acetaldehyde by a phenyl group
CH3 SH 6.5 causes a deshielding of the C⏤O resonance (acetophenone,
CH3 CH2 SH 19.8 17.3 195.7 ppm; benzaldehyde, 190.7 ppm); similarly, 𝛼,𝛽-unsa-
CH3 CH2 CH2 SH 26.4 27.6 12.6 turation causes deshielding (acrolein, 192.1 ppm, compared
CH3 CH2 CH2 CH2 SH 23.7 35.7 21.0 with propionaldehyde, 201.5 ppm).
(CH3 )2 S 19.3 Of the cycloalkanones, cyclopentanone has a particu-
(CH3 CH2 )2 S 25.5 14.8 larly high 13 C chemical shift. Table 4.19 presents chemical
(CH3 CH2 CH2 )2 S 34.3 23.2 13.7
shifts of the C⏤O group of some ketones and aldehydes.
(CH3 CH2 CH2 CH2 )2 S 34.1 31.4 22.0
Because of rather large solvent effects, there are differences
CH3 SSCH3 22.0
CH3 CH2 SSCH2 CH3 32.8 14.5 of several ppm from different literature sources. Replace-
ment of CH2 of alkanes by C⏤O causes a deshielding of the
 Silverstein c04.tex V3 - 07/25/2014 6:26 P.M. Page 213

4.7 CHEMICAL CLASSES AND CHEMICAL SHIFTS 213

TABLE 4.19 13
C Chemical Shifts of the C⏤O Group and Other Carbon Atoms of Ketones and Aldehydes (ppm from TMS)
24.6 30.6
22.7
34.5
O 211.0 47.8 9.9 26.6 24.4
37.9
7.9
219.6 41.8 43.9
30.6 206.7 O 208.2 215.0
O O 209.7
O O
128.4 128.2 O O O
O 137.5
136.4
196.9
132.9 197.6 15.8 202.5
137.1 199.7 192.1 175.3
128.6 Cl 3C
O 30.7 13.8 45.9 O 136.0
26.3
129.5 128.5 H
O O O O O
192.4 O
134.2
136.4 203.5 206.9
O 30.9 24.8 192.6101.1 22.4 197.1 29.6 37.0
58.7
O O

TABLE 4.20 13 C Chemical Shifts of the C⏤O Group and other Carbon Atoms of Carboxylic Acids: Esters, Lactones, Chlorides
Anhydrides, Carbamates, and Nitriles (ppm from TMS)
178.1 168.0 O
H3C COOH Cl3C COOH 169.5
20.6 89.1 C 34.1 COOH 128.0
Cl 184.8
163.0 181.5
33.8 18.8 131.9 COOH
173.2
F3C COOH H3C COO Na
115.0 in D2O

NH2 O O
60.0 27.2 23.4 25.5 51.1
173.3 O
176.5 20.0 170.3 O 13.8 9.2 50.8 14.3
172.1 O
51.5 32.2 33.9
17.2 COOH O
O 129.9 O O 167.2 COOCH3
66.8 142.4 61.0 132.8 52.3
164.5 O
21.4 170.0 O 20.4 128.7 52.0 168.0 O F3C 158.1 O 14.1 135.0 39.5
20.8 97.4
O 114.1
132.8 133.0

166.0 COOCH 3 169.4 COOH

O 167.9 Cl
130.2 51.5 130.3 O O O O
129.9 130.3 133.3 8.4
131.4 O 167.3 170.3 O
128.7 128.7 20.2 27.1
133.1 134.0 129.1
135.4

O O 125.3 O O O O
131.1 177.9 171.2
28.4 171.7 136.7 164.3 136.1 NH2
165.5 27.7 O
O O O O 29.8 166.3
19.1 69.4
22.2 68.6
O O O 22.7

O 18.3 O O
31.1 O NH2 127.2 37.6 60.9
141.3 135.2
C NH2 N C 162.4
171.0 128.6 169.5 N H2N 157.8 O
25.5 174.3 14.5
O
36.2 H 124.0 129.8 127.2 37.6
128.6

18.8 118.7
H H H CN
C N 10.8 149.3 101.2 150.2 100.9 112.3
1.3 117.7 CN
10.6 H CN CN 132.0 132.7
120.8 117.6 17.3 116.0
129.1
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214 CHAPTER 4 CARBON-13 NMR SPECTROSCOPY

𝛼-carbon (∼10 – 14 ppm) and a shielding of the 𝛽-carbon substituents on the nitrogen of amides cause a small (up to
(several ppm in acyclic compounds). In a proton-coupled several ppm) shielding of the C⏤O group (see Table 4.20).
13 C NMR spectrum, the aldehyde CH⏤O resonance is a

doublet. 4.7.11.3 Oximes. The quaternary carbon atom of simple

oximes resonates in the range of 145 ppm to 165 ppm. It is
possible to distinguish between E and Z isomers since the
4.7.11.2 Carboxylic Acids, Esters, Chlorides, Anhy- C⏤O shift is smaller in the sterically more compressed E
drides, Amides, and Nitriles. Carbon-13 chemical shifts form, and the shift of the more hindered substituent (syn to
of the C⏤O groups of carboxylic acids and derivatives the OH) is less than that of the less hindered.
are in the range of 150 ppm to 185 ppm. Dilution and sol-
vent effects are marked for carboxylic acids; anions have HO OH
higher chemical shifts. The effects of substituents and elec- N N
11.00 9.8
tron delocalization are generally similar to those for ketones.
159.2 158.7
Nitriles resonate in the range of 115 ppm to 125 ppm. Alkyl 11.5 29.0 18.8 21.5

REFERENCES

For a list of Chapter References, please visit: www.wiley.com/college/silverstein.

STUDENT EXERCISES

4.1 For each compound given below (a – o), identify all chemically Cl Cl Cl
equivalent carbons. 13 13 13
4.2 For each compound below, predict the chemical shifts for each D C Cl D C Cl D C D
carbon. Give the source (Table or Appendix) that you use for Cl D D
your prediction.
4.3 Sketch the proton-decoupled 13 C NMR spectrum and DEPT 4.6 Interpret the following 13 C∕DEPT spectra (4.6A to 4.6F). Con-
spectra for each of the compounds in question 4.1. firm the structure and assign all the 13 C resonances. Give the
4.4 Confirm the structure and assign all the 13 C resonances in spec- source (Table or Appendix) that you use for your prediction.
tra A–W for the compounds whose structures were determined 4.7 What are the symmetry elements in ortho, meta, para-diethyl
in Problem 3.4 1 H NMR. They were all run at 75.5 MHz in phthalates? How many nonequivalent carbon atoms and hydro-
CDCl3 . The mass spectra were given in Chapter 1 (Question 1.6) gen atoms are there for each compound? Draw the proton-
and the IR spectra were given in Chapter 2 (Question 2.9). decoupled 13 C spectrum and DEPT spectra for each compound.
4.5 Predict the number of lines in 13 C spectra for the following com- The workbook of Forrest et al. (2011) provides numerous addi-
pounds: tional exercises.

OH O
Br
H
OAc
a b c d e

O
S
O N O O O OH S
H
f g h i j

O O
H H OAc
N Cl H
O H
OH F
k l m n o
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Exercise 4.4 (A – C) STUDENT EXERCISES 215

Problem 4.4 A

200 180 160 140 120 100 80 60 40 20 ppm

Problem 4.4 B

85 80 75 70 65 60 55 50 45 40 35 30 25 20 15 10 ppm

Problem 4.4 C

131 ppm

140 130 120 110 100 90 80 70 60 50 40 30 20 10 ppm

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216 CHAPTER 4 CARBON-13 NMR SPECTROSCOPY Exercise 4.4 (D – F)

Problem 4.4 D

95 90 85 80 75 70 65 60 55 50 45 40 35 30 25 20 15 10 ppm

Problem 4.4 E

200 180 160 140 120 100 80 60 40 20 ppm

Problem 4.4 F

180 160 140 120 100 80 60 40 20 ppm

 Silverstein c04.tex V3 - 07/25/2014 6:26 P.M. Page 217

Exercise 4.4 (G – I) STUDENT EXERCISES 217

Problem 4.4 G

95 90 85 80 75 70 65 60 55 50 45 40 35 30 25 20 15 10 ppm

Problem 4.4 H

95 90 85 80 75 70 65 60 55 50 45 40 35 30 25 20 15 10 ppm

Problem 4.4 I

77.5 77.0 ppm

95 90 85 80 75 70 65 60 55 50 45 40 35 30 25 20 15 10 ppm
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218 CHAPTER 4 CARBON-13 NMR SPECTROSCOPY Exercise 4.4 (J – L)

Problem 4.4 J

170 160 150 140 130 120 110 100 90 80 70 60 ppm

Problem 4.4 K

160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 ppm

Problem 4.4 L

170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 ppm

 Silverstein c04.tex V3 - 07/25/2014 6:26 P.M. Page 219

Exercise 4.4 (M – O) STUDENT EXERCISES 219

Problem 4.4 M

180 160 140 120 100 80 60 40 20 ppm

Problem 4.4 N

150 140 130 120 110 100 90 80 70 60 50 40 30 20 ppm

Problem 4.4 O

170 160 150 140 130 120 110 100 90 80 70 60 ppm

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220 CHAPTER 4 CARBON-13 NMR SPECTROSCOPY Exercise 4.4 (P – R)

Problem 4.4 P

148 146 144 ppm

155 150 145 140 135 130 125 120 115 110 105 100 95 90 85 80 ppm

Problem 4.4 Q

180 160 140 120 100 80 60 40 20 ppm

Problem 4.4 R

85 80 75 70 65 60 55 50 45 40 35 30 25 20 15 10 ppm
 Silverstein c04.tex V3 - 07/25/2014 6:26 P.M. Page 221

Exercise 4.4 (S – U) STUDENT EXERCISES 221

Problem 4.4 S

200 180 160 140 120 100 80 60 40 20 ppm

Problem 4.4 T

180 160 140 120 100 80 60 40 20 ppm

Problem 4.4 U

121.2 ppm

155 150 145 140 135 130 125 120 115 110 105 100 95 90 85 80 ppm
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222 CHAPTER 4 CARBON-13 NMR SPECTROSCOPY Exercise 4.4 (V – W)

Problem 4.4 V

150 140 130 120 110 100 90 80 70 60 50 40 30 20 ppm

Problem 4.4 W

200 180 160 140 120 100 80 60 40 20 ppm

 Silverstein c04.tex V3 - 07/25/2014 6:26 P.M. Page 223

Exercise 4.6 (A – C) STUDENT EXERCISES 223

Problem 4.6 A
C5H10Br2

75 70 65 60 55 50 45 40 35 30 25 20 15 10 5 ppm

Problem 4.6 B
C8H8O2

132 130 128 ppm

170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 ppm

Problem 4.6 C
C12H27N

75 70 65 60 55 50 45 40 35 30 25 20 15 10 5 ppm
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224 CHAPTER 4 CARBON-13 NMR SPECTROSCOPY Exercise 4.6 (D – F)

Problem 4.6 D
C16H22O4

170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 ppm

Problem 4.6 E
C7H12O

200 180 160 140 120 100 80 60 40 20 ppm

Problem 4.6 F
C8H14O

82 80 78 ppm

85 80 75 70 65 60 55 50 45 40 35 30 25 20 15 10 ppm
 Silverstein c04.tex V3 - 07/25/2014 6:26 P.M. Page 225

APPENDIX A 225

THE 13 C CHEMICAL SHIFTS, COUPLING CONSTANTS, AND PEAK

APPENDIX A MULTIPLICITIES OF COMMON DEUTERATED NMR SOLVENTS

Formula Name 𝜹 (ppm) J𝐂−𝐃 (Hz) Multiplicity𝐚

CDCl3 Chloroform-d1 77.0 32 Triplet

CD3 OD Methanol-d4 49.0 21.5 Septet
CD3 SOCD3 DMSO-d6 39.7 21 Septet
O
DCN(CD3) 2 DMF-d7 30.1 21 Septet
35.2 21 Septet
167.7 30 Triplet
C6 D6 Benzene-d6 128.0 24 Triplet
D 2C CD2
D2C CD2
O THF-d8 25.2 20.5 Quintet
67.4 22 Quintet
O
D2C CD2

D2C CD2
O Dioxane-d8 66.5 22 Quintet
D
D D

D N D Pyridine-d5 123.5 (C-3,5) 25 Triplet

135.5 (C-4) 24.5 Triplet
149.2 (C-2,6) 27.5 Triplet
O
29.8 (methyl) 20 Septet
CD 3CCD3 Acetone-d6 206.5 (carbonyl) <1 Septetb
CD3 CN Acetonitrile-d3 1.3 (methyl) 32 Septet
118.2 (CN) <1 Septetb
CD3 NO2 Nitromethane-d3 60.5 23.5 Septet
CD3 CD2 OD Ethanol-d6 15.8 (C-2) 19.5 Septet
55.4 (C-1) 22 Quintet
(CD3 CD2 )2 O Ether-d10 13.4 (C-2) 19 Septet
64.3 (C-1) 21 Quintet
[(CD3 )2 N]3 P⏤O HMPA-d18 35.8 21 Septet
CD3 CO2 D Acetic acid-d4 20.2 (C-2) 20 Septet
178.4 (C-1) <1 Septetb
CD2 Cl2 Dichloromethane-d2 53.1 29 Quintet
(Methylene chloride-d2 )
a Triplet intensities = 1∶1∶1, quintet = 1∶2∶3∶2∶1, septet = 1∶3∶6∶7∶6∶3∶1.
b Unresolved, long-range coupling.
Source: Breitmaier, and Voelter (1987) p. 109; used with permission. Also Merck & Co., Inc.
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226 CHAPTER 4 CARBON-13 NMR SPECTROSCOPY

13
C CHEMICAL SHIFTS OF COMMON LABORATORY SOLVENTS AS
APPENDIX B TRACE IMPURITIES IN SELECTED DEUTERATED NMR SOLVENTS

CDCl3 (CD3 )2 CO (CD3 )2 SO C6 D6 CD3 CN CD3 OD D2 O

Solvent signals 77.16 ± 0.06 29.84 ± 0.01 39.52 ± 0.06 128.06 ± 0.02 1.32 ± 0.02 49.00 ± 0.01
206.26 ± 0.13 118.26 ± 0.02
Acetic acid CO 175.99 172.31 171.93 175.82 173.21 175.11 177.21
CH3 20.81 20.51 20.95 20.37 20.73 20.56 21.03
Acetone CO 207.07 205.87 206.31 204.43 207.43 209.67 215.94
CH3 30.92 30.60 30.56 30.14 30.91 30.67 30.89
Acetonitrile CN 116.43 117.60 117.91 116.02 118.26 118.06 119.68
CH3 1.89 1.12 1.03 0.20 1.79 0.85 1.47
Benzene CH 128.37 129.15 128.30 128.62 129.32 129.34
tert-Butyl alcohol C 69.15 68.13 66.88 68.19 68.74 69.40 70.36
CH3 31.25 30.72 30.38 30.47 30.68 30.91 30.29
tert-Butyl methyl OCH3 49.45 49.35 48.70 49.19 49.52 49.66 49.37
Ether C 72.87 72.81 72.04 72.40 73.17 74.32 75.62
CCH3 26.99 27.24 26.79 27.09 27.28 27.22 26.60
BHT C(1) 151.55 152.51 151.47 152.05 152.42 152.85
C(2) 135.87 138.19 139.12 136.08 138.13 139.09
CH(3) 125.55 129.05 127.97 128.52 129.61 129.49
C(4) 128.27 126.03 124.85 125.83 126.38 126.11
CH3 Ar 21.20 21.31 20.97 21.40 21.23 21.38
CH3 C 30.33 31.61 31.25 31.34 31.50 31.15
C 34.25 35.00 34.33 34.35 35.05 35.36
Chloroform CH 77.36 79.19 79.16 77.79 79.17 79.44
Cyclohexane CH2 26.94 27.51 26.33 27.23 27.63 27.96
1,2-Dichloroethane CH2 43.50 45.25 45.02 43.59 45.54 45.11
Dichloromethane CH2 53.52 54.95 54.84 53.46 55.32 54.78
Diethyl ether CH3 15.20 15.78 15.12 15.46 15.63 15.46 14.77
CH2 65.91 66.12 62.05 65.94 66.32 66.88 66.42
Diglyme CH3 59.01 58.77 57.98 58.66 58.90 59.06 58.67
CH2 70.51 71.03 69.54 70.87 70.99 71.33 70.05
CH2 71.90 72.63 71.25 72.35 72.63 72.92 71.63
1,2-Dimethoxyethane CH3 59.08 58.45 58.01 58.68 58.89 59.06 58.67
CH2 71.84 72.47 71.17 72.21 72.47 72.72 71.49
Dimethylacetamide CH3 21.53 21.51 21.29 21.16 21.76 21.32 21.09
CO 171.07 170.61 169.54 169.95 171.31 173.32 174.57
NCH3 35.28 34.89 37.38 34.67 35.17 35.50 35.03
NCH3 38.13 37.92 34.42 37.03 38.26 38.43 38.76
Dimethylformamide CH 162.62 162.79 162.29 162.13 163.31 164.73 165.53
CH3 36.50 36.15 35.73 35.25 36.57 36.89 37.54
CH3 31.45 31.03 30.73 30.72 31.32 31.61 32.03
Dimethyl sulfoxide CH3 40.76 41.23 40.45 40.03 41.31 40.45 39.39
Dioxane CH2 67.14 67.60 66.36 67.16 67.72 68.11 67.19
Ethanol CH3 18.41 18.89 18.51 18.72 18.80 18.40 17.47
CH2 58.28 57.72 56.07 57.86 57.96 58.26 58.05
Ethyl acetate CH3 CO 21.04 20.83 20.68 20.56 21.16 20.88 21.15
CO 171.36 170.96 170.31 170.44 171.68 172.89 175.26
CH2 60.49 60.56 59.74 60.21 60.98 61.50 62.32
CH3 14.19 14.50 14.40 14.19 14.54 14.49 13.92
Ethyl methyl ketone CH3 CO 29.49 29.30 29.26 28.56 29.60 29.39 29.49
CO 209.56 208.30 208.72 206.55 209.88 212.16 218.43
CH2 CH3 36.89 36.75 35.83 36.36 37.09 37.34 37.27
CH2 CH3 7.86 8.03 7.61 7.91 8.14 8.09 7.87
Ethylene glycol CH2 63.79 64.26 62.76 64.34 64.22 64.30 63.17
“Grease” CH2 29.76 30.73 29.20 30.21 30.86 31.29
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APPENDIX C 227

APPENDIX B (Continued)

n-Hexane CH3 14.14 14.34 13.88 14.32 14.43 14.45

CH2 (2) 22.70 23.28 22.05 23.04 23.40 23.68
CH2 (3) 31.64 32.30 30.95 31.96 32.36 32.73
HMPA CH3 36.87 37.04 36.42 36.88 37.10 37.00 36.46
Methanol CH3 50.41 49.77 48.59 49.97 49.90 49.86 49.50
Nitromethane CH3 62.50 63.21 63.28 61.16 63.66 63.08 63.22
n-Pentane CH3 14.08 14.29 13.28 14.25 14.37 14.39
CH2 (2) 22.38 22.98 21.70 22.72 23.08 23.38
CH2 (3) 34.16 34.83 33.48 34.45 34.89 35.30
2-Propanol CH3 25.14 25.67 25.43 25.18 25.55 25.27 24.38
CH 64.50 63.85 64.92 64.23 64.30 64.71 64.88
Pyridine CH(2) 149.90 150.67 149.58 150.27 150.76 150.07 149.18
CH(3) 123.75 124.57 123.84 123.58 127.76 125.53 125.12
CH(4) 135.96 136.56 136.05 135.28 136.89 138.35 138.27
Silicone grease CH3 1.04 1.40 1.38 2.10
Tetrahydrofuran CH2 25.62 26.15 25.14 25.72 26.27 26.48 25.67
CH2 O 67.97 68.07 67.03 67.80 68.33 68.83 68.68
Toluene CH3 21.46 21.46 20.99 21.10 21.50 21.50
C(i) 137.89 138.48 137.35 137.91 138.90 138.85
CH(o) 129.07 129.76 128.88 129.33 129.94 129.91
CH(m) 128.26 129.03 128.18 128.56 129.23 129.20
CH(p) 125.33 126.12 125.29 125.68 126.28 126.29
Triethylamine CH3 11.61 12.49 11.74 12.35 12.38 11.09 9.07
CH2 46.25 47.07 45.74 46.77 47.10 46.96 47.19

13
APPENDIX C C CHEMICAL SHIFT RANGES FOR CHEMICAL CLASSES
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228 CHAPTER 4 CARBON-13 NMR SPECTROSCOPY

APPENDIX C (Continued)
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APPENDIX D 229

13
APPENDIX D C CHEMICAL SHIFTS (ppm) FOR SEVERAL NATURAL PRODUCTS

112.9 16.0 27.2 24.4

145.9 137.2 58.7 72.7 162.1
30.8 139.0 39.7 OH 41.2 145.0 32.5 128.7
124.5 OH
26.1 115.5 26.6 22.6 111.3 27.2 CHO 189.4
124.9 124.6 123.1
124.4
131.0 131.2 130.3 132.9
17.1 25.1 17.4 25.5 17.5 25.3 17.4 25.3
Myrcene Geraniol Linalool cis-Citral
(Neral, Citral b)

23.8 22.2 23.1 21.7 22.1

133.2 131.5 132.9 31.4 31.6
120.8 30.9 119.6 28.5 120.7 30.9 32.9 50.7 34.8 44.9
201.1 71.3
30.6 28.0 116.5 24.8 25.9 23.6 28.5 23.0
41.2 140.9 44.6 131.7
O 49.9
OH
149.7 34.0 71.9 OH 140.8 25.6
20.5 108.4 20.6 26.7 27.1 22.7 21.8 20.9 15.9
Limonene -Terpinene -Terpineol Pulegone Menthol

20.0 19.5
38.7 26.4 22.8 26.1 21.8
46.6
43.2 38.0 40.5
27.4 31.3 23.6
57.0 43.2 40.9 116.1 40.5 23.6
30.1 214.7 31.5 47.2 144.5 27.0 51.9 151.8
36.9 9.7
30.1 O 23.0 105.9
Norbornane Camphor -Pinene -Pinene

18.8
CH 3
35.8 36.4
12.0
CH 3 24.1
28.3 56.5
21.2 22.5
19.4 40.0 39.6
27.0 140.7
O 42.4 22.8
195.5 37.5 CH 3 50.5 56.9 28.0
32.6 134.7 32.3 24.3
38.4 25.2 31.6 36.5
130.7
133.4 71.3 141.2 H
17.5 HO 32.0
31.8 19.7 42.4 121.3
-Ionone Cholesterol

41.4
171.6 51.5
CH 3 N
35.2 22.6 CO 2CH 3
134.9 62.1
68.9 50.8 62.5
57.0 OH
123.6 138.9 N 71.3
35.9 O O
149.5 25.8 167.1 HO
148.5 77.4
CH 3 40.3 65.4
N OC 133.6 71.5
130.5 HO OH
25.8 67.5 129.1
131.0 77.5 OH 97.4

Nicotine Cocaine - D -Glucose

O
165.2
100.9 NH
143.0 152.7
N O
H
Uracil
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CHAPTER 5
TWO-DIMENSIONAL NMR
SPECTROSCOPY

5.1 INTRODUCTION compounds can sometimes be difficult to interpret using

simple one-dimensional 1 H and 13 C NMR spectra.
Chapters 3 and 4 (familiarity with which is assumed) pro- In this chapter, using these four compounds as examples,
vide us with powerful techniques and methods to elucidate we turn our attention to correlation NMR spectroscopy; most
the structures of organic compounds, especially when com- (but not all) of the useful experiments fall into the category
bined with information derived from IR and mass spec- of two-dimensional NMR. Our approach in this chapter is
trometry. These NMR methods are collectively referred to to present the spectra for each compound independently as a
as one-dimensional techniques. To extend our capabilities, logical set. Most of the general aspects of each experiment
we turn once more to NMR. We will use four compounds are given in the discussion of ipsenol; others are only
as examples: ipsenol (see Chapter 3), caryophyllene oxide introduced with the more complicated compounds. The
(a sesquiterpene epoxide), lactose (a 𝛽-linked disaccha- material for ipsenol should be thoroughly covered first. The
ride), and a small peptide (valine-glycine-serine-glutamate, other compounds can be covered independently.
VGSE). The structures of these compounds are shown in Correlation in NMR is not a new concept to us. For
Figure 5.1. instance, the 1 H NMR spectrum of ethylbenzene (Figure
These compounds provide a rich variety of structural 3.24) shows a clean triplet and quartet for the methyl
types and features. The two terpenoids possess the typical and methylene groups, respectively. These two groups are
branched carbon skeletons of isoprenoids; both compounds correlated to each other because the spins within each group
have diastereotopic methylene and methyl groups. Lactose are coupled to the spins within the other group. First-
is a 𝛽-1,4-linked disaccharide of galactose and glucose; order rules helped us to interpret these interactions among
glucose is the reducing residue, which at equilibrium in neighboring nuclei. Coupling among protons is only one type
aqueous solution shows both anomers. The tetrapeptide, of correlation that we will be considering.
VGSE, contains four different amino acid residues and is a We did a reasonable job interpreting the relationship
reasonable model for some of the spectroscopic properties between the structure of ipsenol and its 1 H NMR spectra
of a small protein. The NMR signals associated with these in Chapter 3; however, better, less ambiguous information

OH

CH2 C O
CH3 OH CH2
H CH C H3 CH2 CH2
CH2
HO H2 N CH C N CH2C N CH C N CH C OH
H H H
H3C CH3 O O O O
Ipsenol Valine (V) Glycine (G) Serine (S) Glutamate (E)
Tetrapeptide VGSE

HO OH
H3C H H
CH3 O H OH
H H
H3C O H O
HO O
OH HO H OH
H H
H OH
CH2 H H
Caryophyllene oxide Lactose β-anomer

FIGURE 5.1 Structures of the four compounds used as examples in this chapter.
230
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5.2 THEORY 231

can be obtained more quickly with two-dimensional NMR by irradiating the protons during the experiment; that is, the
correlation spectroscopy. On the other hand, caryophyllene proton decoupler is turned on during the entire experiment.
oxide, lactose, and VGSE are too complex to fully analyze In other experiments, the decoupler for a given nucleus can
using one-dimensional 1 H and 13 C NMR alone. Before turn- be turned on and off to coincide with pulses and delays in
ing our attention to the description of specific experiments another channel (i.e., for another nucleus). This process is
and their interpretation, we will first take a closer look at termed gated decoupling. (See Sections 4.2.5 and 4.4.)
radiofrequency pulse sequences and Fourier transformation. It is worthwhile to review here (see Chapters 3 and 4)
what is happening to the net magnetization vector, 𝐌𝟎 ,
during this pulse sequence. In a frame of reference rotating
5.2 THEORY at the Larmor frequency, 𝐌𝟎 is stationary on the z-axis
(equilibration period in Figure 5.2). A 𝜋∕2 (𝜃, 90∘ ) pulse
We recall that in order to obtain a routine 1 H or 13 C brings 𝐌𝟎 onto the y-axis; when viewed in this rotating
NMR spectrum, the pulse sequence (Figure 5.2) involves an frame, the magnetization vector appears to remain stationary
equilibration in the magnetic field, an rf pulse, and signal after the pulse, although the component of the vector along
acquisition. This sequence is repeated until a satisfactory the y-axis is decreasing with time (T1 and T2 relaxation).
signal/noise ratio is obtained; Fourier transformation of the Returning for a moment to the static laboratory frame,
FID results in the familiar frequency-domain spectrum. we see that the net magnetization vector is actually not
Figure 5.2 reveals a number of interesting features. We static; it is rotating in the xy-plane about the z-axis at the
note that there is a separate line for the 1 H channel and one Larmor frequency. This rotating magnetization generates an
for the 13 C channel. These channels represent the hardware rf signal that is detected as an FID in an NMR experiment.
associated with the irradiation and signal acquisition of each The net magnetization vector soon returns to the z-axis,
relevant nucleus in our experiments. Following equilibration, relaxation is complete, and the sequence can be repeated.
the pulse sequence used to obtain a one-dimensional (1D) In this example, the detector records the component of the
proton NMR spectrum consists of a (𝜋∕2)x pulse, delay, and magnetization which lies along the y-axis. In a simple one-
signal acquisition of the order of seconds (Figure 5.2a). We pulse experiment, a 𝜋∕2 pulse is used because it produces
also notice that the 13 C channel (not shown) is inactive dur- the strongest signal.* A pulse (𝜃) less than (or greater than)
ing a simple proton experiment. Normally, we will not show 𝜋∕2 leaves some of the possible signal on the z (or −z) -
a given channel unless there is some activity in that channel. axis; only the component of the vector on the y-axis generates
Shown in Figure 5.2b is the pulse sequence for a 1D a signal.
13 C NMR experiment. The sequence in the 13 C channel
We now consider multiple-pulse experiments and two-
is exactly the same as the sequence in the 1 H channel in dimensional (2D) NMR. Exactly what does the term “dimen-
Figure 5.2a. The protons are decoupled from the 13 C nuclei sion” in NMR mean? The familiar proton spectrum is a plot
of frequency versus intensity—obviously two dimensions
but called a “1D” NMR experiment, the relevant dimension
(a) being the frequency axis. It is important to remember that the
θ frequency axis, with which we are comfortable, is derived
Relaxation Acquire (t) from the time axis (the acquisition time) of the FID through
delay (Rd) the mathematical process of Fourier transformation. Thus,
1
H: experimentally, the variable of the abscissa of a 1D experi-
ment is in time units.
The so-called 2D NMR spectrum is actually a three-
dimensional plot; the omitted dimension when describing all
NMR experiments (1D, 2D, 3D, etc.) is the intensity. The
(b)
two dimensions referred to in a 2D NMR spectrum are the
1 Decoupler on two frequency axes. It requires two Fourier transformations
H: at right angles to each other on two independent time axes to
Relaxation
θ arrive at two orthogonal frequency axes.
Acquire (t) When the simple one-pulse experiment is again consid-
delay (Rd) ered, there is only one time variable that affects the spec-
13
C: trum, namely the acquisition time, t. We now consider a
multiple-pulse sequence in which the equilibration period
is followed by two pulses with an intervening time inter-
FIGURE 5.2 (a) Pulse sequence for a standard one- val, the final pulse being the 𝜋∕2 acquisition pulse. Thus,
dimensional 1 H NMR spectrum. (b) Pulse sequence we have inserted an “evolution” period between the pulses.
for a standard (proton-decoupled) 13 C NMR
spectrum. 𝜃 is normally a (𝜋∕2)x pulse along the * This is true in the absence of relaxation considerations. The Ernst angle
x-axis. Rd (known as the relaxation delay) is an (cos 𝜃 = exp(−Tr ∕T1 )) may be used to determine the repetition time (Tr )
equilibration period in the magnetic field before and pulse angle (𝜃) to optimize S/N; the angle thus determined is less than
the pulse. 90∘ , e.g., ∼45∘ .
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232 CHAPTER 5 TWO-DIMENSIONAL NMR SPECTROSCOPY

If we now systematically increase this evolution time interval (for now) of spin-spin coupling. In Figure 5.4, we see that,
(t1 ) over many different 1D experiments and collect the after the first 𝜋∕2 pulse along the x-axis, the magnetization
resulting FIDs into one overall dataset, we have the basis for 𝐌𝟎 has rotated onto the y-axis (the magnetization is now
a 2D NMR spectrum. For example, t1 is increased 15 times, labeled 𝐌). The evolution of M for the equivalent protons
meaning that 16 FIDs will have been recorded, each with of acetone during t1 is shown in a rotating frame. In
a different t1 value. Sequential Fourier transformation of this treatment, we ignore spin-lattice relaxation but include
each of these FIDs yields a set of one-dimensional spectra transverse relaxation with time constant T2 . If the Larmor
whose peak intensities vary sinusoidally from one spectrum frequency (𝜈2 ) is at higher frequency than that of the rotating
to the next (see Figure 5.5). This first series of Fourier frame, M precesses clockwise in the xy plane during the time
transformations results in what is labeled as the second interval t1 through the angle 2𝜋𝜈t1 . From trigonometry, the
frequency axis, 𝜈2 , derived from the acquisition time, t2 , of y component of M is 𝐌 cos(2𝜋𝜈t1 ), and the x component is
each FID. The data are now turned by 90∘ , and a second 𝐌 sin(2𝜋𝜈t1 ).
Fourier transformation is carried out at right angles to After time t1 , the acquisition pulse (𝜋∕2)x rotates the y
the first series of transformations. This second series of component of M downward onto the −z-axis; this component
Fourier transformations results in what is labeled as the first therefore contributes no signal to the FID acquired during t2 .
frequency axis, 𝜈1 , a function of the evolution time, t1 , which The x component, on the other hand, remains unchanged (in
we recall was incremented in the pulse sequence for each the xy-plane) and this magnetization is recorded as the FID.
successive FID acquired in t2 . When this FID is Fourier transformed, it gives a peak with
A simple prototype of a 2D experiment should clarify frequency 𝜈2 and amplitude 𝐌 sin(2𝜋𝜈t1 ). If we repeat this
some of these ideas while serving as a template for other experiment many times (e.g., 1024), each time increasing t1
more useful 2D experiments. In this simple case, the pulse in a regular way, we obtain 1024 FIDs. Successive Fourier
sequence (Figure 5.3) consists of a relaxation delay (Rd ), a transformation of each of these FIDs gives a series of 1D
𝜋∕2 pulse, a variable time interval (t1 , the evolution period), spectra each with a single peak of frequency 𝜈2 and amplitude
a second 𝜋∕2 acquisition pulse, and acquisition (t2 ). This 𝐌 sin(2𝜋𝜈t1 ). In Figure 5.5a, 22 of the 1024 spectra are
pulse sequence (individual experiment) is repeated a number plotted; we see that the amplitude of the acetone peak varies
of times (each time resulting in a separate FID) with an sinusoidally as a function of t1 . We have now established
increased t1 interval. one of the frequency axes (𝜈2 ) for our prototypical 2D NMR
We choose for this experiment a simple compound, spectrum.
acetone (CH3 ⏤(C⏤O)⏤CH3 ), to avoid the complication Before we establish our second axis, let us do a little
bookkeeping. Remember that each of these spectra that we
now have is actually a digitized collection of points. Let
(π/2)x (π/2)x Acquire (t2) us assume that each of these 1024 spectra is composed
Rd t1 of 1024 data points. Thus, we have a square matrix of
data. If we mentally rotate this collection of spectra, we
can perform a second series of Fourier transformations on
the data orthogonal to the first. Before we perform these
FIGURE 5.3 Traditional prototypical pulse sequence for two-
transformations though, let us take a closer look at the data
dimensional NMR. Data associated with the incremental delay, in Figure 5.5a.
t1 , and the acquisition time, t2 , are Fourier transformed into By physically rotating the spectra of Figure 5.5a so that
frequencies 𝜈1 and 𝜈2 , respectively. (𝜋∕2)x represents a 90∘ pulse we are looking along the 𝜈2 axis, the data appear as the
along the x-axis. The interval t1 is of the order of microseconds to projections shown in Figure 5.5b. Small circles are drawn at
milliseconds; t2 is of the order of seconds. the maxima of the first seven rows of data of Figure 5.5a.

z z z z
M0

y y y y
M M sin 2 vt1
2πvt1 M cos 2πvt1
x x x M = M0e–t1 T2 x
FIGURE 5.4 Evolution in a rotating frame of the magnetization of the acetone protons is shown during time interval t1
following the first pulse. The second pulse and acquisition give a signal resulting only from the x component of 𝐌; this signal
amplitude varies sinusoidally with t1 . Interval t1 is in the range of microseconds to milliseconds; t2 is of the order of seconds.
The precessional frequency of the protons is higher than that of the rotating frame in this example.
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5.3 CORRELATION SPECTROSCOPY 233

(c) t1

t1

(a)

𝜈2
(b)
t1

FIGURE 5.5 (a) Stacked plot of 22 1 H NMR spectra from acetone in which t1 is varied incrementally in 22 consecutive
experiments. (b) Projection of (a) showing the sinusoidal behavior of the peak intensity as a function of t1 . In this projection, the
frequency axis, 𝜈2 , is perpendicular to the plane of the page. (c) Resulting interferogram which is simply a plot of the intensities
of the peaks in (b) as a function of t1 . The frequency of the sinusoidal oscillation is related to the peak position along the indirect
dimension (𝜈1 ) in the final two-dimensional NMR spectrum.

These circles of the seven maxima are again drawn in For more complex spectra, the data are usually presented
Figure 5.5b (and Figure 5.5c) so that you can follow the as a series of contours just as hills and valleys are represented
rotation and projection. If we replot one column of data from on a topographical map. We see this representation of the
Figure 5.5a (let us choose the column that corresponds to the data in the right part of Figure 5.6. Projections of the data are
maximum (and minimum) for the acetone peak), the data we often included in 2D spectra, which is equivalent to “shining
obtain (Figure 5.5c) look like an FID. In fact, it is a time a light” on the peak to reveal its “shadow.” Often these
domain spectrum, now a function of the interval t1 from our projections are replaced with actual 1D spectra that have
pulse sequence. To distinguish, we refer to data obtained in been acquired separately. So long as there are no negative
real time (a function of t2 ) as an FID and data constructed peaks (e.g., phase sensitive COSY, not covered in this book),
point by point as a function of t1 as an interferogram. we use this method without comment.
We now perform our second series of Fourier transfor-
mations on each of the 1024 interferograms. The end result
is a 2D spectrum. We are now faced, however, with the chal- 5.3 CORRELATION SPECTROSCOPY
lenge of visualizing our results. One way to present the data
is as a stack plot similar to the plot that we have already seen The observant reader will have realized by now that the
in Figure 5.5a. This type of plot, shown in the left part of above experiment, which is a type of frequency modulation,
Figure 5.6, gives a sense of three dimensions. Note that the provides no additional information beyond the simple 1 H
two frequency axes are now labeled F2 and F1 (same as 𝜈2 NMR spectrum of acetone. Actually, that is the beauty of
and 𝜈1 ), which is consistent with the rest of the text and is that experiment; it has all of the elements of a 2D correlation
commonly used. For this spectrum, this type of plot is satis- experiment and we can completely follow the activity of the
factory because there are no peaks being blocked. Thus, one net magnetization vector for acetone using simple vectorial
perspective is sufficient. models. Let us generalize the prototypical 2D NMR pulse
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234 CHAPTER 5 TWO-DIMENSIONAL NMR SPECTROSCOPY

F1

F1

F2
F2
FIGURE 5.6 Fourier transformation of a series of interferograms like the ones in Figure 5.5c to give the frequency-domain spectrum
as both a peak and as contours. The contour plot also shows a projection parallel to F1.

sequence. If we replace the first 𝜋∕2 pulse with a generalized is simple because the magnetization experiences identical
pulse or block of pulses and delays and replace the second modulation during t1 and t2 . In an experiment in which
acquisition 𝜋∕2 pulse with a generalized acquisition pulse the magnetization is identically modulated during t1 and
or block of pulses and delays, we arrive at the general t2 , the resulting peaks will be such that 𝜈1 equals 𝜈2 ; in
pulse sequence for 2D correlation experiments, shown in the parlance of 2D NMR, the experiment gives rise to
Figure 5.7. Unlike 1D NMR, we typically cannot describe, diagonal peaks. For useful 2D information, we are interested
using simple vector models and trigonometry, the result of in experiments in which the magnetization evolves with one
what is happening inside the boxes. For the time being, let frequency during t1 and a different frequency during t2 . In
us ignore the details of what is occurring inside the boxes this case, our experiment will give rise to peaks in which
and concentrate on what is happening during t1 and t2 . 𝜈1 and 𝜈2 are different; this time we call the peaks off-
In all 2D experiments, we detect a signal (during diagonal or cross peaks. In order to interpret a 2D NMR
acquisition) as a function of t2 ; this signal, however, has been spectrum, there are two things that we need to know. First,
modulated as a function of t1 . The acetone experiment above what frequencies do the axes represent? One axis (𝜈2 ) always

1st t1
Acquire (t2) increment

Relaxation Preparation
Evolution
delay period period Acquisition pulse(s)
(Rd) (excitation t1
pulse(s))

nth t1

Repeat n times
FIGURE 5.7 Classical Jeener–Ernst style generalized pulse sequence for 2D NMR. The signal detected during acquisition,
t2 , is modulated during the incremented time, t1 , thus giving rise to cross peaks in the 2D spectrum.
 Silverstein c05.tex V3 - 07/31/2014 12:11 A.M. Page 235

5.4 IPSENOL: 1 H⏤1 H COSY 235

represents the nucleus detected during acquisition (t2 ). The evolution period, t1 , which is systematically incremented,
other axis (𝜈1 , which obviously depends on t1 ) can represent and the acquisition period, t2 .
the same nucleus (e.g., 1 H⏤1 H COSY), a different nucleus The actual pulse sequences used by all modern spec-
(e.g., 1 H⏤13 C COSY also called HMQC or HETCOR), trometers are more complicated than the idealized ones
or a coupling constant (e.g., J-resolved spectroscopy, not given in this text. Many spectrometers employ a technique
covered in this chapter). Second, we need to know how the known as phase cycling in which the phase of the rf pulse
magnetizations are related during t1 and t2 ; in this way, we is changed in a regular manner (through a cycle) for each
can account for and interpret the cross peaks. t1 increment. These phase cycles are extremely important
If we return to our prototype 2D experiment and apply experimental factors that help remove artifacts and other
this pulse sequence to an AX spin system, we will be in a bet- peculiarities of quadrature detection. We will ignore phase
ter position to appreciate the incremented time, t1 . While we cycling in our pulse sequences and discussions because they
can describe mathematically precisely how the spins evolve do not affect our understanding and interpretation of these
during this time, we cannot show this evolution pictorially experiments. The interested reader is referred to Claridge
with vector diagrams. (The mathematical description for this (see References) for these and other experimental param-
system requires quantum mechanics and solution of the den- eters important for 2D experiments. Another factor that is
sity matrix, well beyond the scope of this text. See Levitt ignored in our discussion is the use of gradients. A short
(2008) or Cavanagh et al. (1996) for further reading.) After description of them and their purpose is given at the end of
the first 𝜋∕2 pulse, the system can be described as a sum of this chapter.
two terms; each term contains the spin of only one of the In the description of the 2D experiment above for an
two protons. During the time t1 , the spins precess (evolve) AX spin system, we found that during t1 , spins which are
under the influences of both chemical shifts and their mutual mutually coupled precess under the influence of the chemical
spin-spin coupling. The mutual coupling has the effect of shifts of both nuclei and thus give rise to peaks in which
changing some of the individual spin terms into products 𝜈1 does not equal 𝜈2 . In the general case, 1 H⏤1 H COSY
containing magnetization components of both nuclei. Next, spectra are interpreted as giving rise to off-diagonal or
the second 𝜋∕2 pulse causes the spins that were precess- cross peaks for all protons that have spin-spin coupling;
ing under both chemical shift and coupling influences to put simply, the cross peaks correlate coupled protons. In a
redistribute magnetization among all spins (there is only one sense, the experiment can be thought of as simultaneously
other spin in this case) with which it is associated (coupled). doing all pertinent decoupling experiments to see which
This redistribution of magnetization is detected in t2 ; thus, protons are coupled to which other protons. Of course,
a frequency detected in t2 has its amplitude modulated as a no protons are being decoupled in an 1 H⏤1 H COSY and
function of other spins (again, only one here), with which it this experiment should not be thought of as replacing
is coupled during t1 , leading to cross peaks connecting the homonuclear decoupling experiments (see Section 3.15).
coupled nuclei. Because the magnetization is redistributed
equally in both directions (i.e., from A to X and from X to A),
the cross peaks (at least for this experiment) will be symmet- 5.4 IPSENOL: 1 H⏤1 H COSY
rically disposed about the diagonal. This description of spins
precessing and mixing during t1 and their redistribution dur-
Let us continue our discussion of 2D NMR by considering
ing the acquisition pulse (and detection during t2 ) is admit-
the 1 H⏤1 H COSY spectrum of ipsenol, the monoterpene
tedly difficult to follow without pictures. The pulse sequences
alcohol considered in some detail in Sections 3.12 and 4.6.
are not given detailed explanations in this text because of this
For reference and as a reminder, the typical 1D NMR data
difficulty.
at 300 MHz for ipsenol, and its structure, are provided in
Figure 5.8.
5.3.1 1 H⏤1 H Correlation: COSY The contour display of the simple COSY spectrum for
ipsenol is shown in the top part of Figure 5.9. The pre-
Our simple 2D experiment is actually a very important sentation shown here is typical; F2 is found on the bottom (or
experiment sometimes simply called COSY (COrrelation top) with the proton scale as usual (from right to left). F1 is
SpectroscopY), and which we will call 1 H⏤1 H COSY for displayed on the right (or left) with the proton scale running
the time being in order to clearly indicate what is being from top to bottom. A proton spectrum is displayed opposite
correlated.* The pulse sequence for 1 H⏤1 H COSY is none the F1 scale as a convenience instead of the poorly resolved
other than the one we have already described above in projection; this 1D spectrum is not part of the 1 H⏤1 H COSY
Figure 5.3: two 𝜋∕2 proton pulses separated by the required spectrum but added later. From the upper right to the lower
left runs the “diagonal,” a series of peaks for which 𝜈1 equals
* Many readers will already be aware that acronyms for 2D NMR exper- 𝜈2 ; these diagonal peaks provide nothing in the way of useful
iments have proliferated along with available experiments. This chapter
information beyond the simple 1D 1 H spectrum. On either
attempts neither an encyclopedic approach to describing these acronyms nor
their experimental counterparts. This chapter does, however, cover enough
side of the diagonal and symmetrically disposed (at least
important experiments to enable the reader to interpret nearly any 2D exper- theoretically) are the cross peaks. The symmetry in this type
iment that one is likely to encounter. Acronyms are listed in the index. of spectrum is oftentimes imperfect.
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236 CHAPTER 5 TWO-DIMENSIONAL NMR SPECTROSCOPY

1
H NMR 300 MHz

1950 1900 Hz 1600 1550 Hz 1200 1150 Hz 750 700 Hz

CH2

6
5 7
H
4 8 CH2
HO 3
600 550 Hz 450 400 Hz
H3C 2 CH3
1

6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 ppm

13
C/DEPT NMR 75.5 MHz

DEPT-90

DEPT-135

140 130 120 110 100 90 80 70 60 50 40 30 20 ppm

1 13
FIGURE 5.8 300 MHz H, C, and DEPT spectra for ipsenol in CDCl3 . The structure of ipsenol is given with the numbering used in
the text.
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5.4 IPSENOL: 1 H⏤1 H COSY 237

ppm 7 6 5 4 3 2 1 ppm COSY 300 MHz

CH2
1 1
6
5 7
H
4 8 CH2
2 2
HO 3

F1 3 H3C 2 CH3 3
1

4 4

Diagonal peak
5 5

Symmetric cross peaks

6 6

F2
DQFCOSY 300 MHz
ppm

CH3-, 1

1 1
3, 3'
2, OH
2 2
5, 5'

3 3

F1 4
4 4

5 5 CH2=
8

6 6
7

7 7
7 6 5 4 3 2 1 ppm
F2
FIGURE 5.9 The top part is the 300 MHz simple COSY spectrum for ipsenol; the bottom part is the 300 MHz DQF COSY
spectrum for ipsenol.
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238 CHAPTER 5 TWO-DIMENSIONAL NMR SPECTROSCOPY

Before undertaking detailed discussions of 1 H⏤1 H ipsenol finds the carbinol methine adjacent to two pairs of
COSY and the structure of ipsenol, there is one further exper- diastereotopic methylene groups;* in other words, the proton
imental refinement that decreases the clutter along the diag- at 3.83 ppm is coupled to four protons, and the four protons
onal. Although we can interpret this spectrum without this correspond to two adjacent methylene groups.
refinement, there are instances (e.g., caryophyllene oxide) We could continue to trace correlation paths from these
when this improvement makes a great deal of difference. four protons and the reader is invited to do so at the end
of this section. Let us instead select another equally useful
entry point: the isopropyl methine at 1.81 ppm. We again
5.4.1 Ipsenol: Double Quantum begin at the diagonal and this time we find that the isopropyl
Filtered 1 H⏤1 H COSY methine is correlated with three distinct resonances. Two
of the correlations correspond to the two protons of one of
By simply adding a third 𝜋∕2 pulse immediately following the diastereotopic methylenes that also correlated with the
the second 𝜋∕2 pulse in our simple COSY pulse sequence carbinol methine above. In addition, we find a correlation
and changing nothing else, we have the pulse sequence for to the two overlapping methyl doublets at 0.93 ppm. These
the very popular Double-Quantum Filtered 1 H⏤1 H COSY correlations of course make perfect sense with the structure;
(DQF-COSY) experiment (Figure 5.10). The purpose of in fact, by only considering these two protons (i.e., at
the third 𝜋∕2 pulse is to remove or “filter” single-quantum 3.83 and 1.81 ppm) we have established correlations (also
transitions so that only double-quantum or higher transitions called “connectivities”) through three-fifths of the molecule.
remain. In practical terms, the double quantum filter will A correlation implies a connectivity because the COSY
select only those systems with at least two spins (minimum spectrum will typically only show strong cross peaks for
AB or AX); thus, methyl singlets (noncoupled) will be coupled protons which are on adjacent (bonded) carbon
greatly reduced. Higher quantum filtering is possible but is atoms.
generally not used. For instance, in a triple-quantum filtered Next we consider the two protons on the C-5 methylene
COSY, only systems with three spins or more are selected so at 2.48 and 2.22 ppm. We have already seen that they are
that AB and AX spin systems as well as noncoupled systems coupled to the carbinol methine (you can and should verify
will be eliminated. this from the methylene protons’ perspective) and we see
The DQF 1 H⏤1 H COSY spectrum of ipsenol can be that they are also coupled to each other.† In addition, we see
found at the bottom of Figure 5.9. Note that the spectrum weaker cross peaks from both methylene protons correlating
seems cleaner, especially along the diagonal, making the task to an olefinic proton at 5.08 ppm. This correlation is due
of interpretation significantly easier. Because of the greatly to long range coupling (4 JHH or four-bond coupling) of the
improved appearance of DQF-COSY spectra, all COSYs in methylene protons to the cis-proton of the adjacent double
this book are double-quantum filtered. bond. This is a nice correlation to find because it provides
As we begin our interpretation of the DQF-COSY H⏤H connectivity to the otherwise isolated diene spin
spectrum in Figure 5.9, let us recall that this spectrum shows system. In the absence of these long-range correlations,
correlation between coupled protons. A point of entry (i.e., a such isolated spin systems can be connected to each other
distinctive peak) into a COSY spectrum (and other types of by either HMBC or INADEQUATE sequences, which are
correlation spectra as well) is one of the keys to successfully described below. At this point, the reader is invited to
gleaning information from it. The structure of ipsenol allows complete the correlations for ipsenol in this DQF-COSY
for more than one useful entry point, so let us select the spectrum. Correlations can be found for all protons except
carbinol methine resonance at 3.83 ppm. If we begin at the the hydroxylic proton, which is rapidly exchanging.
diagonal and trace either directly to the right or directly
up (we obtain the same result because the spectrum is
symmetric), we intersect four off-diagonal or cross peaks. 5.4.2 Carbon Detected
By drawing lines through these cross peaks at right angles 13 C⏤1 H COSY: HETCOR
to the one we just traced, we find the chemical shifts of the
four coupled resonances. A quick check of the structure of The 13 C⏤1 H COSY (HETCOR) experiment correlates 13 C
nuclei with directly bonded (i.e., coupled) protons through
one-bond (1 JCH ) couplings. The frequency domains of
θ θ θ F1 (𝜈1 ) and F2 (𝜈2 ) are of different nuclei, and so there is
Acquire (t2) no apparent diagonal or symmetry.
Rd t1
1
H: δ The pulse sequence for this experiment, commonly
called HETCOR (HETeronuclear CORrelation), is shown

* We will reserve further discussion of diastereotopic methylene groups until

FIGURE 5.10 Pulse sequence for double-quantum filtered the next section on 1 H⏤13 C HMQC.
1 ⏤1
H H COSY (DQF-COSY). 𝜃 = 90∘ and 𝛿 is a fixed † Geminal methylene protons (sp3 hybridized carbon) are always coupled
delay of the order of a few microseconds (it is unrelated to to each other and their coupling constant (2 JHH ) is always rather large (see
the chemical shift). Appendices, Chapter 3).
 Silverstein c05.tex V3 - 07/31/2014 12:11 A.M. Page 239

5.4 IPSENOL: 1 H⏤1 H COSY 239

(a) proton and carbon in their relative abundances and sensitiv-

90° 90° ities, the HMQC sequence is greatly preferred today. The
1 1
Rd t1 advantage of inverse experiments over direct detection exper-
2J 3J Decoupler on
1
H: iments is that with inverse experiments the nucleus with
Δ1 Δ2 the highest 𝛾 (usually 1 H) is detected, yielding the highest
180° 90° Acquire (t2) sensitivity.
As mentioned in Chapter 3, the sensitivity of an NMR
13
C: experiment depends on the magnetogyric ratios of the
excited nucleus (𝛾exc ) and of the detected nucleus to the
3
power of 32 (𝛾det 2 ). For the HETCOR experiment, 1 H is
the excited nucleus and 13 C is the detected nucleus; the
3
sensitivity is therefore proportional to 𝛾1H 𝛾13C 2 . For the
(b) inversely detected HMQC experiment, 1 H is both the excited
90° 180° Acquire (t2)
and the detected nucleus and so the sensitivity is pro-
Rd 1 1 5

2J 2J
portional to 𝛾1H 2 . The associated improvement in sensi-
1
H: tivity for the HMQC experiment compared to the HET-
3

90° 90° COR experiment is therefore (𝛾1H ∕𝛾13C ) 2 . Keep in mind

that even though the HMQC experiment excites and detects
13
t1 Decoupler on
1 H, magnetization must still pass through a 13 C nucleus
C: and so the low natural abundance of 13 C adversely affects
FIGURE 5.11 (a) The pulse sequence for HETCOR. the overall S/N compared to a one-dimensional 1 H NMR
(b) The pulse sequence for HMQC. The value for 1 JCH spectrum. One of the challenges of an inverse-detected chem-
is typically 145 Hz. ical shift correlation experiment is that the large signals from
1 H not coupled directly to a 13 C nucleus must be suppressed,

in Figure 5.11a. During the evolution time (t1 ), the large one- which poses a dynamic range problem, and usually requires
bond heteronuclear J-coupling (JCH ) is used for polarization additional phase cycling. The introduction of pulsed field
transfer, and thus only 13 C’s bonded directly to 1 H’s are gradients in high-resolution NMR greatly improved the prob-
detected. To realize maximum polarization transfer, a fixed lem of suppressing signals from 1 H bonded to 12 C. The sup-
delay Δ1 = 1∕(2JCH ) is added after t1 . The short delay (Δ2 ) pression is almost perfect without additional phase cycling,
between the final 13 C pulse and the start of acquisition which significantly improves the quality of the spectrum and
is a refocusing period so that the 13 C lines do not have requires much less time.
opposite phase and thus do not cancel one another when The pulse sequence for the HMQC experiment is shown
1 H-decoupling is applied. The optimal refocusing time (Δ )
2 in Figure 5.11b. Three details in this pulse sequence are
depends on whether the 13 C belongs to a CH, CH2 , or CH3 worth discussing. The F1 axis (𝜈1 ), which is derived from the
group. Typically, a compromise value of Δ2 = 1∕(3JCH ) is incremented delay, t1 , is the carbon axis. The F2 axis (𝜈2 ),
chosen. obtained during t2 , is the proton axis. Thus, our 𝜋∕2 read
The F1 axis (𝜈1 ), which is derived from the incremented pulse is on the 1 H channel, and the FID acquired during t2
delay, t1 , is the proton axis. The F2 axis (𝜈2 ), obtained represents the 1 H nucleus. Lastly, GARP decoupling—which
during t2 , is the carbon axis. Thus, our 𝜋∕2 read pulse is on is a low power, CPD routine—is used to decouple nuclei
the 13 C channel, and the FID acquired during t2 represents with large chemical shift ranges. This GARP (Globally
the 13 C nucleus. Lastly, in an ideal experiment, the carbon optimized, Alternating phase, Rectangular Pulses) CPD
resonances should be singlets rather than multiplets, as technique is applied on the carbon channel during acquisition
composite pulse (broadband) decoupling (CPD) is applied so that the proton signals obtained are not split into doublets
on the proton channel during acquisition. Remember, in a by the 13 C nuclei. Recall that the HMQC experiment works
2D experiment, correlation occurs during t1 and, hence, the through 1 H−13 C J coupling, so only ∼1.1% of the directly
proton decoupler is not turned on during this period. bonded C⏤H pairs will contribute to the spectrum. These
same pairs give rise to 13 C satellite signals in a normal 1D
1 H NMR spectrum.

5.4.3 Proton Detected

1 ⏤13
H C COSY: HMQC
5.4.4 Ipsenol: HETCOR and HMQC
Historically, the HMQC (Heteronuclear Multiple Quantum
Coherence) experiment was preceded by the HETCOR The upper portion in Figure 5.12 is the HETCOR spectrum
experiment. Although experimentally there are many differ- of ipsenol, and the lower portion is a HMQC spectrum of
ences, the essential difference is that, while the HETCOR ipsenol. The presentation of the two spectra is the same
experiment is carbon detected, the HMQC experiment is except that the axes have been switched. Thus, in the
proton detected. Since there are great discrepancies between HETCOR spectrum, the F2 axis on the bottom has the carbon
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240 CHAPTER 5 TWO-DIMENSIONAL NMR SPECTROSCOPY

HETCOR 75.5 MHz

One-dimensional 13C NMR spectrum

ppm

1 CH2

One-dimensional 1H NMR spectrum

6
5 7
2 H
4 8 CH2
3 HO 3
F1
4 H3C 2 CH3
1

7
150 140 130 120 110 100 90 80 70 60 50 40 30 20 ppm

F2 HMQC 300 MHz

CH2 = 2, OH
8 One-dimensional 1H NMR spectrum
5, 5' 3, 3' CH3-, 1
7 4
ppm

20 ppm
2

One-dimensional 13C NMR spectrum

40 5
3
25
60
1.2 1.1 1.0 0.9 0.8 ppm 4

F1 80
100
8
120 CH2 =

140 7

7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 ppm
FIGURE 5.12 The bottom part of the figure is the HMQC spectrum for ipsenol while the top part of the figure is the HETCOR spectrum
of ipsenol. Note that by convention, the spectrum of the directly detected nucleus (during t2 ) is plotted on the x-axis and so the nuclei
represented on the axes of the HMQC spectrum are transposed relative to the HETCOR spectrum.
 Silverstein c05.tex V3 - 07/31/2014 12:11 A.M. Page 241

5.4 IPSENOL: 1 H⏤1 H COSY 241

scale and the F1 axis on the side has the proton scale, whereas Ipsenol has two methyl groups that appear as a “triplet”
in the HMQC spectrum these axes are reversed. The reason at 0.93 ppm in the proton spectrum. A closer look, however,
for this is simply that by convention the data for the directly at the inset in the HMQC spectrum reveals that it is a pair of
detected nucleus (F2) are plotted in the x-dimension. In coincidental doublets. Before moving on to the next section,
theory, the information content of the two spectra is identical; consider the following question: can the alkenyl methylene
in fact, we find exactly the same correlations for ipsenol. The carbon resonances be assigned on the basis of combined
only real practical consideration when comparing the data of information from COSY and HMQC?
the two experiments is the difference in the digital resolution
of the carbon axis.
Let us familiarize ourselves with HMQC spectra by 5.4.5 Ipsenol: Proton-Detected,
considering the HMQC spectrum of ipsenol (Figure 5.12. Long-Range 1 H⏤13 C Heteronuclear
bottom part). Immediately obvious is the fact that there is Correlation: HMBC
no diagonal and no symmetry; this will be true whenever
For the HMQC sequence described above, we wanted an
F1 and F2 represent different nuclei. In this presentation,
experiment that eliminated long-range (i.e., two and three
the F1 axis (carbon) is along the left side and the F2 axis
bond) proton-carbon couplings while preserving the directly
(proton) is along the bottom. Opposite these axes we find the
attached (i.e., one-bond) couplings, which we correlated
corresponding 1D spectra, which are given as a convenience
in a 2D experiment. The HMBC (Heteronuclear Multiple
and are not part of the actual 2D spectrum. Interpretation of
Bond Coherence) experiment, on the other hand, which is
this spectrum is straightforward. We begin with any carbon
also proton detected, capitalizes on these two- and-three-
resonance and mentally draw a line horizontally until a
bond couplings, providing us with an extremely powerful
cross peak is encountered.* Another line is mentally drawn
(although sometimes cluttered) spectrum. In essence, we
perpendicular to the first to find the proton resonance with
indirectly obtain carbon-carbon (although not 13 C⏤13 C)
which the carbon resonance correlates.
correlations, and, in addition, we are able to correlate
There are only three cases possible for each carbon atom.
quaternary carbons with nearby protons. Since both 2 JCH and
If a line drawn encounters no cross peaks, then the car- 3J
bon has no attached hydrogens. If the drawn line encoun- CH couplings are present, interpretation can be tedious; we
must be methodical in our approach and keep in mind the
ters only one cross peak, then the carbon may have either
HMQC correlations.
1, 2, or 3 protons attached; if 2 protons are attached, then
Interpretation of HMBC spectra requires a degree of
they are either chemically equivalent or their chemical shifts
flexibility because we do not always find what we expect
fortuitously overlap. If the horizontal line encounters two
to find. In particular, depending on the hybridization of
cross peaks, then we have the special case of diastereotopic
carbon and other factors, some of the expected two-bond
protons attached to a methylene group. Much of this infor-
correlations (2 JCH ) or three-bond (3 JCH ) correlations are
mation will already be available to us from DEPT spec-
occasionally absent. To add to the confusion, infrequently
tra (see Section 4.6); indeed, the HMQC spectrum should,
we find four-bond (4 JCH ) correlations! The variations in
whenever possible, be considered along with the DEPT.
correlations that we find are due to the variations in the
The reader should also be aware that there are numerous
magnitude of 2 JCH , 3 JCH , and 4 JCH coupling constants.
additional two-dimensional correlation experiments which
The pulse sequence for HMBC is given in Figure 5.13
can give the same sort of information (e.g., variants of
for interested readers. The time delay, 1∕(2J), can be opti-
the heteronuclear single-quantum coherence (HSQC) exper-
mized for different coupling constants. A typical value for J
iment), many of which rely on pulsed field gradients (see
assumes an average long-range coupling constant of 8 Hz.
Section 5.12).
The HMBC spectrum for ipsenol (Figure 5.14) looks
In ipsenol, there are four methylene groups, all of which
like the HMQC spectrum for ipsenol with two obvious dif-
possess diastereotopic pairs of protons. Resonances for two
ferences: there are considerably more cross peaks and the
of these methylene groups occur in the carbon spectrum
one-bond correlations (HMQC) are gone. (The spectrum
at 41 ppm and 47 ppm. Note with which protons these
carbon atoms are correlated and compare these results with
what we found with COSY. As we expect, the results here
confirm our assignments from COSY and help build an Acquire (t2)
90° 180°
ever-strengthening basis for our assignments. The other two 1
Rd
methylene carbon atoms are found at higher frequency in the 1 2J
alkenyl region, and the HMQC cross peaks for these carbon H:
resonances help clarify the overlapping proton resonances
that we find in the proton spectrum. 90° 90°
t1
* We could just as well start on the proton axis and in this case we would 13
C:
obtain exactly the same result. In cases of overlap in the proton spectrum,
we will not always be able to find all of the proper starting points. Overlap FIGURE 5.13 Pulse sequence for HMBC. J is chosen for
is usually not a problem on the carbon axis. long-range CH coupling (2 JHC and 3 JHC ), typically 8 Hz.
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242 CHAPTER 5 TWO-DIMENSIONAL NMR SPECTROSCOPY

HMBC 300 MHz

CH2=
2, OH
8
CH3-, 1
5, 5' 3, 3'
7 4

ppm 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 ppm

20
CH3-or 1

F1
2
25

ppm
5

F1 45
3

ppm

4
68
F1
70

ppm
8
115
F1 CH2=
120

ppm

7
140
F1 6
145

7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 ppm
F2
FIGURE 5.14 The HMBC spectrum for ipsenol. The spectrum is split into five sections for clarity. The arrows in the top section
point to 13 C satellites. Lines are drawn to show correlations.
 Silverstein c05.tex V3 - 07/31/2014 12:11 A.M. Page 243

5.5 CARYOPHYLLENE OXIDE 243

is broken into five sections so that there is sufficient resolu- reference, the 1 H, 13 C, and DEPT NMR spectra are given in
tion to see all of the correlations.) Interpretation for ipsenol is Figure 5.15. As an aid in discussing the DQF-COSY spec-
straightforward. But first, let us note a common artifact: 13 C trum of caryophyllene oxide, note the following description
satellites of intense proton peaks, especially methyl groups. of the proton spectrum: there are three methyl singlets (at
If we trace parallel to the proton axis (F2) at about 23 ppm on 0.98 ppm, 1.01 ppm, and 1.19 ppm), two alkenyl doublets
the carbon axis (F1), we find a cross peak at about 0.93 ppm (small geminal coupling) at 4.86 ppm and 4.97 ppm, and res-
(proton), which is real. On either side, we find two addi- onances from 13 other protons giving multiplets between
tional cross peaks that do not line up (correlate) with any 0.9 ppm and 3.0 ppm. Even though we know the structure, it
proton resonances in F2. These are 13 C satellites and may be is impossible to assign any of these protons unless we make
ignored. The other methyl carbon resonance shows the same one or more unreasonable assumptions.†
phenomenon; the satellite peaks are marked with arrows in
the figure.
We can begin with either a carbon or a proton reso- 5.5.1 Caryophyllene Oxide: DQF-COSY
nance and obtain equivalent results. We will use the car- The DQF-COSY spectrum of caryophyllene oxide can be
bon axis as our starting point because we usually have less found in Figure 5.16. The problem here is that there is
overlap there. For example, a line drawn parallel to the pro- no good entry point. The previous statement is not trivial.
ton axis at about 68 ppm on the carbon axis (the carbinol Without an entry point, it is impossible to relate the many
carbon) intersects five cross peaks; none of the five corre- obvious correlations (drawn in for convenience) that we see
lations corresponds to the directly bonded proton (1 JCH ) at to a structural formula. Our approach therefore will be to
3.8 ppm. Four of the cross peaks correspond to the two pairs record some of the correlations that we do see and wait until
of diastereotopic methylene protons (2.48 ppm, 2.22 ppm, we have other information (i.e., HMQC) before we try to
1.45 ppm, and 1.28 ppm) and these arise due to two-bond translate these correlations into a structure.
couplings. The fifth cross peak (arising due to 3 JCH ) cor- The exocyclic alkenyl methylene protons show obvious
relates this carbon atom (68 ppm) to the isopropyl methine COSY correlations to one another. In addition, we note
proton (1.81 ppm), which is bonded to a carbon atom in the weak cross peaks between the alkenyl protons at 4.86 ppm
𝛽-position. The other carbon atom in a 𝛽-position has no and 4.97 ppm and an apparent diastereotopic methylene
attached protons so we do not have a correlation to it from group (2.11 ppm and 2.37 ppm) and a quartet at 2.60 ppm,
the carbinol carbon atom. Thus, we have indirect carbon con- respectively. These interactions are reminiscent of the long-
nectivities to two 𝛼-carbons and to one of two 𝛽-carbons. range allylic coupling that we saw in ipsenol; we could
Another useful example can be found by drawing a assign these correlations to the diastereotopic methylene C-
line from the carbon resonance at 41 ppm. This carbon is 7 and the methine at C-9. For now, we will be cautious and
the C-5 methylene and we first note that correlations to conservative, and return to this point later in the chapter.
the directly bonded protons at 2.48 ppm and 2.22 ppm are A look at the extreme low-frequency portion of this
absent. There is only one 𝛼-carbon that has one or more COSY spectrum reveals an unexpected interaction. It seems
attached protons; its corresponding correlation is found to the that either one or both of the methyl singlets shows coupling
C-4 carbinol methine proton at 3.83 ppm.* There are three to resonances at 1.65 ppm and at 2.09 ppm. This apparent
𝛽-carbons and they all have directly bonded protons. The C- conflict can be resolved by a close examination of the
3 methylene carbon shows indirect correlation through both methyl singlets at about 0.98 ppm. There is an unusually
of its diastereotopic protons at 1.45 ppm and 1.28 ppm. The low-frequency multiplet (labeled 3′ ), partially buried by
C-7 alkenyl methine proton gives a cross peak at 6.39 ppm the methyl singlets, which we had initially overlooked.
as do the protons of the alkenyl methylene group attached to This type of unexpected dividend is common in correlation
C-6 at 5.16 ppm and 5.09 ppm. Since C-6 is a quaternary car- spectra; both partially and completely obscured resonances
bon, the HMBC experiment enables us to “see through” these usually reveal themselves in 2D spectra (see HMQC below).
normally insulating points in a molecule. Other assignments Before continuing our discussion of caryophyllene oxide,
are left to the reader as an exercise; the quaternary carbon at let us consider 1 H⏤13 C correlations and how 1 H⏤1 H
about 143 ppm (C-6) is a good place to start. correlations interplay with 1 H⏤13 C correlations.

5.5 CARYOPHYLLENE OXIDE 5.5.2 Caryophyllene Oxide: HMQC

The COSY spectrum for caryophyllene oxide can be under-
The structure of caryophyllene oxide is significantly more stood more clearly when interpreted in conjunction with
complicated and is a worthy challenge for the methods that the information from an HMQC spectrum (Figure 5.17).
we introduced with ipsenol. For use here and for future
† Ifpressed, we might assume that the allylic bridgehead methine would be
* The other 𝛼-carbon at C-6, which was a 𝛽-carbon in our first example,
also the most deshielded and assign the doublet of doublets at 2.86 ppm to this
shows no correlation in the HMQC. The reader should show that there are proton (wrong). The methods in this chapter will allow us to make these
useful correlations to this carbon atom in Figure 5.14. assignments without making unsubstantiated assumptions.
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244 CHAPTER 5 TWO-DIMENSIONAL NMR SPECTROSCOPY

1
H NMR 600 MHz

3000 2950 Hz 1750 1700 Hz 1600 1550 Hz 1400 1350 Hz

1300 1250 Hz 1050 1000 Hz 850 800 Hz

15 3
H3C H 2 CH3
4 12

H3C 11 1
14 5 O
9
10 6
8 7
H
CH2
13

5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 ppm

13
C/DEPT 150.9 MHz

DEPT-90

DEPT-135

29.5 ppm

150 140 130 120 110 100 90 80 70 60 50 40 30 20 ppm

1 13
FIGURE 5.15 The H, C, and DEPT NMR spectra for caryophyllene oxide. The numbering for this structure is used in the text.
 Silverstein c05.tex V3 - 07/31/2014 12:11 A.M. Page 245

5.5 CARYOPHYLLENE OXIDE 245

ppm 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 ppm
COSY 600 MHz
1.0 1.0

1.5 1.5

2.0 2.0

2.5 2.5
F1
3.0 3.0
15 3
3.5 H3C H 2 CH3 3.5
4 12

H3C 11 1
4.0 14 5 O 4.0
9
10 6
4.5 H
8 7 4.5
CH2
13 13
5.0 5.0

F2 COSY 600 MHz

ppm 14 or 15
1.0 1.0
3'
12
6'
2'
1.5 1.5
10',2
10
1

F1 2.0 2.0
3,7'
6
7

2.5 2.5
9

5
3.0 3.0
3.0 2.8 2.6 2.4 2.2 2.0 1.8 1.6 1.4 1.2 1.0 ppm
F2
FIGURE 5.16 The DQF COSY spectrum for caryophyllene oxide. The lower portion is an expanded view with correlation
lines drawn in and assignments are given as an aid.
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246 CHAPTER 5 TWO-DIMENSIONAL NMR SPECTROSCOPY

HMQC 600 MHz

13 5 9 7 6 3, 7' 1 10,2,10' 2' 6' 12 3' 15,14

ppm 5.0 ppm 2.8 2.6 2.4 2.2 2.0 1.8 1.6 1.4 1.2 1.0 ppm

12
15 3
H3C H 2 CH3
4 12
20 H3C 1
11 15
14 5 O
9
10 6
8 7
25 H
CH2
13
2

7, 14
30 6

q
35

F1 3
10
40

45

50 1
DEPT 135
CH2 CH 3
ppm
55

30
q
60 2.5 2.0 1.5 1.0 ppm

ppm
13
120
F1
140
q

5.0 ppm 2.8 2.6 2.4 2.2 2.0 1.8 1.6 1.4 1.2 1.0 ppm
F2
FIGURE 5.17 The HMQC spectrum for caryophyllene oxide. In place of the usual 13 C NMR spectrum, the inset uses the DEPT 135
spectrum for better clarity.
 Silverstein c05.tex V3 - 07/31/2014 12:11 A.M. Page 247

5.5 CARYOPHYLLENE OXIDE 247

From the DEPT spectrum (see Figure 5.15), we already to construct structure fragments, or in this case, confirm
know that caryophyllene oxide has three methyl carbon res- structural segments. To correlate C-5, C-6, and C-7, we start
onances (16.4 ppm, 22.6 ppm, and 29.3 ppm), six methy- with H-5 at 2.87 ppm. This proton shows cross peaks with
lene carbon resonances (26.6 ppm, 29.2 ppm, 29.5 ppm, two resonances at 1.32 ppm and 2.24 ppm. From the HMQC,
38.4 ppm, 39.1 ppm, and 112.0 ppm), three methine car- we know that these are diastereotopic and assign them as
bon resonances (48.1 ppm, 50.1 ppm, and 63.0 ppm) and H-6 and H-6′ . The protons attached to C-6 give correlations
three quaternary carbon resonances (33.3 ppm, 59.1 ppm, with protons at 2.11 ppm and 2.37 ppm; we assign these pro-
and 151.0 ppm). tons, which also are diastereotopic, to C-7 at 29.2 ppm. The
The alkenyl methylene group (protons and carbon) and C-7 protons are coupled to each other, as certainly are the
the three methyl groups (protons and carbons) are trivial C-6 protons.
assignments, and they correspond with our previous discus- Other correlations are also straightforward. The C-5,
sion. Of more interest and of greater utility, we assign the C-6, and C-7 spin system is isolated so we must select
three methine protons: the doublet of doublets at 2.86 ppm another entry point. We can start again with the allylic
(correlates with the carbon resonance at 63.0 ppm), the bridgehead methine (H-9) at 2.60 ppm. We have noted
apparent quartet at 2.60 ppm (correlates with the carbon res- already the long-range allylic interaction. In addition, we find
onance at 48.0 ppm), and an apparent triplet at 1.76 ppm three other interactions that the HMQC helps us to assign.
(correlates with the carbon resonance at 50.1 ppm). From One of the correlations is to a methine proton at 1.76 ppm,
the COSY spectrum and from the known structure, we are which we assign to H-1. The other two correlations find two
now able to assign all three methine resonances and feed diastereotopic protons (again, from HMQC) at 1.62 ppm and
this information back into the COSY to establish other 1.68 ppm; we assign them as H-10 and H-10′ . The C-10
correlations. protons are a dead end, and we find no other correlations to
From the long-range, allylic correlation that we found in them.
the COSY, we now confirm our cautious assignments that we H-1 shows coupling to both C-2 protons at 1.45 ppm and
made earlier. The doublet of doublets at 2.86 ppm is assigned 1.63 ppm. The interaction is weak between H-1 and H-2′ at
to the methine proton of the epoxide ring, and its chemical 1.63 ppm. Both C-2 protons are coupled to both C-3 protons
shift is rationalized on the basis of the deshielding effect of at 0.95 ppm and 2.06 ppm and the appropriate cross peaks
the epoxide oxygen. The other bridgehead methine (adjacent can be found. Thus, we have shown indirect connectivities
to the gem-dimethyl group) is assigned to the multiplet at from C-10 through C-9, C-1, and C-2 all the way to C-3. The
1.76 ppm. With these assignments in hand, we could return HMQC has been invaluable in our interpretation. However,
to the COSY spectrum, but instead we will restrain our many questions still remain. We neither have correlations to
enthusiasm for now and assign the methylene protons first. the three quaternary carbons nor to the three methyl groups.
Knowing these assignments first will help speed our way The HMQC and the COSY together support the structure for
through the COSY. caryophyllene oxide, but they do not preclude other possible
Beginning from the low-frequency end of the 13 C spec- structures.
trum, the following assignments can be made: the methylene
carbon peak at 26.6 ppm correlates with proton resonances
5.5.3 Caryophyllene Oxide: HMBC
at 1.45 ppm and 1.63 ppm, the methylene carbon peak at
29.2 ppm correlates with proton resonances at 2.11 ppm and The HMBC spectrum of caryophyllene oxide (Figure 5.18)
2.37 ppm, the methylene carbon at 29.5 ppm correlates with allows us to completely confirm its structure by giving us the
proton resonances at 1.33 ppm and 2.23 ppm, the methy- required indirect carbon-carbon connectivities. An analysis
lene carbon at 38.4 ppm correlates with proton resonances at of the structure of caryophyllene oxide reveals that there
0.96 ppm and 2.09 ppm, the methylene carbon at 39.1 ppm should be 87 cross peaks; this number is derived from
correlates with proton resonances at 1.62 ppm and 1.68 ppm, considering each of the 15 carbon atoms and counting the
and we have already assigned the alkenyl methylene group number of chemically distinct protons at the 𝛼-positions and
above. Thus, with little effort we have assigned a chemical the number of chemically distinct protons at the 𝛽-positions.
shift for all of the protons in caryophyllene oxide and corre- In order to keep track of all of those interactions, one must
lated them with a resonance from the 13 C NMR spectrum; be methodical indeed.
we have grouped the diastereotopic protons together for each One way to keep track of these data is to construct a table
of the methylene groups, and we have obtained three sepa- listing the carbon resonances in one direction and the proton
rate entry points for the COSY spectrum when before we had resonances in the other. In Table 5.1, the carbons are given
none. We are now ready to return to the analysis of the COSY across the top and protons along the side. The numbering
spectrum of caryophyllene oxide and assign the correlations for caryophyllene oxide is the same in Table 5.1 as in all the
in light of the structure. figures.
An expanded section from 0.8 ppm to 3.0 ppm of the Our approach for this spectrum is no different from any
DQF-COSY spectrum of caryophyllene oxide can be found other spectrum. In this case, it is easier to start on the proton
in the bottom part of Figure 5.16. Included in this portion axis and look for the required cross peaks to the carbons as
of the figure are lines connecting proton-proton correlations listed in Table 5.1. If we wished to start on the carbon axis,
to aid our discussion. The COSY connectivities allow us we would, of course, obtain the same results. If we begin
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248 CHAPTER 5 TWO-DIMENSIONAL NMR SPECTROSCOPY

HMBC 600 MHz

13 5 9 7 6 3, 7' 1 10,2,10' 2' 6' 12 3' 15,14

ppm 5.1 5.0 ppm 2.8 2.6 2.4 2.2 2.0 1.8 1.6 1.4 1.2 1.0 ppm

15
2
3 12
H3C H CH3
4 12

H3C 11 1
5
20 14
9
O
10 6 15
8 7
H
CH2
13

25
2

7, 14
30 6

2
35

F1 3
10
40

45

9
50 1

55

4
60

ppm
13
120
F1
140
8
160
5.1 5.0 ppm 2.8 2.6 2.4 2.2 2.0 1.8 1.6 1.4 1.2 1.0 ppm
F2
FIGURE 5.18 The HMBC spectrum for caryophyllene oxide.
 Silverstein c05.tex V3 - 07/31/2014 12:11 A.M. Page 249

5.6 13 C⏤13 C CORRELATIONS: INADEQUATE 249

TABLE 5.1 HMBC Correlations for Caryophyllene Oxide

Carbon C-1 C-2 C-3 C-4 C-12 C-5 C-6 C-7 C-8 C-13 C-9 C-10 C-11 C-15 C-14

Proton 𝛅/ppm 50.1 26.6 38.4 59.1 16.4 63.0 29.5 29.2 151 112 48.0 39.1 33.3 22.6 29.3

H-1 1.76 DB* 𝛼 𝛽 𝛽 𝛼 𝛽 𝛼 𝛽 𝛽

H-2 1.45 𝛼 DB 𝛼 𝛽 𝛽 𝛽 𝛽
H-2′ 1.63 𝛼 DB 𝛼 𝛽 𝛽 𝛽 𝛽
H-3 0.95 𝛽 𝛼 DB 𝛼 𝛽 𝛽
H-3′ 2.06 𝛽 𝛼 DB 𝛼 𝛽 𝛽
H-12 1.19 𝛽 𝛼 DB 𝛽
H-5 2.86 𝛽 𝛼 𝛽 DB 𝛼 𝛽
H-6 1.28 𝛽 𝛼 DB 𝛼 𝛽
H-6′ 2.23 𝛽 𝛼 DB 𝛼 𝛽
H-7 2.11 𝛽 𝛼 DB 𝛼 𝛽 𝛽
H-7′ 2.37 𝛽 𝛼 DB 𝛼 𝛽 𝛽
H-13 4.86 𝛽 𝛼 DB 𝛽
H-13′ 4.97 𝛽 𝛼 DB 𝛽
H-9 2.6 𝛼 𝛽 𝛽 𝛼 𝛽 DB 𝛼 𝛽
H-10 1.43 𝛽 𝛽 𝛼 DB 𝛼 𝛽 𝛽
H-10′ 1.47 𝛽 𝛽 𝛼 DB 𝛼 𝛽 𝛽
H-15 0.98 𝛽 𝛽 𝛼 DB 𝛽
H-14 1.01 𝛽 𝛽 𝛼 𝛽 DB
*Directly bonded proton-carbon pairs, which are not seen in the HMBC spectrum.

at the top left of the table with H-1 at 1.76 ppm, we see 5.6 13 C⏤13 C CORRELATIONS:
first that H-1 is bonded to C-1 at 50.1, a result that we have
INADEQUATE
already determined with HMQC. Going across the row, we
find a total of eight interactions are expected. In the table,
each interaction is labeled either 𝛼 or 𝛽 depending upon The HMBC experiment allows us to trace the skeleton of
whether it is due to a two-bond coupling (2 JCH ) or a three- organic compounds by way of indirect carbon-carbon con-
bond coupling (3 JCH ). Of course, in the spectrum itself, there nectivities, but the process is tedious because we do not know
is no differentiation of the two types of interactions; we label whether the correlations are due to two- or to three-bond
them that way for our own bookkeeping efforts. Each of the couplings. The 2D INADEQUATE (Incredible Natural
interactions for H-1 designated in the table is found in the Abundance DoublE QUAntum Transfer Experiment) spec-
spectrum. trum completes our set of basic through-bond correlations;
There are two protons on C-2, which are labeled H-2 we have COSY for proton-proton coupling, HMQC (or
and H-2′ ; these protons have different chemical shifts. Thus, HETCOR) for one-bond and HMBC for two- and three-
we have a useful independent check of our HMBC assign- bond proton-carbon coupling, and now INADEQUATE for
ments for each pair of diastereotopic protons in caryophyl- directly attached (one-bond) carbon-carbon couplings. For
lene oxide. For H-2 at 1.45 ppm, we have the same five elucidation of the structure of organic compounds, this
correlations that we have for H-2′ at 1.63 ppm. As we study experiment is, without question and without exception, the
the spectrum and the table more closely, we find that we have most powerful and the least ambiguous available, and, to
exquisitely detailed structural information that can be deci- top it off, the experiment is easy to interpret. After read-
phered with a methodical approach. ing that last statement, the naturally pessimistic among us
An important point about quaternary carbons requires inevitably will ask: what’s the catch? Indeed, the catch is
comment. Until now, we have had no direct correlations plain and simple: sensitivity. Recall from Chapter 4 that the
for carbons without protons, nor have we been able to probability of any one carbon atom being a 13 C atom is
establish connectivities through heteroatoms such as oxy- about 0.01. Thus, the probability that any two adjacent car-
gen, nitrogen, sulfur, etc. Both the two- and three-bond cou- bon atoms will both be 13 C atoms (independent events) is
pling correlations of HMBC provide us with both types 0.01 × 0.01 or 0.0001; in rounded whole numbers, that is
of critical information. For example, C-4 of caryophyl- about 1 molecule in 10,000!
lene oxide at 59.1 ppm has no directly-bonded protons, so These long odds are overcome with the aid of dou-
far it has only appeared in the 13 C spectrum of the com- ble quantum filtering. We recall from our DQF-COSY
pound, and we know that it is quaternary from DEPT. experiment that double quantum filtering removes all sin-
If we look in Table 5.1 at the C-4 column, we find four gle spin transitions, which in this case corresponds to iso-
two-bond correlations and four three-bond correlations. The lated 13 C atoms; only those transitions from systems with
HMBC spectrum bears out these expectations fairly well two spins (AB and AX systems) and higher* are detected
and gives us direct evidence of the C-4 position in the * Following the same reasoning as above, the probability of a three-spin
molecule. system in an unenriched sample is 1 in 1,000,000.
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250 CHAPTER 5 TWO-DIMENSIONAL NMR SPECTROSCOPY

during acquisition. The main problem facing us experimen- would be carbon axes, and theoretically this experiment is
tally is sample size, assuming that the compound has the possible. For practical considerations related to obtaining
required solubility in an appropriate lock solvent. For low complete double quantum filtration, the INADEQUATE
molecular weight compounds (atomic weight <500 Da) run experiment is run slightly differently. In the display of
on a modern high field spectrometer, about 50–100 mg dis- the INADEQUATE spectrum of caryophyllene oxide
solved in 0.5 mL of a deuterated solvent is appropriate. (Figure 5.19), we find that the F2 axis is the familiar carbon
One way to imagine this experiment is as a car- axis, which we can, of course, relate to t2 acquisition. The F1
bon analogue of DQF-COSY in which both F1 and F2 axis looks unfamiliar and requires further explanation.

INADEQUATE 150.9 MHz

8 13

Hz

–10000 15 3
–10000
H3C H 2 CH3
4 12

H3C 11 1
14 5
O
9
10 6
8
–5000 H 7 –5000
CH2
13

F1 0 0

5000 5000

10000 10000

160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 ppm

Hz

–9000 –9000
C6-C7
–8000 –8000

F1 –7000 –7000

–6000 –6000

–5000 –5000

–4000 –4000

65 60 55 50 45 40 35 30 25 20 15 ppm
F2
FIGURE 5.19 The INADEQUATE spectrum of caryophyllene oxide. Correlation lines are drawn as an aid.
 Silverstein c05.tex V3 - 07/31/2014 12:11 A.M. Page 251

5.7 LACTOSE 251

During t1 , the frequencies that evolve are not the chem- chemical shifts from Table 5.1 as 29.5 ppm and 29.2 ppm.
ical shifts of the coupled nuclei as they are in a typical Because they are bonded to one another in caryophyllene
DQF-COSY. Instead, it is the sum of the offsets from the oxide, they should show correlation in the INADEQUATE
transmitter frequency of the coupled nuclei that evolve dur- spectrum, but, instead of an AX system, we have an AB
ing t1 , and, because they are double quantum filtered, it is system with Δ𝜈∕J being much less than eight. For this
only the two-spin AB and AX systems that contribute signif- special case, we no longer expect two doublets whose
icantly to the intensity of cross peaks in the INADEQUATE midpoint lies on the diagonal; instead, we predict that an
spectrum. This is why the cross peaks appear as doublets in AB multiplet (see Chapter 3) should fall on the diagonal line
the F2 dimension. Proper selection of experimental param- itself. This prediction is borne out in Figure 5.19 where we
eters in the pulse sequence allows us to select the larger find a cross peak directly below C-6 and C-7, and this cross
one-bond couplings (1 JCC ), thus ensuring that we are only peak intersects the diagonal line.
looking at directly bonded carbon-carbon correlations. The The other connectivities found in the expanded spectrum
F1 axis is usually given in Hz and it is two times the range in are left to the reader as an exercise. We summarize this
F2, whose units are ppm. section with two points:
• 2D INADEQUATE provides direct carbon-carbon con-
nectivities enabling us to sketch the carbon skeleton unam-
5.6.1 INADEQUATE:
biguously.
Caryophyllene Oxide
• In practice, 2D INADEQUATE has limited applicability
The 2D INADEQUATE spectrum of caryophyllene oxide due to its low sensitivity and concomitant long experimen-
is presented in Figure 5.19. Cross peaks or correlations are tal times.
found at (𝜈A + 𝜈X , 𝜈A ) and at (𝜈A + 𝜈X , 𝜈X ) in the (F1, F2)
coordinate system for a given AX system. The actual cross
peaks themselves are doublets (see the expanded portion of
5.7 LACTOSE
the spectrum, bottom of Figure 5.19) with a spacing equal
to the (1 JCC ) coupling constant. The midpoint of the line
connecting the two sets of doublets is (𝜈A + 𝜈X )∕2, (𝜈A + The structure of the 𝛽-anomer of lactose is given in
𝜈X ); thus, the collection of midpoints for all of the pairs of Figure 5.1. The challenges that lactose presents in the inter-
doublets lie on a line running along the diagonal. This is an pretation of its 1 H and 13 C NMR spectra (Figure 5.20) are
important observation because it can be used to distinguish obvious, but the opportunities for correlation NMR are irre-
genuine cross peaks from spurious peaks and other artifacts. sistible. In solution, lactose is an equilibrium mixture of
With a better understanding of the F1 axis and the diag- 𝛼- and 𝛽-anomers. The two diastereomers are epimeric at
onal, we can proceed with interpretation of the spectrum. only 1 stereocenter out of 10. In addition, the protons of
Table 5.1 lists carbon chemical shifts and carbon numbers the two sugar residues in each diastereomer are insulated
based on the structure given earlier; we refer to these num- from each other by the glycosidic oxygen atom, forming iso-
bers in the present discussion. From Figure 5.19, we can lated spin systems. This situation is common to all oligo- and
make the high-frequency connections quite easily. The car- polysaccharides.
bon at highest frequency is C-8 at 151.0 ppm; by tracing We are not going to spend too much time discussing
vertically down from this peak on the F2 axis, we intersect the 1D spectra except to note some of the obvious features.
three cross peak doublets. These cross peaks connect hori- The anomeric proton resonances can be found at 4.45 ppm,
zontally with C-7 at 29.2 ppm, C-9 at 48.0 ppm, and C-13 4.67 ppm, and 5.23 ppm and the anomeric carbon resonances
at 112.0 ppm. Toward lower frequencies, C-13 at 112.0 ppm at 91.7 ppm, 95.6 ppm, and 102.8 ppm. The reason for three
comes next, and it has only one cross peak, namely the recip- anomeric protons and carbons is that the 𝛼- and 𝛽-anomers
rocal connection to C-8 at 151.0 ppm. of glucose give two sets of resonances while the galactose
In order to present the low-frequency section more residue, which exists only in the 𝛽-form, gives a single set of
clearly, the lower portion of Figure 5.19 shows an expanded resonances in both the proton and carbon spectra. The other
view of that area. The higher resolution of this figure enables portions of both spectra, especially the proton spectrum, are
us to see the doublet fine structure more readily. Let us trace quite complicated and show considerable overlap.
one carbon’s connectivities from this expanded view. C-11,
at 33.3 ppm, is a quaternary carbon, and it accordingly shows
5.7.1 DQF-COSY: Lactose
four cross peaks. We have connectivities from C-11 to C-15
at 22.6 ppm, C-14 at 29.3 ppm, C-10 at 39.1 ppm, and C-1 The DQF-COSY spectrum for lactose (Figure 5.21) is rich
at 50.1 ppm. with correlations, and entry points are easy to find. This
Before we conclude our discussion, we note that the figure and others use a simplified notation in which galactose
INADEQUATE spectrum of caryophyllene oxide contains resonances are labeled Gn, where n is the proton or carbon
an uncommon phenomenon worth exploring. Carbons 6 and position, and either 𝛼n or 𝛽n for positions in the 𝛼-glucose
7 of caryophyllene oxide nearly overlap in the 13 C spectrum residue and the 𝛽-glucose residue, respectively. Each of the
with each other and with the C-15 methyl; we list their anomeric protons, which are the protons attached to C-1 for
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252 CHAPTER 5 TWO-DIMENSIONAL NMR SPECTROSCOPY

1
H NMR 600 MHz
HO OH H OH
H O
H O H
HO HO O
H OH
H H β– H
H OH OH
Lactose β–anomer H
HO OH H OH
H O 3.9 3.8 3.7 3.6 ppm
H O H
HO HO O
H OH
H H H H
H OH
Lactose α–anomer OH
G1
HDO
β1
α1

5.3 5.2 5.1 5.0 4.9 4.8 4.7 4.6 4.5 4.4 4.3 4.2 4.1 4.0 3.9 3.8 3.7 3.6 3.5 3.4 ppm
13
C/DEPT 150.9 MHz

DEPT-90

DEPT-135

100 95 90 85 80 75 70 65 60 ppm
FIGURE 5.20 The 1 H, 13 C, and DEPT NMR spectra of lactose. In solution, lactose is an equilibrium mixture of anomers.
 Silverstein c05.tex V3 - 07/31/2014 12:11 A.M. Page 253

5.7 LACTOSE 253

5.2 5.0 4.8 4.6 4.4 4.2 4.0 3.8 3.6 3.4 ppm COSY 600 MHz
ppm

β2
3.4 3.4
G2
3.6 3.6 α2

3.8 3.8

4.0 4.0
F1
4.2 4.2

4.4 4.4
G1
4.6 4.6
β1
4.8 4.8
HDO
5.0 5.0

5.2 5.2 α1

ppm COSY 600 MHz

α6 α4 α2
3.2 G4 G6 β4 β5 G2 β2

3.3

3.4

3.5

F1 3.6 α2
β3
G3
3.7
G5
3.8 β6'
α3
3.9
α5
β6
4.0
4.0 3.9 3.8 3.7 3.6 3.5 3.4 3.3 3.2 ppm
F2
FIGURE 5.21 The DQF COSY spectrum for lactose. See the text for an explanation of the shorthand notation for proton
resonances. Correlation lines are drawn in and assignments are given as an aid.
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254 CHAPTER 5 TWO-DIMENSIONAL NMR SPECTROSCOPY

each sugar residue, show one and only one correlation to their 180y 180y 180y 180y 180y
respective C-2 protons. For instance, the anomeric proton at
4.67 ppm shows a correlation to a proton (obviously attached δ δ δ δ δ δ δ δ δ δ
to C-2) at 3.29 ppm. This C-2 proton at 3.29 ppm shows a (n)
correlation to a C-3 proton at 3.64 ppm.
Continuation of this process quickly becomes dreadfully τm
complicated because of the severe overlap of signals. Many θ Acquire (t2)
Rd
of the correlations have been drawn in with different types of 1
H: t1 Spin-lock(y)
lines for each of the different residues in the expanded view.
The reader is invited to trace some of these correlations but
cautioned to be wary of frustration. Below, lactose will again
be analyzed in light of other experiments that will literally FIGURE 5.22 The pulse sequence for a 2D TOCSY
remove the overlap. experiment. Note that the delays (𝛿) are unrelated to
chemical shifts.
5.7.2 HMQC: Lactose
The HMQC spectrum of lactose is shown in Figure 5.23 the power of COSY, HMQC, HMBC, and INADEQUATE to
in three sections to minimize overlap and to show good provide us with detailed structural information for ipsenol,
resolution on the carbon axis. As with the COSY spectrum, caryophyllene oxide, and lactose. In this section, we will
this figure is labeled with assignments. These assignments develop another method for showing correlations and apply it
were made with information beyond what we have seen so to molecules with distinct, isolated proton spin systems such
far. (By the end of our discussion of lactose, it will be clear as carbohydrates, peptides, and nucleic acids.
that these assignments are correct, and it should be obvious Our goal is to relay or transfer magnetization beyond
how these assignments were made.) Overlap is less severe so directly coupled spins, thus enabling us to see correlations
that some of the assignments can be made quite easily. This among nuclei that are not directly coupled to each other
spectrum is useful in that it allows us to find the chemical but within the same spin system. The experiment is called
shift of most of the protons, many of which are overlapping TOCSY (TOtal Correlation SpectroscopY) and we will
in the 1D spectrum. consider both the 2D and 1D versions. The pulse sequence
for a 2D TOCSY experiment resembles our prototype 2D
5.7.3 HMBC: Lactose experiment, but, instead of a second 𝜋∕2 pulse, we insert a
mixing period during which the magnetization is spin locked
Considering the complexity of lactose, a complex and over- on the y-axis (Figure 5.22). To understand the outcome of
lapping HMBC spectrum is expected. The spectrum found the experiment, we can ignore the particulars of spin locking
in Figure 5.24 measures up to this expectation. Students are and concentrate on the consequences of the mixing period.
encouraged to analyze this spectrum, which is facilitated by During this mixing period, magnetization is relayed from
the labeling. one spin to its neighbor and then to its next neighbor and
An important correlation in this spectrum is high- so on. The longer the mixing period, the further the transfer
lighted in the expanded inset that shows the correlation of magnetization can propagate, traveling, in favorable cases,
between C-4 of glucose (from both 𝛼- and 𝛽-anomers) throughout an entire spin system.
and the C-1 proton of galactose. This three-bond cou- The appearance of a 2D TOCSY spectrum resembles in
pling is extremely important because it shows that the gly- all aspects a COSY spectrum. The F1 and F2 axes are for
cosidic linkage is indeed from galactose C-1 to glucose proton, the diagonal contains 1D information, and even the
C-4. Because there is no overlap in this part of the spec- cross peaks have the same appearance. The difference here is
trum, our conclusion is unambiguous. The reciprocal cor- that the cross peaks in a COSY spectrum are due to coupled
relation between the C-1 carbon of galactose and the spins while the cross peaks in the TOCSY spectrum arise
C-4 protons of glucose (both anomers) is most likely there, from relayed coherence transfer. For long mixing times in
but, because there is overlap among G3 (which also has a a TOCSY spectrum, all spins within a spin system appear
correlation to C-1 of galactose), 𝛼4, and 𝛽4 protons, it is not to be coupled. To appreciate the advantages of TOCSY,
possible to observe this correlation conclusively. we continue with the disaccharide lactose, which has three
distinct (i.e., separate) spin systems.

5.8 RELAYED COHERENCE

TRANSFER: TOCSY 5.8.1 2D TOCSY: Lactose
The 2D TOCSY spectrum of lactose is given in Figure 5.25.
The common theme so far in our correlation experiments has The mixing time for this 2D spectrum was sufficiently long
been to allow spins to evolve during t1 under the influence that magnetic coherence has been transferred more or less
of J couplings between the spins of interest. We have seen throughout each sugar residue’s spin system. Compare this
 Silverstein c05.tex V3 - 07/31/2014 12:11 A.M. Page 255

5.8 RELAYED COHERENCE TRANSFER: TOCSY 255

β4 α4 HMQC 600 MHz

HDO G1 α5 G4 G5 G3 β3
β1 α3 β6' G6 G2 β2
α1 β6 α6 β5 α2

ppm 5.0 ppm 3.9 3.8 3.7 3.6 3.5 3.4 3.3 ppm

α6
60 β6
F1 G6
61

ppm
G4
69

70 α5
G2
71 α2
α3

72
G3

73
F1 β2
74
β3
β5
75
G5

76

77

78 β4
α4

ppm α1
95 β1
F1
100
G1
105
5.0 ppm 3.9 3.8 3.7 3.6 3.5 3.4 3.3 ppm
F2
FIGURE 5.23 The HMQC spectrum for lactose. See text for an explanation of the notation. Assignments are given as an aid.
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256 CHAPTER 5 TWO-DIMENSIONAL NMR SPECTROSCOPY

β4 α4 HMBC 600 MHz

HDO G1 α5 G4 G3
β1 α3 β6' G6 G5 β3
α1 β6 G2 β2
α6 β5 α2

ppm 5.0 ppm 3.9 3.8 3.7 3.6 3.5 3.4 3.3 ppm

α6
60 β6
F1 G6
61

ppm
G4
69

70 α5
G2
71 α2
α3

72
G3

73
F1 β2
74
β3
β5
75 ppm G5

76
78.0

77 78.5
4.50 4.45 ppm
78 β4
α4

ppm α1
95 β1
F1
100
G1
105
5.0 ppm 3.9 3.8 3.7 3.6 3.5 3.4 3.3 ppm
F2
FIGURE 5.24 The HMBC spectrum for lactose. See text for an explanation of the inset.
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5.8 RELAYED COHERENCE TRANSFER: TOCSY 257

5.2 5.0 4.8 4.6 4.4 4.2 4.0 3.8 3.6 3.4 TOCSY 600 MHz
ppm

3.4 3.4

3.6 α2 3.6
α4
3.8 α3 3.8
α6
4.0 α5 4.0

4.2 4.2

4.4 4.4
G1
4.6 4.6
β1
4.8 4.8
HDO
5.0 5.0

5.2 5.2 α1
5.2 5.0 4.8 4.6 4.4 4.2 4.0 3.8 3.6 3.4 ppm
F1
FIGURE 5.25 The 2D TOCSY spectrum of 𝛽-lactose. Correlation lines are drawn in and some assignments
are given as an aid.

figure to the COSY spectrum for lactose in Figure 5.21 and we acquire the 1D spectrum. The only signals that will be
note the similarities and differences. recorded in this spectrum are those to which magnetization
As an example, we can find all of the proton reso- has been transferred. Put another way, all other signals that
nances (and determine their chemical shifts) for the are outside the spin system do not appear.
𝛼-anomer of glucose by starting at its anomeric proton An even better scenario is to run a series of 1D TOCSY
resonance at 5.23 ppm. These correlations have been marked experiments in which the mixing time is systematically
in the figure. Assignment of the proton resonances (which increased while the proton being irradiated is kept constant.
are shown in the figure) cannot be made on the basis of this To illustrate these experiments, we irradiated the anomeric
spectrum alone, but could be made in conjunction with the proton from the 𝛽-anomer of the glucose ring in lactose
COSY spectrum. The same exercise can be carried out for at 4.67 ppm and ran a series of experiments with mix-
the other two anomeric resonances, but these are left for ing times ranging from 20 ms to 400 ms. The results of
the student. these experiments are shown in a series of stacked plots
in Figure 5.26.
At a mixing time of 20 ms, we find only the 𝛽2
5.8.2 1D TOCSY: Lactose
resonance, which is seen clearly as an apparent triplet at
Every 2D experiment has a 1D analogue and we tend to 3.29 ppm. After 40 ms of mixing time, transfer to 𝛽3 is
think that these 1D experiments are less efficient or infor- readily discernable (another apparent triplet) and the 𝛽4
mative, which they usually are. If we think again about our proton is just barely visible. A plot of the experiment with
COSY experiment, we have said that homonuclear decou- a mixing time of 80 ms reveals the 𝛽4 resonance a little
pling would give us the same type of information. We select better, while, after 120 ms, the signal from 𝛽5 has sprouted
a proton resonance, irradiate it, and compare the result with from the baseline. After 400 ms, transfer throughout the
the original 1D proton spectrum. In similar fashion for a 1D entire spin system is evident; the H-5 signal is robust as
TOCSY experiment, often called HOHAHA (Homonuclear that from the diastereotopic 𝛽6 methylene group. This part
Hartmann-Hahn), we select a proton resonance and irradiate of the figure shows the 𝛽6 and 𝛽6′ resonances with clearly
it; we allow for an appropriate mixing time for the magneti- different coupling constants to 𝛽5. One negative aspect of
zation to be relayed during which we apply spin locking, and long mixing times is that both resolution and signal are lost.
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258 CHAPTER 5 TWO-DIMENSIONAL NMR SPECTROSCOPY

Mixing time 400 ms α1 irradiated

α6
α3
α4
α5
α2

Mixing time 400 ms G1 irradiated

G4

G3
G5 G2

Mixing time 400 ms β1 irradiated

β6 β6'

Mixing time 120 ms

β5

Mixing time 80 ms
β4

Mixing time 40 ms
β3

β2
Mixing time 20 ms

1
H NMR 600 MHz

3.9 3.8 3.7 3.6 3.5 3.4 3.3 ppm

FIGURE 5.26 Stacked plots of a series of 1D TOCSY experiments on 𝛽-lactose with increasing mixing times. See text for an
explanation. A portion of the 1 H NMR spectrum is reproduced for reference in the bottom plot.
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5.10 ROESY 259

We can usually offset signal loss by acquiring and summing (a)

more FIDs. Also shown in this figure are the 400 ms (longest 90x 90x 90x Acquire (t2)
mixing time) experiments for the galactose anomeric proton Rd
and the 𝛼-anomeric proton for glucose. t1 τm
1
Both the 1D and 2D versions of TOCSY find wide H:
application in deciphering overlapping signals that originate
from different spin systems. The 1D version is particularly
exciting as it enables us to “walk” through a spin system as
we systematically increase the mixing time. (b)
τm Acquire (t2)
90x
Rd
5.9 HMQC–TOCSY 1 t1 Spin-lock
H:
There are various hybrid 2D correlation experiments that
combine features of two simpler 2D experiments. A pop-
ular and useful example is the HMQC–TOCSY spectrum FIGURE 5.27 Pulse sequences for (a) 2D NOESY and
that correlates one-bond 1 H⏤13 C couplings (HMQC) but (b) 2D ROESY.
shows these correlations throughout an entire spin system
(TOCSY). This experiment simplifies the analysis of com- experiment, NOESY (nuclear Overhauser effect spectros-
plex carbohydrate and peptide systems and allows ready copy), is not very useful for small molecules. NOESY is used
assignments of systems of protons and carbons. primarily with biological macromolecules. Both NOESY
and ROESY experiments correlate protons that are close to
each other in space, typically 4.5 Å or less.
5.9.1 HMQC–TOCSY: Lactose
Because ROESY provides through-space proton-proton
The HMQC–TOCSY spectrum for lactose is given in correlations, its appearance and presentation resembles
Figure 5.28 with all of the proton and carbon resonances COSY. In fact, COSY peaks (generated through J cou-
labeled. The overall appearance of this spectrum is reminis- pling) are present in ROESY spectra; these COSY peaks
cent of an HMBC but the correlations are quite different. are superfluous and should be ignored. Occasionally, another
It is equally interesting and useful to start on the proton complication arises from TOCSY-like transfer of magnetic
axis (F2) or the carbon axis (F1). If we start on the pro- coherence among J-coupled spins. The pulse sequences
ton axis at 5.23 ppm, the anomeric proton for the 𝛼-anomer for 2D NOESY and 2D ROESY experiments are given in
of glucose (𝛼1), and proceed downward vertically, we find Figure 5.27. The only difference between the two experi-
six correlations to the six carbons of this glucose residue. ments is that ROESY uses a spin lock during the mixing
If we refer back to the simple HMQC spectrum for lactose, time 𝜏m .
we find only one correlation for this proton. Likewise, the
anomeric proton of the 𝛽-anomer of glucose at 4.67 ppm also
shows six correlations to the carbons of its respective glucose 5.10.1 ROESY: Lactose
residue. The ROESY spectrum of lactose is given in Figure 5.29.
Correlations to the anomeric proton of galactose Note the overall appearance in the upper part of the figure.
(4.46 ppm), however, only show four interactions along In the lower part, the anomeric region is shown as expanded
the carbon axis. This result is consistent with the 1D insets. The two glucose residues are straightforward to
TOCSY spectrum of the galactose anomeric proton shown interpret. The 𝛼-anomeric proton shows only one correlation
in Figure 5.26, where we find that coherence transfer does and this is the expected COSY interaction. Recall that
not travel beyond H-4 (G4). All six correlations are found if by definition, the 𝛼-anomer has its C-1 hydroxyl in the
we start at H-4 (G4, 3.93 ppm) instead. As an exercise, try axial position and its C-1 proton (𝛼1) in the equatorial
a similar process by starting on the carbon axis and tracing position. In the equatorial position, there are no through
horizontally to the left to find HMQC–TOCSY correlations space interactions likely and none are seen.
to protons. The anomeric carbon resonances are the easiest The other anomer of glucose, in contrast, has its
to try, but it is worthwhile to try others as well. anomeric proton (𝛽1) in the axial position. In the preferred
chair conformation of glucose, protons occupy all of the
other axial positions leading to presumed diaxial interac-
5.10 ROESY tions between H-1 (𝛽1) and H-3 (𝛽3) and between H-1 (𝛽1)
and H-5 (𝛽5). The ROESY spectrum reveals three interac-
The ROESY experiment, rotating-frame Overhauser effect tions with the anomeric proton, 𝛽1, at 4.67 ppm. The H-2
spectroscopy, is a useful 2D analogue of the nuclear Over- COSY interaction is, of course, present, and the two diax-
hauser effect difference experiment. This experiment is ial NOE interactions with H-3 (𝛽3) and H-5 (𝛽5) are quite
useful for molecules of all sizes whereas the related evident.
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260 CHAPTER 5 TWO-DIMENSIONAL NMR SPECTROSCOPY

β4 α4 HMQC-TOCSY 600 MHz

HDO G1 α5 G4 G3
β1 α3 β6' G6 G5 β3
α1 β6 G2 β2
α6 β5 α2

ppm 5.0 ppm 3.9 3.8 3.7 3.6 3.5 3.4 3.3 ppm

α6
60 β6
F1
61 G6

ppm
G4
69

70 α5
G2
71 α2
α3

72
G3

73
F1
β2
74
β3
β5
75
G5

76

77

78 β4
α4

ppm α1
95 β1
F1
100
G1
105
5.0 ppm 3.9 3.8 3.7 3.6 3.5 3.4 3.3 ppm
F2
FIGURE 5.28 The HMQC–TOCSY spectrum of lactose. Assignments are given as an aid.
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5.10 ROESY 261

ppm 5.2 5.0 4.8 4.6 4.4 4.2 4.0 3.8 3.6 3.4 ppm ROESY 600 MHz

3.4 3.4

3.6 3.6

3.8 3.8

4.0 4.0
F1
4.2 4.2

4.4 4.4
G1
4.6 4.6
β1
4.8 4.8
HDO
5.0 5.0

5.2 5.2 α1

ppm
G5 G3 G2

F1 4.45 G1
β6 α6 β6' β4 β5
α5 α4

ppm
β3 β5 β2
4.65
F1 β1

4.70

ppm
α2
5.20

F1 α1
5.25

4.0 3.9 3.8 3.7 3.6 3.5 3.4 3.3 ppm

F2
FIGURE 5.29 Top: the 2D ROESY spectrum of lactose. Bottom: expansions of the three anomeric correlations.
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262 CHAPTER 5 TWO-DIMENSIONAL NMR SPECTROSCOPY

5.11 VGSE systems of protons; in this case there are four moieties. As
an example of “total correlation,” the correlations among
Proteins or polypeptides are polymers or oligomers made the glutamic acid protons are drawn in the figure. As with
from a limited number of (mostly) 𝛼-amino acids linked the COSY spectrum, the amide protons are expedient entry
by amide or peptide bonds. A polypeptide example would points to initiate the process. Can you find an appropriate
be too difficult an undertaking at this point, but a tetra- entry point for the valine, which has no amide proton?
peptide, on the other hand, is quite manageable while still In some ways, the information from the COSY spectrum
illustrating many of the important features of a true polypep- of VGSE is complementary to its TOCSY spectrum, and in
tide. Although many small oligopeptides are found in nature, other ways the information is redundant. Both spectra allow
a plethora of small peptides are now manmade utilizing us to individually assign all of the proton signals of VGSE
automated synthesis equipment. in different ways. In this case, which spectrum furnishes the
The structure of the small peptide being used as an information more easily or more clearly?
example in this chapter is given in Figure 5.1. Starting with
the N-terminus, the peptide contains the amino acids valine,
glycine, serine, and glutamic acid (VGSE) linked in the usual
5.11.3 HMQC: VGSE
way. The 1D NMR spectra for this compound are shown Compared to caryophyllene oxide and lactose, the HMQC
in Figure 5.30. The positions in each amino acid have been spectrum for the tetrapeptide appears relatively simple
labeled and assignments of the protons and carbons have (Figure 5.33). Indeed, VGSE has only 10 carbon atoms with
been made. The assignments have been given in this figure attached protons and the spectrum shows correlations to nine
to facilitate discussion; they cannot be made from these data carbons. Actually, there are 10 correlations as can be seen
alone. in the inset of the shielded methyl portion of the spectrum.
One aspect of the experimental conditions under which Let us summarize the complementary information up to and
these spectra were obtained is important to understand so including the HMQC spectrum.
that the spectra can be rationally interpreted. For solubility Let us start our analysis with the carbon resonance at
and stability purposes, peptides are generally dissolved 43 ppm in the HMQC spectrum, which is a ⏤CH2 ⏤ group
in buffered water. Recall from Chapter 3 that compounds from the DEPT spectra, and note that it correlates with a
prepared for NMR experiments are almost always dissolved diastereotopic methylene group centered at 4.04 ppm. From
in deuterated solvents. The need for deuterated solvents is the DQF-COSY spectrum (see Figure 5.31), the multiplet
so that the spectrometer can remain stable for the duration at 4.04 ppm shows only one correlation to an amide proton
of the experiment by way of the field/frequency lock. The at 8.75 ppm. Thus, the methylene group must belong to the
lock signal comes from the deuterium NMR signal of the glycine residue, and furthermore, the glycine residue cannot
solvent. However, if the peptide sample were dissolved in be the N-terminus, since the N-terminal amino acid must
buffered D2 O, all of the exchangeable protons, including the have a free amino group.
amide protons, would be replaced with deuterons and not The serine residue can be accounted for by starting with
seen in a 1 H NMR spectrum. A compromise is necessary; the the carbon resonance at 62 ppm. DEPT indicates another
sample was dissolved in 95% buffered H2 O containing 5% methylene group, and the HMQC spectrum shows that it
D2 O. Note the presence of the three amide proton resonances correlates with coincident protons resonating at 3.85 ppm.
between 8.0 ppm and 9.0 ppm. These amide resonances, as These protons overlap with another proton. Careful line
we shall see, are extremely important and they would be drawing in the DQF-COSY spectrum (or more easily in
absent if the sample were dissolved in pure D2 O. the TOCSY spectrum) suggests correlation with a proton at
4.48 ppm. This proton shows a correlation to a carbon atom
at 56 ppm in the HMQC spectrum. That proton also shows
5.11.1 COSY: VGSE
a correlation to an amide proton at 8.40 ppm in the COSY
The DQF-COSY spectrum of VGSE can be found in spectrum. Like glycine, the serine residue cannot be the
Figure 5.31. As with lactose, there are several good entry N-terminus.
points, especially the resonances of the three amide pro- Since valine is the only amino acid in the tetrapeptide
tons. Three of the four amino acid residues can be traced that has methyl groups, and since the DEPT spectra show two
using these as starting points. The fourth amino acid can methyl groups at about 17 ppm and 18 ppm, we can safely
be traced starting with the methyl groups (the only ones in start with those in the HMQC. Both methyl carbons fortu-
the molecule) at 1.0 ppm. Verify the correlations that have itously correlate with the same doublet at 1.01 ppm, even
been drawn in Figure 5.31. Watch out for confusion between though they are obviously diastereotopic. (Note that the inte-
valine and serine. gration of this doublet in the proton spectrum [Figure 5.30]
corresponds to six protons.) The methyl groups are coupled
to a methine proton at 2.20 ppm (COSY). In turn, the HMQC
5.11.2 TOCSY: VGSE
reveals a correlation from the methine proton to a carbon
The 2D TOCSY spectrum for VGSE is given in Figure 5.32. resonance at 31.5 ppm. The isopropyl methine (2.20 ppm)
Like lactose, VGSE is composed of several isolated spin shows a further correlation in the COSY to a methine in the
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5.11 VGSE 263

1
H NMR 600 MHz
S NH E NH S3 V2
G NH
G1
S2 E2

2700 2600 2500 2400 Hz

5200 5100 5000 4900 Hz
E4
V3 E3 E3' V4,5

OH
1400 1300 1200 Hz 600 Hz
5 C O
4 CH3 OH 4 CH2
5
3 CH CH3 3 CH2 3 CH2
2 1 1
H2N CH C N CH2 C N CH C N CH C OH
2 1 2 2 1
H H H
O O O O
Valine (V) Glycine (G) Serine (S) Glutamate (E)

8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 ppm

13
C/DEPT 150.9 MHz
DEPT-90

DEPT-135

E5 E1 S3 V4,5
G1, S1 V2 S2 V3
V1 G2 E3
E4
E2

178 176 174 172 ppm 60 55 50 45 40 35 30 25 ppm

FIGURE 5.30 The 1 H, 13 C, and DEPT NMR spectra for the tetrapeptide, VGSE, in 95% H2 O and 5% D2 O.
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264 CHAPTER 5 TWO-DIMENSIONAL NMR SPECTROSCOPY

8 7 6 5 4 3 2 1 COSY 600 MHz

ppm 9

V4,5
1 1

E3'
2 2 E3
V3
E4
3 3

V2,S3
4 4 G2
E2
F1 S2
5 5

6 6

7 7

8 8 E NH
S NH
G NH
9 9
9 8 7 6 5 4 3 2 1 ppm
F2
FIGURE 5.31 The DQF COSY spectrum of VGSE. Correlation lines are drawn in and some assignments are given as an aid.

overlapping multiplet at 3.85 ppm. This proton shows a cor- (except the carbonyls). This collection of spectra, however,
relation in the HMQC to the carbon at 59 ppm. Although it does not allow us to assign or confirm the order of amino
is difficult to see, this methine does not correlate any fur- acids in the peptide, an immensely important task.
ther (i.e., it does not couple with any of the amide protons),
making valine the N-terminus.
5.11.4 HMBC: VGSE
Assignments for the final amino acid (glutamic acid)
logically can begin with the unassigned carbon at 54 ppm. The HMBC spectrum of VGSE is given in Figure 5.34; to
The HMQC spectrum provides us with its proton partner, a improve the resolution of the cross peaks, the spectrum has
multiplet at 4.21 ppm. Correlations in the COSY spectrum been split into four parts. In order to assign the carbonyl
are found for proton resonances at 1.93 ppm and 2.11 ppm. carbon resonances and to completely sequence the amino
These two protons are readily seen as being diastereotopic acids, we can start at either end of the molecule. We have
because they correlate to the same carbon atom (27 ppm) in previously stated that valine is the N-terminal amino acid
the HMQC spectrum. Both of the diastereotopic protons cor- because its 𝛼-amino group is not part of a peptide bond. A
relate (COSY) with a triplet at 2.37 ppm, which represents logical place to start within the valine residue is to assign
the protons of the second methylene group of glutamic acid. its carbonyl. This assignment can be made to the peak at
The carbon resonance for this methylene group is revealed 170.1 ppm, as there are obvious correlations to the valine
in the HMQC spectrum at 31 ppm. It is worth noting from C-2 proton (V2) and the valine C-3 proton (V3). In addition,
the COSY spectrum that the methine proton at 4.21 ppm is there are correlations to the glycine methylene group (G2)
coupled to the amide proton at 8.10 ppm. and to the glycine amide proton (G NH).
For VGSE, the HMQC spectrum is the perfect accom- These two correlations (and generally, ones like them)
paniment to the DQF-COSY and TOCSY spectra for are extremely important in the process of sequencing the
assigning all of the protons and nearly all of the carbons amino acids. Until now, all of the correlations have been
 Silverstein c05.tex V3 - 07/31/2014 12:11 A.M. Page 265

5.12 PULSED FIELD GRADIENT NMR 265

TOCSY 600 MHz

ppm 9 8 7 6 5 4 3 2 1

V4,5
1 1

E3' E3'
2 2 E3
E3
E4 V3
E4
3 3

V2,S3
4 E2 4 G2
E2
F1 S2
5 5

6 6

7 7

8 8 E NH
S NH
G NH
9 9
9 8 7 6 5 4 3 2 1 ppm
F2
FIGURE 5.32 The 2D TOCSY spectrum of VGSE. Some correlation lines are drawn in and assignments are given as an aid.

intra-residue, but the HMBC experiment allows generally the amide proton of serine (S NH) correlates with the C-2
for inter-residue correlations. Develop a line of reasoning protons of glycine (G2), the amide proton of glutamic acid
to sequence the remaining two amino acids (serine and (E NH) correlates with the C-2 proton (and C-3 protons as
glutamic acid). Note that the carbonyl carbons for glycine well) of serine (S2 and S3). The manner in which the data are
and serine overlap in the carbon spectrum. presented in Figure 5.35 greatly simplifies our interpretation
and makes comparisons more meaningful.
5.11.5 ROESY: VGSE
We end our discussion of VGSE by comparing the ROESY 5.12 PULSED FIELD GRADIENT NMR
correlations of the amide protons with the correspond-
ing interactions in COSY and TOCSY. Figure 5.35 shows A well-established area in the field of NMR is the use
comparable sections of each spectrum. We have seen the of pulsed field gradients, or PFG NMR. It is ironic to
COSY and TOCSY portions earlier and showed how these consider that so much effort has been expended over so
spectra, along with the HMQC spectrum, can be used for many years to provide a homogeneous or stable magnetic
intra-residue assignments. The ROESY correlations, on the field. Today, most modern high field NMR spectrometers are
other hand, reinforce the HMBC information and help to routinely equipped with hardware (coils) that rapidly ramps
confirm the sequence of amino acids with inter-residue the magnetic field along one of three mutually orthogonal
correlations. axes. These magnetic field gradients are incorporated into
The boxed cross peaks illustrate the through space the pulse sequence in a large range of applications.
interaction of the amide proton of one amino acid with the We include a brief discussion of gradients here because
adjacent amino acid’s C-2 proton. Thus, the amide proton of there are many applications to correlation experiments. We
glycine (G NH) correlates with the C-2 proton of valine (V2), treat gradients in a general manner; for a more technical
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266 CHAPTER 5 TWO-DIMENSIONAL NMR SPECTROSCOPY

HMQC 600 MHz

V4,5
E4
S3,V2

G2
S2 E2 V3 E3 E3'
ppm

ppm V4,5
20

18 E3
30 V3
E4
F1
1.05 1.00 0.95 ppm
40
G2

50
E2
S2
V2
60 S3

4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 ppm

F2
FIGURE 5.33 The HMQC spectrum for VGSE. Assignments are given as an aid.

treatment and for a myriad of other applications, consult the Dynamic nuclear polarization (DNP), mentioned in
review by Price (1996). Chapter 3, is an alternative emerging method which can also
In Section 5.3.1, we mention phase cycling as an impor- provide even more substantial time savings for multidimen-
tant part of any pulse sequence. The details of phase cycling sional NMR experiments.
are still beyond our treatment (see Claridge, 1999), but we While our initial interest in gradient NMR stems from
can easily appreciate one of their negative aspects: time. In the fact that familiar experiments can be run more quickly
correlation experiments, anywhere from 4 to 64 phase cycles and more efficiently, the most exciting uses of gradients are
must be summed in order to produce one usable FID. If the novel experiments that cannot be run without them. We
signal-to-noise is poor, then the identical cycle is repeated find that gradients allow for improved magnetic resonance
until sufficient signal is acquired. Particularly if signal-to- imaging (MRI), improved magnetic resonance microscopy,
noise is not an issue, these phase cycles can be wasteful of better solvent suppression (especially water), and entirely
spectrometer time and account for at least one reason why new areas of inquiry such as diffusion measurements.
2D experiments take so long. Gradients are also used in a new class of so-called ultra-
In a PFG experiment, the pulse sequence can be rewrit- fast multidimensional NMR experiments. A detailed discus-
ten so that phase cycling can be greatly reduced or elimi- sion of these is beyond the scope of this text. However, the
nated altogether. Thus, if signal-to-noise is sufficient, each reader should be aware that these methods can speed up mul-
run through the pulse sequence can generate one FID in a tidimensional NMR experiments by orders of magnitude.
2D experiment. The saving in instrument time is enormous; Alternatives to the standard method of systematically incre-
experiments that previously took several hours to an entire menting t1 and carrying out two sets of Fourier transforms
day can now be run in a matter of minutes. One reassuring also offer new opportunities in multidimensional NMR. Even
point for us to realize is that, even though the experiment single-scan multidimensional NMR is now possible (see Tal
is run differently, the results, and hence, the interpretation and Frydman, 2010 and Freeman, 2011); one can envis-
remain the same. One should be aware that the use of gra- age real-time two-dimensional NMR monitoring of chemical
dients typically reduces the S/N compared to using phase reactions and dynamic processes. These methods are partic-
cycles. Therefore, for dilute samples where extensive sig- ularly beneficial when one is not sample limited. If the con-
nal averaging is needed anyways, it may be advantageous to centration of the sample is too low, signal averaging will still
avoid gradients. be required to get spectra with good signal-to-noise ratios.
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5.12 PULSED FIELD GRADIENT NMR 267

HMBC 600 MHz

ppm 9.0 8.5 ppm 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 ppm

V4,5
20

E3
30 V3
E4
F1

40
G2

50
E2
S2
V3
60
S3

F2
S NH E NH S3,V2 E4 V4,5
G NH E3,3'
G2
S2 E2 V3
ppm

170 V1
G1,S1
172

F1 174

176

E1
178
E5

180

9.0 8.5 ppm 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 ppm
F2
FIGURE 5.34 The HMBC spectrum for VGSE. Important correlation lines are drawn in and assignments are given as an aid.
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268 CHAPTER 5 TWO-DIMENSIONAL NMR SPECTROSCOPY

COSY 600 MHz TOCSY 600 MHz ROESY 600 MHz

S NH E NH
G NH

ppm

2.0 E3'
E3
V3
E4
2.5

3.0
F1
3.5

V2,S3
4.0 G2
E2
4.5 S2

9.0 8.8 8.6 8.4 8.2 ppm 8.8 8.6 8.4 8.2 ppm 8.8 8.6 8.4 8.2 8.0 ppm
F2 F2 F2
FIGURE 5.35 A comparison of the DQF COSY, 2-D TOCSY, and ROESY spectra showing the interactions of the amide protons.

REFERENCES

For a list of Chapter References, please visit: www.wiley.com/college/silverstein.

STUDENT EXERCISES

5.1 For the compounds of Problem 3.3 a-o, draw the following 5.9 Make as many correlations as possible for lactose using the 2D
spectra: COSY, HMQC, HMBC, and INADEQUATE. Be sure TOCSY spectrum found in Figure 5.25. Compare your results
to label the F1 and F2 axes. Assume experimental conditions for the glucose residue to the results that were found in the 1D
are the same as in Problem 3.3. HOHAHA in Figure 5.26.
5.2 Assign all of the correlations for ipsenol in the DQF COSY 5.10 Given are the structure and 1 H, 13 C/DEPT, COSY, 1D
spectrum found in Figure 5.9. Indicate each type of coupling TOCSY, 2D TOCSY, HMQC, HMQC–TOCSY, HMBC, and
as geminal, vicinal, or long range. ROESY spectra for raffinose. Confirm the structure, assign
5.3 Complete the assignments for ipsenol for the HMBC spectrum all protons and carbons, and show as many correlations as
found in Figure 5.14. To aid in bookkeeping, you may want to possible.
construct a table similar to Table 5.1. 5.11 Given are the structure and 1 H, 13 C/DEPT, COSY, HMQC, and
5.4 Identify the compound C6 H10 O from its 1 H, 13 C/DEPT, COSY, HMBC spectra for stigmasterol. Confirm the structure, assign
and HMQC spectra and show all correlations. all protons and carbons, and show as many correlations as
5.5 Identify the compound C10 H10 O from its 1 H, 13 C/DEPT, possible.
COSY, and HMQC spectra and show all correlations. 5.12 The 1 H, 13 C/DEPT, COSY, 2D TOCSY, HMQC, HMBC,
5.6 Identify the compound C8 H9 NO2 from its 1 H, 13 C/DEPT, and ROESY spectra for a tri-peptide containing the amino
COSY, HMQC, and INADEQUATE spectra and show all cor- acids lysine, serine, and threonine. Sequence the peptide and
relations. assign all protons and carbons. Show as many correlations as
5.7 Assign all of the carbon connectivities for caryophyllene oxide possible.
using the INADEQUATE spectrum found in Figure 5.19. In all exercises, the 13 C NMR spectra shown are, from top to
5.8 Identify compound C10 H18 O from its 1 H, 13 C/DEPT, HMQC, bottom, the DEPT-90, DEPT-135, and full proton-decoupled
13
HMBC, and INADEQUATE spectra. C NMR spectra.
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Exercise 5.4 STUDENT EXERCISES 269

1
H NMR 600 MHz

1300 Hz 1250 Hz 1150 Hz

1050 1000 Hz 860 840 820 Hz 620 600 580 Hz

2.3 2.2 2.1 2.0 1.9 1.8 1.7 1.6 1.5 1.4 1.3 1.2 1.1 1.0 ppm
13
C/DEPT 150.9 MHz

220 200 180 160 140 120 100 80 60 40 20 ppm

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270 CHAPTER 5 Two-Dimensional NMR Spectroscopy Exercise 5.4

ppm 2.4 2.2 2.0 1.8 1.6 1.4 1.2 1.0 ppm COSY 600 MHz

1.0 1.0

1.2 1.2

1.4 1.4

F1 1.6 1.6

1.8 1.8

2.0 2.0

2.2 2.2

F2 HMQC 600 MHz

ppm

15 15

20 20

25 25

F1 30 30

35 35

40 40

45 45

2.4 2.2 2.0 1.8 1.6 1.4 1.2 1.0 ppm

F2
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Exercise 5.5 STUDENT EXERCISES 271

1
H NMR 600 MHz

4800 4750 Hz 4450 4400 Hz 4350 4300 Hz

1750 1700 Hz 1550 1500 Hz 1250 1200 Hz

8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 ppm

13
C/DEPT 150.9 MHz

200 180 160 140 120 100 80 60 40 ppm

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272 CHAPTER 5 Two-Dimensional NMR Spectroscopy Exercise 5.5

ppm 8 7 6 5 4 3 2 ppm COSY 600 MHz

2 2

3 3

ppm 8.0 7.5 7.0 ppm

4 7.0 4

F1 5 5
7.5

6 6
8.0

7 7

8 8

F2 HMQC 600 MHz

ppm

40 40
ppm

125
60 60

130
80 80
F1 135
8.2 8.0 7.8 7.6 7.4 7.2 ppm
100 100

120 120

140 140

9 8 7 6 5 4 3 2 ppm
F2
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Exercise 5.6 STUDENT EXERCISES 273

1
H NMR 600 MHz

5480 5470 Hz 5200 5190 Hz 4910 4900 Hz

4370 4360 Hz 2590 2580 Hz 790 780 Hz

9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 ppm
13
C/DEPT 150.9 MHz

160 150 140 130 120 110 100 90 80 70 60 50 40 30 ppm

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274 CHAPTER 5 Two-Dimensional NMR Spectroscopy Exercise 5.6

ppm 9 8 7 6 5 4 3 2 ppm COSY 600 MHz

2 2

3 3

4 4

F1 5 5

6 6

7 7

8 8

9 9

F2 HMQC 600 MHz

ppm

20 20

40 40

60 60

80 80
F1
100 100

120 120

140 140

160 160

9 8 7 6 5 4 3 2 ppm
F2
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Exercise 5.6 STUDENT EXERCISES 275

INADEQUATE 150.9 MHz

Hz
–25000 –25000

–20000 –20000

–15000 –15000

–10000 –10000

–5000 –5000

F1 0 0

5000 5000

10000 10000

15000 15000

20000 20000

25000 25000

160 140 120 100 80 60 40 20 ppm

F2

Hz

12000 12000

13000 13000
F1
14000 14000

15000 15000

16000 16000

17000 17000

165 160 155 150 145 140 135 130 125 ppm
F2
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276 CHAPTER 5 Two-Dimensional NMR Spectroscopy Exercise 5.8

1
H NMR 600 MHz

3500 3450 Hz 3050 3000 Hz 1400 1350 Hz

1200 1150 Hz 950 900 Hz 750 700 Hz

5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 ppm
13
C/DEPT 150.9 MHz

150 140 130 120 110 100 90 80 70 60 50 40 30 20 ppm

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Exercise 5.8 STUDENT EXERCISES 277

ppm 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 ppm COSY 600 MHz

1.5 1.5

2.0 2.0

2.5 2.5

3.0 3.0
F1 3.5 3.5

4.0 4.0

4.5 4.5

5.0 5.0

5.5 5.5

F2 HMQC 600 MHz

ppm

20 20

40 40

60 60

80 80
F1
100 100

120 120

140 140

6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 ppm
F2
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278 CHAPTER 5 Two-Dimensional NMR Spectroscopy Exercise 5.8

HMBC 600 MHz

ppm

20

40

60

80
F1
100

120

140

160
6.0 5.5 5.0 4.5 4.0 F2 3.5 3.0 2.5 2.0 1.5 ppm

ppm ppm

20 20

40 40

60 60

F1

ppm ppm

120 120

140 140

6.0 5.9 5.8 ppm 5.2 5.0 ppm 2.0 1.5 ppm
F2
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Exercise 5.8 STUDENT EXERCISES 279

INADEQUATE 150.9 MHz

Hz

–15000 –15000

–10000 –10000

–5000 –5000

F1
0 0

5000 5000

10000 10000

15000 15000

140 120 100 80 60 40 20 ppm

F2
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280 CHAPTER 5 Two-Dimensional NMR Spectroscopy Exercise 5.10

1
H NMR 600 MHz
CH 2 OH
HO O H
CH2
H O CH 2 OH H
HO H O H O
H
H H H H O
HO H
H HO O
HO CH 2 OH
H HO HO H

4.1 4.0 3.9 3.8 3.7 3.6 3.5 ppm

HDO

5.4 5.3 5.2 5.1 5.0 4.9 4.8 4.7 4.6 4.5 4.4 4.3 4.2 4.1 4.0 3.9 3.8 3.7 3.6 ppm
13
C/DEPT 150.9 MHz

74.0 73.5 73.0 72.5 72.0 71.5 71.0 70.5 70.0 69.5 69.0 ppm

100 95 90 85 80 75 70 65 ppm
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Exercise 5.10 STUDENT EXERCISES 281

Mixing time 300 ms 5.40 ppm irradiated 1D TOCSY 600 MHz

Mixing time 80 ms

Mixing time 40 ms

Mixing time 20 ms

4.05 4.00 3.95 3.90 3.85 3.80 3.75 3.70 3.65 3.60 3.55 3.50 ppm

Mixing time 300 ms 4.97 ppm irradiated 1D TOCSY 600 MHz

Mixing time 80 ms

Mixing time 40 ms

Mixing time 20 ms

1
H NMR 600 MHz

4.05 4.00 3.95 3.90 3.85 3.80 3.75 3.70 3.65 3.60 3.55 3.50 ppm
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282 CHAPTER 5 Two-Dimensional NMR Spectroscopy Exercise 5.10

Mixing time 80 ms 1D TOCSY 600 MHz

Mixing time 40 ms

Mixing time 20 ms

1
H NMR 600 MHz

4.05 4.00 3.95 3.90 3.85 3.80 3.75 3.70 3.65 3.60 3.55 3.50 ppm
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Exercise 5.10 STUDENT EXERCISES 283

5.4 5.2 5.0 4.8 4.6 4.4 4.2 4.0 3.8 3.6 ppm COSY 600 MHz
ppm

3.6 3.6

3.8 3.8

4.0 4.0

4.2 4.2
F1
4.4 4.4

4.6 4.6 HDO

4.8 4.8

5.0 5.0

5.2 5.2

5.4 5.4

ppm COSY 600 MHz

3.5

3.6

3.7

3.8
F1
3.9

4.0

4.1

4.2
4.2 4.1 4.0 3.9 3.8 3.7 3.6 3.5 ppm
F2
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284 CHAPTER 5 Two-Dimensional NMR Spectroscopy Exercise 5.10

ppm 5.4 5.2 5.0 4.8 4.6 4.4 4.2 4.0 3.8 3.6 ppm TOCSY 600 MHz

3.6 3.6

3.8 3.8

4.0 4.0

4.2 4.2
F1
4.4 4.4

4.6 4.6 HDO

4.8 4.8

5.0 5.0

5.2 5.2

5.4 5.4

TOCSY 600 MHz

ppm

3.5

3.6

3.7

3.8
F1
3.9

4.0

4.1

4.2
4.2 4.1 4.0 3.9 3.8 3.7 3.6 3.5 ppm
F2
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Exercise 5.10 STUDENT EXERCISES 285

HMQC 600 MHz

ppm 5.5 ppm 4.1 4.0 3.9 3.8 3.7 3.6 3.5 ppm

60
F1

65

ppm
69

70

71

72

73

74
F1
75

76

77

78

79

80

81

ppm
95
F1
100

105
5.5 ppm 4.1 4.0 3.9 3.8 3.7 3.6 3.5 ppm
F2
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286 CHAPTER 5 Two-Dimensional NMR Spectroscopy Exercise 5.10

HMQC–TOCSY 600 MHz

ppm 5.5 ppm 4.1 4.0 3.9 3.8 3.7 3.6 3.5 ppm

60
F1

65

ppm
69

70

71

72

73

74
F1
75

76

77

78

79

80

81

ppm
95
F1
100

105
5.5 ppm 4.1 4.0 3.9 3.8 3.7 3.6 3.5 ppm
F2
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Exercise 5.10 STUDENT EXERCISES 287

HMBC 600 MHz

ppm 5.5 ppm 4.1 4.0 3.9 3.8 3.7 3.6 3.5 ppm

60
F1

65

ppm
69

70

71

72

73

74
F1
75

76

77

78

79

80

81

ppm
95
F1
100

105
5.5 ppm 4.1 4.0 3.9 3.8 3.7 3.6 3.5 ppm
F2
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288 CHAPTER 5 Two-Dimensional NMR Spectroscopy Exercise 5.10

ppm 5.4 5.2 5.0 4.8 4.6 4.4 4.2 4.0 3.8 3.6 ppm ROESY 600 MHz

3.6 3.6

3.8 3.8

4.0 4.0

4.2 4.2
F1
4.4 4.4

4.6 4.6
HDO
4.8 4.8

5.0 5.0

5.2 5.2

5.4 5.4

ppm
4.10

F1 4.15
4.20

ppm
4.90
F1
4.95

ppm
5.35
F1
5.40

5.45
4.1 4.0 3.9 3.8 3.7 3.6 3.5 ppm
F2
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Exercise 5.11 STUDENT EXERCISES 289

1
H NMR 600 MHz

3200 3100 Hz 2200 2100 Hz 1300 Hz 1100 1000 Hz

1000 900 Hz 700 600 Hz 600 500 Hz

CH3
CH3 H CH3
HO H

HH

5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 ppm

13
C/DEPT 600 MHz

32.0 ppm 21.5 ppm

140 130 120 110 100 90 80 70 60 50 40 30 20 ppm

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290 CHAPTER 5 Two-Dimensional NMR Spectroscopy Exercise 5.11

COSY 600 MHz

ppm 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 ppm

1 1

2 2

3 3

4 4

5 5

ppm COSY 600 MHz

0.6

0.8

1.0

1.2

1.4
F1
1.6

1.8

2.0

2.2

2.4
2.4 2.2 2.0 1.8 1.6 1.4 1.2 1.0 0.8 0.6 ppm
F2
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Exercise 5.11 STUDENT EXERCISES 291

HMQC 600 MHz

ppm 5.5 ppm 3.6 ppm 2.2 2.0 1.8 1.6 1.4 1.2 1.0 0.8 0.6 ppm

15

20

25

30

35
F1
40

45

50

55

60

65

70

ppm

130

140

5.5 ppm 3.6 ppm 2.2 2.0 1.8 1.6 1.4 1.2 1.0 0.8 0.6 ppm
F2
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292 CHAPTER 5 Two-Dimensional NMR Spectroscopy Exercise 5.11

HMBC 600 MHz

ppm 5.5 ppm 3.6 ppm 2.2 2.0 1.8 1.6 1.4 1.2 1.0 0.8 0.6 ppm

15

20

25

30

35
F1
40

45

50

55

60

65

70

ppm

130

140

5.5 ppm 3.6 ppm 2.2 2.0 1.8 1.6 1.4 1.2 1.0 0.8 0.6 ppm
F2
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Exercise 5.12 STUDENT EXERCISES 293

1
H NMR 600 MHz
0o C in 5%/95% D2O/H 2O

5200 5100 5000 4900 Hz 2500 2400 2300 2200 Hz

Impurity

1560 Hz 900 800 700 600 Hz

1 1 2 # of protons 1 2 3 2 11 2 2 3

9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 ppm

13
C/DEPT 150.9 MHz

175 170 ppm 70 65 60 55 50 45 40 35 30 25 ppm

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294 CHAPTER 5 Two-Dimensional NMR Spectroscopy Exercise 5.12

8 7 6 5 4 3 2 1 COSY 600 MHz

ppm 9 ppm

1 1

2 2

3 3

4 4
F1
5 5

6 6

7 7

8 8

ppm COSY 600 MHz

1.0 1.0

1.5 1.5

2.0 2.0

2.5 2.5
F1
3.0 3.0

3.5 3.5

4.0 4.0

4.5 4.5
4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 ppm
F2
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Exercise 5.12 STUDENT EXERCISES 295

ppm 9 8 7 6 5 4 3 2 1 ppm TOCSY 600 MHz

1 1

2 2

3 3

4 4
F1
5 5

6 6

7 7

8 8

TOCSY 600 MHz

ppm

1.0 1.0

1.5 1.5

2.0 2.0

2.5 2.5
F1
3.0 3.0

3.5 3.5

4.0 4.0

4.5 4.5
4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 ppm
F2
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296 CHAPTER 5 Two-Dimensional NMR Spectroscopy Exercise 5.12

COSY 600 MHz TOCSY 600 MHz ROESY 600 MHz

ppm
1.0

1.5

2.0

2.5
F1
3.0

3.5

4.0

4.5
9.0 8.5 8.0 7.5 ppm 8.5 8.0 7.5 ppm 8.5 8.0 7.5 7.0 ppm
F2 F2 F2
HMQC 600 MHz

ppm

20

30

40
F1

50

60

4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 ppm

F2
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Exercise 5.12 STUDENT EXERCISES 297

HMBC 600 MHz

ppm 9.0 8.5 8.0 ppm 4.0 3.5 3.0 2.5 2.0 1.5 1.0 ppm

20

30

F1
40

50

60

F2

ppm

168

170

F1 172

174

176

178

180
9.0 8.5 8.0 ppm 4.0 3.5 3.0 2.5 2.0 1.5 1.0 ppm
F2
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CHAPTER 6
MULTINUCLEAR MAGNETIC
RESONANCE SPECTROSCOPY

6.1 INTRODUCTION AND GENERAL shifts, although it is still widely done that way in practice.
CONSIDERATIONS Implementation of the IUPAC referencing procedure can
be straightforward, depending on the spectrometer software
used.
The previous three chapters have shown that nuclear
The IUPAC method uses the proton resonance of tetram-
magnetic resonance experiments with 1 H and 13 C nuclei are
ethylsilane (TMS) for organic solvents, and 2,2-dimethyl
enormously useful to the chemist working with organic com-
silapentane-5-sulfonic acid (DSS) for aqueous samples to get
pounds. There is no need, however, to limit ourselves to these
the primary frequency of the spectrometer. This frequency
two important nuclei. Indeed, there are about 130 different
is then used to reference all X nuclei using the following
stable isotopes whose spin quantum number, I, is greater
equation:
than zero and, therefore, theoretically observable in an NMR ( )
experiment. Of these nuclides, 33 have a spin quantum Ξ = 100 vX ∕vTMSobs
number of 12 .
Listed in Appendix A are all magnetically active nuclei where Ξ is the frequency ratio (Appendix A), 𝜈X is the
along with some of their properties. It is worthwhile to absolute frequency for the 0.00 ppm position in the
spend some time exploring Appendix A and to compare X spectrum, and 𝜈TMSobs is the absolute frequency for 1 H
some of the nuclides listed there with 1 H and 13 C (also of TMS that is a measured value on the specific instrument.
listed). First, we find that many elements have more than one The advantage of this method is that once the 1 H frequency is
magnetically active isotope. A small portion of Appendix calibrated, the entire periodic table of spin-active nuclei can
A is reproduced in Table 6.1, with the addition of typical be analyzed without running the typical external or internal
chemical shift ranges. Generally, the range of chemical standard for that nucleus.
shifts observed for various elements increases from left to Let us return to Table 6.1 that lists the nuclides discussed
right across the periodic table, and from top to bottom. in some detail in this chapter. To determine the suitability of a
(Although a detailed discussion is beyond the scope of this particular nuclide for an NMR experiment, we must consider
text, the main factor that contributes to typical chemical several factors such as the natural abundance, receptivity,
shift ranges is the paramagnetic contribution to magnetic and spin quantum number. Consider the element hydrogen
shielding, which in turn depends on the average of the as an example. Hydrogen has three isotopes: 1 H (protium),
2 H (deuterium), and 3 H (tritium). Each isotope has been used
inverse cubed valence electron–nuclear distance.) Compare,
for example, the ranges for 1 H (∼10 ppm), 13 C (∼220 ppm), in NMR studies, and each has different advantages to offer.
1 H and 3 H both have a spin quantum number of 1 and they
and 195 Pt (over 10000 ppm). 2
Recall that chemical shift data are only useful if properly both have high receptivities (proportional to 𝛾 3 (I(I + 1)), but
3 H has zero natural abundance and is radioactive. Tritium
referenced. In fact, excluding 1 H and 13 C data, we must
exercise extreme caution when comparing chemical shifts can therefore only be observed if we intentionally put it
from different sources because many other nuclei have seen into a molecule synthetically, while protium is ubiquitous
more than one compound used as a reference. To attempt to and we are already familiar with its uses. Deuterium has a
standardize chemical shifts, IUPAC has proposed a unified spin of one and a very low natural abundance of 0.0115%;
scale for referencing chemical shifts of any nuclei in any it is not radioactive. It is a useful isotope for mechanistic
sample relative to an established primary reference. With studies in organic chemistry and biochemistry. Its low natural
modern instruments, at a given magnetic field, all resonance abundance allows us to effectively ignore it when we observe
frequencies are derived from a single source: the magnet. other nuclei (couplings to 2 H will not be evident in the
It is therefore possible to relate the observed frequencies spectra), yet with modern instruments we are able to directly
of all nuclides in a particular sample to a single primary record natural abundance 2 H NMR spectra.
reference and, for the sake of simplicity, the proton resonance Besides deuterium, 11 B and 27Al are two other nuclides
of TMS (0.00 ppm) has been chosen as this primary standard. listed in Table 6.1 that have spin quantum numbers greater
Using a suitable secondary reference compound is no longer than 12 . Most of the elements of the periodic table have
the officially recommended method for reporting chemical quadrupolar nuclei (I > 12 ). These so-called quadrupolar

298
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6.2 15 N NUCLEAR MAGNETIC RESONANCE 299

TABLE 6.1 Useful Magnetic Resonance Data for Some of the Nuclides Discussed in This Chapter

Spin Frequency Primary Typical

Quantum Natural Relative𝐚 (MHz) at Reference Chemical Shift
Isotope Number Abundance % Receptivity 7.046 T Compound Range (ppm)
1 1
H 2
99.9885 1.000 300.000 Si(CH3 )4 10 to 0
2 −6
H 1 0.0115 1.11 × 10 46.052 Si(CD3 )4 10 to 0
3 1
H 2
0 0 319.993 Si(CT3 )4 10 to 0
3
11
B 2
80.1 0.132 96.269 BF3 ⋅ Et 2 O in CDCl3 135 to −130
13 1 −4
C 2
1.07 1.70 × 10 75.451 Si(CH3 )4 220 to 0
14 −3 14 b
N 1 99.632 1.00 × 10 21.686 NH3 (1) 900 to 0
15 1 −6 15 b
N 2
0.368 3.84 × 10 30.419 NH3 (l) 900 to 0
17 5 −2 −2
O 2
3.7 × 10 2.91 × 10 40.670 H2 O 1700 to −50
19 1
F 2
100 0.834 282.387 CFCl3 276 to −280
27 5
Al 2
100 0.207 78.232 Al(NO3 )3 (aq) 250 to −200
29 1
Si 2
4.6832 3.68 × 10−4 59.648 Si(CH3 )4 175 to −380
31 1
P 2
100 6.65 × 10−2 121.554 85% H3 PO4 (aq) 270 to −480
195 1
Pt 2
33.832 3.51 × 10−3 65.473 Na2 PtCl6 (aq) 7500 to −6500

a Relative to 1 H.
b At 25∘ C.

nuclei can often be observed in NMR experiments; however, pharmaceutical fields), biochemistry, and polymer chem-
there are also many examples where rapid quadrupolar istry. These four nuclides, 15 N, 19 F, 29 Si, and 31 P, are pre-
relaxation broadens the signals beyond detection. 11 B and sented with a few simple examples and a brief consideration
27Al have good spectroscopic properties in that they have of important experimental factors and limitations.
high natural abundances and good receptivities relative to The theoretical background for understanding the NMR
1 H. In addition to the general considerations of natural spectroscopy of these four nuclides is analogous to that
abundance and receptivity, the quadrupole moment of a which has been presented for 1 H and 13 C in Chapters 3
particular nuclide as well as its environment in the molecule and 4. Our treatment of spin, coupling constants, the NOE,
of interest will determine the rate of quadrupolar relaxation, Fourier transformation, etc. can be applied to these nuclides
which is inversely proportional to the line width in the NMR without modification. We also use the concept of chemical
spectrum. Quadrupolar nuclei with good natural abundances shift without modification, but we must avoid exercising
and which are found in symmetric environments (e.g., the predictive skills that we have developed for 1 H and
tetrahedral or octahedral) can give sharp NMR lines and 13 C chemical shifts for these nuclei. The use of NMR

even give rise to splittings due to J couplings in some spectroscopy of nuclei other than 1 H and 13 C to characterize
cases. Note that the 2nI + 1 rule applies for predicting J and identify organic compounds is now commonplace. The
multiplets for all nuclei, where n is the number of equivalent use of other nuclei in NMR experiments ranges from diverse
nuclei coupled to the observed nucleus. Conversely, nuclides areas such as simply determining whether an unknown
such as 63 Cu, 105 Pd, 127 I, or 187 Re will almost invariably compound contains nitrogen to more complex questions of
give extremely broad lines, and it is not generally practical stereochemistry and reaction mechanisms.
to acquire their spectra. Without isotopic enrichment, the
NMR spectroscopy of nuclei such as 17 O, 33 S, and 43 Ca
is also often impractical due to their very low natural 6.2 15 N NUCLEAR MAGNETIC
abundances. RESONANCE
Our goals for the remainder of this chapter are modest
as we confront such a vast field as multinuclear magnetic After carbon and hydrogen, oxygen and nitrogen are the
resonance. In Section 3.7, we have seen the impact of next two most important elements in organic compounds.
other nuclei that possess a magnetic moment (especially In the mind of the organic chemist, the presence of either
those with spin 12 ) on proton NMR spectra. We will briefly of these elements represents the presence of one or more
examine below the NMR spectroscopy of four spin 12 functional groups and the use of IR spectroscopy may be
nuclides, which were selected for their historic importance invoked. Without detracting in any way from IR, this line
in organic chemistry (and related natural products and of reasoning is nonetheless too restrictive, especially with
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300 CHAPTER 6 MULTINUCLEAR MAGNETIC RESONANCE SPECTROSCOPY

respect to nitrogen. Inspection of Table 6.1 reveals that in fixed value of one-half the ratio of the proton’s magnetogyric
the case of oxygen, we have but a single choice of a nucleus ratio (𝛾) relative to that of the other nuclide is the maximum
on which NMR is possible; 17 O has a spin of 25 and it is not possible enhancement, while the actual enhancement is also
used much in NMR studies due to its low natural abundance, proportional to (ii) the extent of 13 C⏤1 H dipolar relaxation.
while 16 O has a spin of 0 and is thus not NMR-active (not For a proton-decoupled 13 C NMR experiment, the maximum
listed in Table 6.1). NOE enhancement is 𝛾H ∕(2)𝛾C or 26.753/(2)6.728, which
Nitrogen, on the other hand, has two magnetically active equals 1.98. The total sensitivity increase is therefore nearly
isotopes, 14 N and 15 N. Because nitrogen compounds are so threefold because the NOE enhancement is added to the orig-
important in organic chemistry, natural products chemistry, inal intensity.
pharmacology, and biochemistry, both of these isotopes have The actual enhancement for the 13 C⏤1 H system can be
been the subject of intensive NMR investigation. Aside anywhere from 0 to 1.98 depending on the mechanism of
from the various classes of nitrogen containing functional relaxation for each individual nucleus. In practice, for car-
groups with which we are familiar, entire fields of study have bons with no attached protons, the enhancement is essentially
developed based on nitrogen-containing compounds. These zero since there is practically no 13 C⏤1 H dipolar relaxation.
include alkaloids, peptides and/or proteins, and nucleic For small- to medium-sized organic molecules, 13 C⏤1 H
acids. For purposes of study by NMR, nucleic acids are a dipolar relaxation for carbons with attached protons is very
favorite subject because not only is nitrogen ubiquitous in efficient, yielding close to the full 200% increase in signal. If
these compounds but so is phosphorus (see Section 6.5). If we apply the same reasoning to the 15 N nucleus, we arrive at
we again refer to Table 6.1, we find that neither of the two a very different situation. The magnetogyric ratio for 15 N is
isotopes of nitrogen is ideal for NMR. The most abundant small and negative (𝛾 = −2.713 × 107 rad T−1 s−1 ). A quick
isotope of nitrogen, 14 N, which represents greater than 99% calculation shows that the maximum NOE enhancement for
15 N is 𝛾 ∕(2)𝛾 = (26.753/(2) × (−2.713)) which is equal to
of nitrogen’s natural abundance, possesses a spin of 1 and H N
hence an electric quadrupole moment. This nucleus has a −4.93. Generally, a spin 12 nucleus with a positive magne-
low Larmor frequency and typically gives broad NMR peaks togyric ratio gives positive NOE enhancement with proton
due to quadrupolar relaxation. We shall not consider it any decoupling, while a spin 12 nucleus with a negative magnet-
further. ogyric ratio gives negative NOE enhancement.
The other isotope of nitrogen, 15 N, also has a low For the 15 N nucleus, the maximum enhancement is
Larmor frequency, which, when multiplied by a very −4.93 + 1, or −3.93. In the case where 15 N⏤1 H dipolar
low natural abundance, leads to an extremely low absolute relaxation dominates, the signal is inverted (negative) and its
sensitivity. Modern methods have largely overcome the prob- intensity is nearly four times what it would be in the absence
lem of sensitivity (by isotopically enriching samples or by of 1 H irradiation. However, since 15 N dipolar relaxation
indirect 1 H detection) and we focus our attention on 15 N is one of many relaxation mechanisms for 15 N, proton
largely because its spin quantum number is 12 and the NMR decoupling can lead to NOEs ranging from 0 to −4.93
line widths are quite narrow. or a signal ranging from +1 to −3.93. The experimental
There are two important experimental factors that must downside to this situation is that any NOE between 0 and
be accounted for if we are to be successful in running 15 N −2.0 lowers the absolute intensity of the observed signal. In
NMR experiments. The 15 N nucleus tends to relax very fact, an NOE of exactly −1.0 produces no signal at all. In
slowly; T1 ’s of greater than 80 seconds have been mea- general, as we saw for carbon and now for nitrogen, proton
sured. Thus, either long recycle delays must be incorporated decoupling is commonly practiced for routine heteronuclear
into our pulse sequence or, alternatively, we could provide NMR experiments. In so doing, we must always bear in mind
another route for spin relaxation. A common procedure is to the practical outcome of NOE enhancement. It is important
add a trace amount of chromium (III) acetylacetonate, a para- to note that inverse-gated proton decoupling, discussed in
magnetic substance, whose unpaired electrons can efficiently Chapter 4, can be used to overcome the problem of the NOE
decrease the T1 of 15 N. In cases where T1 values are not potentially lowering signal intensity for 15 N.
known (and not intended to be measured), recycle delays and Let us turn our attention to 15 N NMR spectra. As
pulse angles must be considered carefully because the signal we have already mentioned, natural-abundance 15 N NMR
from one (or more) 15 N resonance can accrue too slowly or spectra can be obtained on modern instruments even though
be missed altogether. 15 N is about an order of magnitude less sensitive than 13 C.
We consider the other experimental factor, the NOE, Today, there is general agreement that liquid ammonia* is
which has already been discussed in Chapters 3 and 4, now the standard primary reference compound for 15 N (used
in more detail. Recall that we routinely run 13 C NMR experi-
ments with irradiation of the protons (i.e., proton decoupled) * Nitromethane was used occasionally as an internal reference and set to
that, aside from producing the desired effect of singlets for all 0 ppm, but the resulting 15 N chemical shifts for nitrogen-containing organic
13 C signals, also enhances the signal for carbons with directly compounds are generally negative. The use of liquid ammonia as an external
reference precludes the need for negative numbers because virtually all
bonded protons. This enhancement is due to the NOE; the 15 N atoms are deshielded by comparison, but handling liquid ammonia
changes in signal intensity arise from polarization of spin is awkward. The usual procedure is to add 380 ppm to the shift obtained
populations away from the natural Boltzmann distribution. by reference to nitromethane in order to report the shift relative to liquid
The amount of enhancement depends on two factors: (i) the ammonia.
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6.2 15 N NUCLEAR MAGNETIC RESONANCE 301

externally), although, in the past, many compounds such as tabulated values, prediction and interpretation of 15 N chem-
ammonium nitrate, nitric acid, and nitromethane have been ical shifts are best carried out using modern quantum chem-
used. When consulting the literature, reliable chemical shifts istry methods, as empirical models can fail.
can usually be obtained after correcting for their reported Lest we take this analogy with carbon too far, we must
standard. remember that nitrogen is unique and has peculiar chemical
We are by now familiar with the construction of the shift features. The two most important ones are both due
chemical shift scale and need not consider the details here. largely to the unshared pair of electrons found on nitrogen.
Nitrogen, like carbon, is a second-row element and in many Just as this electron pair has a large impact on the chemistry
ways experiences similar electronic influences. To a first of these compounds, it also has a great influence on the
approximation, the chemical shifts of nitrogen-containing chemical shifts of the nitrogen in certain environments.
organic compounds closely parallel carbon chemical shifts. We find quite often that chemical shift positions are more
The chemical shift range for nitrogen in common organic sensitive to the solvent than are structurally similar carbon
compounds is just over 500 ppm, which is about twice that resonances. The other way that the lone pair on nitrogen
for carbon chemical shifts. Figure 6.1 shows the chemical influences chemical shift is through protonation. Protonation
shift ranges for many types of nitrogen-containing com- can have either a shielding or deshielding effect on the
pounds. The relatively large chemical shift range taken nitrogen chemical shift depending on the functional group.
together with the very narrow lines for 15 N resonances means For example, strong shielding on the order of 100 ppm due
that the chances of fortuitous overlap in an 15 N NMR spec- to protonation is observed for nitrogen atoms in conjugated
trum are even smaller than in a 13 C NMR spectrum. Beyond heterocycles, while slight deshielding can be observed for
a simple comparison of 15 N chemical shifts against a list of alkyl amines. Solvent effects can be as large as 45 ppm;

900 800 700 600 500 400 300 200 100 0

ALIPHATIC AMINES Primary

Secondary
Tertiary
ALIPHATIC AMMONIUM IONS Primary
Secondary
Tertiary
DIMETHYL ENAMINES
ANILINIUM IONS
ANILINES
PIPERIDINES, DECAHYDROQUINOLINES
CYCLIC ENAMINES
AMINOPHOSPHINES
GUANIDINES Imino Amino
UREAS, CARBAMATES, LACTAMS
AMIDES Primary
Secondary
Tertiary
THIOUREAS
THIOAMIDES
NITRAMINES NO2 N
INDOLES, PYRROLES
HYDRAZONES, TRIAZENES =N-NH2 N N N Imino Amino
IMIDES
NITRILES, ISONITRILES Iso
PYRROLE-LIKE NITROGENS
DIAZO Terminal Internal
DIAZONIUM Terminal Internal
PYRIDINES Pyridine
PYRIDINE-LIKE NITROGENS Benzofurazan Furazan Pyrazine Pyrimidine Imidazole
IMINES
OXIMES
AZOXY
NITRO
AZO
RNNN RNNN RNNN
AZIDES
NITROSO Ar-NO S-NO N N O

900 800 700 600 500 400 300 200 100 0

FIGURE 6.1 Chemical shift ranges for various nitrogen-containing compounds and functional groups. Adapted from Levy and Lichter
(1979).
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302 CHAPTER 6 MULTINUCLEAR MAGNETIC RESONANCE SPECTROSCOPY

TABLE 6.2 Typical J-Coupling Constants negative NOE enhancement and therefore the peak should
Involving 15 Na be negative.* When processing an FID, however, peaks
may be phased either up or down; the phase of a single
Coupling Typical Range
Constant of Values (Hz)
peak may be manually phased in an arbitrary manner and the
sign only has meaning if peaks of differing phase are found in
1
JNH −40 to −136 the same spectrum.† The nitrogen in formamide has partial
2
JNH −15 to +15 double bond character and is shifted accordingly (deshield-
1
JNC −77.5 to +36 ing effect).
1
JNN −25 to +15 The proton-coupled and proton-decoupled 15 N NMR
1
JNP −82 to +92 spectra of ethylenediamine are shown in Figure 6.3. First, we
1
JNSi <20
note the relatively shielded position of the nitrogen resonance
a See Witanowski et al. (1986, 1993) and Berger et al. (1997). here compared to formamide. The other noteworthy feature
of these spectra is the inset showing proton coupling. Before
we discuss this part of the figure, a few general comments
pyridine, for example, shows a range of 33 ppm in different are in order. One-, two-, and three-bond 15 N⏤1 H couplings
solvents. These effects are larger than those observed for 13 C are common while long-range couplings usually require
in large part due to the participation of the nitrogen atom intervening 𝜋 bonds. The magnitude and sign of the coupling
in a hydrogen bond with the solvent. Shifts due to aprotic constants have been compiled but detailed consideration here
solvents are typically smaller. The reviews by Witanowski is beyond our goal. We note that the magnitude of 1 JNH varies
et al. (1986, 1993) summarize the effects of protonation, from about 40 Hz to 135 Hz, 2 JNH between 0 Hz and 15 Hz,
solvent, temperature, and hydrogen bonding on the nitrogen and 3 JNH between 0 Hz and 10 Hz. If we again consider
chemical shifts of various functional groups. the inset in Figure 6.3, we note an apparent quintet with a
Nitrogen-15 will J couple to other spins as we have relatively small coupling constant of about 2 Hz to 3 Hz. Our
seen for 1 H and 13 C. Typical ranges of various coupling interpretation is that we see no 1 JNH coupling because of
constants are summarized in Table 6.2. Note that, due to rapid exchange and that the two- and three-bond coupling
the low natural abundance of 15 N, couplings to 15 N are not constants are about the same. In a heteronuclear system (e.g.,
observed in 1 H NMR spectra; however, the converse is not nJ
XH ), first-order rules always apply because Δ𝜈 is of the
true because in an N⏤H bond, for example, practically every order of millions of hertz.
15 N spin is bonded to a 1 H spin. Splittings due to 19 F or 31 P
The proton-decoupled 15 N NMR spectrum of pyridine,
are similarly readily observed in 15 N NMR spectra due to which has an aromatic nitrogen, is shown in Figure 6.4. A
the high natural abundances of the former nuclei. However, comfortable pattern is now emerging and, in fact, we can
couplings between 13 C and 15 N will not be observed in the safely say that there is nothing extraordinary about this or
NMR spectra of either nucleus unless isotopic enrichment is
used.
The proton-decoupled 15 N NMR spectrum of for-
* Note that, in general, the phase of the peak could depend on various
mamide is shown in Figure 6.2. This spectrum looks remark-
experimental parameters including the relaxation delay, pulse angle, T1 , etc.
ably like a 13 C NMR spectrum with a single resonance. This
13 C-like appearance as opposed to a 1 H-like appearance will The discussion here considers only theoretical magnitude of the NOE.
† Although the origin of the positive and negative peaks in the DEPT
be the norm throughout this chapter as long as we apply pro- experiment is different from that discussed here, DEPT spectra are a useful
ton decoupling. The other feature worth noting is the phase example of a scenario where peaks of opposite phase are observed in a single
of the peak. With proton decoupling, formamide experiences spectrum.

15
N NMR 30.4 MHz
O

H NH2

128 126 124 122 120 118 116 114 112 110 108 106 104 ppm
FIGURE 6.2 The proton-decoupled 15 N NMR spectrum of formamide in CDCl3 , referenced to external NH3 (l).
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6.2 15 N NUCLEAR MAGNETIC RESONANCE 303

15
N NMR 30.4 MHz

NH2
H2N

13.0 12.8 12.6 12.4 12.2 p pm

19 18 17 16 15 14 13 12 11 10 9 8 7 6 ppm
15
FIGURE 6.3 The proton-decoupled N NMR spectrum of ethylene diamine in CDCl3 , referenced to external NH3 (l). The
proton-coupled 15 N NMR spectrum is shown in the inset.

15
N NMR 30.4 MHz

328 326 324 322 320 318 316 314 312 310 308 306 304 ppm
FIGURE 6.4 The proton-decoupled 15 N NMR spectrum of pyridine in CDCl3 , referenced to external NH3 (l).

any of the spectra that we have seen thus far. Since our goal considering the proton-decoupled 15 N NMR spectrum of
in this chapter is not to catalog the literally thousands of quinine (Figure 6.5), a well-studied, naturally occurring
chemical shifts that have been reported but to introduce the alkaloid.
NMR of other nuclei besides 13 C and 1 H, let us conclude Both nitrogen atoms of quinine are evident and, with-
our survey of one-dimensional 15 N NMR spectra by briefly out hesitation, we can make assignments. If, instead, we

H2C H
15
N NMR 30.4 MHz

H
N
HO
H
H3C O

320 300 280 260 240 220 200 180 160 140 120 100 80 60 ppm
FIGURE 6.5 The proton-decoupled 15 N NMR spectrum of quinine in CDCl3 , referenced to external NH3 (l).
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304 CHAPTER 6 MULTINUCLEAR MAGNETIC RESONANCE SPECTROSCOPY

OH
5C O
4 CH3 OH 4 CH2
5
3 CH CH3 3 CH2 3 CH2
2 1 1
H2 N CH C N CH2 C N CH C N CH C OH
2 1 2 2 1
H H H
O O O O
Valine (V) Glycine (G) Serine (S) Glutamate (E)
1 15
H– N HSQC 600 MHz

ppm

120

F1 130

140

9.0 8.9 8.8 8.7 8.6 8.5 8.4 8.3 8.2 8.1 8.0 7.9 ppm
F2
15
N Projection from 1H–15N HSQC 600 MHz (1 hour)

170 160 150 140 130 120 110 100 90 ppm

15
N NMR 60.8 MHz (15 hours)

170 160 150 140 130 120 110 100 90 ppm

FIGURE 6.6 The H⏤ N HSQC NMR spectrum and its projection of a tetrapeptide (see the structure) in dilute solution. The
1 15

2D spectrum required 1 hour of instrument time. The bottom spectrum shows an attempt to obtain a 1D 15 N NMR spectrum for
15 hours.
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6.2 15 N NUCLEAR MAGNETIC RESONANCE 305

had isolated quinine as a new unknown, natural compound, detected methods. In the field of biomolecular NMR, pro-
we could envision a procedure in which we extend the teins are prepared for NMR analysis by expressing them
concept of identifying compounds from a combination of with 15 N-labeled amino acid residues. Since 15 N has a nat-
spectra to include heteronuclear NMR; 15 N NMR would ural abundance of 0.368%, labeling to 99% increases the
assume a natural place alongside mass spectrometry, IR, sensitivity of the experiment by a factor of about 270,
and other NMR spectroscopy experiments. Furthermore, as which, when combined with the HSQC type experiment,
we made the transition from simple 1 H and 13 C spectra to yields about an 84000-fold sensitivity increase over natu-
correlation spectroscopy in Chapter 5, we raise the ques- ral abundance directly detected methods. Thus, it is possi-
tion: Is there more to 15 N NMR than proton-decoupled ble to obtain good quality spectra on proteins up to 50 kDa
(and proton-coupled) one-dimensional spectra? The ques- (and beyond under favorable conditions). As an illustra-
tion is rhetorical; it is obvious that correlation experi- tion of the power of this technique, the 600 MHz 1 H⏤15 N
ments are possible and indeed many are commonplace. A HSQC NMR spectrum of myoglobin is shown in Figure 6.7;
good example is the two-dimensional 1 H⏤15 N heteronu- a complete analysis of this spectrum is beyond the scope
clear single-quantum coherence (HSQC) experiment, which of this text. Note that the 1D 1 H NMR spectrum of myo-
is illustrated in Figure 6.6 using the tetrapeptide example globin, which has 153 amino acid residues, is hopelessly
(valine–glycine–serine–glutamate) used in Chapter 5. overlapped in the amide region (see the spectrum along the
(HSQC yields the same type of information as the HMQC; F2 axis). However, by separating these resonances in the
the HSQC has less line broadening in the F1 dimension and 15 N dimension (F1), most of the 1 H⏤15 N correlations are

therefore provides better resolution in F1.) The experiment clearly resolved. This is a nice demonstration of the resolv-
was conducted on a dilute solution (5 mg in 0.5 ml of 95% ing power of two-dimensional correlation spectroscopy. The
H2 O/5% D2 O) of the compound. This spectrum gives us the amide 15 N chemical shift range for peptides covers a 40 ppm
chemical shifts of all three amide nitrogens indirectly. At window from about 110 ppm to 150 ppm. It should be
the bottom of this figure is a comparison of the projection noted that with modern instrumentation, it is possible to
from the 2D spectrum onto the 15 N axis, which took 1 hour acquire 15 N⏤1 H HSQC and HMBC NMR spectra for small
of instrument time to obtain, with an attempt to obtain the molecules with 15 N in natural abundance. Two-dimensional
15 N spectrum directly, which showed no signal even after correlation experiments with 15 N open up many possibili-
15 hours. As discussed in Chapter 5, inverse-detected exper- ties for structural characterization, with spectral interpreta-
( )3 tion being generally analogous to what we have seen for 13 C
iments give a sensitivity increase of 𝛾 1 H∕𝛾 15 N 2 , which
is about 310-fold for 1 H⏤15 N HSQC compared to directly in Chapter 5.

600 MHz 1H – 15N HSQC

5% / 95% D2O / H2O

ppm

120

125
F1
130

135

140

9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 ppm

F2
FIGURE 6.7 The 1 H⏤15 N HSQC spectrum of 15 N-labeled myoglobin.
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306 CHAPTER 6 MULTINUCLEAR MAGNETIC RESONANCE SPECTROSCOPY

6.3 19 F NUCLEAR MAGNETIC for convenience. We emphasize again that the combination
of 1 H, 13 C, and 19 F spectra is more convincing and more
RESONANCE
informative than any one spectrum is by itself.
An example of an aromatic fluorine-containing com-
The NMR of 19 F has great historic importance. Fluorine pound can be found in Figure 6.10, where we have recorded
has only one naturally occurring isotope, 19 F, and Table 6.1 the 19 F NMR spectra (both proton-coupled and decoupled)
shows that it is an ideal nucleus for study by NMR. The of fluorobenzene along with the 1 H and 13 C NMR spec-
sensitivity of 19 F is about 0.83 that of 1 H; this is the main tra. Once again, we find a singlet for the fluorine atom in
reason why 19 F NMR developed contemporaneously with 1 H the proton-decoupled spectrum and a complex multiplet for
NMR. The literature on chemical shifts and coupling con- the fluorine atom in the proton-coupled spectrum. The fluo-
stants is now old, and, again, some caution is needed when rine atom couples differently to the ortho-, meta-, and para-
comparing older chemical shifts with newer literature protons in this mono-substituted compound. Proton–fluorine
because much of it is referenced to external CF3 COOH. coupling constants can be found in Appendix F of Chapter 3.
Today, trichlorofluoromethane, CFCl3 , is the standard 19 F It is notable that all of the aromatic 13 C resonances appear
reference compound (0.00 ppm compared to CF3 COOH at as doublets due to coupling with the fluorine, even though
−78.5 ppm), which is generally inert, volatile, and gives rise the fluorine is up to four bonds away. Such two-, three-,
to a single 19 F resonance. and four-bond couplings to fluorine are not unusual in rigid
Our approach to 19 F NMR is different than was our systems.
approach to 15 N NMR and this section is brief. Fluorine is It is tempting to treat the proton NMR spectrum in a
monovalent and can be thought of as a substitute for hydro- similar fashion to our treatment of fluoroacetone. What we
gen in organic compounds. Fluorine is virtually unknown in have, however, is a higher order system, described by the
naturally occurring organic compounds; our interest in fluo- Pople notation AA′ GG′ MX, where X is the fluorine nucleus.
rine NMR involves synthetic compounds. Proton decoupling The A and A′ protons are not magnetically equivalent since
in 19 F NMR experiments does not involve NOE enhancement they do not couple equally with the G proton or the G′ proton.
in a critical way, and there are no other experimental factors Nor are the G and G′ protons magnetically equivalent since
out of the ordinary. Much of the original chemical shift and they do not couple equally with the A proton or the A′ proton.
coupling constant data for 19 F were published contemporane- The fluorine resonance is deceptively simple and appears
ously with those of 1 H. Figure 6.8 gives chemical shift ranges to be described by first-order rules. However, because the
for various fluorine-containing compounds. fluorine is part of a higher order spin system, it is not
The 1 H NMR spectrum of fluoroacetone was given in properly described by first-order rules and very complicated
Chapter 3 to show the effect of fluorine on 1 H spectra. Recall spectra are obtained depending on the strength of the applied
that resonances from both the methylene group and the magnetic field [see Page Jr. (1967)].
methyl group were split by coupling to the 19 F nucleus, each Chemical shifts for 19 F are difficult to predict empir-
into doublets with different coupling constants. In Figure 6.9, ically and we will make no attempt to offer a predictive
we have an opportunity to see the reciprocal effect of the pro- model. Table 6.3 presents a compilation of 19 F chemical
tons on the 19 F nucleus in fluoroacetone. This figure shows a shifts for various fluorine-containing compounds. One rea-
complete set of 19 F, 1 H, and 13 C NMR spectra. In the proton- son that the chemical shifts for 19 F are difficult to predict
decoupled 19 F spectrum, we see only a singlet for the fluorine and rationalize is that less than 1% of the shielding of the
19 F nucleus in organic compounds is due to diamagnetic
atom, reminding us again of a 13 C spectrum. In the proton-
coupled spectrum, however, we see that the fluorine is cou- shielding. Rather, paramagnetic shielding is the predominant
pled to two sets of hydrogens, producing a triplet with a large factor and is difficult to predict using empirical models.
coupling constant; the triplet is further split into three quar- Quantum chemical calculations are more useful in this con-
tets by a four-bond coupling with the protons of the methyl text. A selection of J-coupling constants involving 19 F is
group. The coupling constants are listed on each spectrum presented in Table 6.4.

–C(F)=O
–CF3–
–CF2–

–ArF-

–CF-

200 140 80 20 –40 –100

δ(19F) (ppm)
FIGURE 6.8 Fluorine-19 chemical shift ranges for compounds with various
fluorine-containing functional groups.
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6.3 19 F NUCLEAR MAGNETIC RESONANCE 307

19 O 19
F NMR 282.4 MHz F NMR 282.4 MHz
1
H decoupled
H 3C CH2F
48 Hz

4.3 Hz

–224.4 –224.6 –224.8 ppm –224.4 –224.6 –224.8 ppm

4.3 Hz
1
H NMR 300 MHz

48 Hz

4.8 4.6 4.4 4.2 4.0 3.8 3.6 3.4 3.2 3.0 2.8 2.6 2.4 2.2 ppm

13
C NMR 75.5 MHz 185 Hz

19.7 Hz

200 180 160 140 120 100 80 60 40 ppm

19
FIGURE 6.9 NMR spectra of fluoroacetone in CDCl3 .Top left: the proton-coupled F NMR spectrum. Top right: the proton-decoupled
version of the same spectrum. Middle: 1 H NMR spectrum showing doublet splittings due to coupling with 19 F. Bottom: 13 C NMR
spectrum showing doublet splittings due to coupling with 19 F.
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308 CHAPTER 6 MULTINUCLEAR MAGNETIC RESONANCE SPECTROSCOPY

19 F 19
F NMR 282.4 MHz F NMR 282.4 MHz
1
H decoupled

–112.0 –112.1 ppm –112.0 –112.1 ppm

1
H NMR 300 MHz

7.45 7.40 7.35 7.30 7.25 7.20 7.15 7.10 7.05 ppm

7.9 Hz 21 Hz
13
C NMR 75.5 MHz

3.1 Hz

245 Hz

165 160 155 150 145 140 135 130 125 120 115 ppm
FIGURE 6.10 Top: the proton-decoupled and proton-coupled 19 F NMR spectra (282.4 MHz) of fluorobenzene in CDCl3 .
Middle: 1 H NMR spectrum. Bottom: 1 H-decoupled 13 C NMR spectrum. There is long-range coupling to 19 F evident in the 1 H
and 13 C NMR spectra (see text for explanation).
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6.4 29 SI NUCLEAR MAGNETIC RESONANCE 309

TABLE 6.3 Chemical Shifts for Various Fluorine-Containing TABLE 6.4 Typical J-Coupling Constants Involving 19 Fa
Compounds
Structure
Compound 𝜹(19 𝐅) (ppm)
2
JHF (Hz)
CFCl3 0 FCH2 CH2 Cl 46
CF2 Cl2 8 CFH3 46
CF3 Cl 28.6 CF2 H2 50
CFBr3 7.4 CF3 H 79
CF2 Br2 7 cis-C2 F2 H2 72.7
CFBr3 7 trans-C2 F2 H2 74.3
CFH3 271.9
CF2 H2 1436 3
JHF (Hz)
CF3 H 78.6 p-fluorobromobenzene 8.62
CF4 62.3 FCH2 CH2 Cl 23
C 4 F8 135.15 F3 CCH3 12.8
C5 F10 132.9 cis-C2 F2 H2 20.4
(CF3 )2 CO 84.6 trans-C2 F2 H2 4.4
CF3 C(O)OH 76.5 FC⏤⏤CH 21
CF3 C(O)OCH3 74.2
CF3 COOEt 78.7 4
JHF (Hz)
(CF3 )3 N 56 (CH3 )3 NBF3 0.8
CH2 FCN 251 p-fluorobromobenzene 4.90
FCH⏤CH2 114 CF3 C(CH3 )⏤CHNO2 1.45
F2 C⏤CH2 81.3 CF3 C⏤⏤CF 4.3
F2 C⏤CF2 135
C 6 F6 164.9 2
JFF (Hz)
C6 H5 F 113.5 CF2 BrCHBrCl 154
p-C6 H4 F2 106 CF2 ClCH2 Cl 170
C6 H5 CFH2 207 CF2 ⏤CBrCl 30
C6 H5 C(O)OCF3 73.9
C6 H5 C(CF3 )2 OH 74.7 3
o-difluorobenzene JFF = −21 Hz
C6 H5 CF3 63.7 4
m-difluorobenzene JFF = 6 Hz
F2 (elemental) 422.9 5
p-difluorobenzene JFF = 18 Hz
SF6 57.4
SiF4 163.3 1
JCF (Hz)
HF (aqueous) 204
CFBr3 372
KF (aqueous) 125.3
CFCl3 337
CF2 H2 235
CF4 257
In closing this section, we mention that beyond routine FClC⏤CCl2 303
1
organic chemistry applications, 19 F NMR has in addition p-hydroxyfluorobenzene JCF = 237 Hz
2
found widespread applications in various specialized areas of JCF = 23 Hz
3
research including polymer chemistry, metabolism studies, JCF = 7.9 Hz
4
JCF = 2.1 Hz
biopharmaceutical sciences, magnetic resonance imaging,
and in studies of fluorine-labeled proteins. The interested 1
NF3 JNF = 160 Hz
reader is referred to recent reviews by Kitevski-LeBlanc and 1
CH3 SiF3 JSiF = 267 Hz
Prosser (2012) and Yu et al. (2013). ClCH2 PF2 1
JPF = −1203 Hz
a See Emsley et al. (1976) Prog. Nucl. Magn. Reson. Spectrosc., 10, 83–756.

6.4 29 SI NUCLEAR MAGNETIC

RESONANCE of 2% to 3% straddles the sharp, intense TMS singlet
(Section 3.7.4). This small doublet represents the 4.7% of
Silicon-containing organic compounds are increasingly used spin 12 29 Si, which naturally occurs in all silicon compounds.
by synthetic organic chemists and by polymer chemists. Table 6.1 reveals that the receptivity of the 29 Si nucleus
The 29 Si nucleus is the only isotope of silicon with a is about two times that of the 13 C nucleus when both are
magnetic moment and has a natural abundance of 4.7%. recorded at natural abundance. The magnetogyric ratio for
We have already come across the 29 Si nucleus in the 1 H 29 Si (𝛾 ) is negative (−5.319 × 107 rad T−1 s−1 ) so, for
Si
NMR spectrum of TMS; a small doublet, characterized by routine proton-decoupled spectra, we again have the possi-
a coupling constant (2 JSiH ) of about 6 Hz, with an intensity bility of negative 29 Si NOE enhancement depending, on the
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310 CHAPTER 6 MULTINUCLEAR MAGNETIC RESONANCE SPECTROSCOPY

RnSiH4–n
4 3 2 1
MenSi(Si≡)4–n
4 3 2 1
MenSi(OSi≡)4–n
4 0
(HO)nSi(OSi≡)4–n
4 0
Si(OSi≡)n(OAl≡)4–n
1 4
SiOn(OH)4–n
SiL6
SiX4 CI Br F
MSi down to –350
Transition metal silyl compounds

50 0 –50 –100 –150 –200

δ(29Si) (ppm)
FIGURE 6.11 Silicon-29 chemical shift ranges for various silicon-containing
compounds and functional groups. Adapted from Bruker Almanac 1995.

relative importance of dipolar spin relaxation. In this case, TABLE 6.5 Some Representative 29 Si Chemical Shiftsa
the maximum NOE is −2.51. This situation is much worse
Compound 𝜹(29 𝐒𝐢) (ppm)
than with 15 N NOEs because only NOEs between −2.01 and
the maximum, −2.51, actually result in an enhancement. All (CH3 )3 Si (TMS) 0.00
other values result in a net decrease in signal intensity com- (((CH3 )3 )Si)2 O 6.53
pared to no proton decoupling. Thus, experimental condi- (EtO)4 Si (TEOS) −82.04
tions must be carefully controlled if we are to realize the max- Silicon oil or silicone grease −22.0
imum signal, especially because the 29 Si nucleus can have Ph4 Si −14
long relaxation time constants. As mentioned for 15 N, such SiF4 −112
intensity problems can be largely overcome with the use of SiCl4 −18
SiBr4 −92
inverse-gated proton decoupling. Two-dimensional correla-
SiI4 −350
tion experiments involving 29 Si (e.g., HMBC) can be used in
SiH4 −91.9
many applications, including, for example, to monitor silyl- Me3 SiSiMe3 −19.7
protecting group migration in organic compounds. Me3 SiMn(CO)5 17.95
The chemical shifts for 29 Si in common organic com- Me3 SiOMe 20.72
pounds are much smaller than for 13 C shifts in common com- Me3 SiOH 14.84
pounds. This smaller shift range is probably due to the lack TBDMS-OMe 21.02
of multiple bonds to silicon in common functional groups. TBDMS-OEt 18.52
Figure 6.11 gives chemical shift ranges for various silicon- a See Williams, E.A. (1983) Ann. Rep. Nucl. Magn. Reson. Spectrosc., 15, 235–289.
containing compounds, and some specific values are given
in Table 6.5. Typical coupling constants that involve 29 Si are
presented in Table 6.6.
The proton-decoupled 29 Si NMR spectrum of TMS is TABLE 6.6 Typical J-Coupling Constants Involving 29 Sia
shown at the top of Figure 6.12 with the proton-coupled Compound Coupling Constant (Hz)
spectrum for comparison as an inset. TMS is the obvious
1
choice for a 29 Si reference compound and we set it at 0 ppm. (EtO)3 SiH JSiH = −287
1
The proton-coupled spectrum is quite interesting because the H4 Si JSiH = −202.5
1
29 Si nucleus is coupled to 12 equivalent protons in TMS. Me3 SiH JSiH = −184.0
1
F3 SiSiF3 JSiF = 321.8
First-order rules predict a multiplet with 13 peaks. There are 1
F3 SiNMe2 JSiF = 201.4
9 peaks clearly visible and 11 with a little imagination; we
CH2 ⏤CHSiCl3 1
JSiC = 113
do not see the full 13 peaks because the outer peaks are too MeSiCl3 1
JSiC = 86.6
weak and are lost in the noise. Me3 SiH 1
JSiC = 50.8
The 29 Si NMR spectra of triethylsilane in both proton- (Cl3 Si)2 SiCl2 1
JSiSi = 186
decoupled and proton-coupled modes are presented in Me3 SiSiMe2 F 1
JSiSi = 98.7
Figure 6.12. The proton-decoupled spectrum gives a sin- 1
(Me3 Si)4 Si JSiSi = 52.5
1
glet that is only slightly shifted from TMS. In triethylsilane, (H3 Si)3 P JSiP = 42.2
1
there is a proton directly attached to silicon, resulting in a Me3 SiPH2 JSiP = 16.2
large one-bond coupling (1 JSiH ) of about 175 Hz. There are a See Williams, E.A. (1983) Ann. Rep. Nucl. Magn. Reson. Spectrosc., 15, 235–289.
 Silverstein c02.tex V3 - 06/10/2014 4:06 P.M. Page 311

6.4 29 SI NUCLEAR MAGNETIC RESONANCE 311

29
Si NMR 59.6 MHz
CH3
H 3C Si CH3
CH3

0 Hz

4 3 2 1 0 –1 –2 –3 –4 –5 ppm

CH3
CH2
H3C CH2 Si CH2 CH3
H

140 120 100 80 Hz –50 –100 Hz

4 3 2 1 0 –1 –2 –3 –4 –5 ppm

CH3 CH3
CH2 CH2
H Si O Si H
CH2 CH2
CH3 CH3

–150 –200 Hz –350 –400 Hz

4 3 2 1 0 –1 –2 –3 –4 –5 ppm
29
FIGURE 6.12 (a) The proton-decoupled and proton-coupled (inset) Si NMR spectra (59.6 MHz) of tetramethylsilane (TMS)
in CDCl3 . The outer peaks of the multiplet are not discernible because of an insufficient signal-to-noise ratio. (b) The proton-
decoupled and proton-coupled (inset) 29 Si NMR spectra (59.6 MHz) of triethylsilane in CDCl3 . (c) Bottom, the proton-decoupled
and proton-coupled (inset) 29 Si NMR spectra (59.6 MHz) of 1,1,3,3-tetraethyldisiloxane in CDCl3 .
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312 CHAPTER 6 MULTINUCLEAR MAGNETIC RESONANCE SPECTROSCOPY

smaller two- and three-bond couplings that lead to identical TABLE 6.7 Phosphorus-31 Chemical Shifts for Various
complex multiplets. Phosphorus-Containing Compoundsa
A final example of 29 Si NMR is presented at the
Phosphorus (III) Phosphorus (V)
bottom of Figure 6.12, where we find the proton-decoupled Compounds 𝜹 (ppm) Compounds 𝜹 (ppm)
and proton-coupled 29 Si NMR spectra of 1,1,3,3-tetraethyl-
disiloxane. This compound is commercially available and is PMe3 62 Me3 PO 36.2
widely used to make various silicon-containing polymers. PEt3 20 Et3 PO 48.3
Before using the sample, a conscientious chemist might P(n-Pr)3 33 [Me4 P]+ 24.4
analyze it using various methods, which we now imagine P(i-Pr)3 19.4 [PO4 ]3− 6
might include 29 Si NMR. In this case, one would find that P(n-Bu)3 32.5 PF5 80.3
P(i-Bu)3 45.3 PCl5 80
there are two types of silicon in the sample (i.e., an unwanted
P(s-Bu)3 7.9 MePF4 29.9
impurity) because we find a peak with an intensity of about P(t-Bu)3 63 Me3 PF2 158
5% to 10% on the shoulder of the main peak in the proton- PMeF2 245 Me3 PS 59.1
decoupled spectrum. The chemical shifts of both peaks are PMeH2 163.5 Et3 PS 54.5
negative, a common feature for silicon bonded to oxygen. PMeCl2 192 [Et4 P]+ 40.1
The proton-coupled spectrum reveals a large one-bond PMeBr2 184 [PS4 ]3− 87
coupling constant (1 JSiH ) of about 215 Hz. The coupling PMe2 F 186 [PF6 ]− 145
pattern derived from the two- and three-bond coupling is PMe2 H 99 [PCl4 ]+ 86
complex but the pattern might serve as a starting point PMe2 Cl 96.5 [PCl6 ]− 295
in the interpretation of 29 Si NMR spectra of reaction PMe2 Br 90.5 Me2 PF3 8
products. Adapted from Bruker Almanac (1995).
a Referenced to 85% H PO (aq) at 0 ppm.
3 4

6.5 31 P NUCLEAR MAGNETIC

in organic synthesis. The spectrum itself is unremarkable
RESONANCE in that we see a single resonance for the single phospho-
rus atom in triphenylphosphine. What is remarkable is the
The last of the four nuclides that we treat briefly in this fact that there is a chemical shift range of less than 10 ppm
chapter is 31 P, the only naturally occurring isotope of phos- for three different compounds (the first two in Figures 6.13
phorus. Phosphorus is of great interest to the organic chemist and 6.14, respectively) and yet the phosphorus atoms differ
because reagents containing phosphorus, which range from widely with respect to oxidation state, attached groups, and
various inorganic forms of phosphorus to the organic phos- so on. We would have a very difficult job trying to rationalize
phines, phosphites, phosphonium salts, phosphorus ylides, these 31 P chemical shifts empirically.
etc., have long been used by organic chemists; the nucleus is The bottom two spectra in Figure 6.13 are the proton-
of great interest to the biochemists primarily because of the decoupled 31 P NMR spectra of triphenylphosphite and
nucleic acids that contain phosphate esters and also smaller triethylphosphite. Both compounds give a sharp single peak
molecules such as ADP and ATP. as expected. The point here is to illustrate that even without
NMR experiments with 31 P are rather straightforward; a set of predictive rules for chemical shift, we can nonethe-
31 P is a spin 1 nucleus with a positive magnetogyric ratio
2 less expect useful information with little chance of over-
(10.840 × 107 rad T−1 s−1 ). 31 P NOE enhancement from pro- lap. By themselves, these spectra might not provide much
ton decoupling is positive with a maximum of 1.23. There information but when combined with other spectra, they
has been a long history and therefore a rich literature of give one more perspective on composition, structure, and
31 P NMR. 31 P chemical shift data are reliable because 85%
stereochemistry.
H3 PO4 (aq) is virtually the only 31 P primary reference com-
pound used (external) and it remains the preferred reference
today (the top spectrum in Figure 6.13). The chemical shift TABLE 6.8 Typical J-Couplings Involving 31 Pa
range for 31 P is rather large and generalizations are danger-
Coupling Typical Range
ous. In fact, even chemical shifts of compounds where phos-
Constant of Values (Hz)
phorus is in different oxidation states are not diagnostic of
this state. All is not lost, however, since there are many reli- 1
JPH 140 to 1115
able published studies of 31 P chemical shifts. Typical values 1
JPP −620 to +766
1
are shown in Table 6.7. Recall that chemical shift values can JPB 13 to 175
1
be positive or negative. Representative proton–phosphorus JPC −43 to 448
1
coupling constants can be found in Appendix F of Chapter 3, JPF −550 to −1441
1
JPN −82 to +92
and a summary of coupling constant ranges due to coupling 1
JPHg 140 to 17500
of 31 P with protons and various other nuclides is given in 1
JPAg 210 to 1100
Table 6.8. Shown in Figure 6.13 is the proton-decoupled 31 P
a See
NMR spectrum of triphenylphosphine, a common reagent Verkade and Quin (1987) and Berger et al. (1997).
 Silverstein c02.tex V3 - 06/10/2014 4:06 P.M. Page 313

6.5 31 P NUCLEAR MAGNETIC RESONANCE 313

31
P NMR 121.5 MHz, 1H Decoupled

H3PO4

140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 ppm

(C6H5)3P

140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 ppm

(C6H5O)3P

140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 ppm

(C2H5O)3P

140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 ppm

31
FIGURE 6.13 From top to bottom, the proton-decoupled P NMR spectrum (121.5 MHz) of 85% phosphoric acid with a small
amount of D2 O, of triphenylphosphine in CDCl3 , of triphenylphosphite in CDCl3 , and of triethylphosphite in CDCl3 .
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314 CHAPTER 6 MULTINUCLEAR MAGNETIC RESONANCE SPECTROSCOPY

31
P NMR 242.9 MHz 1H decoupled 31
P NMR 242.9 MHz 1H coupled

(C2H5)2P(O)Cl

5.8 5.7 5.6 5.5 ppm 5.8 5.7 5.6 5.5 ppm
1 31
H NMR 600 MHz P decoupled

4.32 4.30 4.28 4.26 4.24 4.22 ppm 1.44 1.42 1.40 1.38 1.36 1.34 ppm
1 31
H NMR 600 MHz P coupled

4.32 4.30 4.28 4.26 4.24 4.22 ppm 1.44 1.42 1.40 1.38 1.36 1.34 ppm
13
C NMR 150.9 MHz

6.6 Hz 3.3 Hz

66.0 65.8 ppm 15.8 15.6 ppm

65 60 55 50 45 40 35 30 25 20 15 ppm
FIGURE 6.14 (a–d) From top to bottom, the proton-decoupled and proton-coupled 31 P NMR spectra (242.9 MHz), the
31
P-decoupled 1 H NMR spectrum, the 31 P-coupled 1 H NMR spectrum, and the 31 P-coupled 13 C NMR spectrum of diethyl
chlorophosphate in CDCl3 .
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STUDENT EXERCISES 315

The proton-decoupled 31 P NMR spectrum of diethyl catalysis, for example. The interested reader is referred to
chlorophosphate is found in Figure 6.14 along with the Berger et al. (1997) and Nelson (2002). It is also important to
proton-coupled spectrum. Also included with this figure are note that, as for the other nuclei we have discussed, 31 P can
the 1 H and 13 C NMR spectra for a complete set. The proton- be observed to great effect in two-dimensional HSQC and
coupled 31 P NMR spectrum shows an apparent quintet, HMQC correlation experiments to gain additional structural
suggesting that there is no appreciable coupling of the phos- insights.
phorus nucleus to the protons of the methyl groups. Inspec-
tion of the corresponding proton NMR spectrum reveals,
however, that the methyl resonance is actually a triplet of
doublets with a four-bond 31 P⏤1 H coupling constant of ca. 6.6 CONCLUSIONS
1 Hz. Thus, we conclude that the 1 Hz coupling is not
resolved in the 31 P NMR spectrum but simply results in line We have introduced in this chapter a few other useful nuclei
broadening. The four protons of the two methylene groups and some examples of their spectra. The discussion has inten-
couple equally (approximately) to the phosphorus atom to tionally largely been centered on organic compounds. It is
give the observed quintet. The methylene proton resonances useful to be aware of the possibilities as well as the limi-
in the 1 H NMR spectrum may at first seem too complex. The tations associated with NMR spectroscopy of less common
matter is resolved by noting that the methylene protons in nuclei. Multinuclear magnetic resonance is a very broad
diethyl chlorophosphate are diastereotopic (see Figure 3.42), field of research with diverse applications. For the organic
and therefore they are not chemically equivalent and show chemist, many of the nuclei that potentially will be of interest
strong coupling. First-order analysis is impossible. in addition to 1 H and 13 C have been discussed in this chapter.
In this brief chapter, it is not possible to cover all areas of The interested reader is encouraged to further consult the ref-
application of 31 P NMR. Phosphorus-31 NMR spectroscopy erences as well as the general NMR literature for additional
has broad application in the study of metal–phosphine com- applications in inorganic chemistry, materials science, poly-
plexes and related compounds, and the role of these in mer chemistry, and beyond.

REFERENCES

For a list of Chapter References, please visit: www.wiley.com/college/silverstein.

STUDENT EXERCISES

6.1 Deduce the structure of the compound whose molecular formula 13

C, DEPT, and 31 P (both proton-coupled and proton-decoupled)
is C5 H12 N2 from the combined information from the 1 H, 13 C, NMR spectra.
DEPT, and 15 N NMR spectra. There is no proton-coupled 15 N 6.4 Determine the structure of the fluorine-containing compound for
NMR spectrum provided because it provides no useful informa- which the mass, IR, 1 H NMR, 13 C/DEPT NMR, and 19 F NMR
tion. spectra are given.
6.2 The compound for this exercise is a reagent commonly used in 6.5 Using the information in Appendix A, calculate the Larmor fre-
organic synthesis; its molecular formula is C6 H15 SiCl. Provided quencies of 7 Li, 23 Na, and 207 Pb in a magnetic field of 21.1 T.
are the 1 H, 13 C, DEPT, and 29 Si (proton-decoupled) spectra. 6.6 When the NMR spectra of heteronuclei show J couplings to pro-
6.3 Determine the structure of the phosphorus-containing com- tons, why are these couplings essentially never “strong” in the
pound whose molecular formula is C19 H18 PBr from the 1 H, sense of Pople (AB)?
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316 CHAPTER 6 MULTINUCLEAR MAGNETIC RESONANCE SPECTROSCOPY Exercise 6.1

1
H NMR 300 MHz

2.75 2.70 2.65 2.60 2.55 2.50 2.45 2.40 2.35 2.30 2.25 2.20 2.15 2.10 ppm

13
C/DEPT NMR 75.5 MHz

130 120 110 100 90 80 70 60 50 40 30 20 ppm

15
N NMR 30.4 MHz

240 220 200 180 160 140 120 100 80 60 40 20 ppm

 Silverstein c02.tex V3 - 06/10/2014 4:06 P.M. Page 317

Exercise 6.2 STUDENT EXERCISES 317

1
H NMR 300 MHz

1.3 1.2 1.1 1.0 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 ppm

13
C/DEPT NMR 75.5 MHz

35 30 25 20 15 10 5 0 –5 ppm

29
Si NMR 59.6 MHz

55 50 45 40 35 30 25 20 15 10 5 ppm
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318 CHAPTER 6 MULTINUCLEAR MAGNETIC RESONANCE SPECTROSCOPY Exercise 6.3

1
H NMR 300 MHz

2340 2320 2300 Hz

8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 ppm

13
C/DEPT NMR 75.5 MHz

a b

10200 Hz 10000 Hz

c d e

9800 Hz 9000 8900 Hz 800 750 Hz

ab c d e

130 120 110 100 90 80 70 60 50 40 30 20 10 ppm

31
P NMR 121.5 MHz, 1H decoupled

28 26 24 22 20 18 16 14 12 10 8 6 4 2 ppm
 Silverstein c02.tex V3 - 06/10/2014 4:06 P.M. Page 319

Exercise 6.4 STUDENT EXERCISES 319

MASS
105
% of Base Peak 175
100
244
77
50 127
205

50 100 150 200

m/z
IR
100
%Transmittance

50

717
972
1165
1219
1273
3602

1504
3548

3070

4000 3000 2000 1000

Wavenumber (cm –1)
1 19
H NMR 300 MHz F NMR 282.4 MHz

7.8 7.7 7.6 7.5 ppm

7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 ppm –74.6 –74.7 ppm
13
C/DEPT 75.5 MHz

130 128 126 124 122 120 118 ppm 78 77 76 ppm

320
APPENDIX A PROPERTIES OF MAGNETICALLY ACTIVE NUCLEI

Magnetic Magnetogyric Quadrupole Relative Receptivity

Natural Moment Ratio Moment Frequency Reference
Isotope Spin Abundance (%) 𝝁∕𝝁𝐍 𝜸∕107 rad T−𝟏 s−𝟏 Q∕𝐟 𝐦2 Ratio (𝚵) Compound 𝐃𝐏𝐫𝐨𝐭𝐨𝐧 𝐃𝐂𝐚𝐫𝐛𝐨𝐧
1 1
H 2
99.9885 4.837353570 26.7522128 – 100.000000 Me4 Si 1 5.87 × 103
2
H 1 0.0115 1.21260077 4.106 62791 0.286 15.350609 (CD3 )3 Si 1.11 × 10−6 6.52 × 10−3
3 1
H 2
– 5.159714367 28.5349779 – 106.663974 Me4 Si – –
3 1 −4 −7
He 2
1.37 × 10 −3.685154336 −20.3801587 – 76.179437 He(gas) 6.06 × 10 3.56 × 10−3
6
Li 1 7.59 1.1625637 3.9371709 −0.0808 14.716086 LiCl 6.45 × 10−4 3.79
7 3
Li 2
92.41 4.20407505 10.3977013 −4.01 38.863797 LiCl 0.271 1.59 × 103
9 3
Be 2
100 −1.520136 −3.759666 5.288 14.051813 BeSO4 1.39 × 10−2 81.5
10 −3
B 3 19.9 2.0792055 2.8746786 8.459 10.743658 BF3 ⋅ Et 2 O 3.95 × 10 23.2
11 3
B 2
80.1 3.4710308 8.5847044 4.059 32.083974 BF3 ⋅ Et 2 O 0.132 7.77 × 102
13 1
C 2
1.07 1.216613 6.728284 – 25.145020 Me4 Si 1.70 × 10−4 1
14 −3
N 1 99.632 0.57100428 1.9337792 2.044 7.226317 CH3 NO2 or NH3 (l) 1.00 × 10 5.9
15 1 −6
N 2
0.368 −0.49049746 −2.71261804 – 10.132912 CH3 NO2 or NH3 (l) 3.84 × 10 2.25 × 10−2
17 5
O 2
0.038 −2.24077 −3.62808 −2.56 13.556457 D2 O 1.11 × 10−5 6.50 × 10−2
19 1
F 2
100 4.553333 25.18148 – 94.094011 CCl3 F 0.834 4.90 × 103
21 3
Ne 2
0.27 −0.854376 −2.11308 10.155 7.894296 Ne (gas) 6.65 × 10−6 3.91 × 10−2
23 3
Na 2
100 2.8629811 7.0808493 10.40 26.451900 NaCl 9.27 × 10−2 5.45 × 102
25 5
Mg 2
10.00 −1.01220 −1.63887 19.94 6.121635 MgCl2 2.68 × 10−4 1.58
27 5
Al 2
100 4.3086865 6.9762715 14.66 26.056859 Al(NO3 )3 0.207 1.22 × 103
29 1
Si 2
4.6832 −0.96179 −5.3190 – 19.867187 Me4 Si 3.68 × 10−4 2.16
31 1 −2
P 2
100 1.95999 10.8394 – 40.480742 H3 PO4 6.65 × 10 3.91 × 102
33 3
S 2
0.76 0.8311696 2.055685 −6.78 7.676000 (NH4 )2 SO4 1.72 × 10−5 0.101
35 3 −3
Silverstein

Cl 2
75.78 1.061035 2.624198 −8.165 9.797909 NaCl 3.58 × 10 21
37 3 −4
Cl 2
24.22 0.8831998 2.184368 −6.435 8.155725 NaCl 6.59 × 10 3.87
39 3
K 2
93.2581 0.50543376 1.2500608 5.85 4.666373 KCl 4.76 × 10−4 2.79
c02.tex V3 - 06/10/2014
4:06 P.M.
Page 320
 (40 K) 4 0.0117 −1.4513203 −1.5542854 −7.30 5.802018 KCl 6.12 × 10−7 3.59 × 10−3
3
(41 K) 2
6.7302 0.2773961 0.68606808 7.11 2.561305 KCl 5.68 × 10−6 3.33 × 10−2
43 7
Ca 2
0.135 −1.494067 −1.803069 −4.44 6.730029 CaCl2 8.68 × 10−6 5.10 × 10−2
45 7
Sc 2
100 5.3933489 6.5087973 −22.0 24.291747 Sc(NO3 )3 0.302 1.78 × 103
47 5
Ti 2
7.44 −0.93294 −1.5105 30.2 5.637534 TiCl4 1.56 × 10−4 0.918
49 7
Ti 2
5.41 −1.25201 −1.51095 24.7 5.639037 TiCl4 2.05 × 10−4 1.2
(50 V) 6 0.25 3.6137570 2.6706490 21.0 9.970309 VOCl3 1.39 × 10−4 0.818
51 7
V 2
99.75 5.8380835 7.0455117 −5.2 26.302948 VOCl3 0.383 2.25 × 103
53 3
Cr 2
9.501 −0.61263 −1.5152 −15.0 5.652496 K2 CrO4 8.63 × 10−5 0.507
55 5
Mn 2
100 4.1042437 6.645 2546 33.0 24.789218 KMnO4 0.179 1.05 × 103
57 1
Fe 2
2.119 0.1569636 0.8680624 – 3.237778 Fe(CO)5 7.24 × 10−7 4.25 × 10−3
59 7
Co 2
100 5.247 6.332 42.0 23.727074 K3 [Co(CN)6 ] 0.278 1.64 × 103
61 3
Ni 2
1.1399 −0.96827 −2.3948 16.2 8.936051 Ni(CO)4 4.09 × 10−5 0.24
63 3 −2
Cu 2
69.17 2.8754908 7.1117890 −22.0 26.515473 [Cu(CH3 CN)4 ][ClO4 ] 6.50 × 10 3.82 × 102
65 3
Cu 2
30.83 3.07465 7.60435 −20.4 28.403693 [Cu(CH3 CN)4 ][ClO4 ] 3.54 × 10−2 2.08 × 102
67 5
Zn 2
4.10 1.035556 1.676688 15.0 6.256803 Zn(NO3 )2 1.18 × 10−4 0.692
3
(69 Ga) 2
60.108 2.603405 6.438855 17.1 24.001354 Ga(NO3 )3 4.19 × 10−2 2.46 × 102
71 3
Ga 2
39.892 3.307871 8.181171 10.7 30.496704 Ga(NO3 )3 5.71 × 10−2 3.35 × 102
73 9
Ge 2
7.73 −0.9722881 −0.9360303 −19.6 3.488315 (CH3 )4 Ge 1.09 × 10−4 0.642
75 3 −2
As 2
100 1.858354 4.596163 31.4 17.122614 NaAsF6 2.54 × 10 1.49 × 102
77 1
Se 2
7.63 0.92677577 5.1253857 – 19.071513 Me2 Se 5.37 × 10−4 3.15
79 3 −2
( Br) 2
50.69 2.719351 6.725616 31.3 25.053980 NaBr 4.03 × 10 2.37 × 102
81 3
Br 2
49.31 2.931283 7.249776 26.2 27.006518 NaBr 4.91 × 10−2 2.88 × 102
83 9
Kr 2
11.49 −1.07311 −1.03310 25.9 3.847600 Kr(gas) 2.18 × 10−4 1.28
5
(85 Rb) 72.17 1.6013071 2.5927050 27.6 9.654943 RbCl 7.67 × 10−3 45
Silverstein

2
87 3
Rb 2
27.83 3.552582 8.786400 13.35 32.720454 RbCl 4.93 × 10−2 2.90 × 102
87 9
Sr 2
7.00 −1.2090236 −1.1639376 33.5 4.333822 SrCl2 1.90 × 10−4 1.12
89 1 −4
Y 2
100 −0.23801049 −1.3162791 – 4.900198 Y(NO3 )3 1.19 × 10 0.7
(Continued)
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322
APPENDIX A (Continued)

Magnetic Magnetogyric Quadrupole Relative Receptivity

Natural Moment Ratio Moment Frequency Reference
Isotope Spin Abundance (%) 𝝁∕𝝁𝐍 𝜸∕107 rad T−𝟏 s−𝟏 Q∕𝐟 𝐦2 Ratio (𝚵) Compound 𝐃𝐏𝐫𝐨𝐭𝐨𝐧 𝐃𝐂𝐚𝐫𝐛𝐨𝐧
91 5
Zr 2
11.22 −1.54246 −2.49743 −17.6 9.296298 Zr(C5 H5 )2 Cl2 1.07 × 10−3 6.26
93 9
Nb 2
100 6.8217 6.5674 −32.0 24.476170 K[NbCl6 ] 0.488 2.87 × 103
95 5
Mo 2
15.92 −1.0820 −1.7510 −2.2 6.516926 Na2 MoO4 5.21 × 10−4 3.06
97 5 −4
( Mo) 2
9.55 −1.1050 −1.7880 25.5 6.653695 Na2 MoO4 5.33 × 10 1.95
99 9
Tc 2
– 6.2810 6.0460 −12.9 22.508326 NH4 TcO4 – –
99 5 −4
Ru 2
12.76 −0.7588 −1.2290 7.9 4.605151 K4 [Ru(CN)6 ] 1.44 × 10 0.848
101 5 −4
Ru 2
17.06 −0.8505 −1.3770 45.7 5.161369 K4 [Ru(CN)6 ] 2.71 × 10 1.59
103 1
Rh 2
100 −0.1531 −0.8468 – 3.186447 Rh(acac)3 3.17 × 10−5 0.186
105 5
Pd 2
22.33 −0.7600 −1.2300 66.0 4.576100 K2 PdCl6 2.53 × 10−4 1.49
1
(107 Ag) 2
51.839 −0.19689893 −1.0889181 – 4.047819 AgNO3 3.50 × 10−5 0.205
109 1 −5
Ag 2
48.161 −0.22636279 −1.2518634 – 4.653533 AgNO3 4.94 × 10 0.290
111 1 −3
( Cd) 2
12.80 −1.0303729 −5.6983131 – 21.215480 Me2 Cd 1.24 × 10 7.27
113 1 −3
Cd 2
12.22 −1.0778568 −5.9609155 – 22.193175 Me2 Cd 1.35 × 10 7.94
113 9 −2
( In) 2
4.29 6.1124 5.8845 79.9 21.865755 In(NO3 )3 1.51 × 10 88.50
115 9
In 2
95.71 6.1256 5.8972 81.0 21.912629 In(NO3 )3 0.338 1.98 × 103
1
(115 Sn) 2
0.34 −1.5915 −8.8013 – 32.718749 Me4 Sn 1.21 × 10−4 0.711
117 1 −3
( Sn) 2
7.68 −1.73385 −9.58879 – 35.632259 Me4 Sn 3.54 × 10 20.8
119 1
Sn 2
8.59 −1.81394 −10.0317 – 37.290632 Me4 Sn 4.53 × 10−3 26.6
121 5
Sb 2
57.21 3.9796 6.4435 −36.0 23.930577 KSbCl6 9.33 × 10−2 5.48 × 102
7
(123 Sb) 2
42.79 2.8912 3.4892 −49.0 12.959217 KSbCl6 1.99 × 10−2 1.17 × 102
1
(123 Te) 2
0.89 −1.276431 −7.059098 – 26.169742 Me2 Te 1.64 × 10−4 0.961
125 1 −3
Silverstein

Te 2
7.07 −1.5389360 −8.5108404 – 31.549769 Me2 Te 2.28 × 10 13.40
127 5 −2
I 2
100 3.328710 5.389573 −69.6 20.007486 KI 9.54 × 10 5.60 × 102
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 129 1
Xe 2
26.44 −1.347494 −7.452103 – 27.810186 XeOF4 5.72 × 10−3 33.60
131 3
Xe 2
21.18 0.8931899 2.209076 −11.4 8.243921 XeOF4 5.96 × 10−4 3.50
133 7
Cs 2
100 2.9277407 3.5332539 −0.343 13.116142 CsNO3 4.84 × 10−2 2.84 × 102
3
(135 Ba) 2
6.592 1.08178 2.67550 16.0 9.934457 BaCl2 3.30 × 10−4 1.93
137 3 −4
Ba 2
11.232 1.21013 2.99295 24.5 11.112928 BaCl2 7.87 × 10 4.62
138 −5
La 5 0.09 4.068095 3.557239 45.0 13.19430 LaCl3 8.46 × 10 0.497
139 7 −2
La 2
99.91 3.155677 3.8083318 20.0 14.125641 LaCl3 6.05 × 10 3.56 × 102
141 5
Pr 2
100 5.0587 8.1907 −5.89 30.62 – – –
143 7
Nd 2
12.2 −1.208 −1.4570 −63.0 5.45 – – –
145 7
Nd 2
8.3 −0.7440 −0.8980 −33.0 3.36 – – –
147 7
Sm 2
14.99 −0.9239 −1.1150 −25.9 4.17 – – –
149 7
Sm 2
13.82 −0.7616 −0.9192 7.4 3.44 – – –
151 5
Eu 2
47.81 4.1078 6.6510 90.3 24.86 – – –
153 5
Eu 2
52.19 1.8139 2.9369 241.2 10.98 – – –
155 3
Gd 2
14.80 −0.33208 −0.82132 127.0 3.07 – – –
157 3
Gd 2
15.65 −0.4354 −1.0769 135.0 4.03 – – –
159 3
Tb 2
100 2.6000 6.4310 143.2 24.04 – – –
161 5
Dy 2
18.91 −0.5683 −0.9201 250.7 3.44 – – –
163 5
Dy 2
24.90 0.7958 1.2890 264.8 4.82 – – –
165 7
Ho 2
100 4.7320 5.7100 358.0 21.34 – – –
167 7
Er 2
22.93 −0.63935 −0.77157 356.5 2.88 – – –
169 1
Tm 2
100 −0.4011 −2.2180 – 8.29 – – –
171 1
Yb 2
14.28 0.85506 4.7288 – 17.499306 – – –
173 5
Yb 2
16.13 −0.80446 −1.3025 280.0 4.821 – – –
175 7
Lu 97.41 2.5316 3.0552 349.0 11.404 – – –
Silverstein

2
176
Lu 7 2.59 3.3880 2.16844 497.0 8.131 – – –
177 7
Hf 2
18.60 0.8997 1.0860 336.5 4.007 – 2.61 × 10−4 1.54
179 9 −5
Hf 2
13.62 −0.7085 −0.6821 379.3 2.517 – 7.45 × 10 0.438
(Continued)
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324
APPENDIX A (Continued)

Magnetic Magnetogyric Quadrupole Relative Receptivity

Natural Moment Ratio Moment Frequency Reference
Isotope Spin Abundance (%) 𝝁∕𝝁𝐍 𝜸∕107 rad T−𝟏 s−𝟏 Q∕𝐟 𝐦2 Ratio (𝚵) Compound 𝐃𝐏𝐫𝐨𝐭𝐨𝐧 𝐃𝐂𝐚𝐫𝐛𝐨𝐧
181 7
Ta 2
99.988 2.6879 3.2438 317.0 11.989600 KTaCl6 3.74 × 10−2 2.20 × 102
183 1
W 2
14.31 0.20400919 1.1282403 – 4.166387 Na2 WO4 1.07 × 10−5 6.31 × 10−2
5
(185 Re) 2
37.4 3.7710 6.1057 218.0 22.524600 KReO4 5.19 × 10−2 3.05 × 102
187 5
Re 2
62.6 3.8096 6.1682 207.0 22.751600 KReO4 8.95 × 10−2 5.26 × 102
187 1
Os 2
1.96 0.1119804 0.6192895 – 2.282331 OsO4 2.43 × 10−7 1.43 × 10−3
189 3
Os 2
16.15 0.851970 2.10713 85.6 7.765400 OsO4 3.95 × 10−4 2.32
191 3 −5
( Ir) 2
37.3 0.1946 0.4812 81.6 −1.718 – 1.09 × 10 6.38 × 10−2
193 3
Ir 2
62.7 0.2113 0.5227 75.1 −1.871 – 2.34 × 10−5 0.137
195 1 −3
Pt 2
33.832 1.0557 5.8385 – 21.496784 Na2 PtCl6 3.51 × 10 20.7
199 1 −3
Hg 2
16.87 0.87621937 4.8457916 – 17.910822 Me2 Hg 1.00 × 10 5.89
197 3 −5
Au 2
100 0.191271 0.473060 54.7 −1.729 – 2.77 × 10 0.162
201 3 −4
Hg 2
13.18 −0.7232483 −1.788769 38.6 6.611583 (CH3 )2 Hg 1.97 × 10 1.16
1
(203 Tl) 2
29.524 2.80983305 15.5393338 – 57.123200 Tl(NO3 )3 5.79 × 10−2 3.40 × 102
205 1
Tl 2
70.476 2.8374709 15.6921808 – 57.683838 Tl(NO3 )3 0.142 8.36 × 102
207 1
Pb 2
22.1 1.00906 5.58046 – 20.920599 Me4 Pb 2.01 × 10−3 11.8
209 9
Bi 2
100 4.5444 4.3750 −51.6 16.069288 Bi(NO3 )2 0.144 8.48 × 102
235 7
U 2
0.72 −0.4300 −0.5200 493.6 1.8414 – – –

Nuclei in parentheses are not considered the most favorable for NMR.
Adapted in part from Harris, R.K, Becker, E.D., Cabral de Menezes, S.M., Goodfellow, R., and Granger, P. (2001). NMR nomenclature. Nuclear spin properties and conventions for chemical shifts. Pure Appl. Chem., 73, 1795–1818.
Silverstein
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CHAPTER 7
SOLVED PROBLEMS

7.1 INTRODUCTION Appendix A of Chapter 1 for comparison and determine the

index of hydrogen deficiency for each. In addition to difficul-
The perennial student question: Where do we start? The ties caused by unresolved or overlapping peaks, discrepan-
instructor will be sympathetic but not rigidly prescriptive. cies may appear between the selected molecular formula(s)
There are, however, guidelines that do start with the prescrip- and the 1 H and 13 C counts because of the presence of ele-
tive statement: Go for the molecular formula. Why? Simply ments of symmetry. Although identifying these elements
because it is the single most useful bit of information avail- may initially require some additional effort, such symmetry
able to the chemist and is worth the effort sometimes neces- information is very valuable in the structure determination
sary. It provides an overall impression of the molecule (i.e., process.
the number and kinds of atoms), and it provides the index of Students are urged to develop their own approaches. To
hydrogen deficiency—in other words, the sum of the number provide practice, we have sometimes presented more infor-
of rings and of double and triple bonds (Section 1.5.3). mation than needed, but other Problems should provide com-
Development of the molecular formula starts with pensatory frustration to simulate the real world. Remember
recognition of the molecular ion peak (Section 1.5). We the overall strategy: Play the spectra against one another,
assume the usual situation: high-resolution MS instrumenta- focusing on the more obvious features. Develop a hypothesis
tion is not readily available. Let us also assume for now that from one spectrum: look to the other spectra for confirma-
the peak of highest m∕z (except for its isotope peaks) is the tion or contradictions; modify the hypothesis if necessary.
molecular ion peak and is intense enough so that the isotope The effect is synergistic, the total information being greater
peak intensities can be determined accurately and the pres- than the sum of the individual parts.
ence and number of S, Br, and Cl atoms can be ascertained. With the high magnetic fields now available, many J
Look also at the fragmentation pattern of the mass spectrum coupling multiplets are first order, or nearly so, and can
for recognizable fragments. If the molecular ion peak is an be interpreted by inspection with the leads furnished by
odd number, an odd number of N atoms is present. the mass and infrared spectra. Nevertheless, a rereading of
Difficulty often starts with uncertainty in the choice Sections 3.8 through 3.12 may engender caution.
of a molecular ion peak. Many laboratories use chemical As an example, consider two similar compounds:
ionization as a routine supplement to electron impact, and H O H3 C O
of course, access to a high-resolution instrument is desirable O O
H 5 1 2 H 5 1 2
for more difficult problems.
H 4 3 H H 4 3 H
Next, a search of the infrared spectrum for absorptions
indicative of particular functional groups is in order. Note H H H H
in particular C⏤H stretching, O⏤H and/or N⏤H absorp- A B
tions, and the presence (or absence) of absorptions indicative
of unsaturated functional groups. Both rings exist in rapidly flexing ring conformations,
With this information in hand, search the proton NMR but only in compound A do the protons of each CH2 group
spectrum for confirmation and further leads. If the spec- interchange to become chemically equivalent (enantiotopes).
trum allows, determine the total number of protons and ratios Only compound A has a plane of symmetry in the plane of
of groups of chemically equivalent protons from the inte- the page through which the protons interchange.
gration. Look for first-order coupling patterns and for char- From high frequency to low frequency in the 1 H NMR
acteristic chemical shifts. Look at the 13 C∕DEPT spectra; spectrum, we predict for compound A: H-5, a two-proton
determine the carbon and proton counts and the numbers triplet; H-3, a two-proton triplet; H-4, a two-proton quintet
of CH3 , CH2 , CH, and quaternary C groups. A discrepancy (assuming nearly equal coupling constants). In a moderately
between the proton integration and the number of protons high magnetic field, the spectrum is first order.
represented in the 13 C∕DEPT spectra suggests the presence Compound B has no symmetry element in the planar
of protons bonded to heteroatoms. conformation. C-5 is a stereogenic center and the protons of
Overlap of proton resonances in the one-dimensional each CH2 group are diastereotopic pairs. Each proton of the
spectrum is common, but absolute coincidence of nonequi- pair has its own chemical shift. The resonances due to the
valent 13 C peaks is quite rare with a high-resolution instru- H-4 protons adjacent to the stereogenic center are distinctly
ment. Now, select the most likely molecular formula(s) from separated, but those of the H-3 protons are not, at 300 MHz.

325
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326 CHAPTER 7 SOLVED PROBLEMS

Each proton of a diastereotopic pair couples geminally with and coupling constants may be made, and the iterative
the other and independently (different coupling constants) computer program will adjust the values until the simulation
with the vicinal protons to give complex multiplets. matches the actual spectrum—assuming, of course, that the
The possibility of a stereogenic center should always be identification is valid. Such simulations are nowadays quite
kept in mind; toujours la stereochimie. reliable for proton NMR spectra and continue to improve
The power of 2D spectra will become more evident as for 13 C NMR spectra. The user should keep in mind that
we work through the problems in Chapters 7 and 8. It is while simulation software can be useful, it is based in part
often not necessary to examine all of the spectra in detail on empirical trends and/or databases, and therefore may
before proposing—tentatively—possible structures or frag- not always provide reliable spectral simulations, particularly
ments. Spectral features predicted for the postulated struc- for unusual structures. Quantum chemical calculations can
tures or fragments are compared with the observed spectra, provide more reliable predictions of NMR parameters but are
and structural modifications are made to accommodate dis- much more time consuming.
crepancies. Checklist for logical and pedagogical completeness, not
These suggestions are illustrated by the following solved necessarily in order:
problems presented in increasing order of difficulty. The
1. Show how the molecular formula was derived.
assigned problems in this Chapter and the end of Chapter 8,
again in increasing order of difficulty, will provide essential 2. Calculate the index of hydrogen deficiency.
practice. 3. Assign diagnostic bands in the IR spectrum.
Most students enjoy problem solving and rise to the 4. Assign all resonances in the 1 H NMR spectrum.
challenge. They also begin to appreciate the elegance of
5. Assign all resonances in the 13 C∕DEPT NMR spectra.
chemical structure as they interpret spectra. Good sleuthing!
(Note that the 13 C∕DEPT NMR spectra in this book
Be wary of chirality, diastereotopes, virtual coupling, dihe-
are always displayed in the following order, from
dral angles of about 90∘ , and the concepts of chemical and
top to bottom: DEPT-90, DEPT-135, regular proton-
magnetic equivalence.
decoupled 13 C NMR spectrum.)
Finally, what are the requirements for proof of structure?
Ultimately, it is congruence of all available spectra with those 6. Calculate or estimate 𝛥𝜈∕J where appropriate.
of a pure, authentic sample obtained under the same condi- 7. Explain multiplicity where appropriate. Use J coupling
tions and on the same instruments. Obviously, some com- values wherever possible to provide structural insights
promises are acceptable. Congruence with published spectra (e.g., cis vs trans stereochemistry, vicinal vs geminal
or spectral data is considered acceptable for publication, but couplings, etc.)
this cannot apply to a new compound, which must then be 8. Assign all correlations in 2D spectra.
synthesized.
9. Show how the EI mass spectrum supports the structure.
Computer programs for simulating NMR spectra are
available.* If accurate measurements of chemical shifts and 10. Consider possible isomers.
coupling constants for all of the protons can be obtained, Each problem in this chapter is organized so that the
the simulated spectrum will be congruent with the actual molecular structure and the spectra appear first and are
spectrum. In many cases, at least some of the spin systems followed by the discussion. The molecular structure is
will be first order. If not, reasonable estimates of shifts displayed on most of the individual spectra to minimize back-
and-forth page turning. The purpose of this arrangement is to
* Spectra
encourage students to make their own tentative connections
can be simulated on most modern computers. Companies such as
Bruker Biospin (Billerica, MA, USA), Mestrelab (Santiago de Compostela,
between the molecule and familiar features in the spectra.
Spain), and ACD Labs (Toronto, Canada) offer software to simulate NMR With this preparation, the subsequent discussions will be
spectra. more helpful.
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Problem 7.1A PROBLEM 7.1 DISCUSSION 327

MASS EI HC C CH2 CH2 OH

40 4 3 2 1
100 3-Butyn-1-ol
% of Base Peak

39

31
50
69
52 55
70

0
30 40 50 60 70 80 90 100 110
m/z

MASS CI reagent gas methane

53 71 M+1 (H)
100
% of Base Peak

50
M+29 (C2H5) M+41 (C3H5)
69

99
111

0
30 40 50 60 70 80 90 100 110
m/z

IR
100

95
% Transmittance

90

85

80
1385
1327

1049

852

640
3294

2951
2889

2117

1423

4000 3000 2000 1000

Wavenumber (cm–1)
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328 CHAPTER 7 SOLVED PROBLEMS Problem 7.1B

1
H NMR 600 MHz

HC C CH2 CH2 OH
4 3 2 1
3-Butyn-1-ol

1 OH 2 4

3.7 3.6 3.5 3.4 3.3 3.2 3.1 3.0 2.9 2.8 2.7 2.6 2.5 2.4 2.3 2.2 2.1 2.0 ppm
1313
C/DEPT
C/DEPT600
NMRMHz
150.9 MHz

3 4 1 2

85 80 75 70 65 60 55 50 45 40 35 30 25 20 ppm
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PROBLEM 7.1 DISCUSSION 329

PROBLEM 7.1 DISCUSSION question is whether the triple bond is terminal or internal;
in other words, is there an alkyne proton?
Everything points to a small molecule. There appear to be
no further peaks in the mass spectrum beyond m∕z 69, but H⏤C⏤
⏤C⏤R or R⏤C⏤
⏤C⏤R
′

it is rejected as the molecular ion because the next peak

is found at m∕z 55, a putative loss of 14 mass units. The The 13 C NMR spectrum is unequivocal. It shows two peaks
CI mass spectrum possesses a base peak of m∕z 71, which in the range for alkyne carbons. The peak at 70 ppm is about
represents an M + 1 pseudomolecular ion. The molecular the same intensity as each of the two CH2 peaks, but the
weight of this compound is thus taken as 70 amu. The IR peak at about 81.2 ppm is distinctly less intense, suggesting
spectrum suggests an alcohol with a broad O⏤H stretching that it has no attached proton. Furthermore, the 13 C∕DEPT
band at about 3350 cm−1 and a strong C⏤O stretching at subspectra show that the peak at about 70 ppm represents
1049 cm−1 . a CH group. We can now write two fragments or sub-
The proton NMR spectrum consists of classical first- structures:
order multiplets. From high frequency to low frequency,
the multiplicities and integrations are triplet (2), singlet (1), H⏤C⏤
⏤C⏤ and ⏤CH2 ⏤OH
triplet of doublets (2), triplet (1), which yields six hydro-
gen atoms. The 13 C∕DEPT spectra show four carbon res- Insertion of the missing CH2 group gives a complete
onances which indicate, from high frequency to low fre- molecule:
quency: C, CH, CH2 , CH2 . This discrepancy implies that one
of the protons is bonded to a heteroatom. The OH proton at H⏤C⏤
⏤C⏤CH2 ⏤CH2 ⏤OH
2.68 ppm in the 1 H spectrum accounts for the difference in
proton count between the 1 H spectrum and the 13 C∕DEPT This structure is completely in accord with the 1 H and
spectra. 13 C∕DEPT NMR spectra. The 1 H spectrum provides a nice
The assumption of m∕z 70 as the molecular ion is now demonstration of long-range coupling through the triple
quite valid. The molecular formula is now assumed to be bond (from H-4 to H-2), splitting the triplet further into
C4 H6 O with an index of hydrogen deficiency of two. The doublets.
options are: two double bonds, one double bond and a ring, Returning with hindsight to the infrared spectrum, we
two rings, or a triple bond. We can consider these options may note the strong H⏤C⏤ ⏤ stretching band at 3294 cm
−1

seriatim. superposed on the O⏤H band. There is also a strong

Consider two double bonds. Do any of the proton or ⏤
⏤C⏤H band at 640 cm−1 . Furthermore, there is a weak but
carbon peaks fall in the usual ranges for alkenes? Perusal distinctive C⏤⏤C stretching band at 2117 cm .
−1

of Chapters 3 and 4 eliminates the possibility. This leaves us Several of the major peaks in the mass spectrum are dif-
with rings or a triple bond. ficult to assign since there are two functional groups of simi-
Rings are often difficult to rule out on the basis of lar mass. Although trivial, verification of the assignments of
chemical shifts alone, but the spin-spin couplings would be the proton resonances and their multiplicities are left as an
difficult to explain. Let us consider a triple bond. exercise for the student. Likewise, verification of the assign-
Yes, a triple bound would qualify on the basis of ments of the resonances in the 13 C∕DEPT spectra are left for
chemical shifts for both protons and carbons. The first the student.
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330 CHAPTER 7 SOLVED PROBLEMS Problem 7.2A

O
H H
6 C 4 C 2 CH2 8
H3C 5 C 3 C 1 O 7 CH3
MASS H H 95

100 67 Ethyl sorbate 97

% of Base Peak

140
125
50 41

111

40 50 60 70 80 90 100 110 120 130 140

m/z
IR
100
% Transmittance

50
2981
2912

1716
1647
1620

1327
1246
1142
999
868
4000 3000 2000 1000
Wavenumber (cm‒1)

1
H NMR 600 MHz

4350 4300 Hz 3700 3650 Hz 3450 Hz

2500 Hz 1100 Hz 750 Hz

3 4,5 2 7 6 8
7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 ppm
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Problem 7.2B PROBLEM 7.2 DISCUSSION 331

1
H Homodecoupled 600 MHz

3700 3680 3660 3640 3620 Hz

irr irr
O
H3C CH CH CH CH C OC2H5

irr
O
H3C CH CH CH CH C OC2H5

irr
O
H3C CH CH CH CH C OC2H5

1
H NMR 600 MHz

6.15 6.10 6.05 ppm

O
H H
6 C 4 C 2 CH2 8
13 H3C 5 C 3 C 1 O 7 CH3
C/DEPT NMR 150.9 MHz
H H
Ethyl sorbate

CDCl3

1 3 5 4 2 7 68
170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 ppm
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332 CHAPTER 7 SOLVED PROBLEMS Problem 7.2C

ppm 7 6 5 4 3 2 1 ppm COSY 600 MHz

1 1
8
6
2 2
O
H H
6 C 4 C 2 CH2 8
3 H3C 5 C 3 C 1 O 7 CH3 3
H H
F1 4 Ethyl sorbate
4
7

5 5

2
6 6 4,5

7 7
3
F2 HMQC 600 MHz
3 4,5 2 7 6 8
ppm
8
20 20 6

40 40

60 60 7

CDCl3
80 4 5 80
F1
ppm
100 100

120 130 4 120 2

140 5 4
140 140 5
150 3
6.2 6.1 ppm
160 160

7 6 5 4 3 2 1 ppm
F2
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PROBLEM 7.2 DISCUSSION 333

PROBLEM 7.2 DISCUSSION The ethyl protons are represented by the triplet at
∼1.2 ppm coupled to the deshielded quartet at ∼4.1 ppm.
The relatively intense peak at m∕z 140 in the mass spectrum The other CH3 group is represented by the doublet at
is a reasonable choice for the molecular ion peak, since there ∼1.8 ppm, coupled to one of four alkene CH protons. Rather
are no further peaks, and the fragment at m∕z 125 represents than attempting to interpret the higher order multiplets, we
loss of CH3 . Since 140 is an even number, there are an even turn to the 2D spectra.
number of N atoms, and we assume 0 as a starting point. The In the COSY spectrum, one of the two overlapping CH
very small M + 1 and M + 2 peaks preclude S, Cl, and Br. resonances, which are centered at ∼6.1 ppm (labeled H-5
The strong IR band at 1716 cm−1 indicates a carbonyl and H-4), couples to the CH3 doublet at ∼1.8 ppm; this
⏤
(C O) group. The two sharp bands at 1647 cm−1 and coupling confirms the earlier assumption that the CH3 group
1620 cm−1 indicate one or more carbon—carbon double is terminal. The proton-labeled H-5 also couples with the
bonds (C⏤C) that may be conjugated (see Section 2.6.4.1). other overlapping CH group (labeled H-4), which in turn
There are six different kinds of protons in the 1 H couples with the neighboring CH group at ∼7.2 ppm (labeled
spectrum in the ratios, from high frequency to low fre- H-3). The slightly broadened doublet at ∼5.7 ppm (labeled
quency, 1:2:1:2:3:3, for a total of 12 protons. We now H-2) is a result of coupling to H-3 and long-range coupling.
count eight peaks in the 13 C NMR spectrum (assuming We can summarize as follows:
one carbon atom per peak), and from the 13 C∕DEPT sub- O
spectra we read (from high frequency): (C⏤O) (from IR),
CH, CH, CH, CH, CH2 , CH3 , CH3 . With the present infor- CH3 CH CH CH CH C O CH2 CH3
mation, we write C8 H12 O with unit mass 124, which is 16 1.8 6.1 7.2 5.7 4.1 1.2 ppm
units less than a molecular ion peak at m∕z 140. Is there 6 5 4 3 2 1 7 8
another oxygen atom in the molecular ion?
With the complete proton assignments and the direct
Indeed so. The chemical shift of the CH2 group at
correlations between carbons and attached protons from the
60 ppm suggests a ⏤(C⏤O)OCH2 ⏤ sequence (see
HMQC spectrum, we are able to assign all of the carbon
Table 4.20). Also, the 13 C chemical shift of the carbonyl car-
resonances, except for the quaternary carbon, which is a
bon (168 ppm) suggests a carboxylic acid derivative such as
trivial assignment in this case. An interesting example is
an ester. The partial molecular formula can now be revised
found in the inset of the HMQC spectrum, which shows
to C8 H12 O2 with a hydrogen deficiency of three.
the correlations of the two overlapped protons, H-4 and
The proton NMR spectrum immediately shows that the
H-5. Even though they are overlapped in the one-
CH3 triplet at 1.2 ppm is directly attached to the deshielded
dimensional proton spectrum, they are well resolved in the
CH2 group (quartet) at 4.1 ppm. The COSY spectrum con-
HMQC spectrum because the carbon resonances are not
firms this correlation. The sequence, above, is now one end
overlapped.
of the molecule: ⏤(C⏤O)OCH2 CH3 .
One important question still remains: Are the double
In the 13 C∕DEPT spectra, there are four CH alkene
bonds E (trans) or Z (cis)? This question can be answered if
peaks between ∼119 ppm and ∼145 ppm. There is also
the alkenyl proton J values can be determined. One obvious
the remaining CH3 group at ∼18.5 ppm, which appears in
starting point is the H-2 doublet, which is the result of
the proton spectrum at ∼1.8 ppm as a doublet—obviously
coupling to H-3. The J value is about 16 Hz; this coupling
attached to one of the four CH groups.
constant falls within the range given for E-double bonds
It may seem presumptuous to formulate a molecular
given in Appendix F, Chapter 3.
structure at this early stage, but we do have one end of the
The complex, overlapping multiplets of H-4 and H-2
structure, four CH groups with an attached CH3 group, no
are not inviting. However, H-3 shows a pair of doublets as a
possibility for branching, and do not forget the two remaining
result of the 16 Hz (trans) coupling to H-2 and a 10 Hz single
sites of unsaturation. With some trepidation, we offer the
bond coupling to H-4. Unfortunately, the coupling constant
following structure:
for the 4,5-double bond is not readily accessible. But spin
O decoupling (homodecoupling) is worth investigating (see
CH3 CH CH CH CH C O CH2 CH3 Section 3.15). Irradiation of the H-6 resonance simplifies
6 5 4 3 2 1 7 8 the overlapping H-5, H-4 multiplet considerably; in fact,
there is a 16 Hz doublet (somewhat distorted) at the lower-
The synergism between the 13 C∕DEPT spectra and the frequency edge. Irradiation of H-3, individually, simplifies
proton spectrum should be explored. There are two aspects to the complex multiplet and shows a 16 Hz doublet at the high-
a proton spectrum: The first-order multiplets can usually be frequency edge. Simultaneous irradiation of the H-6 and H-3
resolved, whereas the higher order multiplets are frustrating. resonances results in a pair of 16 Hz doublets. The doublet
In the present proton spectrum, there are five first-order mul- intensities are not ideal because of the small Δ𝜈∕J ratio.
tiplets and two overlapping multiplets that are not first order. There is now no doubt that both double bonds are E.
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334 CHAPTER 7 SOLVED PROBLEMS Problem 7.3A

8 CH3 OH
1
CH 2 H
MASS H 3C 7 6 135
9
3
100
H 5 CH3
4
10
% of Base Peak

H
Thymol 150
50
91 115
65 77

0
40 50 60 70 80 90 100 110 120 130 140 150
m/z
IR
100
% Transmittance

50

590
810
945
1088
1153
1227
1458
1581
1516
1620
2870
2962
3464

4000 3000 2000 1000

Wavenumber (cm–1)
1
H NMR 600 MHz

4260 4240 Hz 4060 4040 Hz 3960 3940 Hz 2800 2780 Hz

1920 1900 Hz 1380 1360 Hz 760 740 Hz

3 4 6 OH 7 10 8,9
7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 ppm
 Silverstein c07.tex V2 - 06/04/2014 12:14 A.M. Page 335

Problem 7.3B PROBLEM 7.3 DISCUSSION 335

DQFCOSY 600 MHz

ppm
8 CH3 OH 8,9
1
CH 2 H
H3C 7 6
2 9
3
5
10
H 4
CH3
10
3 H
Thymol 7

F1 4

OH
5

6
4
7
F2 3

7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 ppm

13
C/DEPT NMR 150.9 MHz

CDCl3
10

1 5 2 3 4 6 7 8,9
150 140 130 120 110 100 90 80 70 60 50 40 30 20 ppm
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336 CHAPTER 7 SOLVED PROBLEMS Problem 7.3C

HMQC 600 MHz

ppm 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 ppm

20 10
8 CH3 OH 8,9
CH 2
1
H 7
40 H 3C 7 6
9
3
60 H 5 CH3
4
10
F1 H
80 Thymol CDCl3

100

6
120 4
3
140

F2 10 8,9
HMBC 600 MHz
OH
3 4 6 7
ppm
20 10
8,9
25
7
30

ppm
6
120 4
F1 3
130 2
5
140

150
1
160
7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 ppm
F2
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PROBLEM 7.3 DISCUSSION 337

PROBLEM 7.3 DISCUSSION is ortho to the OH group (see Chart D.1, Chapter 3). Since
this peak is a broadened singlet, there is no adjacent hydrogen
The molecular ion is certainly the medium-intensity peak atom, but there is a hydrogen atom meta to it with a coupling
in the mass spectrum at m∕z 150; there is a rational loss constant too small to resolve. Furthermore, since the spec-
of a CH3 group to give the base peak at m∕z 135. The trum shows only one proton ortho to the OH substituent, the
isotope peaks for the molecular ion do not permit the other ortho position must be attached to either the methyl or
presence of S, Cl, or Br. Let us assume, tentatively, that the isopropyl group.
the even-numbered molecular ion peak indicates the absence The sharp doublet at 7.1 ppm with a J value of
of N. If so, with the help of Appendix A (Chapter 1), about 8 Hz represents an aromatic hydrogen atom with
the molecular formula can be limited to these possibilities: one ortho coupling. Since the peaks are sharp, there is
C6 H14 O4 , C8 H6 O3 , C9 H10 O2 , or C10 H14 O. The IR spectrum no meta coupling. Its chemical shift places it meta to the
is notable for the intense OH peak at 3464 cm−1 . The OH group, the alkyl groups having little effect on the chem-
immediate question is the presence or absence of aromaticity. ical shift (see Chart D.1, Chapter 3). The broad doublet at
If an aromatic ring is present, is it attached directly to the 6.75 ppm is due to the proton which is para to the OH group,
OH group to give a phenol? The 1 H and 13 C NMR spectra the coupling being ortho and weakly meta. The choice is
provide answers with peaks in the aromatic regions. The between I and II.
strong IR peaks between 1600 and 600 wavenumbers suggest CH3 OH OH
aromaticity and ions at 77 m∕z and 91 m∕z serve to confirm 1 1
our conclusion. CH 2 H H 3C 2 H
6 6
There are seven different kinds of protons in the H3C CH3
1 H NMR spectrum in the ratios, from high frequency to 3 3
H 5 CH3 H 5 CH
4 4
low frequency, of 1:1:1:1:1:3:6 giving a total of 14 pro-
tons. The six-proton doublet at 1.25 ppm probably repre- H H CH3
sents two equivalent CH3 groups of an isopropyl moiety; the Thymol
one-proton septet at 3.2 ppm is the resonance of the corres- I II
ponding methine group of the isopropyl group.
The 13 C NMR spectrum shows nine peaks, but one The COSY spectrum confirms the previous findings
of them (at 23 ppm) is suspiciously intense and since it and shows that the protons of the methyl substituent are
correlates with the six-proton doublet in the HMQC spec- long-range coupled (4 J) to H-4 and H-6. Interestingly, the
trum, we conclude that there are two superposed CH3 isopropyl CH proton does not show long-range coupling to
groups, which makes a total of 10 carbon atoms. The H-3, possibly due to the high multiplicity of the CH peak,
13 C∕DEPT spectra specify, from high to low frequency, which would produce a very diffuse (not visible) cross peak.
C, C, C, CH, CH, CH, CH, CH3 (×2), CH3 , to which we add As expected, the aromatic protons show meta coupling (4 J)
the OH group. For a total mass of 150, the most reason- between H-6 and H-4, and ortho (3 J) coupling between H-4
able molecular formula is C10 H14 O, which has an index of and H-3. Structure I (thymol) is now heavily favored. Note
hydrogen deficiency of four. This degree of unsaturation fully that the definitive long-range coupling between the CH3
accounts for a benzene ring, that is, three double bonds and substituent and H-4 and H-6 was not resolved in the one-
one ring. Furthermore, the 13 C NMR spectrum consists of dimensional 1 H spectrum.
peaks in the aromatic region and the aliphatic region. The HMQC spectrum shows 1 JCH coupling. Table 4.12
In the aromatic region, the three weak peaks represent in Chapter 4 allows us to arrange the aromatic unsubstituted
three quaternary carbon atoms, and the three more intense carbon atoms as C-6, C-4, C-3 from top to bottom. The
peaks represent the carbon atoms with directly bonded HMQC spectrum confirms the same sequence for H-6, H-4,
hydrogen atoms. The most deshielded weak peak at 153 ppm and H-3. The aromatic, unsubstituted carbon atoms can now
represents the carbon atom to which the OH group is attached be correlated with the firmly assigned aliphatic protons. The
(see Table 4.12). substituted aromatic carbon atoms cannot yet be assigned.
The substituents in the aliphatic region must be a methyl The HMBC spectrum permits correlation between iso-
group and an isopropyl group. For confirmation, the aliphatic lated proton spin systems—that is, bridging such “insulat-
region in the proton spectrum shows (from high to low ing” atoms as O, S, N, and quaternary carbon atoms.
frequency) a one-proton septet (i.e., CH), a three-proton
singlet (i.e., CH3 ), and a six-proton doublet. It is a doublet R
because it consists of two identical CH3 groups coupled to C O C C C C
the CH group—hence an isopropyl substituent.
At this point, we distribute the two alkyl substituents H R H
with reference to the OH group and do so somewhat indi- 3
J 3
J
rectly by considering the chemical shifts and coupling con-
stants of the three ring protons. We can assume that the Even in a molecule of modest size, the number of 2 JCH and
proton peak at 6.6 ppm represents the hydrogen atom which 3J
CH couplings can be daunting. Where to start?
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338 CHAPTER 7 SOLVED PROBLEMS

Well, simply pose an important question: How do the correlations of C-1, C-5, and C-2. The assignment earlier
we fully confirm the positions of alkyl substituents? The of C-1 on the basis of its chemical shift is sound, but the
COSY spectrum did detect the long-range coupling for the assignment of C-5 and C-2 on the basis of chemical shift
methyl substituent but not for the isopropyl substituent. alone should be affirmed by correlations. This exercise is left
Confirmation can be found by looking down from the to the student.
CH isopropyl septet in the HMBC spectrum and observ- Bridging across quaternary carbon atoms has been
ing four cross peaks that correlate this CH proton with demonstrated in the course of the above correlations. Two
C-8, 9 (2 J), C-2 (2 J), C-3 (3 J) and C-1 (3 J) in the thymol final points: (1) There are four contours, designated by
structure. Certainly convincing. As overkill, note that in the arrows, that represent 1 JCH couplings (large) that have not
HMBC spectrum, the protons of the methyl substituent cor- been completely suppressed. These CH doublets are obvious
relate with C-6 (3 J), C-4 (3 J), and C-5 (2 J). Further, note since they straddle the proton peaks. They can be ignored.
that the six methyl protons of the isopropyl group correlate (2) The correlations of the OH proton with C-6, C-2, and
with C-7 (2 J) and with C-2 (3 J). It is interesting to note that C-1 should be noted. Correlations to OH protons can be very
the correlations of H-8 to C-9 (3 J) and H-9 to C-8 (3 J) are useful, but are rarely seen in an HMBC spectrum because
also observed. they are typically too broad to detect.
The utility of HMBC in correlating quaternary carbon
atoms with assigned protons can be shown by working out
 Silverstein c07.tex V2 - 06/04/2014 12:14 A.M. Page 339

Problem 7.4A PROBLEM 7.4 DISCUSSION 339

10

3 1
4
MASS 2
OH

5 × 10
69 6
100
% of Base Peak

7
41 8 9
136
Geraniol
50 139
154
93 123
55 81 111

50 60 70 80 90 100 110 120 130 140 150

m/z
IR

100
% Transmittance

3321

2966
2920
2858

1670

1442
1377

1095
1003

833
4000 3000 2000 1000
Wavenumber (cm–1)
1
H NMR 600 MHz

3260 3250 Hz 3060 3050 Hz 2500 2490 Hz 1270 1260 Hz

10
9 8

1230 1220 Hz 1020 1010 Hz 970 960 Hz

OH

2 6 1 5 4 9,10,8
5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 ppm
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340 CHAPTER 7 SOLVED PROBLEMS Problem 7.4B

DQFCOSY 600 MHz

ppm
OH
1.5
9,10,8
2.0 5,4
10

3 1
2.5
4 OH
2
3.0 5 6
F1
3.5 7
8 9
Geraniol
4.0
1
4.5

5.0
6
5.5 2

6.0
6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 ppm
F2
13
C/DEPT NMR 150.9 MHz

CDCl3

3 7 62 1 4 5,9 8,10
140 130 120 110 100 90 80 70 60 50 40 30 20 ppm
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Problem 7.4C PROBLEM 7.4 DISCUSSION 341

HMQC 600 MHz 9,10,8

1
2 6 5,4

ppm 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 ppm

10
15 10
3 1
4
8
20 OH
2
5 6
25 9
5
7
8 9
30 Geraniol

35
F1
40 4

45

50

55

60 1

65

ppm
2
125 6

130
7
135

140 3
6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 ppm
F2
 Silverstein c07.tex V2 - 06/04/2014 12:14 A.M. Page 342

342 CHAPTER 7 SOLVED PROBLEMS Problem 7.4D

INADEQUATE 600 MHz

3 7 6 2 1 4 5 9 8 10

Hz

10
–15000 –15000
3 1
4 OH
2
5 6

–10000 –10000
7
8 9
Geraniol

–5000 –5000

F1 0 0

5000 5000

Hz

10000 10000
5000

10000

15000 15000
15000

135 130 125 ppm

140 130 120 110 100 90 80 70 60 50 40 30 20 ppm

F2
 Silverstein c07.tex V2 - 06/04/2014 12:14 A.M. Page 343

Problem 7.4E PROBLEM 7.4 DISCUSSION 343

NOE Difference Spectra, 600 MHz 1 irradiated

8 irradiated
2 irradiated
10

9,10 irradiated 3 1 6 irradiated

4 OH
2
5 6

7
8 9
2 6 Geraniol 9,10 8

5.4 5.3 5.2 ppm 1.7 1.6 ppm

2 6 1 9 10 8
5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 ppm

8 irradiated 1 irradiated

9 irradiated 2 irradiated
10

10 irradiated 3 6 irradiated
4 2

5 6 1
OH

7
8 9
2 6 Nerol 10 9 8

5.4 5.3 5.2 ppm 1.7 1.6 ppm

2 6 1 10 9 8
5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 ppm
 Silverstein c07.tex V2 - 06/04/2014 12:14 A.M. Page 344

344 CHAPTER 7 SOLVED PROBLEMS

PROBLEM 7.4 DISCUSSION H3C H H3C H

C C CH2 OH or C C CH2 OH
It is quite likely that the m∕z 154 peak, though small (the
gray area is multiplied by 10), is the molecular ion peak. H3C
The m∕z 139 peak, also small, results from rational loss of a
methyl group. The alert interpreter also notes the M-18 peak The structure on the left is in fact a complete molecule
at m∕z 136 and promptly finds the intense, broad OH peak with no open valences; hence, it is rejected as the alcohol
in the “neat” IR spectrum at 3321 cm−1 for confirmation; “fragment.” The fragment on the right however seems plau-
the intense band at 1003 cm−1 is probably due to C⏤O sible.
stretching. Again, as in Problem 7.3 we ask: alcohol or H3C H H 3C H
phenol; aromatic or not?
The very weak molecular ion peak in the present H3C C C and C C CH2 OH
problem, together with loss of H2 O, suggests, but does
not prove, an alcohol rather than a phenol. It may be Another “fragment” can be constructed by considering
worthwhile at this point to entertain the possibility that that we have another double bond with two methyl groups
the base peak (m∕z 69) represents the fragment C5 H9 + and that have no vicinal coupling (i.e., they are geminal) and
results directly from the molecular ion peak by a strongly an alkenyl methine, shown at left above. If we consider the
favored mechanism. If so, the intact molecule probably two fragments that we now have and realize that the two
contains at least one double bond. remaining pieces that have not been used are methylene
The 13 C∕DEPT spectra provide 10 distinct carbons and groups, it is a simple matter of inserting them between the
17 hydrogen atoms arranged thus from high to low fre- two fragments shown above to arrive at the structure below:
quency: C, C, CH, CH, CH2 , CH2 , CH2 , CH3 , CH3 , CH3 .
The first four are very likely alkenyl. If the hydroxylic H3C H H 3C H
hydrogen atom is added, the tentative molecular formula is H3C C C CH2 CH2 C C CH2 OH
C10 H18 O, in accord with the molecular ion, m∕z 154. The
index of hydrogen deficiency is two, which would allow two This is a doubly unsaturated terpene alcohol. The
double bonds, supported by the four alkenyl carbon atoms. cis/trans stereochemistry is more accessible (and more obvi-
At this point, it is possible to solve the overall structure ous) in the following representation:
by using the wealth of information in the one-dimensional
10
NMR spectra. This limited approach will be explored first,
1
followed by an approach which also makes use of the 2D 4 3
NMR spectra. Let us note at this time that the stereochem- 2
OH
istry of this molecule cannot be proved using simple 1 H and 5
13 C NMR spectra. 6

Beginning with the 1 H NMR spectrum, the integration

7
from high to low frequency reads: 1:1:2:2:2:6:3:1, in confor- 8 9
mity with the 18 hydrogen atoms in the molecular formula.
It can also be read: (CH, CH alkenyl), (CH2 , deshielded by The structure has no stereogenic center. There is a plane
OH), CH2 , CH2 , CH3 , CH3 , (almost superposed), CH3 , OH. of symmetry in the plane of the page; thus, the protons
Recall from the 13 C∕DEPT spectra that there are two carbon of each methylene group are interchangeable (enantiotopic).
atoms that have no attached hydrogen atoms. Recall also that The H-4 protons give rise to a distorted triplet by coupling
the 13 C∕DEPT spectra showed three distinct CH3 groups, to the H-5 protons, which give a distorted quartet by coupling
whereas the 1 H NMR spectrum showed H-9 and H-10 peaks to the H-4 protons and to the H-6 proton with a slightly
apparently superposed even at 600 MHz. However, they are different coupling constant. The small 𝛥𝜈∕J ratio for H-4,
not completely superposed when expanded; they are partially H-5 also contributes to the distortion. The methyl groups,
overlapped with some long-range coupling. H-8 and H-9, are in the symmetry plane and are thus
A methylene group (from the 13 C∕DEPT) is repre- not interchangeable. The three methyl proton groups have
sented by a doublet (with some long-range coupling from distinct chemical shift.
H-10) at 4.15 ppm in the 1 H NMR spectrum. Since the only Certainly the story is convincing, but the evidence is
methine groups in the structure are alkenyl (also from the based only on the chemical shifts and on coupling patterns.
13 C∕DEPT), the compound must be an allylic alcohol. The It is unwarranted to base an analysis on chemical shifts
three methyl groups are relatively deshielded and show no and coupling patterns when a detailed analysis can be done
vicinal coupling, forcing us to place them on alkenyl car- unambiguously with 2D experiments.
bon atoms. We consider two possible resulting allylic alcohol A better approach for solving structures relies less on
structures: the 1D spectra and taps the wealth of information in the
 Silverstein c07.tex V2 - 06/04/2014 12:14 A.M. Page 345

PROBLEM 7.4 DISCUSSION 345

2D spectra. We obtain the molecular formula as we did an alkenyl carbon (C-7). These connectivities confirm our
above, noting also the presence of the alcohol functionality assignment of C-10; however, we are unable to distinguish
from the IR spectrum with confirmation in the 13 C∕DEPT between C-8 and C-9. These assignments are made in the
and 1 H NMR spectra. Next, we turn to the 2D NMR data. next section. If we continue from C-3, we see two more con-
Evidence of diastereotopic protons is quickly ascertained in nectivities, one to an alkenyl carbon (C-2) (see inset) and the
the HMQC spectrum by noting if there are two protons with other to an aliphatic carbon (C-4). The rest of the connectiv-
different chemical shifts that show correlations to the same ities are left as an exercise for the student to transform the
13 C peak. No such diastereotopic correlations are seen. correlations into a carbon skeleton.
The connectivity data of the COSY spectrum are most There are still two remaining tasks: assignment of stere-
reassuring and a good place to start. The peaks along ochemistry of the C-2, C-3 double bond and assignment
the diagonal are numbered for convenience. A good entry of the C-8 and C-9 methyl groups. NOE difference spec-
point for the COSY data is the methylene resonance at troscopy reveals 1 H⏤1 H proximities through space because
4.15 ppm (H-1). (If you need convincing that this peak is of enhancement by the nuclear Overhauser effect. The “dif-
CH2 number 1, confirmation can be found in the HMQC and ference” spectrum is obtained by subtracting a standard
13 C∕DEPT spectra.) Correlation by way of vicinal coupling 1 H spectrum from the NOE spectrum; this leaves only the

is found to the alkenyl methine (H-2) at 5.41 ppm and enhanced peak(s).
correlation to a methyl group at 1.68 ppm (H-10) by way The task we face with the present molecule—distin-
of long-range coupling is also evident. How do we know guishing between a trisubstituted (E) double bond and the
that the proton multiplet at 5.41 ppm is associated with a corresponding (Z) double bond—is not a trivial assignment.
methine functionality? By using the natural interplay of Nor is the task of distinguishing between the H-8 and H-9
spectra, the proton multiplet at 5.41 ppm correlates with a methyl groups, as has been mentioned earlier. For conclu-
carbon resonance at 123 ppm in the HMQC spectrum; this sive results, we examine both the (E) isomer (geraniol) and
information is fed back into the 13 C∕DEPT spectra and we the (Z) isomer (nerol) at the C-2 double bond.
find that the carbon resonance at 123 ppm is due to a methine In the top half of the NOE difference spectra, the
carbon. Likewise, the proton resonance at 1.68 ppm is 1 H NMR spectrum of geraniol, along with the NOE dif-

correlated to a methyl carbon atom in the HMQC spectrum. ference subspectra resulting from irradiation of key proton
We can continue the connectivity pattern with the COSY groups, are given and, in the bottom half of the page, the
to H-4 because there is a weak long-range coupling from 1 H NMR spectrum of nerol (the geometric isomer of geran-

methyl H-10 to methylene H-4 at 2.11 ppm. (The student iol) along with the corresponding NOE difference subspectra
is encouraged to confirm that the multiplet at 2.11 ppm is are given. In geraniol, irradiation of alkenyl methine H-2
a methylene group by examining and comparing the COSY, shows no NOE enhancement of the H-10 methyl group; the
HMQC, and 13 C∕DEPT spectra.) The only other correlation reciprocal irradiation of the H-10 methyl group shows no
to H-4 is to H-5; this correlation is seen, but difficult to NOE enhancement of the H-2 methine group. We conclude
discern because the cross peaks are nearly on the diagonal. that these two groups are on opposite sides of the double
The H-5 methylene group shows a correlation to H-6 (the bond and assign geraniol an E-double bond. This assign-
other alkenyl methine) at 2.03 ppm. H-6 shows two other ment is confirmed by irradiation of the H-1 allylic methylene
correlations, both long range, to the methyl groups H-8 group and the concomitant NOE enhancement of the H-10
and H-9. There are no other correlations in this COSY methyl group, thereby proving their disposition on the same
spectrum. The OH proton shows no cross peak because of side of the double bond. Since methyl groups H-9 and H-10
rapid exchange. overlap in the proton spectrum, they are irradiated together
At this point, we have assigned all of the protons and we see an NOE enhancement of alkenyl methine H-6.
but still cannot differentiate between the methyl groups at Check the result of irradiation of methine H-6.
H-8 and H-9. Since we know all the 1 H assignments, it is a Quite often in “real life” problems, especially those
trivial task to transfer assignments to the 13 C signals through involving natural products, the geometric isomer is not
the HMQC spectrum. The quaternary carbons C-3 and C-7 available (although, in principle, it could be synthesized). For
have no attached protons and do not show up in the HMQC pedagogical purposes, the results from nerol are presented.
spectrum. An HMBC spectrum could be used to correlate the In this case, irradiation of alkenyl proton H-2 does result in
quaternary carbon atoms, but for this example we use carbon NOE enhancement of methyl group H-10, and we conclude
connectivities instead. that nerol has a Z-double bond. The assignments of methyl
The INADEQUATE spectrum provides the connectivi- groups H-8 and H-9 are left to the student.
ties between adjacent 13 C atoms. It is a most powerful tool; With hindsight, we can now recognize the fragment peak
after all, organic molecules consist mainly of chains and at m∕z 69 (the base peak) as the result of the allylic cleavage
rings of carbon atoms. Lines showing connectivities between of an alkene. Ordinarily, reliance on this cleavage for location
and among correlated carbons have been added to the INAD- of a double bond is dubious, but in geraniol, cleavage of the
EQUATE spectrum. As a starting point, consider the three bis-allylic bond between C-4 and C-5 results in the stabilized
methyl carbons C-8, C-9, and C-10. We note that C-10 is fragment, m∕z 69. See Section 1.6.1.2 for the analogous
bonded to C-3 whereas C-8 and C-9 are both bonded to allylic cleavage of 𝛽-myrcene into fragments m∕z 69 and 67.
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346 CHAPTER 7 SOLVED PROBLEMS Problem 7.5A

H
H
O
CH2CH3
CH2

MASS cis-jasmone
79 CH3 164
% of Base Peak

100 110
91 122 149
41 55 135
67
50

50 100 150
m/z
IR
100

756
1072
%Transmittance

1342
2877

1442
50
2962

1651
1697

4000 3000 2000 1000

Wavenumber (cm–1)
1
H NMR 600 MHz

3200 3150 Hz 1750 1700 Hz 1450 1400 Hz

1250 Hz 600 550 Hz

5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 ppm
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Problem 7.5B PROBLEM 7.5 DISCUSSION 347

DQFCOSY 600 MHz

ppm
H
H
1 O
CH2CH3
CH2

cis-jasmone
2
CH3

F1 3

6
6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 ppm
F2
13
C/DEPT NMR 150.9 MHz

CDCl3

200 180 160 140 120 100 80 60 40 ppm

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348 CHAPTER 7 SOLVED PROBLEMS Problem 7.5C

HMQC 600 MHz

ppm 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 ppm

H
H
15 O
CH2CH3
CH2
20 cis-jasmone
CH3

25

30

35

F1

ppm

130

140

150

160

170

ppm
205

210

215
6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 ppm
F2
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Problem 7.5D PROBLEM 7.5 DISCUSSION 349

HMBC 600 MHz

ppm 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 ppm

15

20

25 H
H
O
CH2CH3
30 CH2

cis-jasmone

35 CH3

F1

ppm

130

140

150

160

170

ppm
205

210

215
6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 ppm
F2
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350 CHAPTER 7 SOLVED PROBLEMS

PROBLEM 7.5 DISCUSSION this methylene group shows long-range coupling to two
other groups not yet used (one of the two unused methylene
In the mass spectrum, the peak at m∕z 149 represents a ratio- groups and the other methyl group.) So far, we have a
nal loss of a CH3 group (M-15) and indicates that the m∕z 2-pentenyl group, which must be attached to one of the
164 peak is the molecular ion peak. The lack of an M + 2 quaternary alkenyl carbon atoms. The broadened singlet at
peak indicates the absence of Cl, Br, and S. The IR spectrum 2.01 ppm must be due to a methyl group attached to the other
shows an intense peak at 1697 cm−1 , suggestive of a C⏤O quaternary alkenyl methine carbon.
group, which is confirmed by the peak in the 13 C NMR spec- If we take stock of the remaining molecular fragments
trum at 208 ppm (in the range of ketones). In the 1 H NMR from the 13 C∕DEPT spectra (a ketone carbonyl, two methy-
spectrum, the integrals are: 1:1:2:2:2:2:3:3 (16 protons). The lene groups, and two quaternary alkenyl carbons) and the fact
13 C NMR spectrum indicates 11 carbon atoms. Thus, the that there is still the unused degree of unsaturation for a ring,
tentative molecular formula is C11 H16 O, which agrees with we realize that we must draw an unsaturated five-membered
the molecular ion peak of m∕z 164. The index of hydro- ring ketone with these pieces. Further evidence allows us to
gen deficiency is four. From high to low frequency in the order these pieces. First, the COSY spectrum tells us that
13 C∕DEPT spectra, the following functionalities are identi- the two methylene groups (at 2.30 ppm and 2.45 ppm) are
fied: C, C, C, CH, CH, CH2 , CH2 , CH2 , CH2 , CH3 , CH3 . vicinally coupled and therefore adjacent. Second, the 13 C
Three of the four degrees of unsaturation can be dealt chemical shift of one of the quaternary alkenyl carbons is
with directly from the 13 C NMR spectrum. We have already 170 ppm; such deshielding can only be explained by con-
noted the carbonyl peak and because of its chemical shift we jugation with the ketone carbonyl. One obvious structure is
associate it with a ketone. There are four alkenyl carbon reso- shown below. The HMBC spectrum (see the correlations to
nances, which account for two more degrees of unsaturation. the carbonyl carbon) confirms the ring structure and the lack
By inference, the fourth degree of unsaturation is attributed of a stereogenic carbon atom (there is a plane symmetry in
to a ring. the plane of the page) explains the absence of diastereotopic
The 13 C∕DEPT spectra have provided the various methylene protons.
molecular fragments, which is a large step toward decipher-
ing the structure. We turn to the 2D NMR spectra to assem- O H H
ble the pieces. As needed, we will jump from one spectrum
to another. The more shielded of the two methyl groups at CH2 CH2 CH3
0.93 ppm, which correlates with the methyl carbon reso-
nance at 15 ppm in the HMQC, is a good place to start. This CH3
methyl group is coupled to a methylene group at 2.12 ppm,
as evidenced by the strong cross peak in the COSY spec-
trum. The carbon resonance associated with this group is Before we finish, we ask ourselves if there are any
found at 21 ppm in the HMQC spectrum. This methylene constitutional isomers that we need to consider. Yes, if we
group also correlates with one of the alkenyl methines in switch the two substituents (i.e., the 2-pentenyl group and
the COSY spectrum at 5.33 ppm. The methylene group at the methyl group), the resulting structure also fits the data
2.12 ppm shows a nearly first-order quintet. so far. Again, the complex HMBC spectrum resolves the
The other alkenyl methine resonance at 5.18 ppm shows issue. For instance, the ring substituted methyl resonance
a correlation in the COSY spectrum to the first methine (at at 17 ppm shows only one correlation to the methylene
5.33 ppm) strongly suggesting a disubstituted double bond. group at 2.45 ppm. This methylene group is in the 𝛽-position
In addition, the methine resonance at 5.18 ppm is coupled relative to the carbonyl, thereby confirming the structure
to a rather deshielded methylene group at 2.88 ppm. This given above. Are there other correlations in the HMBC
methylene resonance is a broadened doublet and shows no that can confirm the structure? The student can finish the
other vicinal coupling. According to the COSY spectrum, assignments.
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Problem 7.6A PROBLEM 7.6 DISCUSSION 351

LCMS ES
Arginine (R) Glycine (G) Aspartic acid (D) 347
• •• M+1
C6H13N4O C2H3NO C4H6NO4•
100
Mass: 157 Mass: 57 Mass: 132
90 O O O
2 2 2
H2N CH C N CH C N CH C OH
80 1 H 1 H 1
3 CH2 H 3 CH2
70
4 CH2 4C O
C12H22N6O6
% of Base Peak

60 5 CH2 Mass: 346 OH

50 6 NH

40 7C NH
M-16
30 NH2
330

20 112 M-(G,D) M-(D) 232 M+23

157 214 288 369
10

150 200 250 300 350

m/z

HMQC 600 MHz

Arg 5 Arg 3
Gly2
Arg 2 Asp 3Asp 3' Arg 4
Gly 2'
Asp 2
ppm

Arg 4
25 ppm
Arg 3
Asp 2
30 52.5 Arg 2

35 53.0
4.6 4.4 4.2 ppm
F1 Asp 3
40 Arg 5
Gly 2
45

50
Asp 2
Arg 2
55
4.5 4.0 3.5 3.0 2.5 2.0 1.5 ppm
F2
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352 CHAPTER 7 SOLVED PROBLEMS Problem 7.6B

1
H NMR 600 MHz
Arg 5
Asp NH
Gly NH
Arg NH (6) Arg 2 Gly 2
Gly 2'
Asp 2

5200 5000 4800 4600 Hz 2600 2400 2200 2000 Hz

Arg 3 O O O
2 2 2
H2N CH C N CH C N CH C OH
Asp 3 Asp 3' 1 H 1 H 1
Arg 4 3 CH2 H 3 CH2

4 CH2 4C O
5 CH2 Arg-Gly-Asp OH
1800 1600 1400 1200 1000 Hz 6 NH

7C NH
NH2

1 1 1 1 1 # of protons 1 21 2 11 2 2

9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 ppm
13
13 C/DEPT NMR
C/DEPT 600 150.9 MHz
MHz

Asp 1 Asp 4 Arg 1 Gly 1

Arg 2 Asp 2

Arg 5 Arg 3 Arg 4

Arg 7 Gly 2 Asp 3

175 170 165 160 ppm 50 45 40 35 30 25 ppm

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Problem 7.6C PROBLEM 7.6 DISCUSSION 353

ppm 9 8 7 6 5 4 3 2 ppm
COSY 600 MHz
Arg 4
2 2 Arg 3

Asp 3,3'
3 3
Arg 5
Gly 2'
4 4 Arg 2, Gly2
Asp 2
F1 5 5

6 6

7 7
Arg NH (6)

8 8
Asp NH

9 9 Gly NH

F2
ppm TOCSY 600 MHz
Arg 4
2 2
Arg 3

3 3
Arg5

4 4
Arg 2

5 5
F1
6 6

7 7
Arg NH (6)

8 8

9 9

9 8 7 6 5 4 3 2 ppm
F2
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354 CHAPTER 7 SOLVED PROBLEMS Problem 7.6D

ppm 9 8 7 6 5 4 3 2 ppm ROESY 600 MHz

Arg 4
2 2 Arg 3

Asp 3,3'
3 3
Arg 5

Gly 2'
4 4 Arg 2, Gly2
Asp 2
F1 5 5

6 6

7 7
Arg NH (6)

8 8
Asp NH

9 9 Gly NH

F2
COSY 600 MHz TOCSY 600 MHz ROESY 600 MHz

ppm
Gly NH Asp NH Arg NH (6)

2.0

2.5 Asp 3'

3.0
F1
3.5

4.0 Gly 2'

Gly 2
Arg 2
4.5
9.5 9.0 8.5 8.0 7.5 ppm 9.0 8.5 8.0 7.5 ppm 9.0 8.5 8.0 7.5 7.0 ppm
F2 F2 F2
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Problem 7.6E PROBLEM 7.6 DISCUSSION 355

HMBC 600 MHz

ppm 9.5 9.0 8.5 8.0 7.5 7.0 ppm 4.5 4.0 3.5 3.0 2.5 2.0 ppm

Arg 4
25
Arg 3
30

35

F1 Asp 3
40 Arg 5
Gly 2
45

50
Asp 2
55 Arg3

F2
Asp NH Arg 3
Gly NH Arg 5
Arg NH (6) Gly 2
Arg 2 Asp 3 3'
Arg 4
Gly 2'
Asp 2
ppm

156
Arg 7
157
Arg 7

ppm
Gly 1
F1 170 Arg 1
Arg 1 Gly 1

ppm

178 Asp 1
Asp 1 Asp 4

179
9.5 9.0 8.5 8.0 7.5 7.0 ppm 4.5 4.0 3.5 3.0 2.5 2.0 ppm
F2
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356 CHAPTER 7 SOLVED PROBLEMS

PROBLEM 7.6 DISCUSSION 8.26 ppm. There are three correlations to this resonance,
giving a total of four moieties in this spin system. If we again
The last of the solved problems in this chapter is quite take this information directly to the HMQC spectrum, we
different from the other problems presented above, and our can find the corresponding carbon resonances. Of course,
approach takes a different tack as well. The compound is a there is no correlation to the N⏤H resonance. The proton
tripeptide, and structure elucidation of peptides requires two resonance at 4.41 ppm correlates to a carbon resonance at
distinct solutions. First, the individual amino acids (and their 52.4 ppm, and the 13 C∕DEPT spectra confirm that this is a
number) are determined and second, the amino acid units are methine group. The remaining spins in the system are proton
put in order (sequenced). Neither of these exercises is trivial resonances at 2.58 ppm and 2.72 ppm, which correlate to
since there are more than 20 common amino acids, and the a single carbon resonance at 38.6 ppm. The 13 C∕DEPT
nature of the peptide bond means that they can be arranged spectra confirm that this is a methylene group. This residue
in any order. is identified as aspartic acid, and again we conclude that it is
Before discussing the actual data, some discussion not the N-terminus.
of sample handling is worthwhile. The mass spectrum of A starting point for the final spin system is the N⏤H res-
the tripeptide was obtained using an electrospray LCMS onance at 7.35 ppm. There are four other proton resonances
(see Chapter 1). Electrospray (ES) is a “soft” method of in this spin system; the HMQC spectrum and the 13 C∕DEPT
ionization (a type of chemical ionization), which suppresses spectra indicate that these resonances represent one methine
or limits fragmentation and enhances pseudomolecular ions group and three methylene groups. Thus, this amino acid
(depends on the number of charges on the ion, z). The NMR residue is arginine.
experiments were carried out in 95% H2 O and 5% D2 O at The COSY spectrum could be used to confirm our anal-
0∘ C. The reasoning for using these solvents and the details ysis thus far but it has not been necessary. However, the
are given in Section 5.11. COSY and TOCSY are not redundant, and, in fact, they are
The LCMS ES gives an M + 1 peak of m∕z 347, complementary in at least one important aspect. While the
which corresponds to a molecular formula of C12 H22 N6 O6 . TOCSY shows all of the spins in a spin system, it does
Derivation of this formula is not considered in detail since not reveal which spins are actually coupled to one another.
Appendix A in Chapter 1 only goes up to 250 amu. The small For instance, the N⏤H proton at 8.26 ppm (from aspar-
peak at m∕z 369 (M + 23) is due to the presence of sodium tic acid) shows only a correlation to a methine group in
ions, which are ubiquitous in aqueous solutions. Although the COSY; we can safely conclude that this N⏤H group
there is only limited fragmentation, the fragments that do is involved in a peptide linkage and that the methine group
appear can be quite useful to an experienced interpreter, is the 𝛼- or asymmetric carbon of the amino acid.
and some of the cleavages are shown as insets in the mass (Glycine is a trivial case and not considered here.) The N⏤H
spectrum. proton at 7.35 ppm, which we assigned to an aspartic acid
To ascertain the three amino acids, we use informa- residue, correlates with all of the spins in the TOCSY, but
tion from the 1 H NMR spectrum, the 13 C∕DEPT spec- only shows coupling to a methylene group at 2.24 ppm in the
tra, the COSY spectrum, the TOCSY spectrum, and the COSY. This information allows us to draw two conclusions
HMQC spectrum. Chemical shifts for protons of amino acids that were not available from the TOCSY. First, the N⏤H res-
are given in Appendix I of Chapter 3. Peptides are chi- onance is not coupled to the 𝛼-carbon of arginine and there-
ral molecules, and all methylene protons are diastereotopic, fore must represent the N⏤H from the guanadino group and
even those of glycine. (The methylene protons of free not 𝛼-amino group. Second, the arginine residue must be the
glycine are enantiotopic.) A starting point for peptides (and N-terminal residue because there is no correlation between
other compounds made of distinct units such as oligo- and the methine proton at 4.13 ppm and an N⏤H proton in either
polysaccharides) is the TOCSY spectrum. The 2D TOCSY the COSY or the TOCSY. In the discussion of the sequence
spectrum shows correlations among all spins in a spin sys- of the amino acids, we will confirm this second point.
tem, but no correlations to spins outside the system. For a The combined information from the 13 C∕DEPT, COSY,
tripeptide, there are three distinct spin systems, and they are TOCSY, and HMQC spectra enables us to assign all protons
easy to find in the TOCSY spectrum (Problem 7.6C). The in the 1 H spectrum except those that are exchanging rapidly
N⏤H resonance at 8.95 ppm reveals one spin system show- (i.e., the carboxyl and free amino protons) and all of the
ing correlations to two resonances at 3.96 ppm and 4.13 ppm. non quaternary carbon resonances in the 13 C spectrum.
If we feed this information into the HMQC spectrum, we find There is no need to assign the rapidly exchanging protons,
that these two proton-resonances correlate to the same car- and the non-quaternary carbons will be assigned during the
bon atom at 41.9 ppm (i.e., the two methylene protons are sequencing discussion.
diastereotopic). This amino acid is identified as a glycine The second main objective is to “sequence” the peptide
residue, and since there is correlation to an amide N⏤H or place the amino acids in their proper order. Two powerful
group, we conclude that the glycine is not the N-terminus. tools from our NMR experimental repertoire are HMBC
(This point will be confirmed using other methods.) and ROESY (or NOESY). Recall that the HMBC shows
Another spin system may be easily identified through long range 1 H⏤13 C coupling (generally 2-bond, 2 JCH , and
a convenient starting point with the N⏤H resonance at 3-bond, 3 JCH couplings). For sequencing purposes, this
 Silverstein c07.tex V2 - 06/04/2014 12:14 A.M. Page 357

PROBLEM 7.6 DISCUSSION 357

experiment shows correlation between adjacent amino acids, spectrum, which is shown in Problem 7.6E. The bottom part
as it were, “seeing through” the amide (peptide) carbonyl to of this page is pertinent. Before confirming the sequence,
the amide N⏤H. This exercise will also enable us to as- a simple assignment of a quaternary carbon is made. The
sign the carbonyls. assignment of the C-7 carbon of arginine can be made by
The ROESY experiment facilitates sequencing utilizing noting the correlation between the arginine N⏤H (H-6) and
the inevitable through space correlations between adjoining the quaternary carbon at 156.5 ppm.
amino acids. We expect to find through space connectivities The analysis of the HMBC spectrum in the region of the
from one amino acid’s N⏤H to the adjoining amino acid’s carbonyl carbons is hampered by the lack of digital resolution
𝛼- or C-2 proton(s). The data from either experiment should along the F1 axis. Recall that the HMBC experiment is
be sufficient; together they provide strong confirmatory proton detected, which gives good resolution in the proton
evidence. (F2) dimension. The only way to improve resolution along
The full ROESY spectrum is shown in Problem 7.6D the F1 axis is to increase the number of t1 increments in
(top part). ROESY cross peaks show both COSY correla- the experiment, which has serious practical limitations. The
tions and NOE correlations. For easy comparison, therefore, lines drawn in the insets help clarify the correlations.
the area of interest for sequencing (the boxed area) is shown The glycine N⏤H correlates with the arginine car-
along with the corresponding COSY and TOCSY (bottom bonyl (C-1), thereby confirming the arginine–glycine link-
part of Problem 7.6D). The glycine N⏤H, which corre- age. The assignment of the arginine carbonyl resonance is
lates with the adjacent methylene group in both the COSY accomplished by noting the correlation of the carbonyl reso-
and TOCSY spectra, gives an additional correlation in the nance at about 170 ppm with the arginine methine H-2. The
ROESY spectrum to H-2 of arginine. This correlation shows other linkage is established by the correlation of the aspartic
a linkage between glycine and arginine. Some might consider acid N⏤H and the glycine carbonyl (C-1) resonances; the
this correlation inconclusive because of the overlap between glycine carbonyl is pinpointed from its correlations with the
H-2 of arginine and one of the H-2’s of glycine. In this case, diastereotopic methylene protons of glycine. The sequence
confirmation is desirable (see below). of the tripeptide is thus confirmed by two independent
The other connectivity can be established by way of methods.
the NOE interaction between the aspartic acid N⏤H and
the two glycine H-2’s. There is no ambiguity or overlap
in this correlation, thus proving the sequence given in
Problem 7.6A. An interesting aside worth noting is the NOE STUDENT EXERCISES
correlation between the aspartic acid N⏤H and only one
of the two diastereotopic methylene protons of aspartic acid The following exercises are given for the student to work
(H-3). This selective interaction suggests restricted rotation through. The structures and spectra for two compounds
and allows differentiation and assignment of the diastereo- are shown on the following pages. The student should use
topic protons. all available data to prove to themselves the correctness
Confirmation of this sequence and assignment of of the structures shown, and assign all proton and carbon
the quaternary carbons is accomplished with the HMBC resonances.
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358 CHAPTER 7 SOLVED PROBLEMS Exercise 7.7A

MASS
CI Reagent gas methane
% of Base Peak

× 30
57 103
100 100 85
72
43
50 85 50 143
131

40 50 60 70 80 90 100 100
m/z m/z
IR
100

1149
%Transmittance

1388

833
1458
50
2954

972
3417

1049
2870

4000 3000 2000 1000

1
Wavenumber (cm–1)
H NMR 600 MHz

2680 2660 2640 2620 2600 2580 Hz 2140 2120 2100 2080 2060 2040 Hz

4.5 4.0 3.5 3.0 2.5 2.0 1.5 ppm

13
13
C/DEPT
C/DEPT NMR
NMR 150.9 MHz
600 MHz

3-methyl-3-oxetanemethanol
CH2OH
CH3
O

80 75 70 65 60 55 50 45 40 35 30 25 20 ppm
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Exercise 7.7B STUDENT EXERCISES 359

ppm 4.5 4.0 3.5 3.0 2.5 2.0 1.5 ppm COSY 600 MHz

3-methyl-3-oxetanemethanol
1.5 1.5
CH2OH
CH3
2.0 2.0
O

2.5 2.5
F1
3.0 3.0

3.5 3.5

4.0 4.0

4.5 4.5

F2 HMQC 600 MHz

ppm

20 20

30 30

40 40

F1 50 50

60 60

70 70

80 80

4.5 4.0 3.5 3.0 2.5 2.0 1.5 ppm

F2
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360 CHAPTER 7 SOLVED PROBLEMS Exercise 7.8A

MASS
221
% of Base Peak

100

50 97 137
55 81
177 203 236

50 100 150 200

m/z
IR
100

910
1381
1458
%Transmittance

1003
2924

4000 3000 2000 1000

Wavenumber (cm –1)
1
H NMR 600 MHz

2350 2300 Hz 1200 1150 Hz 1050 1000 Hz 900 850 Hz

800 Hz 750 700 Hz 600 Hz 550 500 Hz

(-)-ambroxide
CH3
O
CH3

H3C CH3

4.0 3.5 3.0 2.5 2.0 1.5 1.0 ppm

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Exercise 7.8B STUDENT EXERCISES 361

13
C/DEPT NMR 150.9 MHz

80 75 70 65 60 55 50 45 40 35 30 25 20 15 ppm
HMQC 600 MHz

ppm

20

30

F1 40

(-)-ambroxide
50 CH3
O
CH3
60

H3C CH3

4.0 ppm 1.9 1.8 1.7 1.6 1.5 1.4 1.3 1.2 1.1 1.0 0.9 0.8 ppm
F2
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362 CHAPTER 7 SOLVED PROBLEMS Exercise 7.8C

HMBC 600 MHz

ppm 4.0 3.9 ppm 2.0 1.8 1.6 1.4 1.2 1.0 0.8 ppm

(-)-ambroxide
15 CH3
O
17 CH3

19
H3C CH3
21

23
ppm

34
F1
36

38

40

42

ppm

58

60

62

64

ppm

80

82
4.0 3.9 ppm 2.0 1.8 1.6 1.4 1.2 1.0 0.8 ppm
F2
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Exercise 7.8D STUDENT EXERCISES 363

INADEQUATE 150.9 MHz

Hz

(-)-ambroxide
–7000 CH3 –7000
O
CH3
–6000 –6000

–5000 H3C CH3 –5000

–4000 –4000

–3000 –3000

–2000 –2000

–1000 –1000

F1 0 0

1000 1000

2000 2000

3000 3000

4000 4000

5000 5000

6000 6000

7000 7000

80 75 70 65 60 55 50 45 40 35 30 25 20 15 ppm
F2
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CHAPTER 8
ASSIGNED PROBLEMS

8.1 INTRODUCTION especially with 2D spectra. The first group of problems has
a mass spectrum, an IR spectrum, and a 1 H and 13 C/DEPT
Chapter 7 has been propounded as though unknown prob- NMR spectra. In all cases, the 13 C/DEPT NMR spectra are
lems were being resolved by the authors. Not so. It was displayed in the following order, from top to bottom: DEPT-
inevitable that the authors knew the structures. The students 90, DEPT-135, and regular proton-decoupled 13 C NMR
inevitably consulted the structures as they worked through spectrum. The second group of problems has, in addition to
the explanations. The experience, therefore, has been more these spectra, some 2D NMR spectra. Many of these prob-
rationalization of the given structures than analysis of lems can be completed without recourse to the information
spectra. Nonetheless, the experience was worthwhile. available in the 2D spectra. The third group of problems is
Chapter 8 will be an experience in foresight rather than presented with the compounds’ structures and generally has
hindsight (except for the final group of problems), but the more 2D spectra.
first few modest problems should provide encouragement, The problems in the third group are intended as exercises
as did the problems at the end of each chapter. Admittedly, so that the student can work with more complicated struc-
difficulties will be encountered further along, but satisfac- tures. These problems can be assigned with the objective of
tions also. verifying the structure and making assignments.
The NMR spectra were obtained at either 300 MHz For most of the problems, there is more than enough
or 600 MHz for protons and 75.5 MHz or 150.9 MHz information to fully solve the problem, including stereo-
for carbon; CDCl3 was the solvent unless otherwise indi- chemistry, except, of course, absolute stereochemistry. There
cated. At 600 MHz, all 2D spectra were obtained with gra- are, however, a few problems that lack enough information to
dients except the INADEQUATE spectra. The IR spectra determine stereochemistry. In these cases, the student should
were obtained neat (i.e., no solvent) unless otherwise indi- indicate the possible stereoisomers and suggest ways to dis-
cated. The mass spectra were obtained by EI GC-MS unless tinguish among them. Additional Student Exercises can be
otherwise noted. Methane was used to obtain the chemical found at http://www.wiley.com/college/silverstein.
ionization mass spectra. At this point, we may all enjoy a more literary statement:
The problems that follow cover a wide array of “It is easy to be wise in retrospect, uncommonly difficult in
compound types and range from easy to moderate to diffi- the event.”*
cult. Clearly, these terms are relative; for a beginning stu-
dent, none of these problems are truly easy. With experience, * Stegner,
W. (1954). Beyond the Hundredth Meridian. Boston, MA:
many of the moderately difficult problems will seem easier Houghton Mifflin. Reprint, Penguin Books, 1992, Chapter 3.

364
 Silverstein c08.tex V3 - 06/12/2014 7:53 P.M. Page 365

Problem 8.1 ASSIGNED PROBLEMS 365

MASS
68
55
% of Base Peak

100
41 112
84
50
97

40 50 60 70 80 90 100 110
m/z
IR
100
%Transmittance

50
2858
2927

856
941
1161
1342
1454
1701
4000 3000 2000 1000
1
Wavenumber (cm –1)
H NMR 300 MHz

2.7 2.6 2.5 2.4 2.3 2.2 2.1 2.0 1.9 1.8 1.7 1.6 1.5 ppm

13
C/DEPT NMR 75.5 MHz

200 180 160 140 120 100 80 60 40 ppm

 Silverstein c08.tex V3 - 06/12/2014 7:53 P.M. Page 366

366 CHAPTER 8 Assigned Problems Problem 8.2

MASS
124
% of Base Peak

100
94
50 95
81
53 66

50 60 70 80 90 100 110 120

m/z
IR
100
%Transmittance

50
3398

3005
2947
2839

1601
1493

1284
1149
1041
945
837
768
687
4000 3000 2000 1000
Wavenumber (cm –1)
1
H NMR 300 MHz

2150 2140 Hz 1960 1950 Hz 1930 1920 Hz

7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 ppm

13
C/DEPT NMR 75.5 MHz

190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 ppm
 Silverstein c08.tex V3 - 06/12/2014 7:53 P.M. Page 367

Problem 8.3 ASSIGNED PROBLEMS 367

MASS
55
M-1
% of Base Peak

100
83
39 41
M
50 53 84
65 66

40 45 50 55 60 65 70 75 80 85
m/z
IR
100
%Transmittance

50
3332

2978
2939
2877

2291
2229

1454
1319
1227
1138
1014

741
4000 3000 2000 1000
1
Wavenumber (cm –1)
H NMR 300 MHz

1280 1260 Hz 680 660 Hz

4.0 3.5 3.0 2.5 2.0 1.5 ppm

13
C/DEPT NMR 75.5 MHz

CDCl3

78.0 77.5 77.0 76.5 p pm

95 90 85 80 75 70 65 60 55 50 45 40 35 30 25 20 ppm
 Silverstein c08.tex V3 - 06/12/2014 7:53 P.M. Page 368

368 CHAPTER 8 Assigned Problems Problem 8.4

MASS
m/z %M 111
126 (M) 100.0
% of Base Peak

100 127 (M+1) 8.2

128 (M+2) 4.9 126

50 39
43 83
49 57

40 50 60 70 80 90 100 110 120 130

IR m/z

100
%Transmittance

50
3089

1662

1415
1273

1061
933
856
725
590
4000 3000 2000 1000
1 Wavenumber (cm –1)
H NMR 300 MHz

2300 2280 Hz 2140 2120 Hz

7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 ppm

13
C/DEPT NMR 75.5 MHz

190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 ppm
 Silverstein c08.tex V3 - 06/12/2014 7:53 P.M. Page 369

Problem 8.5 ASSIGNED PROBLEMS 369

MASS
% of Base Peak
× 10
105
100
186
184
50 51 77

50 100 150
IR m/z

100
90
%Transmittance

80
70

594
694
764
964
1211
1450
1496
2985
3032

4000 3000 2000 1000

1 Wavenumber (cm–1)
H NMR 300 MHz

1590 1580 1570 Hz

2260 2250 2240 2230 2220 2210 2200 Hz

640 630 620 Hz

7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 ppm
13
C/DEPT NMR 75.5 MHz

140 130 120 110 100 90 80 70 60 50 40 30 ppm

 Silverstein c08.tex V3 - 06/12/2014 7:53 P.M. Page 370

370 CHAPTER 8 Assigned Problems Problem 8.6

MASS
128
% of Base Peak

100
64
130
50 92
73

50 60 70 80 90 100 110 120 130

m/z
IR
100
%Transmittance

50

679
748
1030
1200
1338
1454
1481
1585
3039
3074
3464
3521

4000 3000 2000 1000

1 Wavenumber (cm –1)
H NMR 300 MHz

7.4 7.2 7.0 6.8 6.6 6.4 6.2 6.0 5.8 5.6 5.4 ppm

13
C/DEPT NMR 75.5 MHz

155 150 145 140 135 130 125 120 115 ppm
 Silverstein c08.tex V3 - 06/12/2014 7:53 P.M. Page 371

Problem 8.7 ASSIGNED PROBLEMS 371

MASS% of Base Peak

× 20
55
87 115
100 196
73 194
50 135 137 163 165

0
50 100 150
m/z
IR
100
%Transmittance

50
2954

1736

1435
1365
1203

748
4000 3000 2000 1000
1 Wavenumber (cm –1)
H NMR 300 MHz

3.6 3.4 3.2 3.0 2.8 2.6 2.4 2.2 2.0 1.8 1.6 ppm

13
C/DEPT NMR 75.5 MHz

33.0 32.5 32.0 p pm

170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 ppm

 Silverstein c08.tex V3 - 06/12/2014 7:53 P.M. Page 372

372 CHAPTER 8 Assigned Problems Problem 8.8

MASS
54
% of Base Peak

100 67 84

93
50
111 126

50 60 70 80 90 100 110 120

m/z
IR
100
%Transmittance

3344

2958
2931
2873

1466
1331

1045

849
4000 3000 2000 1000
1 Wavenumber (cm –1)
H NMR 300 MHz

3.5 3.0 2.5 2.0 1.5 1.0 ppm

13
C/DEPT NMR 75.5 MHz

84 82 80 78 ppm

85 80 75 70 65 60 55 50 45 40 35 30 25 20 ppm
 Silverstein c08.tex V3 - 06/12/2014 7:53 P.M. Page 373

Problem 8.9 ASSIGNED PROBLEMS 373

MASS
82
% of Base Peak

100

50 138
54
67 95
123

50 60 70 80 90 100 110 120 130 140

IR m/z
100
%Transmittance

50

525
903
1246
1381
1670
2870
2958

4000 3000 2000 1000

1 Wavenumber (cm –1)
H NMR 300 MHz

1750 1740 Hz 640 Hz 570 560 Hz 300 290 Hz

6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 ppm

13
C/DEPT NMR 75.5 MHz

200 180 160 140 120 100 80 60 40 ppm

 Silverstein c08.tex V3 - 06/12/2014 7:53 P.M. Page 374

374 CHAPTER 8 Assigned Problems Problem 8.10

MASS
54
% of Base Peak

50 68
149
81 147
93 107 109
79 95 119 121

50 60 70 80 90 100 110 120 130 140 150

IR m/z

100

90
%Transmittance

80

70

756
1250
1435
2245
2970

4000 3000 2000 1000

1 Wavenumber (cm –1)
H NMR 300 MHz

3.6 3.5 3.4 3.3 3.2 3.1 3.0 2.9 2.8 2.7 2.6 2.5 2.4 2.3 2.2 ppm

13
C/DEPT NMR 75.5 MHz

120 110 100 90 80 70 60 50 40 30 20 ppm

 Silverstein c08.tex V3 - 06/12/2014 7:53 P.M. Page 375

Problem 8.11 ASSIGNED PROBLEMS 375

MASS
106
% of Base Peak

100

50 137
77

50 60 70 80 90 100 110 120 130 140

m/z
IR
100
%Transmittance

90

80

825
1049
1442
1512
1620
2931
3194
3348

4000 3000 2000 1000

1 Wavenumber (cm –1)
H NMR 300 MHz

5 4 3 2 ppm

7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 ppm

13
C/DEPT NMR 75.5 MHz

140 130 120 110 100 90 80 70 60 50 40 ppm

 Silverstein c08.tex V3 - 06/12/2014 7:53 P.M. Page 376

376 CHAPTER 8 Assigned Problems Problem 8.12

MASS
163
% of Base Peak

100

50 178
77 91 135

50 100 150
m/z
IR
100
%Transmittance

50

748
1149
1203
1458
2870
2962
3572

4000 3000 2000 1000

1
Wavenumber (cm –1)
H NMR 300 MHz

2150 2100 Hz 1000 950 Hz 450 400 Hz

7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 ppm

13
C/DEPT NMR 75.5 MHz

150 140 130 120 110 100 90 80 70 60 50 40 30 20 ppm

 Silverstein c08.tex V3 - 06/12/2014 7:53 P.M. Page 377

Problem 8.13 ASSIGNED PROBLEMS 377

MASS
106
78
% of Base Peak

100 121

51
50

50 60 70 80 90 100 110 120

m/z
IR
100
%Transmittance

50
3363

3047

1689

1419
1273

957

702
4000 3000 2000 1000
1 Wavenumber (cm –1)
H NMR 300 MHz

2720 2700 Hz 2600 2580 Hz 2440 2420 Hz 2200 2180 Hz

9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 ppm

13
C/DEPT NMR 75.5 MHz

190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 ppm
 Silverstein c08.tex V3 - 06/12/2014 7:53 P.M. Page 378

378 CHAPTER 8 Assigned Problems Problem 8.14

MASS
CI Reagent gas methane
% of Base Peak

× 20
43 159
100 100
85
57 103 158
50 50
187

50 100 150 150 m/z

m/z
IR
100
%Transmittance

50
2962

1720
1651

1319

1149
1034
4000 3000 2000 1000
1
Wavenumber (cm –1)
H NMR 300 MHz

3.5 3.0 2.5 2.0 1.5 1.0 ppm

13
C/DEPT NMR 75.5 MHz

200 180 160 140 120 100 80 60 40 ppm

 Silverstein c08.tex V3 - 06/12/2014 7:53 P.M. Page 379

Problem 8.15 ASSIGNED PROBLEMS 379

MASS
× 20
183 185
% of Base Peak

264
100 262
200 224 226 260
198
75 155 157
50

100 150 200 250

IR m/z

100
%Transmittance

50
3356

3089
3059
2962

1685
1585
1485
1396

1223
1068
995

810

617
4000 3000 2000 1000
1 Wavenumber (cm –1 )
H NMR 300 MHz

7.9 7.8 7.7 7.6 ppm 3.6 3.4 3.2 3.0 2.8 2.6 2.4 ppm

13
C/DEPT NMR 75.5 MHz

190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 ppm
 Silverstein c08.tex V3 - 06/12/2014 7:53 P.M. Page 380

380 CHAPTER 8 Assigned Problems Problem 8.16

MASS 100
CI Reagent gas methane
% of Base Peak

100 55 147

74
50 69
83 128
50
175 187

50 100 150 150 200

m/z
m/z
IR
100
%Transmittance

50
3039
2978

2669

1709

1466
1419
1277
1238

930
4000 3000 2000 1000
1 Wavenumber (cm–1)
H NMR 300 MHz

×64

12 11 ppm 2.6 2.4 2.2 2.0 1.8 1.6 1.4 1.2 ppm

13
C/DEPT NMR 75.5 MHz

180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 ppm
 Silverstein c08.tex V3 - 06/12/2014 7:53 P.M. Page 381

Problem 8.17 ASSIGNED PROBLEMS 381

MASS

91
% of Base Peak CI Reagent gas methane

92

93
100

66
100
50
51
50

50 60 70 80 90 80 90
m/z m/z
IR
100

90
%Transmittance

80

725
802
1065
1342
1720
2962
3055

4000 3000 2000 1000

Wavenumber (cm–1)
1
H NMR 300 MHz

2050 2040 Hz 1090 1080 Hz 615 610 605 Hz

7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 ppm
13
C/DEPT NMR 75.5 MHz

140 130 120 110 100 90 80 70 60 50 ppm

 Silverstein c08.tex V3 - 06/12/2014 7:53 P.M. Page 382

382 CHAPTER 8 Assigned Problems Problem 8.18

MASS M
156
% of Base Peak

100
63 M+2
158
50
98 121

50 60 70 80 90 100 110 120 130 140 150 160

m/z
IR
100

586
%Transmittance

2900

50

933
802
1041
1234
1473
4000 3000 2000 1000
Wavenumber (cm–1)
1
H NMR 600 MHz

6.85 6.80 6.75 6.70 6.65 ppm 6.00 5.95 ppm

1313
C/DEPT
C/DEPTNMR
NMR600 MHz
150.9 MHz

155 150 145 140 135 130 125 120 115 110 105 ppm
 Silverstein c08.tex V3 - 06/12/2014 7:53 P.M. Page 383

Problem 8.19A ASSIGNED PROBLEMS 383

MASS
55
42
% of Base Peak

100

84
50 114
70

40 50 60 70 80 90 100 110
m/z
IR
100
%Transmittance

50

571
856
1057
1165
1442
1728
2931

4000 3000 2000 1000

1 Wavenumber (cm–1)
H NMR 300 MHz

4.0 3.5 3.0 2.5 2.0 1.5 ppm

13
C/DEPT NMR 75.5 MHz

170 160 150 140 130 120 110 100 90 80 70 60 50 40 ppm

 Silverstein c08.tex V3 - 06/12/2014 7:53 P.M. Page 384

384 CHAPTER 8 Assigned Problems Problem 8.19B

ppm 4.5 4.0 3.5 3.0 2.5 2.0 1.5 ppm COSY 300 MHz

1.5 1.5

2.0 2.0

2.5 2.5
F1
3.0 3.0

3.5 3.5

4.0 4.0

F2 HETCOR 75.5 MHz

ppm

1.5 1.5

2.0 2.0

2.5 2.5
F1
3.0 3.0

3.5 3.5

4.0 4.0

4.5 4.5
65 60 55 50 45 40 35 30 25 ppm
F2
 Silverstein c08.tex V3 - 06/12/2014 7:53 P.M. Page 385

Problem 8.20A ASSIGNED PROBLEMS 385

MASS
CI Reagent gas methane
% of Base Peak

55 × 10 137
69
100 120
82 90 118 5
50 92 139

50 m/z 100 130 140 150

m/z
IR
100
%Transmittance

50
3332

2939
2862

1458

1057

725
648
4000 3000 2000 1000
1 Wavenumber (cm–1)
H NMR 600 MHz

3.6 3.4 3.2 3.0 2.8 2.6 2.4 2.2 2.0 1.8 1.6 1.4 ppm
1313
C/DEPT C/DEPTNMR
NMR600 MHz
150.9 MHz

60 55 50 45 40 35 30 25 ppm
 Silverstein c08.tex V3 - 06/12/2014 7:53 P.M. Page 386

386 CHAPTER 8 Assigned Problems Problem 8.20B

ppm 3.5 3.0 2.5 2.0 1.5 ppm COSY 600 MHz

1.5 1.5

2.0 2.0

F1 2.5 2.5

3.0 3.0

3.5 3.5

F2 HMQC 600 MHz

ppm

25 25

30 30

35 35

40 40
F1
45 ppm 45

50 32 50

55 55

60 33 60
2.0 1.8 1.6 1.4 ppm

3.5 3.0 2.5 2.0 1.5 ppm

F2
 Silverstein c08.tex V3 - 06/12/2014 7:53 P.M. Page 387

Problem 8.21A ASSIGNED PROBLEMS 387

MASS
95
% of Base Peak

100

45 67 69
50 55 110 128
81 113

50 60 70 80 90 100 110 120 130

m/z
IR
100
%Transmittance

50

825
1041
1126
1377
1450
2924
2966
3344

4000 3000 2000 1000

1
Wavenumber (cm–1)
H NMR 300 MHz

1540 Hz 1140 Hz 500 480 Hz 440 Hz

5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 ppm

13
C/DEPT NMR 75.5 MHz

130 120 110 100 90 80 70 60 50 40 30 20 ppm

 Silverstein c08.tex V3 - 06/12/2014 7:53 P.M. Page 388

388 CHAPTER 8 Assigned Problems Problem 8.21B

ppm 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 ppm COSY 300 MHz
1.0 1.0

1.5 1.5

2.0 2.0

2.5 2.5

F1 3.0 3.0

3.5 3.5

4.0 4.0

4.5 4.5

5.0 5.0

F2 HETCOR 75.5 MHz

ppm
1.0

1.5

2.0

2.5

3.0
F1
3.5

4.0

4.5

5.0

5.5
120 100 80 60 40 20 ppm
F2
 Silverstein c08.tex V3 - 06/12/2014 7:53 P.M. Page 389

Problem 8.22A ASSIGNED PROBLEMS 389

MASS
88
CI Reagent gas methane
% of Base Peak

100

225
223
69 100
50

253
251
179

263
265
143 177
159 194
50

0
50 100 m/z 150 230 240 250 260
m/z
IR
100
%Transmittance

50

1034
1188
1458
1736
2870
2939

4000 3000 2000 1000

1 Wavenumber (cm–1)
H NMR 300 MHz

4.0 3.5 3.0 2.5 2.0 1.5 ppm

13
C/DEPT NMR 75.5 MHz

170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 ppm

 Silverstein c08.tex V3 - 06/12/2014 7:53 P.M. Page 390

390 CHAPTER 8 Assigned Problems Problem 8.22B

ppm 4.0 3.5 3.0 2.5 2.0 1.5 1.0 ppm COSY 300 MHz
1.0 1.0

1.5 1.5

2.0 2.0

F1 2.5 2.5

3.0 3.0

3.5 3.5

4.0 4.0

F2 HETCOR 75.5 MHz

ppm

1.0 1.0

1.5 1.5

2.0 2.0

F1 2.5 2.5

3.0 3.0

3.5 3.5

4.0 4.0

60 55 50 45 40 35 30 25 20 15 ppm
F2
 Silverstein c08.tex V3 - 06/12/2014 7:53 P.M. Page 391

Problem 8.23A ASSIGNED PROBLEMS 391

MASS
134
% of Base Peak

100
41
94
119
50 65 91
77 105

40 50 60 70 80 90 100 110 120 130

m/z
IR
100
%Transmittance

50

690
752
1242
1496
1601
2866
2916
3032
3066

4000 3000 2000 1000

1 Wavenumber (cm–1)
H NMR 600 MHz

3680 3660 Hz 3300 3280 Hz 3220 3200 Hz 2760 2740 Hz

7.4 7.2 7.0 6.8 6.6 6.4 6.2 6.0 5.8 5.6 5.4 5.2 5.0 4.8 ppm
13
C/DEPT NMR 150.9 MHz

160 150 140 130 120 110 100 90 80 70 ppm

 Silverstein c08.tex V3 - 06/12/2014 7:53 P.M. Page 392

392 CHAPTER 8 Assigned Problems Problem 8.23B

ppm 7.5 7.0 6.5 6.0 5.5 5.0 4.5 ppm COSY 600 MHz

4.5 4.5

5.0 5.0

5.5 5.5
F1
6.0 6.0

6.5 6.5

7.0 7.0

F2 HMQC 600 MHz

ppm

70 70

80 80

90 90

100 100

F1 110 110

120 120

130 130

140 140

150 150

7.5 7.0 6.5 6.0 5.5 5.0 4.5 ppm

F2
 Silverstein c08.tex V3 - 06/12/2014 7:53 P.M. Page 393

Problem 8.24A ASSIGNED PROBLEMS 393

MASS
% of Base Peak
× 20
95
100
110 139
50 55 67 154
109 121 136

50 60 70 80 90 100 110 120 130 140 150

m/z
1
H NMR 600 MHz

2400 Hz 1350 Hz 1150 Hz 1050 Hz 950 Hz 750 Hz 550 Hz 500 Hz

In the above insets each tick mark is 10 Hz

4.0 3.5 3.0 2.5 2.0 1.5 ppm

13
13
C/DEPTNMR
C/DEPT NMR150.9
600 MHz
MHz

75 70 65 60 55 50 45 40 35 30 25 20 15 ppm
 Silverstein c08.tex V3 - 06/12/2014 7:53 P.M. Page 394

394 CHAPTER 8 Assigned Problems Problem 8.24B

ppm 4.0 3.5 3.0 2.5 2.0 1.5 1.0 ppm COSY 600 MHz

1.0 1.0

1.5 1.5

2.0 2.0

F1
2.5 2.5

3.0 3.0

3.5 3.5

4.0 4.0

F2 HMQC 600 MHz

ppm

ppm
20 20
15
30 30
20

40 25 40
0.90 0.85 ppm
F1
50 50

60 60

70 70

4.0 3.5 3.0 2.5 2.0 1.5 1.0 ppm

F2
 Silverstein c08.tex V3 - 06/12/2014 7:53 P.M. Page 395

Problem 8.25A ASSIGNED PROBLEMS 395

MASS
85
% of Base Peak

100

50 57 70
114

50 60 70 80 90 100 110
m/z
IR
100

656
2885

1358
1466
%Transmittance

972
50
2970

1180
1774
4000 3000 2000 1000
1 Wavenumber (cm–1)
H NMR 600 MHz

4.0 3.5 3.0 2.5 2.0 1.5 1.0 ppm

13
C/DEPT NMR 150.9 MHz

29 28 p pm

180 160 140 120 100 80 60 40 20 ppm

 Silverstein c08.tex V3 - 06/12/2014 7:53 P.M. Page 396

396 CHAPTER 8 Assigned Problems Problem 8.25B

ppm 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 ppm COSY 600 MHz

1.0 1.0

1.5 1.5

2.0 2.0

F1 2.5 2.5

3.0 3.0

3.5 3.5

4.0 4.0

F2 HMQC 600 MHz

ppm

10 10

20 20

30 30

40 ppm 40

F1 50 50
28

60 60
30
2.5 2.0 1.5 ppm
70 70

80 80

4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 ppm

F2
 Silverstein c08.tex V3 - 06/12/2014 7:53 P.M. Page 397

Problem 8.26A ASSIGNED PROBLEMS 397

MASS
95
81
% of Base Peak

100
41
55 69 108
50 152
137

50 60 70 80 90 100 110 120 130 140 150

m/z
IR
100

1273

748
%Transmittance

1450

1041
50
2954

1743
4000 3000 2000 1000
1 Wavenumber (cm–1)
H NMR 600 MHz

2.4 2.3 2.2 2.1 2.0 1.9 1.8 1.7 1.6 1.5 1.4 1.3 1.2 1.1 1.0 0.9 ppm
13
13
C/DEPTNMR
C/DEPT NMR150.9
600 MHz
MHz

220 ppm 55 50 45 40 35 30 25 20 15 ppm

 Silverstein c08.tex V3 - 06/12/2014 7:53 P.M. Page 398

398 CHAPTER 8 Assigned Problems Problem 8.26B

ppm 2.4 2.2 2.0 1.8 1.6 1.4 1.2 1.0 0.8 0.6 ppm COSY 600 MHz

0.6 0.6

0.8 0.8

1.0 1.0

1.2 1.2

1.4 1.4
F1
1.6 1.6

1.8 1.8

2.0 2.0

2.2 2.2

2.4 2.4

F2 HMQC 600 MHz

ppm

10 10

20 20

30 30
F1

40 40

50 50

2.4 2.2 2.0 1.8 1.6 1.4 1.2 1.0 0.8 0.6 ppm
F2
 Silverstein c08.tex V3 - 06/12/2014 7:53 P.M. Page 399

Problem 8.26C ASSIGNED PROBLEMS 399

INADEQUATE 150.9 MHz

Hz

–20000 –20000

–15000 –15000

–10000 –10000

–5000 –5000

F1 0 0

5000 5000

10000 10000
220 200 180 160 140 120 100 80 60 40 20 ppm
F2

Hz

–25000 –25000

–24000 –24000

–23000 –23000

–22000 –22000
F1
–21000 –21000

–20000 –20000

–19000 –19000

–18000 –18000

–17000 –17000
65 60 55 50 45 40 35 30 25 20 15 10 5 ppm
F2
 Silverstein c08.tex V3 - 06/12/2014 7:53 P.M. Page 400

400 CHAPTER 8 Assigned Problems Problem 8.27A

MASS
% of Base Peak

43 × 30

100 70

50 55 130
115

40 50 60 70 80 90 100 110 120 130

m/z
IR
100

1466
%Transmittance

2877

1373

1041
2962

50

1242
1743
4000 3000 2000 1000
1 Wavenumber (cm–1)
H NMR 600 MHz

2350 Hz 2300 Hz 1000 Hz 850 Hz 700 Hz 550 Hz

In the above insets, each tick mark is 10 Hz

3.5 3.0 2.5 2.0 1.5 ppm

13
C/DEPT NMR 150.9 MHz

170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 ppm

 Silverstein c08.tex V3 - 06/12/2014 7:53 P.M. Page 401

Problem 8.27B ASSIGNED PROBLEMS 401

ppm 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 ppm COSY 600 MHz

1.0 1.0

1.5 1.5

2.0 2.0
F1
2.5 2.5

3.0 3.0

3.5 3.5

4.0 4.0

F2 HMQC 600 MHz

ppm

10 10
ppm
10
20 20

15
30 30

0.95 0.90 0.85 ppm

40 40
F1
50 50

60 60

70 70

4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 ppm

F2
 Silverstein c08.tex V3 - 06/12/2014 7:53 P.M. Page 402

402 CHAPTER 8 Assigned Problems Problem 8.28A

MASS
111 m/z %M
151 (M-1) 37.5
% of Base Peak

100 152 (M) 100.0

153 (M+1) 12.7
154 (M+2) 5.2 152
50
69 83

50 60 70 80 90 100 110 120 130 140 150

m/z
IR
100 3008
3093
%Transmittance

1057
50

957

725
1419

1234
1651
4000 3000 2000 1000
1 Wavenumber (cm–1)
H NMR 600 MHz

4680 Hz 4560 Hz 4260 Hz 1520 Hz 740 720 Hz 600 Hz

7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 ppm
13
C/DEPT NMR 150.9 MHz

180 160 140 120 100 80 60 40 20 ppm

 Silverstein c08.tex V3 - 06/12/2014 7:53 P.M. Page 403

Problem 8.28B ASSIGNED PROBLEMS 403

ppm 8 7 6 5 4 3 2 1 ppm COSY 600 MHz

1 1

2 2

3 3

4 4
F1

5 5

6 6

7 7

8 8
F2 HMQC 600 MHz
ppm

20 20

40 40

60 60

F1
80 80

100 100

120 120

8 7 6 5 4 3 2 1 ppm
F2
 Silverstein c08.tex V3 - 06/12/2014 7:53 P.M. Page 404

404 CHAPTER 8 Assigned Problems Problem 8.29A

MASS

121
% of Base Peak

164
100

103
77

91

136
50

149
65
60 70 80 90 100 110 120 130 140 150 160
m/z
IR
100

2870

663
%Transmittance

949

764
3201

2962

1412
1550
50

1265
1473
1612
4000 3000 2000 1000
Wavenumber (cm–1)
1
H NMR 600 MHz

3940 3920 Hz 3880 3860 Hz 3720 Hz 1280 Hz 320 300 Hz

9 8 7 6 5 4 3 2 1 ppm
13
C/DEPT NMR 150.9 MHz

171.5 171.0 ppm

170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 ppm

 Silverstein c08.tex V3 - 06/12/2014 7:53 P.M. Page 405

Problem 8.29B ASSIGNED PROBLEMS 405

ppm 7 6 5 4 3 2 1 ppm COSY 600 MHz

ppm 6.8 6.6 6.4 6.2 ppm

1 1

6.2
2 2
6.4
3 3
6.6
F1
4 4

5 5

6 6

7 7

F2 HMQC 600 MHz

ppm

20 20

40 ppm 40

125
60 60
130

F1 80 135
80

140
100 6.8 6.6 6.4 6.2 ppm
100

120 120

140 140

7 6 5 4 3 2 1 ppm
F2
 Silverstein c08.tex V3 - 06/12/2014 7:53 P.M. Page 406

406 CHAPTER 8 Assigned Problems Problem 8.29C

INADEQUATE 150.9 MHz

Hz

–20000 –20000

–15000 –15000

–10000 –10000

–5000 –5000

F1 0 0

5000 5000

10000 10000

15000 15000

20000 20000

160 140 120 100 80 60 40 20 ppm

F2
Hz

0 0

5000 5000
F1
10000 10000

15000 15000

20000 20000

175 170 165 160 155 150 145 140 135 130 125 120 115 ppm
F2
 Silverstein c08.tex V3 - 06/12/2014 7:53 P.M. Page 407

Problem 8.30A ASSIGNED PROBLEMS 407

MASS 123
% of Base Peak
100 83

151 232
50 41 55
69 95 110 230

50 100 150 200

m/z
IR
100
90

1219

1034
1365
1442
1473
%Transmittance

80
2954

70

1751
4000 3000 2000 1000
Wavenumber (cm–1)
1
H NMR 600 MHz

2800 Hz 1350 1300 1250 1200 1150 1100 1050 1000 950 900 850 Hz

4.5 4.0 3.5 3.0 2.5 2.0 1.5 ppm

13
C/DEPT NMR 150.9 MHz

20.0 19.9 19.8 p pm

200 180 160 140 120 100 80 60 40 20 ppm

 Silverstein c08.tex V3 - 06/12/2014 7:53 P.M. Page 408

408 CHAPTER 8 Assigned Problems Problem 8.30B

4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 COSY 600 MHz
ppm 5.0 ppm

1.0 1.0

1.5 1.5

2.0 2.0

2.5 2.5
F1
3.0 3.0

3.5 3.5

4.0 4.0

4.5 4.5

F2 HMQC 600 MHz

ppm

10 10

20 20

30 30
F1

40 40

50 50

60 60

5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 ppm
F2
 Silverstein c08.tex V3 - 06/12/2014 7:53 P.M. Page 409

Problem 8.30C ASSIGNED PROBLEMS 409

INADEQUATE 150.9 MHz

Hz

–20000 –20000

–15000 –15000

–10000 –10000
F1
–5000 –5000

0 0

5000 5000

200 180 160 140 120 100 80 60 40 20 ppm

F2

Hz

–25000 –25000

–24000 –24000

–23000 –23000

–22000 –22000
F1
–21000 –21000

–20000 –20000

–19000 –19000

–18000 –18000

–17000 –17000
60 55 50 45 40 35 30 25 20 15 10 5 ppm
F2
 Silverstein c08.tex V3 - 06/12/2014 7:53 P.M. Page 410

410 CHAPTER 8 Assigned Problems Problem 8.31A

MASS
82
67 CI Reagent gas methane
% of Base Peak

100 155
54 FM (found) = 155.0711 by CI
100
50
50 183 195
110

50 100 160 170 180 190

m/z m/z
IR
100

1450
%Transmittance

2862

50
2947

1859

1219

903
1790
4000 3000 2000 1000
1 Wavenumber (cm–1)
H NMR 600 MHz

3.3 3.2 3.1 3.0 2.9 2.8 2.7 2.6 2.5 2.4 2.3 2.2 2.1 2.0 1.9 1.8 1.7 1.6 1.5 1.4 ppm
13
C/DEPT NMR 150.9 MHz

170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 ppm

 Silverstein c08.tex V3 - 06/12/2014 7:53 P.M. Page 411

Problem 8.31B ASSIGNED PROBLEMS 411

ppm 3.4 3.2 3.0 2.8 2.6 2.4 2.2 2.0 1.8 1.6 1.4 1.2 ppm COSY 600 MHz

1.5 1.5

2.0 2.0
F1

2.5 2.5

3.0 3.0

F2 HMQC 600 MHz

ppm

25 25

30 30

F1
35 35

40 40

45 45
3.4 3.2 3.0 2.8 2.6 2.4 2.2 2.0 1.8 1.6 1.4 1.2 ppm
F2
 Silverstein c08.tex V3 - 06/12/2014 7:53 P.M. Page 412

412 CHAPTER 8 Assigned Problems Problem 8.32A

MASS
104
% of Base Peak

100
121

50 77 91 131
65 164
146

50 60 70 80 90 100 110 120 130 140 150 160

m/z
IR
100

1720
%Transmittance

50
2831

1466

972
1350
2939

748
3402

1088
4000 3000 2000 1000
1 Wavenumber (cm–1)
H NMR 600 MHz

4400 4350 Hz 2750 2700 Hz 2000 1950 Hz 1650 1600 Hz

7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 ppm
13
C/DEPT NMR 150.9 MHz

140 130 120 110 100 90 80 70 60 50 40 ppm

 Silverstein c08.tex V3 - 06/12/2014 7:53 P.M. Page 413

Problem 8.32B ASSIGNED PROBLEMS 413

ppm 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 ppm COSY 600 MHz

3.0 3.0

3.5 3.5

4.0 4.0

4.5 4.5
F1 5.0 5.0

5.5 5.5

6.0 6.0

6.5 6.5

7.0 7.0

F2 HMQC 600 MHz

ppm

40 ppm 40

126

60 60
128

130
7.4 7.3 7.2 ppm
80 80
F1

100 100

120 120

7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 ppm
F2
 Silverstein c08.tex V3 - 06/12/2014 7:53 P.M. Page 414

414 CHAPTER 8 Assigned Problems Problem 8.32C

HMBC 600 MHz

7.5 7.4 7.3 7.2 7.1 ppm 4.5 4.0 3.5 3.0 ppm
ppm ppm

40 40

50 50

60 60

70 70

80 80

F1
90 90

ppm ppm

125 125

130 130

135 135

140 140

145 145
7.5 7.4 7.3 7.2 7.1 ppm 4.5 4.0 3.5 3.0 ppm

F2
 Silverstein c08.tex V3 - 06/12/2014 7:53 P.M. Page 415

Problem 8.33A ASSIGNED PROBLEMS 415

MASS
% of Base Peak

43 × 30

100 131
85 109
95 182 185
50 200

50 100 150 200

m/z
IR
100
90
%Transmittance

80
70

887
1034
1188
1373
1458
1728
2978
3518

4000 3000 2000 1000

1 Wavenumber (cm–1)
H NMR 600 MHz

1260 1240 Hz 780 760 740 Hz

4.5 4.0 3.5 3.0 2.5 2.0 1.5 ppm

13
13
C/DEPT
C/DEPT NMR
NMR 150.9 MHz
600 MHz

170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 ppm

 Silverstein c08.tex V3 - 06/12/2014 7:53 P.M. Page 416

416 CHAPTER 8 Assigned Problems Problem 8.33B

ppm 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 ppm COSY 600 MHz

1.5 1.5

2.0 2.0

2.5 2.5

F1 3.0 3.0

3.5 3.5

4.0 4.0

4.5 4.5

F2 HMQC 600 MHz

ppm

20 20

40 40

60 60

80 80

F1 100 100

120 120

140 140

160 160

5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 ppm

F2
 Silverstein c08.tex V3 - 06/12/2014 7:53 P.M. Page 417

Problem 8.33C ASSIGNED PROBLEMS 417

HMBC 600 MHz

ppm

20

30

40

50

60

F1 70

80

90

100

110

120

130

140

150

160

170

5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 ppm

F2
 Silverstein c08.tex V3 - 06/12/2014 7:53 P.M. Page 418

418 CHAPTER 8 Assigned Problems Problem 8.34A

MASS
121
% of Base Peak

100
136

50
65 93
149 178

50 100 150
m/z
IR
100
%Transmittance

50
3325

2962

1658
1597

1281
1211
1173

841
4000 3000 2000 1000
1 Wavenumber (cm–1)
H NMR 600 MHz

8.0 7.8 7.6 7.4 7.2 7.0 6.8 ppm 3.0 2.5 2.0 1.5 ppm
13
C/DEPT NMR 150.9 MHz

200 180 160 140 120 100 80 60 40 ppm

 Silverstein c08.tex V3 - 06/12/2014 7:53 P.M. Page 419

Problem 8.34B ASSIGNED PROBLEMS 419

ppm 8 7 6 5 4 3 2 1 ppm COSY 600 MHz

1 1

2 2

3 3

4 4
F1
5 5

6 6

7 7

8 8

F2 HMQC 600 MHz

ppm

20 20

40 40

60 60

F1 80 80

100 100

120 120

8 7 6 5 4 3 2 1 ppm
F2
 Silverstein c08.tex V3 - 06/12/2014 7:53 P.M. Page 420

420 CHAPTER 8 Assigned Problems Problem 8.34C

HMBC 600 MHz

8.0 7.5 7.0 ppm 3.0 2.5 2.0 1.5 1.0 ppm
ppm ppm

15 15

20 20

25 25

30 30

35 35

F1
ppm ppm
120 120

130 130

140 140

150 150

160 160

170 170

180 180

190 190

200 200

210 210
8.0 7.5 7.0 ppm 3.0 2.5 2.0 1.5 1.0 ppm

F2
 Silverstein c08.tex V3 - 06/12/2014 7:53 P.M. Page 421

Problem 8.35A ASSIGNED PROBLEMS 421

MASS
68
% of Base Peak

100
108
53
50
79 93 125 153
151 168

0
50 100 150
m/z
IR
100
%Transmittance

50

887
933
1242
1412
1442
1705
2669
2893
2962
3078

3000 2000 1000

1 Wavenumber (cm–1)
H NMR 600 MHz

2900 2850 Hz 1600 1550 Hz 1200 1150 1100 1050 Hz

×64

12 ppm 4.5 4.0 3.5 3.0 2.5 2.0 1.5 ppm

13
C/DEPT NMR 150.9 MHz

180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 ppm
 Silverstein c08.tex V3 - 06/12/2014 7:53 P.M. Page 422

422 CHAPTER 8 Assigned Problems Problem 8.35B

ppm 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 ppm COSY 600 MHz

1.5 1.5

2.0 2.0

2.5 2.5

F1 3.0 3.0

3.5 3.5

4.0 4.0

4.5 4.5

5.0 5.0

F2 HMQC 600 MHz

ppm

20 20

40 40

60 60

80 ppm 80

100 20 100
F1
120 30 120

140 140
40

160 160
50
180 180
3.0 2.5 2.0 1.5 pp m

5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 ppm

F2
 Silverstein c08.tex V3 - 06/12/2014 7:53 P.M. Page 423

Problem 8.35C ASSIGNED PROBLEMS 423

HMBC 600 MHz

ppm 5.0 4.8 ppm 2.6 2.4 2.2 2.0 1.8 1.6 1.4 1.2 ppm

20

25

30

35
F1

40

45

50

ppm

150

5.0 4.8 ppm 2.6 2.4 2.2 2.0 1.8 1.6 1.4 1.2 ppm
F2
 Silverstein c08.tex V3 - 06/12/2014 7:53 P.M. Page 424

424 CHAPTER 8 Assigned Problems Problem 8.36A

MASS 105
% of Base Peak

100

50 91
77 122 151
53 65 133 166
148

50 60 70 80 90 100 110 120 130 140 150 160

m/z
IR
100

787
%Transmittance

1365
50

1466
3332

1049
2916

4000 3000 2000 1000

1 Wavenumber (cm–1)
H NMR 600 MHz

2180 2160 Hz 1440 1420 1400 1380 1360 1340 1320 1300 1280 1260 1240 1220 Hz

5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 ppm
13
C/DEPT NMR 150.9 MHz

140 130 120 110 100 90 80 70 60 50 40 30 ppm

 Silverstein c08.tex V3 - 06/12/2014 7:53 P.M. Page 425

Problem 8.36B ASSIGNED PROBLEMS 425

ppm 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 ppm COSY 600 MHz

1.0 1.0

1.5 1.5

2.0 2.0

2.5 2.5

F1 3.0 3.0

3.5 3.5

4.0 4.0

4.5 4.5

5.0 5.0

5.5 5.5
F2 HMQC 600 MHz
ppm

20 20

40 40

60 60
ppm
F1
30
80 80

35
100 100
40

120 2.5 2.4 2.3 2.2 2.1 ppm 120

5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 ppm
F2
 Silverstein c08.tex V3 - 06/12/2014 7:53 P.M. Page 426

426 CHAPTER 8 Assigned Problems Problem 8.36C

INADEQUATE 150.9 MHz

Hz
–15000 –15000

–10000 –10000

–5000 –5000

F1 0 0

5000 5000

10000 10000

15000 15000

140 130 120 110 100 90 80 70 60 50 40 30 20 ppm

F2

Hz

–16000 –16000

–14000 –14000

–12000 –12000

–10000 –10000

–8000 –8000

–6000 –6000
F1
–4000 –4000

–2000 –2000

0 0

2000 2000

4000 4000

45 40 35 30 25 20 ppm
F2
 Silverstein c08.tex V3 - 06/12/2014 7:53 P.M. Page 427

Problem 8.37A ASSIGNED PROBLEMS 427

OH
7 11
ES MASS -O 3 S O 5
6 8 10 O
9
4 12
3
416
N NH HN 13 NH
100
% of Base Peak

H3 C 2 14
15
1 NH O
C15H21N5O7S 336
50 Mol. Wt.: 415
194 274
136 176 224 293 373 399
0
150 200 250 300 350 400 450
m/z
1
H NMR 600 MHz in D2O

3460 3440 Hz 2800 2780 Hz 2720 Hz 2280 2260 Hz

2220 2200 Hz 2160 2140 Hz 1920 1900 Hz 1440 1420 Hz

1260 1240 Hz 1080 1060 Hz 920 900 880 860 Hz 560 550 540 530 Hz

HDO

5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 ppm
 Silverstein c08.tex V3 - 06/12/2014 7:53 P.M. Page 428

428 CHAPTER 8 Assigned Problems Problem 8.37B

ppm 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 ppm COSY 600 MHz

1.0 1.0

1.5 1.5

2.0 2.0

2.5 2.5

3.0 3.0
F1
3.5 3.5

4.0 4.0

4.5 4.5

5.0 5.0

5.5 5.5

COSY 600 MHz

ppm

1.5 1.5

2.0 2.0

F1 2.5 2.5

3.0 3.0

3.5 3.5

4.0 4.0
4.0 3.5 3.0 2.5 2.0 1.5 1.0 ppm
F2
 Silverstein c08.tex V3 - 06/12/2014 7:53 P.M. Page 429

Problem 8.37C ASSIGNED PROBLEMS 429

13
C NMR 150.9 MHz

156 155 154 153 ppm

q qqq s s s s s ds s d d t

160 150 140 130 120 110 100 90 80 70 60 50 40 30 ppm

HMQC 600 MHz

ppm

10 OH
7 11
–O3SO 5
6 8 10 O
9
4 12
20 3
N NH HN 13 NH
H3 C 2 14
15
30 1 NH O
C15H21N5O7S
Mol. Wt.: 415
40

50

F1
60
ppm

70
45

80 50

90 55

60
100 3.8 3.7 3.6 3.5 3.4 3.3 3.2 3.1 ppm

6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 ppm
F2
 Silverstein c08.tex V3 - 06/12/2014 7:53 P.M. Page 430

430 CHAPTER 8 Assigned Problems Problem 8.37D

HMBC 600 MHz

ppm
10

20

30

40

50
F1
60

70

80

90

100

ppm

155

160

165

170
6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 ppm
F2
 Silverstein c08.tex V3 - 06/12/2014 7:53 P.M. Page 431

Problem 8.38A ASSIGNED PROBLEMS 431

 Silverstein c08.tex V3 - 06/12/2014 7:53 P.M. Page 432

432 CHAPTER 8 Assigned Problems Problem 8.38B

 Silverstein c08.tex V3 - 06/12/2014 7:53 P.M. Page 433

Problem 8.38C ASSIGNED PROBLEMS 433

 Silverstein c08.tex V3 - 06/12/2014 7:53 P.M. Page 434

434 CHAPTER 8 Assigned Problems Problem 8.38D

ppm 9 8 7 6 5 4 3 2 ppm ROESY 600 MHz

2 2

3 3

4 4

F1 5 5

6 6

7 7

8 8

9 9

F2
COSY 600 MHz TOCSY 600 MHz ROESY 600 MHz

ppm

1.5

2.0

2.5

3.0
F1
3.5

4.0

4.5

5.0

9.0 8.5 8.0 7.5 ppm 8.5 8.0 7.5 ppm 8.5 8.0 7.5 ppm
F2 F2 F2
 Silverstein c08.tex V3 - 06/12/2014 7:53 P.M. Page 435

Problem 8.38E ASSIGNED PROBLEMS 435

 Silverstein c08.tex V3 - 06/12/2014 7:53 P.M. Page 436

436 CHAPTER 8 Assigned Problems Problem 8.39A

MASS
161
% of Base Peak

100 121

50 92 189
65 77 133

50 100 150
m/z
IR
100

1334
3240

648
%Transmittance

3093

1466
90

1682

756
80

1620
4000 3000 2000 1000
1 Wavenumber (cm–1)
H NMR 600 MHz
O O
9 10
8 3
4 2 H

7 5 1
6
O NH2

10.0 9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 ppm
13
C/DEPT NMR 600 MHz

190 180 170 160 150 140 130 120 110 ppm
 Silverstein c08.tex V3 - 06/12/2014 7:53 P.M. Page 437

Problem 8.39B ASSIGNED PROBLEMS 437

ppm 10 9 8 7 6 ppm COSY 600 MHz

O O
6.0 6.0
H
6.5 6.5

7.0 O NH2 7.0

7.5 7.5
F1 8.0 8.0

8.5 8.5

9.0 9.0

9.5 9.5

10.0 10.0

F2 HMQC 600 MHz

ppm

100 100

110 110

120 120

130 130

140 140
F1
150 150

160 160

170 170

180 180

190 190

10 9 8 7 6 ppm
F2
 Silverstein c08.tex V3 - 06/12/2014 7:53 P.M. Page 438

438 CHAPTER 8 Assigned Problems Problem 8.39C

HMBC 600 MHz

ppm

100

110 O O

120 H

130 O NH2
F1
140

150

160

170

180

190

10.5 10.0 9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 ppm
F2
1
H- 15N HSQC 600 MHz

ppm

80
F1
90

100
10.5 10.0 9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 ppm
F2
 Silverstein c08.tex V3 - 06/12/2014 7:53 P.M. Page 439

Problem 8.40A ASSIGNED PROBLEMS 439

7 4
MASS 6 5
% of Base Peak
8 3 165
100 9 2
14 H
11 13 194
10 12 1
50 O
82
115 139

50 100 150
m/z
IR
100
3047

2723

1111
90
%Transmittance

1404
80

1604

733
70

1689
4000 3000 2000 1000
1 Wavenumber (cm–1)
H NMR 600 MHz

4850 4800 4750 4700 4650 4600 4550 4500 4450 4400 Hz

10.0 9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 ppm
13
13
C/DEPT NMR
C/DEPT NMR 150.9
600 MHz
MHz

190 180 170 160 150 140 130 ppm 40 35 ppm

 Silverstein c08.tex V3 - 06/12/2014 7:53 P.M. Page 440

440 CHAPTER 8 Assigned Problems Problem 8.40B

ppm 10 9 8 7 6 5 4 ppm COSY 600 MHz

4 4

5 H 5

6 O 6

F1
7 7

8 8

9 9

10 10

F2 HMQC 600 MHz

ppm

20 20
ppm

40 120 40

60 60
125

80 80
130
100 100
F1 8.2 8.1 8.0 7.9 7.8 7.7 7.6 7.5 7.4 ppm
120 120

140 140

160 160

180 180

10 9 8 7 6 5 4 ppm
F2
 Silverstein c08.tex V3 - 06/12/2014 7:53 P.M. Page 441

Problem 8.40C ASSIGNED PROBLEMS 441

HMBC 600 MHz

ppm 10.1 ppm 8.0 7.8 7.6 7.4 ppm 4.0 ppm

36

38

ppm

H
122
O
124

126
F1
128

130

ppm
135

140

145

ppm
190

195
10.2 10.0 ppm 8.0 7.8 7.6 7.4 ppm 4.0 ppm
F2
 Silverstein c08.tex V3 - 06/12/2014 7:53 P.M. Page 442

442 CHAPTER 8 Assigned Problems Problem 8.41A

MASS 222
% of Base Peak

100
120 194
92
50
63 76 165

50 100 150 200

m/z
IR
100
3070

856
%Transmittance

1126

679
50

1466

764
1381
1643
4000 3000 2000 1000
Wavenumber (cm–1) O
1 5
H NMR 600 MHz 6
4 7 8
11
3 10 12
1 O 9
2
13

8.3 8.2 8.1 8.0 7.9 7.8 7.7 7.6 7.5 7.4 7.3 7.2 7.1 7.0 6.9 ppm
13
C/DEPT NMR 150.9 MHz

185 180 175 170 165 160 155 150 145 140 135 130 125 120 115 110 ppm
 Silverstein c08.tex V3 - 06/12/2014 7:53 P.M. Page 443

Problem 8.41B ASSIGNED PROBLEMS 443

ppm 8.4 8.2 8.0 7.8 7.6 7.4 7.2 7.0 6.8 ppm COSY 600 MHz

6.8 O 6.8

7.0 7.0
O
7.2 7.2

7.4 7.4
F1
7.6 7.6

7.8 7.8

8.0 8.0

8.2 8.2

F2 HMQC 600 MHz

ppm

110 110

115 115

120 120
F1

125 125

130 130

135 135

8.4 8.2 8.0 7.8 7.6 7.4 7.2 7.0 6.8 ppm
F2
 Silverstein c08.tex V3 - 06/12/2014 7:53 P.M. Page 444

444 CHAPTER 8 Assigned Problems Problem 8.41C

HMBC 600 MHz

ppm

110

ppm

124

125

126

127
O
128
F1
129
O
130

131

132

133

134

ppm

160

170

180

8.4 8.3 8.2 8.1 8.0 7.9 7.8 7.7 7.6 7.5 7.4 7.3 7.2 7.1 7.0 6.9 6.8 6.7 ppm
F2
 Silverstein c08.tex V3 - 06/12/2014 7:53 P.M. Page 445

Problem 8.42A ASSIGNED PROBLEMS 445

MASS 173
% of Base Peak
100 246
91 135
50 55 69 77 231
203
218

50 100 150 200 250

m/z
IR
100

1458
1373
%Transmittance

2870

841
1034
2939

1134
50

1658
1628
1782
4000 3000 2000 1000
Wavenumber (cm–1)
1
H NMR 600 MHz 14
7 CH3 5
8
6 4
9 3 13
O 11 12 CH3
10 2
1
15 CH3 O

4000 3900 3800 Hz 2900 2850 Hz O

1400 1300 1200 1100 1000 900 800 Hz

6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 ppm
 Silverstein c08.tex V3 - 06/12/2014 7:53 P.M. Page 446

446 CHAPTER 8 Assigned Problems Problem 8.42B

ppm 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 ppm COSY 600 MHz

2 2
CH3

3 3
O CH3

F1 CH3 O
4 4
O

5 5

6 6

COSY 600 MHz

ppm

1.2 1.2

1.4 1.4

1.6 1.6

F1 1.8 1.8

2.0 2.0

2.2 2.2

2.4 2.4

2.6 2.6
2.6 2.4 2.2 2.0 1.8 1.6 1.4 1.2 ppm
F2
 Silverstein c08.tex V3 - 06/12/2014 7:53 P.M. Page 447

Problem 8.42C ASSIGNED PROBLEMS 447

13
C/DEPT NMR 150.9 MHz

41.5 41.0 ppm

180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 ppm

HMQC 600 MHz

ppm

CH3
20

O CH3
40
CH3 O
O
60

F1
80

100

120

140

7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 ppm
F2
 Silverstein c08.tex V3 - 06/12/2014 7:53 P.M. Page 448

448 CHAPTER 8 Assigned Problems Problem 8.42D

HMBC 600 MHz

7.0 6.5 6.0 5.5 5.0 ppm 2.4 2.2 2.0 1.8 1.6 1.4 1.2 ppm
ppm

10

20

30

40

50 CH3

60
O CH3
70 CH3 O
O
80
F1
ppm

120

130

140

150

160

170

180

190
7.0 6.5 6.0 5.5 5.0 ppm 2.6 2.4 2.2 2.0 1.8 1.6 1.4 1.2 ppm
F2
 Silverstein c08.tex V3 - 06/12/2014 7:53 P.M. Page 449

Problem 8.43A ASSIGNED PROBLEMS 449

MASS 124
% of Base Peak
100

50 82 94 289
67 140
272

50 100 150 200 250

IR m/z

100
95
2962

1489
3263
%Transmittance

1257

609
90
85

1728

1026
4000 3000 2000 1000
1 Wavenumber (cm–1)
H NMR in D2O 600 MHz

4450 4400 Hz 3000 Hz 2500 Hz 2350 Hz

2250 Hz 1150 Hz 940 920 900 Hz

14
CH3 HDO
N
5
4 6

2 1
3 7
O
8
O C
15
9 CH CH2OH
10
11

13 12

7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 ppm
 Silverstein c08.tex V3 - 06/12/2014 7:53 P.M. Page 450

450 CHAPTER 8 Assigned Problems Problem 8.43B

7 6 5 4 3 2 ppm COSY 600 MHz

ppm

2 2
N CH3

3 3

F1 4 4

O O
5 C 5
CH
CH2OH
6 6

7 7

ppm COSY 600 MHz

1.5 1.5

2.0 2.0

2.5 2.5

3.0 3.0
F1
3.5 3.5

4.0 4.0

4.5 4.5

5.0 5.0

5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 ppm

F2
 Silverstein c08.tex V3 - 06/12/2014 7:53 P.M. Page 451

Problem 8.43C ASSIGNED PROBLEMS 451

13
C/DEPT NMR 150.9 MHz

170 160 150 140 130 120 110 100 90 80 70 60 50 40 ppm

HMQC 600 MHz

ppm

N CH3
30

40

50 O O
C
CH
CH2OH
F1 60

ppm
130

7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 ppm
F2
ppm ppm

62 34

63 35
4.2 4.0 3.8 3.6 ppm 2.4 2.2 2.0 1.8 ppm
 Silverstein c08.tex V3 - 06/12/2014 7:53 P.M. Page 452

452 CHAPTER 8 Assigned Problems Problem 8.43D

HMQC 600 MHz

ppm 7.5 7.4 ppm 5.0 4.8 4.6 4.4 4.2 4.0 ppm 2.5 2.0 1.5 ppm

25

30

35

ppm

55

F1
60

65

ppm

130

135

ppm

175
7.5 7.4 ppm 5.0 4.8 4.6 4.4 4.2 4.0 ppm 2.5 2.0 1.5 ppm
F2
 INDEX

Absorbance (A), 71 Coupling, geminal, 137, 139, 156, 158, Double focusing, 5, 9
Alternating axis of symmetry 160–161, 185, 238 Double quantum filtered 1 H-1 H COSY
(Sn ), 150, 153 Coupling, vicinal, 137, 139, 158, (DQF-COSY), 238
Angular momentum, 126 160–161, 185 Double resonance, 162
Annulenes, 135–136 Coupling, long-range, 139, 140, 162, 241, Downfield and upfield, 133
Atmospheric pressure ionization (API), 6 247, 302, 309 Dynamic nuclear polarization (DNP),
Axis of symmetry (Cn ), 150, 153, Coupling, strong, weak, 140–141, 155, 131, 266
154, 198 156–158
Coupling, virtual, 156–158 Effective frequency (𝜈ef f ), 132
B0 , 127–129 CPD (composite pulse El (electron impact), 3
Base peak, 1 decoupling), 191, 239
Electrical quadrupole moment, 126, 144,
Bending (bonds), 71–75 Cross peaks, 234, 235, 237, 238, 241,
147, 149, 150, 197, 299, 300,
Boltzmann distribution, 127–129, 243, 247, 251, 254
320–324
131, 200, 300 CW (continuous wave), 127
Electron-impact (EI) mode, 3
Broadband decoupling of Cycloidal frequency, 12
Electronegativity, 134, 135, 193, 204,
protons, 191, 239 205, 211
𝛿 scale (chemical shift) 132 (Section 3.4),
192 (Section, 4.2.2), 298 Electrospray ionization (ESI), 6
13
C satellites, 150, 191, 239, 243 Electrostatic repulsion, 7
Carbon-carbon couplings, 191, 249–251 2D NMR 230 (Chapter, 5), 231
1D TOCSY, 257–259 Elimination of water, 22, 23
Carbon, coupling to 1 H, 150, 196 Enantiomers, 151
13 2D TOCSY, 254–257
C-13 C correlations (INADEQUATE), Enantiotopes, 151
Dalton (Da), 1
238, 249–251 Ernst angle, 231
13 Daughter ions, 12
C/12 C ratio, 191 Equivalence, chemical 150 (Section 3.8),
Decoupling of protons 191 (Section,
Center of symmetry (i), 150 200 (Section, 4.5), 241
13 4.2.1)
C-1 H coupling constants, 150, 196
Decoupling, gated, 191, 196, 231 Equivalence, magnetic 154 (Section, 3.9)
Characteristic group absorptions, 81, 119
Decoupling, inverse gated, 200 Evaporative ionization methods, 6
Chemical equivalence, 150, 200, 241
Decoupling, off resonance, 201 Evolution period, 231, 232, 234, 235
Chemical ionization (CI), 3
Degrees of freedom, 72 Exchangeability of OH proton 144
Chemical shift (𝛿), 132, 192,
Delta scale (𝛿) 132 (Section 3.4), 192 (Section, 3.6.1)
194, 298, 299
(Section, 4.2.2), 298
Chemical shift, effect of DEPT 200 (Section, 4.6), 241, 243, 262 F1 axis (𝜈1 ), 233–235, 238–241
solvent on, 144–149, 188, 204, Deshielding, 133, 135
226, 227, 301, 302 F2 axis (𝜈2 ), 233–235, 238–241
Deuterated solvents, 129, 131, 187, 188, 19
F chemical shifts and coupling
Chemical shifts for 19 F, 306, 309 197, 198, 225–227
Chemical shifts for 15 N, 301 constants, 306–309
Deuterium, 131, 149–150, 197, 198, 298 19
F nuclear magnetic resonance, 306–309
Chemical shifts for 29 Si, 310 Deuterium, exchanged, 146, 149
Chemical shifts for 31 P, 312 FAB (fast atom bombardment), 4
Diamagnetic anisotropy, 133,
Chirality, 151, 158, 200 FD (field desorption), 4, 5, 8
135–136, 204
CI (chemical ionization), 3 Fermi resonance, 75, 79, 94, 97, 98, 100
Diamagnetic shielding, 133, 306
Cn (axis of symmetry), 150, 198 Ferromagnetic impurities, 131, 132
Diamagnetism, 132
Collision-induced dissociation (CID), 12 FID (free induction decay), 127–129, 132,
Diastereomeric molecules, 151
Contours, 233–235 Diastereotopic protons and methyl 192, 194, 231, 232
Correlation spectroscopy 233 (Section, groups, 151, 153, 157, 158, 160, Field desorption (FD), 4, 5, 8
5.3) 161, 200, 230, 238, 241, 243, 247, Fingerprint region, 79
COSY (COrrelation SpectroscopY), 235 249, 251, 257, 262, 264 First-order spin systems, 137–143, 201
Coulombic explosion, 7 Dihedral angle, 160, 161 FM (formula mass), 46
Coupled interactions, 74 Dimension, 231–233 Fourier transform, 6, 127, 192,
Coupling of protons to 13 C, 150, 196 Dipole moment, 72, 74 231–233, 266
Coupling of protons to D, 149 Dispersion IR spectrometer, 76 Fourier transform infrared spectrometer,
Coupling of protons to 19 F, 149, 306–309 Distortionless enhancement by 76
Coupling of protons to 29 Si, 150, 310, 312 polarization transfer (DEPT) 200 Fourier transform MS, 6, 12, 13
Coupling of protons to 31 P, 150, 312, 315 (Section, 4.6), 241, 243, 262 Fragmentations, 1, 3, 16

453
454 INDEX

Free induction decay (FID), 127–129, i (Center of symmetry), 150 μ (magnetic moment), 127, 320–324
132, 192, 194, 231, 232 I (spin number), 126, 127, 191, 298, 299, Magnetic dipole, 126, 128
Frequency axis, 𝜈1 233–235, 238–241 320–324 Magnetic equivalence 154 (Section, 3.9)
Frequency axis, 𝜈2 233–235, 238–241 Impurities, ferromagnetic, 131, 132 Magnetic field strength (B0 ), 127, 132,
Frequency domain spectrum, 127 Impurities, 131, 132, 145, 146, 150, 188, 134, 192
Frequency, Larmor (𝜈L ), 127, 128, 197, 192, 197, 226, 227 Magnetic moment (μ), 127, 320–324
231, 300 INADEQUATE (Incredible Natural Magnetization, net, 128, 129,
Abundance DoublE QUAntum 193, 231, 233
FT IR (Fourier transform infrared), 76, 77
Transfer Experiment), 249–251 Magnetization, spin locked, 254, 257, 259
FT-MS (Fourier transform mass
Index of hydrogen deficiency, 15, 325 Magnetogyric ratio (𝛾), 127, 130, 191,
spectrometry), 6, 12, 13
Integration, 130, 136, 137, 143, 193 193, 198, 239, 300, 320–324
FT-NMR (Fourier transform NMR), 127,
Intensity of peaks, 13, 17, 71, 78, 126, MALDI, 2, 6, 11
192, 231–233, 266 140, 162, 193, 231 Mass/charge (m/z), 1
Functional group region, 79 Interchange by inversion through a center Matrix assisted laser
Fundamental vibrations, 72, 75 of symmetry (i), 150 desorption/ionization
Interchange by reflection through a plane (MALDI), 2, 6, 11
𝛾 (Magnetogyric ratio), 127, 130, 131, of symmetry, 150, 151, 198 McLafferty rearrangement, 18
191–193, 198, 239, 300, 320–324 Interchange by rotation around a simple Micrometers (μm), 71
𝛾 Effect, 204, 206, 210 axis of symmetry (Cn ), 150, 151, 198 Microns (μ, obsolete), 71, 92
Gated decoupling, 191, 196, 231 Interchange through symmetry Mirror image, 151
Gauche rotamers, 153, 211 operations, 150, 151, 200 Mixing time, 235, 254, 257–259
GC-FT-IR, 77 Interchangeable nuclei, 150, 151, 200
Modulation as a function of t1 234, 235
Geminal coupling, 137, 139, 156, 158, Interconversion around a partial double
Molecular and fragment formulas, 13, 15,
160–161, 185, 238 bond, 152
46, 67
Interconversion around the single bonds
Molecular formula, 14, 46, 130, 325
2 of chains, 152–154
H (deuterium), 131, 149–150, 197, 198, Molecular ion, M+ 15,
Interconversion around the single bonds
298, 320 Molecular rotation, 72
3
of rings, 152
H (tritium), 298, 320 Molecular vibration, 71–73
Interconversion, keto-enol, 151–152
Halides, effect of on protons, 149 MS/MS (Tandem Mass Spectrometry), 12
Interferogram, 76, 233, 234
1
H-13 C correlation, 238–243 Mulls, 77–78
Interferometer, 76
HETCOR, 238–239 Internal reflection, 78 Multiple internal reflections, 78
Heavy atom effect, 211 Inverse detected, 239, 305 Multiple pulse experiments, 231
HETCOR (HETeronuclear Chemical Inverse gated decoupling, 200, 201, Multiplicity and relative intensities of
Shift CORrelation), 238–239 300, 310 peaks, 139, 140, 143, 144
Heteronuclear NMR 193, 238–243, Inversion-recovery method, 193, 195 Multiplicity, 13 C peaks, 192,
Chapter, 6 Ion collector, 2 197, 202, 225
1
H-1 H COSY, 235–238 Ion separation, 1, 2
1
H-1 H COSY diagonal, 235, 237, 238 Ion trap, 10 𝜈̃ (wavenumber in cm−1 ), 71, 72
High-resolution molecular ion, 15 Ionization methods, 3 𝜈 (nu, frequency in Hz), 71, 72, 81
14
Irradiation, selective, 162, 163 N isotope, 147, 299, 300, 320
HMBC (Heteronuclear Multiple Bond 15
Isotope peaks, 14 N coupling constants, 302
Coherence), 241–243, 305 15
Isotopes, 14, 15, 126, 191, 299, 320–324 N isotope, 299, 320
HMQC (Heteronuclear Multiple Quantum 15
IUPAC chemical shift referencing, 298 N nuclear magnetic resonance, 299–305
Coherence), 239–241, 305, 315
Nebulization, 6
HMQC-TOCSY, 259 2
J and 3 J 1 H-13 C couplings, 191, Net magnetization, 128, 129,
HOD peak, 146 193, 231
196, 197, 198
HOHAHA (Homonuclear Newman projections, 152, 153, 160
Hartmann-Hahn), 257
𝜆 (Lambda, wavelength), 71 Nitrogen rule, 13
Homomeric molecules, 151 𝜈L (Larmor frequency), 127, 128, 197,
Larmor frequency (𝜈L ), 127,
Homotopic, 151 128, 197, 300 231, 300
Hooke’s law, 72, 74 Laser desorption ionization, 6 NOE (nuclear Overhauser effect), 162,
Hydrogen bonding 75–79, 88–90, Long-range coupling, 139, 140, 143, 162, 193, 196, 200, 300
93–100, 103–108, 144 (Section, 3.6), 185, 186, 241, 302, 309 NOE difference spectroscopy, 162–164
204, 302 Longitudinal relaxation (T1 ) 128–129, NOE enhancement, 162, 193, 200, 300,
Hydroxy substituent, 88, 107, 144–146 193 (Section, 4.2.3), 231, 302, 309, 310, 312
Hydroxylic peak, 144–146 232, 299, 300 NOESY, 259
 INDEX 455

Nuclear magnetic moment (μ), 126, Quantitative 13 C NMR 193, 198 (Section, Spin-spin coupling 137 (Section 3.5),
320–324 4.4) 185, 186, 196 (Section, 4.2.5), 235
Nuclear Overhauser Effect, 162, 193, 196, Quantum chemical calculations, 137, Spin decoupling 162, 191 (Section, 4.2.1),
200, 300 301, 306 239
Quasimolecular ions, 3 Spin lock, 254, 257, 259
Off-diagonal, 235, 238 Quaternary carbons, 193, 198, 200, Spin numbers (I), 126, 127, 191
Off-resonance decoupling, 201 202–204, 241, 243, 247, 249, Spin relaxation 128 (Section 3.2.3), 193
251 (Section, 4.2.3), 231, 232
Stacked plots, 195, 233, 257
31
P coupling constants, 312 Stretching (bonds) 73, 74, Chapter, 2
31 Radiofrequency, 126–129
P nuclear magnetic resonance, Strongly coupled 156, 157 (Section,
Raman, 74, 75
312–315 3.11.2)
Rapid interchange, 136, 150, 151
Paramagnetic substance, 132, Superconducting magnet, 127, 129, 130
Reagent gas, 3, 4
200, 300 Superimposable, 151, 152
Rearrangements, 18
Paramagnetic shielding, 298, 306 Symmetry operations and elements, 150,
Receptivity (NMR), 298, 299, 320–324
Paramagnetism, 132 151
Reciprocal centimeter (cm−1 ), 71
Parent ion, 12 Systems, spin 137–144 (Section, 3.5),
Reference compounds, 133, 134, 204,
Partial double bond, 152 154, 197, 235, 238, 254, 257, 259
298–300, 320–324
Pascal’s triangle, 139, 140, 197
Relaxation processes 128 (Section 3.2.3),
Peak intensity, 13, 17, 71, 78, 191, 193, T1 process, relaxation, 128, 129, 193, 231,
193 (Section, 4.2.3), 231, 232, 299,
195, 200 232, 300
300
Pellet (KBr), 78 T2 process, relaxation, 128, 129, 231, 232
Relayed coherence transfer 254 (Section,
Phase cycling, 235, 239, 266 T (transmittance), 71
5.8)
Plane of symmetry, 150, 151, Tandem MS, 12
Resolution, 2, 13, 129, 241
153, 198 Tautomeric interconversion, 93, 104
Resonance frequency, 127, 132, 192, 299,
Plasma desorption, 5, 8, 11 Thermospray mass spectrometry, 6
320–324
Point of entry, 238 Time-domain signal, 192
Restricted rotation, 152
Polymers 86 (Section2.6.8), Time of flight (TOF), 11
Ring-current effect, 135, 136
Pople notation 140 (Section, 3.5.3) TOCSY (TOtal Correlation
ROESY, 259
ppm (parts per million), 132 SpectroscopY), 254
Rotamers (conformation), 152, 153, 211
Precessional frequency, 127–129, 232, Transfer of coherence, 254, 259
Rotating frame of reference, 231, 232, 259
235 Transmittance (T), 71
Proton-detected HETCOR, 239 Transverse relaxation (T2 ), 128, 129, 231,
Satellite peaks, 13 C, 150, 191, 239, 243
Proton-detected, long range 1 H-13 C 232
Scissoring, 72, 73, 82
heteronuclear correlation, 241
Selective ion monitoring, 11
Proton-proton decoupling, 162
Shielding, 132, 133, 135, 298 Ultrafast NMR, 266
Proximity through space, 162
Shielding constant (𝜎), 132, 133 Unsaturation, degree of, 15
Pulse delay, 191, 193, 200, 231 29
Si coupling constants, 310–312 Upfield and downfield, 133
Pulse sequence 193–195, 231, 232, 234, 29
Si NOE enhancement, 309–310 ,
Chapter, 5 29
Si nuclear magnetic resonance, 309–312 Vapor-phase spectra, 77, 88, 95
Pulsed field gradient (PFG) 265 (Section, 29
Si reference compound, 299, 309, 320 Vibrational spectra Chapter, 2
5.12)
Simple axis of symmetry (Cn ), 150 Vicinal coupling, 137, 139, 158, 160–161,
Pulsed Fourier transform spectroscopy,
Simulated spectra, 134, 155 185
127–129, 231
Sn (alternating axis of symmetry), 150, Virtual coupling, 156–158
Pulsed MS, 6, 12
153, 198
Solved problems 325 (Chapter, 7)
W conformation (coupling), 137, 162
Quadrature detection, 130, 235 Solvent effects 92, 144 (Section, 3.6),
Wavelength (𝜆), 71
Quadrupole mass spectrometry, 9–12 188, 204, 211, 212, 214, 301, 302
Wavenumber (𝜈),
̃ 71
Quadrupole moment, 126, 144, 147, 149, Spin-lattice relaxation (T1 ) 128, 193
Weak coupling, 140–141, 155, 156, 157
150, 197, 299, 300, 320–324 (Section, 4.2.3), 231, 232
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