Organlc

Chemlstry
FrFTH EDrrloN
Marc Loudon
Purdue University
r

ROBERTS AND COMPANY PUBLISHERS

Greenwood Village, Colorado

Contents
Preface Reviewers and Consultants About the Author
1

xxxl xxxvi xxxix

1
1
1 1

CHEMIGAT BONDING AND CHEMIGAT STRUGTURE

1.1

lntroduction
A. What Is Organic Chemistry? B. Emergence of Organic Chemistry C. Why Study Organic Chemistry?

1.2

Classical Theories of Chemical Bonding

A. Electrons in Atoms B. The Ionic Bond
C. The Covalent Bond D. The Polar Covalent Bond

3
3 3

1.3

Structures of Covalent Gompounds

A. Methods for Determining Molecular Geometry B. Prediction of Molecular Geometry

13
13

I4

1.4
1.5 1.6

Resonance Structures Wave Nature of the Electron

20
22 23
23 25 28

Electronic structure of the Hydrogen Atom

A. Orbitals, Quantum Numbers, and Energy B. Spatial Characteristics of Orbitals C. Summary: Atomic Orbitals of Hydrogen

1.7

Electronic Structures of More Complex Atoms

29 32
32 36

1.8

Another took at the Covalent Bond: Molecular Orbitals

A. Molecular Orbital Theory B. Molecular Orbital Theory and the Lewis Structure of H,

1.9

Hybrid Orbitals
A. Bonding in Methane B. Bonding in Ammonia

37
37

40

vii

viii

coNrENrs

Key ldeas in Chapter Additional Problems

42 43

ALKANES

46
46 48 50
50
53

2.1 Hydrocarbons 2.2 Unbranched Alkanes 2.3 conformations of Alkanes

A. Conformation of Ethane B. Conformations of Butane

2.4

Gonstitutional lsomers and Nomenclature

A. Isomers B. Organic Nomenclature
C. Substitutive Nomenclature of Alkanes D. Highly Condensed Structures E. Classification of Carbon Substitution

57
57 58 59

64 66

2.5 Cycloalkanes and skeletal structures 2.6 Physical Properties of Alkanes

A. Boiling Points B. Melting Points
C. Other Physical Properties

67

70
70
73

74

2.7 Gombustion 2.8 occurrence and use of Alkanes 2.9 Functional Groups, Gompound Classes, and the "R" Notation
A. Functional Groups and Compound Classes B. "R" Notation

76

78
81
81

82

Key ldeas in Chapter 2 Additional Problems

83 83

ACIDS AND BASES. THE CURVED.ARROW NOTATION

3.1

87
87
87 88 89

Lewis Acid-Base Association Reactions

A. Electron-Deficient Compounds B. Reactions of Electron-Deficient Compounds with Lewis Bases C. The Curved-Arrow Notation for Lewis Acid-Base Association and
Dissociation Reactions

CONTENTS iX

3.2 Electron-pair oisplacement Reactions

A. Donation of Electrons to Atoms That Are Not Electron-Deficient
B. The Curved-Arrow Notation for Electron-Pair Displacement Reactions

90
90
91

3.3 Review of the Curued-Arrow Notation

A. Use of the Curved-Arrow Notation to Represent Reactions B. Use of the Curved-Arrow Notation to Derive Resonance Structures

94
94 94

3.4 Bronsted-Lowry

Acids and Bases

95
96
98
101

A. Definition of Brgnsted Acids and Bases B. Nucleophiles, Electrophiles, and Leaving Groups
C. Strengths of Brpnsted Acids D. Strengths of Brgnsted Bases E. Equilibria in Acid-Base Reactions

103

104

3.5 Free Energy and Chemical Equilibrium 3.6 Relationship of Structure to Acidity
A. The Element Effect B. The Charge Effect C. The Polar Effect

106
108
108

110

lll

Key ldeas in Chapter 3 Additional Problems

116 117

INTRODUGTION TO AIKENES. STRUCTURE AND REACTIVITY

122
122
r23 r25
128

4"1 Structure and Bonding in Rfkenes

A. Carbon Hybridization in Alkenes B. The n- (Pi) Bond
C. Double-Bond Stereoisomers

4.2 Nomenclature

of Alkenes

131
131

A. IUPAC Substitutive Nomenclature B. Nomenclature of Double-Bond Stereoisomers: The E,Z Svstem

t34 139

4.3 Unsaturation Humber 4.4 Phy$ical Propefties of Alkenes 4.5 Relative $tabilities of Allcene lsomers
A. Heats of Formation B. Relative Stabilities of Alkene Isomers

140
141

I4I
r44

4.5 Additisn Reactions of Alkenes 4"7 Addition of Hydrcgen Halides to nlilrenas

A. Regioselectivity of Hydrogen Halide Addition B. Carbocation Intermediates in Hydrogen Halide Addition

147 147
148

r49

CONTENTS

C. Structure and Stability of Carbocations D. Carbocation Rearrangement in Hydrogen Halide Addition

151

r54

4.8

Reaction Rates
A. The Transition State B. The Energy Barrier C. Multistep Reactions and the Rate-Limiting Step
D. Hammond's Postulate

157
158 160

r62 r64

4.9

catalysis
A. Catalytic Hydrogenation of Alkenes B. Hydration of Alkenes C. Enzyme Catalysis

166
168

r69
172

Key ldeas in Chapter 4 Additional Problems

172 174

ADDITION REACTIONS OF ALKENES

5.1

178
178 181
181 183

An Overuiew of Electrophilic Addition Reactions

Reactions of Alkenes

5.2

with Halogens

A. Addition of Chlorine and Bromine B. Halohydrins

5.3

writing organic Reactions

Gonverion of Alkenes into Alcohols
A. Oxymercuration-Reduction of Alkenes B. Hydroboration-Oxidation of Alkenes C. Comparison of Methods for the Synthesis of Alcohols from Alkenes

186
187
r87
190

5.4

194

5.5

Ozonolysis of Alkenes Free-Radical Addition of Hydrogen Bromide to Rlkenes

A. The Peroxide Effect B. Free Radicals and the "Fishhook" Notation
C. Free-Radical Chain Reactions D. Explanation of the Peroxide Effect E. Bond Dissociation Energies

196
200
200

5.6

20r
202
207

zrl
of Alkenes
214
216
219 220

5.7 Polymeni: Free-Radical Polymerization 5.8 Alkenes in the Ghemical lndustry

Key ldeas in Chapter 5 Additional Problems

CONTENTS

xl

PRINCIPLES OF STEREOCHEMISTRY

226
226
226
229 229

6.1 Enantiomelri, Chirality, and Symmetry

A. Enantiomers and Chirality B. Asymmetric Carbon and Stereocenters C. Chirality and Symmetry

6.2 Nomenclature of Enantiomers: The R,S System 6.3 Physical Properties of Enantiomers: Optical Activity
A. Polarized Light B. Optical Activity C. Optical Activities of Enantiomers

231

234
235 235

238

6.4 Racemates 5.5 Stereochemical Correlation 6.6 Diastereomers 6.7 Meso Compounds 6.8 Enantiomeric Resolution 6.9 Ghiral Molecules without Asymmetric
6.10 6,17
6.12
Conformational Stereoisomers

239 241

242
246 249

Atoms

251

253
253 255

A. Stereoisomers Interconvefied by Internal Rotations B. Asymmetric Nitrogen: Amine Inversion

Drawing Structures That Contain Three-Dimensional lnformation

The Postulation of Tetrahedral Carbon
Key ldeas in Chapter 6 Additional Problems

257

2s9 263 253

cYcHc coMPouNDs.

STEREOCHEMISTRY OF REACTIONS

268
268 269
269
273

7.1 Relative Stabilities of the Monocyclic Alkanes 7.2 Conformations of Gyclohexane

A. The Chair Conformation B. Interconversion of Chair Conformations
C. Boat and Twist-Boat Conformations

274

xtl

CONTENTS

7.3 7.4

Monosubstituted Gyclohexalres. Gonformational Rnalysis

Disu

277
281
281

bstituted Gyclohexanes

A. Cis-Trans Isomerism in Disubstituted Cyclohexanes B. Conformational Analysis C. Use of Planar Structures for Cyclic Compounds
D. Stereochemical Consequences of the Chair Interconversion

283

284
285

7,5

Gyclopentar!, Gyclobutane, and Gyclopropane

A. Cyclopentane B. Cyclobutane and Cyclopropane

288
288

289

7.6

Bicyclic and Polycyclic Gompounds

A. Classification and Nomenclature B. Cis and Trans Ring Fusion C. Trans-Cycloalkenes and Bredt's Rule
D. Steroids

290
290 292 294 296

7.7

Relative Reactivities of Stereoisomers

A. Relative Reactivities of Enantiomers B. Relative Reactivities of Diastereomers

298
298
300

7.8

Reactions That Form Stereoisomers A. Reactions of Achiral Compounds That Give Enantiomeric
B. Reactions That Give Diastereomeric Products

301
Products
301

304

7.9

Stereochemistry of Ghemical Reactions

A. Stereochemistry of Addition Reactions B. Stereochemistry of Substitution Reactions C. Stereochemistry of Bromine Addition D. Stereochemistry of Hydroboration-Oxidation E. Stereochemistry of Other Addition Reactions

305
30s 306
308

312
313

Key ldeas in Chapter 7 Additional Problems

314 316

INTRODUCTION TO ATKYL HAIIDES, ALCOHOLS, ETHERS, THIOLS, AND SUTFIDES

323
324
324

8.1 Nomenclature
A. Nomenclature of Alkyl Halides B. Nomenclature of Alcohols and Thiols C. Nomenclature of Ethers and Sulfides

326
330

8.2 Structures 8.3 Effect of Molecular

332 333
333

Polarity and Hydrogen Bonding on Physical Properties

A. Boiling Points of Ethers and Alkyl Halides

CONTENTS
B. Boiling Points of Alcohols
C. Hydrogen Bonding

XI II 335

336

8,4 8,5 8,6

Solvents in Organic Chemistry

A. Classification of Solvents B. Solubility

339
339

340

Application$ of Solubility and Solvation principle$

A. Cell Membranes and Drug Solubility B. Cation-Binding Molecules

346
346
351

Acidity of Alcohols and Thiols

A. Formation of Alkoxides and Mercaptides B. Polar Effects on Alcohol Acidity C. Role of the Solvent in Alcohol Acidity

3S5
356
358 358

8.7 Bssicity of Alcohols and Ethers 8.8 Grignard and Organolithium Reagents
A. Formation of Grignard and Organolithium Reagents B. Protonolysis of Grignard and Organolithium Reagents

359
361
361

362

8.9 Industrial Prepsration

and Use of Alkyl Halides, Alcohols, and Ethers

A. Free-Radical Halogenation of Alkanes B. Uses of Halogen-Containing Compounds C. Production and Use of Alcohols and Ethers
D. Safety Hazards of Ethers

364
364
365 368

3tl
372 373

Key ldeas in Chapter I l\dditional Problems

THE CHEMISTRY OF ALKYL HALIDES

377
377
377

9.1

An Overview of ruucleophilic Substitution and p-Elimination Reactions

A. Nucleophilic Substitution Reactions

B. B-Elimination Reactions C. Competition between Nucleophilic Substitution and B-Elimination Reactions

378
380

9.2 Equilibria in tUucleophilic 9.3 Reaction Rates

A. Definition of Reaction Rate B. The Rate Law

Substitution Reactaons

381

382
382 383

C. Relationship of the Rate Constant to the Standard Free Energy of Activation

384

9.4

The S*2 Reaction

A. Rate Law and Mechanism of the S*2 Reaction

385
386

XIV

CONTENTS

B. Comparison of the Rates of S*2 Reactions and Bronsted Acid-Base Reactions

C. Stereochemistry of the S*2 Reaction D. Effect of Alkyl Halide Structure on the S0.2 Reaction E. Nucleophilicity in the S*2 Reaction F. Leaving-Group Effects in the S*2 Reaction G. Summary of the S*2 Reaction

388 388

390

392
398

399

9.5

The E2 Reaction
A. Rate Law and Mechanism of theE2 Reaction B. Why theE2 Reaction Is Concerted
C. Leaving-Group Effects on the E2 Reaction D. Deuterium Isotope Effects in the E2 Reaction E. Stereochemistry of the E2 Reaction F. Regioselectivity of the E2 Reaction G. Competition between theE2 and S,o2 Reactions: A Closer Look H. Summary of the E2 Reaction

400
400 400 402 402 404 406
407

4tl

9.5

The S*1 and El Reactions

A. Rate Law and Mechanism of S*1 and El Reactions B. Rate-Limiting and Product-Determining Steps C. Reactivity and Product Distributions in S*1-E1 Reactions
D. Stereochemistry of the S"l Reaction E. Summary of the S*l and El Reactions

412
412

4t4 4t6
418 420

9.7 9.8

Summary of Substitution and Elimination Reactions of Alkyl Halides Carbenes and Carbenoids
A. a-Elimination Reactions
B. The Simmons-Smith Reaction

429 424
424 426

Key ldeas in Chapter 9 Additional Problems

428 429

10

THE CHEMISTRY OF AICOHOIS AND THIOTS

436
435

10.1

Dehydration of Alcohols

1O.2 Reactions of Alcohols with Hydrogen Halides

440 443
443 447 448 449

10.3 Sulfonate and Inorganic

Ester Derivatives of Alcohols

A. Sulfonate Ester Derivatives of Alcohols B. Alkylating Agents C. Ester Derivatives of Strong Inorganic Acids D. Reactions of Alcohols with Thionyl Chloride and Phosphorus Tribromide

1O.4 Conversion of Alcohols intoAlkyl Halides: Summary

450

CONTENTS

XV

10.5 Oxidation and Reduction in Organic Ghemistry

A. Half-Reactions and Oxidation Numbers B. Oxidizing and Reducing Agents

452
452 156

10.6 Oxidation of Alcohols

A. Oxidation to Aldehydes and Ketones B. Oxidation to Carboxylic Acids

459
459

46r

1O"7 Biological Oxidation of Ethanol

462
465
465 469

10.8 Chemlcal
10.9 Oxidation

and Stereochemical Grcup Relationships

A. Chemical Equivalence and Nonequivalence B. Stereochemistry of the Alcohol Dehydrogenase Reaction

of Thiols

471

1O.1O $ynthesis of Alcohols

474 474
476
477

10.11 Desigil of Organic Synthesis

Key ldeas in Chapter 10 Additional Problems

11

THE CHEMISTRY OF ETHERS, EPOXIDES, GLYGOLS, AND SULFIDES

482
482
482
484 485

11.'l

Synthesis of Ethers and Sulfides

A. Williamson Ether Synthesis B. Alkoxymercuration-Reduction of Alkenes C. Ethers from Alcohol Dehydration and Alkene Addition

11,2 Synthesis of Epoxides

A. Oxidation of Alkenes with Peroxycarboxylic Acids B. Cyclization of Halohydrins

488
488

49r

11.3 Gleavage of Ethers 11.4 Nucleophilic Substitutioil Reactisns of Epoxides

A. Ring-Opening Reactions under Basic Conditions B. Ring-Opening Reactions under Acidic Conditions C. Reaction of Epoxides with Organometallic Reagents

492
495
495
497

500

11.5

Preparation and Oxldative Cleavage of Glycols

A. Preparation of Glycols B. Oxidative Cleavage of Glycols

503
503

s06

11.5 oxonium

and sulfonium salts

508
508 509

A. Reactions of Oxonium and Sulfonium Salts B. S-Adenosylmethionine: Nature's Methylating Agent

xvl

CONTENTS

11.7 tntramolecular Reactlons

and the Proximity Effect

5r0
5r0
513

A. Neighboring-Group Participation B. The Proximity Effect and Effective Molarity

C. Stereochemical Consequences of Neighboring-Group Participation

5r6

11.8 Oxidation of Ethers and Sulfides 11.9 The Three Fundamental Operations of Organic Synthesis 11.10 Synthesis of Enantiomerically pure Compounds:
Asymmetric Epoxidation
Key ldeas in chapter 11 Additional Problems

518 520
5e2 5?7

s?8

12

ITUTRODUCTION TO SPECTROSCOPY. INFRARED SPECTROSCOPY AND MASS SPECTROMETRY

s36
536
536 538

12,1 Introduction to Spectroscopy

A. Electromagnetic Radiation B. Absorption Spectroscopy

12.2 lnfrared Spectroscopy

A. The Inf-rared Spectrum B. Physical Basis of IR Spectroscopy

540
540 54?

12.3 lnfrared Absorption and Chemical Structure

A. Factors That Determine IR Absorption Position B. Factors That Determine IR Absorption Intensity

544
545

548

12.4 Functional-Group Infrared Absorptions

A. IR Spectra B. IR Spectra C. IR Spectra D. IR Spectra of of of of
Alkanes

552
5s2 552
553

Alkyl Halides
Alkenes

Alcohols and Ethers

556

12.5 Obtaining an Infrared Spectrum 12.6 lntroduction to Mass Spectrometry

A. Electron-Impact Mass Spectra B. Isotopic Peaks
C. Fragmentation D. The Molecular Ion. Chemical-Ionization Mass Spectra E. The Mass Spectrometer

557

558
558

560
563

566 569

Key ldeas in Chapter 12 Additional Problems

571 571

CONTENTS

XVI

13

NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY

578
578 581

13.1 13.3

An Overview of Proton NMR Spectroscopy

Basls of NMR spectroscopy

13.2 physlcal

The NMR Spectrum: Ghemlcal Shift and htegral

A. Chemical Shift B. Chemical Shift Scales
C. Relationship of Chemical Shift to Structure D. The Number of Absorptions in an NMR Spectrum E. Counting Protons with the Integral F. Using the Chemical Shift and Integral to Determine Unknown Structures

s83
583 585

586 589 592

593

13.4

The NMR Spectrum: spin-spln splltting

A. The n * 1 Splitting Rule B. Why Splitting Occurs
C. Solving Unknown Structures with NMR Spectra Involving Splitting

59S
596 599
601

13.5 Complex NMR Specffa

A. Multiplicative Splitting B. Breakdown of the n * I Rule

603
603 607

13.6

Use of Deuterlum in Proton NMR

611
6',12

13.7 Characterlstic Functlonal-Group NMR Absorptions

A. NMR SPectra B. NMR Spectra C. NMR Spectra D. NMR SPectra
of Alkenes of Alkanes and Cycloalkanes of Alkyl Halides and Ethers of Alcohols

612 614 616 616

13.8

NMR Spectroscopy of Dynamic Systems

619 629

13.9 Carbon NMR 13.10 Solving Structure

Problems with Spectroscopy

6e9 639 634 635 63S

13.11 The NMR Spectrometer

13.12 Other Uses of NMR
Key ldeas in ChaPter 13 Additional Problems

14

THE CHEMISTRV OF ATKYNES

644
644 646

14.1 Nomenclature

of AlkYnes

t{.e

$tructure and Bonding in Alltynes

XViii

CONTENTS

14.3

Physical Properties of Rlkynes

A. Boiling Points and Solubilities B. IR Spectroscopy of Alkynes C. NMR Spectroscopy of Alkynes

649
649 649

6s0

14.4 14.5

Introduction to Addition Reactions of the Triple Bond

Conversion of Alkynes into Aldehydes and Ketones
A. Hydration of Alkynes B. Hydroboration-Oxidation of Alkynes

5s2
654
654
657

14.6

Reduction of Alkynes
A. Catalytic Hydrogenation of Alkynes B. Reduction of Alkynes with Sodium in Liquid Ammonia

659
659 660

14.7

Acidity of l-Alkynes
A. Acetylenic Anions B. Acetylenic Anions
as

662
662 665

Nucleophiles

14.9
14.9

Organic Synthesis Using Alkynes Pheromones

666
668

14.10

Occurrence and Use of Alkynes

Key ldeas in Chapter 14 Additional Problems

574
57
1

671

15

DIENES, RESONANCE, AND AROMATICITY

676
677
677 680

15.1 Structure and Stability of Dienes

A. Stability of Conjugated Dienes. Molecular Orbitals B. Structure of Conjugated Dienes C. Structure and Stability of Cumulared Dienes

682

15.2 Ultraviolet-Visible Spectroscopy

A. The UV-Vis Spectrum B. Physical Basis of UV-Vis Spectroscopy C. UV-Vis Spectroscopy of Conjugated Alkenes

684
684 686
687

15.3

The Diels-Alder Reaction

A. Reaction of conjugated Dienes with Alkenes B. Effect of Diene Conformation on the Diels-Alder Reaction C. Stereochemistry of the Diels-Alder Reaction

690
690 694 696

15.4 Addition of Hydrogen Halides to conjugated

C. Kinetic and Thermodynamic Control

Dienes

700
700 702 705

A. 1,2- and 1,4-Additions B. Allylic Carbocations. The Connection between Resonance and Stabilitv

CONTENTS XIX

15,5 15.6

Diene Polymers Resonance

A. Drawing Resonance Structures B. Relative Importance of Resonance Structures
C. Use of Resonance Structures

708

749 7t0

7Ir

714

15.7 Introduction to Aromatic Compound$

A. Benzene, aPuzzling 'Alkene" B. Structure of Benzene C. Stability of Benzene D. Aromaticity and the Hiickel an | 2 Rule E. Antiaromatic Compounds

716 l17
718

721

72r
728

Key ldeas in Chapter 15 Additional Problems

730
731

16

THE CHEMISTRY OF BENZENE AND ITS DERIVATIVES 74O

16.1 Nomenclature of Benzene Derivatives 16.2

Physical troperties of Benzene Derivatives

744 743 743

143 744

16.3

Spectroscopy of Benzene Derivatives

A. IR SPectroscoPy B. NMR Spectroscopy c. r3C NMR spectroscopy
D. UV Spectroscopy

748 748

16.4 Electrophilic Aromatic Substitution

A. Halogenation of Benzene B. Electrophilic Aromatic Substitution C. Nitration of Benzene
D. Sulfonation of Benzene E. Friedel-Crafts Alkylation of Benzene F. Friedel-Crafts Acylation of Benzene

Reactions of Benzene

750 75r
753 754 755 756
759

16.5 Electrophilicaromatic Substitution

of Substituted Benzenes

Reactions

762
762

A. Directing Effects of Substituents B. Activating and Deactivating Effects of Substituents C. Use of Electrophilic Aromatic Substitution in Organic Synthesis

768
772

16.6 Hydrogenation of Benzene Derivatives

15.7 source and lndustrial
Use of Aromatic ttydrocarbons

776
777 780 780

rey ldeas in ChaPter t6 Additional Problems

XX

CO NTE NTS

17

ALTYLIG AND BENZYLIG REAGTIVITY

788
789

17.1 Reactions tnvolvlng Allylic and Benzyllc Carbocations 17.2 Reactions lnvolvlng Allyllc and Benzylic Radicals 17.3 Reactions tnvolvlng Allylic and Benzyllc Anions
A. Allylic Grignard Reagents B. E2 Eliminations Involving Allylic or Benzylic Hydrogens

793
798
799
801

17.4 Allyllc and Benzylic Sn2 Reactions 17.s Allyllc and Benzylic Oxidation
A. Oxidation of Allylic and Benzylic Alcohols B. Benzylic Oxidation of Alkylbenzenes

802 803
803 805

17.6

Terpenes
A. The Isoprene Rule B. Biosynthesis of Terpenes

807
807

810

Key ldeas in chapter 17 Additional Problems

813 814

18

AND PHENOLS. TRANSITION.METAL 18.1 Lack of Reactivity

under
SNz

THE CHEM|STRY OF ARYL HAL|DES, VtNyLtc HALIDES,

CATALYSIS

822
8?3 825

of vinylic and Aryl Halides Gonditlons

18.2 Elimination Reactions of vinylic Halides 18.3 Lack of Reactivlty of Vinylic and
Aryl Halldes under SNI Gonditions
Reactions of Aryl Halides

826
828

18.4 NucleophilicAromatic substitution 18,5 Introduction to Transition-Metal

A. Transition Metals and Their Complexes B. Oxidation State
C. The d'Notation D. Electron Counting: The 16- and lS-Electron Rules E. Fundamental Reactions of Transition-Metal Complexes

Catalyzed Reactions

831
832 835

836
836 839

18-6

Examples ofTransition-Metal-Catalyzed Reactions

A. The Heck Reaction B. The Suzuki Coupling

845
845 848

CONTENTS XXi
C. Alkene Metathesis D. Other Examples of Transition-Metal-Catalyzed Reactions
852 857

18.7 Acidity of Phenols

A. Resonance and Polar Effects on the Acidity of Phenols B. Formation and Use of Phenoxides

858
858
861

18.8 Oxidation of Phenols to Quinones

862
867

18.9

Electrophillc eromatic Substitution Reactions of Phenols

A. Lack of Reactivity of the Aryl-Oxygen Bond in S*l and S*2 Reactions B. Substitution at the Aryl-Oxygen Bond: The Stille Reaction

18.10 Reactivity of the Aryl-oxygen Bond 18.11 hdustrial Preparation and Use of Phenol
Key ldeas in Chapter 18 Additional Problems

870
870

872

874
875

876

19

THE GHEMISTRY OF ALDEHYDES AND KETONES. CARBONYT.ADDITION REACTIONS

888
890
890

19.1 Nomenclature of Aldehydes and Ketones

A. Common Nomenclature B. Substitutive Nomenclature

892

19.2

Physical Properties of Aldehydes and Ketones of Aldehydes and Ketones

A. IR Spectroscopy

894 895
895 897 898 899 901

19.3 Spectroscopy

B. Proton NMR Spectroscopy C. Carbon NMR Spectroscopy

D. UV Spectroscopy

E. Mass Spectrometry

19.4 Synthesis of Aldehydes and Ketones

903 903 904 997

907

19.5 htroduction to Aldehyde and Ketone Reactions 19.6 Basicity of Aldehydes and Ketones 19.7 Reversible Rddition Reactions of Aldehydes and Ketones
A. Mechanisms of Carbonyl-Addition Reactions B. Equilibria in Carbonyl-Addition Reactions
C. Rates of Carbonyl-Addition Reactions

910
913

19.8

Reduction of Aldehydes and Ketones to Alcohols

914

xxii

coNrENrs

1g.g 19.10

Reactions of Aldehydes and Ketones with Grignard and Related Reagents

918

Acetals and Their Use as Protecting Groups

A. Preparation and Hydrolysis of Acetals B. Protecting Groups

921
921 925

19.11

Reactions of Aldehydes and Ketones with Amines

A. Reaction with Primary Amines and Other Monosubstituted
Derivatives of Ammonia

926
926
929

B. Reaction with Secondary Amines

19,12 19.13 19,14 19.15

Reduction of carbonyl Groups to Methylene Groups

The Wittig Alkene Synthesis

931

933

Oxidation of Aldehydes to Carboxylic Acids Manufacture and use of Aldehydes and Ketones
Key ldeas in Chapter Additional Problems
19

936
938 93e 940

20

THE CHEMISTRY OF CARBOXYLIC ACIDS

20.1

948
948
948
951

Nomenclature of Carboxylic Rcids

A. Common Nomenclature B. Substitutive Nomenclature

20.2 20.3

Structure and Physical Properties of Carboxylic Rcids

Spectroscopy of Carboxylic Rcids
A. IR Spectroscopy B. NMR Spectroscopy

953 955
955 955

2A,4

Acid-Base Properties of Garboxylic Rcids

A. Acidity of Carboxylic and Sulfonic Acids B. Basicity of Carboxylic Acids

957
957

960

20.5 20,6 20.7 20.9

Fatty Acids, Soaps, and Detergents Synthesis of Carboxylic Rcids

960
963

lntroduction to carboxylic Rcid Reactions

Gonversion of carboxylic Rcids into Esters
A. Acid-Cataly zed Esterifi cation B. Esterification by Alkylation

964
965
965 968

CONTENTS

XXI

II

20.9

Gonversion of Carboxylic Acids into Acid Chlorides and Anhydrides

A. Synthesis of Acid Chlorides B. Synthesis of Anhydrides

9IO
970
972

20.10 Reduction of Garboxylic Acids to Primary Alcohols

2O.11 Decarboxylation of Garboxylic Acids
Key ldeas in Chapter 20 Additional Problems

974
976 978 979

21

THE CHEMISTRY OF GARBOXYTIC AGID DERIVATIVES 986

21.1 Nomenclature and Glassification

of Carboxylic Acid Derivatives
C. Anhydrides D. Nitriles E. Amides, Lactams, and Imides F. Nomenclature of Substituent Groups G. Carbonic Acid Derivatives

986
986 988 988 989 989

A. Esters and Lactones B. Acid Halides

99r 99r

21.2 Structures of Carboxylic Acid Derivatives

992

21.3

Physical Propefties of Carboxylic Acid Derivatives

A. Esters B. Anhvdrides and Acid Chlorides C. Nitriles
D. Amides

994
994 994
995

99s

21.4 Spectroscopy of Carboxylic Rcid Derivatives

A. IR Spectroscopy B. NMR Spectroscopy

996
996
997

21.5 Basicity of Garboxylic Acid Derivatives 21.6 Introduction to the Reactions of carboxylic Acid Derivatives 21,7 llydrolysis of Carboxylic Acid Derivatives
A. Hydrolysis of Esters B. Hydrolysis of Amides C. Hydrolysis of Nitriles D. Hydrolysis of Acid Chlorides and Anhydrides E. Mechanisms and Reactivity in Nucleophilic Acyl Substitution Reactions

1000 1003 1004

1004
I
r

008 009
1

1011 101

XX|V

CoNTENTS

21.8

Reactions of Carboxylic ncid Derivatives with Nucleophiles

A. Reactions of Acid Chlorides with Nucleophiles B. Reactions of Anhydrides with Nucleophiles C. Reactions of Esters with Nucleophiles

1016
1016 1019
I

020

21.9 Reduction of Garboxylic Acid Derivatives

A. Reduction of Esters to Primary Alcohols B. Reduction of Amides to Amines

1022 t022
1

023 025 028

s ftt*:ti:t :i xt#nffiT?:*il'ffT*
E. Relative Reactivities of Carbonyl Compounds
'/

t02l
1

21

10

""ff:[3fr]['il:#?$,3"'iva*ves A. Reaction of Esters with Grignard Reagents B. Reaction of Acid Chlorides with Lithium Dialkylcuprates
21.11 Synthesis of Carboxylic Acid Derivatives
21

ffifiit?ll

'1o29
r029
103

1032 1034
1

12

Hi':11

lfilll'ffi

c
031

A. Nylon and Polyesters B. Waxes, Fats, and Phospholipids

"'**iTlox'r

l 036

ffi1,iff::,.;':[il;T"
22

037 1 038
1

THE CHEMISTRY OF ENOTATE IONS, ENOLS, AND a,B-UNSATURATED CARBONYL GOMPOUNDS

1047
1048
r

22.1 Acidity of Garbonyl

Compounds

A. Formation of Enolate Anions B. Introduction to Reactions of Enolate Ions

048
1

105

22.2 Enolization of Carbonyl Compounds 22.3 orHalogenation of Carbonyl Compounds

A. Acid-Catalyzed a-Halogenation B. Halogenation of Aldehydes and Ketones in Base: The Haloform Reaction C. a-Bromination of Carboxylic Acids D. Reactions of a-Halo Carbonyl Compounds

1053 1057
l 057
1

059

1060

r062

22.4 Aldol Addition

and Aldol Gondensation

1063
063 1066
I

A. Base-Catalyzed Aldol Reactions B. Acid-Catalyzed Aldol Condensation C. Special Types of Aldol Reactions D. Synthesis with the Aldol Condensation

r067
I

070

CONTENTS XXV

22.5 Gondensation Reactions |nvolving Ester Enolate lons

A. Claisen Condensation B. Dieckmann Condensation
C. Crossed Claisen Condensation D. Synthesis with the Claisen Condensation

1072
1012
r07 6 r07 6
1

078

22.6 Biosynthesis of Fatty Acids 22,7 Alkylation of Ester Enolate lons

A. Malonic Ester Synthesis B. Direct Alkylation of Enolate Ions Derived from Monoesters C. Acetoacetic Ester Synthesis

1081

1084
084 086 I 089
I
1

22.8 Conjugate-Addition

Reactions

1492
r092
I

A. Conjugate Addition to a,B-Unsaturated Carbonyl Compounds B. Conjugate Addition Reactions versus Carbonyl-Group Reactions C. Conjugate Addition of Enolate Ions

095

t091
1

22.9 Reduction of n,F-Unsaturated Carbonyl Gompounds

22.10 Reactions of c,F-Unsaturated Garbonyl Compounds with Organometallic Reagents
A. Addition of Organolithium Reagents to the Carbonyl Group B. Conjugate Addition of Lithium Dialkylcuprate Reagents

100
101
1101

I 102
1 1

22.11 Organic Synthesis with Conjugate-Addition Reactions

Key ldeas in Chapter 22 Additional Problems

103

105 1146

23

THE CHEMISTRY OF AMINES

1116
1117

23.1 Nomenclature of Amines

A. Common Nomenclature B. Substitutive Nomenclature

IttT

tln

23.2 Structure of Amines

1119

23.3 23.4 23.5

Physical Properties of Amines

1124
1127

Spectroscopy of Amines
A. IR Spectroscopy B. NMR Spectroscopy

ttzl ttzl
1122 tt22 tt23
1 1

Basicity and Acidity of Amines

A. Basicity of Amines B. Substituent Effects on Amine Basicity C. Separations Using Amine Basicity D. Acidity of Amines E. Summary of Aciditv and Basicity

t27
128

rr29

XXVI

CoNTENTS

23.6 Quaternary Ammonium and Phosphonium Salts 23.7 Alltylation and Acylation Reactions of Rmines
A. Direct Alkvlation of Amines B. Reductive Amination C. Acylation of Amines

1129
1131
1131
1 1

133 135

23.8

Hofmann Elimination of Quaternary Ammonium

Hydroxides

1136
1

23.9 Aromatic Substitution Reactions of Aniline Derivatives 23.10 Diazotization; Reactions of Diazonium lons
A. Formation and Substitution Reactions of Diazonium Salts B. Aromatic Substitution with Diazonium Ions C. Reactions of Secondary and Tertiary Amines with Nitrous Acid

138

1139
1

139

Ir42 II44
1145 tr45 t146 tr47
I 150

23.11 Synthesis of Amines

A. Gabriel Synthesis of Primary Amines B. Reduction of Nitro Compounds C. Amination of Aryl Halides and Aryl Triflates
D. Curtius and Hofmann Rearrangements E. Synthesis of Amines: Summary

lt54
1155
1

23.12

Use and Occurrence of Amines

A. Industrial Use of Amines and Ammonia B. Naturally Occurring Amines

155

I 155

Key ldeas in Chapter 23 Additional Problems

1157

1158

24

CARBOHYDRATES

1156
1167 1168

24,1 Glassification and Properties of Carbohydrates 24.2 FischerProiections 24.3 Structures of the Monosaccharides
A. Stereochemistry and Confi guration B. Cyclic Structures of the Monosaccharides

1173 tt73
1178

24.4 Mutarotation of Garbohydrates

1183 1186 1188 1191 1193

24.5 Base-Catalyzed lsomerization of Aldoses and Ketoses 24.6 Glycosides 24.7 Ether and Ester Derivatives of Garbohydrates 24.8 Oxidation and Reduction Reactions of Carbohydrates
A. Oxidation to Aldonic Acids

tt94

CONTENTS XXVI I
B. Oxidation to Aldaric Acids
C. Periodate Oxidation D. Reduction to Alditols
1 1

195

196

rr97 r 198

24.9 Kiliani-Fischer Synthesis

24.10 Proof of Glucose Stereochemistry
A. Which Diastereomer? The Fischer Proof B. Which Enantiomer? The Absolute Configuration of n-(+)-Glucose

1199
1199

r203

24.11 Disaccharides and Polysaf,charides

A. Disaccharides B. Polysaccharides

1205
1205

r209

Key ldeas in Chapter 24 Additional Problems

1212
1213

25

THE CHEMISTRY OF THE AROMATIC HETEROGYCTES 1220

25.1 Nomenclature

and Structure of the Aromatic Heterocycles

1220
r220

A. Nomenclature B. Structure and Aromaticity

r22l

25.2 Sasicity and Acidity of the Nitrogen Heterocycles

A. Basicity of the Nitrogen Heterocycles B. Acidity of Pyrrole and Indole

1224
1224

r226

25.3

The Chemistry of Furan, Pyrrolq and Thiophene

A. Electrophilic Aromatic Substitution B. Addition Reactions of Furan C. Side-Chain Reactions

1226
t226
r229 r230

25.4

The chemistry of eyridine

A. Electrophilic Aromatic Substitution B. Nucleophilic Aromatic Substitution C. N-Alkylpyridinium Salts and Their Reactions D. Side-Chain Reactions of Pyridine Derivatives E. Pyridinium Ions in Biology: Pyridoxal Phosphate

1231
I23T

t234
1238

r239 r240

25.5

tuucleosides, Nucleotides, and Nucleic Acids

A. Nucleosides and Nucleotides B. The Structures of DNA and RNA C. DNA Modification and Chemical Carcinogenesis

1245
t245

t248
t253

25.6 Other Biologically lmportant Heterocyclic

Key ldeas in Chapter 25 Additional Problem$

Compounds

r 255

1?57
1

258

xxviii
26

coNrENrs

AMINO ACIDS, PEPTIDES, AND PROTEINS

26.1 Nomenclature
of Amino Acids and Peptides
A. Nomenclature of Amino Acids B. Nomenclature of Peptides

1255
1266
r266
t267

26.2 Stereochemistry of the rAffiiro Acids 26.3

Acid-Base Properties of Amino Acids and Peptides
A. Zwitterionic Structures of Amino Acids and Peptides B. Isoelectric Points of Amino Acids and Peptides C. Separations of Amino Acids and Peptides Using Acid-Base Properties

1270
1271 r27 |
t273
r271

26.4 Synthesis and Enantiomeric Resolution of a-Ami]ro Acids

A. Alkylation of Ammonia B. Alkylation of Aminomalonate Derivatives
C. Strecker Synthesis D. Enantiomeric Resolution of a-Amino Acids

1279
1279
1279
I

280

128 I

26.5 Acylation and Esterification

Reactions of Amino Acids

1282
r 283
129?^

26.6 Solid-PhasePeptideSynthesis 26.7 Hydrolysis of Peptides

A. Complete Hydrolysis and Amino Acid Analysis B. Enzyme-C ataly zed Peptide Hydrolysis

r292
1295

26.8 Primary Structure of Peptides and Proteins

A. Peptide Sequencing by Mass Spectrometry B. Peptide Sequencing by the Edman Degradation

1296
r299
I 303 I 305
1

C. Protein Sequencing D. Posttranslational Modification of Proteins

305

26.9

Higher-Order Structures of Proteins

A. Secondary Structure B. Tertiary and Quaternary Structure

308
I 308 1310

26.10 Enzymes: Biological Catalysts

A. The Catalytic Action of Enzymes B. Enzymes as Drug Targets: Enzyme Inhibition

131 5
1315 1318
1

Key ldeas in Chapter 26 Additional Problems

323 1324

27

PERICYCLIC REACTIONS

1333
1

27.1

Molecular Orbitals of Gonjugated rrElectron Systems

A. Molecular Orbitals of Conjugated Alkenes

336
I

336

coNrENrs xxix
B. Molecular Orbitals of Conjugated Ions and Radicals
C. Excited States
340 1343
I

27.2 Electrocyclic

Reactions

1343
1343

A. Ground-State (Thermal) Electrocyclic Reactions B. Excited-State (Photochemical) Electrocyclic Reactions

C. Selection Rules and Microscopic Reversibility

r346
t317

27.3 Cycloaddition Reactions 27.4 Thermal Sigmatropic Reaction$

A. Classiflcation and Stereochemistry B. Thermal [3,3] Sigmatropic Reactions C. Summary: Selection Rules for Thermal Sigmatropic Reactions

1349
1

3S3
1353
I

360

t362

27.5 Fluxional Molecules 27.6 Biological Pericyclic

1364 1365
1367 1 368

Reactions: The Formation of Vitamin D

Key ldeas in Chapter 27 Additional Prohlems

APPENDIGES
Appendix l. Appendix ll. Appendix lll. Substitutive Nomenclature of Organic Gompounds lnfrared Absorptions of Organic Compounds
Proton NMR Chemical Shifts in Organic Compounds
A. Protons within Functional Groups B. Protons Adjacent to Functional Groups

A-1
A-1

A-2

A'5
A-5 A-5

APPENDIX IV.

t3C NMR

Chemical Shifts in Organic Gompounds

A-7

A. Chemical Shifts of Carbons within Functional Groups B. Chemical Shifts of Carbons Adjacent to Functional Groups

A-l
A-1

ITPPENDIX V.

Summary of Synthetic Method$

A. Synthesis of Alkanes and Aromatic Hydrocarbons

A-g
A-8 A-9 A-9 A-9 A-9
A-10 A-10
A- 10

B. Synthesis of Alkenes
C. Synthesis of Alkynes

D. Synthesis of Alkyl, Aryl, and Vinylic Halides E. Synthesis of Grignard Reagents and Related Organometallic Compounds F. Synthesis of Alcohols and Phenols G. Synthesis of Glycols H. Synthesis of Ethers, Acetals, and Sulfides I. Synthesis of Epoxides J. Synthesis of Disulfides

A-10 A-10

xxx

loNrENrs K. Synthesis of Aldehydes

L. Synthesis of Ketones
M. Synthesis N. Synthesis O. Synthesis P. Synthesis Q. Synthesis R. Synthesis S. Synthesis T. Synthesis U. Synthesis

of Sulfoxides and Sulfones of Carboxylic and Sulfonic Acids

of Esters of Anhydrides of Acid Chlorides of Amides of Nitriles of Amines of Nimo Compounds

A-11 A-11 A-11 A-11 A-T2 A-T2

A-t2
A-12

A-t2
A.T2
A-13

APPENDIXVI. APPENDIXVII.

Reactions Used to Form Garbon-Carbon Bonds

Typlcal Aclditles and Baslcltles of OGanlc Functlonal
A. Acidities of Groups That Ionize to Give Anionic Conjugate Bases B. Basicities of Groups That Protonate to Give Cationic Conjugate Acids

A-13

Groups

A-14
A-14
A-15

Credits Index

c-1
l-1