Rearrangement and Pericyclic Reactions

(According to the syllabus of HEC and GCUF)

By

Dr. Muhammad Shoaib

BS, M.Phil, Ph.D
Assistant Professor of Chemistry
Government Postgraduate College
Samanabad, Faisalabad.

Dr. Tahir Mahmood

M.Sc., M.Phil, Ph.D
Associate Professor of Chemistry
Government Postgraduate College
Samanabad, Faisalabad.

Mr. Muhammad Bilal

B.S, M.Phil Chemistry Scholar

i
 Preface
Although many books are available on these two topics, these are either very advance or
small chapters are given in different books of organic chemistry. Therefore, there was a gap
between these two, which is being addressed in this booklet. Mainly it is written according to the
syllabus of HEC, GCUF and its affiliated colleges. The main speciality of this book is its colour
scheme. The intermediates are given different colours e.g. migratory groups are given a specific
colour. So, the student can easily understand which group is being migrated from migratory
origin to migratory terminus, which is also given different colours. Similar is the case with
pericyclic reactions which require an extensive differentiation between different bonding and
anti-bonding orbitals and other terms such as supraficial and antraficial etc. which is only
possible by the coloured scheme which is given here and it became very easy for the students to
understand all these.

Keeping in view the financial conditions of the majority of students, its price is kept lower
than that of photocopying any notes and material for this syllabus contents. Publishing of this
book is for the well-being of students and is not meant for business purpose. It is our first effort
so definitely, there is a lot of gap for its improvement. Authors will be highly thankful for every
suggestion to improve it. Some other booklets on advanced topics such as reactive intermediate,
photochemistry, catalysis, and protecting groups are in pipeline and will be available in the
market at the end of this year (2019) INSHA ALLAH.

In the end, thanks to our teachers and colleagues especially Prof. Dr. Abdul Jabbar (VP,
GPCSF), Mr. Zulfiqar Ali (HoD, GPCSF), Dr. Shukat Ali (UAF), Prof. Dr. Aamer Saeed Bhatti
(QAU), Dr. Muhammad Moazzam Naseer (QAU), Dr. Muhammad Yousaf Smor (GCUF), Prof.
Dr. Muhammad Kaleem Khosa (GCUF), Dr. Mtaloob Ahmad Rana (GCUF), Dr. Muhammad
Afzal Qamar, Ms. Rukhsana Kausar, Dr. Ali Bahadur, Mr. Shakeel Ahmad, Mr. Furqan Ahmad,
Mr. Amer Iqbal, Dr. Muhammad Asif Tahir and student Mr. Ishaq Khan Khaleel whose guidance
and help made us able to write this book.

No separate page is kept for the dedication and this contribution is dedicated to our
parents for their hard work, love, and kindness.

Dr. Muhammad Shoaib

03339932997
[email protected]
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 Contents
Chapter No. 1 Molecular Rearrangements ……………03--60
…
1.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 03
1.2 Terminologies used . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 03
1.3 Classification of Rearrangements . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 04
1.4 Anionotropic/Nucleophilic Rearrangements . . . . . . . . . . . . . . . . . . . . . . . . . . . . 04
1.4.1 Rearrangements to Electron-Deficient Carbon . . . . . . . . . . . . . . . . . . . 06
1.4.2 Carbocation Rearrangement without Change in Carbon Skeleton …. 07
1.4.3 Carbocation Rearrangement with Change in Carbon Skeleton. . . . . . . 08
1.4.4 Pinacol–Pinacolone Rearrangement . . . . . . . . . . . . . . . . . . . . . . . . . . 10
1.4.5 Semi Pinacol-Pinacolone Rearrangement. . . . . . . . . . . . . . . . . . . . . . . 15
1.4.6 Benzil Benzilic Acid Rearrangement. . . . . . . . . . . . .. . . . . . . . . . . . . . 16
1.4.7 Semi Benzilic Rearrangement . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18
1.5 Rearrangement Involving Diazomethane . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19
1.5.1 Reaction of Diazomethane with Ketones. . . . . . . . . . . . . . . . . . . . . . . . 19
1.5.2 Wolf Rearrangement . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21
1.5.2.1 Arndt Eistert Synthesis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24
1.6 Rearrangement to Electron Deficient Nitrogen . . . . . . . . . . . . . . . . . . . . .. . . . . 25
1.6.1 Hofmann Rearrangement. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25
1.6.2 Curtius Rearrangement. . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . 29
1.6.3 Schmidt Rearrangement. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 30
1.6.4 Lossen Rearrangement . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 32
1.6.5 Analysis of Rearrangements to Electron-Deficient Nitrogen . . . . . . . . . 34
1.7 Rearrangements to Electron-deficient Oxygen. . . . . . . . . . . . . . . . . . . . . . . . . . 35
1.7.1 Baeyer-Villiger Rearrangement . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 35
1.7.2 Dakin Reaction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 37
1.8 Cationotropic/Electrophilic Rearrangement . . . . . . . . . . . . . . . . . . . . . . . . . . . . 37
1.8.1 Rearrangements to Electron-Rich Carbon . . . . . . . . . . . . . . . . . . . . . . . 37
1.8.2 Steven Rearrangement. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 37
1.8.3 Favorskii rearrangement. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 40
1.9 Aromatic Rearrangements. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 43
1.9.1 Fries Rearrangement . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 43
1.9.2 Benzidine Rearrangement. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 46
1.10 Sigmatropic Rearrangements. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 49
1.10.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 49
1.10.2 Suprafacial and Antarafacial Shifts. . . . . . . . . . . . . . . . . . . . . . . . . . . . 49
1.10.3 [1,3] Sigmatropic Shift. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 50
1.10.4 [1,5] Sigmatropic Shift . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 51
1.10.5 [1,7] Sigmatropic Shift . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 52
1.10.6 Claisen Rearrangement . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 53
1.10.7 Cope Rearrangement . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 56
1.11 Summary. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 59
1.12 Problems. . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 60

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Chapter No. 2 Pericyclic Reactions ………………..62-102
2.1 Introduction. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 62
2.2 Characteristics of Pericyclic Reactions. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . 62
2.3 Classification of Pericyclic Reactions. . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . 62
2.4 Molecular Orbital Theory of Pericyclic Reactions. . . . . . . . . . . . . .. . . . . . . . . . . . 64
2.4.1 Construction ofMolecular Orbitals. . . . . . .. . . . . . . . . . . . . . . . . . . . 64
2.4.2 Symmetry inMolecular Orbital and Carbon-Carbon -Bond . . . . . . 67
2.5 Electrocyclic Reactions. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 69
2.5.1 Types of Electrocyclic Reactions. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 70
2.5.2 Stereochemistry of Electrocyclic Reactions. . . . . . . . . . . . . . . . . . . . . . . 70
2.5.3 Conrotatory and Disrotatory Motions in Ring-Opening Reactions .. . . . 70
2.5.4 Conrotatory and Disrotatory Motion in Ring Closure Reactions. . . . . . . 72
2.5.5 Open Chain Conjugated System Having 4nConjugated Electrons. . . 73
2.5.5.1 Thermal-Induced Ring Opening. . . . . . . . . . . . . . . . . . .. . . . . . . . . . . 73
2.5.5.2 Photo-Induced Ring Opening. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 74
2.5.6 Open Chain Conjugated System Having (4n + 2)π Conjugated Electrons 74
2.5.6.1 Thermal-Induced Cyclization. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 75
2.5.6.2 Photo-Induced Cyclization. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 75
2.5.7 Analysis of Electrocyclic Reactions . . . . . .. . . . . . . . . . . . . . . . . . . . . . . 76
2.5.8 Fukui Theory of Frontier orbitals of Electrocylic Reactions. . . . . . . . . . 77
2.5.9 Woodward Hoffmann Rules . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 79
2.5.10 Mobius-Huckel Theory for Electrocyclic Reactions . . . . . . . . . . . . . . 80
2.6 Cycloaddition Reactions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 84
2.6.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 84
2.6.2 Notation about Cycloaddition Reaction. . . . . . . . . . . . . . . . . . . . . . . . . 84
2.6.3 Theory of Cycloaddition Reaction: FMO Method. . . . . . . . . . . . . . . . . 86
2.6.4 [2 + 2] Cycloaddition Reactions. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 86
2.6.5 [4 + 2] Cycloaddition Reactions. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 87
2.6.6 Diels-Alder Reactions. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 87
2.6.6.1 Dienes and Dienophiles. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 88
2.6.6.2 Mechanism and Stereochemistry of Diels Alder Reactions . . . . . . . . 89
2.6.6.3 Endo and Exo Stereochemistry. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 91
2.6.6.4 Orientation Effects in Diels-Alder Reactions. . . . . . . . . . . . . . . . . . . . 92
2.6.6.5 Intramolecular Diels-Alder Reactions. . . . . . . . . . . . . . . . . . . . . . . . . . 93
2.6.7 Woodward-Hoffmann Rule for Cycloaddition Reactions. . . . . . . . . . . . 95
2.6.8 Frontier Orbitals Description of [4 +2] Cycloadditions. . . . . . . . . . . . . 96
2.6.9 Mobius-Huckel Theory for Cycloaddition Reactions. . . . . . . . . . . . . 98
2.7 Summary. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 100
2.8 Problems. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 101
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 102

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Chapter No. 1
Molecular Rearrangements
1.1 Introduction
In most organic reactions the functional group of the substrate undergoes structural change
without affecting the carbon skeleton of the molecule. There are however many other organic reactions
in which an atom or group of atoms (alkyl or aryl) is shifted from one position to another within the
substrate molecule itself, giving a new isomeric product are called as rearrangement reactions. In other
words, we can say that the reactant undergoes a reorganization or reshuffling of bonds and atoms. The
connectivity of the atoms in the product is changed as compared to the connectivity of the atoms in the
reactants. Rearrangement may be intramolecular or intermolecular and therefore migration of a group
occurs from one carbon atom to another within the same molecule or from one molecule to another.

where, A - Migratory origin

B - Migration terminus
W- Migrating group
Generally, the migrations occur from an atom to an adjacent one are called as 'Whitmore’ 1,2-
shifts, however, longer distance migrations are also possible.
1.2 Terminologies used
Shift/Migration: The change in position of an atom or a group of atoms is known as shift or
migration.
Migratory Group: The group whose position is changed is known as migratory group. ‘W’ is a
migratory group in the above example.
Migration Origin: The point of atom or site, from where migration starts is known as migration origin.
‘A’ is migration origin in the above example.
Migration Terminus: The atom or site, where migratory group attaches is known as migration
terminus. ‘B’ is migration terminus in the above example.
Migratory Aptitude: Trends, in which one migratory group preferably migrate and another
group remains as such attach to migration origin is known as migratory aptitude.

In this general example, two groups Y and Z are attached to A. But, the only Z migrates due to
its high migratory aptitude.

3
1.3 Classification of Rearrangements
Rearrangements can be classified into the following types on the basis of substrate and nature of
the migratory group (whether a migratory group migrates along with its electrons or not).
i. Anionotropic/Nucleophilic rearrangement
ii. Cationotropic/Electrophilic rearrangement
iii. Free radical Rearrangement
iv. Aromatic Rearrangement
v. Rearrangement involving cyclic transition state (Sigmatropic Rearrangement)
1.3.1 Anionotropic/Nucleophilic rearrangement
The rearrangement, in which the migratory group goes along with its bonding electrons pair to
an electron-deficient centre is known as anionotropic or nucleophilic rearrangements i.e. the migratory
group goes in the form of anion. It is the most common type of rearrangement.

The rearrangement of acyl nitrene into isocyanate is an example of this rearrangement.

Characteristics
i. Migration terminus should be electron deficient.
ii. Electron donating groups facilitate the migration.
iii. Migratory aptitude decreases in the order as; Phenyl > 3°Alkyl > 2° Alkyl > 1°Alkyl
1.3.2 Cationotropic/Electrophilic rearrangement
Such type of rearrangement, in which the migratory group goes without its bonding electrons pair
to an electron-rich centre is known as cationotropic or electrophilic rearrangement. In this rearrangement,
the migratory group goes in the form of cation. These rearrangements are less common and when a
migrating group is hydrogen then such rearrangement is called prototropic rearrangement.

4
Characteristics
i. Migration terminus should be electron-rich.
ii. Electron withdrawing groups facilitate the migration.
iii. Migratory aptitude decreases in the order of Phenyl > 1°Alkyl > 2° Alkyl > 3°Alkyl
1.3.3 Free radical rearrangement
Such a type of rearrangement, in which the migratory group migrates along with a single electron.
In this rearrangement, the migratory group goes in the form of a free radical. It is very rare, as there is
much less tendency for a 1° or 2° carbon free radical to rearrange than the corresponding carbocation.

Characteristics
i. The migratory group migrates along with a single electron.
ii. Electron donating groups facilitate the migration.
iii. Migratory aptitude decreases in the order as; Phenyl > 3°Alkyl > 2° Alkyl > 1°Alkyl
1.3.4 Aromatic rearrangements
Rearrangement in which migrating group is shifted from one position to another in an aromatic
system or from a side chain to the aromatic nucleus takes place is known as aromatic rearrangement. The
rearrangement of alkylbenzene to their isomers is observed after IPSO attack. The alkyl migration in these
cases is typical of carbocation intermediate.
These rearrangements involve the migration of a group Y, from a substituted hetero atom X to
the activated positions of the aromatic nucleus e.g. ortho and para positions of the benzene ring.

The rearrangements may be classified on the basis of hetero atoms bearing the migrating groups.
The element X is most commonly nitrogen and in some cases oxygen. Both intermolecular and
intramolecular migrations are known for this type.

5
1.3.5 Sigmatropic rearrangement
Sigmatropic rearrangement involves the migration of a σ-bond that is flanked by one or more
conjugated systems to a new position within the system. The reaction is termed [i,j] sigmatropic shift
when the bond migrates from position [1,1] to position [i,j]. For example, a carbon-hydrogen bond move
across a diene. It is an example of [1,5] sigmatropic rearrangement.

Characteristics
i. The number of sigma and pi-bonds remains the same during rearrangement.
ii. Generally takes place by heat or light only.
iii. Just re-location of sigma bond takes place.
iv. Conjugated system must be needed.
All the above-mentioned rearrangements are given in detail along with examples, mechanisms
and synthetic applications.

1.4 Anioniotropic Rearrangements

1.4.1 Rearrangements to electron-deficient carbon (Carbocation rearrangement)
Carbocation intermediates are generated in the course of various types of reactions, e.g.,
(i) Solvolytic substitution and elimination reactions
(ii) Protonation of alcohols, ethers, alkenes, alkynes, etc.
(iii) Decomposition of diazonium salts etc.
If the carbocation generated in a reaction is unstable, it rearranges to a more stable carbocation by 1,2
shift so that rearrangement is observed in the product. Thus, the driving force of the rearrangement is the
stability of the carbocation which depends on the dispersal of the positive charge on the carbon. The
dispersal of the charge increases with substituents on the cationic carbon by inductive and
hyperconjugative effects. Conjugation of cationic carbon with -electrons increases the stability further
and may reverse the rearrangement.

6
 Thus, the stability order of carbocations is:

Initially formed carbocation and the rearranged carbocation may undergo various substitution
and elimination reactions to yield several products with or without change in the carbon skeleton. This is
illustrated below in detail.
1.4.2 Carbocation rearrangement without change in the carbon skeleton
On diazotization and removal of nitrogen, 1-aminobutane produces 1-butyl cation (1°) which
rearranges to 2-butyl cation (2°). Both 1° and 2° carbocations in the presence of suitable reagent, undergo
substitution and elimination to give alcohols and alkene.

No change in the carbon skeleton of the product is observed. Since stable carbocation has a longer
life, the yield of the product formed through 2° carbocation (2-butyl) is higher than the initially formed
less stable 1° carbocation (1-butyl). This is reflected by the higher yield of 2-butanol as compared to 1-
butanol.
Allylic rearrangement: Another most widely recognized example of this class of rearrangement
is the substitution at an allylic position in which the double bond migrates from one position to an adjacent
position with consequent rearrangement of the carbocation. Thus, solvolysis of 3-chlorobut-1-ene in
EtOH by SN1 path gives two isomeric ethers, 3-ethoxybut-1-ene and 1-ethoxybut-2-ene.

7
 With NaOEt in high concentration, the reaction follows SN2 path with no rearrangement.

However, when the alpha carbon is substituted with bulky groups, direct SN2 displacement with
allylic rearrangement is observed.

1.4.3 Carbocation rearrangement with change in the carbon skeleton

In the presence of Lewis acid, cracking of petroleum produces straight-chain carbocations, which
undergo rearrangements to form branched-chain products. The process has been commercially utilized
for producing anti-knock fuels for automobiles.

Another example is the interconversion of methylcyclopentane and cyclohexane.

In the presence of acids, carbocations generated from alkenes readily undergo rearrangement to
form products with a change in the carbon skeleton.

8
 In the F.C alkylation, alkyl cations are rearranged before reaction with the nucleophile.

Neopentyl rearrangement: Hydrolysis of neopentyl bromide under SN1 conditions gives 2-

methyl-butane-2-ol instead of the expected neopentyl alcohol.

Along with 2-methyl-butane-2-ol, 2-methylbut-2-ene is also obtained. This is due to the

rearrangement of 1° carbocation which rearranges to 3° carbocation.

Reaction under SN2 conditions is slow due to steric factors. However, neopentyl bromide forms
neopentyl ethyl ether by SN2 reaction with sodium ethoxide and no rearrangement takes place.

The phenyl analog of neopentyl-type bromide does not rearrange due to the greater stability of
the benzyl cation over 3° carbocation.

Demjanov rearrangement: The rearrangement of the carbocations generated during the

deamination of alicyclic primary amines is known as Demjanov rearrangement. The rearrangement
results in substitution, elimination and ring contraction or expansion. Thus, cyclobutylamine on treatment
with nitrous acid gives a mixture of cyclobutanol and cyclopropylcarbinol; the latter with ring contraction.

9
 If cyclobutyl methylamine (A) is treated with nitrous acid, four products are obtained, viz.,
cyclobutylcarbinol (02), cyclopentanol (04), methylene cyclobutene (01) and cyclopentene (03) in which
ring expansion is observed in (03) and (04)

 Ring retention: The phenomenon in which the size of the ring remains the same.
 Ring expansion: The phenomenon in which the size of the ring is increased.
 Ring contraction: The phenomenon in which the size of the ring is decreased i.e. an n-membered
ring is converted into a less than n-membered ring.
It is observed that when the positive charge is on the alicyclic ring, the migration of ring
methylene causes ring contraction (I). When the positive charge is placed on the α-carbon outside the
alicyclic ring, expansion of the ring occurs (03) & (04). By this rearrangement, seven- and eight-
membered rings can also be prepared.

1.4.4 Pinacol-Pinacolone rearrangement

Pinacol (2,3-dimethyl-2,3-butanediol) is a vicinal diol, which on treatment with H2SO4 produces

3,3-dimethyl-2-butanone, commonly known as pinacolone (methyl-t-butylketone). The name was given
from the classical example of the conversion of pinacol to pinacolone.

10
 In the presence of H2SO4, it gives a 70 % yield of pinacolone.
Characteristics
 Anionotropic rearrangement ‘C’ to electron deficient ‘C’ migration.
 Electron donating groups attached to the migrating group increase the rate of reaction.
 Mineral acids like H2SO4, HCl, and HBr, etc. are used.
 R group may be aryl or alkyl.
 Elimination of water without rearrangement reaction of alcohols may be achieved under drastic
conditions (Al2O3,450 °C).

Mechanism
The reaction involves the general characteristics of carbocation rearrangement in which the
driving force is the stabilization of the resulting carbocation. The reaction starts with the protonation of
the hydroxyl group followed by elimination of water and formation of carbocation (I). The carbocation
is then stabilized by Whitmore 1,2-shift. Finally, the elimination of a proton from the stable carbocation
(II) gives the carbonyl compound.

The carbocation (I), though tertiary, prefers to form (II) for its resonance stability. The
mechanism is supported by the fact that any carbocation in which the positive charge is on the carbon
adjacent to the one bearing the hydroxyl group also undergo a similar type of rearrangement.
Migratory aptitude: The group with more electron donation has a greater migratory aptitude.
The ease of migration of different groups is in the order: H >>Aryl >> Alkyl

11
 The migratory aptitude of the alkyl group with a longer chain is greater. For example, the
migratory aptitude of Pr- is greater than Et- and that of Et- is greater than Me. The migratory aptitude of
iso-propyl is greater than n-propyl. Ethyl migrates faster than methyl because it give more hyper-
conjugating stable carbocation than methyl. The migratory aptitude of iso-propyl is greater than n-propyl.

Mechanism

As the migrating group migrates with its electron pair, the more nucleophilic group might be
expected to migrate. Thus, the order of migration amongst the aryl groups is

12
 Obviously, electron-withdrawing groups will retard the migration. However, the stability of the
initially formed carbocation may offset the order of migratory aptitude. The initial carbocation is formed
by the loss of that hydroxyl group which results in the formation of the most stable carbocation. Thus, in
1,1-dimethyl-2,2-diphenyl glycol, the resonance-stabilized carbocation is formed and it is the methyl
group which migrates.

Steric hindrance may affect the rate of migration e.g. p-anisyl group migrates 1000 times faster
than the o-anisyl group. The migrating group attacks from the antiperiplanar (backside) to the leaving
group. This has an important effect on cyclic systems. Thus, the two isomers of 1,2-dimethylcyclohexane-
1,2-diol give different products due to different orientations of the methyl and hydroxyl groups. The one
in which the Me- and -OH groups are trans to each other gives 2,2-dimethylcyclohexanone by methyl
shift. The other in which the Me- and -OH groups are cis to each other undergo a shift of ring methylene
instead of Me-shift with consequent ring contraction to give 1-acetyl-1-methylcyclopentane.
1-Methyl-2-phenylcyclohexan-1,2-diol is converted into 2-methyl-2-phenylcyclohexan-1-one
through rearrangement in the presence of an acid.

13
Mechanism

Trans-1,2-dimethylcyclohexan-1,2-diol is converted into 1-(1-methylcyclopentyl)ethan-1-one in

the presence of an acid.

Synthetic Applications
i. Synthesis of carbonyl compounds from alkenes
Isobutyraldehyde may be prepared on a large scale from isobutylene

14
 ii. Ketones from cyclic diols
It is employed to prepare ketones which are otherwise very difficult to synthesize.

Many sterically hindered ketones can be produced by this rearrangement.

iii. Synthesis of Spiro-compounds

This rearrangement provides a synthetic route for the synthesis of spiro-compounds.

1.4.5 Semi Pinacol-Pinacolone rearrangement

In semi pinacol-pinacolone rearrangement, one hydroxyl group must be present in the substrate
along with the other good leaving group such as N2, -OTS, -X, etc.
i) Deamination of Amino alcohol (Tiffeneav-Demjanov Rearrangement)
When amino alcohol is treated with HNO2 (produced in-situ by mixing NaNO2 with HCl at low
T), the amino group (NH2) is converted into a diazonium group (N2+). Nitrogen (N2) is the best leaving
group and leaves to form a carbocation which is then rearranged to give a ketone.

Mechanism

2-Aminocyclohexanol is converted into cyclopentanecarbaldehyde in the presence of nitrous

acid. Ring contraction occurs as six-membered ring changes into a five-membered ring.
15
 2-(Aminomethyl)cyclohexanol is converted into cycloheptanone in the presence of nitrous acid.
Ring expansion occurs as a six-membered ring changes into a seven-membered ring.

ii) Dehalogenation of Haloalcohol

Haloalcohol or hydroxy halide is treated with AgNO3 in an aqueous medium. AgX is
precipitated and settled down leaving behind a carbocation. Halides e.g. -Cl and -Br are good
leaving groups.

iii) Tosyl as a Leaving Group

In this rearrangement, a less-hindered hydroxyl group is converted to tosyloxy group (-
OTs). TsOH easily leaves forming a carbocation. This carbocation rearranges to give a ketone
and ring expansion occurs. Tosyl is a bulky group and replaces hydrogen of the hydroxyl group,
which is not sterically hindered.

Tosyl group (-Ts) Tosyl chloride (TsCl) Tosyl alcohol (TsOH)

Synthetic applications
This rearrangement is used for the synthesis of seven- and eight-membered rings. Cyclohexanone
can be converted to cycloheptanone in good yield.

16
1.4.6 Benzil-Benzilic Acid Rearrangement
The addition of a strong base to a carbonyl group results in the formation of anion. The reversal
of the anionic charge may cause expulsion of the attached group, X, e.g.,

However, in a 1,2-diketone the group X may migrate to the adjacent electron-deficient carbonyl
carbon forming -hydroxy acid. The base-catalyzed rearrangement of -diketones (usually aromatic) to
yield - hydroxy acids in their salt form is known as benzil-benzilic acid rearrangement. Thus, benzil on
treatment with a strong base forms benzilic acid (salt), hence the name benzylic acid rearrangement.

Phenoxide ions are too weak nucleophile to attack. Besides aromatic 1,2-diketones, aliphatic and
heterocyclic diketones as o-quinones undergo this rearrangement.

Mechanism
It has been seen that the rate of reaction is proportional to the concentrations of benzil and the

hydroxide ion, i.e., Rate ∝ [-OH][-diketones]. It has also been found that when the reaction is carried
out in the presence of H2O18, benzil exchanges 18O faster than it rearranges. On the basis of these
observations, it was suggested that a fast reversible nucleophilic attack occurs at the carbonyl carbon in
the first step. The second step is the rate-determining step (RDS) in which the migration occurs. Finally,
a rapid proton transfer completes the process.

17
Characteristics
 Anionotropic rearrangement ‘C’ to electron-deficient ‘C’ migration.

 Bases like KOH, NaOH are used.

 Bronsted acids like H2SO, HCl, etc. are used for the hydrolysis step.

 ‘R’ group may be aryl or alkyl.

 Rate ∝ [OH][alpha diketones]

The carbonyl group which is attached to the less electron releasing of the two aryl groups is
relatively more positively charged and hence, is attacked by -OH. Consequently, the less electron-
donating aryl group migrates to the other carbonyl group.

Synthetic Applications (Synthesis of alpha-hydroxy acids)

This rearrangement is a good synthetic route for the synthesis of alpha-hydroxy acids.

i. Citric acid is generated from ketipic acid by this rearrangement.

Some other examples are

ii.

18
 iii.

Some aliphatic 1,2 diketones give this rearrangement reaction

iv.

1.4.7 Semi Benzilic Rearrangement

Similar benzilic acid rearrangement is observed when halo-ketones which do not have any
hydrogen is treated with alkoxides. This reaction is known as semi-benzilic rearrangement.

This reaction has great synthetic use in synthesis of important drug e.g

1.5 Rearrangements Involving Diazomethane

The resonating structures of diazomethane are:

The diazomethane act as nucleophile and is a good source of carbene (:CH2), which is an
intermediate.

19
 1) Diazomethane can be prepared by primary amines by reacting it with nitrous acid produced in-
situ by mixing sodium nitrite (NaNO2) and hydrochloric acid (HCl).

2) Diazomethane can also be prepared by N-nitrosotoluene-p-sulphonamide in the presence of a

base.

Diazomethane takes part in two types of reaction which lead, to the insertion of a methylene
group into a chain of carbon atoms.

1.5.1 Reactions of diazomethane with ketones

Characteristics
 It is an anionotropic rearrangement.
 It is carbon to electron-deficient carbon migration.
 Electron donating groups attached to the migrating group increase the rate of reaction.
 If unsymmetrical ketone is used, a mixture of products is obtained.
 If O- attack the epoxide is formed.

Migratory aptitude: In an unsymmetrical ketone, the group which is better able to supply
electrons will migrate. Amongst the alkyl group, the ease of migration is tertiary> secondary> primary>
methyl.

20
 Amongst aryl groups, the order is, p-methoxyphenyl > p-tolyl > phenyl > p-chlorophenyl, etc.
Aryl groups migrate in preference to primary alkyl groups.

In the case of cyclic ketones, ring expansion occurs.

In the case of substituted cyclic ketone CH2 is inserted to the side having more electron-
donating group.

1.5.2 Wolff Rearrangement

Conversion of α-diazocarbonyl compound into a ketene on treating with silver oxide (Ag2O)
and H2O, is known as Wolff rearrangement.

Characteristics
 Degradation of α-diazo carbonyl compound occurs.
 It is an anionotropic rearrangement.
 It is carbon to electron-deficient carbon migration.
 Electron donating group attached to migrating atom increases the rate of reaction.
 Removal of N2 takes place in the synthesis of ketene.
 The reaction occurs in the presence of moist Ag2O.

Wolff rearrangement generates ketene in the absence of any nucleophile. However, when this
rearrangement is carried out in the presence of water, alcohol or amine, the ketene is converted into
carboxylic acid, ester or amide, respectively.

21
 Ketene can react with Product formed

Water Carboxylic acid

Alcohol Ester

Amine Amide

Treatment of ketene with water

When ketene reacts with water, a carboxylic acid is formed with a CH2 insertion into the C-chain.
This is known as homologation. The carboxylic acid has one more carbon than the starting carboxylic
acid.

22
Treatment of ketene with alcohol to form an ester

Treatment of ketene with ammonia or its derivative to form amide

Examples

Two-fold Wolff rearrangement in the bis-homologation of dicarboxylic acid is reported when the
substrate is cis substituted cyclohexane. The bis-ketene which cannot be isolated must have the same
stereochemistry because the dimethyl ester formed from bis-ketene by addition of methanol still is cis
disubstituted cyclohexane. The migrating group migrates with retention in configuration.

Synthetic applications
i. Synthesis of ring contracted carboxylic acid
Wolff rearrangement is of particular importance in preparing ring contracted carboxylic acids via
cyclic alpha diazoketone.

23
 The double bond in the substrate remains unaffected

ii. Synthesis of homoveratroyl chloride, an intermediate for papaverine synthesis.

iii. Synthesis of mescaline

1.5.2.1 Arndt Eistert synthesis

Arndt-Eistert reaction is a method to convert a carbonyl compound (e.g. carboxylic acid) to its
higher homologue (i.e. contains one additional carbon atom). Acid chlorides react with diazomethane to
give diazoketones, which rearranges with loss of nitrogen. In the presence of moist Ag2O give ketene.
The ketene is subsequently converted to its higher carboxylic acid homologue.

A higher homologue of an optically active acid (I) obtained by Arndt–Eistert–Wolff

rearrangement which on degradation by Barbier–Weiland method give the original acid with the same
configuration (Lane and Wallis).

24
 The conversion of α-amino acid to β-amino acid can be done by Arndt Eistert synthesis.

1.6 Rearrangement to Electron-Deficient Nitrogen

This is a group of closely related rearrangements in which carbon migrates from carbon to
nitrogen. They may be formulated generally as,

Where R is an alkyl or aryl group and -X is a leaving group which maybe

-Br (Hofmann rearrangement)
-N=N (Curtius and Schmidt rearrangements)
-OCOR (Lossen rearrangement)
In each case, if the alkyl carbon which migrates is asymmetric, it retains its configuration.

1.6.1 Hofmann rearrangement

This reaction was discovered by a German chemist August Wilhelm von Hofmann. Conversion
of an amide into an amine with one less ‘C’ by the action of base and bromine in the presence of water is
known as Hofmann rearrangement.

Characteristics
 Hofmann degradation of amides.
 This is an intramolecular rearrangement i.e. 1,2-shift.
 Rearrangement to electron deficient nitrogen (migration terminus).
25
  Alkyl, aryl or phenyl group migrate during rearrangement
 Only N-unsubstituted amides give this rearrangement.
 The rearrangement results in the shortening of the carbon chain.
 Retention of configuration at the chiral centre of the migrating group takes place.
 Alkyl isocyanate is intermediate.
 Anionotropic rearrangement ‘C’ to ‘N’ (electron deficient) migration.
 Electron donating group attached to migrating atom increase the rate of reaction.
 Base - NaOBr acts as a strong base.
 R group - Aryl or Alkyl, If R = Alkyl with 6, 7 carbons then yields are quite low.
An acid amide is treated with sodium hypobromite, or bromine in alkali. The N-bromo-amide is
formed and reacts with the hydroxyl ion to give its conjugate base which is then rearranged. The
isocyanate which is produced may be isolated in anhydrous conditions, but the reaction is normally
carried out in aqueous or alcoholic solution in which the isocyanate is converted into an amine or a
urethane, respectively.

Mechanism

Migratory Aptitude: There is only one migratory group present in the following molecule. So
the preference of migratory group within a molecule is not present.

26
 The presence of electron-donating groups in aromatic moieties increases the rate of reaction and
vice versa.
Synthetic Applications
This rearrangement provides an efficient route for preparing aliphatic and aromatic primary
amines.
i. Synthesis of β-alanine
β-alanine can be obtained in about 45% yield by treating succinimide with bromine and aqueous
potassium hydroxide, reaction occurs through the half-amide of succinic acid.

ii. Synthesis of Anthranilic acid

Anthranilic acid may be obtained in a similar way from phthalimide.

iii. Synthesis of 3-aminopyridine (β-aminopyridine)

A useful example of the reaction is the preparation of β-aminopyridine (65 to 70%) from nicotinamide
(available from natural sources), as it cannot be obtained in good yield via nitration of pyridine.

27
 iv. Synthesis of 4-Aminopyridine from Pyridine-4-carboxamide

v. Synthesis of Aniline from Benzamide

vi. Synthesis of Methylamine from Acetamide

vii. Formation of Nitriles

Acetylenic amides from nitriles using Hofmann's reaction.

viii. Synthesis of Hydrazine from Urea

Urea gives hydrazine when subjected to Hofmann reaction.

ix. Synthesis of m-Bromoaniline from Benzoic Acid

Meta-bromoaniline can be synthesized from benzoic acid.

1.6.2 Curtius Rearrangement

The Curtius rearrangement (or Curtius reaction or Curtius degradation), first defined by Theodor
Curtius in 1885. Thermal rearrangement of acid azides in non-aqueous solvents such as chloroform,
benzene or ether to an isocyanate, is known as Curtius rearrangement.

28
 Isocyanate on hydrolysis gives primary amines. The reaction converts acid azides into amine with
loss of carbon.
Characteristics
 Curtius degradation of acid azide.

 Anionotropic rearrangement.

 Migration from C to electron-deficient N atom.

 Electron donating group attached to migrating atom increase the rate of reaction.

 Applicable to acid azides of almost all kinds of acids; aliphatic, aromatic, alicyclic,
heterocyclic.

 Isocyanate formed can be isolated in good yields in aprotic solvents.

 Reaction when carried out under aqueous or alcoholic media results into amines or carbamate
ester as products.

Generation of acid azide

29
From carboxylic acid

Mechanism

Synthetic Applications
Synthesis of Glycine: This method is used for the synthesis of aliphatic, aromatic or heterocyclic
amines. α-amino acid may also be synthesized by this method.

1.6.3 Schmidt Rearrangement

Carboxylic acids react with hydrazoic acid in the presence of concentrated sulfuric acid to give
isocyanate directly. Reaction occurs through the acid azide, but under strongly acidic conditions it is
present in the form of conjugate acid from which nitrogen is lost without heating.

30
Characteristics
 Anionotropic rearrangement.

 Migration from C to electron-deficient N.

 Electron donating group attached to migrating atom increase the rate of reaction.

 Conversion of carboxylic acid to primary amine occurs in one step.

 R = Alkyl, Aryl, If R = Alkyl, yields good, R = Aryl, yields variable.

 Commonly used catalyst is H2SO4, lewis acids can also be used.

Ketones react with hydrazoic acid under strong conditions and give amides.

With unsymmetrical ketones, two isomeric amides can be formed. However, with alkyl aryl
ketone, it is usually an aryl group that migrates. For instance, acetophenone gives acetanilide.

31
 Since the hydrolysis of amide gives amines it is a convenient two-step procedure for the
conversion of ketones into amines. The product of Schmidt's reaction in ketones is amide but aldehyde
mainly gives a mixture of nitriles and N-formyl derivatives.

Synthetic Applications
i. Synthesis of Caprolactam: A useful application of Schmidt rearrangement is the synthesis of
caprolactam from cyclohexanone. Caprolactam upon alkaline polymerization gives nylon-6.

ii. Synthesis of other useful compounds

A synthetically useful example is the conversion of cyclobutanecarboxylic acid into
cyclobutylamine.

Similarly

32
1.6.4 Lossen Rearrangement
This rearrangement name is derived from scientist name that is Wilhelm Clemens Lossen (1838-
1906). The rearrangement of acyl derivative of hydroxamic acid to isocyanate followed by the hydrolysis
to the corresponding amine is known as Lossen rearrangement.

Characteristics
 Anionotropic rearrangement.

 Migration from C to electron-deficient N atom.

 Electron donating group attached to migrating atom increase the rate of reaction.

 Runs through o-acyl, phosphoryl intermediated which are derivative of hydroxamic acid.

 Isocyanate formed can be isolated in good yields in aprotic solvents.

Preparation of hydroxamic acid
From aldehydes

From Carboxylic acid derivatives

The Lossen rearrangement involves the generation of an isocyanate via thermal or base-mediated
rearrangement of an activated hydroxamate which can be generated from the corresponding hydroxamic
acid. Activation of the hydroxamic acid can be achieved through O-acylation, O-arylation, or O-
sulfonylation.

Preparation of Hydroxamic acid derivatives

33
Mechanism

Synthetic Applications
i. Preparation of carbamates and amines
With this background, recent examples of the Lossen rearrangement in synthesis include methods
for the preparation of carbamates and amines via environment-friendly routes. For the carbamate product,
a catalytic procedure by tertiary amine bases was achieved, avoiding large amounts of by-product and
offering the possibility for recycling of solvents. Dimethyl carbonate proved to be efficient in situ
activator and has the benefit of being a relatively nontoxic reagent. A range of aliphatic methyl carbamates
were isolated in good yields under mild conditions.

1.6.5 Analysis of Rearrangement to electron-deficient nitrogen

Of these four related processes, the Lossen rearrangement is the least useful in the synthesis of
amines because hydroxamic acids are not readily available. The Schmidt reaction is the most direct
method but is only applicable if the acid does not contain groups which are sensitive to concentrated
sulfuric acid. The Curtius rearrangement involves the mildest conditions but requires the preparation of
the azide (explosive nature). The Hofmann rearrangement is convenient providing that other functional
groups in the molecule do not react with bromine and alkali.

34
1.7 Rearrangement to electron-deficient oxygen
Following are the anionotropic rearrangements to the electron-deficient oxygen atom.
1.7.1 Baeyer-Villiger Rearrangement (Baeyer-Villiger oxidation)
It is the type of rearrangement in which ketones are converted into esters and cyclic ketones into
lactones, by treatment with a peracid.

Commonly used peracid or peroxyacid used are trifluoroperacetic acid, perbenzoic acid, peracetic
acid, performic acid, and monoperoxypthalic acid, etc.
Characteristics
 Anionotropic rearrangement.
 Migration from C to electron-deficient ‘O’.
 Electron donating group attached to migrating atom increase the rate of reaction
 A buffer solution (Na2HPO4) must be added to prevent trans-esterification.
Mechanism

A typical example of Baeyer-villiger oxidation is the reaction of acetophenone with perbenzoic

acid at room temperature to produce phenylacetate.

35
 Another example is the reaction of α-diketones with peracid which gives anhydride.

Migratory aptitude: In an unsymmetrical ketone, that group migrates which is the better able to
supply electrons. Amongst the alkyl group, the ease of migration is tertiary> secondary> primary>
methyl.

Amongst aryl groups, the order is, p-methoxyphenyl > p-tolyl > phenyl > p-chlorophenyl, etc.
Aryl groups migrate in preference to primary alkyl groups.

Synthetic Applications
Baeyer-Villiger rearrangement has great synthetic utility as it permits the transformation of ketones
into esters i.e. oxygen is inserted next to the carbonyl group.
i. Synthesis of Lactones: Baeyer-villiger rearrangement is a very useful method for the
synthesis of cyclic ester called lactone.

36
ii. Synthesis of acid anhydride: Only α-diketones react with peracid to produce anhydrides while
all other diketones do not react with peracid.

iii. Synthesis of medicinal compounds

Baeyer–Villiger oxidation induced by fungus that produces Baeyer-Villiger monooxygenases, is
used to transform the dehydroepiandrosterone (androstenolone) to an anticancer agent. This reaction was
discovered in 2013 by Alina Swizdor.

iv. Elucidation of structure

The ester obtained as a result of the rearrangement may be hydrolyzed to acid and alcohol from which
the structure of the substrate can be determined. The reaction is not successful with aldehydes. Aliphatic
aldehydes are oxidized to acids by the migration of the hydrogen.

Aromatic aldehydes have been converted to formates by the migration of the aryl group.

1.7.2 Dakin Reaction

In Dakin reaction benzaldehyde containing ortho- and para- hydroxyl groups are converted into
catechol and quinols respectively by alkaline hydrogen peroxide.
Mechanism

37
 This mechanism is similar to Baeyer-Villiger oxidation.
Synthetic Applications
Synthesis of Diphenols: The Dakin reaction is used to synthesize diphenols

1.8 Cationotropic Rearrangement

1.8.1 Rearrangements to Electron-Rich carbon (Carbanion rearrangement)
The following examples include migration towards electron-rich carbon only. The
rearrangements involving other electron-rich hetero atoms are rare and are not discussed here.
1.8.2 Stevens Rearrangement
In the Stevens rearrangement, keto-quaternary ammonium or tertiary sulphonium salts rearrange
to amino or mercapto ketones under the influence of strong base. Quaternary ammioun ion which contains
β-hydrogen atoms undergoes E2 (Hofmann elimination reaction) with base.

If, however, none of the alkyl groups possesses β-hydrogen atom but one has a β-carbonyl group,
then α-hydrogen is removed by base to give an ylide (Ylide: negatively charged carbon atom directly
bonded to a positively charged atom of sulfur, phosphorus, nitrogen, or another element) followed by
rearrangement. The rearrangement does not proceed readily when benzoyl group is replaced by phenyl
or alkyl group. The role of the carbonyl group is to assist the formation of the ylide by stabilizing the
negative charge.

Characteristic
 Cationotrophic rearrangement.

 Migration from N to electron-rich C atom occurs.

 Electron withdrawing groups attached to migrating atom increase the rate of reaction.

38
 When the rearrangement is carried out with optically active ammonium ion, then the migrating
group migrates with retention of configuration. The migrating group may be allyl, benzhydryl, or
phenacyl, etc.

When various substitutions are placed in the meta or para position of the benzyl group the rate of
reaction is increased in the order of electron-withdrawing ability of the substituents. In contrast, para
substituent in the phenacyl group increases the rate of rearrangement with the order of their electron
releasing ability. The rearrangement is retarded by the presence of electron-withdrawing substituents in
the phenacyl because of the lower electron density at the negatively charged attacking carbon. The
rearrangement occurs in a concerted manner, probably via formation and combination of radical pair.

The methylene group of a propargyl moiety is similar in chemical behavior to an active methylene
group adjacent to a carbonyl group because of the acidity of α-carbon atom of the acetylenic functional
group. The propargyl group has been shown to the capable of acting as both the migrating group and the
migration terminus in stevens rearrangement, that it forms a carbonanion and promotes the cleavage of
C-N bond. In the following example, the propargyl group act as a migrating group and phenaceyl group
act as a migrating terminus.

39
 When benzyl or allyl group is present instead of phenacyl group then propargyl group act as a
migration terminus.

Similar rearrangements have been observed with sulphonium salt under drastic conditions, e.g.
benzyl methyl sulphonium ion gives a-methyl mercapto-α-benzyl acetophenone.

1.8.3 Favorskii Rearrangement

The transformation of -halo-ketones to esters with rearranged carbon skeleton by the treatment
with alkoxide ions is called Favorskii rearrangement. Alkali hydroxides or amines in place of metal
alkoxides give acids or amides respectively.

Cyclic – -halo-ketones give esters with ring contraction.

40
Characteristics
 Electrophilic, carbanion rearrangement or cationotropic rearrangement.
 Electron withdrawing groups attached to migrating atom increase the rate of reaction.
 The product is rearranged to carbon skeleton with the equal number of ‘C’ atoms.
 Carbon to Carbon migration.
 Halogen are usually Cl–, Br– but not I–
 Base- Only alkoxide ions give the reaction acting as a powerful base; while other bases like
–OH, amines, etc. give carboxylic acids or amides respectively.
Mechanism
When halo ketone reacts with base to enolate ion is produced which then rearranged to formed
an ester via cyclopropanone. When cyclopropanone is formed then the ring is opened in that direction to
produce more stable of the two possible product carboanion is formed. Alkyl group destabilizes the
carboanion and the aryl group stabilizes the carbanion by delocalization of negative charge. It is an
intramolecular rearrangement. In this arrangement migratory group move without its electrons to
electron-rich centre.

The base abstracts an α-hydrogen to produce a carbanion and then intramolecular nucleophilic
attack on the carbon bearing the chlorine takes place and displaces the chloride with the formation of a
transient symmetrical cyclopropanone. Subsequent attack of the alkoxide ion on the carbonyl carbon
opens the ring with equal ease on either side of the carbonyl carbon so that the product contains 50% of
C at the -position and 50% at the β-position.
14

41
 In the case of unsymmetrical ketones, the unsymmetrical cyclopropanone ring which is
formed, opens up to give the most stable carbanion. Thus, the two isomeric ketones (I) and (II)
give the same cyclic intermediate (III) which may open on either side of the carbonyl group to
give two carbanions (IV) and (V).

Mechanism

The carbanion (IV) being resonance-stabilized is preferentially formed so that the

product is VI. Hence, both (I) and (II) give the same product.

42
Synthetic Applications
i. The halo ketones will arrange to amide when it reacts with amine.

ii. This rearrangement is used for ring contraction in the cyclic system.

iii. It is used for the synthesis of highly strained carboxylic acid. An interesting example is
the conversion of the cyclobutyl into cyclopropyl system

1.9 Aromatic rearrangements

1.9.1 Fries rearrangement
Phenolic esters on heating with aluminium trichloride (Lewis acid) give o- and p- acyl phenol is
known as Fries rearrangement.

In this reaction, a mixture of ortho- and para-isomers is obtained. Electron-withdrawing

groups in the substrate retard the reaction as in the case of Friedel–Craft reaction. The amount
of each isomer depends on temperature, solvent, amount of catalyst and on the structure of the
substrate. Solvent is generally not required for the reaction. Nitrobenzene may be used which
reduces the reaction temperature. In general, low temperature favours the para-product and high
temperature favours the ortho-product. This appears to be because the para-derivative is formed
the faster (kinetic control) but the ortho derivative is thermodynamically the more stable by
virtue of possessing a chelate system.

43
Mechanism
The exact mechanism is still not clearly understood. There is evidence for both
intermolecular and intramolecular reaction mechanisms. It is, therefore, suggested that both
mechanisms are operating simultaneously.
Two-step mechanism
It may be taken to be Friedel–Craft acylation in which the acylium ion, is supplied by the
substrate, i.e. self-acylation. At first, AlCl3 forms complexe with the oxygen of the phenoxy
group from which the acylium ion is generated. The acylium ion then attacks the benzene ring
as in the case of Friedel–Crafts reaction.

Similar attack at p-position gives the para-isomer.

44
Concerted or single-step mechanism

Synthetic Applications
i. This reaction is useful for the preparation of aromatic hydroxyketones since direct acylation of
phenols gives very poor yield. The effect of this rearrangement on substrates bearing methyl groups
at the ortho, meta and para positions shows that when the para position is occupied, the acyl group
substitutes exclusively to the ortho position.

The proportions of o- and p-isomers can be varied by controlling the conditions of reaction, viz.,
temperature, solvent and the amount of catalyst. The reaction is useful because it gives both the isomers
which can be easily separated by steam distillation. The ortho-isomer having a lower boiling point due to
H-bonding is distilled first, followed by the para-isomer.

45
 ii. Esters of catechol give acyl catechols.

iii. Diphenyl esters also undergo Fries rearrangement predominantly in the same ring

iv. A very useful application is in the synthesis of ( + ) adrenaline which is a heart stimulant

1.9.2 Benzidine rearrangement

It includes a group of rearrangements in which aromatic hydrozocompound on treatment with
acid give either diaminodiphenyl or aminodiphenylamine. The possible product are 2,2’, 2:4, and 4:4
diaminophenyls known as ortho benzidine, diphenylines, and benzidine respectively while 2 and 4
aminodiphenyl amines known as ortho-para semidine.

46
 It is not necessary that all products are formed in one reaction, usually, the major product is
benzidine which is formed in a 70% yield. The presence of substituents plays an important role in
determining the course of rearrangement. Hydrazobenzenes having substituents in para position give
ortho-semidines

While having a those a single para substituent give derivatives of diphenylenes, or para-
semidines, or ortho semidines or a mixtures of these products

Even para position is occupied still the 4,4’ diamine compound may be formed.
Effect of substituents
The nature of substituents also plays a considerable role in determining the nature of products
formed in a usual manner. But since these rearrangements are very strong process many of the substituents
are ejected which come in their way. Groups like SO3H and COOH are ejected more easily than most
other groups. Cl- and AcO- are ejected less readily and -OR is ejected still less readily. NRAc NR2 and
R groups are not ejected at all. Thus hydrozobenzene 4-carboxylic acid gives benzidine with the loss of
carbonyl group while 4 acetoxy hydrozobenzene gives benzidine in low yield with dinaphthyl hydrazines
(hydrazonaphthalene) the major product is not the 4,4’-diamino derivative but the 2,2’-isomer.

Effect of acid
The acid used for rearrangement is often dilute aqueous or alcoholic solution of strong acid such
as HCl or H2SO4. With the strong acid, the rearrangement is rapid but sometime rearrangement is also
possible with weak acid like acetic acid.

47
Mechanism
The reaction is thoroughly studied and several mechanisms were proposed, and it is now
established that rearrangement is intramolecular.
Polar transition state mechanism
The mechanism was given by given by Banthorpe Hughes and C.K Ingold in 1964. In the
presence of acids, first there is an uptake of proton by each nitrogen atom and then mutual repulsion of
positive charges causes a lengthening of the inter nitrogen bond and finally lead to rupture. An electronic
change takes place in which electrons moves around a ring and links up different position to give final
product .the formation of para benzidine is as follow

When both para position are occupied in the original substrate then ortho-semidine in the product
and the reaction take the following course

The intermediate is not aromatized by the simple loss of protons as in the formation of para
benzidine but undergoes a second rearrangement before giving ortho-semidine. The formation of ortho-
semidine and diphenylene can be explained in a similar manner by a two-step process.

48
 It can also be rearranged to diphenylene

Hughes and Ingold emphasized that all fragments are held together by an electrostatic bond. This
is located where the new bond is to be established. At an interatomic distance of 4 Å, the electrostatic can
be fairly strong. Thus the bond formation begins first as an ionic bond, but as the distance shortens, it
passes into a covalent bond. Many derivatives of the ortho benzidine have not been isolated. It is most
unlikely that the reason is stereochemical. The suggested reason is that para-rearrangement is associated
with grater resonance energy in the transition state than ortho- rearrangement. Therefore, more electrons
are disturbed in a transition from benzenoid to a para-quinonoid rather than to ortho quinoid structure and
this introduces more resonating structure about the para form than the ortho and that is why the para form
is formed easily.

1.10 Sigmatropic rearrangement

Sigmatropic rearrangement involves the migration of a σ bond that is flanked by one or more
conjugated systems to a new position within the system. The reaction is termed [i,j] sigmatropic shift
when the bond migrates from position [1,1] to position [i,j]. For example, a carbon-hydrogen bond may
move across a diene. It is an example of [1,5] sigmatropic rearrangement.

49
Characteristic of Sigmatropic rearrangements
 The number of -bonds and the number of sigma bonds remains the same.
 Only heat and light is needed.
 Just re-location of sigma bond takes place.
 Conjugated system must be needed.
1.10.2 Suprafacial and Antarafacial shifts
All sigmatropic shifts can occur with either retention or inversion of the geometry of the
migrating group. In cases of stereochemical retention, the migrating group translates without rotation into
the bonding position, while in the case of stereochemical inversion the migrating group both rotates and
translates to reach its bonded conformation.

Sigmatropic shift with retention in stereochemistry

Sigmatropic shift with inversion in stereochemistry

If the migrating group remains on the same face of the π system, the shift is known as suprafacial,
while if the migrating group transfers to the opposite face is called an antarafacial shift.
1.10.3 [1,3] Sigmatropic shift
It is a type of sigmatropic rearrangement in which migration of sigma bond adjacent to one or
more  systems to a new position in a molecule.

[1,3] Sigmatropic H-shift

When [1,3] sigmatropic rearrangement takes place, the H-atom of the reactant is shifted from the
first position to the third position to form products. The molecular formula of the substance remains the
same during this rearrangement.

50
[1,3] Sigmatropic hydrogen shift suprafacial and antarafacial

[1,3] Sigmatropic carbon shift

When [1,3] sigmatropic rearrangement takes place, the carbon atom of the reactant is shifted from
first position to third position to form products. The molecular formula of the substance remains the same
during this rearrangement.

51
 1,3-Alkyl shift also occurs in cyclopropane derivative

1.10.4 [1,5] sigmatropic shift

The [1,5] suprafacial shift is symmetry allowed and geometrically feasible. When [1,5]
sigmatropic rearrangement takes place, the H-atom of the reactant is shifted from the first position to the
fifth position to form products.

1.10.5 [1,7] Sigmatropic shift

When [1,7] sigmatropic rearrangement takes place, the H-atom of the reactant is shifted from the
first position to the seven-position to form product. It involves an antarafacial component if carried out
thermally. [1,7] H-shift cannot occur antarafacially because the molecule is a rigid ring, but that can occur
photochemically.

52
 [1,7] shift of carbon take place in a similar manner.

Synthetic Applications
An antarafacial [1,7] shift is observed in the conversion of lumisterol to vitamin D 2, where
following an electrocyclic ring-opening to previtamin D2, a methyl hydrogen shifts. A [1,7]- H Shift
occurs in the final stages of the human body’s synthesis of vitamin D from cholesterol. Here is the last
step of the Biosynthesis

1.10.6 Claisen Rearrangement

Allylic aryl ethers are rearranged on heating to give ortho allyl phenols in a reaction called The
Claisen Rearrangement. It is a powerful carbon-carbon bond-forming intramolecular process. It is a
sigmatropic rearrangement and was discovered by Rainer Ludwig Claisen in 1912.

The group migrates to the ortho position, although some para product has been obtained in some
cases. In general, when both ortho positions are free, the product is ortho compound and when both ortho
positions are occupied, the product is para compound.

53
 When both ortho positions and the para position are occupied, there is no reaction. Migration to
the m-position has not been observed. During the ortho migration, the allyl group undergoes an allylic
shift, i.e., the carbon to the oxygen atom in the substrate becomes - to the ring in the product. However,
in the para migration, no change of attachment of the allyl group in the product is observed. This has been
confirmed by 14C labelling in the allyl group. Reaction follows first-order kinetics, i.e. one molecule is
involved in the rearrangement. Further, when a mixture of allyl ethers is heated, no crossover products
are formed.

Therefore, the allyl group never separates during the reaction, i.e., the reaction is intramolecular
rearrangement. This indicates that the reaction proceeds through a cyclic transition state in which the
breaking of oxygen-allyl bond and the formation of a carbon-carbon bond with the ring are concerted. On
the basis of the above considerations, the following mechanism of the rearrangement has been suggested.

The cyclohexadienone (I) intermediate is converted rapidly into phenol for reasons of aromatic
stability.

Para-migration
Even when the ortho positions are substituted, the migration still occurs at the ortho position to
form ortho-substituted dienone (II). However, the absence of hydrogen at the ortho position prevents

54
enolization, i.e., aromatization. Hence the allyl group undergoes a second migration through a similar
cyclic transition state to form a dienone (III) which aromatizes to phenol with allyl group at position 4.

Since the allyl group undergoes double inversion, it is not rearranged in the final product. This
has been confirmed by isotopically labelled carbon. There is enough evidence in support of this
mechanism. The double inversion of the allyl group is proved by trapping the dienone (II) intermediate
with maleic anhydride in a Diels–Alder reaction. Further, the dienone (II) prepared separately was found
to give rapidly the para product on heating.
The reaction rate is unaffected by the presence or absence of substituents in the aromatic ring
since the reaction is not ionic. The major product of the Claisen rearrangement is derived from a preferred
chair-like transition state in which the larger substituent occupies the pseudo equatorial position. For
example, in the Claisen rearrangement of A, the major product B was obtained.

Extension of Claisen Rearrangement

1: The rearrangement is not restricted to aromatic ring systems only
(a) Allyl ethers of enols, e.g., allyl vinyl ethers also undergo Claisen rearrangement.

The product does not enolize (even when R or R’ = H) because ketones are more stable.

(b) The o-allyl acetoacetic esters also rearrange similarly.

55
2. Out-of-ring Claisen rearrangement
Several examples of out-of-ring Claisen rearrangements are given below.

There is no rearrangement of the allylic group in the final product due to double inversion.

Synthetic applications
i. Synthesis of o-Eugenol
Since aryl allyl ethers can be easily prepared, the rearrangement is employed to
prepare various kinds of compounds, e.g.

Claisen rearrangement is used for the synthesis of unsaturated carbonyl compounds.

56
ii. Synthesis of Prephenate
The enzyme chorismate mutase (EC 5.4.99.5) catalysis the Claisen rearrangement of chorismate to
prephenate, a key intermediate in the shikimate pathway (the biosynthetic pathway towards the synthesis
of phenylalanine and tyrosine.

1.10.7 Cope Rearrangement

Cope rearrangement involves the thermal isomerization of 1,5-dienes with the shift of double
bonds and breaking of 3,4-sigma bond. Any 1,5-diene undergoes this rearrangement.

The reaction is reversible and produces an equilibrium mixture of the dienes. That isomer,
however, predominates which is thermodynamically more stable. The reaction is facile (occurring at a
lower temperature) when there is a phenyl or carbethoxy group at 3- or 4-positions. This is due to the
conjugation of the groups with the double bonds in the product with consequent stabilization. When
catalyzed by transition metal compounds, Cope rearrangement of simple 1, 5-dienes can occur at room
temperature.
Mechanism
The rearrangement is intramolecular since no cross over products were obtained on heating two
different 1, 5-dienes. Stereo-chemical studies (Doering and Roth) indicate that the reaction proceeds via
a cyclic six-carbon transition state in the chair form. This was concluded from the stereospecific nature
of the rearrangement. For example, the meso-isomer of (I) on heating gave 99.7% cis -trans olefin. This
is only possible if the transition state of the meso-isomer is in the chair form in which one methyl group
is on the axial and the other methyl group is on the equatorial bond.

57
 If the cyclic T.S is in the boat form, the product would be either cis-cis or trans-trans, since there
are two boat forms for the meso-isomer. For the d & l pair (racemic) there are three possible
conformations of the T.S (i) one boat form which would give cis-trans olefin, (ii) one chair form with
diaxial methyl groups which would give cis -cis product (less stable due to diaxial interaction) and (iii)
another chair form with both equatorial methyl which could give trans-trans product. In practice, the
product of d-l-isomer (III) is mainly trans-trans olefin (IV).

It is therefore suggested that the isomerization proceeds via a cyclic six-carbon T.S in the
energetically preferred chair conformation. The mechanism of Cope rearrangement is similar to Claisen
rearrangement which involves six-centered rearrangement of five carbons and one oxygen.

When there is a steric restrain to the formation of six-membered cyclic T.S. the reaction may
proceed through the radical pathway (Hammond and De Boer). Thus, cis-1,2 divinylcyclobutane (V)
rearranges through a boat-like six-carbon cyclic T.S to yield 1,5 cyclooctadiene (VI).

Divinylcyclopropane undergoes the rearrangement with ring expansion by four carbons.

Thus, Cope rearrangement may involve either concerted or biradical mechanism the latter
preferred by some substrates. The biradical two steps mechanism may be formulated as below for 1,5-
diene.

58
Degenerate Cope rearrangement
It is seen that Cope rearrangement of symmetrical 1, 5-dienes gives the product which is
indistinguishable from the starting material. This is known as degenerate Cope rearrangement.

Similarly, degenerate carbocation rearrangement is also known

Spectral analysis indicates both A and B exist as equilibrium pair. Cope rearrangement is also
observed with conjugated trienes with the difference that the 3, 4-bond changes from double to a single
bond.

The Oxy-Cope rearrangement

Cope rearrangement is not reversible when there is a hydroxy substituent at 3- or 4-position in 1,
5-dienes since the product tautomerizes to stable aldehyde or ketone.

Aza-Cope rearrangement
The Aza cope rearrangement is an example of a heteroatom version of cope rearrangement which
is [3,3] sigmatropic rearrangement that shifts single and double bonds between two allylic components.
Aza-Cope rearrangements are generally classified by the position of the nitrogen in the molecule.

The transformation of an appropriately substituted unsaturated iminium ion to acyl substituted

pyrrolidine by [3,3] sigmatropic rearrangement followed by Mannich cyclization is an example of aza
cope rearrangement. It is a synthetically powerful reaction, as it is able to create complex cyclic molecules
from simple starting materials. The Mannich cyclization is irreversible and its product, an acyl substituted
pyrrolidine ring, more stable than that of the rearrangement.

59
 Summary
Rearrangement: A rearrangement reaction involves a reshuffling of the sequence of atoms to form a
new structure. Migration of a group from one atom to another within the same molecule occurs.

Nucleophilic Rearrangement: Migration of the migratory group 'W' from a carbon atom, with its
electron pair (as a nucleophilic) to an adjacent electron-deficient atom.

Electrophilic Rearrangement: Migration of the migratory group ‘W’ from a C atom (without bonding
electrons) to an adjacent electron-rich atom.

Anionotropic/Nucleophilic Rearrangements
Rearrangements to Electron-Deficient Carbon
Pinacol–Pinacolone rearrangement: Acid-catalyzed conversion of polysubstituted ethylene glycols to
carbonyl compounds via carbonium ion.

Benzil-Benzilic acid rearrangement: Base catalyzed rearrangement of -diketones (usually aromatic)

to yield -hydroxy acids in their salt form.

Wolff rearrangement: Conversion of α-diazocarbonyl compounds into a ketene on treating with silver
oxide (Ag2O) and H2O, is known as Wolff rearrangement.
Arndt-Eistert Reaction: Conversion of a carboxylic acid to a higher carboxylic acid homologue.

Rearrangement to Electron Deficient Nitrogen

Hofmann rearrangement: Conversion of an amide into an amine with one less ‘C’ by the action of base
and bromine in presence of water is known as Hofmann rearrangement.

Curtius rearrangement: Thermal rearrangement of acid azides in non-aqueous solvents such as

chloroform, benzene or ether to an isocyanate.
Schmidt rearrangement: Carboxylic acids react with hydrazoic acid in the presence of concentrated
sulfuric acid to give isocyanate directly.
Lossen rearrangement: The rearrangement of acyl derivative of hydroxamic acid to isocyanate.
Rearrangement to Electron Deficient Oxygen
Baeyer-Villiger rearrangement: Oxidation of a ketone into an ester and cyclic ketones into lactones by
means of a peracid.

Dakin reaction: The reaction of benzaldehyde containing ortho- and para- hydroxyl groups are converted
into catechol and quinols respectively by alkaline hydrogen peroxide.

Cationotropic/Electrophilic Rearrangement
Steven Rearrangement: The conversion of keto-quaternary ammonium or tertiary sulphonium salts
rearrange to amino or mercapto ketones under the influence of a strong base.

60
Favorskii Rearrangement: Base catalyzed rearrangement of an -halo-ketone to an ester.

Aromatic Rearrangements
Fries Rearrangement The conversion of Phenolic esters on heating with aluminium trichloride (Lewis
acid) give o- and p- acyl phenol.

Benzidine Rearrangement The aromatic hydroazocompound on treatment with acid give benzidine.
Sigmatropic Rearrangements
The relocation of sigma bond in a molecule is known as sigmatropic rearrangement. All sigmatropic shifts
can occur with either retention or inversion of the geometry of the migrating group. [1,3], [1,5] ,[1,7] H-
shifts are sigmatropic rearrangements

Problems
Q No. 1 Justify followings with Mechanism.?
i. cis- and trans-1,2-dimethylcyclohexane-1,2-diol give different products on treatment with
concentrated sulfuric acid.
ii. In the pinacol rearrangements of PhMeC(OH)-C(OH)PhMe and Ph2C(OH)-C(OH)Me2, a
phenyl group migrates in the former case but a methyl group migrates in the latter.
iii. In Fries rearrangement, ortho product is formed at high temperature.
iv. Ketenes react with diazomethane to give cyclopropanone.
v. Semipinacol is reverse of pinacol rearrangement.

Q. No. 2 What products would you expect from the following reactions?

1.

2.

3.

4.

5.

61
 6.

Q No. 3 Draw mechanism of the following reactions.

1.

2.

3.

4.

62
Chapter No. 2
Pericyclic Reactions
2.1 Introduction
(Peri mean around and cyclic mean circle) therefore, Pericyclic mean around the circle. It may
be defined as: “A pericyclic reaction is a concerted reaction that proceeds through a cyclic transition
state.”
2.2 Characteristics of pericyclic reactions
i. Pericyclic reactions are a single step.
ii. These reactions have conjugated cyclic transition state.
iii. These reactions are internally self-sufficient (no extra reagent or catalyst is required) and they are
initiated thermally or photochemically.
iv. These are stereospecific in nature (only one stereoisomer product is formed).
v. They show an equilibrium state (reactants and products have the ability to interchange with each
other).
2.3 Types of pericyclic reactions
There are following types of pericyclic reactions
1) Electrocyclic reactions
2) Cycloaddition reactions
3) Sigmatropic rearrangement
4) Group Transfer reactions
i. Electrocyclic reactions
“An electrocyclic reaction is a reversible reaction that involves a ring closure or ring-opening
reaction.” An electrocyclic reaction is the concerted interconversion of a conjugated polyene and a
cycloalkene. These reactions are induced either thermally or photochemically.

Electrocyclic reactions are reversible reactions and open-chain system in the reaction is always a
conjugated system whereas cyclic one may or may not be a conjugated system. In electrocyclic reactions
either a ring is formed with the generation of a new σ bond and the loss of a π bond or vice versa.

63
 Electrocyclic ring closure reactions: “An electrocyclic ring closure is an intramolecular
reaction that forms a cyclic product containing one more σ bond and one fewer π bond than the reactants.”

Electrocyclic ring-opening reactions: “An electrocyclic ring-opening is a reaction in which a σ

bond of a cyclic reactant is cleaved to form a conjugated product with one more π bond.”

To draw the product in each reaction, use curved arrows and begin from a π bond. Move the π
electrons to an adjacent carbon-carbon bond and continue in a cyclic fashion.
ii. Cycloaddition Reactions
“A cycloaddition is a reaction between two reactants having π bonds to form a cyclic product
with two new σ bonds.”

[4+2] Cycloaddition Reaction: “The Diels-Alder reaction is a thermal [4 + 2] cycloaddition that

occurs between a diene with four π electrons and an alkene (dienophile) with two π electrons.”

64
 [2+2] Cycloaddition Reaction: “A photochemical [2 + 2] cycloaddition occurs between two
alkenes, each with two π electrons, to form a cyclobutane.”

iii. Sigmatropic rearrangement

Sigmatropic rearrangement involves the migration of a σ bond that is flanked by one or more
conjugated systems to a new position within the system. The reaction is termed [i,j] sigmatropic shift
when the bond migrates from position [1,1] to position [i,j]. For example, a carbon-hydrogen bond may
move across a diene. It is an example of [1,5] sigmatropic rearrangement.

iv. Group transfer reaction

A pericyclic process involving the transfer of one or more groups or atoms from one molecule to
another is known as group transfer reactions there are only few reactions in this class. Ene reaction
is one of the most group transfer reaction.

2.4 The Molecular Orbital Theory of Pericyclic Reactions

The frontier orbital theory/Fukui theory/Molecular orbital theory put forth by Kenichi Fukui in
1954. The molecular orbit theory describes bonds as the mathematical combination of atomic orbitals that
forms a new set of orbitals called molecular orbitals (MOs). The number of atomic orbitals used equals
the number of molecular orbitals formed.
2.4.1 Construction of Molecular Orbitals
Construction of Molecular Orbitals of Ethylene
The bonds in ethylene (CH2= CH2) is formed by the side-by-side overlap of two p orbitals on
adjacent carbons. Two p orbitals can combine in two different ways. When two p orbitals of similar phase
overlap, a  bonding molecular orbital (designated as) results. Two electrons occupy this lower-
energy bonding molecular orbital. When two p orbitals of opposite phase combine, a * antibonding
molecular orbital (designated as 2*) results. A destabilizing node between the orbitals occurs when two
orbitals of opposite phase combine.

65
Construction of -Molecular Orbitals of 1,3 Butadiene
The two -bonds of but-1,3-diene (CH2=CH-CH=CH2) are formed by the overlap of four p
orbitals on four adjacent carbons, four p orbitals can combine in four different ways to form four
molecular orbitals designated as ψ1–ψ4. Two are bonding molecular orbitals (ψ1 and ψ2), and two are
antibonding molecular orbitals (ψ3* and ψ4*). The two bonding MOs are lower in energy than the p
orbitals from which they are formed, whereas the two antibonding MOs are higher in energy than the p
orbitals from which they are formed. As the number of bonding interactions decreases and the
number of nodes increases, the energy of the molecular orbital increases.

In the ground-state electronic arrangement, four π electrons occupy the two bonding molecular
orbitals.
HOMO: The highest energy orbital that contains electrons is called the highest occupied
molecular orbital (HOMO). In the ground state of buta-1,3-diene, ψ2 is the HOMO.
LUMO: The lowest energy orbital that contains no electrons is called the lowest unoccupied
molecular orbital (LUMO). In the ground state of buta-1,3-diene, ψ3* is the LUMO.

66
Construction of -Molecular Orbitals of 1,3,5-Hexatriene
The two p-bonds of hexa-1,3,5-triene CH2=CH-CH=CH-CH=CH2) are formed by the overlap of
six p orbitals on six adjacent carbons, six p orbitals can combine in six different ways to form six
molecular orbitals designated as ψ1–ψ6. Three are bonding molecular orbitals (ψ1–ψ3), and three are
antibonding molecular orbitals (ψ4*–ψ6*). In the ground state electronic configuration, the six π electrons
occupy the three bonding MOs, ψ3 is the HOMO, and ψ4* is the LUMO. In the excited state, which results
from the promotion of an electron from ψ3 to ψ4*, ψ4* is the HOMO and ψ5* is the LUMO.

Filling Electrons in Molecular Orbitals

The conjugated polyenes always contain even number of carbon atoms. These polyenes contain
ether (4n)  or (4n+2)conjugated electrons the filling of electrons in the  molecular orbitals of a
conjugated polyene is summarized below
1. The number of bonding  MOs and antibonding  MOs are the same.
2. The number of electrons in any molecular orbital is maximum two.
3. If a molecular orbital contains two electrons, then both electrons are always paired.
4. Molecular orbitals follow the Aufbau principle and Hund’s Rule.
5. The energy of  molecular orbitals is directly proportional to the number of nodal planes.
6. There will be no degenerate molecular orbitals at any energy level.
67
2.4.2 Symmetry in -Molecular Orbital and Carbon-Carbon -Bond
A π molecular orbital possesses either plane of symmetry or center of symmetry. Both
symmetries are not present together in a given πmolecular orbital.
Plane of symmetry: Some molecular orbitals have the symmetry about the mirror plane (m)
which bisect the molecular orbitals and perpendicular to the plane of the molecule.

Both orbitals are mirror images to each other hence in this MO there is a plane of symmetry,
abbreviated as m(S).

In the above figure, both orbitals are not mirror-images to each other. Thus in this MO, there is a
mirror plane asymmetry abbreviated as m(A).
C2- Symmetry or center of symmetry: The center of symmetry is a point in the molecular axis from
which if lines draw on one side and extended an equal distance on the other side, will meet the same
phases of the orbitals.

Both orbitals are symmetrical with respect to the center of the molecular axis. Thus in MO, there
is centre of symmetry. Let’s take an example of the symmetry properties of ethylene and 1,3-butadiene.

Number of nodes Orbitals M C2

0  A S
1  S A

68
 Number of nodes Orbitals M C2
3  A S
2  S A
1  A S
0  S A

On the basis of the above two examples, we can conclude the following very important points for
the linear conjugated p system.
1. The wave function n will have (n-1) nodes
2. When n is odd n will be symmetric with m and asymmetric with C2.
3. When n is even n will be symmetric with C2 and asymmetric with m.
4. In a given molecule the HOMO and LUMO has opposite symmetry.
Wave function Nodes (n-1) M C2
odd… 0 or even S A
even odd A S

Symmetries in carbon-carbon sigma bond have a mirror plane symmetry and since the rotation
of 180o through its mid-point regenerates the same sigma orbital it also has C2 symmetry. A sigma
antibonding molecular orbital is asymmetric with respect to both m and C2.
69
 Orbital M C2
 A A
 S S

2.5 Electrocyclic Reactions

An electrocyclic reaction is a reversible reaction that can involve ring closure or ring-opening of
one molecule of reactant to form one molecule of product. An electrocyclic reaction is the concerted
interconversion of a conjugated polyene and a cycloalkene. Electrocyclic reactions are induced either
thermally or photochemically.

All electrocyclic reactions are reversible reactions. Open chain partner of the reaction is always
a conjugated system whereas cyclic partner may or may not contain a conjugated system. In electrocyclic
reactions either a ring is formed with the generation of a new б bond and the loss of a π bond (i.e., gain
of a б bond and loss of a π bond) or ring is broken with the loss of one б bond and gain of one π bond. It
means cyclic alkene has one π bond lesser than the open-chain conjugated polyene.

kπ electrons (k – 2) π electrons + one σ bond

k=4 (loss of one π bond and gain of one σ bond)

kπ electron (k – 2) π electrons + one σ bond, k = 6

kπ electrons (k – 2) π electrons + one б bond

70
2.5.1 Type of Electrocyclic Reactions
i) Electrocyclic ring closure reactions
Electrocyclic ring closure is an intramolecular reaction that forms a cyclic product containing one
more σ bond and one fewer π bond than the reactants.

ii) Electrocyclic ring-opening reactions

An electrocyclic ring-opening is a reaction in which a σ bond of a cyclic reactant is cleaved to
form a conjugated product with one more π bond.

To draw the product in each reaction, use curved arrows and begin at a π bond. Move the π
electrons to an adjacent carbon-carbon bond and continue in a cyclic fashion.
2.5.2 Stereochemistry of Electrocyclic reactions
There are two possible stereochemistries for ring-opening and ring-closing of electrocyclic
reactions.
1. Conrotatory process (or motion)
2. Disrotatory process ( or motion)
Stereochemistry of the product depends on the stereochemistry of the reactant as well as the mode
of reaction i.e. either thermally or photochemically.
2.5.3 Conrotatory and disrotatory motions in ring-opening reactions
The most common example of the ring-opening reaction is the conversion of cyclobutene to 1,
3-butadiene. This conversion can only be possible if a σ (sigma) bond between C3 -C4 of cyclobutene
must break during the course of the reaction.

Ring-opening by sigma bond may be possible in two ways. First, the two atomic orbital
components of the σ (sigma) bond may both rotate in the same direction, clockwise or counterclockwise.
This process is known as conrotatory motion (Fig. 1).

71
 Fig. 1. Conrotatory ring-opening
Second, the atomic orbital may rotate in opposite directions, one clockwise and the other counter-
clockwise. This process of ring-opening is known as disrotatory motion (Fig 2).

Fig. 2. Disrotatory ring-opening

The substituents present on the carbons of the rotating orbitals may also rotate in the direction of
the rotating orbitals. Thus in the conrotatory motion substituents rotate in the same direction (Fig. 3) and
in disrotatory motion substituents rotate in the opposite directions (Fig.4).

Fig. 3. Conrotatory ring-opening, orbitals and, groups migrate in the same direction

72
 Fig. 4. Disrotatory ring-opening; orbitals and groups migrate in the opposite direction

2.5.4 Conrotatory and disrotatory motion in ring-closing reactions

When an electrolytic reaction takes place, the carbon at each end of the conjugated π system must
turn in concerted fashion so that the p orbital can overlap (and rehybridized) to form σ bond that closes
the ring. This turning can also occur in two stereochemically distinct ways. In a conrotatory closure the
orbitals and groups of the two carbon atoms turn in the same direction, clockwise or counter-clockwise
(Fig. 5).

Fig. 5. Conrotatory ring closure

In a disrotatory closure, the orbitals and groups of the two carbon atoms turn in the opposite
direction, one clockwise and other counter-clockwise (Fig. 6).

Fig. 6. Disrotatory ring closure

From these examples, it is clear that orbitals having m-symmetry always give disrotatory
motion. (Fig. 4 and Fig. 6) whereas orbitals having C2-symmetry gives conrotatory motion (Fig. 3 and
73
Fig. 5). The reason behind this rule can be easily understood by recalling that overlap of wave functions
of the same sign is bonding (and symmetry allowed reactions) whereas overlap of the wave function of
opposite sign is antibonding (and symmetry forbidden process). Electrocyclic reactions are stereospecific.
An intriguing feature of the electrocyclic reaction is that the stereochemistry of the product is dependent
on whether the reaction is thermally induced or photo-induced.
2.5.5 Open chain conjugated system having 4n conjugated electrons
Let us consider the simplest example in which a cyclobutene derivative opens to a 1,3-butadiene
derivative, i.e., the open-chain conjugated system has 4n conjugated π electrons. In thermal condition
trans-3,4-dimethylcyclobutene gives (2E,4E)-2,4-hexadiene. Thus this reaction is completely
stereospecific.
2.5.5.1 Thermal-induced ring opening
In the ring-opening reactions, the stereochemistry of the product is determined by the symmetry
of the ground state of the HOMO of the open-chain partner. The ground HOMO of butadiene and its
derivative will be ψ2 which has C2-symmetry. The cyclobutene ring must open in such a fashion that the
sigma bond orbital transfer into HOMO of the product having C2-symmetry.To get C2-symmetry in the
product HOMO, motion should be conrotatory in ring-opening of the reaction.

Thus, if the open-chain polyene has 4n π electrons then the process is always conrotatory in
thermal condition whether the reaction is ring-opening or ring closure. Let us take the stereochemistry of
the ring-opening of the trans-3, 4-dimethylcyclobutene. There is a possibility of two modes of conrotatory
motion, counter-clockwise and clockwise motion.

Thus, the thermal process is conrotatory with two possible products in the above case. The
conrotation in the first case (clock-wise rotation) leads to severe steric interactions between two methyl
groups. This interaction is avoided in the first process (counter-clockwise) in which two methyl groups
move away from each other and this is the favored process.

74
2.5.5.2 Photo-induced ring opening
In the photochemical condition, the same substrate gives (2E,4Z)-2,4-hexadiene. In this case, the
reaction is completely is stereospecific. Thus the reaction can be performed thermally or photochemically,
and under either condition, the reaction is completely stereospecific. The photo state HOMO of the open-
chain butadiene and its derivative will be ψ3* which has m-symmetry. Thus, the cyclobutene ring must
open in such a fashion that the sigma bond orbital transform into the excited state HOMO of the product
having m-symmetry. To get m-symmetry in the excited state HOMO of the product, the motion should
be disrotatory in the ring-opening of the reaction. There is also two possible modes of the disrotatory
motion.

From the above two examples, it is clear that thermally induced electrocyclic reactions involving
4n conjugated electrons require conrotatory motion and photochemically induced electrocyclic reactions
require disrotatory motion.
2.6 Open chain conjugated system having (4n + 2)π conjugated electrons
The simplest example of this category is the ring-closing of 1,3-cyclohexadiene into 1,3,5-
hexatriene.

In thermal conditions trans-5,6-dimethyl-1,3-cyclohexadiene is converted to (2E,4Z,6Z)-2,4,6-

octatriene only and in the photochemical condition, the same is converted to (2E,4Z,6E)-2,4,6-octatriene.

75
 These two conversions are also highly stereospecific. Stereochemistry of these two reactions can
only be explained if the process is disrotatory in thermal conditions and conrotatory in photochemical
conditions.
1,3,5-Hexatriene is the most common example of the polyene having (4n+2)π conjugated
electrons.

2.5.6.1 Thermal-induced cyclization

Ψ3 is the ground state HOMO of 1,3,5-hexatriene which has m-symmetry. Therefore the thermal
cyclization proceeds by disrotatory motion.

2.5.6.2 Photo-induced cyclization

When an electron of 1,3,5-hexatriene is promoted by photon absorption, ψ4* becomes the HOMO.
This excited state HOMO has C2-symmetry. Therefore, photo-induced cyclization proceeds by
conrotatory motion.

On the basis of these experimental results, the stereochemistry of electrocyclic reactions can be
summarized by noting that thermally induced electrocyclic reactions involving 4nπ electrons require
conrotatory motion. Under similar conditions electrocyclic reactions involving (4n + 2)π electrons follow
the disrotatory motion. Similarly, photo-induced electrocyclic reactions 4nπ electrons require disrotatory
motion. Under similar conditions, electrocyclic reactions involving (4n + 2)π electrons follow the
conrotatory motion.
A summary of the type of motion to be expected from different polyenes under thermal and
photochemical conditions is shown in the table below.

Number of Number of Electrons Mode of Activation Motion

Pi-bonds
Even 4n i. Thermal Conrotatory
ii. Photochemical Disrotatory
Odd 4n + 2 i. Thermal Disrotatory
ii. Photochemical Conrotatory

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 It is a disrotatory reaction involving (4n+2) π electrons because this will give a cis product. This
reaction is allowed reaction. This reaction, therefore, can occur readily by a concerted mechanism.

Following is a conrotatory reaction involving (4n+2) π electrons because conrotatory motion will
give trans product. It does not allow because the reaction is symmetry forbidden reaction.

The following reaction is photo-induced reaction and the reactant has (4n+2)π electrons. Its
excited HOMO is ψ4* which has C2-symmetry. Thus, motion is a conrotatory motion.

The above experimental results can be explained by four theories given for pericyclic reactions.
2.5.7 Analysis of Electrocyclic Reactions
 An electrocyclic reaction occurs only when like phases of orbitals can overlap to form a bond.
Such a reaction is symmetry allowed.
 An electrocyclic reaction cannot occur between lobes of opposite phase. Such a reaction is
symmetry forbidden.
 When like phases of the p orbitals are on the same side of the molecule, the two orbitals must
rotate in opposite directions-one clockwise and one counterclockwise. Rotation in opposite
directions is said to be disrotatory.
 When like phases of the p orbitals are on opposite sides of the molecule, the two orbitals must
rotate in the same direction-both clockwise or both counterclockwise. Rotation in the same
direction is said to be conrotatory.

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  The number of double bonds in the conjugated polyene determines whether rotation is
conrotatory or disrotatory.
 Thermal electrocyclic reactions occur in a disrotatory fashion for a conjugated polyene with
an odd number of π bonds and in a conrotatory fashion for an even number of π bonds.
 Photochemical electrocyclic reactions occur in a conrotatory fashion for a conjugated
polyene with an odd number of π bonds and in a disrotatory fashion for an even number of π
bonds.
2.5.8 Fukui theory of pericyclic reactions
The frontier orbital theory/Fukui theory put forth by Kenichi Fukui in 1954. This theory is applied
for predicting whether a given cyclic reaction is allowed by examining the symmetry of the highest
occupied molecular orbital (HOMO) if the reaction is unimolecular, or by examining the lowest
unoccupied molecular orbital (LUMO) of the second partner if the reaction is bimolecular.
 Frontier orbitals of a system are comprised of a pair of HOMO & LUMO.
 When two reacting systems are separated by an infinite distance their MOs are unperturbed by
each other. When they approach sufficiently close to each other their MOs begin to interact.
 No net stabilization of the system by the interaction of the filled MOs.
 Interaction of one filled MO and one unfilled MO leads to net stabilization of the system.
 Reaction is thermally allowed when interaction of the MOs is of the bonding type in the ground
state.
 Reaction is thermally disallowed when the interaction of HOMO & LUMO is of antibonding type
in ground state electronic configuration.
The electrocyclization reaction is analyzed by the HOMO of the open-chain partner as the
reaction is unimolecular reaction. The stereochemistry of an electrocyclic reaction is determined by the
symmetry of the HOMO of the open-chain partner, regardless of which way the reaction actually
proceeds. In thermal condition, the HOMO is always ground state HOMO and in photochemical mode,
the HOMO is always first excited state HOMO. If the HOMO has m-symmetry the process will be
disrotatory. On the other hand, if HOMO has C2 symmetry then the process will be disrotatory.

Symmetry in HOMO Mode of rotation

m-Symmetry Disrotatory
C2 Symmetry Conrotatory

78
4n+2 electrocyclization

79
The 4+2 electrocyclization in excited state is given below.

2.5.9 Woodward Hoffman Rule

(4q+2)s +( 4r)a =odd Thermally allowed
(4q+2)a +(4r)s = odd Photochemically allowed
 A component is a bond or orbital that takes part in a chemical reaction as one unit.
 We label the components by the type & number of electrons there are in the component.
 The suffix ‘s’ stands for a suprafacial component ( forms new bonds on the same face at both
ends).
 The suffix ‘a’ stands for antarafacial component ( forms new bonds on the opposite face at both
ends).
 ‘q’& ‘r’ are simple integers 1,2,3,.....etc.
Description of the rule
 Draw the mechanism of the reaction
 Choose the components. All the bonds taking part in the reaction must be included and no others.
 Make a three-dimensional drawing of the way the components come together for the reaction,
putting in orbitals at the end of the components only.
 Join up the components where new bonds are to be formed. Make sure you join orbitals that are
going to form new bonds.
 Label each component ‘s’ or ‘r’ depending on whether new bonds are formed on the same or
opposite faces.
 Add up the number of (4q+2)s +( 4r)a = odd reaction is allowed.
Step 1: Draw the mechanism.

Drawing of the orbitals

80
 Case 1: When the component is‘s’. In this case, overlapping will be possible if motion is
disrotatory.

We call the system as ‘s’ when upper lobes of the two p-orbitals are joining together and ‘a’ if
upper lobe of one orbital and lower lobe of another orbital are joined together.
Count the number of components.
Number of( 4q +2)S component = 1
Number of (4r)a component =0
Total = 1 (odd), reaction is thermally allowed & vice versa.
Case 2: When the component is ‘a’. In this case, overlapping is only possible if motion is
conrotatory.

Number of( 4q +2)a component =1

Number of (4r)s component =0
Total = 1 (odd), reaction is photochemically allowed.

2.5.10 Mobius Huckel Theory for Electrocyclic Reactions

This method is used for assessing whether a given pericyclic process is allowed to examine the
cyclic array of orbitals at the transition state of the pericyclic reactions. This method was popularized by
H.Zimmerman and M.J.S.Dewar. Huckel rule of aromaticity states that a monocyclic planar conjugated
system is aromatic if it has (4n+2) conjugated electrons and consequently stable in the ground state.
Similarly, the monocyclic planar conjugated system is anti-aromatic if it has (4n)-conjugated electrons
and unstable in the ground state. However, further studies showed that these rules are reserved by the
presence of a node in the array of aromatic orbitals. Thus, a system with (4n+2) system and a node is
anti-aromatic while the system with (4n) electrons and a node is aromatic.
Thus, the system has no node then:
 (4n+2) electrons, the system is aromatic and stable in the ground state.
 (4n) electrons, the system is anti-aromatic and unstable in the ground state.
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Similarly, a system having a node then:
 (4n) electrons, the system is aromatic and stable in the ground state.

 (4n+2) electrons system is anti-aromatic and unstable in the ground state.

If the system has no node then it is called Huckel system and array is called Huckel array.
Similarly, if the system has no node then it is called Mobius system and array is called Mobius array.
Applications of these rules to pericyclic reactions led to the generalization that thermal reaction takes
place via aromatic transition state[i.e. (4n+2) electrons having no node or (4n)electrons having one
node] whereas, photochemical reactions proceed via anti-aromatic transition state [i.e. (4n) electrons
having no node or (4n+2) electrons having one node].
A cyclic transition state is said to be aromatic with the corresponding aromatic system if the
number of the conjugated atoms and that of the  electrons involved are the same as in the corresponding
aromatic system. Similarly, a cyclic transition state is the number of conjugated atoms and that of the 
electrons involved are the same as in the representing those orbitals which undergo in the transition state
and assigned to the wave function is the best manner of overlap. Then the number of nodes in the array
and the number of electrons involved are counted.
An electrocyclic reaction is an intramolecular reaction in which the formation of a  bond
between the ends of the p system and the rearrangement of the p electrons leads to a cyclic product that
has one less p bond than the reactant. An electrocyclic reaction is completely stereoselective; it is also
stereospecific. Let us consider the following electrocyclic reaction.

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 Similarly, for

Thus, for the thermal reactions involving (4n+2) electron will be disrotatory and involve Huckel
type transition whereas those having 4n -electron will be controtatory and the orbital array will be
Mobius type. Similarly, for photochemical reactions involving (4n+2) electron will be contrary and
involve Mobius type transition whereas those involving 4n electron will be disrotatory and the orbital
array will be Huckel type.
Thermally allowed

Photochemically allowed

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 Thermally allowed

Photochemically allowed

Selection Rules for Electrocyclic Reactions by Mobius-Huckel Method

Array of  Number of nodes Aromaticity Thermally Photochemically
electron involved allowed allowed
4n Zero anti-aromatic --------- Disrotatorty
4n One Aromatic Conrotatory -----------
4n+2 Zero Aromatic Conrotatory ------------
4n+2 One anti-aromatic ---------- Disrotatorty

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 2.6 Cycloaddition Reactions
2.6.1 Introduction
A cycloaddition is a reaction in which two unsaturated molecules undergo an addition reaction
to yield a cyclic product. The formation of a cyclic product takes place at the expense of one  bond in
each of the reacting partner and gain of two sigma bonds at the end of both components having  bonds.
Thus, in this reaction, there is a loss of two  bonds of the reactants and gain to two sigma bonds in the
product.

2.6.2 Notation of cycloaddition reactions

Cycloadditions can be described using two systems of notation. An older, but still common,
notation is based on the size of linear arrangements of atoms in the reactants. It uses parentheses: (i + j +
…) where the variables are the numbers of linear atoms in each reactant. The product is a cycle of size
(i + j + …). For example the standard Diels-Alder (D.A) reaction a (4 + 2) cycloaddition.
A recent, IUPAC-preferred notation uses square brackets to indicate the number of electrons,
rather than carbon atoms, involved in the formation of the product. In the [i + j + …] notation. For
example, the standard Diels-Alder reaction is a [4 + 2] cycloaddition. The addition reactions are classified
with respect to three facts of the reaction:
1) The nature of orbitals undergoing a change.
2) The number of electrons of each unit participating in cycloaddition.
3) The stereochemical mode of cycloaddition (Supra, syn or Antara, anti)
The reaction in equation (1) is a [2 + 2] cycloaddition reaction because the reaction involves two
electrons from one reacting component and also two electrons from the other. The reaction (2) is a [4 +
2] cycloaddition. The stereochemical mode is given by a subscript s or a which indicates whether the
addition occurs in a supra or anthrax mode on each unit. A cycloaddition may in principle occur either
across the same face or across the opposite faces of the planes in each reacting component. If reaction
occurs across the same face of  system, the reaction is said to be suprafacial with respect to that 
system. The suprafacial addition is nothing more than a syn addition.

85
 This addition reaction is thus [4s + 2s] cycloaddition reaction. This can also be represented as
follows:

This mode of addition reaction thus [4a + 2s] cycloaddition reaction. This can be represented as:

In antarafacial, attack takes place with one bond-forming to one surface but other bond-forming
to another surface. It is rare, it does not occur in any reaction. Almost all cycloaddition reactions are
suprafacial on both components.

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2.6.3 Theory of Cycloaddition Reaction: FMO Method
In order, for a cycloaddition to occur, there must be bonding overlap between p-orbitals at the
terminal carbons of each -electron system, this is where the new bonds are formed. Let us explain this
point with a [4 + 2] cycloadditon. Let us suppose that diene behaves as an electron donor and the
dienophile as the electron acceptor. What electrons will the 4 component donate? Obviously, there will
be its valence electrons-the electrons in its HOMO. The 2 component will accept these electrons to form
the new bonds. The molecular orbital used to accept these electrons must be empty since molecular orbital
cannot contain more than two electrons. Therefore, the molecular orbital which accepts electrons should
be LUMO of the 2 component. Thus, one component uses its HOMO and the other component uses its
LUMO for overlapping. Simultaneously with the merging of the  orbitals, these orbitals also undergo
hybridization to yield the new sp3 σ bonds.
2.6.4 [2 + 2] Cycloaddition Reactions
Thermal induced [2 +2] Cycloaddition Reactions: Thermal induced [2 + 2] cycloaddition
reactions are symmetry forbidden reactions. When ethylene is heated, its  electrons are not promoted
but remain in the ground state Ѱ1. If we examine the phase of the ground state HOMO of one ethylene
molecule and the LUMO of another ethylene molecule we can see why cyclization does not occur by the
thermal induction.

If the reaction bridges opposite faces of a  system, it is said to be antarafacial. An antarafacial

addition is just an anti addition. For bonding to occur, the phase of the overlapping orbitals must be the
same. This is not the case for the ground state HOMO and LUMO of two ethylene molecules or any other
[2 + 2] system. Because the phase of the orbitals is incorrect for bonding, a thermally induced [2 + 2]
cycloaddition is said to be symmetry forbidden reaction.
Photo-induced [2 + 2] Cycloaddition reactions: When ethylene is irradiated with photon of UV
light, a -electron is promoted from  to * orbital in some, but not all, of the molecules. The result is
a mixture of ground state and excited state ethylene molecules.

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 Thus photo-induced cycloaddition takes place between photochemical HOMO of one molecule
and ground state LUMO of another molecule. From the example, it is clear that for cycloaddition reaction
both HOMO and LUMO should have the same symmetry otherwise reaction will be symmetry forbidden.
For symmetry allowed reaction if HOMO has m-symmetry then LUMO should also have m-symmetry.
Similarly if HOMO has C2-symmetry then LUMO should also have C2-symmetry.
2.6.5 [4 + 2] Cycloaddition Reactions
Diels-Alder reaction is the best known [4 + 2] cycloaddition reaction. This reaction is thermally
allowed but photochemically forbidden.
2.6.6 Diels Alder Reaction
The Diels–Alder reaction, named for German chemists Otto Diels and Kurt Alder, is an
addition reaction between a 1,3-diene and an alkene called a dienophile, to form a new six-membered
ring.

All Diels–Alder reactions have the following features in common

 They are initiated by heat; that is, the Diels–Alder reaction is a thermal reaction.
 They form new six-membered rings.
 Three o bonds break, and two new C–C bonds and one new C–Cbond form.
 They are concerted; that is, all old bonds are broken and all-new bonds are formed in a single
step.

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2.6.6.1 Diene and Dienophile
The Dienes: The diene of the Diels-Alder reaction is electron-rich, while the dienophile is
electron-poor. Some reactions with electron-poor dienes and electron-rich dienophiles are also known,
but these are relatively rare. Simple diene such as 1, 3-butadiene is sufficiently electron-rich to be
effective dienes for Diels-Alder reaction. The presence of electron releasing groups such as alkyl groups,
phenyl groups or alkoxy groups may further enhance the reactivity of dienes. The diene component of
the Diels-Alder reaction can be open-chain cyclic but it must have s-cis conformation. Butadiene
normally prefers the s-trans conformation with the two double bonds as far away from each other as
possible for steric reasons. The barrier to rotation about the central sigma bond is small and rotation to
the less favorable but reactive s-cis conformation is rapid.

Cyclic dienes that are permanently in the s-cis conformation are exceptionally good for Diels-
Alder reaction. On the other hand, cyclic dienes that are permanently in the s-trans conformation and
cannot adopt the s-cis conformation will not give the Diels-Alder reaction at all. If the diene is in the s-
trans conformation the dienophile cannot reach both ends of the diene at the same time.

This explains why dienes such as those given below will not serve as dienes in the Diels-Alder reaction

The Dienophile: The most common dienophiles are the electron-poor alkenes and alkynes. Since
electron-poor alkenes and alkynes are prone to react with a diene, these are called dienophile. Thus the
simple alkenes and alkynes such as ethylene and acetylene are not good dienophiles. A good dienophile
generally has one or more electron-withdrawing groups pulling electron density away from the bond.
Dienophiles that do undergo the Diels-Alder reaction include conjugate carbonyl compounds, nitro
compounds, nitriles, sulphones, arylalkenes, arylalkynes, vinyl ether, vinyl esters, haloalkanes,
haloalkenes, and dienes.

89
2.6.6.2 Mechanism and Stereochemistry of Diels-Alder Reaction
The mechanism of the Diels-Alder reaction is a simultaneous cyclic movement of six electrons:
four in the diene and two in the dienophile. The simple representation of the mechanism shown below is
fairly accurate. This is called a concerted reaction because all the bond making and bond breaking occurs
simultaneously. For these three pairs of electrons to move simultaneously, however, the transition state
must have a geometry that allows overlap of the two end p-orbitals of the diene with those of the
dienophile.

There are three major stereochemical features of the Diels-Alder reaction that are controlled by
the requirements of the T.S.
1) S-cis conformation of the diene: This mechanism explains why should be in s-cis conformation.
Diels-Alder reaction is a one-step reaction that proceeds through a cyclic transition state. Bond formation
occurs at both ends of the diene system, and the Diels-Alder transition state involves a cyclic array of six
carbons and six  electrons. For this, the diene adopts the s-cis conformation in the transition state.

When the diene is in the s-trans conformation, the end p-orbitals are too far apart to overlap with
the p-orbitals of the dienophile. Structural features that aid or hinder the diene in achieving the s-cis
conformation affect its ability to participate in the Diels-Alder reaction. Thus the diene with functional
groups that hinder the s-cis conformation react slower than butadiene. Dienes with functional groups
hinder the s-trans conformation react faster than butadiene.

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 Syn stereochemistry: The Diels-Alder reaction is a syn addition with respect to both the diene
and dienophile. The dienophile adds to one face of the diene, and the diene adds to one face of the
dienophile. As you can see from the transition state, there is no opportunity for any of the substituents
that are on the same side of the diene or dienophile will be cis on the newly formed ring. Thus, the
stereochemistry of the diene and dienophile are preserved during the adduct formation.
Stereochemistry of the adduct due to stereochemistry of the dienophile
The Diels-Alder reaction is stereospecific. Substituents that are cis in the dienophile remain cis
in the product; substituents that trans in the dienophile remain trans in the product.

Stereochemistry of the product due to the stereochemistry in the diene

The product stereochemistry is controlled by the geometry of the diene. This is slightly more
complicated as the diene can cis, cis; trans, trans or cis, trans. Terminal vinylic carbons of the cis diene
contain two substituents. One is designated as an outside group and the other is designated as inside group
of the diene.

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 Outside group at C-1 and C-4 are always trans to each other. Similarly, two inside groups at C-1
and C-4 are cis to each other. As mentioned earlier that the Diels-Alder reaction is stereospecific.
According to the structure of the transition state of the Diels-Alder reaction, the outside substituents of
the diene are always below the plane of the new six-membered rings of the adduct. Thus the inside
substituents of the diene should always above the plane of the new six-membered rings of the product.

2.6.6.3 Endo and Exo stereochemistry

The Diels-Alder reaction will produce a bicyclic ring system if the diene is monocyclic. Cyclic
dienes are particularly reactive in Diels-Alder reaction because the two double bonds are held in an s-cis
conformation is five or six-membered rings. This can be seen in the reaction of 1, 3-cyclopentadiene with
methyl propenoate.

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 An orientation is said to be endo meaning that the substituents are trans to the bridge carbon or
substituent projects into the cavity on the concave side of the bicyclic ring. Similarly, an orientation is
said to be exo meaning that the substituents are cis to the bridge or substituents projects out of the cavity
on the concave side of the bicyclic ring.

The exo product is expected to be more stable than the endo product for steric reasons. In exo
product, the exo substituent points away from the more congested part, i.e. bicyclic ring but in endo
product the endo substituent points towards the more congested part. Thus steric repulsion in endo is
more than in exo. Due to this reason, exo is expected to be more stable than endo. But in practice it has
been found that the diene has  a bond in its electron-withdrawing group then the en do product is more
stable than the expected exo product. This stereochemical preference for the endo position is often called
the endo rule. The reaction of 1, 3-butadiene with methyl propenoate produces three times as much as
exo product. Endo product is major product due to the secondary interactions.

2.6.6.4 Orientation Effects in Diels-Alder Reaction

Even when the diene and dienophile are both unsymmetrically substituted, the Diels-Alder
product is usually a single isomer rather than a mixture. The product is the isomer that results from
orienting the diene and dienophile so that we can imagine a hypothetical reaction intermediate with a
push-pull flow of electrons from the electron-donating group to the electron-withdrawing group.

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Case 1: When the electron-donating group is present on the middle carbon of the diene.

Imaginary flow of electrons, in this case, is as follows:

Thus, if the electron-donating group is present either at C-2 or at C-3 then in this case product is
always 1,4 and not 1,3.
Case 2: When an electron-donating group is present at the terminal carbon of the diene.

Imaginary flow of electrons, in this case, is as follows:

Thus, if the electron-donating group is present either at C-1 or C-4 then, in this case, the product
is always 1, 2 and not 1,3.
2.6.6.5 Intramolecular Diels-Alder Reactions
When diene and the dienophile are part of the same molecule then such type of molecule gives
Diels-Alder reaction known as intramolecular Diels-Alder reaction.

The above example is an intramolecular Diels-Alder reaction. In the intramolecular Diels-Alder

reaction, the stereochemistry at fused ring carbons depends on the nature of the substituents on the
dienophile part of the molecule.

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 Case 1: When the electron-withdrawing group is not present on dienophile.
In this case, the two ring junction are trans to each other. Thus the substituents on both fused carbons are
always trans to each other.

Case 2: When the dienophile part has an electron-withdrawing group which is present in the
inner carbon of the dienophile.

In this case, both bridges hydrogen are cis to each other and perpendicular to the plane of the
ring.

Case 3: When the electron-withdrawing group is present on the terminal carbon of the dienophile
and geometry is cis. In this case, a mixture of two products are formed. In one product both the hydrogen
of the fused ring carbons are cis. In other product both hydrogens are trans. Electron-withdrawing group
is always below the plane of the ring and trans to the bridged hydrogen

Case 4: When the electron-withdrawing group is present on the terminal carbon of the
electrophile and geometry is trans.

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 In this case, also a mixture of two products are formed. In one product both hydrogens of the
bridge carbons are cis and in other product both are trans. Electron-withdrawing group is always below
the plane of the ring and cis to adjacent hydrogen of the bridge carbon.

2.6.7 Woodward-Hoffmann rule for cycloaddition reactions

Thermal reactions: A thermal (ground state)pericyclic change is symmetry allowed when the
total number of (4q+2)s and (4r)a components are odd.
Photochemical reactions: A pericyclic change in the first electronically excited state is
symmetry allowed when the total number of (4q+2)s and (4r)a is even.
Woodward-Hoffmann rule in (4+2) cycloadditions
Draw the general mechanism of the reaction.

Choose the components. All the bonds taking part in the mechanism must be included and ignore
all substituents which are not directly involved.

Make a three-dimensional drawing of the way of the components come together for reaction
putting the orbitals at the ends of the components.

96
 Join the components where the new bonds are to be formed.

Label each component s or a depending on whether new bonds are formed on the same side or
opposite sides.
Count the number of (4q+2)s and (4r)a components.
Number of (4q+2)s component = 1
Number of (4r)a component = 0
Total=1 (odd) Thermally allowed.
Woodward-Hoffmann rule in 2+2 cycloadditions

Number of (4q+2)s component = 2

Number of (4r)a component = 0
Total= 2 (even) Photochemically allowed.
2.6.8 Frontier Orbital Description of [4 +2] Cycloadditions
The reaction condition of [4 + 22] cycloaddition reactions are different from [2 + 2] cycloaddition
reaction. [4 +2] cycloaddition reaction is thermally allowed whereas [2 + 2] cycloaddition reaction is
photochemically allowed. To see why this is so, we will examine the HOMO-LUMO interactions on only
the p-orbital components that will form the new sigma bonds in a [4 + 2] cycloaddition. We will compare
the HOMO-LUMO interactions for the ground state for a thermal-induced reaction and those for the
excited state for photo-induced reaction.
Case 1: HOMO of diene and LUMO of dienophile

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 Thermal induced reaction: There are two possible interactions, HOMO (diene)-LUMO
(dienophile) and HOMO (dienophile)-LUMO (diene).
Case (ii) LUMO of diene and HOMO of dienophile.

The stronger of these two interactions will control the reaction. In this case, the stronger
interaction is between the HOMO and LUMO pair closer in energy. The strength of the orbitals overlap
and the magnitude of the resulting stabilization depends on the relative energies of the two orbitals. The
closer the two are in energy, the stronger the interaction. In the Diels-Alder reaction of ethylene and
butadiene, the two HOMO-LUMO interactions are of equal energy and orbital symmetry is same in both
reactions. Both interactions involve bonding overlap at the point of formation of the two new sigma
bonds. Accordingly, this reaction is symmetry allowed reaction.
Photoinduced reactions: In photo-induced cycloddition reaction, interaction always takes place
between excited state HOMO of diene and ground state LUMO of dienophile and vice-versa. Thus, there
are two possible interactions.
(i) Excited-state HOMO and ground state LUMO (dienophile), and
(ii) (ii) Excited state HOMO (dienophile) and ground state LUMO(diene)
Let us take the example of excited state HOMO of diene and ground state LUMO of dienophile.
When butadiene is excited by light its HOMO becomes which has m-symmetry. This MO cannot overlap
with ground state LUMO of the ethylene which has C2-symmetry.

Thus, the photochemical cycloaddition of [4+2] system is a symmetry forbidden reaction. On the
basis of the result, we can obtain the following selection rules for the cycloaddition reactions.
Selection rules for cycloaddition reactions
Number of pi bonds Number of electrons Mode of activation Allowed sterecheomistry
Even (4n)π Photochemical Supra-Supra
Odd (4n +2)π Thermal Supra-Supra

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2.6.9 Mobius-Huckel theory for (4n+2) and (4n) thermal cycloaddition reactions
This method is used for assessing whether a given pericyclic process is allowed to examine the
cyclic array of orbitals at the transition state of the pericyclic reactions. This method was popularized by
H.Zimmerman and M.J.S.Dewar. Huckel rule of aromaticity states that a monocyclic planar conjugated
system is aromatic if it has (4n+2) conjugated electrons and consequently stable in the ground state.
Similarly, the monocyclic planar conjugated system is anti-aromatic if it has (4n)-conjugated electrons
and unstable in the ground state. However, further studies showed that these rules are reserved by the
presence of a node in the array of aromatic orbitals. Thus, a system with (4n+2) system and a node is
anti-aromatic while the system with (4n) electrons and a node is aromatic.
Thus, the system has no node then:
 (4n+2) electrons, the system is aromatic and stable in the ground state.

 (4n) electrons, the system is anti-aromatic and unstable in the ground state.
Similarly, a system having a node then:
 (4n) electrons, the system is aromatic and stable in the ground state.
 (4n+2) electrons system is anti-aromatic and unstable in the ground state.
If the system has no node then it is called Huckel system and array is called Huckel array.
Similarly, if the system has no node then it is called Mobius system and array is called Mobius array.
Applications of these rules to pericyclic reactions led to the generalization that thermal reaction takes
place via aromatic transition state[i.e. (4n+2) electrons having no node or (4n)electrons having one
node] whereas, photochemical reactions proceed via anti-aromatic transition state [i.e. (4n) electrons
having no node or (4n+2) electrons having one node].
A cyclic transition state is said to be aromatic with the corresponding aromatic system if the
number of the conjugated atoms and that of the  electrons involved are the same as in the corresponding
aromatic system. Similarly, a cyclic transition state is the number of conjugated atoms and that of the 
electrons involved are the same as in the representing those orbitals which undergo in the transition state
and assigned to the wave function is the best manner of overlap. Then the number of nodes in the array
and the number of electrons involved are counted.
2+2 cycloaddition reactions: A [2 + 2] cycloaddition reaction does not occur under thermal
conditions but does take place under photochemical conditions. Because under thermal condition the
transition state is anti-aromatic

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[4+2] Cycloaddition reactions

Orbital diagram

Selection rules for cycloaddition reactions

m+n Number of Aromaticity Thermally Photochemically
electrons Nodes Allowed Allowed
4n Zero Anti-aromatic Supra-antara
Anrata-supara
4n One Aromatic Supra-antara
Anrata-supara
4n+2 Zero Aromatic Supara-supara
Antara-antara
4n+2 one Anti-aromatic Supara-supara
Antara-antara

Analysis of Cycloaddition Reactions

 Cycloadditions that form four or six-membered rings must take place by suprafacial pathways.
 In a cycloaddition, we examine the bonding interactions of the HOMO of one component with
the LUMO of the second component.
 [4 + 2] cycloaddition occurs readily by suprafacial reaction under thermal conditions.
 Thermal cycloadditions involving an odd number of n: bonds proceed by a suprafacial pathway.
 Stereochemistry of the diene is retained in the Diels-Alder product.

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 [2 + 2] cycloaddition does not occur under thermal conditions but does take place
photochemically. This result is explained by examining the symmetry of the HOMO and LUMO
of the alkene reactants.
 Photochemical cycloadditions involving an even number of 7π bonds proceed by a suprafacial
pathway.

Summary
 Pericyclic reaction is a type of organic reaction wherein transition state in molecule has a cyclic
geometry and the reaction progresses in a concerted fashion.
 Electrons in atoms are associated with wave-like and practical like character.
 As a wave the electrons are defined by wave function called
 Linear combination of atomic orbitals of comparable energy give same number of molecular
orbitals called MOs.
 The wave function of electrons of the same phase interfere constructively which lead to bonding
interaction.
 The electrons in bonding orbitals are more delocalized then they are being in atomic orbitals this
lead to a decrease in the kinetic energy of electrons.
 Number of bonding -molecular orbitals and antibonding -molecular are same.
 The number of electrons in any molecular orbital is maximum two.
 If a molecular orbital contains two electrons, then both electrons are always paired.
 Energy of the -molecular orbitals is directly proportional to the nodal planes.
 There will be no degenerate orbital in any energy level.
 The highest energy orbital that contains electrons is called the highest occupied molecular orbital
(HOMO).
 The electrons in HOMO orbital are like the outer shell of electrons. They can be removed easily
with the least expenditure of energy because they are in higher energy levels.
 The lowest energy orbital that contains no electrons is called the lowest unoccupied molecular
orbital (LUMO).
 The LUMO of the molecule is the orbital through which electrons can be transformed with the
least expenditure of energy.
 The nodes occur between atoms and are arranged symmetrically with respect to the center of the
-electrons.
 The wave function will have n-1 nodes.
 For a given molecule HOMO and LUMO have opposite symmetry. Or both symmetries (m, and
C2) are not present in the same time in -molecular orbitals.
 Thermally allowed reaction are forbidden photochemically and vice versa.
 Pericyclic reactions require light or heat and are completely stereospecific; that is, a particular
stereoisomer of the reactant forms a particular stereoisomer of the product.

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  The product formed in thermal mode has opposite stereochemistry than that of photochemically
product.
 Cycloadditions that form four or six-membered rings must take place by suprafacial pathways.
 In a cycloaddition, we examine the bonding interactions of the HOMO of one component with
the LUMO of the second component.
 [4 + 2] cycloaddition occurs readily by suprafacial reaction under thermal conditions.
 Thermal cycloadditions involving an odd number of π bonds proceed by a suprafacial pathway.
 Stereochemistry of the diene is retained in the Diels-Alder product.
 [2 + 2] cycloaddition does not occur under thermal conditions but does take place
photochemically. This result is explained by examining the symmetry of the HOMO and LUMO
of the alkene reactants.
 Photochemical cycloadditions involving an even number of π bonds proceed by a suprafacial
pathway.
 The reaction in which symmetry of the molecular orbital is conserved involved a relatively low
energy transition state and thus symmetry allowed reaction.
 The reaction where the symmetry of orbitals is destroyed by bringing one or more orbitals out of
the phase the energy of transition state becomes too high because of interaction therefore,
symmetry forbidden reaction.
 Pericyclic reactions are potentially reversible.

Problems
Write the answers to the following question
1. Write the possible product of this reaction.

2. The following all cis cyclic polyenes readily give bicyclic products upon heating. Explain the
reactions and give the structures of the products.
(a) cyclonona-1,3,5-triene
(b) cyclodeca-1,3,5,7,9-pentaene
3. (2 E ,4 Z ,6 Z ,8 E )-Deca-2,4-6-8-tetraene readily undergoes two consecutive electrocyclic
reactions. Explain the reactions and give the structures of the intermediate and final products.
4. 2,5-Dimethylfuran undergoes a Diels–Alder reaction with maleic anhydride to give an adduct
which can be transformed into 3,6-dimethylphthalic anhydride by an acid-catalyzed dehydration.
Give the structure of the Diels–Alder adduct and a mechanism for its acid-catalyzed dehydration.
5. When buta-1,3-diene is heated, it slowly dimerizes in a cycloaddition reaction. By giving the
mechanism, predict the structure with stereochemistry of the dimer of butadiene.

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6. 5-Methoxycyclohexa-1,3-diene gives an equilibrium mixture with 1- and 2
methoxycyclohexa1,3-dienes upon being heated.
a) Give a mechanism for this equilibration.
(b) Which is the most stable isomer?
7: Explain regioselectivity of following reactions

References

1) Christian M. Rojas-Molecular Rearrangements in Organic Synthesis-Wiley (2010).

2) Principles of Organic Synthesis by Sir Richard Norman 3rd Edition Springer Science.
(1968).
3) Essentials of Pericyclic and Photochemistry by Biswanath Dinda Springer Science
(2017).
4) Pericyclic reactions and Organic Photochemistry by Vinay P. Sharma Pragati
Prakashan Educational Publishers (2008).
5) Organic Chemistry by Clayden, Greeves, Warren and Wothers 2nd Edition Oxford
University Press (2012).
6) Mechanisms is advanced Organic chemistry by R.P. Narain New Age International (P)
Ltd., Publishers. (2008)
7) Organic reaction and their Mechanism by P.S Kalsi 4th Edition New Age International
(P) Ltd., Publishers. (2017)
8) Advanced Organic Chemistry by Ashutosh Kar MedTech (2017)

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