Chapter 3..

Rearrangement Reactions
Contents
3.1 Introduction
3.2 Types of Rearrangements
3.3 Types of Reactive Intermediates involved in different Rearrangements
3.4 Beckmann Rearrangement
3.5 Baeyer-Villiger Oxidation
3.6 FavorskiiRearrangement
3.7 Curtius Rearrangement
3.8 Lossen Rearrangement
3.9 Schmidt Rearrangement
3.10 Pinacol-Pinacolone Rearrangement
3.11 Electrocyclic Rearrangements
3.11.1 The Claisen Rearrangement
3.11.2 Cope Rearrangement
3.11.3 Mc-Lafferty Rearrangement
Exercise

3.1 Introduction
A rearrangement reaction is a broad class of organic reactions where the casbon
skeleton of a molecule is rearranged to give a structural isomer of the original molecule.
The migration of an atom or group from one position to another within the same
molecule is known as molecular rearrangement. The rearrangement involves migration of
an atom or group of atoms to an adjacent atom (1,2-shift), or in some cases migration is
over longer distances.
where,
=
M M A Migration origin
B= Migration terminus
1, 2- shift
A -B A- B M= Migrating group
The atom from which migration begins is known as the migration origin and the atom to
which migration group moves is called migration terminus.

(3.1)
 [Link]. Organic Chemistry - I (Sem. V)
3.2 eactions

rearrangement reaction, migrating group shift with its lone pair of electrons callad
In
group shift without electro
nucleophilic (anionotropic) rearrangement and migrating
rearrangement. In the rearrangement, if the
pair is called electrophilic (cationotropic)
migrationof group is with one electron then it is called free radical rearrangement.

The most common migrating atoms

are carbon, hydrogen or heteroatom. The
rearrangement
nucleophilic 1,2-shifts are more common in rearrangement reactions. The
as
reaction involves two possible modes of reaction shown below.
R'
R R
R R' R

) A-B and A
-C A-Band
A

-C with
A B
and A-C
Intermolecular rearrangement
R R' R R'

- -C
(I) A-B and A -C A B
and A

-Intramolecular rearrangement
T type of rearrangements are called as intermolecular rearrangement in which the group
R iscompletely detached from group A and may end up on the B atom or C atom of

another molecule. In II type of rearrangement, R going from A to B in the same

molecule is called intramolecular rearrangement.
3.2 Types of Rearrangements

There are two key rearrangement reactions: 1,2-rearrangements and pericyclic reactions.
() 1,2-Rearrangements : In thistype of reaction the migrating group arries the
electron pair with it, the migration terminus B must be an electron deficient atom with only
six electrons in its outer shell. The first step is the formation of a carbocation intermediate.
Carbocation can be formed from alcohol (the acid treatment of an alcohol to give
carbocation from an intermediate OXonium ion), alkyl halide (reaction with AgN03) and
alkene (electrophilic addition to C=C).
R

JA-B

R R H -H,0 R
OH CC--C-H
H H H
H H
Carbocation intermediate
[Link]. Organic Chemistry -I (Sem. V) 3.3 Rearrangeme

are, Beckmann, Baeyer-Villiger, Lossen, Schmidt,

Examples of these rearrangements
Curtius, Pinacol, Wagner-Meerwein Rearrangement

H*
HO.
-H,0

is a type of reaction with multiple carbon

(ii) Pericyclic reaction : A pericyclic reaction
a
wherein the transition state of the molecule has cyclic
carbon bond making and breaking
a concerted fashion. Examples of pericyclic
geometry and the reaction progresses in
reactions are Claisen, Cope, Diels Alder and McLafferty rearrangements.
R (1,3)
H

R
(1, 5)

H
R R

(1, 7)

3.3 Types of Reactive Intermediates involved in Different

Rearrangemens
electron
Rearrangement reactions usually involve carbocation, carbanion, carbene, and
are most common
deficient nitrogen and oxygen intermediates. Carbocation intermediates
intermediates in rearrangement reactions.
Rearrangements involving Carbocation Intermediate
B-alkyl, aryl or
The skeletal rearrangement of carbocation which involves migration of
In most of the carbocation
o-bond is called Wagner-Meervwein rearrangement.
rearrangement reactions, migration of an atom or group occurs due to the formation of
more stable carbocation from less stable carbocation. Neopentyl alcohol on treatment
with HCI gives the rearranged product 2-chloro-2-methyl butane.
 Rearrangement Reactione
Organic Chemistry - I (Sem.
3.4
[Link]. V)

CH, 1,2-CH, CHa

CH3 CH, OH,

H,C-C-CH,-OHHC-C-CH, HCI
|TH,0 +H4C-C-H shift H,C--H,
CH, H CH,
CH3 CH3
[°-Carbocation III°-Carbocation
(Neopentyl alcohol) . (more
(less stable) stable)
2, 2-dimethyl propanol

CI

H,C-C-CH,-CH,
CH,
2-chloro-2-methyl butane
Rearranged product
This rearrangement occurs via carbocation intermediate and involves migration of alyl
group with its lone pair of electrons to an electron deficient carbon atom. It forms more
stable carbocation which finally react with nucleophile to give rearranged product.
In another case, the addition of HCI to 3,3-dimethyl-1-butene forms 3-chloro-2,2
dimethyl butane (an expected product) and 2-chloro-2,3-dimethyl butane
(rearrangement product). The rearranged product is the major product.
CH, iCH,. H CH,
HCI 1, 2-CH, shift
H,C--C=C-H H,C-¢ -H H,C-C-C-CH
CH, H H CH, H H CH, H
3, 3-dimethyl -1-butene II°-Carbocation
III°-Carbocation
(less stable)
(more stable)

CI CH,

H,C---CH,
CH, H
The order of stability of carbocations 2-chloro-2, 3-dimethyl butane

The carbocations rearrange

is
only
>r>> CH.
if they become more of
rearrangement. stable as a result
CH, CHg
AgNO,
H,C-C-CH,Br
H,0 H,C---CH, 1, 2-CH, shift
CH,
CHa
H,C-C-CH,
1-Bromo-2, 2-dimethyl propane [°-Carbocation CH3
III°-Cartbocation
[Link]. Organic Chemistry -I (Sem. V) 3.5 Rearrangement Reactions

CHs H CH3 1,2–CH3 CH, 1,2 -H

1,2-H shift shift H shift
C-C-H -H C-H
CH3 H
CH3 CHg CH, CH, CHg
III°-Carbocation I[°-Carbocation II°-Carbocation
more stable

H CHs
CH,
III°-Carbocation
Other examples of rearrangements involving carbocation intermediate are Pinacol, semi
pinacol rearrangements.
Rearrangements involving Carbanion Intermediate
Rearrangements inyolving carbanion intermediates are rare. Some examples of carbanion
intermediates in rearrangements are Favorski, Ramberg-Bäcklund, Stevens and Wittig
rearrangements.
Rearrangements involving Carbene
Rearrangement involving carbene intermediates is Wolff rearrangement.
Rearrangements involving Electron Deficient Nitrogen and Oxygen
Rearrangements to electron-deficient nitrogen are Beckmann, Nebe, Hoffmann, Curtius,
Schmidt, Lossen and Baeyer-Villiger rearrangement.
3.4 Beckmann Rearrangement
Rearrangement of oximes to give N-substituted carboxylic amides, the rearrangement of
ketoxime under the influence of acidic reagents to yield N-substituted carboxylic amides,
is called the Beckmann rearrangement. Aldoximes often are less reactive and they form
nitrile.

PCis

R$* OH
R
is anti to OH

PCI,
H,c
H,C OH
H
Upon treatment with a protic acid, the hydroxy group of the oxime is protonated to give
an oxonium derivative which can easily lose a water molecule. The anti group migration
of the substituent R (together with the bonding electrons) and loss of water proceed
[Link]. Organic Chemistry
Rearrangement Reactions
3.6
-I (Sem. V)

iminol
Simultaneously. The cationic species thus formed reacts with water to give the
which tautomerizes to a more stable amide tautomer, the
N-substituted carboxylie
sulfur dioxide
amide. As reagents are concentrated sulfuric acid, hydrochloric acid, liquid
even silica gel MoO, on silica
thionyl chloride, phosphorus pentachloride, zinc oxide and
gel, RuCl3, Y(OT)3, HCI-HOAC-Ac,0, POCls, BiCl3, heat with FeC3, and polyphosphoric
acid can be used for Beckmann rearrangement. Reagents like phosphorus pentachlorid
(as well as thionyl chloride and others) first convert the hydroxy group of the oxime into
a good leaving group.
The reaction with oximes of cyclic ketones leads to ring enlargement and form lactam by
ring enlargement. This particular reaction is performed on an industrial scale:
E-caprolactam is used as a monomer for polymerization to polyamide for the production
of synthetic fibers.
R
-HOE
1.2 - R' shift
R-C=NR

R
H,O
R-C-N-R' R

H-o
H,0:
OH
N

+ HN–OH N-H
H,o
Example of Beckmann rearrangement:

NH,OH

H
N-OH

(H,PO4)n

N-OH
H

Anthrancene-9,10-dioxime dibenzo[b,1[1,4]diazocine
6,11(5H,12H)dione
[Link]. Organic Chemistry - I (Sem. V)
3.7 Rearrangement Reactions

3.5 Baeyer- Villiger Oxidation

The treatment of ketones with peroxy acids or with hydrogen peroxide, in the presence
acid catalysts, a formal insertion of oxygen followed by migration of alkyl or aryl group
can take place to yield a carboxylic ester. This reaction is called the Baeyer-Villiger
rearrangement.
H,0,, H

H R
R +
R--OH
In a first step,the carbonyl group is taking the proton from acid and protonated to form
carbocation intermediate.
In the second step, the peracid adds to the carbocation to form Criegee intermediate.
In the third step, migration of alkyl or aryl takes place with the elimination of carboxylic
acid.

o-H O-H C-R

R R R
R

R
The ease of migration of substituents depends on their ability to stabilize a positive
R1, Rz

charge in the transition state. For unsymmetrical ketones the approximate order of
migration is RC > RzCH > Ar > RCH, > CH3. The CHs group has a low migrating ability,
and the migrating ability of aryl groups is decreased by electron-withdrawing and
increased by electron-donating substituents. The Baeyer-Villiger oxidation of
unsymmetrical ketones is regioselective.
-H Ho
O-0-C-CH,
Bu
FC--00H Bu
Bu

-H +H

+ CF
C0,H
Bu
 Rearrangement Reactions
- I 3.8
[Link]. Organic Chemistry (Sem. V)

expansion to yield lactones (cyclic esters). Hydrogen

Cyclic ketones react through ring
to lactones uSing a catalytic amount of
ketones
peroxide has been used to convert
cyclic

MeReO3.

mCPBA

OBn
OBn
CI
-CI
mCPBA
NaHCO3, CHzl2 BnO
BnO
OBn
OBn
- Villiger
Examples of Baeyer Oxidation:
OH O OH OH

mCPBA H Hydrolysis OH
1.

CHCl,

2.
CF;CO0OH
CH3 CH,
HgC H Hc
3.6 Favorskii Rearrangement
a-Halo ketones (chloro, bromo, or iodo) possessing at least one a-hydrogen when
treated with a base (NaOH or NaOEt or NaNH2), can undergo a rearrangement reaction
via a cyclopropanone intermediate to give a carboxylic acid or an ester or amide
depending on the base used. This reaction is called Favorskii rearrangement.
the
In the first step, the a-halo ketone is deprotonated by the base at the a'-carbon to give
the carbanion,which undergoes a ring-closure reaction by an intramolecular substitution
to give the cyclopropanone derivative. The nucleophilic addition of
the base to the
cyclopropanone intermediate leads to the ring opening. With a
symmetrically substituted
cyclopropanone, cleavage of either Ca-CO bond leads to
the same product. Witn
unsymmetrical cyclopropanone, that bond is broken
preferentially which leads to
thermodynamically more stable carbanion. The
carbanion intermediate is protonated to
give the final product.
[Link]. Organic Chemistry - I (Sem. V)

3.9 Rearrangement Reactions

:
Reaction mechanism

C
CH, CH, ||
dCH, NaõC,Hs a' CH3 H,C CHg
CH, HOC,Hs CHa H,c CH,
CI H CI
Ooc,ts
Protons a' to ketone is acidic Cl is a leaving group Cyclopropanones are
and sodium ethoxide is strong Carbanion attack on the particularly susceptible
base that easily abstract the a' carbon atom and substitution to nucleophilic addition
-proton to form carbanion as reaction takes place to give due to ring strain
nucleophile cyclopropanone
Addition elimination reaction at the carbonyl and cyclopropanone ring opening takes
place to generate a stabilised enolate product.
oc,Hs ROH CH, O
H,C CH, OC,H, H,C ROH
C-C-0G,Hs
H,C CH H,C H,CCH,
H CH, O

H,c
C-C-0c,Hs
H,

OoH
Ph- CH,-C-CH, Ph -g C-CH Ph

CI H

oH

HO
Ph-CH,-CH,-C--OH Ph- CH,-CH,-C-0 Ph- CH–CH-C-OH
Cyclic a-halo ketones on treatment with base give ring contraction as shown in the
following reaction.

oc,Hs
octsOC,Hs
b

C,H,OH
a

*-OEt EtO-C=0
[Link]. Organic Chemistry Rearrangement Reactions
-I (Sem. V)
3.10

The two important variations of Favorskii rearrangement are

:

When B-halo ketones are treated with base, in presence of nucleophile the reaction
is
L.
a
called Homo-Favorskii rearrangement. This reaction takes place via cyclobutanone
intermediate.
R H
R -R
ROH R
R Base R R
H R
R
R
R R R+ -R
R R
RO
R=alkyl / hydrogen

2. a-haloketone does not have any enolizable hydrogen then the reaction
If is called as
Quasi-Favorskii rearrangement.

OR
R
R' R' RO
OR R
R
4

X R' R?
R° R

Examples of Favorskii rearrangement:

H,C-CH-C-CHCHs 2 H,O + CHCH,- ÇH-C-OH

Br HOH,0 CH,

(1) KOH, H,0

MeOH
COOH
(2) dil. HCI

3.7 The Curtius Rearrangement

The Curtius rearrangement involves the thermal decomposition of an acyl azide to yield
an isocyanate by loss of N2. Isocyanate on hydrolysis gives amine. The Curtius
rearrangement can thus be applied to convert carboxylic acids into primary amines.
CICO,Et NaN3
R OEt
Mixed anhydride

SOCI, NaNg Heat

R CI
or R--Ng R-N=C=0
Acid chloride -N,
TMSN, Acyl azide lsocyanate
(PhO),P(O)Ng

Diphenyl phosphoryl azide (DPPA)

[Link]. Organic Chemistry - I (Sem. V) 3.11 Rearrangement Reactions
This reaction can be applied to almost any carboxylic acids such as aliphatic, aromatic,
alicyclic, heterocyclic, unsaturated, and containing many functional groups. The required
acyl azide can be prepared from the corresponding acylchloride and azide ion (e.g. with
sodium azide) or alternatively from an acyl hydrazine by treatment with nitrous acid or
from mixed anhydride.
Acyl azide can be synthesized from carboxylic acid by using diphenyl phosphoryl azide
(DPPA).
H,0
O=C=0* R-NH,
1° Amine

RNH2
R-N=C=0 NHR'
H
Urea derivative

R'- OH

OR
H

Carbamate
Loss of N2 and migration of the group R is likely to be a concerted process, since
evidence for a free acyl nitrene RCON inthe thermal reaction has not been found.

NaNs
+ R
R--C- C

or TMSN,
Alkali azide
Trimethyl silylazide
Nitrous acid

R - NHNH, +
C- HNO,R

NaNa
+ CI-CO,Et
R--OH Ng
Mixed anhydride

OEt
OEt NaNg
N'Pr,Et

N
PhCH,OH
N=0=0 Ph
H
The Curtius rearrangement is catalyzed by Lewis or protic acids, but good yields of
product are often obtained also without a catalyst. Isocyanates are highly reactive and
as a solvent, the
they immediately react with water and form amine. When alcohol is used
an inert solvent
isocyanate reacts with alcohol to form carbamate. From reaction in
(e.g. benzene, chloroform) in the absence of water, the isocyanate can be isolated.
 Rearrangement Reactions
[Link]. Organic Chemistry - I (Sem. V) 3.12

The examples of Curtius rearrangement are

:

ONaN, / A
H,0
H,CNH,

R~NHNH, + HNO, EtOH

R-N--OEt
H

DPPA, Et,N
O

benzene reflux ,NH-C-0CH,Ph

CH,CH,OH

DPPA is prepared from the corresponding acyl chloride and azide ion (e.g. with sodium
azide) or alternatively from an acylhydrazine by treatment with nitrous acid.

R--OH + (PhO),P-N= =N R nNN=N

Diphenyl phosphoryl azide (DPPA)
The example of Curtius rearrangement :

OH OH
HOOC OBn 'o-c=N OBn HN, OBn

DPPA,Et N

Toluene, heat
OMe OMe OMe
3.8 Lossen Rearrangement
The Lossen rearrangement is the conversion
of a hydroxamate ester to an isocyanate.
Typically, O-acyl, sulfonyl, or phosphoryl
O-derivative are employed. The isocyanate can
be used further to generate ureas in presence
the of amines or generate amines in the
presence of H,0.

.Mechanism:
In the first step an O-acylated
hydroxamic acid derivative
coniugate base by abstraction is first converted to
of a hydrogen by a its
releases a carboxylate anion to base. Spontaneous rearrangement
produce the isocyanate intermediate.
[Link]. Organic Chemistry -I (Sem. V)
3.13 Rearrangement Reactions
In the second step the isocyanate the presence of H20.
is hydrolyzed in
In the final step, the respective amine and CO, are generated by
abstraction of a proton
with a base and decarboxylation.

OH H,0
R
R-NH,
H -R'-COz -CO,

OH-H,0
B:
H
I

-R'-CO;
Examples of Lossen Rearrangement :

N CH, e
NH2
NaOH
H -H,0
O,N
N-acetoxy-4-nitrobenzamide 4-Nitroaniline

KOH NH,
-H,0
N-acetoxyfuran-2-carboxyamide Furan-2-amine
3.9 The Schmidt Rearrangement
An azide when reacts with a carbonyl derivative, usually a
aldehyde, ketone, or carboxylic
acid, under acidic conditions give an amine or amide, with
the expulsion of nitrogen is
known as Schmidt rearrangement. It is named after Karl Friedrich Schmidt, who first
reported the synthesis of benzanilide from reaction of benzophenone and hydrazoic acid.
The reaction is effective with carboOxylic acids to give amines,
and with ketones to give
amides.

H
R
H,0

H+ H--NEN R?
H,0
R
 Rearrangement Reactions
[Link]. Organic Chemistry
-I (Sem.
V)
3.14

Mechanism :

rearrangement except that in this reaction

Tne reaction is closely related to the Curtius
acyl azide is produced by reaction of the carboxylic acid with hydrazoic acid via the
the
a process similar to a Fischer esterification. An alternative,
protonated carboxylic acid, in
more important when the reaction
involving the formation of an acylium ion, becomes
Curtius rearrangement,
takes place in concentrated acid (>90% sulfuric acid). (In the
sodium azide and an acyl chloride are combined to quantitatively
generate the acyl azide
intermediate, and the rest of the reaction takes place under neutral conditions.)
This mechanism begins with the formation of an acylium ion 1 from the protonation
of
the carboxylic acid followed by the removal of water.
a
This acylium ion is now reacted with hydrazoic acid, leading to the formation of
protonated azido ketone 2.
Now, the protonated azido ketone 2 and the R group undergo a rearrangement reaction,
resulting in the migration of the carbon-nitrogen bond and the removal of dinitrogen
leading to the formation of a protonated isocyanate 3.
Now, a carbamate 4 is formed when water is introduced to attack the protonated
isocyanate.
The carbamate 4 is now deprotonated. The subsequent removal of CO, yields the
required amine.
10
R R

H H
H

+
-H 3
R-NH,
O5 4
In the reaction mechanism for the Schmidt reaction of ketone,
the carbony! group is
activated by protonation for nucleophilic addition by
the azide, forming azidohydrin 3,
which loses water in an elimination reaction to
diazoiminium 5. One of the alkyl or aryl
groups migrates from carbon to
nitrogen with loss of nitrogen to give a nitrilium
intermediate 6, as in the Beckmann rearrangement.
Attack by water converts 6 to
protonated imidic acid 7, which undergoes loss of proton
to arrive at the imidic acid
tautomer of the final amide 8.
In an alternative mechanism,
the migration occurs at 9, directly after
intermediate 3, in a manner similar to protonation of
the Baeyer-Villiger reaction to give
amide 10. Loss ofa proton again furnishes the amide 8. protonated
[Link]. Organic Chemistry - I (Sem. V) Rearrangement Reactions
3.15

It has been proposed that the dehydration to 3 to give 5 (and, hence, the Beckmann
pathway) is tavored by nonaqueous acids like conc. HSO, while aqueous acids like conc.
HCI favor migration from
9 (the Baeyer-Villiger pathway).
These possibilities have been used to account for the fact that, for certain substrates IKe
a-tetralone, the group that migrates can sometimes change, depending on tne
conditions used, todeliver either of the two possible amides.
H

HN RneH
HO,N H B-V 10
R R' RR' RR' pathway HOR'
1 2 3 9

N, RNeH
N,
Beckmann H,0 R

R-N-R' pathway
RR' R R

R
6 5 4
Tautomerize

H,0 R' R'

R-N R-N
R-N=-R'
OH
7
Examples of Schmidt Rearrangement:
O,N O,N
Ng
-OH
-
H,SO4, 80-100°C, 15 min.
N

H -OH
63%

MeAICl,

CH,Cl, 96%

N.

3.10The Pinacol Rearrangement

When vicinal diol is treated with a catalytic amount of acid, it can rearrange to give an
as Pinacol
aldehyde or ketone by migration of an alkyl or aryl group which is called
Rearrangement. The pinacol-pinacolone rearangement reaction or 1,2- migration can be
viewed as a
special case of the Wagner-Meerwein rearrangement.
 [Link]. Organic Chemistry Rearrangement Reaction
-I(Sem. V)
3.16

OH
OH R
RR R R
R

OH
OH CH,
H,c CH, H,C TCH,
CH,
H, CH,

When Me,COHCOHMe, (pinacol) on treatment with acid gives Me,COHMe, which on

1 2-migration of Me to yield Me,CCOCH, is called as pinacolone.
CH, CH3 CH, CH, CH, CH, 1,2-CH,
H,C-C(-CHg -H,0 shift
H,C-C- -C-CH H,C-CCH,
:OH :OH I.C. OH

Pinacol
CH3 CH, CH,
H,C--(-CH H,C-C-CH,
0-H CH3 CH3
Pinacolone
:
Mechanism
In the first step one hydroxy group is protonated, and thus converted into a good leaving
group. The elimination of water from the molecule proceeds in such a way
that the more
stable carbocation intermediate is formed.
OH OH, OH OH OH

H,C-C-(-H H,C-C-C-H H H,C-(-H

CH, CH, CH, CH
CH, CHg
III° Carbocation
more stable
OHOH
OH
-H,0
H,C-C-C--H H,C-C-(-H
CH, CHg CH, CH,
II° Carbocation
less stable
[Link]. Organic Chemistry
-I (Sem. V)
3.17 Rearrangement Reactions

In the second step, 1,2-shift of a R aroup to the more stable (I) carbocation takes place
to give a more stable hydroxyl carbocation intermediate. The reaction is intramolecular;
the migrating group R is never completely released from the substrate. The driving force
is the formation of the more stable rearranged carbocation, which is stabilized by the

hydroxy group. In the third step, loss ofa proton yields the carbonyl compound.
:ÖH 1,2 CH, CHa(:0H CH O -H
shift -H
H,C-C(H H,C-C H,C-C C-H
CH, :CH3} CH, CH3

III Carbocation Carbocation stabilised by CH O

hydroxyl group
H,C-¢--H
CH,
Reaction with an unsymmetrical diol as starting material may give rise to formation of a
mixture of products. Mixtures are product formed, may depend on the reaction
conditions, which group preferentially migrates as well as on the nature of the substrate.
The order of migration is RsC > RzCH> RCH; > CH > H.

H H,SO4 CsHs CHg CH, CHg

-H,0
H,CG- -C-CH, H,Cg-C--CH, HC-C-
More stable,
H,Cg-C stabilized by two
-C-CH3 Ph groups
OH OH
CgHs CH, 1,2-Ph shift
-H,0
CH,COOH +
H,co -CH,H,c,- s-CH, H,C-¢ CH,

a trace of H,SO4 ÖH OH2

Less stable

The action of cold, conc. H;SO4 on A produces mainly the ketone B (-CHg migration),
while treatment of A with acetic acid containing a trace of H;SO4 gives mostly C (phenyl
migration). If one R is hydrogen, aldehydes can be produced as well as ketones.
Generally, aldehyde formation is favored by the use of mild conditions (lower
temperatures, weaker acids),
Ph Ph Ph Ph
Ph--(-CH, Ph- -C-CH3 +
Ph-C--Ph
OH OH Ph CH
Major Minor
 Rearrangement
[Link]. Organic Chemistry 3.18 Reaction:
-I(Sem. )
Examples of Pinacol Rearrangement :
H H

Ph---CH, Ph-CH,-C-CH,
OH OH

OH OH

OH OH CHg
Ph
Ph
CH, CH, CH,
AgNO,
(4) H,C---H H,C-C--(- CH,

OH Br H

CH, CH3 CH,

NaNO,
6) H,C-(-(-H H,C-C--(-CH,
HO NH, O H

3.11 Electrolytic Rearrangements

An electrocyclic reaction is a type of pericyclic rearrangement where the net result is
one pi bond being converted into one sigma bond or vice versa. These reactions are usualy
categorized by the following criteria :
Reactions can be either photochemical or CH3
CH, 170°c
thermal.
H
Reactions can be either ring-opening or ring
H
closing (electrocyclization). cis cis, trans
Depending on the type of reaction
(photochemical or thermal) and the number of pi CH,
electrons, the reaction can happen 170c
throughH
either a conrotatory or disrotatory mechanism. H

The type of rotation determines whether the cis CHg

or trans isomer of the product willbe formed. trans trans, trans

System Thermally induced Photochemically induced

(ground state) (excited state)
Even number of conjugation Conrotatory
Disrotatoy
Odd number of conjugation | Disrotatory
Conrotatory
3.11.1 The Claisen Rearrangement
Allylic aryl ethers, when heated, rearrange to ortho-allylphenols,
this reaction is called the
Claisen rearrangement. If both ortho positions are filled,
para position (para-Claisen rearrangement). the allylic group migrates tothe
[Link]. Organic Chemistry - I (Sem. V)
3.19 Rearrangement Reactions
The Claisen rearrangement reaction is a concerted pericyclic [3,3]
SigmatroplC
rearrangement reaction. A carbon-oxvgen bond is cleaved and a carbon-carbon bond is
formed followed by tautomerization to the stable
aromatic allyl phernol.
1

OH
2

[3, 3]
Allyl phenyl ether Sigmatropic Ortho
rearrangement allyl
phenol
2
10
3 [3, 3] Sigmatropic.
2 rearrangement
Allyl vinyl ether Y- unsaturated
carbonyl compound

OH

2x [3, 3]
Sigmatropic
Substituted rearrangement
allyl
phenyl
ether Para allyl phenol
Allylic ethers of enols (allylic vinylic ethers) also undergo the Claisen rearrangement.

H
OH

[3, 3]

3,3]
R
-R' R
A
[3, 3]
COOEt co,Et
2
R
R
[Link]. Organic Chemistry-I (Sem. V)
3.20 Rearrangement Reactions

Inthe ortho migration, the allylic group always undergoes an allylic shift. Whereas in the
para-Claisen rearrangement there is never an allylic shift. The allylic group is found
exactly as it was in the original ether.

OH
Me Me
Me Me Me Me Me Me
Me
Me
[3, 3] (3, 3)

3.11.2 The Cope Rearrangement

The Cope Rearrangement is thé thermal isomerization of a 1,5-diene leading to a
regioisomeric 1,5-diene. The main product is the thermodynamically more stable
regioisomer.
R

The Oxy-Cope has a hydroxyl substituent on an sp°-hybridized carbon

of the starting
isomer.
HO.
HO

The driving force for the neutral or aníonic Oxy-Cope Rearrangement

is that the product
is an enol or enolate (resp.), which can
tautomerize to the corresponding carbonyl
compound. This product will not equilibrate back to the other regioisomer.
The Oxy-Cope
Rearrangement proceeds at a much faster rate when the starting alcohol is
e.a. with KH. The reaction is deprotonated,
then up to 10* times faster, and may be conducted at room
temperature. Aqueous work up then gives the carbonyl compound.

HO HO
KH HO

:
Mechanism
R
R

R
[Link]. Organic Chemistry - I (Sem. V)
3.21 Rearrangement Reactions

Two transition states are possible, and the outcome of the reaction can be predicted on
the basis of the most favorable overlap of the orbitals of the double bond, as influenced by
stereoelectronic factors:
OH OH

H 2
H

Examples of Cope and Oxy-Cope Rearrangement :

Heat

3.11.3 The McLafferty Rearrangement

The McLafferty-Rearrangement is observed in compounds in which at least
one
abstractable gamma (y) hydrogen is present with respect to a pi (r) bond. When such
compounds are ionized as molecular ions, in mass spectrometer, usually by the Electron
lonization (ED method. The resultant molecular ion undergoes a special type of
rearrangement. The hydrogen at gamma (y) position transfers to the carbonyl functional
group followed by the hemolytic cleavage of the Ca-Cg sigma bond. This rearrangement
finally results in the formation of an olefin without any charge and
an enol radical cation
as products.
This rearrangement is widely observed in Aldehydes, Ketones, Carboxylic acids,
Esters,
Amides, Imines, Cyanides, Aikenes, and Alkynes. The McLafferty Rearrangement is helpful
in the identification and characterization of various organic molecules.

Mechanism:
H
R

Z, Y = C, N, O
[Link]. Organic Chemistry - I(Sem. V) 3.22 Rearrangement Reactions

Examples of McLafferty Rearrangement:

H +

OH OH OH ÇH,
+
R CH,
R CH, R
R

Exercise
(A) State True or False Questions :

(1) In rearrangement reaction, migrating group shift with its lone pair of electrons
called as electrophilic rearrangement.
(2) The skeletal rearrangement of carbocation which involves migration of B-alkyl, aryl
or G-bond is called Wagner-Meerwein rearrangement.
(3) Rearrangement involving carbanion is Favorskii rearrangement.
(4) Vicinal diol on treatment with a catalytic amount of acid, rearrange to give an
aldehyde or ketone is called as Baeyer Villiger rearrangement.
(5) Allylic aryl ethers, when heated, rearrange to ortho-allylphenols, this reaction is
called the Cope rearrangement.
(6) The McLafferty-rearrangement is observed in compounds in which at least one
abstractable gamma () hydrogen is present with respect to a pi (t) bond.
(7) Allylic ethers of enols (allylic vinylic ethers) also undergo the Claisen rearrangement.
(8) The Cope rearrangement is the thermal isomerization of a 1,5-diene.
(9) In Pinacol rearrangement, the order of migration is RC < R,CH < RCH, < CH < H.
(10) In Lossen rearrangement, azide reacts with a carbonyl derivative, usually an
aldehyde, ketone, or carboxylic aid, under acidic conditions to give an amine or
amide.
(11) When B-halo ketones are treated with base, in the presence of nucleophile the
reaction is called Quasi-Favorskiirearrangement.
(12) In pericyclic rearrangement the net result is one pi bond being converted into one
sigma bond or vice versa.
(13) In Baeyer Viliger rearrangement, for unsymmetrical ketones the approximate order
of migration is R;C >
RCH > Ar> RCH2 > CH3.
(14) In Beckmann rearrangement, aldoximes often are more reactive than ketoximes and
they form nitrile.
ANSWERS
1. False [Link] 3. True 4. False 5. False 6. True 7. True
8. True 9. False 10. False 11. False 12. True 13. True 14. False
 Organic Chemistry Rearrangement Reactions
[Link].
-I (Sem. V)
3.23
:
(B) Multiple Choice Questions
(1) Arrange the following carbocations by increasing order of stability.

CH,
() (II) H,C- CH,- CH, () CH,-C-CH, (V)
H
(a) I< II
IV <I| < (b) II < III <|< V
<
(c) IV <I< IIl<I (d) II < I < II V
(2) The product formed in the following reaction is.
OH
OH 1. TsCI (3 eq.)
DMAP
Pyridine

OH

(a) (b)

(c) (d)
R

OMe is
......
(3) The starting reagent required for the synthesis of

CI OMe
(c) (d)
(a) (b) OMe

......
(4) The product formed in the following reaction is

CHg
HCc CH, NaOMe

H,C Br

CH,
H
C-OMe (b) HC CH,
(a) CHa
H,c
CH, OMe
CH, CH,

o HC CH,

(e) C-C-CH,
H,¢ CH

CH,
CH, CH,
OMe
[Link]. Organic Chemistry 3.24 Rearrangement Reactic
-I (Sem. V)

(5) The product formed in the following reaction is....

CH,
-CH, NaOMe
-Br MeOH
CH, CH. CH,

CH
CH,
H,C NCHa
(a)
CH, (b)
CH3
H,C CHg
H,C CHs CH,

ÓMe

CH,
Me0 -CH3 CHs
(c) (d) H,C
CH,
H,C CHs CH3
CH CH
(6) The product formed in the following reaction is

-OH 1. SOCl,
2. NaN,
3. A

4. H,0
NH NH,
(a) (b)

NH–C-OH NH--OH
(c) (d)

(1) (PhO)2 PN3

(7) H,CG- C-OH ?
(2)CaH,OH
O=

(a) H,C3 -
N- C-OC;H, (b) H,C3- NH,

=O
(c) H,C- N- C;H, (d) H,Ca- N- C-OH

H H
[Link]. Organic Chemistry -I (Sem, V)
Rearrangement Reactions
3.25
1) The intermediate formed in
the Curtius rearrangement is
(a) cyanate (b) isocyanate
(c) thioisocyanate
(9) (d) carbocation
The product formed in the following reaction is

CHa
1. NH,OH,
H
2. BsCI, Et,N, DMAP

-NC-CH, NH,
(a) (b)

-CH,
(c) (d)

(10) The product formed in the following reaction is

1. HONH,HCI, KOH(aq.)

MeOH, Reflux
2. MSCI, Et,N DCM, -25°C

(a) (b)
NH

(C) (d)

(11) The product formed in the following reaction is:

OMe

DME, 120°C

OMe O OMe O

(a) (b)
HO

HO

OMe
OMe

(d)
(c)
HO
HO
H
 - I (Sem. ) Rearrangement Reaction
[Link]. Organic Chemistry 3.26

is
....
(12) The product formed in the following reaction

Heat

(a) (b)

(c) (d)

(13) Which one of the following carbonyl compounds can undergo a Mclaffety
rearrangement ?

(a) (b) (c) (d)

(14) The following reaction is an ...... rearrangement.

EI

OMe OMe
(a) Cope (b) McLafferty
(c) Clasien (d) Pinacol-pinacolone
(15) Conversion of hydroxamic acid to primary amine is .....rearrangement.
(a) Schmidt (b) Wolf
(c) Hoffmann (d) Beckmann
(16) In the Schmidt reaction ...... is formed in the reaction.
(a) ketene (b) carbanion
(c) carbocation (d) isocyanate
(17) Carbamic acid is formed in .... rearrangement.
(a) Wolf (b) Beckmann
(c) Schmidt (d) Cope
ANSWERS
1. (b) 2. (a) 3. (a) 4. (a) 5. (a)
6. (b) 7. (a) 8. (b) 9. (a) 10.(a)
11. (b) 12.(a) 13. (b) 14.(b) 15. (a)
16. (d) 17. (c)
[Link]. Organic Chemistry - I (sem, V)
3.27 Rearrangement Reactions
I) Short and Long Answer Type Questions :
1 Define rearrangement reactions. Explain different types of rearrangement
reactions.
2. Explain the formation and stability of.:
() Carbocation
(ü) Carbanion
3. Explain with suitable example 'Stability of carbocation plays important role in the
rearrangement reaction'.
4. Explain the reaction and mechanism of pinacol-pinacolone rearrangement
witn
suitable example.
5. Explain the reaction and mechanism of Favorski rearrangement with suitable
example.
6. Explain the reaction and mechanism of Curtius rearrangement with suitable example.
7. Explain which intermediate is involved in Curtius rearrangement.
8. Explain the reaction and mechanism of Beckmann rearrangement with suitable
example.
9. Explain, Aldoxime on Beckmann rearrangement gives nitrile.

10. Explain the stereochemistry involved in Beckmann rearrangement.

11. Explain the reaction and mechanism of Baeyer-Villiger rearrangement with suitable
example.
12. With the help of suitable example explain migrating aptitude of migrating group in
Baeyer-Villiger rearrangement.
13. Explain the reaction and mechanism of Claisen rearrangement with suitable example.
14. Write short notes on:
(a) Stability and formation of carbanion
(b) Stability and formation of carbocation
(c) Beckmann rearrangement

(d) Baeyer-Villiger rearrangement

(e) Favorskii rearrangement
rearrangement
() Homo-Favorskii and Quasi-Favorskii
(g) Pinacol rearrangement
(h) Curtius rearrangement

() Schmidt rearrangement
) Lossen rearrangement
(k) Claisen rearrangement

) Cope rearrangement
(m) McLafferty rearrangement
[Link]. Organic Chemistry Rearrangement Reaction
-I(Sem. V) 3.28

15. Predict the products :

OH OH
1. H
()
2. NaBH,, HgsO,

N-OH
PPA
(i)

Br
NaOEt
(ii) +?

-oto
(iv)
2.
1. NaOH,

H,o
H,0

CH,CI 1. NaOEt
()
2. H,o

OH
1. H,C= CH-CH,-Br /K,CO,
(vi)
2. A

CHs

(vii) 1. NaOMe/MeOH
Br
2. H,o0

OH OH

(vii)
-Ph H,SO4
2
Ph
[Link]. Organic Chemistry - I (Sem. V)

3.29 Rearrangement Reactions

CH3
(ix)
-H NaNO,
OH NH,

(x) NHNH, 1. HNO,

2. RNH,

(xi) N3 CzHOH

1. DPPA, Et,N/CgHs
(xi) H,C,-b-oH
2. CoH,CH,OH

E
(xii) ?
?+

(xiv)
OH NaN,
?
PPA

(xv)

(xvi)

Ac,0
NH-OH
OH
CH,OH
 Rearrangement Reactione
[Link]. Organic Chemistry - I (Sem. V) 3.30

(xvi)
COOH
HN,
2
H,SO,

(xvii)
CH,OH
?

(xix)

CMe NaN, H,SO,

benzene

(o)
OH

(oxi)

? + ?

16. Explain the mechanism of following reactions :

OH
OH
-(-Ph H,SO, Ph
Ph
Ph

(i)
OH

OH
o--cts H,S0,
-DT 0--CgtHs

OocH
(m) (H,C),CHCH-C-CH(CH3). (CH;),CHI;CHCO,CH,
Br
[Link]. Organic Chemistry
-I (Sem. V)
3.31 Rearrangement Reactions

N-Co,C,Hs N-co,c,Hs
-Br NaOCH,
(iv)
Lco,cts

H,CCO,H
(v)

(vi) mCPBA

--CH,
CF,CO,H
Do-t-c,
O=0

-OH 1. SOCI,
(vi) 2. NaN,
-H,C,-N--N
3. CzH,NH H

1. SOCI,, Pyridine
2. NaNg
(4) H,Cc-cOoH H,C-NHa
Xylene
Ph Ph

1. (PhO),PNg
Et,N
()
2. tBuOH
HO,C R (H,C),c0,CNH R
[Link]. OrganicChemistry Rearrangement Reactions
3.32
-I(Sem. V)

rearrangements
:

(Xi) Write the products in the following McLafferty

(a) (b)

(d)
(c)