Rearrangement is a reaction in which a group or atom moves from

one position to other within the same molecule.

W W

A B A B

Atom A in example is called migration origin and atom B as migration

terminus.
These rearrangements can be of following types,
i.Nucleophilic or Aninotropic : in which migrating group migrates with its
electron pair.
ii.Electrophilic or cationotropic : in which migrating group migrates
without its electron pair.
iii.Free radical : in which migrating group migrates with only one
electron.
Of these most commonly found are nucleophilic one.
These rearrangements can take place in two possible modes,
i.Intramolecular : In these migrating group do not completely detach
from migration origin and migration of group is within the molecule
only.

W A B A B W

ii. Intermolecular : In these migrating group is completely detached from

migration origin and migration of group can take place to different
molecule.

A B W+ A C U+
W A B+ U A C
A B U+ A C W
Different pathways through which 1,2-rearrngement takes place are
given below.

R R

1. C C C C

R
O C C
2. O C
R

R
C C C CR
3.
 x x
4. + y
a b y a b

x x
+ y
5. a b y a b

Reactions 1 to 3 show first reason for 1,2-rearrangement to take place

viz. formation of valence electron sextet at one of the carbon atoms of
substrate i.e. either carbocation or carbenium ion. Thermodynamic
driving force for potential 1,2-rearrangement will be significant if
rearrangement leads to structure with octets on all atoms [reaction 2 &
3] or generates some other more stable carbocation [reaction 1] i.e. if
newly generated carbocation is stabilized electronically by its
substituents than old carbocation or angle strain is reduced due to
rearrangement in cyclic carbocation or newly generated carbocation is
captured in subsequent irreversible reaction.
Reaction 4 & 5 show second cause for occurrence of rearrangement.
In these reactions atom b is bonded to good leaving group.
Heterolysis of such a bond would give a carbocation. Departure of
leaving group is then assisted by neighboring group. This sometimes
gives a positively charged three membered ring as in reaction 5.
Rearrangement in such reactions is possible only if group x is present
at new position in product than in reactant.
Broadly these reactions consists of three steps ;
a)First step is generation of electron deficient centre in molecule. As the
migrating group migrates with electron pair, the migration terminus
must have an incomplete octet. This can be obtained in two ways ,
i.Through carbocation : Carbocations can be formed in various ways.
The most common being dehydration of alcohol. This step is similar to
that of SN1 or E1 reaction.

R R R
H -H2O
C C OH C C OH2 C C
 Me Me
Me
SN1 C CH2Me
Me C CH2Br Me C CH2
Me
Me Me
Me Me Me

Me C CH2Me + C C

OH Me H

Rearrangement of carbocation is very important reaction in cracking of

petroleum products.

Me Me
H
Me C CH CH2 Me C CH CH3

Me Me

Me Me Me Me

C CH C C

Me Me Me Me
ii.Through nitrenes : nitrenes can be formed by decomposition of acyl
azides.

R C N N N R C N + N2

O O

b)Migrating group migrates to the previously formed electron deficient

centre with its electron pair creating new electron deficient centre.
c)In third step, newly formed electron deficient centre acquires octet
either by accepting a nucleophile or excluding proton.
It is observed in many cases that either two or all three steps take
place simultaneously. As seen in many cases SN1 type of first step is
very common followed by rearrangement to give more stable
carbocation. It is proved by fact that rate of reaction increases with
ionizing power of solvent and it is unaffected by concentration of base.
It has been shown that rate of migration increases with degree of
electron deficiency at migration terminus.
Most of rearrangements are intramolecular. It can be shown by cross
over experiments. But, one more evidence for this fact is that, if
migrating group is chiral, its configuration is retained in the product. In
molecules where stearic nature of migration origin and terminus can
be investigated, mixed results are found i.e. either inversion or
racemisation takes place.
Ph H O Ph
HNO2
Ph C C Me Ph C C Me

OH NH2 H
In this example inversion at migration terminus takes place.
But, it is not always possible for product to have two stearic
possibilities to investigate stereochemistry at migration origin or
terminus.
Eg. In Beckmann rearrangement, only group anti to hydroxyl migrates.

R1 OH
C N R1CONHR
R

This shows the concertedness of reaction. So, if, racemisation is

found at migration terminus, then it is probable that first step takes
place before second step, as in SN1 reaction.

R R R

A B X A B A B product

And, if inversion occurs at migration terminus, then two steps might be

concerted, as in SN2.
 R R
R
A B X A B A B product

In this case, neighboring group assists departure of leaving group, as

in neighboring group nucleophilic substitution reaction. This
assistance increases rate of reaction.
In certain cases of SN1 type process, total retention of configuration of
migrating groups is seen due to conformation of carbocation.
In many reactions like Hofmann, Curtis, there is no question which
group migrates but in certain cases, like Beckman reaction, there
are more than one choices. But, of them, which migrates depends
upon geometry of molecule.
In Beckman reaction, only group anti to hydroxyl migrates, whereas in
case of Wagner-Meerwein and Pinnacol rearrangement, there are
many choices, as substrate contains several groups, that have equal
probability of migration. Such reactions are used for direct study of
relative migratory aptitude.
In Pinacol rearrangement, there is one more question which hydroxyl
group leaves. As it will create electron deficient centre for migration to
take place. The hydroxyl group lost will be that which generates more
stable carbocation.
 Ph H Ph H Ph

Ph C C H Ph C C H Ph C C H

OH OH OH H O

Ph H

Ph C C H

OH

In this example, hydroxyl group is lost from carbon bearing two phenyl
groups as it gives more stable carbocation. It is known that
carbocation stability is enhanced by group in order aryl > alkyl > H.
Hence, depending upon these substituents hydroxyl group is lost in
reaction.
In order to study migratory aptitude in such reactions, substrate should
have structure R1RC(OH)C(OH)RR1 . In this case whichever hydroxyl
group leaves, it will give same carbocation and hence comparison on
migratory tendencies of R and R1 can be done.
Many factors are responsible in deciding migratory aptitude. One of
them is conformational effect. Another factor is, relative ability of group
that remains at migration origin, to stabilize positive charge.
Sometimes, if group that stabilizes positive charge is present on
migration origin, then group which actually is not having good
migratory ability, migrates. Along with this, migratory aptitude is
related to, ability of that particular group in assisting departure of
leaving group.
eg. In decomposition of tosylate, only phenyl group migrates while in
acid treatment of related alkene, competitive migration of methyl
and phenyl group is seen.

Me
Me Ph
H
Ph C C Me reflux in benzene C C
Me Me
Me OTs

Ph C *
C Me
Me

* H Me Me
Ph C C CH2
H +
Me C C* Ph
Me

Me Me

Only migration of phenyl group in first case is due to the fact that,
phenyl group assists in departure of tosyl group. Whereas, no such
possibility for second reaction.
All these factors costs no particular answer to migrating aptitude.
Though, in most cases, aryl migrates preferentially to alkyl group, but
it is not always true. Migratory aptitude of hydrogen is unpredictable.
Hence, mixtures are always obtained.
However, it is seen that in migration of aryl group, those having
electron donating substituents at meta or para position migrates
Preferentially, over those containing substituents on ortho position.
While, aryl group containing electron withdrawing groups show less
migratory aptitude.
A. Wagner-Meerwein rearrangement :
When alcohol containing more than two alkyl or aryl group on β
carbon are treated with acid, the product formed is generally a
rearranged product, rather than simple substitution or elimination
product. This reaction is called Wagner-Meerwein rearrangement.
Newly generated carbocation is stabilized generally by loss of proton
to give olefin and less often by nucleophilic substitution or loss of
some other positive group.

R H R1 R
R1 OH H

R2 R3 R2 R3
Mechanism of rearrangement goes through carbocation intermediate.

R H R H R H

R1 OH H R1 OH2 R1

R2 R3 R2 R3 R2 R3

R1 H R1 R

R2 R3 R2 R3

Wagner-Meerwein rearrangement was first found to take place in

bicyclic terpenes.

OH H

Isoborneol Camphene
 CH3 H
H3C
H
H3C C CH2 Cl C C
CH3 H3C CH3

OH
Camphenilol Santene

In these reactions, double bond is formed according to Zaitsev's rule.

Leaving group in this reaction can be hydroxyl or any other leaving
group which renders carbocationic character to carbon atom.
Direction of rearrangement is usually 30 >20 >10.
Sometimes several of rearrangement occur in one system either
simulataneously or in succession. Example of such a reaction is
rearrangement in triterpene, 3- β-friedelanol. This compound on
treating with acid, 13(8)-oleanene is formed by seven successive 1,2
shifts.
20 20

19 21 19 21

12 12 18
18
22 11 22
11
13 17 13 17
H H H
1 1 9 14
9 14
16 2 16
2
10 8 15
H 10 8 15
5 H
3 5 7
7 3 4
4
HO 6 6
H
3-friedelanol 13(18)-oleanene

A positive charge is generated on C-3, followed by removal of H2O,

then hydride shift from 4 to 3; methyl shift from 5 to 4; hydride shift
from 10 to 5; methyl shift from 9 to 10; hydride shift from 8 to 9; methyl
shift from 14 to 8 and hydride shift from 13 to 14 takes place,
generating carbocation at C-13, which is stabilized by loss of proton
from C-18 to give olefin.
All these shifts are stereospecific.
Alkanes in presence of Lewis acid and some suitable initiator, also
undergo Wagner-Meerwein rearrangement.
Tricyclic molecules containing 10 carbon atoms on conversion give
adamantane, by successive 1,2 and 1,3 shifts of hydride and alkyl

AlCl3
group.
Tricyclic molecules containing more than 10 carbon atoms give alkyl
substituted adamantane.

AlCl3

AlCl3

Tricyclic molecules containing 14 or more carbon atoms, give

diamentane or substituted diamentane.
 AlCl3
tBuBr

These reactions take place because of great thermodynamic stability

of adamantane, diamentane and similar diamond like molecules.
Some examples of Wagner-Meerwein rearrangement are given below.

O O O O

OEt OEt
HO TFA, DCM
72h

76%
 Br

HBr, THF
00C, 10 min
OH

OH
EtOOC
COOEt 1 : 3 HSO3F, SO2ClF
Ph ~00C
Ph

[ JACS, 1982, 104, 2631 ]

 H
O
N
S S
H
Ph
BF3.Et2O
N + +
-780C, 5h
( 74% )
Ph S O H
S
O
N
S S
H
Ph

[ Helvetica Chemica Acta, 1999, 82, 1458 ]

 H
O
N

S S
Bz H
N BF3 Et2O / DCM +
+ -780C H
Bz S O ( 75% )
O
N
S S

Bz H

[ Helvetica Chemica Acta, 1999, 82, 1458 ]

 COOMe
OH
Br
HN
O
OMe
CH3SO3H
N O N 1,2-DCE
500C
N OMe
N H
O
COOMe OMe
Br
HN
O
OMe

N O N
86% N
N H OMe
O
OMe
B.Pinacol rearrangement :
When vicinal diol is treated with acid, it rearranges to give aldehyde or
ketone. This reaction is called as Pinacol rearrangement, reaction was
originally found to take place in molecule.

CH3 CH3 CH3 O

H H3C C C CH3
H3C C C CH3

OH OH CH3
Pinacol Pinacolone

The migrating group can be alkyl, aryl, hydrogen or ethoxycarbonyl

etc.
In case of symmetrical diols which hydroxyl is protonated and which
group migrates does not have much significance, but in case of
unsymmetrical diols it is important. Generally. Hydroxyl group is
protonated which gives more stable carbocation.
 O
OH OH
H2SO4 Ph
Ph
Ph
Ph

In this reaction, hydroxyl group on carbon having two phenyl groups

will be protonated, as it will give more stable benzylic cation and is
formed faster.
When tri or tetra substituted glycol is used, different products
depending upon reaction condition is obtained. It also depends upon
migratory aptitude of different groups, as discussed earlier.

CH3 CH3 Ph CH3 Ph O

cold AcOH +
H2SO4 trace of H C
Ph C C Ph C C CH3 H SO 3 C C Ph
methyl 2 4
migration phenyl
Ph O OH OH migration CH3
When, at least one group in glycol is hydrogen, aldehyde can be
prepared along with ketone. Aldehyde can be prepared in mild
reaction conditions such as weak acidic conditions, low temperature.
Mechanism of reaction is as follows;
R2 R4 R2 R4
H -H2O
R1 C C R3 R1 C C R3

OH OH OH OH2

R2 R4 R2
-H
R1 C C R3 R1 C C R3

OH OH R4

O R2

R1 C C R3

R4
Migration of alkyl group from initially formed carbocation takes place
because, carbocation containing hydroxyl group are more stable than
that of 30 carbocation. Also, these carbocation can readily lose proton
to give corresponding carbonyl compound.

OH OH
H

OH OH
Ph O
H
Me2C C COOEt
Me2C C COOEt
Ph
 O

Ph
Ph

Ph OH
Ph OH
TsOH, +
CDCl3
O Ph
Ph

[ JOC, 2004, 69, 2017 ]

 OH O
Ph
1. MsCl, Et 3N, DCM Ph
OH
00C, 10 min
2. Et3Al, DCM
-780C, 10 min
N N
SO2Ph
SO2Ph
90%

[ Tet. Lett., 2002, 43, 6937 ]

Synthetically useful Pinacol rearrangement reaction is syntheses of
bridged bicyclic compound from a diol in following way.

O OH
OH OH

H LiAlH4 H

OH2

-H2O -H

H
Similar type of reaction is also shown by compounds containing
different group than hydroxyl on adjacent carbon of that containing
hydroxyl group on it.
This reaction is known as Semipinacol rearrangement and involves
1,2 shift of H or alkyl from oxygenated carbon atom to neighboring C
atom i.e. carbocation to carboxonium ion rearrangement.

BF3.Et2O -BF3

O O
BF3
O H
H H
 OTs

LiClO4 in
HO THF, HO -H
CaCO3

O O O O

O O

AgNO3

I
O
OH
C.Expansion and contraction of rings :
When a positive charge is placed on alicyclic carbon, migration of
alkyl group can take place, giving ring smaller than original one. In this
transformation secondary carbocation is converted to primary
carbocation.

CH2

Similarly, when positive charge is present on carbon α to alicyclic ring,

then migration of alkyl group can give ring larger than original one.

CH2

This newly formed carbocation can then be stabilized by either

elimination or substitution.
This reaction represents special case of Wagner-Meerwein
rearrangement.
Generally, a mixture of rearranged and non rearranged products is
formed.

NH2 OH
HNO2 HNO2
+ CH2OH CH2NH2

Reaction in which carbocation is formed by diazotization of amide is

called Demjanov reaction.

HNO2
OH +
NH2 OH
Mechanism is as follows.

H N
N O O -H2O O O O
H
HO O N N
N
H2O O

-HNO2
+O O O H
N N
NH2 HN N O

-H2O
N N OH
N N OH2
H
NO2

-N2 H2O
OH
N N
 NH2 OH
OH

HNO2
+

O O O O
NaNO2
0.25M
LAH / Et2O H2SO4 /
00C H2O +
0-40C
CN
NH2 HO HO
 O
O
NaNO2
LiAlH4 / Et2O OAc 0.25M H2SO4 /
OAc
00C H2O, 0-40C
100%
CN
NH2
O
O

O
O
12 : 1

[ Tetrahedron, 1993, 49, 1649 ]

It is found that, expansion reaction give good yields in smaller rings
where expansion gives relief from angle strain and contraction
reaction give otherwise good yields except for cyclopentyl cation.
An example of such ring expansion is; treatment of
16-methylpentaspiro[2.0.2.0.2.0.2.0.2.1]hexadecan-16-ol with
p-toluenesulfonic acid in acetone-water to give
2-methylhexacyclo[12.2.0.02,5.05,8.08,11.011,14]hexadecan-1-ol.

H3C OH CH3
OH

.
 OH
H H
H
OH
40%H2SO4

H
H

Reaction of certain amino alcohols give analogous reaction to

semipinacol rearrangement. This reaction is known as
Tiffeneau-Demjanov rearrangement.

CH2NH2 O
HNO2

OH
These reactions carried out on four to eight membered ring, give
better results as compared to analogous Demjanov rearrangement.

NaNO2, AcOH,
H2O, 00C, 1h
OH then reflux 1h
O
98%
NH2

SnBu3

SnBu3 O 64%
NaNO2
AcOH +
HO CH2NH2 SnBu3

O 36%

[ Org. Biomol. Chem., 2004, 2, 648 ]

 H2N
CONEt2 CONEt2

OH O

NaNO2, AcOH,
H2O, 0-50C

O N
60%
D.Acid catalyzed rearrangement of aldehyde or ketone :
Aldehyde or ketone on acid treatment give another ketone by
rearrangement.

R1 O R4 O

R2 C C R4 H R2 C C R1

R3 R3

Certain aldehyde or ketone are converted in this way to other ketones.

But, conversion of ketone to aldehyde is not seen in any case.
Mechanism of the reaction goes through protonation of carbonyl
oxygen. Two pathways are possible. One in which migration
of two groups is in opposite direction and other in which migration is
in same direction.
Actual pathway is not certain. But, it is found that in certain cases only
one operates while in others both operate at same time. This can be
demonstrated by labeling carbonyl carbon. In first case, labeled
carbon is carbonyl carbon while in second case labeled carbon is
carbon α to carbonyl group.
Pathway 1:
R1 O R1 OH

R2 C C R4 H R2 C C R4

R3 R3

R4 R4 OH R4 O

R2 C C R1 R2 C C R1 -H R2 C C R
1

R3 OH R3 R3
Pathway 2:

R1 O R1 R3 R1

R2 R4 H R2 R4
C C C C R2 C C R4
O
R3 R3 OH
H
R3 R3

R2 -H
C C R1 R2 C C R1

OH R4 O R4

In case of α hydroxy aldehyde or ketone process may stop after one

migration. This is called α ketol rearrangement.
 R1 O R1 O

R2 C C R3 H R3 C C R2

OH OH

O O
Benzene : conc.H2SO4
7:5
24h

85%
O O
Benzene : conc.H2SO4
7:5
24h

80%

[ J. Chem. Soc., 1956, 2483 ]

E.Dienone-phenol rearrangement :
Cyclohexadienone containing two alkyl groups at position two or four,
on acid treatment undergoes 1,2-shift of one of these alkyl group, to
Give disubstituted phenol. Driving force of reaction is aromatization
of ring.

O OH

R
R R
R
Mechanism is as follows;

O OH OH

H
R

H
R R R R
R
OH

R
R
Particularly useful example is in syntheses of steroidal compound.

OH OH

H H
H2SO4
H H H H

O HO
1-methyloestradiol
F.Wolff rearrangement :
Wolff rearrangement is rearrangement reaction, in which a diazo
ketone is converted into ketene.

R' R'
R'
R -N2 R C O
N2 C
R
O O

The rearrangement reaction takes place in presence of light, heat or

transition metal catalyst such as Ag2O.
The mechanism is supposed to proceed through formation of carbene
in presence of heat or light. It may also proceed through concerted
pathway in which no carbene is formed in presence of Ag2O.
Thermally reaction is possible in range of room temperature to 7500C.
Generated ketene is highly reactive species, hence is more isolated. It
either adds nucleophile or undergoes (2+2) cycloaddition.
If the added nucleophile is water, then it forms carboxylic acid with
one carbon more. This reaction is known as Arndt-Eistert syntheses.
This reaction is of particular use in preparation of carboxylic acids with
one carbon more than starting one.
O COOH

H
N2
h,dioxane
H H Et2O, H2O H H

HO HO

[ Org. Syn. Coll. 1988, 6, 840;1972, 52, 53]

Migratory aptitude of particular group is determined by whether
reaction is proceeding by thermal or photochemical pathway. In
photochemical pathway methyl is migrated preferentially while in
thermal pathway phenyl group migrates.

O
Ph
Ph -N2
Ph C C O
Ph
N2

[ Org. Syn. Coll.1955, 3, 356; 1940, 20, 47 ]

O O O O

H h / O
EtOH : dioxane
N2 1:1
 O COOMe
N2
h / MeOH
O
N O N
90%

Other 1,2 migrations to carbene are also known.

CH3 CH3
H3C
h H 3C C CH C
H3C C CHN2 CHCH3
H3C 52%
CH3 CH3
+

47%
G.Homologation of aldehyde or ketone :
Aldehyde or ketone can be converted to their higher analogs on
treatment with diazomethane.

O O
CH2N2 R'
R R' R

O O
CH2N2
R H R

Though, it appears to be an insertion reaction, it is purely

rearrangement reaction. Carbene is not formed in the reaction.
Mechanism is as follows,

O CH2 N N
-N2
R C R' + H2C N N R C R'

O
CH2 O
H2
R C R' R C C R'

In case of aldehyde, hydrogen migrates preferentially which is evident

from good yields of methyl ketone.
An interesting example of this reaction is, preparation of bicyclic ring
compound using alicyclic compound containing diazo group in side
chain.

O O O

CHN2 +
H.Neighboring group participation:
Rearrangement is seen in reaction of NGP type, when the group
showing anchimeric assistance is detached at one point in substrate
and is attached to other point in final product.

R2
NR2 N
Ph CH CH COPh Ph CH -H
CH COPh

Br H 2O

NR2

Ph CH CH COPh

OH

NR2 :- N O
In this reaction, due to anchimeric assistance of morpholino group,
rearrangement is seen.

Cl OOCCF3
CF3COOH
H3C CH CH2 ONs H3C CH CH2 Cl

ONs :- RO2SO NO2

I.Migration of boron to electron deficient carbon:
On heating non terminal boron at about 100-2000C, boron moves
towards end of chain.

C C C C C C C C C C C C C C C

B B B

Boron can move past a branch.

C C C C C C C C

B C C B
But, boron can not move past double branch.
C C C

C C C C C C C C C C C C C C C

B C C B C B

CH3 CH3 CH3 CH3

H3C C CH CH CH3 H3C C CH2 CH CH2

CH3 B CH3 B

If boron is present on ring, then it moves across ring and if an alkyl

side chain is present on ring, it ends on terminal carbon of side chain.
 1500
B B
diglyme

The reaction is useful in migration of double bond in controlled way.

B
B
RCH CH2
 B OH

B
H2O2 /OH

H2O2 /
BH3, THF H 1100C H OH
BH2 H
CH2BH2

H
H
CH2OH
J.Neber rearrangement:
Neber rearrangement is a reaction in which a ketoxime tosylate is
converted to α-amino ketone upon treatment with base.

NH2
R'
R base R'
R
NOTs
O

R' R'
R R' H 2O
R base R
NOTs N N
OTs
NH2

R'
R

O
Base first abstracts proton α to ketoxime group. This carbanion then
displace tosylate group in nucleophilic displacement and forms azirine
which on hydrolysis gives α-aminoketone.
The reaction is sometimes assisted by Beckmann rearrangement
though it generally occurs in acidic conditions.

F F
NHBz
1. 50% Toluene / KOH
Ph 2. BzCl, Py / DCM, 6N HCl Ph

NOTs O

[ JACS, 2002, 124(26), 7640 ]

 NO2 NO2
H2O,
NaHCO3
O2N CH2 C O2N CH C
NOTs O
NH2

[ JACS, 1953, 75(1), 38 ]

H2O , NaHCO3
Cl CH2 C Cl

NOTs
NH2

Cl CH C Cl

O
 Ph Ph

Ph N Ph N
K2CO3
THF , rt ,18h
H2N

N O
OTs
A.Hofmann rearrangement:
When an unsubstituted amide is treated with sodium hypobromite, it
gives corresponding primary amine with one carbon less. This
reaction is known as Hofmann rearrangement.

O
hydrolysis
R C NH2 + NaOBr R N C O RNH2 + CO2

R in this reaction can be alkyl or aryl.

Mechanism of reaction is as follows,

O O
O
R C NH OH Br Br OH
R C NH R C NH
H Br
O O
H2O
R C N Br R C N R N C O

O O
H
N HN OH RNH2 + CO2
OH O OH
R H R
H

In the first step, base removes proton from amide. This conjugate
base of amide then reacts with bromine to give N-bromoamide.
Acidity of proton on nitrogen is increased by this bromine atom and its
removal becomes easy for base to give nitrene intermediate in which
nitrogen is electron deficient. 1,2-shift of alkyl group takes place in this
nitrene to give corresponding isocynate. This isocynate on hydrolysis
gives primary amine with one carbon less than starting material.

NH2
Br2 /NaOH
H2O NH2
O

O NH2
NH2

NaOBr / H2O

NO2 NO2
If methanol is used as solvent, in place of water then corresponding
carbamate ester is obtained.

O
H
N O
NH2
NBS, DBU,
MeOH, reflux O
O O

O
H
N O
NH2 NBS, Hg(OAc)2,
CH3OH, DMF
O
N N

O O
dibromotin, Hg(OAc)2,
PhCH2OH, DMF (H3C)3C
(H3C)3C NH2 N OCH2Ph
H
 O 1. Pb(OAc)4, O R
R
O O BnOH, DMF H
1000, 15h N OB
NH2 2. TsOH, C9H19 n
C9H19
acetone, H2O, Bn O
Bn
reflux, 2.5h
75%
R :- PhMe2Si

O NH2
t BuO NH
Cl Cl
Pb(OAc)4
tBuOH
N 500 N
O O
H H
70%
 OMe
OMe OPMP OR
OPMP OR

O
O NaOMe, Br 2
MeOH, -780
1h, reflux O
O

HO NH
O
H2N O
O
93%

When optically active α-phenylpropionamide undergoes Hofmann

degradation, α-phenylethylamine of same configuration and optical
purity is obtained i.e. rearrangement proceeds with retention of
configuration.

Ph Ph
NaOH
H C CONH2 H C NH2
B.Curtius rearrangement:
In Curtius rearrangement, acyl azide are pyrolysed into isocynate
which can be hydrolyzed to corresponding amines.

R N C O
R N3

Curtius rearrangement is catalyzed by protic or Lewis acids.

Mechanism is similar to that of Hofmann rearrangement.

O O
-N2
R N C O
R N N N R N

However, there is no evidence of existence of free nitrene. These two

steps may be concerted.
 O

R N C O + N2
R N N N

In the similar reaction, alkyl azides give imines.

R3CN3 R2C NR

R may be alkyl, aryl or hydrogen. In case of tert.alkyl azides, there is

evidence of existence of nitrene.
Cycloalkyl azides give ring expansion.

R
R
H
N + NR
N3
80% 20%
Aryl azides also give ring expansion on heating.
NHPh
N3
PhNH2
N

If the reaction is carried out in di-tert.butyldicarbonate, product will be

Boc protected amine.
O

EtOOC EtOOC NHBoc

OH Boc2O, NaN3
Bu4NBr
Zn(OTf)2
THF, 500C
Ph Ph

[ Org. Lett. 2005, Vol.7, No.19, 4107 ]

 H
OH

H Boc2O, NaN3
O Bu4NBr
Zn(OTf)2
H H THF, 400C

HO H
H
NHBoc
H

H H

HO
H
 1. Et3N, DPPA H2N
HOOC BzOH
COOH NH2
2. HBr / AcOH H2N
HOOC
cis,cis-cyclohexan-1,3,5- cis,cis-1,3,5-triamino-
tricarboxylic acid cyclohexane (82%)

[ Bioorganic and Medicinal Chem. Lett., 9 April 1996, Vol.6, Issue 7,

807 ]
OH O O

O
N3 tBuOH NH
N3 reflux

O NHBoc

[ Tet. Lett., 19 Feb 2007, Vol.48, Issue 8, 1403 ]

 O
PMBO

HO O OTBS Hunigs base

iBuOCOCl
00C, NaN3
O
H2O, toluene
H H 15 min,
O TMSCH2CH2OH
3h,

O OPMB

O
O N
H

TMS

[ JACS, 2001, 123, 12426 ]

 O

O SOCl 2
Me3SiN3
reflux

HOOC
O

N
C.Lossen rearrangement:
O-acyl derivatives of hydroxamic acids on heating with base give
isocynate, this reaction is known as Lossen rearrangement. Isocynate
can be further hydrolyzed to corresponding amines.
O

O R OH H2O
R N C O RNH2
R N
H
O

Mechanism is similar to that of previous reactions.

O O

O R O R
R N R N

H O O
OH

R N C O
 NHR1
CONHOC CNO
2
H NHR
H

H2O

NH2
H

R1 : Et , R2 : (CH2) 3NMe2

[ Appl. and env. Microbiology, 1997, Vol.63, No.9, 3392 ]

 O
H N C O
N COOEt
Cl EtOOC O
Et3N, H2O
Br Br

NH2
EtOH, H2O

Br
The reaction can also be carried out with hydroxamic acid.

O O

Na2CO3
CONHOH PhOSO2Cl NH

OH O O
OH OH

[ J.Braz.Chem.Soc., 1995, Vol.6, No.4, 357 ]

COOH NH2
1. NH2OH.HCl
H3PO4
2. KOH
 O
1. NH2OH.HCl NH2
H3PO4
OH 2. KOH

[ JACS, 1953, 75, 2014 ]

D.Schmidt rearrangement :
Reaction of carboxylic acid or aldehyde or ketone with hydrazoic acid
in presence of mineral or Lewis acid to give corresponding primary
amine or amide respectively is known as Schmidt rearrangement.

H H2O
RCOOH + HN3 R N C O RNH2

O
O
H R1
+ HN3 R N
1
R R H

Cyclic ketones give lactums.

O NH
HN3 / H
O
Mechanism is similar to that of Curtius rearrangement, except that
protonated azide undergo rearrangement.

O O O
H H N N N
-H2O
R OH R R N3

O O

H
R N N N R N N N
H

H 2O
R N C O RNH2 + CO2
H
Mechanism with ketone is,

O OH H N N N
HN3 -H2O
H
1 1 R C R1
R R R R
OH

N N N
-N2 H2O
R C R 1 R1 C N R

O
R1 C N R -H R1 C N R tautomerism R
R1 N
OH2 OH H

In reaction with ketone, ketone is activated by protonation for

nucleophilic addition of azide group to it.
In case of alkyl aryl ketone, aryl group migrates preferentially except
for bulky alkyl group.
Intramolecular Schmidt reaction can be used for preparation of
bicyclic lactums.
O O

MeAlCl2 / DCM N

H Ph
N3 96%

O
N3
MeOOC TFA / 12h MeOOC
N
O
 O
O
1. SPh2 N
N3
2. LiBF4
3. TiCl4

81%

[ JACS, 1991, 113, 896 ]

O
O
TFA
N
N3

[ Org. Syn., 2007, 84, 347 ]

 MeO MeO O
Triflic acid
O dry DCM
-50-00C N
MeO MeO
H3COOC 15 min
H3COOC
N3
54%

[ JOC, 2007, 3, 949 ]

Reaction of tert. alcohol and olefins with hydrazoic acid in acidic

condition to give substituted imines is often termed as Schmidt
rearrangement.
OH R R
HN3 / H2SO4
N
R R
R R
 R R R R
HN3 / H2SO4

R R R N R

Mechanism of the reaction is as follows.

OH
OH2
H -H2O HN3
R R
R R R
R R R
R

N N N
-N2 R
C N R
R R
R
R
R R RH R RH R H
H HN3 -N2
N N N
R R R R R R

RH R
R R
-H
R N R
R N R
H
 O O O
H
H3C N
H3C OEt OEt
CH3 CH3
O
NaN3, CH3SO3H

CHCl3, 0.5-1 h

89%

[ Tet. Lett., 1988, 29, 403 ]

 O O O
H
N
NaN3, CH3SO3H
DME, -300C-rt
ADA O ADA

ADA

ADA :
E.Beckmann rearrangement :
Oximes on treatment with Lewis acid or protic acid rearrange to give
substituted amides. This reaction is called as Beckmann
rearrangement.

R R' O
PCl3
R
N R' N
OH H

Generally group anti to hydroxyl migrates. However this is no hard

and fast rule. R and R’ can be alkyl, aryl or hydrogen. Hydrogen does
not migrate under conditions of reaction but it migrates when reaction
is carried out with nickel acetate under neutral conditions.
Like Schmidt rearrangement, oximes of cyclic ketones give ring
enlargement.

NOH NH
O

Mechanism of reaction usually goes through alkyl migration with

expulsion of hydroxyl group followed by reaction similar to Schmidt
rearrangement.
 OH OH2
N N -H2O
H R1 C N R

R R1 R R1

R1 C N R
R1 C N R
R1 C N R -H

H2O OH2

R1 C O
N R
R
1
R N
OH H

Other reagents convert hydroxyl to an ester leaving group. Course of

mechanism is supported by detection of nitrillium ion by NMR and UV
spectroscopy.
 OH
N H
N
H3PO4
microwave O
MeO
MeO 82%

[ Indian journal of chemistry, 2005, 44B, 18 ]

H
N
OH
N
O
MeCN, 10% Ga(OTf)3
+
850C, 16h O

N
H

[ Catalysis Lett., 2005, 103, 165 ]

 SOCl2, 100C, 1%KOH

HO
N

O
HN

[ Chemistry of natural compounds, 2009, 45, 519 ]

 N
N H2SO4
O
OH microwave
N
1800C N

[ SynComm., 2006, 36, 321 ]

Cl H O
N
N N
N
OH Cl N Cl
DMF, rt, 8h
100%

[ JOC, 2002, 67, 6272 ]

 OH
I N I
H
12% HgCl2, N
MeCN , 8h

[ JOC, 2007, 72, 4536 ]

F.Stieglitz rearrangement :
Stieglitz rearrangement is a general term applied for rearrangement
reaction of trityl-N-haloamines and hydroxylamines to trityl imine.

PCl5
Ar3C NHOH Ar2C NAr
base
Ar 3C NHX Ar2C NAr

Mechanism is as follows,

Cl
Ph OH Cl Cl Ph O Cl
NH + P NH P
Cl Cl Cl
Ph Ph
Ph Cl Ph Cl

Ph
NPh
Ph
Reaction can also be facilited by treatment with lead tetraacetate.

Pb(OAc)4
Ar3CNH2 Ar2C NAr

NH2
Pb(OAc)4 Ph2C N OCH3
Ph2 C OCH3
~98%
+

PhN C OCH3
Ph
~2%

[ JOC, 1974, 39, 3932 ]

When methanolic solution of N-chloroisoquinudine was refluxed for 2h
with AgNO3, AgCl was precipitated and 60% of
2-methoxy-1-azabicyclo[3.2.1]octane was obtained.

AgNO3
MeOH
N
N
Cl MeO
A.Baeyer-Villiger rearrangement :
In Baeyer-Villiger rearrangement, ketone on treatment with peracid
gives ester by oxyinsertion. Reaction is catalyzed by presence of acid
catalyst. O O
PhCO3H

R R1 R OR1

Reaction is particularly useful for synthesis of lactones.

O O
O
CF3CO3H
H H
R
R

R : H, OAc, OCOPh etc.

Mechanism is as follows,
OH
O OH
H R2CO3H
R C R1
R R1 R R1
O O R2

O O
1
RO C R -H

OH RO R1

First step is addition of peroxy acid to carbonyl forming tetrahedral

intermediate. In next step concerted migration of migrating group and
loss of carboxylic acid to give product.
The mechanism is supported by fact that oxidation of Ph2C18O yields
only PhC18OOPh i.e. there is no scrambling of 18O label in product
ester. Loss of carboxylates and migration of R is concerted is by fact
that reaction is speeded up by electron withdrawing
substituent in leaving group and electron donating substituent in
migrating group.
Carboxylates are as such not very good leaving group. But, O-O bond
is very weak and monovalent O can not carry positive charge. So that
once peracid is added loss of carboxylate is concerted with
rearrangement driven.
Synthetic usefulness is syntheses of L-Dopa drug used to treat
Parkinson's disease.
 O
COOH
COOH
AlCl 3, H2O2,
NH2 AcCl NaOH
HO NH2
HO
L-tyrosine

O COOH HO COOH
H3O
O NH2 NH2
HO HO
L-Dopa

If the migrating group is chiral then its stereochemistry is retained. By

looking at orbitals involved in reaction, this can be explained. The
sp3 orbital of migrating carbon just slips from one orbital to next with
minimum amount of structural reorganization.
new sigma bond
forms on same face
of migrating group-
stereochemistry
retained.
Migratory aptitude in unsymmetrical ketones is as,
H>30>cyclohexyl>20>benzyl>aryl>10>methyl. In case of aryl group,
migrating ability is increased by electron donating groups present on
ring.
F F F O
mCPBA /
CHCl3 O Ph Ph
Ph Ph NaHCO Ph + Ph O
3

O O 71% 29%

Migration is favored when migrating group is antiperiplanar to the O-O

bond of leaving group. This is known as primary stereoelectronic
effect. Antiperiplanar alignment of lone pair of electrons on O2 with
migrating group is termed as secondary stereoelectronic effect.
 OCOR'
O
H
primary

R R secondary

In case of unsaturated ketones epoxidation is likely a competitive

reaction. But, Baeyer-Villiger rearrangement is favored because ring
strain can be relieved by oxyinsertion and ring expansion.

BnO
BnO

mCPBA
O

O
O
 H H
O
O
H2O2, AcOH
O

H H

Chemoselective oxidation of β-lactum aldehyde has been achieved

with mCPBA in DCM where only formates are formed in better yields.

H C H H C H

CHO mCPBA, DCM OCHO

rt, 20h
O O

OMe OMe
70%

[ Tet. Lett., 1995, 36, 3401 ]

Aldehyde can be oxidized to carboxylic acid due to preferential
migration of hydride. Group that can stabilize positive charge on
oxygen migrates.
O O

H mCPBA, DCM OH

Br Br

Cl Cl

Other reactions are given below.

O
O
H2O2 BF3
ether
O

[ JOC,1962, 27, 24 ]
 O O

cyclohexanone
oxygenase

O
O O

[ JACS, 1988, 110, 6892 ]

O
O
CF3CO3H in H2O2
(CF3CO) 2O in DCM
Na2HPO4 in DCM O

[ JACS, 1955, 77, 2287 ]

 Cl Cl
O O Cl
BnO Cl BnO
mCPBA O
NaHCO3
BnO DCM BnO O
O
OBn OBn

O O O O
HO HO
O
mCPBA, DCM
HO HO
O
H H
O
 Caro's reagent

O O
O

KHSO5, rt, 24h O

O O
 O O

KHSO5, rt, 24h O

O O

cyclopentanone O
monooxygenase

98% ee

[ Chem.Comm., 1996, 2333 ]

 O O
H
O
H H
H mCPBA, NaHCO3
DCM, rt, 30 min
N H Cl
H N
Cbz Cl
Cbz
85%

[ JOC, 2002, 67, 3651 ]

CbzHN COOMe CbzHN COOMe

H H
0
TFPAA, 0 C,
Ph DCM, >5h PhO

O O 75%

[ JOC, 2008, 73, 2633 ]

 O O
mCPBA O
NaHCO3
DCM, 00C,
30min

60%

[ Tet. Lett., 2009, 50,4519 ]

H3CO O
H3CO O
H2O2,
supported MTO,
tBuOH, 800C
O
O O

MTO : Methyltrioxorhenium
[ Tet. Lett., 2001, 42, 5401 ]
 HO HO
H H
4 eq mCPBA
O 1,2-DCE,
O
rt then 800C
48h
H H OAc
O 65%

[ JACS, 2010, 132, 8219 ]

O O O
1. Fe2O3, O2
C6H5CHO O
benzene O +
2. NaHCO3

97 : 3

[ Tet. Lett., 1992, 33, 7557 ]

 Bu

O O B
Bu
P P O 1. PhCHO,
O Bu2BOTi O
N Pr2NEt N -780C
O DCM, -100C 2. 30% H2O2

O O

P
O O
N

75%

[ JOC, 1993, 58, 4516 ]

 O

Ph
O Ph

mCPBA, DCM O
-400C, 60 min
N N
O CH2Ph CH2Ph
O

[ JOC, 1994, 59, 3123 ]

B.Rearrangement of hydroperoxide :
Hydroperoxides can be cleaved in presence of protic or Lewis acid.
Reaction goes through rearrangement.
R O
H + ROH
R C O O H
R R
R

Mechanism is as follows.
R R H
R H2O
H -H2O
R C O O H R C O O H
R C OR
R R
R O
R C OR + ROH
R R
OH2
Acid converts peroxide to protonated peroxide which loses water
molecule. Simultaneously, shift of alkyl group to electron deficient
oxygen gives rearranged carbocation, which reacts with water to give
hemiketal which breaks down to give alcohol and ketone.

O OH
Ph OOH
AcOH
+

Alkyl group must be showing some sort of anchimeric assistance and

the rearrangement must be going through benzonium ion.
 OH
O
H2O / H
+

OOH

Benzonium ion :

S T
1,2-free radical rearrangements though less common are observed in
some cases. The mechanism is similar. First a free radical is
generated, which rearranges itself by one electron transfer. This is
followed by stabilization of newly formed radical.

R R
product
A B A B

As in carbocation rearrangement reactions, radical rearrangements

also show pattern as primary to secondary to tertiary.
Reaction of 3-methyl-3-phenylbutanal with di-tert.butylperoxide gave
product with and without rearrangement.
Ph Ph Ph
H2 H
Me C C CHO Me C CH2 abstraction Me C CH3

Me Me Me
50%
rearrangement

H2 H H2
Me C C Ph H Me C C Ph
abstraction
Me Me
50%

In this reaction no migration of methyl group is seen. Also, migration of

hydrogen is not seen (seen to lesser extent ) in free radical
rearrangement. As phenyl group, groups like vinyl, acetoxy can also
migrate.
Also, migration for chloro group has been observed.

Cl Cl Br
Br
Cl C CH CH2 Cl C CH CH2

Cl Cl
Cl Br Br Cl Br
Br2
Cl C C CH2 Cl C C CH2
H H
Cl Cl

It is shown that migration of Cl takes place easily if migration origin is

tertiary and migration terminus is primary.
Migration of chlorine and bromine might be taking place because they
can accommodate an odd electron in vacant d-orbital.
In summary, 1,2-free radical rearrangements are less common as
compared to analogous carbocation process and direction of
migration is usually towards more stable radical.
Apart from usual 1,2 shifts, 1,3 and longer distance shifts are also
known. 1,5 being most common. Transannular H shifts are also
known.
Stevens rearrangement :
In Stevens rearrangement, quaternary ammonium salt containing
electron withdrawing group on α carbon atom when treated with strong
base rearrange to give tertiary amine.

Z R3 Z R3
NaNH2
N R2 N

R1 R1 R2

Rearrangement is intramolecular is shown by cross over experiment.

Also, retention of configuration was seen in product.
Two mechanistic pathways are possible. One involving radical pair
trapped in solvent cage. Presence of solvent cage is important in
order to explain retention of configuration.
 Z R3 Z R3 R3 R3
Z Z
base
N R2 N R2 N R2 N R2
R1 R1 R1 R1
Z R3
N
R1 R2

Other is involving ion pair in solvent cage.

Z R3 Z R3 Z R3 Z R3
base
N R2 N R2 N R2 N
R1 R2
R1 R1 R1
Concerted reaction mechanism can also operate. But, it can not be
accounted as it requires antarafacial mode but migrating group retains
its configuration.
Reaction is used for ring enlargement.
Ph
Bz
N N
NaNH2 / NH3

90%

When Z group is an aryl group, the rearrangement is known as

Sommelet-Hauser rearrangement, in which reaction of tert.alkyl
ammonium salt with NaNH2 gives N-dialkylbenzylamine with ortho
substituted aromatic ring.
 N
NaNH2 / NH3 N

Another competing reaction is Hofmann elimination, when one of the

alkyl group contains β hydrogen atom.
Sulfur yields in place of nitrogen yields also give similar reaction.

R1 H
H Z C SR2
Z C S
2 R1
R
Some examples of Steven rearrangement are given below.
O
O N
NaOH Ph
N Ph
Ph
Ph

Et
Et2N
N KOtBu / MeCN
Et

PhLi
N
N
 tBuOK
1,4-dioxane
800C

N N

88%

BnOOC O
H
COOBn
N base

N
O
84%
 nBuLi in
hexane N N
PhHCN N

Ph

[ JOC, 1974, 39, 130 ]

Br K2CO3
EtOOC DMF EtOOC
COOEt COOEt
N 00C-rt N

EtOOC COOEt
N

[ Tet. Lett., 2002, 43, 899 ]

 O
NC N
HN
base

N N
N

O NC
O
NC HN
HN
N
+
N
N N
N N
N N
 R1
Ph Ph

Ph
base
Ph
N 1
R
N

THF, PhLi /
KHMDS
-780C
N
N
OTf

[ Tet. Lett., 2004, 45, 7525 ]

Wittig rearrangement :
Ethers on reaction with alkyl lithium rearrange in similar manner to
that of Stevens rearrangement to give alkoxy lithium. This reaction is
called Wittig rearrangement.

H R3
1 3 R4Li
R C OR R1 C OLi + R4H

R2 R2

This alkoxy lithium can then be converted to alcohol.

R3 R3
H
R1 C OLi R1 C OH

R2 R2
R may be alkyl, aryl or vinyl group.
Migratory aptitude are allylic, benzyl>ethyl>methyl>phenyl.
Mechanism follows radical pair pathway.

H
R1 C OR3 R1 C O R1 C O
R4Li Li
R1 C OR3 R3
R2 R2 R2 R3
R2
R3

R1 C OLi

R2
i.Reaction is largely intramolecular
ii.Migratory aptitude of group is analogs to free radical mechanism.
iii.Product obtained is with retention of configuration.

BuLi H

Ph O
Ph OLi Ph OH

OH
O O TMS
O
nBuLi, THF, TMS
H ether, 00C H
OTBDPS
OTBDPS
60%
 O

O tBuLi

O OH
58%

NOMe NOMe

O 2eq. LDA
THF, -780C OH
MeO MeO
 CH2Ph
Li
O DMSO
Naphthyllithium tBu / H2O /
tBu THF, -780C, 20 min K2CO3
OCH2Ph 4h,
SePh

OH CH2Ph

tBu + tBu

OCH2Ph OH

[ Tet. Lett., 1993, 34, 297 ]

 HO
O

O tBuLi
O
THF
-780C

OMe
OMe

[ Tetrahedron, 2005, 61, 1095 ]

When R2 is a good leaving group and electron withdrawing functional
group like CN, then this group is eliminated and ketone is formed.

H O
R2Li
R1 C OR + R2H + LiCN
R1 R
CN

H Li R
R
R2Li
R1
C OR R1
C O 1
R C OLi R1 C OLi
R
CN CN CN CN

R1 R
 Bt
Ph
LDA OCH3
Ph O OCH3
O
61%

Bt : benzotriazol-1-yl

HO
O O Ph
O
TBSO nBuLi, THF Ph
HO
-780C-00C
TBSO OTBS
TBSO OTBS

[ JACS, 1996, 118, 3317 ]

 F 3C OH
Ph

Ph N
F 3C O Ph O
LiHMDS
THF / ether +
Ph N -780C-rt
O OH
F3C

Ph N
O

[ Org. Lett., 2001, 3, 2529 ]

 OH
H2 MeLi H2
PhH2C O C Ph C C
H

[ JACS, 1962, 84, 4295 ]

OH
Ph O Ph Ph
nBuLi Ph

OH
Ph O Ph
nBuLi Ph + Ph
Ph
Ph
OH
Li

[ JACS, 1966, 88, 78 ]

 Et2O
BuLi
rt, 1.3h O
O

O O
N
29% N

[ Tet. Lett., 2000, 11, 1003 ]

The purpose of crossover experiment is to determine whether reaction
takes place intermolecularly or intramolecularly i.e. whether reactant
break apart to form intermediate which are released into solution
before they combine to give product.
In this experiment two substrate differing in substituent are mixed
together and are reacted in same reaction condition and the product
obtained is analyzed.
Consider, a simple reaction in which A-B reacts to give C-D.

A B + A* B* C D + C* D*

A B + A* B* C D + C* D* + C* D + C D*
There are two possibilities of outcome of reaction.
One in which no crossover of substituent is seen. This is possible if
reaction is intramolecular.
And other possibility is that mixture of products obtained is by
crossover reaction. This is possible in case of intermolecular reaction.
Thus crossover experiment gives useful information about course of
reaction.
The experiment can be illustrated by considering Fries rearrangement.
p-Tolylbenzoate (I) on rearrangement gives
2-hydroxy-5-methylbenzophenone (II).
OH
O Ph
AlCl3
Ph
O
O
I II

In the similar reaction, o-chloro-p-tolylacetate (III) give

2-hydroxy-3-chloro-5-methylacetophenone (IV).
Cl
Cl
OH
O AlCl3

O
O
III IV
When I and II are mixed together and product is analyzed, V and VI,
along with II and IV are obtained.
Cl

OH OH

Ph

O O
V VI

This shows that the reaction proceeds intermolecularly and fragments

are formed in solution.