NEIGHBOURING GROUP PARTICIPATION

• Many nucleophilic substitution occur with complete retention of configuration and the rate of reaction is
exceptionally high.

• In these reactions there is an atom or group with an unshared pair of electrons,(in some cases sigma and
π electrons also) β to the leaving group (some times far away) assisting removal of leaving group.

• The mechanism operating such cases is known as neighboring group mechanism

• It consists of two consecutive SN2 reactions , leading to retention of configuration of configuration

• In the first step , the NG acts as the nucleophile, pushing out the LG.

• In the second step, the external nucleophile pushes out the NG

• All NG mechanism involves formation of cyclic intermediate.

• The reaction is more favorable If the position of the NG and the eliminating groups( leaving groups )
are trans to each other
 slow RDS Fast Z
Z
Z
I step II step
C C C C
Intra molecular SN2 SN2
L reaction Nu
Nu
Product with
retension of
configuration
Rate of reaction a Substrate

• follows first order rate law

• Such reaction occur thousand times faster than intermolecular nucleophilic substitution reactions.

• External ‘Nu’ does not take part in RDS

• Rate enhancement by neighboring group participation is called ‘Anchimeric assistance’ and such reactions
are called anchimerically assisted reactions
 1) Oxygen as a neighboring group :

Eg: Alkaline hydrolysis of 2-bromopropanoate anion to lactate anion.( Ag2O and low concentration of OH- ions)

NG- Carboxylate ion group

O Me
- I step O
HO Me OH
O Me
H H SN2
-H2O O Br H
O Br
OH
R-2-Bromopropanoic acid II step From
milder
SN2 base

O Me

C
H
O OH

R-Lactate anion
with retension of configuration

The same reaction when carried out in presence of NaOH , gives lactic acid with inversion of configuration
(SN2 mechanism)
2) Sulphur as neighboring group

Eg: Base catalyzed hydrolysis of mustard gas (2,2’- Dichloro diethyl sulphide)

NG- Sulphur

Slow
Cl Cl
S S
-Cl
H-OH
SN2
Mustard gas 3- membered cyclic TS
(Sulphonium ion)
SN2

Cl OH
S
3)- Halogen as a neighboring group

Eg: Acetolysis of trans -2- iodo cyclohexyl brosylate is 2.7*10 6 times faster than the acetolysis of its Cis isomer

NG: Iodo group

I I

-OBs I CH3CHOOH

SN2 -H SN2
Cyclic TS
OBs OAc
Trans isomer

BsO

Cis isomer
 4) Nitrogen as a neiboring group

Eg: Hydrolysis of tert- amine

NG- Nitrogen atom

Et Et
Me NEt2
N
SN2
-Cl
Et2N HO
Cl SN2 Me

Me Rearranged product
OH
(57%)
Cyclic TS

Here OH- anion attacks at less hindered Carbon of the ring, ie at CH 2

5) Neighboring group participation by σ bond
Eg CH3

aq AgNO3
CH3 OH

CH2Cl
Cyclopentane derivative Cyclohexane derivative

Mechanism

CH3
CH3 + Ag
d+ d+
CH2 Cl Ag
CH2Cl

-AgCl

CH3
CH3

OH2 CH3

CH2

NGP by s bond
-H
CH3

OH
Acetolysis of exo-2-norbornyl brosylate is 350 times faster than acetolysis of he endo isomer.

Here NG – 1-6 C-C bond

OBs
H
Exo isomer Endo isomer
H
OBs

AcOH
+
OBs -H OAc
6 1 AcO

H H
H
NGP by s bond (C-C) Recimic mixture of two exo acetates

AcOH
H

Endo isomer
OBs
Non classical
carbocation TS
Solvolysis of neo-pentyl tosylate

NG- Methyl group ( σ bond CH3-C)

H3
CH3 C
H3 C
H2
-OTs H2
H3 C C C OTs H3C C CH2 C C CH3

CH3
H3 C HOH
CH3
Cyclic TS
-H
H3C H2
C C CH3

H3C
OH
Rearranged product
6- Neighboring group participation by π bonds

Eg: Acetolysis of 7-norbornenyl tosylate is 10 11 times faster than that of the 7-norbornyl tosylate

Also, it proceeds with retension of configuration.

It gives strong evidence that the C=C π bond can act as a neighboring group in this reaction
AcO
OTs

-OTs AcOH

product with retension

TsO OAc of configuration

OAc

SN2, -OTs
product with incersion of configuration
Acetolysis of 4-methyl pent-3-enyl proceeds about 1200 times faster than that of ethyl tosylate

H3C
Slow H3C H
C CH H2C OTs H
-OTs C C C H
H3C
C
H2 H3C
H H

AcOH

Me
C CH CH2OAc

Me C
H2
NGP by π electrons of aromatic rings

-Br

Et
Et Me
Me B A
HOH
Br

Et

Me
Me
OH
Et
Retension of configuration
OH

Rearranged product
 Br
Br

<

Double bond as neighboring gp

Phenyl gp as NG
2 electron for NGP
6 electrons for NGP
loss of aromaticity,Unsatable
 < OTs
OTs

Endo Exo Exo is like Trans position

OTs
Single bond to push OTs

Trans single bond is the NG,help to push out OTs

Always trans is the favourable position
Br
Br Br Br

< <
<

Double bond Double bond Two double bond

Single bond
Cis to Br Trans to Br One trans to Br
less denser than
double bond
Active threo-3-bromo -2- butanol , upon treatment with HBr, gives rise to (+-) 2,3-dibromobutane . Justify

a
Br
H Br Me
Me Me H
H a b
Me Br H
HBr SN2
Br Br
OH2 Br
-H2O H H
OH -Br Me
H Me
Me
H
Me b
threo-3-bromo-2-butanol
a SN2 b SN2

Br
H Me

Br H
Me
Br H
Me
H
Me

Br

( + ) 2,3-dibromo butane
 Acetolysis of anti-7-norbornenyl tosylate (I) is very much (1011 times) faster than that of its saturated
analogue (II). Explain

OTs OTs

I II

OTs OAc

OTs AcOH
SN1

I Non-classical anti-7-norbornyl acetate

carbocation (retention of configuration)

OTs
AcO
OAc

AcOH, SN2
-OTs
II inversion of configuration
On acetolysis racemic threo-3 phenyl-2-butyl tosylate gives racemic threo-3-phenyl-2-butyl acetate while
racemic erythro isomer gives racemic erythro-3- phenyl -2-butyl acetate of retained configuration
 H3C H
H CH3

OTs
OTs

H3C
CH3 H
H

Threo SN2 -OTs

-OTs SN2

meso phenonium ion

CH3 H
H H3C
CH3 H b H H3C
a
a AcOH
b
-H
Ph
H
H
CH3
CH3 Ph
H
OAc
CH3

OAc H CH3

Threo-3-phenyl2-butyl acetate