NUCLEOPHILIC SUBSTITUTION

A nucleophilic substitution reaction is a reaction that takes place when a

nucleophile reacts with an electrophile.
Concept map
Nucleophilic
substitution
occurs when

OH a nucleophile reacts with

an electrophile CH3Cl

to give

a product in which
the nucleophile is bonded
to the electrophilic centre

CH3-O-H

Nucleophilic substitution is one of the reactions that has received the greatest
attention in organic chemistry for the following reasons:
1. The reaction has enormous synthetic utility.
2. It is possible to predict the course of a nucleophilic substitution with
reasonable precision.
3. It is possible to tailor experimental conditions to maximise conversion
reactants to desired products by employing mechanistic principles.
Nucleophilic reactions may involve several different combinations of charged and
uncharged species as reactants[substrates]. The most common ones fit into the four
categories as below;
a) Neutral substrate + neutral nucleophile
b) Neutral substrate + anionic substrate
c) Cationic substrate + neutral nucleophile

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 d) Cationic substrate + anionic nucleophile.
In our discussion we shall consider factors that influence the reactivity of
nucleophiles and substrates
Examples of reactions in categories above.
a) Neutral substrate +neutral nucleophile
RX + Y R-Y + X
Acentric
CH3CH2I + (CH3CH2CH2CH2)3P CH3CH2CH2CH2)P (CH2CH3) I

-H
PhC(CH3)2Cl + CH3CH2OH PhC(CH3)2 OCH2CH3 PhC(CH3)2OCH2CH3
H 87%

b)Neutral substrate + Anionic nucleophile

RX + Y R-Y + X
NaI
CH3CHCH2C N CH3CHC2CN
Br Acetone
I 96%

CH3CH(CH2)5CH3 + PhS Ethanol CH3CH(CH2)5CH3

OTs SPh

c) Cationic substrate + Neutral Nucleophile

RX + + Y: RY+ + X:
600
Ph-CH S (CH3) + (H2N)2 C=S Ph CH-S-C NH2
CH3
acetonitrile
NH2

CH3CH2OH -H
Ph2CH-N N Ph2CHO CH2CH3 Ph2CH O CH2CH3 + N2
H

d) Cationic subatrate + Anionic Nucleophile

RX + + Y: RY + X:
(CH3CH2)3O + (CH3)3CCOO (CH3)3CCOOCH2CH3
90%
NaI
CH2=CHCH2CH2S Ph dimethylfornamide CH=CHCH2CH2I

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In order to understand mechanisms in the diverse categories above we will begin
by reviewing the limiting cases as defined by Hughes and Ingold. The limiting
cases are the ionisation mechanism SN1 and the direct displacement mechanism
SN2
IONISATION MECHANISM SN1
Characteristics
- Substrate dissociates to a tri coordinate carbocation or carbonium ion[C+] and
leaving group.
- Rapid combination of carbocation with Lewis bases present in the medium.

R,X:,Y:
Potential energy

RX,Y:

RY, X:

Reaction coordinate

SN1- Ionisation mechanism for nucleophilic substitution

The reaction proceeds by a rate determining heterolytic dissociation of substrate to

a tri coordinate carbocation and a leaving group.
The dissociation is followed by rapid combination of the carbocation (electrophile)
with a Lewis base in the medium.

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 Consequences of the mechanism
The reaction exhibits first order kinetics overall with the rate of decomposition of
the substrate being independent of the concentration or nature of the
nucleophile
Slow k1
RX R + X:

Fast k2
R + Y: RY

Rate = - d[RX] = - d[Y: ] = k1[RX]

dt dt
The reaction will be facilitated by factors that either lower the energy of the
carbocation- anion pair or raise the energy of the ground state.
The rate of ionisation will depend on structural and medium effects and
Structural effects may be Electronic or sterric in nature.
[i] Electronic effects
Include:
a) Stabilisation of carbonium ion by electron release
b) Stabilisation of the leaving group by increasing its ability to accept an electron
pair from the initial covalent bond.
[ii] Sterric effects
These are effects that are pronounced because of the change in coordination
between the covalent substrate and the tri coordinate cation.
For example, bulky groups are compressed in the coordinate ground state and in
going to the Transition State [TS] they are spread apart. This facilitates ionization.
This constitutes relief of sterric compression.
The response of the ionisation mechanism to medium effects depends on the
charge type of substrate.

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[iii] Solvent or medium effects
Ionisation of a neutral substrate produces charge separation in the TS and the effect
of solvent polarity is therefore more pronounced in the TS than in the ground state
[GS].
Solvents with higher dielectric constants will lower the energy of the TS more
than solvents of lower dielectric constants. This leads to increase of the rate of the
reaction.
Ionisation of cationic substrates leads to dispersal of charge in the TS and should
be enhanced by less polar solvents

NUCLEOPHILIC SUBSTITUTION ON OPTICALLY ACTIVE

SUBSTRATES

The rate-determining step produces an intermediate that is achiral because it

contains a plane of symmetry.
If the carbonium ion is long-lived enough to diffuse away from the leaving group,
it gets symmetrically solvated. When attacked by NU, It will produce a racemic
product.
If the carbonium ion does not quickly diffuse away from the leaving group, it gets
disymmetrically solvated. Attack by the nucleophile will give an optically active
product retained or inverted configuration.
The carbonium ion can be generated from more than one precursor. Therefore the
reactions C+ undergoes are independent of its origin.