The SN 2 Mechanism of Nucleophilic

Substitution

Kinetics

Many nucleophilic substitutions follow a

second-order rate law.

CH3Br + HO – CH3OH + Br –
rate = k [CH3Br] [HO – ]
What is the reaction order of each starting material?
What can you infer on a molecular level?
What is the overall order of reaction?

Bimolecular mechanism Bimolecular mechanism

one step one step

concerted concerted

HO – + CH3Br HOCH3 + Br – HO – + CH3Br HOCH3 + Br –

 Bimolecular mechanism
δ− δ−
HO CH3 Br
transition state

Stereochemistry of SN2 Reactions

one step
concerted

HO – + CH3Br HOCH3 + Br –

Generalization Inversion of Configuration

Nucleophilic substitutions that exhibit nucleophile attacks carbon

second-order kinetic behavior are from side opposite bond
stereospecific and proceed with to the leaving group
inversion of configuration.

Inversion of configuration (Walden inversion) in an SN2

Inversion of Configuration reaction is due to back side attack

nucleophile attacks carbon three-dimensional

from side opposite bond arrangement of bonds in
to the leaving group product is opposite to
that of reactant
 Stereospecific Reaction Stereospecific Reaction

A stereospecific reaction is one in which

stereoisomeric starting materials give CH3(CH2)5 H H (CH2)5CH3
stereoisomeric products. NaOH
C Br HO C
The reaction of 2-bromooctane
2-bromooctane with NaOH
(in ethanol-water) is stereospecific.
stereospecific. CH3
CH3
(+)-2-Bromooctane
(+)-2-Bromooctane (–)-2-Octanol
)-2-Octanol
(–)-2-Bromooctane
)-2-Bromooctane (+)-2-Octanol
(+)-2-Octanol (S)-(+)-2-Bromooctane
)-(+)-2-Bromooctane (R)-(–
)-(–)-2-Octanol
)-2-Octanol

1) Draw the Fischer projection formula for (+)-S-2-bromooctane

(+)-S-2-bromooctane..
2) Write the Fischer projection of the
(–
(–)-2-octanol
)-2-octanol formed from it by nucleophilic substitution
with inversion of configuration.

A conceptual view of SN2 reactions

CH3 CH3
H Br HO H

CH2(CH2)4CH3 CH2(CH2)4CH3

R- or S- ?

Why does the nucleophile attack from the back side?

CH3(CH2)5 H
–.. ..
HO C Br
.. :
..
H 3C
 CH3(CH2)5 CH3(CH2)5
H H
δ.. – .. δ – δ.. – .. δ –
HO.. C .. :
Br HO.. C .. :
Br

CH3 CH3

CH3(CH2)5 H CH3(CH2)5 H
–.. .. –.. ..
Br Br H (CH ) CH
HO.. C .. : HO.. C .. : 2 5 3
.. .. –
H 3C H 3C HO
.. C Br
.. :
CH3

Crowding at the Reaction Site

The rate of nucleophilic substitution

by the SN2 mechanism is governed
by steric effects.
Steric Effects in SN2 Reactions
Crowding at the carbon that bears
the leaving group slows the rate of
bimolecular nucleophilic substitution.

Reactivity toward substitution by the SN2

mechanism
A bulky substituent in the alkyl halide reduces the
reactivity of the alkyl halide: steric hindrance
RBr + LiI RI + LiBr

Alkyl Class Relative

bromide rate
CH3Br Methyl 221,000
CH3CH2Br Primary 1,350
(CH3)2CHBr Secondary 1
(CH3)3CBr Tertiary too small
to measure
 Decreasing SN2 Reactivity Decreasing SN2 Reactivity

CH3Br CH3Br

CH3CH2Br CH3CH2Br

(CH3)2CHBr (CH3)2CHBr

(CH3)3CBr (CH3)3CBr

Reaction coordinate diagrams for (a) the SN2 reaction of

methyl bromide and (b) an SN2 reaction of a sterically Crowding Adjacent to the Reaction Site
hindered alkyl bromide

The rate of nucleophilic substitution

by the SN2 mechanism is governed
by steric effects.

Crowding at the carbon adjacent

to the one that bears the leaving group
also slows the rate of bimolecular
nucleophilic substitution, but the
effect is smaller.

Effect of chain branching on rate of SN2

substitution

RBr + LiI RI + LiBr

Alkyl Structure Relative

bromide rate
Ethyl CH3CH2Br 1.0
Propyl CH3CH2CH2Br 0.8
Isobutyl (CH3)2CHCH2Br 0.036
Neopentyl (CH3)3CCH2Br 0.00002