Title: 8.3 The SN2 Mechanism of Nucleophilic Substitution
18.3The SN2 Mechanism of Nucleophilic Substitution
2Kinetics
- Many nucleophilic substitutions follow
asecond-order rate law. CH3Br HO Æ
CH3OH Br - rate kCH3BrHO
- inference rate-determining step is bimolecular
3Bimolecular mechanism
4Bimolecular mechanism
5Bimolecular mechanism
68.4Stereochemistry of SN2 Reactions
7Generalization
- Nucleophilic substitutions that
exhibitsecond-order kinetic behavior are
stereospecific and proceed withinversion of
configuration.
8Inversion of Configuration
nucleophile attacks carbonfrom side opposite
bondto the leaving group
9Inversion of Configuration
nucleophile attacks carbonfrom side opposite
bondto the leaving group
three-dimensionalarrangement of bonds inproduct
is opposite to that of reactant
10Stereospecific Reaction
- A stereospecific reaction is one in
whichstereoisomeric starting materials
givestereoisomeric products. - The reaction of 2-bromooctane with NaOH (in
ethanol-water) is stereospecific. - ()-2-Bromooctane Æ ()-2-Octanol
- ()-2-Bromooctane Æ ()-2-Octanol
11Stereospecific Reaction
(CH2)5CH3
NaOH
(S)-()-2-Bromooctane
(R)-()-2-Octanol
12Problem 8.4
- The Fischer projection formula for
()-2-bromooctaneis shown. Write the Fischer
projection of the()-2-octanol formed from it by
nucleophilic substitution with inversion of
configuration.
13Problem 8.4
- The Fischer projection formula for
()-2-bromooctaneis shown. Write the Fischer
projection of the()-2-octanol formed from it by
nucleophilic substitution with inversion of
configuration.
148.5How SN2 Reactions Occur
15CH3(CH2)5
H
..
..
Br
C
HO
..
..
H3C
16CH3(CH2)5
H
d
d
..
..
Br
HO
C
..
..
CH3
CH3(CH2)5
H
..
..
Br
C
HO
..
..
H3C
17CH3(CH2)5
H
d
d
..
..
Br
HO
C
..
..
CH3
CH3(CH2)5
H
..
..
H
Br
(CH2)5 CH3
C
HO
..
..
..
C
HO
H3C
..
CH3
188.6Steric Effects in SN2 Reactions
19Crowding at the Reaction Site
The rate of nucleophilic substitutionby the SN2
mechanism is governedby steric
effects. Crowding at the carbon that bears the
leaving group slows the rate ofbimolecular
nucleophilic substitution.
20Table 8.2 Reactivity toward substitution by the
SN2 mechanism
RBr LiI Æ RI LiBr
- Alkyl Class Relativebromide rate
- CH3Br Methyl 221,000
- CH3CH2Br Primary 1,350
- (CH3)2CHBr Secondary 1
- (CH3)3CBr Tertiary too small to measure
21Decreasing SN2 Reactivity
CH3Br
CH3CH2Br
(CH3)2CHBr
(CH3)3CBr
22Decreasing SN2 Reactivity
CH3Br
CH3CH2Br
(CH3)2CHBr
(CH3)3CBr
23Crowding Adjacent to the Reaction Site
The rate of nucleophilic substitutionby the SN2
mechanism is governedby steric
effects. Crowding at the carbon adjacentto the
one that bears the leaving groupalso slows the
rate of bimolecularnucleophilic substitution,
but the effect is smaller.
24Table 8.3 Effect of chain branching on rate of
SN2 substitution
RBr LiI Æ RI LiBr
- Alkyl Structure Relativebromide rate
- Ethyl CH3CH2Br 1.0
- Propyl CH3CH2CH2Br 0.8
- Isobutyl (CH3)2CHCH2Br 0.036
- Neopentyl (CH3)3CCH2Br 0.00002