8.3 The SN2 Mechanism of Nucleophilic Substitution

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8.3The SN2 Mechanism of Nucleophilic Substitution
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Kinetics

• Many nucleophilic substitutions follow
  asecond-order rate law. CH3Br HO Æ
  CH3OH Br
• rate kCH3BrHO
• inference rate-determining step is bimolecular

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Bimolecular mechanism

• one stepconcerted

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Bimolecular mechanism

• one stepconcerted

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Bimolecular mechanism

• one stepconcerted

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8.4Stereochemistry of SN2 Reactions
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Generalization

• Nucleophilic substitutions that
  exhibitsecond-order kinetic behavior are
  stereospecific and proceed withinversion of
  configuration.

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Inversion of Configuration
nucleophile attacks carbonfrom side opposite
bondto the leaving group
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Inversion of Configuration
nucleophile attacks carbonfrom side opposite
bondto the leaving group
three-dimensionalarrangement of bonds inproduct
is opposite to that of reactant
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Stereospecific 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

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Stereospecific Reaction
(CH2)5CH3
NaOH
(S)-()-2-Bromooctane
(R)-()-2-Octanol
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Problem 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.

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Problem 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.

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8.5How SN2 Reactions Occur
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CH3(CH2)5
H

..
..
Br

C
HO
..
..
H3C
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CH3(CH2)5
H

d
d
..
..

Br
HO
C
..
..
CH3

CH3(CH2)5
H

..
..
Br

C
HO
..
..
H3C
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CH3(CH2)5
H

d
d
..
..

Br
HO
C
..
..
CH3

CH3(CH2)5
H

..
..
H
Br

(CH2)5 CH3
C
HO
..
..
..
C
HO
H3C
..
CH3
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8.6Steric Effects in SN2 Reactions
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Crowding 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.
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Table 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

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Decreasing SN2 Reactivity
CH3Br
CH3CH2Br
(CH3)2CHBr
(CH3)3CBr
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Decreasing SN2 Reactivity
CH3Br
CH3CH2Br
(CH3)2CHBr
(CH3)3CBr
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Crowding 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.
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Table 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