8'14 Sulfonate Esters as Substrates in Nucleophilic Substitution

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8.14Sulfonate EstersasSubstrates in
Nucleophilic Substitution
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Leaving Groups

• we have seen numerous examples of nucleophilic
  substitution in which X in RX is a halogen
• halogen is not the only possible leaving group
  though

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Other RX compounds
Alkylmethanesulfonate(mesylate)
Alkylp-toluenesulfonate(tosylate)

• undergo same kinds of reactions as alkyl halides

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Preparation
Tosylates are prepared by the reaction of
alcohols with p-toluenesulfonyl
chloride(usually in the presence of pyridine)
pyridine

• (abbreviated as ROTs)

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Tosylates undergo typical nucleophilic
substitution reactions
KCN
ethanol-water
(86)
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• The best leaving groups are weakly basic

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Table 8.8Approximate Relative Reactivity of
Leaving Groups

• Leaving Group Relative Conjugate acid Ka
  of Rate of leaving group conj. acid
• F 10-5 HF 3.5 x 10-4
• Cl 1 HCl 107
• Br 10 HBr 109
• I 102 HI 1010
• H2O 101 H3O 56
• TsO 105 TsOH 600 CF3SO2O 108
  CF3SO2OH 106

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Table 8.8Approximate Relative Reactivity of
Leaving Groups

• Leaving Group Relative Conjugate acid Ka
  of Rate of leaving group conj. acid
• F 10-5 HF 3.5 x 10-4
• Cl 1 HCl 107
• Br 10 HBr 109
• I 102 HI 1010
• H2O 101 H3O 56
• TsO 105 TsOH 600 CF3SO2O 108
  CF3SO2OH 106

Sulfonate esters are extremely good leaving
groups sulfonate ions are very weak bases.
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Tosylates can be converted to alkyl halides
NaBr
DMSO
(82)

• Tosylate is a better leaving group than bromide.

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Tosylates allow control of stereochemistry

• Preparation of tosylate does not affect any of
  the bonds to the stereogenic center, so
  configuration and optical purity of tosylate is
  the same as the alcohol from which it was formed.

CH3(CH2)5
TsCl
pyridine
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Tosylates allow control of stereochemistry

• Having a tosylate of known optical purity and
  absolute configuration then allows the
  preparation of other compounds of known
  configuration by SN2 processes.

H
CH3(CH2)5
Nu
C
Nu
OTs
SN2
H3C
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8.15Looking Back Reactions of
AlcoholswithHydrogen Halides
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Secondary alcohols react with hydrogen halides
with net inversion of configuration
H
CH3
C
Br
87
(CH2)5CH3
HBr
13
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Secondary alcohols react with hydrogen halides
with net inversion of configuration
H
CH3
C
Br
87
(CH2)5CH3

• Most reasonable mechanism is SN1 with front side
  of carbocation shielded by leaving group

HBr
13
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Rearrangements can occur in the reaction of
alcohols with hydrogen halides
HBr

93
7
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Rearrangements can occur in the reaction of
alcohols with hydrogen halides
HBr
7
93
Br
Br