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8.14
Sulfonate Esters
as
Substrates in Nucleophilic Substitution
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
Other RX compounds
O
ROSCH3
O
Alkyl
methanesulfonate
(mesylate)
O
ROS
CH3
O
Alkyl
p-toluenesulfonate
(tosylate)
undergo same kinds of reactions as alkyl
halides
Preparation
Tosylates are prepared by the reaction of
alcohols with p-toluenesulfonyl chloride
(usually in the presence of pyridine)
ROH + CH3
SO2Cl
pyridine
O
ROS
O
CH3
(abbreviated as ROTs)
Tosylates undergo typical nucleophilic
substitution reactions
H
KCN
H
CH2OTs
ethanolwater
CH2CN
(86%)
The best leaving groups are weakly basic
Table 8.8
Approximate Relative Reactivity of Leaving Groups
Leaving Group Relative
Rate
F–
Cl–
Br–
I–
H2O
TsO–
CF3SO2O–
10-5
1
10
102
101
105
108
Conjugate acid Ka of
of leaving group conj. acid
HF
HCl
HBr
HI
H3O+
TsOH
CF3SO2OH
3.5 x 10-4
107
109
1010
56
600
106
Table 8.8
Approximate Relative Reactivity of Leaving Groups
Leaving Group Relative
Rate
Conjugate acid Ka of
of leaving group conj. acid
F–
10-5
HF
3.5 x 10-4
Cl–
1
HCl
107
Sulfonate
esters are extremely good leaving groups;
–
Br
10
HBr
109
sulfonate
ions are2 very weak bases.
–
I
10
HI
1010
H2O
101
H3O+
56
TsO–
105
TsOH
600
CF3SO2O–
108
CF3SO2OH
106
Tosylates can be converted to alkyl halides
CH3CHCH2CH3
OTs
NaBr
DMSO
CH3CHCH2CH3
Br
(82%)
Tosylate is a better leaving group than bromide.
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.
H
H
CH3(CH2)5
TsCl
C
CH3(CH2)5
C
OH
pyridine
H3C
H3C
OTs
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
H
CH3(CH2)5
C
Nu–
OTs
(CH2)5CH3
Nu
C
SN2
H3C
CH3
8.15
Looking Back:
Reactions of Alcohols
with
Hydrogen Halides
Secondary alcohols react with hydrogen
halides with net inversion of configuration
H
CH3
Br
C
87%
H
H3C
(CH2)5CH3
HBr
C
CH3(CH2)5
OH
H
13%
H3C
C
CH3(CH2)5
Br
Secondary alcohols react with hydrogen
halides with net inversion of configuration
H
CH3
Br
H
C
87%
(CH2)5CH3
H3C
Most reasonable mechanism
is SN1 with front side
HBr
C
OHshielded by leaving group
of carbocation
CH3(CH2)5
H
13%
H3C
C
CH3(CH2)5
Br
Rearrangements can occur in the reaction of
alcohols with hydrogen halides
OH
HBr
Br
+
Br
93%
7%
Rearrangements can occur in the reaction of
alcohols with hydrogen halides
HBr
OH
7%
+
+
93%
Br –
Br
+
Br
Br –