Chemistry Reference
In-Depth Information
Tab. 4.1.
Chloride substitution of activated alcohols by
triphosgene [13].
ROH
ROCOCl
RCl
CO
2
ROH
Chloride
yield %
Chloroformate
yield %
(
)-Menthol
98
OH
74
OH
90
86
OH
OH
85
OH
80
63
OH
OH
65
The reaction is applicable to benzylic, allylic, and propargylic alcohols. The
chlorides listed in Table 4.1 were each made from the corresponding alcohol in less
than 15 min at room temperature, with the exception of propargyl chloride. Al-
though the chloroformate of propargyl alcohol formed in less than 1 min, gentle
warming was necessary to drive the reaction to completion.
It is significant that under these conditions, with unactivated alcohols, chloro-
formates are isolated readily without a trace of the corresponding chloride; (
)-
menthol chloroformate and sec-butyl chloroformate were prepared in yields of 98%
and 78%, respectively.
By analogy with the reaction of thionyl chloride with alcohols, which results in
the formation of the corresponding chlorides, either an S
N
2 or carbonium ion
mechanism (such as S
N
i and S
N
1) may be invoked for the formation of chlorides
from the intermediary chloroformates. The former mechanism would result in
inversion, whereas the latter two would give retention and racemization of con-
figuration at the site of reaction, respectively [14, 15]. (R)-(
þ
)-1-Phenylethanol
([a]
20
D
45.7
(neat), 99% ee) was converted to 1-(chloroethyl)benzene by this
procedure. Polarimetric measurement of the product ([a]
20
D
¼þ
42.0
(neat)) re-
¼
vealed it to be a 3:7 mixture of (R)-(
þ
)- and (S)-(
)-1-(chloroethyl)benzenes. Thus,
