Chemistry Reference
In-Depth Information
The need to replace phosgene by substitutes not only stems from considerations
relating to its high toxicity, but is also due to the fact that its production and use
involve chlorine as a raw material and result in the generation of large amounts of
halogenated by-products since chlorine is not present in the majority of its end
products [8]. A general discussion on the complex criteria for selecting a phosge-
nation reagent is given in Chapter 6.
In recent years, trichloromethyl chloroformate (diphosgene) [4, 9] and bis-
(trichloromethyl) carbonate (triphosgene) [10-15] (for reviews, see [16-20]) have
frequently been used in organic synthesis as phosgene sources [11, 21]. These liq-
uid and crystalline phosgene equivalents, respectively, have the advantage of being
much easier to handle than the gaseous phosgene.
A long list of phosgene substitutes has been proposed and investigated. Catechol
phosphorus trichloride reacts with compounds containing C
O, RO,
PO, and SiO groups to give the corresponding chloro derivatives. Oxalyl chloride
can be an effective alternative chloroformylating agent to phosgene. The reaction of
oxalyl chloride with diphenyl ketene, for example, proceeds under milder condi-
tions than that with phosgene to give the identical organic product 1 [22].
b
O, P
b
O, S
b
Ph
Ph
COCl
COCl
2
or
CO
C
C
C
1
(COCl)
2
Ph
Ph
COCl
Aryl and alkyl chloroformates, chlorinated chloroformates (diphosgene), and chlori-
nated carbonates (triphosgene) can be used to convert carboxylic acids to the corre-
sponding chlorides. The formation of alkyl chlorides from alcohols using these re-
agents is also possible. In many cases, however, such derivatives are di
cult, or
impossible, to prepare, in which case phosgene has to be employed. Some exam-
ples yielding 2, 3, and 4 are given below [23-25].
COCl
COCl
2
Me
Me
2
N
N
Me
Me
COCl
H
N
COOR
N
COOR
3
COCl
2
N
H
N
H
OH
O
Cl
4
COCl
2
N
N
O
R
R
The carbonylating property of phosgene can be successfully realized using as sub-
stitute reagents lower alkyl chloroformates, such as ethyl chloroformate, which is
particularly suitable as a ring-closing reagent in the synthesis of imidazoline de-
rivatives 5 [26]; see also Chapter 6.
