Chemistry Reference
In-Depth Information
causes dehydration of the amide group to the corresponding nitrile. In this case,
oxalyl chloride is effective [24].
Cl
O
Cl
O
O
O
(COCl)
2
NH
2
NCO
10
Cl
Cl
Chlorosulfonyl isocyanate can be used in place of phosgene to prepare sulfonyl
isocyanates 11 [24]; see also Chapter 4.
O
O
O
O
S
S
NH
2
NCO
11
ClSO
2
NCO
Thionyl chloride, phosphorus(V) chloride, and triphenylphosphine/tetrachloro-
methane can be used to convert monosubstituted amides into chloro imines.
These reagents, as well as oxalyl chloride, also transform disubstituted amides into
the corresponding imidium chloride salts.
Dehydration is a process for which many phosgene ''competitors'' have proved
useful. Thionyl chloride, phosphorus pentoxide, phosphorus oxychloride, triphe-
nylphosphine/tetrachloromethane, and catechol phosphorus trichloride are the re-
agents of choice in many dehydration processes.
Several methodologies are directed toward the development of mild and safe
reagents that can be utilized instead of phosgene in organic synthesis [28]. Most
of these reagents are themselves prepared from phosgene. For example, bis(4-
nitrophenyl)carbonate [29], 1,1-carbonyl-bis(imidazole) (CDI) [30], 1,1-carbonyl-
bis(benzotriazole) [31], phenyl chloroformate [32], and di-tert-butyl dicarbonate,
(Boc)
2
O [33] are prepared from phosgene. In a few exceptions, diphosgene and
triphosgene are used instead. In fact, the term triphosgene applied to bis(tri-
chloromethyl) carbonate is a misnomer, since this compound is not derived from
phosgene but by exhaustive chlorination of dimethyl carbonate [16]. Scheme 2.1
shows the structures of phosgene equivalents and their abbreviations.
There is opinion that employing these reagents is merely a way of circumventing
and not of facing and solving the problem of avoiding the use of phosgene. How-
ever, the question becomes much more complex if process safety is taken into
consideration and used as a reagent selection criterion (see Chapter 6). Phosgena-
tion is undoubtedly a key step in the synthesis of many pharmaceuticals and agro-
chemicals. Small- or medium-scale operations require intrinsic safety, which must
be ensured either by the stabilities of the raw materials (reagents), intermediates,
and products, or by hazard minimization during the operation. Consequently, em-
ploying phosgene-free reagents or phosgene-like raw materials with controlled phosgene
release during reaction, and the design of safer methods, are important goals with
regard to these organic processes.
