Chemistry Reference
In-Depth Information
The preparation of O-(chloroformyl)oximes 124 was previously reported by Jumar
[67], with the obtained yields being between 56 and 88%.
Oximes react with diphosgene or triphosgene to form mixtures of the chloro-
formyl esters and the (trichloromethoxy)formyl esters in variable ratios. With anti-
mony pentachloride, these mixtures give nitrilium salts, which are contaminated
with excess SbCl
5
as the exact amount of this reagent required is di
cult to deter-
mine.
CCl
3
OCOCl
or
(CCl
3
O)
2
CO
O
O
R
1
R
1
R
1
N
N
N
O
Cl
O
OCCl
3
OH
R
2
R
2
R
2
-60°C to 23°C, Et
2
O
123
124
126
Typical procedure. Chloroformyl ester 124 (R
1
,R
2
¼ Me) and the (trichloromethoxy)-
formyl ester 126 (R
1
,R
2
¼ Me) [66]:
A solution of 123 (R
1
,R
2
¼
Me) (0.73 g, 10
40
C) solution of
triphosgene (4.45 g, 15 mmol) in diethyl ether (10 mL). After stirring at 23
C for
30 min, the solvent was evaporated. The
13
C NMR spectrum of the colorless solid
residue (3.33 g) showed signals for 124, 126, and unreacted triphosgene.
Oxalyl chloride proved to be an interesting reagent for the above transformation;
on treating an oxime with 1.5 equivalents of this reagent in diethyl ether at low
temperatures, a precipitate (hydrochloride of the oxime) is formed immediately,
which dissolves after a few minutes affording (chlorooxalyl)oximes in high yields
(68-99%) [66].
Chloroformate 128 of 2-hydroxyethyl methacrylate 127, an intermediate for the
synthesis of azo polymers useful for colon-specific drug delivery, was prepared with
triphosgene [68].
mmol) in diethyl ether (10 mL) was added dropwise to a cold (
Me
Me
O
(CCl
3
O)
2
CO
O
O
OH
O
Cl
THF, rt, 1 week
O
O
127
128
4.2.2
Carbamoyl Chlorides (Chlorocarbonylation of Amines)
The most widely documented aspect of phosgene chemistry is the interaction of
the reagent with nitrogen nucleophiles (for example, R
3
N). The intermediate com-
plex 129 formed is unstable and usually collapses, with elimination of RCl, to give
a stable carbamoyl chloride derivative 130. The carbamoyl chloride thus formed
can eliminate RCl to create a new site of unsaturation (isocyanate, 131) and/or
react further with another molecule of starting material to afford urea, 132, a tri-
coordinated carbonic acid derivative (see Scheme 4.1).
