Chemistry Reference
In-Depth Information
Cl
(CCl
3
O)
2
CO
O
R
1
R
1
N
R
2
or
COCl
2
N
l
R
2
219
220
R
1
Cl
R
2
N
l
O
71 %
221
222
The reaction most probably proceeds according to the mechanism described for
chloroformates. In fact, an equimolar amount of benzyl chloride beside the carba-
moyl chloride was obtained in all the reported reactions. The results in Table 4.7
also show that the method is compatible with various functional groups (ketone,
ester, amide, unsaturations; entries 1 to 4). However, the presence of a phenyl
group on the nitrogen atom seems to inhibit the reaction (entry 5) since, in this
particular case, the starting material is entirely recovered. Interestingly enough, the
same order of reactivity between benzyl and alkyl groups as with chloroformates is
observed (entries 6 and 7): benzyl reacts much more rapidly than ethyl or methyl
groups, thus leading to regioselective N-debenzylation.
Extension of this method to solid-phase procedures would have the advantage
of allowing the removal of benzyl chloride simply by filtration, thus affording
polymer-bound carbamoyl chlorides ready for further reactions.
General procedure. Carbamoyl chlorides 221 from tertiary N-benzylamines 219 [135]:
A
0.3 m solution of the tertiary benzylamine (1 equiv.) in dichloromethane is added to
a 0.1 m solution of triphosgene (0.33 equiv.) in dichloromethane at 0
C under an
inert atmosphere. The mixture is then allowed to warm to room temperature and
stirred until no further change is seen by TLC. The reaction mixture is then
concentrated under reduced pressure and the residue is purified by flash chroma-
tography.
4.2.2.4
Reactions with Amides
Phosgene and phosgene substitutes, particularly oxalyl chloride, dehydrate amides
resulting in various useful phosgene equivalents (see Scheme 4.1). Although de-
hydration is the most important preparative method when amides are subjected to
phosgenation, several accounts of chlorocarbonyl group transfer to amidic nitrogen
have also appeared.
Oxalyl chloride has been used for N-chlorocarbonylation of the aromatic amide
223 [136].
