Chemistry Reference
In-Depth Information
involves a cyclization between the amide carbonyl and C-3 in an acyclic precursor
molecule, i.e. disconnection 201
!
202 [125, 126].
H
H
H
O
O
O
H
H
H
H
H
R
'
R
'
X
NH
3
S
N
N
Y
N
R
O
R
O
CO
2
O
200
201
202
An intermediate carbamoyl chloride of type 202 (Y
Cl) has been prepared using
triphosgene, starting from the imine 205 derived from but-2-enal 203 and benzyl-
amine 204.
The unsaturated carbamoyl cobalt salophen reagent 208 is a precursor of novel
carbamoyl radical intermediates, which undergo facile cyclization to b-lactams.
ΒΌ
PhCH
2
NH
2
204
NaBH
4
, MeOH
N
H
Ph
O
N
h
CH
2
Cl
2
203
205
206
(CCl
3
O)
2
CO
O
.
N
h
N
h
NaCo salophen
N
h
O
Co (salophen)
O l
209
208
207
Typical procedure. N-Benzyl-N-(but-2-enyl)carbamoyl chloride 207 [126]:
A solution of
the amine 206 (918 mg, 5.7 mmol) in dry benzene (2 mL) was added dropwise over
0.5 min to a stirred suspension of triphosgene (563 mg, 1.9 mmol) and pyridine
(450 mg, 5.7 mmol) in dry benzene (30 mL) under an atmosphere of nitrogen. The
resulting suspension was stirred under nitrogen for 96 h and then filtered under
nitrogen. The filtrate was concentrated to dryness under reduced pressure to leave
the carbamoyl chloride (1.27 g, 99.5%) as a yellow liquid.
Carbamoyl chloride 211 of di(2-chloroethyl)amine 210, a useful intermediate in
the preparation of nitrogen mustards and l-phenylalanine mustards as antitumor
agents [127], was prepared in 85% yield using triphosgene and pyridine as acid
scavenger at temperatures below 20
C [128, 129].
