Chemistry Reference
In-Depth Information
ride/DMF. Thus, dehydration of 1437 at room temperature for 5 h gave diphenyl-
methyl 3-cyano-3-cephem-4-carboxylate 1438 in 68% yield [1093].
H
H
S
S
POCl
3
N
NOH
N
DMF
EtOAc
rt, 5 h
CN
O
O
CO
2
CHPh
2
CO
2
CHPh
2
68
1437
1438
Typical procedure. Diphenylmethyl 3-cyano-3-cephem-4-carboxylate 1438 [1093]:
To a
solution of DMF (0.065 mL, 0.84 mmol) in ethyl acetate (0.4 mL), phosphoryl
chloride (0.088 mL, 0.84 mmol) was added at 0
C. The mixture was stirred at
0
C for 30 min, and then a solution of 1437 (220 mg, 0.56 mmol) in ethyl acetate
(4 mL) was added. The resulting mixture was stirred at room temperature for 5 h,
poured into ice-cold 3% aqueous sodium hydrogen carbonate solution (20 mL),
and extracted with ethyl acetate (30 mL). The organic layer was washed with water
and saturated brine, dried over magnesium sulfate, and concentrated in vacuo. The
residue was triturated with diethyl ether to give 1438 as a yellow, amorphous pow-
der (143 mg, 68%); IR (Nujol): n
max
2220, 1785, 1730 cm
1
.
Syntheses of 1-benzyl-4-bromo-5-cyanoimidazole 1439 [1094], 1-cyanoisoquino-
line 1440 [1095], 3-chloro-4-cyano-1-phenylisoquinoline 1441 [1096], and 4-[3-(4-
cyano-1-phenyl)pyrazolo]-3-chloro-5,6-diphenylpyridazine 1442 [1097] have been
accomplished by dehydrating their carbaldoximes with phosphoryl chloride.
ΒΌ
CN
CN
Br
Cl
Cl
N
N
Ph
N
NC
N
N
N
N
N
Ph
Bn
83 %
1439
CN
Ph
Ph
95 %
1440
96 %
1441
1442
Typical procedure. 1-Benzyl-4-bromo-5-cyanoimidazole 1439 [1094]: A mixture of the
requisite oxime (5.0 g, 17.86 mmol) and phosphoryl chloride (20 mL, excess) was
heated under reflux for 30 min, then cooled and poured into ice/water. The pre-
cipitate was collected by filtration and recrystallized from ethyl acetate/light petro-
leum to give 1-benzyl-3-bromo-2-cyanoimidazole 1439 (3.9 g, 83%); mp 75-77
C.
Typical procedure. 1-Cyanoisoquinoline 1440 [1095]:
Phosphoryl chloride (0.54 g, 3.5
mmol) in chloroform (5 mL) was added dropwise to a solution of the requisite
carbaldoxime (0.2 g, 1.2 mmol) in chloroform (10 mL) under ice-cooling. The
mixture was heated under reflux for 4 h, treated with iced water, and the resulting
precipitate was filtered off. The filtrate was basified with 28% ammonia and then
extracted with chloroform to give 1-cyanoisoquinoline 1440; yield 0.17 g (95%).
