Chemistry Reference
In-Depth Information
Work-up; benzonitrile: Solvent chloroform. The solvent was distilled off and the
residue was extracted with petroleum ether (60-95
C) in a Soxhlet apparatus for
16 h. After cooling, the crystallized triphenylphosphine oxide was filtered off and
the filtrate was fractionated to give 9.3 g (90%) of benzonitrile (bp 70-72
C/10
mmHg).
Work-up; 4-nitrobenzonitrile: Solvent chloroform. The solvent was evaporated and
the residue was steam-distilled; 10.5 g (71%) of 4-nitrobenzonitrile was collected;
mp 148
C.
This nitrile synthesis can be applied equally well to aliphatic and aromatic car-
boxamides. It is also applicable to the production of 7-chloro-3-cyano-2,3-dihydro-1-
methyl-2-oxo-5-phenyl-1H-1,4-benzodiazepine 1451, which is not accessible using
the usual strongly acidic dehydrating agents [1100]. 1451 is produced as an inter-
mediate in a synthesis of imidazo[5,1-c]benzodiazepine-1,4 1452 by dehydration of
the carbaldoxime 1450 with triphenylphosphine/tetrachloromethane in 76% yield
[1102].
Ph
3
P
CCl
4
O
O
N
N
CONH
2
CN
N
N
Cl
dioxane
80°C
90 min
Cl
Ph
Ph
76 %
1451
1450
CO
2
Et
O
N
O
N
Cl
NH
H
O
Ph
O
1452
Typical procedure. 7-Chloro-3-cyano-2,3-dihydro-1-methyl-2-oxo-5-phenyl-1H-1,4-benzo-
diazepine 1451 [1102]:
A mixture of triphenylphosphine (104.0 g, 0.4 mol), tetra-
chloromethane (350 mL), dioxane (400 mL), and the carboxamide 1450 (65.5 g, 0.2
mol) was stirred at 80
C for 90 min, in the course of which the amide dissolved
and the solution became orange. The solvent was then evaporated in vacuo and the
residue was redissolved in dichloromethane. The organic solution was washed with
water and then concentrated in vacuo. The resulting oil crystallized on trituration
with a little diethyl ether. The crude product, which still contained some triphe-
nylphosphine oxide, was recrystallized from ethanol to afford 47 g (76%) of pure
product 1451; mp 208-210
C; IR: n
max
2266 cm
1
(CN).
Systematic investigations have been performed to optimize the method by vary-
ing the haloalkane [1103, and refs. cited therein]. In particular, the reaction tem-
¼
