Chemistry Reference
In-Depth Information
Synthesis procedure is given for the first case, the preparation of chloroacetonitrile
in 62-70% yield [1083].
CO
2
Et
N
O
O
N
H
O
1419
TFAA
Et
3
N
dioxane
5-15°C
CO
2
Et
CO
2
Et
N
N
O
O
+
O
O
NC
N
72 %
OH
O
O
hypecumine
O
1420
O
1421
1422
50 %
3 ClCH
2
CONH
2
þ
P
2
O
5
!
3 ClCH
2
CN
þ
2H
3
PO
4
1423
1424
Typical procedure. Chloroacetonitrile 1424 [1083]:
In a 3-L round-bottomed, three-
necked flask fitted with an e
cient mechanical stirrer, a reflux condenser, and a
thermometer were placed phosphorus pentoxide (170 g, 1.2 mol), chloroacetamide
1423 (187 g, 2 mol), and dry technical grade trimethylbenzene (800 mL). The mix-
ture was gently refluxed with vigorous stirring for 1 h. It was then allowed to cool
to about 100
C with continuous stirring, and the reflux condenser was replaced
with a distillation head fitted with a thermometer and a water-cooled condenser.
The crude product and part of the solvent were distilled at atmospheric pressure.
The yield of crude product boiling at 124-128
C was 121-131 g (80-87%). In
order to obtain a pure product, the crude chloroacetonitrile was mixed with phos-
phorus pentoxide (10 g) and redistilled through an e
cient packed fractionating
column. The yield of pure chloroacetonitrile distilling at 123-124
C was 93-106 g
(62-70%).
Similarly to the previous procedure, methyl 2-exo-cyano-bicyclo[6.1.0]non-4-ene-
9-carboxylate was prepared in 80% yield [1084].
A variation on this preparative procedure, the second case mentioned above, is
dehydration by phosphorus pentoxide under solvent-free conditions. An example
of this is the synthesis of 2-ethyl-5-cyanomethyltetrazole, which is achieved in 61%
yield [1085]. Also solvent-free is the preparation of the intermediate p-methoxy-
phenylmalonitrile 1426, which is then condensed with 1427 to afford the corre-
sponding pyrazolo[1,2-a]pyrazole 1428 [1086].
