Organic Syntheses, Coll. Vol. 5, p.772 (1973); Vol. 46, p.75 (1966).
Caution! Methyl isocyanide
should be prepared in a good hood
since it is toxic and has a very unpleasant odor. The reaction and subsequent distillation of the product should be conducted behind safety shields (Note 1)
In a 2-l. four-necked flask (Note 2)
equipped with a 250-ml. pressure-equalizing dropping funnel
, a sealed mechanical stirrer
, a thermometer
, and a receiver trap (Note 3)
are placed 1034 g. (8.0 moles) of quinoline
and 572 g. (3.0 moles) of p-toluenesulfonyl chloride (Note 4)
. The solution is heated to 75° by an oil bath
and the system evacuated to a pressure of 15 mm. The receiver is cooled in a bath of liquid nitrogen (Note 5)
. While the solution is vigorously stirred and maintained at this temperature, 118 g. (2.0 moles) of N-methylformamide (Note 4)
is added dropwise to maintain a smooth distillation rate. The addition is complete in 45–60 minutes.
The material which collects in the receiver is distilled through a 15-cm. Vigreux column
at atmospheric pressure. Methyl isocyanide
, a colorless, vile-smelling liquid, is collected at 59–60°; weight 57–61 g.
) (Note 6)
. Analysis by gas liquid chromatography indicates that the purity exceeds 99% (Note 7)
An explosion involving methyl isocyanide
has been reported.2
For this reason, prudence dictates the use of adequate shielding in all heating operations.
A three-necked flask
may be used by employing a suitable adapter on one of the necks. The checkers used a standard wide-bore, 75-degree side-arm adapter fitted with a long-stemmed thermometer
extending into the reaction solution. A Trubore® stirrer equipped with a semicircular Teflon® paddle
was also used.
A vapor trap having a wide-bore inlet tube
and the appropriate condensate capacity is used. The checkers used a 4.8 cm. × 30.0 cm. trap
having a 2.0 cm. × 18.0 cm. inlet tube
. Best results are obtained when the trap is connected directly to the flask or the adapter (see (Note 2)
) by a wide-bore tube. Ground-glass joints should be used throughout the apparatus.
The checkers found that a bath of dry ice and acetone
worked equally well.
A single transfer under high vacuum afforded a product of identical purity. The major contaminants appear to be small amounts of high-boiling starting materials.
When a 2-m. polypropylene glycol
on firebrick column
at 75° is used, the retention volume of methyl isocyanide
is 55 cc. of helium
. Because of an unknown factor in conditioning the column, it is advisable to perform at least two consecutive analyses.
The checkers employed a 5-ft. 20% Carbowax 20 M
(terminated with terephthalic acid
) on Chromosorb W (acid washed) column at 60°. Methyl isocyanide
showed a retention volume of 300 cc. of helium
. Only traces of lower-boiling impurities were observed.
has been prepared chiefly by minor modifications of the original method of Gautier,3
which is the alkylation of silver cyanide
by an alkyl halide.
4. Merits of the Preparation
The excellent procedures for dehydration of N-alkyl- and N-arylformamides developed by Hertler and Corey4
and by Ugi and co-workers5
are unsuccessful with low-molecular-weight isocyanides. This common failure is probably due to poor efficiency in extraction of these very polar substances from water. The present method also has been successfully employed for the preparation of smaller quantities of methyl (50%), ethyl (45%), s-butyl (35%) and cyclobutyl (24%) isocyanides
The procedure is less laborious than that reported earlier for ethyl isocyanide
For comments on procedures for the preparation of the higher alkyl isocyanides see p. 300
of this volume and reference 8
This preparation is referenced from:
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