Organic Syntheses, CV 5, 772
Submitted by R. E. Schuster, James E. Scott, and Joseph Casanova, Jr.
1.
Checked by John A. Dupont and William D. Emmons.
1. Procedure
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. (
69–74%) (Note
6). Analysis by gas liquid chromatography indicates that the purity exceeds 99% (Note
7).
2. Notes
1. An explosion involving
methyl isocyanide has been reported.
2 For this reason, prudence dictates the use of adequate shielding in all heating operations.
2. 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.
3. 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.
5. The checkers found that a
bath of dry ice and acetone worked equally well.
6. 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.
7. 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.
3. Discussion
Methyl isocyanide 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 Corey
4 and by Ugi and co-workers
5 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.
6 The procedure is less laborious than that reported earlier for
ethyl isocyanide.
7 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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