A Publication
of Reliable Methods
for the Preparation
of Organic Compounds
Annual Volume
Org. Synth. 1966, 46, 16
DOI: 10.15227/orgsyn.046.0016
[Isocyanic acid, anhydride with chloroacetic acid]
Submitted by A. John Speziale and Lowell R. Smith1.
Checked by Leif A. Hoffmann and V. Boekelheide.
1. Procedure
In a 250-ml. round-bottomed flask fitted with a magnetic stirrer (Note 1), a thermometer, and a condenser carrying a calcium chloride tube (Note 2) are placed 46.7 g. (0.5 mole) of α-chloroacetamide (Note 3) and 100 ml. of ethylene dichloride. The mixture is chilled in an ice bath to about 2° and stirred while 76.2 g. (0.6 mole) of oxalyl chloride (Note 4) is added all at once. The mixture is removed from the ice bath, stirred for 1 hour, and then heated to reflux at 83° with stirring for 5 hours (Note 5). The solution is chilled in an ice bath to 0–10°, the condenser is replaced by a 120-mm. distillation column packed with glass helices, and the solvent is removed at 70 mm. pressure with stirring. The ice bath is removed after the solvent boils without foaming and is replaced by a heating mantle or oil bath. Distillation gives 39 g. (65%) of α-chloroacetyl isocyanate, b.p. 68–70° (70 mm.), as a colorless oil, n25D 1.4565.
2. Notes
1. For larger-scale preparations mechanical stirring is recommended.
2. Moisture must be rigorously excluded from the reaction mixture and the product.
3. The α-chloroacetamide was obtained from Eastman Kodak Co. and used without purification.
4. The oxalyl chloride was obtained from Aldrich Chemical Co. and used without purification. Oxalyl chloride vapor is irritating and toxic, and therefore manipulations must be carried out in a hood.
5. Because a large amount of hydrogen chloride is evolved, the reaction must be carried out in a hood.
3. Discussion
The only preparation reported for α-chloroacetyl isocyanate is that described by the submitters.2
4. Merits of the Preparation
The procedure may be adapted for the preparation of other acyl isocyanates (i.e., dichloroacetyl, trichloroacetyl, phenylacetyl, diphenylacetyl, benzoyl, etc.) and is generally more convenient than the reaction of acid chlorides with silver cyanate.3 4 Acyl isocyanates react with amines, alcohols, and mercaptans to yield acyl ureas, carbamates, and thiocarbamates, and have been show to undergo a variety of interesting reactions.5

References and Notes
  1. Research Department, Agricultural Division, Monsanto Company, St. Louis 66, Missouri.
  2. A. J. Speziale and L. R. Smith, J. Org. Chem., 27, 3742 (1962); 28, 1805 (1963).
  3. O. C. Billeter, Ber., 36, 3213 (1903).
  4. A. J. Hill and W. M. Degnan, J. Am. Chem. Soc., 62, 1595 (1940).
  5. L. R. Smith, A. J. Speziale, and J. E. Fedder, J. Org. Chem., 34, 633 (1969).

Chemical Abstracts Nomenclature (Collective Index Number);
(Registry Number)

Isocyanic acid, anhydride with chloroacetic acid

hydrogen chloride (7647-01-0)

ethylene dichloride (107-06-2)

α-chloroacetamide (79-07-2)

oxalyl chloride (79-37-8)

α-Chloroacetyl isocyanate (4461-30-7)

silver cyanate (3315-16-0)

dichloroacetyl isocyanate

trichloroacetyl isocyanate

phenylacetyl isocyanate

diphenylacetyl isocyanate

benzoyl isocyanate