Chloroacetyl isocyanate

Submitted by A John Sfeziale and Lowell R Smith 1 Checked b Leif A Hoffmann and V Boekelheide 

1 For larger-scale preparations mechanical stirring is recommended 

Moisture must be rigorously excluded from the reaction mixture and the product. 

The a-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. 

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Chloroacetic acid, reaction with salicyl-aldehyde, 46, 28 Chloroacetone, 46, 3 Chloroacetyl fluoride, 45, 6 o-Chloroacetyl isocyanate, 46,16 -Chloroaniline, reaction with carbon disulfide and aqueous ammonia,... 

Chlorine, positive , iodometric determination of, 48, 5 reaction with 2-butyne, 46, 34 a-Chloroacetamide, reaction with oxalyl chloride to give a-chloroacetyl isocyanate, 46, 16... 

During investigations of the synthesis of tetracycline ring A analogues, Moska-lyk and co-workers unexpectedly isolated 4(5//)-oxazolones 31 and 33 following reaction of 30 and 32 with sodium ethoxide then chloroacetyl isocyanate. Further reaction of 31 effected ring opening of the 4(5F/)-oxazolone to yield 34 (Scheme 6.11). 

The only preparation reported for a-chloroacetyl isocyanate is that described by the submitters.2... 

Chloroacetyl isocyanate can also be used in this case the initial product is an imide, from which the chloroacetyl group can be removed by NaOH in methanol or by zinc dust in methanol. 

Chloianil, 168,667,674 p-Chloianil, 168 Chloieal, 605 Chlorination, 23, 562 Chlorine, 101-102 Chlorine bromide, 102 Chloroacetaldehyde, 267 Chloroacetonitrile, 102-103 Chloroacetyl fluoride, 103 Chloroacetyl isocyanate, 634 Chloroacetylium hexafluorantimonate,... 

Alkyl isocyanates, like n-butyl isocyanate, do not react with different alkyl azides and aryl azides respectively. In contrast, aryl isocyanates 131 react with alkyl azides 130 like n-butyl azide or cyclohexyl azide to yield 1-alkyl-4-aryl-A -tetrazoline-5-ones 132, however, aryl isocyanates do not react with aryl azides. The reactions take place within some hours and up to several days at elevated temperatures, ranging from 55 to 130 °C, and are performed in benzene or without solvent (Scheme 29A). The addition of aryl azides to acyl isocyanates, such as benzoyl isocyanate or carboalkoxy isocyanates like chloroacetyl isocyanate and trichloroacetyl isocyanate, was unsuccessfully attempted at different reaction conditions [107]. 

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