HYDROXYMETHYLATION AND CYANOETHYLATION OF NITROIMIDAZOLES

A series of nitroimidazoles were subjected to hydroxymethylations under a variety of conditions. Hydroxymethylation of 1‐(2‐hydroxyethyl), 1‐(2‐acetoxyethyl), and 1‐(2‐chloroethyl) substituted 5‐nitroimidazoles with paraformaldehyde in dimethyl sulfoxide yielded the respective 2‐hydroxymethyl analogs (5–7). However, attempts to hydroxymethylate 1‐(2‐hydroxyethyl), 1‐(2‐acetoxyethyl), 1‐(2‐cyanoethyl) substituted 4‐nitroimidazoles and 1‐(2‐hydroxyethyl)‐2‐nitroimidazole were unsuccessful. Treatment of 1‐(2‐acetoxyethyl)‐5‐nitro‐2‐imidazolecar‐baldehyde(10) with hydroxylamine‐O‐sulfonic acid afforded a mixture of corresponding 2‐carbonitrile (12) and 2‐(N‐hydroxy)carboximidamide (13). Hydrolysis of 10 with ethanolic hydrochloric acid yielded 8‐ethoxy‐5,6‐dihydro‐3‐nitro‐8H‐imidazo[2,1‐c] [1,4]oxazine (11) which, on subsequent reaction with hydroxylamine‐O‐sulfonic acid, afforded 1‐(2‐hydroxyethyl)‐5‐nitroimidazole‐2‐(N‐hydroxy)carboximidamide (15). Reaction of 4(5)‐nitroimidazole with chloropropionitrile produced a mixture of the isomeric 1‐(2‐cyanoethyl) substituted 4‐ and 5‐nitroimidazoles. Treatment of 2,4(5)‐dinitroímidazole with chloropropionitrile afforded a mixture of 4(5)‐chloro‐5(4)‐nitroimidazole and 1‐(2‐cyanoethyl)‐4‐nitro‐5‐chloroimidazoIe. Reaction of nitroimidazoles with acrylonitrile in the presence of Triton B yielded the corresponding 1‐(2‐cyanoethyl) substituted derivatives. Copyright © 1979 Journal of Heterocyclic Chemistry