Nitroimidazoles: Part XI. Some Halonitro- & dinitroimidazoles

Abstract

Methylation of 2-chloro-4-nitroimidazole (6), obtained from imidazole in four steps, either with dimethyl sulphate or with diazomethane affords a mixture of 2-chloro-l-methyl-5-nitroimidazole (10) and the 4-nitro-isomer (7). The corresponding dinitro compounds 11 and 8 are formed in the methylation of 2,4-dinitroimidazole (5), 8 being converted to 7 by the action of POCl₃. Reaction of 10 with the sodium salt of N-methanesulphonyl-2-imidazolidinone provides the potent amoebicide, 1-methylsulphonyl-3-(1-methyl-5-nitroimidazol-2-yl)-2-imidazolidinone (2). The isomer 14 is synthesised from 7 in low yield. Ethylation of 5 leads to preponderant N-alkylation, providing a mixture of l-ethyldinitroimidazoles (9) and (12), but a small amount of N,C-diethyl derivative 15 is also obtained. The formation of 15 from 5 is rationalised. The diiodination product of imidazole is shown to be 4,5-diiodoimidazole (19), nitric acid transforming it to 4-iodo-5-nitroimidazole (20). Methylation of 20 affords a mixture of isomeric 1 -methyliodonitro derivatives (21) and (22). The structures of 21 and 22 are established by ¹³C NMR data as well as by conversion into morpholine derivatives 26 and 24 respectively which also arise from 1-methylchloronitroimidazoles (25) and (23). A mechanism is proposed for the reported conversion of 5 into 4-chloro-5-nitroimidazole (32) in boiling 2-chloroethanol.