Nitroimidazoles: Part VI. N-(1-Alkyl-5-nitroimidazol-2-yl)-heteroarenes

Abstract

Condensation of 1-methyl-2-methylsulphonyl-5-nitroimidazole (2) with imidazole affords the corresponding 2-(N-imidazolyl)derivative (7a) with good antiprotozoal activity. Analogous imidazoles (7b-k), pyrrole (5), indole (6), benzimidazole (10), its tetrahydro derivative (11), pyrazoles (12a-d), indazoles (17a and b), triazole (19), benzotriazole (21a and b) and tetrazole (22) are prepared similarly. Condensation of 2 with 2, 5-dimethyi-4-nitropyrazole affords the expected 12f, which partly undergoes reaction with another molecule of 2 to yield 14. Sulphone (2) and 3-methyl-5-pyrazolinone combine to form the O-alkyl derivative (16a), characterised further as the acetyl derivative (16b). ¹³C as well as 1H NMR spectra and solvent-induced shifts are used to assign unique structures, when two or more alternatives are possible, e.g. 7g, 7h, 12d, 16a and 19. The synthesis of l-n-butyl-(9a) and l-(2-methoxyethyl)-(9b) analogues of 7a is also described. 25 and 26 are respectively thiazoiyl and pyridyl analogues of 7a, while 23a, 23b' and 24 are homologues.