Nitroimidazoles: Part XV. 1-Methyl-5-nitro-2-oxy(mercapto)imidazoles, 1-methyl-5-nitroimidazole-2- methanol (carboxaldehyde & glyoxalic ester) derivatives & 1-substitutedalkyl 2-methyl-5 & 4-nitroimidazoles

Abstract

Treatment of l-methyl-2-methylsulphonyl-5-nitroimidazole(2) with p-hydroxybenzaldehyde gives the aldehyde (3a) which is derivatised further to 3b-d. Displacement reactions on 2 with other phenols affords 4a-c. 1-Methyl-2-mercaptoimidazole (5a) is condensed with reactive halides to form sulphides 5b-e which are nitrated further to lead to nitroimidazoles 6a-d among which 6a and 6d undergo oxidation to form sulphone(7n) and sulphoxide(8) respectively; some nitroimidazolyl sulphides(6e-h) are also prepared from 2 by displacement with thiophenbl salts. 6f is further oxidised to 7b. l-Methyl-5-nitroimidazole-2-methanol (9a) is converted into sulphate esters (9b and 9c), chloride (9d), urethanes (lOa-e) and amines (lla-c). l-Methyl-5-nitroimidazole-2-aidehyde(12a) is characterised as the hydrazones(12b-f) and the vinyl derivatives (I3a-f) and (14). Reactions of l-methyl-5-nitroimidazole(15) withethoxalyl and oxalyl chlorides yield 16a and 19 respectively. 16a is further reacted with aminoguanidine to yield 18. Metronidazole (22a) is transformed into the urethane (22b) and via the chloride (22c) into the bases (22d-g). Ornidazole (23a) likewise affords the amines (23b and c) while the isomer 24a yields 24b-g. Alkylation of the sodium salts of 4-nitro and 4-nitro-2-methylimidazole with 3-chloro-4-hydroxysulpholane (25).provides the 4-nitro derivatives (26a) and (26b). Reaction of 2-bromo-l-indanol with 2-methyl-4-nitroimidazoledoes not provide 28, but 30, for Which a mechanism is proposed.