Alkylation of 2-methylimidazole with iodomethyl ketones of the aliphatic, aromatic, and heteroaromatic series

Abstract

A classical procedure for the synthesis of N-alkylimidazoles is based on the reaction of imidazole with alkyl halides under pressure at 100–150°C [8]. Reactions of imidazoles with alkyl halides, α-bromo(chloro) ketones, and chloroalkyl formates in the presence of bases or phase-transfer catalysts give both N-mono[2, 3, 9] and N,N-dialkylation products [10]. Alkylation of imidazole derivatives with α-iodo ketones in the absence of a base and catalyst has not been reported so far. There are grounds to believe that α-iodo ketones can be successfully used in the synthesis of diazolyl ketones in one preparative step due to high reactivity of the C–I bond therein. For this purpose, we examined the reactions of 2-methyl-1H-imidazole (I) with 1-iodopropan-2-one (IIa), 1-(biphenyl-4-yl)-2-iodoethanone (IIb), and 2-iodo-1-(2-thienyl)ethanone (IIc) in acetone at 40°C. These reactions led to the formation of mixtures of 2-methyl-1,3-bis(2-oxopropyl)-3H-imidazol-1-ium, 1,3-bis[2-(biphenyl-4-yl)-2-oxoethyl]-2-methyl-3Himidazol-1-ium, and 2-methyl-1,3-bis-[2-oxo-2-(2thienyl)ethyl]-3H-imidazol-1-ium iodides IIIa–IIIc with the corresponding triiodides IVa–IVc. The ratio of iodides III and triiodides IV is determined by the ability of iodo ketones IIa–IIc to undergo reduction with hydrogen iodide liberated as a result of first alkylation. Triiodide ion is formed via addition of iodide ion to molecular iodine arising from the reduction of ketones IIa–IIc with hydrogen iodide.