Purines, pyrimidines, and imidazoles. Part 58. Synthesis and reactions of some imidazole-2,4-dicarboxylic acid derivatives

Abstract

Diethyl 5-amino-1-(p-methoxybenzyl)imidazole-2,4-dicarboxylate (3b) has been prepared from ethyl 2-amino-2-cyanoacetate and ethyl 1-ethoxycarbonyformimidate hydrochloride or ethyl triethoxyacetate followed by reaction with p-methoxybenzylamine. The diester, with one equivalent of dilute sodium hydroxide solution, furnished ethyl 5-amino-1-(p-methoxybenzyl)imidazole-4-carboxylate (7a). Diazotisation of the diester (3b) and reaction of the diazonium salt with copper(I) chloride produced diethyl 5-chloro-1-(p-methoxybenzyl)imidazole-2,4-dicarboxylate (9a) which, with dilute alkali, gave ethyl 5-chloro-1-(p-methoxybenzyl)imidazole-4-carboxylate (7b). Diazotisation of the diester (3b) in the presence of hypophosphorous acid gave diethyl-1-(p-methoxybenzyl)imidazole-2,4-carboxylate (9b) which, when hydrogenated over palladium–charcoal, produced diethyl imidazole-2,4-dicarboxylate (9c). This with bromine (chlorine) gave diethyl 5-bromo(chloro)imidazole-2,4-dicarboxylate (9d and e). The chloro derivative (9a) was similarly hydrogenated using palladium–charcoal to produce diethyl 5-chloro-imidazole-2,4-dicarboxylate (9e).