Synthesis of 4,5-disubstituted imidazoles

Abstract

Introduction of a triphenylmethyl group on the nitrogen of imidazole-4,5-dicarboxylic acid esters or 4,5-dihydroxymethylimidazole resulted in deactivation of the functional group adjacent to the protecting group and allowed reactions to take place preferably or exclusively on the other functional group. Thus, dimethyl 1-triphenylmethylimidazole-4,5-dicarboxylate (2), on treatment with hydrazine and methylamine produced methyl 4-hydrazinocarbonyl-1-triphenylmethylimidazole-5-carboxylate (3a) and methyl 4-methylaminocarbonyl-1-triphenylmethylimidazole-5-carboxylate (3b), respectively. Reduction of 2 with lithium borohydride gave methyl 4-hydroxymethyl-1-triphenylmethylimidazole-5-carboxylate (4a). Treatment of 4,5-dihydroxymethyl-1-triphenylmethylimidazole (5a), with trimethylacetyl chloride and with acetic anhydride afforded 5-hydroxymethyl-4-trimethylacetoxymethyl-1-triphenylmethylimidazole (6a), and 4-acetoxymethyl-5-hydroxymethyl-1-triphenylmethylimidazole (6c), respectively. Oxidation of 5a with activated manganese dioxide produced the monoaldehydes 9 and 10 in a ratio of 11:1. A new mild process for deprotection of N-triphenylmethylimidazoles, compatible with acid sensitive groups in the molecule, is reported. The synthesis of several 4,5-disubstituted imidazoles is also described.