Synthesis and methylation products of 4(5)-(2-furyl)imidazole

Abstract

There is very little information in the literature on 4(5)-furyl-substituted imidazoles, which is caused, in our opinion, by the difficult availability of furacyl bromide and the negative result of condensing it with formamide. We have developed a preparative method of obtaining furacyl bromide 2 selectively as a result of the reaction of 2-acetylfuran (1) with copper(II) bromide. This enabled the synthesis of 4(5)-(2-furyl)imidazole 4 by the Weidenhagen [1] method by the following scheme. O O Me O O Br O O OAc O N N H CuBr 2 EtOAc / CHCl 3 AcOK MeOH 1 2 3 4 (AcO) 2 Cu · H 2 O, CH 2 O NH 4 OH, 25%On methylating compound 4 with methyl iodide in , in difference to the previously studied alkylation of 2-(2-furyl)imidazole [3], the formation of isomers is possible as a result of the asymmetry of the imidazole anion.

Reaction of 5-(2-furyl)-1-methyl-1H- and 1-methyl-5-(2-thienyl)-1H-imidazoles with electrophilic reagents

“…5-(2-Furyl)-1-methyl-1H-imidazole (1) and 1-methyl-5-(2-thienyl)-1H-imidazole (2) were obtained by the method described in [2].…”

“…In order to confirm this conclusion, 5-(2-furyl)-1-methyl-1H-(1) and 1-methyl-5-(2-thienyl)-1H-imidazole (2) were investigated in reactions with electrophilic reagents: acetyl nitrate, bromine in dichloroethane, sulfuric acid, urotropine and acetic or benzoic acids in PPA, formalin in an acidic medium, and the Vilsmeier reagent.…”

“…In the light of the foregoing our attention was attracted to derivatives of 5-(2-furyl)-(1) and 5-(2-thienyl)imidazole (2). On account of the presence of the two pharmacophoric heterocyclic fragments these compounds can be expected to exhibit various types of biological activity.…”

“…Methods of synthesis and the products of the methylation of 4(5)-(2-furyl)imidazole were studied earlier [2]. Here it was possible to isolate the corresponding 5-(2-furyl)-1-methylimidazole (1) and, later, 1-methyl-5-(2-thienyl)imidazole (2) in chromatographically pure form.…”

“…Here it was possible to isolate the corresponding 5-(2-furyl)-1-methylimidazole (1) and, later, 1-methyl-5-(2-thienyl)imidazole (2) in chromatographically pure form.…”