Method for synthesis of 2-amino-5-(2-thienylmethyl)thiazole

Abstract

α-Halo-substituted aldehydes are convenient reagents in synthesis of thiazole derivatives. However, the range of such aldehydes is limited, and so 5-substituted thiazoles are less accessible than thiazole derivatives containing substituents in the 4 position, which are obtained from α-halo ketones [1, 2]. We previously developed a method for synthesis of 2-amino-5-(R-benzyl)thiazoles from 3-aryl-2-chloropropionic aldehydes, obtained by reaction of arenediazonium chlorides with acrolein [3]. In this report, we propose a method for synthesis of thiazoles containing a 2-thienylmethyl group in the 5 position. We obtained 2-chloro-3-(2-thienyl) propanal (2) by reaction of (2-thienyl)mercury chloride 1 with acrolein in the presence of Li2PdCl4 and excess copper(II) chloride (a variant of the Heck reaction [4, 5]). Aldehyde 2, when reacted with thiourea, undergoes ring closure to form compound 3.