Steric and Electronic Factors Influence Regio-isomeric Thiazole Formations Between Substituted Benzothioamides and Ethyl Bromopyruvate

We observed unexpected thiazole 1B formation when 2,6-dichlorobenzothioamide 1 and ethyl bromopyruvate were reacted under basic conditions at elevated temperatures in ethanol. Thiazole 1B, regio-isomeric to that expected under conventional Hantzsch conditions, was extensively characterized and later confirmed by single crystal X-ray structure. We carried out this transformation with several substituted benzothioamides and found that the formation of the unexpected thiazole regio-isomer was highly dependent on the steric as well as the electronic characteristics of the ortho-substituents on the phenyl ring. A mechanism to account for this novel transformation was proposed.