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.