Reaction of 2-aminothiazoles with reagents containing a C–halogen and a CO electrophilic centre

Abstract

Seven reagents of different types having in common a C–Hal and a CO electrophilic centre have been used in a study of their reactions with 2-aminothiazoles. Three reagents, CHBrAc₂ and ROCHBrCO₂Et (R = Me, Ph), gave imidazo[2,1-b]thiazoles, thus providing useful routes to the 5-acetyl and 5-ethoxycarbonyl derivatives. Unexpectedly, the solvent (acetone) was involved in the reaction of the fourth reagent, CHBr(CO₂Et)₂, with 2-aminothiazole which led to 5,5-di(ethoxy;carbonyl)-6,6-dimethyl-5,6-dihydroimidazo[2,1-b]thiazole (yield 81%). With the last three reagents (AcCHBrNO₂, BzCHBrCN and ICH₂CO₂C₆H₄NO₂-p) the outcome was simpler, viz., the formation of 2-amidothiazoles.

It is proposed that electrophilic attack by the endo-N of the 2-aminothiazole is the first step in all cases. This occurs at the C–Hal centre of the first four reagents and is followed by cyclisation to the exo-N. In the last three electrophiles the presence of groups well suited to leaving as stabilised anions favours addition to the CO group; the intermediates so formed subsequently isomerise to the more stable exo-N substituted products.