The Hantzsch thiazole synthesis under acidic conditions: change of regioselectivity

The condensation of α-halogeno ketones with N-monosubstituted thioureas in neutral solvent leads exclusively to 2-(N-substituted amino)thiazoles. In the present work it was shown that under acidic conditions mixtures of 2-(N-substituted amino)thiazoles and 3-substituted 2-imino-2,3-dihydrothiazoles are formed. (The isomers were distinguished by characteristic differences between their 5-H 1H n.m.r. signals and the i.r. CO bands of their trifluoroacetate derivatives.) The proportions of the 2-imino-2,3-dihydrothiazoles in the mixtures are influenced by experimental features and by the structures of the starting materials. Reactions in 10M-HCl-EtOH (1 :2) at 80 °C for 20 min were found to be the most efficient for generating 2-imino-2,3-dihydrothiazoles; in the most favourable case 2-imino-3,4-dimethyl-2,3-dihydrothiazole was obtained in 73% yield.A possible explanation of the results is discussed.