The ultrasound accelerated solvent-free synthesis of ethyl 7-methyl-5-phenyl-5H-thiazolo[3,2-a]pyrimidine-6-carboxylate through Biginelli reaction catalyzed by Amberlyst-15

Abstract

Multi-component reactions (MCRs) played an important role to produce complex molecular structures in a one-step process. Among all MCRs reported, Biginelli reaction was one of the most well-known and used in organic synthesis to constitute pyrimidine scaffolds. Therefore, a solvent-free Biginelli reaction of 2-aminothiazole, benzaldehyde and ethyl acetoacetate catalyzed by Amberlyst-15 (A-15) had attracted us to pay attention and to do research in order to highly obtain a desired product, a frame of thiazolo[3,2-a]pyrimidine being present in many active biological compounds. Amberlyst-15, polystyrene resin regarded as a green acidic solid, available commercial, inexpensive and reusable catalyst had been firstly and successfully developed for solvent-free Biginelli reaction under ultrasound irradiation to form thiazolo[3,2-a]pyrimidine. Most factors which had influenced on the reaction conversion and yield such as the molar ratios between 2-aminothiazole, benzaldehyde and ethyl acetoacetate, the amounts of catalyst A-15, and reaction time had been investigated. Consequently, the yield of ethyl 7-methyl-5-phenyl-5H-thiazolo[3,2-a]pyrimidine-6-carboxylate had been also found to depend on the amount of the acidic solid catalyst and little excess amounts of the two reactants, e.g. 2-aminothiazole and ethyl acetoacetate. The maximum yield has been obtained 76% after six-hour ultrasound irradiation at 80oC with the molar ratio of 2-aminothiazole : benzaldehyde : ethyl acetoacetate (1.4:1.0:1.4) and 50 mg of catalyst A-15. The results showed that Amberlyst-15 had high capability of recovery and recycling owing to the inconsiderably changes of product yields after two recycle runs.