Comparative study on Lewis acid catalyzed Biginelli reaction for the synthesis of 3,4-dihydropyrimidin-2(1H)-thione

Abstract

One-pot condensation reaction of an aromatic aldehyde, urea/thiourea and ethyl acetoacetate yielding 3,4-dihydropyrimidin-2(1H)-ones (DHPM) is known as the Biginelli reaction or Biginelli condensation. The corresponding thione derivatives are also of much interest for high biological activity. However, there are few examples of Lewis acid catalyzed synthesis of thiones in methodological research, and the product yields are relatively low. In order to explore the reasons for the differences in activity of different types of catalysts for the synthesis of 3,4-dihydropyrimidin-2(1H)-thiones, we chose CuCl2·2H2O, CoCl2·6H2O, NiCl2·6H2O and TsOH(p-Toluenesulfonic acid) for comparative study. Experimental results show that NiCl2·6H2O has the best yield of 50.3 % higher than 6.2 % and 0.7 % of CuCl2·2H2O and CoCl2·6H2O, respectively. The reason for the decrease in catalytic activity may be due to the increased coordination strength between the catalyst and the sulfur atoms in thiourea.