Abstract:

A rapid and efficient synthesis of 3，4-dihydropyrimidin-2（1H）-（thio）ones was achieved under solvent-free conditions using choline chloride/trifluoromethanesulfonic acid （ChCl/TfOH） deep eutectic solvent as a catalyst. The condensation reaction of benzaldehyde， ethyl acetoacetate， and urea was used as a template reaction to investigate the effects of the type and amount of deep eutectic solvent， temperature， and starting material ratio on the reaction. Results showed that the optimized conditions were as follows： benzaldehyde （5 mmol）， ethyl acetoacetate （5 mmol）， urea （7.5 mmol）， ChCl/TfOH （2.5 mmol）， 80 ℃ and 5 min. The yield of the target product was as high as 95% under the optimized conditions. The reaction system also showed good compatibility with different substrates， with product yields ranging from 82% to 95%. In addition， gram-scale synthesis could be realized for this reaction， and the yield was up to 87% after 15 min. The advantages of this system are fast reaction speed， high yields， and no need for further purification of the products. Moreover， the recovery of deep eutectic solvent could be achieved through simple extraction.

Key words: Biginelli reaction, Dihydropyrimidin-2（1H）-（thio）one, Deep eutectic solvent, Green synthesis, Gram-scale synthesis