Catalyst-free Biginelli-type synthesis of new functionalized 4,7-dihydropyrazolo[1,5-a]pyrimidines

Abstract

The Biginelli-type reaction of 5-amino-3-arylpyrazole-4-carbonitriles with aldehydes and 1,3-dicarbonyl compounds was studied in detail. We found that the reaction requires no catalysts and proceeds in boiling DMF to give 2-aryl-6-RC(O)-4,7-dihydropyrazolo[1,5-a]pyrimidin-3-carbonitriles in good yields. The reaction of aminopyrazoles with dicarbonyls leading to 6-unsubstituted pyrazolo[1,5-a]pyrimidines proceeds competitively and becomes the dominant process under acid-promoted conditions. 2-Aryl-8-oxo-4,5,6,7,8,9-hexahydropyrazolo[5,1-b]quinazolin-3-carbonitriles were obtained under catalyst-free conditions in up to 80% yields starting from 5-amino-3-arylpyrazole-4-carbonitriles, aldehydes and 1,3-cyclohexanedione.