Dimethylformamide-mediated synthesis and characterization of novel pyrazole- and pyrimidine-based 3,4-dihydropyrimidine-2(1H)-thione derivatives

Abstract

Pyrimidine, an essential component of nucleic acid is currently reported for its potential application in Acquired Immune Deficiency Syndrome (AIDS) chemotherapy. Also, pyrazole nucleus, a versatile heterocyclic compound is gaining more attention in drug designs owing to its pharmacological therapeutic potentials. Hence, this present study deals with cost effective synthesis of 6-methyl-4-phenyl-5-(substituted-5-phenyl-4H-pyrazol-3-yl)-3,4-dihydropyrimidine-2(1H)-thione derivatives which are concisely known as pyrazole-based pyrimidine scaffolds. The multicomponent reaction of benzaldehyde, acetyl acetone and thiourea in the presence of catalytic amount of hydrochloric acid (HCl)ab initio produced 5-aceto-4-phenyl-2-thioxo-1,2,3,4-tetrahydropyrimidine, 1. Later, room temperature Claisen-Schmidt condensation of precursor 1 with diverse aromatic aldehydes which were benzaldehyde derivatives led to the formation of α,β-unsaturated carbonyl side chain, 2a-h. Finally, the thermal annellation through synthetic cyclization furnished crude products which were purified by recrystallization to afford 6-methyl-4-phenyl-5-(substituted-5-phenyl-4H-pyrazol-3-yl)-3,4-dihydropyrimidine-2(1H)-thione derivatives 3a-h in a cheap condition. The chemical structures were authenticated using IR, UV, 1H-NMR and 13C-NMR as well as analytical data. The final products 3a-h possessed good candidature for further investigation regarding their biological activities and pharmacological potential for new drug discovery.