Synthesis and characterization of novel 1,6-dihydropyrimidine derivatives for their pharmacological properties

ABSTRACT

The present research work involves the use of commercially available thiophene-2-carbaldehyde as a starting materialto construct novel pyrimidine compounds. Synthesis of pyrimidine derivatives has been done by the trimolecularBiginelli condensation reaction, which involves the use of thiophene-2-carbaldehyde with cyano ethylacetate andthiourea to yield 4-oxo-6-(thiophen-2-yl)-2-thioxo-1,2,3,4-tetrahydropyrimidine-5-carbonitrile (1). The intermediate 1was methylated using methyl iodide and K2CO3 in dimethylformamide (DMF) which afforded dimethylated derivative1-methyl-2-(methylthio)-6-oxo-4-(thiophen-2-yl)-1,6-dihydropyrimidine-5-carbonitrile (2). The intermediatecompound 2 when refluxed with hydrazine hydrate in ethanol as a solvent led to the formation of the parent compound2-hydrazineyl-1-methyl-6-oxo-4-(thiophen-2-yl)-1,6-dihydropyrimidine-5-carbonitrile (3), the parent compound 3was used for the synthesis of carboxamides of N′-(5-cyano-1-methyl-6-oxo-4-(thiophen-2-yl)-1,6-dihydropyrimidin2-yl)substituted benzohydrazide (4a–d) and Schiff bases of (E)-2-(2-substituted benzylidenehydrazineyl)-1-methyl6-oxo-4-(thiophen-2-yl)-1,6-dihydropyrimidine-5-carbonitrile (5a–g). Selected title compounds are screened forantibacterial, analgesic, and antifungal activities.