Microwave-assisted synthesis and biological evaluation of pyrazole-4-carbonitriles as antimicrobial agents

An efficient microwave-assisted method of synthesis of pyrazole-4-carbonitriles has been developed. Condensation of pyrazole-4-carbaldehydes with hydroxylamine hydrochloride followed by reaction of the resulting oximes with the Vilsmeier-Haack reagent pre-formed from phthaloyl dichloride and dimethylformamide under microwave irradiation afforded the corresponding pyrazole-4-carbonitriles in 73% to 91% yield. The operational simplicity, avoidance of toxic reagents such as POCl₃, shorter reaction time, higher yield compared to the classical version, easy work up, and the use of the by-product in the regeneration of phthaloyl dichloride are the advantages of this methodology. All the target compounds were tested for antimicrobial activity against Gram-positive bacteria Bacillus cereus and Staphylococcus aureus; Gram-negative bacteria Escherichia coli and Yersinia enterocolitica, and the fungal species Candida albicans.