Crystal Structure, Hirshfeld Surface Analysis, In-Silico and Antimycotic Investigations of Methyl 6-methyl-4-(4-nitrophenyl)-2-oxo-1,2-dihydropyrimidine-5-carboxylate

Herein, we report the preparation of methyl 6-methyl-4-(4-nitrophenyl)-2-oxo-1,2-dihydropyrimidine-5-carboxylate 2, obtained by the regioselective oxidative dehydrogenation of the dihydropyrimidine derivative 1 in the presence of cerium ammonium nitrate. The structure of compound 2 was investigated by single-crystal X-ray diffraction (SC-XRD), which allowed the determination of its tautomeric form. Moreover, the presence of non-covalent interactions and their impact on the crystal structure were analyzed. To better characterize the intermolecular contacts, the Hirshfeld surface and enrichment ratio analyses were performed. Furthermore, the antimycotic activity of compounds 1 and 2 was investigated against Candida albicans, Aspergillus flavus, and Aspergillus niger, and their efficacy was compared to that of fluconazole. Computational investigations on the putative target of the compounds provided insights to explain the better activity of 2 with respect to its synthetic precursor.

Automated summary

In this study, methyl 6-methyl-4-(4-nitrophenyl)-2-oxo-1,2-dihydropyrimidine-5-carboxylate 2 was prepared by the regioselective oxidative dehydrogenation of dihydropyrimidine derivative 1 in the presence of cerium ammonium nitrate. The tautomeric form of compound 2 was determined through single-crystal X-ray diffraction (SC-XRD). Non-covalent interactions and their impact on the crystal structure were analyzed using Hirshfeld surface and enrichment ratio analyses. Furthermore, the antimycotic activity of compounds 1 and 2 against Candida albicans, Aspergillus flavus, and Aspergillus niger was investigated and compared to fluconazole. Computational investigations provided insights into the better activity of compound 2 compared to its synthetic precursor.