Synthesis, DFT, In Silico ADME, and Antimicrobial Study of New 2‐(aryl)‐5‐(3‐(difluoromethyl)‐1‐methyl‐1 <i>H</i> ‐pyrazol‐4‐yl)‐1,3,4‐Oxadiazoles

Abstract The rise of drug‐resistant infections highlights the critical need to discover novel drugs to combat them. In this study, we present the synthesis of a novel 2‐(aryl)‐5‐(3‐(difluoromethyl)‐1‐methyl‐1 H ‐pyrazol‐4‐yl)‐1,3,4‐oxadiazole compounds (3a–b) using benzohydrazide (1a–b) and 3‐(difluoromethyl)‐1‐methyl‐1 H ‐pyrazole‐4‐carboxylic acid (2) . The structures of compounds were confirmed by FT‐IR, 1 H‐NMR, 13 C‐NMR, and HRMS characterizations. DFT calculations were performed using B3LYP/6–311G(d,p) method. The HOMO‐LUMO energy gap, reactivity parameters, and Mulliken atomic charges were determined and discussed. The electrostatic potential surface was mapped to identify active sites in compounds. The electronic absorption spectra were obtained in a chloroform solvent, and the Uv‐vis band assignments were discussed through TD‐DFT simulations. The results obtained from the experiment correspond well with the theoretical DFT analysis. The assessment of synthesized compounds (3a–b) antimicrobial properties is another aspect of the current investigation. Compound 3a was equally efficient as chloramphenicol against E. coli , P. aeruginosa , and S. pyogenes . However, limited antifungal activity was observed for both compounds. The Molinspiration ADME online tool examines drugs likeness properties.