Green MW/US‐Assisted Construction of Pyrano[2,3‐b]pyridines and Pyrazolo[3,4‐d]pyrimidinones: Pathway Control and Antibacterial Evaluation

ABSTRACT

A green, activation‐controlled route was examined for the preparation of biologically relevant fused N/O heterocycles, with particular emphasis on whether the mode of energy delivery can redirect the reaction pathway. A single hydrazine‐derived precursor was treated with acetic anhydride under the same nominal temperature and reaction time while applying ultrasound (US), microwave (MW), or combined MW/US activation. The three modes led selectively to different annulated products: pyrazolo[3,4‐d]pyrimidinone 5 was isolated in 88% yield under US, oxazinyl–pyrazolidinone 6 in 85% yield under MW, and the more extensively fused derivative 7 in 85% yield under combined MW/US conditions. These results indicate that pathway selection can be influenced by the physical manner in which energy is supplied without altering the reagent set. The products were assigned from FT‐IR, NMR, EI–MS, and elemental‐analysis data and were screened against representative Gram‐positive and Gram‐negative bacteria. Compound 5 gave the best overall antibacterial response, including a 32.0 ± 0.6 mm inhibition zone against Staphylococcus aureus and MIC values of ≤ 12.5 µg/mL. Its experimental performance was consistent with favorable docking contacts and stable molecular‐dynamics behavior, while DFT/Mulliken analysis provided a rationale for the reactive sites involved in annulation and dehydration.