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

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.