Synthesis, Spectral Characterization, and Biological Evaluation of Novel Isoxazoline-Based Heterocyclic Derivatives (AOX1–AOX15)

Abstract

Fifteen novel isoxazoline-based heterocyclic derivatives (AOX1–AOX15) were synthesized via a [3+2] cycloaddition reaction between substituted chalcones and nitrile oxide intermediates. The chalcone precursors incorporated both electron-withdrawing (–NO₂, –Br, –Cl) and electron-donating (–OH, –OCH₃) groups to evaluate the effect of substitution on reaction yields, spectral features, and physicochemical properties. The reactions proceeded in moderate to excellent yields (67–85%) to afford yellow to pale-yellow crystalline solids with melting points ranging from 168 °C to 220 °C. Structural confirmation was achieved through Fourier-transform infrared (FT-IR) spectroscopy, proton and carbon nuclear magnetic resonance (¹H and ¹³C NMR) spectroscopy, and elemental analysis. Diagnostic spectral features included a methine proton signal (δ 5.10–5.30 ppm) in ¹H NMR, methine carbon signals (δ 70–75 ppm) in ¹³C NMR, nitro group absorptions (1515–1535 cm⁻¹ and 1335–1365 cm⁻¹) in FT-IR, and elemental compositions consistent with theoretical calculations. Substituent effects were evident in chemical shift variations, IR absorption intensities, and thermal properties. The combination of diverse electronic substituents and the structural stability of these derivatives suggest potential for further antimicrobial and antibiofilm evaluations.