Optimization of Ultrasonic-Assisted Claisen–Schmidt Condensation in Chalcone Synthesis and Its Antioxidant Evaluation

Chalcone (1,3-diphenyl-2-propen-1-one), an important precursor of flavonoids, has attracted considerable interest because of its broad biological potential. This study evaluated the ultrasonic-assisted Claisen–Schmidt condensation of equimolar acetophenone and benzaldehyde (0.04 mol each) using sodium hydroxide as the catalyst. The effects of reaction temperature (30, 40, and 50 °C) and sonication time (10, 20, and 30 min) on product yield were investigated with a 20 kHz ultrasonic bath. The synthesized products were characterized by thin-layer chromatography, melting point determination, FT-IR, UV–Vis, LC–MS/MS, and NMR analyses. Sonication time exerted a greater influence on yield than temperature, with the highest crude yield (91.00%) obtained at 30 °C after 30 min. Spectroscopic analyses confirmed chalcone as the major product; however, the elevated melting point (186.1–186.7 °C), together with TLC and LC–MS/MS results, indicated the presence of co-eluting impurities, suggesting incomplete product purity. Antioxidant activity measured by the DPPH assay produced IC₅₀ values ranging from 75.93 to 191.39 µg/mL, with the strongest activity observed under the optimum synthesis condition (30 °C, 30 min), compared with 5.97 µg/mL for ascorbic acid. Considering the weak intrinsic radical-scavenging activity of pure chalcone, the observed antioxidant effect is likely attributable to co-produced impurities rather than chalcone itself. Ultrasonic-assisted synthesis substantially reduced reaction time while achieving a high crude yield. However, further optimization of purification is required to obtain pure chalcone and improve the overall sustainability of the process as a green synthetic approach.