Abstract: This study presents an optimized synthesis protocol for benzocaine, modifying the conventional experimental procedures described in both Organic Chemistry and Medicinal Chemistry laboratory manuals. Building upon the traditional synthetic route, this experiment substitutes potassium permanganate as the oxidant with tetrabutylammonium bromide as a phase-transfer catalyst, enabling safer oxidation of p-nitrobenzoic acid under neutral conditions. The esterification catalyst is replaced by sodium bisulfate monohydrate coupled with ultrasonic irradiation to enhance ethyl p-nitrobenzoate synthesis efficiency. An ultrasonic assistance is finally applicated to improve yield in the acetic acid-iron powder reduction step. Comparative results demonstrate that the modified protocol achieves an 82.2% increase in overall yield, reduces total reaction time by 35.3%, utilizes fewer reagents, and simplifies post-processing compared to conventional methods. The experimental design consistently incorporates green chemistry principles while integrating multidisciplinary knowledge and techniques, thereby enhancing students’ professional competencies and offering substantial pedagogical value with potential for broader application.

Key words: Benzocaine, Synthesis experiment, Green chemistry, Ultrasonic-assisted synthesis, Phase-transfer catalysis