Preparation of α-Bromoacetophenone via N-Bromosuccinimide-Mediated Bromination

α-Bromoacetophenone is a crucial organic synthetic intermediate with broad applications across multiple domains, particularly in the development of optoelectronic materials and pharmaceutical synthesis. Therefore, developing efficient synthetic methods for α-bromoacetophenone is of great significance. This study presents a systematic optimization of the α-bromination of acetophenone using N-bromosuccinimide (NBS), with the primary objective of maximizing selectivity toward the monobrominated product (α-bromoaceto­phenone) while minimizing dibrominated byproduct formation. Through a comprehensive evaluation of key reaction parameters, including solvent, reaction time, reactant ratio, and catalyst, we identified the following optimal conditions: dichloromethane (DCM) as the solvent, a 1:1 molar ratio of acetophenone to NBS, and a catalytic amount of p-toluenesulfonic acid (TsOH) at 25°C for 8 h. Under these conditions, the desired α-bromoacetophenone was obtained in 92.8% yield with the dibrominated byproduct suppressed to 3.7%, demonstrating high efficiency and selectivity. Mechanistic studies indicated that acetophenone undergoes enol tautomerization under acidic conditions, facilitating electrophilic bromination by NBS. The choice of catalyst, reaction time, and NBS stoichiometry were critical for suppressing over-bromination. This method offers simplicity, high selectivity, and environmental friendliness, providing a practical strategy for the synthesis of α-bromoaromatic ketones and optimization of analogous bromination processes.