Continuous synthesis of 4-bromo-3-methylanisole in modular microreaction system

With the development of microreaction technology and the key issues of liquid-liquid batch bromination process for the synthesis of 4-bromo-3-methylanisole, a modular microreaction system was constructed by taking microreactor and microbead-packed bed as the major functional microdevice units to intensify the bromination of methylanisole. And in this modular microreaction system, the liquid-liquid heterogeneous continuous bromination of 4-bromo-3-methylanisole was studied. The following optimized conditions were obtained, concentration of Br₂ (x_Br2): 17.5 wt%, molar ratio of Br₂ to methylanisole (n_Br2/n_M): 1.01, initial reaction temperature (T): 0℃, residence time (τ): 0.78 min, with yield of 4-bromo-3-methylanisole more than 98%, and percentage of polybrominated side product less than 1%. Comparing with the conventional batch process, the continuous microreaction technology has obvious advantages. For example, it can change the traditional batch process to a continuous one with a significant increase of productivity (space time yield: 6.5×10⁴ kg/(m³·h)). Besides, since this process is mainly controlled by mass transfer, the modular microreaction system with excellent mass transfer could reduce 50% of polybrominated side product. The study might provide a good foundation for the continuously controllable synthesis of 4-bromo-3-methylanisole in safety.