N-(3-Amino-4-methylphenyl)benzamide (1) is a crucial building blocks of many drug candidates. In this paper, a continuous flow microreactor system was developed to synthesize 1 and determine intrinsic reaction kinetics parameters. By screening the acylating reagents and reaction conditions, 1 was obtained by the selective acylation of 4-methylbenzene-1,3-diamine (2) with benzoic anhydride (3). Since the two amine groups in 2 are in different chemical environments, parallel by-products and serial by-products coexist, which makes the selective monoacylation process relatively complicated. To reveal the reaction process clearly, reaction rate constants and their 95% confidence intervals, activation energies, pre-exponential factors were acquired by kinetics study in microflow system. The established kinetic model can calculate the selectivity and conversion of the acylation reaction, which are in good agreement with the experimental results. Subsequently, the kinetic model was used to optimize reaction conditions, as a result, 1 was synthesized in the microreactor with a yield of 85.7% within 10 min.

N- (3-Amino-4-methylphenyl)benzamide ( 1 ) 是许多候选药物的关键组成部分。在本文中，开发了一种连续流动微反应器系统来合成1并确定本征反应动力学参数。通过筛选酰化试剂和反应条件， 4-甲基苯-1,3-二胺( 2 )与苯甲酸酐( 3 )选择性酰化得到1。由于2中的两个胺基在不同的化学环境中，平行副产物和串联副产物并存，使得选择性单酰化过程相对复杂。为了清楚地揭示反应过程，通过微流系统的动力学研究，获得了反应速率常数及其95%置信区间、活化能、指前因子。建立的动力学模型可以计算出酰化反应的选择性和转化率，与实验结果吻合较好。随后，利用动力学模型对反应条件进行优化，结果在微反应器中合成了1，10 min内收率为85.7%。