1,3,5-trimethyl-2-nitrobenzene is a valuable synthetic intermediate with essential applications in the dyes industry. Because of poor micro-mixing and the large consumption of waste acid using the traditional reactor, the content of impurity and the yield of 1,3,5-trimethyl-2-nitrobenzene are not stable. Therefore, a continuous kilogram-scale process for the synthesis strategy of 1,3,5-trimethyl-2-nitrobenzene in microreactor was reported in this paper. Two microreactors and three pumps quickly assemble the microflow system. Mesitylene was first mixed with nitric acid and then combined with sulfuric acid under-designed experimental parameters. The effects of process parameters in the three synthetic strategies, including an organic solvent, temperature, molar ratio, flow rate, and sulfuric acid content, were systemically investigated. Based on the results of process parameter optimization, the production of 1,3,5-trimethyl-2-nitrobenzene at the kilogram level was achieved in a microreactor with two microreactors in series. Compared with the traditional batch reactor, sulfuric acid consumption was decreased by 7.6 times, and the reaction time was reduced from 4h to 60s. Compared with the synthesis methods reported in the literature, the two-step synthesis method proposed in this paper has better advantages in terms of reaction time, product purity, and conversion rate. It provides a new synthetic strategy for the industrial production of aromatic compounds by nitration reaction.

1,3,5-三甲基-2-硝基苯是一种有价值的合成中间体，在染料工业中具有重要应用。传统反应器由于微混合不良，废酸消耗量大，导致1,3,5-三甲基-2-硝基苯的杂质含量和收率不稳定。因此，本文报道了1,3,5-三甲基-2-硝基苯在微反应器中的连续公斤级合成策略。两个微反应器和三个泵快速组装微流系统。均三甲苯首先与硝酸混合，然后在设计的实验参数下与硫酸混合。系统研究了三种合成策略中工艺参数的影响，包括有机溶剂、温度、摩尔比、流速和硫酸含量。根据工艺参数优化结果，在一个微反应器中，两个微反应器串联，实现了千克级1,3,5-三甲基-2-硝基苯的生产。与传统间歇式反应器相比，硫酸消耗量降低7.6倍，反应时间由4h缩短至60s。与文献报道的合成方法相比，本文提出的两步合成法在反应时间、产物纯度、转化率等方面具有更好的优势。为芳族化合物硝化反应的工业化生产提供了一种新的合成策略。与传统间歇式反应器相比，硫酸消耗量降低7.6倍，反应时间由4h缩短至60s。与文献报道的合成方法相比，本文提出的两步合成法在反应时间、产物纯度、转化率等方面具有更好的优势。为芳族化合物硝化反应的工业化生产提供了一种新的合成策略。与传统间歇式反应器相比，硫酸消耗量降低7.6倍，反应时间由4h缩短至60s。与文献报道的合成方法相比，本文提出的两步合成法在反应时间、产物纯度、转化率等方面具有更好的优势。为芳族化合物硝化反应的工业化生产提供了一种新的合成策略。