C-H键溴代的连续流反应过程强化及机理研究

Bromination reaction is one of the most important transformations in organic synthesis. The bromo-organics are mainly used as the important intermediates of pharmaceuticals, agro-chemicals, dyes, flame-retardants, extinguishing-chemicals and other fine chemicals, which are the hotspot of chemical workers. The traditional C-H bond monobromination reaction exist the some disadvantages, such as insufficient selectivity, unsafety, enviromental risks and unstability, especially the use of highly toxic substrates and reagents. Continuous flow reaction technology provides a good choice for solving these problems. We design a suitable photochemical microreactor for C-H bond bromination reaction. Then, we study the kinetics reaction model, the high selectivity monobromination reaction at the position of benzyl, carbonyl and allylic by effective control. Finally, the intermediates of pharmaceuticals and a series of potentially pharmacologically active brominated compounds were prepared by this process. The implementation of this project will reveal the mechanism of continuous flow C-H bond bromination reaction, solve effectively the problems of the traditional bromination reaction, and enrich the study of green bromination technology. This project have the important theoretical study value and widely application prospect.

C-H键溴代反应作为有机合成中的一类重要反应，被广泛应用于医药、农用化学品、染料、阻燃剂、灭火剂等重要精细化学品的合成，一直为合成化学工作者关注的热点。项目针对传统C-H键单溴代反应存在的选择性差、安全环保隐患大、稳定性差、副产物多而且使用高毒性物料等不足，创新性地采用连续流过程强化反应技术，设计适合的C-H键溴代反应的微通道光化反应器，构建反应动力学模型，实现苄位、羰基α位以及烯丙位上烷基C-H键的高选择性单溴代反应的有效调控，进而合成单溴代医化重要中间体及系列潜在的具有药理活性的溴代化合物。本项目的实施，将揭示C-H键溴代连续流管式反应机理，有效解决传统的溴代反应存在的问题，进一步丰富和拓展绿色溴代技术的研究，具有重要的理论研究价值和应用前景。

项目针对传统C-H键单溴代反应存在的选择性差、安全环保隐患大、稳定性差、副产物多而且使用高毒性物料等不足，设计了适合的C-H键溴代反应的微通道光化反应器，构建了反应动力学模型。采用连续流过程强化反应技术，确定各个阶段的反应动力学方程，实现苄位、烯丙位上烷基等C-H键的高选择性反应的有效调控，并实现多个关键医化中间体的应用拓展，如邻硝基苄溴、甲苯溴化、4-溴代巴豆酸衍生物、2-溴丁酸乙酯、洛索洛芬中间体的制备，有效解决了传统的溴代反应存在的问题，丰富和拓展了绿色溴代反应技术的研究，具有重要的理论研究价值和应用前景。项目完成了国家基金所要求的研究内容和任务，达到预期目标。