通过1,3-二羰基化合物或类似物与取代肼合成依达拉奉建立了一种高效的两步流动连续合成工艺;对连续合成的反应温度、停留时间、溶剂用量、环化用碱量等影响产品品质和收率的因素进行优化,确定工业化连续合成依达拉奉最佳工艺条件。结果表明,两步连续法与一步间歇法相比反应所需时间缩短近93%,产品收率提高17%;连续工艺能有效降低生产成本,避免因原料暴露空气而导致产品颜色过深,获得的产品无需纯化、脱色、再结晶即可得到高质量的依达拉奉。

A two-step flow continuous synthesis process is developed for the synthesis of Edaravone from 1,3-dicarbonyl compounds or analogues and substituted hydrazine.The factors affecting the product quality and yield,such as reaction temperature,residence time,the dosages of solvent and cyclization alkali,are optimized.The optimal process conditions are determined for industrial continuous synthesis of Edaravone.It is found that compared with one-step intermittent method,the reaction time required by this two-step continuous method is shortened by nearly 93%,and the product yield is increased by 17%.Continuous process can effectively reduce the production cost and effectively avoid the product color being too dark due to the oxidation of raw materials exposed to air.High quality Edaravone can be obtained without needing purification,decolorization and recrystallization.

周闯(1999-),男,硕士生,研究方向为连续流化工工艺开发,2682644505@qq.com;严生虎(1972-),男,硕士,教授,研究方向为连续流化工工艺开发,通讯联系人,ysh@cczu.edu.cn。