雌三醇关键中间体的连续化合成  

Continuous Synthesis of Key Intermediates of Estriol

作　　者：周英雷 朱祉翡 蒋佳明 艾文 费婷虹[1] 徐伟明[1] ZHOU Yinglei;ZHU Zhifei;JIANG Jiaming;AI Wen;FEI Tinghong;XU Weiming(College of Material Chemistry and Chemical Engineering,Hangzhou Normal University,Hangzhou,Zhejiang 311121,China;Zhejiang Gongtonggongxin Medical Technology Co.,Ltd,Hangzhou,Zhejiang 310014,China)

机构地区：[1]杭州师范大学材料与化工学院,浙江杭州311121 [2]浙江共同共新医药科技有限公司,浙江杭州310014

出　　处：《浙江化工》2023年第11期20-25,共6页Zhejiang Chemical Industry

基　　金：杭州市科研项目(20201203B137、20211231Y089)。

摘　　要：氧化反应速度快、放热量大,传统釜式工艺存在传质传热效率低、安全性低、生产效率低等缺点。本文以冰醋酸、浓硫酸、双氧水、乙酸钠为起始物料,通过连续化技术在线制备过氧乙酸,接着与双酯物I进行环氧化反应制备雌三醇的关键中间体环氧物II(3,17β-二乙酰氧基-16α,17α-环氧基-雌甾-1,3,5(10)-三烯),进一步考察了物料配比、反应温度、停留时间对氧化反应的影响。实验结果显示,双酯物I、乙酸钠、双氧水、浓硫酸、冰醋酸的摩尔比约为2:2:12:1:9,过氧乙酸制备温度为60℃,环氧化反应温度为50℃,反应停留时间为75 s为最优反应条件。本工艺利用连续化技术避免了过氧乙酸储存带来的安全隐患,并且大幅缩短了反应时间,过氧化、氧化反应得到有效控制,实现了工艺的本质安全。The oxidation reaction speed is fast and the heat release is large.Traditional kettle process has disadvantages such as low mass and heat transfer efficiency,low safety,and low production efficiency.The article uses glacial acetic acid,concentrated sulfuric acid,hydrogen peroxide,and sodium acetate as systems to prepare peroxyacetic acid,and immediately undergoes epoxidation reaction with diester I to prepare the key intermediate of estriol(epoxy II,3,17β-diacetoxy-16α,17α-epoxy-estro-1,3,5(10)-triene(epoxy)).The effects of material ratio,reaction temperature,and residence time on the oxidation reaction were investigated.The experimental results showed that the molar ratio of diesters:sodium acetate:hydrogen peroxide:concentrated sulfuric acid:glacial acetic acid was about 2:2:12:1:9,and the preparation temperature of peracetic acid was 60℃,the epoxidation reaction temperature was 50℃,and the residence time was 75 seconds.The reaction conversion rate was optimal.This process utilizes continuous technology to avoid safety hazards caused by the storage of peroxyacetic acid,greatly reducing reaction time,achieving effective control of peroxidation and oxidation reactions,and achieving the intrinsic safety of the process.

关 键 词：过氧乙酸 连续化反应 雌三醇 3 17β-二乙酰氧基-16α 17α-环氧基-雌甾-1 3 5(10)-三烯 过氧化 安全性 

分 类 号：TQ467.92[化学工程—制药化工]