连续微反应加氢技术在脱保护反应中的应用

doi:10.11949/0438-1157.20201299

化工学报 ›› 2021, Vol. 72 ›› Issue (2): 761-771.DOI: 10.11949/0438-1157.20201299

连续微反应加氢技术在脱保护反应中的应用

娄锋炎^1,^2,³(),尹佳滨²,段笑南²,王祁宁^1,³,艾宁^1,⁴,张吉松²()

^1.浙江省生物燃料利用技术研究重点实验室，浙江杭州 310014
^2.化学工程联合国家重点实验室，清华大学化学工程系，北京 100084
^3.浙江工业大学化学工程学院，浙江杭州 310014
^4.嘉兴学院生物与化学工程学院，浙江嘉兴 314001

收稿日期:2020-09-10 修回日期:2020-11-15 出版日期:2021-02-05 发布日期:2021-02-05
通讯作者: 张吉松
作者简介:娄锋炎（1996—），男，硕士研究生，1379170195@qq.com
基金资助:
国家自然科学基金项目(21978146)

Application of continuous micro-reaction hydrogenation technology in deprotection reaction

LOU Fengyan^1,^2,³(),YIN Jiabin²,DUAN Xiaonan²,WANG Qining^1,³,AI Ning^1,⁴,ZHANG Jisong²()

^1.Zhejiang Province Key Laboratory of Biomass Fuel, Hangzhou 310014, Zhejiang, China
^2.State Key Laboratory of Chemical Engineering, Department of Chemical Engineering, Tsinghua University, Beijing 100084, China
^3.School of Chemical Engineering, Zhejiang University of Technology, Hangzhou 310014, Zhejiang, China
^4.College of Biological, Chemical Science and Engineering, Jiaxing University, Jiaxing 314001, Zhejiang, China

Received:2020-09-10 Revised:2020-11-15 Online:2021-02-05 Published:2021-02-05
Contact: ZHANG Jisong

摘要/Abstract

摘要：

保护与脱保护是医药中间体等精细化工领域中较为常见的一种有机合成策略。常用的保护基主要有苄基与苄氧羰基，通常可利用催化加氢法将其脱除。采用高压加氢间歇釜工艺存在气液传质效率低，操作安全性差，氢解效率低等问题。采用连续微反应加氢技术进行非均相催化加氢脱保护，可以利用其较高的气液传质效率和平推流特性实现高选择性脱保护，并显著缩短反应时间。本文阐述了连续微反应加氢技术在脱保护反应中的优点及其在药物中间体合成中的实际应用，并介绍了催化剂与溶剂对脱保护反应的影响。最后对连续微反应加氢技术在脱保护中的应用进行了展望。

关键词: 连续流, 多相反应, 脱保护, 加氢, 微反应器

Abstract:

Protection and deprotection is a common organic synthesis strategy in fine chemical fields such as pharmaceutical intermediates. The commonly used protecting groups are benzyl and benzyloxycarbonyl, which can be removed by catalytic hydrogenation. The conventional high-pressure hydrogenation batch reactors have several drawbacks, such as low mass and heat transfer rate, poor operation safety and slow hydrogenolysis rate. The continuous hydrogenation for heterogeneous catalytic deprotection can achieve high selectivity and significantly shorten the reaction time due to the excellent gas-liquid mass transfer and plug flow characteristics. This paper summarizes the advantages of continuous flow hydrogenation technology in deprotection reaction and its applications in the synthesis of pharmaceutical intermediates, and discusses the effects of catalyst and solvent on the deprotection reaction. Finally, the application of continuous microreaction hydrogenation technology in deprotection is prospected.

Key words: continuous flow, multiphase reaction, deprotection, hydrogenation, microreactor

中图分类号:

TQ 032.4

娄锋炎, 尹佳滨, 段笑南, 王祁宁, 艾宁, 张吉松. 连续微反应加氢技术在脱保护反应中的应用[J]. 化工学报, 2021, 72(2): 761-771.

LOU Fengyan, YIN Jiabin, DUAN Xiaonan, WANG Qining, AI Ning, ZHANG Jisong. Application of continuous micro-reaction hydrogenation technology in deprotection reaction[J]. CIESC Journal, 2021, 72(2): 761-771.

图/表 9

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连续微反应加氢技术在脱保护反应中的应用

Application of continuous micro-reaction hydrogenation technology in deprotection reaction

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