流动化学在卤化反应中的应用

doi:10.6023/cjoc202007051

有机化学 ›› 2021, Vol. 41 ›› Issue (3): 1002-1011.DOI: 10.6023/cjoc202007051 上一篇下一篇

综述与进展

流动化学在卤化反应中的应用

刘玎^a^,^b, 朱园园^c, 古双喜^a^,^b^,^*(), 陈芬儿^a^,^b^,^d^,^*()

a 武汉工程大学化工与制药学院绿色化工过程教育部重点实验室武汉 430205
b 武汉工程大学药物研究院武汉 430205
c 武汉工程大学化学与环境工程学院武汉 430205
d 复旦大学化学系上海 200433

收稿日期:2020-07-22 修回日期:2020-09-14 发布日期:2020-10-12
通讯作者: 古双喜, 陈芬儿
基金资助:
国家自然科学基金(21877087); 国家自然科学基金(21602164); 新型反应器与绿色化学工艺湖北省重点实验室(武汉工程大学)开放基金(K202004)

Application of Flow Chemistry in Halogenation

Ding Liu^a^,^b, Yuanyuan Zhu^c, Shuangxi Gu^a^,^b^,^*(), Fener Chen^a^,^b^,^d^,^*()

a Key Laboratory for Green Chemical Process of Ministry of Education, School of Chemical Engineering and Pharmacy,Wuhan Institute of Technology, Wuhan 430205
b Pharmaceutical Research Institute, Wuhan Institute of Technology, Wuhan 430205
c School of Chemistry and Environmental Engineering, Wuhan Institute of Technology, Wuhan 430205
d Department of Chemistry, Fudan University, Shanghai 200433

Received:2020-07-22 Revised:2020-09-14 Published:2020-10-12
Contact: Shuangxi Gu, Fener Chen
About author:
* Corresponding authors. E-mail: shuangxigu@163.com;
rfchen@fudan.edu.cn
Supported by:
National Natural Science Foundation of China(21877087); National Natural Science Foundation of China(21602164); Open Fund of Hubei Key Laboratory of Novel Reactor and Green Chemical Technology (Wuhan Institute of Technology)(K202004)

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摘要/Abstract

有机物的卤化反应是有机合成中最重要的转化之一. 传统釜式卤化反应存在高放热及选择性差等问题, 且卤化试剂一般具有毒性和腐蚀性. 流动化学在传质和传热方面具有显著优势, 可精确控制反应温度及试剂用量, 并且可在线淬灭危险试剂, 避免其暴露. 按有机化合物卤化反应分类, 系统地归纳了流动化学在氟化反应、氯化反应、溴化反应和碘化反应中的应用进展, 并展望了其发展趋势.

关键词: 流动化学, 微反应器, 连续流, 卤化, 有机合成

The halogenation of organic compounds is one of the most important transformations in organic synthesis. However, there are some problems in traditional batch halogenation, such as high exothermicity, poor selectivity and the use of highly toxic and corrosive halogenating agents. Flow chemistry has its unique advantages such as high mixing efficiency, fast heat and mass transfer performance, accurate control over process parameters and enhanced process safety, reduced energy input and so on. According to the classification of halogenation of organic compounds, the main progress of flow chemistry in fluorination, chlorination, bromination and iodization is summarized systematically, and its development trend is prospected.

Key words: flow chemistry, microreactor, continuous flow, halogenation, organic synthesis

引用此文

刘玎, 朱园园, 古双喜, 陈芬儿. 流动化学在卤化反应中的应用[J]. 有机化学, 2021, 41(3): 1002-1011.

Ding Liu, Yuanyuan Zhu, Shuangxi Gu, Fener Chen. Application of Flow Chemistry in Halogenation[J]. Chinese Journal of Organic Chemistry, 2021, 41(3): 1002-1011.

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图/表 19

图式1. β-二羰基化合物的氟化

Scheme 1. Fluorination of β-dicarbonyl compounds

图式2. 4-甲氧基硝基苯的氟化

Scheme 2. Fluorination of 4-methoxynitrobenzene

图式3. 苯甲醛衍生物的氟化

Scheme 3. Fluorination of benzaldehyde derivatives

图式4. 在连续流微反应器中使用DAST氟化剂

Scheme 4. Use of DAST in continuous flow reactors

图式5. 取代苯基锂的连续流氟化

Scheme 5. Continuous flow fluorination of substituted phenyl lithium

图式6. 硅烷的连续流氯化

Scheme 6. Continuous flow chlorination of silane

图式7. 以丙烯酸为原料合成3-氯-N-苄基丙酰胺

Scheme 7. Synthesis of 3-chloro-N-benzyl-propanamide from acrylic acid

图式8. 使用HCl气体将醇转化为氯化物

Scheme 8. Conversion of alcohols to chlorides using HCl gas

图式9. 利用原位生成的Cl2对烃类进行光化学氯化

Scheme 9. Photochemical chlorination of hydrocarbons using in situ generated Cl2

图式10. 硫酰氯微流氯化环烷烃

Scheme 10. Microflow chlorination of cycloalkanes with sulfuryl chloride

图式11. 噻吩的溴化反应

Scheme 11. Bromination reaction of thiophene

图式12. 原位生成KOBr溴化甲基砜和甲基磺酸盐

Scheme 12. In situ generation of KOBr for bromination of methylsulfones and methanesulfonates

图式13. 烷烃和烯烃的溴化反应

Scheme 13. Bromination of alkanes and alkylarenes

图式14. 1,2,4-三氟苯的溴化反应

Scheme 14. Bromination reaction of 1,2,4-trifluorobenzene

图式15. NBS溴化烯胺酮

Scheme 15. Bromination of enamine bromide using NBS

图式16. 5-甲基嘧啶的溴化反应

Scheme 16. Bromination of 5-methylpyrimidine

图式17. 连续流微反应器中1,3-二甲基苯的选择性单碘化

Scheme 17. Selective monoiodination of 1,3-dimethoxybenene in continuous flow microreactor

图式18. 吲哚的连续流碘代反应

Scheme 18. Continuous flow iodination of indoles

图式19. 用ICl对有机化合物进行碘化

Scheme 19. Iodination of organic compounds using ICl

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流动化学在卤化反应中的应用

Application of Flow Chemistry in Halogenation

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