高价碘试剂参与酰胺的选择性二氟氯乙基化反应研究

doi:10.6023/cjoc202104007

有机化学 ›› 2021, Vol. 41 ›› Issue (9): 3660-3667.DOI: 10.6023/cjoc202104007 上一篇下一篇

研究论文

高价碘试剂参与酰胺的选择性二氟氯乙基化反应研究

颜廷勋^a^,^b, 陈超^b^,^c^,^*(), 文丽荣^a^,^*()

a 青岛科技大学化工与分子工程学院青岛 266042
b 清华大学化学系生命有机磷化学及化学生物学教育部重点实验室北京 100084
c 南开大学元素有机化学国家重点实验室天津 300071

收稿日期:2021-04-04 修回日期:2021-05-17 发布日期:2021-06-17
通讯作者: 陈超, 文丽荣
基金资助:
国家重点研发项目(2016YFB0401400); 国家自然科学基金(22071129); 国家自然科学基金(21871158); 国家自然科学基金(21672120); 霍英东教育基金(151014)

Study on the Selective Difluorochloroethylation Reactions of Amides with Hypervalent Iodine Reagent

Tingxun Yan^a^,^b, Chao Chen^b^,^c(), Lirong Wen^a()

a College of Chemistry and Molecular Engineering, Qingdao University of Science & Technology, Qingdao 266042
b Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology, Ministry of Education,Department of Chemistry, Tsinghua University, Beijing 100084
c State Key Laboratory of Elemental Organic Chemistry, Nankai University, Tianjin 300071

Received:2021-04-04 Revised:2021-05-17 Published:2021-06-17
Contact: Chao Chen, Lirong Wen
Supported by:
National Key Research and Development Program of China(2016YFB0401400); National Natural Science Foundation of China(22071129); National Natural Science Foundation of China(21871158); National Natural Science Foundation of China(21672120); Fok Ying Tong Education Foundation of China(151014)

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摘要/Abstract

含氟乙基化产物在生物医药和材料领域有着广泛的应用, 合成含氟乙基的化合物有着重要意义. 目前对三氟乙基化合物的合成有了相关报道, 但是对于如何合成二氟乙基化产物却鲜有报道. 通过氯二氟高价碘试剂和酰胺进行反应, 选择性生成氮-氯二氟乙基化和氧-氯二氟乙基化产物, 该反应的选择性通过溶剂选择即可调控, 反应高效便捷实用.

关键词: 氯二氟乙基高价碘, 氟乙基化, 二氟乙基化, 三氟乙基化

Fluoroethylation products have a wide range of applications in the fields of biomedicine and materials, and the synthesis of fluorine-containing ethyl compounds is very important. At present, there are related reports on the synthesis of trifluoroethyl compounds, but there are few reports on how to synthesize difluoroethylated products. In this paper, through the reaction of chlorodifluoro iodine reagent and amide, N-chlorodifluoroethylation and O-chlorodifluoroethylation products were selectively generated. The selectivity of the reaction can be controlled by the choice of solvent, and the reaction is efficient, convenient and practical.

Key words: chlorodifluoroethyl hypervalent iodine reagent, fluoroethylation, difluoroethylation, trifluoroethylation

引用此文

颜廷勋, 陈超, 文丽荣. 高价碘试剂参与酰胺的选择性二氟氯乙基化反应研究[J]. 有机化学, 2021, 41(9): 3660-3667.

Tingxun Yan, Chao Chen, Lirong Wen. Study on the Selective Difluorochloroethylation Reactions of Amides with Hypervalent Iodine Reagent[J]. Chinese Journal of Organic Chemistry, 2021, 41(9): 3660-3667.

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图/表 7

图1. 含氟乙基片段的生物活性分子

Figure 1. Biologically active fluoroethylated molecules

图式1. 三氟乙基高价碘制备和应用

Scheme 1. Preparation and application of trifluoroethyl hypervalent iodine

图式2. 氯二氟乙基高价碘试剂的制备

Scheme 2. Preparation of chlorodifluoroethyl hypervalent iodine reagent

Entry	Base	Time/h	Solvent	Temp./℃	Yield^b/%
Entry	Base	Time/h	Solvent	Temp./℃	3a	4a
1	Et₃N	4	DCM	28	7	―
2	Na₂CO₃	4	DCM	28	46	―
3	Na₂CO₃	6	DCM	28	67	―
4	Na₂CO₃	12	DCM	28	52	―
5	NaHCO₃	6	DCM	28	65	4^c
6	t-BuOK	6	DCM	28	45	―
7	CsCO₃	6	DCM	28	60	―
8	None	6	DCM	28	85	―
9	None	6	DCM	0	56	―
10	None	6	DCM	45	70	―
11	None	6	DCM	80	64	―
12	None	12	DCM	80	56	―
13	NaHCO₃	12	DCM	28	―	11
14	t-BuOK	12	DCM	28	―	13
15	None	12	THF	28	―	45
16	None	12	DMF	28	―	61
17	None	6	MeCN	28	―	56
18	None	8	MeCN	28	―	87

表1. 反应条件优化a,b

Table 1. Optimization of reaction conditions

表2. 以二氯甲烷为溶剂氯二氟乙基高价碘和苯甲酰胺类化合物的反应a,b

Table 2. Reaction of chlorodifluoroethyl hypervalent iodine and benzamide compounds using dichloromethane as solvent

表3. 以乙腈为溶剂氯二氟乙基高价碘和苯甲酰胺类化合物的反应a,b

Table 3. Reaction of chlorodifluoroethyl hypervalent iodine and benzamide compounds using acetonitrile as solvent

图式3. N-二氟氯乙基化或O-二氟氯乙基化可能的反应机理

Scheme 3. A plausible mechanism for the N-difluorochloro- ethylation or O-difluorochloroethylation

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高价碘试剂参与酰胺的选择性二氟氯乙基化反应研究

Study on the Selective Difluorochloroethylation Reactions of Amides with Hypervalent Iodine Reagent

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