自由基串联反应合成1,3-苯并恶嗪研究进展

doi:10.6023/cjoc202511006

有机化学 ›› 2026, Vol. 46 ›› Issue (6): 2327-2336.DOI: 10.6023/cjoc202511006 上一篇下一篇

综述与进展

自由基串联反应合成1,3-苯并恶嗪研究进展

鄢东^a, 何卫保^a, 唐裕才^d, 辛翠^b^,^*(), 杨梓^c^,^*(), 陈祥^e^,^*()

^a 湖南化工职业技术学院技术与职业教育研究中心湖南株洲 412000
^b 湖南警察学院食药环及毒品检验技术湖南省普通高等学校重点实验室长沙 410138
^c 长沙医学院功能核酸基础与临床湖南省普通高校重点实验室长沙 410219
^d 湖南文理学院化学与材料工程学院湖南常德 415000
^e 南华大学化学化工学院湖南衡阳 421001

收稿日期:2025-11-11 修回日期:2026-01-28 发布日期:2026-02-28
通讯作者: 辛翠, 杨梓, 陈祥
基金资助:
湖南省自然科学基金(2023JJ40528)

Research Progress in the Synthesis of 1,3-Benzoxazine via Radical Cascade Reaction

Dong Yan^a, Weibao He^a, Yucai Tang^d, Cui Xin^b^,^*(), Zi Yang^c^,^*(), Xiang Chen^e^,^*()

^a Research Center for Technical and Vocational Education Studies, Hunan Chemical Vocational Technology College, Zhuzhou, Hunan 412000
^b Key Laboratory of Food & Environment & Drug Monitoring and Testing of Universities in Hunan Province, Hunan Police Academy, Changsha 410138
^c Hunan Provincial University Key Laboratory of the Fundamental and Clinical Research on Functional Nucleic Acid, Changsha Medical University, Changsha 410219
^d College of Chemistry and Materials Engineering, Hunan University of Arts and Science, Changde, Hunan 415000
^e School of Chemistry and Chemical Engineering, University of South China, Hengyang, Hunan 421001

Received:2025-11-11 Revised:2026-01-28 Published:2026-02-28
Contact: Cui Xin, Zi Yang, Xiang Chen
Supported by:
Natural Science Foundation of Hunan Province(2023JJ40528)

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摘要/Abstract

苯并恶嗪作为一类含氮氧杂环的重要结构单元, 广泛存在于药物分子与功能材料中, 尤其在药物研发领域, 其展现出抗炎、抗真菌等多样的生物活性, 成为极具潜力的活性分子骨架. 不饱和芳香烃衍生物(如N-酰基-2-烯基苯胺)因结构中不饱和键与杂原子位点的协同反应性, 是自由基串联反应构建苯并恶嗪骨架的优良原料, 展现出广阔的学术研究价值与工业应用前景. 围绕光介导自由基串联反应、电化学自由基串联反应、过渡金属介导自由基串联反应三个核心方向, 系统梳理了近10年来该类化合物的自由基串联反应合成研究进展; 重点关注不同合成策略的反应机理及底物适用性范围等科学问题. 最后总结了当前研究存在的挑战, 并对其合成策略的发展方向进行了展望.

关键词: 苯并恶嗪, N-酰基-2-烯基苯胺, 自由基串联反应, 烯烃双官能团化, 光氧化还原反应

As an important structural unit containing nitrogen-oxygen heterocycles, benzoxazine widely exists in drug molecules and functional materials. Especially in the field of drug research and development, it exhibits diverse biological activities such as anti-inflammatory and antifungal properties, becoming a highly potential active molecular skeleton. Unsaturated aromatic hydrocarbon derivatives (such as N-acyl-2-alkenylanilines), due to the synergistic reactivity between unsaturated their unsaturated bonds and heteroatomic sites, are excellent raw materials for constructing benzoxazine skeletons via radical cascade reactions, showing broad academic research value and industrial application prospects. Focusing on three core directions: photo-mediated radical cascade reactions, electrochemical radical cascade reactions, and transition metal-mediated radical cascade reactions, the progress in the synthesis of such compounds via radical cascade reactions over the past 10 years is systematically reviewed. Special attention is paid to such scientific issues as the reaction mechanisms and substrate scopes of different synthetic strategies. Finally, the existing challenges in current research are summarized, and the development directions of the synthetic strategies are prospected.

Key words: benzoxazines, N-acyl-2-alkenylanilines, radical cascade reactions, difunctionalization of alkenes, photoredox reactions

引用此文

鄢东, 何卫保, 唐裕才, 辛翠, 杨梓, 陈祥. 自由基串联反应合成1,3-苯并恶嗪研究进展[J]. 有机化学, 2026, 46(6): 2327-2336.

Dong Yan, Weibao He, Yucai Tang, Cui Xin, Zi Yang, Xiang Chen. Research Progress in the Synthesis of 1,3-Benzoxazine via Radical Cascade Reaction[J]. Chinese Journal of Organic Chemistry, 2026, 46(6): 2327-2336.

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图/表 20

图1. 含苯并恶嗪的药物分子示例

Figure 1. Examples of drug molecules containing benzoxazines

图式1. 自由基串联反应合成1,3-苯并恶嗪

Scheme 1. Synthesis of 1,3-benzoxazine via radical cascade reaction

图式2. 光催化合成4-三氟乙基苯并恶嗪

Scheme 2. Photocatalytic synthesis of 4-trifluoroethylbenzoxa- zine

图式3. 光诱导有机小分子催化合成4-三氟乙基苯并恶嗪

Scheme 3. Photoinduced synthesis of 4-trifluoroethylbenzoxa- zine via organic small-molecule catalysis

图式4. 光诱导铱催化合成4-二氟乙基苯并恶嗪

Scheme 4. Photoinduced iridium-catalyzed synthesis of 4-di- fluoroethylbenzoxazine

图式5. 光诱导合成2-氨基苯并恶嗪

Scheme 5. Photoinduced synthesis of 2-aminobenzoxazine

图式6. 光诱导合成4-芳磺酰甲基苯并恶嗪

Scheme 6. Photoinduced synthesis of 4-arylsulfonylmethylbenzoxazine

图式7. 光诱导合成4-氰乙基基苯并恶嗪

Scheme 7. Photoinduced synthesis of 4-cyanoethylbenzoxazine

图式8. 光诱导合成4-硝基甲基苯并恶嗪

Scheme 8. Photoinduced synthesis of 4-nitromethylbenzoxazine

图式9. 光诱导合成4-磺酰胺甲基苯并恶嗪

Scheme 9. Photoinduced synthesis of 4-sulfonamidomethyl- benzoxazine

图式10. 光诱导合成4-氟磺酰胺甲基苯并恶嗪

Scheme 10. Photoinduced synthesis of 4-fluorosulfonamido- methylbenzoxazine

图式11. 经炔基苯胺与苯醌合成苯并恶嗪

Scheme 11. Benzoxazine synthesis via alkynylaniline and benzoquinone

图式12. 光诱导合成硫代、亚磺酰代、磺酰代苯并恶嗪

Scheme 12. Photoinduced synthesis of thio-, sulfinyl-, and sulfonyl-substituted benzoxazines

图式13. 电化学氧化合成磺酰甲基苯并恶嗪

Scheme 13. Electrochemical oxidation synthesis of 4-sulfonyl- methyl benzoxazines

图式14. 电化学氧化合成磺酰甲基苯并恶嗪

Scheme 14. Electrochemical oxidation synthesis of 4-sulfonyl- methyl benzoxazines

图式15. 电化学氧化合成磺酰甲基苯并恶嗪

Scheme 15. Electrochemical oxidation synthesis of 4-sulfonyl- methyl benzoxazines

图式16. 电化学氧化合成磺酰甲基苯并恶嗪

Scheme 16. Electrochemical oxidation synthesis of 4-sulfonyl- methyl benzoxazines

图式17. 铜催化合成烷基苯并恶嗪

Scheme 17. Copper-catalyzed synthesis of alkyl-substituted benzoxazines

图式18. 银/铈促进自由基串联环化合成砜甲基苯并恶嗪

Scheme 18. Silver/cerium-promoted radical cascade cyclization for the synthesis of sulfonylmethyl benzoxazines

图式19. 锰促进自由基串联环化合成苯并恶嗪-4-甲磺酸盐

Scheme 19. Manganese-promoted radical cascade cyclization for the synthesis of benzoxazine-4-methanesulfonate

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自由基串联反应合成1,3-苯并恶嗪研究进展

Research Progress in the Synthesis of 1,3-Benzoxazine via Radical Cascade Reaction

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