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

doi:10.6023/cjoc202511006

Chinese Journal of Organic Chemistry ›› 2026, Vol. 46 ›› Issue (6): 2327-2336.DOI: 10.6023/cjoc202511006 Previous Articles Next Articles

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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
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: * E-mail: xin-cui@163.com;yangziycy@163.com;lucasphe@163.com
Supported by:
Natural Science Foundation of Hunan Province(2023JJ40528)

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

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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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Fig. & Tab. 20

Figure 1. Examples of drug molecules containing benzoxazines

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

Scheme 2. Photocatalytic synthesis of 4-trifluoroethylbenzoxa- zine

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

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

Scheme 5. Photoinduced synthesis of 2-aminobenzoxazine

Scheme 6. Photoinduced synthesis of 4-arylsulfonylmethylbenzoxazine

Scheme 7. Photoinduced synthesis of 4-cyanoethylbenzoxazine

Scheme 8. Photoinduced synthesis of 4-nitromethylbenzoxazine

Scheme 9. Photoinduced synthesis of 4-sulfonamidomethyl- benzoxazine

Scheme 10. Photoinduced synthesis of 4-fluorosulfonamido- methylbenzoxazine

Scheme 11. Benzoxazine synthesis via alkynylaniline and benzoquinone

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

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

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

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

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

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

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

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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