Research Progress on C—H Functionalization Reactions of Uracil and Its Derivatives

doi:10.6023/A26040138

Acta Chimica Sinica ›› 2026, Vol. 84 ›› Issue (10): 1679-1702.DOI: 10.6023/A26040138 Previous Articles

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尿嘧啶及其衍生物的C—H官能化反应研究进展

胡甜芯, 陈斌斌, 王泽艺, 陈漫仪, 章鹏飞, 徐骏^*()

杭州师范大学材料与化学化工学院全省有机硅材料技术重点实验室浙江杭州 311121

投稿日期:2026-04-27 发布日期:2026-07-29

作者简介:

胡甜芯, 杭州师范大学材料化学与化工学院2024级本科生, 研究方向为绿色有机合成方法学研究.

陈斌斌, 杭州师范大学材料与化学化工学院2023级研究生, 研究方向为电化学有机合成.

王泽艺, 杭州师范大学材料与化学化工学院2024级研究生, 研究方向为光催化有机合成.

陈漫仪, 杭州师范大学材料与化学化工学院2024级研究生, 研究方向为光催化有机合成.

章鹏飞, 杭州师范大学材料与化学化工学院教授、博士生导师, 英国皇家化学会会士, 享受国务院政府特殊津贴专家, 浙江省“万人计划”杰出人才. 主要从事氟/硅精细化学品创制、碳氢键催化活化及光催化自由基偶联研究.

徐骏, 杭州师范大学材料与化学化工学院讲师、硕士生导师, 主要从事绿色有机合成方法学及精细化学品新工艺研发, 相关成果发表于ACS Catal.、Green Chem.、Adv. Funct. Mater.、Chin. Chem. Lett.、Org. Lett.等期刊; 现担任Chin. Chem. Lett.、Chin. J. Org. Chem.等期刊的青年编委.

基金资助:
浙江省自然科学基金(LQN26B060020); 杭州市自然科学基金(2025SZRJJ0081); 国家自然科学基金(22508079)

Research Progress on C—H Functionalization Reactions of Uracil and Its Derivatives

Tianxin Hu, Binbin Chen, Zeyi Wang, Manyi Chen, Pengfei Zhang, Jun Xu^*()

College of Material, Chemistry and Chemical Engineering, Key Laboratory of Organosilicon Chemistry and Material Technology, Ministry of Education, Zhejiang Key Laboratory of Organosilicon Material Technology, Hangzhou Normal University, Hangzhou 311121, China

Received:2026-04-27 Published:2026-07-29
Contact: *E-mail: xujunchem@hznu.edu.cn
Supported by:
Zhejiang Provincial Natural Science Foundation of China(LQN26B060020); Natural Science Foundation of Hangzhou City(2025SZRJJ0081); National Natural Science Foundation of China(22508079)

Uracil and its derivatives are core structural motifs in the fields of biomedicine, life sciences, and agricultural sciences, and their structural modification holds significant research and application value. Traditional modification methods, such as condensation cyclization and nucleophilic substitution, often rely on harsh conditions including high temperatures, strong acids, or strong bases. These approaches suffer from poor site selectivity, low atom economy, narrow substrate scope, and poor environmental compatibility, failing to meet the demands of modern late-stage drug modification and industrial production. In recent years, direct C—H functionalization has emerged as a novel strategy for the efficient and green modification of uracil compounds, leveraging advantages such as the avoidance of pre-functionalization, high step economy, and excellent atom economy. This review systematically summarizes the progress in C—H functionalization of uracil and its derivatives over the past six years, covering various transformation types including alkylation, arylation, trifluoromethylation, acylation, amination, sulfidation/selenization, silicidation, alkenylation, and boronation. This article provides an in-depth comparison of substrate scopes, reaction mechanisms, and application potential. By also incorporating relevant work from our research group, we aim to offer researchers in related fields a systematic and detailed reference framework to facilitate innovative applications of uracil-based molecules in drug discovery and life sciences.

Key words: uracil, C—H functionalization, radical, photocatalysis, coupling reaction

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Tianxin Hu, Binbin Chen, Zeyi Wang, Manyi Chen, Pengfei Zhang, Jun Xu. Research Progress on C—H Functionalization Reactions of Uracil and Its Derivatives[J]. Acta Chimica Sinica, 2026, 84(10): 1679-1702.

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Fig. & Tab. 41

Scheme 1. Uracil derivatives containing pharmaceutical and biological activities

Scheme 2. Two traditional post-modification methods for uracil and its derivatives

Scheme 3. C—H Functionalization of uracil and its derivatives

Scheme 4. Application of sulfur ylide in the C—H alkylation of iminoamide-type azacycles

Scheme 5. Photothermal-driven C—H alkylation of azauracils

Scheme 6. Tungstate photocatalysis enables direct C—H hydroalkylation of N-heteroarenes

Scheme 7. Heterogeneous photocatalytic enables C—H alkylation of N-heterocycles

Scheme 8. Photoredox decarboxylative synthesis of C-glycosides

Scheme 9. Photocatalytic three-component C—H alkylation of N-heterocycles

Scheme 10. C—H Alkylation of N-heterocycles via XAT activation of organic halides

Scheme 11. C—H Alkylation of N-heterocycles via consecutive photoinduced electron transfer (ConPET) mechanism

Scheme 12. C—H Alkylation of N-heterocycles via photoactivation of EDA complexes

Scheme 13. Eosin Y-catalyzed cyanoalkylation of C—H bonds in azauracils

Scheme 14. EDA Complex-driven C—H cyanoalkylation of N-heteroarenes

Scheme 15. Visible light-induced C—H oxyalkylation of azauracil

Scheme 16. Azauracil C—H arylation via the formation of an EDA complex

Scheme 17. Mechanism of C—H arylation of azauracils via EDA complex formation

Scheme 18. C—H Arylation of azauracil with aryl thianthrenium salts and DABCO

Scheme 19. Aryl iodide-mediated C—H arylation of azauracil

Scheme 20. C—H Trifluoromethylation of uracil

Scheme 21. Electrochemical C—H trifluoromethylation of uracil

Scheme 22. Cu(I)-Catalyzed C—H silylation and germylation of azauracil

Scheme 23. Synergistic catalytic C—H silylation of azauracils

Scheme 24. Catalyst-free C—H sulfenylation of uracils

Scheme 25. Iodine-catalyzed C—H thioetherification of uracil

Scheme 26. Visible-light-promoted C—H sulfenylation of 6-aminouracils

Scheme 27. H2O2-Promoted C—H thiocyanation of uracil

Scheme 28. AIBN-mediated C—H thiocyanation of uracil

Scheme 29. Hexachloroethane-promoted C—H thioarylation of uracil via oxidative coupling

Scheme 30. Selected substrates for the C—H thioarylation of uracils enabled by hexachloroethane oxidation

Scheme 31. The C—H selenocyanation of uracil using diselenocyanide

Scheme 32. Electrochemical C—H selenocyanation of uracil

Scheme 33. C—H Selenylation of N-heterocycles without additional supporting electrolytes

Scheme 34. C—H Selenylation of N-heterocycles using DMSO as both solvent and oxidant

Scheme 35. Bromide-mediated oxidative C—H selenation of uracil

Scheme 36. Minisci-type C—H carbamoylation of azauracils

Scheme 37. Sodium decatungstate-catalyzed C—H acylation of azauracils

Scheme 38. Amination of the C—H bond in uracil under metal-free conditions

Scheme 39. Palladium-catalyzed C—H alkenylation of uracil

Scheme 40. Synergistic catalysis for direct C—H borylation of heterocycles

Scheme 41. Mechanism of synergistic catalysis for direct C—H borylation of heterocycles

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尿嘧啶及其衍生物的C—H官能化反应研究进展

Research Progress on C—H Functionalization Reactions of Uracil and Its Derivatives

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