铜催化6-氮杂尿嘧啶与环烷烃的交叉脱氢偶联反应

doi:10.6023/cjoc202603035

有机化学 ›› 2026, Vol. 46 ›› Issue (7): 2770-2778.DOI: 10.6023/cjoc202603035 上一篇下一篇

研究论文

铜催化6-氮杂尿嘧啶与环烷烃的交叉脱氢偶联反应

王雷雷^a^,^†, 吴娟娟^a^,^†, 侯易^a, 王景和^a, 孙岩^a, 刘静^a, 郭佳蕾^a, 齐笑^a, 朱超^a^,^*(), 刘强^c^,^*(), 吕雷阳^b^,^*()

^a 德州学院药学院新型药物辅料与缓控释制剂山东省工程研究中心山东德州 253023
^b 中国人民大学化学与生命资源学院光转换材料与生物光子学实验室北京 100872
^c 大连理工大学医学部大连 116024

收稿日期:2026-03-27 修回日期:2026-05-19 发布日期:2026-06-10
作者简介:
†共同第一作者
基金资助:
山东省自然科学基金(ZR2024QB405); 山东省自然科学基金(ZR2024QB406); 中央高校基本科研业务费专项资金(24XNKJ27); 中国人民大学科研业务费专项资金(202530195)

Copper-Catalyzed Cross-Dehydrogenative Coupling of 6-Azauracils with Cycloalkanes

Leilei Wang^a^,^†, Juanjuan Wu^a^,^†, Yi Hou^a, Jinghe Wang^a, Yan Sun^a, Jing Liu^a, Jialei Guo^a, Xiao Qi^a, Chao Zhu^a^,^*(), Qiang Liu^c^,^*(), Leiyang Lv^b^,^*()

^a Shandong Provincial Engineering Research Center of Novel Pharmaceutical Excipients and Controlled Release Preparations, College of Pharmacy, Dezhou University, Dezhou, Shandong 253023
^b Key Laboratory of Advanced Light Conversion Materials and Biophotonics, Department of Chemistry, Renmin University of China, Beijing 100872
^c Faculty of Medicine, Dalian University of Technology, Dalian 116024

Received:2026-03-27 Revised:2026-05-19 Published:2026-06-10
Contact: *E-mail: zhuchao830111@163.com;andyliu_1844@dlut.edu.cn;lvleiyang2020@ruc.edu.cn
About author:
†(These authors contributed equally to this work).
Supported by:
Shandong Provincial Natural Science Foundation(ZR2024QB405); Shandong Provincial Natural Science Foundation(ZR2024QB406); Fundamental Research Funds for the Central Universities(24XNKJ27); Research Funds of Renmin University of China(202530195)

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摘要/Abstract

6-氮杂尿嘧啶作为一种重要的含氮芳香族化合物, 具有广泛的药理和生物学活性. 报道了铜催化6-氮杂尿嘧啶与环烷烃类化合物的交叉脱氢偶联反应. 该研究以CuI为催化剂, 二叔丁基过氧化物(DTBP)为氧化剂, 140 ℃条件下实现6-氮杂尿嘧啶的烷基化反应, 以中等至良好的收率合成了一系列烷基修饰的尿嘧啶化合物. 该反应具有良好的官能团相容性及广泛的底物普适性.

关键词: 铜催化, 6-氮杂尿嘧啶, 烷基化, 自由基, 交叉脱氢偶联反应

6-Azauracils, as an important class of nitrogen-containing aromatic compounds, exhibit a wide range of pharmacological and biological activities. A copper-catalyzed cross-dehydrogenative coupling reaction of 6-azauracils and cycloalkanes was reported. Using CuI as the catalyst and di-tert-butyl peroxide (DTBP) as the oxidant, the C—H alkylation of 6-azauracils was successfully achieved at 140 ℃. This protocol enables the synthesis of structurally diverse alkylated uracil derivatives in moderate to good yields, featuring good functional group compatibility and broad substrate scope.

Key words: copper catalysis, 6-azauracils, alkylation, radical, cross-dehydrogenative coupling

引用此文

王雷雷, 吴娟娟, 侯易, 王景和, 孙岩, 刘静, 郭佳蕾, 齐笑, 朱超, 刘强, 吕雷阳. 铜催化6-氮杂尿嘧啶与环烷烃的交叉脱氢偶联反应[J]. 有机化学, 2026, 46(7): 2770-2778.

Leilei Wang, Juanjuan Wu, Yi Hou, Jinghe Wang, Yan Sun, Jing Liu, Jialei Guo, Xiao Qi, Chao Zhu, Qiang Liu, Leiyang Lv. Copper-Catalyzed Cross-Dehydrogenative Coupling of 6-Azauracils with Cycloalkanes[J]. Chinese Journal of Organic Chemistry, 2026, 46(7): 2770-2778.

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参考文献 20

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Entry	Variation from standard conditions	Yield^b/%
1	None	76
2	CuCl₂ instead of CuI	70
3	CuCl instead of CuI	69
4	Cu(OAc)₂ instead of CuI	72
5	CuBr instead of CuI	70
6	FeCl₃ instead of CuI	60
7	MnCl₂ instead of CuI	55
8	COCl₂ instead of CuI	45
9	Mn(acac)₃ instead of CuI	40
10	TBHP instead of DTBP	52
11	BPO instead of DTBP	ND
12	TBPB instead of DTBP	ND
13	K₂S₂O₈ instead of DTBP	ND
14	15 mol% CuI instead of 10 mol% CuI	75
15	5 mol% CuI instead of 10 mol% CuI	65
16	2.0 equiv. DTBP instead of 3.0 equiv. DTBP	51
17	4.0 equiv. DTBP instead of 3.0 equiv. DTBP	68
18	120 ℃ instead of 140 ℃	21
19	Without CuI	30
20	Without DTBP	ND

Entry	Variation from standard conditions	Yield^b/%
1	None	76
2	CuCl₂ instead of CuI	70
3	CuCl instead of CuI	69
4	Cu(OAc)₂ instead of CuI	72
5	CuBr instead of CuI	70
6	FeCl₃ instead of CuI	60
7	MnCl₂ instead of CuI	55
8	COCl₂ instead of CuI	45
9	Mn(acac)₃ instead of CuI	40
10	TBHP instead of DTBP	52
11	BPO instead of DTBP	ND
12	TBPB instead of DTBP	ND
13	K₂S₂O₈ instead of DTBP	ND
14	15 mol% CuI instead of 10 mol% CuI	75
15	5 mol% CuI instead of 10 mol% CuI	65
16	2.0 equiv. DTBP instead of 3.0 equiv. DTBP	51
17	4.0 equiv. DTBP instead of 3.0 equiv. DTBP	68
18	120 ℃ instead of 140 ℃	21
19	Without CuI	30
20	Without DTBP	ND

铜催化6-氮杂尿嘧啶与环烷烃的交叉脱氢偶联反应

Copper-Catalyzed Cross-Dehydrogenative Coupling of 6-Azauracils with Cycloalkanes

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