N-Bromosuccinimide-Promoted Direct Phosphorylation of Amines with P(O)—H Compounds

doi:10.6023/cjoc202507034

Chinese Journal of Organic Chemistry ›› 2026, Vol. 46 ›› Issue (3): 1060-1069.DOI: 10.6023/cjoc202507034 Previous Articles Next Articles

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N-溴代丁二酰亚胺促进的P(O)—H化合物参与的胺的直接磷酰化反应

李乔莉^a^,^†, 王华斌^a^,^†, 覃燕^a, 赵加敏^a, 韩芳^a, 刘雄伟^a, 潘博文^a, 黄强^b^,^*(), 周英^a^,^c^,^*()

^a 贵州中医药大学药学院贵阳 550025
^b 遵义医科大学药学院贵州遵义 563000
^c 贵州省现代中药创制全省重点实验室贵阳 550025

收稿日期:2025-10-08 修回日期:2025-11-01 发布日期:2025-11-19
作者简介:
†共同第一作者
基金资助:
贵州省自然科学基金(ZK[2024]046); 贵州省自然科学基金(ZK[2025]170); 贵州省现代中药创新重点实验室(ZSYS[2025]019); 贵州省高层次创新人才(GCC[2023]047)

N-Bromosuccinimide-Promoted Direct Phosphorylation of Amines with P(O)—H Compounds

Qiaoli Li^a, Huabin Wang^a, Yan Qin^a, Jiamin Zhao^a, Fang Han^a, Xiongwei Liu^a, Bowen Pan^a, Qiang Huang^b^,^*(), Ying Zhou^a^,^c^,^*()

^a College of Pharmacy, Guizhou University of Traditional Chinese Medicine, Guiyang 550025
^b School of Pharmacy, Zunyi Medical University, Zunyi, Guizhou 563000
^c Guizhou Key Laboratory of Modern Traditional Chinese Medicine Creation, Guiyang 550025

Received:2025-10-08 Revised:2025-11-01 Published:2025-11-19
Contact: *E-mail: huangqiang65@sina.com; yingzhou71@sina.com
About author:
†The authors contributed equally to this work.
Supported by:
Guizhou Provincial Natural Science Foundation(ZK[2024]046); Guizhou Provincial Natural Science Foundation(ZK[2025]170); Guizhou Key Laboratory of Modern Traditional Chinese Medicine Creation(ZSYS[2025]019); High-Level Innovative Talents of Guizhou Province(GCC[2023]047)

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Abstract

A mild, green, high atom economic, convenient and scalable N-bromosuccinimide (NBS) promoted direct phosphorylation strategy of secondary phosphine oxides and amines has been developed for the synthesis of various valuable phosphamide compounds. A variety of substrates were well-tolerated and afforded the desirable compounds in moderate to excellent yields (up to 93%). This reaction proceeds smoothly at room temperature under air atmosphere, without the need for metal catalysts, bases, or high temperature, thus providing a new strategy for the synthesis of phosphamide derivatives.

Key words: phosphorylation, P(O)—N bond, phosphamide compounds, amines, N-bromosuccinimide (NBS)

Cite this article

Qiaoli Li, Huabin Wang, Yan Qin, Jiamin Zhao, Fang Han, Xiongwei Liu, Bowen Pan, Qiang Huang, Ying Zhou. N-Bromosuccinimide-Promoted Direct Phosphorylation of Amines with P(O)—H Compounds[J]. Chinese Journal of Organic Chemistry, 2026, 46(3): 1060-1069.

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N-溴代丁二酰亚胺促进的P(O)—H化合物参与的胺的直接磷酰化反应

N-Bromosuccinimide-Promoted Direct Phosphorylation of Amines with P(O)—H Compounds

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Entry	Additive	Solvent	T/℃	Yield^b/%
1	NBS	Toluene	25	65
2	NCS	Toluene	25	62
3	NIS	Toluene	25	59
4	NBS	CH₃CN	25	76
5	NBS	DMF	25	None
6	NBS	DMSO	25	None
7	NBS	DCM	25	93
8	NBS	EA	25	65
9	NBS	Dioxane	25	57
10	NBS	CS₂	25	75
11	NBS	Chloroform	25	87
12	NBS	CCl₄	25	85
13	NBS	TH₄	25	67
14	NBS	Acetone	25	65
15	NBS	DCM	0	78
16	NBS	DCM	45	87
17	NBS	DCM	60	76
18	NBS	DCM	80	65
19	NBS	DCM	25	45^c, 64^d, 72^e

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