Catalytic Synthesis of 2-Aminobenz-1,3-oxazin-4-ketone by Copper-Catalyzed Desulfurization and Cyclization of 2-Aminobenzoic Acid and Isothiocyanate

doi:10.6023/cjoc202601010

Chinese Journal of Organic Chemistry ›› 2026, Vol. 46 ›› Issue (7): 2808-2815.DOI: 10.6023/cjoc202601010 Previous Articles Next Articles

ARTICLE

铜催化2-氨基苯甲酸与异硫氰酸酯脱硫环化合成2-氨基苯并-1,3-噁嗪-4-酮

高鹰鹏^a, 张林军^b, 宋基懿^a, 钟品勇^a^,^*(), 刘晋彪^a^,^*()

^a 江西理工大学化学化工学院江西赣州 341000
^b 豫章师范学院智能材料与新能源学院南昌 330103

收稿日期:2026-01-08 修回日期:2026-02-10 发布日期:2026-03-27
基金资助:
国家自然科学基金(21961014)

Catalytic Synthesis of 2-Aminobenz-1,3-oxazin-4-ketone by Copper-Catalyzed Desulfurization and Cyclization of 2-Aminobenzoic Acid and Isothiocyanate

Yingpeng Gao^a, Linjun Zhang^b, Jiyi Song^a, Pinyong Zhong^a^,^*(), Jinbiao Liu^a^,^*()

^a School of Chemistry and Chemical Engineering, Jiangxi University of Science and Technology, Ganzhou, Jiangxi 341000
^b School of Intelligent Materials and New Energy, Yuzhang Normal University, Nanchang 330103

Received:2026-01-08 Revised:2026-02-10 Published:2026-03-27
Contact: *E-mail: zhongpinyong2022@163.com;liujinbiao@jxust.edu.cn
Supported by:
National Natural Science Foundation of China(21961014)

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Abstract

2-Amino-substituted benzoxazinone derivatives have attracted considerable attention due to their remarkable pharmacological activities and play an important role in drug discovery. In this work, an inexpensive copper-catalyzed strategy that utilizes oxygen as a green oxidant to achieve desulfative cyclization of 2-aminobenzoic acids with isothiocyanates has been developed, enabling the efficient synthesis of 2-amino-1,3-benzoxazin-4-one derivatives. Mechanistic studies reveal that the reaction proceeds via a copper-mediated desulfative cyclization mechanism, facilitating the desulfurization of thiourea intermediates and the construction of intramolecular C—O bonds. This approach avoids the use of precious metal catalysts and external oxidants, features mild reaction conditions and simple manipulation, and thus provides a new avenue for the green synthesis of benzoxazinone derivatives.

Key words: copper catalysis, benzoxazinone, molecular oxygen, isothiocyanates, desulfurative cyclization

Cite this article

Yingpeng Gao, Linjun Zhang, Jiyi Song, Pinyong Zhong, Jinbiao Liu. Catalytic Synthesis of 2-Aminobenz-1,3-oxazin-4-ketone by Copper-Catalyzed Desulfurization and Cyclization of 2-Aminobenzoic Acid and Isothiocyanate[J]. Chinese Journal of Organic Chemistry, 2026, 46(7): 2808-2815.

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References 32

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Entry	Photocatalyst	Solvent	Base	Yield/%
1	CuSO₄•5H₂O	DMF	DMAP	84
2	FeCl₃	DMF	DMAP	42
3	AlCl₃	DMF	DMAP	14
4	CoCl₂	DMF	DMAP	52
5	CuI	DMF	DMAP	79
6	CuCl₂	DMF	DMAP	96
7	－	DMF	DMAP	25
8	CuCl₂	DMSO	DMAP	92
9	CuCl₂	DCE	DMAP	83
10	CuCl₂	EtOH	DMAP	17
11	CuCl₂	MeCN	DMAP	18
12	CuCl₂	Toluene	DMAP	23
13	CuCl₂	1,4-Dioxane	DMAP	20
14	CuCl₂	DMF	DBU	10
15	CuCl₂	DMF	DBN	ND
16	CuCl₂	DMF	NaOH	33
17	CuCl₂	DMF	t-BuOK	21
18	CuCl₂	DMF	Na₂CO₃	21
19	CuCl₂	DMF	Et₃N	27
20	CuCl₂	DMF	Na₃PO₄	32

Entry	Photocatalyst	Solvent	Base	Yield/%
1	CuSO₄•5H₂O	DMF	DMAP	84
2	FeCl₃	DMF	DMAP	42
3	AlCl₃	DMF	DMAP	14
4	CoCl₂	DMF	DMAP	52
5	CuI	DMF	DMAP	79
6	CuCl₂	DMF	DMAP	96
7	－	DMF	DMAP	25
8	CuCl₂	DMSO	DMAP	92
9	CuCl₂	DCE	DMAP	83
10	CuCl₂	EtOH	DMAP	17
11	CuCl₂	MeCN	DMAP	18
12	CuCl₂	Toluene	DMAP	23
13	CuCl₂	1,4-Dioxane	DMAP	20
14	CuCl₂	DMF	DBU	10
15	CuCl₂	DMF	DBN	ND
16	CuCl₂	DMF	NaOH	33
17	CuCl₂	DMF	t-BuOK	21
18	CuCl₂	DMF	Na₂CO₃	21
19	CuCl₂	DMF	Et₃N	27
20	CuCl₂	DMF	Na₃PO₄	32

铜催化2-氨基苯甲酸与异硫氰酸酯脱硫环化合成2-氨基苯并-1,3-噁嗪-4-酮

Catalytic Synthesis of 2-Aminobenz-1,3-oxazin-4-ketone by Copper-Catalyzed Desulfurization and Cyclization of 2-Aminobenzoic Acid and Isothiocyanate

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