Base-Catalyzed Chemoselective Substitution of β-Ketonitrile with Azodicarboxylates

doi:10.6023/cjoc202408005

Chinese Journal of Organic Chemistry ›› 2025, Vol. 45 ›› Issue (4): 1249-1260.DOI: 10.6023/cjoc202408005 Previous Articles Next Articles

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碱催化的β-酮腈与偶氮二甲酸酯的化学选择性取代反应

郭怡诗, 桑田, 刘岩^*(), 刘平^*()

石河子大学化学化工学院化工绿色过程兵团重点实验室新疆石河子 832003

收稿日期:2024-08-06 修回日期:2024-10-27 发布日期:2024-11-27
基金资助:
国家自然科学基金(21563025); 国家自然科学基金(22162022)

Base-Catalyzed Chemoselective Substitution of β-Ketonitrile with Azodicarboxylates

Yishi Guo, Tian Sang, Yan Liu(), Ping Liu()

Key Laboratory for Green Processing of Chemical Engineering of Xinjiang Bingtuan, School of Chemistry and Chemical Engineering, Shihezi University, Shihezi, Xinjiang 832004

Received:2024-08-06 Revised:2024-10-27 Published:2024-11-27
Contact: * E-mail: liuyan@shzu.edu.cn; liuping@shzu.edu.cn
Supported by:
National Natural Science Foundation of China(21563025); National Natural Science Foundation of China(22162022)

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Abstract

Base-catalyzed nucleophilic substitution reactions of β-ketonitrile with azodicarboxylates have been developed. A series of disubstituted C—N coupling products were obtained in good to excellent yields under Et₃N catalysis. Monosubstitution C—N bond formation reaction catalyzed by K₂CO₃ also gave novel enol-based target products. This method is simple and mild, with good chemoselectivity, excellent substrate compatibility and tolerance for various functional groups, and achieves gram-scale synthesis. The reaction is a nucleophilic substitution process without the involvement of free radicals.

Key words: base-catalysis, β-ketonitrile, selective substitution, azodicarboxylate

Cite this article

Yishi Guo, Tian Sang, Yan Liu, Ping Liu. Base-Catalyzed Chemoselective Substitution of β-Ketonitrile with Azodicarboxylates[J]. Chinese Journal of Organic Chemistry, 2025, 45(4): 1249-1260.

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Fig. & Tab. 9

References 18

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Entry	1a∶2a	Base (dosage/mol%)	Solvent	T/℃	t/h
1	1∶2.5	K₂CO₃ (20)	DCM	35	12	43
2^c	1∶2.5	KOH (20)	DCM	35	12	20
3	1∶2.5	Na₂CO₃ (20)	DCM	35	12	30
4	1∶2.5	NaOH (20)	DCM	35	12	35
5	1∶1	K₂CO₃ (20)	DCM	35	12	NR
6	1∶1.5	K₂CO₃ (20)	DCM	35	12	72
7	1∶1.5	K₂CO₃ (2)	DCM	35	12	0 (64)^c
8	1∶1.5	K₂CO₃ (10)	DCM	35	12	46 (31)^c
9^d	2∶1	K₂CO₃ (20)	DCM	35	12	NR
10	1∶1.5	K₂CO₃ (20)	DMSO	35	12	68
11	1∶1.5	K₂CO₃ (20)	THF	35	12	61
12	1∶1.5	K₂CO₃ (20)	Toluene	35	12	NR
13	1∶1.5	K₂CO₃ (20)	DCM	60	12	59
14	1∶1.5	K₂CO₃ (20)	DCM	35	16	66

Entry	1a∶2a	Base (dosage/mol%)	Solvent	T/℃	t/h
1	1∶2.5	K₂CO₃ (20)	DCM	35	12	43
2^c	1∶2.5	KOH (20)	DCM	35	12	20
3	1∶2.5	Na₂CO₃ (20)	DCM	35	12	30
4	1∶2.5	NaOH (20)	DCM	35	12	35
5	1∶1	K₂CO₃ (20)	DCM	35	12	NR
6	1∶1.5	K₂CO₃ (20)	DCM	35	12	72
7	1∶1.5	K₂CO₃ (2)	DCM	35	12	0 (64)^c
8	1∶1.5	K₂CO₃ (10)	DCM	35	12	46 (31)^c
9^d	2∶1	K₂CO₃ (20)	DCM	35	12	NR
10	1∶1.5	K₂CO₃ (20)	DMSO	35	12	68
11	1∶1.5	K₂CO₃ (20)	THF	35	12	61
12	1∶1.5	K₂CO₃ (20)	Toluene	35	12	NR
13	1∶1.5	K₂CO₃ (20)	DCM	60	12	59
14	1∶1.5	K₂CO₃ (20)	DCM	35	16	66

碱催化的β-酮腈与偶氮二甲酸酯的化学选择性取代反应

Base-Catalyzed Chemoselective Substitution of β-Ketonitrile with Azodicarboxylates

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Entry	n(1a)∶n(2a)	Base (dosage/mol%)	Solvent	T/℃	t/h
1	1∶2	—	DCM	35	12	75
2^c	1∶2.5	—	DCM	35	12	78
3	1∶2.5	—	n-Hexane	35	12	72
4	1∶2.5	—	EtOH	35	12	71
5	1∶2.5	—	DMSO	35	12	73
6	1∶2.5	—	1,4-Dioxane	35	12	48
7	1∶2.5	—	CH₃CN	35	12	28
8	1∶2.5	—	THF	35	12	57
9	1∶2.5	—	Toluene	35	12	NR
10	1∶2.5	—	H₂O	35	12	23
11	1∶2.5	—	DCM	35	16	57
12	1∶2.5	—	DCM	60	12	33
13	1∶2.5	Quinine (2)＋Cs₂CO₃ (2)	DCM	35	12	58
14	1∶2.5	Cs₂CO₃ (2)	DCM	35	12	67
15	1∶2.5	Et₃N (20)	DCM	35	12	85
16	1∶2.5	Et₃N (2)	DCM	35	12	78
17	1∶2.5	Et₃N (10)	DCM	35	12	84

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