One-Pot Three-Component Synthesis of Novel 1,5-Benzodiazepine Derivatives and Their anti-BVDV (Bovine Viral Diarrhea Virus) Activity

doi:10.6023/202004018

Chinese Journal of Organic Chemistry ›› 2021, Vol. 41 ›› Issue (2): 819-825.DOI: 10.6023/202004018 Previous Articles Next Articles

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“一锅”三组分合成新型1,5-苯并二氮杂䓬类化合物与抗牛病毒性腹泻病毒(BVDV)活性

韩超^a^,^*(), 聂磊^a, 韩晓^b, 张岩^a, 孙克磊^a, 石磊^a, 崔广华^a, 孟伟^a^,^*()

a 华北理工大学化学工程学院河北唐山 063210
b 邯郸学院化学化工与材料学院河北邯郸 056005

收稿日期:2020-04-12 修回日期:2020-06-17 发布日期:2020-09-29
通讯作者: 韩超, 孟伟
作者简介:
* Corresponding authors. E-mail: hanchao@ncst.edu.cn; mengwei@ncst.edu.cn
基金资助:
河北省自然科学基金(B2017209119); 河北省教育厅基金(Z2017013)

One-Pot Three-Component Synthesis of Novel 1,5-Benzodiazepine Derivatives and Their anti-BVDV (Bovine Viral Diarrhea Virus) Activity

Chao Han^a^,^*(), Lei Nie^a, Xiao Han^b, Yan Zhang^a, Kelei Sun^a, Lei Shi^a, Guanghua Cui^a, Wei Meng^a^,^*()

a College of Chemical Engineering, North China University of Science and Technology, Tangshan, Hebei 063210
b College of Chemical Engineering & Material, Handan University, Handan, Hebei 056005

Received:2020-04-12 Revised:2020-06-17 Published:2020-09-29
Contact: Chao Han, Wei Meng
Supported by:
the Natural Science Foundation of Hebei Province(B2017209119); the Education Department of Hebei Province(Z2017013)

The “one-pot” three-component reaction is established to synthesize 1,5-benzodiazepine derivatives containing pyrrolidinone. These reactions were carried out readily with p-toluenesulfonic acid (p-TSA) as the catalyst in good yields. Reaction conditions were mild, and environmental friendly. The benzodiazepine derivatives displayed prominent anti-BVDV (bovine viral diarrhea virus) activity with excellent EC₅₀ values and no significant cytotoxicity. Our research could afford significative compounds for the research of anti-BVDV agents.

Key words: “one-pot” three-component reaction, 1, 5-benzodiazepine derivatives, p-TSA, pyrrolidinone, anti-BVDV

Cite this article

Chao Han, Lei Nie, Xiao Han, Yan Zhang, Kelei Sun, Lei Shi, Guanghua Cui, Wei Meng. One-Pot Three-Component Synthesis of Novel 1,5-Benzodiazepine Derivatives and Their anti-BVDV (Bovine Viral Diarrhea Virus) Activity[J]. Chinese Journal of Organic Chemistry, 2021, 41(2): 819-825.

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Fig. & Tab. 9

References 28

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Entry	Compd.	R¹	R²	R³	Yield^a/%	Dr^b
1	4a	Bn	H	H	88	18∶1
2	4b	Bn	H	3-OH	82	16∶1
3	4c	Bn	H	2-OMe	86	15∶1
4	4d	Bn	H	4-OH	87	16∶1
5	4e	Bn	H	3,4-(OMe)₂	85	>20∶1
6	4f	Bn	H	4-Br	86	9∶1
7	4g	Bn	H	4-NMe₂	83	>20∶1
8	4h	Bn	H	4-F	86	8∶1
9	4i	Bn	H	2-NO₂	86	>20∶1
10	4j	H	Bn	H	87	—^c
11	4k	H	Bn	2-OMe	87	—^c
12	4l	H	Bn	4-Cl	81	—^c
13	4m	H	Bn	3-OH	85	—^c
14	4n	H	Bn	2-NO₂	81	—^c
15	4o	H	Bn	4-NMe₂	82	—^c
16	4p	H	Bn	4-Br	80	—^c
17	4q	H	Bn	4-NO₂	80	—^c

Entry	Compd.	R¹	R²	R³	Yield^a/%	Dr^b
1	4a	Bn	H	H	88	18∶1
2	4b	Bn	H	3-OH	82	16∶1
3	4c	Bn	H	2-OMe	86	15∶1
4	4d	Bn	H	4-OH	87	16∶1
5	4e	Bn	H	3,4-(OMe)₂	85	>20∶1
6	4f	Bn	H	4-Br	86	9∶1
7	4g	Bn	H	4-NMe₂	83	>20∶1
8	4h	Bn	H	4-F	86	8∶1
9	4i	Bn	H	2-NO₂	86	>20∶1
10	4j	H	Bn	H	87	—^c
11	4k	H	Bn	2-OMe	87	—^c
12	4l	H	Bn	4-Cl	81	—^c
13	4m	H	Bn	3-OH	85	—^c
14	4n	H	Bn	2-NO₂	81	—^c
15	4o	H	Bn	4-NMe₂	82	—^c
16	4p	H	Bn	4-Br	80	—^c
17	4q	H	Bn	4-NO₂	80	—^c

Compd.	R¹	R²	R³	EC₅₀^a / (μmol?L^–1)	CC₅₀^b/ (μmol?L^–1)
4a	Bn	H	H	1.25	>20
4b	Bn	H	3-OH	>1.30	—^c
4c	Bn	H	2-OMe	0.20	>20
4d	Bn	H	4-OH	>1.30	—^c
4e	Bn	H	3,4-(OMe)₂	0.25	No^d
4f	Bn	H	4-Br	>1.30	No
4g	Bn	H	4-NMe₂	0.12	No
4h	Bn	H	4-F	>1.30	No
4i	Bn	H	2-NO₂	>1.30	>20
4j	H	Bn	H	1.50	>20
4k	H	Bn	2-OMe	0.28	No
4l	H	Bn	4-Cl	>1.3	>20
4m	H	Bn	3-OH	>1.3	—^c
4n	H	Bn	2-NO₂	>1.30	>20
4o	H	Bn	4-NMe₂	0.25	No
4p	H	Bn	4-Br	>1.3	>20
4q	H	Bn	4-NO₂	>1.30	>20
Ribavirin				1.30	5.08

Compd.	R¹	R²	R³	EC₅₀^a / (μmol?L^–1)	CC₅₀^b/ (μmol?L^–1)
4a	Bn	H	H	1.25	>20
4b	Bn	H	3-OH	>1.30	—^c
4c	Bn	H	2-OMe	0.20	>20
4d	Bn	H	4-OH	>1.30	—^c
4e	Bn	H	3,4-(OMe)₂	0.25	No^d
4f	Bn	H	4-Br	>1.30	No
4g	Bn	H	4-NMe₂	0.12	No
4h	Bn	H	4-F	>1.30	No
4i	Bn	H	2-NO₂	>1.30	>20
4j	H	Bn	H	1.50	>20
4k	H	Bn	2-OMe	0.28	No
4l	H	Bn	4-Cl	>1.3	>20
4m	H	Bn	3-OH	>1.3	—^c
4n	H	Bn	2-NO₂	>1.30	>20
4o	H	Bn	4-NMe₂	0.25	No
4p	H	Bn	4-Br	>1.3	>20
4q	H	Bn	4-NO₂	>1.30	>20
Ribavirin				1.30	5.08

“一锅”三组分合成新型1,5-苯并二氮杂䓬类化合物与抗牛病毒性腹泻病毒(BVDV)活性

One-Pot Three-Component Synthesis of Novel 1,5-Benzodiazepine Derivatives and Their anti-BVDV (Bovine Viral Diarrhea Virus) Activity

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References 28

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Entry	Catalyst^b	T/℃	Time/h	Yield^c/%
1	No	40	6	10
2	p-TSA	40	3	81
3	AcOH	40	3	73
4	CF₃CO₂H	40	3	69
5	HCl	40	3	60
6	H₂SO₄	40	3	53
7	CH₃SO₃H	40	3	65
8	HCO₂H	40	3	55
9	AlCl₃	40	3	41
10	FeCl₃	40	3	32
11	BF₃?Et₂O	40	3	30

Entry	Solvent	p-TSA/mol%	Time/h	Yield^b/%
1	No	20	5	5
2	H₂O	20	3	20
3	EtOH	20	3	81
4	Toluene	20	3	50
5	MeOH	20	3	71
6	i-PrOH	20	3	64
7	CH₃CN	20	3	52
8	THF	20	3	55
9	CHCl₃	20	3	61
10	DMF	20	3	46
11	Dioxane	20	3	58
12	EtOH	30	3	82
13	EtOH	15	3	81
14	EtOH	10	3	72