Four-Component Hydroxythiolation of Styrenes with Imidazopyridines and Potassium Thiocyanate

doi:10.6023/cjoc202506001

Chinese Journal of Organic Chemistry ›› 2026, Vol. 46 ›› Issue (1): 181-188.DOI: 10.6023/cjoc202506001 Previous Articles Next Articles

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苯乙烯化合物与咪唑并吡啶化合物和硫氰化钾的四组分羟基/巯基化反应

王宇^a^,^†, 黄鸿坤^a^,^†, 凌春^a, 陈恬^b, 姚华^a^,^*(), 严兆华^a^,^*()

^a 南昌大学化学化工学院南昌 330031
^b 浙江车头制药股份有限公司浙江仙居 317321

收稿日期:2025-06-01 修回日期:2025-08-05 发布日期:2025-09-11
作者简介:
^† 共同第一作者
基金资助:
国家自然科学基金(21362022)

Four-Component Hydroxythiolation of Styrenes with Imidazopyridines and Potassium Thiocyanate

Yu Wang^a, Hongkun Huang^a, Chun Ling^a, Tian Chen^b, Hua Yao^a^,^*(), Zhaohua Yan^a^,^*()

^a College of Chemistry and Chemical Engineering, Nanchang University, Nanchang 330031
^b Zhejiang Charioteer Pharmaceutical Co., Ltd. Xianju, Zhejiang 317321

Received:2025-06-01 Revised:2025-08-05 Published:2025-09-11
Contact: * E-mail: hyao@ncu.edu.cn; yanzh@ncu.edu.cn
About author:
^† The authors contributed equally to this work
Supported by:
National Natural Science Foundation of China(21362022)

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Abstract

A highly efficient and green four-component difunctionalization of styrenes with KSCN and imidazo[1,2-a]pyri- dines was developed. In this protocol, readily available KSCN was used as a sulfur source and inexpensive K₂S₂O₈ was used as a free radical initiator. A series of C-3 thiolated imidazopyridine analogues were synthesized, in which hydroxyl group and aryl or alkyl group were incorporated. A novel method for the synthesis of multifunctionalized imidazopyridines was established.

Key words: difunctionalization, thiolation, imidazopyridines, styrenes, potassium thiocyanate

Cite this article

Yu Wang, Hongkun Huang, Chun Ling, Tian Chen, Hua Yao, Zhaohua Yan. Four-Component Hydroxythiolation of Styrenes with Imidazopyridines and Potassium Thiocyanate[J]. Chinese Journal of Organic Chemistry, 2026, 46(1): 181-188.

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Fig. & Tab. 7

References 28

[1]	Reen G. K.; Kumar A.; Sharma P. Beilstein J. Org. Chem. 2019, 15, 1612. doi: 10.3762/bjoc.15.165
[2]	(a) Singh M.; Malviya M.; Yadav V. B.; Nikhil A.; Gupta M. RSC Adv. 2024, 14, 5037. doi: 10.1039/D3RA07145F
	(b) Peytam F.; Emamgholipour Z.; Mousavi A.; Moradi M.; Foroumadi R.; Firoozpour L.; Divsalar F.; Safavi M.; Foroumadi A. Bioorg. Chem. 2023, 140, 106831. doi: 10.1016/j.bioorg.2023.106831
	(c) Volpi G.; Layrenti E.; Rabezzana R. Molecules 2024, 29, 2668. doi: 10.3390/molecules29112668
[3]	(a) Langer S.; Arbilla S.; Benavides J.; Scatton B. Adv. Biochem. Psychopharmacol. 1990, 46, 61. pmid: 1677245
	(b) George P.; Rossey H.; Depoortere H.; Mompon B.; Allen J. Farmaco 1991, 46, 277. pmid: 1677245
[4]	Chen C. L.; Chen Y. T.; Demchenko A. P.; Chou P. T. Nat. Rev. Chem. 2018, 2, 131.
[5]	Gayathri P.; Pannipara M.; Al-Sehemi A. G.; Anthony S. P. CrystEngComm 2021, 23, 3771. doi: 10.1039/D1CE00317H
[6]	Tali J. A.; Kumar G.; Sharma B. K.; Rasool Y.; Sharma R.; Shankar K. Org. Biomol. Chem. 2023, 21, 7267. doi: 10.1039/D3OB00849E
[7]	Tran C.; Hamze A. Molecules 2022, 27, 3461. doi: 10.3390/molecules27113461
[8]	Rawat R.; Verma S. M. Synth. Commun. 2020, 50, 3507. doi: 10.1080/00397911.2020.1803915
[9]	Shi L.; Li T.; Mei G.-J. Green Synth. Catal. 2022, 3, 227.
[10]	Tashrifi Z.; Mohammadi-Khanaposhtani M. Larijani B.; Mahdavi M. Eur. J. Org. Chem. 2020, 269.
[11]	(a) Patel O. P. S.; Nandwana N. K.; Legoabe L. J.; Das B.C.; Kumar A. Adv. Synth. Catal. 2020, 362, 4226. doi: 10.1002/adsc.v362.20
	(b) Hooshmand S. E.; Amini Z.; Shiri M.; Al-Harrasi A. J. Fluorescence 2024, 34, 1131. doi: 10.1007/s10895-023-03345-6
	(c) Bagdi, A. K.; Santra, S.; Monir, K.; Hajra, A. Chem. Commun. 2015, 51, 1555. doi: 10.1039/C4CC08495K
[12]	Deng J.-C.; Zhang J.-R.; Li M.-H.; Huang J.-C.; Lai Z. S.; Tong X. Y.; Cui Z. N.; Tang R. Y. Org. Biomol. Chem. 2019, 17, 7854. doi: 10.1039/C9OB01403A
[13]	Sun P.; Yang D.; Wei W.; Jiang M.; Wang Z.; Zhang L.; Zhang H.; Zhang Z.; Wang Y.; Wang H. Green Chem. 2017, 19, 4785. doi: 10.1039/C7GC01891F
[14]	Rahaman R.; Das S.; Barman P. Green Chem. 2018, 20, 141. doi: 10.1039/C7GC02906C
[15]	Yuan Y.; Cao Y.; Qiao J.; Lin Y.; Jiang X.; Weng Y.; Tang S.; Lei A. Chin. J. Chem. 2019, 37, 49. doi: 10.1002/cjoc.v37.1
[16]	Guo Y.-J.; Lu S.; Tian L. L.; Huang E. L.; Hao X.-Q.; Zhu X.; Shao T.; Song M. P. J. Org. Chem. 2018, 83, 338. doi: 10.1021/acs.joc.7b02734
[17]	Gao Y.-C.; Huang Z.-B.; Xu L.; Li Z.-D.; Lai Z.-S.; TanR. Y. Org. Biomol. Chem. 2019, 17, 2279. doi: 10.1039/C8OB03191F
[18]	Zhang J. R.; Liao Y. Y.; Deng J. C.; Feng K. Y.; Zhang M.; Ning Y. Y.; Lin Z. W.; Tang R. Y. Chem. Commun. 2017, 53, 7784. doi: 10.1039/C7CC03940A
[19]	Zhang J.; Xie S.; Liu P.; Sun P. Adv. Synth. Catal. 2020, 362, 2173. doi: 10.1002/adsc.v362.11
[20]	Neogi S.; Kumar Ghosh A.; Mandal S.; Ghosh D.; Ghosh S.; Hajra A. Org. Lett. 2021, 23, 6510. doi: 10.1021/acs.orglett.1c02322
[21]	Tang Q.; Yin X.; Kuchukulla R. R.; Zeng Q. Chem. Rec. 2021, 21, 893. doi: 10.1002/tcr.v21.4
[22]	Zhu F.; Yan Z.; Ai C.; Wang Y.; Lin S. Eur. J. Org. Chem. 2019, 6561.
[23]	Wen J.; Niu C.; Yan K.; Cheng X.; Gong R.; Li M.; Guo G.; Yang J.; Wang H. Green Chem. 2020, 22, 1129. doi: 10.1039/C9GC04068D
[24]	Lin Q.; Yang W.; Yao Y.; Chen S.; Tan Y.; Chen D.; Yang D. Org. Lett. 2019, 21, 7244. doi: 10.1021/acs.orglett.9b02452
[25]	Dey A.; Haira A. Org. Lett. 2019, 21, 1686. doi: 10.1021/acs.orglett.9b00245
[26]	Liu X.; Hao L.; Wang Y.; Ji Y. Chem.-Asian J. 2024, 19, e202300901.
[27]	(a) Yang D.; Yan K.; Wei W.; Li G.; Lu S.; Zhao C.; Tian L.; Wang H. J. Org. Chem. 2015, 80, 11073. doi: 10.1021/acs.joc.5b01637
	(b) Zhu Y.-S.; Xue Y.; Liu W.; Zhu X.; Hao X.-Q.; Song M.-P. J. Org. Chem. 2020, 85, 9106. doi: 10.1021/acs.joc.0c01035
[28]	Godugu K.; Nallagondu C. G. R. J. Heterocycl. Chem. 2021, 58, 259.

Entry	Oxidant (equiv.)	Solvent (mL)	Temp./℃	Yield^b/%
1	DTBP (1.5)	DCE (2)	80	42
2	TBHP (1.5)	DCE (2)	80	0
3	H₂O₂ (1.5)	DCE (2)	80	0
4	DCP (1.5)	DCE (2)	80	0
5	CHP (1.5)	DCE (2)	80	0
6	Na₂S₂O₈ (1.5)	DCE (2)	80	51
7	K₂S₂O₈ (1.5)	DCE (2)	80	63
8	None	DCE (2)	80	Trace
9	K₂S₂O₈ (1.5)	MeCN (2)	80	66
10	K₂S₂O₈ (1.5)	PhCl (2)	80	31
11	K₂S₂O₈ (1.5)	EtOH (2)	80	22
12	K₂S₂O₈ (1.5)	MeCNH₂O (2/1)	80	53
13	K₂S₂O₈ (1.5)	DMSO (2)	80	0
14	K₂S₂O₈ (1.5)	DMSO/H₂O (1/1)	80	70
15	K₂S₂O₈ (1.5)	DMSO/H₂O (2/1)	80	72
16	K₂S₂O₈ (2.0)	DMSO/H₂O (2/1)	80	76
17	K₂S₂O₈ (3.0)	DMSO/H₂O (2/1)	80	85
18	K₂S₂O₈ (4.0)	DMSO/H₂O (2/1)	80	80
19	K₂S₂O₈ (3.0)	DMSO/H₂O (2/1)	70	69
20^c	K₂S₂O₈ (3.0)	DMSO/H₂O (2/1)	90	90
21	K₂S₂O₈ (3.0)	DMSO/H₂O (2/1)	100	84

Entry	Oxidant (equiv.)	Solvent (mL)	Temp./℃	Yield^b/%
1	DTBP (1.5)	DCE (2)	80	42
2	TBHP (1.5)	DCE (2)	80	0
3	H₂O₂ (1.5)	DCE (2)	80	0
4	DCP (1.5)	DCE (2)	80	0
5	CHP (1.5)	DCE (2)	80	0
6	Na₂S₂O₈ (1.5)	DCE (2)	80	51
7	K₂S₂O₈ (1.5)	DCE (2)	80	63
8	None	DCE (2)	80	Trace
9	K₂S₂O₈ (1.5)	MeCN (2)	80	66
10	K₂S₂O₈ (1.5)	PhCl (2)	80	31
11	K₂S₂O₈ (1.5)	EtOH (2)	80	22
12	K₂S₂O₈ (1.5)	MeCNH₂O (2/1)	80	53
13	K₂S₂O₈ (1.5)	DMSO (2)	80	0
14	K₂S₂O₈ (1.5)	DMSO/H₂O (1/1)	80	70
15	K₂S₂O₈ (1.5)	DMSO/H₂O (2/1)	80	72
16	K₂S₂O₈ (2.0)	DMSO/H₂O (2/1)	80	76
17	K₂S₂O₈ (3.0)	DMSO/H₂O (2/1)	80	85
18	K₂S₂O₈ (4.0)	DMSO/H₂O (2/1)	80	80
19	K₂S₂O₈ (3.0)	DMSO/H₂O (2/1)	70	69
20^c	K₂S₂O₈ (3.0)	DMSO/H₂O (2/1)	90	90
21	K₂S₂O₈ (3.0)	DMSO/H₂O (2/1)	100	84

苯乙烯化合物与咪唑并吡啶化合物和硫氰化钾的四组分羟基/巯基化反应

Four-Component Hydroxythiolation of Styrenes with Imidazopyridines and Potassium Thiocyanate

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