Synthesis of Mutisubstituted Dihydropyridino[1,2-a]benzimidazole Derivatives via Tandem Reaction of 2-Arylbenzimidazoles

doi:10.6023/cjoc202103036

Abstract

A new one-pot method for the synthesis of dihydropyridino[1,2-a]benzimidazole derivatives has been developed. Under the mediation of base and oxidant, mutisubstituted dihydropyridino[1,2-a]benzimidazoles were obtained in 38%~85% yields and 4∶1 to >25∶1 d.r. through a tandem intermolecular Michael addition/intramolecular Michael addition/ oxidative dehydrogenation process of 2-arylbenzimidazoles. The structures of these products were characterized by ¹H NMR, ¹³C NMR, HRMS, IR and single-crystal X-ray analysis.

Key words: tandem reaction, one-pot, dihydropyridino[1,2-a]benzimidazoles, addition reaction

Cite this article

Yuyu Guo, Xiangjie Chen, Shiwu Li, Zhihua Cai, Lin He. Synthesis of Mutisubstituted Dihydropyridino[1,2-a]benzimidazole Derivatives via Tandem Reaction of 2-Arylbenzimidazoles[J]. Chinese Journal of Organic Chemistry, 2021, 41(9): 3692-3700.

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References 12

[1]	(a) Zheng, Y.; Xie, Z.-Z.; Chen, K.; Xiang, H.-Y.; Yang, H. Chin. J. Org. Chem. 2021, 41, 1. (in Chinese). doi: 10.6023/cjoc202008037 pmid: 25255204
	( 郑雨, 谢珍珍, 陈凯, 向皞月, 阳华, 有机化学, 2021, 41, 1.) pmid: 25255204
	(b) Vitaku, E.; Smith, D. T.; Njardarson, J. T. J. Med. Chem. 2014, 57, 10257. doi: 10.1021/jm501100b pmid: 25255204
	(c) Reen, G. K.; Ahuja, M.; Kumar, A.; Patidar, R.; Sharma, P. Org. Prep. Proced. Int. 2017, 49, 273. doi: 10.1080/00304948.2017.1320927 pmid: 25255204
	(d) Praveen, C.; Nandakumar, A.; Dheenkumar, P.; Muralidharan, D.; Perumal, P. T. J. Chem. Sci. 2012, 124, 609. doi: 10.1007/s12039-012-0251-3 pmid: 25255204
[2]	(a) Nguyen, T. B.; Ermolenko, L.; Al-Mourabit, A. Green Chem. 2016, 18, 2966. doi: 10.1039/C6GC00902F pmid: 21644541
	(b) Takeshita, H.; Watanabe, J.; Kimura, Y.; Kawakami, K.; Takahashi, H.; Takemura, M.; Kitamura, A.; Someya, K.; Nakajima, R. Bioorg. Med. Chem. Lett. 2010, 20, 3893. doi: 10.1016/j.bmcl.2010.05.024 pmid: 21644541
	(c) Ndakala, A. J.; Gessner, Richard, K.; Gitari, P. W.; October, N.; White, K. L.; Hudson, A.; Fakorede, F.; Shackleford, D. M.; Kaiser, M.; Yeates, C.; Charman, S. A.; Chibale, K. J. Med. Chem. 2011, 54, 4581. doi: 10.1021/jm200227r pmid: 21644541
	(d) Gomha, S; Chem. Biol. Drug Des. 2015, 86, 1292. doi: 10.1111/cbdd.12593 pmid: 21644541
	(e) Huo, X.-Y.; Li, W.-B.; Zhang, B.-Y.; Chen, X.-F.; Zhou, Y.-T.; Zhang, J.; Han, X.-Q., Dai, B. Chin. J. Org. Chem. 2018, 38, 3356. (in Chinese). doi: 10.6023/cjoc201805053 pmid: 21644541
	( 霍新玉, 李文斌, 张博雅, 有机化学, 2018, 38, 3356.) pmid: 21644541
[3]	(a) Yang, K.; Yao, C.; Gao, J.-J.; Chen, S.-H., Zheng, X.-J.; Deng, L.-X.; Zhang, Y.-N.; Liu, M.-J.; Wang, Z.-Y. Chin. J. Org. Chem. 2020, 40, 4168. (in Chinese). doi: 10.6023/cjoc202005074
	( 杨凯, 姚辰, 高娟娟, 陈思鸿, 郑雪洁, 邓璐璇, 张毓娜, 刘美娟, 汪朝阳, 有机化学, 2020, 40, 4168.)
	(b) Kurva, M.; Pharande, S. G.; Quezada-Soto, A.; Gamez-Monta- no, R. Tetrahedron Lett. 2018, 59, 1596. doi: 10.1016/j.tetlet.2018.03.031
	(c) Ge, Y.-Q.; Jia, J.; Yang, H.; Tao, X.-T.; Wang, J.-W. Dyes Pigm. 2011, 88, 344. doi: 10.1016/j.dyepig.2010.08.005
	(d) Yang, H.; Ge, Y.-Q.; Jia, J.; Wang, J.-W. J. Lumin. 2011, 131, 749.
[4]	(a) Yan, H.; Guo, H.; Zhou, X.-Q.; Zuo, Z.-Y.; Liu, J.-L.; Zhang, G.-H.; Zhang, S. Synlett. 2019, 30, 1469. doi: 10.1055/s-0037-1611847 pmid: 26322501
	(b) Rasheed, S.; Rao, D. N.; Das, P. J. Org. Chem. 2015, 80, 9321. doi: 10.1021/acs.joc.5b01396 pmid: 26322501
	(c) Manna, S.; Matcha, K.; Antonchick, A. P. Angew. Chem., nt. Ed. 2014, 53, 8163. pmid: 26322501
	(d) Xie, Y.-J.; Wu, J.; Che, X.-Z.; Chen, Y.; Huang, H.-W.; Deng, G.-J. Green Chem. 2016, 18, 667. doi: 10.1039/C5GC01978H pmid: 26322501
[5]	(a) Cai, Q.; Li, Z. Q.; Wei, J. J.; Fu, L. B.; Ha, C. Y.; Pei, D. Q.; Ding, K. Org. Lett. 2010, 12, 1500. doi: 10.1021/ol1002225
	(b) Nagesh, H. N.; Suresh, A.; Reddy, M. N.; Suresh, N.; Subbalakshmi, J.; Sekhar, K. V. G. C. RSC Adv. 2016, 6, 15884. doi: 10.1039/C5RA24048D
	(c) Lyons, D. M.; Huttunen, K. M.; Browne, K. A.; Ciccone, A.; Trapani, J. A.; Denny, W. A.; Spicer, J. A. Bioorg. Med. Chem. 2011, 19, 4091. doi: 10.1016/j.bmc.2011.05.013
[6]	(a) Rustagi, V.; Aggarwal, T.; Verma, A. K. Green Chem. 2011, 13, 1640. doi: 10.1039/c1gc15346c
	(b) Ouyang, H.-C.; Tang, R.-Y.; Zhong, P.; Zhang, X.-G.; Li, J.-H. J. Org. Chem. 2011, 76, 223. doi: 10.1021/jo102060j
	(c) Chaitanya, T. K.; Prakash, K. S.; Nagarajan, R. Tetrahedron. 2011, 67, 6934. doi: 10.1016/j.tet.2011.06.076
	(d) Mishra, M.; Twardy, D.; Ellstrom, C.; Wheeler, K. A.; Dembinski, R.; Török, B. Green Chem. 2019, 21, 99. doi: 10.1039/C8GC02520G
[7]	(a) Teng, Q.-H.; Peng, X.-J.; Mo, Z.-Y.; Xu, Y.-L.; Tang, H.-T.; Wang, H.-S.; Sun, H.-B.; Pan, Y.-M. Green Chem. 2018, 20, 2007. doi: 10.1039/C8GC00069G
	(b) Thapa, P.; Palacios, P. M.; Tran, T.; Pierce, B. S.; Foss Jr, F. W. J. Org. Chem. 2020, 85, 1991. doi: 10.1021/acs.joc.9b02714
	(c) Sun, X.; Lv, X.-H.; Ye, L.-M; Hu, Y.; Chen, Y.-Y.; Zhang, X.-J.; Yan, M. Org. Biomol. Chem. 2015, 13, 7381. doi: 10.1039/C5OB00904A
	(d) Sun, X.; Hu, Y.; Nie, S.-Z.; Yan, Y.-Y.; Zhang, X.-J.; Yan, M. Adv. Synth. Catal. 2013, 355, 2179. doi: 10.1002/adsc.201300455
[8]	(a) Liu, L.; Yang, D.-Y.; He, Y.-H.; Guan, Z. J. Org. Chem. 2020, 85, 11892. doi: 10.1021/acs.joc.0c01688
	(b) Lu, C.; Su, Z.-S.; Jing, D.; Jin, S.-Y.; Xie, L.-J.; Li, L.-R.; Zheng, K. Org. Lett. 2019, 21, 1438. doi: 10.1021/acs.orglett.9b00191
	(c) Jing, D.; Lu, C.; Chen, Zh.; Jin, S.-Y.; Xie, L.-J.; Meng, Z.-Y.; Su, Z.-S.; Zheng, K. Angew. Chem., nt. Ed. 2019, 58, 14666.
	(d) Xue, D.; Long, Y. Q. J. Org. Chem. 2014, 79, 4727. doi: 10.1021/jo5005179
	(e) O'Connell, J. M.; Moriarty, E.; Aldabbagh, F. Synthesis 2012, 44, 3371. doi: 10.1055/s-00000084
[9]	(a) Wang, X.-B.; Jian, T.-Y., Ma, X.-W.; He, L. Chin. J. Org. Chem. 2012, 32, 2181. (in Chinese). doi: 10.6023/cjoc201205006
	( 王湘波, 简腾跃, 马晓伟, 何林, 有机化学, 2012, 32, 2181.)
	(b) Wang, W.-H.; Wan, H.-W.; Du, G.-F.; Dai, B.; He, L. Org. Lett. 2019, 21, 3496. doi: 10.1021/acs.orglett.9b00659
	(c) Pian, J.-X.; He, L.; Du, G.-F.; Guo, H.; Dai, B. J. Org. Chem. 2014, 79, 5820. doi: 10.1021/jo5003399
	(d) Wan, H.-W.; Yu, J.; Yang, S.-S.; Du, G.-F.; He, L. Chin. J. Org. Chem. 2019, 39, 2549. (in Chinese). doi: 10.6023/cjoc201902003
	( 万洪维, 于健, 杨寿山, 杜广芬, 何林, 有机化学, 2019, 39, 2549.)
[10]	CCDC 2054597 (2a) contains the supplementary crystallographic data for this paper. These data are free of charge from The Cambridge Crystallographic Centre via www.ccdc.cam.ac.uk/data_re- quest/cif.
[11]	Perin, N.; Alić, J.; Liekens, S.; Sandra, L.; Arthur, V. A.; Peter, V.; Bharat, G.; Marijana, H. New J. Chem. 2018, 42, 7096. doi: 10.1039/C8NJ00416A
[12]	Dubey, P. K.; Prasada Reddy, P. V. V. Synth. Commun. 2007, 37, 2259. doi: 10.1080/00397910701397177

Entry	Solvent	Base	Oxidant	Yield^b/%	d.r.^c
1	THF	KOH	MnO₂	36	>25∶1
2	THF	DBU	MnO₂	58	>25∶1
3	THF	t-BuOK	MnO₂	37	>25∶1
4	THF	TBD	MnO₂	66	>25∶1
5	THF	DBN	MnO₂	71	>25∶1
6	THF	DABCO	MnO₂	N.R.	/
7	THF	DBN	H₂O₂	N.R.	/
8	THF	DBN	NaClO	9	>25∶1
9	THF	DBN	KMnO₄	Trace	/
10	THF	DBN	O₂	Trace	/
11	THF	DBN	KClO₃	16	>25∶1
12	THF	DBN	K₂Cr₂O₇	51	>25∶1
13	Toluene	DBN	MnO₂	Trace	/
14	CH₃OH	DBN	MnO₂	16	>25∶1
15	DMSO	DBN	MnO₂	76	>25∶1
16	CH₃CN	DBN	MnO₂	65	>25∶1
17	CH₂Cl₂	DBN	MnO₂	65	>25∶1
18	DMF	DBN	MnO₂	67	>25∶1
19	DCE	DBN	MnO₂	63	>25∶1
20	DMSO	DBN	MnO₂ (15.0 equiv.)	83	>25∶1
21	DMSO	DBN	MnO₂ (10.0 equiv.)	79	>25∶1
22	DMSO	DBN	MnO₂ (5.0 equiv.)	77	>25∶1
23	DMSO	DBN (0. 5 equiv.)	MnO₂ (15.0 equiv.)	76	>25∶1
24	DMSO	DBN (1. 5 equiv.)	MnO₂ (15.0 equiv.)	71	>25∶1
25^d	DMSO	DBN	MnO₂ (15.0 equiv.)	56	>25∶1

Entry	Solvent	Base	Oxidant	Yield^b/%	d.r.^c
1	THF	KOH	MnO₂	36	>25∶1
2	THF	DBU	MnO₂	58	>25∶1
3	THF	t-BuOK	MnO₂	37	>25∶1
4	THF	TBD	MnO₂	66	>25∶1
5	THF	DBN	MnO₂	71	>25∶1
6	THF	DABCO	MnO₂	N.R.	/
7	THF	DBN	H₂O₂	N.R.	/
8	THF	DBN	NaClO	9	>25∶1
9	THF	DBN	KMnO₄	Trace	/
10	THF	DBN	O₂	Trace	/
11	THF	DBN	KClO₃	16	>25∶1
12	THF	DBN	K₂Cr₂O₇	51	>25∶1
13	Toluene	DBN	MnO₂	Trace	/
14	CH₃OH	DBN	MnO₂	16	>25∶1
15	DMSO	DBN	MnO₂	76	>25∶1
16	CH₃CN	DBN	MnO₂	65	>25∶1
17	CH₂Cl₂	DBN	MnO₂	65	>25∶1
18	DMF	DBN	MnO₂	67	>25∶1
19	DCE	DBN	MnO₂	63	>25∶1
20	DMSO	DBN	MnO₂ (15.0 equiv.)	83	>25∶1
21	DMSO	DBN	MnO₂ (10.0 equiv.)	79	>25∶1
22	DMSO	DBN	MnO₂ (5.0 equiv.)	77	>25∶1
23	DMSO	DBN (0. 5 equiv.)	MnO₂ (15.0 equiv.)	76	>25∶1
24	DMSO	DBN (1. 5 equiv.)	MnO₂ (15.0 equiv.)	71	>25∶1
25^d	DMSO	DBN	MnO₂ (15.0 equiv.)	56	>25∶1

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2-芳基乙烯苯并咪唑串联反应合成多取代二氢吡啶并[1,2-a]苯并咪唑衍生物