有机碱驱动合成多取代苯并[b]噻吩-4-醇类化合物

doi:10.6023/cjoc202508019

摘要/Abstract

多取代苯并[b]噻吩骨架是一类重要的合成中间体. 以3-取代基-1-噻吩基-2-丙烯-1-酮类化合物和硝基烷烃类化合物为底物, 通过有机碱驱动环合反应合成了一系列多取代苯并[b]噻吩-4-醇类化合物. 实验结果表明, 最佳实验条件如下: 以2.5 mmol 1,8-二氮杂二环[5.4.0]十一碳-7-烯(DBU)为碱, 1.0 mmol 3-取代基-1-噻吩基-2-丙烯-1-酮类化合物和1.2 mmol硝基烷烃化合物为底物, 在N,N-二甲基甲酰胺(DMF)溶剂中于常温下反应8 h, 合成了一系列多取代苯并[b]噻吩-4-醇类化合物, 产率高达88%. 产物结构经¹H NMR、¹³C NMR以及HRMS (ESI)分析确证, 并对该反应合成机理进行了探讨. 该合成方法具有条件温和、实用高效的特点.

关键词: 有机碱驱动, 苯并[b]噻吩, 合成

Multi-substituted benzo[b]thiophene skeleton is an important synthetic intermediate. A series of multi-substituted benzo[b]thiophene-4-ol derivatives were successfully constructed from 3-substituted 1-(thiophen-3-yl)prop-2-en-1-one and nitroso compound via organobase‑promoted cycloaddition reactions. Optimization experiments showed that the best expe- rimental conditions were as follows: using 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) (2.5 mmol) as base, 3-substituted 1-(thiophen-3-yl)prop-2-en-1-one (1.0 mmol) and nitroso compound (1.2 mmol) reacted in N,N-dimethylformamide (DMF) at room temperature for 8 h, affording multi-substituted benzo[b]thiophen-4-ol derivatives in 88% yield. The compositions and structures have been characterized by ¹H NMR, ¹³C NMR and HRMS (ESI). The mechanism for the reaction was proposed. The menthod has the characteristics of mild conditions and practical efficiency.

Key words: organobase-promoted, benzo[b]thiophene, synthesis

引用此文

任传清, 李欣欣, 郭家伟, 季晓晖, 刘波. 有机碱驱动合成多取代苯并[b]噻吩-4-醇类化合物[J]. 有机化学, 2026, 46(5): 2090-2095.

Chuanqing Ren, Xinxin Li, Jiawei Guo, Xiaohui Ji, Bo Liu. Synthesis of Multi-Substituted Benzo[b]thiophene-4-ol Derivatives Promoted by Organobase[J]. Chinese Journal of Organic Chemistry, 2026, 46(5): 2090-2095.

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参考文献 37

[1]	Singh P. P.; Yadav A. K.; Ila H.; Junjappa H. J. Org. Chem. 2009, 74, 5496. doi: 10.1021/jo900615p
[2]	Sandhya N. C.; Nandeesh K. N.; Rangappa K. S.; Ananda S. RSC Adv. 2015, 5, 29939. doi: 10.1039/C5RA02114F
[3]	Dillon C. C.; Keophimphone B.; Sanchez M.; Kaura P.; Muchalski H. Org. Biomol. Chem. 2018, 16, 9279. doi: 10.1039/C8OB02196A
[4]	Aleksić M.; Bertoša B.; Nhili R.; Uzelac L.; Jarak I.; Depauw S.; David-Cordonnier M.-H.; Kralj M.; Tomić S.; Karminski- Zamola G. J. Med. Chem. 2012, 55, 5044. doi: 10.1021/jm300505h pmid: 22620261
[5]	Chen J. W.; Xiang H. F.; Yang L.; Zhou X. G. RSC Adv. 2017, 7, 7753. doi: 10.1039/C6RA26611H
[6]	Dhage Y. D.; Daimon H.; Peng C.; Kusakabe T.; Takahashi K.; Kanno Y.; Inouyea Y.; Kato K. Org. Biomol. Chem. 2014, 12, 8619. doi: 10.1039/C4OB01576B
[7]	Inamoto K.; Arai Y.; Hiroya K.; Doi T. Chem. Commun. 2008, 43, 5529.
[8]	Qing L. L.; Yu Q. Y.; Wang C. Q.; Lu X.; Yang Y. L.; Chen X.; Li X. X.; Min J.; Pan W. D.; He H.; Zhong H.; Zhang S. L. J. Med. Chem. 2025, 68, 1619. doi: 10.1021/acs.jmedchem.4c02269
[9]	Williams D. R.; Iv L. T.; Miter G. A.; Sheiman J. L.; Wallace J. M.; Allen M. R.; Kohler R.; Medeiros C. ACS Med. Chem. Lett. 2024, 15, 879. doi: 10.1021/acsmedchemlett.4c00078 pmid: 38894928
[10]	Croxtall J. D.; Plosker G. L. Drugs 2009, 69, 339. doi: 10.2165/00003495-200969030-00009 pmid: 19275277
[11]	Mota C.; Diniz A.; Coelho, C.; Silva T. S.; Esmaeeli M.; Leim- kühler S.; Cabrita E. J.; Marcelo F.; Romão M. J. J. Med. Chem. 2021, 64, 13025. doi: 10.1021/acs.jmedchem.1c01125
[12]	Zhang L. M.; Si X. J.; Rominger F.; Hashmi A. S. K. J. Am. Chem. Soc. 2020, 142, 10485. doi: 10.1021/jacs.0c03197
[13]	Roy S.; Budhathoki S.; Iqbal A. D.; Erickson A. N.; Ali M. A.; Alam M. A. J. Org. Chem. 2024, 89, 3781. doi: 10.1021/acs.joc.3c02646
[14]	Rist P. A.; Grainger R. S.; Davies P. W. Org. Lett. 2021, 23, 642. doi: 10.1021/acs.orglett.0c03596
[15]	Efange S. M. N.; Mash D. C.; Khare A. B.; Ouyang Q. J. Med. Chem. 1998, 41, 4486. pmid: 9804688
[16]	González J.; Cavelli M.; Zaballa, S. C.; Mondino A.; Tort A. B. L.; Rubido N.; Carrera I.; Torterolo P. ACS Pharmacol. Transl. 2021, 4, 517.
[17]	Ohshita J.; Lee K.-H.; Kimura K.; Kunai A. Organometallics 2004, 23, 5622. doi: 10.1021/om049656h
[18]	Ebata H.; Miyazaki E.; Yamamoto T.; Takimiya K. Org. Lett. 2007, 9, 4499. doi: 10.1021/ol701815j
[19]	Alzahrani A. Y. A.; Ghoneim A. A.; Farargy A. F. E. Polycyclic Aromat. Compd. 2024, 44, 4895. doi: 10.1080/10406638.2023.2258256
[20]	Jiang W.; Li Y.; Wang Z. Chem. Soc. Rev. 2013, 42, 6113. doi: 10.1039/c3cs60108k pmid: 23628866
[21]	Janni M.; Thirupathi A.; Aroraa S.; Peruncheralathan S. Chem. Commun. 2017, 53, 8439. doi: 10.1039/C7CC03273K
[22]	Tréguier B.; Lawson M.; Bernadat G.; Bignon J.; Dubois J.; Brion J. D.; Alami M.; Hamze A. ACS Comb. Sci. 2014, 16, 702. doi: 10.1021/co500115b pmid: 25229390
[23]	Xing H. C.; Xie P. Z. Chin. J. Org. Chem. 2021, 43, 431 (in Chinese). doi: 10.1002/cjoc.v43.4
	(邢慧聪, 解沛忠, 有机化学, 2021, 41, 431.)
[24]	Cheng H. C.; Guo P. H.; Chen B.; Yao J. W.; Ma J. L.; Hu W. J.; Ji H. B. Chin. J. Org. Chem. 2021, 41, 94 (in Chinese). doi: 10.6023/cjoc202006032
	(程辉成, 郭鹏虎, 陈冰, 姚嘉伟, 马姣丽, 胡炜杰, 纪红兵, 有机化学, 2021, 41, 94.)
[25]	Yu H.; Zhang M. S.; Li Y. Z. J. Org. Chem. 2013, 78, 8898. doi: 10.1021/jo401353w
[26]	Perin G.; Soares L. K.; Hellwig P. S.; Silva M. S.; Neto J. S. S.; Roehrs J. A.; Thiago B. T.; Lenardão E. J. New J. Chem. 2019, 43, 6323. doi: 10.1039/C9NJ00526A
[27]	Ulyankin E. B.; Kostyuchenko A. B.; Chernenko S. A.; Mikhail O.; Bystrushkin M. Q.; Samsonenko A. L.; Shatsauskas A. L.; Fisyuk A. S. Synthesis 2021, 53, 2422. doi: 10.1055/a-1416-4924
[28]	Duc D, X. Curr. Org. Chem. 2020, 24, 2256.
[29]	Kim J.; Jung Y. K.; Kim C.; Shin J. S. Scheers E.; Lee J. Y.; Jung Y. S. Med. Chem. 2017, 60, 5472. doi: 10.1021/acs.jmedchem.7b00175
[30]	Wang M.; Fu Z. Q.; Feng H.; Dong Y.; Liu J.; Liu Q. Chem. Commun. 2010, 46, 9016. doi: 10.1039/C0CC03575K
[31]	Zhang L.; Liang F. S.; Cheng X.; Liu Q. J. Org. Chem. 2009, 74, 899. doi: 10.1021/jo802318p pmid: 19053616
[32]	Wang M. Y.; Ren C. Q.; Ji X. H.; Cao X. Y.; Liu B. Chem. Res. Appl. 2024, 36, 432 (in Chinese).
	(王梦圆, 任传清, 季晓晖, 曹小燕, 刘波, 化学研究与应用, 2024, 36, 432.)
[33]	Wang H.; Zhao Y. L.; Ren C. Q.; Diallo A.; Liu Q. Chem. Commun. 2011, 47, 12316. doi: 10.1039/c1cc14916d
[34]	Ren C. Q.; Ji X. H.; Ji J. W.; Zhang Q.; Song J. Chin. J. Synth. Chem. 2021, 29, 430 (in Chinese).
	(任传清, 季晓晖, 季建伟, 张强, 宋娟, 合成化学, 2021, 29, 430.)
[35]	Ren C. Q.; Ji X. H.; Ji J. W.; Zhang Q. Chem. J. Chin. Univ. 2023, 44, 20230073 (in Chinese).
	(任传清, 季晓晖, 季建伟, 张强, 高等学校化学学报, 2023, 44, 20230073.) doi: 10.7503/cjcu20230073
[36]	Ren C. Q.; Zhang W.; Ji J. W.; Zhang Q. Chem. Res. Appl. 2020, 32, 1284 (in Chinese).
	(任传清, 张伟, 季建伟, 张强, 化学研究与应用, 2020, 32, 1284.)
[37]	Ren C. Q.; Ji X. H.; Zhang Q.; Cao X. Y.; Ji J. W.; Liu B. Chem. J. Chin. Univ. 2024, 45, 20240033 (in Chinese).
	(任传清, 季晓晖, 张强, 曹小燕, 季建伟, 刘波, 高等学校化学学报, 2024, 45(5), 20240033.)

Entry	Base (mmol)	Solvent	Temperature/℃	Time/h	Yield^b/%
1	K₂CO₃ (2.0)	DMF	r.t.	8	0
2	NaOH (2.0)	DMF	r.t.	8	21
3	DBU (2.0)	DMF	r.t.	8	78
4	DBU (2.1)	DMF	r.t.	8	80
5	DBU (2.2)	DMF	r.t.	8	81
6	DBU (2.5)	DMF	r.t.	8	84
7	DBU (3.0)	DMF	r.t.	8	82
8	N(C₂H₅)₃ (2.5)	DMF	r.t.	8	0
9	C₂H₅N[CH(CH₃)₂]₂ (2.5)	DMF	r.t.	8	0
10	C₅H₅N (2.5)	DMF	r.t.	8	56
11	DMAP (2.5)	DMF	r.t.	8	38
12	DBU (2.5)	CH₂Cl₂	r.t.	8	0
13	DBU (2.5)	DMSO	r.t.	8	79
14	DBU (2.5)	CH₃CH₂OH	r.t.	8	68
15	DBU (2.5)	DMF	r.t.	6	79
16	DBU (2.5)	DMF	r.t.	10	81
17	DBU (2.5)	DMF	40	8	82
18	DBU (2.5)	DMF	80	8	65

Entry	Base (mmol)	Solvent	Temperature/℃	Time/h	Yield^b/%
1	K₂CO₃ (2.0)	DMF	r.t.	8	0
2	NaOH (2.0)	DMF	r.t.	8	21
3	DBU (2.0)	DMF	r.t.	8	78
4	DBU (2.1)	DMF	r.t.	8	80
5	DBU (2.2)	DMF	r.t.	8	81
6	DBU (2.5)	DMF	r.t.	8	84
7	DBU (3.0)	DMF	r.t.	8	82
8	N(C₂H₅)₃ (2.5)	DMF	r.t.	8	0
9	C₂H₅N[CH(CH₃)₂]₂ (2.5)	DMF	r.t.	8	0
10	C₅H₅N (2.5)	DMF	r.t.	8	56
11	DMAP (2.5)	DMF	r.t.	8	38
12	DBU (2.5)	CH₂Cl₂	r.t.	8	0
13	DBU (2.5)	DMSO	r.t.	8	79
14	DBU (2.5)	CH₃CH₂OH	r.t.	8	68
15	DBU (2.5)	DMF	r.t.	6	79
16	DBU (2.5)	DMF	r.t.	10	81
17	DBU (2.5)	DMF	40	8	82
18	DBU (2.5)	DMF	80	8	65

Entry	Substrate	R¹	R²	R³	R⁴	Time/h	Product	Yield^b/%
1	1a	CN	Ph	CH₃CH₂	CH₃	8	2a	84
2	1b	CN	4-CH₃C₆H₄	CH₃CH₂	CH₃	8	2b	86
3	1c	CN	4-CH₃OC₆H₄	CH₃CH₂	CH₃	8	2c	87
4	1d	CN	4-CH₃CH₂OC₆H₄	CH₃CH₂	CH₃	8	2d	88
5	1e	CN	2-ClC₆H₄	CH₃CH₂	CH₃	10	2e	76
6	1f	CN	4-ClC₆H₄	CH₃CH₂	CH₃	10	2f	74
7	1g	CN	PhCH=CH	CH₃CH₂	CH₃	12	2g	72
8	1h	CN	3,4-O₂CH₂C₆H₃	CH₃CH₂	CH₃	10	2h	83
9	1i	CN	2-Thienyl	CH₃CH₂	CH₃	8.5	2i	71
10	1j	CN	2-Furyl	CH₃CH₂	CH₃	8.5	2j	73
11	1k	CN	t-Bu	CH₃CH₂	CH₃	10	2k	65
12	1l	COOC₂H₅	Ph	CH₃CH₂	CH₃	12	2l	81
13	1m	CN	Ph	CH₃	CH₃	8	2m	83
14	1n	CN	Ph	CH₃CH₂	CH₃CH₂	9	2n	80
15	1o	CN	4-CH₃OC₆H₄	CH₃CH₂	Ph	11	2o	68

Entry	Substrate	R¹	R²	R³	R⁴	Time/h	Product	Yield^b/%
1	1a	CN	Ph	CH₃CH₂	CH₃	8	2a	84
2	1b	CN	4-CH₃C₆H₄	CH₃CH₂	CH₃	8	2b	86
3	1c	CN	4-CH₃OC₆H₄	CH₃CH₂	CH₃	8	2c	87
4	1d	CN	4-CH₃CH₂OC₆H₄	CH₃CH₂	CH₃	8	2d	88
5	1e	CN	2-ClC₆H₄	CH₃CH₂	CH₃	10	2e	76
6	1f	CN	4-ClC₆H₄	CH₃CH₂	CH₃	10	2f	74
7	1g	CN	PhCH=CH	CH₃CH₂	CH₃	12	2g	72
8	1h	CN	3,4-O₂CH₂C₆H₃	CH₃CH₂	CH₃	10	2h	83
9	1i	CN	2-Thienyl	CH₃CH₂	CH₃	8.5	2i	71
10	1j	CN	2-Furyl	CH₃CH₂	CH₃	8.5	2j	73
11	1k	CN	t-Bu	CH₃CH₂	CH₃	10	2k	65
12	1l	COOC₂H₅	Ph	CH₃CH₂	CH₃	12	2l	81
13	1m	CN	Ph	CH₃	CH₃	8	2m	83
14	1n	CN	Ph	CH₃CH₂	CH₃CH₂	9	2n	80
15	1o	CN	4-CH₃OC₆H₄	CH₃CH₂	Ph	11	2o	68