Selective Synthesis of Unsymmetrical N-Heteroaryl Thioethers byBase-Free Direct Multi-Component Reaction

doi:10.6023/cjoc202008030

Chinese Journal of Organic Chemistry ›› 2021, Vol. 41 ›› Issue (3): 1193-1199.DOI: 10.6023/cjoc202008030 Previous Articles Next Articles

ARTICLES

无碱条件下直接多组分反应选择性合成非对称含氮杂芳基硫醚

王琦^a, 朱柏燃^a, 杨光^a, 马献涛^a^,^b^,^*(), 徐清^a^,^c^,^*()

a 扬州大学化学化工学院江苏扬州 225002
b 信阳师范学院化学化工学院河南信阳 464000
c 温州大学化学与材料工程学院浙江温州 325035

收稿日期:2020-08-17 修回日期:2020-10-04 发布日期:2020-10-28
通讯作者: 马献涛, 徐清
基金资助:
国家自然科学基金(21672163); 扬州大学研究生科研创新计划(XKYCX19_064); 河南省科技攻关(192102310031)

Selective Synthesis of Unsymmetrical N-Heteroaryl Thioethers byBase-Free Direct Multi-Component Reaction

Qi Wang^a, Boran Zhu^a, Guang Yang^a, Xiantao Ma^a^,^b^,^*(), Qing Xu^a^,^c^,^*()

a School of Chemistry and Chemical Engineering, Yangzhou University, Yangzhou, Jiangsu 225002
b College of Chemistry and Chemical Engineering, Xinyang Normal University, Xinyang, Henan 464000
c College of Chemistry and Materials Engineering, Wenzhou University, Wenzhou, Zhejiang 325035

Received:2020-08-17 Revised:2020-10-04 Published:2020-10-28
Contact: Xiantao Ma, Qing Xu
About author:
* Corresponding authors. E-mail: xiantaoma@126.com;
xuqing@yzu.edu.cn, qing-xu@wzu.edu.cn
Supported by:
National Natural Science Foundation of China(21672163); Graduate Research and Innovation Program of Yangzhou University(XKYCX19_064); Key Scientific and Technological Project of Henan Province(192102310031)

Heteroaryl thioethers, especially alkyl heteroaryl thioethers, were usually obtained by catalytic or non-catalytic coupling reactions under strong basic conditions, but these methods usually have many drawbacks such as generation of large amounts of wastes. In this work, a new method for the direct synthesis of N-heteroaryl thioethers through a base-, additive-, and solvent-free one-pot multi-component reaction of N-heteroaryl halides, thiourea, and alkyl bromides was reported. This method can employ thiourea as the sulfur surrogate and tolerate various alkyl bromides and N-heteroaryl halides, providing a concise, selective, and efficient new method for heteroaryl thioether synthesis.

Key words: N-heteroaryl thioethers, base-free, thiourea, sulfur transfer, multi-component reaction

Cite this article

Qi Wang, Boran Zhu, Guang Yang, Xiantao Ma, Qing Xu. Selective Synthesis of Unsymmetrical N-Heteroaryl Thioethers byBase-Free Direct Multi-Component Reaction[J]. Chinese Journal of Organic Chemistry, 2021, 41(3): 1193-1199.

Export EndNote|Reference Manager|ProCite|BibTeX|RefWorks

share this article

Fig. & Tab. 5

References 17

[1]	(a) Xu, X.; Li, C.; Xiong, M.; Tao, Z.; Pan, Y. Chem. Commun. 2017, 53, 6219. pmid: 15598559
	(b) Niazi, M.; Shahsavari, H. R.; Haghighi, M. G.; Halvagar, M. R.; Hatami, S.; Notash, B. RSC Adv. 2016, 6, 95073. pmid: 15598559
	(c) Tasker, S. Z.; Bosscher, M. A.; Shandro, C. A.; Lanni, E. L.; Ryu, K. A.; Snapper, G. S.; Utter, J. M.; Ellsworth, B. A.; Anderson, C. E. J. Org. Chem. 2012, 77, 8220. pmid: 15598559
	(d) Xie, Y.; Zhou, B.; Zhou, S.; Zhou, S.; Wei, W.; Liu, J.; Zhan, Y.; Cheng, D.; Chen, M.; Li, Y.; Wang, B.; Xue, X.-S.; Li, Z. ChemistrySelect 2017, 2, 1620. doi: 10.1002/slct.201700132 pmid: 15598559
	(e) Ye, X.; Moeljadi, A. M.; Chin, K. F.; Hirao, H.; Zong, L.; Tan, C. H. Angew. Chem. Int. Ed. 2016, 55, 7101. doi: 10.1002/anie.201601574 pmid: 15598559
	(f) Seto, M.; Miyamoto, N.; Aikawa, K.; Aramaki, Y.; Kanzaki, N.; Iizawa, Y.; Baba, M.; Shiraishi, M. Bioorg. Med. Chem. 2005, 13, 363. pmid: 15598559
	(g) Dai, W.; Shang, S.; Lv, Y.; Li, G.; Li, C.; Gao, S. ACS Catal. 2017, 7, 4890. pmid: 15598559
	(h) Sun, F.; Liu, X.; Chen, X.; Qian, C.; Ge, X. Chin. J. Org. Chem. 2017, 37, 2211. (in Chinese) pmid: 15598559
	(孙丰莉, 刘学民, 陈新志, 钱超, 葛新, 有机化学, 2017, 37, 2211.) pmid: 15598559
	(i) Tang, H.; Luo, J.; Xie, P. Chin. J. Org. Chem. 2019, 39, 2735. (in Chinese) pmid: 15598559
	(唐灏, 骆钧飞, 解攀, 有机化学, 2019, 39, 2735.) pmid: 15598559
	(j) Huang, B.; Li, X.; Luo, J.; Luo, Z.; Tan, M. Chin. J. Org. Chem. 2019, 39, 617. (in Chinese) pmid: 15598559
	(黄国保, 李秀英, 罗金荣, 罗志辉, 谭明雄, 有机化学, 2019, 39, 617.) pmid: 15598559
[2]	(a) Molaei, S.; Tamoradi, T.; Ghadermazi, M.; Ghorbani-Choghamarani, A. Polyhedron 2018, 156, 35. doi: 10.1016/j.poly.2018.09.014 pmid: 25505857
	(b) Garnier, T.; Danel, M.; Magne, V.; Pujol, A.; Beneteau, V; Pale, P; Chassaing, S. J. Org. Chem. 2018, 83, 6408. pmid: 25505857
	(c) Baker, A.; Graz, M.; Saunders, R.; Evans, G. J. S.; Pitotti, I.; Wirth, T. J. Flow Chem. 2015, 5, 65. doi: 10.1556/1846.2015.00009 pmid: 25505857
	(d) Guo, F.-J.; Sun, J.; Xu, Z.-Q.; Kühn, F. E.; Zang, S.-L.; Zhou, M.-D. Catal. Commun. 2017, 96, 11. pmid: 25505857
	(e) Manivel, P.; Prabakaran, K.; Krishnakumar, V.; Maxivalagan, T. Ind. Eng. Chem. Res. 2014, 53, 7866. pmid: 25505857
	(f) Zhao, J.; Fang, H.; Han, J.; Pan, Y.; Li, G. Adv. Synth. Catal. 2014, 356, 2719. pmid: 25505857
[3]	(a) Gholinejad, M.; Karimi, B.; Mansouri, F. J. Mol. Catal. A: Chem. 2014, 386, 20. pmid: 25298227
	(b) Bhardwaj, M.; Sahi, S.; Mahajan, H.; Paul, S.; Clark, J. H. J. Mol. Catal. A: Chem. 2015, 408, 48. pmid: 25298227
	(c) Ichiishi, N.; Malapit, C. A.; Wozniak, L.; Sanford, M. S. Org. Lett. 2018, 20, 44. pmid: 25298227
	(d) Legarda, P. D.; García-Rubia, A.; Gómez Arrayás, R.; Carretero, J. C. Adv. Synth. Catal. 2016, 358, 1065. pmid: 25298227
	(e) Mao, J.; Jia, T.; Frensch, G.; Walsh, P. J. Org. Lett. 2014, 16, 5304. pmid: 25298227
	(f) Lu, G.; Cai, C. RSC Adv. 2014, 4, 59990. pmid: 25298227
	(g) Hajipour, A. R.; Hosseinia, S. M.; Jaiamia, S. New J. Chem. 2017, 41, 7447. pmid: 25298227
	(h) Hajipour, A. R.; Hosseinia, S. M.; Jaiamia, S. ChemistrySelect 2017, 2, 2388. pmid: 25298227
[4]	(a) Goriya, Y.; Ramana, C. V. Tetrahedron 2010, 66, 7642. b6ad49d1-996f-4a5e-848d-447b5a893994 doi: 10.1016/j.tet.2010.07.032
	(b) Sreedhar, B.; Reddy, P.; Reddy, M. Synthesis 2009,1732.
[5]	(a) Niu, H. Y.; Xia, C.; Qu, G. R.; Wu, S.; Jiang, Y.; Jin, X.; Guo, H. M. Asian J. Chem. 2012, 7, 45. pmid: 25298227
	(b) Mondal, J.; Modak, A.; Dutta, A.; Basu, S.; Jha, S. N.; Bhattacharyya, D.; Bhaumik, A. Chem. Commun. 2012, 48, 8000. pmid: 25298227
	(c) Gholinejad, M.; Karimi, B.; Mansouri, F. J. Mol. Catal. A: Chem. 2014, 386, 20. pmid: 25298227
	(d) Bhardwaj, M.; Sahi, S.; Mahajan, H.; Paul, S.; Clark, J. H. J. Mol. Catal. A: Chem. 2015, 408, 48. pmid: 25298227
	(e) Mao, J.; Jia, T.; Frensch, G.; Walsh, P. J. Org. Lett. 2014, 16, 5304. pmid: 25298227
[6]	(a) Goriya, Y.; Ramana, C. V. Tetrahedron 2010, 66.7642. pmid: 20420378
	(b) Naeimi, H.; Moradian, M. Synlett 2012,2223. pmid: 20420378
	(c) Duan, Z.; Ranjit, S.; Liu, X. Org. Lett. 2010, 12, 2430. pmid: 20420378
	(d) Screedhar, B.; Reddy, P. S.; Reddy, M. A.; Synthesis 2009,1732. pmid: 20420378
	(e) Guo, F.; He, X.; Wang, J.; Sun, J.; Zhou, M. Chin. J. Org. Chem. 2017, 37, 1556. (in Chinese) pmid: 20420378
	(郭芳杰, 何雨轩, 王景芸, 孙京, 周明东, 有机化学, 2017, 37, 1556.) pmid: 20420378
[7]	Bagley, M. C.; Fusillo, V.; Hills, E. G. B.; Mulholland, A. T.; Newcombe, J.; Pentecost, L. J.; Radley, E. L.; Stephens, B. R.; Turrella, C. C. ARKIVOC, 2012, vii, 294. pmid: 17680032
[8]	(a) Liu, H.; Jiang, X. Chem. Asian J. 2013, 8, 2546. pmid: 28177013
	(b) Nguyen, T. B. Adv. Synth. Catal. 2017, 359, 1066. pmid: 28177013
	(c) Wang, N.; Saidhareddy, P.; Jiang, X. Nat. Prod. Rep. 2020, 37, 246. pmid: 28177013
	(d) Distler, H. Angew. Chem. Int. Ed. 1967, 6, 544. pmid: 28177013
	(e) Qiao, Z.; Jiang, X. Org. Biomol. Chem. 2017, 15, 1942. pmid: 28177013
	(f) Cheng, L.; Ge, X.; Liu, X.; Feng, Y. Chin. J. Org. Chem. 2020, 40, 2008. (in Chinese) pmid: 28177013
	(成琳, 葛新, 刘学民, 冯云辉, 有机化学, 2020, 40, 2008.) pmid: 28177013
[9]	(a) Jia, X.; Yu, L.; Liu, J.; Xu, Q.; Sickert, M.; Chen, L.; Lautens, M. Green Chem. 2014, 16, 3444. pmid: 19319207
	(b) Ma, X.; Liu, Q.; Jia, X.; Su, C.; Xu, Q. RSC Adv. 2016, 6, 56930. pmid: 19319207
	(c) Yang, Y.; Ye, Z.; Zhang, X.; Zhou, Y.; Ma, X.; Cao, H.; Li, H.; Yu, L.; Xu, Q. Org. Biomol. Chem. 2017, 15, 9638. pmid: 19319207
	(d) Liu, C.; Zang, X.; Yu, B.; Yu, X.; Xu, Q. Synlett 2011,143. pmid: 19319207
[10]	(a) Ma, X.; Yu, L.; Su, C.; Yang, Y.; Li, H.; Xu, Q. Adv. Synth. Catal. 2017, 359, 1649. pmid: 31393123
	(b) Ma, X.; Yu, J.; Yan, R.; Xu, Q. J. Org. Chem. 2019, 84, 11294. pmid: 31393123
[11]	In our previous work, it has been observed that the contaminant water in the substrates and the reaction vessel (Ref. [10a]) and even the crystal water (Ref. [10b]) can facilitate the sulfur transfer reactions. As having been discussed (Ref. [10] and references cited therein), water plays a key role in the reaction mechanism by hydrolyzing the in situ generated ionic intermediates (such as 4 and 6 in this work, Scheme 3) to the corresponding thiols. However, in this work, addition of water to the reactions of other alkyl halides mostly led to reduce the yields of products. This may be due to the easy hydrolysis of the alkyl halides in the presence of water. This may also mean that, in this work, the contaminant water in the substrates and the reaction vessel is adequate to facilitate the reactions and thus no additional water is needed.
[12]	Brussaard, Y.; Olbrich, F.; Schaumann, E. Inorg. Chem. 2013, 52, 13160. pmid: 24180337
[13]	Guo, F.; Sun, J.; Xu, Z.; Kühn, F. E.; Zang, S.; Zhou, M. Catal. Commun. 2017, 96, 11.
[14]	Du, B.; Quan, Z.; Da, Y.; Zhang, Y.; Wang, X. Adv. Synth. Catal. 2015, 357, 1270.
[15]	Duan, Z.; Ranjit, S.; Zhang, P.; Liu, X. Chem. Eur. J. 2009, 15, 3666. pmid: 19248059
[16]	Zhao, J.; Fang, H.; Han, J.; Pan, Y.; Li, G. Adv. Synth. Catal. 2014, 356, 2719. pmid: 25505857
[17]	Han, X.; Wu, J. Org. Lett. 2010, 12, 5780. pmid: 21090672

Entry	Base (equiv.)	Solvent (mL)	T., t	Yield^b/%
1	Bases^c (2)	None	140 ℃, 24 h	Trace~35
2	None	None	140 ℃, 24 h	33
3	None	None	(i) 80 ℃, 1 h; (ii) 140 ℃, 24 h	43 (A)^d
4	None	None	(i) 80 ℃, 1 h; (ii) 170 ℃, 24 h	59 (A)^d
5	None	None	(i) 80 ℃, 1 h; (i) 170 ℃, 24 h	69 (A)^d^,^e
6	None	CH₃CN (1)	(i) 80 ℃, 1 h; (ii) 170 ℃, 24 h	21 (A)^d^,^e
7	None	EtOH (1)	(i) 80 ℃, 1 h; (ii) 170 ℃, 24 h	10 (A)^d^,^e
8	None	None	(i) 80 ℃, 1 h; (ii) 170 ℃, 24 h	61 (B)^e^,^f

Entry	Base (equiv.)	Solvent (mL)	T., t	Yield^b/%
1	Bases^c (2)	None	140 ℃, 24 h	Trace~35
2	None	None	140 ℃, 24 h	33
3	None	None	(i) 80 ℃, 1 h; (ii) 140 ℃, 24 h	43 (A)^d
4	None	None	(i) 80 ℃, 1 h; (ii) 170 ℃, 24 h	59 (A)^d
5	None	None	(i) 80 ℃, 1 h; (i) 170 ℃, 24 h	69 (A)^d^,^e
6	None	CH₃CN (1)	(i) 80 ℃, 1 h; (ii) 170 ℃, 24 h	21 (A)^d^,^e
7	None	EtOH (1)	(i) 80 ℃, 1 h; (ii) 170 ℃, 24 h	10 (A)^d^,^e
8	None	None	(i) 80 ℃, 1 h; (ii) 170 ℃, 24 h	61 (B)^e^,^f

无碱条件下直接多组分反应选择性合成非对称含氮杂芳基硫醚

Selective Synthesis of Unsymmetrical N-Heteroaryl Thioethers byBase-Free Direct Multi-Component Reaction

RichHTML

PDF

Supporting Info.

Knowledge

Abstract

Cite this article

share this article

Fig. & Tab. 5

References 17

Related Articles 15

Recommended Articles

Metrics

Comments

[1]	Shan Chen, Zhilin Chen, Qiong Hu, Yanshuang Meng, Yue Huang, Pingfang Tao, Liru Lu, Guobao Huang. Recognition of Bis-thiourea Tweezers to Neutral Molecules in Non-Polar Solvent [J]. Chinese Journal of Organic Chemistry, 2024, 44(1): 277-281.
[2]	Xiantao Ma, Xiaoyu Yan, Yingying Zhu, Shuanglin Niu, Yuxuan Wang, Chao Yuan. Water-Promoted Green Synthesis of Heteroaryl Thioether [J]. Chinese Journal of Organic Chemistry, 2023, 43(6): 2136-2142.
[3]	Danfeng Ye, Hao Chen, Zhiyuan Liu, Chuanhu Lei. Transamidation of N-Benzyl-N-Boc-amides under Transition Metal-Free and Base-Free Conditions [J]. Chinese Journal of Organic Chemistry, 2021, 41(4): 1658-1669.
[4]	Hai Ma, Guanghao Yu, Feng Sui, Miyi Yang, Li Liu, Huijie Li, Feng Li, Qinghe Zhao. Triethylamine-Catalyzed Cascade Reaction of γ-Hydroxy-α,β-unsaturated Ketones with Trifluoromethyl Ketones via Hemiketal Intermediates [J]. Chinese Journal of Organic Chemistry, 2021, 41(4): 1614-1621.
[5]	Feng Qin, Lin Tang, Fei Huang, Xiaoyue Li, Wu Zhang. Copper-Catalyzed Three-Component Synthesis of Quinolines via Oxidation and Aza-Diels-Alder Reaction [J]. Chinese Journal of Organic Chemistry, 2021, 41(1): 318-324.
[6]	Sun Xiaohua, Sun Chuance, Feng Lijun, Kang Congmin. Recent Progress in the Synthesis of Thieno[2,3-d]pyrimidine Compounds via Tandem Cyclization [J]. Chinese Journal of Organic Chemistry, 2020, 40(9): 2626-2640.
[7]	Liu Tianbao, Peng Na, Wang Panpan, Peng Yanfen, Gui Meifang, Zhang Min. A New Method for Synthesis of Naphtho[2,1-d]thiazole Derivatives [J]. Chinese Journal of Organic Chemistry, 2020, 40(5): 1355-1360.
[8]	Liu Yaozong, Xu Pengfei, Ma Jianjun, Li Xiaoming, Liang Ruiyuan, Teng Zhijun. Bifunctional Thioureas Catalyzed Asymmetric Michael Addition of 1-Acetylindolin-3-ones to β,γ-Unsaturated α-Keto Esters [J]. Chinese Journal of Organic Chemistry, 2020, 40(5): 1378-1383.
[9]	Zhang Lingjuan, Dang Yujiao, Zhang Xianming. Diversified Synthesis of Imines via Aerobic Oxidation Catalyzed by Dinuclear Butterfly-Like Cu(I) Complex [J]. Chin. J. Org. Chem., 2019, 39(6): 1650-1654.
[10]	Zhao Xinyu, Ding Yangyang, Lü Yingtao, Kang Congmin. Research Progress on Green Synthesis of Imidazo[1,2-a]pyridine Compounds [J]. Chin. J. Org. Chem., 2019, 39(5): 1304-1315.
[11]	Bai Bing, Wang Long, Yang Jing, Cai Lili, Liu Qianjin, Xi Gaolei, Zhao Zhiwei, Mao Duobin, Chen Zhifei. Asymmetric Conjugate Addition of 1,3-Diketone to Nitroalkenes Catalyzed by Bifunctional Thiourea-Amide Organocatalysts [J]. Chin. J. Org. Chem., 2019, 39(4): 1053-1063.
[12]	Sheng Jiajun, Yu Ya'nan, Wang Xin, Qian Yu, Fu Liwu, Zhao Yun, Ma Mingliang, Hu Wenhao. Synthesis of Paclitaxel Side Chain via Multi-Component Reaction and Its Application to the Synthesis of Paclitaxel Analogues [J]. Chin. J. Org. Chem., 2019, 39(2): 377-389.
[13]	Liu Tianbao, Peng Yanfen, Gui Meifang, Zhang Min. Metal-Free Rapid Synthesis of 2-Aroylamino Naphtho[1, 2-d]thiazoles [J]. Chinese Journal of Organic Chemistry, 2019, 39(11): 3199-3206.
[14]	Guan Daokun, Sun Shaofeng, Chen Jing, He Zuopeng, Kong Xiangkai, Wang Ningning, Yao Jianwen, Wang Hongbo. Synthesis and Evaluation of Antitumor Activity of Sorafenib Derivatives Possessing Diphenylamine and Thiourea Structures [J]. Chin. J. Org. Chem., 2018, 38(6): 1414-1421.
[15]	Ma Nan, Zeng Xianghua. Cu₂O-Catalyzed Green Oxidative Terminal Alkynes Homocoupling without Bases [J]. Chin. J. Org. Chem., 2018, 38(6): 1556-1561.