DBDMH-Mediated Regioselective C3-Methylthiolation of Imidazo[1,2-a]pyridines in Dimethylsulfoxide

doi:10.6023/cjoc202510021

Chinese Journal of Organic Chemistry

ARTICLE

DBDMH诱导咪唑并[1,2-a]吡啶在DMSO中C3选择性甲硫基化反应

杨凯^a, 付鑫磊^a, 吴龙辉^a, 余树琴^a, 朱雪^a, 刘昭文^a, 黄志勤^a,*

^a赣南医科大学药学院赣州 341000

收稿日期:2026-01-01 修回日期:2026-02-09
基金资助:
江西省自然科学基金项目（20224BAB203010）和赣州市科技计划项目（2023CYZ17866）资助资助项目.

DBDMH-Mediated Regioselective C3-Methylthiolation of Imidazo[1,2-a]pyridines in Dimethylsulfoxide

Yang Kai^a, Fu Xinlei^a, Wu Longhui^a, Yu Shuqin^a, Zhu Xue^a, Liu Zhaowen^a, Huang Zhiqin^a,*

^a College of pharmacy, Gannan Medical University, Ganzhou 341000, China;
^b Department, Institution, City, Postal code

Received:2026-01-01 Revised:2026-02-09
Contact: ^*E-mail: hzqzll@126.com
Supported by:
Natural Science Foundation of Jiangxi Province (20224BAB203010) and the Science and Technology Projects of Ganzhou (2023CYZ17866).

1. .pdf(3189KB)

Abstract

An efficient DBDMH mediated regioselective C3-methylation of imidazo[1,2-a]pyridines was developed using DMSO as SMe source and solvent. This method exhibits excellent functional group tolerance and offers a metal-free, simple, and efficient approach for the C3-methylthiolation of variously substituted imidazo[1,2-a]pyridines. Diethyl sulfoxide and dibenzyl sulfoxide can also be used as alkyl sulfur sources for this conversion. Under optimized conditions, the scope of this method was successfully extended to 26 target compounds, achieving a maximum yield of 88%.

Key words: imidazo[1,2-a]pyridines, methylthiolation, 1,3-dibromo-5,5-dimethylhydantoin, dimethylsulfoxide

Cite this article

Yang Kai, Fu Xinlei, Wu Longhui, Yu Shuqin, Zhu Xue, Liu Zhaowen, Huang Zhiqin. DBDMH-Mediated Regioselective C3-Methylthiolation of Imidazo[1,2-a]pyridines in Dimethylsulfoxide[J]. Chinese Journal of Organic Chemistry, doi: 10.6023/cjoc202510021.

Export EndNote|Reference Manager|ProCite|BibTeX|RefWorks

share this article

References

[1] (a) Feng, M.; Tang, B.; Liang, S. H.; Jiang, X. Curr. Top. Med. Chem. 2016, 16, 1200.(b) Conroy, S.; Kindon, N.; Kellam, B.; Stocks, M. J. J. Med. Chem. 2016, 59, 9981. (c) Park, S. Y.; Hwang, I.-S.; Lee, H.-J.; Song, C. E. Nat. Commun. 2017, 8, 14877. (d) Zhang, Y.; Ren, Y.; Zhang, J.; Liu, S.; Li, H. Chin. J. Chem. 2023, 41, 3045. (e) Yang, L.; Li, B.; Shu, C. Acta Chim. Sinica 2024, 82, 171 (in Chinese). (杨铃悦, 李赟婷, 舒超. 化学学报, 2024, 82, 171.) (f) Zhou, Q.; Jiang, J.; Luo, N.; Huang, J. Acta Chim. Sinica 2025, 83, 274 (in Chinese). (周泉, 蒋佳怡, 罗年华, 黄家翩. 化学学报, 2025, 83, 274.) (g) Du, Y.; Li, S.; Cheng, S.; Jia, H.; Wang, Z.; Han, L.; Zhu, N. Acta Chim. Sinica 2025, 83, DOI: 10.6023/A25060234 (in Chinese). (杜云哲, 李曙懿, 程思柳, 贾慧劼, 王政, 韩利民, 竺宁. 化学学报, 2025, 83, DOI10.6023/A25060234)
[2] (a) Chen, Y.; Zhou, J.; Wang, H.; Xia, Y.; Yang, Z. Y.; Xia, P. Chin. Chem. Lett. 2008, 19, 925.(b) Giannetti, A. M.; Wong, H.; Dijkgraaf, G. J. P.; Dueber, E. C.; Ortwine, D. F.; Bravo, B. J.; Gould, S. E.; Plise, E. G.; Lum, B. L.; Malhi, V.; Graham, R. A. J. Med. Chem. 2011, 54, 2592. (c) Dunbar, K.L.; Scharf, D.H.; Litomska, A.; Hertweck, C. Chem. Rev. 2017, 117, 5521-5577. (d) Wang, R.; Lu, L.; Shen, Q. Chin. J. Chem. 2023, 41, 2317. (e) Zheng, J.; Lin, J.; Xiao, J. Acta Chim. Sinica 2024, 82, 115-118 (in Chinese). (郑剑, 林锦鸿, 肖吉昌. 化学学报, 2024, 82, 115-118.)
[3] (a) Tashrifi, Z.; Khanaposhtani, M. M.; Larijani, B.; Mahdavi, M.Adv. Synth. Catal. 2020, 362, 65.(b) Wu X.-F.; Natte, K. Adv. Synth. Catal.2016, 358, 336.
[4] (a) Natarajan P.; Basaka A.; Metin O. Green Chem.,2023, 25, 3187.(b) Tian Y.; Zhang J.; Gao W.; Chang, H. Chin. J. Org. Chem.2023, 43, 2391. (c) Chen, X.-H.; Lhazom, T.; Cui, H.-L. J. Org. Chem. 2023, 88, 13598., 566.
[5] (a) Chang M.-Y.; Chen H.-Y.; Tsai Y.-L. Org. Lett.2019, 21, 1832.(b) Huang M.-H.; Zhu C.-F.; He C.-L.; Zhu Y.-L.; Hao W.-J.; Wang D.-C.; Tu S.-J.; Jiang, B. Org. Chem. Front.2018, 5, 1643. (c) Zhao, P.; Wu, X.; Geng, X.; Wang, C.; Zhou, Y.; Wu, Y.-D.; Wu, A.-X. J. Org. Chem. 2019, 84, 8322., 6688.
[6] (a) Toyoda, S.; Iizumi, K.; Yamaguchi, J. Chem. Sci. 2025, 16, 11559.(b) Li, X.; Sun, F.; He, J.; Shi, H.; Zhang, S.; Du, Y. J. Org. Chem. 2025, 90, 9928. (c) Zhou, Y.-J.; Fang, Y.-G.; Yang, K.; Lin, J.-Y.; Li, H.-Q.; Chen, Z.-J.; Wang, Z.-Y. Molecules 2023, 28, 5635. 2024, 44, 1576 (in Chinese). (张娟, 王奕森, 田钰, 徐晶, 高文超, 常宏宏, 孟凡会, 杨朋. 有机化学, 2024, 44, 1576.)
[7] (a) Devi N.; Singh D.;Rawal R. K.; Bariwal J.; Singh, V. Curr. Top. Med. Chem.2016, 16, 2963.(b) Samanta S.; Kumar S.; Aratikatla E. K.; Ghorpade S. R.; Singh, V. RSC Med. Chem.2023, 14, 644.
[8] (a) Abe Y.; Kayakiri H.; Satoh S.; Inoue T.; Sawada Y.; Inamura N.; Asano M.; Aramori I.; Hatori C.; Sawai H.; Oku T.; Tanaka, H. J. Med. Chem.1998, 41, 4587.(b) Okubo T.; Yoshikawa R.; Chaki S.; Okuyama S.; Nakazato, A. Bioorg. Med. Chem.2004, 12, 423. (c) Ismail, M. A.; Arafa, R. K.; Wenzler, T.; Brun, R.; Tanious, F. A.; Wilson, W. D.; Boykin, D. W. Biorg. Med. Chem., 2008, 16, 683., 359.
[9] (a) Bagdi, A. K.; Santra, S.; Monir, K.; Hajra, A. Chem. Commun. 2015, 51, 1555.(b) Patel, O. P. S.; Nandwana, N. K.; Legoabe, L. J.; Das, B. C.; Kumar, A. Adv. Synth. Catal. 2020, 362, 4226. (c) Liu, X.; Li, W.; Liu, H.; Cao, H. Chin. J. Org. Chem. 2021, 41, 1759 (in Chinese). (刘想, 李文, 刘环宇, 曹华. 有机化学, 2021, 41, 1759.) (d) Tali, J. A.; Kumar, G.; Sharma, B. K.; Rasool, Y.; Sharma, Y.; Shankar, R. Org. Biomol. Chem. 2023, 21, 7267. (e) Zhang, Z, Guo, Y.; Yang, J.; Wang, D.; Wang, j.; Hong, X.; Cai, P.; Rong, L. Chin. J. Org. Chem. 2023, 43, 2104 (in Chinese). (张周, 郭钰, 羊静, 吴丹, 王佳昕, 洪欣玥, 蔡佩君, 荣良策. 有机化学, 2023, 43, 2104.) (f) Gao, J.; Fu, X.; Yang, K.; Liu, Z.-W. Molecules 2025, 30, 607.
[10] (a) Yuan Y.; Cao Y.; Qiao J.; Lin Y.; Jiang X.; Weng Y.; Tang S.; Lei, A. Chin. J. Chem.2019, 37, 49.(b) Wen J.; Niu C.; Yan K.; Cheng X.; Gong R.; Li M.; Guo Y.; Yang J.; Wang H. Green Chem.2020, 22, 1129.
[11] Patil S. M.; Kulkarni S.; Mascarenhas M.; Sharma R.; Roopan S. M.; Roychowdhury A. Tetrahedron2013, 69, 8255.
[12] (a) Ravi C.; Mohan D. C.; Adimurthy, S. Org. Biomol. Chem.2016, 14, 2282.(b) Zhang, L.-Y.; Wu, Y.-H.; Wang, N.-X.; Gao, X.-W.; Yan, Z.; Xu, B.-C.; Liu, N.; Wang, B.-Z.; Xing, Y.Eur. J. Org. Chem. 2021, 1446.
[13] Feng Z.; Fan Y.; Qiang C.; Liu P.; Sun P. Green Chem.2024, 26, 3517.
[14] (a) Yang K.; Luo S.; Chen S.; Cao X.; Zhou Y.; Lin J.; Huo Y.; Wang, Z.-Y. Org. Biomol. Chem.2021, 19, 8133.(b) Yang K.; Chen Z.; Zhou Y.; Chen Q.; Yu S.; Luo S.; Wang, Z.-Y. Org. Chem. Front.2022, 9, 1127. (c) Gao, J.; Liu, Z.; Guo, X.; Wu, L.; Chen, Z.; Yang, K. Molecules 2023, 28, 7522., 1756.
[15] (a) Fu D.; Dong J.; Wang J.; Wang J.; Xu, J. Asian J. Org. Chem.2021, 10, 1756.(b) Ma C.-H.; Chen M.; Feng Z.-W.; Zhang Y.; Wang J.; Jiang Y.-Q.; Yu, B. New J. Chem.2021, 45, 9302.
[16] Lu R.; Tao Q.; Qian Q.; Li B.; Zhang Y.; Gao, Y. Adv. Synth. Catal.2024, 366, 4084.
[17] Chen Z.; Cao G.; Zhang F.; Li H.; Xu J.; Miao M.; Ren H. Synlett2017, 28, 1795.

DBDMH诱导咪唑并[1,2-a]吡啶在DMSO中C3选择性甲硫基化反应

DBDMH-Mediated Regioselective C3-Methylthiolation of Imidazo[1,2-a]pyridines in Dimethylsulfoxide

PDF

Supporting Info.

Knowledge

Abstract

Cite this article

share this article

References

Related Articles 11

Recommended Articles

Metrics

Comments

[1]	Juan Zhang, Yisen Wang, Yu Tian, Jing Xu, Wenchao Gao, Honghong Chang, Fanhui Meng, Peng Yang. Regioselective C(2) Methylthiolation and d₃-Methylthiolation of Indoles Based on Dimethyl Sulfoxide (DMSO-d₆) Reagents [J]. Chinese Journal of Organic Chemistry, 2024, 44(5): 1576-1583.
[2]	Cong Wang, Yaoyao Yao, Jun Xie, Jianta Wang, Feiqing Wang, Jiquan Zhang, Lei Tang. Convenient Method for Preparingα-Ketoarylthioamide by Air Oxidation under Base Conditions [J]. Chinese Journal of Organic Chemistry, 2021, 41(1): 370-375.
[3]	Guo Yuanyuan, Liu Zhenwei, Zhu Mingxiang, Li Linlin, Li Jingya, Zou Dapeng, Wu Yusheng, Wu Yangjie. Copper-Promoted Dimethylthiolation of Benzamides under Assistance of 8-Aminoquinoline Group [J]. Chinese Journal of Organic Chemistry, 2020, 40(3): 724-730.
[4]	Chen Pingliang, Lu Shijie, Hu Xingen, Xu Qing. CsOH/DMSO Promoted Reactions of Aryl Halides with Phenols: A Convenient Method for the Synthesis of Diaryl Ethers [J]. Chin. J. Org. Chem., 2014, 34(1): 112-117.
[5]	Li Yanke;Zhang Shufeng;Yang Jinzong. Enzyme-Catalyzed Regioselective Synthesis of Surcrose Esters [J]. Chin. J. Org. Chem., 2003, 23(8): 770-775.
[6]	Liu Xiguang;Wu Jingping;Liang Xiaomei;Wang Daoquan. Application of DMSO as oxidant in organic syntheses [J]. Chin. J. Org. Chem., 2001, 21(8): 549-556.
[7]	Wang Liangyou;Pan Heping;Chen Zhengying. Methods of disulfide formation in peptide synthesis [J]. Chin. J. Org. Chem., 1998, 18(6): 576-580.
[8]	TIAN LAIJIN;FU FANGXIN;ZHU DONGSHENG;PAN HUADE. Synthesis and transesterification of the complexes of β- alkoxycarbonylethyltin trichlorides with monodentate ligands [J]. Chin. J. Org. Chem., 1998, 18(1): 37-42.
[9]	WANG JITAO;YANG XIAOPING;LIU BO;CHENG JINPEI. Acidities of high coordinate bicycloazastannoxides(Ⅳ) in DSMO solution [J]. Chin. J. Org. Chem., 1996, 16(4): 381-384.
[10]	REN ZHONGJIAO;CAO LEI. The study of knoevenagel condensation and solvent effect without catalyst [J]. Chin. J. Org. Chem., 1996, 16(1): 48-52.
[11]	GUO ZONGRU;HOU SHUANGZHOU;YANG GUANGZHONG;CHU FENGMING;JIAO YE. Study of hydrogen exchange of heterocyclic compounds by nuclear magnetic resonance [J]. Chin. J. Org. Chem., 1989, 9(6): 507-511.