DBDMH诱导咪唑并[1,2-a]吡啶在DMSO中C3选择性甲硫基化反应

doi:10.6023/cjoc202510021

有机化学

研究论文

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).

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摘要/Abstract

以二溴海因(DBDMH)为诱导剂,二甲基亚砜(DMSO)为甲硫化试剂和溶剂,实现咪唑并[1,2-a]吡啶的C3甲硫基化反应。该方法表现出优异的官能团耐受性,为各种取代的咪唑并[1,2-a]吡啶的甲硫化提供了一种无金属、简捷、高效的方法。二乙基亚砜和二苄基亚砜也可作为烷硫基源,应用于该转化。该条件下扩展了26种目标化合物,产率最高达88%.

关键词: 咪唑并[1,2-a]吡啶, 甲硫基化反应, 二溴海因, 二甲基亚砜

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

引用此文

杨凯, 付鑫磊, 吴龙辉, 余树琴, 朱雪, 刘昭文, 黄志勤. DBDMH诱导咪唑并[1,2-a]吡啶在DMSO中C3选择性甲硫基化反应[J]. 有机化学, doi: 10.6023/cjoc202510021.

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.

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[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

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