一种无需过渡金属、绿色温和的3-碘代/溴代咪唑并[1,2-a]吡啶类化合物一锅合成法

doi:10.6023/cjoc202509015

综述与进展

一种无需过渡金属、绿色温和的3-碘代/溴代咪唑并[1,2-a]吡啶类化合物一锅合成法

杨利婷^a, 潘慧茹^a, 许晓旭^a, 张益恺^a, 来姝妤^a, 曹信誉^a, 刘国群^*,a, 乔辉杰^*,a, 焦明立^*,a

(^a中原工学院材料电子与储能学院,河南省功能盐材料重点实验室郑州 450007)

收稿日期:2025-09-11 修回日期:2025-12-04
基金资助:
国家自然科学基金项目（No. 52403287）, 河南省高校科技创新团队项目（No. 23IRTSTHN019）,河南省科技攻关项目（No. 252102230155）资助项目.

A Green and Mild One-Pot Protocol for the Synthesis of 3-Iodo-/Bromo-imidazo[1,2-a]pyridines Without Transition Metals

Liting Yang^a, Huiru Pan^a, Xiaoxu Xu^a, Yikai Zhang^a, Shuyu Lai^a, Xinyu Cao^a, Guoqun Liu^*,a, Huijie Qiao^*,a, Mingli Jiao^*,a

(^aSchool of Materials Electronics and Energy Storage, Henan Key Laboratory of Functional Salt Materials, Zhongyuan University of Technology, Zhengzhou, 450007)

Received:2025-09-11 Revised:2025-12-04
Contact: ^*E-mail: liugq@zut.edu.cn; 598405179@qq.com; jml@zut.edu.cn.
Supported by:
Project supported by the National Natural Science Foundation of China (No. 52403287), the Program for Innovative Research Team (in Science and Technology) in University of Henan Province (No. 23IRTSTHN019), the Key Technological Research Project of Henan Province (No. 252102230155).

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摘要/Abstract

以2-氨基吡啶类化合物、甲酰基甲基溴类化合物和碘化钾（KI）为反应物,建立了一种无过渡金属参与的一锅多步策略,用于高效合成3-碘代咪唑并[1,2-a]吡啶衍生物。该方法具有显著优势：无需过渡金属、反应条件温和（在室温下进行）,且使用绿色无毒的碘化试剂。值得注意的是,带有给电子基团（EDGs）和吸电子基团（EWGs）的2-氨基吡啶与甲酰基甲基溴均表现出良好的兼容性,其中带有给电子基团的底物通常能获得略高的产率。通过对照实验进行的机理研究表明,该反应遵循两步反应机理：首先,2-氨基吡啶与甲酰基甲基溴反应生成咪唑并[1,2-a]吡啶中间体;随后,该中间体与KI发生C3位碘化反应。此外,该策略可扩展用于3-溴代咪唑并[1,2-a]吡啶的合成——在调整后的条件（65 ℃,6小时）下,以溴化钾（KBr）为溴源,产物产率可达55%-97%。

关键词: 咪唑并[1,2-a]吡啶衍生物, 一锅多步反应, 碘化反应, 无过渡金属, 碘化钾

A transition-metal-free one-pot multi-step strategy has been established for the efficient synthesis of 3-iodoimidazo[1,2-a]pyridine derivatives, utilizing 2-aminopyridines, formyl methyl bromides, and potassium iodide (KI) as reactants. This protocol boasts notable advantages: freedom from transition metals, mild reaction conditions (proceeding at room temperature), and employment of green, non-toxic iodinating reagents. Notably, 2-aminopyridines and formyl methyl bromides substituted with both electron-donating groups (EDGs) and electron-withdrawing groups (EWGs) exhibit good compatibility, with EDG-substituted substrates generally affording slightly higher yields. Mechanistic investigations through control experiments demonstrate that the reaction follows a two-step mechanism: initially, 2-aminopyridine reacts with formyl methyl bromide to form an imidazo[1,2-a]pyridine intermediate, which then undergoes C3-iodination with KI. Furthermore, this strategy is extendable to the synthesis of 3-bromoimidazo[1,2-a]pyridines by using potassium bromide (KBr) as the bromine source under adjusted conditions (65 °C, 6 h), yielding products with 55-97% yields.

Key words: imidazo[1,2-a]pyridine, one-pot multi-step reaction, iodination reaction, transition-metal-free, potassium iodide

引用此文

杨利婷, 潘慧茹, 许晓旭, 张益恺, 来姝妤, 曹信誉, 刘国群, 乔辉杰, 焦明立. 一种无需过渡金属、绿色温和的3-碘代/溴代咪唑并[1,2-a]吡啶类化合物一锅合成法[J]. 有机化学, doi: 10.6023/cjoc202509015.

Liting Yang, Huiru Pan, Xiaoxu Xu, Yikai Zhang, Shuyu Lai, Xinyu Cao, Guoqun Liu, Huijie Qiao, Mingli Jiao. A Green and Mild One-Pot Protocol for the Synthesis of 3-Iodo-/Bromo-imidazo[1,2-a]pyridines Without Transition Metals[J]. Chinese Journal of Organic Chemistry, doi: 10.6023/cjoc202509015.

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