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

doi:10.6023/cjoc202509015

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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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Abstract

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

Cite this article

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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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

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

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