温和条件下高效合成咪唑并杂环-肼类衍生物的三组分串联反应

doi:10.6023/cjoc202110015

摘要/Abstract

为了合成咪唑[1,2-a]并吡啶-肼类衍生物, 发展了一种以简单易得的甲酰甲基溴化物、2-氨基吡啶衍生物和偶氮二甲酸酯为原料的三分子串联反应的方法. 该串联反应先生成咪唑[1,2-a]并吡啶, 然后紧接着连续发生C(3)—H键肼基化反应, 而不像传统的一步接一步反应的方法. 该方法具有操作简单、反应条件温和(无需过渡金属且反应温度低等)以及底物适用性广的特点. 实验结果表明, 带有给电子取代基的甲酰甲基溴化物和2-氨基吡啶衍生物有利于反应的进行, 并以优秀的产率获得目标产物.

关键词: 三组分反应, 串联反应, 咪唑并杂环化合物, C(3)—H肼基化反应

An three-component tandem reaction for the synthesis of imidazo[1,2-a]pyridine-hydrazines was accomplished with the easily available formyl methyl bromides, pyridin-2-amines and azodiformates. This tandem reaction process includes the generation of imidazo[1,2-a]pyridines followed by C(3)—H hydrazination in a sequential way, instead of the classical step-by-step methods. The approach features simple operation, mild conditions (transition-metal-free and low reaction temperature) as well as good tolerance of substrates. Note that formyl methyl bromides and pyridin-2-amines bearing electron-donating groups are benefit for this reaction, affording target products in excellent yields.

Key words: three-component reaction, tandem reaction, imidazoheterocycle, C(3)—H hydrazination

引用此文

乔辉杰, 杨利婷, 陈雅, 王嘉琳, 孙武轩, 董昊博, 王云威. 温和条件下高效合成咪唑并杂环-肼类衍生物的三组分串联反应[J]. 有机化学, 2022, 42(4): 1188-1197.

Huijie Qiao, Liting Yang, Ya Chen, Jialin Wang, Wuxuan Sun, Haobo Dong, Yunwei Wang. An Efficient Three-Component Tandem Approach for the Synthesis of Imidazoheterocycle-Hydrazine Derivatives under Mild Conditions[J]. Chinese Journal of Organic Chemistry, 2022, 42(4): 1188-1197.

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图/表 7

Scheme 1. Protocols for the preparation of imidazoheterocycle-hydrazines

Entry	Solvent	T/℃	t/h	Yield^b/%
1	CH₃CN	30	8	82
2	CH₃CN/H₂O (V∶V=1∶1)	30	8	71
3	H₂O	30	8	66
4	EtOH	30	8	15
5	THF	30	8	52
6	1,4-Dioxane	30	8	55
7	o-Xylene	30	8	45
8	DMF	30	8	10
9	DMSO	30	8	16
10	Petroleum ether	30	8	37
11	Ethyl acetate	30	8	58
12	1,2-DCE	30	8	80
13	DCM	30	8	84
14	DCM	35	8	91
15	DCM	40	8	90
16	DCM	35	9	91
17	DCM	35	7	86

Table 1. Screening optimal conditionsa

Table 2. Substrate scope of arylformyl methyl bromidesa,b

Table 3. Substrate scope of 2-amino heterocyclic compoundsa,b

Table 4. Substrate scope of azodiformatesa,b

Scheme 2. Control experiments

Scheme 3. Plausible mechanism

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