Accelerated microdroplet synthesis of benzimidazoles by nucleophilic addition to protonated carboxylic acids.
Accelerated microdroplet synthesis of benzimidazoles by nucleophilic addition to protonated carboxylic acids.
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DOI：
10.1039/d0sc02467h
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发表时间：
2020-07-14
期刊：
影响因子：
8.4
通讯作者：
Cooks RG
中科院分区：
文献类型：
--
作者：
Basuri P;Gonzalez LE;Morato NM;Pradeep T;Cooks RG
本文报道了一种在大气中快速合成苯并咪唑及其衍生物的新方法。合成过程涉及1，2-芳族二胺和烷基或芳基羧酸在使用纳米电喷雾（nESI）离子源产生的静电荷微滴中反应。与本体相比，反应加速了几个数量级。不使用其它酸、碱或催化剂。通过质谱法进行微滴加速反应产物的在线分析。我们提供了证据的酸催化反应机理的基础上确定的中间体芳酰胺。在随后的热增强步骤中，它们脱水得到苯并咪唑。有人建议，在液滴表面的非凡的酸性允许羧酸作为C-中心的亲电试剂。这种方法与薄膜和散装合成的数据的比较导致在反应中的三个关键步骤的建议：（i）形成一个不寻常的试剂（质子化羧酸），因为在液滴界面的异常条件，（ii）加速双分子反应，因为有限的溶剂化在界面和（iii）热辅助消除水。11个例子显示作为证据的范围，这种化学。加速合成已按比例扩大，以建立取代基依赖性和分离产物进行NMR表征。本文报道了一种在大气中快速合成苯并咪唑及其衍生物的新方法。
We report a metal-free novel route for the accelerated synthesis of benzimidazole and its derivatives in the ambient atmosphere. The synthetic procedure involves 1,2-aromatic diamines and alkyl or aryl carboxylic acids reacting in electrostatically charged microdroplets generated using a nano-electrospray (nESI) ion source. The reactions are accelerated by orders of magnitude in comparison to the bulk. No other acid, base or catalyst is used. Online analysis of the microdroplet accelerated reaction products is performed by mass spectrometry. We provide evidence for an acid catalyzed reaction mechanism based on identification of the intermediate arylamides. Their dehydration to give benzimidazoles occurs in a subsequent thermally enhanced step. It is suggested that the extraordinary acidity at the droplet surface allows the carboxylic acid to function as a C-centered electrophile. Comparisons of this methodology with data from thin film and bulk synthesis lead to the proposal of three key steps in the reaction: (i) formation of an unusual reagent (protonated carboxylic acid) because of the extraordinary conditions at the droplet interface, (ii) accelerated bimolecular reaction because of limited solvation at the interface and (iii) thermally assisted elimination of water. Eleven examples are shown as evidence of the scope of this chemistry. The accelerated synthesis has been scaled-up to establish the substituent-dependence and to isolate products for NMR characterization. We report a metal-free novel route for the accelerated synthesis of benzimidazole and its derivatives in the ambient atmosphere.
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影响因子：
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作者：
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影响因子：
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发表时间：
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影响因子：
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通讯作者：
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