碘催化的串联氧化环化反应合成多取代咪唑(英文)

A Rapid and Efficient Access to Polysubstituted Imidazoles via Iodine-Catalyzed Tandem Oxidative Cyclization

以苯乙醛和苄胺衍生物为原料,分子碘作为催化剂,过氧叔丁醇作为氧化剂合成了一系列的多取代咪唑.同时对反应过程中催化剂的用量、氧化剂、溶剂和温度进行了优化,得到如下最优反应条件:0.3 equiv.的分子碘作为催化剂,过氧叔丁醇作为氧化剂,乙腈作为溶剂,反应温度为70℃.而苯乙酮和苄胺上的吸电子基团均有利于此氧化反应,对反应机理也进行了探索性研究并有了较明确的认识.与传统的咪唑合成方法相比,该新方法反应条件更温和,原材料更易获得.

Imidazoles represent one of the most important heterocycles which are known to exhibit a wide range of biologi- cal and medical activity. Existing methodologies for the synthesis of imidazoles are limited to the generality and accessibility of substrates, and the harsh reaction conditions. The development of milder and more practical protocols should be still de- sirable and necessary. Here we report a new method for the synthesis of polysubstituted imidazoles. A series of imidazoles was obtained directly from 2-phenylacetaldehyde or acetophenone derivatives and benzylamine derivatives via a metal-free-catalyzed tandem oxidative cyclization. The reaction was performed under mild conditions with iodine as a cata- lyst and TBHP as an oxidant. The effect of catalyst loading, oxidants, solvents and temperature on this transformation was investigated. The optimal reaction conditions were as follows： 0.3 equiv, of iodine as the catalyst, TBHP as the oxidant, ace- tonitrile as the solvent and the reaction being carried out at 70℃. Electron-withdrawing group of acetophenone derivatives and benzylamine derivatives benefit the oxidative reaction. Compared with traditional methods, this reaction was conducted under milder conditions with facile starting materials.