利用多组分反应和微波辐射高效合成咪唑类化合物库。

Efficient library synthesis of imidazoles using a multicomponent reaction and microwave irradiation.

作者信息

Gelens E, De Kanter F J J, Schmitz R F, Sliedregt L A J M, Van Steen B J, Kruse Chris G, Leurs R, Groen M B, Orru R V A

机构信息

Department of Chemistry, Faculty of Exact Sciences, Vrije Universiteit, De Boelelaan 1083, 1081 HV Amsterdam, The Netherlands.

出版信息

Mol Divers. 2006 Feb;10(1):17-22. doi: 10.1007/s11030-006-8695-3.

DOI:10.1007/s11030-006-8695-3

PMID:16404525

Abstract

Optimization of Radziszewski's four-component reaction employing a microwave-assisted protocol, led to a small library of 48 imidazoles with a success rate of 65% (conversion > 45%). All three diversity points of the four-component reaction were varied. Aromatic and aliphatic inputs were successfully implemented and mono-, di-, tri- and tetrasubstituted imidazoles with various substitution patterns were synthesized. Furthermore, unsymmetrical diketones could successfully be used which improved the intrinsic diversity of the method significantly. If the unsymmetrical diketone 1,2-phenylpropanedione (R1 and R2) was used two regioisomers were formed. Depending on the type of amine (R4) and aldehyde (R3) applied, regioselectivity was modest to good. Based on these results, a reaction mechanism is proposed.

摘要

采用微波辅助方案对拉齐谢夫斯基四组分反应进行优化，得到了一个包含48种咪唑的小型库，成功率为65%（转化率>45%）。四组分反应的所有三个多样性点均有所变化。成功引入了芳香族和脂肪族反应物，并合成了具有各种取代模式的单取代、二取代、三取代和四取代咪唑。此外，不对称二酮能够成功使用，这显著提高了该方法的内在多样性。如果使用不对称二酮1,2-苯基丙酮（R1和R2），会形成两种区域异构体。根据所使用的胺（R4）和醛（R3）的类型，区域选择性从中等到良好。基于这些结果，提出了一种反应机理。