树脂负载的 Mitsunobu 酯化和醚化反应动力学

Kinetics of resin-supported Mitsunobu esterification and etherification reactions.

作者信息

Ma Xifeng, Shi Ranran, Zhang Bin, Yan Bing

机构信息

School of Pharmaceutical Sciences, Shandong University, Jinan, China.

出版信息

J Comb Chem. 2009 May-Jun;11(3):438-45. doi: 10.1021/cc900004m.

DOI:10.1021/cc900004m

PMID:19260700

Abstract

Solid-phase Mitsunobu reaction is very useful in organic and parallel synthesis. In this work, we optimize the solid-phase Mitsunobu esterification and etherification reactions and investigated their kinetics by single-bead FTIR microspectroscopy method. Thirteen solid-phase Mitsunobu esterification reactions proceeded at rates between 2.5 x 10(-3) and 19 x 10(-3) s(-1), while five etherification reactions at generally slower rates between 3.3 x 10(-3) and 8.9 x 10(-3) s(-1). We discovered that reaction rates, as in solution phase Mitsunobu reactions, linearly correlated to pK(a) values of acids and phenols used in the reaction. By studying side reactions and intermediates, we found that the solid-phase reaction mechanism also bears remarkable similarities to that of solution phase Mitsunobu reaction.

摘要

固相亲核取代反应在有机合成及平行合成中非常有用。在本研究中，我们优化了固相亲核取代酯化反应和醚化反应，并通过单珠傅里叶变换红外光谱法研究了它们的动力学。13个固相亲核取代酯化反应的速率在2.5×10⁻³至19×10⁻³ s⁻¹之间，而5个醚化反应的速率通常较慢，在3.3×10⁻³至8.9×10⁻³ s⁻¹之间。我们发现，与溶液相的亲核取代反应一样，反应速率与反应中所用酸和酚的pK(a)值呈线性相关。通过研究副反应和中间体，我们发现固相反应机理与溶液相亲核取代反应的机理也有显著相似之处。