Optimization of the Selective Monohydrolysis of Diethyl 4-Aryl-4H-pyran-3,5-dicarboxylates

Jiaojiao Duan,Xiuqing Song,Xiaohui Song,Hong Yan

doi:10.3390/molecules16053845

Jiaojiao Duan, Xiuqing Song + Show 2 more

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https://doi.org/10.3390/molecules16053845

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Abstract

A simple, efficient and eco-friendly procedure for the selective monohydrolysis of diethyl 2,6-dimethyl-4-aryl-4H-pyran-3,5-dicarboxylates under quaternary ammonium salt catalysis conditions is presented. The catalytic activities of various quaternary ammonium salts were investigated using different molar ratios of NaOH and water-organic solvent mixtures. The results indicate that the combination of 1.0 equivalent of tetraethyl-ammonium bromide (TEAB) with 1.2 equivalents of NaOH in a 10% water-ethanol media at 40 °C displays remarkable selectivity for the monohydrolysis of diethyl 2,6-dimethyl-4-aryl-4H-pyran-3,5-dicarboxylates. The utility of this process is demonstrated by the monohydrolysis of a series of 4-aryl-4H-pyran-3,5-dicarboxylate esters to afford the corresponding monoesters in 20–80% yields under the optimized conditions.

Highlights

The 4H-pyran moiety represents a privileged structure because many of its derivatives possess useful pharmacological activities [1,2]
Diethyl 2,6-dimethyl4-aryl-4H-pyran-3,5-dicarboxylates 1 represent an important class of 4H-pyrans that is widely used in Molecules 2011, 16 therapeutic areas, especially for the inhibition of the HIV-1 proteases [5,6,7,8]
We report the synthesis of 4H-pyran hemiesters 2 by the selective monohydrolysis of symmetric diesters 1

Summary

Introduction

The 4H-pyran moiety represents a privileged structure because many of its derivatives possess useful pharmacological activities [1,2]. In recent years, polyfunctionalized 4H-pyrans and their derivatives have been the subject of significant interest from the synthetic community and have been widely recognized as versatile scaffolds with diverse biological activities [3,4]. Diethyl 2,6-dimethyl4-aryl-4H-pyran-3,5-dicarboxylates 1 represent an important class of 4H-pyrans that is widely used in Molecules 2011, 16 therapeutic areas, especially for the inhibition of the HIV-1 proteases [5,6,7,8]. Diethyl 2,6-dimethyl-4-aryl4H-pyran-3,5-dicarboxylates 1 have routinely been efficiently synthesized by the reaction of aryl aldehydes and 1,3-diketones catalyzed by ZnCl2 under ultrasound irradiation [9]. We report the synthesis of 4H-pyran hemiesters 2 by the selective monohydrolysis of symmetric diesters 1

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