One-Pot Syntesis of 3-Functionalized 4-Hydroxycoumarin under Catalyst-Free Conditions.

Yang Gao,Yiliang Li,Guo-Ning Zhang,Xiaoguang Bai,Juxian Wang,Yucheng Wang

doi:10.3390/molecules23010235

Abstract

A concise and efficient one-pot synthesis of 3-functionalized 4-hydroxycoumarin derivatives via a three-component domino reaction of 4-hydroxycoumarin, phenylglyoxal and 3-arylaminocyclopent-2-enone or 4-arylaminofuran-2(5H)-one under catalyst-free and microwave irradiation conditions is described. This synthesis involves a group-assisted purification process, which avoids traditional recrystallization and chromatographic purification methods.

Highlights

As part of our current studies on the development of environmentally friendly routes to heterocyclic compounds [29–32], we report an efficient and clean synthesis of 3-functionalized 4-hydroxycoumarin derivatives under catalyst-free conditions
We initially evaluated the three-component reaction of a 1:1:1 mixture of 4-hydroxycoumarin (1), phenylglyoxal monohydrate (2a) and 3-(p-tolylamino)cyclopent-2-enone (3a) for the optimization of the reaction conditions
The desired product 4a was obtained in 89% yield when the reaction was carried out in ethanol at 100 ◦C for 30 min. under catalyst-free and microwave irradiation conditions (Table 1, entry 1)

Summary

Introduction

Molecules 2018, 23, 235 medicinal chemistry, because of their atom economy, complexity and diversity of products, multiple bond formation efficiency, and environmental friendliness [10] These features make MCRs suitable for the easy construction of complex heterocyclic scaffolds from readily available starting materials [11]. The need to reduce the amount of toxic waste and byproducts arising from chemical processes has resulted in an increasing emphasis on the use of less-toxic and environmentally compatible materials in the design of new synthetic methods. Traditional purification methods such as recrystallization and column chromatography have problems in terms of consumption of organic solvents and energy, waste generation, and pollution. As part of our current studies on the development of environmentally friendly routes to heterocyclic compounds [29–32], we report an efficient and clean synthesis of 3-functionalized 4-hydroxycoumarin derivatives under catalyst-free conditions

Results and Discussion

99 CHCH3O3O Cl Cl 6i 6i

Conclusions