Multicomponent Reaction for the Synthesis of β-Ketosulfides in Deep Eutectic Solvents

TL;DR

A new eco-friendly method uses deep eutectic solvents to synthesize β-ketosulfides, avoiding harmful solvents and improving sustainability.

Contribution

A multicomponent reaction in Type III DESs enables efficient and recyclable synthesis of β-ketosulfides without harmful solvents.

Findings

DES ChCl:Gly (1:2) acts as both solvent and cocatalyst for β-ketosulfide synthesis.

The DES can be reused up to four times without significant loss of activity.

Environmental metrics show improved sustainability when using DES compared to traditional methods.

Abstract

The use of Type III Deep Eutectic Solvents (DESs) as both solvents and cocatalysts enable the one-pot synthesis of several β-ketosulfides, structural motifs commonly found in biologically active compounds, via a multicomponent reaction (MCR) involving 2-bromoketones, alkyl or benzyl halides, and potassium thioacetate in basic medium. Under these conditions, it was possible to avoid not only the use of the non-eco-friendly solvent dimethylformamide (DMF), but also an additional hydrolytic step previously reported for the preparation of these molecules. The MCR conducted in the presence of the DES ChCl:Gly (1:2) was optimized through the evaluation of different reaction parameters. Notably, the non-conventional medium could be recycled up to four times without any appreciable loss of catalytic activity. Environmental metrics, including the E factor, E+ factor, and Global Warming Potential (GWP), were calculated for the process both in the presence and absence of the DES, demonstrating improved environmental performance when the DES was employed.

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