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

Area of Science:

• Green Chemistry
• Organic Synthesis
• Catalysis

Background:

• β-ketosulfides are crucial structural motifs in biologically active compounds.
• Traditional synthesis methods often involve harsh conditions and non-eco-friendly solvents like dimethylformamide (DMF).
• Previous methods required additional hydrolytic steps, increasing process complexity.

Purpose of the Study:

• To develop a more sustainable and efficient one-pot synthesis for β-ketosulfides.
• To explore the dual role of Type III Deep Eutectic Solvents (DESs) as both solvents and cocatalysts.
• To optimize the reaction conditions using DESs and evaluate the environmental impact.

Main Methods:

• A multicomponent reaction (MCR) involving 2-bromoketones, alkyl or benzyl halides, and potassium thioacetate was employed.
• Type III DES, specifically ChCl:Gly (1:2), was used as the reaction medium and cocatalyst.
• Reaction parameters were optimized, and the recyclability of the DES was assessed.

Main Results:

• The one-pot MCR successfully synthesized various β-ketosulfides.
• The use of DES eliminated the need for DMF and an additional hydrolytic step.
• The ChCl:Gly DES could be recycled up to four times without loss of activity.
• Environmental metrics (E factor, E+ factor, GWP) showed improved performance with DES utilization.

Conclusions:

• Type III DESs offer a sustainable and efficient alternative for β-ketosulfide synthesis.
• The developed method provides a greener pathway to important biologically active compound precursors.
• DESs demonstrate significant potential for recyclable catalysis in organic synthesis.