Switchable Deep Eutectic Solvents for Sustainable Sulfonamide Synthesis

Abstract

A sustainable and scalable protocol for synthesizing variously functionalized sulfonamides, from amines and sulfonyl chlorides, has been developed using environmentally responsible and reusable choline chloride (ChCl)‐based deep eutectic solvents (DESs). In ChCl/glycerol (1:2 mol mol–1) and ChCl/urea (1:2 mol mol–1), these reactions yield up to 97% under aerobic conditions at ambient temperature within 2–12 h. The practicality of the method is exemplified by the sustainable synthesis of an FFA4 agonist and a key building block en route to anti‐Alzheimer drug BMS‐299897. A subtle interplay of electronic effects and the solubility characteristics of the starting materials in the aforementioned DESs seem to be responsible for driving the reaction successfully over the hydrolysis of sulfonyl chlorides. The procedure’s eco‐friendliness is validated by quantitative metrics like the E‐factor and the EcoScale, with products isolated by extraction or filtration after decantation.