Sustainable Synthesis of Sulfonamides Under Mild Conditions

Sulfonamides represent a crucial structural motif in numerous pharmacologically active compounds. Recognizing their diverse applications and significance in the pharmaceutical industry, scientists have been actively seeking sustainable methods for their synthesis since the turn of the century. This pursuit aims to eliminate the use of toxic chemicals and volatile organic compounds (VOCs), such as pyridine and dichloromethane, which are commonly employed. Our research contributes to this endeavor by establishing environmentally benign procedures for the synthesis of sulfonamides under sustainable conditions. Deep eutectic solvents (DESs) have proven to be highly effective reaction media3 for facilitating N–S bondforming processes under remarkably mild conditions, notably at room temperature and under ambient air. This innovative approach enables us to circumvent the need for VOCs, stringent pH control, and the issues associated with poor solubility of starting materials, ultimately leading to improved yields and minimized waste generation, thus enhancing the atom economy of the reaction. Utilizing choline chloride (ChCl)-based DESs, we have successfully synthesized various types of sulfonamides from primary and secondary aliphatic and aromatic amines, as well as sulfonyl chlorides. The reactions typically reach completion within two hours, affording the desired products in yields of up to 97%.