Sustainable Synthesis of 1,2,3‐Triazoles using Cyrene as a Biodegradable Solvent in Click Chemistry

Abstract The first successful synthesis of 1,2,3‐triazoles using Cyrene TM as a biodegradable and non‐toxic solvent in click chemistry has been developed. In contrast to previous methods, this sustainable approach allows product isolation by simple precipitation in water, eliminating the need for organic solvent extractions and column chromatography purifications, thus minimizing waste consumption while reducing operational costs. The protocol, performed also at gram scale, has broad applicability and versatility, as shown with complex substrates like biologically active coumarins or triazole‐linked bifunctional molecules. Finally, this protocol is also amenable to a three‐component reaction involving organic halides, terminal acetylenes and sodium azide, thus avoiding the isolation of organic azides, difficult‐to‐handle species known for their environmental sensitivity.