Sulfonamide Metal Complexes: Review on Synthetic Strategies and Processes

Abstract

Sulfonamides, the first commercial broad‐spectrum antibiotics, face escalating bacterial resistance. Forming metal complexes via coordination restores and enhances antibacterial activity while imparting novel antifungal and anticancer properties. Although a recent authoritative review has comprehensively surveyed the biological activities of these complexes, a systematic analysis of synthetic methodologies has been lacking. This review provides the first synthetic‐strategy‐centric framework for sulfonamide metal complexes. We critically examine the reflux‐precipitation method, showing how sodium salt substitution, replacement of strong bases with weaker alternatives, and room‐temperature aqueous conditions have collectively increased yields from 18%–55% to 89%–98%. Three routes for constructing ternary complexes—recrystallization, one‐pot synthesis, and the metal‐complex precursor method—are compared and their application scenarios delineated. Emerging green technologies, including electrochemical synthesis delivering 97% yield in just six minutes for silver complexes, and microwave‐assisted synthesis, are evaluated with a candid assessment of their limitations. Finally, we propose a three‐tier ligand–metal–method conceptual framework with practical design guidelines to help researchers select optimal synthetic routes, accelerating the shift from empirical trial‐and‐error toward rational design.