Sulfanilamide Synthesis with a Modern Silyl-Sulfinylamine Willis Reagent

In this experiment, a novel synthetic approach is performed to produce sulfanilamide, a “sulfa” drug that contributed to the proliferation of many antibacterials in the early 20th century. Despite the early ubiquitous use of sulfanilamide as a front-line remedy, no synthesis pathway is feasibly accomplished with safe reagents and in a timely manner. Commonly, aniline would be protected followed by sulfonation with gaseous SO2 and deprotection. A Willis reagent allows for a modern and convenient alternate route that involves a one step addition with a Grignard to produce the final sulfonamide after workup. The generation of the short-lived Willis reagent from commercially available starting products is confirmed as well as its efficacy to add a sulfinyl group to the substrate.