sulfonamide
/ sul-FON-uh-mide /
A sulfonamide is the nitrogen cousin of an ordinary amide, but built around sulfur instead of carbon: an amine joined to a sulfonyl group, R-SO2-N. Where an amide has C=O next to nitrogen, a sulfonamide has S with two oxygens, R-SO2-NHR'. You make one by letting an amine attack a sulfonyl chloride (R-SO2-Cl), with the nitrogen displacing chloride — a nucleophilic substitution at sulfur.
The same electronic story as amides applies, only stronger. The two electron-hungry oxygens on sulfur, plus delocalization of the nitrogen lone pair toward sulfur, drain electron density off nitrogen. The upshot is that the N-H of a sulfonamide is noticeably acidic (pKa around 10) — acidic enough to be deprotonated by ordinary hydroxide — and the nitrogen is a poor base. A sulfonamide bond is also very robust, hard to hydrolyze, which is part of why these groups are so common in stable drug molecules.
Sulfonamides earned their fame as the original 'sulfa drugs', the first broadly effective antibacterial agents (sulfanilamide and relatives), which work by mimicking a metabolite bacteria need to make folic acid. Today the sulfonamide group is everywhere in medicinal chemistry, from diuretics to diabetes drugs. In the lab the same chemistry underlies the Hinsberg test, where benzenesulfonyl chloride sorts primary, secondary, and tertiary amines apart by whether (and how) they form a sulfonamide and whether it dissolves in base.
Sulfanilamide, H2N-C6H4-SO2-NH2, the prototype sulfa drug, is just aniline-derived with a sulfonamide group; it blocks bacterial folate synthesis by impersonating para-aminobenzoic acid.
From a simple sulfonamide came the first wonder antibiotics.
Despite the name, a sulfonamide nitrogen is a weak base and its N-H is actually acidic (pKa about 10), because the two oxygens on sulfur pull electron density away — the opposite of how a free amine behaves.