Stieglitz rearrangement of N,N-dichloro-β,β-disubstituted taurines under mild aqueous conditions

New topical anti-infectives comprised of N,N-dichloro-β,β-disubstituted taurines [Tetrahedron Lett.2008, 49, 2193; Biorg. Med. Chem. Lett. 2009, 19, 196] have been examined for structure–stability relationships (SSR) based upon various alkyl, heteroalkyl and cycloalkyl β-substitutions. These substitutions affect order-of-magnitude changes in the aqueous stability of these N,N-dichloroamines which can undergo Stieglitz rearrangement of alkyl groups under extremely mild conditions (H2O, pH 4–7, 0–20 mM acetate or phosphate buffer, 20–40 °C). This process produces β-ketosulfonic acids which function as substrates for chlorination by the N-chlorotaurines which leads to their further degradation.

Graphical abstractThe structure–stability relationship (SSR) of alkyl and cycloalkyl β-substitutions on N,N-dichlorotaurines reveals order-of-magnitude changes in their aqueous (pH 4–7, 20–40 °C) stabilities. Stieglitz rearrangement is one of the mechanisms of decomposition and produces β-ketosulfonic acids and chlorinated derivatives thereof.Figure optionsDownload full-size imageDownload as PowerPoint slide