Environmentally friendly catechol-based synthesis of dibenzosultams

Abstract

Sulfonamides, such as cyclic sultams, are widely used structural blocks in drug design. Here, an environmentally friendly route of synthesis is reported for sultams containing a catechol function in the secondary aromatic ring (ring B), making use of water as a solvent. The reaction can also be paired with THF for enhanced solubility. It occurs by the application of a base and heat and proceeds through what is presumably an oxidation of the catechol function followed by nucleophilic addition by the nitrogen of the sulfonamide. The reaction is robust and reproducible, as demonstrated by the successful synthesis of eight different sultams with significant variation possible in both the primary aromatic ring (ring A) and in the group attached to the sultam nitrogen, with isolated yields of 43–86% after purification.