Sulfoximine and Triazine-Acid Adduct Behavior in Aqueous HPMC: A Fast and Convenient N -Functionalization of Sulfoximines

Sulfoximines are valuable scaffolds in pharmaceuticals, yet their aqueous-phase stability and reactivity remain underexplored. We report a systematic study of sulfoximine–carboxylic acid coupling in water using hydroxypropyl methylcellulose (HPMC) as a microenvironment. In situ 19F NMR revealed potential key intermediates and the critical role of LiCl in their stabilization in water. The optimized protocol tolerates diverse functional groups, operates under mild conditions, and scales efficiently. These findings enable efficient sulfoximine functionalization and provide mechanistic insights.