STRUCTURE AND REACTIVITY IN INTRA-MOLECULAR CATALYSIS .4. CATALYSIS OF SULFONAMIDE HYDROLYSIS BY THE NEIGHBORING CARBOXYL GROUP

This paper reports kinetic data for the intramolecular carboxyl-catalyzed hydrolysis of 26 sulfonamides in water and in some mixed aqueous solvents. The effective molarity of the carboxyl group is very high (up to ca. 108 M) but depends markedly on the structure of the sulfonamide. Substituent effects within a series of 4-and 5-substituted 2-carboxy-N,N-dimethyl-benzenesulfonamides are interpreted in terms of nucleophilic catalysis with breakdown of the pentacovalent intermediate 18 rate determining. The role of nonbonded interactions in the initial state and in the transition state is discussed. By using X-ray structural data where available, strain effects have been elucidated for a series of sulfonamides in which the sulfonamide and carboxyl groups are held cis to each other. Striking differences from the corresponding carboxamide systems are attributed to differences in transition state geometries and steric effects. A “gem-dimethyl effect” is found in the hydrolysis of 14. Relative rates within a series of compounds with a variable carbon chain between the sulfonamide and carboxyl groups reflect entropic factors. The results indicate a clear preference for the formation of a five-membered cyclic transition state. Solvent effects on thermodynamic parameters of activation are analyzed for some highly aqueous mixed solvents taking into account the unique solvent properties of water. In t-BuOH-H2O effects originating from hydrophobic hydration give rise to mirror-image behavior of ΔH≠ and -ΔAS≠. © 1979, American Chemical Society. All rights reserved.