Simultaneous Determination of Enantiomerizationand Hydrolysis Kinetic Parameters of ChiralN-Alkylbenzothiadiazine Derivatives

On-column stopped flow multidimensional HPLC (sfMDHPLC) anddynamic high-performance liquid chromatography were applied to investigate the influenceof alkyl substituents at the sulfonamidic and amino moieties of benzothiadiazine1,1-dioxide derivatives on hydrolysis and enantiomerization rate constants. The dataobtained indicate the presence of pyrrolo substituent at the 3,4 positions on benzothiadiazinerings inhibits the hydrolysis, whereas the enantiomerization occurs in acidicmedium. Hydrolysis rates are quite similar for the two benzothiadiazines methyl substitutedto nitrogen at 2- and 4-positions. Conversely, enantiomerization rate of 4-N-methylsubstituted is significantly higher than 2-N-methyl substituted.