Energy barrier determination of enantiomerization of chiral 3,4-dihydro-1,2,4-benzothiadiazine 1,1-dioxide type compounds by enantioselective stopped-flow HPLC

Determination of kinetic parameters of enantiomerization of benzothiadiazines by DCXplorer

“…Among different commercial available chiral stationary phases (CSP), cellulose 3,5‐dimethylphenylcarbamate (Chiracel OD‐RH) was chosen, because it was previously employed successfully for the enantioseparation of chiral benzothiadiazine‐type compounds 4, 29, 30, 32–34…”

Simultaneous determination of enantiomerization and hydrolysis kinetic parameters of chiral N‐alkylbenzothiadiazine derivatives

“…8 Previously, we have studied the stability of several benzothiadiazine derivatives and it turned out a rapid interconversion of the enantiomers (enantiomerization) in aqueous solution and a rapid hydrolysis in acidic medium. [9][10][11][12][13] Rate constants and free energy barriers of enantiomerization of configurationally labile chiral compounds were calculated by several methods, such as dynamic NMR [14][15][16] (DNMR), chiro-optical methods, 17,18 off-column and on-column chromatographic methods [i.e., dynamic gas chromatography (DCG), 19 dynamic high-performance liquid chromatography (DHPLC), 20 dynamic capillary electrophoresis (DCE), 21 and stopped-flow HPLC 22 (sfHPLC)]. As on-column chromatographic methods required minute amounts of the unresolved racemic sample, they are widely used.…”

Enantiomerization of chiral 2,3,3a,4-tetrahydro-1H-pyrrolo[2,1-c][1,2,4]benzothiadiazine 5,5-dioxide by stopped-flow multidimensional HPLC☆

“…Previously, we have reported the resolution of IDRA21 enantiomers by chiral chromatography and found that a rapid interconversion (enantiomerization) of the IDRA21 enantiomers occurred in aqueous solution [12]. A procedure for the determination of apparent rate constants and apparent free energy barriers of enantiomerization without the implementation of computer simulation has been developed [13][14][15][16][17][18][19][20][21][22][23][24][25][26]. The HPLC stopped-flow procedure developed was applied to study on-column enantiomerization of several chiral benzothiadiazines and it turned out a relatively low activation barrier of enantiomerization in aqueous solvents [13].…”

“…More recently it was developed a procedure for the determination of rotational barriers of configurationally labile compounds based on single column stopped-flow HPLC (sfHPLC) and stoppedflow GC (sfGC) where, in contrast to dynamic methods, computer simulation is not necessary [13][14][15][16][17][18][19][20][21][22][23][24][25][26]. Unfortunately, by using single column dynamic and stopped-flow methods, enantiomerization Step 1: (±)(R,S)-2 was injected and a quantitatively separation of enantiomers occurred in the first chiral OD-R column at low temperature conditions.…”