Barriers to Stereoinversion of N-Aryl-1,3,2-benzodithiazole 1-Oxides Studied by Dynamic Enantioselective Liquid Chromatography

Abstract

Free energies of activation for the enantiomerization of a series of racemic N-aryl-1,3,2-benzodithiazole 1-oxides have been determined by dynamic high-performance liquid chromatography (DHPLC) on a chiral stationary phase. From a comparison of experimental and computer-simulated chromatograms, the barriers to stereoinversion at sulfur were found to be around 80 kJ/mol and relatively insensitive to effects from substituents in the N-aryl group. Throughout the series the (+)-forms (436 nm) were found to be of (S)-configuration.

Determination of enantiomerization barriers by dynamic and stopped‐flow chromatographic methods

“…However, the presence of the CSP clearly affects the height of the enantiomerization barrier. The barrier may be enhanced 8,16,17 or lowered, e.g., by catalysis. 43,44 Efforts have been made to combine the advantages of the stopped-flow approach with the option to perform enantiomerization in an achiral and inert environment.…”

“…82 Another example of the application of the SIMUL simulation program was given by Oxelbark and Allenmark. 17 They determined the free activation energies for the enantiomerization at sulfur of a series of racemic N-aryl-1,3,2-benzodithiazole-1-oxides (48, 49) by DHPLC on a (3R,4S)-Whelk-O1 CSP. Villani and Pirkle 83 also observed hindered inversion at sulfinyl and sulfonyl naphthalene derivatives, but did not evaluate the interconversion barrier.…”

Evaluation of reversible and irreversible models for the determination of the enantiomerization energy barrier for N‐(p‐methoxybenzyl)‐1,3,2‐benzodithiazol‐1‐oxide by supercritical fluid chromatography

“…2,5,30À32,36 The simulation procedure was later used and modified by König and co-workers, 6,33À35, 37 Gasparrini et al, 23 Oxelbark and Allenmark, 24 and Boyer. 49 The second group of methods, which allows the calculation of apparent interconversion rate constants directly from the peak areas of the enantiomers or their separate profiles in the interconversion region of the chromatogram, is based on peak deconvolution or stochastic methods.…”

On the use of a peak deconvolution procedure for the determination of energy barrier to enantiomerization in dynamic chromatography

“…A general observation is that the height of the second enantiomer peak in the simulated chromatograms is slightly lower than expected. This might be caused by the different number of theoretical plates found for the first and second enantiomers in the experimental chromatograms [3,11,16].…”

“…While the isolation of single enantiomers followed by classical racemization kinetics using chiroptical methods is cumbersome and time-consuming, dynamic [1,[3][4][5] and stopped-flow [6,[8][9][10] chromatographic techniques are more straightforward since enantiomers are separated and analyzed on-line, thus requiring only minute amounts of the racemic or enriched mixture of enantiomers. The lower energy barrier to interconversion of enantiomers (around 70-100 kJ mol -1 ) can be determined by dynamic HPLC (DHPLC) [11]. Higher energy barriers to interconversion of enantiomers (around 70-200 kJ mol -1 ) can be determined by dynamic gas chromatography (DGC) [9].…”