Enantiorecognition on solid chiral selectors using microbatch technology: an example of limitation in case of strong association in the racemate

When they were independently tested, the enantiomers of N , N ′‐bis(salicylidene)‐ trans ‐1,2‐cyclohexanediamine showed a large difference in adsorption on new chiral selectors using microbatch technology. Surprisingly, when these enantiomers were applied on the same supports as a racemic mixture, no discrimination was observed even though suitable adsorption existed. When a mixture enriched in one enantiomer (scalemic mixture) was applied, the resulting supernatant contained the racemic form and the enantiomer in excess was adsorbed on the support together with a part of racemate. This behavior, which militates in favor of a strong heterochiral dimer formation in the racemate, was revealed using microbatch technology but remained hidden on classical column chromatography on chiral support. Molecular dynamics calculations corroborate this hypothesis, showing a favorite binding mode of the heterochiral dimer, which is stabilized by various inter‐ and intramolecular interactions. Our findings may be considered as a new limitation of microbatch technology, but they may have some inference in case of chiral amplification using the N , N ′‐bis(salicylidene)‐ trans ‐1,2‐cyclohexanediamine enantiomers as chiral ligands. Copyright © 2005 John Wiley & Sons, Ltd.