NMR and molecular modeling of the dimeric self-association of the enantiomers of 1,1 '-bi-2-naphthol and 1-phenyl-2,2,2-trifluoroethanol in the solution state and their relevance to enantiomer self-disproportionation on achiral-phase chromatography (ESDAC)

Molecular modeling of the homo-and heterochiral dimeric self-associates of the enantiomers of 1,1'-bi-2-naphthol and 1-phenyl-2,2,2-trifluoroethanol in solution has been performed in order to understand their NMR behavior and in light of the phenomenon of enantiomer self-disproportionation on achiral-phase chromatography (ESDAC). For 1,1'-bi-2-naphthol in C6D6, distinct NMR signals for each enantiomer arise for some spins in non-racemic mixtures-the phenomenon of self-induced diastereomeric anisochronism (SIDA). The linear divergence of these split signals across an enantiomeric titration (a series of samples in which the percentage of one enantiomer is varied from 50-100% whilst maintaining a constant total concentration), as well as the near linear migration of certain signals in CDCl3 across a similar enantiomeric titration, where signals were not observed to be split, is consistent with the calculated small energy differences between the homo-and heterochiral associates. For an enantiomeric titration of 1-phenyl-2,2,2-trifluoroethanol in n-hexane, NMR signals also remained unsplit but the noticeable migration of some revealed a skew indicative of a preference for the heterochiral associate. This was duly reflected in the calculations which provided a Delta G value favoring the heterochiral associate by 2.4 kJ mol(-1). The relevance of these results to evaluating the likely occurrence of ESDAC is considered.