Enantiomeric separation of alcohols by gas chromatography and QSPR study to predict enantiomeric separation

Abstract

Enantiomeric separation of 55 alcohols (13 aliphatic alcohols and 42 alcohols of aromatic structure) was studied by gas chromatography using octakis(2,3-di-O-acetyl-6-O-tert-butyldimethylsilyl)-γ-CD (or GSiAc) as a chiral stationary phase. For separation under temperature program, 44 alcohols could be enantioseparated. The only aliphatic alcohol that could be completely separated into their enantiomers was 2-hexanol. Twenty-five alcohols, based on 1-phenylethanol, were selected to study under isothermal conditions. For halogen-substituted 1-phenylethanols, temperature strongly affected enantioselectivities of para-substituted alcohols. However, temperature affected enantioselectivities of methyl- or trifluoromethyl-substituted alcohols at ortho-position more than other positions. For para-substituted alcohols, enantioseparations could be improved with the substituent in the order of halogen > trifluoromethyl > alkyl > phenyl. In addition, temperature affected enantioselectivities of alcohols with small alkyl substitution at the stereogenic center rather than bulky alkyl or phenyl group.

Attempt to find model that can predict enantioseparations of these alcohols was made using several molecular modeling techniques. From molecular docking calculations, the best predictive model has an accuracy of 83.64 %. MD simulations were applied for only 5 selected alcohols with different enantioselectivities and the results showed no relationship with enantioselectivity. For QSPR studies, excellent models to predict elution temperatures of the less retained and the more retained enantiomers were developed with the average errors of only 2.30 and 2.68 degrees Celsius, respectively.