Mechanistic Aspects of Chiral Discrimination on an Amylose Tris(3,5-dimethylphenyl)carbamate

The separation of [2R-[2 (R*),3 ]]-5-[[2-[1-[3,5-bis-(trifluoromethyl)phenyl]ethoxy]-3-(S)-(4-fluorophenyl)-4-morpholinyl]-methyl]- N , N -dimethyl-1H-1,2,3-triazole-4-methanamine hydrochloride from its enantiomer was achieved on an amylose tris-3,5-dimethylphenyl carbamate stationary phase. The retention of the enantiomers is dominated by weak hydrogen bonds while the enantioselectivity is governed by other kinds of interactions, e.g., inclusion in the amylose carbamate chains. Van't Hoff plots of ln vs. reciprocal temperature were non-linear and could be divided into two linear regions. One region at low temperature (5C-∼20C) and another one between 25C-70C with the change in slope occurring between 16C and 20C. DSC experiments suggested that the behavior can be attributed to breakage of H-bonds triggering a conformational change. Molecular simulation indicated a correlation between the interaction energies and the elution order obtained experimentally. The most retained enantiomer (R,R,S-enantiomer) interacts with the stationary phase through a hydrogen bond between the triazole proton and the C=O groups of the stationary phase, as well as through an inclusion in the cleft of the stationary phase. The other enantiomer exhibits a bifurcated H-bond between the triazolic proton and the C=O groups of the stationary phase leading to a less stable complex.

Keywords:

• Ftatr-IR
• Amylose Tris-3,5-dimethylphenyl Carbamate
• Conformational Changes
• Van't Hoff Plot
• Molecular Modeling
• Hplc
• Dsc