Investigations of molecular recognition aspects related to the enantiomer separation of 2-methoxy-2-(1-naphthyl)propionic acid using quinine carbamate as chiral selector:: An NMR and FT-IR spectroscopic as well as X-ray crystallographic study

The chiral recognition mechanism of a cinchona alkaloid-based chiral stationary phase (CSP) showing high enantiomer discrimination potential for 2methoxy-2-(1-naphthyl)propionic acid (M alpha NP acid) was investigated. Conformational and structural analyses of the 1:1 complexes of 9-0-(tert-butylcarbamoyl) quinine selector (SO) and M alpha NP acid (selectand, SA) were carried out employing NMR spectroscopy in solution, Fourier-transform infrared (FT-IR) spectroscopy, and solid-state X-ray diffraction analysis. Intramolecular NOEs of a soluble analogue of the CSP afforded the conformational states of the free and complexed form of the selector. The H-1-NMR spectra revealed that the free form of the SO constitutes anti-open as well as anti-closed and/or syn-closed conformers. Upon complexation with the (S)-M alpha NP acid enantiomer to form the more stable diastereomeric associate, a conformational transition of the selector takes place, resulting in the synthesis of the anti-open conformer nearly exclusively. FT-IR spectra reveal that, besides the primary ion-pairing interaction, stereoselective hydrogen bonding stabilizes the more stable complex via the amide hydrogen of the SO. X-ray diffraction analysis of 9-0-(tert-butylcarbamoyl) quinine and (S)-M alpha NP acid complex further revealed the occurrence of a bidentate H-bondmediated ionic interaction between SO and SA as well as the lack of pi - pi interaction in the 1:1 complex, and corroborated the conclusions derived from spectroscopic and chromatographic studies.