Vibrational circular dichroism (VCD) methodology for the measurement of enantiomeric excess in chiral compounds in solid phase and for the complementary use of NMR and VCD techniques in solution: the camphor case

Abstract

For the first time, the success of a methodology for the determination of enantiomeric excesses (% ee) in chiral solid samples by vibrational circular dichroism (VCD) spectroscopy is reported. We have used camphor to determine the % ee in a blind sample constituted by a mixture of its two enantiomers as a test of the validity of our approach. IR and VCD spectra of different enantiomeric mixtures of R/S-camphor in nujol mulls were recorded and linear regressions of VCD intensities (ΔAbs.) vs. % ee for selected bands were found. Finally, the VCD intensities of a blind sample were interpolated in these linear regressions, obtaining its % ee with a rms of 2.4. These results in the solid phase were complemented with the determination of % ee in the liquid phase by VCD and NMR techniques, which are proved to be complementary techniques to carry out this kind of analysis. In the same way as in the VCD solid phase, linear regressions of ΔAbs. vs. % ee for selected bands were established, obtaining a rms of 1.1 in the % ee determination of a blind sample. 1H NMR experiments at 600 MHz using the chiral solvating agent, (S,S)-ABTE, allow to determine in CD2Cl2 solution the proportions of enantiomers with great accuracy. 13C CPMAS NMR spectra prove that this technique cannot be used for conglomerates and/or solid solutions.