One-Dimensional 13C NMR Is a Simple and Highly Quantitative Method for Enantiodiscrimination

Molecules. 2018 Jul 20;23(7):1785. doi: 10.3390/molecules23071785.


The discrimination of enantiomers of mandelonitrile by means of 1D 13C NMR and with the aid of the chiral solvating agent (S)-(+)-1-(9-anthryl)-2,2,2-trifluoroethanol (TFAE) is presented. ¹H NMR fails for this specific compound because proton signals either overlap with the signals of the chiral solvating agent or do not show separation between the (S)-enantiomer and the (R)-enantiomer. The 13C NMR method is validated by preparing artificial mixtures of the (R)-enantiomer and the racemate, and it is shown that with only 4 mg of mandelonitrile a detection limit of the minor enantiomer of 0.5% is obtained, corresponding to an enantiomeric excess value of 99%. Furthermore, the method shows high linearity, and has a small relative standard deviation of only 0.3% for the minor enantiomer when the relative abundance of this enantiomer is 20%. Therefore, the 13C NMR method is highly suitable for quantitative enantiodiscrimination. It is discussed that 13C NMR is preferred over ¹H NMR in many situations, not only in molecules with more than one chiral center, resulting in complex mixtures of many stereoisomers, but also in the case of molecules with overlapping multiplets in the ¹H NMR spectrum, and in the case of molecules with many quaternary carbon atoms, and therefore less abundant protons.

Keywords: CSA; Pirkle’s alcohol; TFAE; chiral solvating agent; chirality; enantiomers; mandelonitrile; qNMR.

MeSH terms

  • Acetonitriles / chemistry*
  • Carbon-13 Magnetic Resonance Spectroscopy* / methods
  • Carbon-13 Magnetic Resonance Spectroscopy* / standards
  • Limit of Detection
  • Molecular Structure
  • Reproducibility of Results


  • Acetonitriles
  • mandelonitrile