Effect of Temperature on Retention and Enantiomeric Separation of Chiral Sulfoxides using Teicoplanin Aglycone Chiral Stationary Phase

Abstract

The effect of temperature on the LC resolution of racemic aromatic sulfoxides was studied between 10 and 50°C in the polar organic mode on a teicoplanin aglycone chiral stationary phase (CSP). The set of 10 chiral sulfoxides compounds consisted of 2‐,3‐,4‐toluyl methyl sulfoxides and phenyl methyl sulfoxides with different 2‐,3‐,4‐halogen substituents on the aromatic ring. The van't Hoff plots were constructed to determine the thermodynamic data, and in order to promote an understanding of the mechanism of enantioseparation. The van't Hoff plots (ln k versus 1/T and ln α versus 1/T) were linear for all enantiomers. Plots of ln α versus 1/T afforded thermodynamic parameters, such as the change in enthalpies Δ(ΔH _2,1 ) and the change in entropies Δ(ΔS _2,1 ) for the sulfoxide enantiomers. If Δ(ΔH _2,1 ) and Δ(ΔS _2,1 ) are invariant with temperature, the Δ(ΔG _2,1 ) values can be determined using the Gibbs‐Helmholtz equation. The influence of different substituents and their position on the aromatic ring of the sulfoxides on their enantioseparation was correlated to the thermodynamic data. The elution order of the sulfoxide enantiomers does not reverse in the temperature range of 10 to 50°C. All chiral sulfoxides separated on teicoplanin aglycone CSP showed the (S)‐(+)‐enantiomer eluting first at all temperatures.

Keywords:

• Chiral separation
• HPLC
• Teicoplanin aglycone CSP
• Thermodynamic study
• Chiral compounds
• Sulfoxides

Acknowledgments

The authors acknowledge the support of the Grant Agency of Slovak Republic (VEGA 1/8213/01 and 1/9127/02), and the Agency for International Science and Technology Cooperation in Slovakia (Grant No. 035/2001, USA‐SK).

Support of this work by the National Institutes of Health, NIH RO1 GM53825‐08, is gratefully acknowledged.