Experimental Determination of a Chiral Ternary Solubility Diagram and Its Interpretation in Gas Antisolvent Fractionation

Abstract

Although crystallization has been widely applied for the enantiomeric enrichment of non-racemates both in research and in industrial applications, the physical–chemical background of chiral crystallizations is not as frequently discussed. A guide for the experimental determination of such phase equilibrium information is lacking. In the current paper, the experimental investigation of chiral melting phase equilibria, chiral solubility phase diagrams and their application in atmospheric and supercritical carbon dioxide-assisted enantiomeric enrichment is described and compared. Benzylammonium mandelate is a racemic compound; it shows eutectic behavior when molten. A similar eutonic composition was observed in its methanol phase diagram at 1 °C. The influence of the ternary solubility plot could be unequivocally discovered in atmospheric recrystallization experiments, which proved that the crystalline solid phase and the liquid phase were in an equilibrium. The interpretation of the results obtained at 20 MPa and 40 °C, using the methanol–carbon dioxide mixture as a pseudo-component, was more challenging. Although the eutonic composition was found to be the limiting enantiomeric excess value in this purification process as well, the high-pressure gas antisolvent fractionation results were only clearly thermodynamically controlled in certain concentration ranges.

Keywords

• ternary solubility plot
• eutonic composition
• enantiomeric enrichment
• self-disproportionation of enantiomers