Experimental investigation of chiral melting phase diagrams in high-pressure CO2 containing organic modifiers

Abstract

A measurement method suitable to investigate the melting behavior of solid mixtures in a high-pressure, co-solvent–modified CO₂ atmosphere was developed, using a variable volume, high-pressure view-cell. The solid sample is added after loading the organic solvents and pressurizing the cell with CO₂. Investigation of the melting behavior was done by a first-and-last melting point method at 16 MPa pressure. The melting point depression depended on the organic modifier (being acetonitrile or the 7:3 mixture of cyclohexane and isopropyl acetate). Adding acetonitrile in 2% to the carbon dioxide atmosphere shifted the chiral melting phase diagram of 3-chloromandelic acid by approx. 8–10 °C compared to the values measured earlier in pure carbon dioxide at the same pressure. The eutectic composition of the racemic compound remained unchanged (around 70–75% ee), which is comparable to the limiting composition observed in our earlier antisolvent recrystallization results aiming the enantiomeric purification of the model molecule.