Mechanism of optical resolutions via diastereoisomeric salt formation. Part 6. Thermoanalytical investigation of the optical resolution of racemic mandelic acid with S-(+)-2-benzylamino-butanol

Abstract

The optical resolution of racemic mandelic acid (I) by S-2-benzylamino-butanol (II) was performed in water, ethyl acetate, and water saturated ethyl acetate. It was found that the efficiency of the resolution is three times higher in water saturated ethyl acetate than in either water or ethyl acetate. The salt mixtures produced during the resolutions and the pure diastereoisomeric salts were analyzed by TG, DSC and X-ray powder diffraction measurements. The R-(-)-I×S-(+)-II salt has the higher melting point and heat of fusion value which indicates that this is the more stable salt. Though the general assumption is that diastereoisomeric salt pairs of successful optical resolutions form eutectic systems, the R-mandelic acid-S-2-benzylamino-butanol and the S-mandelic acid-S-2-benzylamino-butanol system was found to behave in a different way. Melting did not start at or near the estimated eutectic temperature. The difference can be explained either by miscibility in the solid phase (solid solution) or by a blocked interaction between the crystals of the two solid salts. This unusual behaviour of the salt pair should be responsible for the unusual difference in the efficiency of the resolutions performed in different solvents