Separation of non-racemic mixtures of enantiomers: an essential part of optical resolution

Abstract

Non-racemic enantiomeric mixtures form homochiral and heterochiral aggregates in melt or suspension, during adsorption or recrystallization, and these diastereomeric associations determine the distribution of the enantiomers between the solid and other (liquid or vapour) phases. That distribution depends on the stability order of the homo- and heterochiral aggregates (conglomerate or racemate formation). Therefore, there is a correlation between the binary melting point phase diagrams and the experimental ee(I)vs. ee(0) curves (ee(I) refers to the crystallized enantiomeric mixtures, ee(0) is the composition of the starting ones). Accordingly, distribution of the enantiomeric mixtures between two phases is characteristic and usually significant enrichment can be achieved. There are two exceptions: no enrichment could be observed under thermodynamically controlled conditions when the starting enantiomer composition corresponded to the eutectic composition, or when the method used was unsuitable for separation. In several cases, when kinetic control governed the crystallization, the character of the ee(0)-ee(I) curve did not correlate with the melting point binary phase diagram.

Separation of the Mixtures of Chiral Compounds by Crystallization

“…The crystalline material can be separated from the residue by filtration, distillation, sublimation or extraction. 8 A similar separation can be achieved even if the amount of the resolving agent applied is less than an equivalent to the racemate. Then the enantiomeric mixture can be separated from the crystalline diastereisoomer by sublimation or distillation, in accordance with the above mentioned methods.…”

Gas antisolvent fractionation based optical resolution of ibuprofen with enantiopure phenylglycinol

“…Figure 7. presents the experimental data in the form of a general purification diagram suggested by Faigl et al [45]. The purification is not limited in the investigated range by any non-ideal behaviour.…”

“…According to the DSC thermograms, (S)-PhG forms a more stable salt with (S)-IBU than with (R)-IBU [44], because the homochiral (S-S, R-R) interactions are stronger than the interactions in the racemate type crystals [45]. The raffinate is enriched in (S)-IBU-(S)-PhG, the more stable diastereomeric salt, while the fluid phase is enriched in (R)-IBU.…”

A Presumable Mechanism of the Separation of Diastereomeric and Enantiomeric Mixtures

“…In this case the separation of enantiomeric mixtures are based on the exploitation of the distribution of hetero-and homochiral associates between two phases (most often between solid and liquid or vapour phases) [2].…”