Potential of Chiral Solvents for Enantioselective Crystallization. 2. Evaluation of Kinetic Effects

Abstract

In part 1 of this work, the potential of chiral solvents in enantioseparation was studied for two pharmaceutical substances with regard to thermodynamics (Cryst. Growth Des. 2008, 8, 3408−3414). Unfortunately, no measurable chiral recognition in terms of the solubility equilibria was observed between the chiral solvents and the chiral systems investigated. In this part 2, studies are directed toward the potential of chiral solvents in enantioseparation based on differences in crystallization kinetics. For the case study performed, mandelic acid as a racemic compound forming system has been chosen. The crystallization kinetics (metastable zone width data with regard to primary nucleation) determined for mandelic acid in the chiral solvents (S)-ethyl lactate and (2R,3R)-diethyl tartrate are shown and discussed. On that basis successful preferential nucleation/crystallization experiments allowed for racemate resolution. To explain the observed results solvation enthalpy data obtained from dissolution enthalpy measurements are considered. Copyright © 2009 American Chemical Society [accessed March 17, 2009

Processes To Separate Enantiomers

“…Specifically chosen solvents were applied also to verify the feasibility of resolving racemic compounds. [135][136][137][138] Selected results will be depicted in more detail in chapter 3.3.2.…”

Verfahren zur Enantiomerentrennung

“…Spezifisch ausgewählte Lçsungsmittel wurden auf ihre Fähigkeit untersucht, auch die Enantiomerentrennung racemischer Verbindungen zu ermçglichen. [135][136][137][138] Ausgewählte Ergebnisse werden in Abschnitt 3.3.2 näher vorgestellt.…”

“…[136] Beispielsweise ist in DET der metastabile Bereich bezüglich der primären Keimbildung für (R)-Mandelsäure schmaler als für (S)-und racemische Man- Abbildung 11. Ternäre Lçslichkeitsphasendiagramme der Mandelsäure-Enantiomere in a) Wasser [153] und b) (2R,3R)-Diethyltartrat.…”

Surface-induced enantiomorphic crystallization of achiral fullerene derivatives in thin films

“…16 Chiral induction, where an assembly of achiral species acquires structural chirality by interacting with a chiral species, provides a way to create chirality in condensed matter. 17,18 Chiral induction has been reported in self-assembled structures in solution, [19][20][21] crystallization from solution, [22][23][24][25] and liquid crystals. [26][27][28][29] For thin lm form of the materials which is relevant to the applications, chiral dopants can induce structural chirality in lms of achiral semiconducting polymers.…”