Nucleation and Growth Kinetics of (R)-Mandelic Acid from Aqueous Solution in the Presence of the Opposite Enantiomer

Abstract

Resolution of mandelic acid (MA), a racemic compound, is presented in this article using direct crystallization from enantiomeric enriched water solutions. Final crystals with enantiomeric excess (ee) of (R)-MA higher than 96.4% were obtained. Because of the presence of the opposite enantiomer ((S)-MA), it was reported that nucleation and growth of (R)-MA was inhibited at the initial stage of the experiment (Perlberg, et al. Ind. Eng. Chem. Res. 2005, 44, 1012-1020. In order to understand the nucleation and growth kinetics of (R)-MA in the presence of (S)-MA, batch crystallization experiments were performed for controlled linear cooling mode with various operating conditions. Nucleation and growth parameters were then estimated by nonlinear fitting the measured liquid concentrations obtained from the signals of in situ attenuated total reflectance infrared (ATR-IR) spectroscopy and online polarimetry with model predictions. The effects of supersaturation, seed amount, cooling rate, and the presence of opposite enantiomer on the growth and nucleation rate of (R)-MA were discussed.

Optimal operation of batch enantiomer crystallization: From ternary diagrams to predictive control

“…This expression for supersaturation, where S sup 5 w R w R;sat , is consistent with the literature 19 and eliminates the need for the experimentally developed fit for the solubility data utilized by Ref. 39 and instead allows for use of solubility data derived from the ternary diagram in determining the crystal growth and nucleation rates. Specifically, using w sat R computed from Eq.…”

“…Even when crystal data is available that can be used for estimating the parameters of nucleation and growth rate models, the experimental conditions under which that data was obtained may be different from the conditions for which a nucleation and growth rate model is desirable (one approach to deal with this issue is the use of Kinetic Monte Carlo simulation 45 ) In the particular case of mandelic acid, an additional difficulty for determining crystal nucleation and growth rates is that the presence of the opposite enantiomer in the mother liquor can affect the nucleation and growth kinetics of the desired enantiomer. 39 There are few studies in the literature addressing the estimation of kinetic parameters for enantiomeric system crystallization. For example, for the R-MA case, Ref.…”

Kinetics of (R,S)- and (R)-mandelic acid in an unseeded cooling batch crystallizer

“…The population balance equation (PBE) is usually used to describe the particle size distribution of a crystallization process [5,[28][29][30]. The PBE written in terms of length L with size-independent growth reads is given in Eq.…”

Solid Tryptophan as a Pseudoracemate: Physicochemical and Crystallographic Characterization

“…Depending on the type of racemates, two crystallization methods, direct crystallization and crystallization via diastereomeric salt formation, are widely used for chiral resolution. Theoretically, pure enantiomers can be obtained through preferential crystallization of conglomerate‐forming systems or compound‐forming systems with one enantiomer present in a sufficient enantiomeric excess . For pseudoracemates, pure enantiomer cannot be obtained by preferential crystallization, although enrichment of one enantiomer is attainable for Type II and Type III solid solution systems, as demonstrated in Figure .…”