Measurement and Evaluation of the Crystallization Kinetics of l-Asparagine Monohydrate in the Ternary l-/d-Asparagine/Water System

Abstract

Growth kinetics of L-asparagine monohydrate in racemic aqueous solutions as well as nucleation, growth and dissolution kinetics of the same enantiomer crystallized from pure Lasparagine solutions are measured and the kinetic parameters are estimated applying a recently developed shortcut-method. The corresponding experimental procedure is based on a small number of preferential (seeded) cooling crystallizations where the crystal size distribution is monitored with an online microscope. Afterwards, image analysis yields the transient particle size evolution of initially provided crystals, from which the response of the solid phase to the liquid phase driving force can be extracted. Subsequently, parameter estimation is carried out applying this data together with the information of concentration and composition of the liquid phase, to discriminate between different model approaches. The kinetics are validated finally with independent experiments to evaluate their quality. It is proven that growth kinetics of L-and D-asparagine monohydrate from water are identical. In contrast, it can be shown and quantified, that growth kinetics from racemic and enantiopure solutions of asparagine differ significantly from each other. The corresponding calculation of the driving force of enantiomeric systems is discussed in detail by means of ternary phase diagrams.

Systematic Investigations on Continuous Fluidized Bed Crystallization for Chiral Separation

“…Significant gain of the fluidized crystal bed height was not observed during 90 min operation time using the lowest driving force (1.13), and, thus, no product withdrawal could be realized. Previous studies [19] proved that crystal growth of Asn•H 2 O still takes place at this supersaturation. The absent gain of the crystal bed height could be explained by the reduced growth rate of the seed crystals, which are mainly discharged at the top of the crystallizer as a consequence.…”

“…Solubility data of the D-/L-Asn•H2O/ water system was mainly determined in [18]. The accuracy was confirmed by additional measurements in [19] where also the parameters of polynomial (Equation (1)) were estimated to describe the saturation concentration, xsat, as a function of temperature and composition. As shown in Figure 2, asparagine monohydrate forms a conglomerate, as a requirement for the application of Preferential Crystallization directly from a supersaturated racemic liquid phase.…”

“…All axes are given in mass fractions × 100 (wt%). Black and white dots-solubility data from [18] and [19], respectively. Red and blue surface-fitted solubility surface of D-Asn•H 2 O and L-Asn•H 2 O, respectively.…”

“…Red and blue surface-fitted solubility surface of D-Asn•H 2 O and L-Asn•H 2 O, respectively. Reprinted with permission from [19]. Copyright 2020 American Chemical Society.…”

Resolution Control in a Continuous Preferential Crystallization Process

“…14 This measured solubility compares well to literature values. 14,32,33 Furthermore, the measured MSZW of L-asn is substantial, approximately 18°C between clear and cloud points, although it varies by approximately 2°C across different concentrations.…”