Preferential Crystallization (PC) is a popular process to separate enantiomers, however the nucleation and growth of the counter enantiomer during the process can compromise the enantiopurity of the final crystalline product. This research investigates the use of additives to inhibit the nucleation and growth of the counter enantiomer. In this study, we use Lasparagine monohydrate (L-Asn•H2O) as the preferred enantiomer in crystallization from DLAsn•H2O solutions. Additives include both pure enantiomers of several related amino acid species. This allows investigation of differences in inhibition caused by additives that are of the same chirality and different chirality as the preferred enantiomer. The additives had no discernible effect on the solubility but had a small effect on the metastable limit, with additives tending to slightly widen the metastable zone but also make the zone widths more
Preferential crystallization (PC) is a process to separate enantiomers. The efficiency of seeded, isothermal PC was enhanced using tailor‐made additives to inhibit the crystallization of the counter‐enantiomer. The inhibition of D‐asparagine (D‐Asn) monohydrate using D‐glutamic acid (D‐Glu) and D‐aspartic acid (D‐Asp) as additives in PC was investigated by comparing the purity, yield, and particle size distribution after PC of L‐Asn·H2O from DL‐Asn·H2O. The amount of pure L‐Asn·H2O solid product that can be produced before crystallization of the counter‐enantiomer is higher when using the additives D‐Asp and D‐Glu. However, the crystal size of L‐Asn·H2O increases faster in PC without additives than in PC with additives. This means that the additives inhibit not only the crystallization of D‐Asn·H2O but also the crystal growth of L‐Asn·H2O.
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