Effect of additives on the preferential crystallization of L-asparagine monohydrate

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 L-asparagine monohydrate (L-Asn·H₂O) as the preferred enantiomer in crystallization from DL-Asn·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 disperse. D-additives have a small effect on the growth rate of L-Asn·H₂O but L-Asp and L-Glu strongly inhibit the growth rate of L-Asn·H₂O in DL-Asn·H₂O solution; there must also be a corresponding effect for D-Asp and D-Glu on D-Asn·H₂O. Indeed, PC experiments showed that in order to obtain L-Asn·H₂O from a PC while preventing the formation of D-Asn·H₂O, D-Asp and D-Glu are suitable additives, leading to high yield and purity of pure L-Asn·H₂O.