*2.1. Substances*

For the fluidized bed crystallization experiments, racemic asparagine monohydrate (rac Asn·H2O) and the respective enantiopure D- and L-Asn·H2O were purchased from Sigma Aldrich (Purity >99%, Steinheim, (Baden-Württemberg), Germany). Both were used without further treatment. Deionized water (Millipore, Milli-Q Advantage A10) was used as solvent and for washing of the crystalline product together with ethanol, which was purchased from VWR Chemicals (Purity >99.7%, Fontenay-sous-Bois, France).

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.

$$\mathbf{x\_{sat,i}} \left( \mathbf{T\_{\prime}} \frac{\mathbf{x\_{\parallel}}}{\mathbf{x\_{\rm Solvent}}} \right) = 0.0104 + 1.0584 \times 10^{-4} \cdot \mathbf{T} + 2.4432 \times 10^{-5} \cdot \mathbf{T}^2 + 0.0312 \cdot \frac{\mathbf{x\_{\parallel}}}{\mathbf{x\_{\rm Solvent}}}.\tag{1}$$

where

T = temperature [◦C] x = mass fraction [-]

for

$$\text{Si} = \text{D-Asn} \cdot \text{H}\_2\text{O, L-Asn} \cdot \text{H}\_2\text{O and j} = \text{D-Asn} \cdot \text{H}\_2\text{O, L-Asn} \cdot \text{H}\_2\text{O} \neq \text{i}$$

**Figure 2.** Upper 20% section of the ternary phase prism of the asparagine monohydrate enantiomers in water at different temperatures. 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·H2O and L-Asn·H2O, respectively. Reprinted with permission from [19]. Copyright 2020 American Chemical Society.

The selective removal of the seeded enantiomer during Preferential Crystallization leads to an altering of the liquid phase composition during the course of the separation process. Hence, the driving forces of both enantiomers change and a different supersaturation calculation also need to be applied. Thus, Equation (2) is utilized in the present study to describe the supersaturation, S, as a function of temperature and composition.

$$\mathbf{S}\_{\mathbf{i}}(\mathbf{T}, \mathbf{x}\_{\mathbf{i}}) = \frac{\mathbf{x}\_{\mathbf{i}}}{\mathbf{x}\_{\text{sat}, \mathbf{i}}(\mathbf{T}, \frac{\mathbf{x}\_{\mathbf{i}}}{\mathbf{x}\_{\text{Solvent}}})} \tag{2}$$

for

$$\text{ri} = \text{D-Asn} \cdot \text{H}\_2\text{O, L-Asn} \cdot \text{H}\_2\text{O and j} = \text{D-Asn} \cdot \text{H}\_2\text{O, L-Asn} \cdot \text{H}\_2\text{O} \neq \text{ii}$$
