Amines as antisolvents

Crystallization of Sodium Chloride with Amines as Antisolvents... 

ZULEMA ET AL. Crystallization ofNaCl with Amines as Antisolvents 233... 

ZULEMA T AL. CrystaUkotion ofNaCl with Amines as Antisolvents 235... 

The suitability of the amines diisopropylamine (DiPA) and dimethylisopropylamine (DMiPA) as antisolvents for the crystallization of sodium chloride from its aqueous solution has been demonstrated. Both amines decreased the sodium chloride solubility substantially. The presence of a two liquid phase area offered the opportunity to separate the amines from the mother liquor after crystallization by a temperature increase. In the two liquid phase area the mutual solubilities of the water and the amines were low, so the separability was good. Continuous crystallization experiments were carried out at temperatures below the liquid-liquid equilibrium line in the single liquid phase area. The product consisted of cubic agglomerated NaCl crystals with maximum primary particle sizes of 10-70 pm. 

With the experimentally determined solubility data the maximum obtainable magma densities (AfT,max) were calculated for the crystallization of sodium chloride from its saturated solution with DMiPA as antisolvent. Mr,max is defined as the total mass of solids divided by the mass of the suspension times one hundred, if the supersaturation in the crystallizer is zero. In Figure 7 MT,max is displayed as a function of the amine to brine feed ratio. It can be seen that the maximum obtainable magma densities are generally low, which will probably give rise to high supersaturations during crystallization. 

Continuoiis Crystallization Experiments. Continuous crystallization experiments were conducted in the single liquid phase area with DiPA and DMiPA as antisolvents. The size, shape and purity of the sodium chloride crystals formed in these experiments were studied. To investigate the influence of the antisolvent concentration on these product characteristics, experiments were performed at several amine to brine feed ratios. All crystallization experiments were carried out in duplicate and the reproducibility was good. 

The enantioselective synthesis of MK-4305 93 was achieved with the help of classic resolution by using a chiral dibenzoyl-D-tartaric acid (DBT) for resolving the racemic amine intermediate 96. By tedious optimization of the resolution protocol changing the solvent and antisolvent systems, excellent enantioselectivity could be achieved by using 1.85 equivalents of the chiral DBT and a mixture of tetrahydrofuran and dichloromethane as the solvent system. 

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