Continuous separation of racemic 3,5-dinitrobenzoyl-amino acids in a centrifugal contact separator with the aid of cinchona-based chiral host compounds.

Resolution through revolution: It is possible to extract 3,5-dinitrobenzoyl-protected amino acids enantioselectively with the aid of a table-top centrifugal contact separator and a catalytic amount of a chiral host compound based on the Cinchona alkaloids. Enantioselectivities of up to 80 % could be reached in a single pass. This allows the development of a process for the continuous separation of racemates.The resolution of racemates is mostly performed by crystallisation of diastereomeric salts. Direct physical separation could be much more efficient, but so far most concepts, with the exception of SMB, have proven to be non-scaleable. Here we report the first scalable process for the resolution of N-protected amino acid derivatives through selective extraction, with the aid of a catalytic amount of a chiral host compound based on Cinchona alkaloids. The method hinges on the use of centrifugal contact separators (CCSs) for fast mixing and separation. Although the highest ee obtained was only 80 %, the concept can be extended through the use of a series of CCSs in countercurrent mode to effect full separation.

Identification of enantioselective extractants for chiral separation of amines and aminoalcohols.

The major obstacle for the introduction of fractional reactive extraction as a chiral separation method in the chemical and pharmaceutical industries is the lack of versatile enantioselective extractants. Therefore, a rational approach is developed to transfer the extensive knowledge of chiral selectors reported in the literature on chiral recognition and other chiral separation techniques to extraction. Based on a similarity in separation mechanisms, it was expected that chiral selectors originating from a technique in which chiral recognition takes place in the liquid phase are most likely to function as enantioselective extractant. Using this approach, a selection of promising extractants was made from the literature and experimentally evaluated for the enantioseparation of aminoalcohols and amines. As a result, four enantioselective extractant systems, namely, dibutyl-L-tartrate with boric acid, N-(2-hydroxydodecyl)-L-hydroxyproline Cu(II) complex, N-dodecyl-L-hydroxyproline Cu(II) complex, and azophenolic crown ether, have been identified. The azophenolic crown ether system performed the best and demonstrated an enantioselectivity between 1.3-5.0 for five out of six test compounds. Identification of the enantioselective extractant systems was highly facilitated by the developed rational transfer approach that, although partially qualitative, appeared capable of reducing more than 50 encountered candidates to only three promising systems for further experimental evaluation. Therefore, it is expected that this approach can be successfully applied to identify enantioselective extractants for other classes of enantiomers as well.

Investigation and characterization of liquid two-phase systems for the separation of crystal mixtures by interfacial partitioning.

The interfacial partitioning behavior of ampicillin and phenylglycine crystals in different two-phase systems has been investigated. The two-phase systems employed are water/dodecane, water/1-butanol, and water/pentane/methanol. By means of partition experiments and microscopic imaging, it has been shown that the mechanism of separation strongly depends on the choice of the two-phase system. While water/dodecane features a mechanism of sheer competitive adsorption at the interface, separation in water/1-butanol is mainly due to partitioning into both liquid phases, leading to a higher degree of separation. Experiments with water/pentane/methanol have illustrated the large potential of three-component systems, as slight variations in the composition can have large effects on the separation.