Continuous Separation of Racemic 3,5‐Dinitrobenzoyl‐Amino Acids in a Centrifugal Contact Separator with the Aid of Cinchona‐Based Chiral Host Compounds

• Published in: Chemistry : a European journal 2009-02, Vol.15 (9), p.2111-2120
• Main Authors: Hallett, Andrew J., Kwant, Gerard J., de Vries, Johannes G.
• Format: Article
• Language: English
• Subjects: amino acids; Amino Acids - chemistry; Chromatography, Liquid - methods; Cinchona Alkaloids - chemistry; host–guest systems; liquid‐phase separation; membranes; Molecular Structure; process intensification; Stereoisomerism; transport
• ISSN: 0947-6539; 1521-3765
• DOI: 10.1002/chem.200800797

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. 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.