Solvents crystallization-based enantiomer

Even nowadays, particularly in industrial processes, the separation of enantiomers of racemic acids and bases is based on this molecular chiral recognition. The less soluble, i.e. the more stable of these diastereomer salts crystallizes even if the chiral agent in the better soluble salt is replaced by an achiral reagent of similar chemical character, or eventually eliminated, or substituated by a solvent. In this case, a mixture enriched with the more stable diastereomer can be isolated by filtration from the solution of the achiral salt of the enantiomeric mixture or the free enantiomers [2,3]... 

Assume that the racemic alanine (47) must be resolved into pure 1-alanine. If racemic 53 (53mc) reacts with enantiopure 117, the salt of each enantiomer is formed 118 and 119. These diastereomeric salts are separated by fractional crystallization, assuming that one salt is more or less soluble in a given solvent than the other. If 118 can be crystallized from a solution, a highly purified 119 remains in solution. The salt 119 is isolated and recrystallized from a different solvent to high enantiopurity. When this process is complete, 118 is treated with dilute base to regenerate 117 and 1-alanine, 53. The other enantiomer, d-alanine, is similarly obtained from 119. 

One area of chirotechnology which is undergoing rapid development is chiral HPLC, whereby the use of chiral stationary phases (CSPs) permits the direct separation of racemic compounds into constituent enantiomers. Despite the capital outlay required, for example, for columns costing upwards of 3000, the use of preparative chiral HPLC in drug discovery has a number of benefits. After development of an appropriate method based on a previously defined analytical separation has been carried out, rapid and quantitative separation of racemates can be achieved, with evaporation of solvent from column fractions affording pure enantiomers directly. Although preparative chiral HPLC is less amenable to scale-up than other resolution techniques, it may be ideal for preliminary screening of both enantiomers in circumstances where manipulation of small quantities of material, for example, by crystallization, is impractical and prone to contamination problems. 

The majority of the enantiomer separation methods based on crystallization involves solvent or solvent mixtures. Crystallizations from supersaturated solutions can be used both at the sepraration of enantiomeric mixtures, and at the separation of diastereoisomeiic mixtures. 

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