Enantiomer composition determination chiral solvent

One of the most powerful methods for determining enantiomer composition is gas or liquid chromatography, as it allows direct separation of the enantiomers of a chiral substance. Early chromatographic methods required the conversion of an enantiomeric mixture to a diastereomeric mixture, followed by analysis of the mixture by either GC or HPLC. A more convenient chromatographic approach for determining enantiomer compositions involves the application of a chiral environment without derivatization of the enantiomer mixture. Such a separation may be achieved using a chiral solvent as the mobile phase, but applications are limited because the method consumes large quantities of costly chiral solvents. The direct separation of enantiomers on a chiral stationary phase has been used extensively for the determination of enantiomer composition. Materials for the chiral stationary phase are commercially available for both GC and HPLC. 

As was already mentioned, the phenomenon of nonequivalence of NMR spectra of enantiomers in chiral solvents is a basis for the determination of enantiomeric purity of a variety of chiral sulfur compounds. This method, developed by Pirkle, has the advantage over other methods of being absolute that is, the chemical shift difference between enantiotopic nuclei induced by the chiral solvent increases with increasing optical purity of the solvent, whereas the relative intensities of the signals that are used to measure the enantiomeric composition of the solute are not affected. 

The fundamental principle of enantioselective HPLC is based on the formation of labile diastereomeric complexes of the two enantiomers with the chiral selector of the stationary phase [3], The enantiomer that forms the less stable complex will be eluted earlier, while the enantiomer that forms the more stable complex will be eluted later. The ratio of the two retention factors k determines the separation factor for the enantioselectivity [4] a (Eq. 1) of a stationary phase for two enantiomers at a certain temperatrue and for a defined solvent composition. 

Lorazepam and its 3-0-acyl, 1-//-acyl-3-0-acyl-, and 3-0-methyl derivatives were baseline resolved on a silica column (X = 230 nm) using a 90/10 hexane/(2/l ethanol/acetonitrile) mobile phase [732], Elution was complete in <30min. The lorazepam peak was quite tailed. The retention of the enantiomers of each of these compounds was determined on six Pirkle-type chiral columns. Eluent composition ranged from 90/10 hexane/IPA to 95/5-> 91.5/8.5 hexane/(2/l ethanol/ acetonitrile) to 77/20/3 70/20/10 hexane/IPA/1,2-dichloroethane. Retention times ranged from 13.5 to 56min. Each pair was adequately resolved under one or more sets of conditions. All results are tabulated. One topic not often addressed in such studies is compound racemization half-lives. Here, neat solvents and experimental mobile phases were used. Water and neat alcohols resulted in 50% racemization in <30 min. The hexane/1,2-dichloroethane/IPA mobile phases yielded racemization times of >50 min. This time increased as the level of IPA decreased. Essentially no racemization occurred t 2 > 5000 min) in neat 1,2-dichloroethane or acetonitrile. 

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