Enantiomer mixture

Crystallization methods are widely used for the separation, or resolution, of enantiomer pairs. Enantiomer mixtures may essentially crystallize in two different ways. In around 8 per cent of cases, each enantiomer crystallizes separately, giving rise to a mechanical mixture of crystals of the two forms, known as a conglomerate. Conglomerates may usually be separated by physical methods... 

Achiral lanthanide shifting reagents may be used to enhance the anisochrony of diastereomeric mixtures to facilitate their quantitative analysis. Chiral lanthanide shift reagents are much more commonly used to quantitatively analyze enantiomer compositions. Sometimes it may be necessary to chemically convert the enantiomer mixtures to their derivatives in order to get reasonable peak separation with chiral chemical shift reagents. 

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. 

Extension of DKR to polymer chemistry would readily result in chiral polyesters, polycarbonates, or polyamides from an optically inactive monomer mixture. Scheme 10 describes three variants of chemoenzymatic catalysis applied in polymer chemistry that recently appeared in the literature. Route A uses AA and BB monomers to prepare chiral polymers from racemic/diasteromeric diols. Route B converts an enantiomer mixture of AB monomers to homochiral polymers. Route C is the enzymatic ring-opening polymerization of co-methylated lactones to homochiral polyesters. Details will be given in Sect. 3.4.2. 

In the absence of any chiral factors, the probability of the formation of S- and 77-enantiomers is 1 to 1. However, the numbers of the resulting two enantiomers are not exactly the same in almost all cases. Mislow197 described the inevitability of small enantiomeric enrichment in absolute asymmetric synthesis. According to the statistics, it is expected that a fluctuation in the ratio of the S- and 77-enantiomers becomes more and more likely as the numbers in the enantiomer mixture become smaller198. Thus, if the asymmetric autocatalysis is initiated without adding any chiral substance, small fluctuations of enantiomers produced in the initial stage could be enhanced by consecutive asymmetric autocatalytic reaction of pyrimidyl alkanol with amplification of chirality. 

The crystalline nature and physicochemical properties of the crystals belonging to a racemic conglomerate and a racemic compound have been thoroughly investigated.6 8 In contrast, other types of enantiomers mixture crystals except these two are generally categorized as a racemic mixed crystal, namely, a... 

In certain cases, the enantiomer of high purity is usually obtained by recrystallizing the enantiomer mixture which is recovered by decomposing the diastereomeric salt. In such a case, it is favorable to know the crystallizing characteristic of the target compound. For instance, the crystallizing characteristic of an enantiomer mixture can be outlined by its binary phase diagram. 

Enantiomers possess identical physical and chemical properties but diastereoisomers can differ and these differences can be used in appropriate physical chemical procedures to separate enantiomers. The enantiomer mixture is reacted with an appropriate chiral reagent and the diastereoisomers so formed are then separated by classical means. 

A. Collet, M.-J. Brienne, J. Jacques, Optical resolution by direct crystallization of enantiomer mixtures, Chem. Rev. 80 (1980) 215-230. 

At first sight, the use of a chiral catalyst appears to be the potentially most attractive method to achieve asymmetric Diels-Alder reactions of prochiral dienes and dienophiles. Compared to the stoichiometric use of a covalently attached auxiliary, two synthetic steps would be avoided. However, analysis of the resulting enantiomer mixture and purification of the major product may be more laborious. 

The phase diagrams below highlight two typical cases, the first where the eutectic point E is close to the racemate, and the second where the eutectic approaches the single enantiomer as shown in Fig. 18.24. In the first case, it would be preferable to crystallize the enriched enantiomer to optical purity, e.g., methylphenidate. However, in the second case, a very stable racemic compound exists, giving rise to a high eutectic point. Here crystallization of enriched enantiomer mixture will only be successful at high ee. For example, verapamil hydrochloride requires that the ee be greater than 98%for crystallization to yield... 

In practice, SMB processes are controlled using similar manual schemes (Kiisters et al., 1995, Juza, 1999 and Miller et al., 2003). Antia (2003) suggested that these heuristic rules are included in a fuzzy controller to achieve full automatic control of SM B processes, but no applications have been described so far. Cox et al. (2003) recently reported a successful control and monitoring system for the separation of an enantiomer mixture based on the concentration profiles in the recycle loop. 

Estimation of enantiomer ratios is conveniently accomplished using diastereoisomer-forming derivatisation protocols or through separations of enantiomer mixtures over chiral stationary phases. Commercially available chiral coatings for this purpose, such as Chirasil-Val, have been used in the field of amino-acid fossil dating (Section 1.11), exploiting the better resolution of capillary GLC, whereby a thermally stable liquid coats the surface of a narrow tube. 

Optical resolution by direct crystallization of enantiomer mixtures ... 

Compound (enantiomer mixture) Discriminating agent Separation principle References... 

Scheme 11.13 Possible routes for the enantiomer mixture ofAB monomers to...

CDA, chiral derivatizing agent A reagent of known enantiomeric purity that is used for derivatization and analysis of enantiomer mixtures by spectroscopic or chromatographic means. See Section 2.3.1. 

Cox, Khattabi, and Dapremont (2003) reported a successful control and monitoring system for the separation of an enantiomer mixture based on the concentration profiles in the recycle loop. 

This is a technique widely used for the determination of the ee of a mixture of diamagnetic enantiomers. On its own, NMR cannot distinguish between enantiomers, rather it is an indirect method which requires that the enantiomer mixture be converted into a mixture of diastereomers. This can be achieved by ... 

The D-enantiomer of such bidentate compounds was generally retained more than L-enantiomer. Mixtures of methanol/acetonitrile/water or dichloromethane/methanol were often used as eluents. Chiral recognition based on CLEC was also involved in the enantiomer separation of amino acids and (3-adrenergic blocking agents on silica gel plates coated with the copper(II) complex of enantiomeric amino acids (L-proline, L-arginine, and lR,3R,5R-2-azobicyclo [3.3.0]octan-3-carboxylic acid). 

Fig. 15 Variants of the extension of DKR to polymercondensations Route A uses AA and BB monomers to prepare chiral polymers from racemi/diasteromeric diols. Route B converts an enantiomer mixture of AB monomers to homochiral polymers...

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