Medium, achiral racemic

Partially resolved samples of certain compounds show enantiomeric NMR nonequivalence in an otherwise achiral medium, and do so in magnitudes proportional to their enantiomeric purity. This phenomenon, termed self-induced nonequivalence or autononequivalence, has been observed for compounds shown in Table 12. Dihydroquinine (44) was the first of these examples to be reported (14). Figure 6 shows portions of the 100 MHz spectra of optically pure, naturally occurring dihydroquinine, a 1 1 mixture of the natural product and synthetic racemate, and the racemate alone, all at approximately the same concentration in CDCI3 solution. The three spectra are different Figure 6b shows nonequivalence for the H2, Hy, Hg, and H9 resonances, the intensities corresponding to the optical purity of the sample (33%, e.e.). 

Enantiotopic nuclei or groups are capable of fulfilling all or, at least, most of the foregoing symmetry-related expectations. Their chemical shifts depend, in addition, on both the medium in which the NMR experiment is conducted and the spectral resolution of the spectrometer. The latter is influenced by, for example, the magnetic-field strength. Enantiotopic groups are isochronous in achiral or racemic media and constitute A2,X2, etc., systems. Moreover, they are potentially anisochronous in chiral media. 

The term chiral compound also applies to an achiral compound in a chiral, non-racemic medium.)... 

The same equilibria are attained if to a solution of racemate in an initially achiral medium (equal concentrations of d and I species) there is added another chiral species d or L. The equilibrium is then displaced in favour of one or other of the constituents of the racemic mixture. This process has recently been termed enantiomerization, although examples of optically labile systems in equilibria sensitive to the presence of other chiral molecules or ions have long been recognized. A typical example of what was earlier termed an asymmetric transformation of the first kind (no second-phase involved) is that of Read and McMath (1925) in which solutions in dry acetone of (—) or ( ) chlorobromomethanesulphonic acid d-l ) together with (—)-hydroxyhydrindamine (l+) showed a change of optical rotation interpreted in terms of an equilibrium... 

The stereochemical similarity between the additive and the crystal structure of one of the enantiomorphic substrates was found to be of paramount importance [8], while parameters like temperature, concentration or nature of the medium had only a quantitative effect on the induction in this system. Further kinetic and mechanistic studies resulted in the formulation of a mechanism according to which the additive is enantioselectively adsorbed in small amounts at the surface of the growing crystal of the same absolute configuration. The adsorption of the chiral additive causes a drastic decrease in the rate of growth of this same crystal, thus shifting the crystallization equilibrium towards the unaffected enantiomorphous phase. This is illustrated in Scheme 2, where the achiral monomer is represented as a fast racemizing... 

As discussed in the previous section, isomers or impurities can be successfully removed from a host material, if solubilities are sufficiently different. Therefore, a worst-case scenario for any impurity removal or isomeric separation is the resolution of a racemate of enantiomers, since enantiomers have equivalent physical and chemical properties in an achiral medium (ordinary solvent) and hence the same solubility (39,55). Furthermore, 50% of the sample can be regarded as impurity. 

In contrast to the models discussed above for conglomerates, this time it is the solution phase not the solid that can become enantiomerically eruiched, a possibility that had already been pointed out by Morowitz in 1969 (36). From the values shown in Figure 3, it seems at first that only a few selected amino acids allow for high ee s in solution. But further experiments with amino acids revealed ways to influence the eutectic composition. Valine for example has a medium eutectic of 47% ee in water at 25°C. Addition of fumaric acid, itself achiral, results in a rise of the eutectic to >99% ee (37). As it was shown, fumaric acid forms cocrystals with both racemic and enantiopure valine, strongly decreasing the solubility of racemic valine while not changing that of enantiopure valine much (Figure 4). 

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