Pseudoracemic compounds

There is a third form of solid state organization of racemic compounds, called the sohd solution or pseudoracemic compound. This is a rare form in which the arrangement of the enantiomers in the crystal is variable and not defined. The significance of this is that, while the stoechiometry of the two enantiomers in the whole crystal may well be 1 1, it is possible to find homochiral unit cell structures, one enantiomer being substituted for the other. Such disorder arises from the strong similarity of the two enantiomers, particularly in the case of quasispherical molecules. This arrangement is also called a racemic solid solution of the two enantiomers. 

The racemic compound forms crystals containing a 1 1 ratio of d- and /-molecules in a regular array. The pseudoracemate, eventually, forms crystals with both d- and /-molecules in an irregular arrangement and in any ratio. The corresponding phase diagrams are shown in Figure 13. 

The conglomerate shows a lower melting point (and hence, a higher solubility) than the individual enantiomers. From a melt or a solution with an enantiomeric ratio +1 1, the excess enantiomer crystallizes in pure form. The racemic compound may have a lower (curve 1) or a higher (curve 2) melting point (or solubility) than the corresponding enantiomers the eutectic mixture (E), however, always lies at a minimum. Finally, crystallization of pseudoracemates always yields enantiomerically impure samples. 

Enantiomers are stereoisomers, which are mirror images of eath another. An equimolecular mixture of two enantiomers is called a racemate. Crystalline race-mates occur in three different types. The first is termed a conglomerate, that is, a mechanical mixture of crystals of pure enantiomers that is formed from two solid phases. The most common type is the racemic compound, which consists only of one crystalline phase in which the two enantiomers are present in equal quantities. The third type is the pseudoracemate in which a solid solution of the two enantiomers is present. 

Mitchell, A. G. Racemic Drugs Racemic Mixture, Racemic Compound, or Pseudoracemate J. Pharm. Pharm. Sci. 1998, I, 8-12. 

A crystalline racemate may exist as a conglomerate, a racemic compound, or a pseudoracemate (Fig. 1). A racemic conglomerate is an equimolar eutectic mixture consisting of crystals of the two opposite enantiomers. 

Figure 2 Typical phase diagrams of melting point against composition for (a-c) three types of racemic species, (a) racemic conglomerate, C, (b) racemic compound, R, (c) pseudoracemates, P (d-e) terminal solid solutions involving opposite enantiomers, (d) solid solution rich in an enantiomer, (e) solid solution rich in an enantiomer or rich in the racemic compound (f) a pair of diastereomers. (From Ref. 13. Reproduced by permission of John Wiley and Sons.)...

Figure 3 Powder x-ray diffraction patterns of (a) the racemic compound (upper trace) and an enantiomer (lower traces) of norephedrine hydrochloride, and (b) the pseudoracemate (-1-/—) and an enantiomer (—) of atenolol. Shift of peak position is indicated by an asterisk and is characteristic of a solid solution. (From Ref. 17. Reproduced by permission of the American Pharmaceutical Association.)...

Less than 1% of racemic species are pseudoracemates, which show typical phase diagrams of continuous solid solutions. Figure 2c shows the three types of melting phase diagrams of pseudoracemates, which comprise ideal solid solutions, solid solutions with positive deviations from ideality, and solid solutions with negative deviations from ideality, respectively [13]. In real systems, the enantiomers and the racemic compound may display a small mutual solubility, even if they show eutectic behavior, which corresponds to terminal solid solutions for which the phase diagrams are shown in Figs. 2d and 2e. 

Two different approaches have been developed to determine diastereomeric excess in host-guest complexes in solution by MS (Box 2) the relative peak intensity mefliod makes use of an achiral host as a reference compound and compares the two diastereomeric host-guest complexes with it. The enantiomer-labeled method employs pseudoracemates, that is, 1 1 mixtures... 

Compounds 101a,b were used as pseudoracemates in solution, as it was inferred by the authors that methyl and ethyl groups afforded no great differences in the reactivity of allyl groups toward Pd species, supposing almost the same reactivity behaviors for both. 

Mitchell AG. Racemic drugs racemic mixture, racemic compound, or pseudoracemate J. Pharm. Pharmaceut. Sci. 1998 1 8 12. 

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