Pseudoracemates crystallization

Certain pairs of enantiomers, such as 25°C solutions of camphor in aqueous ethanol (Fig. 26a), 2,2,5,5-tetramethyl-l-pyrrolidinoxy-3-carboxylic acid in chloroform (Fig. 26b), or carvoxime in hexane (Fig. 26c), cocrystallize throughout the entire range of mole fractions. The crystals that are in equilibrium with the saturated liquid solution are solid solutions (mixed crystals), since they constitute a single phase. The racemic solid solution is termed a pseudoracemate [141]. 

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. 

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. 

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 1 Schematic representation of the molecular arrangements in three t) es of racemates (a) enantiomeric or homochiral crystal (same chirality) (b) racemic or heterochiral crystal (paired enantiomers) (c) pseudoracemate or solid solution (randomly arranged enantiomers). (Adapted from Ref. 11.)...

Pseudoracemates may exhibit three types of ternary phase diagram, as mentioned previously (Fig. 6c). The change of solubility with composition is relatively small. Therefore we may expect similar solubilities and intrinsic dissolution rates for the enantiomer and the pseudoracemate. For the same reason, resolution of a pseudoracemate by crystallization is practically impossible [10]. 

In such cases, the racemic modification shows nearly ideal mixing and forms a racemic solid solution (pseudoracemate or mixed crystal) [13,14]. 

Mixed crystal, solid solution, racemate, quasiracemate, pseudoracemate, and inversion twin... 

In 1897, Kipping and Pope reported what they termed pseudoracemates and the model that they proposed was consistent with what we now refer to as inversion-twinned crystals. As pointed out by Flack, Kipping and Pope were limited by the technology of the time and what they actually observed was a solid solution in which either enantiomer is able to occupy any molecular position in the crystal structure. Flack suggests that a more suitable name for this type of solid solution is a disordered racemic... 

If the difference between enantiomers is small, the substance may crystallize as an ideal solid solution, known as a pseudoracemate, where the ratio of (+) to (-) has no effect on the melting point, and the graph is flat (Figure 3.6c). A few give nonideal solutions with maxima or minima. 

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