Phase Diagrams and Solubility Rules

Diastereoisomers p and n are distinct compounds and exhibit different structures in the crystal state. It fol lows that all physical properties involving the crystal themselves and the crystal/liquid or crystal/gas equilibria, such as melting points, solubilities, sublimation properties, crystal densities, etc., are different for the p and n species of a given pair. However, the possibility of separating p and n diastereoisomers by crystallization of their 1 : 1 mixture, resulting from the reaction of a racemate with a resolving agent, does not depend only on the properties of the pure p and n compounds: it rests primarily on the existence of favourable solid-liquid phase equilibria for the binary (p, n) or ternary (p, n, E) systems. The phase diagrams of diastereoisomer systems (Figure 4) are basically similar to those of enantiomer systems. There exist, however, several important differences between them: (1) the phase diagrams of diastereomer mixtures are not symmetrical; (2) in contrast to enantiomers, diastereoisomers preferentially form eutectics or solid solutions (Figure 4(A) and (C), respectively); (3) the occurrence of 1 : 1 (pn) addition compounds depicted in Figure 4(B) is by far less than that of (dl) racemic compounds.

Only diastereoisomer systems forming eutectic phase diagrams are suitable for resolution by crystallization. In the solubility isotherm of Figure 4(A), 1 : 1 (p, n) mixtures will afford the pure less soluble diastereoisomer (here p) if the crystallization is carried out between N and P, for instance from solution O. The best yield however will be obtained from solution N. This yield is given by:

„ NE 100 Ep Cn where CN is the concentration of solution N. Since the p/n ratio in the ternary eutectic is usually close to that of the binary eutectic, Y is not very different from RE/AE in the melting point phase diagram. The best systems are those in which the eutectic is close to the edge of the phase diagram, and the maximum value of Y=50% is approached when E is closed to one of the pure components. The occurrence of such good systems has been estimated at 20-25% of dia-stereoisomer mixtures. It is important to recognize that in such cases one or two crystallizations are normally sufficient to obtain the less soluble dias-tereoisomer in pure form.

Systems in which a 1 : 1 [p, n] compound exists, as in Figure 4(B), are totally unsuitable for resolution because crystallization of a 1 : 1 mixture will afford the 1 : 1 compound. Some resolution is possible with systems forming a solid solution, as shown in Figure 4(C), providing that the solubility difference between the pure components is sufficiently large. Most

Figure 4 Melting point (left) and solubility (right) phase diagrams for diastereoisomer systems. (A) eutectic; (B) 1:1 addition compound; (C) solid solution. The arrows indicate the nature of the solid obtained from crystallization of a system of composition O.

often, however, the enrichment is very modest and utilization of systematic fractional crystallization techniques is required. These techniques are very tedious and time-consuming and this is why resolution of (p, n) systems forming solid solutions is not recommended unless alternative methods cannot be found. Note that diastereoisomeric lattice inclusion complexes are more prone to form solid solutions than the other types of diastereoisomers and often need repeated crystallizations to reach good enrichments. In such cases rather than purify the diastereoisomers, it may be advisable to complete the purification on the partially resolved enantiomers, along the lines indicated above.

Solar Panel Basics

Solar Panel Basics

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