Diastereomeric recrystallization

Diastereomeric recrystallisation is a method of chiral resolution of enantiomers from a racemic mixture.

After adding a second chiral center in a determined location, the two isomers are still different, but they are no longer mirror images of each other; rather, they become diastereomers.

The conversion of the enantiomeric mixture into a diastereomer pair, depending on the nature of the chemicals, can be via covalent bond formation with the enantiopure resolving agent, or by salt formation, the latter being particularly convenient since acid base chemistry is typically quite operationally simple and high yielding.

It is these, now different, physical properties e.g. Melting point & Enthalpy of fusion which determine the eutectic composition (see Eutectic system) which correlates with the maximum yield of pure diastereomer in the crystallization (Rmax, see example melting point phase diagram of a diastereomeric system across all compositions in Figure 1).

Various methods have been developed to screening diastereomeric resolutions by determining the eutectic composition as a means of ranking for yield efficiency.

Figure 1: Melting point phase diagram (using the Schroeder – van Laar Equation) of a prototypical diastereomeric system. nb. utility in a solvent mediated crystallization implicitly assumes ideal behaviour (in that changing the solvent will not change the composition of the binary eutectic). In this example, assuming a racemate (50:50 mix of enantiomers), then with a eutectic of 0.23, the maximum yield we can expect from system, via crystallization, is 35%.