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Improving optical resolution
Resolution of a racemic mixture by diastereomeric salt formation with a resolving agent can be made much more efficient by adding a small amount of a compound that resembles the resolving agent but that inhibits the nucleation of the undesired diastereomer. Authors find that 10% of a nucleation inhibitor can increase resolution efficiency by up to 182%, even under nonoptimized conditions. A higher resolution efficiency leads to a better overall process--"more kilograms of product with high enantiomeric excess." The nucleation inhibitors may be methoxylated, nitrated, or halogenated derivatives of the resolving agent. The inhibitor should have some structural resemblance to the resolving agent to block the crystal surface from further growth. But if there's too much resemblance, he says, the inhibitor will be incorporated into the crystal lattice. Whether a derivative will act as a nucleation inhibitor is determined experimentally.
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