Richard M. Kellogg
University of Groningen, Netherlands
Title: Attrition-induced deracemization of racemizable crystal-liquid suspensions for the production of industrially relevant compounds
Biography
Biography: Richard M. Kellogg
Abstract
It has been demonstrated that certain chiral racemic compounds sensitive to catalyzed racemization in solution, when subjected to strong grinding as suspensions, deracemize entirely. A strict additional requirement is that the compounds be conglomerates. How does this happen? It is thought that relatively rare primary nucleation of the racemic conglomerate provides a crystal that must have single handedness. Rapid secondary nucleation under conditions whereby growing crystals are continuously shattered leads to rapid propagation of that handedness. The process resembles closely Ostwald Ripening. The direction of deracemization can be determined by addition of a small amount of enantiomerically pure seed crystal. This process has been used to generate single enantiomers of commercially interesting compounds such as Naproxen, Clopidogrel and Prasugrel. Various extensions of this methodology have been developed and also methods for scale up have been developed both by us and by others.