A cyclic continuous process for converting conglomerates into optically pure enantiomers by crystallization and dissolution with the assistance of 'tailor-made' polymers

An industrially feasible kinetic process for the conversion of D,L racemic mixtures that crystallize in the form of conglomerates into optically pure materials was elaborated. The method takes into consideration the presence of a single-enantiomer polymer that causes crystals that match it in chiral ity to lag far behind their enantiomers both in growth and in dissolution. This phase lag is exploited in a repeated cycle of growth and dissolution t o collect crystals of one kind after partial growth and of the other before complete dissolution. Three major steps are involved: (a) Kinetically cont rolled crystallization of a racemic conglomerate in the presence of chiral polymers at temperature TI, modeled on the basis of the structure and morph ology of the 3D crystals. The polymer inhibits the precipitation of the und esired enantiomorph, collecting the desired one by filtration; (b) Preferen tial dissolution of added racemic mixture of crystals of the substrate in t he mother liquor enriched with the undesired enantiomer and the chiral poly mer at temperature T-2. This step takes advantage of concentration-gradient s of the two enantiomers in the filtrate and the enatioselective dissolutio n induced by the chiral polymer; (c) The separation by filtration followed by racemization of the undesired enantiomer for additional cycles of resolu tion. The process is illustrated for the conversion of D,L methionine . HCl that crystallizes in the form of a conglomerate that displays twinning of enantiomorphous lamellae into the corresponding L or D Met . HCl in kilogra ms scale. (C) 2000 Elsevier Science Ltd. All rights reserved.