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 chirality 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 to collect crystals of one kind after partial growth and of the other before complete dissolution. Three major steps are involved: (a) Kinetically controlled crystallization of a racemic conglomerate in the presence of chiral polymers at temperature T 1 , modeled on the basis of the structure and morphology of the 3D crystals. The polymer inhibits the precipitation of the undesired enantiomorph, collecting the desired one by filtration; (b) Preferential dissolution of added racemic mixture of crystals of the substrate in the mother liquor enriched with the undesired enantiomer and the chiral polymer at temperature T 2 . This step takes advantage of concentration-gradients of the two enantiomers in the filtrate and the enatioselective dissolution induced by the chiral polymer; (c) The separation by filtration followed by racemization of the undesired enantiomer for additional cycles of resolution. 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 kilograms scale.