Investigations on the reciprocal ternary system (+/-)-2-phenylpropionic acid-(+/-)-alpha-methylbenzylamine. Impact of an unstable racemic compound onthe simultaneous resolution of chiral acids and bases by preferential crystallisation

New studies on the reciprocal quaternary system (+/-)-2-phenylpropionic aci d [(+/-)-1]-(+/-)-alpha -methylbenzylamine [(+/-)-2]-ethanol confirm the pr esence of a stable conglomerate (p and p' salts), but polymorphism of the n salt as well as an unstable racemic compound have been detected. The kinet ic parameters of the irreversible transformation of the unstable racemic co mpound into the stable conglomerate have been determined from experimental X-ray powder diffraction data. The simultaneous resolution of (+/-)-1 and ( +/-)-2 by means of preferential crystallisation (auto-seeded process) of th e stable pair of enantiomorphous salts, was achieved. However, the entrainm ent effect (given by the maximum enantiomeric excess of the counter enantio mer in the mother solution, reached at the end of the stereoselective cryst allisation (ee(max)(r) = 5.2%)) is limited. This is consistent with the exi stence of the unstable racemic compound, as accounted for in a recent model of molecular interactions occurring at the crystal-mother solution interfa ce in the course of preferential crystallisation. An extended version of th is model rationalises a kinetic advantage of the crystal growth rate of rac emic compounds over the conglomerates as well as a large supersaturation ca pacity of the mother solution in such a reciprocal quaternary system (+/-)- acid,'(+/-)-base and solvent.