Preferential crystallisation and comparative crystal growth study between pure enantiomer and racemic mixture of a chiral molecule: 5-ethyl-5-methylhydantoin

It is shown that (+/-) 5-ethyl-5-methylhydantoin (12Hyd) can be separated a t a preparative scale by means of the auto-seeded and polythermic preferent ial crystallisation in water, provided that a small proportion of wetting a gent is used. The influences of enantiomeric purity, supersaturation and we tting agent during the crystal growth of 12Hyd in water are investigated. L arge particles in the shape of single crystals obtained from unstirred race mic solutions and grown under smooth conditions of supersaturation exhibit unusual hourglass figures through {101} faces when observed under polarised light. Moreover, they contain almost no enantiomeric excess, which indicat es that they are not true single crystals. This is in apparent contradictio n with the possibility of resolving the racemic mixture by means of prefere ntial crystallisation. Stereoselective dissolutions of these apparent singl e crystals shows that this results from a crystal growth mechanism based on the alternated 2D nucleation of homochiral domains along specific growth d irections, leading to "lamellar polyepitaxy" phenomenon along {101} faces a nd responsible for the formation of hourglass figures by means of different types of crystal defects. Crystal structure analysis and molecular modelli ng tools allow to present some explanations consistent with these data. (C) 2001 Elsevier Science Ltd. All rights reserved.