Crystal Structures, Dehydration Mechanism, and Chiral Discrimination in the Solid State of a Hydantoin Derivative

Abstract

(±) 5-Methyl-5-(4′-ethylphenyl) hydantoin (18H) crystallizes in usual organic solvents as a conglomerate in the P212121 space group. A new monohydrated racemic compound of 18H could however be obtained by antisolvent induced crystallization. The structure of this first hydrate of a hydantoin was successfully resolved by single crystal X-ray diffraction. It crystallizes in space group P21/c, and the crystal packing shows an association of homochiral molecular ribbons resulting from strong hydrogen bonds involving the water molecule and the hydantoin rings. At 30 °C and under low relative humidity (in the range 0–30%), the monohydrate exhibits an efflorescent behavior, with a reversible evolution toward a metastable anhydrous racemic phase through a cooperative zip-like mechanism. But under specific conditions (40–60% R.H., 30 °C), dehydration also leads to the nucleation and growth of the stable conglomerate, as confirmed by dynamic vapor sorption and X-ray powder diffraction analyses. The detailed analyses of solid–solid transformations between a hydrated racemic phase, an anhydrous racemic phase, and/or two anhydrous enantiomerically pure phases provide an opportunity to investigate examples of chiral recognition mechanisms in the solid state. The way the water molecules are released from the racemic monohydrate at 30 °C plays a decisive role in the nucleation and growth of the conglomerate.