Enantiotropically related polymorphs of gaboxadol hydrochloride

Abstract

Gaboxadol hydrochloride, also known as THIP hydrochloride (systematic name: 3-hydroxy-4,5,6,7-tetrahydro-1,2-oxazolo[5,4-c]pyridin-6-ium chloride), C6H9N2O2+·Cl−, exists as two enantiotropically related polymorphs. Transformation between the polymorphs occurs in a single-crystal-to-single-crystal manner at 221 K, and the enthalpy of transformation from the high-temperature form to the low-temperature form is −0.7 kJ mol−1. Single-crystal structures have been determined at 298 and 220 K. At 298 K, the structure is triclinic (space groupP\overline{1}), with two formula units in the crystallographic asymmetric unit. At 220 K, the structure is monoclinic (space groupI2/a), with one formula unit in the asymmetric unit. The structures contain identical hydrogen-bonded layers and the transformation between the polymorphs corresponds to a shift of adjacent layers relative to each other. The transformation is shown to be reversible by differential scanning calorimetry and variable-temperature powder X-ray diffraction.