Pressure-Stabilized Solvates of Xylazine Hydrochloride

High pressure strongly favors the highest-density polymorph Z of active pharmaceutical ingredient 2-(2,6-xylidino)-5,6-dihydro-4H-1,3-thiazine hydrochloride (xylazine hydrochloride, XylHCl) up to about 0.1 GPa only, but still higher pressure destabilizes this structure. Above 0.1 GPa, XylHCl preferentially crystallizes as solvates with CH2Cl2, CHCl3, or (CH3)(2)CHOH depending on the solvent used. However, when XylHCl center dot H2O is dissolved in any of these solvents, the high-pressure crystallizations yield the hydrate XylHCl center dot H2O only. The single crystals of the CH2C12, CHCl3, and (CH3)(2)CHOH solvates could be grown in situ in a diamond anvil cell, which allowed their structure determination from the single-crystal diffraction data. At 0.4 GPa the XylHCl center dot H2O hydrate undergoes a pressure-induced phase transition doubling the unit cell dimensions.