Single-Crystal X-ray Diffraction Structure of the Stable Enol Tautomer Polymorph of Barbituric Acid at 224 and 95 K

Abstract

The thermodynamically stable enol crystal form of barbituric acid, previously prepared as powder by grinding or slurry methods, has been obtained as single crystals by slow cooling from methanol solution. The selection of the enol crystal was facilitated by a density-gradient method. The structure at 224 and 95 K confirms the enol inferred on the basis of powder data. The enol has bond lengths that are consistent with the expected bond order and with DFT calculations that include treatment of hydrogen bonding. In isolation, the enol is higher in energy than the tri-keto form by 50 kJ mol(-1) which must be more than compensated by enhanced hydrogen bonding. Both crystal forms have four normal H-bonds; the enol has two additional H-bonds with O-O distances of 2.49 Å. Conversion into the enol form occurs spontaneously in the solid state upon prolonged storage of the commercial tri-keto material. Slurry conversion of tri-one to enol in ethanol is reversed in direction in ethanol-D1.

Keywords: X-ray diffraction; density gradient separation; deuterium effects; hydrogen bonding; tautomeric polymorphs.