Structural studies of analgesics and their interactions. VII. Stereoisomerism and disorder in the structure of oxyphenbutazone monohydrate

Abstract

Oxyphenbutazone, C₁₉H₂₀N₂0₃, a metabolite and perhaps the active form of phenylbutazone, is a widely used non-narcotic analgesic and anti-inflammatory pyrazolidinedione derivative. The monohydrate of the compound crystallizes in the triclinic space group PI̅ with two molecules in a unit cell of dimensions a = 9.491 (4), b = 10.261 (5), c = 11.036 (3)Å and α = 72.2 (1), β = 64.3 (1), γ = 73.0 (1)°. The structure was solved by direct methods and refined to an R value of 0.107 for 1498 observed reflections. The butyl group in the molecule is disordered. The hydroxyl group occupies two sites with unequal occupancies. On account of the asymmetry at the two N atoms and one of the C atoms in the central five-membered ring, the molecule can exist in eight isomeric states, of which four are sterically unfavourable. The disorder in the position of the hydroxyl group can be readily explained on the basis of the existence, with unequal abundances, of all four sterically favourable isomers. The bond lengths and angles in the molecule are similar to those in phenylbutazone. The crystal structure is stabilized by van der Waals interactions, and O-H···O hydrogen bonds involving the carbonyl and the hydroxyl groups as well as a water molecule.