Studies of nonsteroidal anti-inflammatory drugs: azapropazone

• Published in: Canadian journal of chemistry 1994-02, Vol.72 (2), p.382-389
• Main Authors: Fauconnier, Theresa, Lock, Colin J. L, Bell, Russell A, Britten, James F, Rainsford, K. D
• Format: Article
• Language: English
• Subjects: Analytical, structural and metabolic biochemistry; Aromatic and heterocyclic compounds; Biological and medical sciences; Condensed matter: structure, mechanical and thermal properties; Exact sciences and technology; Fundamental and applied biological sciences. Psychology; Heterocyclic compounds, pigments; Organic compounds; Other biological molecules; Physics; Single-crystal and powder diffraction; Structure of solids and liquids; crystallography; Structure of specific crystalline solids; X-ray diffraction and scattering
• ISSN: 0008-4042; 1480-3291
• DOI: 10.1139/v94-059

The structure of azapropazone, 5-(dimethylamino)-9-methyl-2-propyl-1H-pyrazolo[1,2-a][1,2,4]benzotriazine-1,3(2H)-dione, was determined by single crystal X-ray diffraction. Crystals were orthorhombic (P2 1 2 1 2 1 ), with a = 5.570(1) Å, b = 14.593(3) Å, c = 19.270(4) Å, and Z = 4. Intensities were measured on a Rigaku AFC6-R diffractometer with Cu-Kα radiation and 2316 reflections were used to determine the structure. Contrary to previous postulates, the tricyclic portion of the molecule is not planar. Azapropazone is a zwitterion with the negative charge delocalized over the β-keto-enol system and with the proton on N(6) of the triazine ring. The nonplanarity of the molecule is caused by steric interaction of a methyl group on the exocyclic dimethylamino group with O(3) of the keto-enol system. Bond lengths and angles are normal. NMR studies showed that at room temperature rapid inversion occurs between the two enantiomers, but this inversion slows at low temperatures with ΔG ≠  = 44.9(2) kJ mol −1 . The product derived from opening of the pyrazolidine ring of azapropazone by formic acid is not as previously formulated. The compound is 3-dimethylamino-7-methyl-1-valeryl-1,4-dihydro-1,2,4-benzotriazine. Its structure was determined by single crystal X-ray diffraction. Crystals were monoclinic (P2 1 /n), with a = 10.240(2) Å, b = 12.608(3) Å, c = 13.176(3) Å, β = 108.46(3)°, and Z = 4. Intensities were measured on a Rigaku AFC6-R diffractometer with Cu-Kα radiation and 2209 reflections were used to determine the structure. The conformation of the benzotriazine ring system was very similar to that observed in azapropazone and bond lengths and angles were normal.