1H NMR, 13C NMR, and Computational DFT Studies of the Structure of 2-Acylcyclohexane-1,3-diones and Their Alkali Metal Salts in Solution

• DOI: 10.1021/jo060583g
• Publication Date: 2006-06-02T04:58:21Z
• Authors: Przemysław Szczec...; Adam Gryff-Keller; Sergey Molchanov
• Keywords: Chemical shift

1H and 13C NMR spectra of 2-acyl-substituted cyclohexane-1,3-diones (acyl = formyl, 1; 2-nitrobenzoyl, 2; 2-nitro-4-trifluoromethylbenzoyl, 3) lithium sodium potassium salts 1 have been measured. The compound 3, known as NTBC, is a life-saving medicine applied in tyrosinemia type I. optimum molecular structures the investigated objects solutions found using DFT method with B3LYP functional 6-31G** and/or 6-311G(2d,p) basis set. theoretical values parameters compounds calculated GIAO B3LYP/6-311G(2d,p) method. data obtained for 1−3 exploited to interpret their experimental terms equilibrium between different tautomers. It has that these triketones an endo-tautomer prevails. differences can be rationalized taking into account size cation degree salt dissociation. seems DMSO solution exists mainly ion pair stabilized by chelation two oxygen atoms. activation free energy formyl group rotation this estimated 51.5 kJ/mol. results suggest all objects, including enolate ions, atoms directly bonded carbonyl carbons lie near same plane. Some observations concerning chemical shift changes could indicate strong solvation anion water molecules. Implications work inhibition mechanism (4-hydroxyphenyl) pyruvate dioxygenase NTBC are commented upon.