AM1 calculational and experimental evidence that a β-nitroxyl group significantly enhances the thermodynamic and kinetic acidities of ketones

• Published in: Canadian journal of chemistry 1994-11, Vol.72 (11), p.2348-2350
• Main Authors: Werstiuk, Nick Henry, Roy, Chandra Deo
• Format: Article
• Language: English
• ISSN: 0008-4042; 1480-3291
• DOI: 10.1139/v94-299

The kinetics of NaOD-catalysed H/D exchange of 3,3,5,5-tetramethylcyclohexanone ( 1 ), 1-hydroxy-4-oxo-2,2,6,6-tetrame-thylpiperidine ( 2 ), 4-oxo-2,2,6,6-tetramethylpiperidine-1-oxyl (3), 9-hydroxynorpseudopelletierine ( 4 ), and norpseudopelle-tierine-9-oxyl ( 5 ) have been studied in 60:40 dioxane-D 2 O(v/v) at 25.0 °C. The second-order rate constants are 9.20 × 10 −3 , 6.39 × 10 −2 , 1.59, 2.20 × 10 −2 , and 5.67 × 10 −1  L mol −1  s −1 for 1 , 2 , 3 , 4 , and 5 , respectively. Gas-phase enthalpies of ionization (the values are 363.0, 359.4, 352.0, 360.7, and 354.1 kcal mol −1 for 1, 2, 3, 4, and 5, respectively) calculated with AM1 correlate with the relative rates of enolization. Thus replacement of the β-hydroxylamino groups of 2 and 4 with a nitroxyl group produces sizable increases in the kinetic and thermodynamic acidities of the hydrogens α to the carbonyl group.