Enolization electrostatic acceleration

Results of a study of electrostatic acceleration of enolization in cationic ketones have implications for enzymatic catalysis of enolization.136 Rate constants determined for water-, acetate- and hydroxide ion-catalysed enolizations of cationic ketones (79) (pK 11.13) and (80) (pK 11.90) have been compared with those for (81). It has been estimated that the inductive effects of the charged lings lower the p/y,s of (81) and (79) by 4.2 and 1.2 log units, respectively, whereas for (79) the electrostatic effect lowers the pAa by 6.3 log units, and enhances oh by 330-fold relative to a typical methyl ketone. The rate of enolization of (81) is enhanced 2.3 x 104-fold by the through-space electrostatic effect. 

Enolization of cationic ketones is accelerated by electrostatic stabilization of the enolate anion. Rate constants for water-, acetate-, and hydroxide ion-catalysed enolization of 2-acetyl- 1-methylpyridinium ion (94) have been measured13811 and compared with a 2-acetylthiazolium ion (95), a simple analogue of 2-acetylthiamine pyrophosphate.13811 For (94), qh = 1.9 x 102 M-1 s 1, about 1.1 x 106 times that for a typical methyl ketone such as acetone. Thermodynamically, it is >108 times more acidic (pAa values of 11.1 vs 19.3). These increases in kinetic and thermodynamic acidity are derived from through-bond and through-space effects, and the implications for enzymatic catalytic sites with proximal, protonatable nitrogen are discussed. The results for (94) suggest a pAa value of 8.8 for (95), a value that cannot be measured directly due to competing hydrolysis. 

EnoUzation of cationic ketones is accelerated by electrostatic stabilization of the enolate anion. Rate constants for water-, acetate-, and hydroxide ion-catalysed enolization of 2-acetyl-1-methylpyridinium ion (94) have been measured and compared with a 2-acetylthiazolium ion (95), a simple analogue of 2-acetylthiamine pyrophosphate. For (94), = 1-9 x 10 M s , about 1.1 x 10 times that for... 

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