Rate constants for the addition of the enolate ion of acetone to quinolinium and acridinium cations

Abstract

The reaction of acetone with four heteroaromatic cations (10-methylacridinium (1), 3-aminocarbonyl-1-methylquinolinium (2a), 3-cyano-1-methylquinolinium (2b), and 3-bromo-1-methylquinolinium (2c)) has been investigated in basic aqueous solutions (pH 9–12, ionic strength 0.1, 25 °C). For each of 2a and 2b, the kinetically controlled product is a 35:65 mixture of the C-2 and C-4 enolate ion adducts; the C-2 adduct subsequently isomerizes to give the C-4 adduct as the only observable species under thermodynamic control. For 2c, the C-2 enolate adduct appears to be favoured both kinetically and thermodynamically. Under kinetic control, the pH-dependence of adduct formation from each cation is consistent with rate-determining attack of the enolate ion upon the heterocyclic cation. Comparisons of regiochemical control of acetone enolate ion attack with hydroxide ion attack upon these same cations indicate that acetone enolate ion shows a more pronounced preference for C-4 attack over C-2 attack than does hydroxide ion. The thermodynamically controlled regiochemistry is similar for each of these two nucleophiles. Keywords: nucleophilic addition, regioselectivity, kinetic control, thermodynamic control, quinolinium cations.