Intramolecular catalysis in the enolisation of aminoketones

Abstract

Measurements are reported on the rates of halogenation of the aminoketones PhCO(CH₂)_nNC₅H₁₀, with n= 1–3 [(III),(II), and (IV) respectively], and N-methyl-4-piperidone (V), and their N-methyl derivatives. The reactions are zero order with respect to halogen concentration, with the rate-determining step being the formation of the enol or enolate ion. Large rate accelerations relative to acetophenone and cyclohexanone were observed, and these cannot be explained entirely in terms of inductive (through-bond) effects of NH⁺, NMe⁺, or N groups. Other important factors are (i) intramolecular stabilization of the developing negative charge by the positive ammonium ion, the maximum effects being observed for (II); (ii)electrostatic interactions with negatively charged catalysts; (iii)direct proton transfer from the ionising C–H group to N, acting as an intramolecular base catalyst. Evidence for a direct proton transfer was found only in reactions of the γ-substituted aminoketone (IV).