Aminoketone enolisation: influence of increasing chain length on intramolecular catalysis

Abstract

Kinetic results are reported on the rates of ionisation of piperidino- and morpholino-phenones of varying chain length [PhCO(CH₂)_n [graphic omitted]H₂], X = CH₂ or O; n= 2–5] in buffer and dilute hydroxide solution, as measured by their rates of halogenation. For both series of aminoketones two important factors are responsible for a high reactivity relative to acetophenone: the positive charge on the protonated (and N-methylated) derivatives, which has a strong influence in the α-(n= 1) and β-(n= 2) position, and intramolecular general base catalysis by the neutral amino group, which has a maximum effect for the δ-(n= 4) derivative. Results for the more acidic protonated morpholinoketones are almost identical to those of corresponding piperidinoketones and show no evidence of intramolecular general acid catalysis. The reduced basicity of the morpholino group is reflected in lower rate constants for the intramolecular general base-catalysed reaction.