The cyclisation of substituted phthalanilic acids in acetic acid solution. A kinetic study of substituted N-phenylphthalimide formation

Abstract

One novel and ten known substituted 3′- and 4′-phthalanilic acids have been prepared. These have been cyclised to two novel and nine known substituted N-phenylphthalimides by heating with glacial acetic acid. Both phthalanilic acids and imides have been characterised in detail and spectroscopic data are given. The kinetics of cyclisation for phthalanilic acids has been examined in detail, and it has emerged that a complex mechanism is operating. This initially involves a reversible, solvent assisted intramolecular nucleophilic attack by amide nitrogen on the carboxylic acid carbonyl. Clear evidence is seen for a long-lived intermediate as a precursor to imide formation. The observed kinetics are rationalised using a model of rapid pre-equilibration, followed by the slow breakdown of the intermediate to imide. Observed rate constants for pre-equilibration show a well behaved, linear Hammett plot (ρ = −1.1), whereas those for formation of imide do not.