General acid catalysis and kinetic isotope effects for intramolecular, addition–elimination between amino and amide groups in 1-amino-8-trifluoroacetylaminonaphthalene; observation of a biphasic Brønsted plot

Abstract

The intramolecular addition–elimination of 1-amino-8-trifluoroacetylaminonaphthalene to 2-trifluoromethylperimidine in 70%(v/v) Me2SO–H2O is catalysed by general acids, and catalytic coefficients (kHA) for 11 buffer acids and hydronium ion have been measured. A Brønsted plot of logkHA against pKa gives a slope close to zero for catalysis by acids with pKa < ca. 8.5 and a slope close to unity for acids with pKa > ca. 8.5. The results are explained by a mechanism involving intramolecular addition of the amino group to the amide carbonyl to give a zwitterionic intermediate present in low concentration followed by rate-limiting protonation of the intermediate by hydronium ion and by buffer acids. The break point in the plot of logkHA against pKa which occurs at pKa 8.5 corresponds to the pK value of the hydroxy group of the zwitterionic intermediate. Kinetic solvent isotope effects on the values of kHA have been measured and an average value kHA/kDA 1.52 ± 0.2 is found. The absence of a maximum in the value of kHA/kDA with pKa confirms that the rate-limiting protonation is controlled by diffusion steps. The proposed mechanism is preferred to one in which the biphasic Brønsted plot is explained by a change in rate-limiting step from acid-catalysed intramolecular addition in the presence of strong acids to acid-catalysed elimination from the addition intermediate in the presence of weak buffer acids.