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 (k_HA) for 11 buffer acids and hydronium ion have been measured. A Brønsted plot of logk_HA against pK_a gives a slope close to zero for catalysis by acids with pK_a < ca. 8.5 and a slope close to unity for acids with pK_a > 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 logk_HA against pK_a which occurs at pK_a 8.5 corresponds to the pK value of the hydroxy group of the zwitterionic intermediate. Kinetic solvent isotope effects on the values of k_HA have been measured and an average value k_HA/k_DA 1.52 ± 0.2 is found. The absence of a maximum in the value of k_HA/k_DA with pK_a 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.