Cyclic imine formation by intramolecular nucleophilic addition and elimination between an amino group and amide carbonyl; rate–pH profile for the reaction of 1-amino-8-trifluoroacetylaminonaphthalene to 2-trifluoromethylperimidine

Abstract

The kinetics of the cyclisation of 1-amino-8-trifluoroacetylaminonaphthalene to 2-trifluoromethylperimidine have been studied in the range pH 0.6–13 in 70%(v/v) Me₂SO–H₂O in the presence of buffers and in solutions of hydrochloric acid. The first-order rate coefficient (k) obtained in the presence of hydrochloric acid or determined by extrapolation of the observed rate coefficient in buffers to zero buffer concentration gives a pH dependence with two plateau regions. The results are explained by assuming that reaction of 1-amino-8-trifluoroacetylaminonaphthalene occurs by spontaneous and hydronium-ion catalysed pathways and that forms of the amide in which the amide group is ionised or the amino group is protonated are unreactive. The rate–pH profile is fitted by the expression k=K₁(k₀+k_H[H₃O⁺])[H₃O⁺]/(K₁K₂+K₁[H₃O⁺]+[H₃O⁺]²) in which K₁ is the acid dissociation constant of the protonated amino group in protonated 1-amino-8-trifluoroacetylaminonaphthalene and K₂ is the acid dissociation constant of the amide group in 1-amino-8-trifluoroacetylaminonaphthalene. The rate coefficients k_O and k_H refer, respectively, to spontaneous and hydronium-ion catalysed cyclisation pathways. Catalysis by buffer acids is also observed. The mechanism of the reaction involves intramolecular addition of the amino group in 1-amino-8-trifluoroacetylaminonaphthalene to the amide carbonyl followed by elimination of water.