The kinetics and mechanism of a highly efficient intramolecular nucleophilic reaction. The cyclization of ethyl N-[o-(N-hydroxycarbamoyl)benzoyl]-carbamate to N-hydroxyphthalimide

Abstract

The cyclization of ethyl N-[o-(N-hydroxycarbamoyl)benzoyl]carbamate (SH) to N-hydroxyphthalimide (NHPH) has been studied within the pH range 5.18–7.84 at 30 °C. The observed first-order rate constants are linearly dependent on [^–OH]. Buffer catalysis could not be detected and the value of the second-order rate constant, k_OH, for the specific base-catalysed cyclization reaction is (4.06 ± 0.05)× 10⁴ l mol^–1 s^–1. The magnitude of k_OH is ca. 3 × 10⁵-fold greater than k_OH for hydroxide ion-catalysed hydrolysis of methyl benzoate. The suggested mechanism involves the preequilibrium formation of the anionic substrate which cyclizes to produce anionic tetrahedral intermediate followed by its breakdown as the rate-determining step. The cyclized product, NHPH, reacts rapidly and reversibly with hydroxylamine to produce o-(N-hydroxycarbamoyl)benzohydroxamic acid (P). The equilibrium constants for the processes NHPH + NH₂OH ⇌ P and PH + H⁺+ NH₂OH ⇌ P, where PH is the ionized NHPH, calculated at different pH using authentic NHPH, reveal a non-linear dependence on total hydroxylamine buffer concentrations.