Mechanism of Decarboxylation of p-Aminosalicylic Acid

Abstract

The rate of decarboxylation of p-aminosalicylic acid (1) in aqueous solutions was studied at 25°C (μ=0.5) as a function of pH and buffer concentration. A pH-rate profile was generated by using the rate constants extrapolated to zero buffer concentration. The profile was bell-shaped, with the maximum rate of decarboxylation near the isoelectric pH. The rate constants obtained in buffered solutions indicated general acid catalysis. Bronsted behavior appeared to be adhered to. The two ionization constants of 1 were determined spectrophotometrically at 25°C and at an ionic strength of 0.5. An HPLC method was used to characterize the degradation products of the reaction. Kinetic solvent deuterium isotope effects were studied to further confirm the mechanism of decarboxylation. Below pH 7.0, the mechanism of 1 decarboxylation is the rate controlling proton attack on the carbon-alpha to the carboxylic acid group of 1 anion and the ampholyte, followed by the rapid decarboxylation of the formed intermediate.