Tautomeric and Microscopic Protonation Equilibria of Anthranilic Acid and Its Derivatives

The acid–base chemistry of three zwitterionic compounds, namely anthranilic (2-aminobenzoic acid), N-methylanthranilic and N-phenylanthranilic acid has been characterized in terms of the macroconstants K (a1), K (a2), the isoelectric point pH (I), the tautomerization constant K (z) and microconstants k (11), k (12), k (21), k (22). The potentiometric titration method was used to determine the macrodissociation constants. Due to the very poor water solubility of N-phenylanthranilic acid the dissociation constants pK (a1) and pK (a2) were determined in MDM–water mixtures [MDM is a co-solvent mixture, consisting of equal volumes of methanol (MeOH), dioxane and acetonitrile (MeCN)]. The Yasuda–Shedlovsky extrapolation procedure has been used to obtain the values of pK (a1) and pK (a2) in aqueous solutions. The pK (a1) and pK (a2) values obtained by this method are 2.86 ± 0.01 and 4.69 ± 0.03, respectively. The tautomerization constant K (z) describing the equilibrium between unionized form ⇌ zwitterionic form was evaluated by the K (z) method based on UV–VIS spectrometry. The method uses spectral differences between the zwitterionic form (found at isoelectric pH in aqueous solution) and the unionized form (formed in an organic solvent of low dielectric constant). The highest value of the K (z) constant has been observed in the case of N-methylantranilic acid (log(10) K (z) = 1.31 ± 0.04). The values of log(10) K (z) for anthranilic and N-phenylanthranilic acids are similar and have values of 0.93 ± 0.03 and 0.90 ± 0.05, respectively. The results indicate that the tested compounds, in aqueous solution around the isoelectric point pH(I), occur mainly in the zwitterionic form. Moreover, the influence of the type of substituent and pH of the aqueous phase on the equilibrium were analyzed with regard to the formation and the coexistence of different forms of the acids in the examined systems.