NMR Structural Study of the Prototropic Equilibrium in Solution of Schiff Bases as Model Compounds

An NMR titration method has been used to simultaneously measure the acid dissociation constant (pK(a)) and the intramolecular NHO prototropic constant ΔK(NHO) on a set of Schiff bases. The model compounds were synthesized from benzylamine and substituted ortho-hydroxyaldehydes, appropriately substituted with electron-donating and electron-withdrawing groups to modulate the acidity of the intramolecular NHO hydrogen bond. The structure in solution was established by (1)H-, (13)C- and (15)N-NMR spectroscopy. The physicochemical parameters of the intramolecular NHO hydrogen bond (pK(a), ΔK(NHO) and ΔΔG°) were obtained from (1)H-NMR titration data and pH measurements. The Henderson–Hasselbalch data analysis indicated that the systems are weakly acidic, and the predominant NHO equilibrium was established using Polster–Lachmann δ-diagram analysis and Perrin model data linearization.