Nuclear magnetic resonance studies of the protonation sequence of some oxaaza macrocyclic compounds

Abstract

The sequences of protonation of a series of oxatriaza and dioxadiaza macrocyclic compounds have been studied by ¹H and ¹³C n.m.r. spectroscopy. It is shown that Sudmeier and Reilley's quantitative approach to derive sequences of protonation suffers from several limitations when applied to these (and other) polyaza macrocycles due to the lack of suitable models, but the indications directly provided by the corresponding potentiometric and n.m.r. titration curves may complement the information required for this purpose. The results obtained suggest that the 12-membered oxatriaza and dioxadiaza macrocycles adopt different and more compact conformations when the nitrogen atoms are derivatized (e.g. with methyl or acetate groups); this results in stronger electrostatic repulsions of consecutive protonated nitrogen atoms of the ring, leading to changeable base strength and to protonation–deprotonation steps that produce ‘anomalous’ n.m.r. titration curves. In the case of the N-acetate derivatives, the interpretation of the trends is further complicated by the possibility of formation of CO₂^–⋯ HN⁺ intramolecular hydrogen bonds. The data now available make it possible to predict approximate values for the protonation constants of the various basic centres for the 12-membered polyoxapolyaza macrocycles and, consequently, the corresponding percentages of protonation at different pH values.