Association Equilibria of Organo-Phosphoric Acids with Imines from a Combined Dielectric and Nuclear Magnetic Resonance Spectroscopy Approach

Aggregates formed between organo-phosphoric acids and imine bases in aprotic solvents are the reactive intermediates in Brønsted acid organo-catalysis. Due to the strong hydrogen-bonding interaction of the acids in solution, multiple homo- and heteroaggregates are formed with profound effects on catalytic activity. Yet, due to the similar binding motifshydrogen-bondsit is challenging to experimentally quantify the abundance of these aggregates in solution. Here we demonstrate that a combination of nuclear magnetic resonance (NMR) and dielectric relaxation spectroscopy (DRS) allows for accurate speciation of these aggregates in solution. We show that only by using the observables of both experiments heteroaggregates can be discriminated with simultaneously taking homoaggregation into account. Comparison of the association of diphenyl phosphoric acid and quinaldine or phenylquinaline in chloroform, dichloromethane, or tetrahydrofuran suggests that the basicity of the base largely determines the association of one acid and one base molecule to form an ion-pair. We find the ion-pair formation constants to be highest in chloroform, slightly lower in dichloromethane and lowest in tetrahydrofuran, which indicates that the hydrogen-bonding ability of the solvent also alters ion-pairing equilibria. We find evidence for the formation of multimers, consisting of one imine base and multiple diphenyl phosphoric acid molecules for both bases in all three solvents. This subsequent association of an acid to an ion-pair is however little affected by the nature of the base or the solvent. As such our findings provide routes to enhance the overall fraction of these multimers in solution, which have been reported to open new catalytic pathways.