Molecular interaction between cinchonidine and acetic acid studied by NMR, FTIR and ab initio methods

Abstract

Cinchona alkaloids play a major role as chiral auxiliaries in asymmetric catalysis. Acetic acid is known to be an excellent solvent in the enantioselective hydrogenation over chirally modified platinum metals. The crucial interaction between the chiral auxiliary and the solvent has been investigated using the cinchonidine–acetic acid pair. Solutions containing cinchonidine and acetic acid were studied by means of NMR and IR spectroscopy as well as by ab initio Hartree–Fock calculations. In the presence of the acid cinchonidine is protonated at the quinuclidine N and adopts an open conformation where the quinuclidine N points away from the quinoline moiety. In the most stable 1∶1 and 2∶1 acetic acid–cinchonidine complexes both the N–H⁺ and O–H groups of cinchonidine are involved in hydrogen bonding. The most stable 1∶1 complex is found to be cyclic. The relative arrangement of the N–H⁺ and O–H groups of protonated cinchonidine is ideally suited to bind an acetate anion, and the interaction hardly affects the cinchonidine conformation. Several 2∶1 acid–base complexes coexist in solution. The IR spectra give evidence for the existence of a 2∶1 cyclic complex. Calculated structures, relative energies and vibrational frequencies are in good agreement with the experiment. The findings rationalise the importance of the O–H group of cinchonidine for the enantiodifferentiation in the enantioselective hydrogenation of α,β-unsaturated carboxylic acids over cinchonidine-modified Pd.