A PROTON-IONIZABLE ESTER CROWN OF 3,5-DISUBSTITUTED 1H-PYRAZOLE ABLE TO FORM STABLE DINUCLEAR COMPLEXES WITH LIPOPHILIC PHENETHYLAMINES

A convenient synthesis of the proton-ionizable crown 3 is reported tha t uses dibutyltin oxide. In acetonitrile, the reaction of 3 (LH2) with phenethylamine and homoveratrylamine (molar ratio 1:2) affords solid dinuclear complexes [LH2]2RNH(2) (4a,b), which spectroscopic (FAB-MS, IR, H-1 and C-13 NMR) data point toward a strong participation of the pyrazole nitrogens in the amine complexation. In DMSO-d(6) solution, a C-13 MMR study demonstrates the formation in situ of analogous neutra l 4a-d[LH2]2RNH(2) or charged 5a-d[L2-]2RNH(3)(+) dinuclear complexes by reaction of 3 [LH2] or 3'[L2-]2Na(+) with RNH2 (phenethylamine, hom overatrylamine, dopamine, and norepinephrine) or their RNH3+Cl- salts, respectively. Differences between the structure of complexes 4 and 5 have been evaluated by taking the homoveratrylamine derivatives 4b and 5b as models. An H-1 and C-13 NMR study (by raising the temperature) and measurements of intermolecular NOE effects (from NOESY and ROESY s pectral demonstrate that both complexes behave as prototropic isomers showing different conformations. By increasing the ionic strength, the 4b isomer structure becomes similar to that of 5b. The molecular mode ling (GenMol software) of 4a-d and 5a-d shows that the assemblage in w hich both amine molecules are on the same side of the crown is the mor e stable. Lipophilic amines afford more stable complexes than hydrophi lic ones and charged species are much more stable than the neutral one s.