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 that uses dibutyltin oxide. In acetonitrile, the reaction of 3 (LH(2)) with phenethylamine and homoveratrylamine (molar ratio 1:2) affords solid dinuclear complexes [LH(2)]2RNH(2) (4a,b), which spectroscopic (FAB-MS, IR, (1)H and (13)C NMR) data point toward a strong participation of the pyrazole nitrogens in the amine complexation. In DMSO-d(6) solution, a (13)C NMR study demonstrates the formation in situ of analogous neutral 4a-d[LH(2)]2RNH(2) or charged 5a-d[L(2)(-)]2RNH(3)(+) dinuclear complexes by reaction of 3 [LH(2)] or 3'[L(2)(-)]2Na(+) with RNH(2) (phenethylamine, homoveratrylamine, dopamine, and norepinephrine) or their RNH(3)(+)Cl(-) salts, respectively. Differences between the structure of complexes 4 and 5 have been evaluated by taking the homoveratrylamine derivatives 4b and 5bas models. An (1)H and (13)C NMR study (by raising the temperature) and measurements of intermolecular NOE effects (from NOESY and ROESY spectra) 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 modeling (GenMol software) of 4a-d and 5a-d shows that the assemblage in which both amine molecules are on the same side of the crown is the more stable. Lipophilic amines afford more stable complexes than hydrophilic ones and charged species are much more stable than the neutral ones.
Campayo
Lucrecia
L
Instituto de Química Médica and Instituto de Química Orgánica General, Centro Nacional de Química Orgánica Manuel Lora-Tamayo, Consejo Superior de Investigaciones Científicas (CSIC), c/ Juan de la Cierva 3, 28006 Madrid, Spain, and Laboratoire de Chimie et Matériaux Organiques-Modélisation ERS 158 CNRS, Faculté des Sciences Luminy, 163 Av de Luminy, 13288 Marseille Cédex 09, France.
Bueno
José M.
JM
Navarro
Pilar
P
Ochoa
Carmen
C
Jimenez-Barbero
Jesús
J
Pèpe
Gèrard
G
Samat
André
A