Intramolecular hydrogen-bonding studies by NMR spectroscopy

o-methoxybenzamide and N-methyl-o-methylbenzamide, using the pseudo-contact shifts calculated from the sup 1 H and sup 1 sup 3 C NMR spectra. The main conformation present in solution for o-fluorobenzamide was the one held by an intramolecular N-H...F hydrogen bond. Ab-initio calculations (at the RHF/6-31G* level) have provided additional data for the geometry of the individual molecules. A conformational equilibrium study of some nipecotic acid derivatives (3-substituted piperidines: CO sub 2 H, CO sub 2 Et, CONH sub 2 , CONHMe, CONEt sub 2) and cis-1,3-disubstituted cyclohexane derivatives (NHCOMe/CO sub 2 Me, NHCOMe/CONHMe, NH sub 2 /CO sub 2 H) has been undertaken in a variety of solvents, in order to predict the intramolecular hydrogen-bonding energies involved in the systems. The conformer populations were obtained by direct integration of proton peaks corresponding to the equatorial and axial conformations at low temperature (-80 deg), and by geometrically dependent coupling constants ( sup 3 J sub H sub - sub H) measurement. The free energy differences (DELTA G sub A sub - sub E) for nipecotamide (CONH sub 2) changed from -0.46 kcal mol sup - sup 1 in chloroform to 1.39 kcal mol sup - sup 1 in water. Analysis of these energy differences gave a value for the intramolecular hydrogen bonding of 2.4 to 2.9 kcal mol sup - sup 1 in chloroform and 0.5 to 1.0 kcal mol sup - sup 1 in water solution. The present investigation proves the existence of an intramolecular hydrogen bond in all the piperidine derivatives, and shows that this interaction is strongly dependent on the substituent group, the presence of charges in the molecule, the nature of the solvent and the hydrogen-bond ring size. Finally, an alternative NMR technique for a full conformational analysis has been used in the Lanthanide Induced Shift Investigation of o-fluorobenzamide