Acyl group vs nitrogen protonation of carboxylic and non-carboxylic amidesin the gas phase and water

The site of protonation of carboxylic and non-carboxylic amides (whether th e amido nitrogen or an atom in the acyl group, generally oxygen) was invest igated through quantum chemical calculations and heteronuclear NMR measurem ents. The relative energies of the various ions deriving from protonation a t each site were calculated both in the gas phase and in water, and NMR pro perties of the involved heteronuclei (nuclear shielding and electric field gradient) were also calculated and compared with chemical shins and relaxat ion rates experimentally measured in N-14, O-17 and P-31 spectra. It is sho wn that such a combination of theoretical and experimental tools allows the reliable prediction of spectral parameters and ultimately of the protonati on site. In general, amides are protonated at the acyl group, with the exce ption of (a) when the parent acid is strong (for which the preference is no t marked), (b) the protonation site of sulfinamides may easily shift from N to O as a result of slight structural changes and (c) sulfenamides behave as substituted amines and are nitrogen bases. Copyright (C) 2000 John Wiley & Suns, Ltd.