Solvent Effect on Relative N- and O-Acidity. Inversion of the Deprotonation Site of 2- and 4-[(2,4,6-Trinitrophenyl)amino]benzoic Acids

The deprotonation equilibrium of the title compounds (1 and 2, respectively) was experimentally investigated in DMSO-water(DMSO = dimethyl sulfoxide) mixtures by means of N-15 NMR relaxation, and theoretically by semiempirical (AM1) and ab initio (HF/3-21G) calculations, as isolated species and in dimethyl sulfoxide or water using continuum solvation models (AM1-SM2 and SCRF). Calculations predict the ionization to take place at the nitrogen atom for both acids in the gas phase. AM1-SM2 results again indicate the nitroanion to be more stable in water, whereas SCRF calculations predict the oxyanion to be slightly favoured over the nitroanion in both solvents. NMR results indicate that the preferred ionization site of 2 is the amine nitrogen in Me2SO and the carboxylic oxygen in Me,SO-water 60/40, whereas deprotonation of 1 leads to a nitroanion with an intramolecular N-...H-O hydrogen bond.