Protonation equilibria of some ortho-substituted and annelated aryl and thiophen-2-yl and -3-yl ketones

Abstract

For some phenyl- (1–8) and thiophen-2-yl (9–11) and thiophen-3-yl (12–14) ketones quantum-mechanical (PM3) calculations have been performed, and for compounds 2, 3, 5–8, 10–14 protonation equilibria have been determined. Phenyl ketones have similar values for the m* parameter and show good linear correlation between the proton affinities calculated in the gas phase and the measured pK_BH⁺ values, which in turn parallel the trend for the calculated carbonyl–phenyl ring dihedral angle. It appears that the differences in basicity are governed essentially by “internal” factors (carbonyl–ring conjugation), while the base–conjugate acid differential solvation is not significantly affected by structural changes. In contrast thiophen-2-yl and -3-yl ketones show a complex behaviour, with strong variations in m* values, and no linear correlation between proton affinities and pK_BH⁺. Factors related to the solvent shell organization probably assume an important role here.