The lipophilicity and hydrogen bond strength of pyridine-N-oxides and protonated pyridine-N-oxides

Abstract

Water–solvent partition coefficients for 4-nitropyridine-N-oxide have been determined in six solvent systems, and solubilities measured in water and 37 solvents. The combined data are used to obtain Abraham descriptors for 4-nitropyridine-N-oxide as follows: E = 0.934, S = 1.92, A = 0.21, B = 0.76, V = 0.9082 and L = 5.246; literature data on partition coefficients were used to calculate descriptors for 11 other pyridine-N-oxides as well as quinoline-N-oxide and isoquinoline-N-oxide. In all cases, the N-oxides were shown to be stronger hydrogen bond bases than the corresponding pyridines, thus leading to a decrease in lipophilicity. An unexpected observation is that of the hydrogen bond acidity of the N-oxides due, we suggest, to the positive nitrogen atom in the moiety N(+) → O(−). This leads to an even sharper decrease in the N-oxide lipophilicity in non-polar solvents. We have also used literature data to determine the 1 ∶ 1 hydrogen bond basicity, β^H₂, of a number of pyridine-N-oxides; again, this basicity is significantly larger than that of the corresponding pyridines. Protonation of pyridine-N-oxides removes all hydrogen bond basicity (B = 0.00), but the protonated compounds are strong hydrogen bond acids. For protonated pyridine-N-oxide itself, E = 0.514, S = 2.62, A = 1.51, B = 0.00, V = 0.7555 and the ionic descriptor J⁺ = 0.894; protonated 4-nitropyridine-N-oxide with A = 2.05 is a very strong hydrogen bond acid indeed.