Direct determination of pKa values of cationic acids conjugated to heterocyclic amine N-oxides in polar aprotic and amphiprotic solvents

The applicability of the direct method of pK_a determination in the case of protonated heterocyclic amine N-oxides in a series of polar non-aqueous (aprotic and amphiprotic) solvents has been tested. The method is based on the pH determination of the non-aqueous solution of complex salt (the semiperchlorate in this case) formed by the N-oxides studied. The direct method not only provides for quick (one data point per each pK_a determined), but also relatively accurate estimates of acidic dissociation constants. It has been experimentally shown on the example of substituted pyridine N-oxides that this method is precise enough in all studied non-aqueous solvents when applied to compounds of not too low basicity (the pK_a being of the order of 5 or higher). To prove this, the pK_a values of protonated monocyclic N-oxides obtained by the direct method have been compared with those resulting from the potentiometric titration curve. The agreement between the results found by using both methods is very good in most cases, the differences being within standard deviations. Based upon this observation it can be inferred that the pK_a values of protonated bicyclic N-oxides in solvents studied determined by using the direct method can be also considered reliable, especially in the case of polar aprotic solvents.