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The basicity of a series of 3,5-disubstituted 1,2,4-oxadiazoles in aqueous H2SO4 was examined by means of UV and 1H-NMR spectroscopy. The experimental data were analyzed by the modified Yates–McClelland method to yield the following pK values: 3,5-dimethyl-1,2,4-oxadiazole, −1.66±0.06; 3-methyl-5-phenyl-1,2,4-oxadiazole, −2.61±0.02; 3-phenyl-5-methyl-1,2,4-oxadiazole, −2.95±0.01; 3,5-diphenyl-1,2,4-oxadiazole, −3.55±0.06. A pK value of ca. −3.7 was estimated for the parent unsubstituted 1,2,4-oxadiazole based on substituents' additivity increments. Possible protonation sites of the compounds were discussed in terms of both experimental data and theoretical calculations (HF/6-31G**). Generally, protonation is most likely to occur at N(4) of the 1,2,4-oxadiazole ring. However, concurrent formation of both N(4)- and N(2)-protonated species in comparable amounts is possible in the case of 3-phenyl-1,2,4-oxadiazoles.

Spectral studies of the title compound showed that its intramolecular hydrogen bond is relatively strong. Hydrogen bond formation between some amines and the phenolic -OH group is not inhibited in presence of strong intramolecular hydrogen bonding between the -OH group and the ortho-diethylamino group in the title compound. Proton transfer equilibrium constants (KPT) between the studied compound and different amines in methylene chloride were measured. A linear correlation was found between log KPT and the proton affinities, PA, of amines except for α-picoline. The KPT values due to the proton transfer equilibrium between the Mannich base and α-picoline in different solvents were calculated and they gave a good correlation with the Onsager parameter. The estimated thermodynamic parameters showed that the proton transfer equilibrium in our system is entropy- and enthalpy controlled, and proved more polarizability of the intermolecular OHN bridge with increasing the solvent polarity.