Synthesis and Non-Aqueous Medium Titrations of Some New 4‑Benzylidenamino-4,5-dihydro-1H-1,2,4-triazol-5-one Derivatives

The synthesis of 3-alkyl(aryl)-4-(3-ethoxy-4-hydroxybenzylidenamino)-4,5-dihydro-1H-1,2,4-triazol-5-ones 3 from the reactions of 3-alkyl(aryl)-4-amino-4,5-dihydro-1H-1,2,4-triazol-5-ones 2 with 3-ethoxy-4-hydroxybenzaldehyde is described. The acetylation and methylation reactions of the compounds 3 giving compounds of type 4 and 5, respectively, were investigated. The newly synthesized compounds were characterized using elemental analyses and IR, 1H-NMR, 13C-NMR and UV spectral data. In addition, to investigate the effects of solvents and molecular structure upon acidity, compounds 3 were titrated potentiometrically with tetrabutylammonium hydroxide in four non-aqueous solvents (isopropyl alcohol, tert-butyl alcohol, acetonitrile and N,N-dimethylformamide). The half-neutralization potential values and the corresponding pKa values were determined for all cases.

After the potentiometric titrations of compounds 3 with TBAH in non-aqueous solvents, the mV values from each titration were plotted against TBAH volumes used (mL) and the potentiometric titration curves were obtained for all the cases. From the titration curves, the HNP values and the corresponding pK a values were obtained. As an example, the potentiometric titration curves for 0.001 M solutions of 3-(4-chloro-benzyl)-4-(3-ethoxy-4-hydroxybenzylidenamino)-4,5-dihydro-1H-1,2,4triazol-5-one (3d) titrated with 0.05 N TBAH in isopropyl alcohol, tert-butyl alcohol, acetonitrile and N,N-dimethylformamide are presented in Figure 1.

Compd. no HNP 1 (mV) pKa 1 HNP 2 (mV) pKa 2 3a
-503 The pH of weak acids can be calculated using the following equation: ] is equal to [HA] at the half-neutralization points. Therefore, the pH values at the half-neutralization points were taken as pK a . Taking into consideration the dielectric permittivity of the solvents, the acidity ranking might be expected to be as follows: N,N-dimethylformamide (ε=37) > acetonitrile (ε=36) > isopropyl alcohol (ε=19.4) > tert-butyl alcohol (ε=12). However, as seen in Tables 1-4, the observed acidity ranking for all compounds is isopropyl alcohol > tert-butyl alcohol > acetonitrile > N,N-dimethylformamide. This result thus matches the theoretical arrangement, except for acetonitrile and N,N-dimethylformamide. In N,N-dimethylformamide, all these compounds show the weakest acidic properties, but they show the strongest acidic properties in isopropyl alcohol. This situation may be attributed to the hydrogen bonding between the negative ions formed and the solvent molecules in the amphiprotic neutral solvents.
As seen Scheme 1, there is one weak acidic N-H group in the 4,5-dihydro-1H-1,2,4-triazol-5-one ring and one phenolic group on the aryl substituent in compounds 3a-3e. Thus, these compounds give two end-points as well as two half-neutralization potential (HNP) values. Thus, as expected, the potentiometric titration curves for these compounds 3a-3e titrated with TBAH in isopropyl alcohol, tert-butyl alcohol, acetonitrile and N,N-dimethylformamide resemble the titration curves for diprotic acids.
For compound 3b in isopropyl alcohol, compounds 3d and 3e in tert-butyl alcohol, compounds 3b, 3d and 3e in acetonitrile and compounds 3a and 3e in N,N-dimethylformamide, the second halfneutralization potential (HNP 2 ) values and the corresponding pK a values have not been obtained. In addition, the pK a values bigger than 16.00 have not been determined due to the fact that this value is outside the range of the pH meter.
As it is well known, the acidity of a compound depends on several factors. The two most important ones are the solvent effect and molecular structure [15,16,[18][19][20][21][22][23]. Tables 1-4 and Figure 1 show that the HNP values and corresponding pK a values obtained from the potentiometric titrations depend on the non-aqueous solvents used and the substituents at C-3 in 4,5-dihydro-1H-1,2,4-triazol-5-one ring.

General
Melting points were taken on a Electrothermal 9100 digital melting point apparatus and are uncorrected. IR spectra were registered on a Perkin-Elmer 1600 FTIR spectrometer. 1 H-NMR and 13 C-NMR spectra were recorded in deuterated dimethyl sulfoxide with TMS as internal standard on a Varian Mercury spectrometer at 200 MHz and 50 MHz, respectively. UV absorption spectra were measured in 10-mm quartz cells between 200 and 400 nm using a Shimadzu UV-1201 spectrophotometer. In this study, a Jenway 3040 ion analyser pH meter equipped with an Ingold pH electrode was used for potentiometric titrations. For each compound titrated, a 0.001 M solution was separately prepared in each non-aqueous solvent. A 0.05 M solution of TBAH in isopropyl alcohol, which is widely used in the titration of acids, was used as titrant. The mV values obtained on the pH meter were recorded. Finally, the half-neutralization potential (HNP) values were determined by plotting the volume (mL) (TBAH)-mV graph. The starting compounds 2a-e were prepared from the reactions of the corresponding ester ethoxycarbonylhydrazones 1a-e with an aqueous solution of hydrazine hydrate as described in the literature [17,24].