Acta Chim. Slov. 2002, 49, 783-794. 783 SYNTHESIS AND NON-AQUEOUS MEDIUM TITRATIONS OF SOME NEW 4,5-DIHYDRO-1H-1,2,4-TRIAZOL-5-ONE DERIVATIVES ªule Bahçeci,a Haydar Yüksek,b* Zafer Ocak,c Canan Köksal,a Mustafa Özdemirc aFatih Education Faculty, Karadeniz Technical University, 61335 Trabzon, Turkey bDepartment of Chemistry, Kafkas University, 36100 Kars, Turkey cDepartment of Chemistry, Karadeniz Technical University, 61080 Trabzon, Turkey *Corresponding author : e-mail. hyuksek98@yahoo.com Received 22-03-2002 Abstract 3-Alkyl(Aryl)-4-amino-4,5-dihydro-1H-1,2,4-triazol-5-ones (2) reacted with 3,4-dihydroxy-benzaldehyde to afford the corresponding 3-alkyl(aryl)-4-(3,4-dihydroxybenzylidenamino)-4,5-dihydro-1H-1,2,4-triazol-5-ones (3). The acetylation and methylation reactions of the latter compounds were investigated, and 4 and 5 type compounds were obtained, respectively. The new compounds were characterized using IR, 1H-NMR, 13C-NMR and UV spectral data. In addition, solutions of the compounds 3a-3e were titrated potentiometrically with tetrabutylammonium hydroxide in three different non-aqueous solvents such as acetonitrile, isopropyl alcohol and N,N-dimethylformamide. The half-neutralization potential values and the corresponding pKa values of these compounds were determined in the solvents described above. Thus, the effects of solvents and molecular structure upon acidity were investigated. Key words: 4,5-Dihydro-1H-1,2,4-triazol-5-one, Schiff base, methylation, acetylation, acidity, potentiometric titrations. Introduction Several studies, involving the formation and investigation of biological activities of some N-arylidenamino-1,2,4-triazoles and N-arylidenamino-4,5-dihydro-1H-1,2,4-triazol-5-one derivatives, have been reported.1-12 The acetylation and methylation of 1,2,4-triazole and 4,5-dihydro-1H-1,2,4-triazol-5-one derivatives have also been reported.13-16 On the other hand, it is known that 1,2,4-triazole and 4,5-dihydro-1H-1,2,4-triazol-5-one rings have weak acidic properties, so some 1,2,4-triazole and 4,5-dihydro-1H-1,2,4-triazol-5-one derivatives were titrated potentiometrically with tetrabutylammonium hydroxide in non-aqueous solvents, and the pKa values of the compounds were determined.16-26 ª. Bahçeci, H. Yüksek, Z. Ocak, C. Köksal, M. Özdemir: Synthesis and non-aqueous medium titrations… 784 Acta Chim. Slov. 2002, 49, 783-794. This paper describes the synthesis of a series of 3-alkyl(aryl)-4-(3,4-dihydroxy-benzylidenamino)-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 3,4-dihydroxybenzal-dehyde. In addition, the reactions of compounds 3 with acetic anhydride and NaOH/dimethyl sulphate were investigated, and 4 and 5 type compounds were obtained, respectively, Scheme 1. Furthermore, in order to determine the pKa values of the compounds 3a-3e they were titrated potentiometrically with tetrabutylammonium hydroxide in three non-aqueous solvents, including acetonitrile, isopropyl alcohol and N,N-dimethylformamide. For each new compounds 3a-e, the half-neutralization potential (HNP) values and the corresponding pKa values were determined in the three different non-aqueous solvents. The data obtained from the potentiometric titrations were interpreted, and substituent effects attached to C-3 position in 4,5-dihydro-1H-1,2,4-triazol-5-one ring and solvent effects were studied.22-25 Determination of pKa values of the active constituent of certain pharmaceutical preparations is important because the distribution, transport behavior, bonding to receptors, and contributions to the metabolic behavior of the active constituent molecules depend on the ionization constant.27-29 In order to identify the new compounds synthesized in this study, spectroscopic methods, including IR, 1H-NMR, 13C-NMR and UV, were used, and the observed values were interpreted.30-32 Scheme 1 COCH3 / NNHCOEt N------NH N------NH N------N RC OEt A I R^N O I O I I R N O 1 NH2 n=ch-/QVoh N=ChVQVoCOCH3 1 2 3 OH 4 OCOCH3 1-4 R CH3 / a CH b c CH2C6H5 CH2C6H4.CH3 (p-) N------N 1 1 d CH C H .Cl (p-) n=ch-/QVoch3 e C6H5 5 OCH3 ª. Bahçeci, H. Yüksek, Z. Ocak, C. Köksal, M. Özdemir: Synthesis and non-aqueous medium titrations… Acta Chim. Slov. 2002, 49, 783-794. 785 Experimental Melting points were taken on an Electrothermal digital melting point apparatus and are uncorrected. IR spectra were registered on a Perkin-Elmer 1600 FTIR spectrometer. 1H-NMR and 13C-NMR spectra were recorded in deuterated dimethylsulphoxide on a Varian Mercury Apparatus at 200 MHz with TMS as internal standard. UV absorption spectra were measured in 10 mm quartz cells between 200 and 400 nm with a Shimadzu UV-1201 spectrophotometer. For the potentiometric titrations, a Jenway 3040 ion analyzer pH meter equipped with an Ingold pH electrode was used. Also, a magnetic stirrer, a semi micro burette and a 25 mL beaker were used in the titrations. Before potentiometric titrations, the pH meter was calibrated according to the instructions supplied by the manufactures of the pH meter. During the titrations, the titrant was added in increments of 0.05 mL after each stable reading, and mV values were recorded. The necessary chemicals were supplied from Fluka and Merck. After purifications, isopropyl alcohol was used to prepare 0.05 N-tetrabutylammonium hydroxide (TBAH). For all potentiometric titrations, 0.05 N tetrabutylammonium hydroxide (TBAH) in isopropyl alcohol, which was prepared from the 0.1 N TBAH by dilution, was used. The starting compounds 2a-e were prepared from the reactions of the corresponding ester ethoxycarbonylhydrazones (1a-e) with an aqueous solution of hydrazine hydrate according to the literature.15,33 Preparation of 3-alkyl(aryl)-4-(3,4-dihydroxybenzylidenamino)-4,5-dihydro-1H-1,2,4-triazol-5-ones (3). General Procedure. The corresponding compound 2 (0.01 mole) was dissolved in acetic acid (15 mL) and treated with 3,4-dihydroxybenzaldehyde (1.38 g, 0.01 mole). The mixture was refluxed for 1 h and then evaporated at 50-55 °C in vacuo. Several recrystallizations of the residue from a proper solvent gave pure compound 3. The following compounds were prepared applying this procedure: 3-Methyl-4-(3,4-dihydroxybenzylidenamino)-4,5-dihydro-1H-1,2,4-triazol-5-ones (3a). White crystals (1.88 g, 80%). M.p. 275-276 °C (EtOH). IR: 3440 (OH), 3150 (NH), 1710 (C=O), 1610, 1580 (C=N) cm-1. 1H-NMR (200 MHz, DMSO-d6): ? 2.25 (s, 3H, CH3), 6.84 (d, J=8.2 Hz, 1H, Ar-H), 7.10 (d, J=8.2 Hz, 1H, Ar-H), 7.30 (s, 1H, Ar- ª. Bahçeci, H. Yüksek, Z. Ocak, C. Köksal, M. Özdemir: Synthesis and non-aqueous medium titrations… 786 Acta Chim. Slov. 2002, 49, 783-794. H), 9.45 (s, 2H, CH+OH), 9.73 (s, 1H, OH), 11.78 (s, 1H, NH). 13C-NMR (50 MHz, DMSO-4): 5 11.11 (aliphatic carbon), 112.79, 115.54, 121.76, 124.66, 144.09, 149.20 (aromatic carbons), 145.72 (triazole C3), 151.30 (N=CH), 154.81 (triazole C5). UV (ethanol) W (e, L mol"1 cm"1): 322 (20086), 237 (12086), 214 (16623) nm. Anal. Calculated for C10H10N4O3: C, 51.28; H, 4.30; N, 23.92. Found: C, 51.15; H, 4.38; N, 23.73. 3-Benzyl-4-(3,4-dihydroxybenzylidenamino)-4,5-dihydro-lH-l,2,4-triazol-5-ones (3b). White crystals (2.65 g, 85%). M.p. 265-267 °C (EtOH/water, 1:3). IR: 3380 (OH), 3196 (NH), 1715 (C=0), 1595, 1580 (C=N), 768, 700 (monosubstituted benzenoid ring) cm"1. 'H-NMR (200 MHz, DMSO-d6): 5 4.02 (s, 2H, CH2), 6.83 (d, J=8.2 Hz, 1H, Ar-H), 7.05 (d, J=8.2 Hz, 1H, Ar-H), 7.20-7.34 (m, 6H, Ar-H), 9.43 (s, 2H, CH+OH), 9.52 (s, 1H, OH), 11.93 (s, 1H, NH). 13C-NMR (50 MHz, DMSO-d6): 5 30.00 (aliphatic carbon), 112.83, 115.52, 121.77, 124.64, 126.64, 128.38 (2C), 128.75 (2C), 135.77, 146.07, 149.24 (aromatic carbons), 145.72 (triazole C3), 151.26 (N=CH), 154.51 (triazole C5). UV (ethanol) W (s, L mol"1 cm"1): 323 (14783), 213 (16556) nm. Anal. Calculated for C16H14N4O3: C, 61.93; H, 4.55; N, 18.06. Found: C, 62.15; H, 4.67; N, 18.39. 3-p-Methylbenzyl-4-(3,4-dihydroxybenzylidenamino)-4,5-dihydro-lH-l,2,4-triazol-5-ones (3c). White crystals (2.48 g, 77%). M.p. 266-267 °C (EtOH/water, 1:3). IR: 3455, 3350 (OH), 3100 (NH), 1700 (C=0), 1610, 1580 (C=N), 800 (1,4-disubstituted benzenoid ring) cm"1. !H-NMR (200 MHz, DMSO-d6): 5 2.24 (s, 3H, CH3), 3.95 (s, 2H, CH2), 6.82 (d, J=7.9 Hz, 1H, Ar-H), 7.02-7.27 (m, 6H, Ar-H), 9.41 (s, 2H, CH+OH), 9.72 (s, 1H, OH), 11.90 (s, 1H, NH). 13C-NMR (50 MHz, DMSO-d6): 5 20.51, 30.59 (aliphatic carbons), 112.79, 115.49, 121.74, 124.63, 128.59, 128.92 (2C), 132.64 (2C), 135.66, 146.19, 149.20 (aromatic carbons), 145.70 (triazole C3), 151.25 (N=CH), 154.41 (triazole C5). UV (ethanol) W (s, L mol"1 cm"1): 320 (11813), 213 (15767) nm. Anal. Calculated for CiyHieN^: C, 62.95; H, 4.97; N, 17.27. Found: C, 62.94; H, 4.75; N, 16.94. 3-p-Chlorobenzyl-4-(3,4-dihydroxybenzylidenamino)-4,5-dihydro-lH-l,2,4-triazol-5-ones (3d). White crystals (2.35 g, 68%). M.p. 290-292 °C (EtOH). IR: 3336 §. Bahgeci, H. Yiiksek, Z. Oèak, C. Köksal, M. Özdemir: Synthesis and non-aqueous medium titrations… Acta Chim. Slov. 2002, 49, 783-794. 787 (OH), 3150 (NH), 1715 (C=O), 1590, 1580 (C=N), 805 (1,4-disubstituted benzenoid ring) cm-1. 1H-NMR (200 MHz, DMSO-d6): 5 4.02 (s, 2H, CH2), 6.82 (d, J=7.9 Hz, 1H, Ar-H), 7.05 (d, J=7.6 Hz, 1H, Ar-H), 7.25-7.37 (m, 5H, Ar-H), 9.42 (s, 2H, CH+OH), 9.75 (s, 1H, OH), 11.95 (s, 1H, NH). 13C-NMR (50 MHz, DMSO-d6): 5 30.35 (aliphatic carbon), 112.86, 115.53, 121.75, 124.57, 128.59 (2C), 130.69 (2C), 131.31, 134.72, 145.71, 149.25 (aromatic carbons), 145.71 (triazole C3), 151.24(N=CH), 154.57(triazole C5). UV (ethanol) W (s, L mol-1 cm-1): 323 (15663), 217 (20945) nm. Anal. Calculated for C16H13N4O3Cl: C, 55.74; H, 3.80; N, 16.25. Found: C, 55.43; H, 3.73; N, 16.60. 3-Phenyl-4-(3,4-dihydroxybenzylidenamino)-4,5-dihydro-lH-l,2,4-triazol-5-ones (3e). White crystals (2.14 g, 72%). M.p. 276-277 °C (EtOH/water, 1:3). IR: 3427 (OH), 3232 (NH), 1700 (C=O), 1610, 1590 (C=N), 765, 700 (monosubstituted benzenoid ring) cm-1. 1H-NMR (200 MHz, DMSO-d6): 5 6.85 (d, J=7.9 Hz, 1H, Ar-H), 7.09(d, J=7.6 Hz, 1H, Ar-H), 7.62 (s, 1H, Ar-H), 7.25 (s, 3H, Ar-H), 7.89 (s, 2H, Ar-H), 9.33 (s, 2H, CH+OH), 9.52 (s, 1H, OH), 12.32 (s, 1H, NH). 13C-NMR (50 MHz, DMSO-d6): 5 112.84, 115.57, 122.20, 124.40, 126.73, 127.68 (2C), 128.44 (2C), 129.92, 144.35, 149.50 (aromatic carbons), 145.76 (triazole C3), 151.39 (N=CH), 158.00 (triazole C5). UV (ethanol) W (s, L mol-1 cm-1): 326 (17811), 282 (13297), 216 (20366) nm. Anal. Calculated for C15H12N4O3: C, 60.81; H, 4.08; N, 18.91. Found: C, 61.20; H, 3.77; N, 18.60. Preparation of l-Acetyl-3-alkyl(aryl)-4-(3,4-diacetyloxybenzylidenamino)-4,5-dihydro-lH-l,2,4-triazol-5-ones (4). General Procedure The corresponding compound 3 (0.01 mole) was refluxed with acetic anhydride (15 mL) for 0.5 h. After addition absolute ethanol (50 mL), the mixture was refluxed for 1 h. Evaporation of the resulting solution at 40-45 °C in vacuo and several recrystallizations of the residue from an proper solvent gave pure compound 4. The following compounds were prepared applying this procedure: l-Acetyl-3-methyl-4-(3,4-diacetyloxybenzylidenamino)-4,5-dihydro-lH-l,2,4-triazol-5-ones (4a). White crystals (2.95 g, 82%). M.p. 196-197 °C (EtOH). IR: 1780, 1760, 1705 (C=O), 1630, 1610 (C=N) cm-1. 1H-NMR (200 MHz, DMSO-d6): 5 2.32 (s, ª. Bahçeci, H. Yüksek, Z. Ocak, C. Köksal, M. Özdemir: Synthesis and non-aqueous medium titrations… 788 Acta Chim. Slov. 2002, 49, 783-794. 9H, 3CH3), 2.49 (s, 3H, CH3), 7.45 (d, J=8.9 Hz, 1H, Ar-H), 7.80-7.83 (m, 2H, Ar-H), 9.61 (s, 1H, CH). 13C-NMR (50 MHz, DMSO-d6): 5 11.13, 20.28 (2C), 23.39 (aliphatic carbons), 122.25, 124.25, 126.90, 131.69, 142.46, 146.63 (aromatic carbons), 144.59 (triazole C3), 147.73 (N=CH), 153.74 (triazole C5), 165.96, 167.96, 168.14 (C=0). UV (ethanol) W (s, L mol"1 cm"1): 293 (17500), 254 (18738), 216 (21784) nm. Anal. Calculated for Ci6Hi6N406: C, 53.33; H, 4.48; N, 15.55. Found: C, 53.62; H, 4.18; N, 15.60. l-Acetyl-3-benzyl-4-(3,4-diacetyloxybenzylidenamino)-4,5-dihydro-lH-l,2,4-triazol-5-ones (4b). White crystals (3.72 g, 85%). M.p. 129-130 °C (EtOH). IR: 1780, 1760, 1700 (C=0), 1610, 1590 (C=N), 770, 715 (monosubstituted benzenoid ring) cm"1. ^-NMR (200 MHz, DMSO-d6): 5 2.23 (s, 6H, 2CH3), 2.40 (s, 3H, CH3), 4.06 (s, 2H, CH2), 7.12-7.40 (m, 6H, Ar-H), 7.64-7.78 (m, 2H, Ar-H), 9.55 (s, 1H, CH). 13C-NMR (50 MHz, DMSO-de): 5 20.26 (2C), 23.48, 30.92 (aliphatic carbons), 122.34, 124.35, 126.81, 126.88, 128.42 (2C), 128.93 (2C), 131.68, 134.56, 142.39, 147.89 (aromatic carbons), 144.53 (triazole C3), 148.21 (N=CH), 153.26 (triazole C5), 165.90, 167.98, 168.10 (C=0). UV (ethanol) W (s, L mol"1 cm"1): 295 (17296), 254 (18252), 217 (23879) nm. Anal. Calculated for C22H20N4O6: C, 60.55; H, 4.62; N, 12.84. Found: C, 60.84; H, 4.76; N, 12.62. l-Acetyl-3-(p-methylbenzyl)-4-(3,4-diacetyloxybenzylidenamino)-4,5-dihydro-lH-l,2,4-triazol-5-ones (4c). White crystals (4.02 g, 89%). M.p. 159-160 °C (EtOH). IR: 1775, 1765, 1735 (C=0), 1605, 1585 (C=N), 810 (1,4-disubstituted benzenoid ring) cm"1. 'H-NMR (200 MHz, DMSO-d6): 5 2.09 (s, 3H, CH3), 2.18 (s, 6H, 2CH3), 2.36 (s, 3H, CH3), 3.90 (s, 2H, CH2), 6.97 (d, J=7.6 Hz, 2H, Ar-H), 7.09 (d, J=7.6 Hz, 2H, Ar-H), 7.26 (d, J=7.9 Hz, 1H, Ar-H), 7.54 (s, 1H, Ar-H), 7.56 (d, J=8.9 Hz, 1H, Ar-H), 9.36 (s, 1H, CH). 13C-NMR (50 MHz, DMSO-d6): 5 20.75 (2C), 21.04, 23.92, 31.15 (aliphatic carbons), 122.77, 124.90, 127.38, 129.36 (2C), 129.60 (2C), 131.83, 132.18, 136.77, 142.95, 148.40 (aromatic carbons), 145.10 (triazole C3), 149.02 (N=CH), 153.76 (triazole C5), 166.80, 168.80, 168.90 (C=0). UV (ethanol) Xmax (s, L mol"1 cm"1): 295 (10145), 254 (10973), 217 (18082) nm. Anal. Calculated for C23H22N406: C, 61.32; H, 4.92; N, 12.44. Found: C, 61.24; H, 5.19; N, 12.39. §. Bahgeci, H. Yiiksek, Z. Oèak, C. Köksal, M. Özdemir: Synthesis and non-aqueous medium titrations… Acta Chim. Slov. 2002, 49, 783-794. 789 l-Acetyl-3-p-chlorobenzyl-4-(3,4-diacetyloxybenzylidenamino)-4,5-dihydro-lH-l,2,4-triazol-5-ones (4d). White crystals (3.55 g, 76%). M.p. 167-169 °C (EtOH). IR: 1780, 1760, 1700 (C=O), 1610, 1590 (C=N), 810 (1,4-disubstituted benzenoid ring) cm-1. 1H-NMR (200 MHz, DMSO-d6): 5 2.32 (s, 6H, 2CH3), 2.50 (s, 3H, CH3), 4.17 (s, 2H, CH2), 7.40-7.45 (m, 5H, Ar-H), 7.74-7.79 (m, 2H, Ar-H), 9.58 (s, 1H, CH). 13C-NMR (50 MHz, DMSO-d6): 5 20.29 (2C), 23.48, 30.92 (aliphatic carbons), 122.36, 124.38, 126.82, 128.34 (3C), 130.90 (3C), 131.85, 133.95, 142.35 (aromatic carbons), 144.55 (triazole C3), 148.20 (N=CH), 153.24 (triazole C5), 165.90, 167.98, 168.10 (C=O). UV (ethanol) W (s, L mol-1 cm-1): 295 (17692), 257 (18372), 219 (27571) nm. Anal. Calculated for C22H19N4O6Cl: C, 56.12; H, 4.07; N, 11.90. Found: C, 56.47; H, 4.07; N, 11.91. l-Acetyl-3-phenyl-4-(3,4-diacetyloxybenzylidenamino)-4,5-dihydro-lH-l,2,4-triazol-5-ones (4e). White crystals (3.78 g, 90%). M.p. 133-134 °C (EtOH). IR: 1780, 1765, 1735 (C=O), 1615, 1598 (C=N), 750, 700 (monosubstituted benzenoid ring) cm-1. 1H-NMR (200 MHz, DMSO-d6): 5 2.17 (s, 6H, 2CH3), 2.42 (s, 3H, CH3), 7.28 (d, J=7.9 Hz, 1H, Ar-H), 7.35-7.82 (m, 7H, Ar-H), 9.31 (s, 1H, CH). 13C-NMR (50 MHz, DMSO-d6): 5 20.78 (2C), 23.99 (aliphatic carbons), 123.29, 125.10, 125.49, 127.28, 129.19 (3C), 131.93 (2C), 132.29, 143.00, 146.58 (aromatic carbons), 145.34 (triazole C3), 148.55 (N=CH), 157.60 (triazole C5), 167.13, 168.82, 168.95 (C=O). UV (ethanol) W (s, L mol-1 cm-1): 263 (12768), 217 (12081) nm. Anal. Calculated for C21H18N4O6: C, 59.71; H, 4.30; N, 13.26. Found: C, 59.49; H, 4.24; N, 13.45. Preparation of l-Methyl-3-alkyl(aryl)-4-(3,4-dimethoxybenzylidenamino)-4,5-dihydro-lH-l,2,4-triazol-5-ones (5). General Procedure. The corresponding compound 3 (0.01 mole) was dissolved in 2N NaOH (10 mL) and treated dimethyl sulphate (3.2 mL). After stirring of the mixture at room temperature for 1 h, the solid formed was filtered, washed with cold water (15 mL) and dried in vacuo. Several recrystallizations of crude product from a proper solvent gave pure compound 5. The following compounds were prepared applying this procedure: l,3-Dimethyl-4-(3,4-dimethoxybenzylidenamino)-4,5-dihydro-lH-l,2,4-triazol-5-ones (5a). White crystals (1.88 g, 68%). M.p. 137-139 °C (EtOH). IR: 1710 (C=O), ª. Bahçeci, H. Yüksek, Z. Ocak, C. Köksal, M. Özdemir: Synthesis and non-aqueous medium titrations… 790 Acta Chim. Slov. 2002, 49, 783-794. 1600,1580 (C=N) cm"1. 'H-NMR (200 MHz, DMSO-d6): 5 2.19 (s, 3H, CH3), 3.22 (s, 3H, CH3), 3.80 (s, 6H, 2CH3), 6.96 (d, J=8.1 Hz, 1H, Ar-H), 7.25-7.35 (m, 2H, Ar-H), 9.45 (s, 1H, CH). 13C-NMR (50 MHz, DMSO-d6): 5 10.83, 31.70, 55.35, 55.52 (aliphatic carbons), 108.73, 111.37, 122.76, 125.75, 148.95, 149.31 (aromatic carbons), 142.66 (triazole C3), 151.72 (N=CH), 154.31 (triazole C5). UV (ethanol) W (s, L mol" 1 cm"1): 315 (21065), 235 (15144), 215 (17657) nm. Anal. Calculated for Ci3H16N403: C, 56.51; H, 5.84; N, 20.28. Found: C, 56.22; H, 5.57; N, 20.04. l-Methyl-3-benzyl-4-(3,4-dimethoxybenzylidenamino)-4,5-dihydro-lH-l,2,4-triazol-5-ones (5b). White crystals (2.30 g, 65%). M.p. 150-152 °C (EtOH). IR: 1715 (C=0), 1610, 1580 (C=N), 760, 720 (monosubstituted benzenoid ring) cm"1. ^-NMR (200 MHz, DMSO-d6): 5 3.22 (s, 3H, CH3), 3.82 (s, 6H, 2CH3), 4.07 (s, 2H, CH2), 7.05 (d, J=7.9 Hz, 1H, Ar-H), 7.22-7.45 (m, 7H, Ar-H), 9.54 (s, 1H, CH). 13C-NMR (50 MHz, DMSO-de): 5 30.97, 31.83, 55.31, 55.51 (aliphatic carbons), 108.18, 111.29, 123.03, 125.78, 126.66, 128.37 (2C), 128.72 (2C), 135.64, 148.93, 149.45 (aromatic carbons), 144.56 (triazole C3), 151.70 (N=CH), 153.46 (triazole C5). UV (ethanol) W (s, L mol"1 cm"1): 318 (34597), 216 (25068) nm. Anal. Calculated for Ci9H2oN403: C, 64.76; H, 5.72; N, 15.90. Found: C, 64.89; H, 5.85; N, 15.81. l-Methyl-3-p-methylbenzyl-4-(3,4-dimethoxybenzylidenamino)-4,5-dihydro-lH-l,2,4-triazol-5-ones (5c). White crystals (2.52 g, 69%). M.p. 197-198 °C (EtOH). IR: 1715 (C=0), 1610, 1595 (C=N), 810 (1,4-disubstituted benzenoid ring) cm"1. lH-NMR (200 MHz, DMSO-d6): 5 2.20 (s, 3H, CH3), 3.20 (s, 3H, CH3), 3.80 (s, 6H, 2CH3), 3.96 (s, 2H, CH2), 6.84 (d, J=7.8 Hz, 1H, Ar-H), 7.05-7.35 (m, 6H, Ar-H), 9.40 (s, 1H, CH). 13C-NMR (50 MHz, DMSO-d6): 5 20.82, 30.84, 31.20, 55.30, 55.62 (aliphatic carbons), 108.22, 111.30, 123.12, 125.92, 126.82, 127.22, 128.42 (2C), 128.92 (2C), 135.57, 148.33 (aromatic carbons), 145.32 (triazole C3), 152.10 (N=CH), 153.52 (triazole C5). UV (ethanol) W (s, L mol"1 cm"1): 318 (11210), 224 (23150) nm. Anal. Calculated for C2oH22N403: C, 65.56; H, 6.05; N, 15.29. Found: C, 65.77; H, 6.18; N, 15.20. §. Bahgeci, H. Yiiksek, Z. Oèak, C. Köksal, M. Özdemir: Synthesis and non-aqueous medium titrations… Acta Chim. Slov. 2002, 49, 783-794. 791 Results and Discussion There have been several studies about the potentiometric titrations of some 4,5- dihydro-1 H-1,2,4-triazol-5-on derivatives with tetrabutylammonium hydroxide (TBAH) in the non-aqueous solvents such as isopropyl alcohol, methyl alcohol, tert-butyl alcohol and acetone, and the pKa values were found between 9.79-16.0523-25. In this study, five new 3-alkyl(aryl)-4-(3,4-dihydroxybenzylidenamino)-4,5-dihydro-1 H-1,2,4-triazol-5-ones (3), five new 1-acetyl-3-alkyl(aryl)-4-(3,4-diacetyloxybenzyliden-amino)-4,5-dihydro-1 H-1,2,4-triazol-5-ones (4) and three new 1-methyl-3-alkyl(aryl)-4-(3,4-dimethoxybenzylidenamino)-4,5-dihydro-1 H-1,2,4-triazol-5-ones (5) were synthesized, and 3 type compounds were titrated potentiometrically with tetrabutylammonium hydroxide (TBAH) in non-aqueous solvents such as isopropyl alcohol (?=19.4), N,N-dimethylformamide (?=37) and acetonitrile (?=36). The mV values, which were read from pH meter, were plotted versus TBAH volumes (mL) added, and thus potentiometric titration curves were formed for all the cases. From these curves, the HNP values were measured, and the corresponding pKa values were calculated. As an example, the potentiometric titration curves of 0.001 M 3-benzyl-4-(3,4-dihydroxybenzylidenamino)-4,5-dihydro-1 H-1,2,4-triazol-5-ones (3b) solutions titrated with 0.05 N TBAH in isopropyl alcohol, N,N-dimethylformamide and acetonitrile are presented in Figure 1. -130--260--390 rrt/ -520--650 Figure 1: Potentiometric titration curves of 10-3 M compound 3b solutions titrated with 0.05 N TBAH in isopropyl alcohol (>), N,N-dimethylformamide (¦) and acetonitrile (•) at 25 °C. ª. Bahçeci, H. Yüksek, Z. Ocak, C. Köksal, M. Özdemir: Synthesis and non-aqueous medium titrations… 792 Acta Chim. Slov. 2002, 49, 783-794. The half neutralization potential (HNP) values and the corresponding pKa values of compounds 3a-e, which were obtained from the potentiometric titrations with 0.05 N TBAH in non aqueous solvents such as isopropyl alcohol, N,N-dimethylformamide and acetonitrile, are presented in Tables 1-3. Table 1: The half neutralization potential (HNP) values and the corresponding pKa values of compounds 3a-e in isopropyl alcohol at 25 °C. Compd. no HNP1 (mV) pKa1 HNP2 (mV) pKa2 3a -231 11.41 -327 13.65 3b -242 11.13 -419 14.25 3c -194 10.35 -314 13.42 3d -203 9.75 -394 13.40 3e -224 11.22 -341 13.51 Table 2: The half neutralization potential (HNP) values and the corresponding pKa values of compounds 3a-e in N,N-dimethylformamide at 25 °C. Compd. no HNP1 (mV) pKa1 HNP2 (mV) pKa2 3a -357 12.09 -424 13.81 3b -287 12.03 -429 14.43 3c -255 10.61 -371 13.75 3d -310 12.53 -511 - 3e -326 12.85 -506 - Table 3: The half neutralization potential (HNP) values and the corresponding pKa values of compounds 3a-e in acetonitrile at 25 °C. Compd. no HNP1 (mV) pKa1 HNP2 (mV) pKa2 3a -281 11.74 -424 13.79 3b -243 11.15 -488 15.29 3c -293 12.05 -593 - 3d -182 10.27 -353 13.07 3e -192 10.52 -271 12.08 ª. Bahçeci, H. Yüksek, Z. Ocak, C. Köksal, M. Özdemir: Synthesis and non-aqueous medium titrations… Acta Chim. Slov. 2002, 49, 783-794. 793 As seen in Scheme 1, there is one weak acidic N-H group in 4,5-dihydro-1H-1,2,4-triazol-5-one ring and two phenolic groups in compounds 3a-e. Thus, these compounds give two end points as well as two half neutralization potential values. The potentiometric titration curves of these phenolic compounds 3a-e titrated with TBAH in isopropyl alcohol, N,N-dimethylformamide and acetonitrile resemble the titration curves of diprotic acids. For compound 3d and 3e, the second pKa values have not been obtained in N,N-dimethylformamide. For compound 3c, the second pKa value has not been obtained in acetonitrile, either. As known, the acidity of a compound changes in relation to some factors. The two most important factors are solvent effects and molecular structure.23-26,34-38 Tables 1-3 show that the HNP values and the corresponding pKa values obtained from the potentiometric titrations change in connection with the non-aqueous solvents in which the titration took place. In addition, it is seen from the Tables 1-3 that the molecular structure of titrated compounds affect the HNP values as well as the corresponding pKa values: that is, the HNP values and corresponding pKa values are connected to the substituents linked to C-3 in 4,5-dihydro-1H-1,2,4-triazol-5-one ring for the same solvent. References 1. H. H. Takimoto, G. C. Denault, S. Hotta, J. Heterocycl. Chem. 1966, 3, 119. 2. R. Milcent, C. Redeuilh, J. Heterocycl. Chem. 1979, 16, 403. 3. R. Milcent, P.Vicart, J. Med. Chem. 1983, 18, 215. 4. A. R. Katritzky, K. S. Laurenzo, J. Org. Chem. 1988, 53, 3978. 5. A. A. Ikizler, A. Ikizler, N. Yildirim, Monatsh. Chem. 1991, 122, 557. 6. A. A. Ikizler, H. Yüksek, Collect. Czech. Chem. Commun. 1994, 59, 731. 7. A. A. Ikizler, N. Yildirim, H. Yüksek, Modelling. Measurement & Control C, AMSE Press, 1996, 54, 21. 8. B. Dash, P. K. Mahapatra, D. Pand, J. M. Pattnaik, J. Indian Chem. 1984, 61, 1061. 9. B. Dash, M. Patra, P. K. Mahapatra, J. 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Povzetek Iz 3-alkil(aril)-4-amino-4,5-dihidro-1H-1,2,4-triazol-5-onov (2) smo z 3,4-dihidroksi-benzaldehidom pripravili 3-alkil(aril)-4-(3,4-dihidroksibenzilidenamino)-4,5-dihidro-1H-1,2,4-triazol-5-one. Raziskali smo acetiliranje in metiliranje teh produktov. Nove spojine smo karakterizirali z IR, NMR in UV spektroskopskimi tehnikami. Na osnovi rezultatov potenciometriènih titracij spojin 3a-3e s tetrabutilamonijevim hidroksidom v treh brezvodnih topilih smo doloèili pKa vrednosti. §. Bahçeci, H. Yiiksek, Z. Ocak, C. Köksal, M. Özdemir: Synthesis and non-aqueous medium titrations…