Synthesis and non-aqueous medium titrations of some new 4-benzylidenamino-4,5-dihydro-1H-1,2,4-triazol-5-one derivatives

Article abstract of DOI:10.3390/10080961

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 acetylatio

Full text of DOI:10.3390/10080961

Acta Chim. Slov. 2002, 49, 783−794.
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SYNTHESIS AND NON-AQUEOUS MEDIUM TITRATIONS OF SOME NEW
4,5-DIHYDRO-1H-1,2,4-TRIAZOL-5-ONE DERIVATIVES
Şule 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,
1
respectively. The new compounds were characterized using IR, H-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
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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
N
NH
N
N
NNHCO2Et
OEt
N
NH
R
C
R
R
O
R
O
O
N
N
N
N
N
NH2
CH
OCOCH3
OCOCH3
CH
OH
OH
1
4
2
3
1-4
a
b
c
d
e
R
CH
CH3
3
N
N
CH C H
CH C H .CH (p-)
2 6 4
CH C H .Cl (p-)
2 6 5
3
R
O
N
N
2 6 4
C H
6 5
CH
OCH3
OCH3
5
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Acta Chim. Slov. 2002, 49, 783−794.
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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): δ 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-
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H), 9.45 (s, 2H, CH+OH), 9.73 (s, 1H, OH), 11.78 (s, 1H, NH). 13C-NMR (50 MHz,
DMSO-d6): δ 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) λmax (ε, 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-1H-1,2,4-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=O), 1595, 1580 (C=N), 768, 700 (monosubstituted
1
benzenoid ring) cm-1. H-NMR (200 MHz, DMSO-d6): δ 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,
13
2H, CH+OH), 9.52 (s, 1H, OH), 11.93 (s, 1H, NH). C-NMR (50 MHz, DMSO-d6): δ
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) λmax (ε, 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-1H-1,2,4-
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=O), 1610, 1580 (C=N), 800 (1,4-
1
disubstituted benzenoid ring) cm-1. H-NMR (200 MHz, DMSO-d6): δ 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):
δ 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) λmax (ε, L mol-1 cm-1): 320 (11813), 213
(15767) nm. Anal. Calculated for C17H16N4O3: 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-1H-1,2,4-
triazol-5-ones (3d). White crystals (2.35 g, 68%). M.p. 290-292 °C (EtOH). IR: 3336
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(OH), 3150 (NH), 1715 (C=O), 1590, 1580 (C=N), 805 (1,4-disubstituted benzenoid
ring) cm-1. 1H-NMR (200 MHz, DMSO-d6): δ 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): δ 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) λmax (ε, 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-1H-1,2,4-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
1
benzenoid ring) cm-1. H-NMR (200 MHz, DMSO-d6): δ 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): δ 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) λmax (ε, 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 1-Acetyl-3-alkyl(aryl)-4-(3,4-diacetyloxybenzylidenamino)-4,5-
dihydro-1H-1,2,4-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:
1-Acetyl-3-methyl-4-(3,4-diacetyloxybenzylidenamino)-4,5-dihydro-1H-1,2,4-
triazol-5-ones (4a). White crystals (2.95 g, 82%). M.p. 196-197 °C (EtOH). IR: 1780,
1
1760, 1705 (C=O), 1630, 1610 (C=N) cm-1. H-NMR (200 MHz, DMSO-d6): δ 2.32 (s,
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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): δ 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=O). UV
(ethanol) λmax (ε, L mol-1 cm-1): 293 (17500), 254 (18738), 216 (21784) nm. Anal.
Calculated for C16H16N4O6: C, 53.33; H, 4.48; N, 15.55. Found: C, 53.62; H, 4.18; N,
15.60.
1-Acetyl-3-benzyl-4-(3,4-diacetyloxybenzylidenamino)-4,5-dihydro-1H-1,2,4-
triazol-5-ones (4b). White crystals (3.72 g, 85%). M.p. 129-130 °C (EtOH). IR: 1780,
1760, 1700 (C=O), 1610, 1590 (C=N), 770, 715 (monosubstituted benzenoid ring) cm-1.
1H-NMR (200 MHz, DMSO-d6): δ 2.23 (s, 6H, 2CH3), 2.40 (s, 3H, CH3), 4.06 (s, 2H,
13
CH2), 7.12-7.40 (m, 6H, Ar-H), 7.64-7.78 (m, 2H, Ar-H), 9.55 (s, 1H, CH). C-NMR
(50 MHz, DMSO-d6): δ 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=O). UV (ethanol) λmax (ε, 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.
1-Acetyl-3-(p-methylbenzyl)-4-(3,4-diacetyloxybenzylidenamino)-4,5-dihydro-
1H-1,2,4-triazol-5-ones (4c). White crystals (4.02 g, 89%). M.p. 159-160 °C (EtOH).
IR: 1775, 1765, 1735 (C=O), 1605, 1585 (C=N), 810 (1,4-disubstituted benzenoid ring)
cm-1. 1H-NMR (200 MHz, DMSO-d6): δ 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): δ 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=O). UV (ethanol) λmax (ε, L mol-1 cm-1):
295 (10145), 254 (10973), 217 (18082) nm. Anal. Calculated for C23H22N4O6: C, 61.32;
H, 4.92; N, 12.44. Found: C, 61.24; H, 5.19; N, 12.39.
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1-Acetyl-3-p-chlorobenzyl-4-(3,4-diacetyloxybenzylidenamino)-4,5-dihydro-1H-
1,2,4-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): δ 2.32 (s, 6H, 2CH3), 2.50 (s, 3H, CH3), 4.17 (s, 2H,
13
CH2), 7.40-7.45 (m, 5H, Ar-H), 7.74-7.79 (m, 2H, Ar-H), 9.58 (s, 1H, CH). C-NMR
(50 MHz, DMSO-d6): δ 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) λmax (ε, 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.
1-Acetyl-3-phenyl-4-(3,4-diacetyloxybenzylidenamino)-4,5-dihydro-1H-1,2,4-
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): δ 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): δ 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)
λmax (ε, 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 1-Methyl-3-alkyl(aryl)-4-(3,4-dimethoxybenzylidenamino)-4,5-
dihydro-1H-1,2,4-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:
1,3-Dimethyl-4-(3,4-dimethoxybenzylidenamino)-4,5-dihydro-1H-1,2,4-triazol-
5-ones (5a). White crystals (1.88 g, 68%). M.p. 137-139 °C (EtOH). IR: 1710 (C=O),
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1
1600,1580 (C=N) cm-1. H-NMR (200 MHz, DMSO-d6): δ 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): δ 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) λmax (ε, L mol-
1 cm-1): 315 (21065), 235 (15144), 215 (17657) nm. Anal. Calculated for C13H16N4O3: C,
56.51; H, 5.84; N, 20.28. Found: C, 56.22; H, 5.57; N, 20.04.
1-Methyl-3-benzyl-4-(3,4-dimethoxybenzylidenamino)-4,5-dihydro-1H-1,2,4-
triazol-5-ones (5b). White crystals (2.30 g, 65%). M.p. 150-152 °C (EtOH). IR: 1715
1
(C=O), 1610, 1580 (C=N), 760, 720 (monosubstituted benzenoid ring) cm-1. H-NMR
(200 MHz, DMSO-d6): δ 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-d6): δ 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) λmax
(ε, L mol-1 cm-1): 318 (34597), 216 (25068) nm. Anal. Calculated for C19H20N4O3: C,
64.76; H, 5.72; N, 15.90. Found: C, 64.89; H, 5.85; N, 15.81.
1-Methyl-3-p-methylbenzyl-4-(3,4-dimethoxybenzylidenamino)-4,5-dihydro-
1H-1,2,4-triazol-5-ones (5c). White crystals (2.52 g, 69%). M.p. 197-198 °C (EtOH).
1
IR: 1715 (C=O), 1610, 1595 (C=N), 810 (1,4-disubstituted benzenoid ring) cm-1. H-
NMR (200 MHz, DMSO-d6): δ 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): δ 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) λmax (ε, L mol-1 cm-1): 318 (11210), 224 (23150) nm. Anal.
Calculated for C20H22N4O3: C, 65.56; H, 6.05; N, 15.29. Found: C, 65.77; H, 6.18; N,
15.20.
Ş. Bahçeci, H. Yüksek, Z. Ocak, 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-1H-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-1H-1,2,4-triazol-5-ones (3), five new 1-acetyl-3-alkyl(aryl)-4-(3,4-
.
diacetyloxybenzyliden-amino)-4,5-dihydro-1H-1,2,4-triazol-5-ones (4) and three new
1-methyl-3-alkyl(aryl)-4-(3,4-dimethoxybenzylidenamino)-4,5-dihydro-1H-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 (ε=19.4), N,N-dimethylformamide (ε=37) and
acetonitrile (ε=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-1H-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
mV
-520
-650
mL0.9
0.0
0.3
0.6
1.2
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
(z) at 25 °C.
Ş. Bahçeci, H. Yüksek, Z. Ocak, C. Köksal, M. Özdemir: Synthesis and non-aqueous medium titrations…

Acta Chim. Slov. 2002, 49, 783−794.
792
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)
-231
pKa1
11.41
11.13
10.35
9.75
HNP2 (mV)
-327
pKa2
13.65
14.25
13.42
13.40
13.51
3a
3b
3c
3d
3e
-242
-419
-194
-314
-203
-394
-224
11.22
-341
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)
-357
pKa1
12.09
12.03
10.61
12.53
12.85
HNP2 (mV)
-424
pKa2
13.81
14.43
13.75
-
3a
3b
3c
3d
3e
-287
-429
-255
-371
-310
-511
-326
-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)
-281
pKa1
11.74
11.15
12.05
10.27
10.52
HNP2 (mV)
-424
pKa2
13.79
15.29
-
3a
3b
3c
3d
3e
-243
-488
-293
-593
-182
-353
13.07
12.08
-192
-271
Ş. 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.
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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
potenciometričnih titracij spojin 3a-3e s tetrabutilamonijevim hidroksidom v treh
brezvodnih topilih smo določili pKa vrednosti.
Ş. Bahçeci, H. Yüksek, Z. Ocak, C. Köksal, M. Özdemir: Synthesis and non-aqueous medium titrations…