Synthesis, characterization, and antioxidant activities of new trisubstituted triazoles

Article abstract of DOI:10.3906/kim-1110-43

A series of new 4-(3,4dimethoxyphenethyl)-3,5-akyl/aryl-4H-1,2,4-triazoles (3a-g) were obtained by reaction of ethyl N'-(alkylidene/arylidene)hydrazonate (1) and 2-(3,4-dimethoxy phenyl)ethanamine (2). Compounds 4d, e, and g were synthesized from the reaction of corresponding compounds 3d, e, and g with BBr3 , respectively. The 10 new compounds synthesized were characterized by elemental analyses, IR, ¹ H-NMR, and ¹³C-NMR spectral data. The structure of compound 3g was inferred through IR, ¹ H-, ¹³C-NMR, elemental analyses, and X-ray spectral techniques. In addition, the newly synthesized chemicals were screened for their antioxidant properties. Among the chemicals tested, 4d, e, and g exhibited the highest degree of antioxidant activity. TUeBITAK.

Full text of DOI:10.3906/kim-1110-43

Turk J Chem
36 (2012) , 457 – 466.
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c
ꢀ TUBITAK
doi:10.3906/kim-1110-43
Synthesis, characterization, and antioxidant activities of
new trisubstituted triazoles
∗
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¨
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¨ ˘
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¨
Kemal SANCAK , Yasemin UNVER, Dilek UNLUER, Esra DUGDU, Gu¨lcan KOR,
˙
˙
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Fatih C¸ ELIK, Emrah BIRINCI
Department of Chemistry, Karadeniz Technical University, 61080 Trabzon-TURKEY
e-mail: unver.yasemin@hotmail.com
Received: 25.10.2011
A series of new 4-(3,4dimethoxyphenethyl)-3,5-akyl/aryl-4H-1,2,4-triazoles (3a-g) were obtained by
reaction of ethyl N’-(alkylidene/arylidene)hydrazonate (1) and 2-(3,4-dimethoxy phenyl)ethanamine (2).
Compounds 4d, e, and g were synthesized from the reaction of corresponding compounds 3d, e, and g
with BBr3 , respectively. The 10 new compounds synthesized were characterized by elemental analyses,
IR, 1 H-NMR, and 13 C-NMR spectral data. The structure of compound 3g was inferred through IR, 1 H-,
13 C-NMR, elemental analyses, and X-ray spectral techniques. In addition, the newly synthesized chemicals
were screened for their antioxidant properties. Among the chemicals tested, 4d, e, and g exhibited the
highest degree of antioxidant activity.
Key Words: Synthesis, 1,2,4-triazole, antioxidant activity, boron tribromide, X-ray
Introduction
Triazole and its derivatives represent an important class of heterocycles. They are of biological importance
and are used in the synthesis of drugs12 Triazole derivatives are also used in the synthesis of antibiotics,
fungicides, herbicides, and plant growth hormone insulators and are potentially good corrosion inhibitions3−5
The incorporation of various substituents into the 1,2,4-triazole ring and its fusion with various heterocyclic
systems yield compounds with enhanced biological activities. The arrangement of 3 basic nitrogen atoms
in the triazole ring induces the antiviral activities in the compounds containing this ring.6 The 1,2,4-triazole
nucleus has been incorporated into a wide variety of therapeutically interesting drug candidates including H1/H2
histamine receptor blockers, cholinesterase active agents, CNS stimulants, antianxiety and sedatives,7 and those
∗Corresponding author
457

Synthesis, characterization, and antioxidant activities of..., K. SANCAK, et al.
with antimycotic activity such as fluconazole, itraconazole, and voriconazole.8,9 Moreover, there are some known
drugs containing 1,2,4-triazole moiety, e.g., triazolam, alprazalam, etizolam, furacylin, and ribavirin.10−14 In
the present study, prompted by these observations, the synthesis and antioxidant screening of new trisubstituted
1,2,4-triazole derivatives and as hybrid molecules including different pharmacophores were examined.
Experimental
Materials and measurements
Ethyl N’-(alkylidene/arylidene)hydrazonate (1) was prepared according to procedures reported in the literature.15
All other chemicals were obtained from Merck or Sigma-Aldrich and used as supplied. 1 H-NMR and 13 C-NMR
spectra were recorded on a Varian XL-200 NMR spectrophotometer in DMSO-d6 . IR spectra were recorded
on a Perkin-Elmer Spectrum one FT-IR spectrometer in KBr pellets. The MS spectra were measured with an
Micromass Quattro LC/ULTIMA LC-MS/MS spectrometer with EtOH as solvent. The experiment was per-
formed in the positive ion mode. Elemental analyses were performed on a Hewlett-Packard 185 CHN analyzer.
Melting points were measured on an electrothermal apparatus and are uncorrected.
General procedure for the preparation of compounds (3a-g)
4-(3,4-dimethoxyphenethyl)-3,5-alkyl/aryl-4H-1,2,4-triazole (3a-g): Ethyl N’-(alkylidene/arylidene)
hydrazonate (1) (10 mmol) together with 2-(3,4-dimethoxy phenyl)ethanamine (2) (10 mmol) was heated
without solvent in a sealed tube for 2 h at 130-140 ◦ C. Then the mixture was cooled to r.t. and a solid formed.
The crude product was recrystallized using ethyl acetate/petroleum ether (1:2) to afford the desired compound.
4-(3,4-dimethoxyphenethyl)-3,5-dimethyl-4H-1,2,4-triazole (3a)
Yield: 1.6 g (69%); colorless crystals, mp 154-157 ◦ C. IR (KBr, ν , cm−1): 1649 (C=N), 1591 (C=C), 1260
(C-O-C); 1 H-NMR (DMSO-d6 , δ, ppm): 2.08 (s, 6H, CH3), 2.81 (t, 2H, Ar–CH2), 3.67 (s, 3H, OCH3), 3.70
(s, 3H, OCH3), 4.02 (t, 2H, N-CH2), 6.54-6.61 (m, 2H, arom. H), 6.81-6.85 (m, 1H, arom. H); 13 C-NMR
(DMSOd6 , δ, ppm): 10.01 (2CH3), 34.55 (Ar-CH2), 44.27 (N-CH2), 55.23 and 55.33 (2OCH3), arom. C
[111.56 (CH), 112.62 (CH), 120.80 (CH), 129.91 (C), 147.48 (C), 148.45 (C)], 150.50 (C=N). Anal. Calc. For
C14 H19 N3 O2 MS: m/z 261.32 (M+) C, 64.35; H, 7.33; N, 16.08. Found: C, 64.34; H, 7.44; N, 16.14%.
4-(3,4-dimethoxyphenethyl)-3-ethyl-5-methyl-4H-1,2,4-triazole (3b)
Yield: 2.8 g (80%); colorless crystals, mp 69-70 ◦ C. IR (KBr, ν , cm−1): 1677 (C=N), 1591 (C=C), 1259
(C-O-C); 1 H-NMR (DMSO-d6 , δ, ppm): 1.15 (t, 3H, CH3 -CH2) 2.10 (s, 3H, CH3), 2.44 (q, 2H, CH3 -CH2),
2.80 (t, 2H, Ar–CH2), 3.66 (s, 3H, OCH3), 3.70 (s, 3H, OCH3), 4.01 (t, 2H, N-CH2), 6.55-6.62 (m, 2H,
arom. H), 6.81-6.85 (m, 1H, arom. H); 13 C-NMR (DMSOd6 , δ, ppm): 10.03 (CH3 -CH2), 11.15 (CH3), 17.38
(CH3 CH2), 34.55 (Ar-CH2), 44.27 (N-CH2), 55.23 and 55.33 (2OCH3), arom. C [111.64 (CH), 112.60 (CH),
120.85 (CH), 129.89 (C), 147.52 (C), 148.50 (C)], 150.52 and 154.63 (2C=N). Anal. Calc. For C15 H21 N3 O2
MS: m/z 275.35 (M+) C, 65.43; H, 7.69; N, 15.26. Found: C, 65.40; H, 7.60; N, 16.56%.
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Synthesis, characterization, and antioxidant activities of..., K. SANCAK, et al.
4-(3,4-dimethoxyphenethyl)-3-methyl-5-(thiophene-2-yl-methyl)-4H-1,2,4-triazole (3c)
Yield: 2.9 g (82%); colorless crystals, mp 63-64 ◦ C. IR (KBr, ν , cm−1): 1607 (C=N), 1516 (C=C), 1262
(C-O-C); 1 H-NMR (DMSO-d6 , δ, ppm): 2.10 (s, 3H, CH3), 2.58 (t, 2H, Ar–CH2), 3.67 (s, 3H, OCH3), 3.71
(s, 3H, OCH3), 3.99 (t, 2H, N-CH2), 4.17 (t, 2H, thiophene-CH2), 6.52-6.55 (m, 2H, thiophene H), 6.82-6.86
(m, 1H, thiophene H), 6.97-7.02 (m, 2H, arom. H), 7.40-7.44 (m, 1H, arom. H); 13 C-NMR (DMSOd6 , δ,
ppm): 9.97 (CH3), 24.97 (thiophene-CH2), 34.53 (Ar-CH2), 44.36 (N-CH2), 55.25 and 55.32 (2OCH3), arom.
C [111.60 (CH), 112.44 (CH), 120.75 (CH), 129.65 (C), 138.98 (C)], thiophene C [125.34 (CH) 126.12 (CH),
126.88 (CH), 104.18 (C)] 152.08 and 153.05 (2C=N). Anal. Calc. For C18 H21 N3 O2 S MS: m/z 343.44 (M+)
C, 62.95; H, 6.16; N, 12.23. Found: C, 62.90; H, 6.16; N, 12.28%.
4-(3,4-dimethoxyphenethyl)-3,5-diphenyl-4H-1,2,4-triazole (3d)
Yield: 3.4 g (80%); colorless crystals, mp 209-211 ◦ C. IR (KBr, ν , cm−1): 1648 (C=N), 1591 (C=C), 1235
(C-O-C); 1 H-NMR (DMSO-d6 , δ, ppm): 2.39 (t, 2H, Ar-CH2), 3.46 (s, 3H, OCH3), 3.68 (s, 3H, OCH3), 4.36
(t, 2H, N-CH2), 6.07-6.10 (m, 2H, arom. H), 6.62-6.66 (m, 1H, arom.H), 7.55 (s, 10H, arom. H); 13 C-NMR
(DMSOd6 , δ ppm): 34.86 (Ar-CH2), 46.78 (N-CH2), 55.59 and 56.19 (2OCH3), arom. C [112.10 (CH), 112.30
(CH), 120.80 (CH), 129.20 (CH), 129.50 (CH), 130.4 (CH), 128.50 (C), 148.20 (C), 148.40 (C), 149.20 (C)],
156.25 (C=N). Anal. Calc. For C24 H23 N3 O2 MS: m/z 385.18 (M+) C, 74.78; H, 6.01; N, 10.90. Found: C,
74.79; H, 6.00; N, 10.90%.
4-(4-(3,4-dimethoxyphenethyl)-5-(thiophene-2-yl-methyl)-4H-1,2,4-triazole-3-yl)phenol (3e)
Yield: 4.7 g (75%); colorless crystals, mp 127-130 ◦ C. IR (KBr, ν , cm−1): 3401 (OH), 1611 (C=N), 1590
(C=C), 1281 (C-O-C); 1 H-NMR (DMSO-d6 , δ, ppm): 2.44 (t, 2H, Ar-CH2), 3.61 (s, 3H, OCH3), 3.68 (s,
3H, OCH3), 4.11 (t, 2H, N-CH2), 4.28 (t, 2H, thiophene-CH2), thiophene + arom. H [6.31-6.38 (m, 1H), 7.02
(s, 1H), 6.73-6.77 (m 1H), 7.30-7.34 (m, 2H), 6.83-6.88 (m, 3H), 7.46 (m, 2H)], 9.85 (s, 1H, OH); 13 C-NMR
(DMSOd6 , δ, ppm): 25.09 (thiophene-CH2), 38.84 (Ar-CH2), 40.94 (N-CH2), 55.85 and 56.13 (2OCH3),
thiophene + arom. C [116.13 (CH), 118.96 (C), 119.56 (CH), 121.12 (CH), 123.89 (CH), 124.67 (C), 126.21
(CH), 127.73 (CH), 127.98 (CH), 129.95 (C), 130.69 (CH) 131.67 (CH), 137.45(C), 139.49 (C)], 148.20 and
151.38 (2C=N). Anal. Calc. For C23 H23 N3 O3 S MS: m/z 421.51 (M+) C, 65.54; H, 5.50; N, 9.97. Found: C,
65.64; H, 5.42; N, 9.82%.
3-(4-chlorophenyl)-4-(3,4-dimethoxyphenethyl)-5-(thiophene-2-yl-methyl)-4H-1,2,4-triazole (3f)
Yield: 2.2 g (81%); colorless crystals, mp 121-122 ◦ C. IR (KBr, ν , cm−1): 1604 (C=N), 1513 (C=C), 1266
(C-O-C); 1 H-NMR (DMSO-d6 , δ, ppm): 2.46 (t, 2H, Ar-CH2), 3.56 (s, 3H, OCH3), 3.69 (s, 3H, OCH3), 4.22
(t, 2H, N-CH2), 4.36 (t, 2H, thiophene-CH2), thiophene + arom. H [6.21-6.25 (m, 2H), 6.67-6.71 (m, 1H),
7.01-7.05 (m, 2H), 7.42-7.54 (m, 5H)]; 13 C-NMR (DMSOd6 δ, ppm): 25.09 (thiophene-CH2), 34.65 (Ar-CH2),
40.60 (N-CH2), 54.90 and 55.30 (2OCH3), thiophene + arom. C [111.40 (CH), 111.70 (CH), 118.47 (CH),
120.30 (CH), 126.30 (C), 130.5 (CH), 134.20 (C), 138.50 (C), 147.50 (C), 148.40 (C), 125.49 (CH), 126.42 (CH),
459

Synthesis, characterization, and antioxidant activities of..., K. SANCAK, et al.
126.94 (CH), 128.83 (C)] 153.86 and 153.50 (2C=N). Anal. Calc. For C23 H22 ClN3 O2 S MS: m/z 439.96 (M+)
C, 62.79; H, 5.04; Cl, 8.06; N, 9.55. Found: C, 62.75; H, 7.60; Cl, 8.06; N, 9.59%.
4-(5-benzyl-4-(3,4-dimethoxyphenethyl)-4H-1,2,4-triazole-3-yl)phenol (3g)
Yield: 6.5 g (79%); colorless crystals, mp 120-121 ◦ C. IR (KBr, ν , cm−1): 3402 (OH), 1614 (C=N), 1588
(C=C), 1241 (C-O-C); 1 H-NMR (DMSO-d6 , δ, ppm): 2.37 (t, 2H, Ar–CH2), 3.61 (s, 3H, OCH3), 3.68 (s, 3H,
OCH3), 4.05 (t, 2H, N-CH2), 4.27 (s, 2H, triazole-CH2 -Ar), 6.26 (s, 2H, arom. H), 6.83-6.87 (m, 4H, arom.
H), 7.26-7.36 (m, 6H, arom. H), 9.85 (s, 1H, OH); 13 C-NMR (DMSOd6 , δ, ppm): 30.31 (triazole-CH2 -Ar),
34.47 (Ar-CH2), 45.85 (N-CH2), 55.04 and 55.32 (2OCH3), arom. C [111.50 (CH), 111.80 (CH), 115.30 (CH),
118.3 (C), 120.20 (CH), 126.60 (CH), 128.50 (CH), 129.10 (C), 129.80 (CH), 130.26 (C), 136.40 (CH), 147.40
(CH), 148.40 (C), 158.40 (C)], 153.25 and 153.99 (2C=N). Anal. Calc. For C25 H25 N3 O3 MS: m/z 415.19
(M+) C, 72.27; H, 6.06; N, 10.11. Found: C, 72.27; H, 6.00; N, 11.17%.
General procedure for the preparation of compounds 4-(2,3-diaryl-4H -1,2,4-triazole-4-yl)
ethyl)benzen-1,2-diol (4d, e, g): A solution of the 4-(3,4dimethoxyphenethyl)-3,5-alkyl/aryl-4H-1,2,4-
triazole (3d, 3e, 3g) (10 mmol) in chloroform (100 mL) was added to a solution of boron tribromide (10
mmol) in chloroform (200 mL) at 0 ◦ C. The reaction mixture was then stirred under nitrogen atmosphere, at
ambient temperature, for 1 h, and was poured into ice containing sufficient 50% sodium hydroxide to attain
pH 10. Addition of concentrated sulfuric acid provided a precipitate, which was extracted into ether. The
combined organic extract was washed with water and brine, and then dried and concentrated in vacuo to obtain
compounds (4d, e, g). The crude product was recrystallized using ethyl acetate/petroleum ether (1:4) to afford
the desired compound (Scheme 1).
4-(2-(3,5-diphenyl-4H-1,2,4-triazole-4-yl)ethyl)benzen-1,2-diol (4d)
Yield: 2.4 g (79%); colorless crystals, mp 230-232 ◦ C IR (KBr, ν , cm−1): 3296 (OH), 1606 (C=N), 1584
(C=C); 1 H-NMR (DMSOd6 , δ, ppm): 2.29 (t, 2H, Ar-CH2), 4.20 (t, 2H, N-CH2), 5.85-5.89 (m, 1H, arom.
H), 6.03 (s, 1H, arom. H), 6.42-6.46 (m, 1H, arom. H), 7.55 (t, 10H, arom. H), 8.71 (s, 2H, OH); 13 C-NMR
(DMSO-d6 , δ, ppm): 33.71 (Ar-CH2), 34.03 (CH2 -Ph), 45.99 (N-CH2), arom CH [115.34, 115.56, 118.75,
128.60, 128.72] arom. C [127.19, 127.72, 129.76, 143.88, 145.02], 154.55 (C=N). Anal. Calc. For C22 H19 N3 O2
MS: m/z 357.41 (M+) C, 73.93; H, 5.36; N, 11.76. Found: C, 73.90; H, 5.37; N, 11.78%.
4-[2-[3-(4-hydroxyphenyl)-5-(thiophene-2-yl-methyl)-4H-1,2,4-triazole-4yl]ethyl]benzen-1,2-diol
(4e)
Yield: 2.2 g (59%); colorless crystals, mp 281-284 ◦ C IR (KBr, ν , cm−1): 3412 (OH), 1613 (C=N), 1547
(C=C); 1 H-NMR (DMSOd6 , δ, ppm): 2.71 (t, 2H, Ar-CH2), 4.22 (t, 2H, N-CH2), 4.25 (s, 2H, thiophene-
CH2), thiophene + arom. H [6.17 (d, 1H), 6.32-6.55 (m, 2H), 6.82-7.05 (m, 4H), 7.36-7.44 (m, 3H)], 9.85 (s,
1H, OH), 10.36 (s, 2H, OH); 13 C-NMR (DMSO-d6 , δ, ppm): 25.80 (thiophene-CH2), 38.88 (Ar-CH2), 41.34
(N-CH2), thiophene + arom. CH [105.00, 116.70, 119.68, 120.04, 123.95, 127.01, 128.78, 131.43], thiophene
+ arom. C [118.96, 124.80, 136.90, 139.50, 144.97, 146.02], 153.67 and 154.38 (2C=N). Anal. Calc. For
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Synthesis, characterization, and antioxidant activities of..., K. SANCAK, et al.
C
21 H19 N3 O3 S MS: m/z 393.46 (M+) C, 64.10; H, 4.87; N, 10.68; S, 8.15. Found: C, 63.10; H, 5.87; N, 10.00;
S, 8.87%.
CH3
O
O
C
H2N
Ar/R
C
N
NH
R'/Ar'
+
O
CH3
OCH2CH3
(1)
(2)
160-170 oC
oil bath
N
N
N
N
Ar/R
R'/Ar'
R'/Ar'
Ar/R
N
N
BBr3/H2O
CH3
OH
O
OH
(4)
O
H3C
(3)
3g
3c
3d
3a
3b
3e
3f
S
R/Ar
H3C
H3C
CH3CH2
CH3
S
S
CH3
Cl
HO
R'/Ar'
HO
4d
4e
4g
R/Ar
S
R'/Ar'
HO
HO
Scheme 1. Synthetic pathway for the preparation of compounds 3 and 4.
4-(2-(3-benzyl-5-(4-hydroxyphenyl)-4H-1,2,4-triazole-4-yl)ethyl)benzen-1,2-diol (4g)
Yield: 2.8 g (63%); colorless crystals, mp 243-246 ◦ C IR (KBr, ν , cm−1): 3335 (OH), 1611 (C=N), 1520
(C=C); 1 H-NMR (DMSOd6 , δ, ppm): 2.29 (t, 2H, Ar-CH2), 3.97 (t, 2H, N-CH2), 4.02 (s, 2H, triazole-CH2 -
461

Synthesis, characterization, and antioxidant activities of..., K. SANCAK, et al.
Ar), arom. H [6.08 (d, 1H), 6.29 (s, 1H ), 6.55-6.59 (m 3H), 7.23-7.43 (m, 7H)] 8.78 (s, 1H, OH), 8.80 (s,
1H, OH), 9.93 (s, 1H, OH); 13 C-NMR (DMSO-d6 , δ, ppm): 31.16 (triazole-CH2 -Ar), 35.27 (Ar-CH2), 43.16
(N-CH2), arom CH [104.9, 116.25, 116.64, 119.88, 121.13, 127.46, 129.35, 130.69], arom. C [119.13, 128.45,
137.20, 144.74, 145.89, 159.34], 154.07 and 154.70 (2C=N). Anal. Calc. For C23 H21 N3 O3 MS: m/z 393.46
(M+) C, 71.30; H, 5.46; N, 10.85. Found: C, 71.20; H, 5.54; N, 10.76%.
Results and discussion
This paper has presented the synthesis of new trisubstituted triazole derivatives incorporating different phar-
macophores as hybrid molecules possessing antioxidant activities (Scheme 1).
In the first part of this study, compounds 3a-g were synthesized via the reaction of compounds 1 with
compound 2 (Scheme 1). Analytical and spectroscopic data of compounds 3 confirmed the success of the
cyclization reaction. The IR data indicated the formation of compounds 3 by the disappearance of C=O band
and NH stretching frequency of compounds 1 about at 1700-1750 cm−1 and 3300 cm−1 , respectively, and the
appearance of a new band at 1604-1649 cm−1 belonging to C=N of the 1,2,4-triazole ring. In the 1 H-NMR
spectrum of compounds 3, the existence of 3 was revealed by the disappearance of the chemical shifts belonging
to O-C2 H5 and NH protons (δ=9.15-11.59 ppm) in the precursor 1 after the cyclization and the appearance
of a new peak at δ=3.66-3.69 ppm belonging to O-CH3 protons. 13 C-NMR, elemental analyses, and mass
spectral data were also in agreement with the proposed structure.
The synthesis of 4-(2,3-diaryl-4H-1,2,4-triazole-4-yl)ethyl)benzen-1,2-diol (4d, e, g) was performed by
the reaction of compounds 3 with BBr3 at the reflux temperature in the presence of chloroform (Scheme 1).
Antioxidant activity
DPPH assay: T Radical scavenging activity of synthesized compounds against stable free radical 2,2-diphenyl-
2-picrylhydrazyl hydrate (DPPH, Sigma-Aldrich Chemie, Steinheim, Germany) was determined spectropho-
tometrically. When DPPH reacts with an antioxidant compound, which can donate hydrogen, it is reduced.
Following the reduction, its deep violet color in methanol bleaches to yellow, showing a significant absorption
decrease at 517 nm. Fifty milliliters of various concentrations of the compounds dissolved in methanol was
added to 5 mL of a 0.004% methanol solution of DPPH. After a 30 min incubation period at room temperature,
the absorbance was read against a blank at 517 nm (ATI-Unicam UV-2 UV–Vis spectrophotometer, Cambridge,
UK). Free radical DPPH inhibition as a percentage (I%) was calculated as follows:
I% = (Ablank – Asample /Ablank)× 100, where Ablank is the absorbance of the control reaction (contain-
ing all reagents except the test compound), and Asample is the absorbance of the test compound. Compounds’
concentration providing 50% inhibition (IC50) was calculated from the graph plotted as inhibition percent-
age against compound concentration (Figures 1 and 2). Tests were carried out in triplicate, and butylated
hydroxytoluene (BHT) was used as a positive control.16
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Synthesis, characterization, and antioxidant activities of..., K. SANCAK, et al.
14
120
100
80
60
40
20
0
4e
4d
4e
4g
12
10
8
6
4d
4g
4
2
0
1
2
3
4
5
6
Concentratıon μ/mL
0
Figure 1. %I values of compounds 4d, e, g.
Figure 2. IC50 values of compounds 4d, e, g.
Crystal structure determination of 3g
Data collection
A block single crystal with dimensions 0.570 × 0.357 × 0.110 mm was mounted on a goniometer and data
collection was performed on a STOE IPDS II17 diffractometer by the ω scan technique using graphite-
˚
monochromaticMoKα radiation (λ = 0.71073A) at 296 K. The intensity symmetries indicate the triclinic C2/c
space group. A total of 20,262 reflections (5759 unique) were performed within 2θ range 1.45◦ and 28.50◦ .
Correction for absorption (μ = 0.086), by comparison of the intensities of equivalent reflections, was
applied using X-RED software and cell parameters were determined by using X-AREA software.17 The ini-
tial partial solution obtained by direct methods as implemented in the program SHELXS-97 was expanded
and refined by means of the program SHELXL-97.18 The program ORTEP-3 for Windows was used in the
preparation of the figure.19 All non-hydrogen atoms were refined anisotropically. The refinement carried out
by full matrix least squares method on the positional and anisotropic temperature parameters of non-hydrogen
atoms corresponding to 297 crystallographic parameters. All H atoms were included in calculated positions and
refined using a riding model. The structure was refined to Rint = 0.0591 with 2856 observed reflections by the
condition of I > 2σ(I) threshold. The absorption correction was applied with integration type (Tmin = 0.9573
and Tmax = 0.9889).
Results and riscussion
The crystallized structure of compound 3g (C25 H27 N3 O4) is in the monoclinic space group C 2/c with Z =
8 in the unit cell (Table 1, Figure 3). In the molecule of compound 3g, C25 H27 N3 O4 , contains the 1,2,4-
triazole ring and the aromatic ring groups are bridged by triazole moiety. The whole molecule is not planar
but each ring system is planar individually. The triazole ring is oriented with respect to the 5-benzyl and
3,4-dimethoxyphenethyl rings at dihedral angles of 86.74(1)◦ and 7.44(1)◦ , respectively, which shows that
triazole and benzyl rings are almost perpendicular to each other. The triazole ring system is almost planar
˚
with the maximum deviation of -0.003(2)A for atom C8. In the molecule of compound 3g, the bond lengths
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Synthesis, characterization, and antioxidant activities of..., K. SANCAK, et al.
and angles are within normal ranges and they are comparable with those of the related structure.20 Compound
3g, C25 H27 N3 O4 , containing the triazole ring, displays the characteristic features of 1,2,4-triazole derivatives.
From analysis of the values therein, it can be concluded that for the structure N1=C8 and N2=C9 are well
defined double bonds, and are the shortest bonds in the heterocycle ring. The torsion angle {(N3-C16-C17-C18)
is 161.65(16)◦ } shows that for compound 3g the side chain conformation is induced by the anti-conformation.
Structurally, compound 3g forms C-H. . . O and O-H. . . N type intermolecular hydrogen bonds and an O-
H. . . O type intramolecular hydrogen bond. The intermolecular contacts are C24-H24A. . . O3i , O4-H33. . . N1ii
and O4-H22...N2iii where the H atoms of the water molecule are engaged in hydrogen bonding with N1 and
N2 atoms of the triazole system [symmetry codes: (i) –x + 3/2, –y + 1/2, –z + 1; (ii) x + 1/2, –y + 1/2,
z + 1/2; (iii) –x + 2, y, –z + 1/2]. There is also an intramolecular contact, namely O1-H1. . . O4. C-H. . . π
interaction is present in compound 3g, between the benzene ring and the C17 atom [C17-H17A.. . Cg (2), Cg (2)
is C1/C2/C3/C4/C5/C6 with symmetry code: x, y, z]; the details of the bonds are given in hydrogen bonding
Table 2.
Table 1. Crystal data and structure refinement parameters for compound 3g.
Formula: C25H27N3O4
Formula weight: 433.50
Crystal system: monoclinic
Space group: C2/c
Z = 8
θmin = 1.45◦θmax = 28.50◦
R1 = 0.054
(Δ/σ)max
=
0.000
˚
0.147 eA
−3
(Δρ)max
(Δρ)min
=
−3
˚
=
−0.210 eA
˚
a = 23.8517(17) A
F(000) = 1840
b = 17.7443(7) A
μ = 0.086mm−1
˚
˚
c = 11.2917(7) A
Measurement: STOE IPDS II
Program system: STOE X-RED
Structure determination: Direct methods
β = 106.130(5)
3
˚
V = 4590.9(5) A
No. of reflections used = 20,262 Refinement: Full matrix
Table 2. Hydrogen-bond geometry (A, ◦ ).
˚
D-H. . . A
D-H
0.96
H. . . A
2.46
D. . . A D- H. . . A
C24-H24A...O3i
O4-H33...N1ii
O4-H22...N2iii0.89(3) 1.90(3) 2.768(2)
3.413(2)
2.890(2)
164(3)
170.7
0.86(3) 2.03(3)
176(2)
O1-H1...O4
C17-H17A...Cg (2)iv
0.82
0.97
1.86
2.684(2)
3.670
178.8
154.0
2.770
Symmetry codes: (i) –x + 3/2, –y + 1/2, –z + 1; (ii) x + 1/2, –y + 1/2, z + 1/2; (iii) –x + 2, y, –z + 1/2; (iv) x, y, z
464

Synthesis, characterization, and antioxidant activities of..., K. SANCAK, et al.
Figure 3. Ortep III diagram of compound 3g. Displacement ellipsoids are drawn at the 50% probability level and H
atoms are shown as small spheres of arbitrary radii.
Conclusions
New trisubstituted 1,2,4-triazole derivatives were synthesized and characterized based on elemental analysis,
1 H- and 13 C-NMR spectra, mass spectra, and IR. In addition, compound 3g was characterized by combination
of X-ray crystallography and theoretical methods. The crystal structure of the compound 3g is stabilized by
C-H. . . O and O-H. . . N type intermolecular hydrogen bonds and O-H. . . O type intramolecular hydrogen bond.
To support the solid state structure, the geometric parameters and single crystal X-ray diffraction
technique were used. Good correlation was found between the experimental and computed values. Furthermore,
the antioxidant activities of compounds 4d, e, and g were evaluated. Strong scavenging effects of compounds 4d,
4e, and 4g were noted on the level of DPPH radical. These results show that in vitro the newly synthesized 4-
(2,3-diaryl-4H-1,2,4-triazole-4-yl)ethyl)benzen-1,2-diols (4d, e, g) possess highly potent antioxidant properties.
Acknowledgments
This work was supported by the Research Fund of Karadeniz Technical University (Turkey). We are grateful
to Dr. Yavuz Ko¨ysal (for X-ray data).
465

Synthesis, characterization, and antioxidant activities of..., K. SANCAK, et al.
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466

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