Synthesis of some new 5-(1-phenyl-1H-1,2,3-triazol-4-yl)-1H-tetrazoles and evaluation of their antimicrobial activity

Article abstract of DOI:10.1134/S1070363216120513

a series of new tetrazole derivatives were synthesized by a reaction of triazole oxime with sodium azide catalyzed by copper acetate and isolated with high yield under mild conditions. All synthesized compounds were characterized by IR, NMR, and MS data.

Full text of DOI:10.1134/S1070363216120513

ISSN 1070-3632, Russian Journal of General Chemistry, 2016, Vol. 86, No. 12, pp. 2862–2864. © Pleiades Publishing, Ltd., 2016.
Synthesis of Some New
5-(1-Phenyl-1H-1,2,3-triazol-4-yl)-1H-tetrazoles
and Evaluation of Their Antimicrobial Activity1
E. Naresh*, K. Bhaskar, and G. Linga goud
Green and Medicinal Chemistry Laboratory, Department of Chemistry, Osmania University, Hyderabad, 500007 India
*e-mail: ellendula.naresh@gmail.com
Received July 25, 2016
Abstract—a series of new tetrazole derivatives were synthesized by a reaction of triazole oxime with sodium
azide catalyzed by copper acetate and isolated with high yield under mild conditions. All synthesized
compounds were characterized by IR, NMR, and MS data. Evaluation of antimicrobial activity of the products
against Gram-positive and Gram-negative bacterial and antifungal strains has been carried out. Among the
compounds 3a, 3c, 3e, and 3f exhibited high antibacterial activity and compounds 3a, 3c, 3e demonstrated high
antifungal activity.
Keywords: triazole aldehyde, triazlyl tetrazole, cupper acetate, and antibacterial activity
DOI: 10.1134/S1070363216120513
10 µg/mL and 20 µg/mL). Compounds 3b and 3g
demonstrated zones of inhibition against Staphylo-
coccus aeureus, Bacillus subtilis, Escherichia coli,
and Klebsiella pneumoniae to be almost equal to the
standard drug, whereas the other compounds ex-
hibited the moderate activity.
INTRODUCTION
Tetrazoles found a wide range of applications in
materials science [1], as lipophilic spacers and
metabolically stable carboxylic acid surrogates [2],
nitrogen-containing heterocyclic ligands [3], in
information recording systems [4], and medicine [2–7].
Antifungal activity. Antifungal activity of synt-
hesized compounds 3a–3h was tested against three
pathogenic fungi: Fusarium oxysporum, Aspergillus
nigerzeae and Aspergilus flavus at the concentration
of 100 µg/mL compared to the standard drug
Clotrimazole (100 µg/mL). Compounds 3a, 3c, 3e
demonstrated high activity against Aspergillus
nigerzeae, Aspergilus flavus and Fusarium
oxysporum. The other products exhibited moderate
activity against pathogenic fungi.
RESULTS AND DISCUSSION
Herein we report a simple method of synthesis of 5-
(1-phenyl-1H-1,2,3-triazol-4-yl)-1H-tetrazole via the
reaction of organic oxime with NaN3 in the presence
of 25 mol % of Cu(OAc)2 as a catalyst in DMF
solution (Scheme 1). The newly synthesized
compounds were characterized by NMR and MS. In
1H NMR spectrum of compound 3a the triazole proton
was recorded at δ 8.17. In 13C NMR spectrum the
tetrazole ipso carbon was recorded at 151.9 ppm.
Its LC-MS spectrum contained the peak [M + H]+
at m/z 214. The above data supported the structure of
3a to be 5-(1-phenyl-1H-1,2,3-triazol-4-yl)-1H-tetrazole.
EXPERIMENTAL
Melting points were determined in open glass
capillary tube on a Gallen-Kamp MFB-595 apparatus.
Elemental analysis was performed on a Perkin Elmer
CHN-2400 analyzer. IR spectra (KBr discs) were
Antibacterial activity. Antibacterial activity of
compounds 3a, 3c, 3e, and 3f demonstrated distin-
ctive zones of inhibition in cases of Staphylococcus
aeureus, Bacillus subtilis, Escherichia coli and
Klebsiella pneumoniae (compared to Gatifloxacin at
1
recorded on a Perkin-Elmer FT-IR-8400s. H NMR
(400 MHz) and 13C NMR (100 MHz) spectra were
recorded on a Bruker Avance II 400 spectrometer in
CDCl3 and DMSO-d6 using TMS as the internal
standard. MS were recorded on a SHIMADZU LCMS
1 The text was submitted by the authors in English.
2862

SYNTHESIS OF SOME NEW 5-(1-PHENYL-1H-1,2,3-TRIAZOL-4-YL)-1H-TETRAZOLES
Scheme 1. Synthesis of 5-(1-phenyl-1H-1,2,3-triazol-4-yl)-1H-tetrazoles (3a–3h).
2863
R1 = H (a), 2-Cl (b), 4-Cl, 2-OMe, 4-OMe, 4-NO2, 4-OH, 3-CF3.
2020 mass spectrometers. Progress of the reactions
was monitored by TLC (Silica gel, aluminium sheets
60 F254, Merck).
5-[1-(4-Chlorophenyl)-1H-1,2,3-triazol-4-yl]-1H-
tetrazole (3c). Yield 96%, mp: 158–160°C. IR spec-
1
trum, ν, cm–1: 2341 (N=N–N–), 1570, 1453 (C=C). H
NMR spectrum, δ, ppm: 8.09 s (1H, triazole H), 7.95–
7.97 m (1H, Ar-H), 7.74–7.76 m (2H, Ar-H), 7.05–
7.10 m (2H, Ar-H). 13C NMR spectrum, δ, ppm:
152.4, 145.8, 136.9, 129.6, 128.7 120.4, 119.3. M 248
[M + H]+. Found, %: C 43.62; H 2.46; N
39.58. C9H6ClN7. Calculated, %: C 43.65; H 2.44; N
39.59.
Synthesis of 5-(1-phenyl-1H-1,2,3-triazol-4-yl)-
1H-tetrazole (3a–3h). A mixture of an oxime (2a–2h)
(1 mmol), sodium azide (1.5 mmol), the catalyst
(25 mol %) in DMF (3 mL) was heated at 120°C
in a 25 mL round bottomed flask for 8 h. Upon
completion of the reaction (TLC), the mixture was
cooled down to room temperature and 5 mL of water
were added followed by 5 mL of 2 N HCl. The
mixture was stirred for 10 min and a product was
extracted with ethylacetate. The organic layer was
washed with water and dried over anhydrous sodium
sulfate. The solvent was evaporated under reduced
pressure. The products were purified by column
chromatography (silica gel) using petroleum ether/
ethyl acetate (3 : 1) as the eluent.
5-[1-(2-Methoxyphenyl)-1H-1,2,3-triazol-4-yl]-
1H-tetrazole (4d). Yield 95%, mp 164–166°C. IR, ν,
1
cm–1: 2345 (N=N–N–), 1572, 1453 (C=C). H NMR
spectrum, δ, ppm: 8.31 s (1H, triazole H), 7.81–7.85 m
(2H, Ar-H), 7.26–7.32 m (1H, Ar-H), 7.10–7.15 m (2H,
Ar-H), 3.93 s (1H, OCH3). 13C NMR spectrum, δ,
ppm: 153.3, 147.1, 134.2, 130.8, 129.8, 127.8, 122.7,
121.6, 118.5, 51.0. M 244 [M + H]+. Found, %: C
49.22; H 3.52; N 40.25. C10H9N7O. Calculated, %: C
49.38; H 3.73; N 40.31.
5-(1-Phenyl-1H-1,2,3-triazol-4-yl)-1H-tetrazole
(3a). Yield 95%, mp 166–168°C. IR spectrum, ν,
5-[1-(4-Methoxyphenyl)-1H-1,2,3-triazol-4-yl]-
1H-tetrazole (3e). Yield 95%, mp 168–170°C. IR
spectrum, ν, cm–1: 2344 (N=N–N–), 1571, 1452
1
cm–1: 2340 (N=N–N–), 1572, 1450 (C=C). H NMR
spectrum, δ, ppm: 8.17 s (1H, triazole H), 7.73–7.84 m
1
(2H, Ar-H), 7.41–7.51 m (2H, Ar-H), 6.90–7.02 m
(C=C); H NMR spectrum, δ, ppm: 8.41 s (1H, tria-
13
(2H, Ar-H) C NMR spectrum, δ, ppm: 151.9, 147.4,
zole H), 7.90–7.95 m (2H, Ar-H), 7.41–7.51 m (4H,
Ar-H), 3.79 s (1H, OCH3). 13C NMR spectrum, δ,
ppm: 153.1, 147.1, 137.1, 129.6, 128.5 120.4, 118.6,
50.9. M 244 [M + H]+. Found, %: C 49.20; H 3.53; N
40.27. C10H9N7O. Calculated, %: C 49.38; H 3.73; N
40.31.
129.8, 126.4, 125.4, 122.7, 121.1. M 214 [M + H]+.
Found, %: C 50.58; H 3.22; N 45.78. C9H7N7.
Calculated, %: C 50.70; H 3.31; N 45.99.
5-[1-(2-Chlorophenyl)-1H-1,2,3-triazol-4-yl]-1H-
tetrazole (3b). Yield 95%, mp 175–177°C. IR spec-
trum, ν, cm–1: 2338 (N=N–N–), 1570, 1452 (C=C). 1H
NMR spectrum, δ, ppm: 8.07 s (1H, triazole H), 7.94–
7.97 m (1H, Ar-H), 7.70–7.72 m (2H, Ar-H), 7.04–
7.11 m (2H, Ar-H). 13C NMR spectrum, δ, ppm: 153.3,
147.1, 135.6, 134.2, 130.8 129.8, 127.8, 127.7,
121.6. M 248 [M + H]+. Found, %: C 43.65; H 2.44; N
39.59. C9H6ClN7. Calculated, %: C 43.65; H 2.44; N
39.59.
4-[4-(1H-Tetrazol-5-yl)-1H-1,2,3-triazol-1-yl]
phenol (3f). Yield 92%, mp 174–177°C. IR spectrum,
ν, cm–1: 2343 (N=N–N–), 1570, 1453 (C=C); 1H NMR
spectrum, δ, ppm: 9.89 s (1H, OH), 8.67 s (1H, tria-
13
zole H), 7.42–7.58 m (5H, Ar-H). C NMR spectrum,
δ, ppm: 153.6, 145.2, 136.6, 128.9, 128.5 120.5, 119.5;
M 230 [M + H]+. Found, %: C 47.08; H 3.00; N 42.62.
C9H7N7O. Calculated, %: C 47.16; H 3.08; N 42.78.
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 86 No. 12 2016

2864
NARESH et al.
5-[1-(4-Nitrophenyl)-1H-1,2,3-triazol-4-yl]-1H-
Uiversity, Hyderabad for providing laboratory
facilities. One of the authors Naresh is grateful to
UGC, New Delhi for award of JRF.
tetrazole (3g). Yield 93%, mp 182–184°C. IR spec-
trum, ν, cm–1: 2340 (N=N–N–), 1571, 1453 (C=C). 1H
NMR spectrum, δ, ppm: 7.83–7.89 m (2H, Ar-H,
triazole H), 7.41–7.44 m (1H, Ar-H), 7.05–7.10 m
REFERENCES
13
(1H, Ar-H), 6.89–6.98 m (2H, Ar-H). C NMR spec-
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114.6. M 259 [M + H]+. Found, %: C 41.72; H 2.28;
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1
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CONCLUSIONS
We have synthesized a new series of triazole-
tetrazole hybrids (3a–3h) and evaluated their
antimicrobial activity. The compounds 3a, 3c, 3e, and
3f demonstrated high antibacterial activity and com-
pounds 3a, 3c, and 3e exhibited some antifungal activity.
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ACKNOWLEDGMENTS
Authors are grateful to the Head, Department of
Chemistry, and Director, Central Facilities for
Research and Development (CFRD), Osmania
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RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 86 No. 12 2016