Synthesis of novel 1-benzyl/aryl-4-{[(1-aryl-1H-1,2,3-triazol-4-yl)methoxy]methyl}-1H-1,2,3-triazole derivatives and evaluation of their antimicrobial activity

Article abstract of DOI:10.1134/S107036321606030X

A series of 1-benzyl/aryl-4-{[(1-aryl-1H-1,2,3-triazol-4-yl)methoxy]methyl}-1H-1,2,3-triazole derivatives were synthesized via Cu(I) catalyzed reaction between terminal alkyne and substituted aryl or benzyl azides. The synthesized triazoles were character

Full text of DOI:10.1134/S107036321606030X

ISSN 1070-3632, Russian Journal of General Chemistry, 2016, Vol. 86, No. 6, pp. 1424–1429. © Pleiades Publishing, Ltd., 2016.
Synthesis of Novel 1-Benzyl/Aryl-4-{[(1-aryl-1H-1,2,3-triazol-
4-yl)methoxy]methyl}-1H-1,2,3-triazole Derivatives
and Evaluation of Their Antimicrobial Activity1
B. J. Reddya, V. P. Reddya*, G. L. Gouda, Y. J. Raoa, Premkumarb, and K. Supriyac
a Department of Chemistry, Osmania University, Hyderabad, Telangana, 500007 India
*e-mail: bonamjagadeeshreddy@gmail.com
b Department of Genetics, Osmania University, Hyderabad, Telangana, 500007 India
c Department of Chemistry, University College of Science,
Osmania University, Saifabad, Hyderabad, Telangana, 500004 India
Received February 10, 2016
Abstract—A series of 1-benzyl/aryl-4-{[(1-aryl-1H-1,2,3-triazol-4-yl)methoxy]methyl}-1H-1,2,3-triazole
derivatives were synthesized via Cu(I) catalyzed reaction between terminal alkyne and substituted aryl or
benzyl azides. The synthesized triazoles were characterized by 1H NMR, 13C NMR, IR, and mass spectral
techniques. All the synthesized compounds were screened for their antimicrobial activity.
Keywords: azide, alkyne, click chemistry, 1,3-dipolar cyclo addition, triazole
DOI: 10.1134/S107036321606030X
Triazoles, like many other five membered hetero-
cyclic compounds are used very often in the
pharmacological and medicinal applications. The 1,2,3-
triazole moiety does not occur in nature, although the
synthetic molecules that contain 1,2,3-triazole units
show diverse biological activities. Similarly, 1,2,3-
triazoles and their derivatives have attracted
considerable attention over recent decades due to their
chemotherapeutic value [1]. They have been
considered as an interesting component in terms of
biological activity and could be found in many drugs
[2]. Many 1,2,3-triazoles were found to be potent
antimicrobial [3, 4], analgesic [5], anti-inflammatory,
local anaesthetic [6], anticonvulsant [7], antineoplastic
[8], antimalarial [9], antiviral [10], antitubercular [11],
anti-HIV [12], and antiepileptic [13, 14]. Currently, a
few 1,2,3-triazoles are already in the final stages of
clinical trials [15]. Thus 1,2,3-triazoles have emerged
as powerful pharmacophores on their own [16]. As a
part of our research program, we wish to report the
synthesis of new biologically active 1-benzyl/aryl-4-
{[(1-aryl-1H-1,2,3-triazol-4-yl)-methoxy]methyl}-1-
aryl-1H-1,2,3-triazole derivatives by click chemistry
approach.
RESULTS AND DISCUSSION
Chemistry. The synthesis of new derivatives of
triazoles 4a–4l was carried out as outlined in Scheme 1.
The triazoles were prepared by reacting propargylated
compound with corresponding azide under two
different synthetic conditions: (1) CuSO4·5H2O and
sodium ascorbate in DMF/H2O (1 : 1) or (2) in
presence of CuI in DMF. It was found that the
synthesis of triazoles 4a–4l took a longer time and
gave lower yields with CuSO4·5H2O/sodium ascorbate,
when compared to CuI in which case the reaction
proceeded smoothly with excellent yields (Table 1).
The formation of 1,2,3-triazoles were confirmed by the
resonance of the proton in triazole ring at a δ = 8.0–
1
9.0 ppm as a singlet in H NMR. The structures were
further confiremd by the 13C NMR spectra, which showed
the C-atom signals corresponding to triazole ring [17].
Biological assay. All the compounds 4a–4l shown
promising antimicrobial activity. The outcome of the
antimicrobial results (Table 2) indicates that the
triazole derivatives 4d, 4f, 4i, and 4k exhibited
excellent activity when tested against all the bacterial
and fungal strains. It was observed that, among the
tested triazole derivatives, compounds having 3-
nitrophenyl substituent in the structure 4i exhibited
best activity.
1 The text was submitted by the authors in English.
1424

SYNTHESIS OF NOVEL 1-BENZYL/ARYL-4-{[(1-ARYL-1H-1,2,3-TRIAZOL-...
1425
Scheme 1. Synthesis of 1-benzyl/aryl-4-{[(1-aryl-1H-1,2,3-triazol-4-yl)methoxy]methyl}-1H-1,2,3-triazole derivatives.
Propargyl
N
N
R1−N3
N
N
bromide
N
N
OH
+ R2−N3
R1
R1
DMSO : H2O (9 : 1)/CuI
OH
O
NaH, DMF
1
2a−2c
3a−3c
CuSO4, sodium ascorbate, H2O/DMF
(1 : 1) or CuI/triethylamine/DMF
O
R2
R1
N
N
N
N
N
N
4a−4c
EXPERIMENTAL
Synthesis of 1-aryl-4-[(prop-2-yn-1-yloxy)methyl]-
1H-1,2,3-triazoles (3a–3c) (general procedure). To a
solution of (1-aryl-1H-1,2,3-triazol-4-yl)methanol (2a–
2c) [18] (10 mmol) in dry DMF (5 mL), anhydrous
sodium hydride (15 mmol) was added and stirred for
5 min. After adding propargyl bromide (12 mmol), the
resulting mixture was stirred at room temperature
overnight. Upon completion of the reaction water
(20 mL) was added and the whole was extracted with
dichloromethane (3 × 30 mL). The combined organic
layers were washed with brine and dried over Na2SO4.
The organic layer was concentrated in vacuum and
the residue was purified by silica gel (60–
120 mesh) column chromatography using hexane–
All the chemicals were purchased from Aldrich and
Fluka. Melting points were determined in open
capillary tubes and are uncorrected. The purity of the
compounds was checked by TLC using precoated
silica gel plates 60254 (Merck). IR spectra were
recorded on a Shimadzu FT-IR-8400s spectrophoto-
1
meter in KBr pellets. H NMR and 13C NMR spectra
were recorded on a Bruker Avance II 400 MHz
instrument using tetramethylsilane as an internal
standard. Mass spectra were recorded on a GCMS-QP
1000 EX mass spectrometer. Elemental analysis were
performed using a Thermo Finnigan CHNS analyzer.
Table 1. Yields of synthesized compounds 4a–4l
CuSO4, sodium ascorbate
CuI
Comp. no.
R1
R2
time, h
yield, %
61
time, h
18
yield, %
69
4a
4b
4c
4d
4e
4f
Phenyl
Phenyl
Phenyl
Phenyl
Phenyl
Phenyl
24
23
23
22
24
22
22
23
21
22
20
23
4-Cl phenyl
4-Me phenyl
3-NO2 phenyl
Benzyl
63
18
67
65
17
68
62
18
66
58
17
63
4-Cl Phenyl
4-Cl Phenyl
4-Cl Phenyl
3-NO2 Phenyl
3-NO2 Phenyl
3-NO2 Phenyl
3-NO2 Phenyl
4-Cl phenyl
Benzyl
61
18
64
4g
4h
4i
59
17
63
4-Me phenyl
3-NO2 phenyl
4-Me phenyl
4-Cl phenyl
Benzyl
61
18
67
64
16
72
4j
65
17
71
4k
4l
68
16
75
63
18
69
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 86 No. 6 2016

1426
REDDY et al.
Table 2. Biological activity of compounds 4a–4l
Inhibition zone, mm
gram-negative bacteria
P. aeruginosa A. nigerzeae P. italicum F. oxysporum
Compound
gram-positive bacteria
fungi
S. aureus
14
B. subtilis
E. coli
16
23
22
29
24
29
22
23
32
25
28
26
30
–
4a
6
9
4
6
7
9
14
16
17
22
19
23
16
17
23
21
19
18
–
15
18
21
22
19
26
22
20
27
21
24
20
–
4b
19
4c
17
8
8
8
4d
28
11
7
10
5
12
10
11
8
4e
22
4f
32
12
8
11
7
4g
23
4h
24
10
13
9
8
9
4i
31
12
9
13
11
13
9
4j
4k
24
29
11
8
13
9
4l
25
Amoxicillin
Mycostatin
30
12
–
10
–
–
–
12
20
25
EtOAc, (7 : 3, v/v) as eluent to afford products 3a–3c
as white solids.
(101 MHz, CDCl3), δC, ppm: 147.87, 135.65, 133.43,
126.83, 125.27, 120.76, 78.67, 75.53, 64.25, 59.68.
Found, %: C 58.17; H 4.04; Cl 14.30; N 16.95; O 6.45.
C12H10ClN3O. Calculated, %: C 58.19; H 4.07; Cl
14.31; N 16.97; O 6.46. MS: M 248 [M + H]+.
1-Phenyl-4-[(prop-2-yn-1-yloxy)methyl]-1H-1,2,3-
triazole (3a). Yield 89%, white solid, mp 70–73°C. IR
spectrum, ν, cm–1: 3221 (≡C–H), 2108 (C≡C), 1230
(N=N), 1064, 1041 (C–O). 1H NMR spectrum
(400 MHz, CDCl3), δ, ppm: 7.99 s (1H, triazole H),
7.62 d (J = 8.9 Hz, 2H, Ar-H), 7.58 d (J = 8.9 Hz, 2H,
Ar-H), 7.50 t (J = 7.3 Hz, 1H, Ar-H), 4.65 s (2H,
OCH2), 4.20 s (2H, OCH2), 2.50 t (J = 2.4 Hz, 1H,
≡C–H). 13C NMR spectrum (101 MHz, CDCl3) δC,
ppm: 145.78, 140.09, 129.76, 128.63, 122.57, 121.70,
77.08, 74.22, 62.34, 57.33. Found, %: C: 67.57; H
5.17; N 19.68; O 7.47. C12H11N3O. Calculated, %: C
67.59; H 5.20; N 19.71; O 7.50. MS: M 214 [M + H]+.
1-(3-Nitrophenyl)-4[(prop-2-yn-1-yloxy)methyl]-
1H-1,2,3-triazole (3c). Yield 87%, white solid, mp
106–108°C. IR spectrum, ν, cm–1: 3275 (≡C–H), 2114
(C≡C), 1354, 1529 (N–O), 1222 (N=N), 1085, 1045 (C–O).
1H NMR spectrum (400 MHz, CDCl3), δ, ppm: 8.61 t
(J = 2.1 Hz, 1H, triazole H), 8.32 d.d (J = 8.2, 1.4 Hz,
1H, Ar-H), 8.19 d.d.d (J = 8.1, 2.1, 0.8 Hz, 1H, Ar-H),
8.16–8.13 m (1H, Ar-H), 7.77 t (J = 8.2 Hz, 1H, Ar-H),
4.85 s (2H, OCH2), 4.30 d (J = 2.4 Hz, 2H, OCH2),
2.52 t (J = 2.4 Hz, 1H, ≡C–H). 13C NMR spectrum
(101 MHz, CDCl3), δC, ppm: 148.98, 146.19, 137.72,
131.05, 125.96, 123.29, 120.80, 115.30, 79.02, 75.34,
62.94, 57.92. Found, %: C 55.80; H 3.88; N 21.66; O
18.55. C12H10N4O3. Calculated, %: C 55.81; H 3.90; N
21.70; O 18.59. MS: M 259 [M + H]+.
1-(4-Chlorophenyl)-4[(prop-2-yn-1-yloxy)methyl]-
1H-1,2,3-triazole (3b). Yield 91%, white solid, mp 84–
86°C. IR spectrum, ν, cm–1: 3288 (≡C–H), 2113
(C≡C), 1230 (N=N), 1082, 1047 (C–O). 1H NMR spec-
trum (400 MHz, CDCl3), δ, ppm: 7.99 s (1H, triazole
H), 7.74–7.65 m (2H, Ar-H), 7.57–7.47 m (2H, Ar-H),
4.83 s (2H, OCH2), 4.29 d (J = 2.4 Hz, 2H, OCH2),
2.51 t (J = 2.4 Hz, 1H, ≡C–H). 13C NMR spectrum
Synthesis of 1-benzyl/aryl-4-{[(1-aryl-1H-1,2,3-
triazol-4-yl)methoxy]methyl}-1H-1,2,3-triazoles (4a–4l)
(general procedure). CuSO4·5H2O–sodium ascorbate
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 86 No. 6 2016

SYNTHESIS OF NOVEL 1-BENZYL/ARYL-4-{[(1-ARYL-1H-1,2,3-TRIAZOL-...
1427
method. A mixture of 1-aryl-4[(prop-2-yn-1-yloxy)methyl]-
1H-1,2,3-triazole (3a–3c) (1 mmol), appropriate azide
(1 mmol), CuSO4·5H2O (0.1 mmol) and sodium
ascorbate (0.1 mmol) in DMF : H2O (1 : 1) mixture
(5 mL) was stirred at room temperature for 20–24 h
(Table 1). After completion of the reaction (monitored
by TLC), the resulting mixture was poured into ice
cold water (20 mL) and extracted with dichloro-
methane (3 × 30 mL). The combined organic layer was
washed twice with brine and dried over Na2SO4. The
organic layer was concentrated in vacuum and the
residue was purified by column chromatography on
silica gel eluted with hexane–EtOAc (4 : 6 v/v) to give
title compounds 4a–4l.
mp 92–94°C. IR spectrum, ν, cm–1: 1230 (N=N), 1093,
1047 (C–O). H NMR spectrum (400 MHz, DMSO-
1
d6), δ, ppm: 8.88 s (1H, triazole H), 8.83 s (1H, triazole
H), 7.93 d (J = 7.8 Hz, 2H, Ar-H), 7.80 d (J = 8.2 Hz,
2H, Ar-H), 7.61 t (J = 7.7 Hz, 2H, Ar-H), 7.50 t (J =
7.3 Hz, 1H, Ar-H), 7.40 d (J = 8.1 Hz, 2H, Ar-H), 4.75
13
s (4H, 2OCH2), 2.38 s (3H, CH3). C NMR spectrum
(101 MHz, DMSO-d6), δC, ppm: 144.81, 144.70, 138.28,
136.56, 134.32, 130.18, 129.86, 128.64, 122.37, 122.27,
120.03, 119.91, 62.69, 20.50. Found, %: C 65.8; H
5.21; N 24.25; O 4.61. C19H18N6O. Calculated, %: C
65.88; H 5.24; N 24.26; O 4.62. MS: M 347 [M + H]+.
1-(3-Nitrophenyl)-4-{[(1-phenyl-1H-1,2,3-triazol-
4-yl)methoxy]methyl}-1H-1,2,3-triazole (4d). Brown
solid, mp 142–144°C. IR spectrum, ν, cm–1: 1533,
1352 (N–O), 1232 (N=N), 1093, 1049 (C–O) 1H NMR
spectrum (400 MHz, DMSO-d6), δ, ppm: 9.13 s (1H,
triazole H), 8.88 s (1H, triazole H), 8.76 s (1H, Ar-H),
8.43 d (J = 8.0 Hz, 1H, Ar-H), 8.37–8.31 m (1H,
Ar-H), 7.91 t (J = 7.0 Hz, 3H, Ar-H), 7.61 t (J =
7.8 Hz, 2H, Ar-H), 7.50 t (J = 7.4 Hz, 1H, Ar-H), 4.77
CuI method. A mixture of 1-aryl-4[(prop-2-yn-1-
yloxy)methyl]-1H-1,2,3-triazoles (3a–3c) (1 mmol),
appropriate azide (1 mmol), triethylamine (1.2 mmol)
and CuI (0.1 mmol) in DMF (5 mL) was stirred at
room temperature for 16–18 h. After completion of the
reaction (monitored by TLC), the resulting mixture
was poured into ice cold water (20 mL) and extracted
with dichloromethane (3 × 30 mL). Further treatment/
purification was performed as in CuSO4·5H2O/sodium
ascorbate method.
13
s (2H, OCH2), 4.76 s (2H, OCH2). C NMR spectrum
(101 MHz, DMSO-d6), δC, ppm: 148.52, 145.23,
144.75, 137.20, 136.58, 131.54, 129.87, 128.65, 126.06,
123.09, 122.92, 122.41, 120.05, 114.74, 62.75, 62.62.
Found, %: C 57.27; H 4.00; N 25.97; O 12.70.
C18H15N7O3. Calculated, %: C 57.29; H 4.01; N 25.98;
O 12.72. MS: M 378 [M + H]+.
4,4'-[Oxybis(methylene)]bis(1-phenyl-1H-1,2,3-
triazole) (4a). Brown solid, mp 91–93°C. IR spectrum,
ν, cm–1: 1236 (N=N), 1043 (C–O).1H NMR spectrum
(400 MHz, DMSO-d6), δ, ppm: 8.05 s (2H, triazole H),
7.67–7.74 m (4H, Ar-H), 7.42–7.55 m (6H, Ar-H),
4.85 s (4H, 2OCH2). 13C NMR spectrum (101 MHz,
DMSO-d6), δC, ppm: 144.98, 136.08, 128.45, 126.24,
121.41, 120.71, 63.70. Found, %: % C 65.03; H 4.84;
N 25.26; O 4.79. C18H16N6O. Calculated, %: C 65.05;
H 4.85; N 25.29; O 4.81. MS: M 333 [M + H]+.
1-Benzyl-4-{[(1-phenyl-1H-1,2,3-triazol-4-yl)-
methoxy]methyl}-1H-1,2,3-triazole (4e). White solid,
mp 138–140°C. IR spectrum, ν, cm–1: 1369 (N=N),
1
1220 (C–O). H NMR spectrum (400 MHz, DMSO-
d6), δ, ppm: 8.84 s (1H, triazole H), 8.22 s (1H, triazole
H), 7.91 d (J = 7.7 Hz, 2H, Ar-H), 7.60 t (J = 7.8 Hz,
2H, Ar-H), 7.50 t (J = 7.4 Hz, 1H, Ar-H), 7.42–7.29 m
(5H, Ar-H), 5.60 s (2H, NCH2), 4.67 s (2H, OCH2),
4.64 s (2H, OCH2). 13C NMR spectrum (101 MHz,
DMSO-d6), δC, ppm: 144.81, 143.95, 136.61, 136.04,
129.85, 128.72, 128.61, 128.09, 127.87, 124.23, 122.31,
120.05, 62.80, 62.63, 52.75. Found, %: C 65.86; H
5.22; N 24.24; O 4.60. C19H18N6O. Calculated, %: C
65.88; H 5.24; N 24.26; O 4.62. MS: M 347 [M + H]+.
1-(4-Chlorophenyl)-4-{[(1-phenyl-1H-1,2,3-triazol-
4-yl)methoxy]methyl}-1H-1,2,3-triazole (4b). White
solid, mp 121–123°C. IR spectrum, ν, cm–1: 1241
(N=N), 1084, 1044 (C–O). 1H NMR spectrum (400 MHz,
CDCl3), δ, ppm: 8.12–8.06 m (1H, triazole H), 8.06–
8.00 m (1H, triazole H), 7.79–7.62 m (5H, Ar-H), 7.59–
7.43 m (6H, Ar-H), 7.32–7.22 m (1H, Ar-H), 4.86 s
(4H, 2OCH2).13C NMR spectrum (101 MHz, CDCl3)
δC, ppm: 141.40, 140.95, 138.75, 137.17, 137.00,
135.49, 134.65, 129.98, 129.87, 128.94, 121.81, 120.71,
63.71, 63.63. Found, %: C 58.90; H 4.15; Cl 9.63; N
22.90; O 4.33. C18H15ClN6O. Calculated, %: C 58.94;
H 4.12; Cl 9.67; N 22.91; O 4.36. MS: M 367 [M + H]+.
4,4'-[Oxybis(methylene)]bis[1-(4-chlorophenyl)-
1H-1,2,3-triazole] (4f). White solid, mp 161–163°C.
IR spectrum, ν, cm–1: 1232 (N=N), 1087, 1047 (C–O).
1H NMR spectrum (400 MHz, DMSO-d6), δ, ppm:
8.90 s (2H, triazole H), 7.96 d (J = 8.8 Hz, 4H, Ar-H),
7.68 d (J = 8.8 Hz, 4H, Ar-H), 4.74 s (4H, 2OCH2).
13C NMR spectrum (101 MHz, DMSO-d6), δC, ppm:
1-Phenyl-4-{[(1-(p-tolyl)-1H-1,2,3-triazol-4-yl)-
methoxy]methyl}-1H-1,2,3-triazole (4c). Brown solid,
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 86 No. 6 2016

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REDDY et al.
144.94, 135.39, 132.90, 129.83, 122.49, 121.72, 62.69.
Found, %: % C 53.86; H 3.50; Cl 17.63; N 20.93; O
3.97. C18H14Cl2N6O. Calculated, %: C 53.88; H 3.52;
Cl 17.67; N 20.94; O 3.99. MS: M 401 [M + H]+.
spectrum (400 MHz, DMSO-d6), δ, ppm: 9.11 s (1H,
triazole H), 8.81 s (1H, triazole H), 8.75 t (J = 2.1 Hz,
1H, Ar-H), 8.44–8.39 m (1H, Ar-H), 8.36–8.31 m (1H,
Ar-H), 4.77 s (2H, OCH2), 4.75 s (2H, OCH2), 2.38 s
(3H, CH3).13C NMR spectrum (101 MHz, DMSO-d6),
δC, ppm: 148.51, 145.25, 144.62, 138.25, 137.17,
134.36, 131.53, 130.19, 126.04, 123.07, 122.90, 122.28,
119.91, 114.72, 62.77, 62.62, 20.53. Found, %: C 58.30;
H 4.36; N 25.02; O 12.23. C19H17N7O3. Calculated, %:
C 58.31; H 4.38; N 25.05; O 12.26. MS: M 392 [M + H]+.
1-Benzyl-4-{[(1-(4-chlorophenyl)-1H-1,2,3-triazol-
4-yl)methoxy]methyl}-1H-1,2,3-triazole (4g). White
solid, mp 155–157°C. IR spectrum, ν, cm–1: 1230 (N=N),
1
1074, 1046 (C–O). H NMR spectrum (400 MHz,
DMSO-d6), δ, ppm: 8.87 s (1H, triazole H), 8.21 s (1H,
triazole H), 7.95 d (J = 8.7 Hz, 2H, Ar-H), 7.68 d (J =
8.7 Hz, 2H, Ar-H), 7.35 d.t (J = 15.0, 7.2 Hz, 5H, Ar-H),
5.60 s (2H, N-CH2), 4.67 s (2H, OCH2), 4.67 s (2H,
1-(4-Chlorophenyl)-4-{[(1-(3-nitrophenyl)-1H-
1,2,3-triazol-4-yl)methoxy]methyl}-1H-1,2,3-triazole
(4k). Pale yellow solid, mp 159–161°C. IR spectrum,
ν, cm–1: 1533, 1349 (N–O), 1236 (N=N), 1084, 1053
13
OCH2) C NMR spectrum (101 MHz, DMSO-d6), δC,
ppm: 144.98, 143.90, 136.04, 135.39, 132.88, 129.82,
128.72, 128.09, 127.87, 124.24, 122.41, 121.71, 62.80,
62.58, 52.75. Found, %: % C 59.90; H 4.48; Cl 9.30; N
22.04; O 4.18. C19H17ClN6O. Calculated, %: C 59.92;
H 4.50; Cl 9.31; N 22.07; O 4.20. MS: M 381 [M + H]+.
1
(C–O). H NMR spectrum (400 MHz, DMSO-d6), δ,
ppm: 9.12 s (1H, triazole H), 8.91 s (1H, triazole H),
8.75 s (1H, Ar-H), 8.42 d (J = 7.6 Hz, 1H, Ar-H), 8.33
d (J = 7.5 Hz, 1H, Ar-H), 8.03–7.86 m (3H, Ar-H),
7.68 d (J = 8.6 Hz, 2H, Ar-H), 4.78 s (2H, OCH2), 4.77
s (2H, OCH2).13C NMR spectrum (101 MHz, DMSO-
d6), δC, ppm: 148.48, 145.22, 144.94, 137.14, 135.37,
132.89, 131.50, 129.81, 125.99, 123.04, 122.89, 122.49,
121.67, 114.67, 62.71, 62.64. Found, %: C 52.48; H
3.41; Cl 8.60; N 23.83; O 11.62. C18H14ClN7O3. Cal-
culated, %: C 52.50; H 3.43; Cl 8.61; N 23.81; O
11.66. MS: M 412 [M + H]+.
1-(4-Chlorophenyl)-4-{[(1-(p-tolyl)-1H-1,2,3-
triazol-4-yl)methoxy]methyl}-1H-1,2,3-triazole (4h).
White solid, mp 120–122°C. IR spectrum, ν, cm–1:
1
1225 (N=N), 1076, 1035 (C–O). H NMR spectrum
(400 MHz, DMSO-d6), δ, ppm: 8.07s (2H, triazole H),
7.68–7.69 m (2H, Ar-H), 7.59–7.60 m (2H, Ar-H),
7.49–7.50 m (2H, Ar-H), 7.30–7.32 m (2H, Ar-H),
4.86 s (2H, OCH2), 4.85 s (2H, OCH2), 2.42 s (3H,
CH3). 13C NMR spectrum (101 MHz, DMSO-d6), δC,
ppm: 144.63, 142.52, 138.40, 134.80, 134.63, 134.33,
133.56, 129.10, 128.82, 122.22, 119.12, 68.03, 20.57.
Found, %: % C 59.90; H 4.48; Cl 9.30; N 22.03; O
4.18. C19H17ClN6O. Calculated, %: C 59.92; H 4.50;
Cl 9.31; N 22.07; O 4.20. MS: M 381 [M + H]+.
1-Benzyl-4-{[(1-(3-nitrophenyl)-1H-1,2,3-triazol-
4-yl)methoxy]methyl}-1H-1,2,3-triazole (4l). Brown
solid, mp 130–133°C. IR spectrum, ν, cm–1: 1529,
1
1320 (N–O), 1226 (N=N), 1076, 1045 (C–O). H
NMR spectrum (400 MHz, DMSO-d6), δ, ppm: 9.08 s
(1H, triazole H), 8.74 s (1H, triazole H), 8.37 d.d (J =
31.9, 7.2 Hz, 2H, Ar-H), 8.22 s (1H, Ar-H), 7.90 t (J =
8.2 Hz, 1H, Ar-H), 7.35 d.t (J = 12.7, 7.1 Hz, 5H,
Ar-H), 5.61 s (2H, N-CH2), 4.70 s (2H, OCH2), 4.65 s
(2H, OCH2). 13C NMR spectrum (101 MHz, DMSO-
d6), δC, ppm: 148.98, 145.74, 137.62, 136.45, 132.03,
129.23, 128.63, 128.37, 126.56, 124.74, 123.58, 123.32,
115.24, 63.29, 63.00, 53.28. Found, %: C 58.30; H
4.36; N 25.02; O 12.22. C19H17N7O3. Calculated, %: C
58.31; H 4.38; N 25.05; O 12.26. MS: M 392 [M + H]+.
4,4'-[Oxybis(methylene)]bis[1-(3-nitrophenyl)-1H-
1,2,3-triazole] (4i). Brown solid, mp 180–182°C. IR
spectrum, ν, cm–1: 1529, 1346 (N–O), 1224 (N=N) ,
1
1076, 1041 (C–O). H NMR spectrum (400 MHz,
DMSO-d6), δ, ppm: 9.13 s (2H, triazole H), 8.75 t (J =
2.0 Hz, 2H, Ar-H), 8.43 d.d (J = 8.1, 1.4 Hz, 2H,
Ar-H), 8.34 d.d (J = 8.2, 1.5 Hz, 2H, Ar-H), 7.90 d.d
(J = 16.8, 8.6 Hz, 2H, Ar-H), 4.79 s (4H, 2OCH2). 13C
NMR spectrum (101 MHz, DMSO-d6), δC, ppm:
148.51, 145.21, 137.14, 131.54, 126.04, 123.08, 122.91,
114.72, 62.67. Found, %: C 51.17; H 3.32; N 26.50; O
18.92. C18H14N8O5. Calculated, %: C 51.19; H 3.34; N
26.53; O 18.94. MS: M 423 [M + H]+.
Biological assay. The antimicrobial activity was
determined using disc diffusion method by measuring
zone of inhibition in mm. The newly prepared triazole
derivatives 4a–4l were screened in vitro at a
concentration of 50 μg/mL in DMSO for antibacterial
activity against bacterial strains Staphylococcus aureus
and Bacillus Subtilis (gram positive bacteria),
Escherichia coli and Klebsialla pneumonia (gram
1-(3-Nitrophenyl)-4-{[(1-(p-tolyl)-1H-1,2,3-triazol-
4-yl)methoxy]methyl}-1H-1,2,3-triazole (4j). White
solid, mp 94–96°C. IR spectrum, ν, cm–1: 1519, 1336
1
(N–O), 1224 (N=N), 1070,1043 (C–O). H NMR
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 86 No. 6 2016

SYNTHESIS OF NOVEL 1-BENZYL/ARYL-4-{[(1-ARYL-1H-1,2,3-TRIAZOL-...
1429
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negative bacteria), as well as three fungal strains,
namely: Aspergillus niger, Penicillium italicum and
Fusarium oxysporum. Standard antibiotic drugs
Amoxicillin for bacteria and Mycostatin for fungi were
used at a concentration of 50 µg/mL as references.
Each experiment was done in triplicate and the average
reading was taken. The results of antibacterial activity
are expressed in terms of zone of inhibition and
presented in Table 1. Growth inhibition was calculated
with reference to positive control. The inhibition zones
were measured in millimeters at the end of an
incubation period of 24 h (for bacteria) and 72 h (for
fungal) at (35±2)°C. DMSO alone showed no
inhibition. For bacteria the composition of nutrient
agar medium was agar (15 g), peptone (5 g), yeast
extract (3 g), NaCl (5 g), distilled water (1000 mL) and
for fungal the composition of potato dextrose agar
medium was potatoes (200 g), dextrose (20 g), agar
(20 g), distilled water (1000 mL).
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ACKNOWLEDGMENTS
The authors are thankful to the Head of the
Department of Chemistry, Department of Genetics for
providing laboratory facilities and are also thankful to
the Director of the Central Facilities for Research and
Development (CFRD), Osmania University for
providing IR and NMR spectral analysis. Financial
support from UGC, New Delhi for one of the authors
(B.J. Reddy) is gratefully acknowledged.
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