Design, Synthesis, and Biological Activity of New Bis-1,2,3-triazole Derivatives Bearing Thiophene-Chalcone Moiety

Article abstract of DOI:10.1134/S1070363219090214

A series of novel 1,4-substituted bis-aralkyl and aryl 1,2,3-triazoles bearing thiophene chalcones are synthesized via the Claisen condensation of bis propargyl acetophenone intermediate with thiophene-2-carboxaldehyde followed by the Huisgen cycloaddition of the accumulated bis propargyl chalcone intermediate with various aryl and aralkyl azides. Structures of the synthesized compounds are characterized by IR, NMR and mass spectroscopy. The products are tested for antimicrobial and antioxidant activities, and some of those exhibit antibacterial and antifungal activity. The moderate to poor DPPH free radical scavenging activity is determined for some products.

Full text of DOI:10.1134/S1070363219090214

ISSN 1070-3632, Russian Journal of General Chemistry, 2019, Vol. 89, No. 9, pp. 1859–1866. © Pleiades Publishing, Ltd., 2019.
Design, Synthesis, and Biological Activity
of New Bis-1,2,3-triazole Derivatives
Bearing Thiophene-Chalcone Moiety
a,b
c
d
c
d
e
K. Kiran , M. Sarasija *, Boddu Ananda Rao , V. Namratha , D. Ashok **, and A. Srinivasa Rao
a
Department of Chemistry, Jawaharlal Nehru Technological University, Hyderabad-500085, Telangana, India
b
Integrum Life Sciences Private Limited, Plot no.34, ALEAP Industrial Estate, Pragathi Nagar, Gajularamaram,
Quthubullapur Mandal, Medchal District, Telangana, 500072 India
Department of Chemistry, Satavahana University, Karimnagar, Telangana, 505001 India
c
e-mail: lionsarasija@gmail.com
Green and Medicinal Chemistry Laboratory, Department of Chemistry, Osmania University,
d
Hyderabad, Telangana, 500007 India
*
*е-mail: ashokdou@gmail.com
e
Vagdevi Innoscience Pvt.Ltd, Nacharam, Hyderabad-500007, Telangana, India
Received March 17, 2019; revised August 18, 2019; accepted August 28, 2019
Abstract―Aseries of novel 1,4-substituted bis-aralkyl and aryl 1,2,3-triazoles bearing thiophene chalcones are syn-
thesized via the Claisen condensation of bis propargyl acetophenone intermediate with thiophene-2-carboxaldehyde
followed by the Huisgen cycloaddition of the accumulated bis propargyl chalcone intermediate with various aryl
and aralkyl azides. Structures of the synthesized compounds are characterized by IR, NMR and mass spectroscopy.
The products are tested for antimicrobial and antioxidant activities, and some of those exhibit antibacterial and
antifungal activity. The moderate to poor DPPH free radical scavenging activity is determined for some products.
Keywords: bis-1,2,3-triazole, chalcone, Click reaction, anti microbial, anti-oxidant
DOI: 10.1134/S1070363219090214
INTRODUCTION
2,4-dihydroxyacetophenone using potassium carbonate
as a base that led to bis-acetylene intermediate 2. The
compound 2 underwent the Claisen condensation with
thiophene-2-carboxaldehyde 3 with formation of α,β-
unsaturated ketone (chalcone) 4. The copper-catalyzed
click reaction (Huisgen cycloaddition) of the intermedi-
ate 4 with various aryl 6a–6f and aralkyl 8a–8d azides
in the presence of copper sulfate pentahydrate, sodium
Over recent years 1,2,3-triazoles derivatives and re-
lated heterocyclic scaffolds have attracted close attention
due to applications in drug discovery [1]. 1,4-Substituted
bis-1,2,3-triazoles demonstrate a wide range of biologi-
cal activities including anticancer [2], antimicrobial [3],
antifungal [4], and antioxidant [5]. Likewise, thiophene
chalcones possess various biological activities: antican-
cer [6], antifungal [7], analgesic [8], and antimicrobial
L-ascorbic acid and tert-butanol/H O yielded the target
2
[
9]. Naturally, the compounds containing 1,2,3-triazoles
linked to chalcones are known to possess the enhanced
biological activities including anticancer [10–13].
compounds 9a–9f and 10a–10d in good to excellent
yields. All aryl and aralkyl azides were prepared from
the corresponding anilines 5a–5f and benzyl bromides
In continuation of our earlier research on 1,2,3-tri-
azoles [14–16] and considering the biological activities
demonstrated by thiophene chalcones, we report here the
synthesis of some novel bis-1,2,3-triazoles containing
thiophene substituted chalcones and their in vitro tests
for antimicrobial and antioxidant activities.
7
a–7d according to the literature procedures [17, 18] and
used immediately upon their isolation without further
purification. Homogeneity of all synthesized compounds
was tested by TLC. IR, NMR and mass spectra of the syn-
thesized compounds supported their assigned structures.
Antimicrobial activity . The title compounds 9a–9f
and 10a–10d were screened for their antibacterial activ-
ity against Staphylococcus aureus (MTCC 3160) and
Bacillus cereus (MTCC 1305) as gram-positive, and
RESULTS AND DISCUSSIONS
As presented in Scheme 1, first step of the synthesis
involved bis propargylation of commercially available
1
859

1860
KIRAN et al.
Scheme 1. Synthetic route to bis-1,2,3-triazoles bearing thiophene chalcones 9a–9f and 10a–10d.
R
R
N
N
N
N
N
N
O
O
S
O
1
0aꢀ10d
Br
NaN , DMF
3
N3
NaAsc, CuSO .5H O,
R
4
2
R
room temperature,
t-BuOHꢀH O, room temperature,
2
1
6 h
16 h
7
aꢀ7d
8aꢀ8d
83ꢀ90%
Br
K CO , DMF,
room temperature, 16 h
2
3
HO
OH
O
O
O
9
0%
O
O
1
2
S
3
O
O
KOH, EtOH,
room temperature, 16 h
8
7%
S
O
4
N3
NH2
NaAsc, CuSO ·5H O,
NaNO , HCl
4
2
2
t-BuOHꢀH O, room temperature, 16 h
2
7
6ꢀ89%
R
R
5
aꢀ5f
6
aꢀ6f
N
N
N
N
R
N
N
S
O
O
R
O
9
aꢀ9f
R = 4-Br (5a), 4-OMe (5b), 4-Me (5c), 4-Cl (5d), H (5e), 4-F (5f), 3-OMe (7a), 4-F (7b), H (7c), 4-NO (7d).
2
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 89 No. 9 2019

DESIGN, SYNTHESIS, AND BIOLOGICAL ACTIVITY OF NEW BIS-1,2,3-TRIAZOLE DERIVATIVES
1861
Table 1. Zones of inhibition of compounds 9a–9f and 10a–10d
Zone of inhibition, mm
gram-positive bacteria
gram-negative bacteria
Fungi
Candida albicans
S. aureus
MTCC 3160)
Bacillus cereus
(MTCC 1305)
E. Coli
(MTCC 443)
P. aureoginosa
(MTCC 2453)
Compound
(
9
a
4.5
6.0
5.0
5.0
3.0
4.5
3.0
5.0
5.0
4.0
5.5
6.5
6.0
5.2
4.5
6.0
4.5
5.5
6.0
6.0
7.5
7.0
7.5
5.5
5.6
7.0
5.0
6.0
8.0
7.5
9.5
5.0
6.5
4.5
4.0
5.5
4.0
6.0
3.7
3.5
4.5
3.5
8.0 4.5
5.0
5.5
4.8
5.3
5.2
5.5
6.5
4.8
5.5
5.5
7.5
6.5 4.5 5.0 6.6
6.0 2.0 3.0 3.4
5.0 2.2 3.0 3.4
6.5 5.5 6.0 6.5
7.0 3.5 4.0 4.6
6.0 5.5 6.0 6.5
7.3 2.0 3.0 3.4
5.0 4.0 5.3 5.5
6.0 2.0 3.0 3.3
6.2 4.0 4.5 5.3
8.0 6.0 8.0 7.5
3.0
3.0
3.0
3.0
4.0
3.0
3.0
3.0
3.0
2.0
6.0
5.0 5.6.0
9
b
3.5
3.0
3.5
2.5
4.0
2.5
1.2
3.5
2.5
5.5
5.5 5.0
5.0 4.5
8.5 4.1
6.5 3.5
8.5 4.5
6.5 6.0
5.5 4.5
6.6 4.5
5.0 4.5
4.0
4.0
4.5
5.0
4.0
4.5
4.0
4.0
3.0
8.0
5.0
5.0
5.2
5.6
5.0
5.2
5.0
5.0
4.0
6.0
9
c
9
d
9
e
9
f
1
0a
0b
0c
0d
Streptomycin
1
1
1
10.0 12.0
6.6 13.0 6.6
Escherichia coli (MTCC 443) and Pseudomonas aeru-
ginosa (MTCC 2453) as gram-negative bacterial strains
at concentrations 200, 300, and 500 μg/mL using agar
well diffusion method according to the literature protocol.
Antibacterial activity of the products was compared with
the standard drug streptomycin (Table 1). The accumu-
lated data revealed that all the compounds demonstrated
zones of inhibition.
and used as received unless otherwise noted. Purity of the
compounds was tested and reaction progress controlled by
TLC, the spots were visualized under UV light. Melting
points were determined in open glass capillary tubes on a
Stuart SMP30 apparatus and are uncorrected. IR spectra
were recorded for KBr pellets on a Shimadzu FT-IR-
1
13
8
400s spectrophotometer. H NMR (300 MHz) and C
NMR spectra (75 MHz) were measured on a Bruker DPX
00 spectrometer using TMS as the internal standard and
The corresponding activities of most of compounds
were concentration dependent.
4
DMSO-d as the solvent. Mass spectra were measured on
6
Antioxidant activity. Antioxidant activity of com-
pounds 9a–9f and 10a–10d was carried out by 2,2-diphe-
nyl-1-picrylhydrazyl (DPPH) radical scavenging assay at
different concentrations using 2,6-bis(1,1-dimethylethyl)-
a GCMS-QP 1000 EX mass spectrometer.
Synthesis of 1-[2,4-bis(prop-2-ynyloxy)phenyl]-
ethanone (2). To a stirred solution of 2,4-dihydroxy
acetopheneone (0.0328 mol) in anhydrous DMF
4
-methylphenol (BHT) as a standard (Table 2). Based on
(
(
25 mL) was added anhydrous potassium carbonate
0.0986 mol) at 0°C. The mixture was stirred for 15 min
the experimental results, among synthesized compounds
the product 9f demonstrated good DPPH free radical
scavenging activity at concentration of 25 ꢀM, whereas
compound 9c exhibited good activity at 100 ꢀM. All
other compounds were characterized by moderate to poor
activity when compared with the standard BHT.
before propargyl bromide (0.0723 mol, 70% solution in
toluene) was added drop wise. The reaction mixture was
stirred at 0°C for 1 h and then at room temperature for
1
6 h. After completion of the process (monitored by
TLC), the reaction mixture was diluted with ice water
and stirred for 30 min. The precipitated solid was filtered
off, washed with water and dried under vacuum to obtain
the crude compound which was washed with hexane,
EXPERIMENTAL
All reactions were carried out under argon atmosphere.
All solvents and reagents were obtained commercially
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 89 No. 9 2019

1862
KIRAN et al.
Table 2. Antioxidant activity of compounds 9a–9f and 10a–10d by the DPPH method
Scavenging effect, %
Compound
2
5 ꢀM
50 ꢀM
75 ꢀM
100 ꢀM
125 ꢀM
250 ꢀM
9
a
25.44±1.32
24.69±1.18
20.50±1.53
23.69±1.18
19.50±1.53
17.68±1.03
23.44±1.32
19.69±1.18
26.68±1.03
22.44±1.32
15.56±0.95
35.24±1.35
33.27±1.62
32.36±1.23
36.27±1.62
34.36±1.23
38.92±1.32
33.24±1.35
31.27±1.62
34.92±1.32
35.24±1.35
25.36±1.19
56.56±1.40
56.72±1.34
52.33±1.32
58.72±1.34
54.33±1.32
55.40±1.67
52.56±1.40
53.72±1.34
51.40±1.67
56.56±1.40
45.18±1.48
54.79±1.45
55.39±1.83
51.43±1.42
58.39±1.83
57.43±1.42
52.63±1.49
52.79±1.45
54.39±1.83
54.63±1.49
59.79±1.45
48.58±1.41
62.38±1.50
64.83±1.87
61.29±1.18
65.83±1.87
65.29±1.18
68.18±1.45
63.38±1.50
62.83±1.87
62.18±1.45
66.38±1.50
50.58±1.54
71.26±1.42
72.31± 1.39
74.39±1.12
77.31± 1.39
78.39±1.12
79.42±1.68
76.26±1.42
72.31± 1.39
71.42±1.68
77.26±1.42
60.45±1.42
9
b
9
c
9
d
9
e
9
f
1
0a
0b
0c
0d
Control
1
1
1
filtered and dried under vacuum to obtain compound 2.
Pale yellow solid, yield 90%, mp 87–89°С. IR spectrum,
8.70 Hz), 7.75 d.d (2H, Ar-H, J = 15.54 Hz, J = 3.73 Hz).
C NMR spectrum, δ, ppm: 55.9, 56.5, 78.5, 78.6, 78.7,
1
3
–
1
1
ν, cm : 1647 (C=O). H NMR spectrum (CDCl ), δ,
78.9, 101.3, 107.4, 122.3, 125.5, 128.6, 129.6, 131.9,
132.4, 134.6, 140, 157.7, 161.5, 188.4. MS: 323.12
3
ppm: 2.56 t (2H, C≡CH, J = 2.177 Hz), 2.61 s (3H, CH3),
+
4
2
.75 d (2H, OCH , J = 2.177 Hz), 4.79 d (2H, OCH , J =
[M + H] .
2
2
.177 Hz), 6.63–6.66 m (2H, Ar-H), 7.84 d (1H, Ar-H,
Synthesis of compounds 9a–9f and 10a–10d. Amix-
ture of compound 4 (0.00062 mol) with the corresponding
+
J = 9.32 Hz). MS: 229.18 [M + H] .
Synthesis of (E)-1-[2,4-bis(prop-2-ynyloxy)phenyl]-
compound 6a–6f or 8a–8d (0.0012 mol) in t-BuOH–H O
2
3
-(thiophen-2-yl)prop-2-en-1-one (4). To a solution
(10 mL, 1 : 1) was treated with sodium L-ascorbate
(0.000248 mol) followed by addition of copper sulfate
pentahydrate (0.000025 mol), and stirred at room tem-
perature for 16 h. After completion of the process (TLC)
the reaction mixture was added to ice water and stirred
for 30 min more. The precipitated solid was filtered off,
washed with ice water and dried under vacuum to obtain
crude solid compound which was washed with diethyl
ether, filtered and dried under vacuum to obtain the cor-
responding compound 9a–9f or 10a–10d.
of compound 2 (0.0219 mol) in ethanol (50 mL) was
added KOH (0.0657 mol), upon stirring at room tem-
perature for 15 min followed by addition of thiophene-
2
1
-carbaxaldehyde (3) (0.0219 mol) and stirring for
6 h at room temperature.After completion of the process
(TLC) the reaction mixture was diluted with ice water,
its pH adjusted to 6–7 and stirred for 30 min more. The
precipitated solid was filtered off, washed with water
and dried under vacuum to obtain the crude compound,
which was washed with diethyl ether, filtered and dried
under vacuum to obtain compound 4. Pale brown solid,
(
E)-1-(2,4-Bis{[1-(4-bromophenyl)-1H-1,2,3-tri-
azol-4-yl]methoxy}phenyl)-3-(thiophen-2-yl)prop-2-
–
1
yield 87%, mp 75–77°С. IR spectrum, ν, cm : 1642
en-1-one (9a). Yellow solid, yield 88%, mp 216–219°С.
1
(C=O). H NMR spectrum, δ, ppm: 3.64 t (1H, C≡CH, J =
–1
1
IR spectrum, ν, cm : 1641 (C=O). H NMR spectrum,
δ, ppm: 5.41 s (2H, OCH ), 5.44 s (2H, OCH ), 6.85
2
.48 Hz), 3.67 t (1H, C≡CH, J = 2.48 Hz), 4.90 d (2H,
2
2
OCH , J = 2.48 Hz), 4.96 d (2H, OCH , J = 2.48 Hz),
2
2
d.d (1H, Ar-H, J = 8.78 Hz, J = 1.75 Hz), 7.01 d.d (1H,
Ar-H, J = 5.27 Hz, J = 3.51 Hz), 7.12 d (1H, Ar-H, J =
6
.75 d.d (1H, Ar-H, J = 8.70 Hz, J = 1.86 Hz), 6.83 d
1H, Ar-H, J = 1.86 Hz), 7.16 d.d (1H, Ar-H, J = 4.97
Hz, J = 3.73 Hz), 7.32 d (1H, Ar-H, J = 15.54 Hz),
.56 d (1H, Ar-H, J = 3.73 Hz), 7.63 d (1H, Ar-H, J =
(
1
.75 Hz), 7.35 d (1H, Ar-H, J = 15.56 Hz), 7.39 d (1H,
Ar-H, J = 5.27 Hz), 7.42 d (1H, Ar-H, J = 3.51 Hz), 7.68
d (1H, Ar-H, J = 15.56 Hz), 7.72 d (1H, Ar-H, J = 8.78
7
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 89 No. 9 2019

DESIGN, SYNTHESIS, AND BIOLOGICAL ACTIVITY OF NEW BIS-1,2,3-TRIAZOLE DERIVATIVES
1863
Hz),7.80–7.84 m (6H, Ar-H), 7.91 d (2H, Ar-H, J = 9.03
Hz), 8.98 s (1H, triazole-H), 9.05 s (1H, triazole-H). C
NMR spectrum, δ, ppm: 61.4, 62, 100.3, 107.6, 121.2,
107.6, 121.2, 121.7, 123, 123.2, 125.7, 128.5, 129, 129.8,
132.1, 132.4, 133, 133.1, 133.9, 135.2, 135.3, 140, 143.4,
143.5, 159.1, 162.8, 187.7. MS: 629.13 [M + H]+.
1
3
1
1
1
21.3, 121.4, 121.9, 122.1, 123, 123.1, 125.6, 128.5,
28.9, 132.1, 132.4, 132.8, 133.9, 135.6, 135.7, 140,
43.4, 159, 162.7, 187.6. MS: 719.07 [M + H]+.
(
E)-1-{2,4-Bis[(1-phenyl-1H-1,2,3-triazol-4-yl)me-
thoxy]phenyl}-3-(thiophen-2-yl)prop-2-en-1-one (9e).
Light brown solid, yield 86%, mp 155°С. IR spectrum,
ν, cm : 1639 (C=O). H NMR spectrum, δ, ppm: 5.43 s
2H, OCH ), 5.45 s (2H, OCH ), 6.86 d (1H, Ar-H, J =
.27 Hz), 7.0–7.14 m (2H, Ar-H), 7.35 d (1H, Ar-H, J =
5.56 Hz),7.42–7.73 m (7H,Ar-H), 7.73–7.82 m (2H,Ar-
H), 7.93–7.94 m (5H,Ar-H), 8.98 s (1H, triazole-H), 9.04
s (1H, triazole-H). C NMR spectrum, δ, ppm: 61.4, 62,
(
E)-1-(2,4-Bis{[1-(4-methoxyphenyl)-1H-1,2,3-
triazol-4-yl]methoxy}phenyl)-3-(thiophen-2-yl)prop-
-en-1-one (9b). Grey solid, yield 89%, mp 162–165°С.
–1
1
(
5
1
2 2
2
–1
1
IR spectrum, ν, cm : 1637 (C=O). H NMR spectrum, δ,
ppm: 3.84 s (6H, 2OMe), 5.40 s (2H, OCH ), 5.43 s (2H,
OCH ), 6.85 d.d (1H, Ar-H, J = 8.78 Hz, J = 1.75 Hz),
7
m (5H,Ar-H), 7.36–7.40 m (2H, Ar-H), 7.42 d (1H,Ar-H,
J = 3.26 Hz), 7.69 d (1H, Ar-H, J = 14.05 Hz), 7.72–7.74
m (3H,Ar-H), 7.83 d (2H,Ar-H, J = 9.03 Hz), 8.86 s (1H,
triazole-H), 8.92 s (1H, triazole-H). C NMR spectrum,
δ, ppm: 55.5, 61.4, 62.1, 100.2, 107.5, 114.8, 121.1, 121.6,
2
2
13
.03 d.d (1H, Ar-H, J = 4.76 Hz, J = 3.76 Hz), 7.12–7.16
1
1
1
00.2, 107.6, 120, 120.2, 121.2, 123, 123.1, 125.6, 128.5,
28.7, 128.8, 128.9, 129.9, 132, 132.4, 133.9, 136.4, 140,
43.3, 159.1, 162.8, 187.6. MS: 561.20 [M + H]+.
1
3
(E)-1-(2,4-Bis{[1-(4-fluorophenyl)-1H-1,2,3-triazol-
-yl]methoxy}phenyl)-3-(thiophen-2-yl)prop-2-en-1-
one (9f). Pale yellow solid, yield 83%, mp 170–173°С.
IR spectrum, ν, cm : 1641 (C=O). H NMR spectrum,
δ, ppm: 5.41 s (2H, OCH ), 5.44 s (2H, OCH ), 6.85
4
1
1
21.8, 122.9, 123.1, 125.6, 128.6, 129, 129.9, 130, 132,
32.4, 133.9, 140, 143, 159.1, 159.3, 159.4, 162.8, 187.6.
–
1
1
+
MS: 621.22 [M + H] .
2
2
d.d (1H, Ar-H, J = 8.78 Hz, J = 2.0 Hz), 7.02 d.d (1H,
Ar-H, J = 5.019 Hz, J = 3.76 Hz), 7.12 d (1H, Ar-H,
J = 2.00 Hz), 7.36 d (1H, Ar-H, J = 15.81 Hz), 7.39–7.50
m (6H, Ar-H), 7.69 d (1H, Ar-H, J = 15.81 Hz), 7.73 d
(
E)-1-{2,4-Bis[(1-p-tolyl-1H-1,2,3-triazol-4-yl)me-
thoxy]phenyl}-3-(thiophen-2-yl)prop-2-en-1-one (9c).
Yellow solid, yield 76%, mp 178–180°С IR spectrum, ν,
–1
1
cm : 1637 (C=O). H NMR spectrum, δ, ppm: 2.39 s
6H, 2Me), 5.41 s (2H, OCH ), 5.43 s (2H, OCH ), 6.85
(1H,Ar-H, J = 8.78 Hz), 7.86 d.d (2H,Ar-H, J = 9.03 Hz,
(
2
2
J = 4.76 Hz), 7.98 d.d (2H, Ar-H, J = 9.035 Hz, J =
d.d (1H, Ar-H, J = 8.53 Hz, J = 2.25 Hz), 7.02 d.d (1H,
Ar-H, J = 5.01 Hz, J = 3.76 Hz), 7.12 d (1H, Ar-H, J =
.25 Hz), 7.35–7.43 m (7H,Ar-H), 7.68–7.74 m (4H,Ar-
H), 7.81 d (2H, Ar-H, J = 8.28 Hz), 8.91 s (1H, triazole-
H), 8.98 s (1H, triazole-H). C NMR spectrum, δ, ppm:
0.5, 61.4, 62.0, 100.3, 107.6, 119.9, 120.1, 121.2, 122.8,
23, 125.6, 128.5, 129, 130.2, 130.3, 132, 132.4, 133.9,
34.2, 134.3, 138.3, 138.4, 140, 143.1, 159.1, 162.8,
87.6. MS: 589.23 [M + H]+.
4
.76 Hz), 8.94 s (1H, triazole-H), 9.01 s (1H, triazole-H).
C NMR spectrum, δ, ppm: 61.4, 62, 100.3, 107.6, 116.6,
16.9, 121.2, 122.2, 122.3, 122.5, 122.6, 123.2, 123.4,
1
3
2
1
125.7, 128.5, 129, 132, 132.4, 133, 133.1, 133.9, 140,
143.3, 159.1, 160, 160.1, 162.8, 163.2, 163.3, 187.7. MS:
5
97.18 [M + H]+.
1
3
2
1
1
1
(E)-1-(2,4-Bis{[1-(3-methoxybenzyl)-1H-1,2,3-tri-
azol-4-yl]methoxy}phenyl)-3-(thiophen-2-yl)prop-2-
(
E)-1-(2,4-Bis{[1-(4-chlorophenyl)-1H-1,2,3-tri-
en-1-one (10a). Yield 83%, Yellow solid, mp 112–114°С.
–1
1
azol-4-yl]methoxy}phenyl)-3-(thiophen-2-yl)prop-
-en-1-one (9d). Pale yellow solid, yield 86%, mp
07–209°С. IR spectrum, ν, cm : 1645 (C=O). H
IR spectrum, ν, cm : 1645 (C=O). H NMR spectrum, δ,
ppm: 3.69 s (3H, OMe), 3.72 s (3H, OMe), 5.27 s (2H,
NCH ), 5.31 s (2H, NCH ), 5.54 s (2H, OCH ), 5.59 s
2
2
–
1
1
2
2
2
NMR spectrum, δ, ppm: 5.42 s (2H, OCH ), 5.45 s (2H,
(2H, OCH ), 6.77–6.79 m (2H, Ar-H), 6.87–6.91 m (5H,
2
2
OCH ), 6.85 d.d (1H, Ar-H, J = 8.78 Hz, J = 2.00 Hz),
Ar-H), 7.01 s (1H, Ar-H), 7.12 t (1H, Ar-H, J = 4.01 Hz),
7.22 t (1H, Ar-H, J = 8.03 Hz), 7.29 t (1H, Ar-H, J =
8.03 Hz), 7.34 d (1H, Ar-H, J = 15.81 Hz), 7.47 d (1H,
J = 2.25, Ar-H), 7.65–7.67 m (2H, Ar-H), 7.69 d (1H,
Ar-H, J = 15.81 Hz), 8.30 s (1H, triazole-H), 8.36 s (1H,
triazole-H). C NMR spectrum, δ, ppm: 52.7, 52.8, 55,
55.1, 61.4, 61.8, 100.3, 107.3, 113.5, 113.6, 113.7, 119.9,
120, 121.3, 124.9, 125.5, 128.5, 129.4, 129.8, 129.9, 132,
2
7
.02 d.d (1H, Ar-H, J = 5.01 Hz, J = 8.78 Hz), 7.12 d
(1H,Ar-H, J = 2.00 Hz), 7.35 d (1H,Ar-H, J = 15.56 Hz),
7
.38 d (1H, Ar-H, J = 5.01 Hz), 7.42 d.d (1H, Ar-H, J =
3
.51 Hz), 7.66–7.69 m (5H, Ar-H), 7.73 d (1H, Ar-H,
1
3
J = 8.53 Hz), 7.86 d (2H, Ar-H, J = 8.78 Hz), 7.98 d (2H,
Ar-H, J = 8.78 Hz), 8.99 s (1H, triazole-H), 9.06 s (1H,
13
triazole-H). C NMR spectrum, δ, ppm: 61.4, 62, 100.3,
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 89 No. 9 2019

1864
KIRAN et al.
1
1
32.2, 134, 137.2, 137.3, 140, 142.4, 158.9, 159.3, 159.4,
62.7, 187.8. MS: 649.26 [M + H]+.
E)-1-(2,4-Bis{[1-(4-fluorobenzyl)-1H-1,2,3-triazol-
(MTCC 443), Pseudomonas aureoginosa (MTCC
2453), and Candida albicans were chosen based on their
clinical and pharmacological importance. The bacterial
strains were obtained from Department of Microbiology,
Osmania University. The bacterial stock cultures were
incubated for 24 h at 37°C on nutrient agar. The bacteria
were grown on Mueller–Hinton agar plates at 37°C. The
stock cultures were maintained at 4°C for the growth of
fungi potato dextrose agar were used. Whatman no. 1
filter paper discs of 5 mm diameter were autoclaved by
keeping in a clean and dry Petri plate. The discs were
soaked in a compound solutions for 5 h and used as the
test material. After 5 h the discs were shade dried. The
concentrations of compound solutions per disc were ac-
counted for 0.1 g/mL. Subsequently they were carefully
transferred to spread on cultured Petri plates. Filter paper
discs immersed in ethanol, hexane, benzene, and distilled
water were prepared and used as control.
(
4
1
-yl]methoxy}phenyl)-3-(thiophen-2-yl)prop-2-en-
-one (10b). Yellow solid, yield 88%, mp 142–144°С.
–
1
1
IR spectrum, ν, cm : 1645 (C=O). H NMR spectrum,
δ, ppm: 5.27 s (2H, NCH ), 5.30 s (2H, NCH ), 5.57 s
2
2
(2H, OCH ), 5.62 s (2H, OCH ), 6.77 d.d (1H, Ar-H, J =
2 2
8
7
.78 Hz, J = 2.0 Hz), 7.01 d (1H, Ar-H, J = 2.0 Hz),
.12–7.24 m (5H, Ar-H), 7.30–7.34 m (3H, Ar-H), 7.42
d.d (2H, Ar-H, J = 8.78 Hz, J = 5.52 Hz), 7.47 d (1H,
Ar-H, J = 3.51 Hz), 7.64–7.68 m (2H, Ar-H), 7.69 d (1H,
Ar-H, J = 9.78 Hz), 8.30 s (1H, triazole-H), 8.35 s (1H,
13
triazole-H). C NMR spectrum, δ, ppm: 52.0, 52.1, 61.4,
6
1
1
1
1.9, 100.3, 107.3, 115.3, 115.4, 115.6, 115.7, 121.3,
24.7, 124.8, 125.5, 128.5, 129.5, 130.1, 130.2, 130.3,
30.4, 132, 132.1, 132.2, 132.3, 134, 140, 142.4, 158.9,
60.2, 160.3, 162.7, 163.4, 163.5, 187.9. MS: 625.20
[
M + H]+.
E)-1-{2,4-Bis[(1-benzyl-1H-1,2,3-triazol-4-yl)-
methoxy]phenyl}-3-(thiophen-2-yl)prop-2-en-1-one
10c). Pale yellow solid, yield 90%, mp 133–135°С. IR
To test the antibacterial activity, LB agar medium was
prepared, and the medium was sterilized at 121°C for
(
3
1
0 min. The agar plates were prepared by pouring about
0 mL of the medium into 10 cm Petri dishes under
(
–1
1
aseptic conditions and left undisturbed for 2 h to solidify
the medium. 1 mL of inocculum (containing suspen-
sion) of Staphylococcus aureus (MTCC 3160), Bacillus
cereus (MTCC 1305), E.Coli (MTCC 443), Pseudomonas
aureoginosa (MTCC 2453), or Candida albicans was
poured on to the plates separately containing solidified
agar media. The prepared sterile filter paper discs were
impregnated with the compound solutions and shaken
thoroughly, and the test plates were incubated for 48 h
in BOD at 37°C for the development of inhibitory zones.
The average of 2 independent readings for each organism
in different compound solutions were recorded.
spectrum, ν, cm : 1643 (C=O). H NMR spectrum, δ,
ppm: 5.29 s (4H, 2NCH ), 5.57 s (2H, OCH ), 5.63 s (2H,
OCH ), 6.87–7.66 m (18H, Ar-H), 8.33 s (1H, triazole-
H), 8.41 s (1H, triazole-H). C NMR spectrum, δ, ppm:
5
1
1
1
2
2
2
1
3
2.6, 52.7, 61.3, 61.7, 100.1, 107.1, 121.1, 125.2, 127.6,
27.7, 127.8, 127.9, 128.3, 128.4, 128.5, 129.1, 131.8,
32, 133.8, 135.5, 135.7, 139.8, 142.6, 158.7, 162.4,
87.7. MS: 589.20 [M + H]+.
(E)-1-(2,4-Bis{[1-(4-nitrobenzyl)-1H-1,2,3-triazol-
4
1
-yl]methoxy}phenyl)-3-(thiophen-2-yl)prop-2-en-
-one (10d). Brown solid, yield 90%, mp 134–136°С.
–
1
1
IR spectrum, ν, cm : 1647 (C=O). H NMR spectrum,
δ, ppm: 5.31 s (2H, NCH ), 5.34 s (2H, NCH ), 5.78 s
(
The inhibition zones were measured after storing for
1 day at 37°C for bacteria. With the aid of plastic ruler
the diameter of the inhibition zone was measured and re-
corded. The five paper discs were placed in one Petri plate.
In disc diffusion method the nutrient agar was poured into
Petri plate and allowed to solidify.After 1mLof microbial
suspension was poured into plates, 9a–9f and 10a–10d
compounds were applied on to the discs and placed in a
Petri plate and incubated for 48 h.
2
2
2H, OCH ), 5.83 s (2H, OCH ), 6.78 d (1H, Ar-H, J =
2 2
8
.03 Hz), 7.03–7.09 m (2H, Ar-H), 7.31 d (1H, Ar-H,
J = 15.30 Hz), 7.46–7.50 m (3H,Ar-H), 7.56 d (2H,Ar-H,
J = 7.78 Hz), 7.62–7.65 m (1H, Ar-H), 7.68 d (1H, Ar-H,
J = 15.30 Hz), 8.15 d (2H,Ar-H, J = 7.78 Hz), 8.25 d (3H,
Ar-H, J = 7.52 Hz), 8.41 s (1H, triazole-H), 8.46 s (1H,
13
triazole-H). C NMR spectrum, δ, ppm: 51.9, 52, 61.3,
6
1
1
1
1.8, 100.3, 107.4, 121.4, 123.7, 123.9, 125.3, 125.4,
28.4, 128.8, 128.9, 129.1, 129.2, 129.4, 132, 132.2,
33.9, 140, 143.1, 143.2, 147.1, 147.2, 158.8, 162.6,
87.9. MS: 679.17 [M + H]+.
Antioxidant activity [20]. Free radical-scavenging
ability using stable DPPH radical was determined ac-
cording to the earlier developed method. DPPH (100 μM)
was dissolved in pure ethanol (96%). The radical stock
solution was prepared fresh daily. The DPPH solution
Antibacterial tests [19]. Staphylococcus aureus
MTCC 3160), Bacillus cereus (MTCC 1305), E.Coli
(
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 89 No. 9 2019

DESIGN, SYNTHESIS, AND BIOLOGICAL ACTIVITY OF NEW BIS-1,2,3-TRIAZOLE DERIVATIVES
1865
(
3
1 mL) was added to 1 mL of polyphenol extracts with
mL of ethanol. The mixture was vigorously shaken and
stored undisturbed at room temperature in darkness for
0 min. Decrease in absorbance of the resulting solution
5. Celik, F., Unver, Y., Barut, B., Ozel, A., and Sancak, K.,
Med. Chem., 2018, vol. 14, p. 230.
https://doi.org/10.2174/1573406413666171120165226
1
6. (a) Duddukuri, N. K., Thatikonda, S., Godugu, C.,
Kumar, R.A., and Doijad, N., Chem. Sel., 2018,
vol. 3, p. 6859.
was monitored at 517 nm. The results were corrected for
dilution and expressed in l M trolox per 100 g dry weight
https://doi.org/10.1002/slct.201800613;
(dw). BHT was used as a positive control. All measure-
(b) Solomon, V.R. and Lee, H., Biomed. Pharmacol.,
ments were performed in triplicate.
2
012, vol. 66, p. 213.
CONCLUSIONS
https://doi.org/10.1016/j.biopha.2011.11.013
7
. Ming, L.S., Jamalis, J., Al-Maqtari, H.M., Rosli, M.M.,
Sankaranarayanan, M., Chander, S., and Fun, H.K.,
Chem. DATA Collect., 2017, vol. 9, p. 104.
Aseries of ten 1,4-substituted bis-1,2,3-triazoles bear-
ing thiophene chalcones have been synthesized via the
click reaction of aryl and aralkyl azides with bis propargyl
chalcone intermediate. The synthesized compounds are
evaluated for their antimicrobial and antioxidant activi-
ties. Several compounds demonstrate good antibacterial
activities, while some exhibit good antifungal activ-
ity. According to DPPH radical scavenging results one
compound is characterized by good anti-oxidant activity
while the other compounds demonstrate moderate to poor
activity when compared with the standard BHT.
https://doi.org/10.1016/j.cdc.2017.04.004
8
. Siddesh, M.B., Padmashali, B., Thriveni, K.S., and
Sandeep, C., J. Chem. Sci., 2014, vol. 126, p. 821.
https://doi.org/10.1007/s12039-014-0614-z
9
. Mazimba, O., J. King Saud Univ. Sci., 2015, vol. 27,
p. 42.
https://doi.org/10.1016/j.jksus.2014.06.003
1
0. (a) Zhao, L., Mao, L., Hong, G., Yang, X., and Liu, T.
Bioorg. Med. Chem. Lett., 2015, vol. 25, p. 2540.
https://doi.org/10.1016/j.bmcl.2015.04.051;
FUNDING
(
b) Kamal, A., Prabhakar, S., Ramaiah, M.J., Reddy, P.V.,
The authors are thankful to the Head, Department of
Chemistry, JNTU-H and Osmania University, Hyderabad
for their valuable support. Boddu Ananda Rao thanks
to CSIR, New Delhi, India for a CSIR-RA fellowship.
Authors are also thankful to DST, PURSE-II programe,
UGC UPE FAR, Osmania University for the Financial
assistance.
Reddy, C.R., Mallareddy, A., and Pal-Bhadra, M.,
Eur. J. Med. Chem., 2011, vol. 46, p. 3820.
https://doi.org/10.1016/j.ejmech.2011.05.050;
(c) Yadav, P., Lal, K., Kumar, A., Guru, S.K., Jaglan, S., and
Bhushan, S. Eur. J. Med. Chem., 2017, vol. 126, p. 944.
https://doi.org/10.1016/j.ejmech.2016.11.030
1
1. (a) Singh, G., Arora, A., Rani, S., Maurya, I. K., Aulakh, D.,
CONFLICT OF INTEREST
No conflict of interest was declared by the authors.
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