Design and synthesis of imidazolo-1, 2,3-triazoles hybrid compounds by microwave-assisted method: Evaluation as an antioxidant and antimicrobial agents and molecular docking studies

Article abstract of DOI:10.1016/j.molstruc.2018.11.029

The present manuscript describes synthesis of a new class of antimicrobial and antioxidant agents (imidazole linked 1,2,3-triazole hybrid compounds) and screened for their in-vitro studies for antimicrobial and antioxidant activity. In the present investigation, We have developed a simple and convenient method to design and synthesize imidazole linked mono-triazole (6) as well as imidazole linked bis-triazole (9) derivatives by using the click reaction followed by multi component reaction for compounds (6) and vice-versa for the synthesis of compounds (9). The reactions were carried out by two different techniques, conventional heating and microwave irradiation. Microwave irradiation method offers excellent yields, lesser reaction times and environmental friendly reactions. These compounds were studied for their antimicrobial, antioxidant and molecular docking studies using Schrodinger suite. For their in-vitro antimicrobial activity against gram-positive, gram-negative strains; preliminary results indicated that some target compounds exhibited promising antimicrobial potency especially 6c, 6h, 9d, 9e and 9h. Further these compounds were tested for their in-vitro antioxidant activity using four different methods few of them are exhibited excellent antioxidant activity especially 6d, 6h, 9a, 9c, 9e, 9f, 9h. In addition these compounds activity relationship were further supported by in-silico molecular docking studies some of the active compounds 6c, 6h, 9d and 9e showed maximum dock score.

Full text of DOI:10.1016/j.molstruc.2018.11.029

Accepted Manuscript
Design and synthesis of imidazolo-1, 2,3-triazoles hybrid compounds by microwave-
assisted method: Evaluation as an antioxidant and antimicrobial agents and molecular
docking studies
N.J.P. Subhashini, E. Praveenkumar, Nirmala Gurrapu, Vishwanadham Yerragunta
PII:
S0022-2860(18)31339-5
DOI:
https://doi.org/10.1016/j.molstruc.2018.11.029
MOLSTR 25858
Reference:
To appear in: Journal of Molecular Structure
Received Date: 29 January 2018
Revised Date: 22 September 2018
Accepted Date: 8 November 2018
Please cite this article as: N.J.P. Subhashini, E. Praveenkumar, N. Gurrapu, V. Yerragunta, Design and
synthesis of imidazolo-1, 2,3-triazoles hybrid compounds by microwave-assisted method: Evaluation as
an antioxidant and antimicrobial agents and molecular docking studies, Journal of Molecular Structure
(2018), doi: https://doi.org/10.1016/j.molstruc.2018.11.029.
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ACCEPTED MANUSCRIPT
Design and synthesis of imidazolo-1,2,3-triazoles hybrid compounds by
microwave-assisted method: Evaluation as an antioxidant and antimicrobial agents
and molecular docking studies
Subhashini N. J. Pa *, Praveenkumar Ea, Nirmala Gurrapua, and Vishwanadham Yerraguntab
a Department of Chemistry, University College of science, Osmania University, Hyderabad, Telangana-500 007, India.
bBio- Organic & Medicinal Chemistry Research Division, Vishnu Institute of Pharmaceutical Education and
Research(VIPER), Narsapur, Medak, Telangana-502313, India.

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Design and synthesis of imidazolo-1, 2 ,3-triazoles hybrid compounds by microwave-
assisted method: Evaluation as an antioxidant and antimicrobial agents and molecular
docking studies
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Subhashini N. J. Pa *, Praveenkumar Ea, Nirmala Gurrapua, and Vishwanadham Yerraguntab
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a Department of Chemistry, University College of science, Osmania University, Hyderabad, Telangana-
500 007, India.
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bBio- organic & Medicinal Chemistry Research Division, Vishnu Institute of Pharmaceutical Education
and Research (VIPER), Narsapur, Medak, Telangana-502313, India.
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*Corresponding author: Subhashini N. J. P
Department of Chemistry,
University College of science,
Osmania University,
Hyderabad, Telangana, India.-500 007,
E-mail: njsubhashini@osmania.ac.in
E-mail: njsubhashini@yahoo.co.in
Tel: +91 9849941559
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Abstract:
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The present manuscript describes synthesis of a new class of antimicrobial and antioxidant
agents (imidazole linked 1,2,3-triazole hybrid compounds) and screened for their in-vitro studies for
antimicrobial and antioxidant activity. In the present investigation, We have developed a simple and
convenient method to design and synthesize imidazole linked mono-triazole (6) as well as imidazole
linked bis-triazole (9) derivatives by using the click reaction followed by multi component reaction for
compounds (6) and vice-versa for the synthesis of compounds (9). The reactions were carried out by
two different techniques, conventional heating and microwave irradiation. Microwave irradiation
method offers excellent yields, lesser reaction times and environmental friendly reactions. These
compounds were studied for their antimicrobial, antioxidant and molecular docking studies using
Schrodinger suite. For their in-vitro antimicrobial activity against gram-positive, gram-negative
strains; preliminary results indicated that some target compounds exhibited promising antimicrobial
potency especially 6c, 6h, 9d, 9e and 9h. Further these compounds were tested for their in-vitro
antioxidant activity using four different methods few of them are exhibited excellent antioxidant
activity especially 6d, 6h, 9a, 9c, 9e, 9f, 9h. In addition these compounds activity relationship were
further supported by in-silico molecular docking studies some of the active compounds 6c, 6h, 9d and
9e showed maximum dock score.
Key words: Imidazole, 1, 2, 3-triazole, anti-microbial, anti-oxidant, and molecular docking.

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1. Introduction:
Imidazole and triazole derivatives are widely used as an important class for many natural and
synthetic compounds to displace diverse range of biological activities. Due to their biological
importance of Imidazole and triazole derivatives widely used for many clinical applications such as
mainly antimicrobial1 anti-inflammatory,2 antioxidant agent,3 anticancer,4 antipyretic,5 anticonvulsant,6
,
antidepressant,7 antimalarial,8 antitumor,9 antiviral,10 (Fig.1). In the present manuscript synthesis the
biological studies of Imidazole and triazole derivatives were mainly involved in antimicrobial and
antioxidant studies. The antimicrobial agents are the basic medicines for human and animal health, and
are considered as "miracle drugs” to treat infections caused by microorganisms, fungi, parasites, and
viruses. Antimicrobial susceptibility testing can be used for drug discovery, epidemiology and
prediction of therapeutic outcome. In meanwhile, antioxidants that can scavenge reactive chemical
element species is also of economical worth in preventing the diseases like autoimmune,
cardiovascular and neurovascular diseases.
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Figure. 1
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These health risks encourages us to develop and modification of antioxidant, antimicrobial agents for
developing a convenient method for the synthesis of imidazole linked 1, 2, 3-triazole hybrids with high
potency, low toxicity and broad spectrum. Therefore, the synthesis of imidazole linked 1,2,3-triazole
hybrid compounds in the pursuit of novel and potential compounds to become a new drugs for
antimicrobial, antioxidant agents. In the present investigation, we have designed and synthesized
imidazole linked mono-triazole (6a-h) as well as imidazole linked bis-triazole (9a-h) derivatives by
using the click reaction followed by multi component reaction (MCR) for compounds (6a-h) and vice-
versa for compounds (9a-h). The reactions were carried out by two different techniques, conventional
heating and microwave irradiation.Microwave irradiation method offers excellent yields, lesser the
reaction times and environmental friendly reactions. These compounds were studied for their

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antimicrobial, antioxidant and molecular docking studies using Schrodinger suite. For their in-vitro
antimicrobial activity against gram-positive, gram-negative strains; preliminary results indicated that
some target compounds exhibited promising antimicrobial potency especially 6c, 6h, 9d, 9e and 9h.
Further these compounds were tested for their in-vitro antioxidant activity using four different
methods few of them are exhibited excellent antioxidant activity especially 6d, 6h, 9a, 9c, 9e, 9f, 9h.
In addition these compounds activity relationship were further supported by in-silico molecular
docking studies some of the active compounds 6c, 6h, 9d and 9e showed maximum dock score.
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Figure 2: Compounds (6a-h) and (9a-h)
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2. Results and discussion:
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2.1 Synthesis of imidazole linked 1,2,3-triazole compounds: We have developed a simple and
convenient method for the synthesis of imidazole linked 1,2,3-triazole compounds (6a-h & 9a-h) in
two different methods. Compounds which contains triazole and imidazole ring (6a-h) (Fig. 2),
synthesis first started with proporgylation of 4-hydroxy benzaldehyde (1) and then click reaction with
aryl azides (3a-h) at terminal alkyne position obtained triazole ring of 4-hydroxy benzaldehyde
compounds (4a-h), and performed one-pot multi component reaction for condensation of benzil (5),
benzaldehyde of compounds (4a-h) and ammonium acetate in presence of ethanol, acetic acid in
iodine under the microwave irradiation method afforded our targeted compounds (6a-h) (Scheme-1),
respectively, in good to excellent yields.
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Scheme 1: Synthesis of compounds (6a-h)
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2.2 Synthesis of compounds (9a-h): In this current method, we have fallowed our previous synthetic
route of vice versa for the synthesis of compounds (9a-h). In this method synthesis first started with
one-pot multi component reaction of 4-hydroxy benzaldehyde (1), benzil (5) and ammonium acetate in
presence of ethanol, acetic acid in iodine under microwave methods offered compounds (7) followed
by proporgylation of compound (7) and bis proporgylation takes place at position of free O-H and N-
H groups yielded to bis-propargylated compound (8) which on further click reaction of aryl azides (3a-
h) with bis-propargylated compound (8) in this final reaction observed compounds with imidazole
linked bis-triazole compounds (9a-h) (Scheme-2), respectively, in good to excellent yields.
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Scheme 2: Synthesis of compounds (9a-h)

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2.3 Biological activity
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In view of various biological and pharmacological importance of various series of imidazoles and 1, 2,
3-triazoles, it is felt worthy to evaluate (6a-h & 9a-h) derivatives for attainable activities. These
compounds thus were screened for antimicrobial, antioxidant and molecular docking studies using
Schrodinger suite. The details of these studies along with the observations were recorded in tables.
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2.3.1. Antimicrobial activity
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The antimicrobial activities of all the synthesized imidazole-1,2,3-triazole hybrid derivatives (6a-h &
9a-h) were tested all the synthesized molecules and find the MIC values against 6 microbial strains: S.
aureus, B. cereus ;E. coli , P.vulgaris; A. fumigates and C.albicans. The results from the analysis of
antimicrobial effects measured as (MIC) Minimum Inhibitory concentrations which are summarized in
Table 1. All tested compounds showed good MIC values (1 mg /mL), against gram +ve and gram -ve
bacteria compared to the reference drug ampicillin (100µg /mL). The tested compounds showed
sensible to glorious antimicrobial activities against the strains, similar to the quality drug Ampicillin
and fluconazole as shown in Table 1. Out of the various compounds tested, compounds 6c, 6h, 9d, 9e
and 9h inhibited microrobial growth very effectively compared to others in the series with MIC values
ranging from 8.86 to 33.25ꢀg/mL. The best potent anti-bacterial and anti-fungal compounds 9d
(R1=OCH3), and 9e (R1=OCH3, R3=NO2 respectively). It was observed that the presence of the 9d R1=
OMe, 9e R1=OMe, R3= NO2 R1and R3 position of the 1-phenyl-1H-[1, 2, 3] triazol-4-ylcore brought
about an enhancement of the antimicrobial potency. moreover 6h (R3=NO2), 6c (R3=CH3), showed
good activity, 9h (R3=NO2)showed moderate activity antibacterial and antifungal activity and
remaining compounds showed poor activity .It can be concluded that all the synthesized imidazole-
1,2,3-triazole hybrid derivatives (6a-h & 9a-h ) 9d, 9eshowed excellent activity than compounds 6h,
6c showed good activity compared to 9h.
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Table 1: Minimum inhibition showing antimicrobial activities of the compounds compared with
reference drugs, results given in µg/ml sample
Compounds
6a
S. aureus
B. cereus
E. coli
32.12
P. vulgaris
A. fumigatus
C. albicans
45.78
40.9
43.85
46.32
35.7
6b
49.23
18.21
31.37
100
42.71
14.25
35.75
78.4
31.23
15.62
31.5
35.29
11.58
25.65
81.11
29.76
66.85
23.75
89.92
75.75
41.75
31.75
9.63
51.83
29.25
37.95
121.39
38.73
74.5
39.01
33.25
31.75
105.47
39.5
6c
6d
6e
71.29
32.78
88.5
6f
38.72
75.78
15.45
77.35
72.5
29.56
65.71
13.3
6g
83.7
6h
9.78
28.85
65.73
80.83
35.5
31.9
9a
80.91
73.76
37.72
17.89
9.41
79.37
66.85
41.35
25.5
65.81
69.5
9b
9c
45.47
13.78
16.13
45.75
75.76
30.79
15.5
40.33
23.65
21.86
35.67
73.9
9d
19.75
20.35
42.41
65.75
31.63
-
9e
8.86
9f
9g
36.95
68.5
57.91
73.79
32.38
10.75
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40.5
70.79
35.78
9.45
9h
33.83
8.35
28.2
Ampicillin
Fluconazole
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-
-
-
21.65
25.3
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100
80
S. aureus
B. cereus
E. coli
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P. vulgaris
A. fumigatus
C. albicans
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0
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Fig. 3 Graphical representation of MICs of compounds 6a-h and 9a-h
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:
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2.3.2.1 DPPH radical scavenging activity:
The antioxidant activity of all synthesized compounds were measured against 2,2-diphenyl-1-
picrylhydrazyl (DPPH) radical. Compound 9e (R1=OCH3, R3=NO2 respectively) was the excellent

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radical scavenger with associate % of inhibition worth of 250µg/mL. Furthermore compound 9c
(R3=CH3) showed a best radical scavenging activity with % of inhibition at 250µg/mL. Compounds
6h, 9h (R3=NO2) conjointly showed good scavenging activities with 10, 50, 100, 250µg/mL
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Table 2: DPPH radical scavenging activity analysis of 6a-h and 9a-h
10µg
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50µg
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100µg
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250 µg
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Compounds
Standard
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6c
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6d
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6f
90
6g
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6h
9a
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87
9b
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9c
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9d
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9e
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9f
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9g
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9h
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10µg
50µg
100µg
250 µg
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Fig. 4 Graphical representation of DPPH radical scavenging activity of compounds
6a-h and 9a-h
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2.3.2.2 Hydrogen peroxide radical scavenging activity
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Hydrogen peroxide produces hydroxyl radicals in cells. Scavenging of these radicals by the test drug is
used as a test for antioxidant activity. Compounds 9c (R3=CH3), 9h (R1=NO2, R3= OMe), was the
strongest radical scavenger with associate % of inhibition worth of 250µg/mL. Furthermore compound
6f, 6b showed a good radical scavenging activity with % of inhibition at250µg/mL.
Table 3: Hydrogen peroxide radical scavenging activity of 6a-h and 9a-h
Compounds
10µg
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50µg
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100µg
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250µg
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Standard
6a
6b
6c
6d
6e
6f
6g
6h
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9b
9c
9d
9e
9f
9g
9h
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10µg
50µg
100µg
250µg
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Fig. 5 Graphical representation of Hydrogen peroxide radical scavenging activity
of compounds 6a-h and 9a-h
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2.3.2.3 Nitric oxide scavenging activity assay
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Nitric oxide radical scavenging activity was determined according to the method reported by Garratt.
Sodium nitroprusside in aqueous solution at physiological pH spontaneously generates nitric oxide,
which interacts with oxygen to produce nitrite ions. Compound 6h (R3=NO2) was the excellent nitric
oxide radical scavenger with associate % of inhibition worth of 250µg /mL. Furthermore compound
9a (R2=Cl), 9c (R3=CH3), 9h (R3=NO2) showed a good nitric oxide radical scavenging activity with %
of inhibition at seventy four 250µg/mL.
Table 4: Nitric oxide radical scavenging activity of 6a-h and 9a-h
10µg
50µg
100µg
250µg
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Standard
6a
6b
6c
6d
6e
6f
6g
6h
9a
9b
9c
9d
9e
9f
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39
9g
9h
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77
86
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10µg
50µg
100µg
250µg
Fig6: Graphical representation of Nitric oxide radical scavenging activity of
Compounds 6a-h and 9a-h

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2.3.2.4 Reducing power assay (FRAP)
The synthesized compounds (0.75 ml) at various concentrations was mixed with 0.75 mL of phosphate
buffer (0.2 M ,pH 6.6) and 0.75 mL of potassium hexacyanoferrate [K3Fe(CN)6] (1%, w/v), followed
by incubating at 50oC in a water bath for 20 min. The absorbance at 700 nm was measured as the
reducing power. Higher absorbance of the reaction mixture indicated greater reducing power.
Compound 9c (R3=CH3 is substituted phenyl ring) was the excellent Reducing power assay% of
inhibition worth of 250µg /mL. Further compounds 6d (R1=OCH3), 9d (R1=OCH3), 9h (R3=NO2)
showed good Reducing power assay with % of inhibition at 250µg/mL.
Table 5: FRAP oxide radical scavenging activityof6a-h and 9a-h
10µg
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64
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45
31
60
50µg
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64
67
39
77
27
68
33
58
63
58
71
79
37
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39
69
100µg
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78
79
43
83
32
77
40
69
75
67
84
86
45
62
43
78
250µg
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87
93
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92
38
85
45
87
89
85
97
91
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85
48
87
Standard
6a
6b
6c
6d
6e
6f
6g
6h
9a
9b
9c
9d
9e
9f
9g
9h
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120
100
80
60
40
20
0
10µg
50µg
100µg
250µg
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Fig 7: Graphical representation of FRAP oxide radical scavenging activity of
Compounds 6a-h and 9a-h
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2.3.2.5 In-Silico Molecular Docking Studies:
Considering the results obtained from antimicrobial study, it was thought worthy to perform molecular
docking studies by substantiating the in-vivo results with in-silico studies. The comparative docking of
Penicillin binding protein 4and E.coli Penicillin Binding Protein 6with compounds 6c, 9d, 6h, and 9e
and the standard Ampicillin exhibited good affinity.
Table 6
:
Dock score of synthesized molecules 6a-h and 9a-hfrom Glide Docking:
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Staphylococcus aureus
PDB ID:3HUN
Dock score
Escherichia coli
PDB ID:3ITA
Dock score
compounds
(K cal/mol)
(K cal/mol)
-3.660
-3.471
-6.131
-3.570
-3.101
-2.785
-3.043
-2.470
6a
6b
6c
6d
-4.077
-3.667
-3.458
-3.546
-3.092
-2.958
-2.351
-4.224
6e
6f
6g
6h
-4.484
-4.289
-3.767
-3.367
-2.836
-3.090
9a
9b
9c
-2.900
9d
-7.148
-4.385
-4.347
-4.518
9e
9f
9g
-4.396
-2.814
-3.272
-3.923
-3.181
9h
Ampicillin
-7.730
-4.883
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Fig. 8 Docked pose of 9d(a) and Ampicillin (b) in the protein active site. Showing the hydrogen
bond interaction (yellow lines) with GLU 297, ASN 138 and ARG 300, SER 262 respectively in
Staphylococcus aureus (PDB.ID-3HUN).
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(b)

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Fig. 9 Docked pose of 9e (a) and Ampicillin (b) in the protein active site. Showing the hydrogen
bond interaction (yellow lines) with ALA 306, GLN 331 and ALA 306 , LYS 305respectively in
E.Coli (PDB.ID3ITA).
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(b)
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Figure 10: Docked pose 6c (a) and 6h (b) in the protein active site of Staphylococcus aureus
(PDB.ID-3HUN), E.coli (PDB.ID-3ITA) respectively
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(a)
(b)
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3. Conclusions:
In conclusion, we have synthesized a novel series of imidazole based 1,2,3-riazole moites by using
click reaction followed by MCR and vice versa starting from 4-hydroxy benzaldehyde and all the
newly synthesized compounds were confirmed by 1H NMR C NMR, IR and mass spectra. in- vitro
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antioxidant and anti-microbial activity evaluation showed that most of the synthesized imidazole -
1,2,3-triazole hybrids exhibited good to excellent activity. These results clearly shows that imidazol-
1,2,3 -triazole motifs have biological significance further optimization of these identified compounds

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as well as their structural modifications are in progress in order to enhance the efficacy against above
activities. Microwave irradiation method was the best method as compared with conventional heating
method, because it offered excellent yields, reduced the reaction times and also environmental friendly
reactions.
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4. Experimental:
4.1 General experimental methods:
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All the reactions were performed in oven dried apparatus. Reactions were monitored by thin layer
chromatography (TLC) on silica gel plates (60 F254), visualizing with ultraviolet light/ iodine vapours,
column chromatography was performed on silica gel (60-120 mesh) using distilled hexane and ethyl
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acetate solvents.1H NMR and C NMR spectra were determined in CDCl3 and some of in DMSO by
using 400 and 100 MHz spectrometers respectively (Instrument Bruker Avance II 400MHz). Mass
spectra were recorded on QSTAR XL GCMS mass spectrometer. Infrared spectra were recorded on a
shimadzu FT-IR-8400s spectrometer. Melting points were determined in open glass capillary tube on a
Gallen-Kamp MFB-595 apparatus and were uncorrected.
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4.2.1 General procedure for the preparation of 4-((1-aryl-1H-1,2,3-triazole)methoxy) benzaldehydes
( 4a-h):
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The synthesis of above compounds (4a-h) compounds we started with 4-hydroxy –benzaldehyde (1) was
propargylated by propargyl bromide in dry DMF and dry K2CO3 25-30 oC under stirring affording the o-
propargylated benzaldehyde (2) in high yields. The o-propargylated benzaldehyde (2) were reacted with
different aryl azides (3a-h) using Click reaction in CuSO4·5H2O, Sodium ascorbate to form 1,2,3-triazole
containing benzaldehyde(4a-h) was done according to the previous 11.
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4.2.2 General procedure for the preparation of 4-((4-(4,5-diphenyl-1H-imidazol-2-
yl)phenoxy)methyl)-1-aryl-1H-1,2,3-triazoles (6a-h) using the click followed by MCR reaction:
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The synthesis of title compounds (6a-h) was performed in two different techniques (Scheme-1):
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a. Conventional method:
The synthesis of title compounds (6a-h) (Scheme-1):To a stirred mixture of 4-((1-aryl-1H-1,2,3-
triazol-4-yl)methoxy) benzaldehydes (4a-h) (0.2 mmol), benzil (5) (0.2 mmol) and ammonium
acetate (0.8 mmol) in 5 ml ethanol taken in a 100 ml round bottomed flasks catalytic amounts of

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Iodine and acetic acid were added simultaneously. The reaction vessels were fitted to a reflux
condensers and refluxed at 80°C for 4-5 hours. The completion of reactions were monitored by
TLC. After the completion of reactions the contents of the flasks were cooled to room temperature
and dropped in a 100 ml beakers containing crushed ice. Solids obtained at the bottom was filtered
under buchner funnel and dried in vacuum at reduced pressure to yield crude compounds which
were purified by column chromatography using hexane/ ethyl acetate (1:3 v/v) to afford 4-((4-(4,5-
diphenyl-1H-imidazol-2-yl)phenoxy)methyl)-1-aryl-1H-1,2,3-triazoles (6a-h) gave moderate
yields 60- 64%.
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b. Microwave method:
To the mixture of 4-((1-aryl-1H-1,2,3-triazol-4-yl)methoxy)benzaldehydes (4a-h) (0.2 mmol), benzil
(5) (0.2 mmol) and ammonium acetate (0.8 mmol) in 5 ml ethanol taken in a 100 ml beakers catalytic
amounts of Iodine and acetic acid were added and treated under microwave irradiation at 180 W for 3-
5 min. The completions of reactions were monitored by TLC at regular intervals of 30 sec. After the
completion of reactions the contents of the flasks were cooled to room temperature and dropped in a
100 ml beakers containing crushed ice. Solids obtained at the bottom was filtered under buchner
funnel and dried in vacuum at reduced pressure to yield crude compounds which were purified by
column chromatography using hexane/ ethyl acetate (1:3 v/v) to afford 4-((4-(4,5-diphenyl-1H-
imidazol-2-yl)phenoxy)methyl)-1-aryl-1H-1,2,3-triazoles (6a-h) gave excellent yields 90-95%
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Comparison of the result obtained under conventional heating method and microwave irradiation is
presented in Table 7
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Table 7: Yields of compounds under conventional heating and microwave irradiation methods
Conventional heating (A)
Microwave irradiation (B)
Compound
Number
Time (hr)
Yield (%)
Time (min)
Yield (%)
4
4
5
4
5
5
4
4
62
60
60
63
62
61
64
62
3
5
3
4
4
5
4
3
90
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92
95
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95
90
92
6a
6b
6c
6d
6e
6f
6g
6h

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4.2.3 General experimental procedure for the synthesis of 4-(4,5-diphenyl-1H-imidazol-2-yl)phenol
(7):
One-pot multi component reaction proceeds with 4-hydroxy benzaldehyde (1),benzil (5), ammonium
acetate in presence of ethanol, acetic acid in iodine mixture under microwave activation at 180 W for
3-5 min afford for the target compound (7) according to the known procedure from the previous
reports12
.
4.2.4 General experimental procedure for the synthesis of 4,5-diphenyl-1-(prop-2-yn-1-yl)-2-(4-
(prop-2-yn-1-yloxy)phenyl)-1H-imidazole (8):
To a well stirred suspension of dry (4 equivalents/ 12.7mmol) K2CO3 in 10 ml DMF, was added a
solution of (1 equivalent/ 3.02 mmol) 4-(4,5-diphenyl-1H-imidazol-2-yl)phenol (7)in DMF(5 ml).
After the reaction was stirred for 30 min, a solution of 3-bromoprop-1-yne ( 80% in toluene) (2.4
equivalents/ 7.6mmol) was added in a drop wise manner and the mixture was stirred at room
temperature for 8 hours and the progress of the reaction was monitored by TLC. After the completion
of reactions 50 ml of ice cold water was added to the residue, the solid separated, filtered and washed
with excess of water and dried in vacuum to obtain the pure 4,5-diphenyl-1-(prop-2-yn-1-yl)-2-(4-
(prop-2-yn-1-yloxy)phenyl)-1H-imidazole (8) gave high yields (%) 90,mp 235-237oC; 1H NMR (400
MHz, DMSO) δ 7.88 (m, 2H), 7.55-7.45 (m, 6H), 7.23-7.10 (m, 6H), 4.76 (d, J = 2.32 Hz, 2H, OCH2),
4.47 (d, J = 2.44 Hz, 2H, N-CH2), 2.55 (t, , J = 2.32 Hz, 1H, -CH), 2.45 (t, J = 2.44 Hz, 1H, -CH).
4.2.5 General experimental procedure for the synthesis of 4-((4-(4,5-diphenyl-1-((1-phenyl-1H-1,2,3-
triazol-4-yl)methyl)-1H-imidazol-2-yl)phenoxy)methyl)-1-phenyl-1H-1,2,3-triazol
(9a-h)
derivatives
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The synthesis of title compounds (9a-h) was performed in two different techniques (Scheme-2):
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a. Conventional method:
To a mixture of aryl azides (3a-h) (0.52 mmol) and 4,5-diphenyl-1-(prop-2-yn-1-yl)-2-(4-(prop-2-yn-
1-yloxy)phenyl)-1H-imidazole (8) ( 0.26 mmol) in DMF/ water ( 3:1 v/v) (5 ml), 10 mol%
CuSO4·5H2O and 10 mol% sodium ascorbate were added and stirred for 4 hr at 50°C. After
completion of reaction (as indicated by TLC), the resulting mixture was added to crushed ice taken in
a beaker. The solid separated was filtered and dried under reduced pressure in vacumm. The crude
product thus obtained was purified by column chromatography hexane/ ethyl acetate (2:3 v/v) to
afford
pure
4-((4-(4,5-diphenyl-1-((1-phenyl-1H-1,2,3-triazol-4-yl)methyl)-1H-imidazol-2-
yl)phenoxy)methyl)-1-phenyl-1H-1,2,3-triazole derivatives (9a-h). gave moderate yields (%) 60- 65.

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b. Microwave irradiation method:
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To a mixture of aryl azides (3a-h) (0.52 mmol) and 4,5-diphenyl-1-(prop-2-yn-1-yl)-2-(4-(prop-2-yn-
1-yloxy)phenyl)-1H-imidazole (8) ( 0.26 mmol) in DMF/ water ( 3:1 v/v) (5 ml), 10 mol%
CuSO4·5H2O and 10 mol% sodium ascorbate were added and subjected to microwave irradiation at
100 W for 2-3 min at regular intervals of 20 sec each. The reaction was monitored by TLC and after
completion of reaction the resulting mixture was added to crushed ice taken in a beaker. The solid
separated was filtered and dried under reduced pressure in vacuum. The crude product thus obtained
was purified by column chromatography hexane/ ethyl acetate (2:3 v/v) to afford pure4-((4-(4,5-
diphenyl-1-((1-phenyl-1H-1,2,3-triazol-4-yl)methyl)-1H-imidazol-2-yl)phenoxy)methyl)-1-phenyl-
1H-1,2,3-triazole derivatives (9a-h) gave high yields (%) 80-90.
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Comparison of the result obtained under conventional heating method and microwave irradiation is
presented in Table 8.
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Table 8: Conventional heating and microwave irradiation optimization for the synthesis of title
compounds 9a-h.
Conventional heating (A)
Microwave irradiation (B)
Compound
Number
9a
Time (hr)
Yield (%)
Time (min)
Yield (%)
4
4
5
4
5
5
4
4
61
63
63
65
65
64
60
61
3
5
3
4
4
5
4
3
87
90
82
86
90
85
86
89
9b
9c
9d
9e
9f
9g
9h
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4.3 Biological activities:
4.3.1. Antimicrobial activity
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The antimicrobial activities of all the synthesized imidazole-1,23-triazole hybrid derivatives were
tested by the presence or absence of inhibition zones and zone diameter against 6 microbial strains:
gram-positive bacterium (S. Aureus ATCC 6538P, B. cereus ATCC 11778); two gram-negative
bacteria (E. coli ATCC 853, P.vulgaris ATCC 7829, Aspergillus fumigatus (ATCC 13073), one yeast
(Candida albicans NRRL Y-477). The results from the analysis of antimicrobial effects square
measure summarized in Table1. The compounds were compared with the quality antibacterial
Ampicillin and also the yeast/antifungal drug Fluconazole. The Minimum Inhibitory concentration
(MIC) of all compounds was conjointly screened as listed in Table1. All tested compounds showed
high MIC 1 mg /mL, against gram-positive and gram-negative bacterium compared to the reference
drug Ampicillin (100 µg /mL). It was found that compounds 6c, 6d, 6f, 9d,9e, 9fshowed variable
medicinal drug activity against gram-positive and Gram-negative bacterium. The best potent
molecules showed good MIC values (9d, 6hS. aureus),(9e, 6hB. cereus),(9e, 6hE.
coli),(9e,6cP.Vulgaris). All synthesized compounds were screened for the antifungal activity against
two fungal stains A. fumigates, C.albicans. Among all tested compounds, compound 9d and 9e
showed significant activity against both tested fungal pathogens with MIC values 100 µg/mL,
remaining synthesized compounds almost inactive against tested fungal pathogens strain square
measure tabulated in Table1.
367 4.3.2 Antioxidant activity:
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a. DPPH radical scavenging activity:
The antioxidant activity of all synthesized compounds (6a-h) and (9a-h) were measured against 2,2-
diphenyl-1-picrylhydrazyl (DPPH) radical. The DPPH procedure is one among the foremost effective
strategies for evaluating the concentration of radical scavenging materials active by a chain-breaking
mechanism. Briefly, 0.1 mM solution of DPPH was prepared in ethanol and 0.5 mL of this solution
was added 1.5 mL of synthesised solution in ethanol at different concentrations (10-250 µg/mL).These
solutions were vortexed thoroughly and incubated in dark. A half hour later, the absorbance was
measured at 517 nm against blank samples. Lower absorbance of the reaction mixture indicates higher
DPPH free radical scavenging activity. A standard curve was prepared using different concentrations
of DPPH. The capability to scavenge the DPPH radical was calculated using the following equation-%

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of Inhibition = (A0 - Ab) / A0 100.Where AC is the absorbance of the control which contains DPPH
solution and AS is the absorbance in the presence of synthesized solution. The results of DPPH method
were tabulated in table-2.Compound 9e was the excellent radical scavenger with associate % of
inhibition worth of 250µg/mL. Furthermore compound 9c showed a best radical scavenging activity
with % of inhibition at 250µg/mL. Compounds 6h, 9h conjointly showed good scavenging activities
with 10, 50, 100, 250µg/mL.
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b. Hydrogen peroxide radical scavenging activity
1ml of (10‐250µg/ml) test drug/standard (Ascorbic acid) was added to 0.6ml of Hydrogen peroxide
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solution (PharmaTech labs, Hyderabad) in phosphate buffer (PH‐7.4). After incubating for10 minutes
at 37oC the absorbance was measured at 230nm.Corresponding blanks were taken. The experiment
was performed in triplicate. The absorbance of hydrogen peroxide in phosphate buffer as control was
measured at 230nm. The scavenging effect (%) was measured using equation (1).Hydrogen peroxide
produces hydroxyl radicals in cells. Scavenging of these radicals by the test drug is used as a test for
antioxidant activity. The reduction of these radicals is seen by the decreased absorbance at 230nm with
increasing concentration of the test drug. % of Inhibition = 100 (A0 - Ab) / A0 Compounds 9c, 9f was
the strongest radical scavenger with associate % of inhibition worth of 250µg/mL. Furthermore
compound 6f, 6b showed a good radical scavenging activity with % of inhibition at 250µg/mL. The
results of H2O2 method were given in table-3.
c. Nitric oxide scavenging activity assay
Nitric oxide radical scavenging activity was determined according to the method reported by Garratt.
Sodium nitroprusside in aqueous solution at physiological pH spontaneously generates nitric oxide,
which interacts with oxygen to produce nitrite ions. 2 mL of 10 mM sodium nitroprusside in 0.5 mL
phosphate buffer saline (pH 7.4) was mixed with 0.5 mL of test solution at various concentrations and
the mixture incubated at 25oC for 150 min. From the incubated mixture 0.5 mL was taken out and
added into 1.0 mL sulfanilic acid reagent (33% in 20% glacial acetic acid) and incubated at room
temperature for 5 min. Finally, 1.0 mL naphthyl ethylene diamine dihydrochloride (0.1% w/v) was
mixed and incubated at room temperature for 30 min before measuring the absorbance at 540 nm was
measured with a spectrophotometer. The nitric oxide radicals scavenging activity was calculated.
% of Inhibition = (A0 - Ab) / A0 100. The results of Nitric oxide method were tabulated in table-4.

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Compound 6h was the excellent nitric oxide radical scavenger with associate % of inhibition worth of
250µg /mL. Furthermore compound 9c, 9a, 9h showed a good nitric oxide radical scavenging activity
with % of inhibition at seventy four 250µg/mL.
d. Reducing power assay (FRAP)
The synthesised compounds (0.75 ml) at various concentrations was mixed with 0.75 mL of phosphate
buffer (0.2 M, pH 6.6) and 0.75 mL of potassium hexacyanoferrate [K3Fe(CN)6] (1%, w/v), followed
by incubating at 50°C in a water bath for 20 min. The reaction was stopped by adding 0.75 mL of
trichloroacetic acid (TCA) solution (10%) and then centrifuged at 3000 r/min for 10 min. 1.5 ml of the
supernatant was mixed with 1.5 mL of distilled water and 0.1 mL of ferric chloride (FeCl3)solution
(0.1%, w/v) for 10 min. The absorbance at 700 nm was measured as the reducing power. Higher
absorbance of the reaction mixture indicated greater reducing power. % of Inhibition = 100 (A0 - Ab) /
A0. Higher absorbance of the reaction mixture indicated greater reducing power. The results of FRAP
method were tabulated in table-5.Compound 9c was the excellent Reducing power assay% of
inhibition worth of 250µg /mL. Further compounds 6d, 9d, 9h showed good Reducing power assay
with % of inhibition at 250µg/mL.
4.3.3In Silico Molecular Docking Studies:
The synthesized molecules of series 6a-h and 9a-h were selected for performing molecular docking
studies by using Schrödinger’s molecular docking software. Molecules were built in maestro build
panel and prepared by Lig prep 2.313module by applying default parameters. Crystal structures of
Staphylococcus aureus. Penicillin binding protein 4and E.coli Penicillin Binding Protein 6 (pdb id:
3HUN14 3ITA15were downloaded from protein data bank (www.rcsb.org). The protein was prepared
using protein preparation wizard of Schrödinger’s molecular docking software, in this target
preparation, all water molecules were removed and hydrogen atoms were added to the target. Grid was
generated around the active site of the protein by selecting the co-crystalized ligand. Receptor van der
Waals scaling for the nonpolar atoms was kept 0.916Low energy conformation of the ligands were
selected and docked into the grid using extra precision (XP) docking 17.Dock score and energy of each
ligand was analysed for interactions with the receptor.

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Acknowledgements:
The authors are thankful to the Head, Department of chemistry, Osmania University, Hyderabad for
providing laboratory facilities. E Praveen Kumar is thankful to CSIR-UGC for financial assistance in
the form of fellowship. We thank CFRD analytical team for providing spectral analytical facilities.
443 Spectral data:
444 1-(3-chlorophenyl)-4-((4-(4,5-diphenyl-1H-imidazol-2-yl)phenoxy)methyl)-1H-1,2,3-triazole(6a)
o
445 Yield 90%, mp: 135-138 C; Rf = 0.40 (EtOAc:n-Hexane 2:3); IR (KBr): 3061, 1595,1490, 1026, 833,
446 cm–1;1H NMR (400 MHz, CDCl3) δ 8.07 (s, 1H), 7.88 (d, J = 8.8 Hz, 2H), 7.80 (t, J = 1.9 Hz, 1H), 7.67 –
13
447 7.54 (m, 5H), 7.45 (m, 2H), 7.37 – 7.28 (m, 6H), 7.08 (d, J = 8.8 Hz, 2H), 5.33 (s, 2H); C NMR (100
448 MHz, CDCl3) δ 158.0, 145.9, 144.8, 137.6, 135.6, 130.8, 129.0,128.5, 127.8, 127.3, 127.0, 121.0, 120.8,
449 118.5, 115.0, 61.8; LC-MS m/z: 504[M+H]+; Anal. Calcd for C30H22ClN5O:C, 71.49; H, 4.40; N, 13.90,
450 Found: C, 71.40; H, 4.38; N, 13.85.
451 1-(4-chlorophenyl)-4-((4-(4,5-diphenyl-1H-imidazol-2-yl)phenoxy)methyl)-1H-1,2,3-triazole(6b)
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Yield 94%, mp: 135-138 oC; Rf = 0.40 (EtOAc:n-Hexane 2:3); IR (KBr): 3070, 1606,1498, 1051, 835,
cm–1;1H NMR (400 MHz, DMSO) δ 12.53 (s, 1H), 9.02 (s, 1H), 8.05 (d, J = 8.8 Hz, 2H), 7.98 (d, J =
8.9 Hz, 2H), 7.70 (d, J = 8.8 Hz, 2H), 7.55-7.3 (m,12H), 5.32 (s, 2H).13C NMR (101 MHz, DMSO)
δ163.0, 150.4,148.8 141.7, 140.3, 140.2, , 137.9 , 137.1, 136.1, 134.7, 133.5, 133.2,131.9, 128.5,
127.9, 126.7, 119.8, 66.0. LC-MS m/z: 504[M+H]+; Anal. Calcd for C30H22ClN5O:C, 71.49; H, 4.40;
N, 13.90; Found: C, 71.40; H, 4.38; N, 13.85.
4-((4-(4,5-diphenyl-1H-imidazol-2-yl)phenoxy)methyl)-1-(p-tolyl)-1H-1,2,3-triazole(6c)
Yield 92%, mp: 195-197 oC; Rf = 0.5 (EtOAc:n-Hexane 2:3); IR (KBr): 3053, 1608, 1494, 1243, 1026
cm–1;1H NMR (400 MHz, CDCl3) δ 8.02 (s, 1H), 7.85 (d, J = 8.5 Hz, 2H), 7.57 (m, 6H), 7.30 (m,
13
8H), 7.04 (d, J = 8.5 Hz, 2H), 5.27 (s, 2H), 2.42 (s, 3H); C NMR (101 MHz, CDCl3) δ 158.7,139.1,
130.2, 129.9, 129.0, 128.5, 127.8, 127.3,126.9, 123.3, 121.0,120.5 115.1, 62.0, 21.1; LC-MS m/z: 484
[M+H]+; Anal. Calcd for C31H25N5O: C, 77.00; H, 5.21; N, 14.48; Found: C, 76.92; H, 5.17; N, 14.41.

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4-((4-(4,5-diphenyl-1H-imidazol-2-yl)phenoxy)methyl)-1-(2-methoxyphenyl)-1H-1,2,3-
triazole(6d)
Yield 95%, mp: 188-190oC; Rf = 0.43 (EtOAc:n-Hexane 2:3); IR (KBr): 3055, 1610, 1496, 1246,
1028 cm–1;1H NMR (400 MHz, CDCl3) δ 8.01 (s, 1H), 7.84 (d, J = 8.6 Hz, 2H), 7.55 (m, 6H), 7.30
(m, 8H), 7.01 (d, J = 8.7 Hz, 2H), 5.23 (s, 2H), 2.42 (s, 3H); 13C NMR (101 MHz, CDCl3) δ
160.9,159.0 , 145.8 , 145.1 , 143.9 , 132.0 , 131.9,131.3,129.5,128.5, 128.0 , 127.7, 127.7 ,125.3
,122.7, 119.3,115.1,110.8, 61.6 , 56.4; LC-MS m/z:500 [M+H]+; Anal. Calcd forC31H25N5O2: C,
74.53; H, 5.04; N, 14.02; Found: C, 74.49; H, 5.00; N, 14.00.
4-((4-(4,5-diphenyl-1H-imidazol-2-yl)phenoxy)methyl)-1-(2-methoxy-4-nitrophenyl)-1H-1,2,3-
triazole(6e)
Yield 93%, mp: 105-108oC; Rf = 0.4 (EtOAc:n-Hexane 2:3); IR (KBr): 3059, 1606, 1344, 1249, 1018
cm–1;1H NMR (400 MHz, CDCl3) δ 8.45 (s, 1H), 8.16 (s1,H), 8.02 (d,J = 7.5 Hz, 2H2H), 7.88 (d, J =
8.5 Hz, 2H 2H), 7.75(d, J = 7.5 Hz, 2H), 7.5- 7.38 (m, 7H), 6.97 (d, J = 8.5 Hz, 2H), 5.21 (s, 2H), 4.04
13
(s, 3H); C NMR (101 MHz, CDCl3) δ150.6, 148.1,145.9, 145.6, 143.5 , 130.8 , 130.6, 130.3,128.6,
128.1 ,126.5, 126.4 ,125.3, 125.1, 116.6, 115.1,107.8,61.6,56.9; LC-MS m/z:545 [M+H]+; Anal.
Calcd forC31H24N6O4: C, 68.37; H, 4.44; N, 15.43; Found: C, 68.29; H, 4.40; N, 15.36.
4-((4-(4,5-diphenyl-1H-imidazol-2-yl)phenoxy)methyl)-1-(4-methoxy-2-nitrophenyl)-1H-1,2,3-
triazole(6f)
Yield 95%, mp: 148-151 oC; Rf = 0.4 (EtOAc:n-Hexane 2:3); IR (KBr): 3080, 1612, 1541, 1238, 1029
cm–1;1H NMR (400 MHz, CDCl3) δ8.04(s, 1H),8.01(s, 1H), 7.09 (d, J = 7.5 Hz, 2H), 7.61-
7.42(m,7H) 7.38-7.21(m,6H),6.91 (d, J = 7.1 Hz, 2H), 5.16 (s, 2H), 3.93 (s, 3H); 13C NMR (101 MHz,
CDCl3) δ 160.9, 159.0 , 145.8, 145.1, 143.9, 131.3, 129.5, 128.5, 128.0, 127.7 , 127.3, 125.3,
122.7,119.3, 115.1, 110.8,61.9,56.4; LC-MS m/z: 545 [M+H]+; Anal. Calcd for C31H24N6O4:C, 68.37;
H, 4.44; N, 15.43; Found: C, 68.25; H, 4.33; N, 15.38.
4-((4-(4,5-diphenyl-1H-imidazol-2-yl)phenoxy)methyl)-1-(2-nitrophenyl)-1H-1,2,3-triazole (6g)
Yield 90%, mp: 148-150oC; Rf = 0.5 (EtOAc:n-Hexane 2:3); IR (KBr): 3081, 1608, 1537, 1236, 1010
cm–1;1H NMR (400 MHz, DMSO) δ 12.73 (s, 1H), 8.89 (s, 1H), 8.25 (d, J = 7.9 Hz, 2H), 8.06 (d, J =
8.6 Hz, 2H), 7.92 (m, 4H), 7.53 (d, J = 7.3 Hz, 4H), 7.42 – 7.20 (m, 7H), 5.34 (s, 2H). 13C NMR (101
MHz, DMSO) δ 158.2 , 145.4 , 144.0, 143.3 , 134.4 , 131.2 , 129.0 , 128.4,127.7,127.6 , 126.8 ,126.0 ,
125.5 , 114.9 , 60.9; LC-MS m/z: 515 [M+H]+; Anal. Calcd for C30H22N6O3 ;C, 70.03; H, 4.31; N,
16.33;Found: C, 70.00; H, 4.26; N, 16.21.

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Yield92%, mp: 148-150oC; Rf = 0.5 (EtOAc:n-Hexane 2:3); IR (KBr): 3082, 1602, 1529, 1246, 1045
cm–1;1H H NMR (400 MHz, DMSO) δ 12.55 (s, 1H), 9.21 (s, 1H), 8.48 (d, J = 9.0 Hz, 2H), 8.27 (d, J
= 9.0 Hz, 2H), 8.05 (d, J = 8.7 Hz, 2H), 7.25 (m, 11H), 5.36 (s, 2H).13C NMR (101 MHz, DMSO)
δ158.2 , 145.4 , 144.0, 143.3 , 134.4 , 131.2 , 129.0 , 128.4,127.7,127.6 , 126.8 ,126.0 , 125.5 , 114.9 ,
60.9. ; LC-MS m/z: 515 [M+H]+; Anal. Calcd for C30H22N6O3 ;C, 70.03; H, 4.31; N, 16.33;Found: C,
70.00; H, 4.26; N, 16.21.
1-(3-chlorophenyl)-4-((2-(4-((1-(3-chlorophenyl)-1H-1,2,3-triazol-4-yl)methoxy)phenyl)-4,5-
diphenyl-1H-imidazol-1-yl)methyl)-1H-1,2,3-triazole(9a)
Yield 87%, mp: 188-190oC; Rf = 0.3 (EtOAc:n-Hexane 2:3); IR (KBr): 1595, 1489, 1240, 1037, 837
cm–1;1H NMR (400 MHz, CDCl3) δ 8.16 (s, 1H), 7.82 (m, 3H), 7.65 (d, J = 7.7 Hz, 1H), 7.57 – 7.39
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(m, 14H), 7.23 – 7.11 (m, 4H), 6.97 (s, 1H), 5.32 (s, 2H),5.26(s,2H); C NMR (101 MHz, CDCl3) δ
158.8 , 147.7,144.9,144.7 , 137.7, 137.4, 135.6 ,135.6, 134.0 , 131.2, 131.0 ,130.8, 129.1,129.0, 128.9,
128.1, 126.9 , 126.5 ,123.7, 120.9 - 120.1, 118.5 , 118.2 , 115.0, 61.9 , 40.4; LC-MS m/z: 695[M+H]+;
Anal. Calcd for C39H28Cl2N8O; C,67.34, H, 4.06, N,16.11 Found; C, 67.29; H, 4.02; N, 16.08.
1-(4-chlorophenyl)-4-((2-(4-((1-(4-chlorophenyl)-1H-1,2,3-triazol-4-yl)methoxy)phenyl)-4,5-
diphenyl-1H-imidazol-1-yl)methyl)-1H-1,2,3-triazole(9b)
Yield 90%, mp: 222-225 oC 0C-; Rf = 0.5 (EtOAc:n-Hexane 2:3); IR (KBr): 1593, 1504, 1249, 1041,
827 cm–1;1H NMR (400 MHz, CDCl3) δ 8.05 (s, 1H), 7.82-7.80 (d, J=8.6Hz, 2H), 7.70-7.69 (d,
J=8.8Hz, 2H), 7.53-7.43 (m, 11H), 7.36-7.34 (d, J=7.4Hz, 2H), 7.21-7.18 (m, 2H), 7.15-7.12(m, 3H),
6.95 (s, 1H), 5.34 (s, 2H), 5.27 (s, 2H); 13C NMR (101 MHz, CDCl3) δ158.8, 147.6, 144.8,144.7,
138.0, 135.3, 135.1, 134.7, 134.1, 131.2, 131.0, 129.9, 129.1, 128.8, 128.1,126.9, 126.5,123.8, 121.7,
121.3,120.9,120.0, 115.0, 61.9, 40.4; LC-MS m/z:695 [M+H]+; Anal. Calcd for C39H28Cl2N8O: C,
67.34; H, 4.06; N, 16.11;; Found: C, 67.30; H, 4.01; N, 16.06.
4-((4-(4,5-diphenyl-1-((1-(p-tolyl)-1H-1,2,3-triazol-4-yl)methyl)-1H-imidazol-2-
yl)phenoxy)methyl)-1-(p-tolyl)-1H-1,2,3-triazole(9c)
Yield 82%, mp: 175-178oC; Rf = 0.4 (EtOAc:n-Hexane 2:3); IR (KBr): 1596, 1519, 1242, 1026, 813
cm–1;1H NMR (400 MHz, CDCl3) δ 8.03 (s, 1H), 7.82 (d, J = 8.5 Hz, 2H), 7.62 (d, J = 8.2 Hz, 2H),
7.54 (d, J = 7.4 Hz, 2H), 7.45 – 7.31 (m, 11H), 7.19 (m, 5H), 6.97 (s, 1H), 5.35 (s, 2H), 5.28 (s, 2H),
2.43 (s,3H),2.40(s,3H); 13C NMR (101 MHz, CDCl3) δ 158.9, 144.5, 139.0, 138.0, 134.6, 134.4,
131.2, 131.0, 130.2, 129.1, 128,8,128.1, 126.9, 126.4, 121.0, 120.5, 120.1, 115.0, 62.1, 40.5, 21.1;

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LC-MS m/z: 655 [M+H]+; Anal. Calcd for C41H34N8O: C, 75.21; H, 5.23; N, 17.11;Found: C, 75.18;
H, 5.17; N, 17.06.
1-(2-methoxyphenyl)-4-((2-(4-((1-(2-methoxyphenyl)-1H-1,2,3-triazol-4-yl)methoxy)phenyl)-4,5-
diphenyl-1H-imidazol-1-yl)methyl)-1H-1,2,3-triazole(9d)
Yield 86%, mp: 108-110 oC; Rf = 0.4 (EtOAc:n-Hexane 2:3); IR (KBr): 1604, 1502, 1244, 1020, 839
cm–1;1H NMR (400 MHz, CDCl3) δ 8.21 (s, 1H), 7.75(m,4H), 7.53-7.37 (m, 9H), 7.19-7.03 (m, 10H),
5.34 (s, 2H), 5.27 (s, 2H), 3.88(s, 3H), 3.81 (s, 3H); 13C NMR (101 MHz, CDCl3) δ 157.1, 149.2,
149.1, 145.9, 142.9, 142.2, 136.0, 132.5 1293, 128.9,128.3,127.1, 126.2, 125.0, 123.6, 123.4, 122.3,
119.3, 118.4, 113.3,110.3,60.2, 54.0, 38.9, LC-MS m/z: 687[M+H]+; Anal. Calcd for C41H34N8O3 :C,
71.70; H, 4.99; N, 16.32; Found: C, 71.62; H, 4.87; N, 16.28.
1-(2-methoxy-4-nitrophenyl)-4-((2-(4-((1-(2-methoxy-4-nitrophenyl)-1H-1,2,3-triazol-4-
yl)methoxy)phenyl)-4,5-diphenyl-1H-imidazol-1-yl)methyl)-1H-1,2,3-triazole(9e)
Yield 90%, mp: 96-98 oC; Rf = 0.37 (EtOAc:n-Hexane 2:3); IR (KBr):1610, 1531, 1344, 1242, 1020
cm–1;1H NMR H NMR (500 MHz, CDCl3) δ 8.40 (s ,1H), 8.14 (m, 1H), 8.03 – 7.97 (m, 4H), 7.93 –
7.88 (J=7.2HZ, 2H), 7.79 (d, J = 6.6 Hz, 2H), 7.52 – 7.37 (m, 10H), 7.20 – 7.14 (m, 3H), 5.37 (S, 2H),
5.32 (S, 2H), 4.06 (S, 3H), 4.00 (S, 3H).13C NMR (101 MHz, CDCl3) δ 157.1,, 148.8, 148.6, 146.3
142.4, 142.0, 136.2, 135.9, 132.4, 129.3,128.7, 126.3, , 125.1, 124.7, 124.7, 123.4, 123.2, 122.2, 114.9,
1133 106.0, 71.9, 60.1, 55.1; LC-MS m/z: 777 [M+H]+; Anal. Calcd for C41H32N10O7: C, 63.40; H,
4.15; N, 18.03; Found: C, 63.38; H, 4.11; N, 17.09.
1-(4-methoxy-2-nitrophenyl)-4-((2-(4-((1-(4-methoxy-2-nitrophenyl)-1H-1,2,3-triazol-4-
yl)methoxy)phenyl)-4,5-diphenyl-1H-imidazol-1-yl)methyl)-1H-1,2,3-triazole(9f)
o
Yield 85%, mp: 79-82 C; Rf = 0.36 (EtOAc:n-Hexane 2:3); IR (KBr): 1608, 1535, 1352, 1240, 1041
cm–1; 1H NMR (400 MHz, CDCl3) δ 7.90 (s, 1H), 7.77 (d, J = 8.6 Hz, 2H), 7.58 (s, 1H), 7.53 (m, 4H),
7.45 – 7.39 (m, 5H), 7.30 (s,1H), 7.22 – 7.12 (m, 7H), 6.95 (s, 1H), 5.38 (s, 2H), 5.26(s,2H),
3.96(s,3H), 3.94(s,3H); 13C NMR (101 MHz, CDCl3) δ158.8, 156.7, ,145.6,143.0,
142.1,142.0,135.6,129.1,128.8,127.3,127.05,126.9,125.9,124.8,124.4122.9,121.9,120.7,117.1,113.1,10
8.5,59.8,54.2,; LC-MS m/z: 462 [M+H]+; Anal. Calcd forC41H32N10O7: C, 63.40; H, 4.15; N, 18.03;
Found: C, 63.38; H, 4.11; N, 17.09

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1-(2-nitrophenyl)-4-((2-(4-((1-(2-nitrophenyl)-1H-1,2,3-triazol-4-yl)methoxy)phenyl)-4,5-
diphenyl-1H-imidazol-1-yl)methyl)-1H-1,2,3-triazole(9g)
Yield 86%, mp: 218-220 oC; Rf = 0.5 (EtOAc:n-Hexane 2:3); IR (KBr): 1608, 1531, 1344, 1240, 1020
cm–1; 1H NMR (400 MHz, CDCl3) δ 8.11 – 8.03 (m, 2H), 7.96 (s, 1H), 7.81 – 7.64 (m, 7H), 7.53 (d, J
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= 7.1 Hz, 2H), 7.46 – 7.38 (m, 6H), 7.22 – 7.12 (m, 5H), 7.00 (s, 1H), 5.40 (s, 2H), 5.28 (s, 2H); C
NMR (101 MHz, CDCl3) δ 158.9 , 144.3,133.9, 133.8, 131.2,130.9,130.1,129.8.129.1,
128.1,128.0,127.7,127.0,125.5,124.6,123.6,115.3,61.9,40.5; LC-MS m/z: 717 [M+H]+; Anal. Calcd
for C39H28N10O5: C, 65.36; H, 3.94; N, 19.54; Found: C, 65.25; H, 3.88; N, 19.46.
1-(4-nitrophenyl)-4-((2-(4-((1-(4-nitrophenyl)-1H-1,2,3-triazol-4-yl)methoxy)phenyl)-4,5-
diphenyl-1H-imidazol-1-yl)methyl)-1H-1,2,3-triazole(9h)
Yield 89%, mp: 207-210oC; Rf = 0.5 (EtOAc:n-Hexane 2:3); IR (KBr): 1608, 1534, 1342, 1240, 1020
cm–1;1H NMR (400 MHz, DMSO) δ 9.22 (s, 1H), 8.44 (m, 4H), 8.33 (s, 1H), 8.25 (d, J = 9.1 Hz, 2H),
8.07 (d, J = 9.1 Hz, 2H), 7.78 (d, J = 8.7 Hz, 2H), 7.48-7.35 (m, 7H), 7.21 (m, 4H), 7.13 (m 1H), 5.35
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(s, 2H), 5.25 (s, 2H); C NMR (101 MHz, DMSO) δ 158.3, 146.8,146.7, 144.8, 144.3, 140.7, 140.4,
136.3, 134.5, 130.8, 130.3, 129.4, 128.9, 128.0,126.1, 125.9, 125.5, 123.4, 121.4, 120.7,120.5, 114.8,
60.9; LC-MS m/z: 717 [M+H]+; Anal. Calcd for C39H28N10O5: C, 65.36; H, 3.94; N, 19.54;; Found: C,
65.31; H, 3.83; N, 19.
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Highlights
•
•
A series of new imidazolo-1,2,3-triazoles was synthesized by microwave method.
The newly synthesized imidazolo-1,2,3-triazoles are screened for antioxidant, antimicrobial activities
shows excellent activities.
•
In-silico molecular docking studies were performed using Schrodinger software. (PDB: 3HUN and PDB:
3ITA) compounds 6c, 6h, 9d and 9e showed maximum dock score and found to exhibit Promising activity.