Syntheses, biological evaluation and photophysical studies of novel 1,2,3-triazole linked azo dyes

Article abstract of DOI:10.1039/c3ra44314k

We have reported synthesis of two novel series of 1,2,3-triazole linked azo dyes using 4-hydroxy-5-methyl-2H-pyran-2-one and sesamol as coupling components in view of the increasing resistance to existing antimicrobial drugs and the need for new antioxidant agents and fluorescent materials. All newly synthesized compounds were evaluated for antibacterial activity, antifungal activity, antioxidant activity and photophysical properties. Antimicrobial activity was evaluated against six microbial strains. Compound 6a was found to be the most potent antibacterial and antifungal agent, while other compounds showed good to moderate antimicrobial activity. Antioxidant activity was evaluated using DPPH free radical scavenging assay and nitric oxide radical scavenging assay. Compound 6b was found to be 5 fold more potent than standard antioxidant BHT. Other compounds showed good antioxidant activity. Photophysical properties of all compounds were also investigated in detail.

Full text of DOI:10.1039/c3ra44314k

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Syntheses, biological evaluation and photophysical
studies of novel 1,2,3-triazole linked azo dyes†
Cite this: RSC Adv., 2014, 4, 5915
a
a
a
Harjinder Singh, Jayant Sindhu, Jitender M. Khurana, Chetan Sharmab
*
and K. R. Anejab
We have reported synthesis of two novel series of 1,2,3-triazole linked azo dyes using 4-hydroxy-5-methyl-
2H-pyran-2-one and sesamol as coupling components in view of the increasing resistance to existing
antimicrobial drugs and the need for new antioxidant agents and fluorescent materials. All newly
synthesized compounds were evaluated for antibacterial activity, antifungal activity, antioxidant activity
and photophysical properties. Antimicrobial activity was evaluated against six microbial strains.
Compound 6a was found to be the most potent antibacterial and antifungal agent, while other
compounds showed good to moderate antimicrobial activity. Antioxidant activity was evaluated using
DPPH free radical scavenging assay and nitric oxide radical scavenging assay. Compound 6b was found
to be 5 fold more potent than standard antioxidant BHT. Other compounds showed good antioxidant
activity. Photophysical properties of all compounds were also investigated in detail.
Received 12th August 2013
Accepted 29th November 2013
DOI: 10.1039/c3ra44314k
www.rsc.org/advances
continues with newly discovered antimicrobial entities. There-
fore development of more potent and effective antimicrobial
1. Introduction
agents is important to overcome the emerging multi-drug
resistance strains of bacteria and fungi.22,23 In recent years,
there have been several attempts to prepare novel conjugates
having more than one active pharmacophores. We have
attempted synthesis of some novel conjugates of 1,2,3-triazoles
and azo groups as antimicrobial agents.
Azo compounds constitute one of the most important chemical
classes of organic compounds owing to their diverse applica-
tions in various elds such as dying textile bers, organic
synthesis, lasers, liquid crystalline displays, and electro-optical
devices. Azo compounds also exhibit biological properties
including antibacterial activity,1–3 pesticidal activities,4 anti-
septic5 and antiprotozoal properties. There has been lot of
research on the synthesis, spectroscopic properties and appli-
cations of these dyes in recent years.6–11 1,2,3-Triazoles also
possess a number of desirable features in the context of
medicinal chemistry and industrial applications. They are
stable to acidic/basic hydrolysis, reductive/oxidative conditions,
and resistant to metabolic degradation. Several members of the
1,2,3-triazole family have shown interesting biological proper-
ties, such as antiallergic,12–14 antibacterial,15 anti HIV activity,16
antitumor,17 cytotoxicity,18 and as glycosidase inhibitors.19 Tri-
azoles have also found applications in herbicides, fungicides,
and dyes.20
2. Results and discussion
2.1 Chemistry
In this work, we have reported the synthesis of two novel series
of 1,2,3-triazole linked azo dyes using 4-hydroxy-5-methyl-2H-
pyran-2-one and sesamol as enol coupling components The
antimicrobial activity, antioxidant activity and photophysical
properties of these 1,2,3-triazoles linked dyes have also been
reported.
Multi-drug resistant bacteria and opportunistic mycoses are
becoming increasingly common and are responsible for
morbidity and mortality.21 Although, several new antimicrobial
agents have been reported, the problem of drug resistance
aDepartment of Chemistry, University of Delhi, Delhi-110007, India. E-mail:
jmkhurana@chemistry.du.ac.in; Fax: +91 11 27666605; Tel: +91 11 27667725-1384
bDepartment of Microbiology, Kurukshetra University, Kurukshetra, Haryana, India
† Electronic supplementary information (ESI) available: Detailed experimental
procedure for antibacterial, antifungal, antioxidant activity, copies of 1H NMR,
13C NMR and mass spectra can be found as supplementary material. See DOI:
10.1039/c3ra44314k
Scheme 1 Reagents and reaction conditions: (a) acetic anhydride (1.1
eq.), water, 60 ꢀC, 20 min; (b) propargyl bromide (1.1 eq.), K2CO3 (2.5
eq.), DMF, 80 ꢀC, 4 h; (c) HCl (36%), ethanol, 60 ꢀC, 3 h.
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Scheme 2 Reagents and conditions: (a) HCl–water (1 : 1), NaNO2 (1 eq.), 0 ꢀC, 15 min; (b) aq. NaOH (12.5 eq.), 4-hydroxy-5-methyl-2H-pyran-2-
one (1 eq.), 0 ꢀC, 45 min; (c) THF–water (60 : 40), ArN3 (1 eq.), CuSO4$5H2O (10 mol%), sodium ascorbate (20 mol%), 60 ꢀC, 3–4 h.
1
The two novel series of 1,2,3-triazole linked azo dyes (4a–4f)
The formation of 4a–4f was conrmed by IR, H NMR, 13C
and (6a–6i) were synthesized as depicted in Scheme 2 and 4, NMR and mass spectral analysis. Dyes 4a–4f can exist in a three
respectively. 4-(Prop-2-ynyloxy)aniline (1), which required to tautomeric forms as shown in Scheme 3. The IR spectra of dyes
initiate the synthesis of desired azo dyes, was prepared from p- 4a–4f did not show any absorption band for hydroxyl group.
aminophenol involving24,25 three step procedure as shown in However, it showed a weak absorption band in the range of
Scheme 1. Reaction of p-aminophenol with acetic anhydride in 3147–3140 cmꢁ1, assigned to imino group and two carbonyl
water at 60 ꢀC gave (4-hydroxyphenyl)acetamide, which on absorption band in the range of 1736–1655 cmꢁ1. The data
reaction with propargyl bromide in presence of K2CO3 in DMF suggests that these dyes exist in a hydrazo–keto form in the
and on subsequent deprotection with HCl yielded 4-(prop-2- solid state. Further evidence for this assignment is provided by
ynyloxy)aniline (1) in high yield (Scheme 1).
the observation that the hydroxyazo OH proton resonates 3–5
The triazole linked azo dyes (4a–4f) were then synthesized by ppm lower then NH proton. Hence, the OH proton resonance
a three step procedure using 4-hydroxy-5-methyl-2H-pyran-2- signal of enol forms is expected to be in region of 9–12 ppm.26,27
one as a enol coupling component (Scheme 2). The diazotiza- In fact, the 1H NMR spectra of dyes 4a–4f showed a signal in the
tion of (1) followed by its coupling with 4-hydroxy-5methyl-2H- range of 16.52–16.58 ppm and no signal in range of 9–12 ppm.
pyran-2-one in basic solution at 0 ꢀC led to the formation of This signal undoubtedly corresponds to the hydrazone NH
4-hydroxy-5-methyl-3-((4-(prop-2-ynyloxy)phenyl)diazenyl)-2H- proton resonance related to keto–hydrazo form. Further
pyran-2-one (3). The formation of 3 was conrmed by spectral support for this structure is provided by 13C spectra. In 13C
analysis. IR spectra of compound 3 showed absorption band at spectra, carbon attached to –OH in keto–enol form is expected
2121 cmꢁ1 due to C–C triple bond stretching. 1H NMR spectra of to give signal above 190 ppm, but in 13C spectra of compounds
compound 3 showed a singlet at 4.71 ppm for OCH2 and singlet 4a–4f signal at 180 ppm is observed which is corresponding to
at 2.21 for three methyl protons of 4-hydroxy-5-methyl-3-((4- carbon (C]N–NH–) associated with keto–hydrazo form.
(prop-2-ynyloxy)phenyl)diazenyl)-2H-pyran-2-one.
The
1,3-
dipolar cycloaddition reaction of 3 with various substituted aryl
azides in THF–water (60 : 40, v/v) in the presence of
CuSO4$5H2O (10 mol%) and sodium ascorbate (20 mol%) yiel-
ded the target compounds (4a–4f) in high yield as outlined in
Table 1.
Table 1 Synthesis of triazole linked azo dyes (4a–4f) and (6a–6f)
Entry
Ar
Product
Yield (%)
log Sa
c log Pa
1
2
3
4
5
6
7
8
4-MeOC6H4
C6H5
3-MeOC6H4
4-FC6H4
4a
4b
4c
4d
4e
4f
6a
6b
6c
6d
6e
6f
86
82
85
86
84
85
90
89
91
93
88
92
87
91
93
ꢁ4.45
ꢁ4.43
ꢁ4.45
ꢁ4.75
ꢁ6.04
ꢁ5.27
ꢁ5.63
ꢁ5.61
ꢁ5.96
ꢁ5.93
ꢁ7.24
ꢁ6.07
ꢁ6.66
ꢁ6.45
ꢁ5.63
1.25
1.35
1.25
1.41
2.53
2.05
3.95
4.06
4.37
4.11
5.93
3.93
4.73
4.75
3.95
Napthyl
4-BrC6H4
4-MeOC6H4
C6H5
4-MeC6H4
4-FC6H4
9
10
11
12
13
14
15
Napthyl
4-NO2C6H4
4-F-3-ClC6H3
4-BrC6H4
3-MeOC6H4
6g
6h
6i
a
c log P and solubility (log S) values were calculated using OSIRIS
property explorer soware.
Scheme 3 Tautomeric forms for azo dyes (4a–4f).
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Scheme 4 Reagents and conditions: (a) HCl–water (1 : 1), NaNO2 (1 eq.), 0 ꢀC, 15 min; (b) aq. NaOH (12.5 eq.), sesamol (1 eq.), 0 ꢀC, 30 min; (c)
THF–water, ArN3 (1 eq.), CuSO4$5H2O (10 mol%), sodium ascorbate (20 mol%), 60 ꢀC, 1–2 h.
likeness as high c log P values may cause poor absorption or
permeation across cell membrane which resulted in a lower
biological activity of a molecule.28 Similarly aqueous solubility
(log S) of a compound signicantly affects its absorption and
distribution characteristics, hence low solubility generally
results in lower biological activity. The lipophilicity (c log P) and
Scheme 5 Tautomeric forms for azo dyes (6a–6i).
solubility (log S) values of all newly synthesized compounds
were calculated using OSIRIS property explorer soware and are
Another series of novel 1,2,3-triazole linked azo dyes (6a–6i)
was synthesized by using sesamol as an enol coupling compo-
nent (Scheme 4). The coupling reaction of diazotized prop-
argylated derivative (2) with sesamol under basic conditions at
0 ꢀC afforded pure 6-((4-(prop-2-ynyloxy)phenyl)diazenyl)benzo-
[d][1,3]dioxol-5-ol (5) in 92% yield. The formation of 5 was
conrmed by spectral analysis. IR spectra of compound 5
showed broad absorption band at 3421 cmꢁ1 due to OH group
summarized in Table 1. It can be seen from Table 1 that all
compounds showed good lipophilicity (c log P) and aqueous
solubility (log S) values.
3.1 Antimicrobial activity
Total six microbial strains, two Gram-positive bacteria (Staphy-
lococcus aureus MTCC 96 and Bacillus subtilis MTCC 121); two
Gram-negative bacteria (Escherichia coli MTCC 1652 and Pseu-
domonas aeruginosa MTCC 741) and two fungi, Aspergillus niger
and A. avus, were selected for evaluation of antimicrobial
activity of all compounds under study. Standard antibacterial
drug ciprooxacin and antifungal drug uconazole was used as
positive control.
and carbon–carbon triple bond stretching at 2115 cmꢁ1 1H
.
NMR spectra of compound 5 showed a singlet at 6.39 ppm
because of the aromatic proton ortho to hydroxyl group over
sesamol moiety, another aromatic proton of sesamol ring ortho
to azo group merged with four other aromatic protons. Finally,
1,3-dipolar addition reaction of 5 with various substituted aryl
azides in presence of CuSO4$5H2O (10 mol%) and sodium
ascorbate (20 mol%) yielded the targeted compounds (6a–6i) in
high yields (Table 1). The structures of compounds 6a–6i were
conrmed by spectral analysis.
Dyes 6a–6i can exist in keto–hydrazo and enol–azo tauto-
meric forms as shown in Scheme 5. The IR spectra of dyes 6a–6i
showed broad absorption band at 3422–3446 cmꢁ1 for hydroxyl
group and did not show any absorption band for carbonyl group
which indicates that these dyes exist in a enol–azo tautomeric
form. 1H NMR spectra of compound 6a–6i showed singlet in
range of 11.85–11.78 ppm, corresponding to OH group related
to azo–enol tautomeric form. Further 13C NMR spectra of dyes
6a–6i did not show any signal in the range of 170–180 ppm for
carbonyl carbon atom. All this data conrms that these dyes
exist in an enol–azo tautomeric form predominantly due to
aromatization of the ring (Scheme 5).
3.1.1 Antibacterial activity. Triazole linked azo compounds
4a–4f and 6a–6i showed variable antimicrobial activity, against
Gram positive (Staphylococcus aureus, Bacillus subtilis) and Gram
negative (Escherichia coli) bacteria as shown in Table 2. However,
none of the compounds showed activity against Pseudomonas
aeruginosa bacteria. Compounds 4a–4f containing pyran moiety
showed zone inhibition in the range of 22.6–14.3 mm against
Staphylococcus aureus, 23.6–16.6 mm against Bacillus subtilis and
16.6 mm to 14.6 mm against Escherichia coli. Compounds 4d and
4f however, did not exhibit activity against Gram negative
Escherichia coli bacteria. Compound 4a with a methoxy group at
para position of aromatic ring was found to be most effective
against Gram positive Staphylococcus aureus and Gram negative
Escherichia coli bacteria with zone inhibition diameter of 22.6
mm and 16.6 mm respectively. Compound 4b was found to be
most effective against Gram positive Bacillus subtilis bacteria with
zone inhibition of 23.6 mm, while compound 4a showed zone
inhibition of 23.3 mm. Other compounds showed moderate
inhibition against both Gram positive and Gram negative
bacteria. Compounds 6a–6i having sesamol moiety also showed
variable antibacterial (Table 2). Compounds 6a–6i showed zone
inhibition in the range of 23.3 mm to 14.3 mm against Gram
All these compounds 4a–4f and 6a–6f were then subjected to
antimicrobial activity, antioxidant activity and photophysical
studies.
3. Biological evaluation
The physico-chemical properties such as lipophilicity (c log P) positive Staphylococcus aureus, 24.6 mm to 14.3 mm against
of a molecule play an important role in deciding its drug- Gram positive Bacillus subtilis and 16.3 mm to 14.3 mm against
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Table 2 Antibacterial activity of compounds (4a–4f, 6a–6i)a
Table 3 Minimum inhibitory concentration (MIC) (in mg mLꢁ1) of
compounds (4a–4f, 6a–6i)
Diameter of growth of inhibition zoneb (mm)
Staphylococcus
aureus
Bacillus
Subtilis
Escherichia
coli
Staphylococcus Bacillus Escherichia Pseudomonas
Product
Product
aureus
Subtilis coli
aeruginosa
4a
4b
4c
4d
4e
4f
6a
6b
6c
6d
6e
6f
6g
6h
6i
32
32
32
256
128
128
32
32
32
32
128
128
128
16
128
128
128
nt
256
nt
128
256
256
nt
nt
nt
nt
nt
256
6.25
256
—
4a
4b
4c
4d
4e
4f
6a
6b
6c
6d
6e
6f
6g
6h
6i
22.6
22.3
21.3
14.3
15.6
15.6
23.3
19.6
15.3
14.3
14.6
13.6
14.3
14.3
16.3
26.6
19.5
23.3
23.6
22.6
16.6
17.3
16.6
24.6
21.3
17.6
15.6
15.6
14.3
15.3
16.3
18.3
24.0
21.0
13.9
16.6
15.3
15.6
—
14.6
—
16.3
14.6
14.6
—
—
—
—
—
14.3
25.0
14.7
—
—
—
—
—
—
—
—
—
64
32
128
256
256
256
256
256
128
6.25
64
128
128
128
256
128
128
64
6.25
32
256
—
—
—
—
—
—
22.0
—
—
Ciprooxacina
Sesamol
4-Hydroxy-5-methyl-
2H-pyran-2-one
Amino triazoleb
Ciprooxacinc
Sesamol
4-Hydroxy-5-methyl- 12.1
512
2H-pyran-2-one
256
256
—
Amino triazoled
14.0
14.1
—
—
a
Anti-bacterial drug, nt – not tested. b 4-((1-(4-Methoxyphenyl)-1H-1,2,3-
a
b
—: no activity. Values, including diameter of the well (8 mm), are
triazol-4-yl)methoxy)aniline, —: no activity.
c
d
means of three replicates.
Anti-bacterial drug.
4-((1-(4-
Methoxyphenyl)-1H-1,2,3-triazol-4-yl)methoxy)aniline.
3.1.2 Antifungal activity. Antifungal activity of all
compounds (4a–4f, 6a–6i) was evaluated against Aspergillus niger
and Aspergillus avus. All compounds showed moderate to good
antifungal activity against both strains (Table 4). Compound 4a
Gram negative Escherichia coli bacteria. Compound 6d, 6e, 6f, 6g
and 6h did not exhibit activity against Gram negative Escherichia
coli bacteria. Compound 6a with methoxy group at para position
of aromatic ring was found to be most effective against Staphy-
lococcus aureus, Bacillus subtilis and Escherichia coli with zone
inhibition of 23.3 mm, 24.6 mm and 16.6 mm, respectively. Other
compounds showed moderate antibacterial activity (Table 2).
Minimum inhibitory concentration (MIC) of all compounds
(4a–4f, 6a–6i) was also measured against Gram positive bacteria
(Staphylococcus aureus and Bacillus subtilis) and Gram-negative
bacteria (Escherichia coli) as shown in Table 3. Among
compounds having pyran moiety (4a–4f), compounds 4a, 4b and
4c showed lowest MIC of 32 mg mLꢁ1 against Gram positive
bacteria (Staphylococcus aureus and Bacillus subtilis) and 128 mg
mLꢁ1 against Gram-negative Escherichia coli bacteria. While
among compounds having sesamol moiety (6a–6i), compound
6a was found to most effective against all three strains with
lowest MIC of 32 mg mLꢁ1, 16 mg mLꢁ1 and 126 mg mLꢁ1 against
Gram positive Staphylococcus aureus, Bacillus subtilis and Gram
negative Escherichia coli bacteria, respectively. Other
compounds showed MIC in the range of 32 mg mLꢁ1 to 256 mg
mLꢁ1 in comparison of standard drug ciprooxacin. It can be
inferred from structure activity relationship (SAR) of
compounds 4a–4f and 6a–6i that compounds 4d, 4f, 6d, 6g and
6h having halogen substituent over aromatic ring did not
exhibit activity against Gram negative Escherichia coli bacteria,
while presence of substituent like OMe, Me or H over aromatic
ring enhances the antibacterial activity.
Table 4 Antifungal activity of compounds (4a–4f, 6a–6i) through
poisoned food method
Mycelial growth inhibition (%)
Product
Aspergillus niger
Aspergillus avus
4a
4b
4c
4d
4e
4f
6a
6b
6c
6d
6e
6f
6g
6h
6i
51.1
48.8
50
53.3
51.1
55.5
43.3
42.2
43.3
57.7
56.6
45.5
46.6
44.4
45.8
45.5
38.8
43.3
77.7
45.2
34.2
37.7
35.5
37.7
53.3
52.2
41.1
43.3
37.7
48.8
42.2
35.5
41.1
81.1
47.6
30.8
Fluconazolea
Sesamol
4-Hydroxy-5-methyl-2H-
pyran-2-one
Amino triazoleb
35.1
36.3
a
b
Standard antifungal drug. 4-((1-(4-Methoxyphenyl)-1H-1,2,3-triazol-
4-yl)methoxy)aniline.
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Table 5 Radical scavenging activities of compounds 4a–4f and 6a–6i
having pyran moiety and 4-OMe substituent over aromatic ring
showed highest 51.1% mycelial growth inhibition against Asper-
gillus niger while compound 4c showed 55.5% mycelial growth
inhibition against Aspergillus avus. Compound 4c showed 50%
Mycelial growth inhibition against Aspergillus niger, whereas
compounds 4a and 4b showed more than 50% inhibition of
mycelial growth against Aspergillus avus. Compound 6a with
sesamol moiety and 4-OMe substituent over aromatic ring
showed highest inhibition of mycelial growth against Aspergillus
niger (53.3%) and Aspergillus. avus (57.7%). While compound 6b
showed more than 50% inhibition of mycelial growth against
Aspergillus niger and Aspergillus avus.
DPPH radical
scavenging activity
(IC50 mM)
Nitric oxide radical
scavenging activity
(IC50 mM)
Product
4a
4b
4c
4d
4e
4f
6a
6b
6c
6d
6e
6f
6g
6h
695.32
1717.42
574.38
1365.30
221.984
375.65
33.29
10.35
34.22
30.22
18.35
36.01
70.63
44.51
25.96
50.18
35.50
120.40
1025.75
967.29
748.56
1231.52
866.99
659.34
1105.25
875.52
399.87
5066.49
1146.65
932.23
1437.58
309.88
586.68
366.34
215.10
950.23
For comparison of the antimicrobial activity of all
compounds with their precursors the amino triazole namely,
4-((1-(4-methoxyphenyl)-1H-1,2,3-triazol-4-yl)methoxy)aniline,
which is a part of the parent molecule 6a reported to posses
highest antimicrobial activity was prepared by the reaction of
4-(prop-2-ynyloxy)aniline with 1-azido-4-methoxybenzene in
THF–water (60 : 40, v/v) in the presence of CuSO4$5H2O
6i
BHTa
Sesamol
ꢀ
(10 mol%) and sodium ascorbate (20 mol%) at 60 C. This has
4-Hydroxy-5-methyl-
2H-pyran-2-one
Amino triazoleb
been included in Experimental section. Antibacterial and anti-
fungal activity of all compounds (4a–4f, 6a–6i) was compared
with their coupling components like sesamol, 4-hydroxy-5-
methyl-2H-pyran-2-one and amino triazole i.e. 4-((1-(4-methoxy-
phenyl)-1H-1,2,3-triazol-4-yl)methoxy)aniline. As shown in
Tables 2 and 4 all compounds showed better antimicrobial
—
—
a
b
Standard antioxidant. 4-((1-(4-Methoxyphenyl)-1H-1,2,3-triazol-4-yl)-
methoxy)aniline.
activity as compared to 4-hydroxy-5-methyl-2H-pyran-2-one and activity with IC50 values of 18.25, 25.96, 30.22, 33.29, 34.22,
amino triazole. Compounds 4a, 4b, 4c, 6a and 6b showed better 36.01, 44.51 mM respectively, compared to standard BHT.
antibacterial activity as compared to sesamol against S. aureus
3.2.2 Nitric oxide radical scavenging activity. Nitric oxide
and B. subtilis bacteria, while compounds 4a, 4b, 4c and 6a (NO) is an important chemical mediator generated by endo-
showed better antibacterial activity as compared to sesamol thelial cells, macrophages, neurons, etc. and is involved in the
against E. coli bacteria. Further compounds 4a, 4b, 4c, 6a, 6b regulation of various physiological processes. Excess concen-
and 6f showed better antifungal activity as compared to sesamol tration of NO is associated with several diseases. Oxygen reacts
against A. niger, while compounds 4a, 4b, 4c, 6a, 6b, 6c, 6d, 6f with the excess nitric oxide to generate nitrite and peroxynitrite
and 6g showed better antifungal activity as compared to ses- anions, which act as free radicals.30 All compounds showed
amol against A. avus.
good to moderate nitric oxide radical scavenging activity as
shown in Table 5. Compounds 4a–4f showed moderate antiox-
idant activity against nitric oxide radical with IC50 values
ranging from 659.34 mM to 1231.52 mM compared to BHT with
3.2 Antioxidant activity
In vitro antioxidant activity of all compounds was measured IC50 value of 366.34 mM. Compounds 6a–6i showed good anti-
against 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical and nitric oxidant activity with IC50 values ranging from 309.88 mM to
oxide radical according to literature procedures.29 The results of 5066.49 mM. Compound 6h showed IC50 value of 366.34 mM
antioxidant activity are listed in Table 5. Synthetic antioxidant which is lower than standard BHT. The higher antioxidant
butylated hydroxytoulene (BHT) was used as positive control.
activity of compounds 6a–6i could be due to the formation of
3.2.1 DPPH Free radical scavenging activity. DPPH radical stable sesamolyl free radical.
scavenging activity evaluation is a rapid and convenient assay
Antioxidant activity of all synthesized compounds (4a–4f,
for screening the antioxidant activities of compounds. It can be 6a–6i) was also compared with their precursors as shown in
observed from Table 5 that compounds 4a–4f showed good Table 5. It can be seen from Table 5 that amino triazole did not
DPPH radical scavenging activity compared to synthetic show antioxidant activity, while compounds 6a, 6b, 6c, 6d, 6e
commercial antioxidant BHT with IC50 values ranging from and 6i showed better DPPH antioxidant activity as compare to
375.65 mM to 1717.42 mM using DPPH assay. Compound 4f sesamol, whereas compounds 6a–6i showed better DPPH anti-
showed lowest IC50 value of 375.65 mM. Compounds 6a–6i also oxidant activity as compare to 4-hydroxy-5-methyl-2H-pyran-2-
showed good to excellent DPPH radical scavenging activity one. The nitric oxide radical scavenging activity of all
compared to standard BHT with IC50 values ranging from 10.32 compounds was found to be lower as compared with sesamol,
to 70.63 mM. Compound 6b was found to be 5 fold more potent while compounds 4c, 4e, 4f, 6b, 6c, 6f, 6h and 6i showed better
than BHT with IC50 value of 10.32 mM, whereas compounds 6e, nitric oxide radical scavenging activity as compare to 4-hydroxy-
6i, 6d, 6a, 6c, 6h, 6f, 6h showed better DPPH radical scavenging 5-methyl-2H-pyran-2-one.
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chemosensors for biologically important metal ions.31 Thus in
view of importance of novel uorescent materials and their
photophysical properties like absorption and emission charac-
teristics, we decided to explore the photophysical properties of
all newly synthesized compounds.
Table 6 Photophysical data of compounds 4a–4f and 6a–6i in
chloroform (1 ꢂ 10ꢁ5 M)
lmax
3 ꢂ 105
lem
Stoke shi
(Dn) cmꢁ1
Product
(nm)
(L molꢁ1 cmꢁ1
)
(nm)
4a
4b
4c
4d
4e
4f
6a
6b
6c
6d
6e
6f
441
442
441
442
359
365, 442
342, 447, 530 s
341, 448,527 s
341, 448, 526 s
339, 447, 529 s
338, 448, 529 s
339, 445, 530 s
339, 444, 529 s
342, 453, 529 s
345, 451, 530 s
0.49
0.79
0.70
0.31
0.11, 0.02
0.10, 0.13
0.60, 0.88, 0.48
0.72, 0.95, 054
0.64, 0.93, 0.49
0.55, 0.78, 0.44
0.57, 0.81, 0.43
0.58, 0.81, 0.43
0.49, 0.68, 0.41
0.35, 0.48, 0.29
0.39, 0.50, 0.30
537
543
542
542
517
539
593
571
572
570
577
572
583
575
587
4054
4208
4225
4174
3180
4072
5508
4808
4839
4918
4990
4989
5370
4684
5137
4.1 Absorption and emission characteristics
The spectral characteristics of the all compounds such as
absorption maxima (lmax), emission maxima (lem) and extinc-
tion coefficient (3) were measured in chloroform and are pre-
sented in Table 6. Compounds 4a–4d showed single absorption
band in the region of 441–442 nm, while compounds 4e and 4f
showed two absorption bands in the region of 359–362 nm and
442–444 nm, which suggest that compounds 4e and 4f exist in
two tautomeric forms in chloroform. Compounds 6a–6i showed
three absorption bands, band 1 in the region of 338–345 nm,
band II in the region of 444–453 nm and one shoulder
absorption band in the region of 526–530 nm (Fig. 1).
6g
6h
6i
The uorescence spectrum of all compounds (4a–4f and
6a–6i) was measured in chloroform (Fig. 2). All compounds
showed uorescence even in the presence of azo group which is
known to quench the uorescence intensity, this may be due to
the presence of azo group in conjugation with aromatic sub-
stituent's which resulted in a partial quenching of uorescence
and hence all compounds showed a weak uorescence in
4. Photophysical studies
Development of new uorescent materials is an active area of
research because of their wide applications in different areas of
research such as telecommunications, optical computing,
optical storage, uorescent probes and uorescent
Fig. 1 Absorption spectra of compounds 4a–4f and 6a–6i in chloroform (1 ꢂ 10ꢁ5 M).
Fig. 2 Emission spectra of compounds 4a–4f and 6a–6i in chloroform (1 ꢂ 10ꢁ5 M).
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Fig. 3 Absorption characteristics of compound 4c and 6i in various solvents (1 ꢂ 10ꢁ5 M).
Fig. 4 Emission characteristics of compound 4c and 6i in various solvents (1 ꢂ 10ꢁ5 M).
solution. All compound showed almost similar uorescence absorption and emission spectra of these dyes are shown in
spectra. Compounds 4a–4f showed emission in the range of Fig. 3 and 4, respectively and summarized in Table 7. It is very
517–543 nm while compounds 6a–6i showed emission in the obvious from Table 7 that compounds 4c and 6i showed bath-
range of 570–593 nm. A uorescence excitation wavelength of ochromically shied absorption and emission maxima in polar
435 nm was used for all compounds.
solvents like methanol and THF relative to non-polar heptane.
Stokes shi was calculated as the difference between
absorption and emission maxima obtained from the spectra on
the wavenumber scale. There is a signicant increase in stoke
shi with increasing polarity from non-polar heptane to polar
4.2 Effect of solvent polarity on absorption and emission
spectra
The effect of solvent polarities on photophysical properties was solvents for compounds 4c and 6i.
investigated by studying the absorption and emission charac-
Solvent dependent spectral shi was investigated using
teristics of triazole linked azo dyes 4c and 6i in six different Lippert–Mataga plot31 to comprehend the polarity effect on
solvents of varying polarity. Effects of solvent polarity on compounds 4c and 6i. Lippert–Mataga plot describes the effect
Table 7 Effect of solvent polarity on photophysical properties of compound 4c and 6i
4c
6i
lmax
3 ꢂ 105
lemi
Stoke shi
lmax
3 ꢂ 105
lemi
Stoke shi Dl
(nm)
Solvents
(nm)
(L molꢁ1 cmꢁ1
)
(nm)
Dl (cmꢁ1
)
(nm)
(L molꢁ1 cmꢁ1
)
(nm)
MeOH
DMF
ACN
DMSO
THF
Heptane
438
440
435
441
442
432
0.05
0.5
0.8
0.05
0.08
0.02
542
543
540
546
539
498
4381
4311
4470
4360
4072
3068
449
438
444
448
445
436
0.22
0.20
0.09
0.25
0.21
0.06
581
588
581
591
538
499
5060
5824
5311
5401
3884
2895
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Fig. 5 Lippert–Mataga plot for compound 4c.
Fig. 7 Absorption spectra of compounds 4c and 6i in acidic and basic
solutions (1 ꢂ 10ꢁ5 M).
0.1 mL of base (Fig. 7). However, compound 6i showed bath-
ochromic shi on addition of base from labs at 439 nm to labs
494 nm (bathochromic shi of 55 nm) (Fig. 7). However, addi-
tion of 0.1 mL acid (HCl 0.1 M) to 4c and 6i in acetonitrile
resulted in bathochromic shi. Compounds 4c and 6i showed
same bathochromic shi of 5 nm on addition of acid (Fig. 7).
These results indicate that tautomeric forms of compound 4c
and 6i in acetonitrile changed to another tautomeric form on
addition of acid or base.
The effect of acid and base on emission spectra of compound
4c and 6i in acetonitrile was also investigated (Fig. 8). Addition
of 0.1 mL of acid (HCl, 0.1 M) did not affect the emission spectra
of compound 4c. Whereas addition of 0.1 mL of base (KOH,
0.1 M) resulted in a large blue shi of 40 nm. The large shi
could be due to change in tautomeric form on addition of base.
Emission spectra of 6i was insensitive to addition of acid and
base and showed only slight red shi of 9 nm and 7 nm on
addition of base and acid, respectively.
Fig. 6 Lippert–Mataga plot for compound 6i.
of solvent polarity on the stoke shi of molecule and can be
obtained by plotting stoke shi vs. orientation polarizaibility,
which is a result of both the mobility of electrons in the solvent
and dipole moment of solvent. The Lippert–Mataga plot for
compounds 4c and 6i (Fig. 5 and 6) shows good linear rela-
tionship (correlation factor R2 ¼ 0.9885 and 0.8074 for 4c and 6i,
respectively), suggesting that the dipole–dipole interaction and
dipole-induced dipole interactions between the solute and
solvent are mainly responsible for the solvent-dependent uo-
rescence shi.
4.3 Effect of base and acid on absorption spectra and
emission spectra
The effect of addition of base and acid on the absorption of
compounds 4c and 6i was investigated by addition of 0.1 mL of
base (potassium hydroxide, 0.1 M) and 0.1 mL of acid (hydro-
chloric acid, 0.1 M) to 1 mL solution of compounds 4c and 6i in
acetonitrile. The absorption spectra of compounds 4c and 6i
was sensitive to addition of base (potassium hydroxide, 0.1 M).
Compound 4c showed an hypochromic shi from labs at
Fig. 8 Emission spectra of compounds 4c and 6i in acidic and basic
433 nm to labs at 371 nm (shi of 62 nm) on the addition of solutions (1 ꢂ 10ꢁ5 M).
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6.1 General procedure for the synthesis of 4-hydroxy-5-methyl-
3-((4-(prop-2-ynyloxy)phenyl)diazenyl)-2H-pyran-2-one (3)
5. Conclusion
In conclusion, we have synthesized two novel series of 1,2,3-
triazole linked azo dyes, 4a–4f and 6a–6i using 4-hydroxy-5-
methyl-2H-pyran-2-one and sesamol as coupling components.
4-(Prop-2-ynyloxy)aniline (0.01 mol) was dissolved in a mixture
of water and conc. hydrochloric acid (4 mL, ratio 1 : 1) and the
solution was cooled to 0–5 ꢀC. Sodium nitrite (0.01 mol) was
added slowly with vigorous stirring and reaction mixture was
stirred for about 20 min. Solution of 4-hydroxy-2-methyl-5H-
pyran-2-one (0.01 mol) in water (10 mL) containing sodium
hydroxide (0.125 mol) was then added slowly to the reaction
mixture with stirring at 0–5 ꢀC. The reaction mixture was stirred
at this temperature for another 2 h. Aer completion of reaction
as monitored by TLC using ethyl acetate–petroleum ether,
60 : 40, v/v as eluent, reaction mixture was diluted with water
(20 mL) and the precipitate formed were ltered at pump,
washed with water and recrystallized from ethanol to afford
pure 4-hydroxy-5-methyl-3-((4-(prop-2-ynyloxy)phenyl)diazenyl)-
2H-pyran-2-one (3) in 86% yield.
1
All newly synthesized compounds were characterized by IR, H
NMR, 13C NMR and HRMS analysis. Spectral study suggests that
azo compound 4a–4f exists in keto–hydrazo tautomeric form,
while compound 6a–6i containing sesamol moiety exists in
enol–azo tautomeric form. All compounds were evaluated for
antibacterial activity against Gram positive as well as Gram
negative bacteria. Compound 6a was found to be most potent
against both Gram positive (Staphylococcus aureus, Bacillus
subtilis) and Gram negative (Escherichia coli) bacteria. Other
compounds showed moderate antibacterial activity. Antifungal
activity of all compounds was also evaluated against Aspergillus
niger and Aspergillus. avus. Compound 6a was found to be most
effective against both fungal strains with 53.3% and 57.7%
inhibition of mycelial growth against Aspergillus niger and
Aspergillus. avus, respectively. Thus it can be concluded that
compound 6a showed good antibacterial and antifungal activity
among all the compounds. Antioxidant activity of all
compounds was measured using DPPH free radical assay and
nitric oxide radical scavenging assay. All compounds showed
good DPPH radical scavenging activity and good to moderate
nitric oxide radical scavenging activity. Compounds having
sesamol moiety (6a–6i) showed higher antioxidant activity
compared to compounds with pyran moiety (4a–4i). In DPPH
assay, compound 6b was found to be 5 fold more potent than
standard antioxidant BHT, while compounds 6e, 6i, 6d, 6a, 6c,
6h, 6f, 6h showed better DPPH radical scavenging activity than
BHT. Compound 6h also showed good nitric oxide radical
scavenging activity with IC50 value lower than BHT. Photo-
physical properties of all the compounds were also studied. All
compounds showed uorescence in solution. Effect of solvent
polarity on absorption and emission spectra of compound 4c
and 6i was investigated. It was observed that uorescence
spectra depends on solvent polarity and showed good correla-
tion to Lippert–Mataga plot. Effect of addition of acid and base
on absorption and emission spectra has also been reported.
Red solid, M.p.: 145 ꢀC, 1H NMR (400 MHz, CDCl3) d ¼ 16.57
(s, 1H, N]NH), 7.58 (d, 2H, J ¼ 7.32 Hz, ArH) 7.04–6.97 (m, 3H,
ArH), 4.71 (s, 2H, OCH2), 2.53 (s, 1H, CH), 2.21 (s, 3H, CH3); 13
C
NMR (100 MHz, CDCl3) d ¼ 20.4, 56.1, 75.4, 76.1, 106.7, 114.7,
115.4, 115.7, 116.1, 119.5, 129.5, 166.2, 185.2; IR (nmax cmꢁ1
,
lm): ¼ 3291, 2121, 1728, 1641, 1508, 1219; HRMS (ESI) [M + H]+
calcd for C15H12N2O4: 285.0840, found: 285.0760.
6.2 General procedure for the synthesis of 1,2,3-triazole
linked azo dyes (4a–4f)
A mixture of 4-hydroxy-5-methyl-3-((4-(prop-2-ynyloxy)phenyl)
diazenyl)-2H-pyran-2-one 3 (1 mmol), substituted aryl azide (1
mmol), CuSO4$5H2O (10 mol%), sodium ascorbate (20 mol%)
and 10 mL of THF–water (60 : 40, v/v) was placed in a 50 mL
round-bottomed ask. The reaction mixture was stirred at 60 ꢀC
for 3–4 h. The progress of reaction was monitored by TLC using
ethyl acetate–petroleum ether (60 : 40, v/v) as eluent. Aer
completion of the reaction as indicated by TLC, water (20 mL)
was added to the reaction mixture. The precipitate formed was
collected by ltration at pump and washed with water. The
crude product was puried by ash column chromatography
over silica gel (230–400 mesh) using ethyl acetate–petroleum
ether as eluent to afford pure products (4a–4f).
4-Hydroxy-3-((4-((1-(4-methoxyphenyl)-1H-1,2,3-triazol-4-yl)-
methoxy)phenyl)diazenyl)-5-methyl-2H-pyran-2-one (4a). Brown
6. Experimental
All chemicals were purchased from Sigma-Aldrich and Spec- solid, M.p.: 149 ꢀC, 1H NMR (400 MHz, CDCl3) d ¼ 16.58 (s, 1H,
trochem and were used as received. Silica gel 60 F254 (precoated N]NH), 7.96 (s, 1H, triazolyl-H), 7.62–7.60 (m, 4H, ArH), 7.09–
aluminium plates) from Merck were used to monitor reaction 6.99 (m. 5H, ArH), 5.30 (s, 2H, OCH2), 3.85 (s, 3H, CH3), 2.21 (s,
progress. IR (KBr) spectra were recorded on Perkin Elmer FTIR 3H, CH3); 13C NMR (100 MHz, CDCl3): d ¼ 180.7, 166.2, 160.0,
spectrophotometer and the values are expressed as nmax cmꢁ1
.
159.9, 158.3, 143.8, 134.5, 130.2, 122.2, 121.3, 121.2, 119.6,
The NMR (1H and 13C) spectra were recorded on Jeol JNM ECX- 115.9, 114.7, 107.5, 62.2, 55.6, 20.4; IR (nmax cmꢁ1, lm): ¼ 3142,
400P at 400 MHz and 100 MHz, respectively. The chemical shi 1715, 1650, 1603, 1504, 1437, 1221; HRMS (ESI) [M + H]+ calcd
values are recorded on d scale and the coupling constants ( J) are for C22H19N5O5: 434.1454, found: 434.1381.
in Hertz. The high resolution mass spectra were recorded on an
4-Hydroxy-5-methyl-3-((4-((1-phenyl-1H-1,2,3-triazol-4-yl)-
Agilent 6520 – QTOF LCMS having ESI source in positive mode. methoxy)phenyl)diazenyl)-2H-pyran-2-one (4b). Brown solid,
1
ꢀ
Ultraviolet-visible (UV-Vis) absorption spectra were recorded on M.p.: 239 C, H NMR (400 MHz, CDCl3) d ¼ 16.58 (s, 1H, N]
Analytikjena specord 250 spectrophotometer. The uorescence NH), 8.04 (s, 1H, triazolyl-H) 7.72 (d, 2H, J ¼ 7.36 Hz, ArH), 7.58–
spectra were measured at Cary Eclipse Fluorescence 6.43 (m. 6H, ArH), 7.08 (d, 2H, J ¼ 7.32 Hz, ArH), 5.31 (s, 2H,
spectrophotometer.
OCH2), 2.21 (s, 3H, CH3); 13C NMR (100 MHz, CDCl3): d ¼ 180.7,
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166.2, 161.6, 160.0, 159.1, 142.8, 136.8, 134.6, 129.8, 129.0, (10 mL) containing sodium hydroxide (0.125 mol) was added
124.9, 121.0, 120.6, 119.7, 119.6, 115.97, 107.5, 62.2, 20.2; IR slowly to the reaction mixture with stirring at 0–5 ꢀC. The
(nmax cmꢁ1, lm): ¼ 3140, 3071, 2926, 1734, 1655, 1604, 1519, reaction mixture was stirred at this temperature for another 1 h.
1405, 1250; HRMS (ESI) [M + H]+ calcd for C21H17N5O4: Aer completion of reaction as indicated by TLC using ethyl
404.1354, found: 404.1285.
acetate–petroleum ether (60 : 40, v/v) as eluent, reaction mixture
4-Hydroxy-3-((4-((1-(3-methoxyphenyl)-1H-1,2,3-triazol-4-yl)- was diluted with water (20 mL) and the precipitate formed were
methoxy)phenyl)diazenyl)-5-methyl-2H-pyran-2-one (4c). Brown ltered at pump, washed with water and recrystallized from
solid, M.p.: 173 ꢀC, 1H NMR (400 MHz, CDCl3) d ¼ 16.58 (s, 1H, ethanol to afford pure 6-((4-(prop-2-ynyloxy)phenyl)diazenyl)-
N]NH), 8.03 (s, 1H, triazolyl-H), 7.58 (d, 2H, J ¼ 9.16 Hz, ArH), benzo[d][1,3]dioxol-5-ol (5) in 92% yield.
7.41–7.32 (m, 4H, ArH), 7.08 (d, 2H, J ¼ 7.32 Hz, ArH), 6.96 (d,
Red solid, M.p.: 176 ꢀC, 1H NMR (400 MHz, CDCl3) d ¼ 14.69
2H, J ¼ 7.32 Hz, ArH), 5.30 (s, 2H, OCH2), 3.86 (s, 3H, CH3), 2.21 (s, 1H, OH), 7.68 (d, 2H, J ¼ 9.2 Hz, ArH), 7.05–7.02 (m, 3H,
(s, 3H, CH3); 13C NMR (100 MHz, CDCl3): d ¼ 180.7, 166.2, 160.5, ArH), 6.39 (s, 1H, ArH), 5.99 (s, 2H, OCH2), 4.73 (s, 2H, OCH2),
159.9, 158.3, 144.0, 137.8, 134.6, 134.08, 130.5, 121.1, 119.6, 2.54 (s, 1H, CH); 13C NMR (100 MHz, CDCl3): d ¼ 158.3, 158.0,
115.9, 114.8, 114.7, 112.4, 107.5, 62.2, 55.6, 20.4; IR (nmax cmꢁ1
,
142.8, 141.7, 131.7, 121.9, 115.6, 108.2, 100.0, 99.9, 98.9, 78.0,
lm): ¼ 3140, 3071, 2926, 1736, 1655, 1609, 1507, 1406, 1219; 75.6, 56.0; IR (nmax cmꢁ1, lm): ¼ 3421, 3068, 2916, 2115, 1602,
HRMS (ESI) [M + H]+ calcd for C22H19N5O5: 434.1459, found: 1495, 1219; HRMS (ESI) [M + H]+ calcd for C16H12N2O4:
434.1351.
3-((4-((1-(4-Fluorophenyl)-1H-1,2,3-triazol-4-yl)methoxy)-
297.0870, found: 297.0796.
phenyl)diazenyl)-4-hydroxy-5-methyl-2H-pyran-2-one
(4d).
Brown solid, M.p.: 218 ꢀC, 1H NMR (400 MHz, CDCl3) d ¼ 16.52
6.4 General procedure for the synthesis of 1,2,3-triazole
linked azo dyes (6a–6i)
(s, 1H, N]NH), 7.96 (s, 1H, triazolyl-H), 7.67–7.63 (m, 2H, ArH),
7.53 (d, 2H, J ¼ 7.32 Hz, ArH), 7.19–7.14 (m, 3H, ArH), 7.03 (d, A mixture of 6-((4-(prop-2-ynyloxy)phenyl)diazenyl)benzo[d][1,3]-
2H, J ¼ 9.2 Hz, ArH), 5.26 (s, 2H, OCH2), 2.16 (s, 3H, CH3); 13
C
dioxol-5-ol (5) (1 mmol), substituted aryl azide (1 mmol),
NMR (100 MHz, CDCl3): d ¼ 180.7, 166.2, 161.2, 159.9, 158.3, CuSO4$5H2O (10 mol%), sodium ascorbate (20 mol%) and 10
144.3, 134.6, 122.6, 122.5, 121.2, 119.6, 116.9, 116.6, 115.9, mL of THF–water (60 : 40, v/v) was placed in a 50 mL round-
107.4, 62.2, 20.4; IR (nmax cmꢁ1, lm): ¼ 3147, 3064, 2925, 1735, bottomed ask. The reaction mixture was stirred at 60 ꢀC for 1–2
1654, 1602, 1403, 1217; HRMS (ESI) [M + H]+ calcd for h. The progress of reaction was monitored by TLC using ethyl
C
21H16FN5O4: 422.1259, found: 422.1182.
acetate–petroleum ether (70 : 30, v/v) as eluent. Aer comple-
4-Hydroxy-5-methyl-3-((4-((1-(naphthalen-1-yl)-1H-1,2,3-tri- tion of the reaction as observed by TLC, water (20 mL) was
azol-4-yl)methoxy)phenyl) diazenyl)-2H-pyran-2-one (4e). Brown added to the reaction mixture. The precipitate formed was
solid, M.p.: 106 ꢀC, 1H NMR (400 MHz, CDCl3) d ¼ 16.57 (s, 1H, collected by ltration at pump and washed with water. The
N]NH), 8.01 (s, 1H, triazolyl-H), 7.70–7.56 (m, 7H, ArH), 7.24– product so obtained, was recrystallized from ethanol to afford
7.08 (m, 5H, ArH), 5.30 (s, 2H, OCH2), 2.21 (s, 3H, CH3); 13C pure products in good yield (6a–6i).
NMR (100 MHz, CDCl3): d ¼ 180.6, 166.2, 162.4160.0, 158.3,
6-((4-((1-(4-Methoxyphenyl)-1H-1,2,3-triazol-4-yl)methoxy)-
142.7, 138.6, 134.6, 129.7, 128.9, 126.6, 126.0, 125.4, 125.0, phenyl)diazenyl)benzo[d][1,3]dioxol-5-ol (6a). Dark red solid,
1
ꢀ
121.4, 120.9, 120.6, 119.7, 117.8, 115.9, 107.13, 61.6, 20.6; IR M.p.: 290 C, H NMR (400 MHz, DMSO-d6) d ¼ 11.85 (s, 1H,
(nmax cmꢁ1, lm): ¼ 3144, 3064, 2927, 1675, 1599, 1508; HRMS OH), 8.86 (s, 1H, triazolyl-H), 7.87–7.79 (m, 4H, ArH), 7.15–7.11
(ESI) [M + H]+ calcd for C25H19N5O4: 454.1510, found: 454.1415. (m, 5H, ArH), 6.60 (s, 1H, ArH), 6.06 (s, 2H, OCH2), 5.30 (s, 2H,
3-((4-((1-(4-Bromophenyl)-1H-1,2,3-triazol-4-yl)methoxy)phenyl) OCH2), 3.81 (s, 3H, OCH3); 13C NMR (100 MHz, DMSO-d6) d ¼
diazenyl)-4-hydroxy-5-methyl-2H-pyran-2-one (4f). Brown solid, 159.3, 154.5, 153.2, 152.1, 141.5, 132.1, 123.4, 123.3, 121.6,
M.p.: 215 ꢀC, 1H NMR (400 MHz, CDCl3) d ¼ 16.57 (s, 1H, N]NH), 120.0, 116.6, 115.3, 115.2, 114.7, 103.0, 100.5, 99.4, 61.3, 59.4; IR
8.03 (s, 1H, triazolyl-H), 7.64–7.56 (m, 7H, ArH), 7.07 (d, 2H, J ¼ (nmax cmꢁ1, KBr): ¼ 3421, 3068, 2908, 1600, 1560, 1519, 1461,
9.16 Hz, ArH), 5.30 (s, 2H, OCH2), 2.21 (s, 3H, CH3); 13C NMR 1252; HRMS (ESI) [M + H]+ calcd for C23H19N5O5: 446.1459,
(100 MHz, CDCl3): d ¼ 180.7, 166.3, 163.8, 161.0, 158.2, 134.1, found: 446.1376.
134.8, 132.9, 128.2, 128.0, 127.1, 124.9, 123.6, 122.5, 121.9, 120.8,
6-((4-((1-Phenyl-1H-1,2,3-triazol-4-yl)methoxy)phenyl)diazenyl)-
119.6, 116.9, 115.9, 110.9, 107.4, 62.2, 29.6; IR (nmax cmꢁ1, lm): ¼ benzo[d][1,3]dioxol-5-ol (6b). Dark red solid, M.p.: 180 ꢀC, 1H
3140, 2925, 1735, 1653, 1604, 1508, 1402, 1296; HRMS (ESI) NMR (400 MHz, DMSO-d6) d ¼ 11.78 (s, 1H, OH), 8.83 (s, 1H,
[M + H]+ calcd for C21H16BrN5O4: 482.0459, found: 482.0389.
triazolyl-H), 7.78–7.75 (m, 4H, ArH), 7.43–7.06 (m, 6H, ArH), 6.48
(s, 1H, ArH), 5.94 (s, 2H, OCH2), 5.17 (s, 2H, OCH2); 13C NMR (100
MHz, DMSO-d6): d ¼ 159.5, 154.7, 152.3, 141.9, 136.5, 132.2, 130.0,
129.9, 128.9, 128.8, 123.5, 123.3, 123.2, 120.2, 115.4, 115.3, 102.2,
100.56, 98.4, 61.4; IR (nmax cmꢁ1, KBr): ¼ 3430, 3067, 2917, 1599,
6.3 Procedure for synthesis of 6-((4-(prop-2-ynyloxy)phenyl)-
diazenyl)benzo[d][1,3]dioxol-5-ol (5)
4-(Prop-2-ynyloxy)aniline (0.01 mol) was dissolved in a mixture 1499, 1474, 1239; HRMS (ESI) [M + H]+ calcd for C22H17N5O4:
of water and concentrated hydrochloric acid (4 mL, ratio 1 : 1) 416.4088, found: 416.4011.
and solution was cooled to 0–5 ꢀC. Sodium nitrite (0.01 mol) was
6-((4-((1-4-Tolyl-1H-1,2,3-triazol-4-yl)methoxy)phenyl)diazenyl)-
added slowly with vigorous stirring and reaction mixture was benzo[d][1,3]dioxol-5-ol (6c). Dark red solid, M.p.: 185 ꢀC, 1H NMR
stirred for about 20 min. Solution of sesamol (0.01 mol) in water (400 MHz, DMSO-d6) d ¼ 11.84 (s, 1H, OH), 8.91 (s, 1H, triazolyl-H),
5924 | RSC Adv., 2014, 4, 5915–5926
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7.89–7.76 (m, 4H, ArH), 7.39 (d, 2H, J ¼ 7.36 Hz, ArH), 7.22–7.16 NMR (100 MHz, DMSO-d6): d ¼ 159.2, 154.4, 152.0, 144.7, 140.5,
(m, 3H, ArH), 6.60 (s, 1H, ArH), 6.06 (s, 2H, OCH2), 5.31 (s, 2H, 135.5, 134.2, 132.6, 131.9, 123.2, 122.8, 121.8, 118.5, 115.0,
OCH2), 2.36 (s, 3H, CH3); 13C NMR (100 MHz, DMSO-d6): d ¼ 159.4, 101.9, 100.1, 98.2, 61.2; IR (nmax cmꢁ1, KBr): ¼ 3446, 3114, 2918,
154.6, 152.0, 144.4, 141.7, 138.4, 134.3, 132.0, 130.0, 123.4, 122.9, 1605, 1495, 1472, 1248; HRMS (ESI) [M + H]+ calcd for
122.8, 120.0, 115.2, 102.0, 100.2, 98.3, 61.3, 20.5; IR (nmax cmꢁ1
,
C
22H16BrN5O4: 494.0459, found: 494.0377.
6-((4-((1-(3,5-Dimethoxyphenyl)-1H-1,2,3-triazol-4-yl)methoxy)-
KBr): ¼ 3412, 2918, 1603, 1507, 1474, 1251; HRMS (ESI) [M + H]+
calcd for C23H19N5O4: 430.1510, found: 430.1436.
phenyl)diazenyl)benzo[d][1,3]dioxol-5-ol (6i). Dark red solid,
6-((4-((1-(4-Fluorophenyl)-1H-1,2,3-triazol-4-yl)methoxy)phenyl)- M.p.: 167 ꢀC, 1H NMR (400 MHz, DMSO-d6) d ¼ 11.81 (s, 1H, OH),
diazenyl)benzo[d][1,3]dioxol-5-ol (6d). Dark red solid, M.p.: 207 8.63 (s, 1H, triazolyl-H), 7.89 (d, 2H, J ¼ 7.32 Hz, ArH), 7.24–7.09
ꢀC, 1H NMR (400 MHz, DMSO-d6) d ¼ 11.83 (s, 1H, OH), 8.95 (s, (m, 6H, ArH), 6.60 (s, 1H, ArH), 6.06 (s, 2H, OCH2), 5.31 (s, 2H,
1H, triazolyl-H), 7.95–7.88 (m, 4H, ArH), 7.45–7.16 (m, 5H, ArH), OCH2), 3.79 (s, 3H, OCH3), 3.76 (s, 3H, OCH3); 13C NMR (100
6.60 (s, 1H, ArH), 6.06 (s, 2H, OCH2), 5.32 (s, 2H, OCH2); 13C MHz, DMSO-d6): d ¼ 159.3, 154.4, 153.0, 152.0, 149.3, 145.3,
NMR (100 MHz, DMSO-d6): d ¼ 159.4, 154.5, 152.1, 144.8, 141.6, 144.7, 141.5, 132.0, 126.7, 125.6, 123.4, 115.6, 115.1, 114.1, 110.9,
132.9, 132.1, 123.4, 123.2, 122.5, 122.4, 116.8, 116.6, 115.3, 110.3, 101.8, 98.2, 61.1, 56.3, 55.7; IR (nmax cmꢁ1, KBr): ¼ 3422,
102.0, 100.3, 98.3, 61.3; IR (nmax cmꢁ1, KBr): ¼ 3420, 3084, 2917, 2926, 1601, 1508, 1474, 1226; HRMS (ESI) [M + H]+ calcd for
1601, 1514, 1475, 1238; HRMS (ESI) [M + H]+ calcd for C24H21N5O6: 476.1565, found: 476.1481.
C
22H16FN5O4: 434.1259, found: 434.1175.
Procedure for synthesis of amino triazole i.e. 4-((1-(4-
6-((4-((1-(Naphthalen-1-yl)-1H-1,2,3-triazol-4-yl)methoxy)- methoxyphenyl)-1H-1,2,3-triazol-4-yl)methoxy)aniline.
A
phenyl)diazenyl)benzo[d][1,3]dioxol-5-ol (6e). Dark red solid, mixture of 4-(prop-2-ynyloxy)aniline (1 mmol), 1-azido-4-
1
ꢀ
M.p.: 212 C, H NMR (400 MHz, DMSO-d6) d ¼ 11.82 (s, 1H, methoxybenzene (1 mmol), CuSO4$5H2O (10 mol%), sodium
OH), 8.82 (s, 1H, triazolyl-H), 8.20–8.11 (m, 2H, ArH), 7.92–7.90 ascorbate (20 mol%) and 10 mL of THF–water (60 : 40, v/v) was
(m, 2H, ArH), 7.74–7.61 (m, 4H, ArH), 7.45 (d, 2H, J ¼ 7.32 Hz, placed in a 50 mL round-bottomed ask. The reaction mixture
ArH), 7.27–7.17 (m, 3H, ArH), 6.61 (s, 1H, ArH), 6.07 (s, 2H, was stirred at 60 ꢀC for 2 h. The progress of reaction was
OCH2), 5.39 (s, 2H, OCH2); 13C NMR (100 MHz, DMSO-d6): d ¼ monitored by TLC using ethyl acetate–petroleum ether (70 : 30,
159.3, 154.5, 152.1, 144.8, 141.6, 133.5, 133.0, 132.0, 130.2, v/v) as eluent. Aer completion of the reaction as observed by
128.2, 127.9, 127.8, 127.4, 127.0, 125.3, 123.9, 123.4, 122.70, TLC, water (20 mL) was added to the reaction mixture. The
121.7, 115.3, 102.0, 100.2, 98.3, 61.2; IR (nmax cmꢁ1, KBr): ¼ precipitate formed was collected by ltration at pump and
3413, 3070, 2920, 1601, 1497, 1473, 1240; HRMS (ESI) [M + H]+ washed with water. The product so obtained, was recrystallized
calcd for C26H19N5O4: 466.1510, found: 466.1440.
from ethanol to afford amino triazole as brown solid in 87%
6-((4-((1-(4-Nitrophenyl)-1H-1,2,3-triazol-4-yl)methoxy)phenyl)- yield.
diazenyl)benzo[d][1,3]dioxol-5-ol (6f). Dark red solid, M.p.:
Brown solid, M.p.: 120 ꢀC, 1H NMR (400 MHz, DMSO-d6) d ¼
239 ꢀC, 1H NMR (400 MHz, DMSO-d6) d ¼ 11.81 (s, 1H, OH), 9.19 8.50 (s, 1H, triazolyl-H), 7.93 (s, 1H, ArH), 7.38–7.08 (m, 6H,
(s, 1H, triazolyl-H), 8.45 (d, 2H, J ¼ 9.2 Hz, ArH), 8.24 (d, 2H, J ¼ ArH), 6.78 (s, 2H, NH2), 6.48 (s, 1H, ArH), 5.04 (s, 2H, OCH2),
7.36 Hz, ArH), 7.89 (d, 2H, J ¼ 9.16 Hz, ArH), 7.23–7.16 (m, 3H, 3.75 (s, 3H, OCH3); 13C NMR (100 MHz, DMSO-d6): d ¼ 162.0,
ArH), 6.60 (s, 1H, ArH), 6.07 (s, 2H, OCH2), 5.36 (s, 2H, OCH2); 153.3, 145.4, 126.6, 125.6, 125.3, 115.8, 113.9, 110.8, 61.5, 56.7,
13C NMR (100 MHz, DMSO-d6): d ¼ 159.2, 155.7, 154.6, 152.1, 55.8; IR (nmax cmꢁ1, lm): ¼ 3416, 3349, 2932, 1606, 1510; MS
146.7, 144.8, 141.7, 140.6, 132.2, 125.5, 123.5, 123.4, 120.7, (ESI) [M + H]+ calcd for C24H21N5O6: 297.14, found: 297.12.
115.3, 102.0, 100.2, 98.3, 61.3; IR (nmax cmꢁ1, KBr): ¼ 3422, 3082,
2925, 1597, 1505, 1481, 1341, 1238; HRMS (ESI) [M + H]+ calcd
for C22H16N6O6: 461.1204, found: 461.1105.
Acknowledgements
6-((4-((1-(3-Chloro-4-uorophenyl)-1H-1,2,3-triazol-4-yl)- HS and JS thank UGC, New Delhi, India for the grant of Jun-
methoxy)phenyl)diazenyl)benzo [d][1,3]dioxol-5-ol (6g). iorand Senior Research Fellowships.
Dark red solid, M.p.: 183 ꢀC, 1H NMR (400 MHz, DMSO-d6) d
¼ 11.47 (s, 1H, OH), 9.03 (s, 1H, triazolyl-H), 8.24 (d, 2H, J ¼
References
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