Regioselective synthesis, antibacterial, and antioxidant activities of ester-linked 1,4-disubstituted 1,2,3-triazoles

Article abstract of DOI:10.1007/s00706-020-02604-7

Abstract: Synthesis of ester-linked 1,4-disubstituted 1,2,3-triazoles was carried out in water through cycloaddition between benzoic acid prop-2-yn-1-yl esters and aromatic azides using cellulose-supported cuprous iodide nanoparticles. Structures of all t

Full text of DOI:10.1007/s00706-020-02604-7

Monatshefte für Chemie - Chemical Monthly
https://doi.org/10.1007/s00706-020-02604-7
ORIGINAL PAPER
Regioselective synthesis, antibacterial, and antioxidant activities
of ester‑linked 1,4‑disubstituted 1,2,3‑triazoles
C. P. Kaushik1 · Jyoti Sangwan1
Received: 8 January 2020 / Accepted: 8 April 2020
© Springer-Verlag GmbH Austria, part of Springer Nature 2020
Abstract
Synthesis of ester-linked 1,4-disubstituted 1,2,3-triazoles was carried out in water through cycloaddition between benzoic
acid prop-2-yn-1-yl esters and aromatic azides using cellulose-supported cuprous iodide nanoparticles. Structures of all the
synthesized triazoles were confrmed by various spectral techniques like FT-IR, 1H NMR, 13C NMR spectroscopy, and mass
spectral techniques. The synthesized triazoles were evaluated in vitro for antibacterial and antioxidant activities. Results
revealed that most of the synthesized compounds possess moderate to good activity. The structure of one triazole was further
confrmed by X-ray single crystal difraction.
Graphic abstract
Keywords Click chemistry · Cell-CuI nanoparticles · Triazoles · Water · Crystal structure · Biological evaluation
Introduction
from the past few years in the eco-friendly heteroaromatic
synthetic strategy. In particular, use of recyclable nanocata-
lysts fnds an overwhelming response in triazole synthesis
[5, 6].
During the past few decades, signifcant attention has been
paid to the green synthetic methodologies for the develop-
ment of an environmentally friendly protocol. The use of
eco-benign solvents like water, ionic liquids, and the selec-
tion of reusable green catalysts proved to be an efective
approach in green chemistry. Owing to difculty in the
removal of homogeneous catalysts [1] from the reaction
mixture, the use of heterogeneous catalysts [2–4] took a lead
1,2,3-Triazoles are quite stable against oxidation, reduc-
tion, hydrolysis, and can actively interact with biological
targets through hydrogen bonding and dipole–dipole inter-
actions [7], showing this moiety as an important motif for
upcoming synthetic chemists. This leads to 1,2,3-triazoles as
a key scafolds among heterocycles having diverse applica-
tions in the feld of drug discovery [8], bioconjugation [9],
material science [10], and pharmaceutical chemistry [11].
Huisgen 1,3-dipolar cycloaddition reactions are well
known for the synthesis of 1,2,3-triazole framework [12].
The limitation of this azide–alkyne cycloaddition is forma-
tion of mixture of 1,4- and 1,5-disubstituted 1,2,3-triazoles.
To overcome this drawback, in 2002, Sharpless and Meldal’s
group came forward with a copper catalyzed azide–alkyne
Electronic supplementary material The online version of this
article (https://doi.org/10.1007/s00706-020-02604-7) contains
supplementary material, which is available to authorized users.
* C. P. Kaushik
kaushikcp@gmail.com
1
Department of Chemistry, Guru Jambheshwar University
of Science and Technology, Hisar, Haryana 125001, India
Vol.:(0123456789)
1 3

C. P. Kaushik, J. Sangwan
cycloaddition reaction (CuAAC) between alkynes and
azides, to yield regioselectively 1,4-disubstituted 1,2,3-tria-
zoles [13, 14]. This methodology has been labeled as one
of the earlier click reactions. Click chemistry represents a
group of organic reactions that proceed rapidly under ambi-
ent conditions with excellent selectivity and high yields.
Further, the 1,2,3-triazole nucleus exhibited a broad spec-
trum of biological activities such as antibacterial [15, 16],
antifungal [17, 18], anticancer [19–21], antioxidant [22–24],
antimalarial [25–27], antitubercular [28–30], antiviral [31],
and anti-infammatory activity [32, 33]. Newer antibacte-
rial agents are of immense importance due to the increasing
bacterial resistance for commonly available bactericides in
humans. Also, for preventing the diseases like autoimmune
disorder, aging, cardiovascular and neurodegenerative dis-
eases, antioxidants are of signifcant interest. Drugs like ruf-
namide, cefatrizine, tazobactam, etc. containing 1,2,3-tria-
zole pharmacophore are accessible in the market (Fig. 1).
Cellulose serves as a bio-compatible support for various
metal catalysts as it possess microfbrils for the stabilization
of metal nanoparticles involving metal–oxygen interactions
[34]. Further, the cellulose supported metal nanoparticles
act as a heterogeneous metal catalytic system fnding an
edge over homogeneous catalysts. Owing to this, cellulose
supported copper nanoparticles catalyzed azide–alkyne
cycloaddition is an eco-friendly method for the regioselec-
tive synthesis of substituted 1,2,3-triazoles with promising
yield [35].
Results and discussion
Chemistry
The synthetic strategy for ester-linked 1,4-disubstituted
1,2,3-triazoles has been depicted in Scheme 1. At frst, ben-
zoic acid prop-2-yn-1-yl esters 3a–3d were synthesized from
the reaction of corresponding benzoyl chlorides 1a–1d with
propargyl alcohol (2) in the presence of N,N-dimethylamino-
pyridine (DMAP). Aromatic azides 5a–5f were synthesized
by diazotization of aromatic amines 4a–4f followed by reac-
tion with sodium azide. In the fnal step, benzoic acid prop-
2-yn-1-yl esters 3a–3d were reacted with aromatic azides
5a–5f in the presence of cellulose-CuI nanoparticles (Cell-
CuI NPs) using water as a solvent at 60–70 °C to furnish
ester- linked 1,4-disubstituted 1,2,3-triazoles 6a–6x in good
yields. The catalytic system (Cell-CuI NPs) was recovered
up to 90% and recycled up to three times efectively.
The structural assignments of synthesized compounds
6a–6x were characterized by FT-IR, H NMR, 13C NMR,
1
and HRMS. The formation of triazole was confrmed by the
presence of absorption bands in the region 3159–3130 cm−1
(C–H, str., triazole ring), 1728–1703 cm−1 (C=O str., ester),
1283–1270 cm−1 (C–O asym. str., ester), 1120–1047 cm−1
(C–O sym. str., ester) in IR spectra. Presence of char-
acteristic singlets in the region δ = 5.55–5.67 ppm
1
(OCH2), 7.91–8.29 ppm (CH triazole) in H spectra
and δ = 57.8–58.3 ppm (OCH2), 122.3–125.5 ppm (C-5
triazole ring), 142.7–144.4 ppm (C-4 triazole ring),
165.5–166.6 ppm (C=O, ester) in the 13C NMR spectra also
confrmed the formation of the synthesized triazoles. HRMS
spectral studies of the synthesized compounds showed
good agreement with the theoretically predicted molecular
masses. The structure of compound 6q was further con-
frmed by X-ray crystallography (Fig. 2).
In view of broad biological spectrum of 1,2,3-triazole
pharmacophores and the need of economically viable syn-
thetic methods, it has been thought to explore the synthesis
of ester-linked 1,4-disubstituted 1,2,3-triazoles which may
lead to enthusiastic results. In continuation of our previous
work [36, 37], here, we would like to report the cellulose
supported cuprous iodide nanoparticles (Cell-CuI NPs) that
catalyzed green synthesis of 1,2,3-triazoles, their antibacte-
rial and antioxidant activities.
The structure of compound 6r was characterized
through FT-IR, 1D-NMR (1H, 13C, and DEPT-135),
2D-NMR (COSY, HSQC, HMBC, NOESY), and HRMS
data. FT-IR data of 6r displayed absorption at 3132
(C–H str., triazole ring), 3097 (C–H str., aromatic ring),
2968 (C–H str., aliphatic), 1718 (C=O str., ester), 1595,
1448 (C=C str., aromatic ring), 1274 (C–O str., asym.,
1
ester), 1088 (C–O str., sym., ester). H NMR spectrum
Fig. 1 Selected examples of 1,2,3-triazole derivatives with pharmacological activity
1 3

Regioselective synthesis, antibacterial, and antioxidant activities of ester-linked…
Scheme 1
Compounds
R1
H
H
H
H
H
H
F
F
F
F
F
R2
H
2-CH3
3-CH3
4-CH3
4-NO2
—
Compounds
R1
Cl
Cl
Cl
Cl
Cl
Cl
Br
Br
Br
Br
Br
Br
R2
H
2-CH3
3-CH3
4-CH3
4-NO2
—
6a
6b
6c
6d
6e
6f
6g
6h
6i
6m
6n
6o
6p
6q
6r
6s
H
H
2-CH3
3-CH3
4-CH3
4-NO2
—
2-CH3
3-CH3
4-CH3
4-NO2
—
6t
6u
6v
6w
6x
6j
6k
6l
F
1 3

C. P. Kaushik, J. Sangwan
Fig. 2 1H and 13C NMR of compound 6r
of compound 6r shows two singlets at 8.09 and 5.63 ppm
integrating for one and two protons assigned to C5–H and
OCH2, respectively. A three-proton doublet appeared at
8.03 ppm was attributed to C2″–H and C6″–H and one
proton from the naphthyl ring (C8′–H). Another dou-
blet at 7.43 ppm was assigned to C3″–H and C5″–H. One
multiplet 7.63–7.53 ppm which was integrated for five
protons and one doublet at 7.97 ppm integrating for
one proton attributed to protons C3′–H, C4′–H, C5′–H,
C6′–H, C7′–H, and C2′–H, respectively. In 13C NMR
spectrum of 6r, peak in the most downfield region at
165.68 ppm was assigned to the carbonyl carbon. The
peaks at 142.7, 126.7, and 58.3 ppm were assigned to
C4, C5, and OCH2 carbons, respectively. DEPT-135 spec-
trum of compound 6r confirmed the presence of ten car-
bon signals for methine carbons and one carbon signal
for methylene carbon. These assignments were further
confirmed by 2D NMR spectral techniques like COSY,
X‑ray crystallographic study
Slow evaporation of mixture of chloroform:methanol (4:1)
having [1-(4-nitrophenyl)-1H-1,2,3-triazol-4-yl]methyl
4-chlorobenzoate (6q) leads to orange coloured single crys-
tals for which, single X-ray crystallographic study was car-
ried out (Fig. 3). The details of the crystallographic data are
provided in Table 1, shows that compound crystallises in
the monoclinic space group P21/n with a = 13.6638(6) Å,
b = 5.40944(17) Å, c = 21.4964(10) Å, and Z = 4. CCDC
1937268 encloses all the supplementary crystallographic
details for this paper and is accessible free of cost at http://
www.ccdc.cam.ac.uk/conts/retrieving.html.
Antibacterial activity
All the synthesized triazoles were tested for in vitro anti-
bacterial activity against two Gram-positive bacteria,
Staphylococcus aureus (Microbial Type Culture Collec-
tion, MTCC 7443), Bacillus subtilis (MTCC 441), and two
Gram-negative bacteria, Klebsiella pneumoniae (National
Collection of Dairy Cultures, NCDC 138), Escherichia
coli (MTCC 1231) by employing serial dilution method
[36, 37]. Minimum inhibitory concentration (MIC) is
1
HMQC, HSQC, and NOSEY. The H–1H correlation
between protons of 8.03 ppm (C2″, C6″) and 7.42 ppm
(C3″, C5″) was established through COSY spectrum.
The HSQC spectrum revealed the assignment of carbon
signal at 126.7 ppm (C5), 128.4 ppm (C2′), 128.8 ppm
(C3″), 130.6 ppm (C8′), and 131.2 ppm (C2″) because the
key correlation (1H–13C) observed was at 8.09:126.7,
7.97:128.4, 8.03:(131.2, 130.6), and 7.42:128.8, respec-
tively. Heteronuclear multiple bond correlation (HMBC)
experiment reflected the linkage involving hydrogen with
other carbons through multiple bond correlation of sig-
nals at 5.63–126.7, 142.7, 165.9 ppm; 8.03–128.4, 128.8,
131.2 ppm, 139.8; 7.42–131.2 and 139.8 ppm. In NOESY
spectrum, the naphthyl ring proton was not in proximity
with C5–H which shows no significance effect. Further,
the HRMS of compound 6r i.e., 364.0829 were found in
good agreement with the theoretically predicted molecu-
lar mass (3640775).
Fig. 3 Crystal structure of [1-(4-nitrophenyl)-1H-1,2,3-triazol-4-yl]
methyl 4-chlorobenzoate (6q)
1 3

Regioselective synthesis, antibacterial, and antioxidant activities of ester-linked…
Table 1 Crystal data for [1-(4-nitrophenyl)-1H-1,2,3-triazol-4-yl]-
methyl 4-chlorobenzoate (6q)
Structure activity relationship
1. Presence of fuoro/chloro/bromo group on the benzoate
moiety enhanced the antibacterial activity.
Empirical formula
Formula weight
Temperature/K
Crystal system
Space group
a/Å
b/Å
c/Å
α/°
β/°
C16H11ClN4O4
358.74
293
Monoclinic
P21/n
13.6638(6)
5.40944(17)
21.4964(10)
90
97.565(4)
90
1575.05(11)
4
1.513
2.436
2. Among the halogenated triazoles, generally compounds
having bromo group appeared as more efective antibac-
terial agents compared to the others.
3. Compounds having electron withdrawing nitro group on
phenyl ring attached to N atom of the triazoles showed
better antibacterial activity than the electron releasing
methyl group.
4. Compounds containing naphthyl ring demonstrated bet-
ter activity than those having phenyl ring.
γ/°
Volume/Å3
Z
5. Compound 6w having nitro group on phenyl ring and
bromo group on the benzoate moiety exhibited excellent
activity comparable to norfoxacin, the reference drug
used for antibacterial study.
ρcalc/g cm−3
μ/mm−1
F(000)
736.0
Crystal size/mm3
Radiation
0.927 × 0.267 × 0.159
CuKα (λ = 1.54184)
Antioxidant activity
2,2′-Diphenyl-1-picryl hydrazine (DPPH) radical scaveng-
ing antioxidant activity is due to the feature of synthetic
compounds through donation of hydrogen radical to DPPH.
DPPH is a free radical which accepts an electron/hydrogen
radical to form a stable diamagnetic molecule by reacting
with various antioxidants or reducing agents. When elec-
trons become paired of, bleaching of DPPH solution is the
outcome which results in the formation of the colourless
2,2′-diphenyl-1-picryl hydrazine. The reduction capability of
DPPH radicals was determined by the decrease in its absorb-
ance at 517 nm induced by antioxidants. Hence, DPPH is
usually used as a substrate to evaluate anti-oxidative activ-
ity of antioxidants. Percentage inhibition of synthesized
triazoles and IC50 values are presented in Table 3 and the
graphical representation of percentage (%) DPPH radical
scavenging activity of the synthesized compounds is shown
in Fig. 5.
2θ range for data collection/° 7.258 to 146.902
Index ranges
− 16 ≤ h ≤ 15, − 6 ≤ k ≤ 5, − 24 ≤
l ≤ 26
5575
Refections collected
Independent refections
Data/restraints/parameters
Goodness-of-ft on F2
Final R indexes [I ≥ 2σ (I)]
Final R indexes [all data]
Largest dif. peak/hole/e Å−3
3080 [Rint = 0.0638, Rsigma = 0.0662]
3080/0/227
1.021
R1 = 0.0744, wR2 = 0.1923
R1 = 0.1186, wR2 = 0.2422
0.46/− 0.59
presented in µmol cm−3 as presented in Table 2 and the
graphical representation of the MIC values of the synthe-
sized compounds is shown in Fig. 4. Norfoxacin was used
as a standard drug.
It has been observed from Table 2 that most of the synthe-
sized ester-linked 1,4-disubstituted 1,2,3-triazoles showed
moderate to good activity. Compounds 6e, 6f, 6k, 6l, 6o,
6s, 6u, 6w, and 6x (MIC 0.0771, 0.0760, 0.0731, 0.0720,
Out of the 24 synthesized derivatives, derivatives 6l, 6o,
6p, 6r, 6v, and 6x having IC50 values 2.08, 2.34, 2.09, 2.12,
2.18, 1.68 µg cm−3, respectively, exhibited comparable scav-
enging efects on the DPPH stable radical when compared
with the reference antioxidant compound. Triazoles 6l, 6r,
and 6x having naphthyl ring exhibited better radical scaveng-
ing activity as compared to phenyl ring. Also incorporation
of p-methyl group on the phenyl ring attached to N atom of
the triazoles 6p, 6v showed good scavenging activity. Com-
pound 6o has also shown appreciable hydrogen-donating
ability with DPPH radical. It has been observed that the
antioxidant potential of compounds is related with the posi-
tion of the substituents on the phenyl ring. In this sequence,
compound 6d having methyl group attached to p-position in
phenyl ring showed more antioxidant activity as compared
to compounds 6b and 6c having methyl group attached at
0.0764, 0.0700, 0.0674, 0.0622, and 0.0614 μmol cm−3
,
respectively) against S. aureus; compounds 6e, 6k, 6l, 6t,
6u, 6v, 6w, and 6x (MIC 0.0771, 0.0731, 0.0720, 0.0674,
0.0674, 0.0674, 0.0622, and 0.0614 μmol cm−3, respectively)
against B. subtilis; compounds 6f, 6h, 6j, 6m, 6n,6o, 6p, 6q,
6t, and 6w (MIC 0.0380, 0.0402, 0.0402, 0.0399, 0.0382,
0.0382, 0.0382, 0.0349, 0.0337, and 0.0311 μmol cm−3
,
respectively) against E. coli, and compounds 6e, 6h,
6j, 6k, 6o, 6r, 6u, 6v, 6w, and 6x (MIC 0.0386, 0.0402,
0.0402, 0.0365, 0.0382, 0.0344, 0.0337, 0.0337, 0.0311,
and 0.0307 μmol cm−3, respectively) against K. pneumonia
exhibited comparable antibacterial potency to reference drug
used.
1 3

C. P. Kaushik, J. Sangwan
Table 2 Antibacterial assay of
ester-linked 1,4-disubstituted
1,2,3-triazoles 6a–6x (MIC
Compounds
Gram-positive bacteria
Gram-negative bacteria
Staphylococcus aureus Bacillus subtilis
(MTCC 7443)
Escherichia coli
Klebsiella pneumo-
niae (NCDC 138)
in μmol cm−3
)
(MTCC 441)
(MTCC 1231)
6a
0.0896
0.0853
0.0853
0.0853
0.0771
0.0760
0.1683
0.0804
0.0804
0.0804
0.0731
0.0720
0.0799
0.1529
0.0764
0.1529
0.1396
0.0689
0.0700
0.1348
0.0674
0.1348
0.0622
0.0614
0.078
0.0896
0.0853
0.1706
0.0853
0.0771
0.1519
0.0841
0.0804
0.1607
0.0804
0.0731
0.0720
0.0799
0.0764
0.1529
0.0764
0.0698
0.0689
0.1401
0.0674
0.0674
0.0674
0.0622
0.0614
0.078
0.0896
0.0426
0.0426
0.0853
0.0771
0.0380
0.0841
0.0402
0.0804
0.0402
0.0731
0.0720
0.0399
0.0382
0.0382
0.0382
0.0349
0.0689
0.0700
0.0337
0.0674
0.0674
0.0311
0.0614
0.039
0.0896
0.0426
0.0426
0.0426
0.0386
0.0760
0.0420
0.0402
0.0804
0.0402
0.0365
0.0720
0.0799
0.0764
0.0382
0.1529
0.1396
0.0344
0.0700
0.01384
0.0337
0.0337
0.0311
0.0307
0.039
6b
6c
6d
6e
6f
6g
6h
6i
6j
6k
6l
6m
6n
6o
6p
6q
6r
6s
6t
6u
6v
6w
6x
Norfoxacin
Bold indicate the MIC values are comparable with standard used
Fig. 4 Minimum inhibitory
concentration (MIC) of the
synthesized triazoles 6a–6x
0.18
0.16
0.14
0.12
0.1
S.aureus
B.subꢀlis
E.coli
K.pneumoniae
0.08
0.06
0.04
0.02
0
Compounds
1 3

Regioselective synthesis, antibacterial, and antioxidant activities of ester-linked…
Table 3 Percentage inhibition and IC50 values of synthesized tria-
Conclusion
zoles 6a–6x
In summary, we reported economically viable synthesis of
ester-linked 1,4-disubstituted 1,2,3-triazoles in water using
Cell-CuI nanoparticle catalytic system which can be recov-
ered and recycled up to three times without signifcant loss
in yield and activity. Structure of synthesized triazole 6q
was also confrmed through X-ray crystallography (CCDC
1937268). All synthesized compounds were evaluated for
their in vitro antibacterial and antioxidant activity. Anti-
bacterial activity data exhibited that the compound 6w
showed encouraging activity with reference to norfoxacin
against all bacterial strains. The antioxidant activity data
revealed that triazoles 6p, 6r, and 6v refected excellent
activity, comparable to standard drug.
Comp. % inhibi-
tion w.r.t
IC50/
Comp.
% inhibi-
tion w.r.t
AA
IC50/
µg cm−3
µg cm−3
AA
6a
6b
6c
6d
6e
6f
46.2
45.4
48.8
50.3
43.4
56.6
61.6
57.2
60.4
59.7
52.0
64.3
5.69
4.23
3.61
3.94
4.47
3.3
2.49
3.04
2.69
2.45
2.52
2.08
6m
6n
6o
6p
6q
6r
6s
59.4
60.6
64.6
68.7
48.6
67.3
56.8
58.5
61.7
67.5
48.9
63.2
2.58
2.47
2.34
2.09
2.05
2.12
3.21
3.25
2.93
2.18
3.78
1.68
1.41
6g
6h
6i
6t
6u
6v
6w
6x
6j
6k
6l
Ascorbic 76.4
acid
Experimental
(AA)
All the chemicals and solvents for the present work were
purchased from Sigma Aldrich, Alfa-Aesar, and Hi-Media
and used without further purifcation. Melting points of
the synthesized compounds were recorded on an Elec-
trothermal melting point apparatus in open capillaries.
The IR spectra were recorded on Shimazdu IR Afnity-I
FT-IR spectrophotometer using potassium bromide (KBr)
Bold indicate the MIC values are comparable with standard used
o- and m-position, respectively. Similar behavior was also
observed in compounds 6n, 6o, 6p and 6t, 6u, 6v.
Based on the above observations, it can be inferred that
broadly the presence of chloro group on the benzoate moi-
ety (6m–6r) increased the radical scavenging capacity in
comparison to fuoro/bromo groups. Further, the presence
of tolyl and naphthyl moiety attach to N atom of the triazole
ring also showed excellent DPPH scavenging activities.
1
and the values are given in cm−1. The H and 13C were
recorded on Bruker Avance II 400 MHz at 400 MHz and
100 MHz, respectively, using deuterated chloroform as
solvent (CDCl3) and tetramethylsilane (TMS) as an inter-
nal standard (chemical shift in δ, ppm). Coupling con-
stant (J) values are given in Hertz (Hz) and multiplic-
ity of NMR signals were assigned as singlet (s), doublet
(d), triplet (t), quartet (q), multiplet (m), and doublet of
doublet (dd). High-resolution mass spectra were recorded
Fig. 5 Graphical representation
of percentage DPPH radical
scavenging activity of the syn-
thesized compounds 6a–6x
90
80
70
60
50
40
30
20
10
0
Compounds
1 3

C. P. Kaushik, J. Sangwan
on Water Micremass Q-Tof Micro (ESI) spectrophotom-
eter. The completion of the reaction and the purity of the
compounds were monitored by thin-layer chromatography
(TLC) using silica gel plates (SIL G/UV254, ALUGRAM)
and visualized under ultraviolet lamp.
vacuum to give the corresponding ester-linked 1,4-disubsti-
tuted 1,2,3-triazoles in good yield.
(1‑Phenyl‑1H‑1,2,3‑triazol‑4‑yl)methyl benzoate (6a,
C16H13N3O2) White, crystalline solid; yield: 89%; m.p.: 120–
124 °C; 1H NMR (400 MHz, CDCl3): δ = 8.17 (s, 1H, C–H
triazole), 8.09 (d, J = 8.0 Hz, 2H, ArH), 7.76 (d, J = 8.0 Hz,
2H, ArH), 7.61–7.53 (m, 3H, ArH), 7.49–7.44 (m, 3H, ArH),
5.59 (s, 2H, OCH2) ppm; 13C NMR (100 MHz, CDCl3):
δ = 166.5 (C=O), 143.7 (C4 triazole), 136.9, 133.28, 129.8,
129.7, 128.9, 128.4, 122.3 (C5 triazole), 120.7, 77.4, 77.1,
76.7, 58.1 (OCH2) ppm; FT-IR (KBr): v̄ = 3134 (C–H str.,
triazole ring), 3093 (C–H str., aromatic ring), 2964 (C–H
str., aliphatic), 1720 (C=O str., ester), 1598, 1446 (C=C str.,
aromatic ring), 1273 (C–O str., asym., ester), 1101 (C–O
str., sym., ester) cm−1; HRMS: m/z calcd. for C16H13N3O2
([M+H]+) 280.1008, found 280.1072.
Preparation of cellulose‑supported cuprous iodide
nanoparticles (Cell‑CuI NPs)
Nanoparticles were prepared using method reported by
Chavan et al. [35]. To a stirred suspension of 0.190 g CuI
(1 mmol) in 30 cm3 methanol was added 2 g microcrystalline
cellulose and stirring was continued overnight. The reaction
contents were fltered and residue was washed repeatedly
with methanol and fnally with acetone. It was dried in air
and then at 50–60 °C for 6 h under vacuum.
General procedure for the (Cell‑CuI NPs) catalyzed
synthesis of (1‑substituted‑1H‑1,2,3‑triazol‑4‑yl)‑
methyl benzoates 6a–6x
[1‑(o‑Tolyl)‑1H‑1,2,3‑triazol‑4‑yl]methyl benzoate (6b,
1
C17H15N3O2) White solid; yield: 88%; m.p.: 60–64 °C; H
NMR (400 MHz, CDCl3): δ = 8.10 (d, J = 8.0 Hz, 2H, ArH),
7.92 (s, 1H, C–H triazole), 7.59 (t, J = 7.4 Hz, 1H, ArH),
7.48 (d, J = 8.0 Hz, 2H, ArH), 7.38 (m, 4H, ArH), 5.60 (s,
2H, OCH2), 2.25 (s, 3H, CH3) ppm; 13C NMR (100 MHz,
CDCl3): δ = 166.5 (C=O), 142.8 (C4 triazole), 136.3, 133.7,
133.3, 131.5, 130.0, 129.8, 129.7, 128.4, 126.9, 126.0, 125.5
(C5 triazole), 58.1 (OCH2), 17.9 (CH3) ppm; FT-IR (KBr):
v̄ = 3148 (C–H str., triazole ring), 3061 (C–H str., aromatic
ring), 2926 (C–H str., aliphatic), 1717 (C=O str., ester),
1601, 1462 (C=C str., aromatic ring), 1270 (C–O str., asym.,
ester), 1111 (C–O str., sym., ester) cm−1; HRMS: m/z calcd.
for C17H15N3O2 ([M+H]+) 294.1164, found 294.1230.
The starting materials benzoic acid prop-2-ynyl esters 3a–3d
were synthesized by reacting corresponding benzoyl chlo-
ride 1a–1d (1.0 mmol) and propargyl alcohol (2) (1.0 mmol)
in the presence of N,N-dimethylaminopyridine (DMAP,
1.2 mmol) in dichloromethane at 0–10 °C for 3–4 h. After
completion of the reaction, the desired terminal alkynes
were isolated from the organic solvent through evaporation
under reduced pressure.
Aromatic azides 5a–5f were prepared by dissolving vari-
ous aromatic amines 4a–4f (1.0 mmol) in dichloromethane
and to this solution, 10 cm3 dilute HCl was added. The
reaction contents was cooled below 5 °C in an ice bath and
diazotized with a solution of NaNO2 (1.5 mmol) in distilled
water. The mixture was stirred in an ice bath for 1 h. A
solution of sodium azide (2.0 mmol) in water was added
at 0–5 °C, and the mixture was further stirred for 30 min.
The mixture was allowed come to room temperature, con-
tinued stirring for an additional 2 h. On completion of the
reaction, the mixture was extracted with dichloromethane
(25 × 2 cm3), and evaporated to get the required aromatic
azides.
[1‑(m‑Tolyl)‑1H‑1,2,3‑triazol‑4‑yl]methyl benzoate (6c,
1
C17H15N3O2) Brown solid; yield: 67%; m.p.: 64–68 °C; H
NMR (400 MHz, CDCl3): δ = 8.14 (s, 1H, C–H triazole),
8.09 (d, J = 4.0 Hz, 2H, ArH), 7.59 (s, 2H, ArH), 7.54 (d,
J = 8.0 Hz, 1H, ArH), 7.48–7.40 (m, 4H, ArH), 5.58 (s,
2H, OCH2), 2.47 (s, 3H, CH3) ppm; 13C NMR (101 MHz,
CDCl3): δ = 166.5 (C=O), 143.6 (C4 triazole), 140.0,
136.8, 133.3, 129.8, 129.7, 129.6, 128.4, 122.4 (C5 tria-
zole), 121.3, 117.7, 58.1 (OCH2), 21.4 (CH3) ppm; FT-IR
(KBr): v̄ = 3152 (C–H str., triazole ring), 3067 (C–H str.,
aromatic ring), 2920 (C–H str., aliphatic), 1713 (C=O str.,
ester), 1597, 1452 (C=C str., aromatic ring), 1273 (C–O str.,
asym., ester), 1109 (C–O str., sym., ester) cm−1; HRMS: m/z
calcd. for C17H15N3O2 ([M+H]+) 294.1164, found 294.1230.
In the fnal step, benzoic acid prop-2-ynyl esters 3a–3d
(1 mmol) and aromatic azides 5a–5f (1 mmol) were added
to a suspension of 100 mg Cell-CuI NPs in water. The reac-
tion mixture was warmed up to 60–70 °C and progress of
the reaction was monitored by TLC. After completion of the
synthesis, reaction contents were fltered and 30 cm3 water
was added to the resulting fltrate, followed by addition of
ammonia solution and fnally the product extraction with
ethyl acetate (30 × 2 cm3). The collected organic phases
were washed with water and the solvent was removed under
[1‑(p‑Tolyl)‑1H‑1,2,3‑triazol‑4‑yl]methyl benzoate (6d,
C
17H15N3O2) White solid; yield: 91%; m.p.: 110–114 °C; 1H
NMR (400 MHz, CDCl3): δ = 8.12 (s, 1H, C–H triazole),
8.09 (d, J = 8.0 Hz, 2H, ArH), 7.63 (d, J = 8.0 Hz, 2H, ArH),
7.58 (d, J = 8.0 Hz, 1H, ArH), 7.46 (t, J = 8.0 Hz, 2H, ArH),
1 3

Regioselective synthesis, antibacterial, and antioxidant activities of ester-linked…
7.33 (d, J = 8.0 Hz, 2H, ArH), 5.58 (s, 2H, OCH2), 2.44 (s,
3H, CH3) ppm; 13C NMR (100 MHz, CDCl3): δ = 166.5
(C=O), 143.5 (C4 triazole), 139.1, 134.6, 133.3, 130.3,
129.8, 129.71, 129.6, 128.4, 122.3 (C5 triazole), 120.6, 58.1
(OCH2), 21.1 (CH3) ppm; FT-IR (KBr): v̄ = 3142 (C–H str.,
triazole ring), 3099 (C–H str., aromatic ring), 2916 (C–H
str., aliphatic), 1716 (C=O str., ester), 1600, 1452 (C=C str.,
aromatic ring), 1274 (C–O str., asym., ester), 1111 (C–O
str., sym., ester) cm−1; HRMS: m/z calcd. for C17H15N3O2
([M+H]+) 294.1164, found 294.1230.
v̄ = 3140 (C–H str., triazole ring), 3102 (C–H str., aromatic
ring), 2978 (C–H str., aliphatic), 1722 (C=O str., ester),
1599, 1460 (C=C str., aromatic ring), 1278 (C–O str., asym.,
ester), 1092 (C–O str., sym., ester) cm−1; HRMS: m/z calcd.
for C16H12FN3O2 ([M+H]+) 298.0914, found 298.0972
[1‑(o‑Tolyl)‑1H‑1,2,3‑triazol‑4‑yl]methyl 4‑fuorobenzoate
(6h, C17H14FN3O2) White solid; yield: 87%; m.p.: 94–98 °C;
1H NMR (400 MHz, CDCl3): δ = 8.11 (dd, J = 8.0, 8.0
Hz, 2H, ArH), 7.91 (s, 1H, C–H triazole), 7.46–7.42 (m,
1H, ArH), 7.39 (d, J = 8.0 Hz, 1H, ArH), 7.35 (dd, J = 3.5,
0.9 Hz, 2H, ArH), 7.13 (t, J = 8.0 Hz, 2H, ArH), 5.58 (s,
2H, OCH2), 2.25 (s, 3H, CH3) ppm; 13C NMR (100 MHz,
CDCl3): δ = 167.9 (d, J = 253 Hz), 165.5 (C=O), 142.7 (C4
triazole), 136.3, 133.6, 132.4 (d, J = 9 Hz), 131.5, 130.0,
126.9, 126.0 (d, J = 5 Hz), 125.5 (C5 triazole), 115.6 (d,
J = 22 Hz), 58.2 (OCH2), 17.9 ppm; FT-IR (KBr): v̄ = 3148
(C–H str., triazole ring), 3078 (C–H str., aromatic ring),
2974 (C–H str., aliphatic), 1717 (C=O str., ester), 1603,
1466 (C=C str., aromatic ring), 1267 (C–O str., asym.,
ester), 1096 (C–O str., sym., ester) cm−1; HRMS: m/z calcd.
for C17H14FN3O2 ([M+H]+) 312.1070, found 312.1134.
[1‑(4‑Nitrophenyl)‑1H‑1,2,3‑triazol‑4‑yl]methyl benzoate (6e,
C16H12N4O4) Brown solid; yield: 75%; m.p.: 144–148 °C; 1H
NMR (400 MHz, CDCl3): δ = 8.45 (d, J = 8 Hz, 2H), 8.29
(s, 1H, C–H triazole), 8.09 (d, J = 8.0 Hz, 2H, ArH), 8.02 (d,
J = 8.0 Hz, 2H, ArH), 7.61 (t, J = 8.0 Hz, 1H, ArH) 7.47 (t,
J = 8.0 Hz, 2H, ArH), 5.60 (s, 2H, OCH2) ppm; 13C NMR
(100 MHz, CDCl3): δ = 166.6 (C=O), 147.4, 144.4 (C4 tria-
zole), 141.0, 133.5, 129.8, 129.5, 128.5, 125.6, 122.3 (C5
triazole), 120.6, 57.8 (OCH2) ppm; FT-IR (KBr): v̄ = 3130
(C–H str., triazole ring), 3090 (C–H str., aromatic ring),
2964 (C–H str., aliphatic), 1719 (C=O str., ester), 1599,
1452 (C=C str., aromatic ring), 1531 (N–O str., asym., NO2),
1344 (N–O str., sym., NO2), 1271 (C–O str., asym., ester),
1092 (C–O str., sym., ester) cm−1; HRMS: m/z calcd. for
C16H12N4O4 ([M+H]+) 325.0859, found 325.0929
[1‑(m‑Tolyl)‑1H‑1,2,3‑triazol‑4‑yl]methyl 4‑fuorobenzoate
(6i, C17H14FN3O2) White solid; yield: 61%; m.p.: 92–96 °C;
1H NMR (400 MHz, CDCl3): δ = 8.15–8.09 (3H ArH and
C–H triazole), 7.59 (s, 1H, ArH), 7.53 (d, J = 8.0 Hz, 1H,
ArH), 7.42 (t, J = 8.0 Hz, 1H, ArH), 7.13 (t, J = 8.0 Hz,
[1‑(Naphthalen‑1‑yl)‑1H‑1,2,3‑triazol‑4‑yl]methyl benzoate
(6f, C20H15N3O2) Brown solid; yield: 58%; m.p.: 66–70 °C;
1H NMR (400 MHz, CDCl3): δ = 8.13 (s, 1H, C–H tria-
zole), 8.11 (s, 2H, ArH), 8.05 (dd, J = 6.4, 2.4 Hz, 1H,
ArH), 7.99 (d, J = 8.0 Hz, 1H, ArH), 7.62 (m, 6H, ArH),
7.47 (t, J = 7.6 Hz, 2H, ArH), 5.67 (s, 2H, OCH2) ppm;
13C NMR (100 MHz, CDCl3): δ = 166.5 (C=O), 143.0 (C4
triazole), 134.2, 133.5, 133.3, 130.6, 129.8, 129.7, 128.5,
128.3, 128.00, 127.1, 126.6 (C5 triazole), 125.0, 123.6,
122.3, 58.1 (OCH2) ppm; FT-IR (KBr): v̄ = 3136 (C–H str.,
triazole ring), 3061 (C–H str., aromatic ring), 2965 (C–H
str., aliphatic), 1724 (C=O str., ester), 1599, 1447 (C=C str.,
aromatic ring), 1273 (C–O str., asym., ester), 1099 (C–O
str., sym., ester) cm−1; HRMS: m/z calcd. for C20H15N3O2
([M+H]+) 330.1164, found 330.1226.
2H, ArH), 5.56 (s, 2H, OCH2), 2.47 (s, 3H, CH3) ppm; 13
C
NMR (100 MHz, CDCl3): δ = 166.0 (d, J = 253 Hz), 165.6
(C=O), 143.3 (C4 triazole), 140.1, 136.9, 132.4 (d, J = 9
Hz), 129.7 (d, J = 16 Hz), 125.9, 122.4 (C5 triazole), 121.3,
117.7, 115.6 (d, J = 22 Hz), 58.2 (OCH2), 21.4 ppm; FT-IR
(KBr): v̄ = 3150 (C–H str., triazole ring), 3107 (C–H str.,
aromatic ring), 2953 (C–H str., aliphatic), 1715 (C=O str.,
ester), 1599, 1458 (C=C str., aromatic ring), 1271 (C–O str.,
asym., ester), 1120 (C–O str., sym., ester) cm−1; HRMS:
m/z calcd. for C17H14FN3O2 ([M+H]+) 312.1070, found
312.1134.
[1‑(p‑Tolyl)‑1H‑1,2,3‑triazol‑4‑yl]methyl 4‑fuorobenzoate (6j,
C17H14FN3O2) White solid; yield: 81%; m.p.: 112–116 °C; 1H
NMR (400 MHz, CDCl3): δ = 8.11 (s, 1H, C–H triazole),
8.10 (d, J = 4.0 Hz, 1H, ArH), 8.08 (s, 1H, ArH), 7.62 (d,
J = 8.0 Hz, 2H, ArH), 7.33 (d, J = 8.3 Hz, 2H, ArH), 7.12
(t, J = 8.6 Hz, 2H, ArH), 5.55 (s, 2H, OCH2), 2.43 (s, 3H,
CH3) ppm; 13C NMR (100 MHz, CDCl3): δ = 165.9 (d,
J = 253 Hz), 165.5 (C=O), 143.4 (C4 triazole), 139.1, 134.6,
132.4 (d, J = 10 Hz), 130.3, 126.0 (d, J = 3 Hz), 122.3
(C5 triazole), 120.5, 115.6 (d, J = 22 Hz), 58.1 (OCH2),
21.1 ppm; FT-IR (KBr): v̄ = 3159 (C–H str., triazole ring),
3072 (C–H str., aromatic ring), 2967 (C–H str., aliphatic),
1717 (C=O str., ester), 1599, 1450 (C=C str., aromatic
(1‑Phenyl‑1H‑1,2,3‑triazol‑4‑yl)methyl 4‑fuorobenzoate (6g,
C16H12FN3O2) White solid; yield: 78%; m.p.: 76–80 °C; 1H
NMR (400 MHz, CDCl3): δ = 8.16 (s, 1H, C–H triazole),
8.11 (dd, J = 8.0, 4.0 Hz, 2H, ArH), 7.76 (d, J = 8.0 Hz, 2H,
ArH), 7.58–7.54 (m, 2H, ArH), 7.50–7.45 (m, 1H, ArH),
7.13 (t, J = 8.0 Hz, 2H, ArH), 5.57 (s, 2H, OCH2) ppm;
13C NMR (100 MHz, CDCl3): δ = 166.0 (d, J = 253 Hz),
165.6 (C=O), 143.5 (C4 triazole), 136.9, 132.4 (d, J = 9
Hz), 129.8, 129.0, 125.9 (d, J = 3 Hz), 122.4 (C5 triazole),
120.7, 115.6 (d, J = 22 Hz), 58.1 (OCH2) ppm; FT-IR (KBr):
1 3

C. P. Kaushik, J. Sangwan
ring), 1271 (C–O str., asym., ester), 1099 (C–O str., sym.,
ester) cm−1; HRMS: m/z calcd. for C17H14FN3O2 ([M+H]+)
312.1070, found 312.1134.
([M+H]+) 314.0618, ([M+2]+) 316.0589, found 314.0680,
316.0646.
[1‑(o‑Tolyl)‑1H‑1,2,3‑triazol‑4‑yl]methyl 4‑chlorobenzoate
(6n, C17H14ClN3O2) White solid; yield: 86%; m.p.: 60–64 °C;
1H NMR (400 MHz, CDCl3): δ = 8.03 (d, J = 8.0 Hz, 2H,
ArH), 7.91 (s, 1H, C–H triazole), 7.43 (d, J = 8.0 Hz, 3H,
ArH), 7.39 (d, J = 8.0 Hz, 1H, ArH), 7.35 (d, J = 4.0 Hz,
[1‑(4‑Nitrophenyl)‑1H‑1,2,3‑triazol‑4‑yl]methyl 4‑fuoroben‑
zoate (6k, C16H11FN4O4) Yellow solid; yield: 79%; m.p.:
1
166–170 °C; H NMR (400 MHz, CDCl3): δ = 8.45 (d,
J = 8 Hz, 2H, ArH), 8.28 (s, 1H, C–H triazole), 8.11 (dd,
J = 8.0, 4.0 Hz, 2H, ArH), 8.02 (d, J = 8.0 Hz, 2H, ArH),
2H, ArH), 5.59 (s, 2H, OCH2), 2.25 (s, 3H, CH3) ppm; 13
C
7.14 (t, J = 8.0 Hz, 2H, ArH), 5.59 (s, 2H, OCH2) ppm; 13
C
NMR (100 MHz, CDCl3): δ = 165.6 (C=O), 142.5 (C4 tria-
zole), 139.7, 136.3, 133.6, 131.5, 131.2, 130.0, 128.8, 128.2,
126.9, 126.0, 125.5 (C5 triazole), 58.3 (OCH2), 17.9 ppm;
FT-IR (KBr): v̄ = 3154 (C–H str., triazole ring), 3088 (C–H
str., aromatic ring), 2926 (C–H str., aliphatic), 1726 (C=O
str., ester), 1593, 1464 (C=C str., aromatic ring), 1283 (C–O
str., asym., ester), 1092 (C–O str., sym., ester) cm−1; HRMS:
m/z calcd. for C17H14ClN3O2 ([M+H]+) 328.0775, ([M+2]+)
330.0745, found 328.0837, 330.0803.
NMR (100 MHz, CDCl3): δ = 166.0 (d, J = 253 Hz), 165.6
(C=O), 147.4, 144.4 (C4 triazole), 141.0, 132.4 (d, J = 10
Hz), 132.4, 125.7 (d, J = 3 Hz), 125.6, 122.3 (C5 triazole),
120.6, 115.7 (d, J = 22 Hz), 57.8 (OCH2) ppm; FT-IR (KBr):
v̄ = 3142 (C–H str., triazole ring), 3103 (C–H str., aromatic
ring), 2957 (C–H str., aliphatic), 1703 (C=O str., ester),
1601, 1413 (C=C str., aromatic ring), 1526 (N–O str., asym.,
NO2), 1342 (N–O str., sym., NO2), 1273 (C–O str., asym.,
ester), 1112 (C–O str., sym., ester) cm−1; HRMS: m/z calcd.
for C16H11FN4O4 ([M+H]+) 343.0764, found 343.0837
[1‑(m‑Tolyl)‑1H‑1,2,3‑triazol‑4‑yl]methyl 4‑chlorobenzoate
(6o, C17H14ClN3O2) Brown solid; yield: 69%; m.p.: 114–
118 °C; 1H NMR (400 MHz, CDCl3): δ = 8.14 (s, 1H, C–H
triazole), 8.01 (d, J = 8.0 Hz, 2H, ArH), 7.59 (s, 1H, ArH),
7.53 (d, J = 8.0 Hz, 1H, ArH), 7.42 (d, J = 8.0 Hz, 3H,
ArH), 7.26 (s, 1H, ArH), 5.56 (s, 2H, OCH2), 2.46 (s, 3H,
CH3) ppm; 13C NMR (100 MHz, CDCl3): δ = 165.7 (C=O),
143.2 (C4 triazole), 140.1, 139.8, 136.8, 131.2, 129.7, 129.6,
128.8, 128.2, 122.4 (C5 triazole), 121.3, 117.7, 58.2 (OCH2),
21.4 ppm; FT-IR (KBr): v̄ = 3148 (C–H str., triazole ring),
3103 (C–H str., aromatic ring), 2955 (C–H str., aliphatic),
1717 (C=O str., ester), 1595, 1421 (C=C str., aromatic
ring), 1271 (C–O str., asym., ester), 1092 (C–O str., sym.,
ester) cm−1; HRMS: m/z calcd. for C17H14ClN3O2 ([M+H]+)
328.0775, ([M+2]+) 330.0745, found 328.0837, 330.0803.
[1‑(Naphthalen‑1‑yl)‑1H‑1,2,3‑triazol‑4‑yl]methyl
4‑fuorobenzoate (6l, C20H14FN3O2) White solid; yield: 52%;
1
m.p.: 68–72 °C; H NMR (400 MHz, CDCl3): δ = 8.15–
8.11 (2H ArH and C–H triazole), 8.06 (dd, J = 5.9, 3.4
Hz, 1H, ArH), 7.99 (d, J = 8.0 Hz, 1H, ArH), 7.67–7.55
(m, 5H, ArH), 7.14 (t, J = 8.6 Hz, 2H, ArH), 5.65 (s, 2H,
OCH2) ppm; 13C NMR (100 MHz, CDCl3): δ = 166.0 (d,
J = 255 Hz), 165.6 (C=O), 142.8 (C4 triazole), 134.2,
133.5, 132.4 (d, J = 10 Hz), 130.6, 128.4, 128.3, 128.0,
127.2, 126.7 (C5 triazole), 126.0 (d, J = 3 Hz), 125.0, 123.7,
122.2, 115.7 (d, J = 22 Hz), 58.2 (OCH2) ppm; FT-IR (KBr):
v̄ = 3146 (C–H str., triazole ring), 3048 (C–H str., aromatic
ring), 2972 (C–H str., aliphatic), 1724 (C=O str., ester),
1599, 1444 (C=C str., aromatic ring), 1265 (C–O str., asym.,
ester), 1105 (C–O str., sym., ester) cm−1; HRMS: m/z calcd.
for C20H14FN3O2 ([M+H]+) 348.1070, found 348.1125.
[1‑(p‑Tolyl)‑1H‑1,2,3‑triazol‑4‑yl]methyl 4‑chlorobenzoate
(6p, C17H14ClN3O2) White solid; yield: 80%; m.p.: 108–
112 °C; 1H NMR (400 MHz, CDCl3): δ = 8.11 (s, 1H, C–H
triazole), 8.02 (d, J = 8.0 Hz, 2H, ArH), 7.63 (d, J = 8.0 Hz,
2H, ArH), 7.43 (d, J = 8.0 Hz, 2H, ArH), 7.34 (d, J = 8.0
Hz, 2H, ArH), 5.56 (s, 2H, OCH2), 2.45 (s, 3H, CH3) ppm;
13C NMR (100 MHz, CDCl3): δ = 165.7 (C=O), 143.2 (C4
triazole), 139.8, 139.2, 134.6, 131.2, 130.3, 128.8, 128.2,
122.3 (C5 triazole), 120.6, 58.2 (OCH2), 21.1 ppm; FT-IR
(KBr): v̄ = 3148 (C–H str., triazole ring), 3099 (C–H str.,
aromatic ring), 2911 (C–H str., aliphatic), 1726 (C=O str.,
ester), 1595, 1458 (C=C str., aromatic ring), 1271 (C–O str.,
asym., ester), 1092 (C–O str., sym., ester) cm−1; HRMS:
m/z calcd. for C17H14ClN3O2 ([M+H]+) 328.0775, ([M+2]+)
330.0745, found 328.0837, 330.0803.
(1‑Phenyl‑1H‑1,2,3‑triazol‑4‑yl)methyl 4‑chlorobenzoate
(6m, C16H12ClN3O2) White solid; yield: 83%; m.p.: 90–94 °C;
1H NMR (400 MHz, CDCl3): δ = 8.16 (s, 1H, C–H triazole),
8.02 (d, J = 8.0 Hz, 2H, ArH), 7.77 (d, J = 4.0 Hz, 1H,
ArH), 7.75 (s, 1H, ArH), 7.55 (t, J = 7.6 Hz, 2H, ArH), 7.48
(d, J = 4.0 Hz, 1H, ArH), 7.43 (d, J = 8.0 Hz, 2H, ArH),
5.57 (s, 2H, OCH2) ppm; 13C NMR (100 MHz, CDCl3):
δ = 165.7 (C=O), 143.5 (C4 triazole), 139.8, 136.9, 131.2,
129.8, 129.0, 128.8, 128.1, 122.4 (C5 triazole), 120.7, 58.2
(OCH2) ppm; FT-IR (KBr): v̄ = 3134 (C–H str., triazole
ring), 3094 (C–H str., aromatic ring), 2968 (C–H str., ali-
phatic), 1724 (C=O str., ester), 1597, 1466 (C=C str., aro-
matic ring), 1273 (C–O str., asym., ester), 1096 (C–O str.,
sym., ester) cm−1; HRMS: m/z calcd. for C16H12ClN3O2
[1‑(4‑Nitrophenyl)‑1H‑1,2,3‑triazol‑4‑yl]methyl 4‑chlo‑
robenzoate (6q, C16H11ClN4O4) Orange solid; yield: 78%;
1 3

Regioselective synthesis, antibacterial, and antioxidant activities of ester-linked…
m.p.: 164–168 °C; 1H NMR (400 MHz, CDCl3): δ = 8.44
(d, J = 8.0 Hz, 2H, ArH), 8.28 (s, 1H, C–H triazole), 8.02
(d, J = 12.0 Hz, 4H, ArH), 7.44 (d, J = 8.0 Hz, 2H, ArH),
5.59 (s, 2H, OCH2) ppm; 13C NMR (100 MHz, CDCl3):
δ = 165.7 (C=O), 147.4, 144.4 (C4 triazole), 141.0, 140.0,
131.2, 128.9, 127.9, 125.6, 122.3 (C5 triazole), 120.6, 57.9
(OCH2) ppm; FT-IR (KBr): v̄ = 3144 (C–H str., triazole
ring), 3098 (C–H str., aromatic ring), 2952 (C–H str., ali-
phatic), 1705 (C=O str., ester), 1595, 1487 (C=C str., aro-
matic ring), 1530 (N–O str., asym., NO2), 1344 (N–O str.,
sym., NO2), 1275 (C–O str., asym., ester), 1090 (C–O str.,
sym., ester) cm−1; HRMS: m/z calcd. for C16H11ClN4O4
([M+H]+) 359.04688, ([M+2]+) 361.0439, found 359.0539,
361.0508.
ArH), 7.35 (d, J = 4.0 Hz, 2H, ArH), 5.58 (s, 2H, OCH2),
2.24 (s, 3H, CH3) ppm; 13C NMR (100 MHz, CDCl3):
δ = 165.8 (C=O), 142.5 (C4 triazole), 136.3, 133.6, 131.8,
131.5, 131.3, 130.0, 128.7, 128.4, 126.9, 126.0, 125.6 (C5
triazole), 58.3 (OCH2), 17.9 ppm; FT-IR (KBr): v̄ = 3154
(C–H str., triazole ring), 3084 (C–H str., aromatic ring),
2980 (C–H str., aliphatic), 1724 (C=O str., ester), 1587,
1464 (C=C str., aromatic ring), 1273 (C–O str., asym.,
ester), 1119 (C–O str., sym., ester) cm−1; HRMS: m/z calcd.
for C17H14BrN3O2 ([M+H]+) 372.0269, ([M+2]+) 374.0249,
found 372.0308, 374.0308.
[1‑(m‑Tolyl)‑1H‑1,2,3‑triazol‑4‑yl]methyl 4‑bromobenzoate
(6u, C17H14BrN3O2) Brown solid; yield: 63%; m.p.: 114–
118 °C; 1H NMR (400 MHz, CDCl3): δ = 8.14 (s, 1H, C–H
triazole), 7.93 (d, J = 8.0 Hz, 2H, ArH), 7.59–7.57 (m, 3H,
ArH), 7.53 (d, J = 8.0 Hz, 1H, ArH), 7.41 (t, J = 8.0 Hz, 1H,
ArH), 7.27 (d, J = 8.0 Hz, 1H, ArH), 5.56 (s, 2H, OCH2),
2.45 (s, 3H, CH3) ppm; 13C NMR (100 MHz, CDCl3):
δ = 165.8 (C=O), 143.4 (C4 triazole), 140.1, 136.8, 131.8,
131.3, 129.7, 129.6, 128.6, 128.5, 122.5 (C5 triazole), 121.3,
117.7, 58.3 (OCH2), 21.4 ppm; FT-IR (KBr): v̄ = 3146 (C–H
str., triazole ring), 3103 (C–H str., aromatic ring), 2955
(C–H str., aliphatic), 1715 (C=O str., ester), 1591, 1479
(C=C str., aromatic ring), 1269 (C–O str., asym., ester),
1047 (C–O str., sym., ester) cm−1; HRMS: m/z calcd. for
C17H14BrN3O2 ([M+H]+) 372.02694, ([M+2]+) 374.0249,
found 372.0308, 374.0308.
[1‑(Naphthalen‑1‑yl)‑1H‑1,2,3‑triazol‑4‑yl]methyl 4‑chlo‑
robenzoate (6r, C20H14ClN3O2) Brown solid; yield: 56%;
1
m.p.: 72–76 °C; H NMR (400 MHz, CDCl3): δ = 8.09
(s, 1H, C–H triazole), 8.03 (d, J = 8.0 Hz, 3H, ArH), 7.97
(d, J = 8.0 Hz, 1H, ArH), 7.63–7.53 (m, 5H, ArH), 7.42
(d, J = 8.0 Hz, 2H, ArH), 5.63 (s, 2H, OCH2) ppm; 13C
NMR (100 MHz, CDCl3): δ = 165.7 (C=O), 142.7 (C4
triazole), 139.8, 134.2, 133.5, 131.2, 130.6, 128.8, 128.4,
128.3, 128.2, 128.0, 127.2, 126.7 (C5 triazole), 125.0, 123.6,
122.2, 58.3 (OCH2) ppm; FT-IR (KBr): v̄ = 3132 (C–H str.,
triazole ring), 3097 (C–H str., aromatic ring), 2968 (C–H
str., aliphatic), 1718 (C=O str., ester), 1595, 1448 (C=C str.,
aromatic ring), 1274 (C–O str., asym., ester), 1088 (C–O
str., sym., ester) cm−1; HRMS: m/z calcd. for C20H14ClN3O2
([M+H]+) 364.0775, ([M+2]+) 366.0745, found 364.0829,
366.0799.
[1‑(p‑Tolyl)‑1H‑1,2,3‑triazol‑4‑yl]methyl 4‑bromobenzoate
(6v, C17H14BrN3O2) White, crystalline solid; yield: 83%;
m.p.: 132–136 °C; 1H NMR (400 MHz, CDCl3): δ = 8.11
(s, 1H, C–H triazole), 7.93 (d, J = 8.0 Hz, 2H, ArH), 7.61
(dd, J = 12.0, 8.0 Hz, 4H, ArH), 7.33 (d, J = 8.0 Hz, 2H,
ArH), 5.56 (s, 2H, OCH2), 2.44 (s, 3H, CH3) ppm; 13C NMR
(100 MHz, CDCl3): δ = 165.8 (C=O), 143.3 (C4 triazole),
139.1, 134.6, 131.8, 131.3, 130.3, 128.6, 128.4, 122.4 (C5
triazole), 120.5, 58.3 (OCH2), 21.1 ppm; FT-IR (KBr):
v̄ = 3148 (C–H str., triazole ring), 3100 (C–H str., aromatic
ring), 2959 (C–H str., aliphatic), 1728 (C=O str., ester),
1587, 1485 (C=C str., aromatic ring), 1281 (C–O str., asym.,
ester), 1101 (C–O str., sym., ester) cm−1; HRMS: m/z calcd.
for C17H14BrN3O2 ([M+H]+) 372.0269, ([M+2]+) 374.0249,
found 372.0308, 374.0308.
(1‑Phenyl‑1H‑1,2,3‑triazol‑4‑yl)methyl 4‑bromobenzoate (6s,
C16H12BrN3O2) White solid; yield: 81%; m.p.: 106–110 °C;
1H NMR (400 MHz, CDCl3): δ = 8.15 (s, 1H, C–H triazole),
7.93 (d, J = 8.0 Hz, 2H, ArH), 7.75 (d, J = 8.0 Hz, 2H, ArH),
7.59–7.52 (m, 4H, ArH), 7.46 (t, J = 8.0 Hz, 1H, ArH),
5.56 (s, 2H, OCH2) ppm; 13C NMR (100 MHz, CDCl3):
δ = 165.8 (C=O), 143.4 (C4 triazole), 136.9, 131.8, 131.6,
131.3, 129.8, 129.0, 128.6, 128.5, 122.3 (C5 triazole), 120.6,
83.8, 58.2 (OCH2) ppm; FT-IR (KBr): v̄ = 3138 (C–H str.,
triazole ring), 3086 (C–H str., aromatic ring), 2951 (C–H
str., aliphatic), 1724 (C=O str., ester), 1589, 1442 (C=C str.,
aromatic ring), 1267 (C–O str., asym., ester), 1103 (C–O
str., sym., ester) cm−1; HRMS: m/z calcd. for C16H12BrN3O2
([M+H]+) 358.0113, ([M+2]+) 360.0092, found 358.0146,
360.0146.
[1‑(4‑Nitrophenyl)‑1H‑1,2,3‑triazol‑4‑yl]methyl 4‑bromoben‑
zoate (6w, C16H11BrN4O4) Orange solid; yield: 73%; m.p.:
1
183–187 °C; H NMR (400 MHz, CDCl3): δ = 8.44 (d,
[1‑(o‑Tolyl)‑1H‑1,2,3‑triazol‑4‑yl]methyl 4‑bromobenzoate
(6t, C17H14BrN3O2) White solid; yield: 82%; m.p.: 58–62 °C;
1H NMR (400 MHz, CDCl3): δ = 7.94 (d, J = 8.0 Hz, 2H,
ArH), 7.91 (s, 1H, C–H triazole), 7.59 (d, J = 8.0 Hz, 2H,
ArH), 7.45–7.41 (m, 1H, ArH), 7.38 (d, J = 8.0 Hz, 1H,
J = 8.0 Hz, 2H, ArH), 8.28 (s, 1H, C–H triazole), 8.01 (d,
J = 8.0 Hz, 2H, ArH), 7.93 (d, J = 7.4 Hz, 2H, ArH), 7.60
(d, J = 8.0 Hz, 2H, ArH), 5.58 (s, 2H, OCH2) ppm; 13C
NMR (100 MHz, CDCl3): δ = 165.8 (C=O), 147.4, 144.4
(C4 triazole), 141.0, 131.9, 131.3, 128.7, 128.4, 125.6,
1 3

C. P. Kaushik, J. Sangwan
122.3 (C5 triazole), 120.6, 57.9 (OCH2) ppm; FT-IR (KBr):
v̄ = 3142 (C–H str., triazole ring), 3098 (C–H str., aromatic
ring), 2961 (C–H str., aliphatic), 1724 (C=O str., ester),
1593, 1442 (C=C str., aromatic ring), 1531 (N–O str., asym.,
NO2), 1341 (N–O str., sym., NO2), 1273 (C–O str., asym.,
ester), 1113 (C–O str., sym., ester) cm−1; HRMS: m/z calcd.
for C16H11BrN4O4 ([M+H]+) 401.9964, ([M+2]+) 403.9943,
found 401.0036, 403.0036.
37 °C for 24 h. After incubation, the results were recorded
in terms of minimum inhibitory concentration (MIC). The
antibacterial potency of the compounds was compared
with a broad-spectrum antibiotic norfoxacin.
Antioxidant activity
The free radical scavenging activity of the synthesized
compounds was studied in vitro by 1,1-diphenyl-2-picryl-
hydrazyl (DPPH) assay method [41]. Stock solution of the
compounds was prepared for diferent concentrations in
the range of 100, 50, 25, 12.5, 6.25 μg cm−3. Test samples
dissolved in 1 cm3 methanol were added to 1 cm3 metha-
nolic solution of DPPH (0.004 g DPPH in 100 cm3 metha-
nol). The samples were allowed to stand for 30 min in dark
for any reaction to occur after which the optical density
was measured at 517 nm with UV–Vis spectrophotometer
and the percentage of scavenging activity was calculated.
Ascorbic acid (AA) was used as reference at the same
concentration with respect to tested compounds in metha-
nol. The inhibition ratio (I%) of the tested compounds was
calculated according to the following equation:
[1‑(Naphthalen‑1‑yl)‑1H‑1,2,3‑triazol‑4‑yl]methyl 4‑bro‑
mobenzoate (6x, C20H14BrN3O2) Brown solid; yield: 59%;
m.p.: 66–70 °C; 1H NMR (400 MHz, CDCl3): δ = 8.11 (s,
1H, C–H triazole), 8.06 (dd, J = 5.8, 3.6 Hz, 1H, ArH), 8.01
(s, 1H, ArH), 7.99 (d, J = 8.0 Hz, 2H, ArH), 7.66–7.56 (m,
7H, ArH), 5.65 (s, 2H, OCH2) ppm; 13C NMR (100 MHz,
CDCl3): δ = 165.8 (C=O), 142.7 (C4 triazole), 134.2, 133.5,
131.8, 131.4, 130.6, 128.6, 128.5, 128.4, 128.4, 128.0, 127.2,
126.7 (C5 triazole), 125.0, 123.6, 122.2, 58.3 (OCH2) ppm;
FT-IR (KBr): v̄ = 3130 (C–H str., triazole ring), 3096 (C–H
str., aromatic ring), 2965 (C–H str., aliphatic), 1719 (C=O
str., ester), 1591, 1456 (C=C str., aromatic ring), 1277 (C–O
str., asym., ester), 1105 (C–O str., sym., ester) cm−1; HRMS:
m/z calcd. for C20H14BrN3O2 ([M+H]+) 408.0269, ([M+2]+)
410.0249, found 408.0320, 410.0320.
(
)
I% = A0 − A1 ∕A0 × 100,
where A0 is the absorbance of the control and A1 is the
absorbance of the sample. All tests and analyses were per-
formed in triplicate and the average absorbance was noted
for each concentration. IC50 values were calculated from
the plot of percentage inhibition against concentration
(μg cm−3).
X‑ray crystallographic study
Single crystals of compound 6q (C16H11ClN4O4) was
selected and determined on a SuperNova, Single source at
ofset, Titan difractometer. The crystal was kept at 293 K
during data collection. Using Olex2 [38], the structure was
solved with the ShelXT [39] structure solution program
using Direct Methods and refned with the ShelXL [40]
refnement package using Least Squares minimization.
Acknowledgements Authors are highly thankful to the Haryana State
council for Science and Technology (HSCST) for fnancial assistance.
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