One-pot facile synthesis, crystal structure and antifungal activity of 1,2,3-triazoles bridged with amine-amide functionalities

Article abstract of DOI:10.1080/00397911.2018.1544371

A library of twenty five 1,2,3-triazoles bridged with amine-amide functionalities have been synthesized from reaction of N-substituted(prop-2-yn-1-yl)amines (2a–2e), 2-bromo-N-arylacetamides (4a–4e) and sodium azide through copper(I)-catalyzed alkyne-azide cycloaddition. The synthesized compounds were characterized by using FTIR, ¹H NMR, ¹³C NMR, and HRMS techniques. The structures of synthesized 5a (CCDC 1569245) and 5h (CCDC 1569249) were also confirmed by X-ray crystallography. Antifungal evaluation of newly synthesized triazoles was carried out against–Candida albicans and Aspergillus niger. Biological screening of synthesized 1,2,3-triazoles revealed moderate to good antifungal activity against tested strains.

Full text of DOI:10.1080/00397911.2018.1544371

Synthetic Communications
An International Journal for Rapid Communication of Synthetic Organic
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ISSN: 0039-7911 (Print) 1532-2432 (Online) Journal homepage: http://www.tandfonline.com/loi/lsyc20
One-pot facile synthesis, crystal structure and
antifungal activity of 1,2,3-triazoles bridged with
amine-amide functionalities
C. P. Kaushik, Raj Luxmi, Mukesh Kumar, Dharmendra Singh, Krishan Kumar
&
Ashima Pahwa
To cite this article: C. P. Kaushik, Raj Luxmi, Mukesh Kumar, Dharmendra Singh, Krishan
Kumar & Ashima Pahwa (2019): One-pot facile synthesis, crystal structure and antifungal activity
of 1,2,3-triazoles bridged with amine-amide functionalities, Synthetic Communications, DOI:
10.1080/00397911.2018.1544371
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https://doi.org/10.1080/00397911.2018.1544371
One-pot facile synthesis, crystal structure and antifungal
activity of 1,2,3-triazoles bridged with amine-amide
functionalities
a
a
b
c
a
C. P. Kaushik , Raj Luxmi , Mukesh Kumar , Dharmendra Singh , Krishan Kumar ,
a
and Ashima Pahwa
a
Department of Chemistry, Guru Jambheshwar University of Science & Technology, Hisar, Haryana,
b
India; Radiation Biology & Health Sciences Division, Bhabha Atomic Research Centre, Mumbai,
Maharashtra, India; Centrefor Research & Development, IPCA Lab Ltd, Mumbai, Maharashtra, India
c
ABSTRACT
ARTICLE HISTORY
A library of twenty five 1,2,3-triazoles bridged with amine-amide
functionalities have been synthesized from reaction of N-substitu-
Received 19 September 2018
ted(prop-2-yn-1-yl)amines
4a–4e) and sodium azide through copper(I)-catalyzed alkyne-azide
cycloaddition. The synthesized compounds were characterized by
(2a–2e),
2-bromo-N-arylacetamides
KEYWORDS
Antifungal activity; click
synthesis; X-ray
(
1
13
using FTIR, H NMR, C NMR, and HRMS techniques. The structures
of synthesized 5a (CCDC 1569245) and 5h (CCDC 1569249) were
also confirmed by X-ray crystallography. Antifungal evaluation of
newly synthesized triazoles was carried out against – Candida albi-
cans and Aspergillus niger. Biological screening of synthesized 1,2,3-
triazoles revealed moderate to good antifungal activity against
tested strains.
crystallography; 1,4-
disubstituted 1,2,3-triazoles
GRAPHICAL ABSTRACT
Introduction
The continuous escalation in microbial infections has emerged as a threat to human
[
1]
beings throughout the world. A number of antimicrobials have been discovered so far
to combat microbial diseases. In spite of this, cases with microbial resistance against the
present drugs are increasing steadily. In this regard, nitrogen heterocycles attracted the
attention of researchers due to drugs like rufinamide, pyrazinamide, isoniazid, rifampi-
cin etc., possess N-heterocyclic ring system. Nitrogen-containing heterocycles exhibited
[
2,3]
a wide range of biological activities,
among these heterocycles, significant emphasis
has been given to the triazole nucleus, on account of pharmacological activities like
[
4]
[5]
[6–9]
[10,11]
antidiabetic,
anticonvulsant,
antimicrobial,
antitrypanosomal,
antimalar-
[
12–14]
[15,16]
[17–20]
[21–23]
[24,25]
ial,
anti-HIV,
anticancer,
antitubercular,
anti-inflammatory,
[
26]
[27–29]
antiallergic,
antioxidant,
etc.
ꢀ
CONTACT C. P. Kaushik
Science & Technology, Hisar, Haryana 125001, India.
kaushikcp@gmail.com
Department of Chemistry, Guru Jambheshwar University of
Supplemental data for this article can be accessed on the publisher’s website.
ß 2019 Taylor & Francis Group, LLC

2
C. P. KAUSHIK ET AL.
[
30]
Huisgen’s 1,3-dipolar alkyne-azide cycloaddition reaction
was traditionally used
for accessing substituted 1,2,3-triazoles. This classical reaction of alkyne-azide lacks
selectivity yielding both 1,4 and 1,5 disubstituted 1,2,3 triazoles. Owing to this, Cu (I)
[
31,32]
catalyzed 1,3-dipolar cycloaddition,
between azides and terminal alkynes, came out
as an effective method for the selective synthesis of 1,4-disubstituted 1,2,3-triazoles,
nailed as one of the important examples of the “click” reaction. Major advantage of
click chemistry protocol is product selectivity with high yield under milder reac-
tion conditions.
Thereby, keeping the above factors, we herein report the synthesis of amine-amide
disubstituted 1,2,3-triazoles from N-substituted(prop-2-yn-1yl)amines and 2-azido-N-
arylacetamides (synthesized in situ from the reaction of 2-bromo-N-arylacetamides and
sodium azide) using click chemistry approach. Structural elucidation of all the triazole
1
13
derivatives was carried out by using FTIR, H NMR, C NMR, and HRMS techniques.
Further, structure of the compounds of 5a (CCDC 1569245) and 5h (CCDC 1569249)
were also confirmed through single crystal X-ray crystallography. The synthesized tria-
zoles were evaluated for in vitro antifungal activity against – Candida albicans and
Aspergillus niger by the serial dilution method.
Results and discussion
Chemistry
The synthetic route for preparation of target compounds (5a–5y) is given in Scheme 3.
The terminal alkynes i.e. N-substituted(prop-2-yn-1yl)amines (2a–2e) were synthesized
from reaction of secondary amines (1a–1e) and propargyl bromide at room temperature
for 4–5 h in dimethylformamide solvent using potassium carbonate as a base (Scheme
1). 2-Bromo-N-arylacetamides (4a–4e) were synthesized from the reaction of aromatic
amine (3a–3e) with bromoacetyl bromide in the presence of potassium carbonate in
ꢁ
dichloromethane at 0–5 C for 15–20 min (Scheme 2). In the last step for the synthesis
of amine-amide linked 1,4-disubsituted 1,2,3-triazoles (5a–5y), N-substituted(prop-2-yn-
1
2
yl)amines (2a–2e) were reacted to 2-bromo-N-arylacetamides (4a–4e), sodium azide at
5-40 C for 6–10 h in the presence of copper sulfate pentahydrate and sodium ascor-
ꢁ
bate in dimethylformamide.
The structures of synthesized compounds were supported by FTIR, H NMR,
1
13
C
NMR spectroscopy and HRMS data. In FTIR spectra, absorption frequencies at
ꢂ1
3
294–3260 cm were corresponding to N–H stretching of amide group. Absorption
ꢂ1
ꢂ1
bands at 3172–3132 cm and 3098–3047 cm corresponds to C–H str. of triazole and
aromatic ring, respectively. Band at 1720–1670 cm
ꢂ1
was corresponding to C = O
stretching of amide group.
1
H NMR showed singlets at d 11.08–10.30 for amide proton and at d 8.04–7.95 for
triazolyl proton whereas, the singlets at d 5.52–5.24 and at d 4.62–3.52 were observed
for methylene protons of NCH CO and NCH moiety, respectively.
2
2
1
3
C NMR signals for carbonyl carbon of amide group appeared in range of d
1
1
65.9–164.2. Whereas, signals for C-4 and C-5 of triazole ring appeared in region d
45.2–143.3 and d 126.1–124.9, respectively. Further, HRMS data of all the compounds
confirmed the assigned structures.

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3
Scheme 1. Synthesis of N-substituted(prop-2-yn-1yl)amines (2a–2e).
Compound
R2
4a
6 5
C H
4
b
4-CH
3
OC
6
H
4
4c
4-FC
6
H
4
4
d
4-NO
2
C
6 4
H
4e
7
α-C10H (α-naphthyl)
Scheme 2. Synthesis of 2-Bromo-N-arylacetamides (4a–4e).
X-ray crystallographic study
Single crystals of 2-(4-(Morpholinomethyl)-1H-1,2,3-triazol-1-yl)-N-phenylacetamide
5a) (Table 1, Figure 1) and N-(4-fluorophenyl)-2-(4-(piperidin-1-ylmethyl)-1H-1,2,3-
(
triazol-1-yl)acetamide (5h) (Table 2, Figure 2) were grown in ethyl acetate using the
slow evaporation technique. Single crystal data for compounds 5a and 5h has been
deposited in the Cambridge Crystallographic Data Center and assigned to the CCDC
1569245 and CCDC 1569249, respectively, which is available online at www.ccdc.cam.
ac.uk/conts/retrieving.html.
Antifungal activity
In vitro antifungal activity of the synthesized compounds (5a–5y) was carried out
against two fungal strains – Candida albicans (MTCC 227) and Aspergillus niger
(MTCC 282) by the standard serial dilution method. Fluconazole was used as standard
drug and minimum inhibitory concentrations (MIC in mmol/mL) were recorded and
presented in Table 3.
Results indicated that some of the synthesized compounds possess significant activity.
The compound 5d (MIC, 0.0361 mmol/mL), 5e (MIC, 0.0356 mmol/mL), 5n (MIC,

4
C. P. KAUSHIK ET AL.
R1
R2
Yield %
Reaction
Time (h)
Compound
5
a
C
6
H
5
7
9
92
88
91
88
90
92
88
82
86
90
86
90
82
88
84
5
b
3 6 4
4-CH OC H
5
c
4-FC
6
H
4
7
5
d
4-NO
2
C
6
H
4
6
α-C10
α-naphthyl)
H
7
5
e
10
9
(
5
f
6 5
C H
5
g
4-CH
3
OC
6
H
4
7
5
h
4-FC
6
H
4
8
5
i
4-NO
2
C
6
H
4
6
5
j
α-C10
H
7
10
9
5
k
6 5
C H
5
l
4-CH
3
OC
6
H
4
9
5
m
4-FC
6
H
4
8
5
n
4-NO
2
C
6
H
4
7
5
o
α-C10
H
7
9
Scheme 3. Synthesis of amine-amide linked 1,4-disubstituted 1,2,3-triazoles
0
.0378 mmol/mL), 5o (MIC, 0.0373 mmol/mL), 5t (MIC, 0.0336 mmol/mL) and 5 y
(MIC, 0.0324 mmol/mL) showed good activity against C. albicans. Whereas, in case of

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SYNTHETIC COMMUNICATIONS
5
5
5
p
q
C
6
H
5
7
9
7
6
8
8
9
8
6
8
88
90
86
82
88
76
82
86
81
78
3 6 4
4-CH OC H
5
r
4-FC
6
H
4
5
s
4-NO
2
C
6
H
4
5
t
α-C10
H
7
5
u
6 5
C H
5
v
3 6 4
4-CH OC H
5
w
4-FC
6
H
4
5
5
x
y
4-NO
2
C
6
H
4
α-C10
H
7
Scheme 3. Continued.
A. niger compounds 5e (MIC, 0.0178 mmol/mL), 5i (MIC, 0.0181 mmol/mL), and 5n
(MIC, 0.0189 mmol/mL) showed appreciable activity.
From the above result, it was observed, that compounds having naphthyl moiety
exhibited better activity in comparison to phenyl moiety. The results also supported the
fact that the presence of morpholine contributed to better antimicrobial efficacy as com-
pared to piperidine against the tested stains.
Conclusion
In present work, we have synthesized a library of twenty five 1,2,3-triazole having
amine-amide functionalities through one pot three-component reaction of N-substitu-
ted(prop-2-yn-1-yl)amines, 2-bromo-N-arylacetamides, sodium azide in the presence of
copper sulfate pentahydrate and sodium ascorbate. Further, for confirmation of struc-
tures, X-ray crystallography of synthesized 5a (CCDC 1569245) and 5h (CCDC

6
C. P. KAUSHIK ET AL.
Table 1. Crystal data and structure refinement for 2-(4-(Morpholinomethyl)-1H-1,2,3-triazol-1-yl)-N-phenylaceta-
mide (5a).
Property
Data
Empirical formula
Formula weight
Temperature/K
Crystal system
Space group
a/Å
15 19 5 2
C H N O
301.35
293
Orthorhombic
Pca2
1
9.8849(7)
b/Å
9.5292(7)
c/Å
a/ b/ c/
Volume/Å
Z
32.354(2)
90, 90, 90
3047.6(4)
ꢁ
ꢁ
ꢁ
3
8
3
qcalc g/cm
1.314
0.744
-
1
l/mm
F(000)
Crystal size/mm
Radiation
1280.0
0.284 ꢃ 0.116 ꢃ 0.067
CuKa (k ¼ 1.54184)
9.28 to 146.696
3
ꢁ
2H range for data collection/
Index ranges
ꢂ11 ꢄ h ꢄ 10, ꢂ10 ꢄ k ꢄ 8, ꢂ39 ꢄ l ꢄ 36
Reflections collected
Independent reflections
Data/restraints/parameters
6955
3939 [Rint ¼ 0.0656, Rsigma ¼ 0.0690]
3939/1/397
2
Goodness-of-fit on F
1.022
Final R indexes [I> ¼2r (I)]
Final R indexes [all data]
Largest diff. peak/hole / e Å
Flack parameter
R
R
1
¼ 0.0697, wR
2
2
¼ 0.1656
¼ 0.2177
1
¼ 0.1217, wR
-3
0.36/ꢂ0.29
ꢂ0.4(9)
1
569249) was also carried out. All the triazoles were evaluated for in vitro antifungal
activity. The preliminary structure-activity relationship analysis suggested that the pres-
ence of Naphthyl ring enhanced antifungal activities of these compounds in comparison
to the phenyl ring. Triazole derivatives having morpholine moiety showed better anti-
microbial activity as compared to derivatives having piperidine moiety.
Experimental section
Material and methods
The chemicals used in the synthesis were purchased from Alfa-Aesar, Sigma-Aldrich
and used without further purification. Thin layer chromatography was used to monitor
the progress of the reactions and visualized by UV light. Melting points were deter-
mined by the open capillary method and are uncorrected. IR spectra were recorded on
a
SHIMADZU AFFINITY-I FT-IR spectrophotometer (Shimadzu Corporation,
Nishinokyo-Kuwabaracho Nakagyo-Ku, Kyoto 604-8511, Japan) using KBr powder and
ꢂ1
1
13
the values are expressed in cm . The H NMR and C NMR spectra of the synthe-
sized compounds were recorded at 400 MHz and 100 MHz, respectively, using Bruker
Avance II 400 MHz NMR spectrometer (Bruker Biospin International AG, Aegeristrasse
5
2, CH-6301 Zug (Switzerland)) in DMSO-d solvent, and the chemical shifts were
6
expressed in d and coupling constants (J) in Hz. Splitting patterns were indicated as s:
singlet, d: doublet, t: triplet, q: quartet, m: multiplet. HRMS were obtained using Waters
Micromass Q-Tof Micro (ESI) spectrophotometer and values were quoted in m/z.

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7
Table 2. Crystal data and structure refinement for N-(4-fluorophenyl)-2-(4-(piperidin-1-ylmethyl)-1H-1,2,3-triazol-1-yl)a-
cetamide (5h).
Property
Data
Empirical formula
Formula weight
Temperature/K
Crystal system
Space group
a/Å
16 20 5
C H N OF
317.37
293
Monoclinic
C2/c
34.1018(6)
b/Å
9.53697(18)
c/Å
a/ , b/ , c/
Volume/Å
9.89235(16)
90, 90.3176(15), 90
ꢁ
ꢁ
ꢁ
3
3217.22(10)
Z
q
8
3
calcg/cm
1.310
0.775
-
1
l/mm
F(000)
Crystal size/mm
Radiation
1344.0
0.3 ꢃ 0.3 ꢃ 0.15
3
CuKa (k ¼ 1.54184)
ꢁ
2H range for data collection/
9.63 to 146.224
Index ranges
ꢂ42 ꢄ h ꢄ 41, ꢂ8 ꢄ k ꢄ 11, ꢂ11 ꢄ l ꢄ 12
11066
Reflections collected
Independent reflections
Data/restraints/parameters
3175 [Rint ¼ 0.0408, Rsigma ¼ 0.0259]
3175/0/288
2
Goodness-of-fit on F
1.023
Final R indexes [I> ¼2r (I)]
Final R indexes [all data]
Largest diff. peak/hole / e Å
R
R
1
¼ 0.0473, wR
2
2
¼ 0.1255
¼ 0.1314
1
¼ 0.0513, wR
-3
0.22/ꢂ0.23
Table 3. In vitro antifungal activity of 1,4-disubstituted 1,2,3-triazoles (5a–5y).
Minimum Inhibitory Concentration (MIC, mmol/mL).
Compound
Candida albicans
Aspergillus Niger
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
a
b
c
d
e
f
g
h
i
j
k
l
m
n
o
p
q
r
0.0830
0.0754
0.0782
0.0361
0.0356
0.0836
0.0759
0.0788
0.0726
0.0716
0.0876
0.0793
0.0824
0.0378
0.0373
0.0778
0.0711
0.0736
0.0682
0.0336
0.0745
0.0684
0.0708
0.0657
0.0324
0.0408
0.0415
0.0377
0.0391
0.0361
0.0178
0.0418
0.0379
0.0394
0.0181
0.0358
0.0438
0.0396
0.0412
0.0189
0.0373
0.0389
0.0356
0.0368
0.0341
0.0336
0.0373
0.0342
0.0354
0.0328
0.0324
0.0102
s
t
u
v
w
x
y
Fluconazole
The bold numbers represents the activity of synthesized compound comparable to standard drug used.

8
C. P. KAUSHIK ET AL.
Figure 1. Crystal structure of 2-(4-(Morpholinomethyl)-1H-1,2,3-triazol-1-yl)-N-phenylacetamide (5a).
Figure 2. Crystal structure of N-(4-fluorophenyl)-2-(4-(piperidin-1-ylmethyl)-1H-1,2,3-triazol-1-yl)aceta-
mide (5h)
Procedure for the preparation of 2-(4-(morpholinomethyl)-1H-1,2,3-triazol-1-yl)-N-
phenylacetamide
The starting reactant, 4-(prop-2-yn-1-yl)morpholine (2a) was synthesized by drop-wise
addition of propargyl bromide (1.2 mmol) to the stirred solution of morpholine (1a, 1.0
mmol) in dimethylformamide (15 mL) in the presence of potassium carbonate (2.0
mmol), stirring was continued for 4 h at room temperature. After the completion of
reaction as indicated by TLC water (20 mL) was added in the reaction mixture. The
product was extracted with ethyl acetate (3 ꢃ 30 mL) from the reaction mixture. The
separated organic layer was evaporated under reduced pressure to get 4-(prop-2-yn-1-
yl)morpholine (2a).
For synthesis of 2-bromo-N-phenylacetamides (4a), to the stirred solution of aniline
(
3a–3e, 1.0 mmol) in dichloromethane (20 mL), 2-bromoacetyl bromide (1.2 mmol)
ꢁ
was added in the presence of potassium carbonate at 0–5 C and stirring of the mixture
was continued for 15–20 min at the same temperature. After the completion of reaction
dilute hydrochloric acid was added, solid product was precipitated out which was fil-
tered and dried.
Further, to synthesize 2-(4-(Morpholinomethyl)-1H-1,2,3-triazol-1-yl)-N-phenylaceta-
mide (5a), 2-bromo-N-phenylacetamides (4a, 1.0 mmol) dissolved in dimethylforma-
mide (16 mL), aqueous sodium azide (3.0 mmol) was added and stirring was continued
ꢁ
at 25–40 C for 30 min. To this mixture 4-(prop-2-yn-1yl)morpholine (2a, 1.0 mmol),
aqueous copper sulfate pentahydrate (0.1 mmol) and sodium ascorbate (0.4 mmol) were
added and stirring was continued for 7 h at the same temperature. After completion of
reaction, ice cold water was added to reaction mixture, precipitated product was filtered
and washed with ammonia solution. Crude product was washed with ethyl acetate (30
mL) and dried under vacuum to get pure product in good yield.

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2
-(4-(Morpholinomethyl)-1H-1,2,3-triazol-1-yl)-N-phenylacetamide (5a)
ꢁ
Appearance: white crystalline solid; Yield: 92%; m.p. 186–190 C; FTIR (KBr): 3276
(
N–H str. amide), 3140 (C–H str. triazole), 3098 (C–H str. aromatic ring), 2935 (C–H
ꢂ1
1
str., aliphatic), 1686 (C = O str. amide), 1557 (C = C str., aromatic ring) cm ; H
NMR (400 MHz, DMSO-d ): d 10.48 (s, 1 H, N–H amide), 8.02 (s, 1 H, C–H triazole),
6
7
3
1
.58 (d, 2 H, J = 8 Hz), 7.34 (t, 2 H, J = 8 Hz), 7.09 (t, 1 H, J = 8 Hz), 5.31 (s, 2H),
1
3
.58-3.51 (m, 6H), 2.40 (4H); C NMR (100 MHz, DMSO-d ): d 164.7 (C = O amide),
6
43.3 (C triazole), 138.9, 129.4, 126.0 (C triazole), 124.3, 119.7, 66.6, 53.2, 52.6; HRMS
4
5
þ
(m/z) calculated for C H N O [M þ H] : 302.1539. Found: 302.1612.
1
5
19 5 2
X-ray crystallographic study
Single crystals of C H N O (5a) and C H N OF (5h) were selected and determined
1
5
19
5
2
16 20 5
on a SuperNova, Single source at offset, Titan diffractometer. The crystal was kept at
[
33]
2
93 K during data collection. Using Olex2,
the structure was solved with the
[
34]
ShelXT
ShelXL
structure solution program using Direct Methods and refined with the
refinement package using Least Squares minimization.
[
35]
Antifungal activity
The antifungal activity of newly synthesized compounds was assessed in vitro against
fungal strains – Candida albicans (MTCC 227) and Aspergillus niger (MTCC 282) as
[
36]
per the serial dilution method.
Fluconazole was used as a standard drug for fungal
strains. Results were recorded in terms of minimum inhibitory concentration (MIC)
expressed in mmol/mL in Table 3.
Acknowledgments
Authors are highly thankful to University Grants Commission, New Delhi for finan-
cial assistance.
References
[
1] Pissinate, K.; Villela, A. D.; Rodrigues-Junior, V.; Giacobbo, B. C.; Grams, E. S.; Abbadi,
B. L.; Trindade, R. V.; Roesler Nery, L.; Bonan, C. D.; Back, D. F.; et al. 2-(Quinolin-4-
Yloxy)Acetamides Are Active against Drug-Susceptible and Drug-Resistant
Mycobacterium Tuberculosis Strains. ACS Med. Chem. Lett. 2016, 7, 235–239. doi:
10.1021/acsmedchemlett.5b00324
[2] Bonandi, E.; Christodoulou, M. S.; Fumagalli, G.; Perdicchia, D.; Rastelli, G.; Passarella, D.
The 1,2,3-Triazole Ring as a Bioisostere in Medicinal Chemistry. Drug Discov. Today.
2
017, 22, 1572–1581. doi:10.1016/j.drudis.2017.05.014
[
3] Vidyacharan, S.; Adhikari, C.; Krishna, V. S.; Reshma, R. S.; Sriram, D.; Sharada, D. S. A
Robust Synthesis of Functionalized 2H-Indazoles via Solid State Melt Reaction (SSMR)
and Their anti-Tubercular Activity. Bioorg. Med. Chem. Lett. 2017, 27, 1593–1597. doi:
10.1016/j.bmcl.2017.02.021
[4] Chinthala, Y.; Thakur, S.; Tirunagari, S.; Chinde, S.; Domatti, A. K.; Arigari, N. K.;
Srinivas, K.V.N.S,.; Alam, S.; Jonnala, K. K.; Khan, F.; et al. Synthesis, Docking and

1
0
C. P. KAUSHIK ET AL.
ADMET Studies of Novel Chalcone Triazoles for anti-Cancer and anti-Diabetic Activity.
P. Eur. J. Med. Chem. 2015, 93, 564–573., doi:10.1016/j.ejmech.2015.02.027
[
5] Karakurt, A.; Aytemir, M. D.; Stables, J. P.; Ozalp, M.; Betul, F. K.; Ozbey, S.; Dalkara, S.
Synthesis of Some Oxime Ether Derivatives of 1-(2-Naphthyl)-2-(1,2,4-Triazol-1-
yl)Ethanone and Their Anticonvulsant and Antimicrobial Activities. Arch. Pharm.
(Weinheim) 2006, 339, 513–520. doi:10.1002/ardp.200500248
[
[
[
[
6] Kaushik, C. P.; Kumar, K.; Singh, D.; Singh, S. K.; Jindal, D. K.; Luxmi, R. Synthesis,
Characterization, and Antimicrobial Potential of Some 1,4-Disubstituted 1,2,3-Bistriazoles.
Synth. Commun. 2015, 45, 1977–1985. doi:10.1080/00397911.2015.1056796
7] Kaushik, C. P.; Luxmi, R. Facile Expeditious One-Pot Synthesis and Antifungal Evaluation
of Disubstituted 1,2,3-Triazole with Two Amide Linkages. Synth. Commun. 2017, 47,
2225–2231. doi:10.1080/00397911.2017.1369124
8] Kaushik, C. P.; Luxmi, R.; Singh, D.; Kumar, A. Synthesis and Antimicrobial Evaluation of
Ester-Linked 1,4-Disubstituted 1,2,3-Triazoles with a Furyl/Thienyl Moiety. Mol. Divers.
2
017, 21, 137–145. doi:10.1007/s11030-016-9710-y
9] Dofe, V. S.; Sarkate, A. P.; Lokwani, D. K.; Kathwate, S. H.; Gill, C. H. Res. Chem.
Intermed. 2017, 43, 15–28. doi:10.1007/s11164-016-2602-z
[
10] Porta, E. O. J.; J €a ger, S. N.; Nocito, I.; Lepesheva, G. I.; Serra, E. C.; Tekwani, B. L.;
Labadie, G. R. Antitrypanosomal and Antileishmanial Activity of Prenyl-1,2,3-Triazoles.
Medchemcomm. 2017, 8, 1015–1021. doi:10.1039/C7MD00008A
[
[
11] Cassamale, T. B.; Costa, E. C.; Carvalho, D. B.; Cassemiro, N. S.; Tomazela, C. C.;
Marques, M. C. S.; O.; et al. J. Braz. Chem. Soc. 2016, 27, 1217–1228.
12] Kumar, K.; Pradines, B.; Madamet, M.; Amalvict, R.; Benoit, N.; Kumar, V. 1H-1,2,3-
Triazole Tethered Isatin-Ferrocene Conjugates: Synthesis and in Vitro Antimalarial
Evaluation. Eur. J. Med. Chem. 2014, 87, 801–804. doi:10.1016/j.ejmech.2014.10.024
13] Devender, N.; Gunjan, S.; Tripathi, R.; Tripathi, R. P. Synthesis and Antiplasmodial
Activity of Novel Indoleamide Derivatives Bearing Sulfonamide and Triazole
Pharmacophores. Eur. J. Med. Chem. 2017, 131, 171–184. doi:10.1016/j.ejmech.2017.03.010
14] Pereira, G. R.; Brand ~a o, G. C.; Arantes, L. M.; de Oliveira, H. A.; de Paula, R. C.; do
Nascimento, M. F. A.; dos Santos, F. M.; da Rocha, R. K.; Lopes, J. C. D.; de Oliveira,
A. B. c, 7-Chloroquinolinotriazoles: Synthesis by the Azide–Alkyne Cycloaddition Click
Chemistry, Antimalarial Activity, Cytotoxicity and SAR Studies. Eur. J. Med. Chem. 2014,
[
[
7
3, 295–309. doi:10.1016/j.ejmech.2013.11.022
[
[
[
15] Głowacka, I. E.; Balzarini, J.; Wr oꢀ blewski, A. E. Novel Acyclic Phosphonylated 1,2,3-
Triazolonucleosides with an Acetamidomethyl Linker: Synthesis and Biological Activity.
Arch. Pharm. Chem. Life. Sci. 2014, 347, 506–514. doi:10.1002/ardp.201300468
16] Olomola, T. O.; Klein, R.; Mautsa, N.; Sayed, Y.; Kaye, P. T. Synthesis and Evaluation of
Coumarin Derivatives as Potential Dual-Action HIV-1 Protease and Reverse Transcriptase
Inhibitors. Bioorg. Med. Chem. 2013, 21, 1964–1971. doi:10.1016/j.bmc.2013.01.025
17] Ruddarraju, R. R.; Murugulla, A. C.; Kotla, R.; Tirumalasetty, M. C. B.; Wudayagiri, R.;
Donthabakthuni, S.; Maroju, R.; Baburao, K.; Parasa, L. S. Design, Synthesis, Anticancer,
Antimicrobial Activities and Molecular Docking Studies of Theophylline Containing
Acetylenes and Theophylline Containing 1,2,3-Triazoles with Variant Nucleoside
Derivatives. Eur. J. Med. Chem. 2016, 123, 379–396. doi:10.1016/j.ejmech.2016.07.024
18] Kraljevic, T. G.; Harej, A.; Sedic, M.; Pavelic, S. K.; Stepanic, V.; Drenjancevic, D.;
Talapko, J.; Raic, M.; S. Synthesis, in vitro anticancer and antibacterial activities and in sil-
ico studies of new 4-substituted 1,2,3-triazole-coumarin hybrids. Eur. J. Med. Chem. 2016,
[
1
24, 794–808. doi:10.1016/j.ejmech.2016.08.062
[
19] Huang, M.; Deng, Z.; Tian, J.; Liu, T. Synthesis and Biological Evaluation of Salinomycin
Triazole Analogues as Anticancer Agents. Eur. J. Med. Chem. 2017, 127, 900–908. doi:
10.1016/j.ejmech.2016.10.067
[
20] Narsimha, S.; Kumar, N. S.; Swamy, B. K.; Reddy, N. V.; Hussain, S. K. A.; Rao, M. S.
Indole-2-Carboxylic Acid Derived Mono and Bis 1,4-Disubstituted 1,2,3-Triazoles:
Synthesis, Characterization and Evaluation of Anticancer, Antibacterial, and DNA-

V
R
SYNTHETIC COMMUNICATIONS
11
Cleavage Activities. Bioorg. Med. Chem. Lett. 2016, 26, 1639–1644. doi:10.1016/
j.bmcl.2016.01.055
[
[
21] Ghiano, D. G.; de la Iglesia, A.; Liu, N.; Tonge, P. J.; Morbidoni, H. R.; Labadie, G. R.
Antitubercular Activity of 1,2,3-Triazolyl Fatty Acid Derivatives. Eur. J. Med. Chem. 2017,
1
25, 842–852. doi:10.1016/j.ejmech.2016.09.086
22] Anand, A.; Kulkarni, M. V.; Joshi, S. D.; Dixit, S. R. One Pot Click Chemistry: A Three
Component Reaction for the Synthesis of 2-Mercaptobenzimidazole Linked Coumarinyl
Triazoles as anti-Tubercular Agents. Bioorg. Med. Chem. Lett. 2016, 26, 4709–4713. doi:
10.1016/j.bmcl.2016.08.045
[
23] Surineni, G.; Yogeeswari, P.; Sriram, D.; Kantevari, S. Click-Based Synthesis and
Antitubercular Evaluation of Dibenzofuran Tethered Thiazolyl-1,2,3-Triazolyl Acetamides.
Bioorg. Med. Chem. Lett. 2016, 26, 3684–3689. 268 doi:10.1016/j.bmcl.2016.05.085
24] Rao, P. S.; Kurumurthy, C.; Veeraswamy, B.; Kumar, G. S.; Poornachandra, Y.; Kumar,
C. G.; Vasamsetti, S. B.; Kotamraju, S.; Narsaiah, B. Synthesis of Novel 1,2,3-Triazole sub-
stituted-N-Alkyl/Aryl Nitrone Derivatives, Their anti-Inflammatory and Anticancer
Activity. Eur. J. Med. Chem. 2014, 80, 184–191.
[
[
25] Gonzaga, D. T. G.; Ferreira, L. B. G.; Costa, T. E. M. M.; Ranke, N. L.; Pacheco, P. A. F.;
Simoes, A. P. S.; Arruda, J. C.; Dantas, L. P.; Freitas, H. R.; Reis, R. A. M.; et al. 1-Aryl-
1H- and 2-aryl-2H-1,2,3-triazole derivatives blockade P2X7 receptor in vitro and inflam-
matory response in vivo. Eur. J. Med. Chem. 2017, 139, 698–717. doi:10.1016/
j.ejmech.2017.08.034
[
26] Buckle, D. R.; Rockell, C. J. M.; Smith, H.; Spicer, B. A. Studies on 1,2,3-Triazoles. 13.
(
Piperazinylalkoxy) [1]Benzopyrano[2,3-d]-1,2,3-Triazol-9(1H)-Ones with Combined H1-
Antihistamine and Mast Cell Stabilizing Properties. J. Med. Chem. 1986, 29, 2262–2267.
doi:10.1021/jm00161a022
[
[
[
27] Mistry, B.; Patel, R. V.; Keum, Y. Access to the Substituted Benzyl-1,2,3-Triazolyl
Hesperetin Derivatives Expressing Antioxidant and Anticancer Effects. Arab. J. Chem.
2
017, 10, 157–166. doi:10.1016/j.arabjc.2015.10.004
28] Saraei, M.; Ghasemi, Z.; Dehghan, G.; Hormati, M.; Ojaghi, K. Synthesis of Some Novel
,2,3-Triazole Derivatives Containing Kojic Acid Moiety and Evaluation for Their
1
Antioxidant Activity. Monatsh. Chem. 2017, 148, 917–923. doi:10.1007/s00706-016-1844-1
29] Shyma, P. C.; Kalluraya, B.; Peethambar, S. K.; Vijesh, A. M. Regioselective One Pot
Synthesis of 1,2,3-Triazole Derivatives Bearing Phthalazine Moiety and Their
Pharmacological Activity. Med. Chem. Res. 2016, 25, 2680–2690. doi:10.1007/s00044-016-
1629-4
[
[
30] Huisgen, R.; Padwa, A. (Eds). 1,3-Dipolar cycloaddition chemistry. Vol. 1, pp. 1–176. New
York, NY: Wiley. 1984.
31] Kolb, H. C.; Finn, M. G.; Sharpless, K. B. Click Chemistry: Diverse Chemical Function
from a Few Good Reactions. Angew. Chem. Int. Ed. Engl. 2001, 40, 2004–2021. doi:
10.1002/1521-3773(20010601)40:11<2004::AID-ANIE2004>3.0.CO;2-5
[
[
32] Tornøe, C. W.; Christensen, C.; Meldal, M. Peptidotriazoles on Solid Phase: [1,2,3]-
Triazoles by Regiospecific Copper(i)-Catalyzed 1,3-Dipolar Cycloadditions of Terminal
Alkynes to Azides. J. Org. Chem. 2002, 67, 3057–3064. doi:10.1021/jo011148j
33] Dolomanov, O. V.; Bourhis, L. J.; Gildea, R. J.; Howard, J. A. K.; Puschmann, H. OLEX2 :
A Complete Structure Solution, Refinement and Analysis Program. J. Appl. Crystallogr.
2
009, 42, 339–341. doi:10.1107/S0021889808042726
[
[
[
34] Sheldrick, G. M. Acta Crystallogr. C Struct. Chem. 2015, A71, 3–8.
35] Sheldrick, G. M. Acta Cryst. 2015, C71, 3–8.
36] Kaushik, C. P.; Luxmi, R. Synth. Comm. 2017, 57, 3618–3625.,