A convenient synthesis and crystal structure of disubstituted 1,2,3-triazoles having ether functionality

Article abstract of DOI:10.1080/00397911.2019.1672744

A series of 27 ether-linked 1,4-disubstituted 1,2,3-triazoles (8a–8z₁) has been synthesized by 1,3 dipolar cycloaddition of 1-substituted-4-(prop-2-yn-1-yloxy)benzene (3a–3c) and aromatic azides (5a–5c, 7a–7f). The synthesized compounds were ex

Full text of DOI:10.1080/00397911.2019.1672744

Synthetic Communications
An International Journal for Rapid Communication of Synthetic Organic
Chemistry
ISSN: 0039-7911 (Print) 1532-2432 (Online) Journal homepage: https://www.tandfonline.com/loi/lsyc20
A convenient synthesis and crystal structure
of disubstituted 1,2,3-triazoles having ether
functionality
Raj Luxmi, C. P. Kaushik, Devinder Kumar, Krishan Kumar, Ashima Pahwa,
Jyoti Sangwan & Manisha Chahal
To cite this article: Raj Luxmi, C. P. Kaushik, Devinder Kumar, Krishan Kumar, Ashima
Pahwa, Jyoti Sangwan & Manisha Chahal (2019): A convenient synthesis and crystal structure
of disubstituted 1,2,3-triazoles having ether functionality, Synthetic Communications, DOI:
10.1080/00397911.2019.1672744
To link to this article: https://doi.org/10.1080/00397911.2019.1672744
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https://doi.org/10.1080/00397911.2019.1672744
A convenient synthesis and crystal structure of
disubstituted 1,2,3-triazoles having ether functionality
Raj Luxmi, C. P. Kaushik, Devinder Kumar, Krishan Kumar, Ashima Pahwa,
Jyoti Sangwan, and Manisha Chahal
Department of Chemistry, Guru Jambheshwar University of Science and Technology, Hisar, India
ABSTRACT
ARTICLE HISTORY
A series of 27 ether-linked 1,4-disubstituted 1,2,3-triazoles (8a–8z1)
has been synthesized by 1,3 dipolar cycloaddition of 1-substituted-4-
Received 26 May 2019
(
7
prop-2-yn-1-yloxy)benzene (3a–3c) and aromatic azides (5a–5c,
a–7f). The synthesized compounds were explicated by FTIR, H
13
1
KEYWORDS
Disubstituted 1,2,3-triazoles;
synthesis; X-ray
NMR, C NMR and HRMS techniques. The structures of synthesized
triazoles 8c (CCDC 1840219) and 8f (CCDC 1840220) were also con-
firmed by X-ray crystallography.
crystallography
GRAPHICAL ABSTRACT
Introduction
The microbial strains are steadily developing resistance toward the existing microbicidal
through a brain-storming task for the synthetic chemists to develop new effective enti-
ties with spectacular mode of action. Therefore, the synthesis of new moieties and
assessing their biological activities are the prime concern in the present scenario. In this
respect, heterocyclic rings are considered as potent entities, endowed with key biological
[
1,2]
and pharmaceutical properties.
A quantum research on synthesis and biological
activities of triazoles is in full swing from the last few years, proving it as a significant
[
3]
pharmaceutical motif reflecting the importance of this heterocyclic nucleus.
CONTACT C. P. Kaushik
kaushikcp@gmail.com
Department of Chemistry, Guru Jambheshwar University of
Science and Technology, Hisar, Haryana 125001, India.
Color versions of one or more of the figures in the article can be found online at www.tandfonline.com/lsyc.
Supplemental data for this article can be accessed on the publisher’s website.
ß 2019 Taylor & Francis Group, LLC

2
R. LUXMI ET AL.
Literature also reveals 1,2,3-triazoles as highly privileged structure which exhibit
[
4–7]
[8–10]
excellent biological activities in form of antimicrobial,
antiviral,
antitubercu-
[
11–14]
[15–18]
[19]
[20–22]
[23–26]
lar,
antimalarial,
antihistaminic,
and anti-inflammatory
,4-disubstituted 1,2,3-triazoles, Huisgen’s 1,3-dipolar cycloaddition reaction between
anticancer,
antioxidant,
im-
[
27]
[28]
mune potentiators
agents. For the synthesis of
1
[
29–31]
terminal alkynes and azides was put forwarded by Sharpless and Meldal
by using
copper(I) as catalyst. In continued to this, biological importance of ether-linked 1,4-
[
32,33]
disubstituted 1,2,3-triazoles was also highlighted by the various researchers.
Encouraged from above considerations, we have synthesized 27 ether linked disubsti-
tuted 1,2,3-triazoles from click reaction of 1-substituted-4-(prop-2-yn-1-yloxy)benzene
(
3a–3c) and azides (5a–5c, 7a–7f) using copper(I) as a catalyst and characterized by
1
13
FTIR, H NMR, C NMR and HRMS techniques. The structures of synthesized tria-
zoles 8c (CCDC 1840219) and 8f (CCDC 1840220) were also confirmed by X-ray
crystallography.
Result and discussion
Chemistry
The synthetic strategy for the synthesis of compound (8a–8z ) was outlined in
1
[
34]
Scheme 1. The terminal alkynes i.e. 1-substituted-4-(prop-2-yn-1-yloxy)benzene
3a–3c) were synthesized by reaction of 4-substituted phenol (1a–1c) in dimethylforma-
mide with propargyl bromide in the presence of potassium carbonate as base.
(
[
35]
The aromatic azides
(5a–5c) were synthesized from reaction of aminophenol
(4a–4c) in a dilute hydrochloric acid with sodium nitrite and sodium azide. Further, for
the synthesis of substituted azides (7a–7f) the aromatic azides (5a–5c) were reacted
with (bromomethyl)benzene (6a)/(2-bromoethyl)benzene (6b) using potassium carbon-
ate as base at room temperature with continuous stirring for 5–6 h.
Finally, targeted 1,4-disubstituted 1,2,3-triazoles with ether functionality were synthe-
sized by click reaction of aromatic azides (5a–5c, 7a–7f) and 1-substituted-4-(prop-2-
yn-1-yloxy)benzene (3a–3c) in dimethylformamide using catalytic amount of copper
[
5]
sulfate pentahydrate and sodium ascorbate.
All the synthesized 1,4-disubstituted 1,2,3-triazoles (8a–8z ) were characterized by
1
1
13
FTIR, H NMR, C NMR and HRMS. In FTIR spectra, the emergence of band at
380–3362 cm was due to OH stretching of phenol. Absorption band appeared at
186–3125 cm due to C–H stretching vibration of triazole ring, while absorption band
due to C–H stretching vibration of aromatic ring appeared at 3088–3045 cm . The
absorption band owing to N¼N of triazole ring was observed at 1542–1528 cm .
Strong bands due to C–O asymmetric and symmetric stretching appeared at 1267–1228
ꢀ
ꢀ
1
3
3
1
ꢀ
1
ꢀ
1
ꢀ
1
and 1060–1001 cm , respectively.
1
In H NMR spectra, singlet due to triazole proton displayed in the region at d
8.58–8.99 and OH proton resonated at d 9.95–10.62. Methylene protons attached to C4
of triazole appeared as singlet at d 5.20–5.42, whereas, aromatic protons appeared in
region d 6.90–8.25.
1
3
Moreover, in C NMR spectra signal in region d 141.9–144.5 and d 121.1–124.9
were attributed to C and C of triazole ring, respectively. Peak due to aromatic carbon
4
5

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SYNTHETIC COMMUNICATIONS
3
attached to oxygen of phenoxy ring appeared at d 156.4–163.8, while other aromatic
carbons displayed signal in region at d 111.0–130.5.
The HRMS data of all the products were in good agreement with calculated values.
X-ray crystallographic study
Single crystals of 4-(4-(phenoxymethyl)-1H-1,2,3-triazol-1-yl)phenol 8c (Fig. 1) and
1-(4-(benzyloxy)phenyl)-4-(phenoxymethyl)-1H-1,2,3-triazole 8f (Fig. 2) were grown in
Scheme 1. Synthesis of ether linked 1,4-disubstituted 1,2,3-triazoles.

4
R. LUXMI ET AL.
Scheme 1. Continued
1
2
Compound
R
R
Reaction time (h)
Yield %
8
8
8
8
8
8
8
8
8
8
8
8
8
8
8
8
8
8
8
8
8
8
8
8
8
8
8
a
b
c
d
e
f
g
h
i
j
k
l
m
n
o
p
q
r
H
H
H
H
H
H
H
H
H
CH
CH
CH
CH
CH
CH
CH
CH
CH
NO
NO
NO
NO
NO
NO
NO
NO
NO
2-OH
3-OH
4-OH
2-OCH
3-OCH
4-OCH
2-OCH
3-OCH
4-OCH
2-OH
4
5
5
5
6
5
4
7
7
4
6
4
5
7
6
6
7
5
4
6
5
5
6
4
7
7
6
86
90
86
93
84
79
93
84
79
92
84
88
89
84
90
89
84
90
94
89
84
87
90
92
87
90
92
2
C
6
6
6
H
H
H
5
2
2
2
2
2
C
C
CH
CH
CH
5
5
2
2
2
C
C
C
6
6
6
H
H
H
5
5
5
3
3
3
3
3
3
3
3
3
3-OH
4-OH
2-OCH
3-OCH
4-OCH
2-OCH
3-OCH
4-OCH
2-OH
2
2
2
2
2
2
C
C
C
CH
CH
CH
6
6
6
H
H
H
5
5
5
2
2
2
C
C
C
6
6
6
H
5
H
5
H
5
s
t
2
2
2
2
2
2
2
2
2
3-OH
4-OH
u
v
w
x
y
z
2-OCH
3-OCH
4-OCH
2-OCH
3-OCH
4-OCH
2
2
2
2
2
2
C
C
C
CH
CH
CH
6
6
6
H
H
H
5
5
5
2
2
2
C
6
6
6
H
5
H
5
H
5
C
C
z
1
Figure 1. Crystal structure of compound 8c.
Figure 2. Crystal structure of compound 8f.

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ethyl acetate using the slow evaporation technique. Single crystal data for compounds
c and 8f has been deposited in the Cambridge Crystallographic Data Center and
8
assigned to the CCDC 1840219 and CCDC 1840220 numbers, respectively, which is
available at www.ccdc.cam.ac.uk/conts/retrieving.html.
Experimental
The chemicals were purchased from Alfa-Aesar, Sigma-Aldrich, and used without fur-
ther purification. Thin layer chromatography was used to monitor the progress of the
reactions and visualized by UV light. Melting points were determined by capillary
method and are uncorrected. IR spectra were recorded on a SHIMAZDU AFFINITY-I
ꢀ
1
FT-IR spectrophotometer using KBr powder and the values are expressed in cm . The
1
13
H NMR and C NMR spectra of the synthesized compounds were recorded at 400
and 100 MHz, respectively, using Bruker Avance II 400 MHz NMR spectrometer in
DMSO-d solvent, and the chemical shifts were expressed in d and coupling constants
6
(J) in Hz. Splitting patterns were indicated as s: singlet, d: doublet, t: triplet, m: multi-
plet. HRMS were obtained using Waters Micromass Q-Tof Micro (ESI) spectrophotom-
eter (Waters Corporation, MA) and values were quoted in m/z.
Procedure for the synthesis of 2-(4-(phenoxymethyl)-1H-1,2,3-triazol-1-yl)
phenol (8a)
[
35]
To a stirred solution of azido phenol
(5a) (1.0 mmol) and (prop-2-yn-1-yloxy)ben-
zene (3a) (1.0 mmol) in dimethylformamide (15 mL), copper sulfate pentahydrate
(
0.2 mmol) and sodium ascorbate (0.5 mmol) were added. The reaction mixture was
ꢁ
stirred for 4 h at 30–40 C. After completion of reaction, ice cold water was added to
reaction mixture. Product was precipitated, filtered and washed with ammonia solution.
Crude product was dissolved in ethyl acetate and precipitated out by hexane, which was
ꢁ
filtered and dried to get white solid product in 86% yield, mp: 152–154 C; FTIR (KBr):
3362 (OH, str.), 3128 (C–H str., triazole ring), 3075 (C–H str., aromatic ring), 2937
(
C–H str., aliphatic), 1580, 1477 (C¼C str., aromatic ring), 1244, 1017 (C–O str., ether)
-
1 1
cm ; H NMR (400 MHz, DMSO-d ): d 5.23 (s, 2H, OCH ), 6.95–7.14 (m, 5H, ArH),
6
2
7
.31–7.36 (m, 3H, ArH), 7.61 (d, 1H, ArH, J¼ 8.0 Hz), 8.60 (s, 1H, CH-triazole), 10.59
13
(s, 1H, OH); C NMR (100 MHz, DMSO-d ): d 61.3 (OCH ), 115.2, 117.5, 120.0 (C
6 2 5
triazole), 121.3, 124.9, 125.74, 126.71, 130.0, 130.7, 142.9 (C triazole), 150.2 (COH),
4
þ
1
58.6 (CH OC); HRMS (m/z) calculated for C H N O [M þ H] : 268.101,
2
15 13 3 2
found: 268.108.
X-ray crystallography
Single crystals of compounds 8c and 8f were selected and determined on a SuperNova,
Single source at offset, Titan diffractometer. The crystal was kept at 293 K during data
[
36]
collection. Using Olex2, the structure was solved with the ShelXT
program using Direct Methods and refined with the ShelXL
using Least Squares minimization.
structure solution
refinement package
[
37]

6
R. LUXMI ET AL.
Conclusion
In this work, a series of 1,4-disubstituted 1,2,3-triazoles (8a–8z ) have been synthesized
1
through straightforward click reaction between terminal alkynes and azide. The synthe-
sized compounds were characterized by various analytical techniques, further, the struc-
tures of synthesized compounds 8c (CCDC 1840219) and 8f (CCDC 1840220) were also
confirmed by X-ray crystallography.
1
13
Full experimental details, H NMR, C NMR and HRMS data, this material can be
found via the “Supplementary Content” section of this article webpage.
Disclosure statement
No potential conflict of interest was reported by the authors.
Funding
Authors are highly thankful to DST, New Delhi for financial assistance sanctioned to GJU S&T,
Hisar under PURSE program No. SR/PURSE Phase 2/40(G) and Central Instrumentation
Laboratory, GJU S&T, Hisar.
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