Highly Efficient Ultrasonic-Assisted CuCl-Catalyzed 1,3-Dipolar Cycloaddition Reactions in Water: Synthesis of Coumarin Derivatives Linked with 1,2,3-Triazole Moiety

Article abstract of DOI:10.1002/jhet.2175

By introducing ultrasound irradiation into “on water” CuCl-catalyzed 1,3-dipolar Huisgen cycloaddition, the reaction efficiencies were notably promoted toward a wide variety of applicable azides and alkynes at room temperature, and a series of coumarin de

Full text of DOI:10.1002/jhet.2175

Month 2016
Highly Efficient Ultrasonic-Assisted CuCl-Catalyzed 1,3-Dipolar Cyclo-
addition Reactions in Water: Synthesis of Coumarin Derivatives Linked
with 1,2,3-Triazole Moiety
a
a
b
a
a,c
a
c
a
*
*
Zhibo Qu, Jinwei Yuan, and Hanyu Shi
Xu Li, Xiaolan Chen, Yuqin Jiang, Senshen Chen, Lingbo Qu,
aCollege of Chemistry and Molecular Engineering, Zhengzhou University, Key Laboratory of Organic Chemistry and
Chemical Biology, Henan Province, Zhengzhou, 450052, People’s Republic of China
bCollege of Chemistry and Environmental Science, Henan Normal University, Xinxiang, 453007,
People’s Republic of China
cChemistry and Chemical Engineering School, Henan University of Technology, Henan Province, Zhengzhou, 450001,
People’s Republic of China
*
E-mail: chenxl@zzu.edu.cn; qulingbo@zzu.edu.cn
Received November 5, 2013
DOI 10.1002/jhet.2175
Published online 00 Month 2016 in Wiley Online Library (wileyonlinelibrary.com).
By introducing ultrasound irradiation into “on water” CuCl-catalyzed 1,3-dipolar Huisgen cycloaddition,
the reaction efficiencies were notably promoted toward a wide variety of applicable azides and alkynes at
room temperature, and a series of coumarin derivatives linked with 1,2,3-triazole moiety were synthesized
using the optimized conditions.
J. Heterocyclic Chem., 00, 00 (2016).
INTRODUCTION
quite often in this case need to add additional bases or ligands
such as triethylamine [8], N,N-diisopropylethylamine [7c,9],
and tris(benzyltriazolylmethyl)amine [10] to form stable
complexes with Cu(I) ion.
Azole antifungals, which were discovered around
30 years ago, are currently the largest class of antifungal
agents in clinical use [1]. Several 1,2,3-triazole containing
compounds show diverse biological activities such as anti-
HIV [2], antimicrobial [3], anti-allergic [4], and selective
β3 adrenergic receptor agonist [5]. 1,2,3-Triazole moiety
does not occur in nature, although the synthetic molecules
containing 1,2,3-triazole unit show diverse biological
activities. 1,2,3-Triazole moieties are stable to metabolic
degradation and are capable of hydrogen bonding, which
can be favorable in binding of biomolecular targets and
for solubility [6]. With respect to introducing 1,2,3-triazole
groups into organic molecules, Huisgen’s 1,3-dipolar
cycloaddition of terminal acetylenes and organic azides is
a useful approach. However, the regioselectivity of the
cycloaddition reaction is generally low, and the reaction
usually leads to a mixture of 1,4-regioisomers and 1,5-regi
oisomers. In 2002, K. B. Sharpless and M. Meldal improved
the regioselectivity of the reactions by introducing Cu(I)
catalyst systems into the cycloaddition (click chemistry) of
organic azides and terminal alkynes (Scheme 1) [7]. The Cu
(I) catalyst systems not only play an important role in raising
regioselectivity but also noticeably affect the conversion
efficiency of a chemical process. The most common catalyst
systems for copper-catalyzed azide–alkyne cycloaddition
(CuAAC) employ Cu(II) salt in the presence of a reducing
agent (often sodium ascorbate or metallic copper) to generate
the required Cu(I) catalyst in situ, or sometimes directly
employ copper(I) salts, such as CuCl, CuBr, and CuI, but
Green or sustainable chemistry has now attained the
status of a major scientific discipline, and the studies in this
area have led to the development of cleaner and relatively
benign chemical processes with many new technologies
being developed each year. Green chemistry encourages
the design of processes that minimize the use of hazardous
substance and seeks to reduce and prevent pollution at its
source. Examples of applied green chemistry are supercrit-
ical water oxidation, dry media reactions, and on water
reactions. On water reactions are a group of organic
reactions that take place as an emulsion in water and
exhibit an unusual reaction rate acceleration compared
with the same reaction in an organic solvent or compared
with the corresponding dry media reaction. During the past
two decades, many reactions that were conventionally
believed to occur only in organic solvents have been
developed to run in water. It is worth mentioning that the
most commonly employed solvents for CuAAC are
water/organic cosolvent mixtures, probably because
general organic reactants are relatively soluble in organic
solvent, whereas most of the related catalysts are relatively
soluble in water. The fact that very little CuAAC work has
previously been reported in pure water [11] is probably due
to poor solubility of the most widely used organic reactants
in water, even though organic reactions in water are of
great interest in relation to today’s environmental concerns.
© 2016 Wiley Periodicals, Inc.

X. Li, X. Chen, Y. Jiang, S. Chen, L. Qu, Z. Qu, J. Yuan and H. Shi
Vol 000
Scheme 1. The copper-catalyzed azide–alkyne 1,3-dipolar cycloaddition.
RESULTS AND DISCUSSION
The 1,3-dipolar cycloaddition reaction between 7-(3-azi
dopropoxy)coumarin (4) and propargyl phenyl ether (5)
was chosen as a model reaction to optimize the reaction
conditions (Scheme 2). The three-step synthetic process of
compound 4 is shown in Scheme 2. 1-Bromo-3-chlo
ropropane (1) was first reacted with sodium azide in DMSO
at room temperature to form 1-azido-3-chloropropane (2). 1-
Azido-3-iodiopropane (3) was synthesized by treating 2 with
KI in acetone under reflux [13], considering that the iodine
group is a relatively good nucleophile as well as a leaving
group than the chlorine group in nucleophilic substitution
reaction. Then, 3 was reacted with 1 equiv of coumarin to
form compound 4 using a reported procedure [14]. Azido-
containing intermediate 4 was purified by column chroma-
tography (CHCl3:CH3OH = 30:1, v/v) before it was used
for the next step.
The experiment was initially designed to investigate how
or to what extent Et3N could promote the CuAAC model
reaction efficiency under designed conditions as mentioned
in the following. The cheap and easily available CuCl
(10 mol%) was preferentially chosen as the catalyst. The
efficiencies of the model reactions performed in water,
selected organic solvents, and water/organic cosolvents
(v:v = 1:1) were investigated in the presence of Et3N or
the absence of Et3N without US irradiation at room
temperature for about 45 min, respectively, as shown in
Figure 1. The result shows that the model reactions
carried out in the absence of Et3N generally were less
efficient in promoting the cycloaddition reactions than
those in the presence of Et3N. Different degrees of Et3N
in promoting the cycloaddition reactions were shown
when different solvent systems were employed: tremen-
dous differences were shown when pure organic solvent
was employed, on the basis of the fact that only trace
products were isolated in the absence of Et3N, whereas
relatively small differences were shown when water/or-
ganic cosolvent was employed and relatively big differ-
ences were shown when pure water was employed. The
The reportedly few CuAAC reactions carried out in
aqueous reaction medium nearly unavoidably employed
additional ligands for forming stable Cu(I) complex. For
example, Zhao and coworkers employed water as the
solvent and 10 mol% CuBr as the catalyst in the presence of
50 mol% PhSMe as the ligand to stabilize Cu(I) salt
[11e,11f]. Even though the related Cu(I) complex, synthesized
by Miquel A. Pericàs such as tris(triazolyl)methanol–Cu(I)
complex [11g] and [(NHC)CuBr] complex (NHC═N-
heterocyclic carbene) [11c], reportedly can act as the catalyst
for the CuAAC reaction at very low catalyst loading in water,
the less popular Cu(I) complex requires tedious and time-
consuming preparation.
It is reported that the ultrasound (US) irradiation can lead
to the apparent improvement of the reaction efficiency with
increased rates and reduced reaction time [12]. Ultrasonic-
assisted organic synthesis is a powerful technique that is
being used more and more to accelerate organic reaction rate.
The notable features of the US approach are enhanced
reaction rates, formation of pure products in high yields,
and easier manipulation. In the work described in this
article, 7-hydroxycoumarin, a representative of natural
products, initially reacted with 1-azido-3-iodiopropane
through substitution reaction to form 7-(3-azidopropoxy)
coumarin, which subsequently was employed as a starting
reactant of Huisgen 1,3-dipolar cycloaddition to optimize
the relevant reaction condition (Scheme 2). The CuAAC
reaction, promoted by ultrasonic irradiation in water at
room temperature, using CuCl as the catalyst, without
adding any additional bases or ligands, was then applied
to the syntheses of a series of triazole-containing com-
pounds and 7-hydroxycoumarin derivatives linked with
triazole moiety.
Scheme 2. Synthetic routine of the coumarin linked with 1,2,3-triazoles.
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Highly efficient ultrasonic-assisted CuCl-catalyzed 1,3-dipolar cycloaddition reactions in water
Figure 2. The yield of the model reaction in different solvents. , in the
Figure 1. The yield of the model reaction in different solvents. , in the
absence of triethylamine and US irradiation; , in the presence of
triethylamine (2 equiv) without US irradiation condition. The model reac-
tion was carried out using compound 4 (1 mmol) and propargyl phenyl
ether 5 (1 mmol) in the presence of CuCl (10 mol%) in the solvent
(3 mL) at room temperature for 45 min. Mixing equal volume of water
and organic solvent results in the corresponding cosolvent.
presence of triethylamine (2 equiv) but without US irradiation; , in the
absence of triethylamine with US irradiation condition, 150 W. The model
reaction was carried out using compound 4 (1 mmol) and propargyl
phenyl ether 5 (1 mmol) in the presence of CuCl (10 mol%) in the solvent
(3 mL) at room temperature for 45 min.
the results shown in Figures 1 and 2, the model reaction
carried out in water and promoted by Et3N had only about
a one-time increase in yield, from 29 to 55%, whereas the
model reaction carried out in water and promoted by US
irradiation had twice increases in yield, from 29 to 91%,
implying an enormously promotive role of US irradiation
toward the model reaction carried out in water. The
influences of US power on the cycloaddition reaction were
also investigated. The result showed that the yields
increased along with the increased US power as shown in
Figure 3.
Other Cu(I) salts and oxide such as CuBr, CuI, CuCN,
and Cu2O, respectively, were employed to compare the
catalytic efficiency of the “on water” model reaction in
the presence of US irradiation (150 W) at room temperature
for 45 min. As it can be seen in Figure 4, CuCl showed a
remarkably high catalytic efficiency among the tested
catalysts. A 91% yield was obtained from CuCl catalytic
yield obtained in water in the presence of Et3N is 55%,
almost twice than that in water in the absence of Et3N.
It is especially worth mentioning that the yield obtained
in water in the presence of Et3N is the highest among
the tested solvents, even though 55% is not a relatively
high yield.
It seems that Et3N was especially crucial in promoting
the CuAAC reaction efficiency when CuCl was employed
as the catalyst and pure water as the reaction solvent in
the experiments previously shown. Is there any alternative
method, for example, using US irradiation instead of using
Et3N, a compound giving off a strong fishy odor that is
reminiscent of ammonia, to achieve the same or even
higher yields from the model reaction? The following
experiment was especially designed to investigate whether
the use of US irradiation could lead to more efficient
chemical reactions. Under US irradiation condition and in
the absence of Et3N, the model reaction was performed
again in water, selected organic solvents, and water/or-
ganic cosolvents at room temperature for 45 min, respec-
tively (Fig. 2). The results interestingly show that US
irradiation indeed led to more efficient chemical reactions
than Et3N did when the model reactions were carried out
in water or water-containing solvents, whereas US
irradiation could not always achieve a better promotion ef-
ficiency than could Et3N when the model reactions were
carried out in organic solvents such as t-BuOH, DMF,
and toluene as shown in Figure 2, even though the two
reactants 7-(3-azidopropoxy)coumarin (4) and propargyl
phenyl ether (5) were observed to have low aqueous
solubility in water. It is especially worth mentioning that
a profoundly greater conversion efficiency of CuAAC
reaction in water was shown when US irradiation was
employed to promote the reaction. As can be seen from
Figure 3. Yield versus US power using CuCl (10 mol%) as the catalyst
and water as the reaction solvent. The model reaction was carried out
using compound 4 (1 mmol) and propargyl phenyl ether 5 (1 mmol) in
the presence of catalyst (10 mol%) in water (3 mL) at room temperature
for 45 min.
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X. Li, X. Chen, Y. Jiang, S. Chen, L. Qu, Z. Qu, J. Yuan and H. Shi
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oxide in water—the better water solubility, the higher
catalytic efficiency for the “on water” model reaction in
this case.
The CuCl catalyst loading on the model reaction was
further investigated in water under US irradiation for
45 min, using the catalyst loadings of 20, 15, 10, 5, and
2 mol%, respectively, as shown in Figure 5. As can be seen
from Figure 5, the yield increased with the increase in
catalyst loading before the 10 mol% catalyst loading was
reached, whereas the yields did not change a lot after the
loading exceeded 10 mol%. It deserves to be pointed out
that under the design condition previously mentioned, not
all but few reactions could be completed within 45 min.
For example, the model reactions catalyzed by 15 or
20 mol% CuCl were observably completed in less than
45 min, whereas the model reactions catalyzed by 5 or
2 mol% CuCl were observably completed in more than
45 min. A complementary experiment showed that a 91%
yield could also be obtained from the model reaction when
using 5 mol% CuCl not in 45 min but in about 2 h, indicat-
ing the fact that the rate of the reaction increases with the
increase in the catalyst loading in this case.
Figure 4. Screening of catalysts for the model reaction in water at room
temperature under US irradiation for 45 min. The model reaction was car-
ried out using compound 4 (1 mmol) and propargyl phenyl ether 5
(1 mmol) in the presence of catalyst (10 mol%) in water (3 mL) at room
temperature for 45 min.
It can be seen that by introducing US irradiation into the
“on water” CuCl-catalyzed model reaction, the reaction
efficiencies were notably promoted. The following experi-
ment was especially carried out to discuss the impact of the
ultrasonic irradiation forces on the model reaction. The in-
fluence of temperature on the model reaction was preferen-
tially investigated by performing the model reaction in the
absence of US irradiation. CuCl (5 mol%) was chosen as
the catalyst to promote the model reaction for 45 min at
five different temperatures, 20, 40, 60, 80, and 100°C,
respectively, as shown in Figure 6. It can be seen that the
yield increased quickly over the temperature range of 20
to 60°C, from 12 to 60%, and increased slightly over the
range of 60 to 80°C, from 60 to 83%, and then decreased
slightly over the temperature range of 80 to 100°C, from
83 to 78%, indicating that in the absence of US irradiation,
the 1,3-dipolar cycloaddition reaction can be promoted by
appropriately raising the temperature to a certain degree,
for instance, 80°C in this case, but with the exception of
relatively high temperatures. The dropping in the yield
over the temperature range of 80 to 100°C was probably
caused by some side reactions triggered by a relatively
high temperature, such as an oxidation reaction of CuCl
to CuCl2 or azide thermal decomposition. As is known,
US can greatly enhance chemical reactivity in a number
of systems by as much as a millionfold [15], although upon
irradiation with US, cavitation—the formation, growth,
Figure 5. Catalyst loading versus the yield in 45 min under US irradia-
tion. The model reaction was carried out using compound 4 (1 mmol)
and propargyl phenyl ether 5 (1 mmol) in different catalyst loadings in wa-
ter (3 mL) at room temperature for 45 min.
Figure 6. Yield of compound 6 versus temperature using direct heating
method for 45 min. The model reaction was carried out using compound
4 (1 mmol) and propargyl phenyl ether 5 (1 mmol) in the presence of CuCl
(5 mol%) in water (3 mL) using direct heating for 45 min.
reaction, whereas a 33% yield from CuBr, a 10% yield
from CuI, and two trace yields were obtained from CuCN-
and Cu2O-catalytic reactions, respectively, approximately
corresponding to the varying solubility of Cu(I) salt or
Scheme 3. Syntheses of 6′a–m.
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Highly efficient ultrasonic-assisted CuCl-catalyzed 1,3-dipolar cycloaddition reactions in water
Table 1
Various terminal alkynes were investigated to be reacted with different azide.
Entry
Azide (4′)
Alkyne (5′)
Product (6′)
Time (min)
15
Yield (%)a
90
a
b
c
15
90
15
92
91
93
d
e
20
93
f
10
10
15
93
95
94
g
h
i
100
91
j
10
10
15
92
94
92
k
l
m
120
89
Condition: Alkyne (1 mmol), azide(1 mmol), and CuCl (10 mol%) as the catalyst in water (3 mL) at room temperature under ultrasonic power of 150 W.
aIsolated yield.
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Scheme 4. Syntheses of 6a–j.
C, was further carried out to compare the reaction
efficiency of the same reaction carried out for 2 h at room
temperature, using CuCl (5 mol%) as the catalyst, in the
presence of US irradiation mentioned previously. The
result showed that about 83% yield was obtained at 80°C
in the absence of US irradiation; however, a 91% yield
was obtained from the model reaction at room temperature
in the presence of US irradiation. The obvious difference in
the reaction efficiencies with or without sonication
suggests again that the reaction under US condition
proceeded in not the same but in more efficient way than
did the reaction under the heating conditions. It is known
that once cavitation occurs near the solid surface, cavity
collapse is nonspherical and drives high-speed jets of
liquid to the solid surface [18]. These collisions break up
the azide reactants into pieces in this case, which gives
the azide reactants larger surface areas and increases the
frequencies of collisions between azides and other
reactants. It might be concluded that the US played a
significant role in promoting the efficiency of the cycload-
dition reaction in terms of increasing reactant contact
surfaces through cavitation phenomena—the formation,
growth, and implosive collapse of bubbles. With liquids
containing solids, once cavitation occurs near an extended
solid surface, cavity collapse drives high-speed jets of
liquid to the surface [18c]. These jets and associated shock
waves can damage the now highly heated surface. Liquid-
powder suspensions produce high velocity interparticle
collisions. The chemical enhancement of reactions by US
shows an obvious beneficial result in this mixed phase
synthesis.
Table 2
Coumarin derivatives linked with 1,2,3-triazole moiety.
Entry
R1
R2
R3
Yield (%)a
6a
6b
6c
6d
6e
6f
6g
6h
6i
H
NO2
H
OMe
OEt
H
Me
H
H
H
H
H
H
H
H
Me
H
H
H
H
NO2
H
H
OMe
H
H
Cl
Cl
92
89
91
88
89
90
88
86
95
90
H
Cl
6j
Condition: Compound 4 (0.5 mmol), various substituted terminal alkynes
(0.5 mmol), and CuCl (10 mol%) as the catalyst in water (3 mL) at room
temperature under ultrasonic power of 150 W.
aIsolated yield.
and implosive collapse of bubbles irradiated with US—can
create extreme physical and chemical conditions in liquids
[16]. The bubbles produced by US have temperatures of
around 5000 K, pressures of roughly 1000 atm, and heating
and cooling rates above 1010 K/s [17]. The implosion of
cavities reportedly established an unusual environment
for reactions. The gases and vapors inside the cavity are
compressed, generating intense heat that raises the temper-
ature of the liquid immediately surrounding the cavity and
creates a local hot spot. The short-lived localized hot spot
produced by US irradiation can greatly accelerate the
reaction rate. Even though the temperature of this region
is extraordinarily high, the region itself is so small that
the heat dissipates quickly. Therefore, when we mentioned
the high reaction temperature, we especially refer to the
temperature of the liquid surrounding the cavity, but not
the temperature of the reaction solution. Of course,
detection of the temperature reached in cavitation bubbles
has remained a difficult experimental problem, but the
temperature changes of the reaction solution during sonica-
tion inside the reaction flask can be detected directly by
placing a thermometer into the reaction solution. It was
found that the temperature of the reaction liquid did not
exceed 30°C during sonication, a relatively mild tempera-
ture at which the side reactions could be efficiently
prevented to a great extent. The model reaction, performed
in water in the absence of US irradiation, using CuCl
(5 mol%) as the catalyst, not for 45 min but for 2 h at 80°
The scope of the reactants was then enlarged to various
terminal alkynes and azides as shown in Scheme 3 and
Table 1. All the reactions were performed in water at room
temperature using 10 mol% CuCl as the catalyst and under
ultrasonic power of 150 W. The reaction completion times
varied with the reactants. The reaction completion times
were within 20 min when liquid reactants were employed
and within longer times, some even 2 h, when solid termi-
nal alkynes with poor water solubility were employed, but
very high yields, for instance, more than 90% for each case
as shown in Table 1, were achieved under the optimized
reaction conditions.
The application of CuAAC reaction promoted by ultra-
sonic irradiation in water at room temperature then led to
successful syntheses of a series of coumarin derivatives
linked with triazole moiety (Scheme 4), using various
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Highly efficient ultrasonic-assisted CuCl-catalyzed 1,3-dipolar cycloaddition reactions in water
General procedure for the reaction between 4′ and 5′.
Different azide (4′) (1.0 mmol) and various terminal alkynes (5′)
(1.0 mmol) were suspended in 5 mL H2O in a 10-mL round-
bottomed flask followed by CuCl (10 mol%). The mixture was
substituted terminal alkynes and 4 as reactants. As could be
seen from Table 2, in all cases, coumarin derivatives linked
with 1,2,3-triazoles were obtained in good yields.
sonicated in
a laboratory ultrasonic cleaning bath. After
completion of the reaction, as indicated by TLC, the reaction
mixture was diluted with saturated aq. NH4Cl (20 mL) and
extracted by CH2Cl2 (3 × 15 mL). The combined organic layers
were washed with brine (10 mL) and dried over anhydrous
Na2SO4 and filtered. The products (6′a–m) were isolated by
column chromatography on silica gel using C2H5OH:CHCl3
CONCLUSIONS
In summary, an environmentally friendly and economi-
cally efficient method for synthesis of 1,4-disubstituted
1,2,3-triazoles was developed with the help of US irradiation
in water. The model CuAAC reaction above features an
enormous reaction rate acceleration in water compared with
the same reaction in an organic solvent or water/organic
cosolvent at room temperature. The application of CuAAC
reaction promoted by ultrasonic irradiation in water finally
led to successful syntheses of a series of coumarin deriva-
tives linked with triazole moiety.
(1:30, v/v) as eluent.
2-(4-Phenyl-1H-1,2,3-triazol-1-yl)ethyl acetate (6′a). White
solid, mp 97–99°C (Ref. [22], 93–95°C). 1H-NMR (400 MHz,
CDCl3): δ =7.93 (s, 1H, 8-H), 7.85 (t, J= 7.6 Hz, 2H, 3, 5-H), 7.44
(t, J= 7.6 Hz, 2H, 2, 6-H), 7.35 (t, J= 7.2 Hz, 1H, 4-H), 5.21 (s, 2H,
9-H), 4.31–4.25 (q, 2H, 11-H), 1.31 (t, J= 7.2 Hz, 3H, 12-H). 13C-
NMR (100 MHz, CDCl3): δ =166.3 (C-10), 148.2 (C-1), 130.4 (C-
7), 128.9 (C-2, 6), 128.3 (C-4), 125.8 (C-3, 5), 121.0 (C-8), 62.5
(C-11), 51.0 (C-9), 14.1 (C-12); ESI-MS m/z: 232 [M + H]+.
2-(4-(Phenoxymethyl)-1H-1,2,3-triazol-1-yl)ethyl acetate (6′b).
Pale yellow solid, mp 67–68°C (Ref. [23], 116–118°C; Ref. [24], pale
yellow oil). 1H-NMR (400 MHz, CDCl3): δ =7.74 (s, 1H, 9-H), 7.30–
7.26 (m, 2H, 3, 5-H), 6.99–6.94 (m, 3H, 2, 4, 6-H), 5.21 (s, 2H, 7-H),
5.13 (s, 2H, 10-H), 4.26–4.21 (q, 2H, 12-H), 1.27 (t, J= 7.2 Hz, 3H,
13-H). 13C-NMR (100 MHz, CDCl3): δ = 166.3 (C-11), 158.2 (C-1),
144.6 (C-8), 129.5 (C-3, 5), 124.2 (C-9), 121.2 (C-4), 114.8 (C-2, 6),
62.4 (C-12), 61.8 (C-7), 50.9 (C-10), 14.0 (C-13). ESI-MS m/z: 262
[M + H]+.
EXPERIMENTAL SECTION
General: All the chemicals were obtained from Tianjin Kermel
Chemical Reagent Co., Ltd (Tianjin, China) and used as received.
Melting points were recorded on an electrothermal apparatus and
were uncorrected. Sonication was performed in Kunshan KQ-
250B ultrasonic cleaner (Kunshan, China) with a frequency of
40 kHz and a power of 150 W. The reaction flasks were located
in the maximum energy area in the cleaner, and the addition or re-
moval of water controlled the temperature of the water bath. Infra-
red (IR) spectra were recorded on a Shimadazu IR-408 (Kyoto,
2-(4-(7-Coumarinoxymethyl)-1H-1,2,3-triazol-1-yl)ethyl acetate
(6′c). Pale yellow solid, mp 104–106°C. IR (KBr) ν: 3150, 3084,
3068, 2995, 2958, 1715, 1743 1613, 1378, 1275, 1231, 1126, 1052,
Japan). H and 13C spectra were recorded on a Bruker Avance
1
1
1012 cmÀ1. H-NMR (400 MHz, CDCl3): δ =7.83 (s, 1H, 13-H),
400-MHz spectrometer (Billerica, MA) operating at 400.13 and
100.61 MHz, respectively. All NMR spectra were recorded in
CDCl3 at room temperature (20 2°C). 1H and 13C chemical
shifts are quoted in parts per million downfield from
tetramethylsilane. Electrospray ionization mass spectrometry
(ESI-MS) spectra were recorded on a Bruker Esquire 3000
(Billerica, MA). High-resolution mass spectrometry (HRMS)
were performed on a Micromass Q-TOF MicroTM mass spec-
trometer with an ESI source (Waters, Manchester, UK).
Substituted terminal alkynes were synthesized according to the
literature [19]. Benzyl azide [20] and phenyl azide [21] were also
synthesized according to previous reports.
Synthesis of 7-(3-azidopropoxy)coumarin (4). 1-Azido-3-
iodopropane (35.8 mmol) and coumarin (35.8 mmol) in acetone
(60 mL) with potassium carbonate (71.6 mmol) were refluxed
for 28 h. Thin-layer chromatography (TLC) followed the
reaction. After the completion of the reaction, the excess
potassium carbonate was filtered off, and after evaporating the
solvent under reduced pressure, the crude product was obtained,
which was purified by column chromatography to afford 4.
White solid, mp 72–73°C. 1H-NMR (400 MHz, CDCl3):
δ = 7.64 (d, J = 9.6 Hz, 1H, 4-H), 7.38 (d, J = 8.8 Hz, 1H, 5-H),
6.80 (dd, J = 8.4, 2.4 Hz, 1H, 6-H), 6.77 (d, J = 2.4 Hz, 1H, 8-
H), 6.27 (d, J = 9.2 Hz, 1H, 3-H), 4.12 (t, J = 6.0 Hz, 2H, 13-H),
3.55 (t, J = 6.6 Hz, 2H, 11-H), 2.13–2.07 (m, 2H, 12-H). 13C-
NMR (100 MHz, CDCl3): δ = 161.8 (C-7), 161.1 (C-2), 155.9
(C-9), 143.3 (C-4), 128.8 (C-5), 113.3 (C-3), 112.8 (C-10),
112.7 (C-6), 101.5 (C-8), 65.1 (C-11), 48.0 (C-13), 28.5 (C-12).
HRMS Calcd for C12H12N3O3 [M + Na]+: m/z 246.0873, Found
246.0877.
7.64 (d, J= 9.6 Hz, 1H, 4-H), 7.39 (d, J= 9.6 Hz, 1H, 5-H), 6.95–
6.93 (m, 2H, 6, 8-H), 6.26 (d, J= 9.2 Hz, 1H, 3-H), 5.29 (s, 2H, 11-
H), 5.19 (s, 2H, 14-H), 4.31–4.26 (m, 2H, 16-H), 1.31 (t, J=7.0Hz,
1H, 17-H). 13C-NMR (100 MHz, CDCl3): δ =166.1 (C-15), 161.3
(C-7), 161.0 (C-2), 155.7 (C-9), 143.4 (C-12), 143.3 (C-4), 128.9
(C-5), 124.4 (C-13), 113.5 (C-3), 113.0 (C-10), 112.8 (C-6), 102.1
(C-8), 62.6 (C-16), 62.3 (C-11), 50.9 (C-14), 14.0 (C-17). HRMS
Calcd for C16H15N3NaO5 [M + Na]+: m/z 352.0909, Found 352.0918.
2-(4-p-Tolyl-1H-1,2,3-triazol-1-yl) ethyl acetate (6′d). White
solid, mp 100–102°C. 1H-NMR (400 MHz, CDCl3): δ =7.88
(s, 1H, 5-H), 7.75 (d, J= 8.0 Hz, 2H, 2′, 6′-H), 7.26 (d, J=8.0Hz,
2H, 3′, 5′-H), 5.20 (s, 2H, 4-H), 4.32–4.26 (q, 2H, 2-H), 2.39
(s, 3H, 7-H), 1.32 (t, J= 7.2 Hz, 3H, 1-H). 13C-NMR (100 MHz,
CDCl3): δ =166.3 (C-3), 148.4 (C-6), 138.1 (C-4′), 129.5 (C-3′, 5′),
127.6 (C-1′), 125.7 (C-2′, 6′), 120.6 (C-5), 62.5 (C-2), 50.9 (C-4),
21.3 (C-7), 14.1 (C-1). ESI-MS m/z: 246 [M + H]+.
2-(4-((4-Methoxyphenoxy)methyl)-1H-1,2,3-triazol-1-yl)ethyl
acetate (6′e). White solid, mp 103–104°C (Ref. [25], 103–104°C).
1H-NMR (400 MHz, CDCl3): δ = 7.75 (s, 1H, 9-H), 6.95–6.92 (m,
2H, 2, 6-H), 6.87–6.83 (m, 2H, 3, 5-H), 5.21 (s, 2H, 7-H), 5.17 (s,
2H, 10-H), 4.31–4.26 (q, 2H, 12-H), 3.78 (s, 3H, ―OCH3), 1.31
(t, J = 7.2 Hz, 3H, 13-H). 13C-NMR (100MHz, CDCl3): δ = 166.4
(C-11), 154.1 (C-4), 152.3 (C-1), 144.5 (C-8), 124.5 (C-9), 115.8
(C-2, 6), 114.6 (C-3, 5), 62.4 (C-10), 62.3 (C-12), 55.6
(―OCH3), 50.8 (C-7), 14.0 (C-13). ESI-MS m/z: 314 [M+ Na]+.
1,4-Diphenyl-1H-1,2,3-triazole (6′f). White solid, mp 180–182°C
(Ref. [22], 183–184°C). 1H-NMR (400 MHz, CDCl3): δ =8.22 (s, 1H,
8-H), 7.93 (d, J= 7.6 Hz, 2H, 3, 5-H), 7.82 (d, J= 7.6 Hz, 2H, 10, 14-
H), 7.57 (t, J= 8.0 Hz, 2H, 11, 13-H), 7.50–7.47 (m, 3H, 2, 4, 6-H),
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

X. Li, X. Chen, Y. Jiang, S. Chen, L. Qu, Z. Qu, J. Yuan and H. Shi
Vol 000
7.39 (t, J= 7.4 Hz, 1H, 12-H). 13C-NMR (100 MHz, CDCl3): δ = 148.4
(C-1), 137.1 (C-9), 130.2 (C-7), 129.8 (C-11, 12), 129.0 (C-2, 6), 128.8
(C-12), 128.5 (C-4), 125.9 (C-3, 5), 120.5 (C-10, 14), 117.6 (C-8). ESI-
MS m/z: 222 [M + H]+.
1-Benzyl-4-(7-coumarinoxymethyl)-1H-1,2,3-triazole (6′m). Pink
solid, mp 153–155°C. IR (KBr) ν: 3141, 3079, 2926, 1711, 1614, 1278,
1
1231, 1204, 1128, 1055, 1032 cmÀ1. H-NMR (400 MHz, CDCl3):
δ =7.63 (d, J= 9.6 Hz, 1H, 4–H), 7.57 (s, 1H, 13-H), 7.42–7.36 (m,
4H, 3′, 4′, 5′, 5-H), 7.32–7.27 (m, 2H, 2′, 6′-H), 6.93–6.90 (m, 2H, 6,
8-H), 6.26 (d, J=9.2Hz, 1H, 3-H), 5.55 (s, 2H, 14-H), 5.23 (s, 2H,
11-H). 13C-NMR (100 MHz, CDCl3): δ =161.3 (C-7), 161.0 (C-2),
155.7 (C-9), 143.3 (C-4), 143.3 (C-12), 134.3 (C-1′), 129.2
(C-3′, 5′), 128.9 (C-4′, 5), 128.2 (C-2′, 6′), 122.9 (C-13),
113.4 (C-3), 113.0 (C-10), 112.7 (C-6), 102.1 (C-8), 62.3
(C-11), 54.3 (C-14). HRMS Calcd for C19H15N3NaO3
[M + Na]+: m/z 356.1011, Found 356.1020.
General procedure for the synthesis of the target molecules
(6a–j). Substituted terminal alkyne (5.0 mmol) and 4 (4.0 mmol)
were suspended in 30 mL H2O in a 50-mL round-bottomed flask
followed by CuCl (10 mol%). The mixture was sonicated for 2 h in
a laboratory ultrasonic cleaning bath. After completion of the
reaction, as indicated by TLC, the reaction mixture was diluted
with 20mL water, and the precipitate was collected and washed
with cold water and saturated ammonium chloride. The crude
product was purified by column chromatography on silica gel
using CH3OH:CHCl3 (1:30, v/v) as eluent.
4-(Phenoxymethyl)-1-phenyl-1H-1,2,3-triazol (6′g). White
solid, mp 80–81°C (Ref. [26], 89.5–90.5°C). 1H-NMR (400 MHz,
CDCl3): δ = 8.07 (s, 1H, 9-H), 7.76 (d, J = 8.0 Hz, 2H, 11, 15-H),
7.54 (t, J = 3.6, 2H, 12, 14-H), 7.47 (t, J = 3.1 Hz, 1H, 13-H), 7.33
(t, J = 3.7 Hz, 2H, 3, 5-H), 7.06–6.99 (m, 3H, 2, 4, 6-H), 5.33
(s, 2H, 7-H). 13C-NMR (100 MHz, CDCl3): δ = 158.2 (C-1),
145.0 (C-8), 137.0 (C-10), 129.8 (C-12, 14), 129.63 (C-3, 5),
128.9 (C-13), 121.4 (C-4), 121.0 (C-9), 120.6 (C-11, 15), 114.7
(C-2, 6), 61.9 (C-7). ESI-MS m/z: 252 [M + H]+.
4-((4-Methoxyphenoxy)methyl)-1-phenyl-1H-1,2,3-triazole
(6′h). White solid, mp 102–104°C (Ref. [27], 97–99°C). 1H-NMR
(400 MHz, CDCl3): δ =8.06 (s, 1H, 9-H), 7.75 (d, J= 8.0 Hz, 2H, 11,
15-H), 7.55 (t, J= 8.0 Hz, 2H, 12, 14-H), 7.46 (t, J= 8.0 Hz, 1H, 13-
H), 6.97 (m, 2H, 2, 6-H), 6.88 (m, 2H, 3, 5-H), 5.27 (s, 2H, 7-H), 3.80
(s, 3H, ―OCH3). 13C-NMR (100 MHz, CDCl3): δ = 154.2 (C-4),
152.3 (C-1), 145.1 (C-8), 136.9 (C-10), 129.8 (C-12, 14), 128.9
(C-13), 121.0 (C-9), 120.5 (C-11, 15), 115.8 (C-2, 6), 114.7 (C-3, 5),
62.6 (C-7), 55.7 (―OCH3). ESI-MS m/z: 282 [M + H]+.
4-(7-Coumarinoxymethyl)-1-phenyl-1H-1,2,3-triazol (6′i). Pale
7-(3-(4-(Phenoxymethyl)-1,2,3-triazol-1-yl)propoxy)coumarin
(6a). White solid, mp 104–106°C. IR (KBr) ν: 3133, 3093, 2927, 2880,
yellow solid, mp 160–162°C. IR (KBr) ν: 3141, 3075, 2930, 2879,
1729, 1617, 1296, 1241, 1133, 1047 cmÀ1 1H-NMR (400 MHz,
.
1724, 1614, 1344, 1278, 1228, 1121, 1040 cmÀ1 1H-NMR
.
CDCl3): δ =7.64 (d, J= 9.2 Hz, 1H, 4-H), 7.63 (s, 1H, 14-H), 7.37
(d, J= 8.8 Hz, 1H, 5-H), 7.30–7.28 (m, 2H, 2′, 6′-H), 6.98–6.95
(m, 3H, 3′, 4′, 5′-H), 6.81 (dd, J= 8.8, 2.4 Hz, 1H, 6-H), 6.77
(d, J= 2.4 Hz, 1H, 8-H), 6.27 (d, J= 9.6 Hz, 1H, 3-H), 5.22 (s, 2H,
16-H), 4.61 (t, J= 6.8 Hz, 2H, 13-H), 4.04 (t, J= 5.8 Hz, 2H, 11-H),
2.49–2.43 (m, 2H, 12-H). 13C-NMR (100 MHz, CDCl3): δ =161.5
(C-7), 161.0 (C-2), 158.1 (C-1′), 155.8 (C-9), 144.4 (C-15),
143.3 (C-4), 129.5 (C-2′, 6′), 128.9 (C-5), 123.1 (C-14), 121.3
(C-4′), 114.7 (C-3′, 5′), 113.4 (C-3), 112.9 (C-10), 112.5 (C-6),
101.6 (C-8), 64.7 (C-11), 62.9 (C-16), 47.0 (C-13), 29.7 (C-12).
HRMS Calcd for C21H19N3NaO4 [M+ Na]+: m/z 400.1273,
Found 400.1291.
(400MHz, CDCl3): δ = 8.11 (s, 1H, 13-H), 7.76–7.74 (m, 2H, 2′,
6′-H), 7.65 (d, J = 9.2 Hz, 1H, 4-H), 7.56–7.52 (m, 2H, 3′, 5′-H),
7.48–7.45 (m, 1H, 4′-H), 7.41 (d, J = 9.2 Hz, 1H, 5-H), 6.99–6.96
(m, 2H, 6, 8-H), 6.27 (d, J = 9.2 Hz, 1H, 3-H), 5.36 (s, 2H, 11-H).
13C-NMR (100 MHz, CDCl3): δ = 161.2 (C-7), 161.1 (C-2), 155.7
(C-9), 143.7 (C-12), 143.3 (C-4), 136.8 (C-1′), 129.8 (C-3′, 5′),
129.1 (C-4′), 129.0 (C-5), 121.30 (C-13), 120.6 (C-2′, 6′), 113.5
(C-3), 113.1 (C-10), 112.7 (C-6), 102.1 (C-8), 62.3 (C-11).
HRMS Calcd for C18H13N3NaO3 [M+ Na]+: m/z 342.0855,
Found 342.0835.
1-Benzyl-4-phenyl-1H-1,2,3-triazole (6′j). White solid, mp
1
131–133°C (Ref. [22], 130–132°C). H-NMR (400 MHz, CDCl3):
7-(3-(4-((2-Nitrophenoxy)methyl)-1,2,3-triazol-1-yl)propoxy)
coumarin (6b). Yellow solid, mp 135–137°C. IR (KBr) ν: 3154,
3078, 2917, 2839, 1724, 1617, 1345, 1277, 1124, 1044 cmÀ1. 1H-
NMR (400 MHz, CDCl3): δ = 7.83 (dd, J = 8.0, 1.2 Hz, 1H, 3′-H),
7.51 (s, 1H, 14-H), 7.64 (d, J = 9.2 Hz, 1H, 4-H), 7.57–7.53
(m, 1H, 5′-H), 7.38 (d, J = 8.8 Hz, 1H, 5-H), 7.29 (dd, J = 8.4,
0.8 Hz, 1H, 6′-H), 7.09–7.05 (m, 1H, 4′-H), 6.82 (dd, J = 8.8,
2.4 Hz, 1H, 6-H), 6.74 (d, J = 2.4 Hz, 1H, 8-H), 6.26
(d, J = 9.6 Hz, 1H, 3-H), 5.37 (s, 2H, 16-H), 4.63 (t, J = 6.8 Hz,
2H, 13-H), 4.03 (t, J = 5.6 Hz, 2H, 11-H), 2.50–2.44
(m, 2H, 12-H). 13C-NMR (100 MHz, CDCl3): δ = 161.5 (C-7),
161.1 (C-2), 155.8 (C-9), 151.4 (C-1′), 143.4 (C-15), 143.3
(C-4), 140.1 (C-2′), 134.3 (C-5′), 129.0 (C-5), 125.7 (C-3′),
123.5 (C-14), 121.1 (C-4′), 115.3 (C-6′), 113.4 (C-3), 112.9
(C-10), 112.7 (C-6), 101.5 (C-8), 64.6 (C-11), 63.8 (C-16), 47.1
(C-13), 29.6 (C-12). HRMS Calcd for C21H18N4NaO6
[M + Na]+: m/z 445.1124, Found 445.1139.
δ =7.82 (d, J= 7.2 Hz, 2H, 3, 5-H), 7.68 (s, 1H, 8-H), 7.43–7.38
(m, 5H, 2, 4, 6, 12, 14-H), 7.35–7.31 (m, 3H, 11, 13, 15-H), 5.60
(s, 2H, 9-H). 13C-NMR (100 MHz, CDCl3): δ = 148.1 (C-1), 134.8
(C-10), 130.6 (C-7), 129.1 (C-12, 14), 128.9 (C-2, 6), 128.7 (C-4),
128.2 (C-13), 128.0 (C-11, 15), 125.7 (C-3, 5), 119.8 (C-8), 54.1
(C-9). ESI-MS m/z: 236 [M + H]+.
1-Benzyl-4-(phenoxymethyl)-1H-1,2,3-triazole (6′k). Pale
yellow solid, mp 120–121°C (Ref. [24], 119–121°C). 1H-NMR
(400MHz, CDCl3): δ = 7.55 (s, 1H, 9-H), 7.41–7.38 (m, 3H 13,
14, 15-H), 7.32–7.27 (m, 4H, 3, 5, 12, 16-H), 6.98 (m, 3H, 2, 4,
6-H), 5.55 (s, 2H, 10-H), 5.20 (s, 2H, 7-H). 13C-NMR (100 MHz,
CDCl3): δ = 158.2 (C-1), 144.6 (C-8), 134.6 (C-11), 129.6 (C-3,
5), 129.2 (C-13, 15), 128.8 (C-14), 128.1 (C-12, 16), 122.8 (C-9),
121.3 (C-4), 114.8 (C-2, 6), 62.0 (C-7), 54.2 (C-10). ESI-MS m/z:
266 [M + H]+.
1-Benzyl-4-((4-methoxyphenoxy)methyl)-1H-1,2,3-triazole
1
(6′l). Pale yellow solid, mp 86–88°C (Ref. [28], 86–88°C). H-
7-(3-(4-((4-Nitrophenoxy)methyl)-1,2,3-triazol-1-yl)propoxy)
NMR (400 MHz, CDCl3): δ = 7.52 (s, 1H, 9-H), 7.40–7.37
(m, 3H, 13, 14, 15-H), 7.29–7.26 (m, 2H, 12, 16-H), 6.92–6.89
(m, 2H, 2, 6-H), 6.85–6.82 (m, 2H, 3, 5-H), 5.54 (s, 2H, 10-H),
5.15 (s, 2H, 7-H), 3.77 (s, 3H, ―OCH3). 13C-NMR (100 MHz,
CDCl3): δ =154.2 (C-4), 152.3 (C-1), 144.7 (C-8), 134.6 (C-11),
129.1 (C-13, 15), 128.7 (C-14), 128.1 (C-12, 16), 122.8 (C-9),
115.9 (C-2, 6), 114.6 (C-3, 5), 62.7 (C-7), 55.6 (―OCH3), 54.1
(C-10). ESI-MS m/z: 296 [M + H]+.
coumarin (6c).
Yellow solid, mp 150–152°C. IR (KBr) ν:
3150, 3074, 2939, 2884, 1707, 1610, 1338, 1254, 1125,
1
1048 cmÀ1. H-NMR (400 MHz, CDCl3): δ = 8.20–8.17 (m, 2H,
3′, 5′-H), 7.70 (s, 1H, 14-H), 7.64 (d, J = 9.6 Hz, 1H, 4-H), 7.38
(d, J = 8.4 Hz, 1H, 5-H), 7.10–7.04 (m, 2H, 2′, 6′-H), 6.80
(dd, J = 8.4, 2.4 Hz, 1H, 6-H), 6.76 (d, J = 2.4 Hz, 1H, 8-H),
6.27 (d, J = 9.2 Hz, 1H, 3-H), 5.31 (s, 2H, 16-H), 4.65
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2016
Highly efficient ultrasonic-assisted CuCl-catalyzed 1,3-dipolar cycloaddition reactions in water
1
1713, 1616, 1400, 1284, 1237, 1160, 1127, 1052 cmÀ1. H-NMR
(t, J= 6.8 Hz, 2H, 13-H), 4.05 (t, J= 5.6 Hz, 2H, 11-H), 2.51–2.45
(m, 2H, 12-H). 13C-NMR (100 MHz, CDCl3): δ = 163.1 (C-1′),
161.4 (C-7), 161.0 (C-2), 155.8 (C-9), 143.3 (C-4), 142.9 (C-15),
141.9 (C-4′), 129.0 (C-5), 125.9 (C-3′, 5′), 123.5 (C-14), 114.8
(C-2′, 6′), 113.5 (C-3), 113.0 (C-10), 112.4 (C-6), 101.6 (C-8),
64.7 (C-11), 62.4 (C-16), 47.2 (C-13), 29.6 (C-12). HRMS
Calcd for C21H18N4NaO6 [M + Na]+: m/z 445.1124, Found
445.1139.
(400 MHz, CDCl3): δ =7.63 (d, J= 9.6 Hz, 1H, 4-H), 7.59 (s, 1H,
14-H), 7.37 (d, J= 8.8 Hz, 1H, 5-H), 7.16–7.12 (m, 2H, 3′, 5′-H),
6.93 (d, J = 8.0 Hz, 1H, 6′-H), 6.86 (t, J = 7.2 Hz, 2H, 4′-H), 6.27
(d, J = 9.6 Hz, 1H, 3-H), 5.22 (s, 2H, 16-H), 4.62 (t, J = 6.8 Hz,
2H, 13-H), 4.03 (t, J = 5.8 Hz, 2H, 11-H), 2.50–2.43 (m, 2H, 12-
H), 2.18 (s, 3H, CH3). 13C-NMR (100MHz, CDCl3): δ = 161.5
(C-7), 161.0 (C-2), 156.3 (C-1′), 155.8 (C-9), 144.9 (C-15),
143.3 (C-4), 130.8 (C-3′), 128.9 (C-5), 126.9 (C-2′), 126.9
(C-5′), 122.8 (C-14), 121.0 (C-4′), 115.6 (C-2′), 113.5 (C-3),
112.9 (C-10), 112.5 (C-6), 111.5 (C-6′), 101.6 (C-8), 64.7
(C-11), 62.3 (C-16), 47.0 (C-13), 29.6 (C-12), 16.2 (CH3).
HRMS Calcd for C22H21N3NaO4 [M + Na]+: m/z 414.1430,
Found 414.1446.
7-(3-(4-((2-Methoxyphenoxy)methyl)-1,2,3-triazol-1-yl)
propoxy)coumarin (6d). White solid, mp 113–115°C. IR (KBr)
ν: 3129, 3083, 2988, 2951, 2834, 1727, 1626, 1404, 1298,
1251, 1135, 1047 cmÀ1 1H-NMR (400 MHz, CDCl3): δ = 7.65
.
(s, 1H, 14-H), 7.64 (d, J = 9.6 Hz, 1H, 4-H), 7.37 (d, J = 8.4Hz,
1H, 5-H), 7.03 (dd, J = 8.0, 1.6 Hz, 1H, 6′-H), 6.97–6.93
(m, 1H, 4′-H), 6.90–6.85 (m, 2H, 3′, 5′-H), 6.80 (dd, J = 8.4,
2.4 Hz, 1H, 6-H), 6.77 (d, J = 2.4Hz, 1H, 8-H), 6.27
(d, J= 9.6 Hz, 1H, 3-H), 5.30 (s, 2H, 16-H), 4.59 (t, J=7.0Hz, 2H,
13-H), 4.03 (t, J = 5.8 Hz, 2H, 11-H), 3.85 (s, 3H, ―OCH3),
2.48–2.41 (m, 2H, 12-H). 13C-NMR (100 MHz, CDCl3):
δ = 161.5 (C-7), 161.0 (C-2), 155.8 (C-9), 149.5 (C-2′), 147.5
(C-1′), 144.6 (C-15), 143.3 (C-4), 128.9 (C-5), 123.2 (C-14),
121.9 (C-4′), 120.9 (C-5′), 114.2 (C-6′), 113.5 (C-3), 112.9
(C-10), 112.5 (C-6), 111.8 (C-3′), 101.6 (C-8), 64.7 (C-11),
63.2 (C-16), 55.9 (―OCH3), 47.0 (C-13), 29.6 (C-12). HRMS
Calcd for C22H21N3NaO5 [M + Na]+: m/z 430.1379, Found
430.1397.
7-(3-(4-(m-Tolyloxymethyl)-1,2,3-triazol-1-yl)propoxy coumarin
(6h). Pale yellow solid, mp 102–104°C. IR (KBr) ν: 3146, 3088, 2942,
2913, 2868, 1723, 1614, 1395, 1282, 1263, 1170, 1122, 1050 cmÀ1
.
1H-NMR (400 MHz, CDCl3): δ =7.63 (d, J= 9.6 Hz, 1H, 4-H), 7.63
(s, 1H, 14-H), 7.37 (d, J= 8.4 Hz, 1H, 5-H), 7.16 (t, J= 7.8 Hz, 1H,
5′-H), 6.82–6.76 (m, 5H, 6, 8, 2′, 4′, 6′-H), 6.25 (d, J= 9.6 Hz, 1H,
3-H), 5.19 (s, 2H, 16-H), 4.61 (t, J= 6.8 Hz, 2H, 13-H), 4.03
(t, J= 5.8 Hz, 2H, 11-H), 2.49–2.42 (m, 2H, 12-H), 2.31 (s, 3H,
CH3). 13C-NMR (100 MHz, CDCl3): δ =161.5 (C-7), 161.0 (C-2),
158.2 (C-1′), 155.8 (C-9), 144.5 (C-15), 143.3 (C-4), 139.6
(C-3′), 129.3 (C-5′), 128.9 (C-5), 123.0 (C-14), 122.1 (C-4′),
115.6 (C-2′), 113.4 (C-3), 112.9 (C-10), 112.5 (C-6), 111.5 (C-6′),
101.6 (C-8), 64.7 (C-11), 61.9 (C-16), 47.0 (C-13), 29.7 (C-12), 21.5
(CH3). HRMS Calcd for C22H21N3NaO4 [M + Na]+: m/z 414.1430,
7-(3-(4-((2-Ethyoxyphenoxy)methyl)-1,2,3-triazol-1-yl)propoxy)
coumarin (6e). White solid, mp 93–95°C. IR (KBr) ν: 3142, 3083,
2978, 2935, 2872, 1733, 1614, 1394, 1328, 1283, 1123, 1046,
1
1030 cmÀ1. H-NMR (400 MHz, CDCl3): δ = 7.67 (s, 1H, 14-H),
Found 414.1443.
7-(3-(4-((4-Chlorophenoxy)methyl)-1,2,3-triazol-1-yl)propoxy)
coumarin (6i). Pale yellow solid, mp 147–149°C. IR (KBr) ν:
7.63 (d, J= 9.6 Hz, 1H, 4-H), 7.36 (d, J= 8.8Hz, 1H, 5-H), 7.00
(dd, J= 8.0, 1.6 Hz, 1H, 6′-H), 6.94–6.82 (m, 3H, 3′, 4′, 5′-H),
6.79 (dd, J= 8.8, 2.4 Hz, 1H, 6-H), 6.74 (d, J= 2.4Hz, 1H, 8-H),
6.24 (d, J= 9.6 Hz, 1H, 3-H), 5.27 (s, 2H, 16-H), 4.59
(t, J= 6.8 Hz, 2H, 13-H), 4.09–4.03 (m, 2H, ―OCH2CH3), 4.01
(t, J= 5.8 Hz, 2H, 11-H), 2.46–2.39 (m, 2H, 12-H), 1.40
(t, J= 7.0 Hz, 3H, ―OCH2CH3). 13C-NMR (100 MHz, CDCl3):
δ =161.5 (C-7), 161.0 (C-2), 155.7 (C-9), 149.1 (C-2′), 147.9 (C-1′),
144.7 (C-15), 143.4 (C-4), 128.9 (C-5), 123.2 (C-14), 122.1 (C-4′),
120.9 (C-5′), 115.3 (C-6′), 113.6 (C-3′), 113.3 (C-3), 112.9
(C-10), 112.5 (C-6), 101.5 (C-8), 64.7 (C-11), 64.4
(―OCH2CH3), 63.5 (C-16), 47.0 (C-13), 29.6 (C-12), 14.9
(―OCH2CH3). HRMS Calcd for C23H23N3NaO5 [M + Na]+: m/z
444.1535, Found 444.1550.
3142, 3067, 2930, 2876, 1725, 1614, 1282, 1244, 1127, 1097,
1
1026 cmÀ1. H-NMR (400MHz, CDCl3): δ = 7.64 (d, J = 9.6 Hz,
1H, 4-H), 7.62 (s, 1H, 14-H), 7.38 (d, J = 9.6 Hz, 1H, 5-H), 7.22
(m, 2H, 3′, 5′-H), 6.90 (m, 2H, 2′, 6′-H), 6.81–6.77 (m, 2H, 6, 8-
H), 6.27 (d, J = 9.6 Hz, 1H, 3-H), 5.18 (s, 2H, 16-H), 4.62 (t,
J = 6.8 Hz, 2H, 13-H), 4.04 (t, J = 5.6 Hz, 2H, 11-H), 2.49–2.43
(m, 2H, 12-H). 13C-NMR (100 MHz, CDCl3): δ = 161.4 (C-7),
161.0 (C-2), 156.7 (C-1′), 155.8 (C-9), 144.0 (C-15), 143.2
(C-4), 129.4 (C-3′, 5′), 128.9 (C-5), 126.2 (C-4′), 123.1 (C-14),
116.1 (C- 2′, 6′), 113.5 (C-3), 113.0 (C-10), 112.4 (C-6), 101.6
(C-8), 64.9 (C-11), 62.2 (C-16), 47.1 (C-13), 29.6 (C-12). HRMS
Calcd for C21H18ClN3NaO4 [M+ Na]+: m/z 434.0884, Found
7-(3-(4-((4-Methoxyphenoxy)methyl)-1,2,3-triazol-1-yl)propoxy)
coumarin (6f). Pale yellow solid, mp 138–140°C. IR (KBr) ν: 3141,
3087, 2996, 2958, 2922, 2888, 1729, 1629, 1386, 1300, 1234, 1140,
1106, 1033 cmÀ1. 1H-NMR (400 MHz, CDCl3): δ =7.66 (s, 1H, 14-
H), 7.59 (d, J= 9.6 Hz, 1H, 4-H), 7.32 (d, J= 8.8 Hz, 1H, 5-H), 7.13
(t, J= 7.8 Hz, 1H, 5′-H), 6.76 (dd, J=5.6, 2.4Hz, 1H, 6-H), 6.70
(d, J= 2.4 Hz, 1H, 8-H), 6.54–6.47 (m, 3H, 2′, 4′, 6′-H), 6.19
(d, J= 9.2 Hz, 1H, 3-H), 5.13 (s, 2H, 16-H), 4.57 (t, J=6.8Hz, 2H,
13-H), 3.99 (t, J= 5.8 Hz, 2H, 11-H), 3.72 (s, 3H, OCH3), 2.44–
2.38 (m, 2H, 12-H). 13C-NMR (100 MHz, CDCl3): δ =161.5 (C-7),
161.0 (C-2), 160.8 (C-3′), 155.7 (C-1′), 155.7 (C-9), 144.1 (C-15),
143.4 (C-4), 129.8 (C-5′), 129.0 (C-5), 123.3 (C-14), 113.2 (C-3),
112.8 (C-10), 112.5 (C-6), 106.8 (C-6′), 106.7 (C-4′), 101.5 (C-8),
101.3 (C-2′), 64.8 (C-11), 61.9 (C-16), 55.3 (―OCH3), 47.0 (C-
13), 29.6 (C-12). HRMS Calcd for C22H21N3NaO5 [M + Na]+: m/z
430.1379, Found 430.1391.
434.0883.
7-(3-(4-((2,4-Dichlorophenoxy)methyl)-1,2,3-triazol-1-yl)propoxy)
coumarin (6j). White solid, mp 124–126°C. IR (KBr) ν: 3100, 3075,
2938, 2876, 1739, 1614, 1285, 1230, 1124, 1050, 1032 cmÀ1. H-
1
NMR (400 MHz, CDCl3): δ =7.67 (s, 1H, 14-H), 7.65 (d, J=9.6Hz,
1H, 4-H), 7.38 (d, J= 8.8 Hz, 1H, 5-H), 7.34 (d, J= 2.4 Hz, 1H, 3′-
H), 7.17 (dd, J= 8.8, 2.4 Hz, 1H, 5′-H), 7.04 (d, J= 8.8 Hz, 1H, 6′-
H), 6.80 (dd, J= 8.4, 2.4 Hz, 1H, 6-H), 6.77 (d, J= 2.0 Hz, 1H, 8-H),
6.27 (d, J= 9.6 Hz, 1H, 3-H), 5.27 (s, 2H, 16-H), 4.63 (t, J=6.6Hz,
2H, 13-H), 4.03 (t, J = 5.6 Hz, 2H, 11-H), 2.50–2.44 (m, 2H,
12-H). 13C-NMR (100 MHz, CDCl3): δ = 161.4 (C-7), 161.0
(C-2), 155.8 (C-9), 152.5 (C-1′), 143.7 (C-15), 143.3 (C-4),
130.1 (C-3′), 128.9 (C-5), 127.7 (C-5′), 126.5 (C-4′), 123.9
(C-2′), 123.3 (C-14), 115.0 (C-6′), 113.5 (C-3), 113.0 (C-10),
112.5 (C-6), 101.6 (C-8), 64.6 (C-11), 63.5 (C-16), 47.1
(C-13), 29.6 (C-12). HRMS Calcd for C21H17Cl2N3NaO4
[M + Na]+: m/z 468.0494, Found 468.0496.
7-(3-(4-(o-Tolyloxymethyl)-1,2,3-triazol-1-yl)propoxy)coumarin
(6g). Pink solid, mp 95–97°C. IR (KBr) ν: 3140, 3065, 2926, 2855,
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

X. Li, X. Chen, Y. Jiang, S. Chen, L. Qu, Z. Qu, J. Yuan and H. Shi
Vol 000
Acknowledgments. The authors would like to thank the National
Natural Science Foundation of China (no. 21072178), the
Innovation Specialist Projects of Henan Province (no.
114200510023), and the Innovation Scientists and Technicians
Troop Construction Projects of Zhengzhou City (no.
112PLJRC359) for their financial support.
Commun 2008, 741; (e) Wang, F.; Fu, H.; Jiang, Y.-Y.; Zhao, Y.-F.
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