Water as a solvent for Ru-catalyzed click reaction: Highly efficient recyclable catalytic system for triazolocoumarins synthesis

Article abstract of DOI:10.1002/aoc.5156

A new family of Ru (III) complexes has been synthesized, characterized and their catalytic performance has been tested for alkyne–azide cycloaddition (AAC) in water under ultrasonic irradiation conditions. These complexes are found to be effective heterog

Full text of DOI:10.1002/aoc.5156

Received: 23 April 2019
DOI: 10.1002/aoc.5156
Revised: 30 June 2019
Accepted: 14 July 2019
F U L L P A P E R
Water as a solvent for Ru‐catalyzed click reaction: Highly
efficient recyclable catalytic system for triazolocoumarins
synthesis
1,2
1,3
Wael Abdelgayed Ahmed Arafa
| Abd El‐Aziz Ahmed Nayl
1
Chemistry Department, College of
A new family of Ru (III) complexes has been synthesized, characterized and
Science, Jouf University, P.O. Box 2014,
Sakaka, Aljouf, Kingdom of Saudi Arabia
their catalytic performance has been tested for alkyne–azide cycloaddition
2
Chemistry Department, Faculty of
(AAC) in water under ultrasonic irradiation conditions. These complexes are
Science, Fayoum University, P.O. Box
found to be effective heterogeneous catalysts for the regioselective synthesis
of 1,4‐disubstituted‐1,2,3‐triazoles giving access to these products in excellent
yields. The catalyst system is equally active for one‐pot multi‐component pro-
tocol of the AAC reactions. Also, successive sequencing of Huisgen reaction
with Knoevenagel condensation reaction results in the effective assembly of a
diversified hitherto unreported 1,2,3‐triazolyl coumarin frameworks. In present
strategy, the catalyst could be easily isolated by simple filtration and reused up
to eight consecutive cycles without significant drop in the reaction yields. Dur-
ing the leaching experiment, there is no leaching amount of the catalyst was
detected, suggesting true heterogeneity in the catalytic system. The results of
gram‐scale reaction and green metrics calculations also confirmed the sustain-
ability and industrial applicability of the current catalytic protocol.
6
3
3514, Fayoum City, Egypt
Hot Laboratories Center, Atomic Energy
Authority of Egypt, P.O. 13759, Inshas,
Cairo, Egypt
Correspondence
Wael Abdelgayed Ahmed Arafa,
Chemistry Department, Faculty of
Science, Fayoum University, P.O. Box
63514, Fayoum City, Egypt.
Email: waa00@fayoum.edu.eg
Funding information
Jouf University, Grant/Award Number:
634/39; Jouf University
KEYWORDS
click chemistry, heterogeneous catalyst, regioselectively, Ru‐diamide complexes, triazolocoumarins
[
5]
1
| INTRODUCTION
al
−
independently reported Cu(I)‐catalyzed alkyne
azide click reaction (Cu‐AAC) under moderate condi-
N‐Substituted 1,2,3‐triazoles are important nitrogen het-
tions, to afford regiospecifically 1,4‐disubstituted‐1,2,3‐
triazole derivatives. After that time, the utilization of
Cu(I) salts as homogeneous catalysts to promote such click
erocycles, exhibiting enormous spectrum of biological
[
1]
activities and are broadly utilized as pharmaceuticals.
[6]
Therefore, these compounds have received widespread
interest not only from industrial application but also from
reaction became one of the most generally protocols.
They were effective catalysts but restricted in terms of
recycling and cannot be commercialized specifically for
biological applications, due to the toxicity of Cu com-
[2]
academic research.
Nevertheless, the conventional
Huisgen 1,3‐dipolar cycloaddition methodology for their
preparation needs harsh reaction conditions and a mix-
ture of regioisomers is commonly obtained especially
[
7]
pounds. Moreover, the utilization of copper salts is lim-
ited as they frequently lead to the production of
diacetylene and bis‐triazoles as by products in alkyne‐
[
3]
when asymmetrically substituted alkynes are used.
[
8]
Consequently, numerous procedures have been devel-
azide reactions. In order to minimize the aforemen-
tioned disadvantages, the copper salts were immobilized
as heterogeneous catalysts in Cu‐AAC reactions via
oped for the assembly of a variety of N‐substituted 1,2,3‐
[4]
triazoles. A decade ago, Sharpless et. al and Meldal et.
Appl Organometal Chem. 2019;e5156.
wileyonlinelibrary.com/journal/aoc
© 2019 John Wiley & Sons, Ltd.
1 of 12
https://doi.org/10.1002/aoc.5156

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ARAFA AND NAYL
[
9]
[10]
[11]
graphene oxide,
nanoparticles,
zeolites,
char-
improve mixing, accelerate the reaction rate, afford
higher yields and effectively enhance the reaction condi-
tions that are inaccessible by traditional methodologies.
In continuation of our ongoing work to develop green
[12]
[13]
[14]
coal, silica, and polymers. In spite of these hetero-
geneous catalysts display many merits, some of them
suffer from metal leaching after a number of runs and a
series of tedious, laborious, and time consuming steps
and efficient practical protocols under ultrasound irradia-
[15]
[25]
are required during their synthesis.
tion,
herein we report the preparation of new family of
In the last decade, diversified alkyne–azide cycloaddi-
Ru‐complexes for use in the regioselectivity assembly of
tion reactions utilizing metals other than copper have
1,4‐disubstituted‐1,2,3‐triazoles in H O under ultrasonic
2
[16]
[17]
been reported,
displayed a remarkable scope.
out of them, ruthenium (Ru‐AAC)
irradiation. Also, these catalytic systems mediated three‐
component Ru‐AAC reactions comprising sodium azide,
alkyl halides and alkynes. Moreover, the scope of the
reaction was tested with new azide and alkyne precur-
sors, such as coumarins and bipyridines.
[18]
In contrast to Cu‐AAC
reactions, which are restricted to terminal alkynes, the
Ru‐AAC reactions were found to tolerate both terminal
[19]
and internal alkynes.
In the original report by Jia
and co‐workers, it was found that using Ru‐complexes
that lacking a cyclopentadienyl ligand such as RuHCl
(
CO)(PPh3)3 RuCl (PPh ) , and Ru (OAc) (PPh ) ,
2 | RESULTS AND DISCUSSION
2
3 3
2
20]
3 2
[
furnished the 1,4‐disubstituted 1,2,3‐triazoles.
While,
Ru‐complex comprising the cyclopentadienyl ligand,
Our investigation commenced with the sonosynthesis
of diamide ligands (3a–g) through the condensation of
o‐phenylene diamines (1a–d) and picolinic acids (2a–c)
in the presence of triphenyl phosphite as the coupling
CpRuCl (PPh ) , resulted in 50% conversion of the
3
2
reactants to a mixture of 1,4‐ and 1,5‐disubstituted 1,2,3‐
triazoles. Interestingly, a simple switch to the more steri-
cally hindered pentamethyl analogue, Cp*RuCl (PPh ) ,
[26]
reagent according to our reported protocol (Scheme 1).
3
2
led up to the formation of 1,5‐regioisomer with complete
Ru‐catalysts (4a–g) were synthesized via the reaction of
diamide ligands (3a–g) and [Ru (DMSO) ]Cl under son-
[18]
conversion.
Liu and colleagues reported that the Ru‐
4
2
AAC could be carried out in H O, with a lower catalyst
ication at 70 °C followed by the addition of 4‐picoline and
sonication for another 5 h (Scheme 1). The magnetic
moment values of the synthesized Ru‐complexes at room
temperature were measured and found to be: 1.73 for 4a,
1.79 for 4b, 1.75 for 4c, 1.84 for 4d, 1.88 for 4e, 1.74 for 4f
and 1.86 B.M. for 4 g. These values indicate that the
obtained complexes are one electron paramagnetic which
2
[21]
loading than when utilizing organic solvents.
Also,
an appropriate one‐pot protocol for directly synthesizing
the 1,4‐regioisomer thorough generation of the azide
[
22]
from the corresponding alkyl bromide was reported.
Even though Ru‐AAC reactions achieved acceptable
yields, the offered procedures, in most cases, suffer from
several drawbacks such as long reaction time, limited
scopes, thermal activation, needs an inert atmosphere
[
27]
corresponding to the +3 state of ruthenium.
The struc-
ture of the newly obtained ligands as well as their Ru‐
complexes was elucidated by several tools, for example
UV–vis, NMR, FT‐IR, HRMS and elemental analyses. At
[23]
and Schlenk techniques.
Therefore, the search for
novel competent protocols providing mild conditions,
high yield, waste avoidance, recyclability and address
some of the aforesaid restrictions is still highly desirable
from the environmental standpoint.
1
first, the H NMR spectra of the as‐synthesized complexes
3
+
4a–g showed broad signals of the paramagnetic Ru .
Additionally, when excess amount of reducing agents
such as ascorbic acid was added to the complex solution
in deuterated chloroform, we could successfully record
the spectra of the complexes with distinct signals which
prove the conversion of ruthenium from the paramag-
Notwithstanding merits of heterogeneous protocols for
the preparation of organic compounds, the catalyst load-
ing, reaction time and yield are concerns which can be
significantly improved by utilizing a new sustainable
[24]
III
II
energy source such as ultrasonic irradiation.
During
netic high oxidation state (Ru ) to the diamagnetic Ru .
1
13
ultrasound‐assisted reactions, an acoustic cavitation phe-
Upon reduction, H and C NMR confirmed the sug-
gested structures of complexes (See Supporting Informa-
tion). Moreover, the elemental analyses confirmed the
presence of Cl which will mostly exist as a counter ion
in the complex structure, which also agrees with the pres-
[
24a,b]
nomenon takes place in the irradiated solution.
The ultrasound waves have two cycles: rarefaction and
compression, during the rarefaction cycle a vacuum pres-
sure generates cavitation bubbles, when the compression
cycle takes place these bubbles will collapse immediately
and release the stored energy within a short time forming
liquid jet sprays with high velocities and localized
hotspots with high temperatures (>5000 K) and pressures
III
ence of Ru . Moreover, HRMS measurements of the
complexes 4a–g in positive mode resulted in a peak with
a characteristic isotope pattern which could be assigned
+
to [LRu (pic) ] (See Supporting Information). The UV–
2
[24c]
III
(>1000 atm).
Therefore, applying such technique can
vis absorption spectra of Ru
complexes (4a–g) in

ARAFA AND NAYL
3 of 12
SCHEME 1 Sonosynthesis of diamide
ligands 3a–g and Ru‐complexes 4a–g
CH CN at neutral pH displayed three bands, at about
resulted in diminishing the reaction yields to 94% and
notable amount of starting substances remain unchanged
(Table 1, entry 4). Upon studying the role of solvents
other than water viz. ethanol (EtOH), dioxane, dichloro-
methane (DCM) and acetonitrile (Table 1, entries 5–8),
we observed that water was found superior than the other
solvents, afforded the desired product (7a) in excellent
yield (Table 1, entry 2). On performing the model reac-
tion (Scheme 2) under solvent‐free condition, a very poor
yield was observed (Table 1, entry 9). Moreover, moderate
yields were obtained using other ecofriendly solvents e.g.
Glycerol (Gly):Choline chloride (ChCl) 1:1 or ionic liq-
3
2
50, 330 and 420 nm (See Supporting Information). The
first intense band was ascribed to π–π* transitions within
the ancillary ligands while the latter two broad absorp-
tion bands were assigned to metal‐to‐ligand charge trans-
III
[28]
fer (MLCT) transitions as expected for a Ru complex.
After successful synthesis of Ru–complexes, their cata-
lytic efficiency towards the regioselectivity assemble of
1
,4‐disubstituted‐1,2,3‐triazole derivatives was investi-
gated. The reaction between benzyl azide (5a, 1 mmol)
and phenyl acetylene (6a, 1.1 mmol) was selected as a
model reaction (Scheme 2). On sonicating the model
reactants (5a and 6a) in water (3 ml) under catalyst‐free
conditions at ambient temperature (23 °C), the formation
of the desired product (7a) was not observed even after
sonicating the reaction mixture for a long time (Table 1,
entry 1).
Whilst, on performing the model reaction using cata-
lytic amount of Ru‐catalyst (4b, 0.1 mol%) under the
same conditions, the required product (7a) was obtained
in quantitative yield (99%) within a short reaction time
uids e.g. [BMIM][BF ] as a reaction medium (Table 1,
4
entries 10 and 11). Anticipating further improvement of
the reaction rate, the model reaction was studied at differ-
ent operating temperatures i.e. 23 (rt), 50 and 95 °C. At
low temperature, although the rate of bubbles formation
is low, they collapse with high intensity. This high cavita-
tion intensity makes the diffusion phenomenon is pre-
dominant and thus more mass transport of the
substrates on the catalytic sites, viz high reaction rate
[
29a]
(7 min, Table 1, entry 2). Next, we investigated the opti-
and yield.
While, at high temperatures it was
mum loading of Ru‐catalyst (4b) needed to the current
Huisgen reaction (Scheme 2). It was observed that
observed that the reaction yield was slightly decreased
(Table 1, entries 12–14). This result can be explained in
the fact that an increase in reaction temperature can
enhance the vapor pressure of the water inside cavitation
bubbles and therefore strengthen them, at the same time;
a large number of cavitation bubbles are produced. These
bubbles will act as a barrier to the transmission of ultra-
sound waves and thus slightly inhibit the effective ultra-
sound energy from the source entering the reaction
0
.1 mol% of Ru‐catalyst afforded quantitative yield (99%)
of the required product (7a) in 7 min (Table 1, entry 2).
Moreover, an increasing in the molar ratio of 4b up to
0
3
.3 mol% did not enhance the reaction rate (Table 1, entry
). While, lowering the molar ratio of 4b to 0.07 mol%
[
29]
medium.
Finally, on order to investigate the role of
ultrasonic irradiation, the model reaction (Scheme 2)
was performed under magnetic stirring condition at
70 °C (Table 1, entry 15). It was observed that both reac-
tion yield and rate have diminished confirming the
SCHEME 2 Sonosynthesis 1‐benzyl‐4‐phenyl‐1H‐1,2,3‐triazole
7
a

4
of 12
ARAFA AND NAYL
TABLE 1 Study of the 1,3‐dipolar cycloaddition of benzyl azide and phenyl acetylene catalyzed by the 4b complex in various reaction
a
conditions
Entry
Catalyst
Catalyst mol%
Solvent
Time (min)
Temperature (°C)
Yield(%)
1
2
3
4
5
6
7
8
9
–
–
H
H
H
H
2
2
2
2
O
O
O
O
24 h
7
23
23
23
23
23
23
23
23
23
23
23
50
90
90
70
0
99
99
94
87
86
77
78
25
80
78
97
97
94
4b
4b
4b
4b
4b
4b
4b
4b
4b
4b
4b
4b
4b
4b
0.1
0.3
0.07
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0.1
7
15
15
15
15
15
30
15
15
7
EtOH
Dioxane
DCM
3
CH CN
–
10
11
12
13
14
15
Gly/ChCl
4
[BMIM][BF ]
H
2
H
2
H
2
H
2
O
O
O
O
7
5
b
30
68
a
5a (1.0 mmol), 6a (1.1 mmol), and catalyst (4b) in solvent under ultrasonic irradiation (40 kHz).
b
Stirring without sonication.
important role of ultrasonic irradiation on accelerating
TABLE 2 Study of the 1,3‐dipolar cycloaddition of benzyl azide
a
(5a) and phenyl acetylene (6a) catalyzed by Ru‐complexes 4a–g
the reaction and improving the results. Possibility seems
that cavitation formed in ultrasound system leads to:
removal of mass transfer resistance, help in uniform
mixing and provide special physical (powerful stirring)
and chemical (highly reactive species) conditions for the
reaction to occur efficiently. Together, these factors pro-
vide a synergetic impact that improves both reaction rate
Entry
Catalyst
mol%
Yield(%)
1
2
3
4
5
6
7
8
9
4a
4a
4b
4b
4c
4c
4d
4d
4e
4e
4f
0.1
99
92
99
93
98
89
92
82
98
85
98
88
98
87
0.07
0.1
0.07
0.1
[29]
and yield.
Thence, it is logically to conclude that the
use of ultrasonic technique leads to a significant reduc-
tion in energy consumption compared with the silent
reactions.
The promising results obtained from the aforemen-
tioned model reaction (Scheme 2) encouraged us to
investigate the catalytic activities of the other synthesized
Ru‐complexes (Table 2). Interestingly, all the tested Ru‐
complexes (4a–g) were capable of selectively catalyzing
the model reaction under the optimized conditions (using
0.07
0.1
0.07
0.1
1
1
1
0
1
2
0.07
0.1
4f
0.07
0.1
0
.1 mol% of the catalysts) and furnishing the desired
13
4 g
4 g
product (7a) in excellent yields (92–99%). These catalytic
behaviors were slightly changed on performing the reac-
tion at lower catalytic loading (0.07 mol%). It was found
that, catalysts comprised methoxy group (4a, Table 2,
entry 2) or both chloro and nitro groups (4b, Table 2,
entry 4) have similar catalytic behaviors; affording the
desired product (7a) in excellent yields. Moreover, the
reaction yield was slightly decreased on using catalyst
14
0.07
a
5a (1.0 mmol), 6a (1.1 mmol), and a catalyst in water (3.0 ml) at rt under
ultrasonic irradiation for 7 min.
on conducting the reaction using one of the catalysts
comprising trifluoro moiety (4d–g, 0.07 mol%), the reac-
tion yields were further diminished in comparison with
the obtained yields using 0.1 mol% of the catalyst (Table 2,
4
c that comprised chloro atoms (Table 2, entry 6). While

ARAFA AND NAYL
5 of 12
a
TABLE 3 Scope of cycloaddition reaction of various alkynes and organic azides
Entry
Azides
Alkynes
Triazoles
Time (min)
Yield(%)
Podducts
[
30b]
1
7
99
7a
[
31]
2
7
99
7b
[
32]
3
4
5
9
7
7
98
99
99
7c
[
30b]
7d
[
30b]
7e
[
30b]
6
7
7
6
99
99
7f
[
33]
7 g
[
34]
8
9
9
7
7
96
99
99
7 h
[
30a]
7i
[
30a]
1
1
0
1
7j
[
35]
6
99
7 k
(Continues)

6
of 12
ARAFA AND NAYL
TABLE 3 (Continued)
Entry
Azides
Alkynes
Triazoles
Time (min)
Yield(%)
Podducts
[
32]
1
2
6
99
7 l
[
36]
1
1
3
4
4
5
99
99
7 m
[
36]
7n
[
37]
1
1
5
6
5
5
99
99
7o
7p
[
30b]
a
Azides (1.0 mmol), alkynes (1.1 mmol), and catalyst (4b, 0.1 mol%) in water (3.0 ml) at rt under ultrasonic irradiation.
entries 8, 10, 12 and 14). Therefore, we can conclude that
the electronic nature of the catalysts had notable impact
on the reaction efficiency.
of Ru‐complex (4b, 0.2 mol%) under ultrasonic irradiation
in water (Table 4). From the tabulated results, it demon-
strated that the reaction worked smoothly and efficiently
and the corresponding products (7a–h and 7q–u) were
obtained in excellent yields but taking longer time in
comparison with the sequential reaction (Scheme 2). In
all the aforementioned examples (Table 4), the reactions
afforded the desired products in almost quantitative
yields (95–99%) without the detection of the correspond-
ing benzyl alcohols (TLC, GC–MS). This might be attrib-
uted to the fact that such reaction required strong bases
Having established an effective and regioselective pro-
tocol for the Huisgen reaction, we then set out to assess
the generality and scope of the reaction by performing a
diversified range of organic azides and functionalized
alkynes (Table 3, entries 1–16). It is worth mentioning
that the aqueous click reactions were performed well
with both electron withdrawing groups and electron
donating groups affording excellent yields of the required
products (7a–p). In all reactions, the above‐mentioned
[
41a]
or photocatalysts
and benzyl halides are attacked by
methodology
afforded
solely
1,4‐disubstituted
the azide nucleophile (good nucleophile) more faster than
their attack by water (weak nucleophile).
[
10,21,22a,30a,41]
regioisomer while the other 1,5‐disubstituted regioisomer
was not detected. More recent reports supported our
In a quest to confirm effectiveness, merits and general-
ity of the present methodology, a comparison with other
reported methods for the assembly of derivative 7a using
Ru‐complex (4b), was established (Table 5). As displayed
in Table 5, Ru‐complex (4b) was the most effective cata-
lyst; afforded the desired product (7a) with higher yield
in shorter reaction time (highest yield economy). Thus,
the current protocol that catalyzed by the as‐synthesized
Ru‐complexes in water under ultrasonic irradiation can
be considered as eco‐friendly and more effective.
[30]
results.
The structure of all the synthesized cycloaddi-
tion derivatives (7a–p) was established on the basis of
spectral analyses (NMR and HRMS).
Generally, organic azides with high molar mass are
stable and safe to handle especially on exposing to oxygen
[
38]
and water,
mostly explosive.
mended to use the organic azides of low molar mass. In
while, azides with low molar mass are
[39]
Thus, for safety, it is not recom-
[21,30a,40]
this context, one pot three‐component reaction
was designed that comprised sodium azide, benzyl
halides (8a–e), alkynes (6a–f, 6i–k) and catalytic amount
Form industrial point of view, we performed a gram‐
scale preparation of 7a using one of our designed catalyst

ARAFA AND NAYL
7 of 12
a
TABLE 4 One‐pot three‐component preparation of 1,2,3‐triazoles utilizing 4b as a catalyst
Entry
R
R`
Triazoles
Time (min)
Yield(%)
1
2
3
4
5
6
7
8
9
H
Ph
Ph
Ph
7a
7b
7c
15
10
10
10
7
95
97
97
97
98
98
99
95
98
97
95
99
95
p‐Me
p‐NO
H
2
C
C
C
6
6
6
H
H
H
4
4
4
‐p‐Me
‐p‐OMe
‐p‐F
7d
7e
7f
H
H
10
8
H
Thiophen‐2‐yl
Pyridin‐2‐yl
7 g
7 h
7q
7r
H
10
8
H
C
C
C
6
6
6
H
H
H
4
4
4
‐p‐Br
‐m‐F
10
11
12
13
H
8
H
‐p‐CN
7 s
7 t
7u
10
7
m‐CF
m‐Br
3
Ph
Ph
7
a
8
3
(1.0 mmol), NaN (1.0 mmol), 6 (1.1 mmol), and 4b (0.2 mol%) in water (3.0 ml) at rt under ultrasonic irradiation.
TABLE 5 Comparison of reaction conditions, times, yields and yield economies for the synthesis of compound 7a under several protocols
Entry Catalyst
Conditions
Time (min) Yield(%) Yield economy(%) Ref.
[
[
[
[
[
[
[
[
[
36]
42]
43]
44]
45]
46]
47]
48]
21]
1
2
3
4
5
6
7
8
9
1
CuNPs‐HT
Cu@Fe
Ethylene glycol, rt
DCM, rt
60
97
92
91
83
95
93
98
99
89
99
1.61
0.126
9.10
3
O
4
on Chitosan
12 h
10
Cu NPs on charcoal
Cu‐Zeolite
H
2
O, 100 °C
Toluene, rt
15 h
24 h
12 h
0.092
0.066
0.129
0.204
1.10
CuO NAP,
H
H
H
2
2
2
O:THF, 60 °C
O, 70 °C
2
Cu/SiO composite
CuBr on graphene oxide/Fe
CuI
3
O
4
O, 80 °C, Microwave, one pot 8 h
Glycerol, rt
Bu NBr, H
O, rt, US
90
120
7
RuH
2
(CO)(PPh
3
)
3
4
2
O, 80 °C
0.741
14.14
0
Ru‐complex (4b)
H
2
This work
(
1
4b). Thus, sonication of benzyl azide (5a, 15 mmol,
.99 g), phenyl acetylene (6a, 15.5 mmol, 1.58 g) and Ru
catalyst (4b, 0.15 mol%) in 50 mL of H O (Scheme 2) for
standards, for instance Yield Economy (9.8), Carbon Effi-
ciency (100%), Atom Economy (100%) and Reaction Mass
Efficiency (96.64%) as well as small value of Process Mass
Intensity (1.034) and E‐factor (0.0186) emphasized that
the developed methodology is eco‐friendly green syn-
thetic procedure. Catalyst leaching is also one of the most
important problems facing the drugs manufacture that
based on the use of metal‐catalyzed organic reactions.
Therefore, 0.1 g of Ru‐catalyst (4b) was added to 5 ml of
water and the resulting solution was sonicated for 5 hrs
at ambient temperature. Then, the catalyst was filtered
2
8
min (TLC) at room temperature afforded the
regioisomer 7a in excellent yield (98%). Accordingly, the
present methodology can be considered as a selective pro-
tocol for the industrial assembly of 1,4‐disubstituted tri-
azole derivatives. Further, to assess the aforesaid
protocol (Scheme 2) in terms of waste, carbon efficiency
and use of energy, several green metrics have been inves-
[49]
tigated.
The high value of environmental compatibility

8
of 12
ARAFA AND NAYL
off and the obtained filtrate (water) was reused as a reac-
tion medium for the model substrates (5a and 6a). After
sonication for 5 hours, no new product (7a) was observed
(TLC) and only the substrates were restored. As a result
of the study, we can conclude there was no leaching of
the tested catalyst (4b). Also, potential Ru leaching into
the reaction mixture was analyzed with ICP/OES analysis
(Inductively coupled plasma‐optical emission spectrome-
try). For this purpose, after the removal of the catalyst
by filtration, water was evaporated, and the residue was
dissolved in HNO solution (5%). The solution was mea-
3
sured several times with ICP. In all cases, Ru values (<
0
.16 ppm) in the solution of the reaction mixture were
below the detection limit.
Furthermore, reusability of the catalyst is one of the
most advantages associated with eco‐friendly green syn-
thetic protocol. Thus, we tested the catalyst reusability
for the model reaction (Scheme 2). It was found that,
the catalyst (4b) could be reused up to eight successive
runs without any appreciable loss of its activity (Figure 1).
As displayed in Figure 1, the desired product 7a was
obtained within seven minutes in quantitative yields up
to four cycles, after that it took more than nine minutes
to complete the reaction.
SCHEME 3 Sonosynthesis of derivatives 11 and 13
to afford the unreported triazole derivatives 13a–d in
excellent yields (Scheme 3). Furthermore, unprecedented
6‐ethynyl‐2H‐chromen‐2‐ones (15a, b) were also
After investigating the catalytic efficiency of the syn-
thesized Ru‐complexes (4a–g) for well‐known 1,3‐dipolar
Huisgen cycloaddition reactions, diversified hitherto
unreported coumarin hybrids tethered 1,2,3‐triazole moi-
ety (13a–d) were also synthesized under the optimal con-
ditions. To carry out this study, firstly, two new
derivatives of 6‐azido‐2H‐chromen‐2‐ones (11a, b) were
prepared form the sonication of active methylenes (10a,
b) and 5‐azido‐2‐hydroxybenzaldehyde (9) utilizing
DABCO as basic catalyst in ethanol (Scheme 3).
Secondly, with these two substrates (11a, b) in hand,
we employing the click reaction with dialkyl
acetylenedicarboxylate derivatives (12a, b) utilizing Ru‐
complex 4b as a catalyst in water at room temperature
SCHEME 4 Sonosynthesis of derivatives 15 and 16
FIGURE 1 Reusability of the catalyst
b in the preparation of 7a
4

ARAFA AND NAYL
9 of 12
SCHEME 5 Sonosynthesis of
derivatives 18, 19 and 20
synthesized and involved in a click reaction with benzyl
azide utilizing Ru‐complex 4b as a catalyst in water at
room temperature to furnish the unprecedented 1,4‐
disubstitued triazole derivatives 16a, b in excellent yields
catalyst loading and tolerates an assortment of function-
alities of alkynes and organic azides. The remarkable
merits for example, recyclability, reusability, no leaching
of the catalyst and no tedious work‐up make the present
method economically and environmentally applicable.
We believe this method will significantly contribute to
the fast growth of click chemistry in industrial applica-
tions and anticipate enhancing the studies of biological
features of the newly synthesized triazolocoumarins.
(Scheme 4).
Additionally, N‐oxide bipyridyl azide (17) and 5‐ethy-
nyl‐2‐hydroxybenzaldehyde (14) were also effective in
this Ru‐complex‐catalyzed click reaction, affording the
[50]
desired triazole derivative 18
as a regioisomer in excel-
lent yield (Scheme 5). Also, with these reactants (14, 15),
we did not observe the isolation of the 1,5‐regioisomers.
Interestingly, compound 18 smoothly underwent
Knoevenagel condensation reaction with active methy-
lene derivatives (10a, b) to give new coumarin derivatives
3.1 | Experimental section
3.1.1 | General information
(
19a, b) in excellent yields (Scheme 5). Finally, under the
optimized conditions, the azido derivative 17 furnished
the 1,2,3‐triazoles 20a, b on treating with dialkyl
acetylenedicarboxylates (12a, b) (Scheme 5). The chemi-
cal structures of all the newly prepared compounds have
been elucidated by their satisfying spectral data (HRMS
and NMR; See Supporting Information).
[Ru (DMSO) ]Cl was prepared according to literature
4
2
[
51]
methods.
Freshly distilled water (Milli Q) was used
as solvent. Alkynes, azides and other chemicals were
obtained commercially and were used without further
purification. High resolution mass spectra (HRMS) were
performed utilizing a Bruker Daltonics microTOF spec-
1
13
trometer. H and C NMR spectra were collected on
Bruker AV 400 and 100 MHz instrument, respectively.
1
13
3
| CONCLUSIONS
H and C NMR chemical shifts are relative to TMS or
residue of deuterium solvents. Ultrasonication was per-
formed in a SY5200DH‐T ultrasound cleaner (with a fre-
quency of 40 kHz and a nominal power 250 W), the
total acoustic power injected into the sample solution
In summary, we herein demonstrated a highly effective
and regioselective protocol for the sono‐synthesis of the
pharmaceutically
important
1,4‐disubstituted‐1,2,3‐
[
52]
triazoles using several heterogeneous Ru‐complexes in
water at room temperature. Furthermore, this catalytic
system could be efficiently performed one pot three com-
ponent reaction comprising sodium azide, alkyl halides
and alkynes. This versatile and convergent methodology
could be accessible on a large scale, amenable at low
was found to be 1.63 W by calorimetry.
or removed in order to regulate the bath temperature.
Water is added
[53]
IR spectra of the sample were recorded on a Perkin‐Elmer
Spectrum One spectrometer, using pressed KBr discs.
UV–vis spectra were recorded on Varian Cary 50 Bio
UV–vis spectrometer using 10 mm quartz cuvettes. The

10 of 12
ARAFA AND NAYL
melting points of the synthesized compounds were deter-
mined on Electrothermal IA9100 melting point apparatus
ultrasonication. Thus, in order to quickly control the bath
temperature, 10 ml of water from the bath was removed
[
53]
(UK). Magnetic susceptibility measurements were carried
and replaced with cold water (25 ml, 23 °C)).
Then
out on a Vibrating Sample Magnetometer (VSM). All
known organic products (3a, 3c, 4a and 7a–u) were iden-
tified by comparison of their physical and spectral data
with those of authentic samples.
the formed precipitate was isolated by filtration and
redissolved in diethyl ether. The solvent was evaporated
under reduced pressure to afford the desired product.
The catalyst was washed with diethyl ether (3x5 ml)
and reused in the next run. In case of 18 and 20, after iso-
lation of the formed products (containing both catalyst
and product), the precipitate was washed with chilled
methanol (4x5 ml) in order to isolate the catalyst. Then,
by evaporating the solvent under reduced pressure, the
remaining residue (catalyst) was used directly in the next
cycle.
3
.1.2 | General procedure for synthesis of
diamide ligands 3a–g
The title compounds (3a–g) were synthesized according
[
26]
to our published method, with some modifications.
1
,2‐Phenylenediamines (0.5 mmol) and triphenyl phos-
phite (0.25 ml, 1.0 mmol) was added to a stirred solution
of 2‐picolinic acids (1.0 mmol) in pyridine (5.0 ml). The
yellow solution was sonicated at 50 °C for 5 hr. Evapora-
tion of the solvent gave a solid which was washed with
H O/MeOH (1:1) and Et O to yield the crude product.
Typical procedure for one‐pot synthesis of 1,2,3‐
triazoles from benzyl bromides, sodium azide, and
alkynes
To a mixture of benzyl halides (1.0 mmol), sodium azide
2
2
(
1.1 mmol), alkynes (1.1 mmol) and H O (3.0 ml) was
2
The crude product was purified by crystallization or flash
chromatography.
added catalyst (4b, 0.2 mol%). The resulting solution
was sonicated at room temperature (23 °C) for the men-
tioned time in Table 4. Then the formed precipitate was
isolated by filtration and redissolved in diethyl ether.
The solvent was evaporated under reduced pressure to
afford the desired product. The catalyst was washed with
diethyl ether (3x5 ml) and reused in the next run.
3
.1.3 | General procedure for the synthesis
of ruthenium complexes 4a–g
Ligands 3a–g (0.50 mmol) and Et N (0.60 ml, 4.30 mmol)
3
were dissolved in MeOH (3.0 ml). To this solution [Ru
(
DMSO) Cl ] (242.0 mg, 0.50 mmol) was added and the
General procedure for the synthesis of coumarin deriv-
atives (11, 15, 19)
4
2
reaction mixture was sonicated for 3 hr at 60 °C. Then
4
‐picoline (1.2 ml, 12.0 mmol) was added, and the mix-
The salicylaldehydes (1.0 mmol), active methylenes
(1.0 mmol) and DABCO (0.15 mol%) were dissolved in
ethanol (20.0 ml) and sonicated at 70 °C for 15 min. After
the completion of reaction as indicated by TLC, the reac-
tion mixture was cooled and the solid product obtained
was filtered and recrystallized from ethanol containing
few drops of dioxane.
ture was further sonicated for 5 hr at 60 °C. Addition of
H O (3.0 ml) gave a dark precipitate. This precipitate
was isolated by centrifugation, washed with water (5x10
ml) and Et O (3x10 ml), and dried under vacuum to
afford a dark brown solid. The crude product was purified
by automated flash chromatography on silica column
2
2
(MeCN/MeOH as eluent, 0% to 10% gradient of MeOH).
The fractions containing the desired product were com-
bined, concentrated under reduced pressure and evacu-
ated to afford the desired complexes 4a–g as dark
brown crystals.
ACKNOWLEDGMENTS
We gratefully acknowledge financial support from the
Jouf University, project No. 634/39.
ORCID
3.1.4 | General procedures for the synthe-
sis of 7a–u, 13a–d, 16a–d, 18 and 20a–d
Wael Abdelgayed Ahmed Arafa
002-9288-4143
https://orcid.org/0000-
0
Typical procedure for the Ru‐catalyzed cycloaddition
of various alkynes and organic azides
To a mixture of azides (1.0 mmol), alkynes (1.1 mmol)
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