Direct access to stabilized CuI using cuttlebone as a natural-reducing support for efficient CuAAC click reactions in water

Article abstract of DOI:10.1039/c6ra13314b

Cuttlebone@CuCl₂ has efficiently catalyzed the one-pot azidonation of organic bromides, followed by a regioselective azide-alkyne 1,3-dipolar cycloaddition (CuAAC) reaction to produce the corresponding 1,4-disubstituted 1,2,3-triazole derivativ

Full text of DOI:10.1039/c6ra13314b

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Direct access to stabilized CuI using cuttlebone as a natural-
reducing support for efficient CuAAC click reactions in water
Received 00th January 20xx,
Accepted 00th January 20xx
Sara S. E. Ghodsinia,a Batool Akhlaghinia,*a Roya Jahanshahia
DOI: 10.1039/x0xx00000x
Cuttlebone@CuCl2 has efficiently catalyzed the one-pot azidonation of organic bromides, followed by regioselective azide-
alkyne 1,3-dipolar cycloaddition (CuAAC) reaction to produce the corresponding 1,4-disubstituted 1,2,3-triazole derivatives
in excellent yields, in water. Importantly, cuttlebone not only used for successful immobilization of CuCl2 in order to its
heterogenation, but also utilized as a natural-reducing platform which can reduce CuII to the click-active stabilized CuI. This
mild three component synthetic approach avoids handling of hazardous and toxic azides, because of their in situ
generation. Moreover, the catalyst has the advantages of being ligand-free, leaching-free, thermal stable, easy to
synthesize from inexpensive commercially available precursors, environmentally friendly and recyclable for at least seven
times without a significant decrease in its activity and selectivity.
www.rsc.org/
homogeneous catalysts which cannot be separated easily from the
reaction media.8,11
1. Introduction
Copper(I)-catalyzed Huisgen1,3-dipolar cycloaddition of organic
azides and alkynes (click reaction) which was pioneered by
Sharpless and co-investigators,1 has received impressive attention
in green chemistry scope due to the mild reaction conditions, as
well as the high efficiency involved.2 Accordingly, a great deal of
methods have prospered around this reaction to afford the
corresponding 1,2,3-triazoles.3 These compounds are predominant
building blocks of the numerous classes of nitrogen-containing
heterocyclic compounds4 and are widely used as a powerful tool in
several fields of chemistry such as pharmaceuticals, agrochemicals,
dyes, corrosion inhibitors, photostabilizers and photographic
materials.5 In spite of providing excellent yields and good
regioselectivity of the products obtained through the Cu(I)-
catalyzed click reaction, thermodynamic instability and also
formation of undesired alkyne–alkyne coupling by-product
restricted the use of Cu(I) catalysts, directly.6 Instead, the favorable
approach is the in situ generation of Cu(I) species through the
reduction of Cu(II) salts,7 oxidation of Cu(0) metals,8 and
Cu(II)/Cu(0) comproportionation9 or using Cu(I) salts in the
presence of bases and/or ligands which protect Cu(I) intermediates
from oxidation and disproportionation, and hamper undesired side-
product formation.10 However, most of the existing methods
involve handling of unstable, toxic organic azides and using
In this context, to promote the existing synthetic protocols, many
efforts have been made on the heterogeneous copper based
catalytic systems and the in situ generation of organic azides from
suitable precursors which would avoid the difficulties associated
with the hazardous and explosive nature of the azides. Using
heterogeneous catalysts is accompanied with several advantages
such as fast and efficient recyclability of the catalyst, as well as
facile separation of the products. Consequently, the number of
steps and time involved in the reaction strategy would be
diminished. For this purpose, immobilization of Cu(I) species on
various supports such as alumina,12 polymers,13 Amberlyst,14
zeolites,15 activated charcoal,16 titanium dioxide,17 silica-supported
N-heterocyclic carbene,18 clay,19 magnetic materials,20 and
aluminum oxyhydroxide nanofibers,21 has received a remarkable
attention in the Huisgen1,3-dipolar cycloaddition. Additionally, solid
supported CuII species as heterogeneous catalytic systems without
employing any reducing agents or additives have been reported in
alkyne-azide cycloaddition reaction.22 In accordance with our
previous study on cuttlebone23 and to continue our research
interest in developing new efficient and environmentally benign
heterogeneous catalysts,24 herein, we are willing to report synthesis
and characterization of cuttlebone@CuCl2 as an efficient
heterogeneous catalyst for the first time (Scheme 1). The catalytic
activity of this newly synthesized catalyst was proved for the one-
pot synthesis of 1,4-disubstituted 1,2,3-triazoles via a three-
component reaction between terminal alkynes, organic bromides,
and sodium azide, in water (see Scheme 2).
a.Department of Chemistry, Faculty of Sciences, Ferdowsi University of Mashhad,
Mashhad 9177948974, Iran.
*E-mail: akhlaghinia@um.ac.ir, Fax: +98-51-3879-5457; Tel.: +98-51-3880-5527.
Electronic Supplementary Information (ESI) available: [General Information,
spectral data of organic compounds]. See DOI: 10.1039/x0xx00000x
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electron energy analyzer (Specs model EA10 plus) suitable for X-ray
photoelectron spectroscopy (XPS). Inductively coupled plasma (ICP)
was carried out on a Varian, VISTA-PRO, CCD, Australia and
76004555 SPECTRO ARCOS ICP-OES analyzer. All yields refer to
isolated products after purification by recrystallization.
2.3. Pre-preparation of cuttlebone
In order to remove pollution on the surface of cuttlebone, it was
powdered, washed with distilled water and dried at 100 °C, for 2 h.
2.4. Preparation of catalyst
In a round-bottom flask, cuttlebone (5.0 g) was mixed with CuCl2
(1.5 g, 0.011 mol) in deionized water (50 mL). The mixture was
stirred at room temperature for 10 h. The catalyst was filtered and
washed with water and ethanol several times (to remove excess of
copper salt), and then was dried at 50 °C for 12 h.
2.5. Typical procedure for preparation of 1-benzyl-4-phenyl-1,2,3-
triazole
Catalyst 0.048 g (8.5 mol%) was added to a solution of phenyl
acetylene (1 mmol), benzyl bromide (1 mmol) and sodium azide (1.2
mmol), in H2O (5 mL). The reaction mixture was stirred at 40 °C and
monitored by TLC until total conversion of the starting materials.
After 5 min, the reaction mixture was cooled to room temperature.
The catalyst was separated by simple filtration and washed with
water, ethanol and EtOAc, successively and then was dried at 60 °C,
for 3 h. Afterwards, water (10 mL) was added to the resulting
reaction mixture, followed by extraction with EtOAc (3 × 15 mL).
The recovered catalyst was used directly in the next cycle. The
organic phase was washed with water and dried with Na2SO4.
Solvent was removed under vacuum and the crude product was
purified by a simple crystallization from ethanol to provide the
corresponding triazole (1-benzyl-4-phenyl-1H-1,2,3-triazole) as a
white solid (0.222 g, 95% isolated yield).
Scheme 1 Preparation of catalyst.
2. Experimental
2.1. Materials
All chemical reagents and solvents were purchased from Merck and
Sigma-Aldrich chemical companies and were used as received
without further purification. Cuttlebone was taken out from
cuttlefish (Sepia esculenta),25-28 which is commonly found in
saltwater beaches like Persian Gulf in Iran.
2.2. Instrumentation analysis
The purity determinations of the products and the progress of the
reactions were accomplished by TLC on silica gel polygram STL
G/UV 254 plates. The melting points of the products were
determined with an Electrothermal Type 9100 melting point
apparatus. The FT-IR spectra were recorded on pressed KBr pellets
using an AVATAR 370 FT-IR spectrometer (Therma Nicolet
spectrometer, USA) at room temperature in the range between
4000 and 400 cm-1 with a resolution of 4 cm-1, and each spectrum
was the average of 32 scans. NMR spectra were recorded on a NMR
Bruker Avance spectrometer at 400 and 300 MHz in CDCl3 as
solvent in the presence of tetramethylsilane as the internal
standard and the coupling constants (J values) are given in Hz.
Elemental analyses were performed using a Thermo Finnigan Flash
EA 1112 Series instrument (furnace: 900 ˚C, oven: 65 ˚C, flow
carrier: 140 mL min-1, flow reference: 100 mL min-1). Mass spectra
were recorded with a CH7A Varianmat Bremem instrument at 70 eV
electron impact ionization, in m/z (rel %). Elemental compositions
were determined with an SC7620 Energy-dispersive X-ray analysis
(EDX) presenting a 133 eV resolution at 20 kV. Surface analysis
spectroscopy of the catalyst was performed in an ESCA/AES system.
This system was equipped with a concentric hemispherical (CHA)
3. Results and Discussion
An extremely porous hard tissue in the cuttlefish (Sepia esculenta),
which acts as a rigid buoyant tank in the animal is called
"cuttlebone".29 It is a natural material which has the multifunctional
properties of high flexural stiffness, high porosity and compressive
strength.31 Cuttlebone framework is an inorganic–organic
composite consist of aragonite, protein and β-chitin.29 The principal
component of the organic matrix derived from the cuttlebone
framework is β-chitin.29 However, an attractive application of
cuttlebone-derived organic matrix, that has not yet received much
attention, is related to its application as a reducing agent for the
preparation of metal nanoparticles and a scaffold for their
assembly, which will lead to a new class of functional materials.29 β-
Chitin as the main component of the cuttlebone-derived organic
matrix is a natural carbohydrate (polysaccharide) composed of
parallel
arranged
poly[2-acetamido-2-deoxy-(1,4)-β-
D-
glucopyranose].29
Recently,
carbohydrates (including
monosaccharide, oligosaccharides and polysaccharides) as
biodegradable, renewable natural materials, have been employed
2 | J. Name., 2012, 00, 1-3
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as stabilizers or reducing agents for the green providing of
nanomaterials and nanocomposites.29 Hence, cuttlebone can be
used as a natural platform for immobilization of CuCl2, which
subsequently reduced CuII to the click-active stabilized CuI.
Fascinatingly, the resulted CuI was long-term stabilized in the
cuttlebone network. On the other hand, during the reaction, when
the catalyst has been treated with sodium azide, Cu2+ has reduced
to Cu1+ oxidation state, much more than before.30 Then, this newly
synthesized heterogeneous catalyst was characterized by different
techniques such as fourier transform infrared spectroscopy (FT-IR),
energy-dispersive X-ray analysis (EDX), X-ray photoelectron
spectrum (XPS) and inductively coupled plasma (ICP).
Fig. 1 FT-IR spectrum of (a) Cuttlebone; (b) Catalyst; (c) 7th
recovered catalyst.
3.1. Characterization of catalyst
3.1.1. FT-IR spectroscopy
The FT-IR spectrum of the cuttlebone was shown in Fig. 1a. It is
worth to note that the observed absorption bands for aragonite
phases (calcium carbonate) in cuttlebone structure are related to
CuCl2 on the cuttlebone as a reducing stabilizer support, CuII was
partially reduced to CuI state and thus is present as CuII/CuI mixed
valency dinuclear species, but with the predominance of CuII (Fig.
3a).
2-
the planar CO3 ions. As can be seen, there are four main
2-
vibrational modes in the free CO3 ions.32 The peak appearing at
about 1082 cm-1 is assigned to the symmetric stretching vibration of
the carbonate ion. The peak positioned at about 857 cm-1 is
ascribed to out-of plane bending vibration of carbonate ion.
Moreover, the asymmetric stretching vibration at about 1400-1500
cm-1 and the split in-plane bending vibration at about 700 cm-1 are
clearly demonstrate the free CO32- ions of the cuttlebone structure.
Also, the FTIR spectrum of cuttlebone shows the absorption bands
at 3448 and 3318 cm-1, which are attributed to the OH and NH
stretching vibrations of the β-chitin segment in cuttlebone,
respectively. The absorption bands in the range of 2977–2855 cm-1
were corresponded to the symmetric stretching vibrations of CH,
CH3 and the asymmetric stretching vibrations of CH2 in the
cuttlebone structure. Furthermore, the CH bending, CH3 symmetric
deformation and CH2 wagging bands were appeared at 1384 to
1312 cm−1. In the FTIR spectrum of cuttlebone@CuCl2 (Fig.1b and c),
the peaks positioned at 442, 453 and 428 cm−1 are assigned to the
Cu–Cl,33 Cu–O33,24a and Cu–N24a stretching vibrations, respectively.
On the other hand, as proved by XPS analysis, it is evident that the
treatment of catalyst with sodium azide during the reaction, leads
to reduction of Cu2+ to Cu1+ oxidation state, much more than
before. Thus, meanwhile the click reaction the dominant species
would be Cu1+ (Fig. 3b).
Fig. 2 EDX analysis of the catalyst.
3.1.2. EDX analysis
Energy-dispersive X-ray analysis (EDX) indicates the presence of C,
O, Ca, Cl and Cu elements in the cuttlebone structure (Fig. 2). This
analysis confirms the successful immobilization of copper on the
cuttlebone surface.
3.1.3. XPS Characterizations of the catalyst
Fig. 3 shows the high resolution narrow X-ray photoelectron spectra
(XPS) for fresh catalyst and the 7th recovered catalyst. As observed
in Fig. 3 binding energy peaks at 937 eV and 956.5 eV can be
attributed to 2p3/2 and 2p1/2 spin-orbit split-doublets,
respectively, which are characteristic of Cu in +2 oxidation
state.30a,34 However, binding energy peaks at 934.6 eV and 954.6 eV
can be attributed to 2p3/2 and 2p1/2 spin-orbit split-doublets,
respectively, which are characteristic of Cu in +1 oxidation state.34
These results led us to conclude that after the immobilization of
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Journal Name
Peak
Label/ID
Cu+
BE
(eV)
FWHM
(eV)
Height
Norm.
Area
25.4235 76.165
Rel.
Area %
39.30%
934.63
937
2.81
Cu2+
3.08
35.8022 117.419 60.70%
Fig. 3 (a) XPS spectrum of fresh catalyst.
Scheme 2. One-pot synthesis of 1,4-disubstituted 1,2,3-triazoles
using catalyst.
catalytic activity was examined for the mild one-pot synthesis of
1,4-disubstituted 1,2,3-triazoles, by the reaction between terminal
alkynes and the in situ generated substituted azides from their
corresponding organic bromides, in water (Scheme 2).
Initially the 1,3-dipolar cycloaddition reaction between phenyl
acetylene, benzyl bromide and sodium azide, was selected as a
model reaction to optimize the different reaction conditions. The
obtained results were represented in Table 1. The in situ generated
azide from the reaction mixture of benzyl bromide and NaN3
reacted well with phenyl acetylene and the desired 1-benzyl-4-
Peak
Label/ID
Cu+
BE
(eV)
934.4
937
FWHM
(eV)
Height
Norm.
Area
Rel.
phenyl-1H-1,2,3-triazole was obtained through
a one pot
Area %
procedure. However, when the model reaction was performed at
100 ˚C in aqueous media, in the absence of any catalyst, no desired
product was formed, even after a prolonged reaction time (Table1,
entry 1). It was observed that the click reaction occurred smoothly
in the presence of several different catalysts including cuttlebone,
3.52
4.1
103.576 387.97 68.60%
41.0254 178.874 31.40%
Cu2+
Fig. 3 (b) XPS spectrum of 7th recovered catalyst.
Cu(SO4)2,
Cu(OAc)2,
CuCl2,
cuttlebone@Cu(SO4)2,
cuttlebone@Cu(OAc)2 and cuttlebone@CuCl2.
3.2. Catalytic synthesis of 1,4-disubstituted 1,2,3-triazoles
Thermal evaluation of the reaction revealed that the higher the
temperature, the greater the reaction progress. Among the
different catalysts screened, cuttlebone@CuCl2 in water, was found
to be excellent for this tandem reaction. Other protic solvents such
After the successful preparation and full characterization of
catalyst, to evaluate this novel synthesized catalyst efficiency, its
Table 1. Catalyst optimization studies for one-pot synthesis of 1-benzyl-4-phenyl-1H-1,2,3-triazole, under different reaction conditions.a
Entry
Catalyst
Solvent
Temperature
(°C)
Time
(min)
15 h
2 h
30
Isolated
Yield (%)
0
1
2
None
Cuttlebone
H2O
H2O
H2O
H2O
H2O
H2O
H2O
H2O
H2O
H2O
H2O
MeOH
100
r.t
45
3
Cuttlebone
100
65
4
Cu(SO4)2
100
40
80
5
Cu(OAc)2
100
20
89
6
CuCl2
100
10
89
7
CuCl2
r.t
60
70
8
Cuttlebone@Cu(SO4)2
Cuttlebone@Cu(OAc)2
Cuttlebone@CuCl2
Cuttlebone@CuCl2
Cuttlebone@CuCl2
100
20
90
9
100
10
95
10
11
12
100
5
95
r.t
40
72
Reflux
30
75
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13
14
15
16
17
18
19
20
Cuttlebone@CuCl2
Cuttlebone@CuCl2
Cuttlebone@CuCl2
Cuttlebone@CuCl2
Cuttlebone@CuCl2
Cuttlebone@CuCl2
Cuttlebone@CuCl2
Cuttlebone@CuCl2
MeOH/H2O (1:1)
THF
60
Reflux
Reflux
100
30
60
60
60
60
30
5
87
Trace
20
CH3CN
DMSO
Acetone
Neat
Trace
25
Reflux
100
70
H2O
40
95
H2O
50
5
95
a
Reaction conditions: phenyl acetylene (1 mmol), benzyl bromide (1 mmol), NaN3 (1.2 mmol), catalyst
(0.048 g) in H2O (5 mL).
as MeOH and a solution of MeOH/H2O (1:1, v:v) have proved to be substituted benzyl bromides (Table 3, entries 11-20). As it is evident
less suitable for such a click reaction (Table 1, entries 12,13). On the from Table 3, in all cases the clean reactions were performed to
other hand, aprotic solvents like THF, CH3CN, DMSO and acetone produce the corresponding triazoles, smoothly. Afterwards, we
were ineffective for this transformation (Table 1, entries 14-17). focused our attention on using allyl bromide instead of benzyl
Similarly, the improvement of the reaction was not promising by bromide. Similarly, the Huisgen 1,3-dipolar cycloaddition reactions
using neat condition (Table1, entry 18). The obtained results of terminal alkynes and allyl bromide were clean and high-yielding
confirmed that cuttlebone@CuCl2 catalyst renders a promising (Table 3, entries 21-24).
catalytic activity in water, at 40 ˚C, with enhanced regioselectivity Also, to investigate the on water effect on the reaction progress of
towards the desired 1,4-disubstituted 1,2,3-triazole product (Table polar propargyl alcohol and 2-bromo ethanol, the model reactions
1, entry 19).
were performed in the presence of catalyst (Table 3, entry 9 and
Having identified cuttlebone@CuCl2 as the most efficient catalyst 25). As can be observed, using polar alkynes and alkyl bromides
for the Huisgen1,3-dipolar cycloaddition reaction in H2O at 40 ˚C, as reduced the reaction efficiency. Although, nonpolar organic
the optimized reaction conditions, the catalyst and also sodium compounds have more interactions together in the aqueous media
azide amounts were next investigated for the representative phenyl and would increase the effective efficiency of the reaction, as well
acetylene, benzyl bromide and sodium azide reaction (Table 2). This as reducing the reaction time as a result of their lack of solubility in
reaction gives high yields of the corresponding 1-benzyl-4-phenyl-
1H-1,2,3-triazole, in the presence of 0.048 g (8.5 mol%) of the propargyl alcohol and 2-bromo ethanol in the aqueous media, the
present catalyst and 1.2 mmol of sodium azide (Table 2, entry 2). efficiency of the corresponding reactions reduced.
water (water solvation effect), in contrast due to the solubility of
With the optimal conditions in hand, the scope of this methodology As it was expected, by using this methodology in the reaction of
has been explored using a variety of organic bromides and terminal sodium azide, benzyl or allyl bromides with different terminal
alkynes. The results are illustrated in Table 3. It was found that the alkynes, only one of the possible regioisomers was produced,
electron-rich, electron neutral and electron-poor phenyl acetylenes through an efficient three-component click reaction.
reacted with organic bromides and NaN3 successfully to provide the All of the obtained triazoles were known and their physical (color,
desired products in good to excellent yields. Aliphatic alkynes also melting points) and spectral (mass spectrometry) data found to be
underwent the successful coupling reactions with the in situ identical with those of authentic compounds. The selected
1
generated corresponding azide from the reaction mixture of benzyl compounds were further identified by elemental analysis, FT-IR, H
bromide and NaN3 (Table 3, entries 9, 10).
NMR and 13C NMR spectroscopy, which compared with literature
Moreover, 2-ethynylpyridine as a heteroaryl substituted acetylene data. In the FT-IR spectra of the products, the disappearance of the
was converted to the corresponding triazoles, efficiently (Table 3, absorption bands related to C≡C and ≡C–H stretching bands (at
entries 5, 15 and 20). In an attempt to develop the scope of our about 2250-2100 and 3300 cm-1, respectively) along with the
methodology, the model reaction was accomplished with a range of appearance of the characteristic bands corresponding to the
Table 2 Copper-catalyzed azide–alkyne cycloaddition with different amounts of NaN3 and catalyst. a
Entry
1
Catalyst (mol%)
9.5
NaN3 (mmol)
1.2
Time (min)
5
Isolated Yield (%)
95
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2
3
4
5
6
7
8.5
7.5
6.5
10.5
8.5
8.5
1.2
1.2
1.2
1.2
1.1
1.4
5
15
20
5
95
90
80
95
70
95
10
5
a Reaction conditions: phenyl acetylene (1 mmol) and benzyl bromid (1 mmol) in H2O
(5 mL) at 40 °C.
Table 3. One-pot click reaction between a variety of acetylenes, organic bromides and sodium azide by using the present catalyst.
Entry
Benzyl halide
Alkyne
Product
Time
(min)
Isolated
Yield (%)
1
5
95
93
CH
2
3
15
30
35
85
90
N
4
N
N
t-Bu
5
6
30
7
82
90
7
10
87
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8
4
95
N
N
N
OH
9
60
65
73
77
CH
10
11
12
15
30
95
91
CH
13
14
40
50
55
87
88
15
16
17
18
74
85
84
89
25
40
50
CH
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65
65
19
77
72
20
21
N
N
N
35
90
CH
22
23
50
65
85
84
75
80
24
25
93
76
1
out-of plane bending vibrations of the =C–H in the triazole ring (at Fig. 4 shows the NOESY HNMR spectrum of 1-benzyl-4-phenyl-1H-
about 815 cm-1), were document for the formation of 1,4- 1,2,3-triazole. As it is evident from the spectrum, cross-peak is
disubstituted 1,2,3-triazoles. Moreover, the FT-IR spectra of all obtained due to the interaction between benzyl protons (Hb) and
products show absorption bands at about 1293–1217 cm-1 (due to (Hx) of triazole ring (see the encircled area in Fig. 4). However, if the
N–N=N–) related to the triazole ring. Structural assignments of product was 1-benzyl-5-phenyl-1H-1,2,3-triazole (b), no cross-peak
1
triazoles were made by comparison of the H and 13C NMR spectra should have appeared due to the lack of spatial vicinity between Hx
with those reported, previously. In fact, the click condensations and Hb (lack of interaction between benzyl protons (Hb) and (Hx) of
were confirmed by the appearance of a singlet resonating at around triazole ring). According to the results of NOESY 1HNMR spectrum, it
8.5–7.5 ppm in 1H NMR spectra, which corresponds to the hydrogen has been proved that 1-benzyl-4-phenyl-1H-1,2,3-triazole is the only
on 5-position of triazole ring and corroborates the regioselective isomer obtained from the click reaction in our study.
preparation of 1,4-disubstituted triazole regioisomers (see ESI).
By analogy with our investigation and based on reports in the
To evaluate the regioselectivity of this click reaction towards the literature,22b a possible mechanism for the click synthesis of 1,4-
1,4-disubstituted triazole regioisomers instead of 1,5-disubstituted disubstituted 1,2,3-triazoles catalyzed by using the present catalyst
1
triazole regioisomers, and since HNMR and 13CNMR spectra could is proposed in Scheme 3. The 1,2,3-triazole formation proceeds
not conclusively distinguish between such two isomers, the through the formation of copper acetylide (I), which then followed
structure
of
1-benzyl-4-phenyl-1H-1,2,3-triazole
(a)
was by the coordination of the in situ generated organic azide to the
investigated through the NOE technique.
copper center of acetylide. Subsequently, Huisgen 1,3-dipolar
8 | J. Name., 2012, 00, 1-3
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Fig. 4 NOESY 1HNMR spectrum of the 1-benzyl-4-phenyl-1H-1,2,3-triazole isomer in the presence of the catalyst.
was dried at 60 °C, for 3 h. The recovered catalyst was then utilized
directly in the next cycle. The results revealed that this simple
Ph
Ph
Br
Ph
N
N
N
NaN3
CuI
Ph C
C
N
N
N
Ph
cycloaddition reaction between organic azide and copper acetylide
(I) leads to the formation of complex (II).
CuI
H
CuI
+
N
Ph C
C
N
N
Finally, the desired 1,2,3-triazole was obtained by copper exchange
with the acidic hydrogen which has been generated in the first step
and then the re-generated catalyst re-enters the catalytic cycle. It is
worth to note that, the formation of complex (II) would be proceed
through an “on water” effect, because of the insolubility of organic
azides and terminal acetylenes in aqueous media.22f,35 Further
studies to elucidate the details of the mechanism are ongoing.
One of the principal advantages of a heterogeneous catalyst is its
ease of separation and possible reusability in the further runs. Thus,
the recyclability of the catalyst was examined in a one-pot synthesis
of 1-benzyl-4-phenyl-1H-1,2,3-triazole, under the optimized
reaction conditions. The catalyst was separated easily from the
reaction mixture by simple filtration, followed by washing with
water, ethanol and EtOAc, successively. Afterwards, the catalyst
(I)
Ph
(II)
H
CuI
Ph C
C H
Ph
N
H
N
N
Ph
Cuttlebone@CuI
=
CuI
Scheme 3. Plausible mechanism of one-pot CuAAC protocol using
present catalyst.
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previously. To prove the superiority of the present catalyst over
some of the reported catalysts in the literature, its catalytic activity
in the synthesis of 1-benzyl-4-phenyl-1H-1,2,3-triazole, was
compared with various reported catalyst (Table 4). Although, other
copper catalysts afford high yield of the product, some of these
methods suffer from one or more of the following drawbacks, such
24f, 37-41
as using organic solvents,18,36,37 higher temperatures,18,
certain and difficult conditions as mw irradiation39,41 or ball-
milling,22d and some additives or reducing agents37 and require
longer reaction times to achieve reasonable yields. However,
compared to these catalysts, the present catalytic system, offered
higher activity with lower amount of catalyst, without using any
reducing agents or additives, under mild conditions for the
synthesis of 1-benzyl-4-phenyl-1H-1,2,3-triazole, in water (Table 4,
bold in entries). These findings significantly confirm the high
efficiency of the present catalyst in three-component click synthesis
of the desired triazole.
Fig. 5 Recycling of the catalyst, in the click synthesis of 1-benzyl-4-
phenyl-1H-1,2,3-triazole.
separation method could be repeated for seven consecutive runs
and the recovered catalyst showed remarkably constant catalytic
activity in all seven cycles (Fig. 5).
The copper content of freshly prepared cuttlebone@CuCl2 which
was acquired by inductively coupled plasma (ICP) was 1.77 mmol of
Cu per 1.000 g of the catalyst, whereas ICP illustrates that the 7th
reused cuttlebone@CuCl2 contains 1.54 mmol of Cu per 1.000 g of
7th reused catalyst. It means that, the amount of leached metal
from the surface of catalyst is very low.
4. Conclusion
In summary, cuttlebone@CuCl2 as
a novel and efficient
heterogeneous catalyst was synthesized and characterized by
different techniques such as, FT-IR, EDX, XPS, and ICP. The newly
synthesized catalyst revealed a privileged catalytic efficiency
towards the highly efficient and economical synthesis of 1,4-
disubstituted 1,2,3-triazoles, through a one-pot Huisgen 1,3-dipolar
cycloaddition reaction. The present protocol involves a rapid
formation of 1,4-disubstituted 1,2,3-triazoles via a shorter reaction
pathway, as well as easy workup and also avoids the isolation of
unstable and toxic azides, by using recyclable and reusable catalyst,
in water as a green solvent. Mildness of the reaction conditions,
compatibility with a wide range of substrates with high functional
group tolerance, high yields of the products, ligand-free and
leaching-free feature of the catalyst, along with its ease of
preparation and handling, make this protocol very attractive and
environmentally compatible process for the regioselective synthesis
of a variety of 1,2,3-triazoles. Most importantly, this approach does
not require additional reducing agent, since cuttlebone as a natural-
reducing platform can reduce CuII to the click-active stabilized CuI,
in the freshly prepared catalyst, which would be followed by more
reduction of CuII species while the catalyst treated with NaN3 during
the reaction.
To confirm the presence of contaminant copper ions in the reaction
medium after extraction with organic solvent, ICP–OES technique
was employed for the selected products including 1-allyl-4-(p-tolyl)-
1H-1,2,3-triazole and 1-benzyl-4-(4-nitrophenyl)-1H-1,2,3-triazole,
and the exact amounts of contaminant copper ions was measured
(90 ppm; 75 ppm), in the reaction medium. Moreover, ICP–OES
technique was employed for the isolated triazole compounds
including
1-allyl-4-(p-tolyl)-1H-1,2,3-triazole,
and
1-benzyl-4-(4-
nitrophenyl)-1H-1,2,3-triazole,
1-benzyl-4-(4-(tert-
butyl)phenyl)-1H-1,2,3-triazole (the exact amounts of contaminant
copper ions was measured to be 43 ppm; 37 ppm; 46 ppm,
respectively), and the minimum copper contamination was
detected in the corresponding compounds. These results can rule
out almost any contribution of leached copper ions in to the
reaction medium, as well as the isolated triazole compounds, and
confirms that the presented catalyst is heterogeneous.
As can be seen in the FT-IR spectrum of the 7th recovered catalyst
(Fig. 1c), all of the characteristic peaks are well preserved in terms
of shape, position and relative intensity.
Acknowledgements
These results demonstrate no significant changes have been
occurred on the chemical structure of functional groups and the
hydrogen bonding network of the catalyst.
The authors gratefully acknowledge the partial support of this study
by Ferdowsi University of Mashhad Research Council (Grant no.
p/3/39490).
The present catalyst was exhibited much more catalytic efficiency
compared with some of the catalysts used for this transformation,
Table 4. Comparison of catalytic activity of the present catalyst with some other reported methods in the click reaction of phenyl acetylene,
benzyl bromide and sodium azide.
Entry
1
Catalyst (mol%)
Reaction conditions
EtOH, 78 ˚C, 24 h
Yield (%)
92
Ref.
18
Silica-APTS-Cu(I),a (5)
10 | J. Name., 2012, 00, 1-3
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2
Cu/Al2O3, 10
Ball-milling, 1 h
92
94
93
99
93
96
91
92
97
90
95
91
91
95
22d
3
γ-Fe2O3@TiO2-EG-CuII,b (4)
H2O, 50 °C, 5 min
22f
4
Cu NP, (5)
MeOH, r.t, 8 h
36
5
MNPs@FGly,c (0.5)
CuFe2O4, (5)
H2O/t-BuOH; (3/1), 55 ˚C, 2 h
H2O, 70 °C, 3 h
37
6
38
7
MNP–CuBr, (1.46)
H2O/PEG, 80 °C, mw, 0.3 h
39
8
Copper nanoparticles on charcoal, (1)
Cu/SiO2, (10)
H2O, 100 ˚C, 0.6 h
40
9
H2O, 70 ˚C, mw, 10 min
PEG2000,d 70 °C, 0.5 h e
PEG2000, 70 °C, 0.5 h e
PEG2000, 70 °C, 6 h e
H2O, r.t, 20-30 min
DMF, 50 °C, 15 h h
H2O, 40 °C, 5 min
41
10
11
12
13
14
15
CuI, (1)
42
CuNP,( 1)
42
CuT,g (40)
42
Nanoporous Au/TiO2, (2 mg)
Zn/C, (10)
43
44
Cuttlebone@CuCl2, (8.5)
Present study
b
a Copper(I) on 3ꢀaminopropyl functionalized silica. CuII immobilized on guanidinated epibromohydrin functionalized γꢀ
d
c
Fe2O3@TiO2.
Fe3O4–silicaꢀcoated@functionalized 3ꢀglycidoxypropyltrimethoxysilane.
Polyethylene glycol of
e
molecular weight 2000.
hydroxypropyl)ꢀ4ꢀphenylꢀ1,2,3ꢀtriazole.
CuAAC between 3ꢀazidopropanol and phenylacetylene for the synthesis of 1ꢀ(3ꢀ
h
g
Copper turnings (CuT).
CuAAC between 4ꢀnitrophenyl azide and
phenylacetylene for the synthesis of 1ꢀ(4ꢀnitrophenyl)ꢀ4ꢀphenylꢀ1Hꢀ1,2,3ꢀtriazole.
7
For some selected examples, see: (a) V. V. Rostovtsev, L. G.
Notes and references
Green, V. V. Fokin, K. B. Sharpless, Angew. Chem., Int. Ed.,
2002, 41, 2596; (b) C. W. Tornoe, C. Christensen, M. Meldal,
J. Org. Chem., 2002, 67, 3057; (c) J. Y. Kim, J. C. Park, H. Kang,
H. Song, K. H. Park, Chem. Commun., 2010, 46, 439; (d) C.
Shao, X. Wang, J. Xu, J. Zhao, Q. Zhang, Y. Hu, J. Org. Chem.,
2010, 75, 7002; (e) C. Deraedt, N. Pinaud, D. Astruc, J. Am.
Chem. Soc., 2014, 136, 12092; (f) K. B. Mishra, V. K. Tiwari, J.
Org. Chem., 2014, 79, 5752; (g) H. K. Akula, M. K. Lakshman,
J. Org. Chem., 2012, 77, 8896; (h) J. T. Fletcher, J. E. Reilly,
1
2
H. C. Kolb, M. G. Finn and K. B. Sharpless, Angew. Chem., Int.
Ed., 2001, 40, 2004–2021.
(a) V. K. Tiwari, B. B. Mishra, K. B. Mishra, N. Mishra, A. S.
Singh, X. Chen, Chem. Rev., 2016, 116, 3086–3240; (b) G.
Franc, A. K. Kakkar, Chem. Soc. Rev., 2010, 39, 1536–1544;
(c) Ch. Wanga, D. Ikhlef, S. Kahlalb, J-Y. Saillard, D. Astruc,
Coord. Chem. Rev., 2016, 316, 1–20; (d) J. E. Hein, V. V.
Fokin, Chem. Soc. Rev., 2010, 39, 1302–1315.
Tetrahedron Lett., 2011, 52
Westermann, Chem. Commun., 2005, 2852; (j) Y. Jiang, D.
Kong, J. Zhao, Q. Qi, W. Li, G. Xu, RSC Adv., 2014, , 1010; (k)
, 5512; (i) S. Dörner, B.
3
For reviews, see: (a) V. D. Bock, H. Hiemstra, J. H. van
Maarseveen, Eur. J. Org. Chem., 2006, 2006, 51–68; (b) M.
Meldal, C. W. Tornøe, Chem. Rev., 2008, 108, 2952–3015; (c)
P. Appukkuttan, E. Van der Eycken, Eur. J. Org. Chem., 2008,
2008, 1133–1155; (d) C. O. Kappe, E. Van der Eycken, Chem.
Soc. Rev., 2010, 39, 1280–1290.
4
A. Pathigoolla, R. P. Pola, K. M. Sureshan, Appl. Catal. A:
Gen., 2013, 453, 151; (l) M. Arslan, G. Yilmaz, Y. Yagci, Polym.
Chem., 2015, 6, 8168.
8
(a) R. Huisgen, Angew. Chem., Int. Ed. Engl., 1963, 2, 565; (b)
4
5
C. Zhou, J. Zhang, P. Liu, J. Xie and B. Dai, RSC Adv., 2015, 5,
6661-6665.
L. D. Pachón, J. H. van Maarseveen, G. Rothenberg, Adv.
Synth. Catal., 2005, 347, 811; (c) G. Molteni, C. L. Bianchi, G.
Marinoni, N. Santo, A. Ponti, New J. Chem., 2006, 30, 1137;
(d) A. Sarkar, T. Mukherjee, S. Kapoor, J. Phys. Chem. C.,
2008, 112, 3334; (e) D. Raut, K. Wankhede, V. Vaidya, S.
Bhilare, N. Darwatkar, A. Deorukhkar, G. Trivedi, M.
Salunkhe, Catal. Commun., 2009, 10, 1240; (f) P. Cintas, A.
Barge, S. Tagliapietra, L. Boffa, G. Cravotto, Nat. Protoc.,
2010, 5, 607; (g) E. D. Pressly, R. J. Amir, C. J. Hawker, J.
Polym. Sci., Part A: Polym. Chem., 2011, 49, 814.
(a) S. Quader, S. E. Boyd, I. D. Jenkins, T. A. Houston, J. Org.
Chem., 2007, 72, 1962; (b) P. Appukkuttan, W. Dehaen, V. V.
Fokin, E. Van der Eycken, Org. Lett., 2004, 6, 4223.
(a) W. Xi, T. F. Scott, C. J. Kloxin and C. N. Bowman, Adv.
Funct. Mater., 2014, 24, 2572; (b) W. Tang and M. L. Becker,
Chem. Soc. Rev., 2014, 43, 7013; (c) X. Xiong and H. Chen,
Chin. J. Org. Chem., 2013, 33, 1437; (d) P. Thirumurugan, D.
Matosiuk and K. Jozwiak, Chem. Rev., 2013, 113, 4905; (e) G.
C. Tron, T. Pirali, R. A. Billington, P. L. Canonico, G. Sorba and
A. A. Genazzani, Med. Res. Rev., 2008, 28, 278; (f) M. K.
Singh, R. Tilak, G. Nath, R. S. K. Awasthi and A. Agarwal, Eur.
J. Med. Chem., 2013, 63, 635–644; (g) M. Whiting, J.
Muldoon, Y. C. Lin, S. M. Silverman, W. Lindstrom, A. J.
Olson, H. C. Kolb, M. J. Fine, K. B. Sharpless, J. H. Elder and V.
V. Fokin, Angew. Chem., Int. Ed., 2006, 45, 1435–1439; (h) Z.
Ke, H. F. Chow, M. C. Chan, Z. Liu and K. H. Sze, Org. Lett.,
2012, 14, 394– 397; (i) Y. Hua and A. H. Flood, Chem. Soc.
Rev., 2010, 39, 1262–1271.
9
10 For some selected examples, see: (a) A. Marra, A. Vecchi, C.
Chiappe, B. Melai, A. Dondoni, J. Org. Chem., 2008, 73, 2458;
(b) S. Ozçubukçu, E. Ozkal, C. Jimeno, M. A. Pericas, Org.
Lett., 2009, 11, 4680; (c) I. Cano, M. C. Nicasio, P. J. P´ erez,
6
(a) V. Aucagne, D. A. Leigh, Org. Lett., 2006, 8, 4505; (b) P.
Siemsen, R. C. Livingston, F. Diederich, Angew. Chem., Int.
Ed., 2000, 39, 2632.
Org. Biomol. Chem., 2010,
Dıez, J. Gimeno, Green Chem., 2010, 12, 2127; (e) T. R. Chan,
R. Hilgraf, K. B. Sharpless, V. V. Fokin, Org. Lett., 2004,
8, 536; (d) J. Garcıa-Álvarez, J.
6
,
2853; (f) W. G. Lewis, F. G. Magallon, V. V. Fokin, M. G. Finn,
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 11
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Please do not adjust margins
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DOI: 10.1039/C6RA13314B
ARTICLE
J. Am. Chem. Soc., 2004, 126, 9152; (g) V. O. Rodionov, S. I.
Journal Name
29 X. Jia, W. Qian, D. Wu, D. Wei, G. Xu, X. Liu, Colloids Surf., B,
2009, 68, 231–237.
Presolski, S. Gardinier, Y. H. Lim, M. G. Finn, J. Am. Chem.
Soc., 2007, 129, 12696; (h) V. O. Rodionov, S. I. Presolski, D.
Diaz Diaz, V. V. Fokin, M. G. Finn, J. Am. Chem. Soc., 2007,
129, 12705; (i) S. Dı´ez-Gonza´lez, S. P. Nolan, Angew. Chem.
Int. Ed., 2008, 47, 8881; (j) S. Dı´ez-Gonza´lez, Catal. Sci.
30 (a) Sh. Mohammeda, A. K. Padala, B. A. Dar, B. Singh, B.
Sreedhar, R. A. Vishwakarma, S. B. Bharate, Tetrahedron,
2012, 68, 8156-8162; (b) Y. Jiang, Duanyang Kong, J. Zhao,
W. Zhang, W. Xu, W. Li, G. Xu, Tetrahedron Lett., 2014, 55
2410–2414.
,
Technol., 2011, 1, 166; (k) S. Guo, M. H. Lim, H. V. Huynh,
Organometallics, 2013, 32, 7225; (l) H. D. Velázquez, Y. R.
García, M. Vandichel, A. Madder, F. Verpoort, Org. Biomol.
Chem., 2014, 12, 9350.
31 J. Cadman, S. Zhou, Y. Chen, W. Li, R. Appleyard, Q. Li, Acta
Mech. Sin., 2010, 26, 27-35.
32 B. Plavsic, S. Kobe and B. Orel, KZLTET, 1999, 33, 517.
33 C. Sarkar and S. K. Dolui, RSC Adv., 2015, 5, 60763.
34 R. E. Loehman, in Characterization of Ceramics, ed. R. E.
Loehman and L. E. Fitzpatrick, Momentum Press, LLC, New
York, 2010,
35 H. X. Siyang, H. L. Liu, X. Y. Wu and P. N. Liu, RSC Adv., 2015,
, 4693.
36 L. Huang, W. Liu, J. Wu, Y. Fu, K. Wang, C. Huo and Z. Du,
Tetrahedron Lett., 2014, 55, 2312–2316.
37 F. Matloubi Moghaddam and S. E. Ayati, RSC Adv., 2015, 5,
3894.
38 S. P. Anil Kumar, K. H. V. Reddy, B. Madhav, K. Ramesh and Y.
V. D. Nageswar, Tetrahedron Lett., 2012, 53, 4595–4599.
39 X. Xiong and L. Cai, Catal. Sci. Technol., 2013, 3, 1301–1307.
40 H. Sharghi, R. Khalifeh and M. M. Doroodmand, Adv. Synth.
Catal., 2009, 351, 207.
41 C. S. Radatz, L. d. A. Soares, E. f. R. Vieira, D. Alves, D.
11 (a) R. Huisgen, G. Szeimies, L. Moebius, Chem. Ber. 1965, 98
,
4014; (b) R. Huisgen, Pure Appl. Chem. 1989, 61, 613.
12 (a) M. L. Kantam, V. S. Jaya, B. Sreedhar, M. M. Rao, B. M.
Choudary, J. Mol. Catal. A: Chem., 2006, 256, 273. (b) T.
Katayama, K. Kamata, K. Yamaguchi, N. Mizuno,
6, p. 107.
ChemSusChem., 2009, 2, 59.
5
13 A. Coelho, P. Diz, O. Caamaño, E. Sotelo, Adv. Synth. Catal.,
2010, 352, 1179.
14 C. Girard, E. Nen, M. Aufort, S. Beauvire, E. Samson, J.
Herscovici, Org. Lett., 2006, 8, 1689.
15 (a) S. Chassaing, A. S. S. Sido, A. Alix, M. Kumarraja, P. Pale, J.
Sommer, Chem. Eur. J., 2008, 14, 6713; (b) S. Chassaing, M.
Kumarraja, A. S. S. Sido, P. Pale, J. Sommer, Org. Lett., 2007,
9, 883.
16 B. H. Lipshutz, B. R. Taft, Angew. Chem. Int. Ed., 2006, 45
8235.
,
17 K. Yamaguchi, T. Oishi, T. Katayama, N. Mizuno, Chem. Eur.
J., 2009, 15, 10464.
18 T. Miao, L. Wang, Synthesis, 2008, 3, 363.
19 I. Jlalia, H. Elamari, F. Meganem, J. Herscovici, C. Girard,
Tetrahedron Lett., 2008, 49, 6756.
20 A. Megia-Fernandez, M. Ortega-Muñoz, J. Lopez-Jaramillo, F.
Hernandez-Mateo, F. Santoyo-Gonzalez, Adv. Synth. Catal.,
2010, 352, 3306.
21 I. S. Park, M. S. Kwon, Y. Kim, J. S. Lee, J. Park, Org. Lett.,
2008, 10, 497.
22 (a) A. N. Prasad, B. M. Reddy, E. Y. Jeong, S. E. Park, RSC Adv.,
Russowsky and P. H. Schneider, New J. Chem., 2014, 38
1410–1417.
,
42 I. Billault, F. Pessel, A. Petit, R. Turgisa, M-Ch. Scherrmann,
New J. Chem., 2015, 39, 1986-1995.
43 M. Boominathan, N. Pugazhenthiran, M. Nagaraj, Sh.
Muthusubramanian, S. Murugesan, N. Bhuvanesh, ACS
Sustainable Chem. Eng., 2013, 1, 1405−1411.
44 X. Meng, X. Xu, T. Gao, B. Chen, Eur. J. Org. Chem., 2010,
2010, 5409–5414.
2014,
Baghbanian, R. Hosseinzadeh, M. Tajbakhsh, New J. Chem.
4, 29772; (b) M. Tajbakhsh, M. Farhang, S. M.
,
2015, 39, 1827-1839; (c) K. Namitharan, M. Kumarraja, K.
Pitchumani, Chem. Eur. J., 2009, 15, 2755; (d) N. Mukherjee,
S. Ahammed, S. Bhadra, B. C. Ranu, Green Chem., 2013, 15
389; (e) Y. Masuyama, K. Yoshikawa, N. Suzuki, K. Hara and
A. Fukuoka, Tetrahedron Lett., 2011, 52 6916; (f) R.
Jahanshahi and B. Akhlaghinia, RSC Adv., 2016, , 29210.
, 49849-
,
,
6
23 S. S. E. Ghodsinia, B. Akhlaghinia. RSC Adv., 2015,
5
49860.
24 (a) N. Razavi and B. Akhlaghinia, RSC Adv., 2015, 5, 12372; (b)
M. Zarghani and B. Akhlaghinia, Appl. Organomet. Chem.,
2015, 29, 683; (c) Z. Zarei and B. Akhlaghinia, Chem. Pap.,
2015, 69, 1421; (d) M. Zarghani and B. Akhlaghinia, RSC Adv.,
2015,
Chem., 2016, 40, 477; (f) R. Jahanshahi and B. Akhlaghinia,
RSC Adv., 2015, , 104087; (g) N. Yousefi Siavashi, B.
5, 87769; (e) N. Razavi and B. Akhlaghinia, New J.
5
Akhlaghinia and M. Zarghani, Res. Chem. Intermed., 2016,
42, 5789-5806; (h) E. Karimian, B. Akhlaghinia and S. S. E.
Ghodsinia, J. Chem. Sci., 2016, 128, 429; (i) M. Zarghani and
B. Akhlaghinia, RSC Adv., 2016, 6, 31850-31860.
25 J. D. Birchall and N. L. Thomas, J. Mater. Sci., 1983, 18, 2081.
26 S. Vogel, J. Biosci., 2006, 31, 309.
27 J. Cadman, Y. Chen, Sh. Zhou and Q. Li, Adv. Mater. Res.,
2010, 123, 295.
28 N. Jothi and R. Kunthavai Nachiyar, Global J. Biotechnol.
Biochem., 2013, 8, 33.
12 | J. Name., 2012, 00, 1-3
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Graphical Abstract
Direct access to stabilized CuI using cuttlebone
as a green-reducing support for efficient
CuAAC click reactions in water
Sara S. E. Ghodsinia, Batool Akhlaghinia,* Roya Jahanshahi
Cuttlebone@CuCl2 as a highly active, versatile and green heterogeneous catalyst for the efficient preparation of 1,4-
disubstituted 1,2,3-triazoles through one-pot Huisgen 1,3-dipolar cycloaddition reaction in water, was investigated. This
approach does not require additional reducing agent, since cuttlebone as a green reducing platform can reduce CuII to the click-
active stabilized CuI.