Polystyrene resin-supported CuI-cryptand 22 complex: A highly efficient and reusable catalyst for three-component synthesis of 1,4-disubstituted 1,2,3-triazoles under aerobic conditions in water

Article abstract of DOI:10.1016/j.tet.2014.09.092

Polystyrene resin-supported copper(I) iodide-cryptand-22 complex (PS-C22-CuI) was synthesized and characterized by FT-IR, EDX, SEM, XPS, and TG-DTA analysis. This complex was found to be a highly active and robust heterogeneous catalyst for either three-component reaction of organic halides, sodium azide, and terminal alkynes, or the reaction of organic azides and alkynes to form 1,4-disubstituted 1,2,3-triazoles in good to excellent yields at room temperature, using water as the green solvent. The catalyst can be not only easily isolated from the final product by filtration but also reused without significant loss of catalytic activity.

Full text of DOI:10.1016/j.tet.2014.09.092

Tetrahedron xxx (2014) 1e8
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Polystyrene resin-supported CuI-cryptand 22 complex: a highly
efficient and reusable catalyst for three-component synthesis of
1,4-disubstituted 1,2,3-triazoles under aerobic conditions in water
*
Barahman Movassagh , Nasrin Rezaei
Department of Chemistry, K. N. Toosi University of Technology, P. O. Box 16315-1618, Tehran, Iran
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 29 May 2014
Received in revised form 19 September 2014
Accepted 29 September 2014
Available online xxx
Polystyrene resin-supported copper(I) iodide-cryptand-22 complex (PSeC22eCuI) was synthesized and
characterized by FT-IR, EDX, SEM, XPS, and TG-DTA analysis. This complex was found to be a highly active
and robust heterogeneous catalyst for either three-component reaction of organic halides, sodium azide,
and terminal alkynes, or the reaction of organic azides and alkynes to form 1,4-disubstituted 1,2,3-
triazoles in good to excellent yields at room temperature, using water as the green solvent. The cata-
lyst can be not only easily isolated from the final product by filtration but also reused without significant
loss of catalytic activity.
Keywords:
1,2,3-Triazoles
Ó 2014 Elsevier Ltd. All rights reserved.
Polymer-supported cryptand-22
Heterogeneous catalysis
Three-component reaction
Terminal alkyne
1. Introduction
situ reduction of Cu(II).11,13e16 On the other hand, heterogeneous
catalytic systems can have advantages, such as more surface area
1,2,3-Triazoles have recently received a considerable amount of
resulting higher loading of the active sites, simpler isolation of the
interest in organic synthesis and industry. They have been used in
reaction products and recycling of the catalyst systems by filtra-
1
17,18
combinatorial chemistry, pharmaceuticals (drug discovery), opti-
tion.
Cu(I) AAC catalysts have been immobilized onto various
cal brighteners,2 dyes, agrochemicals, the synthesis of macro-
3
4
supports, such as zeolites, polymers, silica-supported N-het-
erocyclic carbene, activated charcoal, alumina, and titanium
19
20
5
6
21
22
23
molecular architectures, and biologically active agents. The 1,2,3-
triazole core is a key structural motif in many bioactive compounds,
exhibiting a wide range of activities, such as anti-HIV, anti-mi-
2
4
dioxide. However, heterogeneous catalysts immobilized with
Cu(I) species frequently suffer from its inherent thermodynamic
instability, which results in its easy oxidation to Cu(II) and/or dis-
proportionation to Cu(0) and Cu(II). Moreover, the use of copper(I)
iodide has been avoided in many cases, because the in situ formed
copper(I) acetylides derived from CuI undergo homocoupling upon
exposure to air, yielding side products (Glaser coupling); besides,
the copper(I) acetylides are formed with extremely high reactivity
and explosive nature in open air.
7
8
9
10
crobial, anti-allergic, and anti-convulsant.
The Huisgen 1,3-dipolar cycloaddition reaction between a ter-
minal alkyne and an azide to generate substituted 1,2,3-triazoles is
one of the most extensively studied click reactions to date. The
formation of triazoles in ‘click chemistry’ has represented definitive
advances: high yield and selectivity, optimal atom economy, the
possibility of the application of solvents like water, and gentle re-
action conditions. Usually, 1,4-disubstituted 1,2,3-triazoles are
formed by stepwise cycloaddition of azides and terminal alkynes in
2
5
2
6,27
Consequently, using Cu(I)
catalysts requires an inert atmosphere and anhydrous solvents.
Nevertheless, nitrogen- or phosphorus-based ligands are known to
protect the metal center from oxidation and disproportionation.
The use of these ligands usually causes an enhancement of
11
the presence of copper catalysts. When the reaction is performed
12
with a ruthenium catalyst, the 1,5-adduct is preferred instead. In
homogeneous regiospecific alkyne-azide cycloaddition (AAC) re-
actions, the catalyst can be introduced as either a Cu(I) salt, or in
17
cuprousecatalytic activity. Very recently, as part of our attempts
to identify a robust and easily prepared system to catalyze car-
bonecarbon and carbon-heteroatom bond-forming reactions of
terminal alkynes, we demonstrated that the complexes of Pd(II)
and Cu(I) with the commercially available diazacrown ether,
*
Corresponding author. Tel.: þ98 21 23064323; fax: þ98 21 22853650; e-mail
Ò
addresses: movassagh@kntu.ac.ir, bmovass1178@yahoo.com (B. Movassagh).
1,4,10,13-tetraoxa-7,16-diazacyclooctadecane (Kryptofix 22 or
http://dx.doi.org/10.1016/j.tet.2014.09.092
0
040-4020/Ó 2014 Elsevier Ltd. All rights reserved.
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2
B. Movassagh, N. Rezaei / Tetrahedron xxx (2014) 1e8
cryptand-22) operate as active homogeneous catalysts under aer-
nitrogen atoms and the Cu(I) ion (Fig. 1c). The SEM images of the
polymer-anchored ligand (PSeC22) and its copper(I) complex
clearly show the morphological change, which occurred on the
surface of the polymer matrix after loading of the metal (Fig. 2).
EDX data also supports the metal attachment on the surface of
polymer matrix with energy bands of 8.04, 8.90 KeV (K lines) and
0.93 KeV (L line) (Fig. 3). Moreover, the copper loading of polymer-
anchored Cu(I) complex, as determined by inductively coupled
plasma (ICP) was obtained to be 1.1% (0.17 mmol/g). The X-ray
diffraction (XRD) pattern of the catalyst did not show any signifi-
cant peak for the metal due to the low copper loading weight or the
obic conditions.2
8e30
We thought that the flexible macrocyclic and
chelating effect of such N- and O-containing ligand may assist in
stabilizing the reactive palladium and copper intermediates. In an
effort to find an efficient catalyst for Cu(I) AAC reaction, here, we
introduce the heterogeneous, recyclable, heat- and air-stable Cu(I)
complex (PSeC22eCuI).
The utilization of multi-component reactions (MCRs) to syn-
thesize novel chemicals, drug-like scaffolds, and natural product
compounds has pervaded in organic transformations.3
1,32
This is
due to the fact that these products can be prepared directly in
a single step and diversity can be achieved simply by varying the
reaction substrates.33
4
0
small crystal domains. Further evidence for the attachment of C22
and metal on to the polymeric support is confirmed by X-ray
photoelectron spectroscopy (XPS) of the complex (Fig. 4). The peaks
at 282.2, 399.7, and 530.9 eV are attributed to C, N, and O, atoms,
respectively; Cu2p3/2 and 2p1/2 peaks appeared at 931.6 and
Due to their versatile processing capabilities and ease of sepa-
ration and recycling, polymer-supported catalysts offer many ad-
vantages for industrial applications. These catalysts can prevent the
contamination of the ligand residue in the products. Chlor-
omethylated polystyrene is one of the most widely studied het-
erogeneous supports, because it is sufficiently flexible with good
catalytic activity. Polymer-supported ligands, such as 1-nitroso-2-
18,41
952.7 eV, respectively (inset).
Thermogravimetric-differential
thermal analysis (TG-DTA) showed that the polymer-anchored
ꢁ
Cu(I) complex was stable up to 428 C (Fig. 5).
naphthol,34 ethylenediamine,
35
N-heterocyclic carbenes,
36
2-
37
38
2.2. Catalytic performance of PSeC22eCuI catalyst for the
synthesis of triazoles from organic azides and terminal
alkynes
aminophenanthroline, anthranilic acid, and macrocyclic Schiff
base that can form effective complexes with transition metals
Pd, Zn, Cd) have been utilized in the Sonogashira, Heck and Suzuki
3
9
(
cross-coupling reactions.
Our initial investigation was focused on the catalytic activity of
C22-functionalized polystyrene resin-supported Cu(I) complex 2 in
the Cu AAC synthesis of triazoles. Therefore, we chose benzyl azide
and phenylacetylene as model substrates, and examined their re-
action in the presence of PSeC22eCuI complex (0.2 mol %) under
various aerobic conditions (Table 1, entries 1e14). The reaction
rates were markedly dependent on the solvent and the catalyst
We now wish to report a new reusable and efficient heteroge-
neous polystyrene resin-supported copper(I) iodide cryptand-22
complex (PSeC22eCuI) for the synthesis of 1,4-disubstituted
1,2,3-triazoles either from organic azides and terminal alkynes or
from organic halides, sodium azide, and terminal alkynes in water
at room temperature.
t
loading. When solvents, such as DMSO, DMF, EtOH, BuOH, and
2
2
. Results and discussion
even solvent-less condition were used, moderate to good yields of
the cyclization products were obtained (Table 1, entries 1e5). When
organic/aqueous mixed solvents were used, a slight boost in the
product yields was observed (Table 1, entries 6e7). Finally, to our
delight, the reaction showed a good compatibility when water was
used as the solvent. Then, different catalyst loadings between 0.1
and 0.5 mol % were investigated for the reaction (Table 1, entries
9e12). Among the various catalyst loadings, 0.3 mol % of the cata-
lyst was found to be the best (Table 1, entry 10). To find out if the in
situ formation of PSeC22/CuI in the reaction vessel would drive the
reaction, the reaction was also performed in the presence of CuI
(0.3 mol %) and PSeC22 (40 mg); stirring the reaction mixture for
10 h under the same reaction conditions produced the corre-
sponding product in 18% yield (Table 1, entry 13). Also, the above
cycloaddition reaction was performed using CuI (0.003 mmol,
0.3 mol %) and C22 ligand (0.006 mmol, 0.6 mol %); the corre-
sponding triazole was obtained in 23% yield under the same re-
action conditions (Table 1, entry14). Therefore, we decided to use
.1. Synthesis and characterization of PSeC22eCuI catalyst
First, polymer-bound C22 (PSeC22) 1 was easily prepared by
treating chloromethylated polystyrene (containing 6.2 wt % of Cl
per gram of resin, 1.75 mmol/g Cl) with an appropriate amount of
cryptand-22 in Et O at room temperature for 24 h (Scheme 1); the
2
PSeC22 ligand was characterized by elemental analysis. The ni-
trogen content of this resin was 1.95% (1.39 mmol/g), indicating that
only 40% of all the chlorine atoms were replaced by amine groups.
The presence of the C22 ligand on the polystyrene was also con-
firmed by FT-IR spectra with disappearance of the CeCl peak at
3
5
ꢀ1
2
1263 cm (due to eCH Cl groups) of the starting polymer and
ꢀ
1
appearance of a sharp band around 3457 cm due to the NeH
vibrations (Fig. 1aeb). Then, C22-functionalized polystyrene resin-
supported CuI (PSeC22eCuI) complex 2 was prepared by the
treatment of the resulting PSeC22 with a solution of copper(I) io-
dide in refluxing EtOH for 24 h (Scheme 1). This catalyst was
characterized by FT-IR, EDX, SEM, XPS, and TG-DTA. FT-IR spectrum
2
H O as solvent and 0.3 mol % PSeC22eCuI catalyst as the optimal
conditions in further studies.
To examine the scope of the Huisgen [3þ2] cycloaddition of
alkynes and organic azides, a variety of terminal alkynes reacted
with organic azides smoothly and generated the corresponding
ꢀ
1
of the complex 2 showed a
frequency than that observed for the free ligand in PSeC22
y
NeH stretch at 3446 cm , a lower
ꢀ1
(
3457 cm ), indicating a coordination between the cryptand
H
N
PS
PS
N
N
O
O
O
O
Et O
2
O
O
O
O
CuI
O
O
O
I
O
PS
CH
Cl
+
Cu
2
EtOH
N
H
N
H
N
H
1
2
Scheme 1. Preparation of the PSeC22eCuI.
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B. Movassagh, N. Rezaei / Tetrahedron xxx (2014) 1e8
3
Fig. 1. FT-IR spectra of (a) chloromethylated polystyrene, (b) polymer-supported C22 (PSeC22), and (c) PSeC22eCuI complex.
Fig. 2. SEM images of the PSeC22 ligand (a), and the PSeC22eCuI (b).
Fig. 3. EDX spectra of PSeC22 (a) and PSeC22eCuI complex (b).
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4
B. Movassagh, N. Rezaei / Tetrahedron xxx (2014) 1e8
2
2
1
1
500
000
500
000
O 1s
850
931.6
C 1s
952.7 eV
8
7
7
6
00
50
00
50
9
25 935 945 955 965
Cu 2p
5
00
0
N 1s
400
-200
0
200
600
800
1000
1200
1400
Binding Energy (eV)
Fig. 4. XPS spectrum of PSeC22eCuI with expansion (inset).
Fig. 5. TG-TDA curves of PSeC22 (a) and PSeC22eCuI complex (b).
1
2
,4-disubstituted-1,2,3-triazoles in high to excellent yields (Table
). The results indicated that primary, secondary, and tertiary
15e21). It was found that water is the suitable solvent, which gives
the best result for the one-pot three-component click reaction in
the presence of 0.6 mol % of PSeC22eCuI catalyst (Table 1, entry
18). Under these optimized reaction conditions, the generality and
scope of this one-pot three-component protocol was explored,
using various alkyl halides (benzylic, primary, secondary, and ter-
tiary) and terminal alkynes (aliphatic and aromatic). The results are
summarized in Table 2. As shown in Table 2, a range of structurally
diverse alkyl halides (chlorides, bromides, and iodides), such as
benzylic, primary, secondary, and tertiary, as well as phenacyl ha-
lides were examined and coupled with different terminal alkynes.
In most cases, the three-component reaction proceeded smoothly
in water to give the corresponding 1,2,3-triazoles in good to high
yields, and only 1,4-regioisomers were detected as the products.
However, in some cases, the one-pot reaction gave lower yields
than those expected (Table 2, entries 4e6 and 14e16). This was
attributed to lower miscibility of the substrates in water at room
aliphatic as well as the traditional benzylic azides coupled with
aromatic and aliphatic alkynes to generate a range of triazoles.
Generally, the more electron-rich azides reacted with the high-
ꢁ
est efficiency [benzyl (entries 1, 3, 11, 13, 16) ꢂ1 alkyl (entries 6
ꢁ
ꢁ
and 14) >2 alkyl (entry 4) >3 alkyl (entries 5 and 15)]. The
exceptions in this trend are phenacyl azides (Table 2, entries 7
and 8). Among alkynes, phenylacetylene reacted slightly better
than other terminal alkynes. The system also proved robust to-
ward alcohol-substituted alkyne, propargyl alcohol (Table 2,
entry 9).
2
.3. Catalytic one-pot three-component synthesis of triazoles
To further improve the utility and user friendliness of
PSeC22eCuI-catalyzed synthesis of triazoles, we developed its
practical one-pot three-component variant described herein. The
azides are generated in situ from corresponding halides, where-
upon they are captured by copper(I) acetylides forming the corre-
sponding 1,4-disubstituted 1,2,3-triazoles.
We initially carried out the standard three-component click
reaction of benzyl bromide and sodium azide with phenylacetylene
in water to investigate the role of solvents and the catalyst loading
using PSeC22eCuI as heterogeneous catalyst (Table 1, entries
2
temperature; therefore, when DMSO/H O (1:2) was used as solvent
in the reactions, a significant boost in product yields was observed.
A comparative study of the reaction conditions and results for
copper-catalyzed reactions of: (i) benzyl azide with phenyl-
acetylene, and (ii) benzyl bromide, phenylacetylene, and sodium
azide using other methods and those reported in this work is given
in Table 3, which clearly demonstrates the advantages of the
present methodology.
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B. Movassagh, N. Rezaei / Tetrahedron xxx (2014) 1e8
5
Table 1
Table 3
Influence of different reaction parameters on the PSeC22eCuI-catalyzed click
reaction
Comparison of the reaction conditions and results for the copper-catalyzed click
reaction
Ph
Ph
+ Ph
N
Entry Catalyst (mol %)
Condition
Time/temp.
( C)
Yield Ref.
(%)
3
N
ꢁ
Ph
N
Catalyst
N
a
46
1
2
3
4
Cu/CR11 (12)
Cu/CR20 (7)
Neat/NEt
3
4 h, 70
4 h, 70
10 min, r.t.
98
Solvent, r.t.
a
Br + NaN
3
Neat
93
100
+
Ph
Ph
a
t
47
ZnOeCuO (3)
H
2
O/ BuOH (2:1)
Entry
Catalyst
2a
2
2
2
2
2
2
2
2
2
2
Mol % of Cu
Solvent
Yield (%)c
Ultrasonic
CuOeCeO b
Amberlite-supported 65 min, reflux 91
azide/EtOH
48
2
1
2
3
4
5
6
7
8
9
0.2
0.2
0.2
0.2
0.2
0.2
0.2
0.2
0.1
0.3
0.4
0.5
0.3
0.3
0.2
0.4
0.5
0.6
0.8
0.6
0.6
d
58
78
68
69
71
83
75
84
73
99
99
99
18
23
56
63
86
99
99
99
81
a
DMSO
DMF
O (10)a
43
CuSO
4
$5H
2
H
H
2
O/N
O/N
2
H
H
4
4
45 min, r.t.
4 h, r.t.,
then 1 h
100
3 h, 70
1 h, r.t.
4 h, r.t.
95
81
a
2
2
a
t
BuOH
a
EtOH
O (10)b
CuSO
4
$5H
2
a
H
2
H
2
H
2
H
2
H
2
H
2
H
2
H
2
H
2
H
2
H
2
H
2
H
2
H
2
H
2
H
2
O/DMSO (2:1)
O/DMF (2:1)
b
40
41
49
5
6
7
Cu NP/C (0.5)
H
2
O
98
96
97
a
(10)b
Cu/Al
CuI (15)
2
O
3
b
Ball-milling/neat
[bmim][BF ]/H O/
-Proline/Na CO
a
O
O
O
O
O
O
O
O
O
O
O
O
4
2
a
L
2
3
a
10
11
12
13
14
15
16
17
18
19
20
21
PS-eC22eCuI (0.3)a
8
H
H
2
O
O
10 h, r.t.
15 h, r.t.
99 This
99 work
a
2
a
2
PSeC22eCuI (0.6)b
1/CuIa
a
a
Reaction of benzyl azide with phenylacetylene.
Three-component reaction of the benzyl bromide, phenylacetylene and NaN3.
C22/CuI
2
2
2
2
2
2
2
b
b
b
b
methods of synthesizing triazoles, using the reaction of benzyl
azide with phenylacetylene (0.3 mol % of the catalyst), and one-pot
three-component reaction from benzyl bromide, phenylacetylene,
and sodium azide (0.6 mol % of catalyst). In both methods, the
catalyst was separated from the reaction mixture by filtration after
each experiment, then washed with water and ethyl acetate, and
air-dried carefully before being used in subsequent runs. As shown
in Fig 6, it was found that while the product (5a) yield, which was
prepared by benzyl azide decreased slightly over four recycling
runs, a sharp fall in yield ending up in 71%, was observed when one-
pot three-component reaction was followed (Fig. 6).
b
b
b
O/DMSO (2:1)
O/DMF (2:1)
b
Two results in bold values signify the best optimized conditions in the two exper-
iments, (two- and three-components).
Azideealkyne reaction conditions: benzyl azide (1 mmol), phenylacetylene
1 mmol) and catalyst in solvent (3 mL) at room temperature for 10 h in air.
Three-component reaction conditions: benzyl bromide (1 mmol), NaN 1.1.
3
mmol), phenyacetylene (1 mmol) and catalyst in solvent (3 mL) at room tempera-
ture for 15 h in air.
a
(
b
c
Isolated yields.
Table 2
a
PSeC22eCuI-catalyzed synthesis of 1,2,3-triazoles
R1
N
PS-C22-CuI (0.3 mol%)
O, r.t.
PS-C22-CuI(0.6 mol%)
1
R2
N
R N
N
1
2
3
+
R X + R
+
NaN3
H
2
2
H O, r.t.
3
4
R2
5
Entry
R1
X
R2
Product
Yield (%)b
Two component
Three component/time (h)
7
1
2
3
4
5
6
7
8
9
PhCH
PhCH
2
Br
Cl
Br
Br
Br
I
Cl
Br
Br
Cl
Br
Cl
Br
I
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
CH
CH
5a1
99
d
99/15
98/15
96/16
57 (84) /20
45 (78) /20
17
2
5a
5b
44
p-NO
Cyclohexyl
1-Adamantyl
n-C
PhCOCH
p-BrC
2
C
6
H
4
CH
2
98
88
81
97
86
82
78
d
1
7
c
5c
11
c
5d
4
4
c
8
H
17
5e
5f
62 (93) /21
4
2
2
82/17
81/17
73/20
68/20
85/17
83/17
91/17
61 (91) /21
56 (73) /21
61 (84) /20
42
6
H
4
COCH
2
5g
5h
5h
4
4
3
3
PhCH
PhCH
PhCH
PhCH
2
2
2
2
2
OH
OH
10
11
12
13
14
15
16
2
4
4
CO
2
CO
2
CO
2
CO
2
CO
2
CH
CH
CH
CH
CH
3
5i
5i
5j
93
d
4
4
4
4
3
3
3
3
p-NO
n-C
1-Adamantyl
PhCH
2
C
6
H
4
CH
2
97
93
78
92
44
c
8
H
17
5k
4
5
c
Br
Br
5l
41
c
2
n-C
H
4 9
5m
a
Two component reaction conditions: organic azide (1 mmol), alkyne (1 mmol), PSeC22eCuI (0.3 mol %), H
2
O (3 mL) at room temperature for 10 h under aerial atmosphere;
Three-component reaction conditions: Alkyl halide (1 mmol), NaN
3
(1.1 mmol), alkyne (1 mmol), catalyst (0.6 mol %), H O (3 mL) at room temperature.
2
b
Isolated yields.
c
2
At room temperature for 20 h, using DMSO/H O (1:2 v/v, 3 mL).
2
.4. Recycling of the catalyst
3. Conclusion
The recyclability of heterogeneous catalysts is a very important
issue, especially for commercial applications. Thus, the feasibility of
repeated use of PSeC22eCuI was also examined for the two
We have demonstrated that the polystyrene-anchored crypt-
and-22 copper(I) iodide, PSeC22eCuI, complex is a highly efficient
and reusable catalyst for the alkyne-azide cycloaddition (AAC)
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6
B. Movassagh, N. Rezaei / Tetrahedron xxx (2014) 1e8
atmosphere. The product formed was filtered off, washed with
ꢁ
EtOH (3ꢃ30 mL) and finally dried in vacuum at 50 C for 24 h.
4.2. General procedure for [3D2] cycloaddition of terminal
alkynes and organic azides
In a 10 mL round-bottom flask, catalyst 2 (20 mg, containing
0
(
.3 mol % of Cu), terminal alkyne (1.0 mmol), organic azide
1.0 mmol), and water (3 mL) were added. The mixture was stirred
at room temperature for 10 h under aerial conditions. Then EtOAc
(
(
5 mL) was added to the mixture, filtered and washed with water
2ꢃ3 mL) and EtOAc (2ꢃ3 mL); the organic layer was separated,
4
dried (MgSO ), and concentrated in vacuum to give the crude
product, which was almost pure.
4
.3. General procedure for the one-pot 3-component syn-
Fig. 6. Recycling activity of the PSeC22eCuI catalyst.
thesis of azides
reactions in water at room temperature. This heterogeneous cata-
lyst can be used for either the Huisgen [3þ2] cycloaddition of al-
kynes and organic azides or one-pot three-component synthesis of
Alkyne (1 mmol), sodium azide (1.1 mmol), organic halide
(1 mmol), and water (3 mL) were placed together in a 10 mL
round-bottom flask. PSeC22eCuI (40 mg, containing 0.6 mol % of
Cu) was then added to the above solution. The suspension was
magnetically stirred for 10 h at room temperature. After com-
pletion of the reaction as followed by TLC, EtOAc (5 mL) was added
to the mixture, filtered, and washed with water (2ꢃ3 mL) and
1,4-disubstituted 1,2,3-triazoles from alkynes, sodium azide, and
alkyl halides at room temperature in water. The catalyst is easily
separated and can be recycled for four runs. Simple preparation of
the complex, oxygen insensitivity, low catalyst loading, and excel-
lent catalytic performance in aqueous media make it a good het-
erogeneous system and a useful alternative to other heterogeneous
copper catalysts.
EtOAc (2ꢃ3 mL). The organic phase was separated, dried (MgSO ),
4
and concentrated in vacuum to give the crude product that was
further purified by recrystallization with ethanol/water (3:1 v/v).
In the case of triazole 5h, after completion of the reaction, water
was evaporated and EtOAc (5 mL) was added. The mixture was
filtered to separate the catalyst and the filtrate was concentrated
under vacuum to obtain the desired product, which was almost
pure.
4
. Experimental section
All chemicals were commercial reagent grades and purchased
from Merck and Aldrich. Chloromethylated polystyrene (CM PS)
resin cross-linked with 1% DVB (70e90 mesh, 1.5e2.0 mmol/g of Cl)
was purchased from Aldrich. XPS (X-ray photoelectron spectros-
copy) data was recorded with 8025-BesTec twin anode XR3E2 X-ray
source system. Thermogravimetric-diffraction thermal analysis
All compounds were characterized by IR, 1H and 13C NMR
spectroscopy.
17
4.3.1. 1-Benzyl-4-phenyl-1H-1,2,3-triazole (5a). White solid; mp
ꢁ
1
(
TG-DTA) was carried out using a thermal gravimetric analysis in-
129e130 C; H NMR (300 MHz, CDCl ):
d
¼7.81 (d, J¼8.5 Hz, 2H),
3
13
strument (NETZSCH TG 209 F1 Iris) with a heating rate of
7.69 (s, 1H), 7.28e7.42 (m, 8H), 5.54 (s, 2H); C NMR (75 MHz,
CDCl ):
¼148.2, 134.7, 130.5, 129.2, 128.84, 128.77, 128.2, 128.1,
125.7, 119.7, 54.2; Calculated for C
N¼17.86%: Found C¼76.48%, H¼5.42%, N¼17.86%.
ꢁ
ꢀ1
1
0 C min . XRD patterns were recorded by an Xpert MPD, X-ray
d
3
1
13
diffractometer using Cu K
a
radiation. H NMR (300 MHz) and
C
15 13 3
H N
C¼76.57%, H¼5.57%,
NMR (75 MHz) spectra were recorded using a Bruker AQS-300
Avance spectrometer. The scanning electron microscopy (SEM)
images were obtained using a scanning electron microscope
VEGAyyTESCAN-LMU. FT-IR spectra were recorded on ABB
Bomem model FTLA 2000 instrument. The Cu content of the
complex was determined using inductively coupled plasma (ICP,
Varian vista-mpx), and surface morphology of the catalyst was
analyzed using Energy-dispersive-X-ray (VEGA, TESCAN-LMU)
equipped with EDX facility. Micro analytical data was collected by
a PerkineElmer, USA, 2400C elemental analyzer.
4.3.2. 1-(4-Nitrobenzyl)-4-phenyl-1H-1,2,3-triazole (5b).44 White
ꢁ
1
solid; mp 158e161 C; H NMR (300 MHz, CDCl ):
3
d
¼8.25 (d,
J¼8.7 Hz, 2H), 7.82 (d, J¼7.5 Hz, 2H), 7.76 (s, 1H), 7.33e7.47 (m, 5H),
1
3
5.71 (s, 2H); C NMR (75 MHz, CDCl ):
3
d
¼148.7, 148.1, 141.7, 130.1,
128.9, 128.54, 128.5, 125.7, 124.4, 119.7, 53.2; Calculated for
C15H12N O C¼64.28%, H¼4.32%, N¼19.99%: Found C¼64.37%,
4 2
H¼4.28%, N¼19.92%.
1
7
4
.3.3. 1-Cyclohexyl-4-phenyl-1H-1,2,3-triazole (5c). White solid;
ꢁ
1
4
.1. Preparation of the polymer-anchored PSeC22eCuI (2)
In a 100 mL round-bottom flask equipped with a magnetic
mp 104e106 C; H NMR (300 MHz, CDCl
H), 7.77 (s, 1H), 7.42 (t, J¼7.3 Hz, 2H), 7.27e7.35 (m, 1H), 4.45e4.55
(m, 1H), 2.26 (d, J¼7.6 Hz, 2H), 1.97 (d, J¼6.0 Hz, 2H), 1.77e1.82 (m,
3
):
d
¼7.83 (d, J¼8.1 Hz,
2
13
stirrer bar, chloromethylated polystyrene resin (2 g, almost
.75 mmol/g of Cl) was allowed to swell in diethyl ether (40 mL) for
4 h; then cryptand-22 (0.65 g, 2.5 mmol) was added to the flask
3H), 1.32e1.52 (m, 3H); C NMR (75 MHz, CDCl
128.8, 127.9, 125.6, 117.3, 60.1, 33.6, 25.20, 25.16; Calculated for
C¼73.98%, H¼7.53%, N¼18.45%: Found C¼73.82%,
H¼7.49%, N¼18.43%.
3
):
d
¼147.3, 130.9,
1
2
14 17 3
C H N
and stirred for 72 h at room temperature. The polymer beads were
filtered and the residue was washed sequentially with diethyl ether
11
(
4ꢃ40 mL), and then dried in an oven to obtain the polymer-
4.3.4. 1-Adamantyl-4-phenyl-1H-1,2,3-triazole (5d). White solid;
ꢁ
1
supported cryptand-22 (1).
mp 218e222 C; H NMR (300 MHz, CDCl
3
):
d
¼7.80 (d, J¼8.2 Hz,
Then, the C22-functionalized polymer (1) was swollen in EtOH
2H), 7.67 (s, 1H), 7.40 (t, J¼8.0 Hz, 2H), 7.27e7.33 (m, 1H), 2.36 (s,
13
(
50 mL) for 1 h; then, CuI (0.42 g, 2.2 mmol) was added and the
6H), 2.10 (s, 3H), 1.73 (s, 6H); C NMR (75 MHz, CDCl ):
3
d
¼148.3,
mixture was heated at reflux in that solvent for 24 h in N
2
130.5, 128.2, 128.1, 125.7, 119.5, 66.9, 49.3, 35.5, 32.6; Calculated for
Please cite this article in press as: Movassagh, B.; Rezaei, N., Tetrahedron (2014), http://dx.doi.org/10.1016/j.tet.2014.09.092

B. Movassagh, N. Rezaei / Tetrahedron xxx (2014) 1e8
7
C
18
H
21
N
3
C¼77.37%, H¼7.58%, N¼15.05%: Found C¼77.21%,
49.3, 35.4, 32.6; Calculated for C14
N¼16.08%: Found C¼64.58%, H¼7.12%, N¼15.84%.
H
19
N
3
O
2
C¼64.35%, H¼7.33%,
H¼7.45%, N¼14.97%.
4
4
4.3.13. 1-Benzyl-4-butyl-1,2,3-triazole (5m).41 White solid; mp
4
.3.5. 1-Octyl-4-phenyl-1H-1,2,3-triazole (5e). White solid; mp
ꢁ
1
ꢁ
1
74e78 C; H NMR (300 MHz, CDCl
3
):
d
¼7.84 (d, J¼8.3 Hz, 2H), 7.75
61e64 C; H NMR (300 MHz, CDCl
3
):
d
¼7.31e7.36 (m, 3H),
(
2
3
1
C
s, 1H), 7.43 (t, J¼7.2 Hz, 2H), 7.30e7.36 (m, 1H), 4.39 (t, J¼7.3 Hz,
7.20e7.23 (m, 3H), 5.45 (s, 2H), 2.66 (t, J¼7.6 Hz, 2H), 1.60 (quin,
13
H), 1.94 (quin, J¼7.0 Hz, 2H), 1.26e1.34 (m, 10H), 0.88 (t, J¼5.9 Hz,
J¼7.3 Hz, 2H), 1.33 (sext, J¼7.4 Hz, 2H), 0.88 (t, J¼7.3 Hz, 3H);
NMR (75 MHz, CDCl ):
¼148.9, 135.0, 129.0, 128.5, 127.9, 120.6,
53.9, 31.5, 25.4, 22.3, 13.8; Calculated for C13
C
13
H); C NMR (75 MHz, CDCl
3
):
d
¼147.7, 130.7, 128.8, 128.1, 125.7,
3
d
19.4, 50.4, 31.7, 30.4, 29.1, 28.97, 26.5, 22.6, 14.1; Calculated for
C¼74.65%, H¼9.01%, N¼16.34%: Found C¼74.87%,
H¼8.92%, N¼16.33%.
17
H N
3
C¼72.52%,
H
16 23
N
3
H¼7.96%, N¼19.52%: Found C¼72.35%, H¼7.83%, N¼19.38%.
Acknowledgements
4
.3.6. 1-Phenyl-2-(4-phenyl-1H-1,2,3-triazol-1yl)-1-ethanone
4
2
ꢁ
ꢀ1
;
(
5f). Pale yellow solid; mp 144e146 C; IR (KBr):
y
¼1700 cm
This work was supported by a research grant from the K. N. Toosi
University of Technology Research Council. We are indebted to Dr.
Sogand Noroozizadeh for editing the English content of the
manuscript.
1
H NMR (300 MHz, CDCl
.37e7.43 (m, 5H), 7.27e7.34 (m, 3H), 5.58 (s, 2H); C NMR
75 MHz, CDCl ):
¼196.8, 148.2, 137.6, 134.7, 132.5, 130.1, 129.2,
28.8, 128.3, 128.1, 125.7, 54.2; Calculated for C16
O C¼72.99%,
H¼4.98%, N¼15.96%: Found C¼73.16%, H¼4.87%, N¼15.85%.
3
): d
¼7.81 (d, J¼8.2 Hz, 2H), 7.67 (s, 1H),
13
7
(
1
3
d
13 3
H N
Supplementary data
4
.3.7. 1-(4-Bromophenyl)-2-(4-phenyl-1H-1,2,3-triazol-1yl)-1-
42
ꢁ
ethanone (5g). Pale yellow solid; mp 179e181 C; IR (KBr):
Supplementary data related to this article can be found at http://
dx.doi.org/10.1016/j.tet.2014.09.092.
ꢀ1 1
y
¼1696 cm ; H NMR (300 MHz, CDCl
3
):
d
¼8.21 (d, J¼8.6 Hz, 2H),
7
.81 (d, J¼8.6 Hz, 2H), 7.76 (s, 1H), 7.40e7.47 (m, 4H), 7.35e7.37 (m,
1
1
H), 5.76 (s, 2H); 13C NMR (75 MHz, CDCl
3
):
37.6, 132.4, 130.1, 128.9, 128.5, 128.4, 128.3, 125.7, 53.2; Calculated
for C16 12BrN
O C¼56.16%, H¼3.53%, N¼12.28%: Found C¼55.94%,
H¼3.46%, N¼12.27%.
d¼196.8, 148.0, 141.8,
References and notes
H
3
1. Hein, C. D.; Liu, X. M.; Wang, D. Pharm. Res. 2008, 25, 2216e2230.
2. Whiting, M.; Muldoon, J.; Lin, Y. C.; Silverman, S. M.; Lindstrom, W.; Olson, A. J.;
Kolb, H. C.; Fine, M. J.; Sharpless, K. B.; Elder, J. H.; Fokin, V. V. Angew. Chem. Int.
Ed. 2006, 45, 1435e1439.
4
3
4
.3.8. (1-Benzyl-1H-1,2,3-triazol-4-yl)methanol (5h). White solid;
3. Lee, T.; Cho, M.; Ko, S. Y.; Youn, H. J.; Baek, D. J.; Cho, W. J.; Kang, C. Y.; Kim, S. J.
ꢁ
ꢀ1 1
mp 74e77 C; IR (KBr):
d
y
¼3263 cm ; H NMR (300 MHz, CDCl
3
):
Med. Chem. 2007, 50, 585e589.
4. Bock, V. D.; Hiemstra, H.; Maarseveen, J. H. V. Eur. J. Org. Chem. 2006, 51e68.
5. Ke, Z.; Chow, H. F.; Chan, M. C.; Liu, Z.; Sze, K. H. Org. Lett. 2012, 14, 394e397.
6. Hua, Y.; Flood, A. H. Chem. Soc. Rev. 2010, 39, 1262e1271.
¼7.46 (s, 1H), 7.31e7.40 (m, 3H), 7.24e7.27 (m, 2H), 5.49 (s, 2H),
13
4
1
.74 (s, 2H), 3.37 (brs, 1H); C NMR (75 MHz, CDCl
3
):
d
¼134.5,
29.1, 128.8, 128.1, 121.8, 56.3, 54.2; Calculated for C10
C¼63.48%, H¼5.86%, N¼22.21%: Found C¼63.73%, H¼5.72%,
H
11
N
3
O
7. Velazquez, S.; Alvarez, R.; Perez, C.; Gago, F.; Clercq, E. D.; Balzarini, J.; Ca-
marasa, M. J. Antivir. Chem. Chemother. 1998, 9, 481e489.
8
. Singh, M. K.; Tilak, R.; Nath, G.; Awasthi, R. S. K.; Agarwal, A. Eur. J. Med. Chem.
013, 63, 635e644.
. Buckle, D. R.; Rockell, C. J. M.; Smith, H.; Spicer, B. A. J. Med. Chem. 1986, 29,
262e2267.
0. Kelley, J. L.; Koble, C. S.; Davis, R. G.; Mclean, E. W.; Soroko, F. E.; Cooper, B. R. J.
N¼22.17%.
2
9
2
4
.3.9. 1-Benzyl-4-methoxycarbonyl-1,2,3-triazole
(5i).44 White
¼1721 cm ; H NMR (300 MHz,
¼7.99 (s, 1H), 7.34e7.36 (m, 3H), 7.25e7.27 (m, 2H), 5.55 (s,
ꢁ
ꢀ1 1
1
solid; mp 104e105 C; IR (KBr):
CDCl ):
H), 3.88 (s, 3H); C NMR (75 MHz, CDCl
11 3 2
29.3, 129.1, 128.3, 127.5, 54.4, 52.2; Calculated for C11H N O
y
Med. Chem. 1995, 38, 4131e4134.
11. Rostovtsev, V. V.; Green, L. G.; Fokin, V. V.; Sharpless, K. B. Angew. Chem. Int. Ed.
3
d
13
2
1
3
):
d
¼161.1, 140.2, 133.7,
2002, 41, 2596e2599.
12. Boren, B. C.; Narayan, S.; Rasmussen, L. K.; Zhang, L.; Zhao, H.; Lin, Z.; Jia, G.;
Fokin, V. V. J. Am. Chem. Soc. 2008, 130, 8923e8930.
C¼60.82%, H¼5.10%, N¼19.34%: Found C¼60.98%, H¼5.02%,
13. Rodionov, V. O.; Presolski, S. I.; Gardinier, S.; Lim, Y. H.; Finn, M. G. J. Am. Chem.
N¼19.27%.
Soc. 2007, 129, 12696e12704.
14. Li, C. J. Chem. Rev. 2005, 105, 3059.
1
5. Rodionov, V. O.; Presolski, S. I.; Diaz, D. D.; Fokin, V. V.; Finn, M. G. J. Am. Chem.
Soc. 2007, 129, 12705e12712.
4
.3.10. 1-(4-Nitrobenzyl)-4-methoxycarbonyl-1,2,3-triazole
4
4
ꢁ
ꢀ1
;
(
5j). Pale yellow solid; mp 188e190 C; IR (KBr):
y
¼1721 cm
16. Wang, D.; Li, N.; Zhao, M.; Shi, W.; Ma, C.; Chen, B. Green. Chem. 2010, 12,
2120e2123.
1
H NMR (300 MHz, DMSO-d
.55 (d, J¼8.6 Hz, 2H), 5.84 (s, 2H), 3.82 (s, 3H); C NMR (75 MHz,
DMSO-d ):
¼160.5, 147.3, 142.8, 138.9, 129.8, 129.2, 123.99, 52.2,
1.9; Calculated for C11
C¼50.38%, H¼3.84%, N¼21.37%:
Found C¼50.90%, H¼3.64%, N¼21.37%.
6
): d
¼8.96 (s,1H), 8.23 (d, J¼8.6 Hz, 2H),
1
1
7. Hudson, R.; Li, C. J.; Moores, A. Green. Chem. 2012, 14, 622e624.
8. Jacob, K.; Stolle, A.; Ondruschka, B.; Jandt, K. D.; Keller, T. F. Appl. Catal. A: Gen.
2013, 451, 94e100.
13
7
6
d
19. Chassaing, S.; Sido, A. S. S.; Alix, A.; Kumarraja, M.; Pale, P.; Sommer, J. Chem.
5
10 4 4
H N O
Eur. J. 2008, 14, 6713e6721.
€
20. Girard, C.; Onen, E.; Aufort, M.; Beauviere, S.; Samson, E.; Herscovici, J. Org. Lett.
2006, 8, 1689e1692.
4.3.11. 1-Octyl-4-methoxycarbonyl-1,2,3-triazole
(5k).44 White
H NMR (300 MHz,
¼8.08 (s, 1H), 4.40 (t, J¼7.3 Hz, 2H), 3.95 (s, 3H), 1.92
21. Miao, T.; Wang, L. Synthesis 2008, 363e368.
ꢁ
ꢀ1 1
;
2
2
2. Lipshutz, B. H.; Taft, B. R. Angew. Chem. Int. Ed. 2006, 45, 8235e8238.
3. Kantam, M. L.; Jaya, V. S.; Sreedhar, B.; Rao, M. M.; Choudary, B. M. J. Mol. Catal.
A: Chem. 2006, 256, 273e277.
solid; mp 76e78 C; IR (KBr):
CDCl ):
quin, J¼6.9 Hz, 2H), 1.24e1.30 (m, 10H), 0.86 (t, J¼6.2 Hz, 3H);
y
¼1730 cm
3
d
24. Yamaguchi, K.; Oishi, T.; Katayama, T.; Mizuno, N. Chem. Eur. J. 2009, 15,
(
1
3
10464e10472.
C NMR (75 MHz, CDCl ):
0.1, 28.9, 28.8, 26.3, 22.6, 14.0; Calculated for C12H N O
21 3 2
3
d
¼161.3, 139.9, 127.3, 52.2, 50.7, 31.6,
2
5. Siemsen, P.; Livingston, R. C.; Diederich, F. Angew. Chem. Int. Ed. 2000, 39,
2632e2657.
3
C¼60.23%, H¼8.84%, N¼17.56%: Found C¼60.52%, H¼8.69%,
26. Alberico, D.; Scott, M. E.; Lautens, M. Chem. Rev. 2007, 107, 174e238.
2
7. Beccalli, E. M.; Broggini, G.; Martinelli, M.; Sottocornola, S. Chem. Rev. 2007, 107,
318e5365.
8. Movassagh, B.; Yasham, S.; Navidi, M. Synlett 2013, 2671e2674.
N¼17.52%.
5
2
4
5
4
.3.12. 1-Adamantyl-4-methoxycarbonyl-1,2,3-triazole (5l). White
29. Mohammadi, E.; Movassagh, B.; Navidi, M. Helv. Chim. Acta. 2014, 97, 70e74.
30. Navidi, M.; Movassagh, B. Monatsh. Chem. 2013, 144, 1363e1367.
ꢁ
ꢀ1 1
solid; mp 100e103 C; IR (KBr):
y
¼1727 cm ; H NMR (300 MHz,
¼161.1, 140.3, 127.4, 66.9, 52.2,
Please cite this article in press as: Movassagh, B.; Rezaei, N., Tetrahedron (2014), http://dx.doi.org/10.1016/j.tet.2014.09.092
3
1. Toure, B. B.; Hall, D. G. Chem. Rev. 2009, 109, 4439e4486.
2. Aron, Z. D.; Overman, L. E. Chem. Commun. 2004, 253e265.
33. Houck, J. E. B.; Younai, A.; Shaw, J. T. Curr. Opin. Chem. Biol. 2010, 14, 371e382.
CDCl ):
3
d
¼7.98 (s, 1H), 3.91 (s, 3H), 2.34 (s, 6H), 2.08 (s, 3H), 1.71 (s,
3
1
3
6
3
H); C NMR (75 MHz, CDCl ): d

8
B. Movassagh, N. Rezaei / Tetrahedron xxx (2014) 1e8
3
3
3
4. Islam, S. M.; Mondal, P.; Roy, A. S.; Mondal, S.; Hossain, D. Tetrahedron Lett.
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5. Keivanloo, A.; Bakherad, M.; Bahramian, B.; Rahmani, M.; Taheri, S. A. N. Syn-
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2
17e20.
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4
3
Please cite this article in press as: Movassagh, B.; Rezaei, N., Tetrahedron (2014), http://dx.doi.org/10.1016/j.tet.2014.09.092