[bmim]BF4/[Cu(Im12)2]CuCl2 as a novel catalytic reaction medium for click cyclization

Article abstract of DOI:10.1016/j.crci.2013.02.011

Herein, a new application of an ionic liquid containing copper (I), ([Cu(Im¹²)₂]CuCl₂), is introduced. This ionic liquid was used as an efficient catalyst for the click cyclization between organic azides and terminal alkyn

Full text of DOI:10.1016/j.crci.2013.02.011

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Full paper/Memoire
[bmim]BF4/[Cu(Im12)2]CuCl2 as a novel catalytic reaction medium for
click cyclization
a
b
Mosadegh Keshavarz a, , Bahador Karami , Amanollah Zarei Ahmady ,
*
Abdolmohammad Ghaedi c, Hakimeh Vafaei c
a Yasouj University, Yasouj 75918–74831, Iran
b Nanotechnology Research Center, Faculty of Pharmacy, Jundishapur University of Medical Sciences, Ahvaz, Iran
c Department of Chemistry, Gachsaran Branch, Islamic Azad University, Gachsaran, Iran
A R T I C L E I N F O
A B S T R A C T
Herein, a new application of an ionic liquid containing copper (I), ([Cu(Im12)2]CuCl2), is
introduced. This ionic liquid was used as an efficient catalyst for the click cyclization
between organic azides and terminal alkynes in various solvents. Then, the mixture of
[bmim]BF4/[Cu(Im12)2]CuCl2 was used as a green catalytic medium for the multicompo-
Article history:
Received 8 October 2012
Accepted after revision 12 February 2013
Available online xxx
nent click synthesis of 1,4-disubstituted-1H-1,2,3-triazoles from
a-halo ketones. The
Keywords:
reactions were performed efficiently in this mixture and excellent yields were obtained in
all cases. This catalytic reaction medium was recycled five times without significant loss of
activity.
Ionic liquid
Multicomponent reaction
Click chemistry
Triazole
ß 2013 Published by Elsevier Masson SAS on behalf of Acade´mie des sciences.
a-Halo ketone
1. Introduction
served in their presence [7,8]. Almost all of them are
applicable and suitable for certain kinds of solvents. For
Multicomponent reactions (MCRs) are one of the most
important concepts in modern synthetic organic chemis-
try. MCRs have received significant demand as a direct
route for the synthesis of diverse compounds and
compound libraries [1–5]. For example, multicomponent
Cu(I)-catalyzed 1,3-dipolar azide–alkyne cycloaddition
(CuAAC) leads to a diversity of 1,4-disubstituted 1,2,3-
triazole compounds; this is best known as the click
reaction [6]. Many kinds of copper (I) catalysts have been
reported for CuAAC reactions. However, some of these
catalysts have serious drawbacks. For instance, some of the
reported catalysts suffer from their instability or high
tendency toward oxidation, which leads to catalytic
inactivity. In some cases, the formation of undesired
alkyne–alkyne coupling and other by-products are ob-
example, simple coordination complexes of Cu(P(O-
Me)3)3Br [9] and Cu(PPh3)3Br [10,11] are often used in
reactions in organic solvents, in which cuprous salts have
limited solubility. A report describes the bis(phosphine)
complex Cu(PPh3)2OAc as an excellent catalyst for the
CuAAC reaction in toluene and dichloromethane [12]. In
situ-prepared Cu (I) from Cu (II), using sodium ascorbate
was introduced by Fokin et al. for click cyclization in water
[6]. Although the immobilization of copper (I) salts on
various supports makes them recoverable and somewhat
more stable than their free copper (I) salt counterparts, the
leaching of the catalysts from support into the reaction
mixture leads to product contamination and catalyst
deficiency during the recycling process.
Click chemistry principles are consistent with the goals
of green chemistry, focusing on minimizing the hazard and
maximizing the efficiency of any chemical choice. They
have attracted an enormous amount of interest over the
past decade [13].
* Corresponding author.
E-mail address: Chem.mosadegh@gmail.com (M. Keshavarz).
1631-0748/$ – see front matter ß 2013 Published by Elsevier Masson SAS on behalf of Acade´mie des sciences.
http://dx.doi.org/10.1016/j.crci.2013.02.011
Please cite this article in press as: Keshavarz M, et al. [bmim]BF4/[Cu(Im12)2]CuCl2 as a novel catalytic reaction medium
for click cyclization. C. R. Chimie (2013), http://dx.doi.org/10.1016/j.crci.2013.02.011

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Although CuAAC reactions can often be carried out in
water as a green solvent, the solubility of organic azide and
acetylene reactants can sometimes be a serious obstacle in
using this reaction medium. In particular, a phase transfer
catalyst or elevated temperatures seems to be necessary
when organic azides are prepared in situ from their halide
forms. Using ionic liquids as a reaction medium can
overcome these problems. The user-friendly and adjust-
able properties of ionic liquids have prompted numerous
applications as environmentally benign reaction media,
catalysts [14], task-specific reagents [15], and chirality
transfer media [16]. From this perspective, combining the
synthetic potential of MCRs with the dual properties of
room temperature ionic liquids (RTILs) as solvents and
catalysts has resulted in the development of new and
promising eco-compatible organic transformations [17].
Recently, a diversity of ionic liquids containing copper
(I) and (II) have been synthesized and were used
as catalysts for the oxidative carbonylation of alkanols
to dialkyl carbonates [18,19]. This paper aims to
introduce new application for the ionic liquid containing
copper (I), [Cu(Im12)2]CuCl2, and demonstrates that
the mixture of 1-butyl-3-methylimidazolium tetrafluor-
2.3. General procedure for the synthesis of 1,4-disubstituted-
1H-1,2,3-triazoles using [Cu(Im12)2]CuCl2 as a catalyst
[Cu(Im12)2]CuCl2 (0.07 g, 0.1 mmol) was added to a
round-bottomed flask containing [bmim]BF4/H2O 1:1
(8 mL), a-halo ketone (1 mmol), terminal alkyne (1 mmol)
and sodium azide (1.2 mmol). The reaction mixture was
stirred at room temperature for 20 min. The organic phase
was extracted with ethyl acetate (2 Â 8 mL), washed with
brine, dried over anhydrous Na2SO4, filtered and concen-
trated in vacuo. The solid residual was recrystallized in hot
ethanol to give pure crystals of the product. In some cases,
water was added dropwise to precipitate the pure product
(Table 3, entries 6–8). The aqueous phase was kept for the
next runs. The pure products were dried under vacuum at
room temperature, which resulted in 80–89% yields.
2.4. Typical procedure for multicomponent synthesis of 2-(4-
{4-[1-(2-oxo-2-phenylethyl)-1H-1,2,3-triazol-4-yl]phenyl)}-
1H-1,2,3-triazol-1-yl-1-phenyl-1-ethanone
[Cu(Im12)2]CuCl2 (0.14 g, 0.2 mmol) was added to a
round-bottomed flask containing [bmim]BF4/H2O 1:1
(16 mL), 1,3-diethynylbenzene (1 mmol), phenyl acetylene
(2 mmol) and sodium azide (2.4 mmol). The reaction
mixture was stirred at room temperature for 20 min
(Table 3, entry 11b). The organic phase was extracted with
ethyl acetate (2 Â 16 mL), washed with brine, dried over
anhydrous Na2SO4, filtered and concentrated in vacuo. The
solid residual was recrystallized in hot ethanol to give pure
crystals of the product. The latter was dried under vacuum
at room temperature as a white solid crystal [20] (0.360 g,
80%). IR (cmÀ1):1696 (CO), 1226, 686; 1H-NMR (500 MHz
oborate ([bmim]BF4)/[Cu(Im12)2]CuCl2 is
a versatile,
recyclable catalytic reaction medium for multicompo-
nent Huisgen preparation of 1,4-disubstituted 1,2,3-
triazoles, adapted with the principles of green chemistry.
2. Experimental
2.1. Materials and methods
All
a-halo ketones, ionic liquids and other chemicals
DMSO-d6) d 8.64 (2H, s, CH triazole), 8.44 (1H, s), 8.13–8.12
were purchased from Fluka and Merck in high purity, and
[Cu(Im12)2]CuCl2 was synthesized according to the litera-
ture [18]. All of the triazole compounds were prepared
using our procedure. Their spectroscopic data were
recorded on a BOMEM MB-Series 1998 FT-IR spectropho-
tometer, Bruker Avance DPX 500 MHz and DPX 400 MHz
spectrometers using TMS as internal standard. Mass
spectral analyses were made on an Agilent HP 5973
Network Mass Selective Detector. The analyzer made its
determination according to the ASTM method. Elemental
analyses were performed on a Thermo Fin-nigan CHNS-O
analyzer, 1112 series.
(4H, m), 7.87 (2H, q, J = 2.33 Hz,), 7.76 (2H, t, J = 4.95 Hz),
7.64 (4H, t, J = 5.17 Hz,), 7.58 (1H, t, J = 5.17 Hz), 6.30 (4H, s,
COCH2); 13C-NMR (125 MHz DMSO-d6)
d 193.0, 146.9,
135.1, 135.0, 132.2, 130.5, 129.9, 129.1, 125.5, 122.7, 56.9;
anal. calcd. for C28H20N6O2: C 69.63, H 4.49, N 18.74%,
found: C 69.22, H 5.56, N 18.81.
1-phenyl-2-(4-phenyl-1H-1,2,3-triazole-1-yl)-1-ethanon
(1b of Table 3, 89%, white solid crystals) [21]: IR (cmÀ1):
1704 (CO), 1H-NMR(400 MHz, DMSO-d6):
d 8.54 (1 H, s),
8.11 (2H, d; J = 8.10 Hz), 7.90–7.88 (2H, m), 7.78–7.74 (1H,
m), 7.63 (2H, t; J = 7.7 Hz), 7.47(2 H, t; J = 7.7 Hz), 7.38–7.34
(1H, m), 6.28(2H, s). 13C-NMR (100 MHz, DMSO-d6):
d
2.2. Preparation of [Cu(Im12)2]CuCl2
192.7 (CO), 146.8, 134.8, 134.6, 131.2, 129.5, 129.4, 128.7,
128.4, 125.6, 123.5, 56.5. HRMS (CI): MH+, C12H12BrN3O2
requires 263.2939, found: 263.3413.
To
a Schlenk flask charged with CuCl (1.21 g,
12.22 mmol), a solution of 1-dodecylimidazole (3.06 g,
12.95 mmol) in CH3CN (5 mL) was added. It was placed in
an ultrasonic bath at room temperature for 30 min. The
solvent was evaporated in vacuo and the precipitate was
washed with ether and dried under vacuum to give
[Cu(Im12)2]CuCl2 as a fine crystalline colorless solid; anal.
calc. for C30H56Cl2Cu2N4: C 53.72, H 8.41, N 8.35%; found:
C 53.87, H 8.58, N 8.45%; mp 73 8C (Lit. [18] 73 8C),
decomp. 281.4 8C. IR (cmÀ1): 3122, 3050, 2950, 2847,
1690, 1615, 1520, 1466, 1442, 1399, 1357, 1288, 1240,
1110, 1053, 1039, 1028, 1006, 962, 895, 845, 760, 730, 655,
500, 442.
1-(4-phenyl-1H-1,2,3-triazole-1-yl)acetone (5b of Table
3, white solid crystals). IR (cmÀ1): 1710 (CO), 1H-
NMR(500 MHz, CDCl3):
J = 7.50 Hz), 7.40–7.36(1H, m), 5.28(2H, s), 2.30(3H, s). 13C-
NMR(125 MHz, CDCl3): 199.61 (CO), 148.64, 130.77,
d 7.88–7.87(3H, m), 7.46(2H, t,
d
129.30, 128.74, 126.22, 121.55, 58.96, 27.66. HRMS (CI):
MH+, C12H12BrN3O2 requires 201.2, found: 201.2.
1-(4-bromophenyl)-2-[(4-(1-hydroxyethyl)-1H-1,2,3-tria-
zole-1-yl)]-1-ethanone (7b of Table 3, 0.191 g, 83%, white
solid crystals) [21]. IR (cmÀ1): 3417 (OH), 1704 (CO), 1599,
1497, 1250 cmÀ1; 1H-NMR (400 MHz DMSO-d6)
d
8.37 (1H,
s, CH triazole), 7.95 (2H, d, J = 8.6 Hz), 7.79 (2H, d,
Please cite this article in press as: Keshavarz M, et al. [bmim]BF4/[Cu(Im12)2]CuCl2 as a novel catalytic reaction medium
for click cyclization. C. R. Chimie (2013), http://dx.doi.org/10.1016/j.crci.2013.02.011

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3
Table 1
J = 8.60 Hz,), 5.96 (2H, s, COCH2), 4.95 (1H, s, OH), 4.19–4.16
(1H, m), 1.54 (3H, d, J = 5.20 Hz, CH3); 13C-NMR (125 MHz
Evaluation of the efficiency of [Cu(Im12)2]CuCl2 for click reaction between
phenacyl azide and phenyl acetylene in various solvents.
CDCl3)
121.47, 52.37, 45.97, 28.13; HRMS (CI): MH+,
12H12BrN3O2 requires 310.2, found: 310.2; anal. calcd.
d 189.82, 153.86, 148.81, 132.67, 130.86, 130.48,
Entry
Solvent
Time (min)
Yield (%)a
C
1
2
3
4
5
6
7
8
Neat
25
10
60
60
15
60
60
60
87
89
73
75
90
83
77
82
[bmim]BF4
DMF/H2O 1:1
CH2Cl2
for C12H12BrN3O2: C 46.47, H 3.90, N 13.55%; found: C
46.34, H 3.91, N 13.34.
2-[4-(1-hydroxyethyl)-1H-1,2,3-triazole-1-yl]-1-(4-
methoxyphenyl)-1-ethanone (8b of Table 3, 0.212 g, 81%,
white solid crystals). IR (cmÀ1): 3503 (OH), 1694 (CO),
1597, 1232, 1170 cmÀ1 1H-NMR (500 MHz CDCl3)
; d 8.06
(2H, d, J = 8.74 Hz,), 7.87 (1H, s, CH triazole), 7.13 (2H, d,
J = 8.75 Hz), 6.07 (2H, s, COCH2), 5.28 (1H, s), 4.89–4.86 (1H,
m), 3.89 (3H, s), 1.44 (3H, d, J = 8.75 Hz); 13C-NMR
[bmim](BF4/H2O 1:1)
CH3CN
THF
THF/H2O 1:1
a
Isolated yield.
(125 MHz CDCl3)
d
189.82, 153.86, 148.81, 132.67,
effective click cyclization [22–24]. These reports do not
represent the catalytic activity of ionic liquids and are used
only as a suitable medium to increase the solubility of the
reactants.
It is clear that the task-specific ionic liquid, [Cu(Im12)2]-
CuCl2, works very well as a catalyst in various solvents
even under neat condition and reduces the reaction times
compared with the reported catalysts. This catalytic ionic
liquid is the first type of ionic liquids that can catalyze click
cyclization. Encouraged by these successful results, we
decided to design a green methodology for the synthesis of
130.86, 130.48, 121.47, 52.37, 45.97, 28.13; anal. calcd.
for C13H15N3O3: C 59.76, H 5.79, N 16.08%; found: C 60.11,
H 5.65, N 16.25; HRMS (CI): MH+, C13H15N3O3 requires
261.3, found: 260.3.
2.5. Reusing of the reaction medium
The aqueous phase from Section 2.3 (using phenacyl
bromide and phenyl acetylene) was used for synthesis of
1-phenyl-2-(4-phenyl-1H-1,2,3-triazol-1-yl)ethanone
by adding phenacyl bromide (1 mmol), phenyl acetylene
(1 mmol) and sodium azide (1.2 mmol) in the next
similar runs.
1,4-disubstituted 1,2,3-triazoles directly from
a-halo
ketones using task-specific ionic liquids (TSILs) as the
reaction medium and catalyst. To the best of our
knowledge, there is no extant report describing this
methodology. We first embarked on the evaluation of
RTILs and the comparison of their efficiency in the MCR.
Multicomponent click cyclization between phenacyl bro-
mide and phenyl acetylene was selected as the model
reaction and its behavior was investigated using a diversity
of ionic liquids as solvents (Scheme 2 and Table 2).
Looking at the anions of ionic liquid, BF4–produced a
higher yield than PF6À(Table 2, entries 1, 2). The
imidazolium cation has a critical role in the first step of
the reaction (Scheme 3). The formation of a hydrogen bond
between the acidic C2 hydrogen of imidazolium cation [25]
and the carbonyl group of phenacyl halide activates this
substrate (Fig. 1 and Table 2, entries 1 and 3). The absence
of this proton decreases the reactivity (Table 2, entry 4).
In addition, the branch of imidazolium cation has
affected the reaction yields (Table 1, entries 1 and 3).
The acidity of ionic liquids with BF4Àanion can be finely
tuned via cation variation, whereas ionic liquids with
PF6Àare more stable and result in neutral aqueous
solutions [26].
3. Results and discussion
An ionic liquid containing copper (I), [Cu(Im12)2]CuCl2,
was prepared according to the reported method [18]. To
evaluate the efficiency of this ionic liquid as the catalyst for
the azide–alkyne cycloaddition reaction in various sol-
vents, click cyclization between phenacyl azide and phenyl
acetylene to afford 1-phenyl-2-(4-phenyl-1H-1,2,3-tria-
zole-1-yl)-1-ethanone (1b) was selected as
reaction (Scheme 1).
a model
The reaction progress was studied in [bmim]BF4, H2O,
[bmim]BF4/H2O, THF/H2O, DMF/H2O, dioxane/H2O and
CH2Cl2 under neat conditions. The results of using this
task-specific ionic liquid in various solvents are reported
(Table 1). The IR spectra of Fig. 1b exhibited a strong band
at about 1702 cmÀ1, indicating the presence of a ketonic
functionality. Its 1H-NMR showed a characteristic singlet
at d 8.53 for triazolyl C5–H. High-resolution mass spectra of
the title compound exhibited the molecular ion peak at m/z
263.34, which is in agreement with the calculated value,
m/z 263.29.
Although some efforts have been made on the use of
ionic liquids as green solvents for CuAAC reaction, these
methods have long reaction times or require additive for
From Table 2 and the discussion above, the mixture of
[bmim]BF4/H2O (1:1 v/v) stands out as the solvent of
preference with its fast reaction rate and high yield of the
product. Water, as a co-solvent, makes sodium azide to be
N
O
O
N
[Cu(Im12)2]CuCl2
Solvent, r.t.
N3
N
Ph
Ph
+
Ph
Ph
Scheme 1. Evaluation of ionic liquid containing copper (I) for click cyclization in various solvents.
Please cite this article in press as: Keshavarz M, et al. [bmim]BF4/[Cu(Im12)2]CuCl2 as a novel catalytic reaction medium
for click cyclization. C. R. Chimie (2013), http://dx.doi.org/10.1016/j.crci.2013.02.011

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O
N
O
N
NaN3, Solvent, r.t.
Br
N
Ph
+ Ph
Ph
Ph
[Cu(Im12)2]CuCl2 (10%mol)
Scheme 2. Evaluation of various solvents for the multicomponent reaction catalyzed by ionic liquid containing copper (I).
N
O
O
N
O
R2
NaN3, r.t.
N3
N
X
R2
R1
[Cu(Im12)2]CuCl2
r.t.
R1
R1
Green solvent
Scheme 3. Stepwise synthesis of 1,4-disubstituted-1H-1,2,3-triazoles.
soluble during nucleophilic substitution reaction. More-
over, water increases the acidity of [bmim]BF4 [26] (Table
2, entries 5 and 6), because BF4À is hydrolyzed into H+ and
HOBF3À in this medium [27–30]. These effects have a direct
relationship with the observed rate of the reaction.
Consequently, in order to exhibit the efficiency of
[bmim]BF4/H2O as a solvent for a wide range of substrates,
multicomponent click cyclization reaction between vari-
reused in the next run. Almost consistent activity was
observed using [bmim]BF4/H2O as solvent and
[Cu(Im12)2]CuCl2 as a catalyst over five runs (Fig. 2).
The yield difference between the first and fifth runs was
only 4%. These observations suggest that the efficiency of
the introduced catalytic ionic liquid medium is maintained
through repeated uses. The copper contents of the fresh
and the reused catalyst (after the fifth run) were measured
using the ICP–AES technique. In both cases, the results
were identical and showed that the title catalyst was
almost perfectly extracted into the aqueous phase.
In order to compare the efficiency of the ionic liquid
containing the copper (I) catalyst with some of the
traditional copper (I) catalysts, the CuAAC reaction
between phenacyl azid and phenyl acetylene was investi-
gated using these catalysts in [bmim]BF4/H2O (Table 4).
Although using copper (I) salts leads to the synthesis of 1,4-
disubstituted-1H-1,2,3-triazoles, they do not give good
yields, have long reaction times and suffer from the
difficulty of separation and reusability (Table 4, entries
ous types of
a-halo ketones and terminal alkynes was
explored in [bmim]BF4/H2O (1:1 v/v) using [Cu(Im12)2]-
CuCl2 as a catalyst. The results of using TSIL, [Cu(Im12)2]-
CuCl2, as a catalyst and [bmim]BF4/H2O as a solvent are
reported (Scheme 4 and Table 3). Structural assignments of
the products were confirmed by the appearance of a singlet
in the 7.8–8.5 ppm range in 1H-NMR spectra and approved
the regioselective synthesis of 1,4-disubstituted triazole
regioisomers.
In all cases, multicomponent click cyclization was
completed in excellent time and the 1,2,3-triazole
derivatives were isolated with high yields. These observa-
tions clearly indicate the generality and scope of the
reaction with respect to various terminal alkynes and
halo ketones.
a-
-
X
N3
A true and efficient catalyst can be simply recovered
and reused. To investigate these properties for our
introduced catalyst, the reaction of phenacyl bromide
and phenyl acetylene was selected again as a model
reaction. After completion of click cyclization, the product
was easily extracted from ionic liquid solvent and catalyst
using EtOAc. The recovered ionic liquid mixture was
H
-
BF4
N
O
R1
N
Fig. 1. Acidic hydrogen of imidazolium cation promotes the nucleophilic
substitution at the
a-position of a-halo ketones.
Table 2
The effect of ionic liquids as solvent for multicomponent click cyclization.
NaN3, R2
[Cu(Im12)2]CuCl2
N
O
N
Yield (%)a
O
Entry
Solvent
Time (min)
N
R2
X
R1
1
2
3
4
5
6
[bmim]BF4
60
60
60
60
20
20
78
62
73
65
89
81
R1
[bmim]BF4/H2O 1:1
r.t., 20 min
[bmim]PF6
[hmim]BF4
[bmmim]BF4
[bmim]BF4/H2O 1:1
[bmim]BF4/H2O 1:3
Scheme 4. Multicomponent synthesis of 1,4-disubstituted-1H-1,2,3-
triazoles in the [bmim]BF4/H2O medium using Cu(I)-based ionic liquid
catalyst.
a
Yields refer to isolated and pure products.
Please cite this article in press as: Keshavarz M, et al. [bmim]BF4/[Cu(Im12)2]CuCl2 as a novel catalytic reaction medium
for click cyclization. C. R. Chimie (2013), http://dx.doi.org/10.1016/j.crci.2013.02.011

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5
Table 3
Synthesis of 1,4-disubstituted-1H-1,2,3-triazoles in the [bmim]BF4/H2O medium using Cu(I)-based catalytic ionic liquid.
Entry
1
a
-halo ketone(a)
Product(b)
Melting point
146
Yield (%)a
89
O
O
N
N
Br
N
2
3
4
5
145
142
152
138
86
81
84
84
O
O
N
N
Br
N
Br
Br
O
O
N
N
N
Br
MeO
MeO
O
O
N
N
Br
N
Cl
Cl
O
O
O
O
N
N
N
Cl
N
N
H3C
H3C
EtO
N
6
7
112
108
84
83
Cl
EtO
Br
O
O
N
N
Br
N
OH
CH3
Br
8
118
81
O
O
N
N
Br
N
OH
CH3
MeO
MeO
9
146
163
82
82
O
O
N
N
Br
O
N
O
NH2
10
N
N
Br
N
NH2
MeO
MeO
11
More than 300
80
O
O
N
N
N
N
O
Br
N
N
a
Yields refer to pure and isolated products.
Please cite this article in press as: Keshavarz M, et al. [bmim]BF4/[Cu(Im12)2]CuCl2 as a novel catalytic reaction medium
for click cyclization. C. R. Chimie (2013), http://dx.doi.org/10.1016/j.crci.2013.02.011

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100
90
80
70
60
50
40
30
20
10
0
Table 4
Comparison of the efficiency of the copper-containing ionic liquid with
some of the traditional catalysts for the CuAAC reaction.
Entry
Catalyst
Time (min)
Yield (%)a,b
1
2
3
4
5
CuCl
90
90
90
90
20
58
65
68
87
89
89
89
88
87
85
CuCN
CuBr
CuSO4/NaAsc
[Cu(Im12)2]CuCl2
a
All reactions were carried out using 0.5 mmol phenacyl bromide,
0.5 mmol phenyl acetylene, copper(I) catalyst (10 mol%), 0.6 mmol NaN3
in [bmim]BF4/H2O (4 mL 1:1) at room temperature.
Run 1 Run 2 Run3 Run4 Run 5
b
Isolated yields.
Fig. 2. Recyclability and reusability study of the reaction medium.
1–3). Another deficiency of such catalysts is that they have
not been recommended for aqueous mediums [31].
Although in situ-prepared Cu(I) forms CuSO4, sodium
ascorbate is a suitable catalyst for aqueous medium and
gives high yields, this catalyst needs relatively long
reaction times and is not recyclable (Entry 4). [Cu(Im12)2]-
CuCl2 is a greener catalyst; thermodynamically more
stable (its thermal decomposition temperature is 234 8C)
[18], gives the product in shorter times at higher yields and
can be simply recovered.
The mechanistic pathway mediated by [Cu(Im12)2]-
CuCl2 is depicted in Fig. 3.
R2
R2
Cu Im12
Cu Im12
N
O
O
R2
H
N
O
N
N
N
R1
R1
N
N
N
R1
N
HIm12 CuCl2
R2
Cu Im12
N
[Cu(Im12)2]CuCl2
O
N
R1
N
R2
H
Cu Im12
R1
O
N3
R1
N3
H
-
H
N
BF4
N
-
BF4
N
O
N
R1
O
X
R1
NaX
X
NaN3
H
-
BF4
N
O
R1
N
Fig. 3. Proposed mechanism for multicomponent synthesis of 1,4-disubstituted-1H-1,2,3-triazoles using task-specific ionic liquids as solvent and catalyst.
Please cite this article in press as: Keshavarz M, et al. [bmim]BF4/[Cu(Im12)2]CuCl2 as a novel catalytic reaction medium
for click cyclization. C. R. Chimie (2013), http://dx.doi.org/10.1016/j.crci.2013.02.011

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triazoles from
a-halo ketones usage of ionic liquids as
solvent and catalyst for this reaction. Obtaining of high
yields in short times, use of a recoverable and reusable
task-specific copper-containing ionic liquid as a catalyst,
and its cost effective and eco-friendly properties make this
method interesting and adjustable with sustainable
chemistry.
Acknowledgment
The authors gratefully acknowledge the Research
Council of Yasouj University for financial support.
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Please cite this article in press as: Keshavarz M, et al. [bmim]BF4/[Cu(Im12)2]CuCl2 as a novel catalytic reaction medium
for click cyclization. C. R. Chimie (2013), http://dx.doi.org/10.1016/j.crci.2013.02.011