Fe3O4 nanoparticle-supported Cu(ii)-β- cyclodextrin complex as a magnetically recoverable and reusable catalyst for the synthesis of symmetrical biaryls and 1,2,3-triazoles from aryl boronic acids

Article abstract of DOI:10.1039/c3gc40753e

We report here on the preparation of an efficient, easily recoverable and reusable Fe₃O₄ magnetic nanoparticle-supported Cu(ii)-β-cyclodextrin complex catalyst for the synthesis of symmetrical biaryls and 1,2,3-triazoles from arylboronic acids. The presented Fe ₃O₄ magnetic nanoparticle-supported Cu(ii)-β- cyclodextrin complex catalyst was characterized by TEM, XRD, VSM, TGA, and FT-IR spectrometer. By using the catalyst, we have developed an efficient protocol for the homocoupling of aryl boronic acids for the synthesis of biaryls. The catalyst is also active in the synthesis of 1,2,3-triazoles via a one-pot reaction of an arylboronic acid with sodium azide in water followed by a click cyclization reaction with an alkyne at room temperature in air without any additives. The reusability of the prepared nanocatalyst was successfully examined four times with only a very slight loss of catalytic activity.

Full text of DOI:10.1039/c3gc40753e

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Fe3O4 nanoparticle-supported Cu(II)-β-cyclodextrin
complex as a magnetically recoverable and reusable
catalyst for the synthesis of symmetrical biaryls and
1,2,3-triazoles from aryl boronic acids†
Cite this: DOI: 10.1039/c3gc40753e
Babak Kaboudin,*a Ramin Mostafalua and Tsutomu Yokomatsub
We report here on the preparation of an efficient, easily recoverable and reusable Fe3O4 magnetic nano-
particle-supported Cu(II)-β-cyclodextrin complex catalyst for the synthesis of symmetrical biaryls and 1,2,3-
triazoles from arylboronic acids. The presented Fe3O4 magnetic nanoparticle-supported Cu(II)-β-cyclo-
dextrin complex catalyst was characterized by TEM, XRD, VSM, TGA, and FT-IR spectrometer. By using the
catalyst, we have developed an efficient protocol for the homocoupling of aryl boronic acids for the syn-
thesis of biaryls. The catalyst is also active in the synthesis of 1,2,3-triazoles via a one-pot reaction of an
arylboronic acid with sodium azide in water followed by a click cyclization reaction with an alkyne at
room temperature in air without any additives. The reusability of the prepared nanocatalyst was success-
fully examined four times with only a very slight loss of catalytic activity.
Received 22nd April 2013,
Accepted 7th June 2013
DOI: 10.1039/c3gc40753e
www.rsc.org/greenchem
Since the first copper-mediated coupling reaction of aryl
halides performed by Ullmann over a century ago,7 consider-
Introduction
During the past decade, a great deal of attention has been paid able efforts have led to variety of methods and catalysts for the
to developing greener chemical processes and synthetic synthesis of symmetrical biaryls.8 The copper-mediated homo-
methods.1 Catalysts bound to inorganic solids are widely used coupling of aryl boronic acids proved to be a valuable method
for organic transformations due to environmental and econ- to obtain symmetrical biaryls due to its compatibility with a
omical considerations.2 Nanoparticles supported on a metal variety of functional groups, stability and the lower toxicity of
oxide as an inorganic solid, in particular magnetic nanoparti- the boronic acids than other organometallic reagents.9
cles (MNPs), have been extensively studied in the field of Copper-mediated 1,3-dipolar cycloaddition (click reaction) of
chemical catalysis, environmental protection, sensors, mag- organic azides with alkynes to give 1,2,3-triazoles has also
netic storage media, and clinical diagnosis treatments.3 MNPs received considerable attention because of their useful wide-
have great potential in view of the their recovery, since the spread applications in the fields of material science and mole-
magnetic separation of MNPs from the reaction mixture with cular structure design.10 One-pot synthesis of 1,2,3-triazoles
an external magnet is simpler and more efficient than conven- via the in situ generation of aryl azides from aryl boronic acids
tional separation with filtration or centrifugation. On the other in the presence of the alkyne using copper-catalysts minimizes
hand, MNPs are accessible from inexpensive materials and can the hazards derived from their isolation and handling.11
be easily supported by organic and inorganic materials.4
With the increasing demand for environmentally friendly
Recently, MNP-supported-copper ions have been used exten- methods, recently we have found that the Cu(II)-β-cyclodextrin
sively in organic transformations.5,6
complex is an efficient nanocatalyst for the homocoupling and
one-pot synthesis of 1,2,3-triazoles from arylboronic acids
under base-free homogenous conditions.12 Cu(II)-β-cyclo-
dextrin complex is a binuclear complex with a good stability
constant that can be prepared readily by the addition of a
copper sulfate solution to a mixture of β-cyclodextrin in a
sodium hydroxide solution.13 This readily available binuclear
supramolecular copper complex is already known, but for the
first time we have employed it as a nanocatalyst in organic
transformations.12 Although homogeneous copper catalysts
have many advantages, such as a high turnover number, good
aDepartment of Chemistry, Institute for Advanced Studies in Basic Sciences, Gava
zang, Zanjan, Iran. E-mail: kaboudin@iasbs.ac.ir; Fax: +98 241 4214949;
Tel: +98 241 4153220
bSchool of Pharmacy, Tokyo University of Pharmacy and Life Sciences,
14321-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan
†Electronic supplementary information (ESI) available: Details of the analytical
data of the products of the homocoupling and 1,2,3-triazoles. See DOI:
10.1039/c3gc40753e
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activity and selectivity, and are widely used in a variety of
industries, separation of the soluble catalyst from the product
and reaction medium remains difficult. Recovery of the copper
catalyst and its reuse are two important features for the syn-
thesis of symmetrical biaryls and 1,2,3-triazoles from arylboro-
nic acids. Herein, we report on the preparation and
characterization of a Fe3O4 magnetic nanoparticle-supported
Cu(II)-β-cyclodextrin complex (Fe3O4-β-CD-Cu2). In addition we
describe its utility for the synthesis of symmetrical biaryls and
1,2,3-triazoles from arylboronic acids.
Results and discussion
The magnetic nanoparticle-supported Cu(II)-β-cyclodextrin
complex (Fe3O4-β-CD-Cu2) was prepared by a simple one-pot
co-precipitation of a mixture of iron precursors (Fe2+ and Fe3+)
and the Cu(II)-β-cyclodextrin complex (prepared according to
our previously reported method12) in the reaction medium
(Scheme 1). The morphology and structure of the prepared
Fe3O4-β-CD-Cu2 nanoparticles were characterized by TEM,
TGA, XRD and FT-IR analyses, which confirmed the successful
preparation of the supported Fe3O4 nanoparticles.
Fig.
1 shows the FT-IR spectra of the unsupported
Fe3O4, Cu(II)-β-cyclodextrin, and Fe3O4-β-CD-Cu2 in the
400–4000 cm−1 wave number range. It shows that the adsorp-
tion band of the Fe–O bonds in the tetrahedral sites is
581 cm−1, which is shifted to 634 cm−1 after being supported
with Cu(II)-β-cyclodextrin. The broad band at 3000–3500 cm−1
is due to the hydroxy stretching vibration. The spectrum of
Fe3O4-β-CD-Cu2 shows the peaks at the 800–1620 cm−1 range,
which correspond to the characteristic vibrations of β-cyclo-
dextrin. The peak at 1030 cm−1 corresponds to the anti-
symmetric C–O–C vibrations. The intense peak at 1620 cm−1
may be assigned to the deformation vibrations of water mole-
cules trapped into the Fe3O4 colloidal particles.14 The assign-
ments are concordant with the Keiser et al.15 and Racuciu
et al.14 reports on Fe3O4-supported β-cyclodextrin. Therefore, it
can be concluded that Cu(II)-β-cyclodextrin has been supported
successfully on the surface of Fe3O4 nanoparticles. The adsorp-
tion and coating of Cu(II)-β-cyclodextrin onto nano-size crystal
planes of the Fe3O4 nanoparticles was brought about by the
strong hydrogen bonding of Cu(II)-β-cyclodextrin, with a multi-
ple hydroxyl group, and the hydroxide groups of the Fe3O4
nanoparticles.16
Fig. 1 FT-IR spectrum of (a) Fe3O4 and (b) Fe3O4-supported Cu(II)-β-
cyclodextrin.
The amount of the Cu(II)-β-cyclodextrin complex supported
on the surface of the Fe3O4 was estimated by thermogravi-
metric analysis (TGA) of Fe3O4-β-CD-Cu2. As shown in Fig. 2,
the TGA curve of the Fe3O4-supported Cu(II)-β-cyclodextrin
shows a weight loss of 3.69% below 160 °C, which is due to
the loss of the adsorbed water in the sample. The mass loss of
about 8.33% by weight in the range of 160–340 °C is attributed
to the thermal decomposition of Cu(II)-β-cyclodextrin. The
Scheme 1 Preparation of the Fe3O4 magnetic nanoparticle-supported Cu(II)-
β-cyclodextrin complex catalyst.
Fig. 2 TGA curve of the Fe3O4-supported Cu(II)-β-cyclodextrin.
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Fig. 3 TEM of Fe3O4 (a) and Fe3O4-supported Cu(II)-β-cyclodextrin (b).
amount of copper (5.12%) of Fe3O4-β-CD-Cu2 was determined
by atomic absorption analysis. The TGA curve and atomic
absorption analysis also confirmed the successful supporting
of the Cu(II)-β-cyclodextrin complex onto the magnetic surface.
A transmission electron microscope (TEM) was used to
obtain direct information about the structure and morphology
of the Fe3O4-β-CD-Cu2 nanoparticles. Fig. 3 shows the TEM
images of the Fe3O4 and Fe3O4-β-CD-Cu2 nanoparticles. The
mean diameter of Fe3O4 is about 10–20 nm with a mostly
spherical shape. The boundary between the particles (low con-
trast) was not detectable in the TEM of the Fe3O4-β-CD-Cu2
which may be due to interactions between the neighboring
particles. No significant layer of Cu(II)-β-cyclodextrin could be
observed on these nanoparticles.
Fig. 4 (a) Magnetic hysteresis loops of the Fe3O4. (b) Magnetic hysteresis loops
of the Fe3O4-supported Cu(II)-β-cyclodextrin.
The excellent magnetically controllable aggregation behav-
ior of Fe3O4-β-CD-Cu2 was verified by placing a magnet near
the vessels containing the aqueous dispersion of the nano-
particles, which were further investigated by vibrating sample
magnetometer (VSM) studies. Fig. 4 shows the magnetic hys-
teresis loops of Fe3O4 (a) and Fe3O4-β-CD-Cu2 (b) in an applied
magnetic field of 10 000 Oe at 298 K. The hysteresis loops of
the Fe3O4-β-CD-Cu2 nanoparticles show a superparamagnetic
behaviour with their re-dispersion stability in solution,
without aggregation. The saturation magnetization of the
Fe3O4-β-CD-Cu2 nanoparticles in Fig. 4b is about 33.0 emu g−1
,
relatively lower than the unsupported Fe3O4 in Fig. 4a, which
is due to the non-magnetic properties of the Cu(II)-β-cyclo-
dextrin moiety in the prepared catalyst.
The crystal structures of the Fe3O4 and Fe3O4-supported
Cu(II)-β-cyclodextrin nanoparticles were also studied by XRD
analysis (Fig. 5).
The XRD patterns of the Fe3O4 and Fe3O4-β-CD-Cu2 nano-
particles indicate six characteristic peaks at 2θ = 30.2°, 35.6°,
43.2°, 53.7°, 57.2°, and 62.9°, as shown in Fig. 5a and b. All
diffraction peaks and positions for Fe3O4 match well with
those from the JCPDS card (no. 76-1849) for the spinel cubic
structure of Fe3O4. This shows that the prepared Fe3O4 nano-
particles are pure with a spinel structure and the supporting of
the surface of Fe3O4 with Cu(II)-β-cyclodextrin did not result in
Fig. 5 (a) XRD pattern of the Fe3O4. (b) XRD pattern of the Fe3O4-supported
Cu(II)-β-cyclodextrin.
a phase change of the magnetic nanoparticles. The crystal
sizes of the Fe3O4 and Fe3O4-β-CD-Cu2 nanoparticles were
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determined from the XRD pattern by using Scherrer’s
equation.17 The values provided by the above equation for the
Fe3O4 and Fe3O4-β-CD-Cu2 nanoparticles were 28 and 17 nm,
respectively. This reveals that the Cu(II)-β-cyclodextrin plays a
surfactant role, which assists in reducing the nanoparticle
size.
Table 1 Fe3O4-β-CD-Cu2-catalyzed homocoupling reaction of various arylboro-
nic acids
Entry
1
T [°C]
Product 2
t (h)
Yielda [%]
90
The catalytic behavior of the Fe3O4-β-CD-Cu2 nanoparticles
was studied for the synthesis of symmetrical biaryls and 1,2,3-
triazoles from arylboronic acids. Initially, the homocoupling of
phenylboronic acid 1a was chosen as the model reaction.
Recently, we reported on the experimental data for the screen-
ing of different copper salts and Cu2-β-cyclodextrin for the
homocoupling of phenylboronic acids.12a When the reaction
was carried out using Fe3O4-β-CD-Cu2 nanoparticles (0.1
equiv.) with respect to 2 equiv. of 1a for 3 h at room tempera-
ture in DMF, biaryl 2a was obtained in 90% isolated yield. The
blank experiment showed that without the Fe3O4-β-CD-Cu2
nanoparticles, the reaction could not occur. It should be noted
that the use of common organic solvents, such as THF or
CH2Cl2 (as a solvent) did not afford the biphenyl, and low
yields (<40%) of biaryl 2a were obtained using ethanol and
methanol as a solvent at room temperature for 24 h. Under the
above optimized conditions, the homocoupling of various aryl-
boronic acids was examined using Fe3O4-β-CD-Cu2 nanoparti-
cles in DMF at room temperature in air.
r.t.
3
2
3
r.t.
r.t.
2
89
74
14
4
r.t.
7
66
5
6
r.t.
r.t.
10
10
32
82
7
8
9
r.t.
r.t.
r.t.
2
4
85
40
48
10
The obtained results are summarized in Table 1. The homo-
coupling of different para-substituted arylboronic acids gave
corresponding biaryls in good to excellent yields (Table 1,
entries 2–6). An arylboronic acid bearing an aldehyde group,
in the para-position, gave the corresponding biaryl in 32%
yield (Table 1, entry 5). meta-Substituted arylboronic acids pro-
duced the corresponding products 2g–i in moderate to good
yields (Table 1, entries 7–9). An arylboronic acid bearing a
weakly coordinating group of –NO2 could also be used to give
the desired product 2h in a 40% yield (Table 1, entry 8). It is
also possible to carry out this homocoupling for ortho-substi-
tuted arylboronic acids. The homocoupling of different ortho-
substituted arylboronic acids gave corresponding biaryls in
moderate to good yields (Table 1, entries 10–12). Whereas the
3,5-difluorophenylboronic acid provided the corresponding
biaryl 2m in a 75% yield (Table 1, entry 13), while 2,6-
dimethylphenylboronic acid failed to give the desired biaryl 2n
due to the steric congestion around the boronic acid (Table 1,
entry 14). This result showed that the reaction suffers from
substrate size restrictions under these conditions. This
method was also applied to the homocoupling of 1- and
2-naphthylboronic acid. 2-Naphthylboronic acid gave the
corresponding binaphthyl 2p in a 90% yield (Table 1, entry15,
however, 1-naphthylboronic acid produced the corresponding
product 2o in a lower yield of 50% (Table 1, entry 16), which is
possibly due to the steric effect. The homocoupling of thio-
phen-3-ylboronic acid, as an heteroarylboronic acid, gave a
31% yield of the desired product 2q (Table 1, entry 17),
whereas with benzofuran-2-ylboronic acid gave a 36% yield
of the desired product 2r (Table 1, entry 18). Finally, the
reaction of trans-2-phenylvinylboronic acid in the presence of
10
11
12
r.t.
r.t.
r.t.
2
1
7
80
82
35
13
70
6
75
14
15
70
24
15
—
r.t.
50
16
r.t.
7
90
17
18
19
r.t.
r.t.
r.t.
2
4
2
31
36
50
a Isolated yields.
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Fe3O4-β-CD-Cu2 nanoparticles gave 2s in a 50% yield (Table 1, in excellent yields (Table 2, entries 2–10). The arylboronic acid
entry 19). bearing an aldehyde group, in the para-position, gave the
Thus, the conditions reported herein tolerate the homo- corresponding triazole product (Table 2, entry 8). It is also
coupling reaction of a wide variety of arylboronic acids. Of possible to carry out this reaction on ortho-substituted aryl-
particular note is the homocoupling reaction of the arylboro- boronic acids (Table 2, entries 2 and 3). This method was also
nic acid bearing an aldehyde group in the para-position, since applied to the one-pot synthesis 1,2,3-triazoles of 1- and
the reaction failed in our previous conditions using the Cu(II)- 2-naphthylboronic acid (Table 2, entries 9 and 10).
β-cyclodextrin complex as a catalyst.12a
Treatment of phenylboronic acid with sodium azide in
On the basis of literature precedents18 and the structure water followed by a click cyclization reaction with different
reported for Cu(II)-β-cyclodextrin,13 we propose a bimetallic substituted phenylacetylenes using Fe3O4-β-CD-Cu2 nanoparti-
coupling mechanism for Fe3O4-β-CD-Cu2 nanoparticles cles at room temperature in air, gave desired products in excel-
catalyzed homocoupling reaction of arylboronic acids lent yields (Table 2, entries 11–13). Finally, the reaction of
(Scheme 2).18 It should be noted that the reaction failed to give phenylboronic acid with sodium azide in water in the presence
a biaryl compound under an atmosphere of argon instead of Fe3O4-β-CD-Cu2 nanoparticles followed by a click cyclization
of air.
reaction with aliphatic alkynes gave the corresponding 1,2,3-
Next we turned our attention to applying this method to the triazole in excellent yields (Table 2, entries 14 and 15). Thus, a
one-pot synthesis of 1,2,3-triazoles via the cross-coupling reac- wide variety of 1,2,3-triazole were synthesized using the con-
tion of aryl boronic acids with azides and subsequent click ditions reported herein.
reaction with alkynes (Scheme 3). Recently we reported the
The results suggest that the reaction was initiated by the
experimental data for the screening of several different copper transmetalation of the aryl group from boron to copper via the
salts and Cu(II)-β-cyclodextrin catalysts in water as a green attack of the hydroxide ligand to the oxophilic boron center.
solvent for the preparation of 1,2,3-triazoles from phenylboro- The resulting aryl copper intermediate (similar to that in
nic acids.12b According to the previous reported conditions, Scheme 2) undergoes subsequent reductive azidation to the
phenylboronic acid (1a) was treated with sodium azide and aryl azide compound. The 1,2,3-triazole formation proceeds
phenylacetylene in water in the presence of 15 mol% of Fe3O4- through the formation of copper acetylide followed by coordi-
β-CD-Cu2 for 4 h at room temperature. As expected, under the nation of the aryl azide to the copper center of the acetylide
reaction conditions the cross coupling reaction and click reac- initiates an azide–alkyne 1,3-dipolar cycloaddition.19
tion occurred in one-pot to give 3a in 95% isolated yield. The
The reusability of the Fe3O4-supported Cu(II)-β-cyclodextrin
blank experiment showed that without the catalyst, the reac- nanoparticles was also studied for both transformations. The
tion could not occur. Due to these results, the one-pot syn- Fe3O4-supported Cu(II)-β-cyclodextrin nanoparticles were col-
thesis of 1,2,3-triazoles from arylboronic acids and alkynes was lected by a magnet and washed four times with deionized
examined using Fe3O4-β-CD-Cu2 at room temperature in air water and methanol and reused for the homocoupling and
without any additives.
one-pot preparation of 1,2,3-triazoles from arylboronic acids
The results obtained are summarized in Table 2. The one- (Fig. 6). The catalytic activity did not decrease considerably
pot reaction of different substituted arylboronic acids with after four catalytic cycles (Table 3). Atomic absorption analysis
sodium azide in water followed by a click cyclization reaction of the liquid phase after separation of the catalyst by an exter-
with phenylacetylene using Fe3O4-β-CD-Cu2 nanoparticles at nal magnet showed that there was no leaching of the copper
room temperature in air, gave the corresponding 1,2,3-triazoles ions from the catalyst to the reaction mixture.
Conclusion
In conclusion, we have developed an efficient copper-catalyzed
protocol for the preparation of biaryls and 1,2,3-triazoles form
arylboronic acids. An efficient, easily recoverable and reusable
Fe3O4-β-CD-Cu2 catalyst was prepared and characterized by
TEM, XRD, VSM, TGA, and FT-IR spectrometer. The catalyst
was suitable for the homocoupling of arylboronic acids for the
Scheme 2 The suggested mechanism for the Fe3O4-supported Cu(II)-β-cyclo-
dextrin nanoparticle-catalyzed homocoupling of aryl boronic acids.
synthesis of symmetrical biaryls and one-pot synthesis of
1,2,3-triazoles through in situ azidation of arylboronic acids
and subsequent click cyclization in water. The Fe3O4-β-CD-Cu2
nanoparticles were collected easily by a magnet and the reusa-
bility of the prepared nanocatalyst was successfully examined
for four runs with only a very slight loss of catalytic activity.
This new, efficient process offers several advantages over many
Scheme 3 One-pot synthesis of 3a using Fe3O4-supported Cu(II)-β-
cyclodextrin.
of the previously published procedures.
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Table 2 Fe3O4-supported Cu(II)-β-cyclodextrin-catalyzed one-pot synthesis of 1,2,3-triazoles from arylboronic acids
Entry
1
Ar (1)
Alkyne
Product 3
t (h)
Yielda [%]
95
C6H5–
4
2
3
4
o-FC6H4–
2
2
2
95
95
95
o-MeC6H4–
3,5-F2C6H3–
5
6
7
p-MeC6H4–
p-MeOC6H4–
p-ClC6H4–
2
3
5
95
95
91
8
9
p-OHCC6H4–
α-Naphthyl
4
4
93
90
10
11
β-Naphthyl
C6H5–
6
3
96
94
12
13
C6H5–
C6H5–
2
6
96
60
14
15
C6H5–
C6H5–
6
6
90
93
a Isolated yields.
Gas chromatography was performed on a Varian CP 3800 chro-
matograph. Analytical TLC was carried out with Merck plates
precoated with silica gel 60 F254 (0.25 mm thick). Column
Experimental
General methods
All melting points were taken on Yanagimoto and Buchi 510 chromatography was performed either with FLUKA silica gel
apparatus and are uncorrected. Mass spectra were recorded on 60 (70–230 mesh) in common glass columns. Copper sulfate
a VG Auto Spec. using electron impact ionization (EI) tech- was recrystallized before use. DMF was dried over CaH2 for 2 h
niques. NMR spectra were obtained on a Bruker Avance 400 and filtered. Aryl boronic acids and amines were used as
NMR Spectrometer (1H NMR: 400 MHz; 13C NMR: 100 MHz). received. All solvents were distilled before use.
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resulting mixture was stirred at 25 °C for 4 h. The nano-
particles were collected with a permanent magnet from the
reaction mixture. Water (100 mL) was added to the reaction
mixture, extracted with CH2Cl2 (2 × 80 mL) and dried over
Na2SO4. The product was purified by immediate flash chrom-
atography (silica gel 60, particle size 230–400 mesh, n-hexane–
EtOAc) to afford 0.57 g of biphenyl 2a as a white solid.
General procedure for the one-pot synthesis of 1,2,3-triazoles
from aryl boronic acids
Fig. 6 Separation of catalyst using an external magnet.
To a mixture of Fe3O4-supported Cu(II)-β-cyclodextrin nano-
particles (0.15 mmol based on copper) in 3 mL distilled water
was added arylboronic acid (1 mmol) and sodium azide
(3 mmol), and the resulting mixture was stirred at an ambient
temperature for 2–6 h. The alkyne (1 mmol) was added to the
reaction mixture and the mixture was stirred at an ambient
temperature for 4 h. The nanoparticles were collected with a
permanent magnet from the reaction mixture and washed
with distilled water and methanol repeatedly. Water (50 mL)
was added to the reaction mixture and extracted with EtOAc
(2 × 20 mL) and dried over Na2SO4. The solvent was removed
under reduced pressure to give the crude product. The solid
was recrystallized from a solvent mixture CH2Cl2–n-hexane or
CH2Cl2–methanol to afford purified 1,2,3-triazole 3a–o in
60–96% yields. All products are known and most of them are
commercially available (see ESI†).
Table 3 Recyclability test of Fe3O4-supported Cu(II)-β-cyclodextrin catalyst in
the homocoupling (biphenyl, 2a) and one-pot synthesis of 1,4-diphenyl-H-1,2,3-
triazole (3a) from phenylboronic acids
Yield (%)
1st run
Average yield
(%)
Product
2nd run
3rd run
4th run
2a
3a
90
95
89
92
87
90
83
87
87
91
Preparation of Fe3O4-supported Cu(II)-β-cyclodextrin
nanoparticles
The Fe3O4-supported Cu(II)-β-cyclodextrin nanoparticles were
prepared by a traditional chemical co-precipitation method.5d
Cu(II)-β-cyclodextrin (1.5 g, prepared by our previously reported
method),12 FeCl3·6H2O (2.36 g), and FeCl2·4H2O (0.86 g) were
dissolved in distilled water (10 mL) under intense stirring at
90 °C under N2. Subsequently, ammonia (25%) was added
Gram-scale procedure for the one-pot synthesis of 1,4-
diphenyl-1H-1,2,3-triazole (3a) from phenylboronic acids
dropwise to the reaction mixture with stirring. The formed To a mixture of Fe3O4-supported Cu(II)-β-cyclodextrin nano-
particles (1.53 g, 1.23 mmol based on copper) in 15 mL dis-
tilled water was added phenylboronic acid (1.0 g, 8.2 mmol)
and sodium azide (1.6 g, 24.6 mmol), and the resulting
mixture was stirred at ambient temperature for 4 h. Phenyl-
acetylene (0.84 g, 8.2 mmol) was added to the reaction mixture
and the mixture was stirred at ambient temperature for 4 h.
The nanoparticles were collected with a permanent magnet
from the reaction mixture and washed with distilled water and
methanol repeatedly. Water (100 mL) was added to the reac-
tion mixture and extracted with EtOAc (3 × 100 mL) and dried
over Na2SO4. The solvent was removed under reduced pressure
to give 1.59 g of 3a (88% yield in this scale) as a white solid.
The solid was recrystallized from a solvent mixture of CH2Cl2–
n-hexane.
nanoparticles were collected with a permanent magnet under
the reaction flask and the liquid reaction mixture was
removed. The particles were washed with distilled water repeat-
edly and dried for 24 h at room temperature in a vacuum oven
(unsupported Fe3O4 nanoparticles were obtained according to
the above procedure without adding Cu(II)-β-cyclodextrin).
General procedure for the homocoupling of aryl boronic acids
To a mixture of Fe3O4-supported Cu(II)-β-cyclodextrin nano-
particles (0.01 mmol based on copper) in 1 mL DMF was
added arylboronic acid (0.2 mmol), and the resulting mixture
was stirred at 25–70 °C for 2–24 h. The nanoparticles were col-
lected with a permanent magnet from the reaction mixture.
Water (20 mL) was added to the reaction mixture, extracted
with CH2Cl2 (2 × 20 mL) and dried over Na2SO4. The product
was purified by immediate flash chromatography (silica gel 60,
particle size 230–400 mesh, n-hexane–EtOAc) to afford biaryls
2a–s in 31–90% yields. All products are known and most of
them are commercially available (see ESI†).
Acknowledgements
The authors gratefully acknowledge the support of the Institute
for Advanced Studies in Basic Sciences (IASBS).
Gram-scale procedure for the homocoupling of phenyl boronic
acid
References
To a mixture of Fe3O4-supported Cu(II)-β-cyclodextrin nano-
particles (0.510 g, 0.41 mmol based on copper) in 5 mL DMF
was added phenylboronic acid (1.0 g, 8.2 mmol), and the
1 For example: (a) J. H. Clark, Green Chem., 1999, 1, 1–8;
(b) A. R. Sheldon, Green Chem., 2005, 7, 267–278;
This journal is © The Royal Society of Chemistry 2013
Green Chem.

View Article Online
Paper
(c) C. E. Song and S. G. Lee, Chem. Rev., 2002, 102, 3495–
Green Chemistry
(g) N. Miyaura and A. Suzuki, Main Group Met. Chem., 1987,
10, 295–300; (h) D. J. Koza and E. Carita, Synthesis, 2002,
2183–2186; (i) G. W. Kabalka and L. Wang, Tetrahedron
Lett., 2002, 43, 3067–3068; ( j) A. Suzuki, Cross coupling
reaction of organoboron compounds with organic halides,
in Metal-catalysed cross-coupling reactions, ed. F. Diederich
and P. T. Stang, Wiley-VCH, Weinheim, 1998;
(k) S. P. Stanforth, Tetrahedron, 1998, 54, 263–303;
(l) H. Hachiya, K. Hirano, T. Satoh and M. Miura, Chem-
CatChem, 2010, 2, 1403.
9 (a) A. W. Thomas and S. V. Ley, Angew. Chem., Int. Ed.,
2003, 42, 5400–5449 and references cited therein;
(b) J.-B. Lan, G.-L. Zhang, X.-Q. Yu, J.-S. You, L. Chen,
M. Yan and R.-G. Xie, Synlett, 2004, 1095–1097;
(c) M. L. Kantam, G. T. Venkanna, C. Sridhar, B. Sreedhar
and B. M. Choudary, J. Org. Chem., 2006, 71, 9522–9524;
(d) G. Cheng and M. Luo, Eur. J. Org. Chem., 2011, 2519–
2523; (e) J. X. Qiao and P. Y. S. Lam, Synthesis, 2011, 829;
(f) B. Kaboudin, T. Haruki and T. Yokomatsu, Synthesis,
2011, 91–95; (g) A. S. Demir, O. Reis and M. Emrullahoglu,
J. Org. Chem., 2003, 68, 10130–10134; (h) N. Kirai and
Y. Yamamoto, Eur. J. Org. Chem., 2009, 1864–1867.
3524; (d) E. Serrano, N. Linares, J. Garcia-Martines and
J. R. Berenguer, ChemCatChem, 2013, 5, 844–860;
(e) S. Trakhtenberg and J. C. Warner, Chem. Rev., 2007, 107,
2174–2182; (f) B. P. Mason, K. E. Price, J. L. Steinbacher,
A. R. Bogdan and D. T. McQuade, Chem. Rev., 2007, 107,
2300–2318; (g) C. Descorme, P. Gallezot, C. Geantet and
C. George, ChemCatChem, 2012, 4, 1897–1906.
2 For example: (a) I. Sadaba, Y. Y. Gorbanov, S. Kegnaes,
S. S. R. Putluru, R. W. Berg and A. Riisager, ChemCatChem,
2013, 5, 284–293; (b) S. Shimura, H. Miura, S. Tsukada,
K. Wada, S. Hosokawa and M. Inoue, ChemCatChem, 2012,
4, 2062–2067; (c) H. Kapper, K. Bouchmella, P. H. Mutin
and F. Goettmann, ChemCatChem, 2012, 4, 1813–1818;
(d) Review: D. S. Liu, S.-Q. Bai, Y. Zheng, K. W. Shah and
M.-Y. Han, ChemCatChem, 2012, 4, 1462–1484.
3 For example: (a) J. Chen, L. N. Xu, W. Y. Li and X. L. Gou,
Adv. Mater., 2005, 17, 582; (b) H. Zeng, J. Li, J. P. Liu,
Z. L. Wang and S. H. Sun, Nature, 2002, 420, 395;
(c) A. Jordan, R. Scolz, K. Maier-Hauff, M. Johannsen,
P. Wust, J. Nadobny, H. Schirra, H. Schmidt, S. Deger,
S. Loening, W. Lanksch and R. Felix, J. Magn. Magn. Mater.,
2001, 225, 118; (d) Y. Wu, M. Chu, B. Shi and Z. Li, Appl. 10 For example: (a) A. K. Feldman, B. Colasson and
Biochem. Biotechnol., 2011, 168, 813–825.
V. V. Fokin, Org. Lett., 2004, 6, 3697–3699;
(b) P. Appukuttan, W. Dehan, V. V. Fokin and E. van der
Eycken, Org. Lett., 2004, 6, 4223–4225; (c) K. Barral,
A. D. Moorhouse and J. E. Moses, Org. Lett., 2007, 9, 1809–
1811; (d) F. Alonso, Y. Moglie, G. Radivoy and M. Yus, Adv.
Synth. Catal., 2010, 352, 3208–3214; (e) D. Kumar and
V. Buchi Reddy, Synthesis, 2010, 1687; (f) F. Alonso,
Y. Moglie, G. Radivoy and M. Yus, Org. Biomol. Chem.,
2011, 9, 6385.
4 For example: (a) R. Zhang, C. Miao, S. Wang, C. Xia and
W. Sun, ChemCatChem, 2013, 5, 142–145; (b) Z. Zheng,
J. Wang, M. Zhang, L. Xu and J. Ji, ChemCatChem, 2013, 5,
307–312; (c) L. Yu, M. Wang, P. Li and L. Wang, Appl. Orga-
nomet. Chem., 2012, 26, 576–582; (d) B. Karimi and
E. Farhangi, Chem.–Eur. J., 2011, 17, 6056–6060;
(e) Q. Zhang, H. Su, J. Luo and Y. Wei, Catal. Sci. Technol.,
2013, 3, 235–243; (f) R. Abu-Aeziq, D. Wang, M. Post and
H. Alper, Chem. Mater., 2008, 20, 2544–2550.
5 For example: (a) Q. Zhang, H. Su, J. Luo and Y. Wei, Green
Chem., 2012, 14, 201–208; (b) C. Che, W. Li, S. Lin, J. Chen,
J. Zheng, L.-C. Wu, Q. Zheng, G. Zhang, Z. Yang and
B. Jiang, Chem. Commun., 2009, 5990–5992; (c) P. Li,
L. Wang, L. Zhang and G.-W. Wang, Adv. Synth. Catal.,
2012, 354, 1307–1318; (d) X. Chen, J. Rao, J. Wang,
J. J. Gooding, G. Zou and Q. Zhang, Chem. Commun., 2011,
47, 10317–10319.
11 (a) C.-Z. Tao, X. Cui, J. Li, A.-X. Liu, L. Liu and Q.-X. Guo,
Tetrahedron Lett., 2007, 48, 3525–3529; (b) H. Sharghi,
R. Khalifeh and M. M. Doroodmand, Adv. Synth. Catal.,
2009, 351, 207; (c) M. I. Aliaga, D. J. Raman and M. Yus,
Org. Biomol. Chem., 2010, 8, 43–46; (d) R. B. N. Baig and
R. S. Varma, Green Chem., 2012, 14, 625–652; (e) F. Alonso,
Y. Moglie and G. Radivoy, Adv. Synth. Catal., 2010, 352,
3208; (f) R. Hudson, C. J. Li and A. Moores, Green Chem.,
2012, 14, 622; (g) N. Mukherjee, S. Ahammed, S. Bhadra
and B. C. Ranu, Green Chem., 2013, 15, 389–397;
(h) K. Namitharan, M. Kumarraja and K. Pitchumani,
Chem.–Eur. J., 2009, 15, 2755–2758.
6 (a) T. Zeng, L. Yang, R. Hudson, G. Song, A. R. Moores and
C. J. Li, Org. Lett., 2011, 13, 442–445; (b) L. Yu, M. Wang, P. Li
and L. Wang, Appl. Organomet. Chem., 2012, 26, 576–582.
7 (a) F. Ullmann, Ber. Dtsch. Chem. Ges., 1903, 36, 2389–2391; 12 (a) B. Kaboudin, Y. Abedi and T. Yokomatsu, Eur. J. Org.
(b) F. Ullmann, Ber. Dtsch. Chem. Ges., 1904, 37, 853–857;
(c) I. Goldberg, Ber. Dtsch. Chem. Ges., 1906, 39, 1691–1696.
Chem., 2011, 6656–6662; (b) B. Kaboudin, Y. Abedi and
T. Yokomatsu, Org. Biomol. Chem., 2012, 10, 4543–4548.
8 (a) C. F. Nising, U. K. Schmid, M. Nieger and S. Bräse, 13 (a) E. Z. Messmer, Phys. Chem., 1927, 126, 369;
J. Org. Chem., 2004, 69, 6830–6833; (b) Y. Miyake, M. Wu,
M. J. Rahman, Y. Kuwatani and M. Iyoda, J. Org. Chem.,
2006, 71, 6110; (c) X. Xu, D. Cheng and W. Pei, J. Org.
Chem., 2006, 71, 6637; (d) Z. Xu, J. Mao and Y. Zhang,
Catal. Commun., 2008, 9, 97; (e) G. Cahiez, A. Moyeux,
J. Buendia and C. Duplais, J. Am. Chem. Soc., 2007, 129,
13788; (f) M. K. Robinson, V. S. Kochurina and
J. M. Hanna, Tetrahedron Lett., 2007, 48, 7687;
(b) Y. Matsui, T. Kurita and Y. Date, Bull. Chem. Soc. Jpn.,
1972, 45, 3229; (c) Y. Matsui, T. Kurita, M. Yagi,
T. Okayama, K. Mochida and Y. Date, Bull. Chem. Soc. Jpn.,
1975, 48, 2187; (d) K. Mochida and Y. Matsui, Chem. Lett.,
1976, 963; (e) Y. Matsui and K. Kinugawa, Bull. Chem. Soc.
Jpn., 1985, 58, 2981; (f) E. Norkus, G. Grinciene,
T. Vuorinen, E. Butkus and R. Vaitukus, Supramol. Chem.,
2003, 15, 425–431.
Green Chem.
This journal is © The Royal Society of Chemistry 2013

View Article Online
Green Chemistry
Paper
14 M. Racuciu, D. E. Creanga, V. Badescu and A. Airinei,
J. Optoelectron. Adv. Mater., 2007, 9, 1530–1533.
15 J. T. Keiser, C. W. Brown and R. H. Heidersbach, J. Electro-
chem. Soc., 1982, 129, 2686.
16 X. Sun, C. Zheng, F. Zhang, L. Li, Y. Yang, G. Wu and
N. Guam, J. Phys. Chem. C, 2008, 112, 17143.
Chem., 1974, 86, 321–335, (Angew. Chem., Int. Ed. Engl.,
1974, 13, 291–356); (d) For the bimetallic mechanism of
copper salts for the homocoupling reactions see:
G. Harada, M. Yoshida and M. Iyoda, Chem. Lett., 2000,
160–161; (e) N. Kirai and Y. Yamamoto, Eur. J. Org. Chem.,
2009, 1864–1867.
17 A. Z. M. Badruddoza, G. S. S. Hazel, K. Hidajat and 19 For example: (a) J. E. Hein, J. C. Tripp, L. B. Krasnova,
M. S. Uddin, Colloids Surf., A, 2010, 367, 85–95.
K. B. Sharpless and V. V. Fokin, Angew. Chem., Int. Ed.,
2009, 48, 8018–8021; (b) M. Fuchs, W. Goessler, C. Pilger
and C. O. Kappe, Angew. Chem., Int. Ed., 2010, 352, 323–328
and references cited therein (c) C. W. Tornøe and
M. Meldal, Chem. Rev., 2008, 108, 2952–3015 and refer-
ences cited therein (d) C. D. Bradley, M. J. Scanlon and
J. S. Simpson, Org. Lett., 2011, 13, 537–539.
18 The mechanism of transmetallation of (hydroxide) metal
complexes with arylboronic acids has been discussed, see:
(a) T. Hayashi, M. Takahashi, Y. Takaya and M. Ogasawara,
J. Am. Chem. Soc., 2002, 124, 5052–5058; (b) T. Nishikawa,
Y. Yamamoto and N. Miyaura, Organometallics, 2004, 23,
4317–4324; (c) For a review, see: T. Kauffmann, Angew.
This journal is © The Royal Society of Chemistry 2013
Green Chem.