CuII immobilized on guanidinated epibromohydrin functionalized γ-Fe2O3@TiO2 (γ-Fe2O3@TiO2-EGCuII): A novel magnetically recyclable heterogeneous nanocatalyst for the g

Article abstract of DOI:10.1039/c6ra05468d

Cu^II immobilized on guanidinated epibromohydrin functionalized γ-Fe₂O₃@TiO₂ (γ-Fe₂O₃@TiO₂-EG-CuII) as a novel magnetically recyclable heterogeneous catalyst was synthesized and c

Full text of DOI:10.1039/c6ra05468d

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CuII immobilized on guanidinated epibromohydrin functionalized
γ-Fe2O3@TiO2 (γ-Fe2O3@TiO2-EG-CuII): a novel magnetically
recyclable heterogeneous nanocatalyst for the green one-pot
synthesis of 1,4-disubstituted 1,2,3-triazoles through alkyne-azide
cycloaddition in water
Received 00th January 20xx,
Accepted 00th January 20xx
DOI: 10.1039/x0xx00000x
www.rsc.org/
Roya Jahanshahia and Batool Akhlaghinia*a
CuII immobilized on guanidinated epibromohydrin functionalized γ-Fe2O3@TiO2 (γ-Fe2O3@TiO2-EG-CuII) as
a novel
magnetically recyclable heterogeneous catalyst was synthesized and characterized by various techniques such as FT-IR,
TGA/DTA, HRTEM, XRD, EDX, VSM, ICP and elemental analysis. The catalyst was demonstrated a superior catalytic activity
towards the green one-pot synthesis of 1,4-disubstituted 1,2,3-triazoles via the three-component reactions between
terminal alkynes, organic bromides, and sodium azide, in water. This method avoids isolation and handling of organic
azides, because of their in situ generation. Importantly, the synthesized catalyst was separated easily by using an external
magnet and recycled for six runs without appreciable leaching of copper from the surface of the catalyst.
species through the reduction of Cu(II) salts,11,12,13b,14 oxidation of
Cu(0) metal,10c-i and copper(II)/copper(0) comproportionation15 or
1. Introduction
N-Heterocyclic compounds such as 1,2,3-triazoles, have
tremendous applications in various research fields. In this context,
numerous examples were reported in literatures including anti-HIV
activity,1,2 antibacterial activity,3 antiallergic activity,4 and selective
β3 adrenergic receptor agonism.5 1,2,3-Triazoles have also a range
of important applications in biological science,6 synthetic organic
chemistry,7 medicinal chemistry,8 material chemistry9 and
industries such as dyes, corrosion inhibition, photostabilizers,
photographic materials, and agrochemicals.10 Thermal 1,3-dipolar
cycloaddition of organic azides with alkynes was reported as the
classical method for 1,2,3-triazoles preparation which suffered from
some disadvantages such as elevated temperature, low yields of the
products and lack of selectivity.11 To remove these limitations, the
most versatile protocol for the synthesis of 1,4-disubstituted 1,2,3-
triazoles with high regioselectivity, low temperature reaction and
enlarged scope has been developed, through the Cu(I)-catalyzed
azide–alkyne cycloaddition (CuAAC, better known as click
chemistry).11,12,13 Because of thermodynamical instability of Cu(I)
salts and also formation of undesired alkyne–alkyne coupling by-
product, this method (CuAAC reaction) which has been extensively
studied and widely used, was modified by in situ generation of Cu(I)
using Cu(I) salts in the presence of bases and/or ligands which
protect Cu(I) intermediates from oxidation and disproportionation
and hamper undesired side-product formation.16
Recently, heterogeneous catalysts have gained prominent
attention in economical and environmentally benign chemical
processes, due to their efficient recyclability and facile separation of
the products. Numerous supports such as polymers,17 aluminum
oxyhydroxide nanofibers,18 activated charcoal,19 zeolites,20
magnetic material,21 alumina,22 clay,23 silica-supported N-
heterocyclic carbene24 and titanium dioxide,25 have been attempted
for CuAAC reaction. Moreover, solid supported CuII species as
heterogeneous catalytic systems without reducing agents have
been reported in alkyne-azide cycloaddition reaction.26
In recent years, magnetic nanoparticles (MNPs) have received
remarkable attention by organic chemists as a new alternative to
porous materials for homogeneous catalysts supporting.27 Because
of the magnetic nature of MNPs, the appropriate removal and
recycling of the MNPs-supported catalysts is feasible by means of
an external magnet. This separation approach is not time-
consuming in comparison with standard methods (filtration and
centrifugation), and prevents the heterogeneous catalyst
loss during the separation process. Additionally, it increases the
purity of the products, as well as optimizing the operational costs.28
Besides,
a great deal of efforts have been devoted to the
incorporation of MNPs into core shell structures, in order to control
the size, shape and magnetic features of the hybrid materials.29
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Coating of the MNPs avoids their aggregation/oxidation and serves magnetization isotherms were obtained using a vibrating sample
as the catalyst platform.30
magnetometer (VSM, LakeShore 7400). X-ray powder diffraction
On the other hand, it is worth mentioning that a recyclable (XRD) was performed on a X’Pert Pro MPD diffractometer with Cu
catalyst needs an appropriate reaction media for implementation in Kα (λ = 0.154 nm) radiation. All yields refer to isolated products
large scale in chemical industries. Recently, organic reactions in after purification by recrystallization.
water as a benign reaction media, have attracted a number of
interest in both academic and industrial research, because water is
nontoxic, readily available, environmentally friendly and cheap.
TiO
2
FeCl3.6H2
O
TiCl4
Calcination
Furthermore, reactions in aqueous media represent unique
selectivities and reactivities, as well as cleaner chemical processes,
in comparison with those performed in organic media.
γ-Fe2O3
1) Ar, 400 °C, 1 h
2) O2, 250 °C, 2 h
NH4OH, Ar, rt
γ-Fe2O3@TiO2 (I)
O
As part of our continuing interests in developing new
heterogeneous catalysts,31 in the synthetic organic chemistry,
herein, we wish to report the preparation of CuII immobilized on
guanidinated epibromohydrin functionalized γ-Fe2O3@TiO2 (γ-
FeCl2.4H2O
Br
60 °C, 24h
O
O
NH2
NH2
N
HO
O
O
TiO2
Fe2O3@TiO2-EG-CuII) as
a novel and magnetically recyclable
Guanidinehydrochloride
NaHCO3
TiO2
O
O
O
O
O
γ-Fe2O3
O
γ-Fe2O3
dry toluene,reflux,48 h
heterogeneous catalyst (Scheme 1). The catalytic activity of γ-
Fe2O3@TiO2-EG-CuII, was proved for the one-pot synthesis of 1,4-
disubstituted 1,2,3-triazoles, through alkyne-azide cycloaddition, in
water (see Scheme 2).
O
NH2
NH2
HO
N
O
O
O
O
O
-Fe O @TiO2-EG (III)
γ
2
3
-Fe O3@TiO2-E (II)
γ
2
Cu(OAc)2 . H2
O
EtOH,Ar, rt, 4 h
AcO
HO
OAc
Cu
2. Experimental
2.1. Materials
H2
N
H2
N
AcO
AcO
OAc
Cu
N
N
OH
N
Cu
Cu
TiO2
N
N
OAc
H2
H2
All chemical reagents and solvents were purchased from Merck and
Sigma-Aldrich chemical companies and were used as received
without further purification. γ-Fe2O3/TiO2 nanoparticles were
prepared by the previously reported method in literature.32
O
O
O
O
γ-Fe2O3
AcO
AcO
H2
N
NH2
OAc
OAc
Cu
HO
OH
N
N
H2
N
H2
Cu
γ-Fe2O3@TiO2-EG-CuII (IV)
AcO
OAc
2.2. Instrumentation analysis
Scheme
1
Preparation of CuII immobilized on guanidinated
The purity determinations of the products and the progress of the
reactions were accomplished by TLC on silica gel polygram STL
G/UV 254 plates. The melting points of the products were
determined with an Electrothermal Type 9100 melting point
apparatus. The FTIR spectra were recorded on pressed KBr pellets
using an AVATAR 370 FT-IR spectrometer (Therma Nicolet
spectrometer, USA) at room temperature in the range between
4000 and 400 cm-1 with a resolution of 4 cm-1, and each spectrum
was the average of 32 scans. NMR spectra were recorded on a NMR
Bruker Avance spectrometer at 400 and 300 MHz in CDCl3 as
solvent in the presence of tetramethylsilane as the internal
standard and the coupling constants (J values) are given in Hz.
Elemental analyses were performed using a Thermo Finnigan Flash
EA 1112 Series instrument (furnace: 900 ˚C, oven: 65 ˚C, flow
carrier: 140 mL min-1, flow reference: 100 mL min-1). Mass spectra
were recorded with a CH7A Varianmat Bremem instrument at 70 eV
electron impact ionization, in m/z (rel %). Thermogravimetric
analyses (TGA and DTG) were carried out using a Shimadzu
Thermogravimetric Analyzer (TG-50) in the temperature range of
25–900 ˚C at a heating rate of 10 ˚C min-1, under air atmosphere.
HRTEM analysis was performed using HRTEM microscope (Philips
CM30). Inductively coupled plasma (ICP) was carried out on a
Varian, VISTA-PRO, CCD, Australia. Elemental compositions were
determined with an SC7620 Energy-dispersive X-ray analysis (EDX)
presenting a 133 eV resolution at 20 kV. Room temperature
epibromohydrin functionalized γ-Fe2O3@TiO2 (γ-Fe2O3@TiO2-EG-
CuII).
2.3. Preparation of γ-Fe2O3@TiO2 nanoparticles (I)
FeCl3·6H2O (5.11 g, 18.9 mmol) and FeCl2·4H2O (2.21 g, 17.43 mmol)
were dissolved in deionized water (50 mL) under argon atmosphere
at room temperature. The solution was stirred magnetically for 5
min, and then titanium tetrachloride (2 mL, 18 mmol) was added
into the solution. NH4OH solution (0.6 M, 400 mL) was then added
drop by drop (drop rate = 1 mL min-1) into the solution using a
syringe pump under vigorous stirring at room temperature. When
pH was adjusted to 9.0, addition of NH4OH solution was stopped.
The mixture was diluted with 200 mL deionized water and stirred
vigorously for 30 min at 50 ˚C, in water bath. Then the mixture was
placed on a strong magnet and the particles were then separated
from the solution. The particles were washed with deionized water
(5×20 mL) and then dried at 40 ˚C for 24 h. Afterwards, the particles
were crushed and calcinated under argon atmosphere at 400 ˚C for
1
h to obtain crystallized anatase TiO2. Then the obtained
nanoparticles were calcinated under oxygen at 250 ˚C for 2 h. γ-
Fe2O3@TiO2 (I) was stored in a desiccator for further use.
2.4. Preparation of epibromohydrin functionalized γ-Fe2O3@TiO2
(γ-Fe2O3@TiO2-E) (II)
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γ-Fe2O3@TiO2 nanoparticles (I) (2 g) was dispersed in 6 mL pure sample magnetometer (VSM), inductively coupled plasma (ICP) and
epibromohydrin by sonication for 30 min. The resultant suspension elemental analysis (CHN). The results obtained from these
was heated at 60 ˚C with vigorous stirring. After 24 h, techniques, confirmed the successful preparation of the new
epibromohydrin-functionalized γ-Fe2O3@TiO2-E (II) was separated catalyst.
by an external magnet and washed with MeOH (5×10 mL) until
Fig. 1 illustrates the FT-IR spectra of γ-Fe2O3@TiO2 (I),
removing additional amount of epibromohydrin and then dried at epibromohydrin functionalized γ-Fe2O3@TiO2 (II), guanidinated
40 ˚C under vacuum for 14 h.
epibromohydrin functionalized γ-Fe2O3@TiO2 (III) and CuII
immobilized on guanidinated epibromohydrin functionalized γ-
2.5. Preparation of guanidinated epibromohydrin functionalized γ- Fe2O3@TiO2 (γ-Fe2O3@TiO2-EG-CuII (IV)). As can be seen, the
Fe2O3@TiO2 (γ-Fe2O3@TiO2-EG) (III)
stretching vibration of Fe–O bond in γ-Fe2O3 was assigned at around
The γ-Fe2O3@TiO2-E (II) (1.5 g), was dispersed in dry toluene (7 ml), 698-571 cm-1,33 which was covered by the broad characteristic
by placing in an ultrasonic bath for 20 min. Subsequently, guanidine stretching vibration band of Ti–O at 850-500 cm-1 in the TiO2
hydrochloride (0.38 g, 0.004 mmol) and sodium bicarbonate (0.67 g, lattice.34 Furthermore, the absorption band at 1619 cm-1 (related to
0.008 mmol) were added and the mixture was refluxed for 48 h. bending vibration) and the broad band appearing at 3500-3100 cm-1
Then, the final product was separated by magnetic decantation and (related to stretching vibration of both symmetrical and
washed with dry CH2Cl2 (3×15 mL) and EtOH (3×15 mL), respectively asymmetrical modes) were attributed to the physisorbed water and
and then dried under vacuum at 40 ˚C.
the hydroxyl groups which are attached to the surface of γ-
Fe2O3@TiO2.35 The epoxy ring which was grafted to the γ-
2.6. Preparation of CuII immobilized on guanidinated Fe2O3@TiO2 framework was recognized by the methylene C–H
epibromohydrin functionalized γ-Fe2O3@TiO2 (γ-Fe2O3@TiO2-EG- stretching and bending vibration bands at 2923–2872 and 1454 cm-
CuII) (IV)
1, respectively.36 An absorption band at 1112 cm-1 was attributed to
To a solution of Cu(OAc)2.H2O (0.6 mmol, 0.11 g) in absolute EtOH C–O–C vibrational stretching. These results indicated that the γ-
(5 mL), γ-Fe2O3@TiO2-EG (III) (1 g) was added at room temperature. Fe2O3@TiO2 surface has been immobilized by covalent bonded
The reaction mixture was stirred under argon atmosphere for 4 h. organic epoxy rings. Ring opening of epoxy ring with guanidine was
The resulting suspension was separated and washed with acetone asserted by appearance of the absorption bands around 3378 and
(4×5 mL) and ethanol (4×5 mL), respectively and then dried under 1454 cm-1 corresponding to the N–H and C–N stretching vibrations,
vacuum at ambient temperature for 16 h.
respectively.35c Absorption bands at 428, and 450 cm-1 document
the coordination of CuII on guanidinated epibromohydrin
2.7. Typical procedure for preparation of 1-benzyl-4-phenyl-1H- functionalized γ-Fe2O3@TiO2 which is allocated to Cu–N and Cu–O
1,2,3-triazole (4a)
vibrations, respectively.31a These two absorption bands were
γ-Fe2O3@TiO2-EG-CuII (0.054 g, 4 mol%), was added to a solution of covered by stretching vibration frequencies of Fe–O and Ti–O
phenylacetylene (0.102 g, 1 mmol), benzyl bromide (0.171 g, 1 bonds. Upon coordination of CuII, the intensities of –NH2 and
mmol) and NaN3 (0.078 g, 1.2 mmol) in H2O (5 mL). The mixture was probably –OH stretching frequencies (at around 3378-3162 cm-1)
magnetically stirred at 50 ˚C, for 5 min and the progress of the were diminished, significantly. The –NH bending vibration
reaction was monitored by TLC (n-hexane: EtOAc, 3:1). Upon the (positioned at 1617 cm-1) and probably OH bending vibration
completion of the reaction, the catalyst was removed by an (positioned at 1619 cm-1) were also shifted to lower frequencies
external magnet, washed with methanol (2×10 mL) and dried due to coordination with CuII. Moreover C–N stretching vibration
overnight to be ready for the next run. The resulting mixture was (positioned at 1454 cm-1) and C=N stretching vibration (positioned
diluted with deionized water (10 mL) and extracted with EtOAc at 1662 cm-1), were shifted to lower frequencies assigned to
(3×15 mL). The organic layer was dried over anhydrous Na2SO4, coordination with CuII. Also, peaks depicted at 1634 and 1401 cm-1
followed by evaporation under reduced pressure to remove the in the spectrum of γ-Fe2O3@TiO2-EG-CuII were related to COO (in
solvent. The residue was purified by recrystallization from ethanol acetate),33 confirming the presence of Cu in the catalyst. These
to afford 1-benzyl-4-phenyl-1H-1,2,3-triazole (0.22 g, 94 %).
absorption bands were covered by broad and strong C–N stretching
vibration frequency.
3. Results and Discussion
3.1. Characterization of γ-Fe2O3@TiO2-EG-CuII (IV)
According to the pathway shown in Scheme 1, γ-Fe2O3@TiO2-EG-
CuII was synthesized as
a novel efficient and reusable
heterogeneous catalyst. This newly synthesized catalyst was fully
characterized by different techniques such as fourier transform
infrared
spectroscopy
(FT-IR),
thermogravimetric
analysis/differential thermal analysis (TGA/DTA), high resolution
transmission electron microscopy (HRTEM), X-ray powder
diffraction (XRD), energy-dispersive X-ray analysis (EDX), vibrating
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Fig. 1 FT-IR spectrum of (a) γ-Fe2O3@TiO2 nanoparticles (I); (b) sample magnetometry (VSM). As illustrated in Fig. 6, the value of
epibromohydrin functionalized γ-Fe2O3@TiO2 (II); (c) guanidinated
epibromohydrin functionalized γ-Fe2O3@TiO2 (III); (d) CuII
immobilized on guanidinated epibromohydrin functionalized γ-
Fe2O3@TiO2 (γ-Fe2O3@TiO2-EG-CuII); (e) 6th recovered γ-
Fe2O3@TiO2-EG-CuII.
saturation magnetic moments of γ-Fe2O3@TiO2 NPs (Fig. 6a) and γ-
Fe2O3@TiO2-EG-CuII (Fig. 6b) are 23.79 and 22.12 emμ g-1,
respectively. It indicates both γ-Fe2O3@TiO2 and γ-Fe2O3@TiO2-EG-
CuII are superparamagnetic. Small decreasing in the saturation
magnetization of γ-Fe2O3@TiO2 NPs after the surface grafting, can
be attributed to the contribution of the non-magnetic materials.
a
b
Fig. 3 HRTEM images of γ-Fe2O3@TiO2-EG-CuII (a, b).
Fig. 2 Thermogram of γ-Fe2O3@TiO2-EG-CuII.
The thermogravimetric analysis/differential thermal analysis
(TGA/DTA) of γ-Fe2O3@TiO2-EG-CuII was used to determine the
thermal stability and content of organic functional groups on the
surface of the MNPs (Fig. 2). TGA curve of γ-Fe2O3@TiO2-EG-CuII
showed the weight loss below 200 ˚C, which was related to the
adsorbed water molecules on the support. The organic parts were
decomposed completely in the temperature range of 200–670 ˚C
(17.23 wt%). According to the TGA, the amount of organic segment
supported on γ-Fe2O3@TiO2 is estimated to be 0.70 mmol/g. These
results were in a good agreement with the elemental analysis data
(N = 3.01% and C = 7.02%) and ICP. The ICP analysis showed that
0.74 mmol of copper was anchored on 1.000 g of the catalyst.
HRTEM images of γ-Fe2O3@TiO2-EG-CuII displayed a dark γ-Fe2O3
core with the average size of about 10-20 nm which was
surrounded by a grey titania shell with a thickness of about 5–10
nm (Fig. 3).
Fig. 4 XRD pattern of γ-Fe2O3@TiO2 MNPs.
XRD measurement was used to identify the crystalline structure
of γ-Fe2O3@TiO2 MNPs. As shown in Fig. 4, all the peaks which can
be indexed to (2 2 0), (3 1 1), (4 0 0), (4 2 2), (5 1 1) and (4 4 0)
reflections, agree well with the cubic structure of maghemite (γ-
Fe2O3) (JCPDS file No. 04-0755). In addition, weak diffraction peaks
appeared at angles corresponding to (0 1 1), (0 0 4) and (0 2 0)
crystallographic faces, could be assigned to anatase XRD diffraction
peaks. The average crystallite size of maghemite and TiO2 (anatase),
calculated using the Debye–Scherrer equation d = Kλ/(βcosθ) are
about 13 and 7 nm, respectively.
Fig. 5 EDX analysis of γ-Fe2O3@TiO2-EG-CuII.
The Energy-dispersive X-ray analysis (EDX) reveals the existence
of C, O, Fe, Ti and Cu elements (Fig. 5). This analysis confirms that
CuII is supported on guanidinated epibromohydrin functionalized γ-
Fe2O3@TiO2 (γ-Fe2O3@TiO2-EG).
3.2. Catalytic synthesis of 1,4-disubstituted 1,2,3-triazoles
After the successful preparation and full characterization of the γ-
Fe2O3@TiO2-EG-CuII, its catalytic activity was examined for the
The magnetization curves of γ-Fe2O3@TiO2 and γ-Fe2O3@TiO2-
EG-CuII were measured at ambient temperature with a vibrating
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green one-pot synthesis of 1,4-disubstituted 1,2,3-triazoles from obtained at 50 ˚C (Table 1, entry 6). The model reaction was
the reaction of various terminal alkynes, different organic bromides, performed in the presence of different amounts of the catalyst
and sodium azide (1,3-dipolar Huisgen cycloaddition reaction), in (Table 1, entries 9-11).
R2
water (Scheme 2).
N
γ-Fe2O3@TiO2-EG-CuII (4 mol%)
N
R1
+
R2 Br NaN
+
3
N
To find an appropriate reaction medium for the preparation of
1,4-disubstituted 1,2,3-triazoles in the presence of the catalytic
amount of γ-Fe2O3@TiO2-EG-CuII, the one pot reaction between
H2O, 50 °C
R1
R1 = Ph, 4-MeC6H4, 4-OMeC6H4, 4-tBuC6H4, 4-ClC6H4, 4-BrC6H4, 4-NO2C6H4, 2-pyridine
R2 = PhCH2, p-ClC6H4CH2, p-NO2C6H4CH2, H2C CHCH2
Scheme 2 Synthesis of different structurally 1,4-disubstituted 1,2,3-
triazoles in the presence of γ-Fe2O3@TiO2-EG-CuII, in water.
Increasing the amount of the catalyst to 5 mol% showed no
further increase in the yield of the product. However, decreasing
the catalyst loading, led to lower product yield, in longer reaction
time.
During our optimization studies, screening solvent free conditions
and different solvents (Table 1, entries 12-16), revealed that H2O
clearly stands out as the solvent of choice with its fast reaction rate,
high isolated yield and selectivity. It can be seen that, applying
lower amounts of sodium azide resulted in 65% and 76% yields of
the product, in water after a long time (Table 1, entries 17-18).
However, higher amounts of sodium azide had no more effect on
the reaction progress (Table 1, entry 19). The obtained results
demonstrated that the γ-Fe2O3@TiO2-EG-CuII catalyst exhibits
promising catalytic activity in water at 50 ˚C, with enhanced
regioselectivity, towards the desired 1,4-disubstituted 1,2,3-triazole
product (Table 1, entry 6). To probe the reaction scope and
performance of γ-Fe2O3@TiO2-EG-CuII catalyst, we also examined
benzyl chloride (instead of benzyl bromide) under the optimized
reaction conditions. Control experiment conducted in the presence
of benzyl chloride illustrated the longer reaction time, due to the
lower activity of benzyl chloride (Table 1, entry 20).
Fig. 6 Magnetization curves of (a) γ-Fe2O3@TiO2 nanoparticles (I)
and (b) γ-Fe2O3@TiO2-EG-CuII.
phenylacetylene (1 mmol), benzyl bromide (1 mmol), and sodium
azide (1.2 mmol), was selected as a model reaction. The model
reaction behaviour was studied under a variety of conditions, and
the results are summarized in Table 1. It can be seen that, when the
model reaction was carried out at 100 ˚C in aqueous media, in the
absence of the catalyst, no desired product was formed, even after
a prolonged reaction time (Table1, entry 1). Similarly, in the
presence of (I), (II) and (III) as catalyst, the product yields were
poor, even after 3 h (Table1, entries 2-4). This reaction gives high
yields of 1-benzyl-4-phenyl-1H-1,2,3-triazole (4a), in the presence of
γ-Fe2O3@TiO2-EG-CuII (Table 1, entry 5). Then, we investigated the
effect of different temperatures on the model reaction (Table 1,
entries 6-8). According to the data of Table 1, the best result was
Table 1 One-pot synthesis of 1-benzyl-4-phenyl-1H-1,2,3-triazole under different reaction conditions.
Entry
Molar ratio
1:2:3
Catalyst
(mol%)
none
Temp.
(˚C)
Solvent
Time
(min)
15 h
Isolated
Yield (%)
-
1
2a
3b
4c
5
1:1:1.2
100
H2O
H2O
H2O
H2O
H2O
H2O
H2O
1:1:1.2
1:1:1.2
1:1:1.2
1:1:1.2
1:1:1.2
1:1:1.2
0.054 g
100
100
100
100
50
3 h
3 h
3 h
5
Trace
Trace
Trace
94
0.054 g
0.054 g
4
4
4
6
5
94
7
40
1 h
62
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Journal Name
8
1:1:1.2
1:1:1.2
1:1:1.2
1:1:1.2
1:1:1.2
1:1:1.2
1:1:1.2
4
3
2
5
4
4
4
R.T.
50
50
50
50
50
H2O
H2O
H2O
H2O
-
1 h
30
30
5
41
89
74
94
49
57
83
9
10
11
12
13
14
45
30
30
MeOH
50
MeOH : H2O
(1:1)
15
16
17
18
19
1:1:1.2
1:1:1.2
1:1:1
4
4
4
4
4
4
50
50
50
50
50
50
CH3CN
THF
30
30
10
10
5
Trace
Trace
65
H2O
H2O
H2O
H2O
1:1:1.1
1:1:1.4
1:1:1.2
76
94
20d
15
90
a
b
The reaction was performed in the presence of γ-Fe2O3@TiO2 (I). The reaction was performed in the presence of γ Fe2O3@TiO2-E (II). c
The reaction was performed in the presence of γ-Fe2O3@TiO2-EG (III). d The reaction was performed by using benzyl chloride instead of
benzyl bromide.
With the optimized reaction conditions in hand, we then handling of potentially unstable organic azides and provides the
investigated the generality and versatility of this method. The triazole products in pure form. The scope of the cycloaddition using
reaction was extended to various structurally diverse terminal our catalyst is quite broad; various terminal alkynes react readily
alkynes and organic bromides (Table 2). In all cases, [3+2] with benzyl and allyl bromides at 50 ˚C, in water.
cycloadditions were complete in a short time and 1,2,3-triazole
However, having at least two active sites in each ligand that has
derivatives were isolated in good to excellent yields. Using this been attached to the support (see Scheme 1), leads to high copper
methodology in the reaction of sodium azide, benzyl or allyl loading capacity of the catalyst, as this has been confirmed by
bromides with different terminal alkynes, produced only one of the inductively coupled plasma (ICP). Accordingly, γ-Fe2O3@TiO2-EG-CuII
possible regioisomers, as expected. The same methodology was catalyst was exhibited much more catalytic efficiency compared
successfully applied to the aryl acetylenes bearing both electron- with some of the catalysts used for this transformation, previously
releasing and electron-withdrawing groups attached to the (see Table 3). It is worthy of note that, although the small amounts
aromatic ring. Additionally, the heteroaryl substituted acetylenes of catalyst was utilized (4 mol%), it could be separated from the
(2-ethynylpyridine) underwent clean reactions to produce the reaction medium simply by using an external magnet and reused for
corresponding triazoles (Table 2, entries 8, 13 and 18). Excitingly, at least six consecutive trials without significant decrease in the
the results shown in Table 2 (entries 9-18) demonstrate that the catalytic activity.
reaction was compatible successfully with
a
broad range of
Most of the obtained triazoles (4a-j, 4m-p and 4r-v) were known
substituted benzyl bromides. In an attempt to broaden the scope of and their physical (color, melting points) and spectral (mass
our methodology, the possibility of performing the reaction with spectrometry) data found to be identical with those of authentic
allyl bromide instead of benzyl bromide was also investigated. From compounds. The selected compounds were further identified by FT-
Table 2, it can be observed that the Huisgen 1,3-dipolar IR, 1H NMR and 13C NMR spectroscopy which compared with
cycloaddition reaction of terminal alkynes and allyl bromide literature data. The novel synthesized compounds (4k, 4l and 4q)
proceeded smoothly and the corresponding 1,4-disubstituted 1,2,3- were also characterized by using elemental analysis technique.
triazoles were obtained in high yields (Table 2, entries 19-22).
In the FT-IR spectra of the products, the disappearance of the
With this catalyst, safe and efficient three-component absorption bands due to C≡C and ≡C–H stretching bands (at about
a
reaction for the regioselective generation of 1,4-disubstituted 1,2,3- 2250-2100 and 3300 cm-1, respectively) accompanied by the
triazoles has been developed. The method avoids isolation and appearance of the characteristic bands due to the out of plane
6 | J. Name., 2012, 00, 1-3
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bending vibrations of the =C–H in the triazole ring (at about 815 comparison of the 1H and 13C NMR spectra with those reported
cm-1), were evidence for the formation of 1,4-disubstituted 1,2,3- previously. In particular, click condensations were confirmed by the
triazoles. Also, the FT-IR spectra of all products show absorption appearance of a singlet resonating at around 8.5–7.5 ppm in 1H
bands at about 1293–1217 cm-1 (due to N–N=N–) related to the NMR
triazole ring. Structural assignments of triazoles were made by
Table 2. Huisgen 1,3-dipolar cycloaddition catalyzed by γ-Fe2O3@TiO2-EG-CuII.
Entry
R1
R2
Product
Time
(min)
Isolated Yield
(%)
1
2
3
4
5
Ph
PhCH2
PhCH2
PhCH2
PhCH2
4a
94
92
91
88
5
4b
4c
4d
4e
4f
4-MeC6H4
4-MeOC6H4
4-t-BuC6H4
10
20
35
5
4-ClC6H4
4-BrC6H4
4-NO2C6H4
2-pyridine
Ph
PhCH2
95
94
96
90
93
92
90
86
6
PhCH2
6
PhCH2
4g
4h
4i
7
5
8
PhCH2
20
10
20
30
40
9
p-ClC6H4CH2
p-ClC6H4CH2
10
11
12
4-MeC6H4
4j
4-MeOC6H4
4-t-BuC6H4
2-pyridine
p-ClC6H4CH2
p-ClC6H4CH2
p-ClC6H4CH2
4k
4l
13
14
15
16
17
4m
88
91
89
86
86
33
20
35
35
60
Ph
p-NO2C6H4CH2
p-NO2C6H4CH2
p-NO2C6H4CH2
p-NO2C6H4CH2
4n
4o
4p
4q
4-MeC6H4
4-MeOC6H4
4-t-BuC6H4
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18
19
84
90
2-pyridine
Ph
p-NO2C6H4CH2
4r
4s
35
30
CH2CHCH2
20
21
22
4-MeC6H4
4-MeOC6H4
4-t-BuC6H4
CH2CHCH2
CH2CHCH2
CH2CHCH2
4t
42
50
75
87
84
82
4u
4v
spectra, which corresponds to the hydrogen on 5-position of
triazole ring and confirms the regioselective synthesis of 1,4-
disubstituted triazole regioisomers (see electronic supplementary To investigate the reusability of the catalyst, the reaction of
information). phenylacetylene, benzyl bromide and sodium azide was
By analogy with our investigation, the plausible mechanistic accomplished under the above-mentioned optimized reaction
pathways for the synthesis of 1,4-disubstituted 1,2,3-triazoles with conditions (Table1, entry 6). The isolated yield of the product was
γ-Fe2O3@TiO2-EG-CuII catalyst are shown in Scheme 3. The one-pot measured exactly, after the first run. Then, the catalyst was
click reaction involves the in situ generation of organic azide, in separated by using an external magnet, followed by washing twice
water, within a short reaction time. Copper in the γ-Fe2O3@TiO2- with methanol and drying overnight at room temperature. These
EG-CuII catalyst promotes the formation of Cu(II)–acetylide complex recovered MNPs were reused in next run under the same reaction
(I) which diminishes the electron density of the alkyne. conditions. This procedure was repeated six times and in each time
Subsequently, Huisgen 1,3-dipolar cycloaddition reaction between the isolated yield of the product was evaluated precisely. As it is
organic azide and Cu(II)–acetylide complex (I) leads to formation of shown in Fig. 7 no considerable decrease in the product yield was
II. However, according to the Sharpless et al. definition about the observed after repeated cycles of the reaction. These results
"on water" reactions,37 the significant beneficial effects, in terms of suggest that the catalyst is efficient for six run.
the rates and selectivity of such a reactions have been observed. In
The copper content of freshly prepared γ-Fe2O3@TiO2-EG-CuII
this cases, the participated reactants in the reaction are insoluble in which was obtained by inductively coupled plasma (ICP) was 0.74
aqueous media and therefore the reaction would take place under mmol of Cu per 1.000 g of γ-Fe2O3@TiO2-EG-CuII, whilst ICP shows
suspension in water.38 So, it is worth to note that, the formation of that the 6th reused γ-Fe2O3@TiO2-EG-CuII contains 0.64 mmol of Cu
complex (II) would be proceed through an "on water" effect, per 1.000 g of 6th reused γ-Fe2O3@TiO2-EG-CuII. It means that, the
because of the insolubility of organic azides and terminal acetylenes amount of leached metal from the surface of the catalyst is very
in aqueous media.38b Finally, the corresponding 1,2,3-triazole was low.
obtained and the re-generated catalyst re-enters the catalytic cycle.
The FT-IR spectrum of the 6th recovered γ-Fe2O3@TiO2-EG-CuII
Since the formation of diynes (which usually generated during the was shown in Fig. 1e. As can be seen, the shape, position and
reduction process of CuII to CuI) was not detected in the present relative intensity of all characteristic peaks are well preserved. The
study, we assume that the reaction proceeds via a pathway results indicate no considerable changes on the chemical structure
involving CuII as postulated by Pitchumani et al.26c,e Further studies of functional groups and the hydrogen bonding network.
to elucidate the details of the mechanism are ongoing.
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R1
H
+NaN3
R2 Br
R1
H
CuII
R2 N3
I
R2
N
N N
CuII
H
C
C
R1
CuII
R2
H
N
R2
H
N
N
N
N
N
R1
R1
CuII
Fig 7. Synthesis of 1-benzyl-4-phenyl-1H-1,2,3-triazole in the
presence of the reused γ-Fe2O3@TiO2-EG-CuII.
II
-Fe O @TiO -EG-CuII
γ
CuII
2
3
2
=
Scheme 3. Plausible reaction mechanism for 1,4-disubstituted 1,2,3-
triazole synthesis using γ-Fe2O3@TiO2-EG-CuII.
Table 3. Comparison of various catalysts in the synthesis of 1-benzyl-4-phenyl-1H-1,2,3-triazole.
Entry
Catalyst
Reagents and reaction condition
Time
(h)
Yield
(%)
Ref.
26a
26b
26c
26e
39
Cu(II)-PBS-HPMO a
MNPs@BiimCu(II) b
CuII –Hydrotalcite
alumina-supported Cu(II)
copper(II) acetate
CuCl2/CuSO4.5H2O
phenylacetylene (1.1 mmol), benzyl bromide (1 mmol), NaN3 3.5
(1.2 mmol), catalyst (10 mg), H2O,100 ˚C.
96
1
2
3
4
5
6
7
8
9
phenylacetylene (1 mmol), benzyl bromide (1 mmol), NaN3 (1.1
1
mmol), catalyst (0.85 mol%), H2O, r.t.
92
phenylacetylene (0.44 mmol), benzyl azide (0.37 mmol), catalyst
(10 mg), ACN, r.t.
6
1
86
phenylacetylene (1 mmol), benzyl bromide (1 mmol), NaN3 (1
mmol), catalyst (10 mol%), ball-milling/600 rpm.
96
phenylacetylene (1.2 mmol), benzyl azide (1 mmol), catalyst (20 20
mol%), H2O, r.t.
77
phenylacetylene (0.5 mmol), benzyl bromide (0.6 mmol), NaN3
(0.6 mmol), catalyst (0.025 mmol), MeOH, r.t.
8
6
82/83
98
40
ammonium salt-tagged
NHC–Cu(I) complexes
phenylacetylene (1.2 mmol), benzyl bromide (1.0 mmol), NaN3
(1.2 mmol), catalyst (5 mol%), H2O, r.t.
41
copper nanoparticles on
charcoal
phenylacetylene (1 mmol), benzyl bromide (1 mmol), NaN3 (1.1 0.6
mmol), catalyst(1 mol%), H2O, 100 ˚C.
91
42
CuNPs/MagSilica c
phenylacetylene (1 mmol), benzyl bromide (1 mmol), NaN3 (1.1
mmol), catalyst (40 mg), H2O, 70 ˚C.
1
98
30
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10
11
silica–Cu2O
phenylacetylene (1.2 mmol), benzyl chloride (1 mmol), NaN3 (1 3.5
mmol), 0.2 g catalyst (5 mol% Cu), H2O, r.t.
96
92
43
24
Silica-APTS-Cu(I) d
phenylacetylene (0.5 mmol), benzyl bromide (0.5 mmol), NaN3 24
(0.5 mmol), catalyst (5 mol%), EtOH, 78 ˚C.
phenylacetylene (0.5 mmol), benzyl bromide (0.5 mmol), NaN3
(0.5 mmol), sodium ascorbate (10 mol%), Cu (0.5 mol%), H2O/t-
12
13
14
MNPs@FGly e
2
99
44
BuOH; (3/1), 55 ˚C.
CuSO4.5H2O
phenylacetylene (1.5 equiv.), benzyl azide (1 equiv.), N2H4.H2O 45min 95
azide (1 equiv.), catalyst (0.1 equiv.), H2O, r.t.
14h
γ-Fe2O3@TiO2-EG-CuII
phenylacetylene (1 mmol), benzyl bromide (1 mmol), NaN3 (1.2 5min
mmol), catalyst (4 mol%), H2O, 50 ˚C.
94
Present
study
a
b
Cu(II)-porphyrin-bridged silsesquioxane bridged hybrid periodic mesoporous organosilica. biimidazole Cu(II) ion complexe
immobilized on core–shell magnetic nanoparticles. c copper nanoparticles on silica coated maghemite nanoparticles. d copper(I) on 3-
aminopropyl functionalized silica. e Fe3O4–silica-coated@functionalized 3-glycidoxypropyltrimethoxysilane.
To show the advantages of γ-Fe2O3@TiO2-EG-CuII over some of the reagents, excellent regioselectivity and high yields, short reaction
reported catalysts in the literature, the catalytic performance of γ- times, easy work-up procedure, using water as a green reaction
Fe2O3@TiO2-EG-CuII in the synthesis of 1-benzyl-4-phenyl-1H-1,2,3- medium, besides high metal loading capacity and reusability of the
triazole, was compared with various reported catalyst (Table 3). catalyst, make this protocol very attractive and environmentally
However, some of these methods suffer from one or more of the compatible process for the synthesis of a variety of 1,2,3-triazoles.
following drawbacks, such as using environmentally hazardous
catalysts or solvents, handling of toxic and hazardous organic
Acknowledgements
azides, using some additives (reducing agents such as sodium
ascorbate and hydrazine monohydrate),14h,44 tedious purification of
The authors gratefully acknowledge the partial support of this study
by Ferdowsi University of Mashhad Research Council (Grant no.
products and moreover, require long reaction times to achieve
p/3/39490).
reasonable yields.
However, such difficulties were removed by
using γ-Fe2O3@TiO2-EG-CuII as an efficient and reusable
nanomagnetic catalyst for the synthesis of 1-benzyl-4-phenyl-1H-
1,2,3-triazole, in water as a green solvent.
Notes and references
1
R. Alvarez, S. Velazquez, A. San-Félix, S. Aquaro, E. De Clercq,
C. F. Perno, A. Karlsson, J. Balzarini and M. J. Camarasa, J.
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4. Conclusion
Conclusively, CuII immobilized on guanidinated epibromohydrin
functionalized γ-Fe2O3@TiO2 (γ-Fe2O3@TiO2-EG-CuII) as
a new
2
S. Velazquez, R. Alvarez, C. Perez, F. Gago, E. De Clercq, J.
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heterogeneous catalyst was synthesized and characterized by
different techniques such as, FT-IR, TGA/DTA, HRTEM, XRD, EDX,
VSM, ICP and CHN. The obtained average particle size of γ-Fe2O3
core and TiO2 shell calculated by HRTEM and XRD was 10-20, 5-10
and 13, 7 nm, respectively. The newly synthesized catalyst showed
superior catalytic activity for the synthesis of 1,4-disubstituted
1,2,3-triazoles, through the Huisgen 1,3-dipolar cycloaddition
reaction, in the absence of any reducing agent or additive. This one
pot preparation of 1,2,3-triazoles involves initial substitution of
benzyl/allyl bromides with sodium azide for the in situ generation of
benzyl/allyl azides, which is followed by γ-Fe2O3@TiO2-EG-CuII
catalyzed cycloaddition reaction without using any reducing agent
on water, at 50 ˚C. Mildness of the reaction conditions,
3
4
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DOI: 10.1039/C6RA05468D
Graphical Abstract
CuII
immobilized
on
guanidinated
epibromohydrin functionalized γ-Fe2O3@TiO2
(γ-Fe2O3@TiO2-EG-CuII): a novel magnetically
recyclable heterogeneous nanocatalyst for
the green one-pot synthesis of 1,4-
disubstituted 1,2,3-triazoles through alkyne-
azide cycloaddition in water
Roya Jahanshahi and Batool Akhlaghinia *
The catalytic activity of novel synthesized γ-Fe2O3@TiO2-EG-CuII catalyst, in the green and efficient preparation of 1,4-
disubstituted 1,2,3-triazoles, was investigated.