Copper nanoparticles supported on silica coated maghemite as versatile, magnetically recoverable and reusable catalyst for alkyne coupling and cycloaddition reactions

Article abstract of DOI:10.1016/j.apcata.2013.01.023

A versatile and magnetically recoverable catalyst consisting of copper nanoparticles on silica coated maghemite nanoparticles (MagSilica ) is presented. The catalyst has been prepared under mild conditions by fast reduction of anhydrous CuCl

Full text of DOI:10.1016/j.apcata.2013.01.023

Applied Catalysis A: General 455 (2013) 39–45
Contents lists available at SciVerse ScienceDirect
Applied Catalysis A: General
journal homepage: www.elsevier.com/locate/apcata
Copper nanoparticles supported on silica coated maghemite as
versatile, magnetically recoverable and reusable catalyst for alkyne
coupling and cycloaddition reactions
F. Nadora, M.A. Volpeb, F. Alonsoc, A. Feldhoffd, A. Kirschninge, G. Radivoya,∗
a Instituto de Química del Sur, INQUISUR (CONICET-UNS), Departamento de Química, Universidad Nacional del Sur, Av. Alem 1253, 8000 Bahía Blanca,
Argentina
b Planta Piloto de Ingeniería Química, PLAPIQUI (CONICET-UNS), Camino La Carrindanga Km 7, CC 717, 8000 Bahía Blanca, Argentina
c Departamento de Química Orgánica, Facultad de Ciencias and Instituto de Síntesis Orgánica (ISO), Universidad de Alicante, Apdo. 99, E-03080, Alicante,
Spain
d Institut für Physikalischie Chemie and Electrochemie, Leibniz Universität Hannover, Callinstr. 3a, D-30167 Hannover, Germany
e Institut für Organische Chemie and Zentrum für Biomolekulare Wirkstoffe (BMWZ), Leibniz Universität Hannover, Schneiderberg 1B, D-30167 Hannover,
Germany
a r t i c l e i n f o
a b s t r a c t
Article history:
A versatile and magnetically recoverable catalyst consisting of copper nanoparticles on silica coated
maghemite nanoparticles (MagSilica®) is presented. The catalyst has been prepared under mild con-
ditions by fast reduction of anhydrous CuCl2 with lithium sand and a catalytic amount of DTBB
(4,4’-di-tert-butylbiphenyl) as electron carrier, in the presence of the magnetic support. The catalyst
has been fully characterized and its performance in different coupling and cycloaddition reactions of ter-
minal alkynes has been studied. This new copper-based catalyst has shown to be very efficient and easily
reusable in the Glaser alkyne dimerization reaction in THF, the multicomponent Huisgen 1,3-dipolar
cycloaddition reaction in water and the three-component synthesis of propargylamines under solvent
free conditions.
Received 29 September 2012
Received in revised form 8 January 2013
Accepted 19 January 2013
Available online 9 February 2013
Dedicated to Prof. Miguel Yus on occasion
of his 65th birthday.
Keywords:
© 2013 Elsevier B.V. All rights reserved.
Copper nanoparticles
Magnetic support
Alkyne
Coupling
Cycloaddition
1. Introduction
mentioned transformations, copper catalysts have been by far the
most studied ones, however, most of the catalytic systems are
Alkynes are core building blocks for the construction of highly
functionalized organic substructures, which are essential in the
synthesis of many industrial products, molecular materials and
bioactive compounds. In particular, metal-catalyzed coupling and
cycloaddition reactions of terminal alkynes provide a key tool for
accessing to complex organic structures from simple and readily
available starting materials [1]. Prominent examples in this regard
are the coupling of terminal alkynes for the synthesis of 1,3-diynes
(Glaser dimerization) [2], multicomponent reactions (MCR) involv-
ing aldehydes, amines and terminal alkynes [3] for the synthesis
of propargylamines, and the 1,3-dipolar cycloaddition of azides
and terminal alkynes to yield 1,2,3-triazoles (Huisgen reaction)
[4] which is the paradigm of a click reaction. In all the above
homogeneous, hampering the recovery and recycling of the cat-
alyst. Regardless of the chemical transformation considered, it is
broadly accepted that homogeneous catalysts are intrinsically more
active and selective than heterogeneous ones, while these latter
allow an easier and more economical separation and reuse of the
catalyst. In any case, the use of highly efficient, economic and recov-
erable catalysts, with low or null toxicity is essential from the
green chemistry perspective. In this context, the synthesis of tran-
sition metal nanoparticles and their application in catalysis have
received considerable attention in recent years [5]. Due to their
high surface area, these nanosized metal particles often show a
remarkable catalytic performance, and are considered to be on the
frontier between the homogeneous and heterogeneous catalysis,
preserving the main advantages of both methodologies. However,
in practice, the separation and recovery of these nanocatalysts from
the reaction medium by using standard techniques (filtration, cen-
trifugation) is not always easy due to the nanometric size of the
∗
Corresponding author. Tel.: +54 02914595187.
E-mail address: gradivoy@criba.edu.ar (G. Radivoy).
0926-860X/$ – see front matter © 2013 Elsevier B.V. All rights reserved.
http://dx.doi.org/10.1016/j.apcata.2013.01.023

40
F. Nador et al. / Applied Catalysis A: General 455 (2013) 39–45
particles. To overcome this drawback, metal nanoparticles are sup-
ported over a variety of organic and inorganic supports. Among
them, magnetic nanomaterials have emerged lately as a very attrac-
tive alternative since their high surface area allows higher catalyst
loading than many conventional supports, and their magnetic prop-
erties enables the simple and efficient recovery of the catalyst by
means of an external magnet [6]. The magnetic nanoparticles uti-
lized as supports usually consist of core-shell structures, being
iron oxides (FexOy) the most commonly used ones. The coating of
these magnetic nanomaterials prevents aggregation/oxidation and
serves as platform for the catalyst. For this purpose, silica has been
widely used because of its stability under different reaction con-
ditions and due to the fact that it can be easily functionalized for
diverse applications [7].
nanoparticles (NPs) and their application in important organic
transformations, mainly in reduction and coupling reactions. The
methodologies that we developed are simple and economic ones,
and consist in the fast reduction of transition metal chlorides with
lithium sand and a catalytic amount of an arene as electron carrier,
in tetrahydrofuran as solvent and at room temperature. We have
found that by using this methodology, CuCl2 or CuCl2·2H2O are suit-
able precursors for the synthesis of very reactive CuNPs, with a size
distribution in the range of 3.0 1.5 nm [14]. These naked CuNPs,
generated in situ, efficiently promoted the Glaser dimerization of
terminal alkynes [15] and the Huisgen 1,3-dipolar cycloaddition of
azides and terminal alkynes [16]. More recently, the same method-
ology was applied for the synthesis of CuNPs supported on activated
carbon and titania. The CuNPs/C catalyst showed a remarkable ver-
satility in the multicomponent Huisgen cycloaddition in water [17],
while the CuNPs/titania efficiently catalyzed the homocoupling of
terminal alkynes [18] and the solvent-free three-component cou-
pling of aldehydes, amines and alkynes [19].
Driven by our continuing interest in this family of CuNPs-based
catalysts and with the aim to expand and improve their catalytic
applications, we want to present herein a new magnetically recov-
erable catalyst consisting in the synthesis of CuNPs (3.0 0.8 nm)
over commercially available silica coated maghemite nanoparticles
(MagSilica®, 5–30 nm), and the study of its catalytic performance
in three important synthetic transformations involving terminal
alkynes (Scheme 1).
On the other hand, besides recovery and reuse, the simplic-
ity in catalyst preparation is a very important issue from the
practical and utility point of view. Examples of heterogeneous
copper-catalysts that are easy to prepare, versatile and reusable
in the three above mentioned alkyne transformations, are scant.
The heterogeneous copper-catalyzed homocoupling of terminal
alkynes has been a subject of recent interest but have rarely
been studied. For instance, a CuAl hydrotalcite exhibited excel-
lent recyclability at room temperature in acetonitrile, although
stoichiometric amounts of N,N,N,N-tetramethylethylenediamine
(TMEDA) and catalyst (110 mol%) were required [8]. Copper(I) zeo-
lites were tested for the title reaction in N,N-dimethylformamide
(DMF) at 110 ◦C and 30 mol% copper loading, with no apparent pos-
sibility of catalyst recycling [9]. Mizuno and co-workers reported
a catalyst consisting of Cu(OH)x/TiO2 (5 mol% Cu) that did not
require the presence of a base and showed high catalytic activ-
ity in toluene at 100 ◦C under 1 atm O2 [10]. Only one recycling
experiment was described in this article, which showed a slight
decrease in yield (from 90 to 82%). A very similar scenario can
be found in the literature with regard to the A3 coupling reac-
tion for the synthesis of propargylamines. The catalytic activation
of the C H bond of terminal alkynes has been achieved with
complexes or salts of the late transition metals (e.g., Ir, Zn, Fe,
Co, Ni, Ag, Au, Ir, Ru, but also In), but copper has been by far
the most studied metal [11]. However, most of the catalytic sys-
tems reported are homogeneous in nature, making the recovery
and recycling of the catalyst troublesome. Impregnated copper on
magnetite has been reported to be a heterogeneous and reusable
copper-based catalyst for the A3 coupling [12], but some copper
and iron leaching has been observed, and the preparation of the
catalyst requires 24 h of stirring and several days of drying before
its use. With regard to the three-component 1,3-dipolar cycload-
dition reaction, examples about the use of heterogeneous catalysts
that can be recovery and reuse for this important transformation
are also scarce. In this sense, some reports on the copper-catalyzed
multi-component synthesis of triazoles in water, using heteroge-
neous catalysts, have appeared in the literature [13]. For example,
copper nanoparticles on alumina catalyzed the multicomponent
synthesis of 1,2,3-triazoles, in modest to good yields, however,
only activated organic halides were reported and the preparation
of the catalyst seems rather tedious, through an aerogel method
under supercritical conditions [13a]. Porphyrinatocopper nanopar-
ticles onto activated multi-walled carbon nanotubes has been also
used as heterogeneous catalyst in the three-component 1,3-dipolar
cycloaddition reaction with epoxides (not with the more abun-
dant organic halides) [13b]. Reactions proceed at room temperature
although the catalyst preparation is rather laborious and time con-
suming (synthesis of carbon nanotubes followed by oxidation, UV
and microwave radiation, and anchoring of the complex through
ultrasonic, microwave, and dichloromethane treatment).
2. Experimental
2.1. Materials
All moisture sensitive reactions were carried out under a nitro-
gen atmosphere. Anhydrous tetrahydrofuran was freshly distilled
from sodium/benzophenone ketyl. Other solvents were treated
prior to use by standard methods [20]. All starting materials were of
the best available grade (Aldrich, Fluka, Merck) and were used with-
out further purification. Commercially available copper(II) chloride
dihydrate was dehydrated upon heating in oven (150 ◦C, 45 min)
prior to use for the preparation of CuNPs. MagSilica® was provided
by Evonik Industries AG (Essen, Germany). Column chromatog-
raphy was performed with Merck silica gel 60 (0.040–0.063 ␮m,
240–400 mesh). Thin layer chromatography (TLC) was performed
on precoated silica gel plates (Merck 60, F254, 0.25 mm).
2.2. Instrumentation and analysis
Nuclear magnetic resonance (NMR) spectra were recorded on
a Bruker ARX-300 spectrophotometer using CDCl3 as the solvent
and tetramethylsilane (TMS) as internal reference. Mass spec-
tra (EI) were obtained at 70 eV on a Hewlett Packard HP-5890
GC/MS instrument equipped with a HP-5972 selective mass detec-
tor. Infrared (FT-IR) spectra were obtained on a Nicolet-Nexus
spectrophotometer. The purity of volatile compounds and the chro-
matographic analyses (GC) were determined with a Shimadzu
GC-14B instrument equipped with a flame-ionisation detector and
a 30 m column (HP-5MS, 0.25 mm, 0.25 ␮m), using nitrogen as car-
rier gas.
2.3. CuNPs/MagSilica catalyst preparation
A mixture of lithium sand (21 mg, 3.0 mmol) and 4,4ꢀ-di-tert-
butylbiphenyl (DTBB, 26 mg, 0.1 mmol) in THF (3 mL), was stirred at
room temperature under nitrogen atmosphere. When the reaction
mixture turned dark green (15–30 min), indicating the formation
of the corresponding lithium arenide, anhydrous CuCl2 was added
(134 mg, 1.0 mmol). The resulting suspension was stirred until it
In the last years, some of us have been actively working
on new methodologies for the preparation of transition metal

F. Nador et al. / Applied Catalysis A: General 455 (2013) 39–45
41
Scheme 1.
turned black (15–30 min), indicating the formation of copper(0)
nanoparticles. Then, it was diluted with THF (10 mL) and MagSilica
(500 mg) was added. The resulting suspension was stirred for 1 h,
and then bidistilled water (2 mL) was added for eliminating the
excess of lithium. The resulting solid was filtered under vacuum in
a Buchner funnel and washed successively with water (10 mL) and
acetone (10 mL). Finally, the solid was dried under vacuum (5 Torr)
for 2 h.
conversion of the starting alkyne (TLC, GC). The above described
procedure was followed for the catalyst recovery and reaction prod-
ucts isolation.
2.6. CuNPs/MagSilica catalyzed multicomponent Huisgen
1,3-dipolar cycloaddition reaction. General procedure
To a vigorously stirred suspension of the CuNPs/MagSilica cat-
alyst (40 mg) and NaN3 (72 mg, 1.1 mmol) in water (2 mL), the
corresponding alkyl halide (1.0 mmol) was added dropwise, fol-
lowed by the addition of the terminal alkyne (1.0 mmol). The
reaction mixture was stirred at 70 ◦C until total conversion of the
starting alkyne (TLC, GC). The triazole product formation can be
easily visualized as a solid floating on the water surface. Then, the
catalyst was immobilized by means of a permanent magnet placed
on the outer wall of the reaction flask, and was successively washed
with water (2 mL) and CH2Cl2 (10 mL). Finally, the catalyst was
dried under vacuum (5 Torr) for its recovery and reuse.
2.4. CuNPs/MagSilica catalyst characterization
The freshly prepared catalyst was characterized by Trans-
mission Electron Microscopy (TEM) in a JEOL JEM-2100F-UHR
instrument, operated at an acceleration voltage of 200 kV. Approxi-
mately one hundred metal particles were measured to perform the
particle size distribution.
Copper content in the supported catalyst was determined by
Inductively Coupled Plasma Atomic Emission Spectroscopy (ICP-
AES), in a Spectro Arcos instrument.
The catalyst specific surface area was measured by BET method,
from a N2 isotherm at 77 K in NOVA 1200e apparatus.
The reducibility of the supported catalysts was analyzed by
Temperature Programmed Reduction (TPR) in a home-made equip-
ment. Before reduction, the samples were treated with flowing Ar
at 300 ◦C. Then, a flowing mixture (20 mL/min) of 10% H2/Ar was
introduced, raising the temperature at 8 ◦C/min from room tem-
perature up to 550 ◦C. The TPR profile was obtained following the
H2 consumption with a TCD detector.
The possibility of catalyst leaching in the reaction media was
evaluated by measuring the copper concentration in the reaction
mixture, by means of atomic absorption spectroscopy.
2.7. CuNPs/MagSilica catalyzed three-component coupling of
aldehyde, amine and terminal alkyne. General procedure
The corresponding aldehyde (1.0 mmol), amine (1.1 mmol)
and terminal alkyne (1.0 mmol) were successively added to the
CuNPs/MagSilica catalyst (10 mg), and then stirred at 100 ◦C until
total conversion of the starting alkyne (TLC, GC). The catalyst was
immobilized by means of a permanent magnet placed on the outer
wall of the reaction flask, and washed twice with Et2O (10 mL each).
Finally, the catalyst was dried under vacuum (5 Torr) for its recovery
and reuse.
X-ray diffraction (XRD) analysis were performed using a Bruker
AXS D8 Advance diffractometer, equipped with a Cu-K␣1,2 radia-
tion source.
Atomic absorption spectroscopy was carried out in a Perkin
Elmer AA700 spectrometer.
2.5. CuNPs/MagSilica catalyzed homocoupling of terminal
alkynes. General procedure
3. Results and discussion
3.1. Preparation and characterization of the catalyst
To a vigorously stirred suspension of the CuNPs/MagSilica cat-
alyst (70 mg) in THF (4 mL) the corresponding alkyne (1.0 mmol)
was added, followed by the dropwise addition of piperidine (85 mg,
99 ␮L, 1.0 mmol). The reaction flask was introduced in a preheated
silicon oil bath at a temperature high enough to ensure the reflux
of the solvent (66 ◦C), and stirred at this temperature until total
As described in the Experimental section, the catalyst was pre-
pared by addition of MagSilica to a suspension of CuNPs readily
generated from anhydrous copper(II) chloride, lithium sand, and
a catalytic amount of DTBB (10 mol%) in THF at room tempera-
ture. The CuNPs/MagSilica catalyst was characterized by means of

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F. Nador et al. / Applied Catalysis A: General 455 (2013) 39–45
weight (63.5 g/mol), ꢀsite the copper surface density (13.5
Cu atoms/nm2 [23]), d is the particle size (in nm), ꢀmetal, the metal
density (8.96 g/cm3) and N the Avogadro number. Thus a copper
dispersion of 32% was obtained for the catalysts.
Energy dispersive X-ray analysis on various regions confirmed
the presence of copper, with energy bands of 8.04, 8.90 (K lines)
and 0.92 keV (L line). The XRD diffractogram showed the support
diffraction pattern, but no diffraction peaks owing to copper species
were detected, this could be attributed to the amorphous charac-
ter of the oxidized CuNPs deposited on the support and/or to the
existence of crystal domains below 10 nm in size.
The BET surface area of CuNPs/MagSilica was 27 m2/g, which is
the same as the corresponding to the bare support. It is important to
note that the dispersion of copper attained in the CuNPs/MagSilica
catalyst is relatively high (32%), considering that the surface area
of the support is rather low.
3.2. Evaluation of the catalyst performance in alkyne coupling
and cycloaddition reactions
Fig. 1. TPR profile for CuNPs/MagSilica catalyst.
The CuNPs/MagSilica catalyst was tested in three different
terminal-alkyne transformations: the homocoupling of terminal
alkynes (Glaser dimerization), the multicomponent 1,3-dipolar
cycloaddition of terminal alkynes, sodium azide and alkyl halides,
and the three-component synthesis of propargylamines from alde-
hydes, amines and terminal alkynes (A3 coupling). The catalyst
was used as prepared, without any pre-treatment. The amount of
CuNPs/MagSilica catalyst needed and the optimal reaction con-
ditions were determined independently for each of the three
reactions studied.
transmission electron microscopy (TEM), energy dispersive X-ray
(EDX), powder X-ray diffraction (XRD), temperature programmed
reduction (TPR), and inductively coupled plasma atomic emission
spectroscopy (ICP-AES).
The copper loading fixed to MagSilica was 6.8 wt% as determined
by ICP-AES. The TPR profile of the catalyst is shown in Fig. 1. The con-
sumption peak is assigned to copper oxidized species. The amount
of hydrogen consumed corresponds to the reduction of the whole
CuO present in the catalyst, which is being reduced to Cu(0). Since
the samples were not previously calcined, the presence of these
species indicates that CuNPs are being oxidized during handling of
the catalyst under air. Besides, no peaks attributable to the support
reduction were detected. Since maghemite reduction occurs in the
temperature range of the TPR experiments [21], the lack of iron
species available for reduction strongly suggests that the magnetic
core is fully coated by the SiO2 shell.
Analysis by TEM showed the presence of well dispersed spher-
ical nanoparticles on the magnetic support, with a narrow size
distribution and an average particle size of 3.0 0.8 nm (Fig. 2),
thus demonstrating that the nanometric dimension of the CuNPs is
not lost upon supporting on the silica coated maghemite nanopar-
ticles. This is a remarkable result since previous attempts by some
of us for supporting CuNPs on SiO2, using this same methodology,
led to the formation of CuNPs with an average size of around 20 nm.
The average particle size of copper in CuNPs/MagSilica was
recalculated to metal dispersion (D), following the relationship
from Scholten et al. [22]: D = 1021 × 6 × M × ꢀsite/(d × ꢀmetal × N),
where D is the copper dispersion (Cusup/Cutotal) M, the atomic
3.2.1. Direct homocoupling of terminal alkynes catalyzed by
CuNPs/MagSilica
As shown in Table 1, the reaction conditions were optimized
using phenylacetylene as model compound. The addition of piperi-
dine as base (1 equiv. referred to the starting alkyne), in order
to promote a base-assisted deprotonation of the starting alkyne,
and heating at 66 ◦C (reflux temperature of THF) was essential
to obtain the maximum yield of the desired 1,3-diyne product in
minimum reaction time. Other bases tested, such as triethylamine,
pyridine, sodium carbonate and cesium carbonate, under the same
reaction conditions gave poorer results in terms of conversion to
the alkyne dimerization product. These reaction conditions were
applied at different catalyst loading, and it was found that 70 mg of
CuNPs/MagSilica (7.5 mol% Cu) was the optimum amount of cata-
lyst for this reaction (Table 1, entry 2).
For the optimized conditions the specific rate, expressed as
moles of alkyne converted per g copper was 1.7 × 10−5 while the
TOF number was 3.5 × 10−3 s−1
.
Fig. 2. TEM micrograph and size distribution graphic of CuNPs/MagSilica catalyst.

F. Nador et al. / Applied Catalysis A: General 455 (2013) 39–45
43
Table 1
Optimization of reaction conditions for alkyne homocoupling reaction.a
Entry
Amount of catalyst (mg)
Copper content (mol%)b
Base
T (◦C)
t (h)
Yield (%)c
1
2
3
4
5
6
100
70
40
20
70
70
10.7
7.5
4.3
2.2
7.5
7.5
Piperidine
Piperidine
Piperidine
Piperidine
Otherd
66
66
66
66
66
25
2
2
10
20
8
94
95
10
Traces
Traces
5
piperidine
8
Bold in entry highlight the optimal reaction conditions.
a
Alkyne (1 mmol), base (1 mmol), in THF as solvent and under air.
Referred to the starting alkyne.
GC yield based on the starting alkyne.
b
c
d
Other bases tested: sodium carbonate, triethylamine, pyridine, cesium carbonate.
Table 2
alkynes and organic azides generated in situ from sodium azide and
different organic halides. As shown in Table 3, phenylactelylene and
benzyl bromide were selected as model starting compounds for the
optimization of the reaction conditions. Interestingly, from the dif-
ferent solvents and solvent/co-solvent mixtures tested, water was
found to be the most effective for this reaction (Table 3, compare
entries 1, 4, 5 and 6). Thus, using 40 mg of CuNPs/MagSilica cat-
alyst (4.3 mol% Cu) and heating at 70 ◦C in water, the reaction of
phenylacetylene with benzyl bromide and sodium azide, gave 1-
benzyl-4-phenyl-1H-1,2,3-triazole almost quantitatively in only 1
hour of reaction time (Table 3, entry 1).
CuNPs/MagSilica catalyzed homocoupling of terminal alkynes.a
Entry
R1
t (h)
Yield (%)b
1
2
3
4
5
6
7
Ph
2
2
95
83
58
90
88
72
75
4-CH3C6H4
4-(CH3)2NC6H4
n-C6H13
n-C10H21
c-C6H9
14
15
18
24
24
Ph(CH2)2
a
Reaction conditions: alkyne (1 mmol), piperidine (1 mmol), CuNPs/MagSilica
(70 mg), 66 ◦C, in THF as solvent and under air.
b
The specific rate for this reaction at the above described con-
ditions is 6 × 10−5 moles converted per gram of copper and per
second, while the TOF number is 0.012 s−1. When THF is employed
Isolated yield after column chromatography (hexane-EtOAc), based on the start-
ing alkyne.
as the solvent, the TOF number is notably lower (1 × 10−4 s−1
)
Under the optimized conditions phenylacetylene gave the
homocoupled diyne product in only 2 h of reaction time and in
high yield (Table 2, entry 1). A similar reactivity was observed
for 4-methylphenylacetylene (Table 2, entry 2). In contrast, 4-N,N-
dimethylaminophenylacetylene showed to be less reactive under
the same reaction conditions (Table 2, entry 3), probably due to the
presence of a strong electron releasing group at the 4-position of
the phenyl group, which could be hampering the formation of the
corresponding copper acetylide.
than that of the reaction performed in water. The depletion in
the rate would be related to the fact that the in situ generation
of the organic azide is hampered in the organic solvent, due to
the low solubility of the starting sodium azide in the reaction
medium.
The same methodology was successfully applied to other
aryl acetylenes bearing both electron-withdrawing or electron-
releasing groups attached to the aromatic ring (Table 4, entries
2 and 3). Aliphatic alkynes, such as 1-hexyne and cyclohexy-
lacetylene also gave the corresponding triazole products in good
yield, although in longer reaction times compared with their
aryl counterparts (Table 4, entries 4 and 5). The propargyl ether
tetrahydro-2-(prop-2-ynyloxy)-2H-pyran, gave a doubly hetero-
cyclic triazole product in good yield (Table 4, entry 6). Then,
the catalyst was tested for the reaction of phenylacetylene and
alkyl halides other than benzyl bromide. Benzyl chloride, 4-
methylbenzyl bromide, 2-nitrobenzyl bromide and 4-vinylbenzyl
chloride gave the corresponding triazole products in good yield
(Table 4, entries 7–10), whereas the strongly deactivated 4-
methoxybenzyl chloride, as expected, gave poorer results (Table 4,
entry 11). Finally, n-nonyl iodide reacted sluggishly and heating
Aliphatic alkynes such as 1-octyne, 1-dodecyne, 1-
ethynylcyclohex-1-ene and 4-phenyl-1-butyne, gave the
corresponding 1,3-diyne products in good to excellent yields
but in higher reaction times (Table 2, entries 4–7). These results
are in agreement with the fact that aliphatic terminal alkynes are
sluggish in undergoing Glaser dimerization, probably due to the
weaker acidity of the acetylenic proton [24].
3.2.2. Multicomponent synthesis of 1,2,3-triazoles in water
catalyzed by CuNPs/MagSilica
The CuNPs/MagSilica catalyst demonstrated to be very effi-
cient in the multicomponent 1,3-dipolar cycloaddition of terminal
Table 3
Optimization of reaction conditions for the multicomponent synthesis of 1,2,3-triazoles.a
Entry
Amount of catalyst (mg)
Copper content (mol%)b
Solvent
T (◦C)
t (h)
Yield (%)c
1
2
3
4
5
6
40
20
40
40
40
40
4.3
2.2
4.3
4.3
4.3
4.3
H2O
H2O
H2O
DMF/H2O (9:1)
MeOH/H2O (9:1)
THF
70
70
25
70
70
70
1
12
10
12
12
10
98
10
25
15
85
8
Bold in entry highlight the optimal reaction conditions.
a
Phenylacetylene (1 mmol), benzyl bromide (1 mmol), sodium azide (1.1 mmol), under air.
Referred to the starting alkyne.
GC yield based on the starting alkyne.
b
c

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F. Nador et al. / Applied Catalysis A: General 455 (2013) 39–45
100 ◦C, and the amount of catalyst from 40 to 2.5 mg. As shown in
Table 5, the best conditions, in order to obtain the A3 coupling prod-
uct while minimizing the dimerization of the starting alkyne, were
found to be the use of 10 mg of CuNPs/MagSilica (1.1 mol% Cu) at
100 ◦C; under these conditions the reaction proceeded to the for-
mation of the corresponding propargylamine in only 1 h of reaction
time and in 84% yield (Table 5, entry 5).
Under the optimized reaction conditions, other alkynes such as
4-methylphenylacetylene, 1-ethynylcyclohexene and 1-dodecyne
were reacted with benzaldehyde and morpholine which also gave
the A3 coupling product in good yield and in short reaction times
(Table 6, entries 2, 3 and 4, respectively).
Table 4
CuNPs/MagSilica catalyzed multicomponent synthesis of 1,2,3-triazoles.a
Entry R1
R2-X
t (h) Yield (%)b
1
2
3
4
5
6
7
8
9
Ph
PhCH2Br
PhCH2Br
PhCH2Br
PhCH2Br
PhCH2Br
1
3
2
8
6
5
2
4
2
8
8
9
98
95
98
93
95
85
83
75
77
70
50
74c
4-BrC6H4
4-(CH3)2NC6H4
n-C4H9
c-C6H11
(2-Tetrahydropyranyloxy)methyl PhCH2Br
Ph
Ph
Ph
Ph
Ph
Ph
PhCH2Cl
4-CH3C6H4CH2Br
2-NO2C6H4CH2Br
4-CH2 CHC6H4Cl
4-CH3OC6H4CH2Cl
10
11
12
n-C9H19
I
a
Reaction conditions: alkyl halide (1 mmol), alkyne (1 mmol), sodium azide
(1.1 mmol), CuNPs/MagSilica (40 mg), 70 ◦C, in water as solvent and under air, unless
otherwise stated.
b
Isolated yield after column chromatography (hexane-EtOAc), based on the start-
ing alkyne.
Then, different aldehydes were reacted with pheny-
lacetylene and morpholine under the same conditions, thus
4-methoxybenzaldehyde and the aliphatic aldehyde (S)-(−)-
citronellal gave the corresponding propargylamine products in
good yield (Table 6, entry 5 and 6). In the case of citronellal,
the diastereoselectivity of the coupling reaction was practically
negligible.
c
Reaction performed at 100 ◦C.
Table 5
Optimization of reaction conditions for the three-component synthesis of
propargylamines.a
Entry
Amount of
Copper content
(mol%)b
T (◦C)
t (h)
Yield (%)c
catalyst (mg)
1
2
3
4
5
6
40
40
20
20
10
5
4.3
4.3
2.2
2.2
1.1
0.6
50
76
76
100
100
100
10
8
8
14
1
5
20
48
53
68
84
60
Finally, we examined the reaction with amines other than mor-
pholine. As shown in Table 6 (entries 7–9) pyrrolidine, a cyclic
secondary amine, gave similar results to those obtained with mor-
pholine when reacted with benzaldehyde and phenylacetylene,
whereas acyclic amines such as diethylamine and diisopropy-
lamine rendered the corresponding A3 coupling products after
longer reaction time and in modest yield.
Bold in entry highlight the optimal reaction conditions.
a
Phenylacetylene (1 mmol), benzaldehyde (1 mmol), morpholine (1.1 mmol),
under air.
b
Referred to the starting alkyne.
GC yield based on the starting alkyne.
c
to 100 ◦C was necessary to enhance the yield and minimize the
reaction time (Table 4, entry 12).
3.3. Recovery and reuse of the catalyst
We selected the three-component synthesis of propargylamines
as model reaction for the study of the catalyst performance after
various cycles of recovery and reuse. It is worthy of note that,
even though the small amount of catalyst utilized (10 mg), it could
be separated from the reaction medium, washed and reused very
easily, simply with the aid of a permanent magnet placed on the
outer wall of the reaction flask, thus minimizing the loss of cat-
alyst which usually occurs in filtration processes. Fig. 3 shows
the catalyst performance for the A3 coupling of benzaldehyde, 4-
methylphenylacetlyene and morpholine, after three consecutive
cycles without significant loss of catalytic activity. The low diminu-
tion in the activity from the first to the third cycle would be related
with small losses of catalyst mass during washing procedure. It is
important to note that the total mass of catalyst employed is very
It is worthy of note that the degree of copper leaching during
these experiments was below the atomic absorption spectrometry
sensitivity threshold, since no presence of copper was detected in
the aqueous phase of three different samples.
3.2.3. Three-component synthesis of propargyl amines from
aldehydes, alkynes and amines (A3 coupling) catalyzed by
CuNPs/MagSilica
The reaction conditions were optimized using benzaldehyde,
phenylacetylene and morpholine (1:1:1.1) in the absence of sol-
vent (Table 5). The reaction temperature was varied from 50 to
Table 6
CuNPs/MagSilica catalyzed three-component synthesis of propargylamines.a
Entry
R1
R2
Amine
t (h)
Yield (%)b
1
2
3
4
5
6
7
8
9
Ph
Ph
Ph
Ph
Ph
Morpholine
Morpholine
Morpholine
Morpholine
Morpholine
Morpholine
Pyrrolidine
1
1
1
3
3
2
3
15
20
84
83
95
89
76
82
77
40
20
4-CH3C6H4
c-C6H9
n-C10H21
Ph
Ph
Ph
4-CH3OC6H4
(CH3)2C CH(CH2)2CH(CH3)CH2
Ph
Ph
Ph
Ph
Ph
Diethylamine
Diisopropylamine
a
Reaction conditions: alkyne (1 mmol), aldehyde (1 mmol), amine (1.1 mmol), CuNPs/MagSilica (10 mg), 100 ◦C, under air, unless otherwise stated.
Isolated yield after column chromatography (hexane-EtOAc), based on the starting alkyne.
b

F. Nador et al. / Applied Catalysis A: General 455 (2013) 39–45
45
Fig. 3. Recovery and recycling of the catalyst in the synthesis of propargylamines.
low (10 mg), thus the loss of only 1 mg of catalyst when handling
the sample, means loss of 10% of the total mass of catalyst.
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This work was generously supported by the CONICET (Project
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Appendix A. Supplementary data
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.apcata.2013.01.023.
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