Cu2O/nano-CuFe2O4: A novel and recyclable magnetic catalyst for three-component coupling of carbonyl compounds-alkynes-amines under solvent-free condition

Article abstract of DOI:10.1016/j.catcom.2015.03.009

Cu₂O/nano-CuFe₂O₄ magnetic composite with different loadings of Cu₂O has been synthesized by feasible and low-cost method. The as-prepared composite was fully characterized by FT-IR, XRD, FEG-SEM, EDS and VSM analyzer. The catalytic activity of magnetic composite for synthesis of propargylamines was evaluated. The catalyst has many obvious advantages and easily separated via an external magnet. It can be reused for five successive runs.

Full text of DOI:10.1016/j.catcom.2015.03.009

Catalysis Communications 66 (2015) 15–20
Contents lists available at ScienceDirect
Catalysis Communications
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Short communication
Cu2O/nano-CuFe2O4: A novel and recyclable magnetic catalyst for
three-component coupling of carbonyl compounds–alkynes–amines
under solvent-free condition
⁎
Firouzeh Nemati , Ali Elhampour, Hadi Farrokhi, Mahshid Bagheri Natanzi
Department of Chemistry, Semnan University, Semnan 35131-19111, Iran
a r t i c l e i n f o
a b s t r a c t
Article history:
Cu2O/nano-CuFe2O4 magnetic composite with different loadings of Cu2O has been synthesized by feasible and
low-cost method. The as-prepared composite was fully characterized by FT-IR, XRD, FEG-SEM, EDS and VSM
analyzer. The catalytic activity of magnetic composite for synthesis of propargylamines was evaluated. The
catalyst has many obvious advantages and easily separated via an external magnet. It can be reused for five
successive runs.
Received 24 January 2015
Received in revised form 7 March 2015
Accepted 9 March 2015
Available online 11 March 2015
© 2015 Elsevier B.V. All rights reserved.
Keywords:
Magnetic composite
Terminal alkynes
Propargylamines
Green chemistry
1. Introduction
biologically active compounds and pharmaceutical important compounds
[11,12].
The catalysts with magnetic nanoparticle-based materials have
attracted significant attention in organic transformations, because they
posses specific futures including reduce temperature, increase reaction
yield, great selectivity, high stability, efficient recovery and good reusabil-
ity [1]. Among them, the iron oxides are usually applied as simplest mag-
netically recoverable catalysts, as they are nontoxic, cheap in preparation,
amenable to functionalization and easy to handle [2]. They have been
extensively used in some organic reactions such as, C–C and C–X
couplings [3,4], reduction [5], oxidation [6] and multi-component reac-
tions [7]. While iron oxide NPs could catalyze several reactions, the cata-
lytic scope of magnetic NPs could be expanded by incorporation of a
second metal (for example Cu) in the spinal structure of Fe3O4. The sec-
ond metal opens up new catalytic avenues, while the residual iron com-
ponent continues to provide an effective way in order to do magnetic
recovery [8].
The most conventional methods for the synthesis of propargylamines
involve three-component coupling of aldehydes, amines and terminal al-
kynes in the presence of appropriate catalyst. In recent years, some het-
erogeneous catalysts are developed for A3-coupling reactions [13–16].
Although all these methods are effective, these have some drawbacks
such as, use of expensive or toxic solvents, tedious work-up procedures,
low yields, long reaction times and complex catalyst preparation process.
Hence, development of a facile, environmentally friendly and low cost
protocol for one-pot synthesis of propargylamine derivatives is an attrac-
tive goal for researchers.
We reported herein, synthesis of inexpensive, reusable and magnet-
ically separable Cu2O/nano-CuFe2O4 magnetic composite and applica-
tion of it in synthesis of various propargylamine derivatives under
solvent-free reaction conditions (Scheme 1).
Multi-component coupling reactions (MCRs) are a very powerful
tool to synthesize various organic compounds from simple starting
material via a one-pot methodology. An attractive example of such a
process that has been widely studied in recent years is (A3‐coupling)
via C–H activation of terminal alkynes [9,10]. The propargylamines
that result from A3 coupling reactions are high valuable building blocks
in organic synthesis. They are considered as an important synthetic
intermediates for the preparation of various nitrogen-containing
2. Experimental
2.1. Preparation of composite
2.1.1. Preparation of nano-CuFe2O4
The CuFe2O4 nano-particles were prepared according to literature
report [17].
2.1.2. Preparation of CuFe2O4/Cu2O composite
Four types of composite with different molar ratios of CuFe2O4:Cu2O
were synthesized. Nano-CuFe2O4 (0.036–0.324 g) was dispersed in
⁎
Corresponding author.
E-mail addresses: fnemati_1350@yahoo.com, fnemati@semnan.ac.ir (F. Nemati).
http://dx.doi.org/10.1016/j.catcom.2015.03.009
1566-7367/© 2015 Elsevier B.V. All rights reserved.

16
F. Nemati et al. / Catalysis Communications 66 (2015) 15–20
e
.
H
9
F N
O
)
3 3
2O
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C C 2
80oC/24 h
.
a
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. oven
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.
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1 N OH
=
ano- u e
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.
2 NH2OH/HCl
=
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2O
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O
H
N
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o
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Scheme 1. Synthesis of propargylamines using Cu2O/nano-CuFe2O4 magnetic composite.
80 mL of deionized water. 5 mL of (0.1 mol/L) CuCl2 solution was added
into the aqueous CuFe2O4 and sonicated for 15 min. Then, 1.8 mL of
(1.0 mol/L) NaOH solution was added drop-by-drop under sonication.
The resulting solution turned light blue immediately, indicating the
formation of Cu(OH)2 precipitate. Eventually, 12 mL of (0.1 mol/L)
NH2OH·HCl was rapidly injected over 5 s into the solution. The
solutions were kept in the water bath for 1 h and centrifuged for
3 min. After the top solution was decanted, the precipitate was washed
with 6 mL of a 1:1 volume ratio of water and ethanol three times. The
Cu2O/nano-CuFe2O4 was collected as a brown solid and can be stored
in a tight vessel for several months without any change in color or
reactivity.
diluted with hot ethanol (10 mL). Then, the catalyst was separated by an
external magnet from the cooled mixture, washed with acetone, dried in
oven and re-used for a consecutive run under the same reaction condi-
tions. The filtrate was concentrated and the resulting residue was purified
by short column chromatography on silica gel to afford the desired prod-
uct in excellent yield (96%).
3. Results and discussion
3.1. Characterization of Cu2O/nano-CuFe2O4 composite
The FT-IR spectra of the CuFe2O4 in the region of 400–4000 cm−1
clearly indicated the bands centered at 3400 and 563 cm−1, which
justify the OH and metal-O stretching mode, respectively. Compared
to CuFe2O4, the composite had same absorption peaks, with more inten-
sity at metal-O region (see ESI).
2.2. General procedure for synthesis of 1-(1,3-diphenylprop-2-
ynyl)piperidine (4a)
A mixture of benzaldehyde (0.106 g, 1.0 mmol), piperidine (0.102 g,
1.2 mmol), phenylacetylene (0.153, 1.5 mmol) and Cu2O/nano-CuFe2O4
magnetic composite (0.010 g) (the Cu2O content in the catalyst was
0.002 g or 0.015 mmol, so for 1 mmol of reactant, 0.015 mmol of Cu2O
is needed, which is equal to 0.01 g magnetic composite) were mixed
and heated at 90 °C for 1 h under solvent free condition. After completion
of the reaction, the reaction mixture was cooled to room temperature and
The morphology, chemical purity and their stoichiometry of CuFe2O4
and Cu2O/nano-CuFe2O4 composite (optimized amount) were visual-
ized by SEM and EDX analyses (Figs. 1 and 2). It can be observed that
the as-prepared nano-CuFe2O4 particles are uniform and nearly spherical
in shape and possess a smooth and clean surface. Fig. 1B shows the SEM
image of Cu2O/nano-CuFe2O4 composite. Numerous Cu2O particles can
be clearly seen in composite. Compared to the CuFe2O4, the composite
Fig. 1. The SEM image of the (A) nano-CuFe2O4, (B) Cu2O/nano-CuFe2O4 (2:8 mol ratio) magnetic composite.

F. Nemati et al. / Catalysis Communications 66 (2015) 15–20
17
Fig. 2. The EDX curves of the (A) nano-CuFe2O4, (B) Cu2O/nano-CuFe2O4 (2:8) magnetic composite.
has a rougher surface because the Cu2O particles are randomly diffused in
CuFe2O4 nano-particles. The elemental composition of the CuFe2O4 from
EDX analysis was also exhibited in Fig. 2A and shows the presence of
Cu, Fe and O elements. The EDX spectrum of Cu2O/nano-CuFe2O4 was
shown in Fig. 2B and it implies that the composite mainly consists of
CuFe2O4:Cu2O.
Room-temperature magnetization study shows that the composites
have super-paramagnetic properties (Fig. 3). There was no hysteresis in
the magnetization for the two types of materials. The saturation magneti-
zation of CuFe2O4 and Cu2O/nano-CuFe2O4 was 33.86 and 18.39 emu/g,
respectively. Obviously, after the preparation of Cu2O/nano-CuFe2O4,
its magnetic response was affected due to mixing with non-magnetic
material. Nonetheless, this magnetic property is enough and the Cu2O/
nano-CuFe2O4 could be completely and quickly separated from the
reaction mixture.
Fig. 4 shows the X-ray diffraction patterns of CuFe2O4 and as-made
samples with different Cu2O molar ratios (from 9:1 to 6:4 mole ratio
of CuFe2O4 to Cu2O). The typical diffraction peaks can be well assigned
to the diffraction of CuFe2O4 nanoparticles with spinal phase from the
(101), (200), (211), (221), (303) and (224) planes, respectively. Com-
pared to CuFe2O4, new diffraction peaks located at 29.5 (110), 36.7
(111), 42.5 (200), 52.7 (211), 61.6 (220), and 73.7 (311) can be indexed
to the diffraction of Cu2O rhombic dodecahedral crystals in the cubic
phase, which suggest the presence of Cu2O in as-made composites. No
additional diffraction peaks were observed, which could be attributed to
complete reduction of copper(II) to copper(I). Because of the different
Fig. 3. The magnetization curves of CuFe2O4 and Cu2O/nano-CuFe2O4 (2:8) magnetic composite.

18
F. Nemati et al. / Catalysis Communications 66 (2015) 15–20
Fig. 4. The X-ray diffraction patterns of CuFe2O4and Cu2O/nano-CuFe2O4 with different weight ratios.
content of Cu2O in samples the intensity of all the peaks in the XRD
patterns becomes gradually stronger with the increase of the Cu2O/
CuFe2O4 weight ratio, but the intensity of peak (111) increased obviously.
The reaction of benzaldehyde, phenylacetylene and piperidine was
selected as a template reaction in various solvents, temperatures and
loadings of magnetic composite (see ESI). Interestingly, the reaction
was performed under the solvent-free condition at 90 °C in high yield
of product. We carried out the model reaction in the presence of
CuFe2O4 as a catalyst under solvent-free condition at 90 °C and the
poor yield of product was formed even after 2 h. Moreover, the reaction
did not occur in the absence of the catalyst after prolonged reaction
time. A higher reaction temperature or the catalyst amount does not
make an obvious difference in the yield of product. Accordingly, the
best condition was found when the reaction was performed under
solvent-free condition in the presence of 0.01 g Cu2O/nano-CuFe2O4 at
90 °C, confirming that the Cu2O was essential in the composite for this
transformation.
3.2. Catalytic application of Cu2O/nano-CuFe2O4 magnetic composite
The catalytic activity of the magnetic composite with different
weight ratios was tested by the model reaction of benzaldehyde, phenyl
acetylene and piperidine using 0.01 g magnetic composite in solvent
free condition at 90 °C. The catalytic performance of Cu2O/nano-
CuFe2O4 magnetic composite with a weight ratio of 8:2 was the best.
It was found that no change in yield was obtained with increase of
Cu2O loading in magnetic composite. Therefore, the optimal weight
ratio of CuFe2O4:Cu2O 8:2 was selected for optimization of the reaction
(see ESI).
So, with the optimized reaction condition in hand, the generality of
reaction was studied with arylacetylenes including electron-donating
Table 1
Three-component coupling of aromatic aldehydes, secondary-amines and terminal alkynes.a
Product
Ar
R1
R2
R3
Time (min)
Yieldb (%)
4a
4b
4c
4d
4e
4f
4g
4h
4i
4j
4k
4l
4m
4n
4o
4p
4q
4r
1a: C6H5
1b: p-Cl-C6H4
1c: o-Cl-C6H4
1d: p-Br-C6H4
1e: p-Me-C6H4
1f: p-MeO-C6H4
1g: o-Thiophene
1h: p-CHOC6H4
2a: –(CH2)5–
2a
2a
2a
2a
2a
2a
2a
3a: C6H5
3a
3a
3a
3a
3a
3a
3a
60
60
60
55
65
70
60
65
50
80
95
60
75
80
65
75
65
60
96
93
86
94
92
89
95
92
95
84
82
95
90
88
86
85
80
60
1i: 2-Naphthyl
2a
2a
2a
3a
1a
1a
1a
1b
1e
1d
1a
1a
1a
3b: p-CH3C6H4
3c: p-F-C6H4
2b: –(CH2)2–O–(CH2)2–
2b
2b
2b
3a
3a
3a
3a
3b
3a
3a
2b
2c: –(CH2)4–
2d: C2H5
C2H5
a
Reaction condition: aldehydes (1 mmol), amines (1.2 mmol), alkynes (1.5 mmol), and Cu2O/nano-CuFe2O4 (0.010 g) under solvent-free conditions at 90 °C.
Isolated yield.
b

F. Nemati et al. / Catalysis Communications 66 (2015) 15–20
19
Table 2
Table 4
Three-component coupling of aliphatic aldehydes, secondary-amines and terminal
Comparison of catalytic activity of Cu2O/nano-CuFe2O4 with reported magnetically
separable catalysts for synthesis of propargyl amines 4a and 6a.
alkynes.a
Product
Catalyst
Time
Condition
Yield (%)
Ref.
4a
4a
4a
4a
4a
4a
6a
6a
6a
Graphene-Fe3O4
CuFe2O4
Fe3O4
24 h
4 h
24 h
16 h
3 h
60 min
24 h
24 h
40 min
CH3CN/80 °C
Toluene/80 °C
THF/80 °C
Toluene/110 °C
S.F/120 °C
S.F/90 °C
CH3CN/80 °C
THF/80 °C
Trace
86
45
75
99
96
92
80
94
[21]
[22]
[23]
[24]
[25]
This work
[21]
[23]
This work
Fe3O4
Product R1
R2, R3
R4
Time Yieldb
(min) (%)
Cu(OH)X.Fe3O4
Cu2O/CuFe2O4
Graphene-Fe3O4
Fe3O4
6a
6b
5a: H
5a
2a: –(CH2)5–
2a
3a: C6H5
3b:
p-CH3C6H4
40
40
94
85
Cu2O/CuFe2O4
S.F/90 °C
6c
6d
6e
6f
6g
6h
6i
5a
5a
5a
5b: C6H11
5b
5b
5b
5b
5b
2b: –(CH2)2–O–(CH2)2– 3a
40
40
45
45
45
45
45
45
45
93
85
75
90
80
89
82
65
85
2c: –(CH2)4–
3a
2d: C2H5
2a
C2H5
3a
3a
field and therefore, this restriction necessitates the development of
new catalyst for KA2 coupling reaction [18–20].
2b
3b
The reaction condition for KA2 coupling reaction was optimized and
the desired quaternary carbon-containing propargylamine 7d could be
isolated in 87% yield. The scope of the KA2 coupling reaction was evaluat-
ed using cyclic ketones, secondary amines and alkynes, applying the opti-
mal condition, and exhibited good reactivity (Table 3). It is worth nothing
that, aromatic ketones gave none of the desired product, which is in
accordance with earlier studies [18–20].
2b
3a
2c
3a
6j
6k
2d
3a
2a
3c:
p-F-C6H4
3a
6l
5c: –(CH2)2–Me 2a
45
45
45
45
92
90
81
70
6m
6n
6o
5c
5c
5c
2b
2c
2d
3a
3a
3a
The comparison of the catalytic activity of Cu2O/nano-CuFe2O4
magnetic composite with the reported magnetically recoverable cata-
lyst for the synthesis of propargyl amines of 4a and 6a is depicted in
Table 4. The results clearly indicate that Cu2O/nano-CuFe2O4 has many
merits over the reported methods in terms of catalytic activity, reaction
time, yields and diversity of products.
a
Reaction condition: aliphatic aldehydes (1 mmol), amines (1.1 mmol), alkynes
(1.1 mmol), and Cu2O/nano-CuFe2O4 (0.010 g) under solvent-free conditions at 90 °C.
b
Isolated yield.
and electron-withdrawing groups, secondary aliphatic amines and aro-
matic aldehydes (Table 1). We further investigated the reaction of some
aliphatic aldehydes in the reaction and results were listed in Table 2.
In general, both aromatic aldehydes and arylacetylenes bearing
electron-donating substituents as well as electron-withdrawing
groups and aliphatic aldehydes provided the desired products in good
to moderate yields within short reaction time. The cyclic amines such as
morpholine and pyrrolidine gave similar results to those obtained with
piperidine, whereas diethylamine rendered the corresponding product
in modest yield. Unfortunately, the amines with aromatic substituted
were examined and gave poor results.
3.2.1. Recycling of the catalyst
The recyclability of Cu2O/nano-CuFe2O4 magnetic composite was
studied in synthesis of diphenylprop-2-ynyl piperidine 4a under the
optimized condition. No significant loss in catalytic activity was ob-
served after five runs, suggesting that Cu2O leaching is not meaningful
for Cu2O/nano-CuFe2O4 magnetic composite.
4. Conclusion
The excellent catalytic activity of Cu2O/nano-CuFe2O4 magnetic com-
posite toward the synthesis of propargylamines (A3 coupling) prompted
us to explore its further application for the three-component coupling
of ketones, secondary amines and arylacetylenes (KA2 coupling)
(Table 3). To date, only few methods have been developed in this
In conclusion, we have developed an efficient method for the syn-
thesis of tertiary and quaternary carbon-containing propargylic amines
catalyzed by Cu2O/nano-CuFe2O4 magnetic composite under solvent-
free condition. Ready availability of starting materials, mild reaction
condition, simple experimental procedure and easy recovery and reus-
ability of catalyst are some conspicuous features of this methodology.
Table 3
Acknowledgments
Three-component coupling of cyclic aliphatic ketones, secondary-amines and terminal
alkynes.a
The authors gratefully acknowledge the Semnan University
Research Council (266/93/2501) for the financial support of this work.
Appendix A. Supplementary data
Product Cyclic
ketone
R2, R3
R4
Time Yieldb
(min) (%)
Supplementary data to this article can be found online at http://dx.
doi.org/10.1016/j.catcom.2015.03.009.
7a
7b
7c
7d
7e
7f
7g
7h
7i
c-Pentanone 2a: –(CH2)5–
c-Pentanone 2b: –(CH2)2–O–(CH2)2– 3a
3a: C6H5
140
140
140
150
83
80
83
87
80
84
79
88
81
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c-Pentanone 2c: –(CH2)4–
c-Hexanone 2a
c-Hexanone 2a
c-Hexanone 2b
c-Hexanone 2b
c-Hexanone 2c
c-Hexanone 2b
3a
3a
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