Nano-magnetic Fe3O4@TiO2/Cu2O composite: a simple, effective and reusable heterogeneous catalyst for ligand-free N-arylation of amines and nitrogen heterocycles

Article abstract of DOI:10.1007/s11164-016-2556-1

Abstract: A practical and mild synthetic strategy has been investigated for the arylation of aromatic amines and nitrogen heterocycles using nano-magnetic-Fe₃O₄@TiO₂/Cu₂O composite and KOH as the base. The protocol does not require the use of expensive ligands. Notably, the catalyst is easily recoverable and reused by magnetic separation up to five runs without appreciable loss of catalytic activity. Graphical Abstract: [Figure not available: see fulltext.]

Full text of DOI:10.1007/s11164-016-2556-1

Res Chem Intermed
DOI 10.1007/s11164-016-2556-1
Nano-magnetic Fe3O4@TiO2/Cu2O composite: a simple,
effective and reusable heterogeneous catalyst for
ligand-free N-arylation of amines and nitrogen
heterocycles
Firouzeh Nemati1 Ali Elhampour1
•
Received: 11 March 2016 / Accepted: 22 April 2016
Ó Springer Science+Business Media Dordrecht 2016
Abstract A practical and mild synthetic strategy has been investigated for the arylation
of aromatic amines and nitrogen heterocycles using nano-magnetic-Fe3O4@TiO2/Cu2O
composite and KOH as the base. The protocol does not require the use of expensive
ligands. Notably, the catalyst is easily recoverable and reused by magnetic separation up
to five runs without appreciable loss of catalytic activity.
Graphical Abstract
G
G
Het or
Alkyl
Het or
Alkyl
Fe3O4@TiO2/Cu2O
N
X
HN
100 oC/ DMSO
KOH
X= I, Cl, Br
27 examples
Keywords Nano-chemistry Á Nano-magnetic Á Green chemistry Á Heterogeneous
catalyst Á N-Arylation
Introduction
Transition metal-catalyzed cross-coupling reactions are one of the most efficient and
powerful tools in organic synthesis for the connection of two fragments through C–
C or C–N bond formation. The development of an efficient methodology for C–N
Electronic supplementary material The online version of this article (doi:10.1007/s11164-016-2556-1)
contains supplementary material, which is available to authorized users.
&
Firouzeh Nemati
fnemati@semnan.ac.ir
1
Department of Chemistry, Semnan University, Semnan, Iran
123

F. Nemati, A. Elhampour
bond formation is one of the most important reactions since the resultant N-arylated
heterocyclic products play an important role in a wide range of pharmaceuticals and
biologically active compounds and natural products [1]. Among the many reported
C–N coupling reactions such as Ullmann coupling, Chan–Lam coupling [2] and
Buchwald–Hartwig amination [3], the Ullmann-type coupling reactions are
particularly attractive because they often allow the usage of low-cost starting
materials and readily available copper complexes. The Ullmann-type coupling
reactions can be mediated by palladium, nickel or copper catalysts with different
coordinating ligands [4–8]. In this context, various types of ligands have been
developed to facilitate the copper-catalyzed N-arylation reaction under different
conditions. Although these catalysts and ligands or many copper/ligand combina-
tions are used in low loading, they are very expensive and the toxicity caused by the
presence of metal in the products is a serious disadvantage of these reactions.
Therefore, development of new methodology taking into consideration a decrease of
reaction time, minimum metal contamination of products, a simple catalyst system
involving easy isolation and reusability of catalysts, and ligand-free conditions is
highly desirable.
Magnetic nanoparticles are particularly attractive structures since they are
favorable as one of the most powerful heterogeneous catalysts in organic synthesis,
for their high surface area, more active sites, low density, hybrid functionalities and
ease of handling that result in improving the efficiency, selectivity and yields of the
catalytic process [9, 10]. As important, the magnetic separation technique as one of
the advantages of magnetic nanoparticles has major significance for nano-sized
structures in which the conventional filtration method results in the loss of catalyst
particles and product contaminations [11, 12].
In recent years, titanium dioxide (TiO2) nanoparticles have been extensively
considered in various applications, including purification of wastewater, hydrogen
production [13], sensors [14] and organic pollutant degradation [15], due to its high
photocatalytic activity, chemical stability, low cost, non-toxicity and environmen-
tally friendly advantages. Despite their wide use in photocatalytic activity, much
less attention has been focused on the catalytic behavior of titanium dioxide
nanoparticles in organic transformations because of the difficult separation of them
from products for recycling [16, 17]. In this regard, a variety of nanostructures have
been designed, such as core/shell, mesoporous, nanotube, and hollow sphere
structures, providing an excellent chance to explore their unique surface properties
[15, 18–20]. Among the various structures, an interesting nanoparticle system is that
of core/shell structure nanoparticles in which the magnetic core is coated with a
layer of a nonmagnetic, antiferromagnetic, or ferro/ferri-magnetic shell. In this
regard, TiO2 can be considered as a shell due to its unique surface properties, its
high chemical and thermal stability, non-toxicity, as well as its great accessibility
and moderate cost [21, 22]. Furthermore, the inclusion of an Fe3O4 core into TiO2
nanospheres makes them easy to be recovered [23].
In our continuing efforts towards the development of efficient and environmen-
tally benign synthetic methodologies [24–30], very recently, we have reported on
the preparation and characterization of a new Fe3O4@TiO2/Cu2O magnetic
composite, which demonstrated an efficient catalysis for the synthesis of 1,2,3-
123

Nano-magnetic Fe3O4@TiO2/Cu2O composite: a simple…
triazoles [31]. The catalyst was readily prepared through a simple method and
composed of micro-sized Cu2O in Fe3O4@TiO2 core/shell magnetic particles.
In this report, we would like to disclose our findings towards the development of
ligand-free amination of aryl halides, in which N-arylated amines were synthesized
in high yields, promoted by the heterogeneous Fe3O4@TiO2/Cu2O magnetic
composite as a catalyst. The magnetic composite could be easily separated from the
crude reaction mixture and recycled in five consecutive runs without significant loss
of catalytic activity.
Materials and methods
Chemical reagents in high purity were purchased from Merck and Sigma-Aldrich and
were used without further purification. 1H NMR and 13C NMR spectra were recorded
using a Bruker DRX-400 spectrometer at 400 and 100 MHz, respectively. The progress
of the reaction was monitored by thin layer chromatography (TLC) on commercial
aluminum-backed plates of silica gel 60 F254, visualizing using ultraviolet light.
Preparation of nano-magnetic Fe3O4@TiO2/Cu2O composite
The nano-magnetic composite was prepared in accordance to our earlier report (For
details, see ESI) [31]. We explored that the most appropriate ratio of nano-
Fe3O4@TiO2:Cu2O was 80:20 % (Table S1). Therefore, the optimal weight ratio of
Fe3O4@TiO2:Cu2O, 8:2, was selected for the N-arylation of aryl iodides.
General procedure for the N-arylation of aryl iodide
A mixture of aryl iodide (1.0 mmol), Het-NH (1.2 mmol), KOH (2 mmol), nano-
magnetic Fe3O4@TiO2/Cu2O (0.010 g equal to 1.4 mol% Cu2O) and anhydrous
DMSO (2 mL) was stirred at 100 °C. After completion of the reaction as indicated
by TLC, the reaction mixture was cooled to room temperature and diluted by ethyl
acetate and the catalyst was separated by an external magnet from the mixture,
washed with acetone, dried in an oven at 80 °C for 3 h and re-used for a consecutive
run under the same reaction conditions. The combined ethyl acetate layer was
washed with water and dried over anhydrous MgSO4. The residue was purified by
recrystallization or short column chromatography on silica gel to afford the target
products in excellent yield.
Results and discussion
To access the catalytic activity of Fe3O4@TiO2/Cu2O, it was applied in the model
reaction for N-arylation of aryl halides. In order to find out the appropriate
conditions, the reaction of iodobenzene 1a (1 mmol) and imidazole 2a (1.2 mmol)
was studied, (Table 1), in which the effects of solvents, loading of catalyst and
temperature were evaluated (Table 1).
123

F. Nemati, A. Elhampour
Table 1 Optimization of the model reaction
N
Fe3O4@TiO2/Cu2O
HN
N
I
N
Condition
KOH
Entry
Catalyst (g)
Fe3O4@TiO2 (0.02)
Conditions
Time/h
Yield/%
1
DMSO/100 °C
DMSO/25 °C
DMSO/80 °C
DMSO/100 °C
DMSO/100 °C
DMSO/110 °C
DMSO/100 °C
DMSO/100 °C
Water/reflux
2
2
2
2
5
2
2
2
2
2
5
2
2
6
23
2
Fe3O4@TiO2/Cu2O (0.01)
Fe3O4@TiO2/Cu2O (0.01)
Fe3O4@TiO2/Cu2O (0.01)
Fe3O4@TiO2/Cu2O (0.01)
Fe3O4@TiO2/Cu2O (0.01)
Fe3O4@TiO2/Cu2O (0.015)
Fe3O4@TiO2/Cu2O (0.02)
Fe3O4@TiO2/Cu2O (0.01)
Fe3O4@TiO2/Cu2O (0.01)
Fe3O4@TiO2/Cu2O (0.01)
Fe3O4@TiO2/Cu2O (0.01)
Fe3O4@TiO2/Cu2O (0.01)
–
Trace
87
3
4
92
5
91
6
93
7
90
8
83
9
Trace
49
10
11
12
13
14
Ethanol/reflux
CH2Cl2/Reflux
Toluene/100 °C
Solvent free/100 °C
DMSO/100 °C
53
62
Trace
Trace
Bold value indicates the optimized condition
a
Reaction conditions: imidazole (1.2 equiv.) and iodobenzene (1 equiv.) and Fe3O4@TiO2/Cu2O as
catalyst
b
Isolated yield
In our initial screening experiments, we carried out the model reaction in DMSO
at 100 °C in the presence of 20 mg of Fe3O4@TiO2/Cu2O magnetic composite as a
catalyst and only 23 % conversion was obtained even after 4 h. It seems noteworthy
to mention that the reaction was not successful in the absence of a base. Thus, to
promote the initial abstraction of the activated proton of imidazole 1a, the addition
of several bases such as KOH, NaOH, Na2CO3, K2CO3, Et3N and pyridine to the
reaction mixture was examined. The screening of bases revealed that inorganic
bases due to more basicity were more efficient than the soluble organic bases for this
coupling reaction. Thus, the reaction yield was improved up to 92 % when 2 mmol
KOH was added.
A further increase in the base amount to 3 mmol did not provoke any
improvements of the reaction time or yield. Moreover, the reaction did not occur in
the absence of the catalyst after a prolonged reaction time (Table 1, entry 14).
According to the reported literature, Cu2O could catalyze the synthesis of 1-phenyl-
1H-imidazole 3a for 24 h in the presence of KOH in DMSO under Ar atmosphere
[32]. The model reaction was performed using 20 mg of Fe3O4@TiO2, in which no
desired product was observed. Hence, it established the synergetic effect of Cu2O
and magnetic-Fe3O4@TiO2 in this system. The catalyst loading for this reaction
123

Nano-magnetic Fe3O4@TiO2/Cu2O composite: a simple…
could be reduced from 20 to 10 mg without affecting the product yields. Hence,
10 mg of nanocomposite Fe3O4@TiO2/Cu2O is optimum and sufficient for this
reaction during 2 h.
Having determined the optimum base and loading of catalyst for the reaction,
investigation pertaining to the choice of an appropriate solvent was performed.
From the data in Table 1, it was found that DMSO is a suitable solvent to give the
desired product in high yield; while others solvents such as water, ethanol, CH2Cl2
and toluene and even solvent-free conditions gave relatively low yields (Table 1,
entries 9–13). Furthermore, the reaction temperature exerted an impact on this
coupling reaction. As indicated in Table 1, it was noted that at lower temperature
(25–80 °C) the reaction gave the product in low yield and the best temperature was
found to be 100 °C.
Thus, the best condition was found to be Fe3O4@TiO2/Cu2O (0.01 g) as the
catalyst, DMSO (2 ml) as the solvent, KOH (2 mmol) as the base, ligand-free and
conducting the reaction at 100 °C. The reaction proceeds smoothly and the
corresponding product resulted in high yields without observing any side-product.
Encouraged by these results, and in order to expand the scope of this methodology,
we initiated our investigation into the variety of substituted aryl halide derivatives
with heterocyclic amines in this cross-coupling reaction, and the results are reported
in Table 2. As shown in Table 2 (entries 1–9 and 19–27), the coupling reactions
were performed well by the reaction of heterocyclic amines with various aryl
halides, and the desired products were isolated in moderate to excellent yields.
Notably, when the reaction was carried out with iodobenzene, the expected products
were obtained in high yields, in accordance with the bond reactivity order of C–
I [ C–Br [ C–Cl (Table 2).
Generally, the aryl halides containing electron-withdrawing and electron-
donating groups are reacted with imidazole to afford the corresponding N-arylated
products in good to excellent yields. Electron-deficient p-substituted aryl iodides
were found to proceed in higher yields than those with electron-donating substituent
groups (e.g. Table 2, entries 2 and 3). Instead of imidazoles, other nitrogen-
containing heterocycles such as 2-methyl imidazoles, benzo[a]imidazoles, pyrrole
and indole could be used in the arylation process with use of aryl iodide and good
results were obtained (Table 2, entries 6–9). Owing to the excellent results obtained
in the N-arylation of aryl iodides with nitrogen-containing heterocycles, a similar
protocol was employed with aliphatic and aromatic amines, and only with
increasing the reaction time, the corresponding products were obtained in high to
good yields (Table 2, entries 10–14).
To show the superiority of the present method over previous ones, we compared
our results with some other results reported in the literature (Table 3). For example,
the CuFe2O4 was used as a catalyst for amination of aryl iodides (Table 3, entry 12).
It has some merits including being ligand and additive-free, using a recyclable
media and magnetically separable catalyst.
As shown in Table 3, Fe3O4@TiO2/Cu2O magnetic composite as a simple
catalyst has some other advantages such as short reaction times, excellent yields,
simple recovery of the magnetic catalyst and avoiding the separation of other
ligands or media in the reaction system.
123

F. Nemati, A. Elhampour
Table 2 N-Arylation of various heterocyclic, aliphatic and aryl amines with aryl halides
G
G
Het or
Alkyl
Het or
Alkyl
Fe3O4@TiO2/Cu2
O
N
X
HN
100 oC/ DMSO
KOH
X= I, Cl, Br
Entry
1
X
I
G
H
Amine
Product
Time
h:min
Yielda
(%)
M.P.C
[References]
H
N
2
93
Yellow oil [33]
N
N
N
3a
H
N
2
3
I
I
p-NO2
p-CH3
1:25
6:40
94
77
199–201
(200–202)
[33]
N
N
O2N
Me
N
3b
H
N
Colorless oil
[33]
N
N
N
3c
H
N
4
5
6
7
I
I
I
I
p-
7:50
86
92
79
58
120–122
(120–122)
[34]
N
N
OCH3
MeO
N
3d
H
N
p-Cl
H
5
Colorless oil
[33]
N
N
Cl
N
3e
H
N
11:30
Yellow oil [35]
Yellow oil [34]
N
N
Me
N
3f
H
6
N
N
H
3g
H
N
N
8
I
H
7
55
91–93 (93–95)
[33]
N
N
3h
N
H
N
9
I
I
H
H
5
2
85
84
62–64 (64–66)
[33]
3i
H
N
10
Colorless oil
[34]
N
3j
123

Nano-magnetic Fe3O4@TiO2/Cu2O composite: a simple…
Table 2 continued
Entry
X
G
Amine
Product
Time
h:min
Yielda
(%)
M.P.C
[References]
H
N
11
I
H
2
87
73
69
53–55 (53–54)
[34]
N
O
3k
O
12
13
I
I
H
H
2:40
4:15
Colorless liquid
[34]
N
NH
3l
H
Me
Me
Colorless liquid
[36]
N
N
3m
H
N
OH
14
I
H
3
94
55–57 (56–58)
[37]
HO
N
OH
3n
15b
16b
I
I
H
H
1:30
18
90
30
33–35 (33–34)
[34]
NH2
NH
3o
NH2
H
N
50–52 (50–52)
[38]
3p
H
N
17
18
I
H
18
61
81
126–128
(128–130)
[39]
N
3q
H2N
OH
I
H
H
5:30
Yellow oil [10]
Yellow oil [33]
OH
NH
3r
H
N
19
20
21
Br
9
2:25
9
87
93
82
N
N
N
3a
H
N
Br p-NO2
Br p-CH3
199–201
(200–202)
[33]
N
N
O2N
Me
N
3b
H
N
Colorless oil
[33]
N
N
N
3c
123

F. Nemati, A. Elhampour
Table 2 continued
Entry
X
G
Amine
Product
Time
h:min
Yielda
(%)
M.P.C
[References]
H
N
22
Br p-OH
Br p-NH2
9
58
138–143
(138–139)
[34]
N
N
HO
N
3s
3t
H
N
23
10
78
200–203
(202–205)
[33]
N
N
H2N
N
H
N
24
26
27
Cl C6H5
Cl p-NO2
Cl p-CH3
14
88
84
59
Yellow oil [33]
N
N
N
3a
H
N
3:30
24
199–201
(200–202)
[33]
N
N
O2N
Me
N
3b
3c
H
N
Colorless oil
[33]
N
N
N
Reaction condition: Het–NH (1.2 mmol) or aliphatic amine (4 mmol), aryl halide (1 mmol), KOH
(2 mmol), and Fe3O4@TiO2/Cu2O (0.010 g) in DMSO (2 mL) at 100 °C
a
Isolated yield
b
Under the same conditions, but aromatic amine and benzylamine (1 mmol) was used
In order to check that the catalyst is heterogeneous, the model reaction was
performed at 100 °C and after 45 min, the catalyst was immediately separated under
hot conditions. After that, the reaction was continued without the catalyst, for a
further 2 h at the same temperature. However, the yield of the reaction was only
45 %, indicating that no homogeneous catalyst was involved.
Finally, we carried out the recovery and reusability testing of the nano-magnetic
Fe3O4@TiO2/Cu2O catalytic system in the C–N coupling reaction of 1-phenyl-1H-
imidazole 3a. After the reaction was completed, the catalyst system was recovered
by using an external magnet (the saturation magnetization of the core/shell
composite was 24.11 emu/g) [31], washed with acetone, followed by distilled water
and ethanol, then dried in a desiccator and subjected to the next run. Hence, the
catalyst can be used for five times with almost consistent activity. Even at the end
run, the yield of N-arylated product is 88 %, indicating a good reusability and
chemical stability of the catalyst. The slight decrease in the yield could probably be
due to the gradual loss of the catalyst during washing. The performance of the
recycled heterogeneous catalyst in N-arylation reactions for five successive runs
was: 92, 92, 90, 89, 88 which demonstrates the practical and excellent recyclability
of this catalyst. Additionally, the field emission scanning electron microscopy (FE-
123

Nano-magnetic Fe3O4@TiO2/Cu2O composite: a simple…
123

F. Nemati, A. Elhampour
SEM) of fresh and recovered composite and X-ray diffraction (XRD) of recycled
catalyst were also investigated and revealed that there was no change in the
morphology of the composite after the coupling reactions (Figs. 1, 2).
Based on reports in the literature [50], a plausible mechanism for N-arylation is
proposed in Scheme 1. In the first step, the intermediate II was formed from the aryl
halide and magnetic composite. Then, the imidazole could be deprotonated using
Fig. 1 FE-SEM of nano-Fe3O4@TiO2/Cu2O (a) fresh (b) recycled after five times
Fig. 2 XRD of recycled catalyst after five times
123

Nano-magnetic Fe3O4@TiO2/Cu2O composite: a simple…
N
N
N
N
III
= Fe3O4@TiO2
= Cu2O
I
X
Base H+
X-
X = I, Br, Cl
H
N
Base
N
X
II
Scheme 1 The proposed mechanism
the base and instantly replaced with halide anion leading to intermediate III. Finally,
the intermediate III is converted to the desired product and the catalyst would be
regenerated, completing the catalyst cycle.
Representative spectral data
1
1-phenyl-1H-imidazole 3a [31]; H NMR (400 MHz, CDCl3): d 7.90 (s, 1H), 7.45
(t, J = 7.8 Hz, 2H), 7.37–7.31 (m, 3H), 7.20 (d, J = 7.8 Hz 1H), 7.12 (s, 1H) ppm.
13C NMR (100 MHz, CDCl3): 139.3, 138.6, 133.0, 132.7, 129.0, 120.2, 117.3 ppm.
1-(4-nitrophenyl)-1H-imidazole 3b [31]; 1H NMR (400 MHz, CDCl3): d 8.35–8.31
(m, 2H), 8.03 (s, 1H), 7.63–7.53 (m, 2H), 7.30 (s, 1H), 7.09 (d, J = 8.8 Hz, 1H)
ppm. 13C NMR (100 MHz, CDCl3): 146.3, 142.0, 135.4, 131.7, 125.8, 121.0,
117.8 ppm.
1
1-(4-methylphenyl)-1H-imidazole 3c [31]; H NMR (400 MHz, CDCl3): d 7.80 (s,
1H), 7.28–7.25 (m, 5H), 7.16 (s, 1H), 2.41 (s, 3H) ppm. 13C NMR (100 MHz,
CDCl3): 137.5, 135.6, 133.9, 130.3, 130.2, 121.5, 118.3, 20.9 ppm.
123

F. Nemati, A. Elhampour
1-(4-Chlorophenyl)imidazole 3e [31]; 1H NMR (400 MHz, CDCl3): d 7.88 (s, 1H),
7.51–7.22 (m, 5H), 7.16 (s, 1H) ppm, 13C NMR (100 MHz, CDCl3): 137.8, 136.1,
130.3, 125.7, 123.3, 120.0, 112.0 ppm.
1
1-Phenyl-2-methyl-1H-imidazole 3f [33]; H NMR (400 MHz, CDCl3): d 7.51 (s,
1H), 7.35–7.03 (m, 6H), 2.35 (s, 3H) ppm, 13C NMR (100 MHz, CDCl3): 147.1,
139.1, 129.3, 128.0, 127.2, 123.6, 118.7, 14.3 ppm.
1
1-Phenyl-1H-indole 3g [32]; H NMR (400 MHz, CDCl3): d 7.95 (d, J = 8.8 Hz,
1H), 7.71–7.60 (m, 1H), 7.46–7.42 (m, 4H), 7.31–7.26 (m, 2H), 7.24–7.20 (m, 2H),
6.90–6.89 (m, 1H) ppm, 13C NMR (100 MHz, CDCl3): 144.0, 141.3, 130.1, 129.3,
129.0 127.4, 125.5, 124.6, 123.3, 119.6, 113.7, 108.5 ppm.
1
1-Phenyl-1H-benzimidazole 3h [31]; H NMR (400 MHz, CDCl3): d 8.21 (s, 1H),
7.91–7.85 (m, 1H), 7.61–7.25 (m, 6H), 7.27–7.20 (m, 2H) ppm, 13C NMR: 148.4,
146.3, 135.5, 134.3, 134.0, 129.3, 124.7, 124.0, 123.6, 120.3, 112.7 ppm.
1
N-Phenylmorpholine 3k [10]; H NMR (400 MHz, CDCl3): d 7.35–7.31 (m, 2H),
6.87–6.81 (m, 3H), 3.78 (t, J = 7.8 Hz, 4H), 3.18 (t, J = 7.8 Hz, 4H) ppm; 13C
NMR (100 MHz, CDCl3): 151.5, 129.3, 120.9, 114.7, 57.2, 49.6 ppm.
1
N-Phenylpyrrolidine 3l [10]; H NMR (400 MHz, CDCl3): d 7.47 (t, J = 7.8 Hz,
2H), 6.92 (t, J = 7.8 Hz, 1H), 6.54–6.50 (m, 2H), 3.35 (d, J = 8.4 Hz, 4H), 1.96 (d,
J = 8.4 Hz, 4H) ppm.
1
N,N-Diethylaniline 3m [34]; H NMR [(CD3)2SO, 400 MHz]: d 7.22–7.18 (m, 2
H), 6.60 (d, J = 7.6 Hz, 2 H), 6.33 (t, J = 8 Hz, 1 H), 3.29 (q, J = 7.5 Hz, 4 H),
1.02 ppm (t, J = 7.5 Hz, 6 H). 13C NMR [(CD3)2SO, 100 MHz]: 147.3, 128.5,
117.8, 112.0, 43.6, 12.3 ppm.
N-Phenylbenzylamine 3o [10]; 1H NMR (400 MHz, CDCl3): d 7.39–7.28 (m, 5H),
7.21–7.16 (m, 2H), 6.68–6.50 (m, 3H), 4.19 (s, 2H), 3.91 (br, 1H) ppm; 13C NMR
(100 MHz, CDCl3): 148.3, 135.5, 129.3, 128.8, 128.1, 127.3, 118.8, 112.8,
46.6 ppm.
Triphenylamine 3q [37]; 1H NMR (400 MHz, CDCl3): d 7.58–7.50 (m, 6H),
7.36–7.29 (m, 6H), 7.13–6.97 (m, 3H) ppm. 13C NMR (100 MHz, CDCl3): 157.8,
127.4, 124.2, 123.0 ppm.
Conclusions
In conclusion, nano-magnetic Fe3O4@TiO2/Cu2O composite as a cheap, air-
stable and highly active reusable heterogeneous green catalyst was used for the C–N
cross-coupling reaction of heterocycles and aliphatic or aromatic amines with a
variety of aryl halides. Most importantly, the protocol was simple, general, ligand-
free and efficient to afford the cross-coupled products in high yield in short reaction
times. The nano-magnetic Fe3O4@TiO2/Cu2O as an inexpensive heterogeneous
catalyst can be easily separated from the reaction mixture as well as reused for five
cycles without significant loss of activity.
Acknowledgments The authors gratefully acknowledge Semnan University Science and Technology
Park, Research Council and Vice-chancellor for Education and Postgraduate Student for financial support
of this work.
123

Nano-magnetic Fe3O4@TiO2/Cu2O composite: a simple…
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