Received: November 27, 2015 | Accepted: November 30, 2015 | Web Released: December 5, 2015
CL-151097
Cu O/Nano-CuFe O : An Efficient and Magnetically Recoverable Catalyst for the Ligand-free
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N-Arylation of Amines and Nitrogen Heterocycles with Aryl Halides
Ali Elhampour, Firouzeh Nemati,* and Mahdieh Kaveh
Department of Chemistry, Semnan University, Semnan 35131-19111, Iran
(
E-mail: fnemati@semnan.ac.ir)
An efficient strategy has been developed for the N-arylation
of azoles and aliphatic amines with aryl halide using a Cu2O/
nano-CuFe2O4 magnetic composite as the catalyst and KOH
as the base. The methodology is found to be applicable to a
variety of nitrogen-containing heterocycles, such as imidazole,
indole, and pyrrole, as well as aliphatic amines in high yields
with practical simplicity under cost-effective “ligand-free”
conditions. The magnetic property of the catalyst allowed its
fast separation from the reaction medium by an external magnet.
Additionally, the inexpensive catalyst could be recycled for five
consecutive runs with small drops in catalytic activity.
Figure 1. TGA of (a) nano-CuFe2O4 and (b) Cu2O/nano-CuFe2O4.
The development of efficient methodologies for carbon
nitrogen bond formation is one of the challenging and important
tasks in the field of organic reactions, since the final products
play important roles in pharmaceuticals, natural products, and
in high yields, promoted by the heterogeneous Cu O/nano-
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CuFe2O4 (20:80) magnetic composite as the catalyst (see
Supporting Information (SI) for details of the preparation and
optimization of magnetic catalyst).
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biologically active compounds. The standard protocol for CN
The initial design of our work was pioneered by choosing
iodobenzene (1 mmol) and 1H-imidazole (1.2 mmol) as model
substrates. The thermal stability of the nano-magnetic composite
(Figure 1) shows a weight loss of ca. 8% between 60150 °C,
which can be due to the removal of surface hydroxy groups or
surface adsorbed water in the nanocomposite. The second mass
loss (approximately 8%) observed at higher temperature could
be mainly attributed to the decomposition of Cu(OH)2 that
remained in the nanocomposite. Thus, it can concluded that
the nanocomposite is sufficiently stable and could be used at
elevated temperatures.
coupling reactions is either nucleophilic aromatic substitution of
an activated aryl halide or metal-mediated coupling of hetero-
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cycles with aryl halides. In these reactions a variety of different
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metal catalysts such as Pd, Ni, and Cu are employed alone or
with different coordinating ligands such as bisamines, amino
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acids, DPPF, phosphor amides, and oxime-phosphine oxides.
Generally, Cu catalysts are preferred over other metal catalysts
from the industrial and economical point of view. Therefore,
a number of copper catalysts have been reported as catalysts
for CN coupling reactions.5 Although these catalysts have
wide scope and excellent compatibility with many functional
groups for the N-arylation reaction, further development of
new catalysts in terms of superior activity, easy recovery, and
reusability is highly desirable. Catalysts with magnetic nano-
particle (NP)-based materials represent one of the most
attractive heterogeneous catalysts that have been widely used
for important chemical reactions, because of their unique
In the preliminary test, we carried out the model reaction
between iodobenzene and 1H-imidazole in DMSO at 100 °C
with 0.01 g of Cu O/nano-CuFe O as the catalyst under an
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aerobic atmosphere. Unfortunately, the desired product, 1-
phenyl-1H-imidazole (Table 1, Entry 1) formed in 32% yield
during 2 h. Thus, to promote the initial abstraction of the
activated proton of imidazole, the addition of 2 equiv of several
bases such as KOH, NaOH, Na2CO3, K2CO3, and Et3N to the
reaction mixture was examined. Consequently, when KOH
was added, the yield of 1-phenyl-1H-imidazole was remarkably
increased to 94%. In the next attempt, the model reaction was
performed by employing 0.01 and 0.02 g of nano-CuFe O as
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properties and potential applications such as, increase reaction
yield, great selectivity, and high stability. Notably, the major
significance of magnetic NPs is their simple recovery at the end
of the reaction by an external magnet. They can be reused
several times without considerable loss of activity.7
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Very recently, we have reported on the preparation and
characterization of a new Cu2O/nano-CuFe2O4 magnetic com-
posite, which was demonstrated to be a very efficient catalyst
the catalyst at 100 °C in DMSO for 2 h. However, very poor
yield of the product was obtained.
Recently, Panda et al. reported that nano-CuFe2O4 catalyzed
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t
for the synthesis of propargylamines. The catalyst was readily
N-arylation aryl halides in the presence of BuOK in DMF
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prepared through a simple method and was composed of
microsize Cu2O in ca. 30 nm nearly spherical CuFe2O4 magnetic
particles. It can be separated by an external magnet after the end
of the reaction. In our continuing efforts towards the develop-
during 24 h reflux under N2 atmosphere. Hence, this estab-
lished the essential nature of Cu2O in the model reaction.
Interestingly, Cu O could catalyze the synthesis of 1-
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phenyl-1H-imidazole with a very long reaction time, as reported
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ment of an efficient synthetic methodology, in this report, we
earlier in the literature. Therefore, it may be concluded that
would like to evaluate our results towards the development of a
new methodology in which N-arylated amines were synthesized
Cu O/nano-CuFe O , due to the synergistic effect of Cu O and
nano-CuFe2O4, is an efficient catalyst for this methodology.
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