Copper oxide supported on magnetic nanoparticles (CuO@γ-Fe2O3): An efficient and magnetically separable nanocatalyst for addition of amines to carbodiimides towards synthesis of substituted guanidines

Article abstract of DOI:10.1002/aoc.3695

Copper oxide supported on magnetic nanoparticles was used as a green magnetic nanocatalyst for hydroamination of carbodiimides towards the synthesis of guanidines. Easy preparation and separation, low cost, non-sensitivity to moisture and reusability of the catalyst along with diversity and high yield of products are significant features of this method.

Full text of DOI:10.1002/aoc.3695

Received: 30 August 2016
DOI 10.1002/aoc.3695
Revised: 11 October 2016
Accepted: 31 October 2016
C O M M U N I C A T I O N
Copper oxide supported on magnetic nanoparticles (CuO@γ‐
Fe2O3): An efficient and magnetically separable nanocatalyst for
addition of amines to carbodiimides towards synthesis of
substituted guanidines†
Sepideh Abbasi1 | Dariush Saberi2 | Akbar Heydari1
1 Chemistry Department, Tarbiat Modares
Copper oxide supported on magnetic nanoparticles was used as a green magnetic
nanocatalyst for hydroamination of carbodiimides towards the synthesis of guani-
dines. Easy preparation and separation, low cost, non‐sensitivity to moisture and
reusability of the catalyst along with diversity and high yield of products are signif-
icant features of this method.
University, PO Box 14155‐4838 Tehran, Iran
2 Fisheries and Aquaculture Department, College
of Agriculture and Natural Resources, Persian Gulf
University, Bushehr 75169, Iran
Correspondence
Akbar Heydari, Chemistry Department, Tarbiat
Modares University, PO Box 14155‐4838, Tehran,
Iran.
KEYWORDS
Email: heydar_a@modares.ac.ir
†This article is dedicated to memory of
Mohammad Jahanara
carbodiimide, copper oxide, guanidine, heterogeneous catalysis, magnetic
nanoparticles
1
|
INTRODUCTION
Because of their presence as building blocks in natural
products and biologically active compounds, guanidines are
an important class of organic compounds.[4] Moreover, they
are used as base catalysts as well as ancillary ligands for
metal complexes.[5] Hence, the development of green syn-
thetic methods for their preparation is of high importance.
Common methods developed for the synthesis of guani-
dine scaffolds include treatment of an amine with various
activated guanidinylating reagents,[6] transamination of
guanidines,[7] and hydroamination of carbodiimides.[8] It
seems that the latter one is a more popular method, in view
of product diversity and atom efficiency, although a catalyst
is needed for convenience of this transformation. In recent
years, various catalytic systems such as metal salts, alumin-
ium alkyl complexes, transition metal imido complexes and
rare earth metal organic complexes have been employed to
promote this reaction and satisfactory results have been
obtained in terms of reaction efficiency, conditions and cata-
lyst recyclability, although the problems of isolation and
recycling of the catalyst as well as strict conditions for their
preparation accompany these methods.
Catalysis is a prominent feature in most chemical reactions so
that one of the twelve principles of green chemistry revolves
around this matter. Features such as high activity and stabil-
ity, great selectivity, efficient recovery, good recyclability
and low preparation cost restrict the choice of catalyst.
Catalysts are conventionally divided into two categories,
homogeneous and heterogeneous, each with its own advan-
tages and disadvantages: that is, high activity and selectivity
of homogeneous catalysts against easy isolation and separa-
tion of heterogeneous ones.[1] Efforts to achieve a catalyst
system including most of the features mentioned above have
involved the use of magnetic nanoparticles. Due to their
magnetic properties and large surface‐to‐volume ratio,
magnetic nanoparticles are easily separable from a reaction
mixture, using an external magnet, along with having good
activity and selectivity. These salient properties lead
magnetic nanoparticles to play an important role in catalytic
systems used in chemical reactions, either directly as catalysts
or as supports.[2] Among magnetic nanoparticles, magnetite
(Fe3O4) and maghemite (γ‐Fe2O3) are magnetic iron oxides
that are extensively used as supports for magnetic heteroge-
neous catalysts.[3] Easy production, low cost and non‐toxicity
make them ideal for this purpose.
Recently, we have reported the preparation, characteriza-
tion and catalytic evaluation of maghemite‐supported copper
oxide nanocatalyst for the N─H insertion reaction with ethyl
diazoacetate.[9] Continuing our work of designing and using
Appl Organometal Chem 2017; e3695;
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Copyright © 2017 John Wiley & Sons, Ltd.
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DOI 10.1002/aoc.3695

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ABBASI ET AL.
magnetic heterogeneous catalysts,[10] in the work reported
herein we used this magnetic nanocatalyst for the addition
of amines to carbodiimides towards the synthesis of
substituted guanidines. Facile preparation of the catalytic
system from low‐cost starting materials, easy separation from
reaction mixture using an external magnet, with the ability to
re‐use and recycle, as well as the synthesis of various
guanidines under mild reaction conditions are significant
features of this procedure.
vessel was cooled to room temperature. EtOAc (10 ml)
was added to it and placed in an ultrasonic bath for
2 min. Magnetic nanocatalyst was then adsorbed onto the
surface of the stir bar and was separated from the solution
using an external magnet. The product was obtained by
evaporation of the volatiles under reduced pressure and
the residue was purified by column chromatography, if nec-
essary. In the case of secondary amines, a slightly modified
procedure was employed, which utilized Et3N as the base.
All compounds were identified from melting point and
1
FT‐IR and H NMR spectra. The spectral data of known
compounds were compared with those reported in the
2
| EXPERIMENTAL
literature.
2.1 | Chemicals, instrumentation and analysis
All reagents were purchased from commercial suppliers and
used without further purification. All experiments were car-
ried out under air. Inductively coupled plasma (ICP) analysis
was accomplished using a VISTA‐PRO, CCD simultaneous
ICP analyser. Fourier transform infrared (FT‐IR) spectra were
obtained in the region 400–4000 cm−1 with a Nicolet IR100
3
|
RESULTS AND DISCUSSION
determine the optimum conditions,
To
N,N‐
dicyclohexylcarbodiimide and aniline were chosen as model
substrates. Solvent, temperature and amount of catalyst were
the parameters studied. The results are listed in Table 1.
Firstly, N,N‐dicyclohexylcarbodiimide (1 mmol) and aniline
(1.2 mmol) reacted in water (2 ml) as solvent in the presence
of CuO@γ‐Fe2O3 (20 mg, 19.2 mol% of CuO) at 60 °C.
After 6 h of reaction time, the corresponding guanidine was
obtained in only 20% yield (Table 1, entry 1). The effect of
some organic solvents, tetrahydrofuran (THF), n‐hexane,
CH2Cl2 and toluene, was investigated on the reaction effi-
ciency but none of them were promising (Table 1, entries
2–5). When the model reaction was conducted under
1
FT‐IR spectrometer with spectroscopic grade KBr. H NMR
spectra were recorded with a Bruker Avance (DRX
500 MHz) in pure deuterated CDCl3 solvent with
tetramethylsilane as internal standard.
2.2 | Preparation of nanostructured cuO@γ‐Fe2O3
catalyst
CuO@γ‐Fe2O3 as a magnetically separable nanostructured
catalyst was synthesized by hydrolysing cupric chloride in a
suspension of freshly prepared maghemite nanoparticles.
Maghemite nanoparticles were first synthesized according
TABLE 1 Optimization of reaction conditionsa
to
a
previously reported procedure,[11] starting from
FeCl2⋅4H2O and FeCl3⋅6H2O in 1:2 ratio as iron sources
and using ammonia for precipitation. The pH of the mixed
iron solution was adjusted to 11 by adding concentrated
ammonia and the resulting mixture was refluxed for about
1 h without using inert atmosphere. After multiple times
washing with distilled water, a 0.01 M solution of
CuCl2⋅2H2O was added to the precipitates and then the pH
of the solution was adjusted to 13 with 1 M NaOH. The
amount of copper was adjusted to yield ca 30% w/w
CuO@γ‐Fe2O3 (Cu/Fe atomic ratio of 0.29). After 24 h stir-
ring at room temperature, particles were precipitated by a
magnet, washed several times with distilled water to neutral-
ization and were dried at 110 °C for 24 h.
Entry
1
Solvent
H2O
Catalyst (mg)
Temp. (°C)
Yield (%)b
20
20
20
20
20
20
20
20
20
10
30
—
20c
60
60
60
60
60
60
80
100
r.t
20
10
20
50
20
70
94
94
10
50
90
—
—
2
THF
3
n‐Hexane
4
CH2Cl2
5
Toluene
6
Solvent‐free
Solvent‐free
Solvent‐free
Solvent‐free
Solvent‐free
Solvent‐free
Solvent‐free
Solvent‐free
7
8
9
10
11
12
13
80
80
80
80
2.3 | General procedure for synthesis of products 3a–x
Carbodiimide (1 mmol) and CuO@γ‐Fe2O3 (40 mg,
19.2 mol% of CuO, calculated by ICP analysis) were
placed in a 10 ml round‐bottomed flask and the mixture
heated for 10 min at 80 °C. Then, amine (1.2 mmol) was
added to it and allowed to stir for 6 h. Progress of the reac-
tion was followed by TLC. After completion, the reaction
aReaction conditions: N,N‐dicyclohexylcarbodiimide (1 mmol), aniline
(1.2 mmol), solvent (2 ml).
bIsolated yield.
cγ‐Fe2O3 was used as catalyst.

ABBASI ET AL.
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solvent‐free conditions, efficiency was increased, with a yield
of up to 70% (Table 1, entry 6). Fortunately, it was observed
that increasing the temperature to 80 °C enhanced the yield
up to 94%, whereas reducing it to room temperature led to
a significant reduction in the efficiency of the reaction. More-
over, increasing the temperature to 100 °C did not enhance
the yield (Table 1, entries 7–9).
By reducing the amount of catalyst, the yield was
decreased; on increasing the amount, the yield did not change
(Table 1, entries 10 and 11). In the absence of catalyst or in
the presence of γ‐Fe2O3 nanoparticles, no product was
formed, indicating that CuO plays an important role in this
transformation (Table 1, entries 12 and 13).
After establishment of the optimized reaction conditions,
the scope of starting materials was investigated. As shown in
Figure 1, various derivatives of aniline bearing electron‐
donating and electron‐withdrawing substituents at ortho,
meta and para positions reacted
with
N,N‐
dicyclohexylcarbodiimide, and the corresponding guanidines
were obtained in high yields. The results show that the reac-
tion was not sensitive to the electronic nature and ring posi-
tion of the substrates. Also, 1‐naphthylamine, a polycyclic
amine, was well coupled with N,N‐dicyclohexylcarbodiimide
and the corresponding guanidine was formed in good yield
(product 3p). When secondary amines such as morpholine
and pyrrolidine, aliphatic cyclic amines, were subjected to
the reaction conditions with N,N‐dicyclohexylcarbodiimide,
Et3N (1.5 equiv.) as base was added to the reaction mixture
to afford the corresponding guanidines (products 3q and
3r). Also, N,N‐diisopropylcarbodiimide was a good reaction
partner, and the corresponding products were obtained in
good yields, when reacted with some aniline derivatives
(products 3r–3x).
The ability of the catalyst to be re‐used and recycled was
evaluated in the model reaction. For this purpose, after com-
pletion of the first run of the reaction, the catalyst was
removed from the reaction mixture by simple decantation
using an external magnet, washed with methanol, dried at
ambient temperature and reused for the next run. The catalyst
was recycled up to four times without any significant loss of
its catalytic activity (Table 2).
FIGURE 1 Scope of starting materials. Reaction conditions: carbodiimide
(1 mmol), aniline (1.2 mmol), 80 °C, 6 h. The yields refer to the isolated
pure products. In the case of secondary amines, Et3N (1.5 equiv.) as base was
added to the reaction mixture
TABLE 2 Catalyst recyclability in model reactiona
Run
Yield of product 3a (%)
1
2
3
4
94
94
93
92
A hot filtration test was performed to prove the hetero-
geneous nature of the catalyst. For this purpose, the cata-
lyst was allowed to stir under the reaction conditions.
After 6 h, EtOAc (10 ml) was added and the catalyst was
aReaction conditions were similar to those shown in Figure 1.
TABLE 3 Comparison of performance of our catalyst with that of some previously reported catalysts
Entry
Catalyst
Yttrium complex
Conditions (temp./ solvent/ time)
Yield (%)
Ref.
1
2
3
4
5
6
7
8
9
80 °C, C6D6, 1 h
99
91
93
74
93
95
96
97
96
[8p]
[12]
Samarium amido complex
Neodymium complex
[Ca{N(SiMe3)2}2(THF)2]
AlClMe2
60 °C, THF, 12 h
60 °C, solvent‐free, 24 h
80 °C, hexane, 1 h
r.t., toluene, 18 h
[13]
[14]
[8q]
[(Me3Si)2N]3Yb(í‐Cl)Li(THF)3
Cy[NC═CH2)‐2‐(C5H4N)AlMe2]2
Nano ZnO
60 °C, THF, 4 h
[8h]
r.t., toluene, 1 h
[15]
80 °C, toluene, 8 h
80 °C, solvent‐free, 6 h
[8s]
CuO@γ‐Fe2O3
This work

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ABBASI ET AL.
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Scheme 1.
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4
| CONCLUSIONS
We have developed the use of magnetic nanoparticles as
support in the catalytic synthesis of guanidines via
hydroamination reaction of carbodiimides. CuO stabilized
on maghemite nanoparticles was used as an efficient and
magnetically separable as well as reusable catalyst for this
goal. Various derivatives of guanidines were synthesized
under mild and clean reaction conditions in high yields.
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ACKNOWLEDGMENTS
We acknowledge Tarbiat Modares University for partial
support of this work.
[11] L. M'amani, A. Heydari, M. Sheykhan, Appl. Catal. A 2010, 384, 122.

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