N-arylation of amines: C-N coupling of amines with arylboronic acids using Fe3O4 magnetic nanoparticles-supported EDTA-Cu(ii) complex in water

Article abstract of DOI:10.1039/c4ra08137d

Fe₃O₄ magnetic nanoparticles-supported EDTA-copper(ii) complex (Fe₃O₄-EDTA-Cu(ii)) has been prepared and characterized by TEM, SEM, XRD, VSM, TGA, and FT-IR spectrometers. The catalyst was applied for the C-N coupling of arylboronic acids with amines for the preparation of N-aryl compounds. Recovery tests confirm that the catalyst can be easily recovered and reused up to eight times without significant loss of its catalytic activity.

Full text of DOI:10.1039/c4ra08137d

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N-arylation of amines: C–N coupling of amines
with arylboronic acids using Fe O magnetic
3
4
Cite this: RSC Adv., 2014, 4, 49273
nanoparticles-supported EDTA–Cu(II) complex in
water†
a
a
a
b
Ramin Mostafalu, Babak Kaboudin,* Foad Kazemi and Tsutomu Yokomatsu
3 4 3 4
Fe O magnetic nanoparticles-supported EDTA–copper(II) complex (Fe O -EDTA–Cu(II)) has been
Received 5th August 2014
Accepted 16th September 2014
prepared and characterized by TEM, SEM, XRD, VSM, TGA, and FT-IR spectrometers. The catalyst was
applied for the C–N coupling of arylboronic acids with amines for the preparation of N-aryl compounds.
Recovery tests confirm that the catalyst can be easily recovered and reused up to eight times without
significant loss of its catalytic activity.
DOI: 10.1039/c4ra08137d
www.rsc.org/advances
indole alkaloids with an arylamine moiety have been isolated
from microorganisms (Streptomyces and Streptoverticillium)
Introduction
In the past several years, ‘Green Chemistry’ has become one of and blue-green alga (Lyngbya species) and used as strong
the hottest terms in chemistry. If we relate the coupling reac- tumour promoters. Benzolactam V8, an articially designed
1
tions and the 12 principles of Green Chemistry, the use of a cyclic dipeptide derived from an arylamine, is a protein
9
green solvent and non-toxic catalyst are the most obvious kinase C inhibitor.
aspects we can consider. Concerning the green solvent, water is
An essential methodology for the preparation of aromatic
10
the most obvious candidate, because it is the cheapest and amines is based on the C–N cross-coupling reaction. Ullmann
2
11
safest solvent and is non-toxic. Regarding the green catalyst, and Goldberg for the rst time used copper for the C–N cross-
superparamagnetic nanoparticles (SMNPs) have attracted much coupling reaction. However, the synthetic scope of their reac-
attention because of their low toxicity, large ratio of surface area tion is strongly limited by the high reaction temperatures
ꢀ
to volume, superparamagnetic behaviour, convenient surface required (200 C) and the sensitivity of the substituted aryl
modication, and their easy separation from a reaction halide to the harsh reaction conditions applied. Since copper
3
mixture. Besides the easy separation, the small size of the can easily access Cu(0), Cu(I), Cu(II), and Cu(III) oxidation states,
magnetic nanoparticles (typically <50 nm) make them highly allowing it to act through one-electron or two-electron
12
dispersible in solvents. Utilizing these advantages of magnetic processes, a number of research groups have examined the
nanoparticles over other supporting materials, various catalysts utility of a copper catalyst in the synthetic method for C–N
4
and ligands have been immobilized on these particles.
Aromatic amines have attracted considerable attention
because of their signicant biological activities, and they are
used in a range of applications, from natural products to
coupling reactions.
5
–7
medicinal agents. Several synthetic and naturally occurring
arylamines are known to act as scaffolds and show diverse
biological activities (Scheme 1). For example, folic acid
(
vitamin B ) is well known to be essential for numerous bodily
9
8
functions, teleocidins [ex. teleocidin B-1], olivoretins [ex.
olivoretin A], and lyngbyatoxins [ex. lyngbyatoxin B], and
a
Department of Chemistry, Institute for Advanced Studies in Basic Sciences, Gava Zang,
Zanjan, Iran. E-mail: kaboudin@iasbs.ac.ir; Fax: +98 241 4214949; Tel: +98 241
4
153220
b
School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 14321-1
Horinouchi, Hachioji, Tokyo 192-0392, Japan
†
Electronic supplementary information (ESI) available. See DOI:
0.1039/c4ra08137d
1
Scheme 1 Structures of biologically active aromatic amines.
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Breakthroughs in copper-catalysed cross-coupling reactions
13
14
15
have been driven independently by Lam, Chan, and Evans
in 1998, who demonstrated that C–N bond formation could be
rendered by the use of arylboronic acids as arylating agents
instead of aryl halides under milder conditions in the presence
of more than an equimolar amount of Cu(OAc)
2
. Though
dramatic progress has been made with regards to N-arylation
16
using arylboronic acids, little progress has been made to
develop green copper catalysts for this reaction. Recently
1
7,18
though, copper catalysts supported on the resin,
chlor-
19
20
21
omethyl polystyrene, cellulose, and uorapatite have all
been used as recyclable catalysts in heterogeneous systems to
promote the copper-catalyzed C–N coupling reaction. However,
despite these important contributions, more work still needs to
be done to identify new supports and hence the search for a
highly effective catalyst system is still challenging and
interesting.
3 4
Fig. 1 FT-IR spectrum of the Fe O -EDTA–Cu(II) nanoparticles.
be concluded that EDTA was supported successfully on the
surface of the Fe nanoparticles.
Recently, we used magnetic nanoparticles-supported Cu(II)-
b-cyclodextrin complex for the synthesis of symmetrical biaryls
3 4
O
The presence of EDTA on the surface of the magnetic
nanoparticles was proved by thermogravimetric analysis (TGA)
22
and 1,2,3-triazoles. Herein, the aim of this work is to prepare
and characterize a magnetically separable copper(II)–EDTA
ꢀ
ꢁ1
at a heating rate of 10 C min in the air over a temperature
complex (Fe
3
O
4
-EDTA–Cu(II)), and to test its application as a
ꢀ
range of 25–600 C (Fig. 2). The TGA curve of the Fe
3
O
4
-EDTA–

ltration-free and recyclable heterogeneous catalyst for the
ꢀ
Cu(II) nanoparticles shows a weight loss of 1.93% below 160 C,
which is due to the loss of the adsorbed water in the sample.
synthesis of N-arylamines through the coupling reaction of aryl/
alkyl amines with arylboronic acids in water under aerobic
conditions.
ꢀ
The mass loss in the range of 200–400 C is attributed to the
thermal decomposition of EDTA. Accordingly, it is revealed that
EDTA indeed is attached onto the surface of the Fe
particles. The decomposition of EDTA on the Fe -EDTA–Cu(II)
nanoparticles at a lower temperature than pure EDTA shows the
3 4
O nano-
3 4
O
Results and discussion
EDTA-functionalized magnetic nanoparticles (Fe O -EDTA–
3
4
NMP) were prepared by the method described by Bahadur
23
et al. with some modications. The Fe
were treated with aqueous CuSO solution at room temperature
for 1 h to provide Fe -EDTA–Cu(II) nanoparticles (Scheme 2).
3 4
O -EDTA nanoparticles
4
3 4
O
The structure of the prepared catalyst was characterized by
various spectroscopic analyses, including FT-IR, TGA, SEM,
TEM, VSM, and AAS.
ꢁ1
Fig. 1 shows the FT-IR spectra (in the 400–4000 cm wave-
number range) of the magnetic Fe O -EDTA–Cu(II) nano-
3
4
particles. It shows that the intense adsorption band of the Fe–O
ꢁ1
bonds in the tetrahedral sites is 585.9 cm . The broad band at
ꢁ
1
3
000–3500 cm is due to the hydroxy stretching vibration. The
ꢁ
1
presence of peaks at 2917, 1626, and 1049 cm are ascribed to
the C–H stretching, C]O stretching, and the aliphatic C–N
stretching vibration, respectively, indicating the existence of
EDTA. The assignments are concordant with those of that Yang
24
25
et al. and Liu et al. reported on Fe O -EDTA. Therefore, it can
3
4
Scheme 2 Possible structure and preparation method of the Fe
supported EDTA–Cu(II) nanoparticles.
3
O
4
-
3 4
Fig. 2 TGA curves of EDTA (a), and the Fe O -EDTA–Cu(II) nano-
particles (b).
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3 4
good interaction of EDTA with the Fe O nanoparticles. In
addition, TG analysis indicated that the prepared Fe O -EDTA–
3
4
Cu(II) nanoparticles have high thermal stability and negligible
ꢀ
EDTA leaching up to about 200 C.
Scanning and transmission electron microscope (SEM and
TEM) images were used to obtain direct information about the
structure and morphology of the Fe
particles. The SEM image revealed that the Fe
3
O
4
-EDTA–Cu(II) nano-
-EDTA–Cu(II)
3 4
O
particles are nearly spherical in shape and tend to agglomerate
into larger aggregates (Fig. 3). TEM images of the Fe O and
3
4
Fe O -EDTA–Cu(II) nanoparticles are shown in Fig. 4. The TEM
3
4
image of Fe O particles clearly shows the formation of roughly
3
4
spherical Fe
nm. The TEM image of the Fe
shows that the presence of EDTA during the production of the
Fe nanoparticles leads to a decrease in the size of the
3
O
4
nanoparticles, with a mean size range of 10–20
3 4
O
-EDTA–Cu(II) nanoparticles
Fig. 5 VSM curves of Fe
O
3 4
(a) and Fe O
3 4
-EDTA–Cu(II) nanoparticles.
3 4
O
nanoparticles (ꢂ12 nm) and that the synthesized nanoparticles
are nearly monodisperse. This reveals that EDTA plays a
surfactant role to reduce the nanoparticle size. No detectable
layer of EDTA can be observed on the TEM of the Fe O -EDTA–
Cu(II) nanoparticles, which is due to the small amount of EDTA
attached on the surface (ꢂ3 wt% from the TG analysis).
It is known that magnetic particles with sizes less than about
Fig. 5 shows the VSM curves of the Fe
Cu(II) particles (b), respectively in an applied magnetic eld of
0 000 Oe at 298 K measured by the Meghnatis Daghigh Kavir
Company (Iran). The hysteresis loops of the Fe -EDTA–Cu(II)
3 4 3 4
O (a), and Fe O -EDTA–
3
4
1
3 4
O
nanoparticles show superparamagnetic behaviour with their re-
dispersion stability in solution without aggregation. The satu-
3
0 nm with zero coercivity and zero remanence exhibit super-
ꢁ1
ration magnetization of 16.3 emu g is sufficient for magnetic
26,27
paramagnetism.
3 4
The magnetic properties of the Fe O and
separation of the magnetic nanoparticles with a conventional
Fe O -EDTA–Cu(II) nanoparticles were investigated using a
28
3
4
permanent magnet. The saturation magnetizations of the
vibrating sample magnetometer (VSM) at room temperature.
magnetic Fe
3
O
4
and Fe
3
ꢁ
O
4
-EDTA–Cu(II) nanoparticles were
1
ꢁ1
found to be 65.58 emu g and 58.75 emu g , respectively.
These values are high enough to separate magnetic Fe
3 4
O and
Fe O -EDTA–Cu(II) nanoparticles from aqueous solution
3
4
(Fig. 6).
Fig. 7 shows the XRD patterns of Fe O and Fe O -EDTA–
3
4
3
4
Cu(II) nanoparticles. The XRD patterns of Fe
and Fe
formation of a single phase magnetite with lattice constant, a ¼
3
O
4
(Fig. 7a)
3 4
O -EDTA–Cu(II) nanoparticles (Fig. 7b) indicate the
˚
˚
8
.374 A (JCPDS Card no. 88-0315, a ¼ 8.375 A). Six characteristic
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
peaks at 2q ¼ 30.3 , 35.7 , 43.4 , 53.9 , 57.8 , and 63.1 were
simultaneously found in all the XRD patterns of Fe O and
3
4
Fe O -EDTA–Cu(II) nanoparticles, which related to the (220),
3
4
(
311), (400), (422), (511), and (440) phases of Fe O , respectively.
3 4
3 4
This disclosed that the resultant nanoparticles were pure Fe O
3 4
Fig. 3 SEM image of the Fe O -EDTA–Cu(II) nanoparticles.
Fig. 4 TEM images of the Fe
O
3 4
3
(a), and Fe O
4
-EDTA–Cu(II) nano- Fig. 6 Digital photographs showing the magnetic separation of the
particles (b).
as-prepared magnetic particles.
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aniline (1a) with phenylboronic acid (2a) was initially chosen as
the model reaction. The results are shown in Table 1.
No reaction occurred in the absence of the copper catalyst
(entry 1). A control experiment also showed that both reactions
with Fe and Fe -EDTA nanoparticles did not occur (entries
3
O
4
3 4
O
Table
3 4
2 Fe O -EDTA–Cu(II) nanoparticles catalyzed C–N cross-
coupling reaction of amines with arylboronic acids
a
Entry Amine
Boronic acid Product3
t (h)
Yield (%)
3 4 3 4
Fig. 7 XRD pattern of the Fe O (a), and Fe O -EDTA–Cu(II) nano-
particles (b).
1
2
C
6
H
5
–
2
2
95
95
p-MeC
6
H
4
–
with a spinel cubic structure, and that the supporting of the
surface of Fe nanoparticles with EDTA–Cu(II) complex did
not result in the phase change of Fe . The XRD results also
demonstrate the high crystallinity of prepared magnetic
nanoparticles. The crystal size of the magnetic Fe and
Fe -EDTA–Cu(II) nanoparticles were determined from the
XRD pattern using Scherrer's equation. The values provided
for the magnetic Fe O and Fe O -EDTA–Cu(II) nanoparticles by
3
O
4
3
4
o-MeC
6
H
4
–
2
2
93
99
3 4
O
p-MeOC
6 4
H –
3 4
O
3
O
4
5
o-MeOC H –
6
4
2
89
2
9
3
4
3
4
6
7
m-HOC H –
2
1
96
96
6
4
the above equation were 28 nm and 14 nm, respectively. The
amount of copper (1%) needed for the Fe -EDTA–Cu(II)
nanoparticles was determined by atomic absorption analysis
AAS).
3 4
The catalytic behaviour of the prepared Fe O -EDTA–Cu(II)
6
C H
5
–
3 4
O
(
8
9
C
6
H
H
5
5
–
–
1
2
93
96
C
6
nanoparticles was studies in the cross-coupling reaction of
amines with arylboronic acids in water as a green solvent. The
efficiency of the cross-coupling of amines with arylboronic acids
in water may be hampered by the side reactions of boronic acids
themselves, such as the homo-coupling reaction, or the hydro- 11
lytic deboronation with water. Therefore, the cross-coupling of
1
0
n-Pr–
1 : 45 43
1 : 30 83
n-Bu–
1
1
1
2
3
4
n-Hex–
n-Oct–
1
1
80
97
Table 1 Optimization of the cross-coupling reaction of aniline with
phenylboronic acid
6
C H
11
–
1 : 30 85
15
Allyl–
4
35
1
1
6
7
HO–CH
CH
2 2
–
2
1
96
96
ꢀ
a
Entry Catalyst
Temp ( C) t (h) Yield (%)
Ts–
1
2
3
4
5
6
7
8
None
r.t.
r.t.
r.t.
r.t.
r.t.
12
12
12
5
8
5
N.R
N.R
N.R
85
95
86
Fe
Fe
3
O
O
4
(100 mg)
-EDTA (100 mg)
b
1
8
C
6
H
5
CO–
1 : 30
—
3
4
EDTA–Cu(II)(10 mol%)
Fe
3
Fe
3
Fe
3
Fe
3
O
O
O
O
4
4
4
4
-EDTA–Cu(II) (5 mol%)
-EDTA–Cu(II) (10 mol%) r.t.
-EDTA–Cu(II) (15 mol%) r.t.
b
1
9
i-Pr
2
—
3
2
71
95
-EDTA–Cu(II) (5 mol%)
50
a
GC yields.
a
b
Isolated yields. Only phenol was detected.
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Table 3 Comparison of activity for different catalytic systems in the N-phenylation of phenylboronic acid with aniline
Entry
Catalyst
Reaction conditions
t (h)
Yield (%)
Reference
1
2
3
4
5
Wang resin supported
Resin-supported
Cu-FAP
Cat 1.5 equiv., CH
Cat 10 mol%, CH
Cat 100 mg, MeOH, r.t.
2
Cl
2
, NEt
, 1 atm O
3
, r.t.
, r.t.
24
24
3
12
2
66
32
90
86
95
18
17
21
19
2
Cl
2
2
ꢀ
Polymer supported
Cat 2.6 mol%, DMSO, 140 C, K
2
CO
3
ꢀ
Fe
3
O
4
-EDTA–Cu(II)
5 mol%, H
2
O, 50 C
This study
2
and 3). When the reaction was carried out with 10 mol% of the
The coupling reaction of ethanol amine and 3-aminophenol
EDTA–Cu(II) complex and the Fe -EDTA–Cu(II) catalyst at with phenylboronic acid gave the corresponding N-arylamines
3 4
O
room temperature (entries 4 and 6) in water for 5 h, biphenyl- in a high yield, without any C–O cross-coupling product
amine (3a) was obtained in 85% and 86% yields, as expected. (Table 2, entries 6 and 16).
Aer evaluation of the catalytic amounts, the reaction time, and
A comparison with other supported copper catalytic systems
the reaction temperature (entries 5–8), the best result was in the cross-coupling reaction of aniline with phenylboronic
ꢀ
obtained from the conditions at 50 C for 2 h using 5 mol% of acids demonstrated that our present catalytic system exhibited
the catalyst in air (entry 8).
To survey the generality of this C–N coupling reaction, the (Table 3).
scope and limitations of this protocol were examined using a Control experiments using CuCl
a higher conversion and yield in green and milder conditions
2 4
, CuSO , and CuI as a
series of primary aromatic and aliphatic amines, along with catalyst also revealed the yields of N-arylation product in the
amide derivatives, under optimized reaction conditions (Table 2). coupling reaction of aniline with 4-methylephenylboronic acid
ꢀ
In the cross-coupling of aniline derivatives containing various in water at 50 C were very low and a homo-coupling product
0
0
substituents with phenylboronic acid, the corresponding N-phe- (4,4 -dimethyl-1,1 -biphenyl) was detected as a by-product
nylated products were obtained in excellent to good yields (Table 4).
(Table 2, entries 1–6). para-Substituted anilines were found to be
For a supported catalyst, the lifetime and recycling of the
better substrates than ortho-substituted analogues (Table 2, catalyst are important issues to be resolved. To address these
entries 2, 4 vs. 3, 5). These results show that the coupling reaction issues, we turned our attention to the reusability of
was slightly affected by steric congestion around the amino Fe O -EDTA–Cu(II) nanoparticles in the N-arylation reaction of
3 4
functionality of the aniline derivatives. No signicant steric effect aniline with 4-methylephenylboronic acid under the same
was observed with the reaction of 2-methylphenylboronic acid reaction conditions. Aer carrying out the reaction, the catalyst
(entry 7 vs. 8). N-Dealkylation has been reported to be a poten- was collected by a magnet and washed with deionized water and
tially serious side reaction in the N-arylation of aliphatic amines acetone and reused without further purication. From the
30
using arylboronic acids. The cross-coupling of primary aliphatic results, it was shown that the catalyst retained its high catalytic
amines produced the corresponding N-arylamines in good to activity over eight repeating cycles (Fig. 8). To conrm whether
excellent yields (Table 2, entries 10–16) and no trace of the dia- the un-leached copper catalyst in the solution promoted the
rylated, alkyldiphenylamine or N-dealkylated (aniline or diphe- cross-coupling reaction, the following experiment was con-
nylamine) by-products were detected. Aliphatic amines bearing ducted. Aer suspending the Fe O -EDTA–Cu(II) nanoparticles
3
4
olen moieties and cyclohexylamine as a branched amine also in water overnight and then ltering off the catalyst, the cross-
gave the corresponding amine products in good yield, while the coupling reaction of aniline and 4-methylephenylboronic acid
reaction with isopropylamine gave only phenol as a product
(Table 2, entries 14, 15, 19). Moreover, the cross-coupling of tol-
uenesulfonamide with phenylboronic acid was also accom-
plished with a high yield under the same conditions (Table 2,
entry 17). We then applied this method to amides, including
benzamide, but the cross-coupling reaction failed and only the
phenol product was detected.
Table 4 Comparison of different copper salts with our catalyst used in
the N-arylation reaction of aniline with 4-methylephenylboronic acid
Entry
Catalyst
CuI
Yield (%)
1
2
3
4
10
25
16
98
CuCl
CuSO
Fe
2
4
3
O
4
-EDTA–Cu(II)
3 4
Fig. 8 Recycling of the Fe O -EDTA–Cu(II) catalyst.
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Experimental
General method
All melting points were taken on a Yanagimoto and Buchi 510
apparatus and are uncorrected. Mass spectra were recorded on a
VG Auto Spec. using electron impact ionization (EI) techniques.
NMR spectra were obtained on a Bruker Avance 400 NMR
1
13
Spectrometer ( H NMR: 400 MHz, C NMR: 100 MHz). Gas
chromatography was performed on a Varian CP 3800 chro-
matograph. Analytical TLC was carried out with Merck plates
pre-coated with silica gel 60 F254 (0.25 mm thick). Column
chromatography was performed with a FLUKA Silica gel 60 (70–
230 mesh) in common glass columns. Copper sulfate was
recrystallized before use. Arylboronic acids, amines, and Na
4
-
EDTA were used as-received. All solvents were distilled before
use.
3 4
Scheme 3 Possible mechanism for N-arylation by the Fe O -EDTA–
Cu(II) catalyst.
Preparation of Fe
was performed in the ltrate. Aer 12 h, no conversion was EDTA-functionalized Fe
detected following gas chromatography analysis (GC). An precipitation method, followed by the in situ graing of EDTA.
3
O
4
-EDTA nanoparticles
O
3 4
were prepared by the co-
atomic absorption analysis also showed that there was no Briey, FeCl
leaching of the copper ion from the catalyst aer ten cycles. red to dissolve in distilled water (40 mL) at 90 C under a N
3
$6H
2
O (2.36 g) and FeCl
2
$4H
2
O (0.86 g) were stir-
ꢀ
2
That there was no leaching of copper aer ten cycles showed atmosphere. Subsequently, 20 mL ammonia solution (25%) was
that this method can be used as a powerful method in phar- added dropwise to the reaction mixture under vigorous stirring.
maceutical applications.
An aqueous solution containing Na EDTA (5 g in 10 mL water)
4
A possible mechanism for N-arylation is outlined in was added and the reaction mixture was stirred for 60 min.
Scheme 3. We believe that a copper(I)/copper(III) catalytic system Finally, the temperature was cooled to room temperature and
is in place, because a reductive elimination of a copper(II) the prepared nanoparticles were collected by a permanent
intermediate to copper(0) would dissociate the copper from the magnet and washed with distilled water repeatedly, and nally
catalyst, rendering it non-recyclable. The mechanism is based dried for 24 h at room temperature in a vacuum oven.
31
32
33
on those proposed by Collman, Lam, and Demir. Initially,
coordination of the amine to Fe -EDTA–Cu(II) and oxidation
3 4
O
Preparation of Fe O -EDTA–Cu(II) nanoparticles
3
4
by oxygen gives a copper(III) intermediate 4. The trans-
metalation of 4 with the arylboronic acid gives 5, which
undergoes reductive elimination to give product 7, and also
provides the copper(I)-bound catalyst 6. Coordination of the
amine and oxidation by oxygen leads to regeneration of the
copper(III) intermediate 4.
Fe O -EDTA nanoparticles (1 g) were dispersed in distilled water
3
4
(
20 mL) containing CuSO $5H O (100 mg) and the mixture was
4 2
stirred at room temperature. Aer 1 h, the nanoparticles were
collected using an external magnet and washed repeatedly with
distilled water and nally dried at room temperature in a
vacuum oven.
General procedure for the C–N coupling of arylboronic acid
with amines
Conclusion
In conclusion, we developed a rapid, efficient, and convenient
protocol for the preparation of N-arylated amines by the
coupling of arylboronic acids with amines in the presence of
Fe O -EDTA–Cu(II) catalyst. Our inexpensive catalytic system
To a mixture of Fe O -EDTA–Cu(II) (0.05 mmol) and amine
3
4
(
3 mmol) in distilled water (2 mL), arylboronic acid (1 mmol)
ꢀ
was added and the resultant mixture was stirred at 50 C for 1–4
h. Then, the reaction mixture was diluted with water (20 mL),
extracted with dichloromethane (2 ꢃ 20), and the combined
3
4
showed a great functional group tolerance in the presence of
multiple potentially reactive groups at moderate temperature.
The short reaction time and simple reaction conditions render
this method particularly attractive for the efficient construction
of library synthesis and for the preparation of biologically
and medicinally interesting molecules. Furthermore, the
Fe O -EDTA–Cu(II) catalyst can be collected easily by a magnet
2 4
extracts were dried with Na SO . The product was puried
immediately by ash chromatography (silica gel 60; particle size
30–400 mesh; n-hexane/EtOAc) to afford arylamines 3a–n.
2
3 4
Recyclability of Fe O -EDTA–Cu(II) catalyst
3
4
and reused, with the reusability of the prepared nanocatalyst Aer carrying out the reaction, the catalyst was collected by a
being successfully tested eight times with only a very slight loss magnet and washed with deionized water and acetone and
of catalytic activity.
reused directly without further purication.
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3 P. Y. S. Lam, C. G. Clark, S. Saubern, J. Adams, M. P. Winters,
D. M. T. Chan and A. Combs, Tetrahedron Lett., 1998, 39,
2941–2944.
References
1
(a) P. Anastas and J. Warner, Green Chemistry: Theory and
Practice, Oxford University Press, New York, 1998; (b) 14 D. M. T. Chan, K. L. Monaco, R. P. Wang and M. P. Winters,
P. Anastas and N. Eghbali, Chem. Soc. Rev., 2012, 39, 301–
12.
M. O. Simon and C. J. Li, Chem. Soc. Rev., 2012, 41, 1415–
427.
(a) A. H. Lu, E. L. Salabas and S. Ferdi, Angew. Chem., Int. Ed.,
Tetrahedron Lett., 1998, 39, 2933–2936.
15 D. A. Evans, J. L. Katz and T. R. West, Tetrahedron Lett., 1998,
39, 2937–2940.
3
2
3
1
16 For example:(a) B. Kaboudin, Y. Abedi and T. Yokomatsu,
Eur. J. Org. Chem., 2011, 6656–6662; (b) M. Nobis and
B. Driessen-Holscher, Angew. Chem., Int. Ed., 2001, 40,
3983–3985; (c) D. Hollmann, S. Bahn, A. Tillack and
M. Beller, Angew. Chem., Int. Ed., 2007, 46, 8291–8294; (d)
G. C. Kobeci and J. M. J. Williams, Chem. Commun., 2004,
1072–1073; (e) M. Larrosa, C. Guerrero, R. Rodriguez and
J. Cruces, Synthesis, 2010, 2101–2105.
2
8
007, 46, 1222–1244; (b) W. Schaertl, Nanoscale, 2010, 2, 829–
43; (c) S. Sankaranarayanapillai, S. Volker and R. T. Werner,
Angew. Chem., Int. Ed., 2010, 49, 3428–3459; (d) S. Laurent,
D. Forge, M. Port, A. Roch, C. Robic, L. V. Elst and
R. N. Muller, Chem. Rev., 2008, 108, 2064–2110.
V. Polshettiwar, R. Luque, A. Fihri, H. Zhu, M. Bouhrara and
J. M. Basset, Chem. Rev., 2011, 111, 3036–3075.
4
5
17 A. Biffis, F. Filippi, G. Palma, S. Lora, C. Macc `a a and
B. Corain, J. Mol. Catal. A: Chem., 2003, 203, 213–220.
M. L. Quan, P. Y. S. Lam, Q. Han, D. J. P. Pinto, M. Y. He,
R. Li, C. D. Ellis, C. G. Clark, C. A. Teleha, J. H. Sun, 18 C. H. G. Chiang and T. Olsson, Org. Lett., 2004, 6, 3079–3082.
R. S. Alexander, S. Bai, J. M. Luettgen, R. M. Knabb, 19 S. M. Islam, S. Mondal, P. Mondal, A. S. Roy, K. Tuhina,
P. C. Wong and P. R. Wexler, J. Med. Chem., 2005, 48,
729–1744.
N. Salam and M. Mobarak, J. Organomet. Chem., 2012, 696,
4264–4274.
1
6
7
8
B. K. Singh, V. S. Christian, R. J. A. Davy, S. P. Virinder and 20 K. R. Reddy, N. S. Kumar, B. Sreedhar and M. L. Kantam, J.
V. V. E. Erik, Tetrahedron Lett., 2009, 50, 15–18.
Mol. Catal. A: Chem., 2006, 252, 136–150.
N. Yamazaki, I. Washio, Y. Shibasaki and M. M. Ueda, Org. 21 M. L. Kantam, G. T. Venkanna, C. Sridhar, B. Sreedhar and
Lett., 2006, 8, 2321–2324.
M. B. Choudary, J. Org. Chem., 2006, 71, 9522–9524.
(a) S. Gilbody, S. Lewis and T. Lightfoot, Am. J. Epidemiol., 22 B. Kaboudin, R. Mostafalu and T. Yokomatsu, Green Chem.,
007, 165, 1–13; (b) M. J. Taylor, S. M. Carney,
2013, 15, 2266–2274.
G. M. Goodwin and J. R. Geddes, J. Psychopharmacol., 2004, 23 S. Singh, K. C. Barick and D. Bahadur, AIP Conf. Proc., 2013,
2
18, 251–256; (c) C. Keshava, N. Keshava, W. Z. Whong,
1512, 440–441.
J. Nath and T. M. Ong, Mutat. Res., 1998, 397, 221–228.
(a) M. Takashima and H. Sakai, Bull. Agric. Chem. Soc. Jpn.,
24 J. Yang, Q. Zeng, L. Peng, M. Lei, H. Song, B. Tie and J. Gu, J.
Environ. Sci., 2013, 25, 413–418.
9
1
960, 24, 647–651; (b) M. Takashima and H. Sakai, Bull. 25 Y. Liu, M. Chen and Y. Hao, Chem. Eng. J., 2013, 218, 46–54.
Agric. Chem. Soc. Jpn., 1960, 24, 652–655; (c) H. Nakata, 26 B. Li, D. Jia, Y. Zhou, Q. Hu and W. Cai, J. Magn. Magn.
H. Harada and Y. Hirata, Tetrahedron Lett., 1966, 7, 2515–
Mater., 2006, 306, 223–227.
522; (d) Y. Endo, K. Shudo, A. Itai, M. Hasegawa and 27 S. M. O'Brien, O. Thomas and P. Dunnill, J. Biotechnol., 1996,
2
S.-I. Sakai, Tetrahedron, 1986, 42, 5905–5924; (e)
50, 13–26.
J. H. Cardellina, F.-J. Marner and R. E. Moore, Science, 28 Z. Y. Ma, Y. P. Guan and H. Z. Liu, J. Polym. Sci., Part A: Polym.
979, 204, 193–195; (f) Y. Hitotsuyanagi, K. Yamaguchi,
Chem., 2005, 43, 3433–3439.
K. Ogata, N. Aimi, S.-I. Sakai, Y. Koyama, Y. Endo, 29 A. Z. M. Badruddoza, G. S. S. Hazel, K. Hidajat and
1
K. Shudo, A. Itai and Y. Iitaka, Chem. Pharm. Bull., 1984,
2, 3774–3778.
0 F. Ullmann, Ber. Dtsch. Chem. Ges., 1903, 36, 2389–2391.
1 I. Goldberg, Ber. Dtsch. Chem. Ges., 1906, 39, 1691–1692.
2 (a) E. A. Scott, R. R. Walvoord, P. S. Rosaura and C. K. Marisa,
M. S. Uddin, Colloids Surf., A, 2010, 367, 85–95.
30 Y. Liu, M. Chen and Y. Hao, Chem. Eng. J., 2013, 218, 46–54.
31 (a) J. P. Collman and M. Zhong, Org. Lett., 2000, 2, 1233–
1236; (b) J. P. Collman, M. Zhong, L. Zeng and S. Costanzo,
J. Org. Chem., 2001, 66, 1528–1531.
3
1
1
1
Chem. Rev., 2013, 113, 6234–6458; (b) J. Bariwalab and 32 J. C. Antilla and S. L. Buchwald, Org. Lett., 2001, 3, 2077–
E. V. Eycken, Chem. Soc. Rev., 2013, 42, 9283–9303; (c)
2079.
G. Evano, N. Blanchard and M. Toumi, Chem. Rev., 2008, 33 P. Y. S. Lam, G. Vincent, C. G. Clark, S. Deudon and
08, 3054–3131.
P. K. Jadhav, Tetrahedron Lett., 2001, 42, 3415–3418.
1
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