Magnetic silica supported copper: A modular approach to aqueous Ullmann-type amination of aryl halides

Article abstract of DOI:10.1039/c3ra45606d

One-pot synthesis of a magnetic silica supported copper catalyst has been described via in situ generated magnetic silica (Fe₃O ₄@SiO₂); the catalyst can be used for the efficacious amination of aryl halides in aqueous medium under microwave irradiation.

Full text of DOI:10.1039/c3ra45606d

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DOI: 10.1039/C3RA45606D
Magnetic Silica Supported Copper: A Modular Approach to
Aqueous Ullmann-type Amination of Aryl Halides
R. B. Nasir Baig and Rajender S. Varma*
One-pot synthesis of magnetic silica supported copper catalyst has been described via in situ
generated magnetic silica (Fe3O4@ SiO2); the catalyst can be used for the efficacious amination
of aryl halides in aqueous medium under microwave irradiation.
Cu
Cu
Cu
Cu
Cu
Cu
Cu
Cu
Br
N
Fe3O4@SiO2Cu- catalyst
+
O2N
N
K2CO3, MW, H2O
O2N
H

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DOI: 10.1039/C3RA45606D
Journal Name
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ARTICLE
Magnetic Silica Supported Copper: A Modular
Approach to Aqueous Ullmann-type Amination of Aryl
Halides
Cite this: DOI: 10.1039/x0xx00000x
R. B. Nasir Baig and Rajender S. Varma*
Received 00th January 2012,
Accepted 00th January 2012
One-pot synthesis of magnetic silica supported copper catalyst has been described via in
situ generated magnetic silica (Fe3O4@SiO2); the catalyst can be used for the efficacious
amination of aryl halides in aqueous medium under microwave irradiation.
DOI: 10.1039/x0xx00000x
www.rsc.org/
(Fe3O4) was generated in-situ via hydrolysis method by stirring the
Introduction
solution of FeSO4·7H2O and Fe2(SO4)3 in water in (1:1) ratio at pH
10 (adjusted using (25 %) ammonia (NH3) solution) followed by
Amination of aryl halides is a very important transformation and a
method of choice for the synthesis of fascinating motifs containing
the N-aryl moiety;1 they are widely present in many biologically
important natural products and pharmaceuticals. The Buchwald-
Hartwig amination using palladium catalyst has been well explored.2
However, this method requires phosphine, N-heterocyclic carbenes,
and many other complex organic ligands. The main limitation of this
amination reaction is that these ligands are often air-sensitive, many
of them are expensive and often require longer reaction times.1-2 In
recent years, there has been significant progress in the discovery of
copper-catalyzed coupling reaction of aryl halides with amines,3 a
pathway that has been highly dependent on the use of organic
ligands.4 Although these ligands have been very important for
accelerating copper-catalyzed coupling of aryl halides with amines,
none of them has displayed general efficiency for promoting copper-
catalyzed N-arylation.
o
heating in water bath at 50 C for 1 h. The reaction mixture was
cooled down to room temperature and tetraethyl orthosilicate
(TEOS) was added to this solution with vigorous stirring which was
continued for 18 h at ambient conditions. The supernatant liquid was
decanted, fresh water added and to this solution, CuSO4 was added
and stirring was continued for another 24 h (Scheme 1).
TEOS
NH4OH/H2O
FeSO4.7H2O
+ Fe2(SO4)3
18 h, rt
1h, 50 o
C
Fe3O4@SiO2
CuSO4
24 h, rt
Fe3O4
Cu
Thus, the development of a mild and efficient method for the
amination of aryl halides under eco-friendly conditions for the
synthesis of arylamines that can circumvent the extravagant use of
stoichiometric reagents is highly desirable. Magnetic nanoparticles
have emerged as a robust, high-surface-area heterogeneous catalyst
support.5 Magnetic recoverability, which eliminates the necessity of
catalyst filtration after completion of the reaction is an additional
positive attribute of these materials6 compared to most of the
heterogeneous catalysts deployed. These catalysts work well but
suffer from following drawbacks a) synthesis of the catalyst is an
elaborate and tedious procedure which involves three steps, i)
synthesis of nano ferrite, ii) post-synthetic modification via
anchoring of ligand which may be toxic and, iii) immobilization of
catalytically active metal. To overcome these drawbacks and to
avoid the use of toxic ligands and reagents we have developed a one-
step procedure for the synthesis of magnetic silica supported CuSO4
as a magnetically retrievable catalyst and have demonstrated its
application for the amination of aryl halides in a benign aqueous
media, which circumvents the use of organic solvents.
Cu
Cu
Cu
Cu
Cu
Cu
Cu
Fe3O4@SiO2Cu- catalyst
Scheme 1 Synthesis of Magnetic silica supported copper catalyst
Results and discussion
The first step in the accomplishment of this goal was the easy
synthesis of magnetic silica supported copper catalyst (Scheme 1) by
sequential addition of reagents in one-pot. The magnetic nano ferrite
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DOI: 10.1039J/oCu3RrAn4a5l6N06aDme
or at 150 oC, even after 60 min of MW exposure (Table 1, entries 2-
3). The magnetic silica supported copper catalyst Fe3O4@SiO2Cu
was then tested for the amination of 4-nitro bromobenzene with
o
pyrrolidine at 100 C using MW and conventional heating. Under
conventional heating, it gives trace amount of product whereas MW
exposure for 1 h at 100 oC leads to the nearly quantitative conversion
of 4-nitro bromobenzene to corresponding aryl amines (Table 1,
entry 4). The variation in base did not influence the outcome of the
reaction; results with Cs2CO3 were similar to those obtained using
K2CO3. Using the above optimized conditions, the scope of magnetic
silica supported copper catalyst Fe3O4@SiO2Cu was then explored
for the amination of a variety of aryl halides (Table 2). The catalyst
displayed high activity for amination of aryl bromide and iodide
using primary, secondary, cyclic, and acyclic amines in pure water
(Table 2 entry1-17). The rates were barely influenced by the
electronic effects of the substituent’s on the aromatic ring of the aryl
halides (Table 2 entry 1-15). The cyclic (Table 2, entry1-10 and
entry 16-17) and acyclic amines (Table 2, entry 11-15) do not show
any difference in reactivity. Primary and secondary amines react
efficiently. It was interesting to observe that 1- bromo-4-iodo
benzene can be selectively converted to corresponding bromo aryl
Magnetic silica supported CuSO4 catalyst was separated using an
external magnet, washed with water followed by acetone and dried
under vacuum at 50 C for 8 hours. The catalyst was characterized
o
amines (Table 2 entry 16) after 60 min exposure to MW at 100 C
o
with 1 equivalent of pyrrolidine. The reaction of aryl halides bearing
both halide (Br) and boronic acid functional groups with amines
leads to the formation of corresponding aryl amines along with the
removal of boronic acids moiety (Table 2, entry 17). The aryl
chlorides were not reactive enough to be converted into the
corresponding amines, however. We have not observed any product
when similar reaction was performed with benzene chloride and
pyrrolidine (Table 2 entry 18). TON and TOF of the reactions (Table
2) clearly indicates that the method will be very useful for aryl amine
synthesis.
by transmission electron microscopy (TEM) (Fig 1a) and X-ray
diffraction (XRD) (Fig 1b) which confirmed the formation of single-
phase silica coated Fe3O4 nanoparticles Fe3O4@SiO2Cu, with
spherical morphology and a size range of 5-30 nm. The weight
percentage of Cu was found to be 4.92% by inductively coupled
plasma-atomic emission spectroscopy (ICP-AES) analysis.
The application of magnetic silica supported copper catalyst was
then demonstrated in a heterogeneous catalyzed amination of aryl
halides in aqueous medium as a benign solvent under microwave
(MW) irradiation conditions (Scheme 2). Use of MW-assisted
chemistry is due to the efficiency of the interaction of polar nano
catalysts as well as water molecules with microwaves and the
reaction mixture is rapidly heated to requisite temperatures under
MW irradiation with a precise control of the reaction temperature.7
Initially, experiments were performed to optimize the reaction
conditions for the amination of 4-nitro bromobenzene by pyrrolidine
in aqueous medium (Table 1).
The lifetime of the catalyst and its level of reusability are important
considerations in terms of practical applications. To clarify this
issue,
a set of experiments for the amination of 4-nitro-1-
bromobenzene with pyrrolidine using Fe3O4@SiO2Cu catalyst were
established. After the completion of the first reaction to afford the
corresponding aryl amine, the catalyst was recovered magnetically,
o
washed with acetone, and dried at 50 C. A new reaction was then
performed with fresh 4-nitro-1-bromobenzene under the similar
condition. The magnetic silica supported copper catalyst
Fe3O4@SiO2Cu could be reused at least three times without any
change in the activity (ESI, Table 1). Metal leaching was studied by
ICP-AES analysis of the catalyst before and after the three reactions.
The Cu concentration was found to be 4. 92 % before the reaction
and 4.87 % after the reaction. The TEM image of the catalyst taken
after the third cycle of the reaction did not show any significant
change in the morphology or in the size of the catalyst nanoparticles
(ESI, Fig. 1), which indicates the retention of the catalytic activity
after recycling. No Cu metal was detected in the reaction solvent
(water) after completion of the reaction. This confirms the fact that
nano magnetic silica held the copper catalyst very tightly,
minimizing the deterioration of the catalyst and thus metal leaching
and facilitating efficient catalyst recycling.
Br
Fe3O4@SiO2Cu
N
+
N
K2CO3 / Water
MW/60 min/100 oC
O2N
H
O2N
Scheme 2 Amination of 4-nitro bromobenzene using
Fe O @SiO Cu
3
4
2
Table 1 optimization of reaction condition
Temperature (oC)
100
Entry
1a
Catalyst
Fe3O4
Time
24 h
Yield
-
2b
3b
60 min
60 min
Fe3O4
Fe3O4
100
150
-
-
4b
5a
Fe3O4@SiO2Cu
Fe3O4@SiO2Cu
60 min
24 h
96%
100
100
traces
a) Reactions were performed under conventional heating; b) Reaction were
performed under MW irradiation
First, the reaction was conducted using nanoferrites nano-Fe3O4.
The amination reaction did not proceed under conventional heating
o
o
(24 h, 100 C, Table 1, entry 1), or under MW irradiation at 100 C
2 | J. Name., 2012, 00, 1-3
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Table 2 Amination of aryl halides
magnet, washed with water followed by acetone and dried under
vacuum at 50 oC for 8 hours. Catalyst characterization by X-ray
diffraction (XRD) (Fig 1a MS) and transmission electron
microscopy (TEM) (Fig 1b, MS) confirms the formation of single-
phase silica coated Fe3O4 nanoparticles Fe3O4@SiO2Cu, with
spherical morphology and a size range of 5-30 nm. The weight
percentage of Cu was found to be 4.92% by inductively coupled
plasma-atomic emission spectroscopy (ICP-AES) analysis.
Amines
Time
Yielda,b
TON/TOFc
Entry
Aryl halides
Prodcut
Br
N
N
60 min
60 min
60 min
1
2
95%
96%
772/193
780/195
NH
O2
O2
N
N
Br
I
O2
N
NH
NH
O2
N
N
3
4
94%
95%
764/191
772/193
NO2
I
NO2
N
60 min
NH
Amination of aryl halides
NO2
I
NO2
Aryl halide (1.0 mmol), Amine (1.1 mmol), K2CO3 (2.0 mmol) and
Fe3O4@SiO2Cu (25 mg) were placed in a crimp-sealed thick-walled
glass tube equipped with a pressure sensor and a magnetic stirrer.
Water (4 mL) was added to the reaction mixture. The reaction tube
was placed inside the cavity of a CEM Discover focused microwave
N
5
6
60 min
60 min
92%
92%
747/186
747/186
NH
NH
MeO
MeO
MeO
MeO
I
N
I
N
7
60 min
86%
699/174
682/170
NH
o
synthesis system, operated at 100 C (temperature monitored by a
I
O
O
N
N
O
O
8
9
NH
NH
NH
60 min
60 min
84%
89%
built-in infrared sensor), 100 Watts for 60-90 min. After completion
of the reaction, the catalyst was easily removed from the reaction
mixture using an external magnet. Product were extracted using
ethyl acetate, dry over sodium sulfate, concentrated under reduced
pressure and purified using column chromatography.
I
723/180
731/182
I
N
10
60 min
90%
Br
Br
H
NH2
N
11
12
60 min
60 min
83%
82%
674/168
666/166
O2
N
N
H
N
O2
O2
N
N
Acknowledgements
NH2
NH2
R.B. Nasir Baig was supported by the Postgraduate Research
Program at the National Risk Management Research Laboratory
administered by the Oak Ridge Institute for Science and Education
through an interagency agreement between the U.S. Department of
Energy and the U.S. Environmental Protection Agency. We thank Dr
Nadagouda Mallikarjuna for recording XRD data and valuable
suggestions.
O2
O2
H
N
Br
Br
Br
691/172
13
14
60 min
60 min
85%
95%
N
N
N
O2N
N
NH
772/193
788/197
O2
O2
O2N
H
N
NH2
15
16
60 min
60 min
97%
78%
O2N
Notes and References
I
N
N
NH
634/158
601/150
-
Sustainable Technology Division, National Risk Management
Research Laboratory, U. S. Environmental Protection Agency,26
West Martin Luther King Drive, MS 443, Cincinnati, Ohio 45268,
USA. E-mail:Varma.Rajender@epa.gov, Fax: +1 513-569-7677;
Tel: +1 513-487-2701
Br
S
Br
Br
17
18
60 min
90 min
74%
N.R
NH
NH
B(OH)2
Cl
S
N.R
a) Reaction condition: 1) Fe3O4@SiO2Cu (25 mg), amine ( 1.1mmol), K2CO3 (2 mmol), Water (4 mL), MW,
100 oC, 60 min; b) Isolated yield; c) TON/TOF calculated based on 10 mmol reaction, reaction time 4 h
Electronic supplementary information (ESI) available:
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Conclusion
A novel one-step procedure for the synthesis of magnetic silica-
supported copper catalyst has been developed, which can be readily
prepared in gram quantities in aqueous media. It catalyzed the
amination of aryl halides and the desired reactions proceeded
smoothly to deliver the corresponding aryl amines in very good
yields. Because of the magnetic nature of the catalyst, it can be
separated using an external magnet, which eliminates the
requirement of catalyst filtration after completion of the reaction,
which is an additional attribute of the catalyst.
Experimental section
Synthesis of magnetic silica supported ruthenium hydroxide
nanoparticles
FeSO4·7H2O (1.39 g) and Fe2(SO4)3 (2.0 g) were dissolved in 100
mL water in a 250 mL beaker. Ammonia solution (25%) was added
slowly to adjust the pH of the solution to 10. The reaction mixture
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o
was then continually stirred for 1 h at 50 C. The reaction mixture
was cooled down to room temperature, tetraethyl orthosilicate
(TEOS, 10 mL) was added and vigorous stirring was continued for
18 h at ambient conditions. The supernatant liquid was decanted,
fresh water added and to this solution, CuSO4 (400 mg) was added
and stirring was continued for another 24 h (Scheme 1). Magnetic
silica supported CuSO4 catalyst was separated using an external
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