An efficient heterogeneous ligand free C-N coupling reaction catalyzed by palladium supported on magnetic nanoparticles

Article abstract of DOI:10.1016/j.tetlet.2015.12.020

The catalytic activity of palladium supported on magnetic nanoparticles in the amination coupling reaction of different nitrogen containing substrates with aryl halides was investigated. C-N bond formation was achieved in moderate to excellent yields and the catalyst could be separated by magnetic decantation.

Full text of DOI:10.1016/j.tetlet.2015.12.020

Accepted Manuscript
An Efficient Heterogeneous Ligand Free C-N Coupling Reaction Catalyzed by
Palladium Supported on Magnetic Nanoparticles
Ezzat Rafiee, Ali Ataei, Mohammad Joshaghani
PII:
S0040-4039(15)30439-1
DOI:
http://dx.doi.org/10.1016/j.tetlet.2015.12.020
TETL 47067
Reference:
To appear in:
Tetrahedron Letters
Received Date:
Revised Date:
Accepted Date:
25 April 2015
19 October 2015
3 December 2015
Please cite this article as: Rafiee, E., Ataei, A., Joshaghani, M., An Efficient Heterogeneous Ligand Free C-N
Coupling Reaction Catalyzed by Palladium Supported on Magnetic Nanoparticles, Tetrahedron Letters (2015), doi:
http://dx.doi.org/10.1016/j.tetlet.2015.12.020
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Graphical Abstract
An Efficient Heterogeneous Ligand Free C-N Coupling
Reaction Catalyzed by Palladium Supported on Magnetic
Nanoparticles
Leave this area blank for abstract info.
Ezzat Rafiee, Ali Ataei, Mohammad Joshaghani

1
Tetrahedron Letters
An Efficient Heterogeneous Ligand Free C-N Coupling Reaction Catalyzed by
Palladium Supported on Magnetic Nanoparticles
a, b,
a
a, b
Ezzat Rafiee
, Ali Ataei , Mohammad Joshaghani
a
Faculty of Chemistry, Razi University, Kermanshah 67149, Iran
Institute of Nano Science and Nano Technology, Razi University, Kermanshah, 67149, Iran
b
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
The catalytic activity of palladium supported on magnetic nanoparticles in the amination
coupling reaction of different nitrogen containing substrates with aryl halides was investigated.
C–N bond formation was achieved in moderate to excellent yields and the catalyst could be
separated by magnetic decantation.
Available online
2
009 Elsevier Ltd. All rights reserved.
Keywords:
Palladium
Magnetic nanoparticle
Amination coupling
Triphenylamine
Catalyst
28,29
1. Introduction
magnet.
Recently we reported results concerning the utility of
palladium supported on magnetic nanoparticles coated by oleic
The palladium-catalyzed amination coupling reaction of aryl
acid (Fe@OA-Pd) in the ligand-free Heck coupling of various
halides with nitrogen containing substrates is an important
reaction with major roles in various areas of chemistry,
including, agrochemicals, dyes, pigments, rubber and
28,29
aryl halides in various media.
Considering the importance of
the ligand-free Buchwald–Hartwig type amination reaction in
organic synthesis, and in continuation of our studies on Pd-
1,2
pharmaceuticals. Since the discovery of the catalytic amination
30-34
catalyzed carbon–carbon coupling reactions,
herein, we report
3-7
method, increased efforts have been undertaken in order to
the carbon–nitrogen coupling reaction using Fe@OA-Pd.
8
-10
determine the best conditions for this transformation. Despite
1
1-15
Initially, attempts to couple bromobenzene with aniline using
considerable advances,
drawbacks such as the use of
16
expensive, air and moisture sensitive ligands, low yields using
catalytic Fe@OA-Pd and
2
K CO
3
as base in N,N-
35
non-aromatic amines, long reaction times, harsh reaction
dimethylformamide (DMF) were unsatisfactory, (Table 1, entry
1) giving only 21% diphenylamine (DPA) as the main product
after 24 hours. Use of additives such as water to increase the
nucleophilic strength of the base gave only 35% of the desired
product after 20 h (Table 1, entry 2). Increasing the catalyst
loading had no effect on the yield (Table 1, entry 3). Use of t-
BuONa as base, significantly reduced the reaction time, however
the extended reaction time led to trace amounts of triphenylamine
(TPA) as a by-product (Table 1, entry 4). Because diarylamine
17, 18
conditions,
tedious work-up, poor ligand stability, and the
formation of toxic side products are features of some methods.
Thus, improved methods for this reaction are still of interest.
Palladium nanoparticles, particularly those smaller than 10 nm,
have been found to exhibit unexpectedly high catalytic activities
toward different types of reactions when compared to bulk
19-21
palladium.
Recently, many attempts have been made to
immobilize palladium nanoparticles on diverse solid supports
2
2,23
24
25-28
such as polymers,
carbon, and metal oxides
in order to
2
derivatives (Ar NH) are expensive, the double arylation of
aniline with haloarenes should offer a practical synthetic route to
produce various triarylamines. Thus, the arylation of aniline with
bromobenzene was carried out with Fe@OA-Pd as catalyst in
construct heterogeneous palladium catalysts with high catalytic
activity for various coupling reactions such as the amination of
aryl halides.
2
DMF in the presence of H O as an additive; the arylation took
Recovery of the catalyst from the reaction mixture is not only
useful for catalyst reusability but also simplifies the work-up
procedure. To overcome problems with separation, magnetic
nanoparticles, such as Fe O nanoparticles, have been used as
3 4
support materials due to their unique physical properties and easy
place twice on the aniline nitrogen to give the corresponding
triarylamine. Increasing the catalyst loading to 3 mol% of Pd in
the presence of t-BuONa markedly improved the yield and
reduced the reaction time, however the selectivity was low (Table
1, entry 5). Next, we screened nonpolar solvents such as toluene
separation from the reaction mixture using an external
—
——
in order to reduce the amount of triphenylamine (Table 1, entry

Corresponding author: Tel/Fax: +98 83-34274559; E-mail: e.rafiei@razi.ac.ir, ezzat_rafiee@yahoo.com

2
Tetrahedron Letters
6
). Attempts to promote coupling by inclusion of halide
additives such as aluminum chloride (AlCl or
tetrabutylammonium bromide (TBAB) were also unsatisfactory
methylaniline gave a low yield compared with aniline under
3
)
similar reaction conditions (Table 1, entries 6 and 9), but in the
case of piperidine, excellent yields were obtained (>99%)
without by-product formation (Table 1, entry 10).
(Table 1, entries 7 and 8). Using a secondary amine such as N-
a
Table 1. Optimization of the amination coupling reaction
b
Catalyst loading
Yield (%)
DPA
Time (h)
Entry
Amine
Base
Additive Temp. (°C)
(
mol%)
0.3
0.3
1.5
0.3
3
TPA
0
c
1
Aniline
Aniline
K
2
CO
CO
CO
3
3
3
ꢀ
120
120
120
120
120
105
105
105
105
21
35
43
42
60
62
67
64
35
24
20
20
5
c
2
K
2
H
H
H
H
H
2
2
2
2
2
O
O
O
O
O
0
c
3
Aniline
K
2
0
c
4
Aniline
t-BuONa
t-BuONa
t-BuONa
t-BuONa
t-BuONa
t-BuONa
7
c
5
Aniline
40
~5
~5
~5
0
3
d
6
Aniline
1.5
3
5
d
7
Aniline
TBAB
AlCl
7
d
8
Aniline
3
3
10
20
d
9
N-methyl aniline
1.5
H
2
O
˃
99
d,e
1
0
Piperidine
1.5
t-BuONa
H
2
O
105
-
1
(
98, 98, 96)
a
b
c
d
e
Reaction conditions: bromobenzene (2 mmol), amine (2.5 mmol), base (3 mmol), solvent (5 mL), additives (H
2
O, 1 mL; TBAB or AlCl
3
, 3 mmol).
Isolated yield.
DMF.
Toluene.
Results in parenthesis are related to successive runs.
The scope of the heterogeneous catalytic amination was then
investigated under the optimized reaction conditions: Table 1
entry 10. Various aryl bromides were reacted with piperidine and
converted into the corresponding coupling products (Table 2,
entries 1-8). For example, the reaction of 1-bromo-4-
methylbenzene with piperidine gave the corresponding amine in
5
6
70
95
5
2
9
0% yield (Table 2, entry 1). The reactions of 4-bromoanisole, 4-
7
8
No reaction
41
20
20
bromobenzaldehyde and 4-bromoacetophenone proceeded in
good to excellent yields to give the corresponding coupling
products (Table 2, entries 2-4). Next, 4-bromoaniline was reacted
with piperidine in moderate yield without any Ullman by-
products (Table 2, entry 5). Amination of 1-bromonaphthalene
was complete within 2 h in 95% yield. However, the reaction of
piperidine with 1-bromo-4-nitrobenzene gave only 41% yield and
the reaction with 4-bromobenzonitrile did not proceed after 20 h,
probably due to a competitive dehalogenation reaction which has
been reported in the literature to occur when using aryl halides
bearing electron-withdrawing substituents (Table 2, entries 7 and
a
Reaction conditions: aryl bromide (2 mmol), piperidine (2.5 mmol), t-
BuONa (3 mmol), Fe@OA-Pd (1.5 mol%), toluene (5 mL), H O (1 mL), 105
2
°
C.
b
Isolated yield.
Because of the high reactivity of this catalyst system, we were
encouraged to explore aryl chlorides under the optimum reaction
conditions. Various aryl chlorides were reacted with piperidine
and converted into the corresponding coupling products (Table 3,
entries 1-8). However, in the cases of 4-chlorobenzonitrile and 1-
chloro-4-nitrobenzene the yields of the corresponding products
decreased dramatically to 42% and 63%, respectively presumably
due to a competitive dehalogenation reaction (Table 3, entries 7
and 8). As reported in Table 3, 1-choloro-4-methylbenzene and
36,37
8).
a
Table 2. Palladium-catalyzed amination of aryl bromides
4
-chloroanisole reacted with piperidine in good to excellent yield,
(
entries 1 and 2). No significant difference in yield was observed
b
using aryl chloride substrates with electron-donating or electron-
withdrawing groups (Table 3, entries 3-5). 4-Chloroaniline
reacted with piperidine with complete selectivity (˃ 97:3) for
amination coupling over Ullman coupling (entry 5). The
amination of sterically hindered 1-chloronaphthalene also
afforded the coupled product in high yield (Table 3, entry 6).
Entry
Aryl halide
Product
Yield (%)
Time (h)
1
2
3
4
90
86
92
94
10
4
4
6

3
a
Table 3. Palladium-catalyzed amination of aryl chlorides
2
3
65
70
4
3
b
Entry
Aryl halide
Product
Yield (%)
Time (h)
1
2
71
82
9
6
3
4
5
83
80
76
5
8
9
4
5
6
No reaction
24
2
6
90
3
28
55
7
8
42
63
20
20
10
a
Reaction conditions: aryl chloride (2 mmol), piperidine (2.5 mmol), t-
BuONa (3 mmol), Fe@OA-Pd (1.5 mol%), toluene (5 mL), H O (1 mL), 105
2
°
C.
a
Reaction conditions: aryl bromide (2 mmol), diphenylamine (2.5 mmol), t-
BuONa (3 mmol), Fe@OA-Pd (1.5 mol%), DMF (5 mL), H O (1 mL), 120
b
Isolated yield.
2
°
C.
Considering the utility of the triarylamine motif as
b
37, 38
Isolated yield.
optoelectroactive materials,
we decided to study the catalytic
aromatic amination of diarylamines (Table 4). In the initial
optimization, the coupling of bromobenzene with aniline was
carried out in DMF at reflux using t-BuONa as base for 24 h in
the presence of 3.0 mol% Fe@OA-Pd (Table 1, entry 5). This
To test the reusability of the catalyst, recycling experiments
were carried out for the coupling of piperidine with
bromobenzene (entry 10, Table 1). Upon reaction completion, the
catalyst was removed from the reaction vessel with the aid of an
external magnet. The Pd content in the Fe@OA–Pd catalyst after
the first and fourth runs was determined as 8.4 wt.% and 7.6
wt.%, respectively, using atomic absorption spectroscopic
analysis. This shows that the palladium content of the catalyst
does not significantly change after reaction or recycling
processes, indicating that no significant leaching of palladium
occurs.
3
gave the desired Ph N in 40% yield (conversion = 100%). Next,
we examined the amination reaction of bromobenzenes with
diphenylamine under the following reaction conditions: aryl
bromide (2 mmol), diphenylamine (2.5 mmol), t-BuONa (3
mmol), Fe@OA-Pd (1.5 mol%), DMF (5 mL), H
2
O (1 mL) at
120 °C (Table 4). The catalytic efficiency was strongly affected
by substituents at the ortho position of the bromoarenes. Thus,
amination of diphenylamine with 1-bromo-2-methylbenzene
gave only 43% yield (Table 4, entry 1), whereas in the case of
meta- and para-tolyl bromides, the corresponding product was
obtained in 65% and 70% yield, respectively (Table 4, entries 2
and 3). 4-Bromobenzonitrile did not give any product and in the
case of 1-bromo-4-nitrobenzene the yield of corresponding
product dramatically decreased to 28% possibly due to
competitive dehalogenation (Table 4, entries 4 and 5). Use of 4-
bromoaniline in this reaction gave 4-amino N, N-diphenylaniline
in moderate yield (55%) but with a longer reaction time (Table 4,
entry 6).
In summary, the use of a ligand free heterogeneous palladium
supported on magnetic nanoparticle has been shown to be a
simple and highly efficient system for the C-N coupling of
different nitrogen containing substrates with aryl halides. Good
to high yields of products with excellent functional group
tolerance was found. Increasing the electron withdrawing nature
of the substituted group dramatically decreased the yield of the
reaction probably due to a competitive dehalogenation reaction.
Acknowledgment
The authors thank Razi University Research Council for support
of this work.
a
Table 4. Palladium-catalyzed amination of diphenylamine
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mol%), base (3 mmol), solvent (5 mL) and additive. The resulting
mixture was stirred for the appropriate time and temperature. After
reaction completion the reaction mixture was then cooled to room
temperature and the catalyst separated using a magnet, taken up in
Et
2
O (4 mL), and washed with brine (5 mL). The resulting solution
, filtered and concentrated. The
was dried over anhydrous MgSO
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