Synthesis of tertiary aryl amines of various aryl halides and secondary amines using ortho-palladated complex of tribenzylamine

Article abstract of DOI:10.1002/aoc.3044

The activity of dimeric [Pd{C₆H₄(CH ₂N(CH₂Ph)₂)} (μ-Br)]₂ complex as an efficient, air- and moisture-tolerant catalyst was investigated in amination reactions of various aryl halides with secondary amines. Substituted tertiary aryl amines were produced in excellent yields and short reaction times using catalytic amounts of this dimeric complex in DMSO at 120°C. Copyright

Full text of DOI:10.1002/aoc.3044

Full Paper
Received: 30 April 2013
Revised: 19 June 2013
Accepted: 19 July 2013
Published online in Wiley Online Library: 24 September 2013
(wileyonlinelibrary.com) DOI 10.1002/aoc.3044
Synthesis of tertiary aryl amines of various aryl
halides and secondary amines using ortho-
palladated complex of tribenzylamine
Abdol R. Hajipoura,b*, Fatemeh Dordahana and Fatemeh Rafieea
The activity of dimeric [Pd{C6H4(CH2N(CH2Ph)2)} (μ-Br)]2 complex as an efficient, air- and moisture-tolerant catalyst was inves-
tigated in amination reactions of various aryl halides with secondary amines. Substituted tertiary aryl amines were produced
in excellent yields and short reaction times using catalytic amounts of this dimeric complex in DMSO at 120°C. Copyright ©
2013 John Wiley & Sons, Ltd.
Keywords: palladium catalyst; ortho-palladated complex; C―N cross-coupling reaction
stable and oxygen-insensitive catalyst in the C―N cross-coupling
reaction. In this paper, the efficiency of this dimeric complex of
Introduction
The synthesis of N-arylamines and N-arylheterocycles is an
active area in organic synthesis because of the occurrence
of these moieties in biologically important natural products
and pharmaceuticals, and their applications in materials
research. In addition, these compounds are important for
the preparation of new ligands, artificial dyes, polymers, elec-
tronic materials and xerographic materials.[1] The palladium-
catalyzed cross-coupling of amines with aryl halides has
become a principal method for the formation of C―N bonds
in aromatic systems.[2–10] Generally, the combination of
palladium catalysts with various phosphine ligands and also
N-heterocyclic carbenes results in excellent yields and high
efficiency in cross-coupling reactions. However, most
phosphine ligands are air and moisture sensitive, and eco-
nomically and environmentally undesirable due to difficulties
with their recovery and the formation of toxic phosphines as
by-products in these reactions. Carbene-type Pd catalysts are
in several cases more stable than phosphine Pd catalysts,
but they must often be synthesized in multistep proce-
dures.[11] Thus development of new and efficient palladium
catalytic systems remains a potentially promising field in
organic synthesis.[12] Among new methods, palladacycle
catalysts are important classes of catalysts that are very
efficient at very low concentration in organic synthesis,[13]
biologically active compounds[14] and macromolecular
chemistry.[15] The high productivity of the palladacycle
catalysts is due to the slow generation of low ligated Pd(0)
complexes from a stable palladium(II) pre-catalyst.[16]
palladium and tribenzylamine was investigated in an amination
reaction with various aryl halides and secondary amines
(Scheme 1).
The efficiency of ortho-palladated complex (A) in the
amination reaction was examined by optimizing the reaction
conditions in the cross-coupling reaction between iodobenzene
with N-benzyl-N-methylamine as a model reaction. The results
are summarized in Table 1. Among the tested conditions, DMSO
as solvent, KOH as base and 0.2 mol% of catalyst gave the best
result.
The optimized reaction conditions were applied to the cross-
coupling reactions of various aryl halides with different second-
ary amines using the dimeric ortho-palladated catalyst (A)
(Table 2). As this catalyst is thermally stable and not sensitive to
oxygen and moisture, the reactions were carried out under air
atmosphere.
The substituent effects on the aryl iodides proved to be less
significant than in the aryl bromides and the reactivity of aryl
bromides with electron-withdrawing substituent was higher than
that of aryl bromides with electron-donating substituent.
Because of the inexpensiveness and availability of aryl chlorides,
they are the best substrates for coupling reactions in comparison
with the corresponding bromide or iodide compounds. This
method can be used for the C―N cross-coupling reaction of
even less reactive aryl chloride derivatives with longer reaction
*
Correspondence to: Abdol R. Hajipour, Pharmaceutical Research Laboratory,
Department of Chemistry, Isfahan University of Technology, Isfahan 84156, IR
Iran. Email: haji@cc.iut.ac.ir
Results and Discussion
a Pharmaceutical Research Laboratory, Department of Chemistry, Isfahan
University of Technology, Isfahan 84156IR, Iran
In continuation of our recent investigations on the synthesis and
applications of palladacycle catalysts in cross-coupling reac-
tions,[17–24] we now report the extension of dimeric [Pd{C6H4
(CH2N(CH2Ph)2)} (μ-Br)]2 homogeneous complex as a thermally
b Department of Pharmacology, University of Wisconsin, Medical School, 1300
University Avenue, Madison, WI, 53706-1532, USA
Appl. Organometal. Chem. 2013, 27, 704–706
Copyright © 2013 John Wiley & Sons, Ltd.

Amination coupling reaction
Experimental
General
1H NMR spectra were recorded at 400 MHz in CDCl3 solution at
room temperature (tetramethylsilane was used as an internal
standard) on a Bruker Avance 500 instrument (Rheinstetten,
Germany) and Varian 400 NMR. FT-IR spectra were recorded on
a spectrophotometer (Jasco-680, Japan). Spectra of solids were
carried out using KBr pellets. Vibrational transition frequencies
are reported as wavenumber (cmÀ1). We used gas chromatogra-
phy (GC; BEIFIN 3420 gas chromatograph equipped a Varian CP
SIL 5CB column: 30 m, 0.32 mm, 0.25 μm) for examination of
reaction completion and yields. Palladium acetate, aryl halides
and all chemicals were purchased from Merck and Aldrich and
were used as received.
Scheme 1. Amination reaction using ortho-palladated complex (A).
times. Aromatic and also aliphatic secondary amines containing
N-benzyl-N-methylamine, diphenylamine, morpholine, indole,
dicyclohexylamine and N-methylcyclohexanamine were coupled
with various aryl halides in excellent yields and acceptable
reaction times. This catalytic system was also applied to primary
amines such as aniline, but in these reactions secondary and
tertiary amines were obtained in 70:30 ratios.
General Procedure for C―N Cross-Coupling Reaction of Aryl
Halides
A mixture of aryl halide (1 mmol), amine (1.2 mmol), KOH (3
mmol) and ortho-palladated catalyst (A) (0.2 mol%) in DMSO (2
mL) in a round-bottom flask equipped with a condenser was
placed in an oil bath at 120°C. The mixture was stirred continu-
ously using an appropriate magnet during the reaction. After
the reaction was complete, the mixture was cooled to room
temperature and diluted with H2O (30 ml) and Et2O (30 ml). The
organic phase was dried over MgSO4. The solution was filtered
and the solvent evaporated using a rotary evaporator. The resi-
due was purified by silica gel column chromatography (n-hexane
or n-hexane/EtOAc (9:1)).
Conclusions
In this work, a general protocol was applied to the C―N cross-
coupling reaction of various aryl halides with secondary amines
using ortho-palladated complex of tribenzylamine. The catalytic
amounts of this efficient dimeric complex converted various aryl
halides to the corresponding substituted tertiary aryl amines in
excellent yields and acceptable reaction times.
Table 1. Optimization of reaction conditions for the amination coupling reactiona
Catalyst (A)
Base, Solvent
X
NR2R3
HNR2R3
R1
+
R1
Entry
Solvent
Base
Catalyst (mol%)
Temp (°C)
Time (min)
Conversion (%)b
1
NMP
KOH
0.1
1
120
120
120
100
80
120
180
105
50
25
20
2
DMF
KOH
3
4c
DMSO
DMSO
CH3CN
Dioxane
H2O
KOH
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0.05
0.2
0.3
0.2
100
100
—
KOH
5
KOH
180
120
180
120
180
180
180
200
10
6
KOH
90
70
7
KOH
100
120
120
120
120
120
120
120
140
—
8
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
K2CO3
Na2CO3
NaOAc
NaHCO3
KOH
75
9
50
10
11
12
13c
14
15
10
30
53
KOH
100
100
100
KOH
10
KOH
10
aReaction conditions: iodobenzene (1 mmol), N-benzyl-N-methylamine (1.2 mmol), base (2 mmol), solvent (2 ml), catalyst (A).
bGC yield.
cBase (3 mmol).
Appl. Organometal. Chem. 2013, 27, 704–706
Copyright © 2013 John Wiley & Sons, Ltd.
wileyonlinelibrary.com/journal/aoc

A. R. Hajipour et al.
Table 2. C―N cross-coupling reaction of aryl halides using ortho-palladated catalyst (A)a
Catalyst (A)
KOH, DMSO
100 °C
X
NR2R3
HNR2R3
R1
+
R1
Entry
1
Ar-X
Amine substrate
Time
(min)
Yield
(%)b
R2
R3
Ph―I
PhCH2
Me
10
45
98
97
70
80
70
98
95
90
97
96
94
95
96
94
98
96
80
94
97
95
85
96
94
98
96
93
95
94
96
97
95
Ph―Br
Ph―Cl
480
55
2
3
p-MeO―Ph―I
p-MeO―Ph―Br
p-O2N―Ph―I
p-O2N―Ph―Br
p-O2NPh―Cl
p-NC―Ph―Br
Ph―I
PhCH2
PhCH2
Me
Me
180
10
30
360
50
4
5
PhCH2
Ph
Me
Ph
40
Ph―Br
90
Ph―Cl
600
180
300
75
6
7
p-MeO―Ph―I
p-MeO―Ph―Br
p-O2N―Ph―I
p-O2N―Ph―Br
p-O2NPh―Cl
p-NC―Ph―Br
Ph―I
Ph
Ph
Ph
Ph
120
300
135
25
8
9
Ph
Ph
Morpholine
Ph―Br
30
Ph―Cl
240
60
10
11
12
13
14
p-MeO―Ph―I
p-MeO―Ph―Br
p-O2N―Ph―I
p-O2N―Ph―Br
Ph―I
Morpholine
Morpholine
Indole
90
10
25
10
Ph―Br
15
Ph―I
Cy-hexyl
Cy-hexyl
Cy-hexyl
Me
20
Ph―Br
25
Ph―I
30
Ph―Br
45
aReaction conditions: aryl halide (1 mmol), amine (1.2 mmol), KOH (3 mmol), DMSO (2 ml), catalyst (A) (0.2 mol%), oil bath (120 °C).
bIsolated yield.
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Acknowledgements
We gratefully acknowledge the funding support received for this
project from the Isfahan University of Technology (IUT), IR Iran
and Isfahan Science and Technology Town (ISTT), IR, Iran. Further
financial support from the Center of Excellence in Sensor and
Green Chemistry Research (IUT) is gratefully acknowledged.
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Copyright © 2013 John Wiley & Sons, Ltd.
Appl. Organometal. Chem. 2013, 27, 704–706