Homogenous bimetallic catalysis on amination of ArX and ArX2 in aqueous medium-synergistic effect of dicopper complexes

Article abstract of DOI:10.1016/j.catcom.2012.11.027

A dicopper complex [Cu₂(bpnp)(OH)(CF₃COO) ₃] (1) (bpnp = 2,7-bis(pyridin-2-yl)-l,8-naphthyridine) was found to be an excellent catalyst on amination of aryl halides and aryl dihalides with ammonia in aqueous solutions leading to the corresponding anilines and aryldiamines, respectively. Catalytic activity of 1 toward amination appears to be superior to those of other mono nuclear copper complexes. Furthermore, the bimetallic catalyst 1 gave exclusively diamination product in the reaction of ArX₂ with ammonia, but other copper complexes showed poor selectivity. Kinetic product distribution study suggests that the dicopper metal ions in this catalysis promote the second amination efficiently.

Full text of DOI:10.1016/j.catcom.2012.11.027

Catalysis Communications 32 (2013) 28–31
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Catalysis Communications
journal homepage: www.elsevier.com/locate/catcom
Short Communication
Homogenous bimetallic catalysis on amination of ArX and ArX2 in aqueous
medium-synergistic effect of dicopper complexes
⁎
Bei-Sih Liao, Shiuh-Tzung Liu
Department of Chemistry, National Taiwan University, Taipei, 106, Taiwan
a r t i c l e i n f o
a b s t r a c t
Article history:
A dicopper complex [Cu2(bpnp)(OH)(CF3COO)3] (1) (bpnp=2,7-bis(pyridin-2-yl)-l,8-naphthyridine) was
found to be an excellent catalyst on amination of aryl halides and aryl dihalides with ammonia in aqueous
solutions leading to the corresponding anilines and aryldiamines, respectively. Catalytic activity of 1 toward
amination appears to be superior to those of other mono nuclear copper complexes. Furthermore, the bime-
tallic catalyst 1 gave exclusively diamination product in the reaction of ArX2 with ammonia, but other copper
complexes showed poor selectivity. Kinetic product distribution study suggests that the dicopper metal ions
in this catalysis promote the second amination efficiently.
Received 8 September 2012
Received in revised form 27 October 2012
Accepted 27 November 2012
Available online 5 December 2012
Keywords:
Amination
Copper
© 2012 Elsevier B.V. All rights reserved.
Bimetallic catalysis
Aqueous
Synergistic effect
1. Introduction
2. Experimental
Aniline derivatives are highly useful compounds for synthetic, bio-
logical, pharmaceutical, and material applications. Conventional meth-
odology for the preparation of anilines starts with aromatic nitration
followed by reduction [1], which involves multi-step processes and
complicated separations. In order to meet the environmental concern,
the development of new methodologies for C\N bond formations by
new catalytic systems for tandem reactions has received much atten-
tion [1]. Among this context, transition metal-catalyzed C\N bond for-
mations to produce the desired amines, typically palladium-catalyzed
Buchwald–Hartwig coupling reactions [2,3] and copper-catalyzed
Ullman-type transformations [4–6], have been demonstrated to be a
powerful tool for the production of arylamines [2–28]. However, the
use of dihaloarenes as the starting source to generate aryldiamines di-
rectly via the amination in aqueous system is less reported [27,29].
In terms of catalysts, quite a number of mononuclear copper com-
plexes have been proved to be active in the amination of ArX with am-
monia [7–26], some palladium complexes also show such an activity
[27,28]. However, there is no precedent report concerning the use of di-
nuclear metal complexes as catalysts. Dinuclear complexes, where two
metal ions are arranged in close proximity, provide an ideal focus for the
simultaneous activation of substrates particularly for di-functional sub-
strates, thus increasing the catalytic activity of the complexes. Here we
describe the use of a dicopper complex 1 catalyzed amination of aryl
halides including dihalides with ammonia in an aqueous solution lead-
ing to the corresponding anilines or aryldiamines.
2.1. General information
Nuclear magnetic resonance spectra were recorded on a Bruker
AVANCE 400 spectrometer. All reactions were carried out in a sealed
high pressure tube. Chemicals were purchased from commercial
source and were used without further purification. All compounds
were characterized by 1H, 13C NMR and MS. Dicopper complex 1 was
prepared according to the method previously reported [30].
2.2. General procedure for amination
A mixture of substrate (0.25 mmol), complex 1 (2.5×10−3 mmol),
Cs2CO3 (1 mmol), Conc. NH3(aq) (0.5 mL) and TBAB (0.25 mmol) in
water (0.5 mL) were loaded in a sealed reaction tube. The reaction tem-
perature was increased to 110–140 °C and the reaction mixture was
stirred for 8–24 h. After cooling to RT, the reaction mixture was poured
into a saturated NaCl solution, extracted with ethyl acetate and dried
over anhydrous MgSO4. After removal of solvents, the residue was
re-crystallized or chromatographed on silica gel. All products were
characterized by NMR spectroscopy and were consistent with the liter-
ature data.
3. Results and discussion
3.1. Mono-amination
Initially, the amination of p-methoxyphenyl bromide with ammonia
was chosen to examine the catalytic activity of 1 in C\N bond formation.
⁎
Corresponding author. Tel.: +886 2 2366 0352; fax: +886 2 2363 6359.
E-mail address: stliu@ntu.edu.tw (S.-T. Liu).
1566-7367/$ – see front matter © 2012 Elsevier B.V. All rights reserved.
http://dx.doi.org/10.1016/j.catcom.2012.11.027

B.-S. Liao, S.-T. Liu / Catalysis Communications 32 (2013) 28–31
29
Table 1
Amination of p-bromoanisole with ammonia catalyzed by 1.a
Table 3
Amination of various aryl halides with ammonia catalyzed by 1.a
Entry
catalyst
Base (1 mmol)
Additiveb
Temp (°C)
Yieldc
Entry
Substrate
Product
Yield
1
2
3
4
5
6
7
–
1
1
1
1
1
1
1
1
1
Cs2CO3
–
TBAB
–
110
110
110
30
5%
1
2
3
4
5
6
7
8
9
p-MeOC6H4I
m-MeOC6H4I
C6H5I
p-MeC6H4I
p-NO2C6H4I
o-HOC6H4I
m-HOC6H4Br
o-MeOC6H4Br
3-ClC6H4Br
2-BrC6H4COOH
p-MeOC6H4NH2
m-MeOC6H4NH2
C6H5NH2
p-MeC6H4NH2
p-NO2C6H4NH2
o-HOC6H4NH2
m-HOC6H4NH2
o-CH3OC6H4NH2
3-ClC6H4NH2
95%
55%
79%
91%
50%
99%
95%
72%
55%
Trace
96%
0
0
0
76%
86%
70%
Trace
Cs2CO3
Cs2CO3
Cs2CO3
CsF
Na2CO3
K2CO3
Cs2CO3
Cs2CO3
TBAB
TBAB
TBAB
TBAB
TBAB
TBAB
TBAB
–
70
110
110
110
110
110
8
9d
10
10
2-NH2C6H4COOH
71%b
a
Reaction conditions: p-MeOC6H4Br (0.5 mmol), catalyst (0.005 mmol), conc.
Br
N
NH2
N
11
100%
NH3(aq) (0.3 mL) and water (0.3 mL) in a sealed tube for 16 h.
b
TBAB = tetrabutylammonium bromide.
NMR yield based on ArBr.
c
Br
NH2
12
100%
0
d
In DMF as the solvent.
N
N
13
2,4,6-Me3C6H2Br
No reaction
a
Reaction conditions: aryl halide (0.5 mmol), catalyst (0.005 mmol), TBAB (0.25 mmol),
conc. NH3(aq) (0.3 mL) and water (0.3 mL) in a sealed tube at 110~120 °C for 16 h.
Reactions were conducted with 1.0 mol% of 1 as catalyst in water with
an excess of aqueous ammonia, an additional base and tetrabutylam-
monium bromide. A screening of this model reaction (Table 1) revealed
that complex 1 triggered the amination of the aryl abromide with NH3
smoothly, but additives and bases have a significant impact on the
yield of p-methoxyaniline. Although ammonia is a basic substance in
the aqueous medium, the reaction requires the additional base such
Cs2CO3 to promote the reaction. Furthermore, the addition of tetra-
butylmmonium bromide (TBAB) readily improves the production of
the desired product presumably acting as a phase-transfer reagent.
The best reaction condition is following: a mixture of p-BrC6H4OCH3
(0.5 mmol), Cs2CO3 (1 mmol), TBAB (0.25 mmol), concentrated
NH3(aq) (0.3 mL) and 1 (1 mol% based on ArBr) in water (0.3 mL) was
heated at 110 °C for 16 h (Table 1, entry 3). This result proves that com-
plex 1 can act a catalyst for C\N bond formation in aqueous medium.
For comparison, we screened various copper catalysts on this model
reaction and the results are summarized in Table 2. As expected, most of
the copper complexes do exhibit the catalytic activity on the amina-
tion of aryl bromide. However, complex 1 appears to be more efficient
as compared to other copper catalysts in term of turnover frequency
under the similar conditions, suggesting the possible synergistic effect
on this dimetallic system.
Having this catalytic system and reaction conditions for the C\N
coupling of ammonia with aryl halides, we also explored this amination
with a wide range of bromides and iodides (Table 3). It showed good
catalytic activities for the amination of both iodides and bromides
with various substituents, indicating the potential application of this
catalytic system. Excellent isolated yields were achieved with the sub-
strates of o-HOC6H4I and m-HOC6H4Br (Table 3, entries 6 and 7). How-
ever, chloro-substituted substrates could not be aminated under the
catalytic conditions. Thus, reaction of 3-chlorophenyl bromide with
ammonia provided 3-chloroaniline in 55% yield (Table 3, entry 9).
b
2-NH2C6H4CONH2 (21%) as the side product.
More interesting, pyridinyl halides also coupled with ammonia to give
the corresponding primary amines in excellent yields (Table 3, entries
11–12). It is noticed that 2,4,6-trimethylbromobenzene gave no ami-
nation product with the substrate recovered; this is presumably due
to the steric hindrance of ortho substituents.
3.2. Diamination
The above results provided the impetus to evaluate the prepara-
tion of aryldiamines via the copper-catalyzed double amination of
aryl dihalide, i.e. one step process. We have explored the double ami-
nation of aryl dihalides in the early work [29]. Here, the aim of this
study was to evaluate the catalytic efficiency of 1.
First, we screened a series of copper complexes as catalysts for the
amination of o-C6H4Br2 with NH3(aq) (Eq. (1)) to establish the degree
of bimetallic cooperativity of complex 1. The reaction yields were de-
termined by 1H NMR spectroscopy at the end of the reaction, where
percentage of products was established by 1H NMR spectroscopy. Re-
sults are summarized in Table 4. It is noticed that all the Cu(II) and
Cu(I) salts catalyzed the C\N bond formation, but produced both
mono- and di-amination products (2 and 3), i.e. poor selectivity. The
reaction catalyzed by the dicopper complex [Cu2(CF3COO)4], bridged
by CF3COO− ligands, provided the desired product 3 in 60% yield,
but still accompanied with 28% of 2 (Table 4, entry 2). On the other
hand, complex 1 gave the diamination product exclusively (Table 4,
Table 4
Diamination of o-C6H4Br2 catalyzed by various complexes.a
Entry
Complex
Ligand
Yield (%)
Table 2
Comparison of catalytic activity among various copper complexes.a
2
3
1
2
3
4
5
6
7
8
1
–
0
28
50
38
40
42
47
42
44
54
40
35
100
60
25
39
35
41
41
40
40
19
45
45
Entry
Catalystb
Yield
TOFc
Cu2(CF3COO)4
Cu(CH3COO)2
Cu(CH3COO)2
CuBr2
CuBr2
CuSO4
CuCl2
CuCl
CuI
CuI
–
1
2
3
4
5
6
7
8
Complex 1
CuI
CuCl2
96%
85%
83%
80%
70%
75%
61%
85%
6.0
5.3
5.2
5.0
4.4
4.7
3.8
5.3
–
TMEDA
PPh3
Bipyridine
–
CuBr2
Cu(OAc)2
Cu(ClO4)2
Cu(CF3COO)2
Cu(cyclam) (ClO4)2
–
9
–
10
11
12
–
dppe
TMEDA
a
Reaction conditions: p-MeOC6H4Br (0.5 mmol), catalyst, conc. NH3(aq) (0.3 mL)
CuI
and water (0.3 mL) in a sealed tube at 110 °C for 16 h.
b
a
2 mol% of copper catalyst except complex 1 (1 mol%).
TOF: turnover frequency, (mol. of product)/(mol. of catalyst)h.
Reaction conditions: o-C6H4Br2 (0.25 mmol), complex (0.005 mmol), water (0.5 mL),
c
conc. NH3(aq) (0.5 mL), Cs2CO3(1 mmol) and Bu4NBr (0.25 mmol) at 120 °C for 16 h.

30
B.-S. Liao, S.-T. Liu / Catalysis Communications 32 (2013) 28–31
system is a fast step. We believe that the copper ions bound in close
proximity of 1 could be one of the key factors for the efficient double
amination. Possibly, the intermediate generated by the coordination
of the first amination might be responsible for the facilitation of the
second amination. More important, the ligand bpnp readily confines
the metal ions closely, allowing the cooperative interaction between
them. In a separated experiment, we found that the rate of amination
of o-C6H4Br(NH2) was about 3.5 time faster than that of C6H5Br
under the same amination conditions. This observation provides an
evidence to support the proposal.
We have showed the synthetic application of this diamination in
a previous report [29]. Here we extended the substrate scope for this
catalysis as summarized in Table 5. Besides aryl dibromides, the
diamination proceeded smoothly with iodobromobenzenes (Table 5,
entries 1, 2 and 5). The replacement of the solvent from water to ethyl-
ene glycol may improve the yield (Table 5, entries 4 vs. 5). Dibromides
of hetero-aromatic compounds such as thiophene and pyridine also
reacted smoothly, producing the corresponding diamines with good
to excellent yields (Table 5, entries 6 and 7), but the substituted imidaz-
ole did not provide the diamino product (Table 5, entry 8). In the case of
2,5-dihalothiophenes, these substrates yielded a black polymeric mate-
rial under the amination conditions (Table 5, entries 9–10).
Fig. 1. Product distribution during the amination of o-, m- and p-C6H4Br2.
entry 1), indicating the importance of the chelating ligand bpnp on
this catalytic reaction.
Catalyst
oꢀC6H4Br2
oꢀC6H4ðNH2Þ þ oꢀC6H4ðNH2Þ
ð1Þ
Cs2CO3;NH3ðaqÞ
2
3
In order to know more detail, the diaminations of o-, m- and
p-C6H4Br2 catalyzed by 1 were monitored to analyze the product dis-
tribution and the results are summarized in Fig. 1. It clearly shows the
mono-amination product remains in a very low percentage during
the reaction, indicating that the second amination via the dicopper
4. Conclusion
In summary, the present study reports a development of highly effi-
cient protocol for amination of ArX and ArX2 with aqueous ammonia.
The dimetallic catalyst was optimized with respect to various parame-
ters, affording excellent yields in amination. Particularly, the synergistic
effect of the dimetallic system might play a key role of its activity on
aminations.
Table 5
Diaminationof various aryl dihalides.a
Acknowledgment
Entry
Substrate
Product
Yield
1
2
3
p-BrC6H4I
o-C6H4IBr
m-IC6H4I
p-H2NC6H4NH2
o-C6H4(NH2)2
m-C6H4(NH2)2
98%
95%
99%
This work was supported by National Science Council, Taiwan, for
the financial support (NSC100-2113-M-002-001-MY3).
H2N
NH2
NH2
I
Br
Br
b
4
–
Appendix A. Supplementary data
F
F
Supplementary data to this article can be found online at http://
dx.doi.org/10.1016/j.catcom.2012.11.027.
H2N
I
5c
6c
7c
8
96%
94%
55%
0%
F
F
H2N
Br
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a
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