A simple and efficient catalytic system for coupling aryl halides with aqueous ammonia in water

Article abstract of DOI:10.1002/ejoc.201000060

The cross-coupling reaction between aryl halides and aqueous ammonia was efficiently catalyzed by the sulfonatoCu(salen) complex in water with high yields. A variety of substituted aryl bromides and aryl iodides were found to be applicable to the environmentally benign system. Substituted 1H-benzimidazole could also be easily prepared by coupling aqueous ammonia with 2-iodoacetanilide in one pot with this catalytic system.

Full text of DOI:10.1002/ejoc.201000060

SHORT COMMUNICATION
DOI: 10.1002/ejoc.201000060
A Simple and Efficient Catalytic System for Coupling Aryl Halides with
Aqueous Ammonia in Water
Zhiqing Wu,[a] Zhaoqiong Jiang,[a] Di Wu,[a,b] Haifeng Xiang,[a] and Xiangge Zhou*[a,b]
Keywords: Amination / Cross-coupling / Copper / Nitrogen heterocycles / Water chemistry
The cross-coupling reaction between aryl halides and
aqueous ammonia was efficiently catalyzed by the sulfonato–
Cu(salen) complex in water with high yields. A variety of
substituted aryl bromides and aryl iodides were found to be
applicable to the environmentally benign system. Substi-
tuted 1H-benzimidazole could also be easily prepared by
coupling aqueous ammonia with 2-iodoacetanilide in one pot
with this catalytic system.
worthy that these protocols are generally performed in or-
ganic solvents, which contributed the largest amount of
“auxiliary waste” in most chemical productions.[10] There-
fore, it is highly desirable to find an ideal, nontoxic, cheap,
and readily available “green” solvent. Obviously, water is
the most inexpensive and environmentally benign one.[11]
In continuation of our efforts in aqueous catalysis,[12]
herein we disclose an environmentally friendly protocol for
the amination of aryl halides with aqueous ammonia cata-
lyzed by sulfonato–Cu(salen) complex 1 (Figure 1), which
was successfully applied in C–N cross-coupling reactions by
us recently.[12a]
Introduction
Ammonia is one of the most attractive sources of nitro-
gen for synthesis due to its low cost and wide availability.[1]
The use of ammonia as a coupling partner with simple aryl
halides in cross-coupling reactions allows the direct synthe-
sis of valuable primary anilines, which are widely used in
the synthesis of natural products, pharmaceuticals, agro-
chemicals, and material science.[2] In contrast to other well-
established palladium- or copper-catalyzed C–N bond-for-
mation reactions,[3,4] the direct amination of aryl halides
with ammonia has proved to be a great challenge due to
competition between ammonia and the more reactive ani-
line products, which results in the formation of considerable
amounts of diaryl- and triarylamines.[5,7c] Furthermore,
traditional methods to form primary amines suffer from
several drawbacks such as high pressure, high temperature,
and low toleration of functional groups, which make those
methodologies less attractive.[6] Recently, Hartwig and
Buchwald and co-workers reported the catalyzed selective
coupling reactions of aryl halides with ammonia by palla-
dium catalysts.[7] Following these pioneering works, as an
alternative, several Cu-catalyzed coupling reactions of aryl
halides with ammonia have been reported.[8] Furthermore,
Fu and co-workers also introduced a copper-catalyzed am-
ination protocol between aromatic boronic acids and aque-
ous ammonia at room temperature.[9] Although the exam-
ples mentioned above have led to remarkable progress in
the development of primary aniline synthesis, it is note-
Figure 1. Structure of sulfonato–Cu(salen) complex 1.
Results and Discussion
To optimize the reaction conditions, iodobenzene was
firstly chosen as the model substrate. Selected results from
our screening experiments are summarized in Table 1. As
expected, no product could be detected in the absence of a
copper catalyst (Table 1, Entry 1). Several simple copper
salts were also examined, and only trace amounts of prod-
ucts were obtained (Table 1, Entries 2–4). To our delight,
catalysis with complex 1 (5 mol-%) afforded 86% yield of
the desired aniline product at 120 °C for 24 h (Table 1, En-
try 5). Further investigation revealed that 12 h was enough
for the coupling reaction (Table 1, Entries 5–7). Notably,
the addition of (nBu)4NBr (10 mol-%) as phase-transfer
[a] Institute of Homogeneous Catalysis, College of Chemistry,
Sichuan University,
Chengdu 610064, China
Fax: +86-28-85412026
E-mail: zhouxiangge@scu.edu.cn
[b] State Key Laboratory of Coordination Chemistry, Nanjing
University,
Nanjing 210093, China
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201000060.
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Eur. J. Org. Chem. 2010, 1854–1857

Catalytic System for Coupling Aryl Halides with Aqueous Ammonia
catalyst (PTC) did not improved the results (Table 1, En- Table 2. Sulfonato–Cu(salen) complex 1 catalyzed amination of
aryl iodides with aqueous ammonia.[a]
try 8). The dosage of catalyst was also screened, and the
yield decreased sharply to 32% when only 2 mol-% of cata-
lyst was used. Meanwhile, increasing the amount of catalyst
to 10 mol-% did not improve the yield (Table 1, Entries 9
and 10). Furthermore, low temperatures decelerated the re-
action rate. For example, only 42% yield was obtained when
the reaction was carried out at 100 °C (Table 1, Entry 11).
Base is another important factor to affect the catalysis. A
poor yield of 24% was obtained in the absence of base
(Table 1, Entry 12). Among various bases examined,
NaOH, K2CO3, K3PO4, Na2CO3, and Cs2CO3 were all ef-
fective for the catalysis, but the use of CH3COONa and
organic bases such as triethylamine led to lower yields
(Table 1, Entries 13–18). Thus, NaOH was selected as the
base in the following studies.
Table 1. Catalytic amination of iodobenzene with aqueous ammo-
nia by the sulfonato–Cu(salen) complex in water.[a]
Entry
Catalyst (mol-%)
Base
T [h] Yield [%][b]
1
2
3
4
5
6
–
NaOH
NaOH
NaOH
NaOH
NaOH
NaOH
NaOH
NaOH
NaOH
NaOH
NaOH
–
12
12
12
12
24
12
9
12
12
12
12
12
12
12
12
12
0
trace
trace
trace
86
87
59
80
32
86
42
24
83
80
86
84
17
50
Cu2O (5)
CuSO4 (5)
Cu(OAc)2 (5)
[a] Reaction conditions: aryl iodide (0.5 mmol), 25–28% aqueous
ammonia (1 mL), catalyst (5 mol-%), NaOH (1 mmol), H2O
(2 mL), 120 °C, 12 h. [b] Isolated yield.
sulfonato–Cu(salen) (5)
sulfonato–Cu(salen) (5)
sulfonato–Cu(salen) (5)
sulfonato–Cu(salen) (5)
sulfonato–Cu(salen) (2)
sulfonato–Cu(salen) (10)
sulfonato–Cu(salen) (5)
sulfonato–Cu(salen) (5)
sulfonato–Cu(salen) (5)
sulfonato–Cu(salen) (5)
sulfonato–Cu(salen) (5)
sulfonato–Cu(salen) (5)
sulfonato–Cu(salen) (5)
sulfonato–Cu(salen) (5)
7
8[c]
9
Next, we were intrigued by the possibility of using aryl
bromides as coupling partners, which are less reactive elec-
trophiles. However, low yields were found under the pre-
viously optimized reaction conditions. After careful optimi-
zation of the reaction conditions it was found that doubling
the amount of catalyst to 10 mol-% resulted in comparable
catalytic abilities when aryl bromides were used instead of
aryl iodides. Thus, a variety of substituted aryl bromides
were then examined, and the results are shown in Table 3.
The electronic effects on the reactivity were limited; most
of the substrates afforded good to excellent yields. It is note-
worthy that heterocyclic bromides could also be coupled
with aqueous ammonia to afford the corresponding anilines
with excellent yields (Table 3, Entries 13 and 14). Further-
more, the catalytic system could tolerate a variety of func-
tional groups including the nitro, acetyl, and ether groups.
10
11[d]
12
13
14
15
16
17
18
K2CO3
K3PO4
Na2CO3
Cs2CO3
CH3COONa 12
Et3N 12
[a] Unless otherwise noted, the reactions were carried out with
iodobenzene (0.5 mmol), 25–28% aqueous ammonia (1 mL), base
(1 mmol) in water (2 mL) at 120 °C. [b] Determined by GC–MS
with the use of 1,4-dichlrobenzene as internal standard. [c] (nBu)4-
NBr (10 mol-%) was added as PTC. [d] The reaction temperature
was 100 °C.
The scope of substrates was then investigated by using Sterically hindered 1,3-dimethylbromobenzene afforded the
this catalytic system under the optimized reaction condi- product in low yield (Table 3, Entry 11).
tions. All the aryl iodides, especially those with electron-
Substituted benzimidazoles are important heterocycles
withdrawing substituents, provided good to excellent yields found in a variety of natural products.[13] The standard ap-
as shown in Table 2, and the highest yield (95%) was ob- proach to the synthesis of benzimidazole derivatives is cy-
tained by using 4-iodoacetophenone. Notably, the sterically clocondensation of the corresponding 1,2-diaminobenzene
demanding ortho substituents did not hamper the reaction with carboxylic acids.[14] However, the exploration of more
as much as that in the coupling reaction between imidazole efficient methods for constructing the benzimidazole frame-
and iodobenzene reported by us.[12a] For instance, 2-meth- work is highly desirable. Thus, this catalytic system was ap-
yliodobenzene and 2-nitroiodobenzene could be catalyti- plied in the synthesis of substituted 1H-benzimidazole from
cally aminated in 71 and 79% yield, respectively (Table 2, 2-iodoacetanilide and aqueous ammonia in one pot
Entries 3 and 8).
(Scheme 1).[15]
Eur. J. Org. Chem. 2010, 1854–1857
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Z. Wu, Z. Jiang, D. Wu, H. Xiang, X. Zhou
SHORT COMMUNICATION
Table 3. Sulfonato–Cu(salen) complex 1 catalyzed amination of aryl halides with aqueous ammonia in neat water catalyzed
aryl bromides with ammonia.[a]
by the water-soluble sulfonato–Cu(salen) complex. A wide
range of aryl bromides and aryl iodides were found to be
applicable to the catalytic system. In addition, substituted
1H-benzimidazole was prepared easily by coupling of aque-
ous ammonia with 2-iodoacetanilide in one pot with this
catalytic system. Overall, we believe this environmentally
benign system will find wide application in organic synthe-
sis. Further application of the inexpensive, water-soluble
complex catalysts is currently under investigation in this
laboratory.
Experimental Section
Typical Procedure for the Catalysis: Catalyst (0.025 mmol), aryl ha-
lide (0.5 mmol), NaOH (1 mmol), aqueous ammonia (1 mL), and
water (2 mL) were added to a sealed tube. The reaction mixture
was stirred at 120 °C for 12 h and then cooled to room temperature
and extracted with ethyl acetate. The organic layer was then dried
with anhydrous Na2SO4, and the solvent was removed under re-
duced pressure. The aniline product was finally obtained by column
chromatography on silica gel. All the products were confirmed by
1H and 13C NMR spectroscopic analysis.
Supporting Information (see footnote on the first page of this arti-
cle): Experimental procedures and characterization data; 1H and
13C NMR spectra of all products.
Acknowledgments
This project was sponsored by the Natural Science Foundation of
China (Nos. 20672075, 20771076, 20901052) and the Sichuan Prov-
incial Foundation (08ZQ026-041). We also thank the Analysis and
Testing Center of Sichuan University for NMR measurements.
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Eur. J. Org. Chem. 2010, 1854–1857

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Received: January 18, 2010
Published Online: February 19, 2010
Eur. J. Org. Chem. 2010, 1854–1857
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
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