Copper/oxalohydrazide/ketone catalyzed synthesis of primary arylamines via coupling of aryl halides with aqueous ammonia in water

Article abstract of DOI:10.1016/j.tet.2011.05.068

The coupling reaction of aryl halides with aqueous ammonia was catalyzed by copper/oxalohydrazide/ketone system in water to yield primary arylamines without inert atmosphere. This method was fast and facile. The coupling reaction proceeded at 90 °C for 20-80 min, or at room temperature for a prolonged reaction time. A variety of aryl bromides and iodides were found to be applicable to this three-component catalytic system, which afforded good to excellent isolated yields.

Full text of DOI:10.1016/j.tet.2011.05.068

Tetrahedron 67 (2011) 5450e5454
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Copper/oxalohydrazide/ketone catalyzed synthesis of primary arylamines via
coupling of aryl halides with aqueous ammonia in water
*
Ying Li, Xinhai Zhu , Fei Meng, Yiqian Wan
School of Chemistry and Chemical Engineering, Sun Yat-Sen University, Guangzhou 510275, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
The coupling reaction of aryl halides with aqueous ammonia was catalyzed by copper/oxalohydrazide/
ketone system in water to yield primary arylamines without inert atmosphere. This method was fast and
facile. The coupling reaction proceeded at 90 C for 20e80 min, or at room temperature for a prolonged
reaction time. A variety of aryl bromides and iodides were found to be applicable to this three-
component catalytic system, which afforded good to excellent isolated yields.
Ó 2011 Elsevier Ltd. All rights reserved.
Received 15 March 2011
Received in revised form 11 May 2011
Accepted 17 May 2011
ꢀ
Available online 25 May 2011
Keywords:
Copper
Primary arylamine
Water
Coupling reaction
1. Introduction
coupling reactions were all performed in organic solvents, which are
toxic, expensive, and less environmentally benign.
Aromatic amines are ubiquitous in biological systems, and
commonly used for various applications, such as pharmaceutical,
agrochemicals, dyestuffs, and conductive and emissive polymers.
Among them, primary aromatic amine is probably one of the most
More recently, it was demonstrated that water can be applied as
the solvent for various organic syntheses, of which the copper-
7
catalyzed CeN coupling reactions in aqueous media have attrac-
8
ted much attention. However, there are only a few reports on the
1
important species. Significant effort has been made to prepare
copper-catalyzed coupling of aryl halides with aqueous ammonia in
9
primary amine due to its importance. Although ammonia is an
abundant and cheap nitrogen source for the industrial production
water. In addition, those reported approaches are all limited by the
somewhat stringent reaction conditions, such as the high temper-
ature and the long reaction time.
2
of organic amino compounds, the synthesis of primary aromatic
amines by coupling of aryl halides with ammonia has proven to
be impractical due to the undesirable side reaction between the
reactive aniline product and excessive ammonia, which yields
diaryl amine.
Previously, we have demonstrated three-component catalyst
CuO/oxalyldihydrazide/hexane-2,5-dione was an effective catalytic
10
system for the amination of aryl halides in water. As an extension,
we herein report copper/oxalohydrazide/ketone as an effective
catalytic system for coupling of aryl bromides and iodides with
aqueous ammonia in water. The current method is attractive due to
a few reasons. First, it can be applied for both aryl iodides and
bromides. Second, it can tolerate a wide range of functional groups.
Moreover, the catalytic system employed is easily accessible and
inexpensive. Importantly, aqueous ammonia is used as nitrogen
source, which can significantly reduce the cost of the production.
Finally, the reaction can proceed at much lower temperature in
short time (or even at room temperature for a prolonged reaction
time) with no need for the protection of inert atmosphere.
The traditional methods to obtain anilines require the usage of
3
ammonia surrogates with palladium or copper catalysts. Recently,
the Pd-catalyzed selective amination of aryl halides with ammonia
were reported.4 In addition, Cu-catalyzed coupling of aryl halides
with ammonia to afford the desired anilines under mild conditions
5
were reported too. Chang and Zhao reported, respectively, that us-
ing CuI as the catalyst, with
ligand, the coupling reaction between aryl iodides with NH
aq) readily took place even at room temperature. However, these
L-proline as the ligand or without any
4
Cl or NH
3
(
methods did not work well for aryl bromides with electron-donating
6
groups. It is noted that the above-mentioned metal-catalyzed
2. Results and discussion
Initially, we screened the reaction parameters with the coupling
reaction of 4-bromotoluene and aqueous ammonia as a model
*
Corresponding author. Tel./fax: þ86 20 84113610; e-mail address: zhuxinh@
mail.sysu.edu.cn (X. Zhu).
0
040-4020/$ e see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2011.05.068

Y. Li et al. / Tetrahedron 67 (2011) 5450e5454
5451
reaction. Consistent with our previous results,10 we found that
when using water as the solvent, the CuO/oxalohydrazide/hexane-
Table 2
Amination of 4-bromotoluene: optimization of the other catalytic conditionsa
[
Cu] /oxalohydrazide
2
8
,5-dione catalyzed model reaction generated the target product in
0% GC yield (Table 1, entry 2). We then examined other ketones as
hexane-2,5-dione (L1)
Me
Br
+
NH3 H O
2
Me
NH2
2
equiv base
PTC, H
additives for the model reaction. As shown in Table 1, hexane-2,5-
dione (L1) gave the highest conversion and yield. Furthermore,
when hexan-2-one (L5) was added, the reaction provided good
conversion and yield (Table 1, entry 6), only slightly lower than L1
but much higher than other ketones tested (Table 1, entries 3e5).
Almost no product was detected in the absence of ketone (Table 1,
entry 1), verifying the importance of ketone additives. It is also
interesting to find that 3-methylcyclopent-2-enone (L6, entry 7),
which could be derivatized from L1 under the given reaction con-
dition, only shows limited acceleration of the reaction compared to
L1. Thus, L1 was chosen as the additive for the following studies.
2
O
1a
3a
ꢀ
Entry [Cu]
Base
KOH
2/1 Oxalohydrazide/L1 T (
C) Time Conversion/
(min.) Yield b(%)
(mol %)
1
2
3
4
5
6
7
8
9
1
CuO
CuO
CuO
CuO
CuO
4
4
4
4
6
6
6
6
6
6
6
6
6
50/100
50/100
50/100
50/100
50/100
50/100
50/100
50/100
50/100
50/100
20/100
10/100
20/50
120
120
120
120
120
120
120
120
120
90
8
8
100/80
91/85
K
K
K
K
2
3
2
2
CO
PO
CO
CO
3
4
8
71/66
3
10
10
10
10
10
10
80
80
80
80
97/91
99/96
80/78
88/79
98/86
15/14
100/92
98/95
96/91
3
CuSO4 K2CO3
CuI
K
K
K
K
2
CO
2
CO
2
CO
2
CO
3
3
3
3
Cu
Cu
2
O
0
CuO
CuO
CuO
CuO
Table 1
11
12
K2CO3
K2CO3
90
90
90
a
Amination of 4-bromotoluene using different ketones as additive
c
13
K
2
CO
3
99/94, 96/88
97/89
5
mol% CuO
0 mol% oxalohydrazide
equiv ketone
d
5
1
e
9
9
7/91
Me
Br
+
NH
3
H
2
O
Me
NH
2
1/84f
2
equiv KOH
14
CuO
K
2
CO
3
6
20/25
90
80
90/76
1a
25 mol% TBAB
2
3a
0
H
O, 120 C, 8 min.
a
Reaction conditions: 4-bromotoluene (1.0 mmol), commercial 28% aqueous
, [Cu]-catalyst, oxalohydrazide, hexane-2,5-dione (L1), base (2 mmol), TBAB
O (1 mL).
NH
3
Conversion b(%)
Yield b(%)
1
(25 mol %), H
2
Entry
Ligands
b
Calculated by GC/MS.
1
d
2
c
d
e
f
TBAC (25 mol %) was used as PTC.
TEBAC (25 mol %) was used as PTC.
TBAB (15 mol %).
O
2
L1
100
80
CuO (2.5 mol %).
O
O
3
4
L2
L3
9
3
9
3
of bases tested, K
selectivity simultaneously (Table 2, entries 1e3), in comparison to
KOH and K PO
2 3
CO can yield both the high conversion and
O
3
4
.
Further investigation of reaction time and temperature revealed
ꢀ
that the reaction performed at 90 C for 80 min had the comparable
ꢀ
yield as that performed at 120 C for 10 min (Table 2, entries 5 and
O
10). In order to avoid the higher reaction pressure, and for the
convenience of the experimentation, the rest of the reactions were
performed at 90 C. A more thorough screening of experimental
conditions shows that the yield of the target product did not change
significantly even if the ratio of oxalyldihydrazide and L1 were
reduced to 20 mol % and 50 mol %, respectively (Table 2, entry 13).
However, when the catalyst concentration was decreased to
5
6
L4
L5
7
6
ꢀ
O
92
72
2
.5 mol % or the concentration of TBAB was reduced to 15 mol %, the
7
O
L6
14
10
yields were decreased (Table 2, entry 13). Based on these results, we
chose CuO (5 mol %), oxalohydrazide (20 mol %), L1 (50 mol %),
K
2
CO
3
(200 mol %), and TBAB (25 mol %) as the optimized feeding
a
Reaction conditions: 4-bromotoluene (1.0 mmol), commercial 28% aqueous NH
3
ꢀ
recipe, 90 C for the reaction temperature, and 80 min of reaction
for further investigation.
(
(
6.0 mmol), CuO (0.05 mmol), oxalohydrazide (0.5 mmol), ketone (1 mmol), KOH
ꢀ
2 mmol), H
2
O (1 mL), 120 C, 8 min.
b
To demonstrate the scope of the application of this catalytic
system, a wide range of functionalized aryl bromides were coupled
with aqueous ammonia under the optimized condition. As expec-
ted, both aryl bromides with electron-rich or electron-poor para or
meso-substituents and neutral aryl bromide afforded good to ex-
cellent yields (Table 3, entries 1e10,12) when reacted with aqueous
ammonia. The electronic effect on the reactivity was limited, except
for the aryl bromides with electron-withdrawing groups, which
show faster reaction rate (Table 3, entries 9, 10). In comparison,
steric hindrance shows a significant influence on the amination of
aryl bromides (Table 3, entry 11). The moderate yield was obtained
Calculated by GC/MS.
To further optimize the reaction conditions, copper sources,
bases, reaction time and temperature, phase-transfer catalysts,
and the proportions among the starting materials, copper sources,
ligand, and additives were screened using the same model sub-
strate and additives (oxalohydrazide and hexane-2,5-dione). As
shown in Table 2, all copper sources were effective in accelerating
the reactions (Table 2, entries 5e8), except for copper powder
(
Table 2, entry 9). In particular, CuO provided the best catalytic
ꢀ
effect. The tested quaternary ammonium salts used as phase-
transfer catalyst show similar catalytic efficiency. Among them,
TBAB provided the best catalytic effect (Table 2, entry 13). In term
even with prolonged reaction time (120 min) at 120 C. It is note-
worthy that heterocyclic bromides could also be coupled with
aqueous ammonia with excellent yield (Table 3, entry 13).

5452
Y. Li et al. / Tetrahedron 67 (2011) 5450e5454
Table 3
electron-donating para-substituents could afford high yields
Table 4, entries 1e3). It is noteworthy that L3 shows low efficiency
a
Copper/ligand-catalyzed amination of aryl bromides
(
5
mol% CuO
0 mol% oxalohydrazide
0 mol% L1
for accelerating amination of 4-bromotoluene (Table 1, entry 4), but
was effective for coupling reaction between aryl iodides and
aqueous ammonia (Table 4, entry 1e3). Therefore, based on the
selectivity of L1 and L3, the amination of 1-bromo-4-iodobenzene
was successful with L3 as additive, providing 4-bromoaniline in
moderate yield (Table 4, entry 6) with little detection of
2
R
R
5
+
NH2
Br
NH3 H O
2
2
equiv K CO
2 3
2
5 mol% TBAB
1
3
0
H O, 90
C
2
4
-iodoaniline. The relatively lower yield was due to the side
Entry
Aryl bromide
Product
Time (min.)
Yield b (%)
reactions of dehalogenation and coupling reaction between
1
2
3
4
5
6
7
8
9
1a: R¼4-Me
1b: R¼H
3a
3b
3c
3d
3e
3f
3g
3h
3i
80
80
80
80
80
80
80
80
40
40
120
80
79
73
78
90
95
89
68
73
90
81
4-bromoaniline and 1-bromo-4-iodobenzene.
Finally, the coupling of 4-iodoanisole with aqueous ammonia
1c: R¼4-Et
1d: R¼4-OMe
1e: R¼4-Ph
1f: R¼4-Cl
1g: R¼4-F
was carried out at room temperature. With prolonged reaction
time, the reaction proceeded as efficiently as that at high temper-
ature. Based on this observation, a various functionalized aryl io-
dides and aryl bromides were tested and the results were
summarized in Table 5. The result shows that after 24 h, para- or
meso-substituents and neutral aryl iodides reacting with aqueous
ammonia at room temperature afforded good to excellent yields
1h: R¼4-CF
1i: R¼4-Ac
3
10
11
12
1j: R¼4-NO
2
3j
3k
3l
c
1k: R¼2-OMe
1l: R¼3-OMe
23, 57
85
(Table 5, entries 1e4, 6, 7). Even for the aryl iodide bearing ortho-
substituent, the good yield was obtained by extending the reaction
to 72 h (Table 5, entry 5). Compared to the aryl iodides, the aryl
bromides show lower reactivity; the moderate yields were
obtained when the reactions were carried out for 72 h at room
temperature with an increase in the loadings of CuO, oxalohy-
drazide and L1 to 10 mol %, 50 mol % and 100 mol %, respectively
N
1
3
Br
3m
80
90
1
m
a
Reaction conditions: aryl bromide (1 mmol), commercial 28% aqueous NH
6 mmol), CuO (0.05 mmol), oxalohydrazide (0.2 mmol), hexane-2,5-dione (L1,
3
(Table 5, entries 8e14).
(
0
ꢀ
.5 mmol), K
2
CO
3
(2 mmol), H
2
O (1 mL), 90 C.
b
Isolated yield.
c
ꢀ
1
20 C.
Table 5
a
Amination of aryl halides at room temperature
The coupling reactions of aryl iodides with aqueous ammonia
CuO or CuSO
4
oxalohydrazide
under the similar reaction conditions were carried out except for
the shorter reaction time. Most of the coupling reaction was com-
plete within 60 min with high yields, except for 2-iodoanisole,
R
R
L1 or L3
+
NH2
X
3 2
NH H O
2
equivKOH
1
or 2
25 mol% TBAB
3
ꢀ
which was reacted at 120 C for 100 min due to steric hindrance
H O, r.t.
2
(Table 4, entry 7). In contrast, 4-iodoanisole afford lower yield be-
cause of corresponding bis (4-methoxyphenyl) amine was detected
under the same reaction conditions (Table 4, entry 3). However,
when using CuSO , 3-methylbutan-2-one (L3), and KOH as catalyst
4
Yieldb (%)
Entry
Aryl halide
Product
Time (h)
1
2
3
4
5
2a
2b
2c
2d
2g
3a
3b
3d
3i
24
24
24
24
24
48
85
81
91
86
38
51
73
72
80
and base, respectively, iodobenzene and the aryl iodides with
3k
Table 4
a
Copper/ligand-catalyzed amination of aryl iodides
72
5
mol% CuO
0 mol% oxalohydrazide
0 mol% L1
6
7
8
9
10
11
2h
2i
3o
3p
3a
3d
3g
3h
3i
24
24
72
72
72
72
72
72
72
2
R
R
5
c
+
NH2
1a
1d
1g
1h
1i
55
58
53
43
83
60
57
I
NH3 H O
2
c
2
equiv K CO
2
3
c
2
5 mol% TBAB
3
2
0
c
H O, 90
C
2
c
1
1
1
2
3
4
c
1l
1m
3l
3m
Entry
Aryl iodide
Product
Time (min.)
Yieldb (%)
c
c
1
2
3
2a: R¼4-Me
2b: R¼H
3a
3b
3d
20
20
60
84
77
a
Reaction conditions: aryl halide (1 mmol), commercial 28% aqueous NH
(0.05 mmol), oxalohydrazide (0.2 mmol), 3-methyl-2-butanone (L3, 1 mmol),
KOH (2 mmol), H O (1 mL), r.t.
3
(1 mL),
c
CuSO
4
2c: R¼4-OMe
75
c
2
20
86
b
Isolated yield.
4
5
6
7
8
9
2d: R¼4-Ac
3i
3j
3n
3k
3o
3p
30
20
20
100
60
60
86
79
c
CuO (0.1 mmol), oxalohydrazide (0.5 mmol), hexane-2,5-dione (L1, 1.0 mmol).
2e: R¼4-NO
2f: R¼4-Br
2
c
42
d
2g: R¼2-OMe
2h: R¼3-Cl
81
87
80
3. Conclusion
2i: R¼3,5-Dimethyl
a
Reaction conditions: aryl iodide (1 mmol), commercial 28% aqueous NH
3
We have established a universal, efficient, low-cost, and envi-
ronmentally benign method for converting aryl halides into primary
arylamines in water with a three-component catalyst system in-
cluding copper catalytic system, [Cu]/oxalyldihydrazide/ketone. A
variety of functionalized aryl iodides and aryl bromides were cou-
pled with aqueous ammonia efficiently under mild conditions,
(
0
6 mmol), CuO (0.05 mmol), oxalohydrazide (0.2 mmol), hexane-2,5-dione (L1
ꢀ
.5 mmol), K
2
CO
3
(2 mmol), H
2
O (1 mL), 90 C.
b
Isolated yield.
c
CuSO
4
(0.05 mmol), oxalohydrazide (0.2 mmol), 3-methyl-2-butanone (L3,
1
mmol), KOH (2 mmol).
1
d
ꢀ
20 C.

Y. Li et al. / Tetrahedron 67 (2011) 5450e5454
5453
affording good to excellent isolated yields. This method has two
main advantages: (1) Fast and flexible. Compared to the methods
reported in the existing literature, the coupling reaction described
water and brine, dried over anhydrous Na
2
SO
4
, and concentrated in
vacuo. The residue oil was purified by column chromatography on
silica gel (eluting with petroleum ether/ethyl acetate) to afford the
desired products.
ꢀ
here proceeded at lower temperature (90 C) with shorter time
(
20e80 min). The amination of aryl iodides could even be accom-
4.2.1. p-Toluidine (3a) . White solid; mp: 41e44 C; 1H NMR
5
c
ꢀ
plished in water at room temperature within 24 h; the yield was
excellent. Even for the aryl bromides, the good isolation could be
achieved at room temperature via prolonging the reaction time to
(300 MHz, CDCl
3
)
d
: 6.93 (d, J¼8.4 Hz, 2H), 6.58 (d, J¼8.3 Hz, 2H),
13
3.40 (br s, 2H), 2.22 (s, 3H); C NMR (75 MHz, CDCl
3
)
d: 144.0,
þ
7
2 h. Thus, the optimized experimental conditions can be adjusted
130.0, 128.0, 115.5, 20.9; ESI-MS: m/z¼108 [MþH] .
based on the different substrates and synthetic requirements. (2)
Low-cost and environmentally friendly. The ammonia was used as
nitrogen source and the nontoxic and cheap water was selected as
solvent in current study. Moreover, the ingredients of catalytic sys-
tem are all commercially available and inexpensive. The low reaction
temperature producing the lower operational pressure allows the
reactions to be performed without special autoclaves. This is a sig-
nificantly advantage considering both cost and safety for further
scaling-up. We believe that the current method can adopted in
custom synthesis and applied to industrial-scale production. Further
application of this flexible three-component copper catalytic system
for Cu-catalyzed organic reactions in water is under investigation.
5
c
1
4.2.2. Aniline (3b) . Pale yellow oil; H NMR (300 MHz, CDCl
3
) d:
7.18e7.09(m, 2H), 6.74e6.71(m, 1H), 6.69e6.62(m, 2H), 3.46(br s,
2H); C NMR (75 MHz, CDCl
1
3
3
)
d
: 146.9, 129.6, 118.8, 115.5; ESI-MS:
þ
m/z¼94 [MþH] .
4.2.3. 4-Ethyl-aniline (3c) . Pale yellow oil; 1H NMR (300 MHz,
CDCl
: 6.96 (d, J¼8.5 Hz, 2H), 6.59 (d, J¼8.4 Hz, 2H), 3.37 (br s,
2H), 2.53 (q, J¼7.6 Hz, 2H), 1.18 (t, J¼7.6 Hz, 3H); C NMR (75 MHz,
CDCl
: 144.2, 134.7, 128.8, 115.6, 28.4, 16.4; ESI-MS: m/z¼122
[MþH] .
11
3
) d
13
3
) d
þ
5
c
ꢀ
4
.2.4. 4-Methoxybenzenamine (3d) . Dark red solid; mp: 56e58 C;
H NMR (300 MHz, CDCl
1
4
4
. Experimental section
3
)
d
: 6.72 (d, J¼8.8 Hz, 2H), 6.62 (d,
13
J¼8.8 Hz, 2H), 3.72 (s, 3H), 3.24 (br s, 2H); C NMR (75 MHz, CDCl
3
)
þ
.1. General
d
: 152.9, 140.2, 116.6, 115.0, 56.1; ESI-MS: m/z¼124 [MþH] .
5
All aryl halides and 28% aqueous ammonia were commercially
4.2.5. Biphenyl-4-amine (3e) b. Pale yellow solid; mp: 52e54 ꢀC;
1
available and used as received. Flash column chromatography was
performed with silica gel (200e300 mesh). Thin-layer chroma-
tography was carried out with Merck silica gel 60 F254 plates. All
yields reported in the publication represent an average of at least
3
H NMR (300 MHz, CDCl ) d: 7.62e7.50 (m, 2H), 7.47e7.35 (m, 4H),
13
7.33e7.21 (m, 1H), 6.76 (d, J¼8.6 Hz, 2H), 3.73 (br s, 2H); C NMR
(75 MHz, CDCl
3
)
d
: 146.1, 141.4, 131.8, 128.9, 128.2, 126.6, 126.5,
þ
115.7; ESI-MS: m/z¼170 [MþH] .
1
two independent runs. All products were characterized by MS, H
NMR, and 13C NMR data with which compared to the previously
reported data. NMR spectra were recorded at room temperature on
a Mercury-Plus 300 instrument with TMS as an internal reference.
ESI-MS was run on a LCMS-2010A. EI-MS was run on a Thermo EI-
mass spectrometer. GC/MS was run on a Voyager GC/MS in-
strument with an electron impact (70 eV) mass selective detector.
4.2.6. 4-Chloroaniline (3f) . Pale yellow solid; mp: 67e69 C; 1
NMR (300 MHz, CDCl
: 7.09 (d, J¼8.8 Hz, 2H), 6.60 (d, J¼8.8 Hz,
2H), 3.68 (br s, 2H); C NMR (75 MHz, CDCl : 145.2, 129.3, 123.3,
5f
ꢀ
H
3
) d
13
3
) d
þ
þ
116.5; MS (EI ): m/z¼127 [M ].
4.2.7. 4-Fluoroanline (3g)9a. Pale yellow oil; 1H NMR (300 MHz,
CDCl : 6.83 (t, J¼8.7 Hz, 2H), 6.64e6.53 (m, 2H), 3.48 (br s, 2H);
3
) d
13
4
.2. General procedure for the coupling of aryl halides with
C NMR (75 MHz, CDCl : 158.1, 155.0, 142.6, 116.3, 116.0, 115.7;
3
) d
þ
aqueous ammonia in water
ESI-MS: m/z¼112 [MþH] .
Under heating conditions: A 10 mL of vessel was charged with
4.2.8. 4-(Trifluoromethyl)anline (3h)6a. Yellow oil; 1H NMR
CuO (4 mg, 0.05 mmol)/CuSO
drazide (24 mg, 0.2 mmol), hexane-2,5-dione (57 mg, 0.5 mmol) or
-methylbutan-2-one (86 mg, 1.0 mmol), TBAB (81 mg, 0.25 mmol),
aryl halide (1 mmol), commercial 28% aqueous ammonia (6 mmol),
CO (276 mg, 2 mmol) or KOH(112 mg, 2 mmol), H O(1.0 mL). The
4
(13 mg, 0.05 mmol), oxalyldihy-
(300 MHz, CDCl
3.90 (br s, 2H); C NMR (75 MHz, CDCl
120.5, 120.1, 119.7, 114.4; MS (EI ): m/z¼161 [M ].
3
)
d
: 7.35 (d, J¼8.2 Hz, 2H), 6.64 (d, J¼8.3 Hz, 2H),
13
3
)
d: 149.6, 126.8, 123.3,
þ
þ
3
5
f
ꢀ
K
2
3
2
4.2.9. 4-Aminoacetophenone (3i) . White solid; mp: 103e105 C;
1
vessel was sealed with a septum and placed into an oil bath, which
H NMR (300 MHz, CDCl
3
)
d
: 7.76 (d, J¼8.7 Hz, 2H), 6.61 (d,
ꢀ
13
was pre-heated to 90 C. The reaction mixture was stirred for
J¼8.8 Hz, 2H), 4.09 (br s, 2H), 2.47 (s, 3H); C NMR (75 MHz, CDCl
3
)
þ
8
0 min at this temperature. After cooling to room temperature, the
d: 196.7, 151.7, 131.0, 127.7, 113.9, 26.4; ESI-MS: m/z¼136 [MþH] .
reaction mixture was extracted with ethyl acetate. The combined
organic phases were washed with water and brine, dried over an-
5
f
ꢀ
1
4.2.10. 4-Nitroanline (3j) . Yellow solid; mp: 146e147 C; H NMR
(300 MHz, DMSO)
: 7.90 (d, J¼9.2 Hz, 2H), 6.67 (s, 2H), 6.56 (d,
J¼9.2 Hz, 2H); C NMR (75 MHz, CDCl : 156.3, 136.3, 127.03,
hydrous Na
2
SO
4
, and concentrated in vacuo. The residual oil was
d
1
3
purified by column chromatography on silica gel (eluting with
petroleum ether/ethyl acetate) to afford the desired products.
3
) d
þ
þ
113.03; MS (EI ): m/z¼138 [M ].
At room temperature: A 10 mL of vessel was charged with CuSO
13 mg, 0.05 mmol, for aryl iodides) or CuO (8 mg, 0.10 mmol, for
aryl bromides), oxalyldihydrazide (24 mg, 0.2 mmol or 59 mg,
.5 mmol), hexane-2,5-dione(57 mg, 0.5 mmol or 114 mg,
.0 mmol), TBAB (81 mg, 0.25 mmol), aryl halide (1 mmol), com-
mercial 28% aqueous ammonia (1 mL), KOH(112 mg, 2 mmol),
O(1.0 mL). The vessel was sealed with a septum and the reaction
4
4.2.11. 2-Methoxybenzenamine (3k) . Pale red oil; 1H NMR
(300 MHz, CDCl
NMR (75 MHz, CDCl
ESI-MS: m/z¼124 [MþH] .
5
f
(
13
3
)
d
: 6.78(m, 4H), 3.87(s, 3H), 3.80(br s, 2H);
C
0
1
3
)
d
: 147.5, 136.4, 121.3, 118.7, 115.3, 110.7, 55.8;
þ
4.2.12. 3-Methoxybenzenamine (3l) . Pale yellow oil; 1H NMR
5c
H
2
mixture was stirred at room temperature for 24 h (for aryl iodides)
or 72 h (for aryl bromides). Then the reaction mixture was extracted
with ethyl acetate. The combined organic phases was washed with
(300 MHz, CDCl
3.45(br s, 2H); C NMR (75 MHz, CDCl
104.2, 101.4, 55.4; ESI-MS: m/z¼124 [MþH] .
3
)
d
: 7.02(t, J¼8.0 Hz, 1H), 6.26(m, 3H), 3.73(s, 3H),
1
3
3
)
d
: 160.9, 147.9, 130.3, 108.2,
þ

5454
Y. Li et al. / Tetrahedron 67 (2011) 5450e5454
ꢀ
4
.2.13. Pyridine-3-amine (3m)5b. Pale yellow solid; mp: 61e63 C;
Ahman, J.; Sadighi, J. P.; Singer, R. A.; Buchwald, S. L. Tetrahedron Lett. 1997, 38,
6367e6370; (d) Figueroa, S. J.; Liu, Y.; Muchowski, J. M.; Putman, D. G. Tetra-
hedron Lett. 1998, 39, 1313e1316; (e) Gao, X.; Fu, H.; Qiao, R.; Jiang, Y.; Zhao, Y. J.
Org. Chem. 2008, 73, 6864e6866; (f) Trabanco, A. A.; Vega, J. A.; Fern ꢀa ndez, M.
A. J. Org. Chem. 2007, 72, 8146e8148; (g) Prashad, M.; Hu, B.; Lu, Y.; Draper, R.;
Har, D.; Repi ꢁc , O.; Blacklock, T. J. J. Org. Chem. 2000, 65, 2612e2614; (h) Lee, D.;
1
H NMR (300 MHz, CDCl
.49(br s, 2H); 13C NMR (75 MHz, CDCl
) d
3
3
)
d
: 8.07e7.96(m, 2H), 7.05e6.93(m, 2H),
3
: 143.0, 139.7, 137.4, 124.0,
þ
121.7; ESI-MS: m/z¼95 [MþH] .
Hartwig, J. F. Org. Lett. 2005, 7, 1169e1172; (i) Lee, S.; Jørgensen, M.; Hartwig, J.
F. Org. Lett. 2001, 3, 2729e2732; (j) Huang, X.; Buchwald, S. L. Org. Lett. 2001, 3,
3417e3419.
ꢀ
4
.2.14. 4-Bromoaniline (3n)5b. Pale solid; mp: 60e63 C; 1H NMR
: 7.21 (d, J¼8.6 Hz, 2H), 6.53 (d, J¼8.6 Hz, 2H),
.60 (s, 2H); C NMR (75 MHz, CDCl : 145.6, 132.2, 116.9, 110.4;
(
3
300 MHz, CDCl ) d
13
4. (a) Shen, Q.; Hartwig, J. F. J. Am. Chem. Soc. 2006, 128, 10028e10029; (b) Surrry,
D. S.; Buchwald, S. L. J. Am. Chem. Soc. 2007, 129, 10354e10355; (c) Schulz, T.;
Torbog, C.; Enthaler, S.; Schaffner, B.; Dumrath, A.; Spannenberg, A.; Neumann,
H.; Borner, A.; Beller, M. Chem.dEur. J. 2009, 15, 4528e4533; (d) Wills, M. C.
Angew. Chem., Int. Ed. 2007, 46, 3402e3404; (e) Vo, G. D.; Hartwig, J. F. J. Am.
Chem. Soc. 2009, 131, 11049e11061; (f) Lundgren, R. J.; Sappong-Kumankumah,
A.; Stradiotto, M. Chem.dEur. J. 2010, 16, 1983e1991; (g) Lundgren, R. J.;
Peters, B. D.; Alsaben, P. G.; Stradiotto, M. Angew. Chem., Int. Ed. 2010, 49,
4071e4074.
. (a) Diao, X.; Wang, Y.; Jiang, Y.; Ma, D. J. Org. Chem. 2009, 74, 7974e7977; (b)
Xia, N.; Taillefer, M. Angew. Chem., Int. Ed. 2009, 48, 337e339; (c) Xu, H.; Wolf, C.
Chem. Commun. 2009, 3035e3037; (d) Guo, Z.; Guo, J.; Song, Y.; Wang, L.; Zou,
G. Appl. Organomet. Chem. 2009, 23, 150e153; (e) Jiang, L.; Lu, X.; Zhang, H.;
Jiang, Y.; Ma, D. J. Org. Chem. 2009, 74, 4542e4546; (f) Wang, D.; Cai, Q.; Ding, K.
Adv. Synth. Catal. 2009, 351, 1722e1726; (g) Wu, X.; Darcel, C. Eur. J. Org. Chem.
3
3
) d
þ
þ
MS (EI ): m/z¼173 [M ].
5
c
1
4
7
2
.2.15. 3-Chloroaniline (3o) . Red oil; H NMR (300 MHz, CDCl ) d:
3
.01(t, J¼7.9 Hz, 1H), 6.70e6.62(m, 2H), 6.51e6.48(m, 1H), 3.68(br s,
13
3
H); C NMR (75 MHz, CDCl ) d: 147.8, 135.0, 130.5, 118.7, 115.1,
þ
113.5; ESI-MS: m/z¼128 [MþH] .
5
5c
4
.2.16. 3,5-Dimethylaniline (3p) . Yellow oil; 1H NMR (300 MHz,
3
CDCl ) d
: 6.41(s, 1H), 6.32(s, 2H), 3.37(br s, 2H), 2.22(s, 6H);
1
3
C NMR (75 MHz, CDCl
3
)
d
: 146.5, 139.2, 120.8, 113.4, 21.7; ESI-MS:
þ
m/z¼122 [MþH] .
2009, 4753e4756; (h) Lang, F.; Zewge, D.; Houpis, I. N.; Volante, R. P. Tetrahe-
dron Lett. 2001, 42, 3251e3254.
6
. (a) Kim, J.; Chang, S. Chem. Commun. 2008, 3052e3054; (b) Tao, C.; Liu, W.; Lv,
A.; Sun, M.; Tian, Y.; Wang, Q.; Zhao, J. Synlett 2010, 1355e1358.
Acknowledgements
7
. (a) Dallinger, D.; Kappe, C. O. Chem. Rev. 2007, 107, 2563e2591; (b) Li, C. J.; Chen,
L. Chem. Soc. Rev. 2006, 35, 68e82; (c) Li, C. J. Chem. Rev. 2005, 105, 3095e3165;
d) Li, C.; Chan, T. In Comprehensive Organic Reactions in Aqueous Media John
The authors are grateful to the National Natural Science Foun-
dation of China (grant nos. 20802095 and 20872182) for their fi-
nancial support.
(
Wiley: New Jersey, 2007; (e) Carril, M.; SanMartin, R.; Dominguez, E. Chem. Soc.
Rev. 2008, 37, 639e647; (f) Herrerias, C. I.; Yao, X.; Li, Z.; Li, C. J. Chem. Rev. 2007,
107, 2546e2562; (g) Chen, G.; Zhu, X.; Cai, J.; Wan, Y. Synth. Commun. 2007, 37,
1
355e1361; (h) Chen, G.; Weng, J.; Zheng, Z.; Zhu, X.; Cai, Y.; Cai, J.; Wan, Y. Eur.
Supplementary data
J. Org. Chem. 2008, 3524e3528.
8
. (a) Oshovsky, G. V.; Ouali, A.; Xia, N.; Zablocka, M.; Boere, R. T.; Duhayn, C.;
Taillefer, M.; Majoral, J. P. Organometallics 2008, 27, 5733e5736; (b) Barbero, N.;
Carril, M.; SanMartin, R.; Dominguez, E. Tetrahedron 2008, 64, 7283e7288; (c)
Wang, Y.; Wu, Z.; Wang, L.; Li, Z.; Zhou, X. Chem.dEur. J. 2009, 15, 8971e8974;
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.tet.2011.05.068.
(d) Liang, L.; Li, Z.; Zhou, X. Org. Lett. 2009, 11, 3294e3297; (e) Xu, H.; Zheng, F.;
References and notes
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3
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1