An improved protocol for synthesis of N-arylamides and benzoxazoles by the copper-catalyzed reaction of aryl halides with nitriles

Article abstract of DOI:10.1016/j.tet.2013.09.059

An improved protocol for the synthesis of N-arylamides and benzoxazoles by the copper-catalyzed reaction of aryl halides with nitriles has been developed. Use of acetaldoxime as the hydrolysis reagent instead of H₂O facilitates the operation of the reaction. The significantly decreased amount of nitriles, along with use of weak base K₂CO₃ instead of strong base KOH, makes this transformation atom-efficient and environmentally benign. A variety of N-arylamides and benzoxazole derivatives can be synthesized according to this approach.

Full text of DOI:10.1016/j.tet.2013.09.059

Accepted Manuscript
An improved protocol for synthesis of N-arylamides and benzoxazoles by the copper-
catalyzed reaction of aryl halides with nitriles
Dong-Xue Zhang, Shi-Kai Xiang, Hao Hu, Wen Tan, Chun Feng, Bi-Qin Wang, Ke-
Qing Zhao, Ping Hu, Hua Yang
PII:
S0040-4020(13)01481-6
10.1016/j.tet.2013.09.059
TET 24834
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 24 July 2013
Revised Date: 9 September 2013
Accepted Date: 19 September 2013
Please cite this article as: Zhang D-X, Xiang S-K, Hu H, Tan W, Feng C, Wang B-Q, Zhao K-Q, Hu P,
Yang H, An improved protocol for synthesis of N-arylamides and benzoxazoles by the copper-catalyzed
reaction of aryl halides with nitriles, Tetrahedron (2013), doi: 10.1016/j.tet.2013.09.059.
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An improved protocol for synthesis of N-
arylamides and benzoxazoles by the copper-
catalyzed reaction of aryl halides with
nitriles
Leave this area blank for abstract info.
Dong-Xue Zhang, Shi-Kai Xiang,* Hao Hu, Wen Tan, Chun Feng, Bi-Qin Wang,* Ke-Qing Zhao, Ping Hu and
Hua Yang
College of Chemistry and Material Sciences, Sichuan Normal University, Chengdu 610068, Sichuan, China
H
I
R2
N
R1
R1
CuI (10%),
O
DMEDA (15%)
2
or + R CN
or
K CO (2~3 equiv.),
2
3
X1
CH CH=NOH (3 equiv.),
3
O
toluene, 120 °C , 15h
R2
X2
N
1
2
up to 95% yield
X , X = I, Br, Cl

ACCEPTED MANUSCRIPT
1
Tetrahedron
journal homepage: www.elsevier.com
An improved protocol for synthesis of N-arylamides and benzoxazoles by the copper-
catalyzed reaction of aryl halides with nitriles
Dong-Xue Zhang, Shi-Kai Xiang,* Hao Hu, Wen Tan, Chun Feng, Bi-Qin Wang,* Ke-Qing Zhao, Ping Hu
and Hua Yang
College of Chemistry and Material Sciences, Sichuan Normal University, Chengdu 610068, Sichuan, China
*
Corresponding author. e-mail address: xiangsk@hotmail.com (Shi-Kai Xiang); wangbiqin1964@126.com (Bi-Qin Wang)
ARTICLE INFO
ABSTRACT
Article history:
Received
An improved protocol for the synthesis of N-arylamides and benzoxazoles by the copper-
catalyzed reaction of aryl halides with nitriles has been developed. Use of acetaldoxime as the
Received in revised form
Accepted
hydrolysis reagent instead of H
decreased amount of nitriles, along with use of weak base K
2
O facilitates the operation of the reaction. The significantly
CO instead of strong base KOH,
2
3
Available online
makes this transformation atom-efficient and environmentally benign. A variety of N-arylamides
and benzoxazole derivatives can be synthesized according to this approach.
Keywords:
copper;
aryl halides;
nitriles;
2
009 Elsevier Ltd. All rights reserved.
amides
benzoxazoles
1
. Introduction
H
I
R2
N
R1
N-Arylamides are present in a wide variety of biologically
R1
1
O
active molecules and organic materials. Synthesis of them has
aroused great interest of organic chemists. As a common
method for the synthesis of N-Arylamides, Goldberg reactions
are usually carried out under harsh conditions. In recent decades,
ligands assisted copper-catalyzed Goldberg reaction has been
developed greatly, which makes it possible to synthesize N-
arylamides under mild conditions. General, aryl monohalides are
CuI, DMEDA, K CO
2
3
1
-3
2
or + R CN
X1
or
CH CH=NOH, toluene
3
2
O
R2
X2
N
3
1
2
X , X = I, Br, Cl
used as coupling partner of amides in Goldberg reaction.
Scheme 1. An improved protocol.
However, if aryl o-dihalides are utilized as substrates,
4
2. Results and Discussion
benzoxazoles can be produced through a domino C-N and C-O
5
coupling. Moreover, the reactant amides in the Goldberg
Initially, we investigated the coupling reaction of iodobenzene
a with benzonitrile 2a in toluene using KOH/Cs CO as the
mixed base and H O as the hydrolysis reagent according to our
6
-8
reaction can be prepared easily from nitriles by hydrolysis.
1
2
3
Recently we developed an amination reaction of aryl halides with
9
2
nitriles. The use of nitriles as nitrogen nucleophiles can make the
9
previous method. Under this condition, the product N-arylamide
a was obtained in a yield of 42% (entry 1, Table 1). It was very
regretful that no product was available if only weak base Cs CO
or K CO was used in the reaction (entry 2-3, Table 1). It implied
that weak base Cs CO or K CO could not promote in-situ
synthesis of N-arylamides simpler than that from amides through
in-situ hydrolysis. A variety of N-arylamides or benzoxazoles can
be synthesized by the approach utilizing aryl monohalides or aryl
o-dihalides as the partners of the nitriles respectively. Despite
above-mentioned advantages, however, the reaction still suffered
from several limitations: (1) It is difficult to control the amount
3
2
3
2
3
2
3
2
3
hydrolysis of nitriles in this condition. Inspired by related
8
literature, we decided to utilize acetaldoxime as the hydrolysis
of H O strictly; (2) Use of reactant nitriles as the solvent deviated
2
reagent instead of H
reaction can undergo smoothly under the condition of weak base
Cs CO or K CO to generate the desired product 3a in a good
2
O. The experimental results showed the
from atom economy; (3) It is bad for functional group tolerance
to use strong base KOH. Herein, we will report an improved
protocol for the synthesis of N-arylamides and benzoxazoles by
the copper-catalyzed reaction of aryl halides with nitriles
2
3
2
3
yield with the aid of acetaldoxime (entries 4-5, Table 1). It was
pleased, with the temperature raised to 110 °C or 120 °C, the
yields were increased to 79%, 94% respectively (entries 6-7,
(
Scheme 1). The improved protocol can effectively overcome the
above-mentioned shortcomings and make the synthesis of N-
arylamides and benzoxazoles more efficient.

ACCEPTED MANUSCRIPT
2
Tetrahedron
Table 1). Lower catalyst loading reduced the yield significantly
entry 8, Table 1).
desired products 3 in good yields (entries 1-6, Table 3).
However, it was observed that the reaction could be affected by
steric effects by comparing the data from entries 2-4 in Table 3.
It is notable that heteroaryl nitriles 2g, 2h and aliphatic nitriles 2i,
(
Table 1. Copper-catalyzed reaction of iodobenzene 1a with
benzonitrile 2a in different conditions.
a
2j can also smoothly undergo this reaction to generate the
CuI (10 mmol %),
H
corresponding products 3 in moderate yields (entries 7-10, Table
3).
I
CN
DMEDA (15 mmol %)
N
+
base, additive, toluene
O
Table 2. Copper-catalyzed reaction of different aryl halides 1
100 °C , 15h
a
1a
2a
3a
with benzonitrile 2a.
CuI (10 mmol %),
H
entry base (2.0 equiv.) additive (equiv.) T ( °C ) yield (%)
I
DMEDA (15 mmol %)
N
Ph
1b
2
KOH/Cs CO
H O (8.5)
100
100
100
42
0
R
+ PhCN
2
3
2
R
K CO , CH CH=NOH,
2
3
3
O
Cs CO
H O (8.5)
2
3
2
toluene,120 °C , 15h
1
2
1
3
3
K CO
H O (8.5)
0
2
3
2
entry
3
yield (%)
94
4
Cs CO
CH3CH=NOH (3.0) 100
CH3CH=NOH (3.0) 100
64
63
2
3
5
K CO
H
2
3
I
N
Ph
Ph
6
K CO
CH CH=NOH (3.0) 110
79
94
36
1
2
3
4
1a
3a
3b
3c
3d
2
3
3
O
O
7
8c
K CO
CH CH=NOH (3.0) 120
2
3
3
3
K CO
CH CH=NOH (3.0) 120
Me
I
Me
H
2
3
a
N
1b
25
86
85
Reaction conditions: 1a (0.5 mmol), 2a (1.0 mmol), CuI
0.05 mmol), DMEDA (N, N’-dimethyl-1, 2-ethanediamine,
.075 mmol), base (1.0 mmol), additive, toluene (2.0 mL), 15h,
(
0
H
N
Me
I
I
under Ar. The yields were isolated yields.
Me
Ph
1c
b
KOH (0.25 mmol.), Cs
2
3
CO (0.75 mmol).
O
O
c
0.025 mmol CuI and 0.0375 mmol DMEDA were used.
H
N
Ph
1d
The scope of the coupling reaction of aryl halides with nitriles
was expanded to a variety of substituted aryl halides 1. Aryl
halides 1 with both electron-donating groups and electron-
withdrawing groups smoothly underwent the transformation
generating the desired products 3 in moderate to excellent yields
Me
MeO
Cl
Me
H
I
N
Ph
5
6
7
1e
1f
3e
3f
88
95
88
79
O
(
25-95%, Table 2). 2-Methyliodobenzene 1b gave the desired
MeO
Cl
product in a lower yield than 3-methyliodobenzene 1c and 4-
methyliodobenzene 1d, which indicated that the reaction wound
be affected by steric effects (entries 2-4, Table 2). 4-
Methoxyiodobenzene 1e underwent this transformation to
generate the desired product 3e in a good yield of 88% (entry 5,
Table 2). Substituted iodobenzene with Cl, F smoothly led to
corresponding amides in excellent yields of 95%, 88%
respectively, with the halogen substituent group intact (entries 6-
, Table 2). It is notable that strong electron-withdrawing group
nitro almost does not affect the reaction, and the yield is 79%
entry 8, Table 2). Surprisingly, 4-aminoiodobenzene 1i and 3-
hydroxyiodobenzene 1j could also form the corresponding
products 3i and 3j in yields of 85%, 46% respectively, with the
H
I
N
Ph
Ph
O
H
I
N
1g
1h
3g
3h
O
F
F
7
H
I
N
Ph
8
(
O
O N
2
O N
2
H
N
I
Ph
Ph
2
functional groups NH , OH compatible under the catalytic
conditions which could be further transformed into other
functionalities (entry 9-10, Table 2). The heterocyclic compound
9
1i
3i
3j
85
46
35
O
H N
2
H N
2
H
2
-iodothiophene 1k sucsessfully underwent the reaction despite a
HO
I
HO
N
10b
1j
low yield of 35% (entry 11, Table 2). In addition, MOM
protected 3-hydroxyiodobenzene could also be transformed into
the corresponding product 3l in a good yield of 76% (entries 12,
Table 2).
O
H
N
Ph
11
1k
3k
I
To investigate the scope of the nitriles in this transformation,
iodobenzene 1a was selected as the partner to react with different
nitriles. The results in Table 3 show that various kinds of aryl
nitriles, heteroaryl nitriles and aliphatic nitriles can undergo this
transformation to generate the desired products in moderate to
excellent yields (38-94%). The experimental data showed that the
electronic properties of the substituents of aryl nitriles had little
effect on the reation. Both electron-donating groups and electron-
withdrawing groups smoothly underwent this reaction generating
S
S
O
H
N
MOMO
I
MOMO
Ph
3l
12
1l
76
O
a
Reaction conditions: 1 (0.5 mmol), 2a (1.0 mmol), CuI (0.05
mmol), DMEDA (N, N’-dimethyl-1, 2-ethanediamine, 0.075
mmol), K CO (1.0 mmol), CH CH=NOH (1.5 mmol), toluene
2.0 mL), 120℃, 15h, under Ar. The yields were isolated yields.
2
3
3
(

ACCEPTED MANUSCRIPT
3
b
1
.5 mmol K
2
CO
3
were used.
that aryl nitriles with electron-donating groups gave higher
yields than ones with electron-withdrawing groups (entries 1-7,
Table 4). Moreover, 2-methylbenzonitrile 2b gave a lower yield
than 3-methylbenzonitrile 2c and 4-methylbenzonitrile 2d
indicating the annulation reaction can also be affected by steric
effects (entries 2-4, Table 4). It is notable that pentanenitrile 2i
also smoothly led to desired product 4h in a yield of 41% (entry
8, Table 4). In addition, other o-dihalobenzenes 1, 2-
diiodobenzene 1n, 1-chloro-2-iodobenzene 1o, 1, 2-
dibromobenzene 1p also successfully underwent the reaction
despite lower yields than 1-bromo-2-iodobenzene 1m (entries 9-
Table 3. Copper-catalyzed reaction of iodobenzene 1a with
different nitriles 2.
a
CuI (10 mmol %),
H
I
DMEDA (15 mmol %)
N
R
+
RCN
K CO , CH CH=NOH,
2
3
3
O
toluene,120 °C , 15h
1a
2
2
3
entry
3
yield (%)
94
11, Table 4).
CN
H
N
1
2a
3a
O
Me
Me
H
CN
2
2b
2c
N
3m 56
O
O
Me
Me
CN
H
N
3
3n
84
Me
CN
CN
CN
H
4
5
6
2d
2e
2f
N
3o
3p
3q
86
85
91
Me
O
O
O
Cl
F
H
N
Cl
F
H
N
H
N
7
8
9
2g
2h
2i
S
3r
3s
3t
63
38
51
CN
S
O
O
H
N
O
CN
O
H
N
CN
O
H
N
10
2j
3u 52
CN
O
a
Reaction conditions: 1a (0.5 mmol), 2 (1.0 mmol), CuI (0.05
mmol), DMEDA (N, N’-dimethyl-1, 2-ethanediamine, 0.075
mmol), K CO (1.0 mmol), CH CH=NOH (1.5 mmol), toluene
2.0 mL), 120℃, 15h, under Ar. The yields were isolated yields.
2
3
3
(
When o-dihalobenzenes were selected as reaction partners of
nitriles, benzoxazole derivatives can be obtained through a
domino hydrolysis, C-N and C-O coupling (Table 4). Firstly, a
variety of nitriles were employed to react with 1-bromo-2-
iodobenzene 1m. The experimental data from entries 1-7 in Table
4
showed that the annulation reaction can be affected by
electronic properties of the substituents of aryl nitriles. It seemed

ACCEPTED MANUSCRIPT
4
Tetrahedron
Table 4. Copper-catalyzed annulation reactions of o-
which are exposed to the copper catalyst A to generate the
metallic intermediates C. Aryl halides 1 undergo an oxidative
addition to intermediates C to form the metallic intermediates D,
which produce the amide products 3 through the reductive
elimination reaction. The amides 3 subsequently enter into the
next cycle, in which metallic intermediates E are formed by the
reactions of amides 3 with copper catalyst A under basic
condition. Next, intermediates E undergo an oxidative addition
reaction to get the metallic intermediates F. Subsequent reductive
a
dihalobenzenes 1 with nitriles 2.
CuI (10 mmol %),
X1
N
DMEDA (15 mmol %)
+
RCN
R
K CO , CH CH=NOH,
2
3
3
X2
O
toluene,120 °C, 24h
1
2
4
1
2
entry 1 (X , X )
2
4
yield (%)
CN
N
elimination reactions of intermediates
benzoxazole products 4 and release the catalyst A to complete the
F
generate the
1
I, Br
82
O
catalytic cycle.
1m
2a
4a
Me
N OH
X
Y
Me
N
R'
N +
H
R
2
3
I, Br
CN
2b
55
N
R'
2
Ln(I)Cu
base
O
1
O
1m
4b
+
-
C
MH N
R'
O
Me
Me
CN
CN
CN
N
B
I, Br
86
X = I, Br
Y = H, I, Br, Cl
O
4c
H
X
1m
2c
2d
N
R'
Ln(III)Cu
N
CuX + n L
Cu(I)XLn
Y
O
4
5
I, Br
Me 87
OMe 72
Cl 34
A
D
O
Me
1m
4d
4e
R
N
I, Br
H
N
R'
O
MeO
1m
2k
2e
2f
R
3
O
CN
CN
Y
N
6
7
I, Br
base
O
Cl
F
1m
4f
N
R'
Cu(I)XLn
N
R
I, Br
F
51
A
O
X = I, Br
Y = I, Br, Cl
Y
O
4g
Cu(I)Ln
1m
E
N
8
9
I, Br
41
58
CN
N
R'
N
O
O
4h
R
R'
1m
2i
R
O
F
CN
N
Ln(III)Cu
4
I, I
Y
O
4a
Scheme 2. A proposed mechanism.
1n
2a
CN
N
3. Conclusion
1
0b I, Cl
44
33
In summary, we have developed an improved protocol for the
synthesis of N-arylamides and benzoxazoles by the copper-
catalyzed reaction of aryl halides with nitriles. Use of
acetaldoxime as the hydrolysis reagent instead of H O facilitates
the operation of the reaction. The significantly decreased amount
of nitriles, along with use of weak base K CO instead of strong
base KOH, makes this transformation atom-efficient and
environmentally benign. variety of N-arylamides and
benzoxazole derivatives can be synthesized according to this
approach utilizing aryl monohalides or aryl o-dihalides as the
partners of the nitriles, respectively. Studies on other reactions of
nitriles and the applications are ongoing in our laboratory.
O
4a
1o
2a
CN
N
2
11 Br, Br
O
4a
2
3
1p
2a
a
Reaction conditions: 1 (0.5 mmol), 2 (1.0 mmol), CuI (0.05
A
mmol), DMEDA (N, N’-dimethyl-1, 2-ethanediamine, 0.075
mmol), K CO (1.5 mmol), CH CH=NOH (1.5 mmol), toluene
2.0 mL), 120℃, 24h, under Ar. The yields were isolated yields.
2
3
3
(
b
0
.10 mmol CuI and 0.15 mmol DMEDA were used.
The probable catalytic mechanism for this transformation is
illustrated in Scheme 2. Two catalytic cycles may be involved.
Initially, the hydrolysis of nitriles 2 under basic condition using
acetaldoxime as hydrolysis reagent produces the amide salts B,

ACCEPTED MANUSCRIPT
5
4
. Experimental
N-(4-Methoxyphenyl)benzamide (3e): The reaction of 4-
methoxyiodobenzene 1e (117.0 mg, 0.5 mmol) with benzonitrile
a (103.0 mg, 1.0 mmol) afforded 99.9 mg (88%) of 3e; IR(KBr)
4.1 General information
2
ν
-
1 1
max 3333, 1647, 1602, 1515, 1458, 1414, 825, 715, 692 cm ; H
NMR (400 MHz, CDCl , ppm) δ 7.86 (d, J = 7.2 Hz, 2H), 7.80
s, 1H), 7.56-7.53 (m, 3H), 7.50-7.46 (m, 2H), 6.93-6.90 (m, 2H),
3
.82 (s, 3H); C NMR (100 MHz, CDCl , ppm) δ 165.6, 156.6,
All manipulations were conducted with Schlenk tube under
1
3
Ar. H NMR spectra were recorded on the Varian 400 MHz WB
spectrometers. Chemical shifts (in ppm) were referenced to
tetramethylsilane (δ = 0 ppm) as an internal standard in CDCl
and DMSO-d6. C NMR spectra were obtained by the same
NMR spectrometers and were calibrated with CDCl (δ = 77.00
(
3
1
3
3
1
3
135.0, 131.7, 130.9, 128.7, 126.9, 122.1, 114.2, 55.5; MS (ESI)
+
m/z: [M+Na] 250.1.
3
ppm) or DMSO-d6 (δ = 39.50 ppm). Mass spectra were obtained
using electrospray ionization (ESI) mass spectrometer. Toluene
was freshly distilled over Na. Without otherwise note, other
materials obtained from commercial suppliers were used without
further purification.
N-(4-Chlorophenyl)benzamide (3f): The reaction of 4-
chloroiodobenzene 1f (119.3 mg, 0.5 mmol) with benzonitrile 2a
(
ν
103.0 mg, 1.0 mmol) afforded 110.0 mg (95%) of 3f; IR(KBr)
max 3350, 1655, 1596, 1519, 1493, 1399, 825, 718 cm ; H
-1 1
NMR (400 MHz, DMSO-d6, ppm) δ 10.39 (s, 1H), 7.95 (d, J =
.6 Hz, 2H), 7.83 (d, J = 8.8 Hz, 2H), 7.63-7.52 (m, 3H), 7.42 (d,
7
4.2 General procedure for the synthesis of N-arylamides
13
J = 8.8 Hz, 2H); C NMR (100 MHz, DMSO-d6, ppm) δ 165.7,
38.2, 134.7, 131.7, 128.5, 128.4, 127.7, 127.3, 121.8; MS (ESI)
1
To a suspension of CuI (9.5 mg, 0.05 mmol), K
mg, 1.0 mmol) in toluene (2.0 mL) were added aryl monohalides
(0.5 mmol), nitrile 2 (1.0 mmol), DMEDA (8.0 uL, 0.075
2 3
CO (138.2
+
+
m/z: [M+H] 242.1, [M+Na] 254.1.
1
N-(4-Fluorophenyl)benzamide (3g): The reaction of 4-
fluoroiodobenzene 1g (111.0 mg, 0.5 mmol) with benzonitrile 2a
mmol), acetaldoxime (92.0 uL, 1.5 mmol) under argon. The
reaction mixture was stirred for 15 h at 120 ℃ under argon. The
solution was cooled to room temperature and the solvent was
removed under vacuum. The crude product was purified by
column chromatography on silica gel (eluent: petroleum ether /
ethyl acetate = 5:1) to afford the N-arylamides 3.
(
ν
103.0 mg, 1.0 mmol) afforded 94.5 mg (88%) of 3g; IR(KBr)
max 3349,1653, 1509, 1406, 716 cm ; H NMR (400 MHz,
-1
1
DMSO-d6, ppm) δ 10.31 (s, 1H), 7.95 (d, J = 6.8 Hz, 2H), 7.83-
13
7
.77 (m, 2H), 7.62-7.52 (m, 3H), 7.23-7.17 (m, 2H); C NMR
(
100 MHz, DMSO-d6, ppm) δ 165.5, 159.5, 157.1, 135.5 (d, J =
2
.2 Hz), 134.8, 131.6, 128.4, 127.6, 122.1(d, J = 7.9 Hz),,
N-Phenylbenzamide (3a): The reaction of iodobenzene 1a
102.0 mg, 0.5 mmol) with benzonitrile 2a (103.0 mg, 1.0 mmol)
+
115.2(d, J = 22.3 Hz),; MS (ESI) m/z: [M+H] 216.1.
(
afforded 92.6 mg (94%) of 3a; IR(KBr) νmax 3345, 1655, 1532,
N-(4-Nitrophenyl)benzamide (3h): The reaction of 4-
nitroiodobenzene 1h (124.5 mg, 0.5 mmol) with benzonitrile 2a
-
1 1
750 cm ; H NMR (400 MHz, CDCl
3
, ppm) δ 7.95 (s, 1H), 7.88-
7
.85 (m, 2H), 7.66-7.63 (m, 2H), 7.56-7.52 (m, 1H), 7.49-7.44
(
ν
103.0 mg, 1.0 mmol) afforded 95.6 mg (79%) of 3h; IR(KBr)
13
(
m, 2H), 7.38-7.33 (m, 2H), 7.17-7.13 (m, 1H); C NMR (100
MHz, CDCl , ppm) δ 165.8, 137.9, 134.9, 131.8, 129.0, 128.7,
27.0, 124.5, 120.2; MS (ESI) m/z: [M+H] 198.1.
-1 1
max 3335, 1656, 1506, 1345, 848, 719 cm ; H NMR (400 MHz,
3
DMSO-d6, ppm) δ 10.83 (s, 1H), 8.30-8.26 (m, 2H), 8.10-8.06
+
1
(
7
1
m, 2H), 7.99 (d, J = 6.8 Hz, 2H), 7.67-7.63 (m, 1H), 7.57 (t, J =
13
.2 Hz, 2H); C NMR (100 MHz, DMSO-d6, ppm) δ 166.3,
N-o-Tolylbenzamide (3b): The reaction
of
o-
45.5, 142.5, 134.2, 132.2, 128.5, 127.9, 124.8, 119.8; MS (ESI)
methyliodobenzene 1b (109.0 mg, 0.5 mmol) with benzonitrile
a (103.0 mg, 1.0 mmol) afforded 26.4 mg (25%) of 3b; IR(KBr)
+
m/z: [M+H] 204.0.
2
-
1
1
νmax 3245, 1649, 1524, 1489, 1310, 748 cm ; H NMR (400
MHz, CDCl , ppm) δ 7.96 (d, J = 7.6Hz, 1H), 7.89 (d, J = 7.2
N-(4-Aminophenyl)benzamide (3i): The reaction of 4-
aminoiodobenzene 1i (109.5 mg, 0.5 mmol) with benzonitrile 2a
3
Hz, 2H), 7.70 (s, 1H), 7.57 (t, J = 6.8 Hz, 1H), 7.51 (t, J = 7.6
Hz, 2H), 7.29-7.23 (m, 2H), 7.13 (t, J = 7.6 Hz, 1H), 2.35 (s,
(
ν
103.0 mg, 1.0 mmol) afforded 90.1 mg (85%) of 3i; IR(KBr)
-1
1
max 3339, 1641, 1514, 1426, 1322, 1261, 823, 702 cm ; H
1
3
3
H); C NMR (100 MHz, CDCl
3
, ppm) δ 165.7, 135.7, 134.9,
NMR (400 MHz, DMSO-d6, ppm) δ 9.89 (s,1H), 7.91 (d, J = 7.6
1
31.8, 130.5, 129.4, 128.8, 127.0, 126.8, 125.4, 123.2, 17.8; MS
Hz, 2H), 7.57-7.48 (m, 3H), 7.37 (d, J = 8.4 Hz, 2H), 6.54 (d, J =
+
(
ESI) m/z: [M+H] 212.1.
13
8
.8 Hz, 2H), 4.95 (s, 2H); C NMR (100 MHz, DMSO-d6, ppm)
δ 164.7, 145.3, 135.3, 131.2, 128.3, 128.1, 127.5, 122.3, 113.6;
MS (ESI) m/z: [M+Na] 235.1.
N-m-Tolylbenzamide
methyliodobenzene 1c (109.0 mg, 0.5 mmol) with benzonitrile
a (103.0 mg, 1.0 mmol) afforded 90.7 mg (86%) of 3c; IR(KBr)
(3c):
The
reaction
of
m-
+
2
ν
N-(3-Hydroxyphenyl)benzamide (3j): The reaction of 3-
iodophenol 1j (110.0 mg, 0.5 mmol) with benzonitrile 2a (103.0
mg, 1.0 mmol) afforded 49.0 mg (46%) of 3j; IR(KBr) νmax 3369,
-
1 1
max 3266, 1648, 1538, 1308, 1259, 781, 710 cm ; H NMR (400
MHz, CDCl , ppm) δ 7.86-7.84 (m, 3H), 7.56-7.45 (m, 4H), 7.41
d, J = 7.6 Hz, 1H), 7.26-7.22 (m, 1H), 6.96 (d, J = 7.6 Hz, 1H),
3
(
-1
1
1
631, 1539, 1450, 1281, 1210, 713, 683 cm ; H NMR (400
13
2
1
2
3
.36 (s, 3H); C NMR (100 MHz, CDCl , ppm) δ 165.8, 138.9,
MHz, DMSO-d6, ppm) δ 10.13 (s, 1H), 9.43 (s, 1H), 7.92 (d, J =
37.8, 134.9, 131.7, 128.8, 128.6, 127.0, 125.3, 120.9, 117.4,
1.4; MS (ESI) m/z: [M+H] 212.1.
7
6
1
1
.2 Hz, 2H), 7.59-7.50 (m, 3H), 7.36 (s, 1H); 7.18-7.11 (m, 2H),
.50 (d, J = 7.6 Hz, 1H), C NMR (100 MHz, DMSO-d6, ppm) δ
+
13
65.5, 157.5, 140.2, 135.2, 131.5, 129.3, 128.4, 127.7, 111.1,
N-p-Tolylbenzamide
methyliodobenzene 1d (109.0 mg, 0.5 mmol) with benzonitrile
a (103.0 mg, 1.0 mmol) afforded 89.7 mg (85%) of 3d; IR(KBr)
(3d):
The
reaction
of
p-
+
10.8, 107.5; MS (ESI) m/z: [M+Na] 236.1.
2
ν
N-(Thiophen-2-yl)benzamide (3k): The reaction of 2-
iodothiophene 1k (105.0 mg, 0.5 mmol) with benzonitrile 2a
-
1 1
max 3311, 1647, 1597, 1511, 1317, 813, 714 cm ; H NMR (400
MHz, CDCl , ppm) δ 7.89 (s, 1H), 7.84 (d, J = 7.2 Hz, 2H), 7.54-
.51 (m, 3H), 7.45 (t, J = 7.2 Hz, 2H), 7.15 (d, J = 8.0 Hz, 2H),
3
(
ν
103.0 mg, 1.0 mmol) afforded 35.3 mg (35%) of 3k; IR(KBr)
max 3421, 1622, 1501, 1243, 746 cm ; H NMR (400 MHz,
7
2
1
-1
1
13
.33 (s, 3H); C NMR (100 MHz, CDCl
3
, ppm) δ 165.7, 135.3,
DMSO-d6, ppm) δ 11.56 (s, 1H), 8.01-7.99 (m, 2H), 7.64-7.54
35.0, 134.2, 131.7, 129.5, 128.7, 127.0, 120.3, 20.9; MS (ESI)
13
(
m, 3H), 7.03-7.01 (m, 1H), 6.95-6.90 (m, 2H); C NMR (100
+
m/z: [M+H] 212.1.
MHz, DMSO-d6, ppm) δ 163.2, 140.0, 133.1, 131.9, 128.6,
+
1
27.6, 124.1, 117.4, 112.1; MS (ESI) m/z: [M+H] 204.0.

ACCEPTED MANUSCRIPT
6
Tetrahedron
N-(3-(Methoxymethoxy)phenyl)benzamide
(3l):
The
137.5, 130.8, 129.1, 128.4, 127.8, 124.6, 120.2; MS (ESI) m/z:
+
reaction of 1-iodo-3-(methoxymethoxy)benzene 1l (132.0 mg,
[M+H] 204.1.
0
9
2
.5 mmol) with benzonitrile 2a (103.0 mg, 1.0 mmol) afforded
N-phenylfuran-2-carboxamide (3s): The reaction of
iodobenzene 1a (102.0 mg, 0.5 mmol) with furan-2-carbonitrile
7.7 mg (76%) of 3l; IR(KBr) νmax 3306, 3087, 3068, 2991, 2946,
-
1 1
3
901, 2826, 1649, 1601, 1014 cm ; H NMR (400 MHz, CDCl ,
2
h (93.0 mg, 1.0 mmol) afforded 35.5 mg (38%) of 3s; IR:(KBr)
ppm) δ 7.90 (s, 1H), 7.87-7.84 (m, 2H), 7.55-7.52 (m, 1H), 7.50-
-1
ν
max 3435, 3282, 3141, 1655, 1599, 1479, 1324, 758 cm ;
7
3
1
9
.43 (m, 3H), 7.28-7.26 (m,2H), 6.85-6.81 (m, 1H), 5.19 (s, 2H),
.49 (s, 3H); C NMR (100 MHz, CDCl , ppm) δ 165.7, 157.8,
3
39.0, 134.9, 131.9, 129.9, 128.8, 127.0, 113.6, 112.5, 108.2,
4.4, 56.1; MS (ESI) m/z: [M+Na] 280.1.
1
13
3
HNMR (400 MHz, CDCl , ppm) δ 8.11 (s, 1H), 7.66 (d, J = 8.4
Hz, 2H), 7.52 (s, 1H), 7.38 (t, J = 7.6 Hz, 2H), 7.27-7.25 (m, 1H),
13
+
7.15 (t, J = 7.2 Hz, 1H), 6.58-6.57 (m, 1H); C NMR (100 MHz,
CDCl , ppm) δ 156.0, 147.7, 144.2, 137.3, 129.1, 124.5, 119.9,
3
+
2
-Methyl-N-phenylbenzamide (3m): The reaction of
iodobenzene 1a (102.0 mg, 0.5 mmol) with 2-methylbenzonitrile
b (117.1 mg, 1.0 mmol) afforded 59.1 mg (56%) of 3m;
IR(KBr) νmax 3286, 1652, 1597, 1533, 1439, 1321, 1260, 889,
115.3, 112.6; MS (ESI) m/z: [M+H] 188.2.
N-phenylpentanamide (3t): The reaction of iodobenzene 1a
2
(
102.0 mg, 0.5 mmol) with pentanenitrile 2i (83.0 mg, 1.0 mmol)
-
1
1
afforded 45.1 mg (51%) of 3t; IR(KBr) νmax 3246, 2931, 1657,
757 cm ; H NMR (400 MHz, CDCl
3
, ppm) δ 7.61 (d, J = 7.6
-1 1
1
547, 760 cm ; H NMR (400 MHz, CDCl
3
, ppm) δ 8.48 (s, 1H),
Hz, 2H), 7.57 (s, 1H), 7.45 (d, J = 7.2 Hz, 1H), 7.36 (t, J = 8.0
Hz, 3H), 7.26-7.22 (m,2H), 7.14 (t, J = 7.2 Hz, 1H), 2.49 (s, 3H);
7.54 (d, J = 8.0 Hz, 2H), 7.27-7.23 (m, 2H), 7.08-7.04 (m, 1H),
13
2.32 (t, J = 7.6 Hz, 2H), 1.69-1.62 (m, 2H), 1.38-1.29 (m, 2H),
13
C NMR (100 MHz, CDCl
3
, ppm) δ 168.1, 138.0, 136.3, 136.3,
0
.88 (t, J = 7.2 Hz, 3H); C NMR (100 MHz, CDCl
3
, ppm) δ
131.1, 130.2, 129.0, 126.6, 125.8, 124.4, 119.9, 19.7; MS (ESI)
+
172.3, 138.1, 128.6, 123.9, 120.1, 37.1, 27.7, 22.2, 13.7; MS
m/z: [M+H] 212.1.
+
(
ESI) m/z: [M+Na] 200.1.
3
-Methyl-N-phenylbenzamide (3n): The reaction of
N-phenylisobutyramide (3u): The reaction of iodobenzene 1a
102.0 mg, 0.5 mmol) with isobutyronitrile 2j (69.0 mg, 1.0
iodobenzene 1a (102.0 mg, 0.5 mmol) with 3-methylbenzonitrile
c (117.1 mg, 1.0 mmol) afforded 89.0 mg (84%) of 3n; IR(KBr)
max 3266, 1650, 1597, 1541, 1490, 1442, 1328, 856, 754 cm ;
H NMR (400 MHz, CDCl
.64 (d, J = 7.2 Hz, 3H), 7.39-7.36 (m, 4H), 7.15 (t, J = 7.2 Hz,
H), 2.43 (s, 3H); C NMR (100 MHz, CDCl , ppm) δ 166.0,
3
38.6, 138.0, 134.9, 132.5, 129.0, 128.6, 127.8, 124.5, 123.9,
20.2, 21.3; MS (ESI) m/z: [M+H] 212.1.
(
2
-
1
mmol) afforded 42.4 mg (52%) of 3u; IR(KBr) νmax 3301, 3263,
ν
-1 1
1
1662, 1549, 1442, 759 cm ; H NMR (400 MHz, CDCl
3
, ppm) δ
3
, ppm) δ 7.84 (s, 1H), 7.69 (s, 1H),
7
.54 (d, J = 7.6 Hz, 2H), 7.48 (s, 1H), 7.32-7.26 (m, 2H), 7.11-
7
1
1
1
13
1
3
7.07 (m, 1H), 2.55-2.49 (m, 1H), 1.24 (d, J = 6.8 Hz, 6H);
NMR (100 MHz, CDCl , ppm) δ 175.4, 138.0, 128.9, 124.1,
119.8, 36.6, 19.6; MS (ESI) m/z: [M+Na] 186.0.
C
3
+
+
4
.3 General procedure for the synthesis of benzoxazoles
4
-Methyl-N-phenylbenzamide (3o): The reaction of
iodobenzene 1a (102.0 mg, 0.5 mmol) with 4-methylbenzonitrile
d (117.1 mg, 1.0 mmol) afforded 90.8 mg (86%) of 3o; IR(KBr)
To a suspension of CuI (9.5 mg, 0.05 mmol), K CO (207.3
2
3
2
mg, 1.5 mmol) in toluene (2.0 mL) were added aryl o-dihalides 1
0.5 mmol), nitrile 2 (1.0 mmol), DMEDA (8.0 uL, 0.075 mmol),
-
1
1
ν
max 3352, 1650, 1524, 754 cm ; H NMR (400 MHz, CDCl
ppm) δ 7.82 (s, 1H), 7.77 (d, J = 8.0 Hz, 2H), 7.65-7.63 (m, 2H),
.39-7.35 (m, 2H), 7.28 (d, J = 8.0 Hz, 2H), 7.17-7.13 (m, 1H),
.43 (s, 3H); C NMR (100 MHz, CDCl
38.0, 132.1, 129.4, 129.1, 127.0, 124.4, 120.1, 21.5; MS (ESI)
m/z: [M+Na] 234.1.
3
,
(
acetaldoxime (92.0 uL, 1.5 mmol) under argon. The reaction
mixture was stirred for 15 h at 120 ℃ under argon. The solution
was cooled to room temperature and the solvent was removed
under vacuum. The crude product was purified by column
chromatography on silica gel (eluent: petroleum ether / ethyl
acetate = 30:1) to afford the benzoxazoles 4.
7
2
1
13
3
, ppm) δ 165.7, 142.4,
+
4-Chloro-N-phenylbenzamide (3p): The reaction of
iodobenzene 1a (102.0 mg, 0.5 mmol) with 4-chlorobenzonitrile
e (92.0 mg, 1.0 mmol) afforded 98.6 mg (85%) of 3p; IR(KBr)
2
-Phenylbenzoxazole (4a): The reaction of 1,2-diiodobenzene
m (141.5 mg, 0.5 mmol) with benzonitrile 2a (103.0 mg, 1.0
mmol) afforded 80.0 mg (82%) of 4a; IR(KBr) νmax 3060, 1551,
2
1
1
νmax 3353, 1653, 1599, 1487, 1439, 847, 755; H NMR (400MHz,
DMSO-d6, ppm) δ 10.32 (s, 1H), 7.99 (d, J=8.8Hz, 2H), 7.77 (d,
J=8Hz, 2H), 7.62 (d, J=8.4Hz, 2H), 7.36 (t, J=7.6Hz, 2H), 7.11(t,
-1
1
1
446, 744 cm ; H NMR (400 MHz, CDCl
m, 2H), 7.80-7.78 (m, 1H), 7.61-7.53 (m, 4H), 7.37-7.35 (m,
H); C NMR (100 MHz, CDCl , ppm) δ 163.0, 150.7, 141.9,
31.6, 128.9, 127.6, 127.0, 125.1, 124.6, 120.0, 110.6; MS (ESI)
3
, ppm) δ 8.28-8.26
(
2
13
J=7.6Hz, 1H); C NMR (100 MHz, DMSO-d6, ppm) δ 164.4,
39.0, 136.4, 133.6, 129.6, 128.6, 128.5, 123.8, 120.4; MS (ESI)
13
3
1
1
+
m/z: [M+H] 232.1.
+
m/z: [M+H] 196.1.
4
-Fluoro-N-phenylbenzamide (3q): The reaction of
2
-o-Tolylbenzoxazole (4b): The reaction of 1,2-diiodobenzene
m (141.5 mg, 0.5 mmol) with 2-methylbenzonitrile 2b (117.2
mg, 1.0 mmol) afforded 57.9 mg (55%) of 4b; IR(KBr) νmax
iodobenzene 1a (102.0 mg, 0.5 mmol) with 4-fluorobenzonitrile
f (121.0 mg, 1.0 mmol) afforded 97.9 mg (91%) of 3q; IR(KBr)
max 3353, 1655, 1506, 752 cm ; H NMR (400 MHz, DMSO-d6,
ppm) δ 10.28 (s, 1H), 8.08-8.03 (m, 2H), 7.80-7.77 (m, 2H),
.41-7.34 (m, 4H), 7.13-7.10 (m, 1H); C NMR (100 MHz,
DMSO-d6, ppm) δ 165.3, 164.4, 162.8， 139.1, 131.4 (d, J = 3.2
Hz), 130.4 (d, J = 8.3 Hz), 128.6, 123.7, 120.4, 115.3 (d, J = 21.8
Hz); MS (ESI) m/z: [M+H] 216.1.
1
2
ν
-
1 1
-1 1
3
8
7
1
1
060, 1551, 1446, 744 cm ; H NMR (400 MHz, CDCl , ppm) δ
.19-8.17 (m, 1H), 7.82-7.80 (m, 1H), 7.61-7.58 (m, 1H), 7.42-
.26 (m, 5H), 2.82 (s, 3H); C NMR (100 MHz, CDCl
63.4, 150.2, 142.1, 138.8, 131.8, 130.9, 129.9, 126.2, 126.0,
3
13
7
13
3
, ppm) δ
+
25.0, 124.4, 120.1, 110.5, 22.2; MS (ESI) m/z: [M+H] 210.1.
+
2
-m-Tolylbenzoxazole (4c): The reaction of 1,2-
N-Phenylthiophene-2-carboxamide (3r): The reaction of
iodobenzene 1a (102.0 mg, 0.5 mmol) with thiophene-2-
carbonitrile 2g (109.2 mg, 1.0 mmol) afforded 63.9 mg (63%) of
diiodobenzene 1m (141.5 mg, 0.5 mmol) with 3-
methylbenzonitrile 2c (117.1 mg, 1.0 mmol) afforded 89.9mg
86%) of 4c; IR(KBr) νmax 3433, 1551, 1446, 744 cm ; H NMR
400 MHz, CDCl , ppm) δ 8.11 (s, 1H), 8.05 (d, J = 7.6 Hz, 1H),
.79-7.77 (m, 1H), 7.60-7.58 (m, 1H), 7.42 (t, J = 8.0 Hz, 1H),
-1
1
(
(
7
7
-1
3
r; IR(KBr) νmax 3303, 1631, 1595, 1535, 1445, 1323, 755 cm ;
1
3
H NMR (400 MHz, CDCl
3
, ppm) δ 7.75 (s, 1H), 7.64-7.61 (m,
3
H), 7.55 (d, J = 5.2 Hz, 1H), 7.36 (t, J = 7.2 Hz, 2H), 7.17-7.12
13
3
.38-7.35 (m, 3H), 2.46 (s, 3H); C NMR (100 MHz, CDCl ,
1
3
(
3
m, 2H); C NMR (100 MHz, CDCl , ppm) δ 159.9, 139.2,

ACCEPTED MANUSCRIPT
7
ppm) δ 163.2, 150.7, 142.0, 138.7, 132.4, 128.8, 128.1, 126.9,
References and notes
+
125.0, 124.7, 124.5, 119.9, 110.5, 21.4; MS (ESI) m/z: [M+H]
10.1.
2
1. (a) Gracia, S. R.; Gaus, K.; Sewald, N. Future Med. Chem. 2009,
(7), 1289-1310; (b) El-Faham, A.; Albericio, F. Chem. Rev. 2011,
1
2
-p-Tolylbenzoxazole (4d): The reaction of 1,2-diiodobenzene
111(11), 6557-6602; (c) Valeur, E.; Bradley, M. Chem. Soc. Rev.
2009, 38, 606-631; (d) Joullié, M. M.; Lassen, K. M. ARKIVOC
1
m (141.5 mg, 0.5 mmol) with 4-methylbenzonitrile 2d (117.1
mg, 1.0 mmol) afforded 90.9 mg (87%) of 4d; IR(KBr) νmax
054, 2919, 1502, 746 cm ; H NMR (400 MHz, CDCl
.15 (d, J = 8.4 Hz, 2H), 7.78-7.75 (m, 1H), 7.59-7.56 (m, 1H),
.36-7.32 (m, 4H), 2.45 (s, 3H); C NMR (100 MHz, CDCl ,
3
ppm) δ 163.3, 150.6, 142.1, 142.1, 129.6, 127.6, 124.9, 124.5,
24.3, 119.8, 110.5, 21.6; MS (ESI) m/z: [M+H] 210.1.
2
010, 189-250; (e) Allen, C. L.; Williams, J. M. J. Chem. Soc.
-
1
1
Rev. 2011, 40, 3405-3415; (f) Roy, S.; Roy, S.; Gribble, G. W.
Tetrahedron 2012, 68, 9867-9923 (g) Zhang, D.-W.; Zhao, X.;
Hou, J.-L.; Li, Z.-T. Chem. Rev. 2012, 112, 5271-5316; (h)
García-Álvarez, R.; Crochet, P.; Cadierno, V. Green Chem. 2013,
15, 46-66.
(a) Goldberg, I. Ber. Dtsch. Chem. Ges. 1906, 39, 1691-1692; (b)
Bacon, R. G. R.; Karim, A. J. Chem. Soc., Perkin Trans. 1 1973,
272-278; (c) Freeman, H. S.; Butler, J. R.; Freedman, L. D. J. Org.
Chem. 1978, 43, 4975-4977; (d) Yamamoto, T.; Kurata, Y. Can. J.
Chem. 1983, 61, 86-91; (e) Ito, A.; Saito, T.; Tanaka, K.; Yamabe,
T. Tetrahedron Lett. 1995, 36, 8809-8812; (f) Lange, J. H. M.;
Hofmeyer, L. J. F.; Hout, F. A. S.; Osnabrug, S. J. M.; Verveer, P.
C.; Kruse, C. G.; Feenstra, R. W. Tetrahedron Lett. 2002, 43,
1101-1104.
3
8
7
3
, ppm) δ
1
3
+
2
.
1
2-(4-Methoxyphenyl)benzoxazole (4e): The reaction of 1,2-
diiodobenzene 1m (141.5 mg, 0.5 mmol) with 4-
methoxybenzonitrile 2k (133.1 mg, 1.0 mmol) afforded 80.6mg
(
72%) of 4e; IR(KBr) νmax 3435, 1619, 1501, 1453, 831, 741, 729
-1 1
cm ; H NMR (400 MHz, CDCl
3
, ppm) δ 8.20 (d, J = 9.2 Hz,
2
7
H), 7.76-7.73 (m, 1H), 7.58-7.55(m,1H), 7.35-7.32 (m, 2H),
13
3. For the reviews, see: (a) Jiang, Y.; Ma, D. in: Catalysis without
Precious Metals, (Ed. Bullock, R. M.), Wiley-Blackwell,
Weinheim, 2010, pp 213-233; (b) Surry, D. S.; Buchwald, S. L.
Chem. Sci. 2010, 1, 13-31; (c) Wang, Y.; Zeng, J.; Cui, X. Chin. J.
Org. Chem. 2010, 30, 181-199 (in Chinese); (d) Monnier, F.;
Taillefer, M. Angew. Chem. Int. Ed. 2009, 48, 6954-6971; (e) Ma,
D. W.; Cai, Q. A. Acc. Chem. Res. 2008, 41, 1450-1460; (f)
Evano, G.; Blanchard, N.; Toumi, M. Chem. Rev. 2008, 108,
3054-3131.
.04 (d, J = 8.8 Hz, 2H), 3.90 (s, 3H); C NMR (100 MHz,
, ppm) δ 163.2, 162.3, 150.6, 142.2, 129.4, 124.6, 124.4,
CDCl
19.6, 119.6, 114.3, 110.4, 55.4; MS (ESI) m/z: [M+H] 226.2.
3
+
1
2-(4-Chlorophenyl)benzoxazole (4f): The reaction of 1,2-
diiodobenzene 1m (141.5 mg, 0.5 mmol) with 4-
chlorobenzonitrile 2e (92.0 mg, 1.0 mmol) afforded 42.8mg
34%) of 4f; IR(KBr) νmax 3060, 1551, 1446, 744 cm ; H NMR
400 MHz, CDCl , ppm) δ 8.20 (d, J = 8.0 Hz, 2H), 7.79-7.77
m, 1H), 7.61-7.58 (m, 1H), 7.51 (d, J = 8.0 Hz, 2H), 7.40-7.36
-
1 1
(
(
(
(
4
.
(a) Lokwani, P.; Nagori, B. P.; Batra, N.; Goyal, A.; Gupta, S.;
Singh, N. J. Chem. Pharm. Res. 2011, 3(3), 302-311; (b)
Shrivastava, B.; Sharma, V.; Lokwani, P. Pharmacologyonline
3
1
3
m, 2H); C NMR (100 MHz, CDCl
3
, ppm) δ 162.0, 150.7,
2
011, 236-245; (c) Evindar, G.; Batey, R. A. J. Org. Chem. 2006,
1
41.9, 137.7, 129.3, 129.3, 128.8, 125.4, 124.7, 120.0, 110.6; MS
71, 1802-1808; (d) Saha, P.; Ramana, T.; Purkait, N.; Ali, M. A.;
Paul, R.; Punniyamurthy, T. J. Org. Chem. 2009, 74, 8719-8725;
+
(
ESI) m/z: [M+H] 230.1.
(e) Kantam, M. L.; Venkanna, G. T.; Shiva Kumar, K. B.;
2
-(4-Fluorophenyl)benzoxazole (4g): The reaction of 1,2-
Balasubrahmanyam, V.; Bhargava, S. Synlett 2009, 1753-1756.
Altenhoff, G.; Glorius, F. Adv. Synth. Catal. 2004, 346, 1661-
5
.
diiodobenzene 1m (141.5 mg, 0.5 mmol) with 4-
fluorobenzonitrile 2f (121.0 mg, 1.0 mmol) afforded 54.3 mg
51%) of 4g; IR(KBr) νmax 1617, 688 cm ; H NMR (400 MHz,
CDCl , ppm) δ 8.24-8.22 (m, 2H), 7.72-7.70 (m, 1H), 7.69-7.52
m, 3H), 7.33-7.26 (m, 1H), 7.14-7.09 (m, 1H); C NMR (100
1
664.
-
1
1
6. For the review, see: (a) Ahmed, T. J.; Knapp, S. M. M.; Tyler, D.
R. Coord. Chem. Rev. 2011, 255, 949-974; (b) Kukushkin, V. Y.
Pombeiro, A. J. L. Chem. Rev. 2002, 102, 1771-1802.
7. (a) Chemat, F.; Poux, M.; Berlan, J. J. Chem. Soc. Perkin Trans. 2
1996, 1781-1784; (b) Yamaguchi, K.; Matsushita, M.; Mizuno, N.
Angew. Chem. Int. Ed. 2004, 43, 1576-1580; (c) Siegfried, L.;
Comparone, A.; Neuburger, M.; Kaden, T. A. Dalton Trans. 2005,
(
3
13
(
MHz, CDCl
3
, ppm) δ 164.8 (d, J = 250.7 Hz), 162.2, 150.7,
1
1
2
42.0, 129.8 (d, J = 9.9 Hz), 125.1, 124.7, 123.4 (d, J = 3.0 Hz),
19.9, 116.2 (d, J = 22.2 Hz), 110.6; MS (ESI) m/z: [M+H]
14.2.
+
3
0-36; (d) Mitsudome, T.; Mikami, Y.; Mori, H.; Arita, S.;
Mizugaki, T.; Jitsukawa, K.; Kaneda, K. Chem. Commun. 2009,
258-3260; (e) Sahnoun, S.; Messaoudi, S.; Peyrat, J.-F.; Brion,
3
2-butylbenzoxazole (4h): The reaction of 1,2-diiodobenzene
J.-D.; Alami, M. Tetrahedron Lett. 2012, 53, 2860-2863; (f) Li,
Z.; Wang, L.; Zhou, X. Adv. Synth. Catal. 2012, 354, 584-588; (g)
Hirano, T.; Uehara, K.; Kamata, K.; Mizuno, N. J. Am. Chem.
Soc. 2012, 134, 6425-6433.
1
m (141.5 mg, 0.5 mmol) with pentanenitrile 2i (83.0 mg, 1.0
mmol) afforded 35.9 mg (41%) of 4h; IR(KBr) νmax 3059, 2960,
933, 2873, 1615, 1572, 746 cm ; H NMR (400 MHz, CDCl
ppm) δ 7.69-7.66 (m, 1H), 7.49-7.46 (m, 1H), 7.32-7.27 (m, 2H),
.94 (t, J = 7.6 Hz, 2H), 1.97-1.84 (m, 2H), 1.51-1.41 (m, 2H),
3
.97 (t, J = 7.6 Hz, 3H); C NMR (100 MHz, CDCl , ppm) δ
67.3, 150.7, 141.2, 124.3, 124.0, 119.4, 110.2, 28.8, 28.3, 22.2,
3.7; MS (ESI) m/z: [M+H] 176.1.
-
1 1
2
3
,
8
9
.
.
(a) Lee, J.; Kim, M.; Chang, S.; Lee, H.-Y. Org. Lett. 2009,
1
1(24), 5598-5601; (b) Kim, E. S.; Kim, H. S.; Kim, J. N.
2
0
1
1
Tetrahedron Lett. 2009, 50, 2973-2975; (c) Kim, E. S.; Lee, H. S.;
Kim, S. H.; Kim, J. N. Tetrahedron Lett. 2010, 51, 1589-1591; (d)
Kiss, Á.; Hell, Z. Tetrahedron Lett. 2011, 52, 6021-6023; (e) Ma,
X.-Y.; He, Y.; Hu, Y.-L.; Lu, M. Tetrahedron Lett. 2012, 53, 449-
13
+
4
52.
Xiang, S.-K.; Zhang, D.-X.; Hu, H.; Shi, J.-L.; Liao, L.-G.; Feng,
C.; Wang, B.-Q.; Zhao, K.-Q.; Hu, P.; Yang, H.; Yu, W.-H. Adv.
Synth. Catal. 2013, 355, 1495-1499.
Acknowledgments
Financial support from National Natural Science Foundation
of China (Nos. 21202109 and 21072140), Sichuan Provincial
Department of Education (No. 11ZA108), Special Funds of
Sichuan Normal University for Sharing the Large Precision
Equipments (Nos. DJ2013-20 and DJ2013-21), Sichuan Province
Higher Education System Key Laboratory of Advanced
Functional Materials (KFKT2013-02) and Sichuan Normal
University (xyz2013-14-39) are greatly appreciated.

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An improved protocol for synthesis of N-arylamides and
benzoxazoles by the copper-catalyzed reaction of aryl halides
with nitriles
Dong-Xue Zhang, Shi-Kai Xiang,* Hao Hu, Wen Tan, Chun Feng, Bi-Qin Wang,*
Ke-Qing Zhao, Ping Hu and Hua Yang
College of Chemistry and Materials Science, Sichuan Normal University, Chengdu
6
10068, Sichuan, China;
E-mail: xiangsk@hotmail.com；wangbiqin1964@126.com
Fax: +86-028-84766730

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