Copper catalyzed synthesis of 1-aryl-1,2,3-triazoles from aryl iodides, alkynes, and sodium azide

Article abstract of DOI:10.1016/j.jorganchem.2013.10.005

Aryl azides were synthesized using heterogeneous porous Cu (0) catalyst via a coupling reaction of aryl iodides with sodium azide under mild conditions. Under the same conditions, one-pot Cu-catalyzed azide-alkyne cycloaddition of aryl iodides, alkynes, and sodium azide yielded 1-aryl-1,2,3-triazoles.

Full text of DOI:10.1016/j.jorganchem.2013.10.005

Accepted Manuscript
Copper Catalyzed Synthesis of 1-Aryl-1,2,3-Triazoles from Aryl Iodides, Alkynes, and
Sodium Azide
Ying Chen, Zi-Jian Zhuo, Dong-Mei Cui, Chen Zhang
PII:
S0022-328X(13)00722-5
10.1016/j.jorganchem.2013.10.005
JOM 18291
DOI:
Reference:
To appear in: Journal of Organometallic Chemistry
Received Date: 21 August 2013
Revised Date: 26 September 2013
Accepted Date: 1 October 2013
Please cite this article as: Y. Chen, Z.-J. Zhuo, D.-M. Cui, C. Zhang, Copper Catalyzed Synthesis of 1-
Aryl-1,2,3-Triazoles from Aryl Iodides, Alkynes, and Sodium Azide, Journal of Organometallic Chemistry
(2013), doi: 10.1016/j.jorganchem.2013.10.005.
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ACCEPTED MANUSCRIPT
Porous Cu (0) was found to be a highly efficient heterogeneous catalyst for the one-pot
synthesis of 1-aryl 1,2,3-triazoles from aryl iodides, alkynes, and sodium azide. A wide range
of alkynes and aryl iodides can be tolerated can be tolerated. The porous Cu (0) catalyst can
be easily recovered and reused for five cycles with consistent activity.

ACCEPTED MANUSCRIPT
Copper Catalyzed Synthesis of 1-Aryl 1,2,3-Triazoles from Aryl Iodides, Alkynes,
and Sodium Azide
N
N
I
N
1
) porous Cu, NaN3
R2
2) R2
R1
R1

ACCEPTED MANUSCRIPT
Copper Catalyzed Synthesis of 1-Aryl-1,2,3-Triazoles from
Aryl Iodides, Alkynes, and Sodium Azide
1
1
,1
,2
Ying Chen , Zi-Jian Zhuo , Dong-Mei Cui* , and Chen Zhang*
1
Address: College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou 310014,
2
PR China and School of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, PR China
Email: Dong-Mei Cui – cuidongmei@zjut.edu.cn
Tel. and Fax: 86-0571-88320320
*
Corresponding author
Abstract
Aryl azides were synthesized using heterogeneous porous Cu (0) catalyst via a coupling reaction of
aryl iodides with sodium azide under mild conditions. Under the same conditions, one-pot Cu-
catalyzed azide-alkyne cycloaddition of aryl iodides, alkynes, and sodium azide yielded 1-aryl-1,2,3-
triazoles.
Keywords
click reaction; porous copper; aryl azides; 1-aryl-1,2,3-triazoles
1. Introduction
Copper-catalyzed azide-alkyne cycloaddition (CuAAC), also known as the “click reaction,” has
1
, 2
become one of the most important reactions for the preparation of 1,2,3-triazoles. This important
reaction is widely applied in organic synthesis, biochemistry, medicinal chemistry, and material
3
-9
science. Most of the reported CuAAC studies are on two-component (organic azide and alkyne)
reaction systems, especially in the synthesis of 1-aryl-1,2,3-triazoles. In this system, the organic azides
1

ACCEPTED MANUSCRIPT
need to be synthesized in advance, and the potential hazards of organic azides, especially in isolation
or purification processing, can be problematic. Thus, it is desirable to develop an efficient one-pot
1
0
methodology that uses aryl halides and sodium azide for direct cycloaddition with alkynes. On the
other hand, the most common method reported in the literature for synthesis of aryl azides involves the
1
1-13
replacement of diazonium salts or some activated aryl halide with sodium azide.
Recently,
syntheses of aryl azides have also been reported using coupling of aryl halides with sodium azide
1
4, 15
catalyzed by CuI.
However, it is worth noting that other copper catalysts have not been used in this
coupling reaction, especially Cu (0) metal. Porous metals with a large surface-to-volume ratio that are
light weight with excellent electrical/thermal conductivity have attracted much attention because of a
1
6-18
wide range of applications in chemistry, mechanics, and nanotechnology.
Porous Cu, which has
excellent structural characteristics and is basically harmless to the human body, has mostly been used
as filter material. It is commercially available and can also be prepared according to published
1
9-20
methods.
Recently, it has been reported that fabricated nanoporous Cu materials were highly
2
1
efficient heterogeneous catalysts for click reactions, and exhibited high reusability. We have recently
reported the click reaction of sodium azide with alkyl halides and alkynes to afford 1,2,3-triazoles in
2
2
water using porous Cu catalyst. In continuation of our studies, herein, we report an efficient method
for the preparation of aryl azides from the corresponding aryl iodides in the presence of porous Cu
catalyst, as well as a one-pot procedure to prepare 1-aryl-1,2,3-triazoles from aryl iodides via in situ
formation of aryl azides.
2. Results and discussion
In an initial attempt to prepare aryl azides using a commercially available procedure with Cu porous
material as a catalyst, we investigated the coupling reaction of 4-methoxy phenyl iodide (1a) with
sodium azide in DMSO as solvent. Our catalytic system consists of commercially available sintered
copper porous material. It was found that under the action of 5 mol% porous Cu (~5 µm), 20 mol% L-
proline, and 20% diisopropylamine in DMSO, this reaction gave 4-methoxyphenyl azide (2a) in 96%
yield at 80°C (Table 1, entry 1). While treatment of 1a and sodium azide with triethylamine or NaOH
or Cs CO also resulted in good yields, use of diethylamine or ethylenediamine or K PO produced 2a
2
3
3
4
in moderate yields (Table 1, entries 2-8). In addition, we noticed that other amino acids, such as L-
2

ACCEPTED MANUSCRIPT
threnine and L-alanine, efficiently accelerated this reaction but gave slightly lower yields (Table 1,
entries 9 and 10). On further optimization of the solvent conditions, replacement of DMSO by DMF or
H O gave decreased yield and no product 2a was obtained in EtOH (Table 1, entries 11-13). A
2
decreased yield was observed using Cu with larger pores (Table 1, entries 15 and 16). Furthermore,
the reaction gave lower yields in the absence of L-proline or diisopropylamine (Table 1, entries 18
and 19). Although the source of the catalytic activity of L-proline as an additive in unclear, a possible
1
4
role is coordination to Cu in this reaction.
a
Table 1. Catalyst screening in the synthesis of 2a
N3
I
5
mol% Cu
o
NaN , 80 C
3
MeO
MeO
1a
2a
b
Entry Base
(Me
Et NH
NH (CH
Et
Additive
L-proline
L-proline
L-proline
L-proline
L-proline
L-proline
L-proline
L-proline
Solvent
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMF
Time (h)
24
Yield of 2 (%)
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
2
CH)
2
NH
96
49
54
82
80
62
74
63
81
79
55
Trace
65
72
79
67
4
2
38
2
2
)
2
NH
2
38
3
N
29
NaOH
LiOH
30
79
CsCO
3
54
K
3
PO
4
34
(Me CH) NH
L-threonine
17
2
2
2
2
0
1
2
3
4
5
6
7
8
(Me
2
CH)
CH)
NH
NH
L-alanine
L-proline
L-proline
L-proline
L-proline
L-proline
L-proline
L-proline
-
17
(Me
2
29
(Me CH) NH
EtOH
29
2
2
2
2
(Me
2
CH)
CH)
NH
NH
H
2
O
65
c
d
e
f
(Me
2
DMSO
DMSO
DMSO
DMSO
DMSO
24
(Me CH) NH
24
2
2
2
2
(Me
2
2
CH)
CH)
NH
NH
24
(Me
24
(Me CH) NH
63
23
2
2
3

ACCEPTED MANUSCRIPT
1
9
-
L-proline
L-proline
DMSO
DMSO
24
24
30
0
g
20
2 2
(Me CH) NH
a
3
The reactions were performed with 1a (1.0 mmol), NaN (2.0 mmol), base (20 mol%), ligand (20 mol%) and Cu (5 µm , 5
mol %) in solvent (4 mL) at 80
.
b
e
f
c
d
3
Isolated yields; NaN (1.1 mmol) was used; Cu (15 µm) was used.
Cu (25 µm) was used.
at 60
.
g
Cu was not used.
With the optimal reaction conditions in hand, we explored the reaction scope by testing other aryl
iodides with different substituents; the results are summarized in Table 2. Aryl iodide with an electron-
donating alkyl group on the benzene ring gave good isolated yields of the corresponding aryl azides
(
Table 2, entry 3). With a more electron-donating alkoxy or amine group, the expected adducts were
obtained in excellent yields (Table 2, entries 1-2, 6). In addition, the reaction of aryl iodides bearing an
electron-withdrawing chloro or bromo group on the benzene ring with sodium azide also took place
smoothly, and the corresponding aromatic amines were also detected in small amounts (Table 2,
entries 4-5).
a
Table 2. 1-Aryl 1,2,3-Triazoles from Aryl Iodides with Sodium Azide
5
mol% Cu, NaN3
ArI
ArN3
2
2
0 mol% L-proline
i
0 mol% Pr NH
2
1
2
b
Entry
Ar
Time (h)
Temp. (℃)
2
Yield (%)
1
2
4-MeOC
4-EtOC
4-MeC
4-BrC
4-ClC
4-NH
4-AcNHC
6
H
4
24
26
13
14
15
28
27
80
80
80
80
80
60
60
2a
2b
2c
2d
2e
2f
96
87
67
6
H
4
c
3
6 4
H
c
d
4
6
H
4
88
e
5
6
H
4
57
c
6
2
C
6
H
4
96
48
c
7
6
H
4
2g
a
i
The reactions were performed with 1 (1.0 mmol), NaN
5 mol %) in DMSO (4 mL) at 60-80
.
Isolated yields.
3
(2.0 mmol), Pr
2
NH (20 mol%), L-proline (20 mol%) and Cu (5 µm
,
b
4

ACCEPTED MANUSCRIPT
c
d
e
Ascorbic acid (5 mol%) was added.
-Bromoaniline was also isolated (7% yield).
-Chloroaniline was also isolated (6% yield).
4
4
Having established the coupling of aryl iodides with sodium azide, we next focused our attention to
one-pot synthesis of 1-aryl-1,2,3-triazoles from aryl iodides, alkynes, and sodium azide using porous
Cu catalysts. As shown in Table 3, the reaction was performed with 1a and sodium azide in the
presence of 5 mol% porous Cu (~5 µm), 20 mol% L-proline, and 20% diisopropylamine in DMSO at
80°C for 24 h. Phenylacetylene was subsequently added at 50°C, and this reaction proceeded
efficiently to form 1-aryl-1,2,3-triazole 3a in 73% yield (Table 3, entry 1). To further look at the
possible electronic effects and to expand the scope of this method, acetylenes bearing aromatic groups
of various electron densities were also studied. Alkynes with either an electron-donating group or an
electron-withdrawing group on the benzene ring gave moderate to good isolated yields of the expected
adducts (Table 3, entries 2-4). Under the same reaction conditions, alkyl-substituted phenylacetylenes
were catalyzed, affording 1-aryl-1,2,3-triazoles in excellent yields (Table 3, entries 5 and 6). Various
aryl iodides were then examined, and also obtained corresponding products (Table 3, entries 7-12).
a
Table 3. One-pot Synthesis of 1-Aryl-1,2,3-triazoles from aryl iodides, alkynes, and sodium azide
N N
I
N
R2
1) 5 mol% Cu, NaN3
2) R2
R1
R1
1
3
1
2
6
b
Entry
R
R
Time (h)
Temp. (℃)
3
Yield (%)
1
2
MeO
MeO
MeO
C
H
5
24/34
24/31
21/40
80/50
80/50
80/50
3a
3b
3c
73
68
69
4-MeOC H5
6
c
3
3,4-
6 5
MeOC H
c
4
MeO
MeO
MeO
4-ClC
6
H
5
14/28
24/30
24/30
80/50
80/50
80/50
3d
3e
3f
48
84
82
c
5
6 13
n-C H
c
6
1-
5

ACCEPTED MANUSCRIPT
cyclohexenyl
c
7
8
9
1
1
Me
C
C
6
6
H
5
5
5
5
5
5
11/11
22/26
22/45
14/31
15/20
35/22
80/50
80/50
60/50
80/50
80/50
80/50
3g
3f
3f
3f
3f
3f
66
55
90
63
44
77
AcNH
NH2
Br
H
C H
6
0
1
2
C
C
6
6
H
H
Cl
1
EtO
C H
6
a
i
The reactions were performed with 1 (1.0 mmol), NaN
3
(2.0 mmol), Pr
2
NH (20 mol%), L-proline (20 mol%) and Cu (5 µm
,
5 mol %) in DMSO (4 mL) for 11-35 h at 60-80
; and the subsequent reaction of the mixture was added alkynes (1.1
mmol) and than was stired for 11-45 h at 50
.
b
Isolated yields.
c
Ascorbic acid (5 mol%) was added.
The reusability of porous Cu catalyst was studied for the coupling reaction of 1a with sodium azide in
DMSO. The results are summarized in Table 4. The Cu catalyst was recovered using simple filtration
and reused with consistent activity even after the fifth cycle (Table 4).
a
Table 4. Recycling of catalyst
N3
I
5
mol% Cu
o
NaN , 80 C
3
MeO
MeO
1a
2a
Entry
Yield (%)
1
96
2
85
3
82
4
80
CH)
5
76
b
a
The reactions were performed with 1a (1.0 mmol), NaN
3
(2.0 mmol), (Me
2
2
NH (20 mol%), L-proline (20 mol%) and
Cu (5 µm , 5 mol %) in DMSO (4 mL) at 80
for 24 h.
b
Isolated yields.
3. Conclusion
In conclusion, a very efficient procedure for the one-pot synthesis of 1-aryl-1,2,3-triazoles was
developed using a cheaper, commercially available, and easily recyclable heterogeneous porous Cu
catalyst. A wide range of alkynes and aryl iodides can be tolerated, giving the corresponding 1-aryl-
1,2,3-triazoles.
6

ACCEPTED MANUSCRIPT
4. Experemental
4.1. General
Unless otherwise noted, materials were obtained from commercial suppliers and used without further
purification. Thin layer chromatography (TLC) was performed on glass plates coated with silica gel 60
F254 and visualized by UV light (254nm). Column chromatography was performed with silica gel
(
mesh 300-400). Infrared spectra (IR) were obtained on 370 FT-IR spectrometer; absorptions were
-1
reported in cm . Mass spectra were obtained under electron impact mode (EI) and high resolution
mass spectra were measured on a high resolution mass spectrometer (GCT Premier).
4.2. General procedure for the synthesis of aryl azides and recycling studies
i
To a reactor containing aryl iodides (1.0 mmol), sodium azide (2.0 mmol), Pr
2
NH (20 mol%), L-
proline (20 mol%) and DMSO (4 mL) was added porous Cu (0.05 mmol). The mixture was then
sealed and stirred at 60℃ or 80℃ until the the reaction was completed as judged by TLC. Water was
poured into the mixture and filtered. The recovered Cu catalyst was washed with water and methanol
with no further purification before reuse. The filtrate was extracted with ethyl acetate (3 x 10 mL). The
2 4
organic layer was washed with brine, dried over Na SO and concentrated in vacuo. The residue was
purified by flash chromatography to give the pure product. For recycling studies, the recovered Cu
catalyst was added to the reaction mixture of aryl iodides (1.0 mmol), sodium azide (2.0 mmol),
i
2
Pr NH (20 mol%), L-proline (20 mol%) and DMSO (4 mL) for the next cycle.
4.3. General procedure for the one-pot synthesis of 1-aryl-1,2,3-triazoles
i
To a reactor containing aryl iodides (1.0 mmol), NaN
3
(2.0 mmol), Pr
2
NH (20 mol%), L-proline (20
mol%), and DMSO (4 mL) was added porous Cu (0.05 mmol). The mixture was then sealed and
stirred at 60℃ or 80℃ for 11-35 h. The disappearance of the starting material was determined by TLC.
Then alkynes (1.1 mmol) was added and the reaction mixture was stired at 50℃ for 11-45 h until the
the reaction was completed as judged by TLC. Water was poured into the mixture and filtered. The
filtrate was extracted with ethyl acetate (3 x 10 mL). The organic layer was washed with brine, dried
over Na
2
SO
4
and concentrated in vacuo. The residue was purified by flash chromatography to give the
pure product.
7

ACCEPTED MANUSCRIPT
2
3
1-azido-4-methoxybenzene (2a)
1
Yellew oil, yield: 96%; H NMR (500 MHz, CDCl
3
) δ 6.98 (d, J = 9.0 Hz, 2H), 6.91 (d, J = 9.0 Hz,
) δ 6.96 (d, J = 9.0 Hz, 2H), 6.89 (d, J = 9.0 Hz,
2H), 3.81 (s, 3H).
2
4
1
-azido-4-ethoxybenzene (2b)
1
Yellew oil, yield: 87%; H NMR (500 MHz, CDCl
3
2H), 4.02 (q, J = 7.0 Hz, 2H), 1.43 (t, J = 7.0 Hz, 3H).
2
5
1-azido-4-methylbenzene (2c)
1
Colorless oil, yield: 67%; H NMR (500 MHz, CDCl
3
) δ 7.17 (d, J = 8.0 Hz, 2H), 6.94 (d, J = 8.0 Hz,
2H), 2.35 (s, 3H).
2
6
1-azido-4-bromobenzene (2d)
1
Yellew oil, yield: 88%; H NMR (500 MHz, CDCl
3
) δ 7.46 (d, J = 8.8 Hz, 2H), 6.91 (d, J = 8.8 Hz,
2H).
2
4
1-azido-4-chlorobenzene (2e)
1
Colorless oil, yield: 57%; H NMR (500 MHz, CDCl ) δ 7.32 (d, J = 8.7 Hz, 2H), 6.97 (d, J = 8.7 Hz,
3
2H).
2
7
4-azidobenzenamine (2f)
1
Brown solid, M.p. 60-62
, yield: 96%; H NMR (500 MHz, CDCl
3
) δ 6.85 (d, J = 8.7 Hz, 2H), 6.69
(
d, J = 8.7 Hz, 2H), 3.66 (br, 2H).
2
8
N-(4-azidophenyl)acetamide (2g)
1
White solid, M.p. 126-127
, yield: 48%; H NMR (500 MHz, CDCl ) δ 7.51 (d, J = 8.8 Hz, 2H), 7.30
3
(
s, 1H), 6.99 (d, J = 8.8 Hz, 2H), 2.19 (s, 3H).
-(4-Methoxyphenyl)-4-phenyl-1H-1,2,3-triazole (3a)
Orange solid, M.p. 161-162
, yield: 73%, M.p. 161-163℃; H NMR (500 MHz, CDCl ) δ 8.13 (s,
2
9
1
1
3
1H), 7.92 (d, J = 7.4 Hz, 2H), 7.71 (d, J = 8.9 Hz, 2H), 7.49-7.46 (m, 2H), 7.40-7.27 (m, 1H), 7.06 (d,
J = 8.9 Hz, 2H), 3.90 (s, 3H).
3
0
1-(4-Methoxyphenyl)-4-(4-methoxyphenyl)-1H-1,2,3-triazole (3b)
1
White solid, M.p. 194-195
, yield: 68%; H NMR (500 MHz, CDC1
3
) δ 8.04 (s, 1H), 7.84 (d, J = 8.7
Hz, 2H), 7.69 (d, J = 8.9 Hz, 2H), 7.05 (d, J = 8.9 Hz, 2H), 7.01 (d, J = 8.7 Hz, 2H), 3.89 (s, 3H), 3.87
s, 3H).
(
3
0
1-(4-Methoxyphenyl)-4-(3,4-dimethoxyphenyl)-1H-1,2,3-triazole (3c)
1
White solid, M.p. 136-138
, yield: 69%; H NMR (500 MHz , CDC1
3
) δ 8.06 (s, 1H), 7.70 (d, J = 9.0
Hz, 2H), 7.56 (s, 1H), 7.37 (d, J = 8.3 Hz, 1H), 7.05 (d, J = 9.0 Hz, 2H), 6.95 (d, J = 8.3 Hz, 1H), 4.00
s, 3H), 3.94 (s, 3H), 3.89 (s, 3H).
(
1-(4-Methoxyphenyl)-4-(4-chlorophenyl)-1H-1,2,3-triazole (3d)
1
White solid, M.p. 218-219
, yield: 48%; H NMR (500 MHz, DMSO) δ 9.25 (s, 1H), 7.96 (d, J = 8.5
13
Hz, 2H), 7.85 (d, J = 9.0 Hz, 2H), 7.58 (d, J = 8.5 Hz, 2H), 7.19 (d, J = 9.0 Hz, 2H), 3.85 (s, 3H); C
NMR (125 MHz, DMSO) δ 159.37, 145.99, 132.55, 129.96, 129.29, 129.02, 126.94, 121.70, 119.97,
8

ACCEPTED MANUSCRIPT
-1
1
14.93, 55.58. IR (KBr, cm ): 3117.62, 2935.54, 1646.69, 1610.77, 1518.86, 1480.91, 1303.78,
3
1254.26, 1232.79, 1097.06, 1045.04, 1031.47, 818.11, 804.30. HRMS (ESI) calcd for C15H12ClN O
+
(
M + H) 286.0747, found 286.0713.
3
1
1-(4-Methoxyphenyl)-4-hexyl-1H-1,2,3-triazole (3e)
1
White solid, M.p. 52-53
, yield: 84%; H NMR (500 MHz, CDC1
3
) δ 7.64 (s, 1H), 7.61 (d, J = 9.0
Hz, 2H), 7.00 (d, J = 9.0 Hz, 2H), 3.85 (s, 3H), 2.78 (d, J = 7.7 Hz, 2H), 1.75-1.69 (m, 2H), 1.41-1.37
m, 2H), 1.35-1.30 (m, 4H), 0.89 (t, J = 7.0 Hz, 3H).
(
1-(4-Methoxyphenyl)-4-cyclohexenyl-1H-1,2,3-triazole (3f)
1
White solid, M.p. 106-108
, yield: 82%; H NMR (500 MHz, CDCl
3
) δ 7.74 (s, 1H), 7.63 (d, J = 9.0
Hz, 2H), 7.02 (d, J = 9.0 Hz, 2H), 6.63-6.62 (m, 1H), 3.87 (s, 3H), 2.47-2.44 (m, 2H), 2.26-2.23 (m,
1
3
2
1
2
3
H), 1.82-1.78 (m, 2H), 1.73-1.70 (m, 2H); C NMR (125 MHz, CDCl ) δ 159.65, 149.91, 130.75,
-1
27.09, 125.55, 122.04, 116.51, 114.72, 55.61, 26.43, 25.32, 22.48, 22.20; IR (KBr, cm ): 3154.53,
930.53, 2855.17, 1611.13, 1518.98, 1437.65, 1303.40, 1254.03, 1231.35, 1039.22, 830.48, 785.68.
+
HRMS (ESI) calcd for C H N O (M + H) 256.1450, found 256.1451.
15
17
3
29
1-(4-methylphenyl)-4-phenyl-1H-1,2,3-triazole (3g)
1
White solid, M.p. 166-167
, yield: 66%; H NMR (500 MHz, CDCl ) δ 8.17 (s, 1H), 7.93 (d, J = 8.4
3
Hz, 2H), 7.69 (d, J = 8.4 Hz, 2H), 7.49-7.46 (m, 2H), 7.38-7.34 (m, 3H), 2.46 (s, 3H).
1-(4-acetylaminophenyl)-4-phenyl-1H-1,2,3-triazole (3h)
1
White solid, M.p. 231-232℃, yield: 55%; H NMR (500 MHz, DMSO) δ 10.24 (s, 1H), 9.22 (s, 1H),
7.96-7.94 (m, 2H), 7.88 (d, J = 9.0 Hz, 2H), 7.82 (d, J = 9.0 Hz, 2H), 7.52-7.49 (m, 2H), 7.40 -7.37
1
3
(
m, 1H), 2.10 (s, 3H); C NMR (125 MHz, DMSO) δ 168.60, 147.14, 139.63, 131.62, 130.32, 128.94,
-1
1
28.15, 125.30, 120.64, 119.70, 119.40. 24.02; IR (KBr, cm ): 3353.77, 3126.43, 1686.94, 1662.70,
1557.24, 1524.13, 1405.88, 1322.90, 1047.28, 955.48, 832.71, 763.18, 692.51. HRMS (ESI) calcd for
+
C
16
H
14
N
4
O (M + H) 279.1264, found 279.1241.
32
1-(4-aminophenyl)-4-phenyl-1H-1,2,3-triazole (3i)
1
White solid, M.p. 146-147℃, yield: 90%; H NMR (500 MHz, CDCl
3
) δ 8.08 (s, 1H), 7.92-7.90 (m,
2
2
1
H), 7.54 (d, J = 8.7Hz, 2H), 7.48-7.45 (m, 2H), 7.38-7.35 (m, 1H), 6.80 (d, J = 8.7 Hz, 2H), 3.92 (br,
H).
3
3
-(4-bromophenyl)-4-phenyl-1H-1,2,3-triazole (3j)
1
White solid, M.p. 222-223℃, yield: 63%; H NMR (500 MHz, CDC1 ) δ 9.35 (s, 1H), 7.96-7.93 (m,
3
4H), 7.87-7.85 (m, 2H), 7.53-7.50 (m, 2H), 7.42-7.39 (m, 1H).
3
4
1-(4-chlorophenyl)-4-phenyl-1H-1,2,3-triazole (3k)
1
White solid, M.p. 223-224℃, yield: 44%; H NMR (500 MHz, DMSO) δ 9.35 (s, 1H), 8.01 (d, J =
8.9Hz, 2H), 7.96-7.94 (m, 2H), 7.73 (d, J = 8.9 Hz, 2H), 7.53-7.50 (m, 2H), 7.42-7.40 (m, 1H).
1-(4-Ethoxyphenyl)-4-phenyl-1H-1,2,3-triazole (3l)
9

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1
Yellow solid; M.p. 141-142℃, yield: 77%; H NMR (500 MHz, CDCl
3
) δ 8.12 (s, 1H), 7.93-7.91 (m,
2H), 7.68 (d, J = 9.0 Hz, 2H), 7.49-7.46 (m, 2H), 7.39-7.38 (m, 1H), 7.04 (d, J = 9.0 Hz, 2H), 4.11 (q,
1
3
3
J = 7.0 Hz, 2H), 1.47 (t, J = 7.0 Hz, 3H); C NMR (125 MHz, CDCl ) δ 159.24, 148.18, 130.42,
-1
1
30.37, 128.88, 128.29, 125.81, 122.13, 117.84, 115.30, 63.93, 14.72; IR (KBr, cm ): 3131.54,
2984.09, 1757.01, 1644.10, 1518.54, 1374.74, 1247.07, 1046.68, 827.90, 766.92, 691.15. HRMS
+
(
ESI) calcd for C16
H
15
N
3
O (M + H) 266.1293, found 266.1290.
Acknowledgements
We thank the Hangzhou Natural Scienece Foundation (No. Y4100558) for financial support and
HENGKO Technology Co., Ltd. for support of porous Cu catalyst.
References
[
[
1] C. W. Tornoe, C. Christensen, M. Meldal, J. Org. Chem. 2002, 67, 3057.
2] V. V. Rostovtsev, L. G. Green, V. V. Fokin, K. B. Sharpless, Angew. Chem., Int. Ed. 2002, 41,
2596.
[
3] M. Meldal, C. W. Tornøe, Chem. Rev. 2008, 108, 2952.
[
[
4] J. E. Moses, A. D. Moorhouse, Chem. Soc. Rev. 2007, 36, 1249.
5] G. C. Tron, T. Pirali, R. A. Billington, P. L. Canonico, G. Sorba, A. A. Genazzani, Med. Res. Rev.
2008, 28, 278.
[
[
[
6] J.-F. Lutz, and Z. Zarafshani, Adv. Drug Delivery Rev. 2008, 60, 958.
7] V. V. Fokin, ACS Chem. Biol. 2007, 2, 775.
8] J. A. Johnson, J. T. Koberstein, M. G. Finn, N. J. Turro, Macromol. Rapid Commun. 2008, 29,
1052.
[
[
[
9] P. Wu, and V. V. Fokin, Aldrichimica Acta 2007, 40, 7.
10] J. Andersen, S. Bolvig, X. F. Liang, Synlett 2005, 2941.
11] E. F. V. Scriven and K. Turnbull, Chem. Rev., 1988, 88, 297.
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[
12] J. A. R. Rodrigues, R. A. Abramovitch, J. D. F. de Souse, G. C. Leiva, J. Org. Chem. 2004, 69,
2920.
[
[
[
[
[
[
[
13] Q. Liu, Y. Tor, Org. Lett., 2003, 5, 2571.
14] W. Zhu, D. W. Ma, Chem. Commun., 2004, 888.
15] U. Madsen, F. Björkling, X. F. Liang, Synlett 2005, 2209.
16] C. Christofides, A. Mandelis, J. Appl. Phys. 1990, 68, R1.
17] F. Favier, E. C. Walter, M. P. Zach, T. Benter, R. M. Penner, Science 2001, 293, 2227.
18] D. Ding, Z. Chen, AdV. Mater. 2007, 19, 1996.
19] Y.M.Z. Ahmed, M.I. Riad, A.S. Sayed, M.K. Ahlam, M.E.H. Shalabi, Powder Technology, 2007,
175, 48.
[
[
20] I. Salvatori, La Metallurgia Italiana, 2006, 98, 41.
21] T. N. Jin, M. Yan, M. Bateer, T. Minato, M. Bao, Y. Yamamoto, Adv. Synth. Catal. 2011, 353,
3095.
[
22] C. Zhang, B. Huang, Y. Chen, D. M. Cui, New J. Chem. DOI:10.1039/C3NJ00468F
[
[
[
[
[
[
[
[
23] L. Di Nunno, A. Scilimati, Tetrahedron, 1986, 42, 3913.
24] M. Y. Hu, J. Q. Li, S. Q. Yao, Org. Lett., 2008, 10, 5529.
25] J. T. Markiewicz, O. Wiest, P. Helquist, J. Org. Chem., 2010, 75, 4887.
26] Z. Jia, Q. Zhu, Bioor. Med. Chem. Lett., 2010, 20, 6222.
27] W. Zhu, D. W. Ma, Chem. Commun., 2004, 888-889.
28] N. T. Pokhodylo, V. S. Matiichuk, N. D. Obushak, Russ. J. Org. Chem., 2010, 46, 556.
29] X. Meng, X. Y. Xu, T. T. Gao, B. H. Chen, Eur. J. Org. Chem. 2010, 5409.
30] F. Pagliai, T. Pirali, E. D. Grosso, R. D. Brisco, G. C. Tron, G. Sorba, A. A. Genazzani,
J. Med. Chem., 2006, 49, 467.
[
[
[
[
31] J. C. Yan, L. Wang, Synthesis, 2010, 3, 447.
32] Y. B. Zhao, Z. Y. Yan, Y. M. Liang, Tetrahedron Lett., 2006, 47, 1545.
33] R. Hosseinzadeh, H. Sepehrian, F. Shahrokhi, Heteroat. Chem., 2012, 23, 415.
34] D. Wang, N. Li, M. M. Zhao, W. L. Shi, C. W. Ma, B. H. Chen, Green Chem., 2010, 12,
2
120.
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Highlights
An efficient one-pot synthesis of 1-aryl 1,2,3-triazoles from aryl iodides, alkynes, and
sodium azide using porous Cu (0) heterogeneous catalyst has been reported.
The spent catalyst can be easily recovered and reused for five cycles with consistent
activity.
►
►

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Supporting Information
Copper Catalyzed Synthesis of 1-Aryl 1,2,3-Triazoles from Aryl Iodides, Alkynes,
and Sodium Azide
Yin Chen, Zi-Jian Zhuo, Dong-Mei Cui, and Chen Zhang

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