A novel approach to 1-monosubstituted 1,2,3-triazoles by a click cycloaddition/decarboxylation process

Article abstract of DOI:10.1055/s-0030-1258357

The synthesis of 1-monosubstituted 1,2,3-triazoles was achieved using azides and propiolic acid by copper-catalyzed click cycloaddition/ decarboxylation, which was easily carried out in N,N-dimethylformamide at room temperature or 60 C with yields ranging

Full text of DOI:10.1055/s-0030-1258357

PAPER
223
A Novel Approach to 1-Monosubstituted 1,2,3-Triazoles by a
Click Cycloaddition/Decarboxylation Process
S
ynthesis of 1-Monosu
e
bstituted 1,
i
2,3-Triazoles
X
U
sing
P
ropiolic
A
ucid ,a Chunxiang Kuang,*a Zhuo Wang,a Qing Yang,b Yubo Jianga
a
Department of Chemistry, Tongji University, Siping Road 1239, Shanghai 200092, P. R. of China
Fax +86(21)65983191; E-mail: kuangcx@tongji.edu.cn
b
Department of Biochemistry, School of Life Sciences, Fudan University, Handan Road 220, Shanghai 200433, P. R. of China
Received 12 October 2010; revised 9 November 2010
interesting result inspired us to investigate this transfor-
mation further. A preliminary study to screen optimum re-
action conditions was performed with 1-azido-4-
methylbenzene (1a, 0.2 mmol) as the starting material
Abstract: The synthesis of 1-monosubstituted 1,2,3-triazoles was
achieved using azides and propiolic acid by copper-catalyzed click
cycloaddition/decarboxylation, which was easily carried out in N,N-
dimethylformamide at room temperature or 60 °C with yields rang-
ing from moderate to excellent. The reaction conditions were found (Table 1). We investigated the effects of different bases
to be successful for aryl and vinyl azide reactants, including ana-
logues with various functionalities.
and various amounts of copper(I) iodide in various sol-
vents on the formation of the triazole 2a. When 1-azido-
4-methylbenzene (1a) reacted with propiolic acid in the
presence of copper(I) iodide (0.2 equiv) and sodium
ascorbate (0.4 equiv) in N,N-dimethylformamide (25 °C,
16 h), product 2a was obtained in low yield (entry 1). In
Key words: click chemistry, copper catalysis, decarboxylation,
heterocycle, 1-monosubstituted 1,2,3-triazole
Various 1,2,3-triazole derivatives display a wide range of order to improve the yield, different bases were added. As
applications in the fields of pharmacy, agriculture, and in- expected, of the bases that we tested (using a catalytic
dustry.1 The click chemistry reaction between azide and amount of CuI), triethylamine and DBU led to higher
terminal alkyne catalyzed by copper(I) has enabled the yields with DBU giving the highest yield of up to 93%
practical and efficient preparation of 1,4-disubstituted (entries 2–4). The solvent system, on the other hand, was
1,2,3-triazoles.2 Nevertheless, there are only a few reports found to be important for the reaction outcome: pure N,N-
in the literature concerning synthetic methods for 1- dimethylformamide was more effective than other single
monosubstituted 1,2,3-triazoles. One strategy is the decar- or mixed solvents (entries 5–8). Furthermore, product 2a
boxylation of triazoles bearing a carboxylic acid substitu- was not observed when water was used as the solvent; the
ent, but the reactions require extreme temperatures and reason may lie in the decrease in the solubility of the reac-
long reaction times.3 Another method is the cycloaddition tant in this reaction system. Decreasing the amount of
of azides to acetylene4 and its analogues such as copper(I) iodide resulted in a reduction in the yield, and
acetylides5 as well as vinyl compounds.6
the reaction time was shortened by increasing the amount
of catalyst (entries 9 and 10). Unsurprisingly, increasing
the temperature had a dramatic impact on the efficiency of
the triazole-forming process as well as the yield (entry
11). Moreover, the yield was lower when a lower amount
or no sodium ascorbate was used (entries 12 and 13). It
was concluded that the optimum reaction conditions in-
volved copper(I) iodide (0.2 equiv), DBU (0.5 equiv), and
sodium ascorbate (0.4 equiv) in N,N-dimethylformamide
at room temperature for 16 hours or at 60 °C for two hours
(entries 4 and 11).
N
N
CuI, Na ascorbate
R
N
R
N3
CO2H
+
DBU, DMF
1
2
Scheme 1 Synthesis of 1-monosubstituted 1,2,3-triazoles 2
Recently, we synthesized a series of 1-monosubstituted
1,2,3-triazoles using calcium carbide as a source of acety-
lene.7 Herein we described a convenient and efficient
method for the preparation of 1-monosubstituted 1,2,3-tri-
azoles 2, in which propiolic acid was reacted with aryl
azides 1 via copper-catalyzed click cycloaddition/
decarboxylation8 (Scheme 1).
Next, we turned our attention to the scope of this click re-
action/decarboxylation. A variety of prepared aryl azides
1 were reacted with propiolic acid under the optimized re-
action conditions; the reactions finished in various times
and afforded 1-monosubstituted 1,2,3-triazoles 2 in mod-
erate to excellent yields. The results summarized in
Table 2 show that aryl azides 1 carrying either an elec-
tron-donating, such as methyl, methoxy, and hydroxy
groups (entries 1–3, 5, 16), or an electron-withdrawing
substituent, including chloro, bromo, fluoro, sulfamoyl,
ethoxycarbonyl, and nitro groups (entries 6–15), all pro-
ceeded smoothly. Most reactions can be conducted at
room temperature or 60 °C. Substrates bearing an o-sub-
An unexpected decarboxylation product, 1-phenyl-1H-
1,2,3-triazole, was observed, in the preparation of 1-phe-
nyl-1H-1,2,3-triazole-4-carboxylic acid through ‘click
chemistry’ using azidobenzene and propiolic acid. This
SYNTHESIS 2011, No. 2, pp 0223–0228
x
x
.
x
x
.2
0
1
1
Advanced online publication: 07.12.2010
DOI: 10.1055/s-0030-1258357; Art ID: F18110SS
© Georg Thieme Verlag Stuttgart · New York

224
M. Xu et al.
PAPER
Table 1 Optimization of the Synthesis of 1-p-Tolyl-1,2,3-triazole (2a)
N
CuI, Na ascorbate
CO2H
N
N
N3
+
base, solvent
2a
1a
Entry
1
CuI (equiv) Sodium ascorbate (equiv) Base
Solvent
DMF
DMF
DMF
DMF
Temp (°C) Time (h)
Yielda of 2a (%)
0.2
0.2
0.2
0.2
0.2
0.2
0.2
0.2
0.1
0.5
0.2
0.2
0.2
0.40
0.40
0.40
0.40
0.40
0.40
0.40
0.40
0.20
1.00
0.40
0.3
0
25
25
25
25
25
25
25
25
25
25
60
25
25
16
16
16
16
16
16
16
16
16
10
2
20
10
70
93
30
15
83
0
2
L-proline
Et3N
DBU
DBU
DBU
DBU
DBU
DBU
DBU
DBU
DBU
DBU
3
4
5
MeCN–H2O (9:1)
MeOH–H2O (9:1)
DMSO
6
7
8
H2O
9
DMF
64
91
92
82
55
10
11
12
13
DMF
DMF
DMF
16
16
0
DMF
a Isolated yield.
stituent had low reaction rates due to steric hindrance (en- with propiolic acid to provide adducts 3s–u with complete
tries 3, 15, 17), while the reactions proceed smoothly by stereocontrol in good yields; previous synthetic methods
increasing the reaction temperature to 120 °C. To our de- used the regioselective reaction of vinyl halides with
light, aryl azides with active groups such as hydroxy and trizole9 (entries 19–21). However, benzyl azide gave a
heterocyclic azides afforded products 2p and 2r in 89% low yield of 2v at 150 °C due to its lower activity in com-
and 75% yields, respectively (entries 16 and 18). In addi- parison with aryl azides (entry 22).
tion, under the same conditions, vinyl azides also reacted
Table 2 Synthesis of 1-Monosubstituted 1,2,3-Triazoles 2a
Entry
Azide 1
Product 2
Temp (°C)
Time (h)
Yieldb (%)
1
2
3
2a (p-)
2b (m-)
2c (o-)
25
60
120
16
3
5
93
88
66
N
N
N3
N
Me
Me
N
N
4
5
6
2d
2e
2f
25
60
60
14
3
87
94
79
N3
N
N
N
MeO
Br
N3
MeO
Br
N
N
N
3
N3
N
N
7
8
2g (p-)
2h (m-)
25
60
18
7
85
86
N
N3
N
Cl
F
Cl
F
N
N
9
2i
60
3
90
N3
N
Synthesis 2011, No. 2, 223–228 © Thieme Stuttgart · New York

PAPER
Synthesis of 1-Monosubstituted 1,2,3-Triazoles Using Propiolic Acid
225
Table 2 Synthesis of 1-Monosubstituted 1,2,3-Triazoles 2a (continued)
Entry
10
Azide 1
Product 2
Temp (°C)
25
Time (h)
12
Yieldb (%)
Cl
Cl
2j
91
N
N
F
N3
F
N
N
N
11
12
2k
2l
25
60
3
2
95
78
H2NO2S
N3
H2NO2S
EtO2C
N
N
N
EtO2C
N3
N
13
14
15
2m (p-)
2n (m-)
2o (o-)
25
60
60
10
2
3
81
89
68
N
N
N3
N
O2N
HO
O2N
HO
N
N
16
2p
60
4
89
N3
N
N
N
N3
N
17
2q
120
24
74
N
S
N
N
S
N
18
19
20
2r
2s
2t
60
60
60
4
14
14
75
85
87
N
N3
N
N3
N
N
N
N3
N
N
N
N3
N
21
22
2u
2v
60
24
14
72
50
N
N
COOEt
COOEt
N
N
N3
150
a Conditions: azide (0.3 mmol), propiolic acid (0.45 mmol), CuI (0.06 mmol), Na ascorbate (0.12 mmol), DBU (0.15 mmol), DMF (2 mL),
stirred for the indicated temperature and time.
b Isolated yield.
In order to elucidate the probable reaction mechanism, stable 1-monosubstituted 1,2,3-triazole 2 is formed even-
compound 3 was synthesized using ethyl propiolate as a tually through protonation and decarboxylation, simulta-
starting material and subjected to decarboxylation neously releasing the CuLn, carbon dioxide, and the free
(Scheme 2). Surprisingly, the direct decarboxylation triazole.
product 2a was not observed at room temperature and
In summary, we have showed a novel and useful protocol
only a low yield of the target molecule was achieved at
for the synthesis of 1-monosubstituted 1,2,3-triazoles by
130 °C. Based on the experimental data a proposed mech-
click reaction/decarboxylation under mild conditions. It
anism is described in Scheme 3. In the initial stage of the
demonstrates that propiolic acid is equivalent to gaseous
catalytic cycle, the dehydrogenation of propiolic ion with
acetylene in the click cycloaddition and provides a mild
DBU and CuLn produces the copper acetylide carbonate
access to 1-monosubstituted aryl- and vinyl-1,2,3-tria-
ion A. The triazole B is readily formed by the [3+2] cy-
zoles, which are important heterocycle compounds in me-
dicinal chemistry and materials science. Further studies
on the application of the present methodology to the syn-
cloaddition reaction between the C≡C bond of the copper
acetylide carbonate ion A and the azide; additionally, we
propose that the CuLn is coordinated with one oxygen
thesis of biological active compounds are proceeding.
atom from carbonate ion and one carbon atom of the tria-
zole to give a key five-member cyclic intermediate C. A
Synthesis 2011, No. 2, 223–228 © Thieme Stuttgart · New York

226
M. Xu et al.
PAPER
CuI, DMF
N
HO–
N
N
Na ascorbate
N
COOEt
N3
CO2Et
N
CuI (20 mol%), DBU
Na ascorbate (40 mol%)
N
N
N
N
DMF
CO2H
3
2a
25 °C, 24 h yield: 0%
130 °C, 24 h yield: 50%
Scheme 2 Synthesis of 2a from 3
1H NMR (500 MHz, CDCl3): d = 7.95 (d, J = 1.0 Hz, 1 H), 7.83 (d,
J = 1.0 Hz, 1 H), 7.62 (d, J = 8.0 Hz, 2 H), 7.32 (d, J = 8.0 Hz, 2 H),
2.43 (s, 3 H).
HO2C
O2C
H
DBU
+
CO2
H
DBU⋅H+
N
Ar
N
1-m-Tolyl-1H-1,2,3-triazole (2b)11
Yellow solid.
N
2
CuLn
1H NMR (500 MHz, CDCl3): d = 7.98 (d, J = 0.7 Hz, 1 H), 7.84 (d,
J = 0.7 Hz, 1 H), 7.59 (s, 1 H), 7.52 (d, J = 8.0 Hz, 1 H), 7.42 (d,
J = 8.0 Hz, 1 H), 7.27–7.25 (m, 1 H), 2.46 (s, 3 H).
2H+
H+
O
O
Ln
Ar
Cu
1-o-Tolyl-1H-1,2,3-triazole (2c)10
Light-yellow liquid.
1H NMR (500 MHz, CDCl3): d = 7.86 (d, J = 0.9 Hz, 1 H), 7.76 (d,
J = 0.9 Hz, 1 H), 7.43–7.34 (m, 4 H), 2.20 (s, 3 H).
O2C
CuLn
N
N
A
N
C
1-Phenyl-1H-1,2,3-triazole (2d)10
Light-yellow solid.
1H NMR (500 MHz, CDCl3): d = 8.0 (d, J = 0.9 Hz, 1 H), 7.86 (d,
J = 0.9 Hz, 1 H), 7.76–7.74 (m, 2 H), 7.56–7.53(m, 2 H), 7.45 (t,
J = 16.0 Hz, 1 H).
O2C
CuLn
ArN3
1
N
N
N
Ar
B
Scheme 3 A proposed mechanism for the reaction
1-(4-Methoxyphenyl)-1H-1,2,3-triazole (2e)11
Yellow solid.
1H and 13C NMR spectra were recorded with a Bruker AM-500
spectrometer in CDCl3 solns with TMS as an internal standard. MS
data were measured with a Varian-310 mass spectrometer. HRMS
were determined using a Finnigan-MAT GC/MS/DS 8430 spec-
trometer. Commercially obtained reagents were used without fur-
ther purification. Solvents used were dried over 4 Å molecular
sieves. All reactions were monitored by TLC with Huanghai GF
254 silica gel coated plates. Column chromatography was carried
out using 300–400 mesh silica gel at medium pressure.
1H NMR (500 MHz, CDCl3): d = 7.91 (d, J = 0.8 Hz, 1 H), 7.83 (d,
J = 0.8 Hz, 1 H), 7.64 (d, J = 6.8 Hz, 2 H), 7.03 (d, J = 6.8 Hz, 2 H),
3.87 (s, 3 H).
1-(4-Bromophenyl)-1H-1,2,3-triazole (2f)11
Light-yellow solid.
1H NMR (500 MHz, CDCl3): d = 7.98 (s, 1 H), 7.87 (s, 1 H), 7.69–
7.64 (m, 4 H).
1-(4-Chlorophenyl)-1H-1,2,3-triazole (2g)10
Light-yellow solid.
1H NMR (500 MHz, CDCl3): d = 7.98 (s, 1 H), 7.86 (s, 1 H), 7.71
(d, J = 8.8 Hz, 2 H), 7.51 (d, J = 8.8 Hz, 2 H).
1-Aryl-1H-1,2,3-triazoles 2a–r, 1-Vinyl-1H-1,2,3-triazoles 2s–u,
and 1-Benzyl-1H-1,2,3-triazole (2v); General Procedure
A solution of azide (50 mg, 0.3 mmol), propiolic acid (32 mg,
0.45mmol), CuI (11 mg, 0.06 mmol), Na ascorbate (24 mg, 0.12
mmol), and DBU (23 mg, 0.15 mmol) in DMF (2 mL) in a sealed
tube was stirred under N2. The mixture was heated to the tempera-
ture indicated in Table 2, until the starting azide had been complete-
ly consumed (monitored by TLC). The mixture was diluted with
H2O and then extracted with EtOAc or CH2Cl2 (3 × 15 mL). The
combined organic layers were washed with sat. brine, dried (anhyd
Na2SO4), and concentrated under reduced pressure to afford the
crude product. The crude product was purified by flash chromatog-
raphy (silica gel). Compound characterization data are available in
the Supporting Information. Spectroscopic data were identical to
those reported in the literature.
1-(3-Chlorophenyl)-1H-1,2,3-triazole (2h)11
Yellow solid.
1H NMR (500 MHz, CDCl3): d = 8.00 (d, J = 1.0 Hz, 1 H), 7.86 (d,
J = 1.0 Hz, 1 H), 7.80 (t, J = 2.0 Hz, 1 H), 7.66 (d, J = 0.9 Hz, 1 H),
7.50–7.43 (m, 2 H).
1-(4-Fluorophenyl)-1H-1,2,3-triazole (2i)10
White solid.
1H NMR (500 MHz, CDCl3): d = 7.95 (d, J = 1.0 Hz, 1 H), 7.85 (d,
J = 1.0 Hz, 1 H), 7.73 (d, J = 9.0 Hz, 2 H), 7.23 (d, J = 7.6 Hz, 2 H).
1-p-Tolyl-1H-1,2,3-triazole (2a)10
Light-yellow solid.
Synthesis 2011, No. 2, 223–228 © Thieme Stuttgart · New York

PAPER
Synthesis of 1-Monosubstituted 1,2,3-Triazoles Using Propiolic Acid
227
1-(3-Chloro-4-fluorophenyl)-1H-1,2,3-triazole (2j)12
Gray solid.
1H NMR (500 MHz, CDCl3): d = 7.96 (s, 1 H), 7.87 (s, 1 H), 7.86–
7.85 (m, 1 H), 7.66–7.63 (m, 1 H), 7.34–7.31 (m, 1 H).
1H NMR (500 MHz, CDCl3): d = 8.02 (s, 1 H), 7.88 (d, J = 1.0 Hz,
1 H), 7.61(d, J = 1.1 Hz, 1 H), 7.35 (t, J = 7.4 Hz, 1 H), 7.25 (t,
J = 7.6 Hz, 2 H), 6.80 (d, J = 7.3 Hz, 2 H), 4.32 (q, J = 7.2 Hz, 2 H),
1.31 (t, J = 7.1 Hz, 3 H).
13C NMR (125 MHz, CDCl3): d = 163.1, 140.5, 134.1, 131.4, 130.9,
130.3, 128.9, 125.4, 125.3, 62.4, 14.1.
4-(1H-1,2,3-Triazol-1-yl)benzenesulfonamide (2k)10
Yellow solid.
MS (ESI): m/z (%) = 243(M+).
HRMS: m/z [M]+ calcd for C13H13N3O2: 243.1008; found:
1H NMR (500 MHz, DMSO-d6): d = 8.94 (s, 1 H), 8.14 (d, J = 8.7
Hz, 2 H), 8.03 (s, 1 H), 8.02 (d, J = 8.7 Hz, 2 H), 7.53 (s, 2 H).
243.1009.
Ethyl 4-(1H-1,2,3-Triazol-1-yl)benzoate (2l)11
Yellow solid.
1H NMR (500 MHz, CDCl3): d = 8.22 (d, J = 8.5 Hz, 2 H), 8.07 (s,
1 H), 7.89 (s, 1 H), 7.86 (d, J = 8.5 Hz, 2 H), 4.42 (q, J = 7.0 Hz, 2
H), 1.42 (t, J = 7.1 Hz, 3 H).
1-Benzyl-1H-1,2,3-triazole (2v)11
Yellow solid.
1H NMR (500 MHz, CDCl3): d = 7.71(s, 1 H), 7.47 (s, 1 H), 7.40–
7.35 (m, 3 H), 7.26 (m, 2 H), 5.57 (s, 2 H).
1-(4-Nitrophenyl)-1H-1,2,3-triazole (2m)10
Yellow solid.
Supporting Information for this article is available online at
http://www.thieme-connect.com /ejournals/toc/synthesis.
1H NMR (500 MHz, CDCl3): d = 8.44 (d, J = 9.1 Hz, 2 H), 8.12 (s,
1 H), 8.01 (d, J = 9.1 Hz, 2 H), 7.93 (s, 1 H).
Acknowledgment
1-(3-Nitrophenyl)-1H-1,2,3-triazole (2n)11
The work was supported by the Natural Science Foundation of Chi-
na (No. 30873153), the Key Projects of Shanghai in Biomedical
(No. 08431902700), and the Scientific Research Foundation of
State Education Ministry for the Returned Overseas Chinese Scho-
lars. We would like to thank the Center for Instrumental Analysis,
Tongji University, China.
Light-yellow solid.
1H NMR (500 MHz, CDCl3): d = 8.61 (t, J = 2.0 Hz, 1 H), 8.34–
8.31 (m, 1 H), 8.23–8.21 (m, 1 H), 8.12 (d, J = 1.0 Hz, 1 H), 7.92
(d, J = 1.0 Hz, 1 H), 7.77 (t, J = 8.2 Hz, 1 H).
1-(2-Nitrophenyl)-1H-1,2,3-triazole (2o)10
Yellow solid.
References
1H NMR (500 MHz, CDCl3): d = 8.11–8.09 (m, 1 H), 7.89–7.88 (m,
2 H), 7.83–7.79 (m, 1 H), 7.74–7.70 (m, 1 H), 7.65–7.63 (m, 1 H).
(1) Irgolic, K. J. In Houben-Weyl, 4th ed., Vol. E12b; Klamann,
D., Ed.; Georg Thieme Verlag: Stuttgart, 1990, 150.
(a) Hoogenboom, R.; Schubert, U. S. Chem. Soc. Rev. 2007,
36, 1369. (b) Nandivada, H.; Jiang, X.; Lahann, J. Adv.
Mater. 2007, 19, 2197. (c) Lutz, J. F. Angew. Chem. Int. Ed.
2007, 46, 1018. (d) Tron, G. C.; Pirali, T.; Billington, R. A.;
Canonico, P. L.; Sorba, G.; Genazzani, A. A. Med. Res. Rev.
2008, 28, 278. (e) Hanelt, S.; Liebscher, J. Synlett 2008,
1058. (f) Aufort, M.; Herscovici, J.; Bouhours, P.; Moreau,
N.; Girard, C. Bioorg. Med. Chem. Lett. 2008, 18, 1195.
(g) Xie, J.; Seto, C. T. Bioorg. Med. Chem. 2007, 15, 458.
(h) Cogan, D. A.; Aungst, R.; Breinlinger, E. C.; Fadra, T.;
Goldberg, D. R.; Hao, M. H.; Kroe, R.; Moss, N.; Pargellis,
C.; Qian, K. C.; Swiname, A. D. Bioorg. Med. Chem. Lett.
2008, 18, 3251.
4-(1H-1,2,3-Triazol-1-yl)phenol (2p)13
White solid.
1H NMR (500 MHz, DMSO-d6): d = 9.91 (s, 1 H), 8.63 (d, J = 1.0
Hz, 1 H), 7.90 (d, J = 1.0 Hz, 1 H), 7.66 (q, J = 9.0 Hz, 2 H), 6.93
(d, J = 9.0 Hz, 2 H).
1-(Naphthalen-1-yl)-1H-1,2,3-triazole (2q)14
Light-yellow liquid.
1H NMR (500 MHz, CDCl3): d = 8.05–8.02 (m, 1 H), 7.98–7.95 (m,
3 H), 7.61–7.53 (m, 5 H).
1-(Thiazol-2-yl)-1H-1,2,3-triazole (2r)15
Light-yellow solid.
(2) (a) Rostovtsev, V. V.; Green, L. G.; Fokin, V. V.; Sharpless,
K. B. Angew. Chem. Int. Ed. 2002, 41, 2596. (b) Tornoe, C.
W.; Christensen, C.; Meldal, M. J. Org. Chem. 2002, 67,
3057. (c) Zhang, L.; Chen, X.; Xue, P.; Sun, H. H. Y.;
Williams, I. D.; Sharpless, K. B.; Fokin, V. V.; Jia, G. J. Am.
Chem. Soc. 2005, 127, 15998. (d) Rasmussen, L. K.; Boren,
B. C.; Fokin, V. V. Org. Lett. 2007, 9, 5337. (e) Boren, B.
C.; Narayan, S.; Rasmussen, L. K.; Shang, L.; Zhao, H.; Lin,
Z.; Jia, G.; Fokin, V. V. J. Am. Chem. Soc. 2008, 130, 8923.
(f) Meldal, M. C.; Tornoe, W. Chem. Rev. 2008, 108, 2952.
(3) (a) Ebner, D. C.; Culhane, J. C.; Winkelman, T. N.;
Haustein, M. D.; Ditty, J. L.; Ippolitia, J. T. Bioorg. Med.
Chem. 2008, 16, 2651. (b) Naud, J.; Lemke, C.; Goudreau,
N.; Beaulieu, E.; White, P. D. Bioorg. Med. Chem. Lett.
2008, 18, 3400. (c) Zhou, W.; Zheng, F.; Li, Y.; Guo, G.;
Chen, Q.; Wu, M. CN 101,497,586, 2009; Chem. Abstr.
2009, 115, 327352. (d) Li, H.; Jiang, W.; Tong, X. CN
101,104,607, 2008; Chem. Abstr. 2008, 148, 215054.
(e) Xu, W.-L.; Li, Y.-Z.; Zhang, Q.-S.; Zhu, H.-S. Jingxi
Huagong 2003, 20, 628. (f) Deng, Y.; Shen, Y.; Zhong, Y.
1H NMR (500 MHz, CDCl3): d = 8.44 (d, J = 1.0 Hz, 1 H), 7.84 (d,
J = 1.0 Hz, 1 H), 7.69 (d, J = 3.5 Hz, 1 H), 7.28 (d, J = 3.5 Hz, 1 H).
(Z)-1-Styryl-1H-1,2,3-triazole (2s)9
Light-yellow solid.
1H NMR (500 MHz, CDCl3): d = 7.60 (s, 1 H), 7.39 (s, 1 H), 7.35–
7.32 (m, 3 H), 7.29 (d, J = 9.6 Hz, 1 H), 7.13 (t, J = 7.5 Hz, 2 H),
6.58 (d, J = 9.6 Hz, 1 H).
(E)-1-Styryl-1H-1,2,3-triazole (2t)9
Light-yellow solid.
1H NMR (500 MHz, CDCl3): d = 7.88 (s, 1 H), 7.78 (t, J = 14.7 Hz,
2 H), 7.48 (d, J = 7.5 Hz, 2 H), 7.40 (t, J = 7.3 Hz, 2 H), 7.34 (t,
J = 7.3 Hz, 1 H), 7.19 (d, J = 14.7 Hz, 1 H).
Ethyl (Z)-3-Phenyl-2-(1H-1,2,3-triazol-1-yl)acrylate (2u)
Light-yellow solid.
Synthesis 2011, No. 2, 223–228 © Thieme Stuttgart · New York

228
M. Xu et al.
PAPER
Huaxi Yaoxue Zazhi 2001, 16, 273. (g) Brian, I.; Martin, N.
J. Chem. Soc., Perkin Trans. 1 1996, 12, 1341.
(h) Yoshinobu, N.; Koichi, H.; Hiroshi, N. Bull. Chem. Soc.
Jpn. 1987, 60, 2931.
(8) (a) Gooßen, L. J.; Rodriguez, N.; Gooßen, K. Angew. Chem.
Int. Ed. 2008, 47, 3100. (b) Baudoin, O. Angew. Chem. Int.
Ed. 2007, 46, 1373. (c) Voutchkova, A.; Coplin, A.;
Leadbeater, N. E.; Crabtree, R. H. Chem. Commun. 2008,
6312. (d) Feng, C.; Loh, T. P. Chem. Commun. 2010, 4779.
(e) Yoshino, Y.; Kurahashi, T.; Matsubara, S. J. Am. Chem.
Soc. 2009, 131, 7494. (f) Kolarovič, A.; Fáberová, Z. J. Org.
Chem. 2009, 74, 7199. (g) Jia, W.; Jiao, N. Org. Lett. 2010,
12, 2000.
(9) Taillefer, M.; Ouali, A.; Renard, B.; Spindler, J.-F. Chem.
Eur. J. 2006, 12, 5301.
(10) Jiang, Y.; Kuang, C.; Yang, Q. Synlett 2009, 3163.
(11) Wu, L.; Xie, Y.; Chen, Z.; Niu, Y.; Liang, Y. Synlett 2009,
1453.
(4) (a) Wu, L.; Xie, Y.; Chen, Z.; Niu, Y.; Liang, Y. Synlett
2009, 1453. (b) De, O.; Ronaldo, N.; Sinou, D. R.;
Srivastava, M. J. Carbohydr. Chem. 2006, 25, 407.
(5) (a) Aher, N. G.; Pore, V. S.; Mishra, N. N.; Kumar, A.;
Shukla, P. K.; Sharma, A.; Bhat, M. K. Bioorg. Med. Chem.
Lett. 2009, 19, 759. (b) Fletcher, J. T.; Walz, S. E.; Keeney,
M. E. Tetrahedron Lett. 2008, 49, 7030. (c) Chan, D. C. M.;
Laughton, C. A.; Queener, S. F.; Stevens, M. F. G. Bioorg.
Med. Chem. 2002, 10, 3001.
(6) (a) Biagi, G.; Livi, O.; Scartoni, V.; Verugi, E. Farm. Ed.
Sci. 1988, 43, 597. (b) Haebich, D.; Barth, W.; Roesner, M.
Heterocycles 1989, 29, 2083. (c) Kadaba, P. K. J. Org.
Chem. 1992, 57, 3075. (d) Sasaki, T.; Eguchi, S.;
(12) Fritz, R. US 4,499,280, 1985.
(13) Jones, H.; Fordice, M. W.; Greenwald, R. B.; Hannah, J.;
Jacobs, A.; Ruyle, W. V.; Walford, G. L.; Shen, T. Y.
J. Med. Chem. 1978, 21, 1100.
Yamaguchi, M.; Esaki, T. J. Org. Chem. 1981, 46, 1800.
(7) Jiang, Y.; Kuang, C.; Yang, Q. Synlett 2009, 3163.
(14) Nagawa, Y.; Honda, K.; Nakanishi, H. Bull. Chem. Soc. Jpn.
1987, 60, 2931.
(15) Zanirat, P.; Cerinib, S. Org. Biomol. Chem. 2005, 3, 1508.
Synthesis 2011, No. 2, 223–228 © Thieme Stuttgart · New York