Regioselective synthesis of 1,2,3-triazoles by use of a silica-supported copper(I) catalyst

Article abstract of DOI:10.1055/s-2008-1032037

A 1,3-dipolar cycloaddition reaction catalyzed by copper(I) immobilized on organic-inorganic hybrid materials was developed. Terminal alkynes reacted with benzyl- or alkyl halides and sodium azide in the presence of a copper(I) catalyst immobilized on 3-aminopropyl- or 3-[(2-aminoethyl)amino]propyl- functionalized silica gel in ethanol. The reactions exclusively generated the corresponding regiospecific 1,4-disubstituted 1,2,3-triazoles in good to excellent yields. The azide intermediates do not need to be isolated during this procedure, and this should prove to be useful especially when unstable low-molecular-weight and polyvalent azides are used. Furthermore, the silica-supported copper could be recovered and recycled by simple filtration of the reaction solution and reused for ten consecutive trials without decrease in activity. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2008-1032037

PAPER
363
Regioselective Synthesis of 1,2,3-Triazoles by Use of a Silica-Supported
Copper(I) Catalyst
Regioselective
S
a
ynthesis
o
o
f
1,2,3-Triazoles Miao,a Lei Wang*a,b
a
Department of Chemistry, Huaibei Coal Teachers College, Huaibei, Anhui 235000, P. R. of China
State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences,
Shanghai 200032, P. R. of China
b
Fax +86(561)3090518; E-mail: leiwang@hbcnc.edu.cn
Received 12 September 2007; revised 8 November 2007
The high costs of transition-metal catalysts coupled with
the toxic effects associated with many transition metals
have led to an increased interest in immobilizing catalysts
onto a support. The classic supported reagents can facili-
Abstract: A 1,3-dipolar cycloaddition reaction catalyzed by cop-
per(I) immobilized on organic–inorganic hybrid materials was de-
veloped. Terminal alkynes reacted with benzyl- or alkyl halides and
sodium azide in the presence of a copper(I) catalyst immobilized on
3-aminopropyl- or 3-[(2-aminoethyl)amino]propyl-functionalized tate both the isolation and recycling of the catalyst by fil-
silica gel in ethanol. The reactions exclusively generated the corre-
tration, thus providing environmentally cleaner
processes.13 Recent examples include the use of polysty-
sponding regiospecific 1,4-disubstituted 1,2,3-triazoles in good to
excellent yields. The azide intermediates do not need to be isolated
rene-supported palladium as a catalyst for Suzuki cou-
during this procedure, and this should prove to be useful especially
pling and the Sonogashira reaction.14 The development of
when unstable low-molecular-weight and polyvalent azides are
organic reagents grafted onto silica gels has attracted
more and more attention in recent years, because the in-
dustry seeks more environmentally friendly chemical
manufacturing processes.15 Very recently, we reported a
silica-supported palladium-catalyzed Sonogashira cou-
pling reaction and a silica-supported copper(II)-catalyzed
Ullmann diaryl etherification.16
used. Furthermore, the silica-supported copper could be recovered
and recycled by simple filtration of the reaction solution and reused
for ten consecutive trials without decrease in activity.
Key words: 1,2,3-triazoles, supported catalysis, organic–inorganic
hybrid material, copper(I) catalyst, 1,3-dipolar cycloaddition
Huisgen 1,3-dipolar cycloaddition of azides and alkynes1
to afford 1,2,3-triazole rings has been widely used in in-
dustrial applications and synthetic intermediates.2 The
high tolerance of other functionalities and the almost
quantitative transformation under mild conditions make
this reaction an ideal prototype to demonstrate the concept
of click chemistry developed by Sharpless and co-work-
ers.3 However, the regioselectivity of this cycloaddition
reaction is generally low and the reaction usually leads to
a mixture of 1,4- and 1,5-regioisomers. In 2002, K. B.
Sharpless4a and M. Meldal4b showed that the rate of this
coupling is dramatically accelerated (up to 107 times) un-
der copper(I) catalysis, and that only one specific regioi-
somer of 1,4-disubstituted 1,2,3-triazole could be
obtained. The required copper(I) catalysts are usually pre-
pared by in situ reduction of copper(II) salts with ascor-
bate,5 or by comproportionation of copper(0) and
copper(II).6 The catalysts might be copper(0) nanosize
clusters,7 or appropriate copper(I) salts (CuI or CuBr)
with triphenylphosphine,8 iminopyridine,9 or mono-4 or
polydentate10,11 nitrogen ligands. However, the use of
transition metals (copper powder, copper salts, or rutheni-
um salts12) and ligands has led to the problem of waste dis-
posal.
Although organic azides are generally safe compounds,
those of low molecular weight can be unstable and, there-
fore, difficult to handle.17 This is especially true for small
molecules with several azide functionalities that would be
of much interest for the generation of polyvalent struc-
tures. Thus, a method that avoids isolation of organic
azides is desirable. In situ generation of organic azides
from suitable precursors followed by addition of alkyne in
one pot to form the corresponding 1,2,3-triazoles would
avoid the difficulties associated with the explosive nature
of the azides. Maksikova described an in situ formation of
1,2,3-triazoles from alkyl halides, alkynes, and sodium
azide.18 This method requires the reagents to be heated at
high temperatures for extended periods of time, resulting
in a mixture of regioisomers and giving low yields. Re-
cently, Fokin demonstrated a very effective one-pot prep-
aration of 1,4-disubstituted 1,2,3-triazoles from a variety
of readily available aromatic and aliphatic halides cata-
lyzed by a combination of copper(I) and L-proline without
isolation of potentially unstable organic azide intermedi-
ates.19,20 At the same time, Eycken also found that micro-
wave irradiation could accelerate the one-pot reaction,
and a series of 1,4-disubstituted 1,2,3-triazoles were gen-
erated from the corresponding alkyl halides, sodium
azide, and alkynes in the presence of copper(0) and cop-
per(II) sulfate.20 Kacprzak recently developed an efficient
one-pot method for the synthesis of 1,4-disubstituted
1,2,3-triazoles from benzyl or alkyl halides, sodium azide,
and alkynes in the presence of copper(I) in N,N-dimethyl-
formamide.21
SYNTHESIS 2008, No. 3, pp 0363–0368
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Advanced online publication: 10.01.2008
DOI: 10.1055/s-2008-1032037; Art ID: F16507SS
© Georg Thieme Verlag Stuttgart · New York

364
T. Miao, L. Wang
PAPER
Here we wish to report an efficient, safe, and green one- Table 1 IR and Microanalysis of Functionalized Silica and Func-
tionalized-Silica-Immobilized Copper Catalysts
pot synthesis of 1,4-disubstituted 1,2,3-triazoles from
benzyl and alkyl halides, sodium azide, and alkynes in
Sample
FT-IR (KBr, cm–1) Microanalysis (wt%)
ethanol catalyzed by silica-supported copper(I) without
any additives. The reactions proceeded smoothly to gen-
erate the corresponding 1,4-disubstituted 1,2,3-triazole
derivatives in high yields. It is important to note that the
silica-supported copper catalyst could be recovered and
recycled by a simple filtration of the reaction solution. It
could be reused for ten consecutive trials without signifi-
cant loss of activity.
nSi–O
1074
1049
1088
1053
nC–H
Ca
Na
Cub
Silica-APTS
Cu(I) cat. 1
Silica-AAPTS
Cu(I) cat. 2
2926
2918
2941
2937
3.85
3.43
6.56
6.05
1.31
1.18
2.57
2.32
–
2.76
–
5.28
a CHN microanalysis results.
b AAS analysis results.
The copper catalysts immobilized on organic–inorganic
hybrid materials were readily prepared in two-step proce-
dures (Scheme 1). The silica gel (100–200 mesh, Aldrich)
was treated with (3-aminopropyl)triethoxysilane or {3-
[(2-aminoethyl)amino]propyl}triethoxysilane in dry tolu-
ene at 120 °C for 24 hours to afford 3-aminopropyl- or 3-
[(2-aminoethyl)amino]propyl-functionalized silica gel
(Silica-APTS or Silica-AAPTS, respectively; Scheme 1).
The organic–inorganic hybrid materials were then treated
with copper(I) iodide in N,N-dimethylformamide at room
temperature for four hours to generate the silica-supported
copper(I) catalysts 1 and 2 (Scheme 1).
2 was found to be 2.76 and 5.28 wt%, respectively, on the
basis of atomic absorption spectroscopy analysis.
For our initial screening experiments, the 1,3-dipolar cy-
cloaddition reactions between benzyl chloride, sodium
azide, and phenylacetylene was chosen as the model reac-
tion (Table 2). We observed that when the reaction of the
alkyne, alkyl halide, and sodium azide, in a 1:1:1 molar
ratio, was catalyzed by the copper(I) catalyst 2 (5 mol%)
in ethanol, stirring at 78 °C for 24 hours, the correspond-
ing 1,4-disubstituted 1,2,3-triazole was obtained in 82%
yield (Table 2, entry 3). Encouraged by this result, we
continued our research to improve the yield of the product
by the optimization of the reaction conditions. We exam-
ined the effect of the copper source on the one-pot synthe-
sis of 1,4-disubstituted 1,2,3-triazoles (Table 2, entries 1–
5). Copper(I) catalyst 1 prepared from copper(I) iodide
was found to be the most effective one (Table 2, entry 2).
This may be due the effect of the anion in silica-supported
copper(I) catalysts on the catalytic activity. As a result,
copper(I) catalyst 1 was used in the subsequent investiga-
tions because of its high efficiency, easy separation, and
recyclability.
The infrared absorption bands of 3-aminopropyl-func-
tionalized silica gel (Silica-APTS) and 3-[(2-aminoeth-
yl)amino]propyl-functionalized silica gel (Silica-AAPTS)
were compared with those of their respective copper com-
plexes, namely copper(I) catalysts 1 and 2 (Table 1). The
wave number at which nSi–O appears in the spectra of cop-
per(I) catalysts 1 and 2 was lower than that in the spectra
of the corresponding Silica-APTS and Silica-AAPTS, re-
spectively. This is probably the coordination effect of
copper(I) with the monodentate and bidentate ligands 3-
aminopropyl and 3-[(2-aminoethyl)amino]propyl. The el-
emental analysis data given in Table 1 shows that for Sil-
ica-APTS and Silica-AAPTS the loading could be readily
quantified by CHN microanalysis, and was found on the
basis of the nitrogen percentage to be 0.935 mmol/g of 3-
aminopropyl and 0.918 mmol/g of 3-[(2-aminoethyl)ami-
no]propyl. The copper content of copper(I) catalysts 1 and
Then we turned our attention to investigating the effect of
the solvent on the coupling reaction (Table 3). When the
reactions were conducted in dimethyl sulfoxide and etha-
nol, the products were isolated in good to excellent yields
O
O
O
OH
OH
O
Si
Si
NH2
NH2
Si
Si
NH2
NH2
(EtO)3Si(CH2)3NH2
(APTS)
CuI
O
O
O
O
OH
OH
Cu(I)
DMF
toluene
O
O
O
O
OH
OH
1
Silica-APTS
(EtO)3Si(CH2)3NH(CH2)2NH2
(AAPTS)
OH
OH
OH
O
O
CuI
O
O
Si
N
O
O
Si
HN
NH2
NH2
H
toluene
DMF
Cu(I)
2
Silica-AAPTS
Scheme 1
Synthesis 2008, No. 3, 363–368 © Thieme Stuttgart · New York

PAPER
Regioselective Synthesis of 1,2,3-Triazoles
365
yields under the present reaction conditions from the reac-
tions of benzyl halides (BnBr, BnCl) with various termi-
nal arylalkynes or aliphatic alkynes, including acetylenes
with substituents containing functional groups, such as
phenylacetylene, p-tolylacetylene, (p-chlorophenyl)acet-
ylene, (p-bromophenyl)acetylene, dec-1-yne, oct-1-yne,
or propargyl alcohol (Table 4, entries 1–8). Apart from
benzyl halide derivatives, primary aliphatic bromides
such as n-butyl bromide, n-hexyl bromide, n-octyl bro-
mide, n-decyl bromide, and n-hexadecyl bromide also re-
acted with phenylacetylene and sodium azide under the
standard reaction conditions to afford the corresponding
1,4-disubstituted 1,2,3-triazoles in good yields (Table 4,
entries 9–13). As is evident from Table 4, electron-donat-
ing group (such as Me) or electron-withdrawing groups
(such as NO2) and their location on the aromatic ring in
substituted benzyl chlorides had little effect on the reac-
tion (Table 4, entries 14 and 15). However, the reaction of
aryl iodide, phenylacetylene, and sodium azide under the
present reaction conditions gave the product in poor yield
(Table 4, entry 16). Unfortunately, disubstituted acety-
lenes, such as diphenylacetylene, did not react with sodi-
Table 2 Effect of the Copper Source on the One-Pot Synthesis of 1-
Benzyl-4-phenyl-1H-1,2,3-Triazolea
N
Cu cat.
EtOH
N
N
BnCl + NaN3
+
PhC CH
Ph
Bn
Entry Cu catalyst
Yieldb (%)
1
2
3
4
5
CuI
75
91
82
15
8
1
2
Silica-supported Cu(II)c
Silica-supported Cu(II)c + sodium ascorbate
a Reagents and conditions: BnCl (0.50 mmol), PhC≡CH (0.50 mmol),
NaN3 (0.50 mmol), Cu cat. (0.025 mmol Cu, 5 mol%), EtOH (2 mL),
78 °C, 24 h.
b Isolated yield.
c The silica-supported Cu(II) catalyst was prepared from Silica-APTS
and Cu(OAc)2.
Table 3 Effect of Solvent on the One-Pot Synthesis of 1-Benzyl-4-
phenyl-1H-1,2,3-Triazolea
Table 4 One-Pot Synthesis of 1,4-Disubstituted 1,2,3-Triazoles
from Alkyl Halides, Sodium Azide, and Alkynesa
N
1 (5 mol%)
N
BnCl + NaN3
+
PhC CH
Ph
solvent
N
N
1 (5 mol%)
Bn
N
R2
R1X + NaN3
R2C CH
+
EtOH
N
Entry
Solvent/temperature (°C)
DMSO/100
Yieldb (%)
R1
R1
X
R2
Yieldb (%)
1
2
3
4
5
80
91
58
30
24
Entry
1
EtOH/78
Bn
Bn
Bn
Bn
Bn
Bn
Bn
Bn
Cl
Br
Cl
Cl
Cl
Cl
Cl
Br
Br
Br
Br
Br
Br
Cl
Cl
I
Ph
Ph
Tol
91
92
85
95
90
90
84
77
95
93
82
84
88
89
90
42
MeCN/81
2
dioxane/101
toluene/110
3
4
p-ClC6H4
p-BrC6H4
n-C8H17
n-C6H13
CH2OH
Ph
a Reagents and conditions: BnCl (0.50 mmol), PhC≡CH (0.50 mmol),
NaN3 (0.50 mmol), 1 (57.5 mg, 0.025 mmol Cu), EtOH (2 mL),
5
78 °C, 24 h.
6
b Isolated yield.
7
(80 and 91%, respectively; Table 3, entries 1 and 2). The
use of acetonitrile, dioxane, and toluene as solvents led to
slower reactions (Table 3, entries 3–5).
8
9
n-Bu
10
11
12
13
14
15
16
n-C6H13
n-C8H17
n-C10H21
n-C16H33
CH2Tol
p-NO2C6H4CH2
Ph
Ph
During the course of further optimization of the reaction
conditions, it was found that when a 5 mol% loading of
copper(I) catalyst 1 was used, the reactions were generally
completed in a matter of hours, but the time, as expected,
was inversely proportional to the temperature. A reaction
temperature of 78 °C was found to be optimal. Thus, the
optimal conditions for this reaction consist of the use of
copper(I) catalyst 1 (5 mol%) in ethanol at 78 °C for 24
hours.
Ph
Ph
Ph
Ph
Ph
Ph
We investigated the reaction, using a variety of benzyl-
and alkyl halides and alkynes as the substrates under the
same conditions, and the results are summarized in
Table 4. The corresponding 1,4-disubstituted 1,2,3-tri-
azoles were isolated as regiospecific products in excellent
a Reagents and conditions: R1X (0.50 mmol), R2C≡CH (0.50 mmol),
NaN3 (0.50 mmol), 1 (57.5 mg, 0.025 mmol Cu), EtOH (2 mL), 78 °C,
24 h.
b Isolated yield.
Synthesis 2008, No. 3, 363–368 © Thieme Stuttgart · New York

366
T. Miao, L. Wang
PAPER
condenser. Concd H2SO4 (80 mL) and HNO3 (15 mL) were added
and the mixture was heated in an oil bath at 140 °C for 24 h. The
soln was filtered and the white powder was washed with distilled
H2O until a neutral pH was attained. The solid was again washed
consecutively with acetone (30 mL), MeOH (30 mL), and CH2Cl2
(30 mL), and dried under vacuum at 150 °C for 48 h.
um azide and benzyl chloride under these optimized
reaction conditions.
The recyclability of the silica-supported copper(I) catalyst
1 was also surveyed (Table 5). After a reaction, the solu-
tion was vacuum-filtered through a sintered glass funnel
and washed successively with dichloromethane (1 mL),
diethyl ether (1 mL), ethanol (1 mL), and hexane (1 mL).
After being dried, the catalyst can be reused directly with-
out further purification. Copper(I) catalyst 1 can be recov-
ered, recycled, and reused for 10 consecutive trials
without loss of activity (Table 5). Moreover, copper
leaching in copper(I) catalyst 1 was also determined, and
inductively coupled plasma analysis of the clear filtrates
indicated that the copper content was <0.21 ppm.
Preparation of Silica-APTS: Anhyd toluene (20 mL), the activated
silica obtained from the above procedure (3.00 g), and (3-aminopro-
pyl)triethoxysilane (APTS) (10 mL) were introduced successively
into a 50-mL round-bottomed flask. The mixture was refluxed for
24 h, and then filtered. The solid was washed consecutively with
acetone (10 mL) and CH2Cl2 (10 mL), and dried under reduced
pressure at 60 °C; yield (Silica-APTS): 3.26 g.
Loading with Cu(I): In a small Schlenk tube, Silica-APTS [1.00 g,
0.935 mmol (CH2)3NH2/g] was mixed with CuI (0.096 g, 0.5 mmol)
in DMF (5 mL). The mixture was stirred for 4 h under a N2 atmo-
sphere at r.t. The soln was filtered and the solid was washed consec-
utively with acetone (5 mL) and MeOH (5 mL), and the solid was
dried under reduced pressure at r.t. for 16 h; this gave copper(I) cat-
alyst 1 as a pale blue powder; yield:1.03 g.
Table 5 Use of Recovered Copper(I) Catalyst 1 in Successive
Trialsa
N
1 (5 mol%)
N
N
BnCl + NaN3
+
PhC CH
Ph
EtOH
Copper(I) Catalyst 2
Bn
In a 50-mL round-bottomed flask were introduced successively an-
hyd toluene (20 mL), activated silica (3.00 g) and {3-[(2-aminoeth-
yl)amino]propyl}triethoxysilane (AAPTS) (10 mL). The soln was
refluxed for 24 h. The soln was filtered and the solid was washed
consecutively with acetone (10 mL) and CH2Cl2 (10 mL), and dried
under reduced pressure at 60 °C; yield (Silica-APPTS): 3.38 g.
Entryb
Yieldc (%)
Entryb
Yieldc (%)
1
2
3
4
5
91
87
94
81
86
6
7
93
90
87
81
84
In a small Schlenk tube, the Silica-AAPTS [1.00 g, 0.918 mmol
(CH2)3NH(CH2)2NH2/g] was mixed with CuI (0.191 g, 1.0 mmol)
in DMF (5 mL). The mixture was stirred under a N2 atmosphere at
r.t. for 4 h. The soln was filtered and the solid was washed consec-
utively with acetone (5 mL) and MeOH (5 mL), and the solid was
dried under reduced pressure at r.t. for 16 h; this gave 2 as a pale
blue powder; yield: 1.06 g.
8
9
10
a Reagents and conditions: BnCl (0.50 mmol), PhC≡CH (0.50 mmol),
NaN3 (0.50 mmol), 1 (57.5 mg, 0.025 mmol Cu), EtOH (2 mL),
78 °C, 24 h.
One-Pot Synthesis of 1,2,3-Triazoles; General Procedure
Under an atmosphere of N2, a two-necked round-bottomed flask
containing a stirrer bar was charged with organic halide R1X (1.0
mmol), NaN3 (1.0 mmol), terminal alkyne R2C≡CH (1.0 mmol),
copper(I) catalyst 1 (115 mg, 0.05 mmol), and EtOH (3.0 mL). The
mixture was heated and stirred at 78 °C for 24 h. After cooling to
r.t., the reaction mixture was vacuum-filtered through a sintered-
glass funnel and washed with CH2Cl2 (5 mL). The combined organ-
ic layers were dried (MgSO4) and evaporated under reduced pres-
sure. The residue was finally purified by flash chromatography
(silica gel) to give the desired product.
b The entry number corresponds to the trial number.
c Isolated yield.
In conclusion, a safe and efficient three-component reac-
tion for the regioselective generation of 1,4-disubstituted
1,2,3-triazoles has been developed. The method avoids
isolation and handling of potentially unstable small organ-
ic azides and provides triazole products in pure form. Fur-
thermore, copper(I) catalyst 1 can be recovered and
recycled by simple filtration of the reaction solution and
reused for ten consecutive trials without decrease in activ-
ity.
Recycling of the Silica-Supported Copper Catalyst
After the reaction had been carried out, the mixture (containing ca.
1 g catalyst 1) was vacuum-filtered onto a sintered-glass funnel, and
the residue was consecutively washed with CH2Cl2 (5 mL), Et2O (5
mL), EtOH (5 mL), and hexane (5 mL). After the catalyst had been
dried in an oven at 60 °C for 4 h, it could be reused directly without
further purification.
Melting points were recorded on a WRS-2B melting point apparatus
and are uncorrected. All 1H and 13C NMR spectra were recorded on
a 300-MHz Bruker T-NMR spectrometer. Chemical shifts d are re-
ported relative to TMS as internal standard. IR spectra were ob-
tained on a Nicolet NEXUS 470 spectrophotometer. The CHN
analysis was performed on a Vario El III elementary analyzer. Prod-
ucts were purified by flash chromatography (silica gel, 230–400
mesh). The chemicals were purchased from commercial suppliers
(Aldrich, USA and Shanghai Chemical Company, China) and used
without further purification.
1-Benzyl-4-phenyl-1H-1,2,3-triazole20
IR (KBr): 1494, 1469, 1450, 1361, 1224, 1140, 1076, 1046, 972,
807, 769, 731 cm–1.
1H NMR (300 MHz, CDCl3): d = 5.58 (s, 2 H), 7.42–7.75 (m, 8 H),
7.67 (s, 1 H), 7.82 (d, J = 7.1 Hz, 2 H).
13C NMR (75 MHz, CDCl3): d = 53.66, 119.10, 124.74, 125.47,
126.08, 129.97, 134.17, 147.64.
Copper(I) Catalyst 1
Activation of silica gel: Silica gel (100–200 mesh, Aldrich; 10.00 g)
was introduced into a round-bottomed flask equipped with a reflux
Synthesis 2008, No. 3, 363–368 © Thieme Stuttgart · New York

PAPER
Regioselective Synthesis of 1,2,3-Triazoles
367
1-Benzyl-4-(4-tolyl)-1H-1,2,3-triazole
Anal. Calcd for C12H15N3: C, 71.61; H, 7.51; N, 20.88. Found: C,
71.80; H, 7.39; N, 20.81.
1H NMR (300 MHz, CDCl3): d = 2.35 (s, 3 H), 5.55 (s, 2 H), 7.18–
7.21 (m, 2 H), 7.26–7.38 (m, 5 H), 7.64 (s, 1 H), 7.70 (d, J = 7.8 Hz,
2 H).
1-Hexyl-4-phenyl-1H-1,2,3-triazole
1H NMR (300 MHz, CDCl3): d = 0.86 (t, J = 6.8 Hz, 3 H), 1.25–
1.37 (m, 6 H), 1.88–1.98 (m, 2 H), 4.38 (t, J = 7.2 Hz, 2 H), 7.26–
7.35 (m, 1 H), 7.39–7.44 (m, 2 H), 7.75 (s, 1 H), 7.84 (t, J = 3.6 Hz,
2 H).
13C NMR (75 MHz, CDCl3): d = 21.20, 54.16, 119.20, 125.55,
126.04, 127.50, 128.67, 129.42, 134.62, 137.99, 148.15.
Anal. Calcd for C16H15N3: C, 77.08; H, 6.06; N, 16.85. Found: C,
76.90; H, 5.93; N, 17.17.
13C NMR (75 MHz, CDCl3): d = 13.85, 22.32, 26.07, 30.22, 31.06,
50.44, 119.49, 125.61, 128.00, 130.54, 147.62.
1-Benzyl-4-(4-chlorophenyl)-1H-1,2,3-triazole
1H NMR (300 MHz, CDCl3): d = 5.55 (s, 2 H), 7.28–7.33 (m, 2 H),
7.35–7.38 (m, 5 H), 7.67 (s, 1 H), 7.72 (d, J = 9.0 Hz, 2 H).
Anal. Calcd for C14H19N3: C, 73.33; H, 8.35; N, 18.32. Found: C,
73.15; H, 8.51; N, 18.34.
13C NMR (75 MHz, CDCl3): d = 54.24, 119.62, 126.87, 128.03,
1-Octyl-4-phenyl-1H-1,2,3-triazole21
128.92, 129.11, 133.84, 134.37, 146.95.
IR (KBr): 2954, 2918, 2847, 1465, 1216, 1079, 762, 696 cm–1.
Anal. Calcd for C15H12N3Cl: C, 66.79; H, 4.48; N, 15.58. Found: C,
66.68; H, 4.42; N, 15.72.
1H NMR (300 MHz, CDCl3): d = 0.86 (t, J = 6.8 Hz, 3 H), 1.25–
1.33 (m, 10 H), 1.88–1.97 (m, 2 H), 4.37 (t, J = 7.2 Hz, 2 H), 7.26–
7.34 (m, 1 H), 7.38–7.44 (m, 2 H), 7.74 (s, 1 H), 7.83 (t, J = 4.4 Hz,
2 H).
13C NMR (75 MHz, CDCl3): d = 14.00, 22.52, 26.42, 28.90, 30.28,
31.63, 50.39, 119.39, 125.62, 128.02, 130.60, 147.58.
1-Benzyl-4-(4-bromophenyl)-1H-1,2,3-triazole
1H NMR (300 MHz, CDCl3): d = 5.58 (s, 2 H), 7.26 (s, 1 H), 7.31–
7.33 (m, 2 H), 7.40–7.41 (m, 2 H), 7.51–7.54 (m, 2 H), 7.66–7.69
(m, 3 H).
13C NMR (75 MHz, CDCl3): d = 54.20, 119.42, 126.07, 128.17,
1-Decyl-4-phenyl-1H-1,2,3-triazole
128.97, 129.41, 133.95, 134.85, 147.11.
1H NMR (300 MHz, CDCl3): d = 0.86 (t, J = 6.8 Hz, 3 H), 1.24–
1.32 (m, 14 H), 1.87–1.94 (m, 2 H), 4.36 (t, J = 7.2 Hz, 2 H), 7.26–
7.34 (m, 1 H), 7.38–7.43 (m, 2 H), 7.76 (s, 1 H), 7.80–7.84 (m, 2 H).
Anal. Calcd for C15H21N3Br: C, 57.34; H, 3.85; N, 13.37. Found: C,
57.42; H, 3.73; N, 13.25.
13C NMR (75 MHz, CDCl3): d = 14.18, 22.71, 26.61, 28.99, 30.58,
1-Benzyl-4-octyl-1H-1,2,3-triazole
31.70, 50.51, 119.42, 125.60, 128.72, 130.66, 147.64.
1H NMR (300 MHz, CDCl3): d = 0.85 (t, J = 6.5 Hz, 3 H), 1.23–
1.27 (m, 10 H), 1.59–1.63 (m, 2 H), 2.66 (t, J = 7.7 Hz, 2 H), 5.46
(s, 2 H), 7.18–7.34 (m, 6 H).
Anal. Calcd for C18H27N3: C, 75.74; H, 9.53; N, 14.72. Found: C,
75.89; H, 9.38; N, 14.73.
13C NMR (75 MHz, CDCl3): d = 14.00, 22.55, 25.61, 29.09, 31.72,
1-(4-Methylbenzyl)-4-phenyl-1H-1,2,3-triazole
53.86, 120.45, 127.83, 128.92, 134.91, 148.83.
1H NMR (300 MHz, CDCl3): d = 2.35 (s, 3 H,), 5.50 (s, 2 H), 7.18–
721 (m, 4 H), 7.30–741 (m, 3 H), 7.66 (s, 1 H), 7.79–781 (m, 2 H).
Anal. Calcd for C10H11N3O: C, 75.23; H, 9.28; N, 15.48. Found: C,
75.11; H, 9.11; N, 15.78.
13C NMR (75 MHz, CDCl3): d = 21.06, 53.86, 119.36, 125.53,
127.98, 128.66, 129.66, 131.54, 138.55, 147.96.
1-Benzyl-4-hexyl-1H-1,2,3-triazole
1H NMR (300 MHz, CDCl3): d = 0.86 (t, J = 6.6 Hz, 3 H), 1.28–
1.32 (m, 6 H), 1.58–1.68 (m, 2 H), 2.68 (t, J = 7.7 Hz, 2 H), 5.46 (s,
2 H), 7.18–7.37 (m, 6 H).
Anal. Calcd for C16H15N3: C, 77.08; H, 6.06; N, 16.85. Found: C,
76.87; H, 6.12; N, 17.01.
1-(4-Nitrobenzyl)-4-phenyl-1H-1,2,3-triazole20
IR (KBr): 1608, 1601, 1581, 1518, 1465, 1442, 1426, 1351, 1223,
1111, 1079, 1046, 1016, 862, 802, 764 cm–1.
1H NMR (300 MHz, CDCl3): d = 5.62 (s, 2 H), 7.18–7.38 (m, 5 H),
7.67–7.75 (m, 3 H), 8.15–8.18 (m, 2 H).
13C NMR (75 MHz, CDCl3): d = 14.00, 22.49, 25.67, 28.86, 31.48,
53.91, 120.42, 127.88, 128.98, 134.95, 148.92.
Anal. Calcd for C15H21N3: C, 74.03; H, 8.70; N, 17.27. Found: C,
73.90; H, 8.62; N, 17.48.
(1-Benzyl-1H-1,2,3-triazol-4-yl)methanol
1H NMR (300 MHz, CDCl3): d = 3.10 (br s, 1 H), 4.71 (s, 2 H), 5.46
(s, 2 H), 7.20–7.39 (m, 6 H).
13C NMR (75 MHz, CDCl3): d = 52.21, 55.09, 122.15, 127.31,
128.84, 129.58, 135.67, 146.39.
13C NMR (75 MHz, CDCl3): d = 53.61, 119.89, 123.92, 124.37,
125.67, 128.59, 128.71, 130.09, 141.64, 142.59, 148.02.
1,4-Diphenyl-1,2,3-triazole22
IR (KBr): 3123, 3059, 2374, 1596, 1504, 1481 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.26–7.32 (m, 1 H), 7.38–7.40 (m,
3 H), 7.47 (t, J = 5.8 Hz, 2 H), 7.74 (d, J = 6.2 Hz, 2 H), 7.91 (d,
J = 6.0 Hz, 2 H), 8.12 (s, 1 H).
Anal. Calcd for C10H11N3O: C, 63.48; H, 5.86; N, 22.21. Found: C,
63.32; H, 5.78; N, 22.38.
1-Butyl-4-phenyl-1H-1,2,3-triazole
13C NMR (75 MHz, CDCl3): d = 117.8, 120.1, 125.2, 128.9, 127.9,
1H NMR (300 MHz, CDCl3): d = 0.99 (t, J = 7.4 Hz, 3 H), 1.34–
1.41 (m, 2 H), 1.87–1.96 (m, 2 H), 4.40 (t, J = 6.5 Hz, 2 H), 7.26–
7.34 (m, 1 H), 7.39–7.44 (m, 2 H), 7.75 (s, 1 H), 7.82 (d, J = 3.6 Hz,
2 H).
128.4, 129.7, 130.9, 137.5, 148.7.
Acknowledgments
13C NMR (75 MHz, CDCl3): d = 13.39, 19.24, 31.80, 49.78, 119.08,
125.56, 127.97, 128.59, 128.72, 130.63, 147.59.
We gratefully acknowledge financial support from the National Na-
tural Science Foundation of China.
Synthesis 2008, No. 3, 363–368 © Thieme Stuttgart · New York

368
T. Miao, L. Wang
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Synthesis 2008, No. 3, 363–368 © Thieme Stuttgart · New York