One-pot synthesis of 1,2,3-triazoles from boronic acids in water using Cu(ii)-β-cyclodextrin complex as a nanocatalyst

Article abstract of DOI:10.1039/c2ob25061f

We report here the one-pot synthesis of 1,2,3-triazoles of arylboronic acids in water. An efficient method has been developed for the synthesis of 1,2,3-triazoles via a one-pot reaction of an arylboronic acid with sodium azide in the presence of Cu₂-β-CD (CD = Cyclodextrin) as a nanocatalyst in water followed by a click cyclization reaction with an alkyne at room temperature in air without any additives. This method is simple, rapid, and high yielding.

Full text of DOI:10.1039/c2ob25061f

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PAPER
One-pot synthesis of 1,2,3-triazoles from boronic acids in water using
Cu(II)–β-cyclodextrin complex as a nanocatalyst†
Babak Kaboudin,*a Yaghoub Abedia and Tsutomu Yokomatsub
Received 10th January 2012, Accepted 20th April 2012
DOI: 10.1039/c2ob25061f
We report here the one-pot synthesis of 1,2,3-triazoles of arylboronic acids in water. An efficient method
has been developed for the synthesis of 1,2,3-triazoles via a one-pot reaction of an arylboronic acid with
sodium azide in the presence of Cu2–β-CD (CD = Cyclodextrin) as a nanocatalyst in water followed by a
click cyclization reaction with an alkyne at room temperature in air without any additives. This method is
simple, rapid, and high yielding.
Recently many studies have been reported on the in situ gener-
Introduction
ation of required azides in the Cu(I)-catalyzed azide–alkyne 1,3-
dipolar cycloaddition reaction.12
1,2,3-Triazoles compounds are an important class of organic
compounds for both synthetic and medicinal chemistry.1 1,2,3-
One-pot synthesis of 1,2,3-triazoles via the in situ generation
Triazoles are traditionally obtained using the thermal 1,3-dipolar
cycloaddition of organic azides with alkynes (Huisgen reaction)
that has been known for nearly five decades.2 In 2002, the
groups of Fokin et al.3 and of Medal et al.4 independently
reported the Cu(I)-catalyzed azide–alkyne 1,3-dipolar
cycloaddition that has attracted a significant attention, due to the
formation of 1,4-substituted-1,2,3-triazoles with high regioselec-
tivity and biological properties.5
Organic azides are useful intermediates in the synthesis of
various heterocyclic compounds specially 1,2,3-triazoles.6
Although the preparation of alkyl azides is straightforward,
methods for the preparation of aryl azides are rather limited.
They are prepared from the corresponding amines via their dia-
zonium salts,7 or the reactions of organometallic aryls with p-
tosyl azide.8 Recently, copper catalyzed coupling of aryl
amines,9 halides,10 and boronic acids with an azide sources such
as NaN3, TMSCN and TfN3 have been reported.11 Unfortu-
nately, the methods need special ligands or catalysts, organic sol-
vents, specific temperatures, and the limited substrate scope
greatly limits the use of these methods. Among the limited
methods for the synthesis of arylazides, the coupling of arylboro-
nic acids with sodium azide11a has attracted attention due to its
compatibility with a variety of functional groups, stability and
the lower toxicity of the boronic acids than other organometallic
reagents used, and the ease of working up the reaction mixture.
of aryl azides in the presence of the alkyne minimizes hazards
derived from their isolation and handling. Fokin et al. reported
the copper catalyzed one-pot synthesis 1,2,3-triazoles from
in situ generation of azides from aryl halides followed by reac-
tion with an alkyne in the presence of L-proline and sodium
ascorbate.12a It is worth nothing that due to slow azidonation of
aryl halides the above method usually suffers from long reaction
times (∼overnight) even at elevated temperature. Fokin et al.
also reported three-component 1,3-dipolar cycloaddition using
aliphatic bromides as the azide precursors catalyzed by copper
using microwave irradiation.12b Moses et al. reported an efficient
method for the in situ generation of aromatic azides from aro-
matic amines using tert-butyl nitrite and azidotrimethylsilane for
the synthesis of 1,2,3-triazoles via Cu(I)-catalyzed azide–alkyne
1,3-dipolar cycloaddition, but this method suffers from hazards
associated with tert-butyl nitrile.12c In 2010, Alonso et al.
reported three-component 1,3-dipolar cycloaddition using ali-
phatic halides as the azide precursors catalyzed by copper nano-
particles on activated carbon.12d
With the increasing demand for environmentally friendly
methods, organic reactions in aqueous media have attracted
much recent attention.13 Recently we have found that the Cu(II)–
β-cyclodextrin complex is an efficient nanocatalyst for the
homo- and chemoselective cross-coupling of arylboronic acids
under base-free conditions in water.14 Cu(II)–β-cyclodextrin is a
binuclear complex with a good stability constant that can be pre-
pared readily by addition of copper sulfate solution (0.04 M) to a
mixture of β-cyclodextrin in sodium hydroxide solution (0.5 M)
(Scheme 1).15
aDepartment of Chemistry, Institute for Advanced Studies in Basic
Sciences, Gava zang, Zanjan, Iran. E-mail: kaboudin@iasbs.ac.ir;
Fax: +98 241 4214949; Tel: +98 241 4153220
bSchool of Pharmacy, Tokyo University of Pharmacy and Life Sciences,
1432-1 Horonouchi, Hachioji, Tokyo 192-0392, Japan
†Electronic supplementary information (ESI) available. See DOI:
10.1039/c2ob25061f
We have now found that Cu2–β-CD complex is an effective
binuclear macrocyclic nanocatalyst for the one-pot synthesis
1,2,3-triazoles via a one-pot reaction of an arylboronic acid with
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Under the above optimized conditions, arylboronic acids were
employed in the coupling reaction with azide in water followed
by a click cyclization reaction with an alkyne using Cu2–β-CD
complex at room temperature in air without any additives. The
obtained results are summarized in Table 2. The one-pot reaction
of different substituted arylboronic acids with sodium azide in
water followed by a click cyclization reaction with phenylacety-
lene using Cu2–β-CD complex at room temperature in air gave
the corresponding 1,2,3-triazoles in excellent yields (entries
2–8).
Scheme 1 The suggested formula of Cu(II)–β-CD complex.
Scheme 2 One-pot synthesis 3a using copper catalysts in water.
Arylboronic acid bearing an aldehyde group, in the para pos-
ition gave the corresponding triazole product (entry 8). Aryl-
boronic acid bearing a weakly coordinating group of –NO2
could also be used to obtain the desired product 3c in 96% yield
(entry 3). It is also possible to carry out this reaction for ortho-
substituted arylboronic acid (entry 2).
Table 1 Copper-catalyzed one-pot synthesis of 3a from phenylboronic
acid (1a)
Entry
Catalyst
Mol%
t (h)a
Yield (%)b
1
2
3
4
5
6
7
8
Cu(OAc)2
CuI
CuSO4
10
10
10
10
10
5
24
24
24
24
24
4
21
60
28
24
58
94
—
<12
This method was also applied to the one-pot synthesis of the
1,2,3-triazole of 2-naphthylboronic acid. 2-Naphthylboronic acid
gave the corresponding triazole 3i in 94% yield (entry 9).
Treatment of phenylboronic acid with sodium azide in water
followed by a click cyclization reaction with different substituted
phenyacetylenes using Cu2–β-CD complex at room temperature
in air gave the desired products in excellent yields (entries 10,
11). Finally, the reaction of phenylboronic acid with sodium
azide in water in the presence of Cu2–β-CD followed by a click
cyclization reaction with aliphatic alkynes gave the correspond-
ing 1,2,3-triazoles in excellent yields (entries 12–17). Thus, a
wide variety of 1,2,3-triazoles were synthesized using the con-
ditions reported herein.
CuCl2
Cu(NO3)2
Cu2–β-CD
—
—
10
24
4
β-CD + CuSO4
a Reaction time is the time of formation of phenylazide (first step).
b Isolated yield of product 3a.
sodium azide in water followed by a click cyclization reaction
with an alkyne at room temperature in air without any additives.
In the previous paper, we presented a proposed mechanism for
Cu2–β-CD catalyzed homocoupling reaction of arylboronic
acids.14 The Cu2–β-CD played an important role in the formation
of a bimetallic aryl copper intermediate, via the attack of the
hydroxide ligand to the oxophilic boron center, which undergoes
subsequent reductive elimination to the symmetrical biaryl com-
pound.16 In this work, we further investigated the role of the cat-
alyst in the formation of bimetallic aryl copper intermediate.
Transition metal complexes usually have two absorption
bands in UV-vis spectroscopy in the visible region leading to
their coloration. These bands come from a combination of d–d
transfer and charge transfer transition. The charge transfer tran-
sition is stronger and out of scale in high concentrations. In the
Cu2–β-CD complex, it is impossible to observe both kinds of
absorption due to charge transfer transition between copper and
the alkoxide anion. Moreover, sodium azide also has a strong
absorption in the UV region that intensifies this phenomenon.
The copper sulfate and Cu2–β-CD show completely different
manners in azidation of arylboronic acid that could be observed
in their UV-vis spectrum pattern. Fig. 1 shows the UV-vis spec-
trum of Cu2–β-CD in aqueous solution (spectrum a). The
absorption spectrum of Cu2–β-CD in aqueous solution contain-
ing NaN3 (spectrum b) becomes similar to that of Cu2–β-CD in
aqueous solution. On the other hand, according to the literature,
the reaction of NaN3 with copper(II) salts gives copper azide.17
UV-vis spectra of copper(II) sulfate solution and a mixture of
copper sulfate with sodium azide show a good interaction of
azide with copper(II) (see ESI†). It seems that the hardly soluble
copper azide acts a catalyzing reagent in the case of copper
sulfate. These results show that there is no interaction between
Results and discussion
Initially, treatment of phenylboronic acid 1a with sodium azide
followed by a click cyclization reaction with a phenylacetylene
2a at room temperature in water was chosen as the model reac-
tion (Scheme 2). When the reaction was carried out using
copper(II) acetate (Cu(OAc)2) for 24 h at room temperature, 1,4-
diphenyl-1H-1,2,3-triazole 3a was obtained in 21% isolated
yield (Table 1). Next, various copper salts were screened in the
one-pot synthesis 1,2,3-triazoles of phenylboronic acid 1a in
water (entries 2–5). When the reaction was carried out using
copper(I) iodide (CuI) for 24 h at room temperature, triazole 3a
was obtained in 60% yield (entry 2). The reaction yield did not
increase when the reaction was carried out using CuSO4, CuCl2
and Cu(NO3)2 (entries 3–5). Finally, the one-pot reaction of phe-
nylboronic acid (1a) with sodium azide in water followed by a
click cyclization reaction with an alkyne with 5 mol% of
Cu2–β-CD complex for 4 h at room temperature gave 3a in 94%
isolated yield (entry 6). The blank experiment showed that
without Cu2–β-CD, the reaction could not occur (entry 7). When
the reaction was carried out using copper(II) sulfate (0.1 equiv,
CuSO4) in the presence of β-CD (0.1 equiv) for 4 h at room
temperature, 1,4-diphenyl-1H-1,2,3-triazole 3a was obtained in a
very low yield (<12%, entry 8). According to these results, the
one-pot reaction of an arylboronic acid with sodium azide in
water followed by a click cyclization reaction with an alkyne
was examined using Cu2–β-CD complex at room temperature in
air without any additives.
4544 | Org. Biomol. Chem., 2012, 10, 4543–4548
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Table 2 Cu2–β-CD-catalyzed one-pot reaction of arylboronic acids with sodium azide in water followed by a click cyclization with an alkyne
Entry
1
Ar (1)
C6H5–
Alkyne 2
Product 3
t (h)
Yield (%)a
94
4
2
o-FC6H4–
2
94
3
4
m-NO2C6H4–
3,5-F2C6H3–
6
2
95
96
5
6
7
p-MeC6H4–
p-MeOC6H4–
p-ClC6H4–
4
4
4
94
97
96
8
p-OHCC6H4–
β-Naphthyl
C6H5–
4
4
4
4
94
94
95
95
9
10
11
C6H5–
12
C6H5–
4
93
13
14
15
C6H5–
C6H5–
C6H5–
4
4
4
89
91
92
16
17
C6H5–
C6H5–
4
4
90
94
a Isolated yields.
Cu2–β-CD and NaN3. In contrast to the azide ion, phenylboronic
acid interacts very well with the copper ion in Cu2–β-CD. The
addition of phenylboronic acid to an aqueous solution of
Cu2–β-CD changes the absorption spectra (see ESI†). The effect
of added phenylboronic acid on the absorption is due to the for-
mation of an intermediate aryl copper complex (see ESI†).18 The
aryl copper intermediate undergoes subsequent reductive
azidation to the arylazide compound and the catalyst is regener-
ated in the solution (spectra c and e). The addition of phenyl-
boronic acid to an aqueous solution of Cu2–β-CD followed by
an addition of NaN3 also changes the absorption spectra (spec-
trum e).
We suggest that the Cu2–β-CD complex is stable in the reac-
tion process and copper ions with cyclodextrin have a synergetic
This journal is © The Royal Society of Chemistry 2012
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with sodium azide in water followed by a click cyclization reac-
tion with an alkyne at room temperature in air without any addi-
tives. We have developed an efficient Cu catalyzed protocol for
the one-pot synthesis of 1,2,3-triazoles of arylboronic acids.
Cu2–β-CD complex was found to be effective catalyst for this
transformation, which is readily available and structurally simple
as a nanocatalyst.
Experimental
General methods
All melting points were taken on a Yanagimoto and Buchi 510
apparatus and are uncorrected. Mass spectra were recorded on a
VG Auto Spec. using electron impact ionization (EI) techniques.
NMR spectra were obtained on a Bruker Avance 400 NMR
Spectrometer (1H NMR: 400 MHz, 13C NMR: 100 MHz). UV-
vis spectra were obtained on Ultrospec 4000 single beam.
Analytical TLC was carried out with plates precoated with silica
gel 60 F254 (0.25 mm thick). Copper sulfate was recrystallized
before use. All solvents were distilled before use.
Fig. 1 Spectral properties (UV-vis spectra in cell 0.1 cm) of Cu2–β-CD
in aqueous solution. (a) [Cu2–β-CD] = 0.06 M in aqueous solution,
(b) [Cu2–β-CD] = 0.06 M in aqueous solution containing 1.8 M of
NaN3. (c) [Cu2–β-CD] = 0.0006 M in aqueous solution, (d) [Cu2–β-CD]
= 0.0006 M in aqueous solution containing 0.018 M of NaN3 and
(e) [Cu2–β-CD] = 0.0006 M in aqueous solution containing 0.012 M
phenylboronic acid and 0.018 M of NaN3.
effect to catalyze azidation reaction fast and effectively. Strong
evidence to prove this suggestion is the UV-vis spectra of
Cu2–β-CD in the reaction mixture at the end of the typical azida-
tion reaction (see ESI†).
Preparation of Cu–β-cyclodextrin complex
UV-vis spectra of cyclodextrin (CD), 3-nitrophenylazide, and
a mixture of CD with 3-nitrophenylazide do not show a good
interaction of arylazide with cyclodextrin (see ESI†). However
UV-vis of a mixture of Cu2–β-CD complex with 3-nitrophenyl-
azide shows a good interaction of ayrl azide with the complex.
The data described above lead to the following proposed
mechanism for Cu2–β-CD catalyzed in situ azidation of aryl-
boronic acids for the synthesis of 1,2,3-triazoles. The reaction is
initiated by transmetallation of the aryl group from B to copper
via the attack of the hydroxide ligand to the oxophilic boron
center. The resulting arylcopper intermediate undergoes sub-
sequent reductive azidation to the arylazide compound
(Scheme 3).
This complex was prepared by the method described by Matsui
et al.15b In a 250 ml Becker containing 50 ml of 0.5 M NaOH,
β-cyclodextrin (1 mmol) was dissolved with stirring. To this
clear solution 75 ml of 0.04 M CuSO4·(H2O)5 (3 mmol) solution
was added. A dark blue solution was obtained immediately that
was stirred at room temperature. After 6 h, this solution was
filtered to remove excess of copper salt which precipitated as a
blue solid (copper hydroxide). To this blue solution was added
ethanol (about 400 ml) until a light blue suspension was formed,
then it was filtrated and wash with ethanol and air-dried at room
temperature. This complex was converted to fine powder before
use as catalyst.
General procedure for the one-pot synthesis 1,2,3-triazoles of
aryl boronic acids
To a mixture of Cu2CD (0.05 mmol, 65 mg, in this complex the
number of water molecule has not been exactly determined so
far and so we suppose its molecular weight to be 1300 mg
mmol−1) in 3 mL distilled water was added arylboronic acid
(1 mmol) and sodium azide (3 mmol), and the resulting mixture
was stirred at ambient temperature for 4–6 h. The alkyne
(1 mmol) was added to the reaction mixture and the mixture was
stirred at ambient temperature for 4 h. Water (50 mL) was added
to the reaction mixture and extracted with CH2Cl2 (2 × 20 ml)
and dried over Na2SO4. The solvent was removed under reduced
pressure to give the crude product. The solid was recrystallized
from a solvent mixture CH2Cl2–n-hexane or CH2Cl2–methanol
to afford purified 1,2,3-triazoles 3a–q in 89–97% yields.
Scheme 3 The suggested mechanism of Cu(II)–β-CD catalyzed con-
version of aryl boronic acids to aryl azides.
According to literature reports for the Cu-catalyzed azide–
alkyne 1,3-dipolar cycloaddition,5 we believe that the 1,2,3-tria-
zole formation proceeds through attack of the hydroxido ligand
of Cu2–β-CD complex to the terminal hydrogen of acetylene to
give copper acetylide. Continuing, coordination of the arylazide
to the copper center of the acetylide initiates an azide–alkyne
1,3-dipolar cycloaddition.
1,4-Diphenyl-1H-1,2,3-triazole
(3a). White
solid;
mp
1
170–172 °C (lit.12a 165–171 °C); H NMR (400 MHz, CDCl3)
δ: 8.27 (s, 1H), 7.95 (d, J = 7.2 Hz, 2H), 7.83 (d, J = 7.6 Hz,
2H), 7.58 (t, J = 8 Hz, 2H), 7.48–7.51 (m, 3H), 7.40 (t, J = 7.2
Hz, 1H); 13C NMR (100 MHz, CDCl3) δ: 132.6, 130.2, 129.8,
Conclusion
We reported here the transition-metal-catalyzed one-pot synthesis
of 1,2,3-triazoles via a one-pot reaction of an arylboronic acid
4546 | Org. Biomol. Chem., 2012, 10, 4543–4548
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1-(β-Naphthyl)-4-phenyl-1,2,3-triazole (3i). White solid; mp
205–207 °C; H NMR (400 MHz, DMSO-d6) δ: 9.48 (s, 1H),
128.9, 128.8, 128.4, 128.0, 127.8, 125.8, 120.5; HRMS calcd
for C14H12N3 (MH+): 222.1031 Found: 222.1031.
1
8.55 (s, 1H), 8.21 (d, J = 8.8 Hz, 2H), 8.05–8.16 (m, 2H), 8.06
(d, J = 7.6 Hz, 2H), 7–61–7.68 (m, 2H), 7.53 (t, J = 7.6 Hz,
2H), 7.41 (t, J = 7.2 Hz, 1H); 13C NMR (100 MHz, DMSO-d6)
δ: 147.9, 134.5, 133.3, 132.8, 130.7, 130.4, 129.5, 128.7, 128.7,
128.4, 128.0, 127.4, 125.8, 120.2, 119.0, 118.0; HRMS calcd
for C18H14N3 (MH+): 272.1188 Found: 272.1183.
1-(o-Fluorophenyl)-4-phenyl-1,2,3-triazole (3b). White solid;
mp 101–102 °C; H NMR (400 MHz, CDCl3) δ: 8.37 (s, 1H),
1
8.04 (t, J = 8 Hz, 1H), 7.95 (d, J = 7.6 Hz, 2H), 7.44–7.51 (m,
3H), 7.34–7.43 (m, 3H). 13C NMR (100 MHz, CDCl3) δ: 153.2
(d, JCP = 249 Hz), 130.1 (d, JCP = 8 Hz), 130.1, 128.9, 128.5,
125.9, 125.3 (d, JCP = 4 Hz), 125.3, 124.8, 117.1, 116.9; HRMS
calcd for C14H11N3F(MH+): 240.937 Found: 240.938.
1-Phenyl-4-p-tolyl-1,2,3-triazole (3j). White solid; mp
1
171–172 °C; H NMR (400 MHz, CDCl3) δ: 8.19 (s, 1H), 7.83
(m, 4H), 7.57 (t, J = 8 Hz, 2H), 7.48 (t, J = 7.6, 1H), 7.30 (d,
J = 9.2 Hz, 2H), 2.43 (s, 3H); 13C NMR (100 MHz, CDCl3) δ:
138.3, 129.8, 129.6, 128.7, 127.4, 125.7, 120.5, 117.2, 21.3;
HRMS calcd for C15H14N3 (MH+): 236.1188 Found: 236.1186.
1-(m-Nitrophenyl)-4-pheny-1, 2, 3-triazole (3c). Yellow solid;
mp 202–204 °C; H NMR (400 MHz, DMSO-d6) δ: 9.55 (s,
1
1H), 8.77 (t, J = 2 Hz, 1H), 8.56 (dd, J = 7.6, 1.2 Hz, 1H), 8.42
(dd, J = 8, 1,6 Hz, 1H), 7.91–7.97 (m, 3H), 7.51 (t, J = 7.6 Hz,
2H), 7.40 (t, J = 7.2 Hz, 1H); 13C NMR (100 MHz, DMSO-d6)
δ: 1149.0, 148.1, 137.6, 132.0, 130.3, 129.5, 128.9, 126.3,
125.8, 123.5, 120.4, 114.9; HRMS calcd for C14H11N4O2
(MH+): 267.0882 Found: 267.0877.
1-Phenyl-4-(m-aminophenyl)-1,2,3-triazole (3k). Yellow solid;
1
mp 122–125 °C, H NMR (400 MHz, acetone-d6) δ: 8.86 (s,
1H), 7.98 (d, J = 8 Hz, 2H), 7.64 (t, J = 7.6 Hz, 2H), 7.52 (t, J =
7.6, 1H), 7.38 (d, J = 1.6 Hz, 1H), 7.15–7.22 (m, 2H), 6.71 (dd,
J = 7.2, 1.2 Hz, 1H), 4.70–4.90 (br, 2H); 13C NMR (100 MHz,
acetone-d6) δ: 148.9, 148.55, 137.4, 131.4, 129.8, 129.4, 128.4,
120.0, 118.2, 114.2, 114.2, 111.3; HRMS calcd for C14H13N4
(MH+): 237.1140 Found: 237.1132.
1-(3,5-Difluorophenyl)-4-phenyl-1,2,3-triazole
(3d). White
solid; mp 153–155 °C; 1H NMR (400 MHz, CDCl3) δ: 8.23
(s, 1H), 7.92 (d, J = 7.6 Hz, 2H), 7.39–7.47 (m, 5H), 6.91–6.96
(m, 1H); 13C NMR (100 MHz, CDCl3) δ: 163.4 (dd, JCP = 250,
14 Hz), 138.6, 129.6, 129.0, 128.8, 125.9, 118.2, 104.0 (t, JCP
=
1-Phenyl-4-propyl-1,2,3-triazole (3l). White solid, mp
47–48 °C; H NMR (400 MHz, CDCl3) δ: 7.80 (s, 1H), 7.70
1
25 Hz), 103.9 (d, JCP = 20 Hz), 103.8; HRMS calcd for
C14H10N3F2 (MH+): 258.0843 Found: 258.0843.
(d, J = 7.6 Hz, 2H), 7.47 (t, J = 7.6 Hz, 2H), 7.37 (t, J = 7.6 Hz,
1H), 2.75 (t, J = 6.8 Hz, 2H), 1.75 (m, 2H), 0.99 (t, J = 7.2 Hz,
3H); 13C NMR (100 MHz, CDCl3) δ: 139.5, 130.1, 129.2,
128.4, 123.3, 120.9, 27.7, 21.9, 13.8; HRMS calcd for
C11H14N3 (MH+): 188.1188 Found: 188.1184.
4-Phenyl-1-p-tolyl-1H-1, 2, 3-triazole (3e). White solid, mp
1
159–160 °C; H NMR (400 MHz, CDCl3) δ: 8.19 (s, 1H), 9.94
(d, J = 7.2 Hz, 2H), 7.70 (d, J = 7.6 Hz, 2H), 7.49 (t, J = 7.6 Hz,
2H), 7.36–7.41 (m, 3H), 2.47 (s, 3H); 13C NMR (100 MHz,
CDCl3) δ:138.9, 134.4, 130.4, 130.3, 128.9, 128.3, 125.8, 120.4,
117.6, 21.1; HRMS calcd for C15H14N3 (MH+): 236.1188
Found: 236.1198.
1-Phenyl-4-butyl-1,2,3-triazole (3m). White solid; mp
1
44–46 °C; H NMR (400 MHz, CDCl3) δ: 7.77 (s, 1H), 7.67
(d, J = 8Hz, 2H), 7.43 (t, J = 8 Hz, 2H), 7.33 (t, J = 7.2 Hz,
1H), 2.74 (t, J = 7.2 Hz, 2H), 1.65–1.68 (m, 2H), 1.34–1.37
(m, 2H), 0.90 (t, J = 6.4, 3 H); 13C NMR (100 MHz, CDCl3) δ:
136.4, 130.1, 130.0, 129.4, 123.1, 128.8, 30.8, 24.2, 22.2, 13.7;
HRMS calcd for C12H16N3 (MH+): 202.1344 Found: 202.1350.
1-(p-Methoxyphenyl)-4-phenyl-1, 2, 3-triazole (3f). White
1
solid, mp 167–168 °C; H NMR (400 MHz, CDCl3) δ: 8.16 (s,
1H), 7.94 (d, J = 7.6, 2H), 7.72 (d, J = 8.8 Hz, 2H), 7.49 (t, J =
7.2 Hz, 2H), 7.39 (t, J = 7.2 Hz, 1H), 7.07 (d, J = 8.6 Hz, 2H),
3.91 (s, 3H); 13C NMR (100 MHz, CDCl3) δ: 159.8, 130.4,
128.6, 128.3, 125.8, 122.4, 114.8, 55.6; HRMS calcd for
C15H14N3O (MH+): 252.1137 Found: 252.1143.
1-Phenyl-4-hexyl-1,2,3-triazole
(3n). White
solid;
mp
1
40–42 °C; H NMR (400 MHz, CDCl3) δ: 7.77 (s, 1H), 7.35
(d, J = 7.6 Hz, 2H), 7.50 (t, J = 7.2 Hz, 2H), 7.40 (t, J = 7.2 Hz,
1H), 2.79 (t, J = 7.2 Hz, 2H), 1.70–1.78 (m, 2H), 1.32–1.40
(m, 6H), 0.89 (t, J = 6.8 Hz, 3H), 13C NMR (100 MHz, CDCl3)
δ: 137.3, 129.6, 128.3, 120.3, 118.8, 31.6, 29.3, 28.9, 25.6, 22.5,
14.7; HRMS calcd for C14H20N3 (MH+): 230.1657 Found:
230.1658.
1-(p-Chlorophenyl)-4-phenyl-1,2,3-triazole (3g). White solid;
mp 185–186 °C; 1H NMR (400 MHz, DMSO-d6) δ: 9.35
(s, 1H), 8.01 (d, J = 8.8 Hz, 2H), 7.95 (d, J = 7.2 Hz, 2H), 7.73
(d, J = 8.8 Hz, 2H), 7.52 (t, J = 7.6 Hz, 2H), 7.40 (t, J = 7.2 Hz,
1H); 13C NMR (100 MHz, DMSO-d6) δ: 147.9, 135.9, 133.4,
130.5, 130.4, 129.3, 128.8, 125.8, 122.1, 120.1; HRMS calcd
for C14H11N3Cl (MH+): 256.0642 Found: 256.0642.
(1-Phenyl-1H-1,2,3-triazol-4-yl)methanol (3o). White solid;
1
mp 101–103 °C; H NMR (400 MHz, CDCl3) δ: 8.06 (s, 1H),
7.73 (d, J = 7.2 Hz, 2H), 7.53 (t, J = 7.2 Hz, 2H), 7.63 (t, J =
7.6 Hz, 1H), 4.90 (s, 2H), 3.13 (br, 1H). 13C NMR (100 MHz,
CDCl3) δ: 137.0, 129.8, 128.8, 120.6, 56.4; HRMS calcd for
C9H10N3O (MH+): 176.0824 Found: 176.0817.
4-(4-Phenyl-1H-1,2,3-triazol-1-yl)benzaldehyde (3h). Yellow
solid; mp 220–221 °C; 1H NMR (400 MHz, DMSO-d6) δ: 10.10
(s, 1H), 9.49 (s, 1H), 8.24 (d, J = 8.8 Hz, 2H), 8.18 (d, J = 8.4
Hz, 2H), 7.97 (d, J = 7.6 Hz, 2H), 7.53 (t, J = 8 Hz, 2H), 7.42
(t, J = 7.2 Hz, 1H); 13C NMR (100 MHz, DMSO-d6) δ: 192.6,
148.1, 140.9, 136.1, 131.8, 130.4, 129.5, 128.9, 125.8, 120.6,
120.2; HRMS calcd for C15H12N3O (MH+): 250.980 Found:
250.980.
1-(1-Phenyl-1,2,3-triazol-4-yl)hexan-1-ol (3p). White solid;
mp 75–76 °C; 1H NMR (400 MHz, CDCl3) δ: 8.05 (s, 1H), 7.40
(d, J = 7.6 Hz, 2H), 7.52 (t, J = 7.2 Hz, 2H), 7.44 (t, J = 7.2 Hz,
1H), 5.00–5.08 (br, 1H), 3.18 (br, 1H), 1.93–1.98 (m, 2H),
1.35–1.53 (m, 6H), 0.90 (t, J = 6 Hz, 3H); 13C NMR (100 MHz,
This journal is © The Royal Society of Chemistry 2012
Org. Biomol. Chem., 2012, 10, 4543–4548 | 4547

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CDCl3) δ: 137.2, 129.7, 129.5, 128.7, 120.5, 115.5, 66.9, 37.4,
31.6, 25.1, 22.6, 14.0; HRMS calcd for C14H20N3O (MH+):
246.1606 Found: 246.1606.
1-Phenyl-1, 2, 3-triazole-4-carboxylic acid (3q). White solid;
1
mp 90–92 °C; H NMR (400 MHz, acetone-d6) δ: 9.12 (s, 1H),
8.01 (d, J = 8 Hz, 2H), 7.67 (m, 2H), 7.58 (t, J = 7.2 Hz, 1H);
13C NMR (100 MHz, acetone-d6) δ: 161.7, 140.8, 136.5, 130.0,
129.4, 126.6, 120.6; HRMS calcd for C9H8N3O2 (MH+):
190.0617 Found: 190.0615.
Acknowledgements
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The authors gratefully acknowledge support by the Institute for
Advanced Studies in Basic Sciences (IASBS) Research Council
under grant No. G2011IASBS120.
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4548 | Org. Biomol. Chem., 2012, 10, 4543–4548
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