Microwave-assisted click chemistry synthesis of 1,2,3-triazoles from aryldiazonium silica sulfates in water

Article abstract of DOI:10.1055/s-0032-1316783

A microwave-assisted click chemistry synthesis of 1,4-disubstituted 1,2,3-triazoles is studied by in situ generation of aryl azides via the reaction of aryldiazonium silica sulfates and sodium azide, followed by coupling with a terminal alkyne in the presence of copper catalyst. These reactions are carried out in water under mild and heterogeneous conditions without using any additional ligands.

Full text of DOI:10.1055/s-0032-1316783

PAPER
▌3353
paper
Microwave-Assisted Click Chemistry Synthesis of 1,2,3-Triazoles from
Aryldiazonium Silica Sulfates in Water
Click Chemistry Synthesis of 1,2,3-Triazoles
Amin Zarei,*a Leila Khazdooz,b Abdol R. Hajipour,c,d Hamidreza Aghaei,e Ghobad Azizid
a
Department of Science, Fasa Branch, Islamic Azad University, PO Box 364, Fasa 7461713591, Fars, Iran
Fax +98(311)2289113; E-mail: aj_zarei@yahoo.com
b
Department of Science, Khorasgan Branch, Islamic Azad University, Isfahan 81595158, Iran
c
Pharmaceutical Research Laboratory, College of Chemistry, Isfahan University of Technology, Isfahan 84156, Iran
d
Department of Pharmacology, University of Wisconsin, Medical School, 1300 University Avenue, Madison, WI 53706-1532, USA
e
Department of Chemistry, Shahreza Branch, Islamic Azad University, Shahreza 31186145, Isfahan, Iran
Received: 26.06.2012; Accepted after revision: 31.08.2012
imizes the risk of handling hazardous azides,15 and the use
of microwave or ultrasound irradiation has been shown to
reduce the reaction times.16 In view of environmental and
economic reasons, the development of catalytic systems
Abstract: A microwave-assisted click chemistry synthesis of 1,4-
disubstituted 1,2,3-triazoles is studied by in situ generation of aryl
azides via the reaction of aryldiazonium silica sulfates and sodium
azide, followed by coupling with a terminal alkyne in the presence
of copper catalyst. These reactions are carried out in water under without employing an additional ligand and using water
mild and heterogeneous conditions without using any additional li-
gands.
instead of organic solvents are attractive fields in this area
of research.
Key words: aryldiazonium silica sulfates, click reaction, 1,2,3-tri-
Aromatic azides are significant intermediates with a vari-
azoles, microwave irradiation
ety of applications in organic and bioorganic chemistry.
They are very useful starting materials for the click reac-
tion and are commonly prepared by reaction of diazonium
The copper(I)-catalyzed Huisgen 1,3-dipolar cycloaddi-
salts with azide ion. Although organic azides are often sta-
tion of azides and terminal alkynes (CuAAC)1 for the re-
ble under most reaction conditions, derivatives with low
gioselective syntheses of 1,4-disubstituted 1,2,3-triazole
molecular weight can sometimes be explosive. Moreover,
derivatives is an important example of click chemistry.2
high temperatures lead to decomposition of the aryl
Because of their wide applications in chemical, material,
azides. Therefore, the in situ generation of organic azides
and biological sciences,3 these compounds have increas-
followed by their immediate reaction, is a desirable and
ingly received significant attention. For example, some of
attractive method to minimize the potential explosive risk
these compounds show a variety of biological properties
of organic azides. In continuation of our studies on the sta-
including anti-HIV,4 antiallergic,5 antidiabetic,6 antifun-
bilization of diazonium salts on silica sulfuric acid and
gal,7 and antibacterial.8 Moreover, 1,2,3-triazoles are sta-
their application in organic synthesis,17 we report herein
ble and tolerant to many functional groups and conditions.
an efficient, convenient, and one-pot synthesis of 1,4-di-
Therefore, they have been widely used in organic synthe-
substituted 1,2,3-triazoles by the in situ generation of aryl
sis, industrial applications, bioconjugation, and drug dis-
azides via reaction of aryldiazonium silica sulfates and so-
covery.9 A number of methods have been reported to
dium azide followed by coupling with a terminal alkyne
develop the 1,3-dipolar cycloaddition of alkynes with or-
(Scheme 1). Unlike traditional methods, these reactions
ganic azides. For example, using – Cu(II) in the presence
were carried out in water by microwave irradiation with-
of reductants,1e,10 Cu(I) directly,11 a variety of ligands to
out using any additional ligand.
stabilize the Cu(I) oxidation state,12 copper containing
Aryldiazonium salts are useful intermediates in organic
synthesis due to their ready availability and high reactivi-
ty.18 These compounds, however, have a serious draw-
back in their intrinsic instability. Therefore, these salts are
nanoparticles,13 and copper(I) immobilized on various
supports.14 The in situ generation of organic azides not
only simplifies the experimental procedure, but also min-
Ar
N
N
NaN3
CuSO4, Na ascorbate, H2O
N
ArN2OSO3-SiO2
ArN3
R
C
CH, MW, 65 °C, 15 min
H2O, r.t.
R
Scheme 1 Microwave-assisted one-pot synthesis of 1,4-disubstituted 1,2,3-triazoles.
SYNTHESIS 2012, 44, 3353–3360
Advanced online publication: 12.09.2012
0
0
3
9
-
7
8
8
1
1
4
3
7
-
2
1
0
X
DOI: 10.1055/s-0032-1316783; Art ID: SS-2012-Z0543-OP
© Georg Thieme Verlag Stuttgart · New York

3354
A. Zarei et al.
PAPER
usually synthesized at around 10 °C and, to avoid their de- microwave irradiation that led to the acceleration of the
composition, they are handled below 0 °C. Moreover, be- reaction rate.
cause of this instability, subsequent reactions with
diazonium salts must be carried out under the same condi-
tions. Thus, diazonium salts with higher stability and ver-
Table 1 One-Pot Synthesis of 1,4-Diphenyl-1H-1,2,3-triazole under
Different Conditions
satility that can be easily made and stored under solid state
conditions with explosion-proof properties are desir-
able.19,20 For example, many diazonium tetrafluoroborates
are relatively stable and can be stored over extended peri-
ods of time without decomposition.21 Recently, we report-
ed an efficient, fast, and convenient method for the
preparation of aryldiazonium salts supported on the sur-
face of silica sulfuric acid (aryldiazonium silica sul-
fates).17a We found that these new aryldiazonium salts,
ArN2+ –OSO3-SiO2, could be stored at room temperature
under anhydrous conditions. Moreover, these aryldiazoni-
um salts were stable and could be used under different re-
action conditions.17
Entry
Conditionsa
Time
Yield (%)b
1
r.t.
6 h
78
83
86
90
2
50 °C
3 h
3
70 °C
1 h
4c
MW, 65 °C
15 min
a The reaction was carried out in H2O.
b The yield refers to isolated pure product.
c The reaction was irradiated by using a microwave reactor (Mile-
stone, Microsynth model, 1024) at a power level of 400 W.
After optimization of the reaction conditions, the general-
ity of these reactions were studied to other substrates. Us-
ing the present method a variety of aryldiazonium silica
sulfates and terminal alkynes were reacted in water at 65
°C under microwave irradiation. As shown in Table 2, the
reactions were carried out under mild and heterogeneous
conditions and the corresponding 1,4-disubstituted 1,2,3-
triazoles were obtained in short reaction times and good
yields. Aryldiazonium silica sulfates with electron-with-
drawing groups or electron-donating groups also reacted
effectively. The steric effects of ortho substituents on the
aryl rings of the aryldiazonium silica sulfates had relative-
ly little influence on the yields (Table 2, entries 3, 6, 8, 13,
and 15).
Initially, to minimize the potential explosive risk and also
to optimize the reaction conditions, in situ generation of
phenyl azides was studied by the reaction of phenyldiazo-
nium silica sulfates with sodium azide in water. This reac-
tion was carried out at room temperature in a few
minutes.17c After completion of the azide formation, an
aqueous solution of sodium ascorbate and catalytic
amount of CuSO4 (12 mol%) was added to generate the
Cu(I) catalyst in situ, followed by addition of phenylacet-
ylene under different conditions (Table 1). It was found
that the best result was obtained when the reaction was
carried out under microwave irradiation at 65 °C (Table 1,
entry 4). Use of water having a high dielectric constant
and ionic compounds provided suitable conditions to use
Table 2 Microwave-Assisted Synthesis of 1,4-Disubstituted 1,2,3-Triazoles Using Aryldiazonium Silica Sulfatesa
Entry
Diazonium salt
Alkyne
Product
Yield (%)
Mp (°C)
Found
Reported
1
PhN2+ –OSO3-SiO2
90
182–184
180–18211b
N
N
N
N
N
N
N
N
N
N
N
N
2
3
4
4-MeC6H4N2+ –OSO3-SiO2
2-MeC6H4N2+ –OSO3-SiO2
4-MeOC6H4N2+ –OSO3-SiO2
83
77
81
165–167
71–72
166–16811b
7313d
162–164
164–16511b
OMe
Synthesis 2012, 44, 3353–3360
© Georg Thieme Verlag Stuttgart · New York

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Click Chemistry Synthesis of 1,2,3-Triazoles
3355
Table 2 Microwave-Assisted Synthesis of 1,4-Disubstituted 1,2,3-Triazoles Using Aryldiazonium Silica Sulfatesa
Entry
Diazonium salt
Alkyne
Product
Yield (%)
Mp (°C)
Found
Reported
5
4-BrC6H4N2+ –OSO3-SiO2
83
228–230
23110c
N
N
N
Br
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
Cl
6
2-ClC6H4N2+ –OSO3-SiO2
3-ClC6H4N2+ –OSO3-SiO2
2-O2NC6H4N2+ –OSO3-SiO2
3-O2NC6H4N2+ –OSO3-SiO2
4-O2NC6H4N2+ –OSO3-SiO2
4-NCC6H4N2+ –OSO3-SiO2
4-AcC6H4N2+ –OSO3-SiO2
2-HO2CC6H4N2+ –OSO3-SiO2
4-PhCOC6H4N2+ –OSO3-SiO2
81
89
78
91
83
80
76
70
82
124–126
164–166
142–144
201–203
233–235
230–232
220–222
236 (dec.)
206–208
128–12913d
Cl
7
–
O2N
8
140–14110b
N
NO2
9
204–20510b
N
N
N
N
10
11
12
13
14
236–23810b
NO2
23410c
CN
O
–
–
–
HO2C
N
N
O
N
N
N
N
N
Ph
Ph
O
N
15
2-PhCOC6H4N2+ –OSO3-SiO2
78
108–110
–
© Georg Thieme Verlag Stuttgart · New York
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A. Zarei et al.
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Table 2 Microwave-Assisted Synthesis of 1,4-Disubstituted 1,2,3-Triazoles Using Aryldiazonium Silica Sulfatesa
Entry
16
Diazonium salt
Alkyne
Product
Yield (%)
Mp (°C)
Found
Reported
3-pyridylN2+ –OSO3-SiO2
N
77
176–178
–
N
N
N
N
17
18
PhN2+ –OSO3-SiO2
83
80
167–169
195–197
166–16911b
196–19911b
N
N
4-MeC6H4N2+ –OSO3-SiO2
N
N
N
N
N
N
N
N
N
19
20
PhN2+ –OSO3-SiO2
85
81
thick oil
111–113
thick oil22
O
4-MeCOC6H4N2+ –OSO3-SiO2
113–11513a
a The yield refers to isolated pure products, which were characterized from their spectral data and by comparison with authentic samples.
Although most of the CuAAC reactions proceed either in crude products were obtained by simple extraction and if
organic solvents or in mixtures with water (i.e., water– necessary, were purified by short column chromatogra-
MeCN or water–t-BuOH), only a few reactions have been phy.
reported in water alone.23 However, in all of these, it was
To show the merit of this in comparison with those report-
necessary to use an appropriate ligand to accelerate the re-
ed recently, we compared our results with those obtained
action rate. Recently, Alonso and co-workers have devel-
from various methods including the use of different sour-
oped a one-pot method for the CuAAC reaction using
ces of Cu(I). The results show that the reaction yields are
+
–
ArN2 BF4 , NaN3, and terminal alkynes in water cata-
lyzed by copper nanoparticles on activated carbon.13c
These reactions are carried out at 70 °C in 2–8 hours with-
out using any ligand.
comparable with those reported, and in some cases, the re-
sults using the aryldiazonium silica sulfates are superior
(Table 3). In some of these procedures, aryl azides are in
situ generated by azidation of arylamines, aryldiazonium
In the present work, by using inexpensive materials and tetrafluoroborates, or by azidation of diaryliodonium
convenient procedure, all CuAAC reactions were carried salts, followed by coupling with a terminal alkyne (Table
out in water without using any additional ligand. Further- 3, entries 6, 7, 8, 11, 24, 27, 28, 30, 34, and 36). In com-
more, by supporting the aryldiazonium salt on silica sul- parison with the reported ones, in the present work, the in
furic acid, the surface area of the reaction site was situ generation of aryl azides was more convenient with-
increased thereby lowering the reaction time.17,24 Another out using any organic solvent and any expensive material.
advantage of this method was the easy workup since the
Table 3 Comparison of the Present Work with a Number of Recently Reported Methods in Click Reaction
Ar
N
N
copper catalyst, R
C
CH
N
ArN3
R
Entry Ar
R
Conditions
Time
Yield (%) Ref.
1
2
3
4
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
CuSO4 (1 mol%), sodium ascorbate, ligand, DMSO, H2O, r.t.
CuBr (5 mol%), ligand, neat, r.t.
4 h
88
86
98
88
10c
23e
13b
15b
1.5 h
10 min
10 h
Cu nanoparticle (10 mol%), Et3N–THF, 65 °C
CuI (10 mol%), ligand, [BMIM]BF4, 60 °C
Synthesis 2012, 44, 3353–3360
© Georg Thieme Verlag Stuttgart · New York

PAPER
Click Chemistry Synthesis of 1,2,3-Triazoles
3357
Table 3 Comparison of the Present Work with a Number of Recently Reported Methods in Click Reaction
Ar
N
N
copper catalyst, R
C
CH
N
ArN3
R
Entry Ar
R
Conditions
Time
Yield (%) Ref.
5
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
CuCl (0.5 mol%), ligand, H2O, r.t.
4 h
99
88
85
85
90
80
82
99
81
71
83
98
89
45
78
85
79
77
59
71
76
61
92
78
80
87
70
98
85
82
81
79
83
76
23e
15c
11b
13c
6a
CuSO4 (10 mol%), sodium ascorbate, MeCN, H2O, r.t.
CuI (10 mol%), PEG 400, H2O, r.t.
16 h
1 h
7b
8c
Cu nanoparticle on activated carbon (0.5 mol%), H2O, 70 °C
CuSO4 (12 mol%), sodium ascorbate, H2O, MW, 65 °C
CuSO4 (1 mol%), sodium ascorbate, ligand, DMSO, H2O, r.t.
CuI (10 mol%), PEG 400, H2O, r.t.
2 h
9
15 min
2 h
this work
10c
10
11b
12
13
14
15
16
17
18
19
20
21
22
23
24c
25
26
27a
28c
29
30a
31
32
31
32
33
34b
35
36b
4-MeOC6H4
4-MeOC6H4
4-MeOC6H4
4-MeOC6H4
4-BrC6H4
4-BrC6H4
3-ClC6H4
3-ClC6H4
2-O2NC6H4
2-O2NC6H4
2-MeC6H4
2-MeC6H4
2-MeC6H4
4-AcC6H4
4-AcC6H4
4-AcC6H4
4-NCC6H4
4-NCC6H4
4-NCC6H4
4-NCC6H4
2-HO2CC6H4
2-HO2CC6H4
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Bu
Bu
Bu
Bu
1 h
11b
Cu(PPh3)2NO3 (0.5 mol%), neat, r.t.
2 h
12b
CuSO4 (12 mol%), sodium ascorbate, H2O, MW, 65 °C
CuSO4 (1 mol%), sodium ascorbate, ligand, DMSO, H2O, r.t.
CuSO4 (12 mol%), sodium ascorbate, H2O, MW, 65 °C
Cu(PPh3)2NO3 (0.5 mol%), neat, r.t.
15 min
2 h
this work
10c
15 min
30 min
5 h
this work
12b
CuSO4 (12 mol%), sodium ascorbate, H2O, MW, 65 °C
Cu(PPh3)2NO3 (0.5 mol%), neat, r.t.
this work
12b
24 h
15 min
24 h
10 h
15 min
24 h
4 h
CuSO4 (12 mol%), sodium ascorbate, H2O, MW, 65 °C
Cu(PPh3)2NO3 (0.5 mol%), neat, r.t.
this work
12b
CuI (10 mol%), ligand, [BMIM]BF4, 60 °C
15b
CuSO4 (12 mol%), sodium ascorbate, H2O, MW, 65 °C
CuI (10 mol%), ligand, [BMIM]BF4, 100 °C
Cu nanoparticle on activated carbon (0.5 mol%), H2O, 70 °C
CuSO4 (12 mol%), sodium ascorbate, H2O, MW, 65 °C
CuI (10 mol%), ligand, [BMIM]BF4, 100 °C
this work
15b
13c
15 min
24 h
this work
15b
CuSO4 (10 mol%), sodium ascorbate, MeCN, H2O, MW, 80 °C 10 min
16a
Cu nanoparticle on activated carbon (0.5 mol%), H2O, 70 °C
CuSO4 (12 mol%), sodium ascorbate, H2O, MW, 65 °C
CuSO4 (10 mol%), sodium ascorbate, MeCN, H2O, r.t.
CuSO4 (12 mol%), sodium ascorbate, H2O, MW, 65 °C
Cu nanoparticle (10 mol%), Et3N–THF, 65 °C
CuSO4 (12 mol%), sodium ascorbate, H2O, MW, 65 °C
Cu nanoparticle (10 mol%), Et3N–THF, 65 °C
CuSO4 (12 mol%), sodium ascorbate, H2O, MW, 65 °C
CuI (10 mol%), PEG 400, H2O, r.t.
4 h
13c
15min
16 h
this work
15c
15 min
10 min
15 min
2 h
this work
13b
Ph
this work
13a
4-AcC6H4
4-AcC6H4
Ph
15 min
1 h
this work
11b
4-MeC6H4
4-MeC6H4
4-MeC6H4
Ph
CuSO4 (12 mol%), sodium ascorbate, H2O, MW, 65 °C
CuI (10 mol%), PEG 400, H2O, r.t.
15 min
1 h
this work
11b
4-MeC6H4
© Georg Thieme Verlag Stuttgart · New York
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A. Zarei et al.
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Table 3 Comparison of the Present Work with a Number of Recently Reported Methods in Click Reaction
Ar
N
N
copper catalyst, R
C
CH
N
ArN3
R
Entry Ar
R
Conditions
Time
Yield (%) Ref.
37
38
39
4-MeC6H4
4-MeC6H4
CuSO4 (12 mol%), sodium ascorbate, H2O, MW, 65 °C
(CuOTf)2C6H6 (10 mol%), toluene, 100 °C
7 h
80
91
77
this work
12f
3-pyridyl
3-pyridyl
Ph
Ph
2 h
CuSO4 (12 mol%), sodium ascorbate, H2O, MW, 65 °C
15 min
this work
a ArN3 is in situ generated by using ArNH2, t-BuONO, and TMSN3 in MeCN at 0 °C.
b ArN3 is in situ generated by using Ar2I+ –OTf, NaN3, and CuI in H2O–PEG 400 at r.t.
c ArN3 is in situ generated by using ArN2 BF4 , NaN3, and Cu nanoparticle on activated carbon in H2O at 70 °C.
+
–
13C NMR (125 MHz, DMSO-d6): δ = 148.3, 138.5, 135.1, 132.6,
130.9, 129.9, 129.4, 129.2, 126.2, 120.7, 120.6, 119.4.
To summarize, we have reported an efficient, one-pot,
safe, and experimentally simple method for the synthesis
of 1,4-disubstituted 1,2,3-triazoles in good yields and
short reaction time. These reactions were carried out by
using aryldiazonium silica sulfates, sodium azide, termi-
nal alkynes, and a catalytic amount of CuSO4 in the pres-
ence of sodium ascorbate. It was notable that all reactions
were carried out in pure water under microwave irradia-
tion without using any additional ligand.
Anal. Calcd for C14H10ClN3: C, 65.76; H, 3.94; N, 16.43. Found: C,
65.70; H, 4.03; N, 16.35.
1-[4-(4-Phenyl-1H-1,2,3-triazol-1-yl)phenyl]ethanone (Table 2,
entry 12)15b,c
Yield: 0.200 g (76%); yellow solid; mp 220–222 °C.
IR (KBr): 3129, 3100, 1678, 1605, 1517, 1456, 1409, 1359, 1264,
1231, 1178, 1039, 962, 835, 766, 694 cm–1.
1H NMR (500 MHz, DMSO-d6): δ = 9.44 (s, 1 H), 8.20 (d, J = 8.5
Hz, 2 H), 8.13 (d, J = 8.4 Hz, 2 H), 7.96 (d, J = 8.0 Hz, 2 H), 7.51
(t, J = 7.6 Hz, 2 H), 7.40 (t, J = 7.6 Hz, 1 H), 2.86 (s, 3 H).
13C NMR (125 MHz, DMSO-d6): δ = 197.8, 148.5, 140.5, 137.3,
131.0, 130.9, 129.9, 129.3, 126.3, 120.6, 120.5, 27.8.
All reagents were purchased from Merck and Aldrich and used
without further purification. All yields refer to the isolated products
after purification.
The products were characterized by comparison with authentic
1
samples and by spectroscopic data (IR, H and 13C NMR spectra).
Anal. Calcd for C16H13N3O: C, 72.99; H, 4.98; N, 15.96. Found: C,
72.87; H, 5.05; N, 15.88.
All melting points were taken on a Gallenkamp melting apparatus
and are uncorrected. IR spectra were recorded on a Jasco FT/IR-680
1
2-(4-Phenyl-1H-1,2,3-triazol-1-yl)benzoic Acid (Table 2, entry
13)15c
Yield: 0.185 g (70%); white solid; mp 236 °C (dec.).
PLUS spectrometer. H NMR spectra were recorded on a Bruker
500 MHz spectrometer. The reactions were irradiated by using a mi-
crowave reactor (Milestone, Microsynth model, 1024).
IR (KBr): 3142–2571, 1716, 1601, 1507, 1484, 1458, 1222, 1207,
1183, 1143, 1078, 997, 794, 767, 967 cm–1.
1H NMR (500 MHz, DMSO-d6): δ = 13.19 (br s, 1 H), 8.99 (s, 1 H),
7.97 (d, J = 7.6 Hz, 1 H), 7.94 (d, J = 7.7 Hz, 2 H), 7.81–7.78 (m, 1
H), 7.73–7.69 (m, 2 H), 7.49 (t, J = 7.6 Hz, 2 H), 7.37 (t, J = 7.4 Hz,
1 H).
1,4-Diphenyl-1H-1,2,3-triazole (Table 2, entry 1);
Typical Procedure
To a stirred solution of NaN3 (0.085 g, 1.3 mmol) in H2O (5 mL)
was gradually added freshly prepared phenyldiazonium silica
sulfate17 (0.261 g, 1 mmol) and the reaction mixture was stirred at
r.t. for 5 min. Then, a mixture of CuSO4·5H2O (0.03 g, 12 mol%),
sodium ascorbate (0.17 g, 0.85 mmol), and phenylacetylene (0.14
mL, 1.3 mmol) in H2O (5 mL) was added and the reaction mixture
was irradiated at 65 °C for 15 min by using a microwave reactor
(Milestone, Microsynth model, 1024) at a power level of 400 W.
The mixture was diluted with EtOAc (15 mL) and filtered after vig-
orous stirring. The filtrate was extracted with EtOAc (3 × 15 mL)
and the combined organic layers were washed with H2O (20 mL),
dried (Na2SO4), and evaporated. The residue was washed with n-
hexane (5 mL) to afford the pure product; yield: 0.196 g (90%); off-
white solid; mp 182–184 °C (Lit.11b mp 180–182 °C).
13C NMR (125 MHz, DMSO-d6): δ = 167.4, 147.3, 136.2, 133.4,
131.4, 131.3, 130.9, 129.9, 129.5, 128.9, 127.4, 126.1, 123.9.
Anal. Calcd for C15H11N3O2: C, 67.92; H, 4.18; N, 15.84. Found: C,
67.80; H, 4.22; N, 15.73.
Phenyl [4-(4-Phenyl-1H-1,2,3-triazol-1-yl)phenyl] Ketone
(Table 2, entry 14)
Yield: 0.266 g (82%); pale yellow solid; mp 206–208 °C.
IR (KBr): 3130, 3055, 1647, 1604, 1411, 1319, 1281, 1230, 1041,
927, 852, 771, 703 cm–1.
1H NMR (500 MHz, DMSO-d6): δ = 9.45 (s, 1 H), 8.17 (d, J = 8.6
Hz, 2 H), 7.98 (m, 4 H), 7.79 (d, J = 7.6 Hz, 2 H), 7.72 (t, J = 7.4
Hz, 1 H), 7.60 (t, J = 7.6 Hz, 2 H), 7.52 (t, J = 7.6 Hz, 2 H), 7.40 (t,
J = 7.4 Hz, 1 H).
13C NMR (125 MHz, DMSO-d6): δ = 195.8, 148.5, 140.1, 137.6,
137.6, 133.8, 132.4, 130.9, 130.5, 129.9, 129.6, 129.3, 126.3, 120.3,
120.5.
1-(3-Chlorophenyl)-4-phenyl-1H-1,2,3-triazole (Table 2, entry
7)12b,13c
Yield: 0.227 g (89%); cream colored solid; mp 164–166 °C.
IR (KBr): 3121, 3099, 1591, 1494, 1481, 1454, 1399, 1227, 1078,
1041, 886, 791, 766, 696 cm–1.
1H NMR (500 MHz, DMSO-d6): δ = 9.37 (s, 1 H), 8.08 (s, 1 H),
7.97 (d, J = 7.4 Hz, 1 H), 7.93 (d, J = 7.3 Hz, 2 H), 7.66 (t, J = 8.1
Hz, 1 H), 7.58 (d, J = 7.3 Hz, 1 H), 7.50 (t, J = 7.6 Hz, 2 H), 7.39 (t,
J = 7.3 Hz, 1 H).
Anal. Calcd for C21H15N3O: C, 77.52; H, 4.65; N, 12.91. Found: C,
77.39; H, 4.69; N, 12.81.
Synthesis 2012, 44, 3353–3360
© Georg Thieme Verlag Stuttgart · New York

PAPER
Click Chemistry Synthesis of 1,2,3-Triazoles
3359
Phenyl [2-(4-Phenyl-1H-1,2,3-triazol-1-yl)phenyl] Ketone
(Table 2, entry 15)
(5) (a) Buckle, D. R.; Rockell, C. J. M.; Smith, H.; Spicer, B. A.
J. Med. Chem. 1986, 29, 2262. (b) Buckle, D. R.; Outred, D.
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1983, 26, 251. (c) Buckle, D. R.; Rockell, C. J. M. J. Chem.
Soc., Perkin Trans. 1 1982, 627.
Yield: 0.253 g (78%); yellow solid; mp 108–110 °C.
IR (KBr): 3136, 3103, 3061, 1663, 1600, 1579, 1501, 1483, 1449,
1316, 1288, 1262, 1226, 929, 767, 749, 691 cm–1.
(6) Olesen, P. H.; Sorensen, A. R.; Urso, B.; Kurtzhals, P.;
Bowler, A. N.; Ehrbar, U.; Hansen, B. F. J. Med. Chem.
2003, 46, 3333.
(7) Vicentini, C. B.; Brandolini, V.; Guarneri, M.; Giori, P.
Farmaco 1992, 47, 1021.
1H NMR (500 MHz, DMSO-d6): δ = 9.06 (s, 1 H), 7.87 (m, 2 H),
7.77 (d, J = 7.8 Hz, 2 H), 7.73 (m, 2 H), 7.61 (d, J = 7.7 Hz, 2 H),
7.52 (t, J = 7.3 Hz, 1 H), 7.42 (m, 4 H), 7.33 (t, J = 7.4 Hz, 1 H).
13C NMR (125 MHz, DMSO-d6): δ = 194.8, 147.9, 136.9, 135.2,
134.74, 134.2, 132.8, 130.8, 130.6, 130.4, 129.8, 129.4, 129.1,
126.1, 125.0, 122.9.
(8) Genin, M. J.; Allwine, D. A.; Anderson, D. J.; Barbachyn,
M. R.; Emmert, D. E.; Garmon, S. A.; Graber, D. R.; Grega,
K. C.; Hester, J. B.; Hutchinson, D. K.; Morris, J.; Reischer,
R. J.; Ford, C. W.; Zurenko, G. E.; Hamel, J. C.; Schaadt, R.
D.; Stapert, D.; Yagi, B. H. J. Med. Chem. 2000, 43, 953.
(9) (a) Kolb, H. C.; Sharpless, K. B. Drug Discovery Today
2003, 8, 1128. (b) Moses, J. E.; Moorhouse, A. D. Chem.
Soc. Rev. 2007, 36, 1249. (c) Tron, G. C.; Pirali, T.;
Billington, R. A.; Canonico, P. L.; Sorba, G.; Genazzani, A.
A. Med. Res. Rev. 2008, 28, 278. (d) Aragao-Leoneti, V.;
Campo, V. L.; Gomes, A. S.; Field, R. A.; Carvalho, I.
Tetrahedron 2010, 66, 9475. (e) Norgren, A. S.; Budke, C.;
Majer, Z.; Heggemann, C.; Koop, T.; Sewald, N. Synthesis
2009, 488. (f) Kamal, A.; Shankaraiah, N.; Reddy, C. R.;
Prabhakar, S.; Markandeya, N.; Srivastava, H. K.; Sastry, G.
N. Tetrahedron 2010, 66, 5498.
Anal. Calcd for C21H15N3O: C, 77.52; H, 4.65; N, 12.91. Found: C,
77.43; H, 4.76; N, 12.83.
3-(4-Phenyl-1H-1,2,3-triazol-1-yl)pyridine (Table 2, entry 16)12f
Yield: 0.171 g (77%); cream-colored solid; mp 176–178 °C.
IR (KBr): 3121, 3098, 1710, 1638, 1584, 1492, 1479, 1466, 1449,
1229, 1036, 1026, 992, 808, 766, 695 cm–1.
1H NMR (500 MHz, DMSO-d6): δ = 9.38 (s, 1 H), 9.23 (br s, 1 H),
8.75 (br s, 1 H), 8.38 (d, J = 8.2 Hz, 1 H), 7.95 (d, J = 7.6 Hz, 2 H),
7.72–7.69 (m, 1 H), 7.51 (t, J = 7.6 Hz, 2 H), 7.40 (t, J = 7.6 Hz, 1
H).
13C NMR (125 MHz, DMSO-d6): δ = 150.6, 148.4, 142.1, 130.9,
129.9, 129.3, 128.7, 126.3, 120.9.
(10) (a) Petrini, M.; Shaikh, R. R. Synthesis 2009, 3143.
(b) Dururgkar, A. K.; Gonnade, R. G.; Ramana, C. V.
Tetrahedron 2009, 65, 3974. (c) Campbell-Verduyn, L. S.;
Mirfeizi, L.; Dierckx, R. A.; Elsing, P. H.; Feringa, B. L.
Chem. Commun. 2009, 2139. (d) Huang, Y.; Gard, G. L.;
Shreeve, J. M. Tetrahedron Lett. 2010, 51, 6951.
(11) (a) Meldal, M.; Christensen, C.; Tornoe, C. W. J. Org.
Chem. 2002, 67, 3057. (b) Kumar, B.; Reddy, V. B.
Synthesis 2010, 1687. (c) Conte, M. L.; Grotto, D.;
Chambery, A.; Dondonia, A.; Marra, A. Chem. Commun.
2011, 47, 1240.
Anal. Calcd for C13H10N4: C, 70.26; H, 4.54; N, 25.21. Found: C,
70.15; H, 4.62; N, 25.13.
Acknowledgment
We gratefully acknowledge the funding support received for this
project from the Islamic Azad University, Fasa Branch.
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© Georg Thieme Verlag Stuttgart · New York