ZnO nanoparticles: Efficient and versatile reagents for synthesis of 1,4-disubstituted 1,2,3-triazoles

Article abstract of DOI:10.3184/174751912X13247429490396

Reaction between azides and acetylenes catalysed by ZnO nanoparticles (ZnO NPs) in solvent EtOH at room temperature provide a simple and efficient one-pot route for the synthesis of 1,4-disubstituted 1,2,3-triazoles in excellent yields. 1,2,3-Triazoles ar

Full text of DOI:10.3184/174751912X13247429490396

JOURNAL OF CHEMICAL RESEARCH 2012
RESEARCH PAPER 9
JANUARY, 9–11
ZnO nanoparticles: efficient and versatile reagents for synthesis of
1,4-disubstituted 1,2,3-triazoles
Bahareh Sadeghia*, Alireza Hassanabadib and Mohammad Kamalia
aDepartment of Chemistry, Islamic Azad University, Yazd Branch, PO Box 89195-155, Yazd, Iran
bDepartment of Chemistry, Islamic Azad University, Zahedan Branch, PO Box 98135-978, Zahedan, Iran
Reaction between azides and acetylenes catalysed by ZnO nanoparticles (ZnO NPs) in solvent EtOH at room tem-
perature provide a simple and efficient one-pot route for the synthesis of 1,4-disubstituted 1,2,3-triazoles in excellent
yields. 1,2,3-Triazoles are used in various agricultural, industrial and medical fields.
Keywords: ZnO nanoparticles, azides, acetylenes, triazoles, solid acid
1,2,3-Triazoles are important heterocyclic compounds. They
are used in several industrial fields,1 such as agrochemicals,2
corrosion inhibitors3 dyes,4 optical brighteners,5 biologically
active agents,6 cytostatic,7 virostatic,8 antiproliferative agents9
and GABA-antagonists10,11 and as synthetic intermediates of
antibiotics12–14 and antihistaminic agents.15
Fokin demonstrated a very effective one-pot preparation of
1,4-disubstituted 1,2,3-triazoles from a variety of readily avail-
able aromatic and aliphatic halides catalysed by a combination
of Cu(I) and L-proline without isolation of potentially unstable
organic azide intermediates.20 Meanwhile, Van der Eycken
et al. also found that a microwave irradiation could accelerate
the one-pot reaction and a series of 1,4-disubstituted-1,2,3-
triazoles were generated from corresponding alkyl halides,
sodium azide, and alkynes in the presence of Cu(I).21 Most
recently, Kacprzak 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
Cu(I) in DMF.29 To the best of our knowledge, there has been
no report of the reaction between azides and acetylenes cata-
lysed by ZnO nanoparticles (ZnO NPs) in solvent EtOH at
room temperature.
Numerous synthetic methods for the preparation of 1,2,3-
triazole derivatives have been developed. Among them
Huisgen 1,3-dipolar cycloaddition between an alkyne and an
azide is the classical and extensively used method.16 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.17 In 2002, Sharpless improved the regiose-
lectivity of the reactions by Cu(I)-catalysed ligation (Click
Chemistry) of organic azides and terminal alkynes.18 Exclusive
regioselectivity, wide substrate scope, mild reaction condi-
tions, effective catalysis system (accelerates the reaction by up
to 107 times), and high yields have made it the method of
choice for making 1,4-disubstituted 1,2,3-triazoles in the pres-
ence of copper catalyst. The catalyst can be directly introduced
as a Cu(I) salt (CuI or CuBr)19 or generated in situ by reduction
of Cu(II) salts,20,21 disproportionation of Cu(0) and Cu(II),22
Cu(0) nanosize cluster,23 Cu(II) salt,24 or Ru(II) complex.25 It
should be noted that the high cost of transition metal catalysts
coupled with the toxic effects associated with many transition
metals has led to an increasing interest in transition-metal-
catalyst-free organic synthetic reactions recently.26 Although
organic azides are generally safe compounds, those of low
molecular weight can be unstable and, therefore, difficult
to handle.27 This is especially true for small molecules with
several azide functionalities that would be of great interest for
the generation of polyvalent structures. Thus, a method that
avoids isolation of organic azides is desirable. In situ genera-
tion of organic azides from suitable precursors followed
by addition of alkyne in one pot, to form the corresponding
1,2,3-trizoles 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.28 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. Recently,
Results and discussion
In continution of our investigation of solid acids in organic
synthesis30,31 we investigated the synthesis of triazoles in the
presence of ZnO NPs as a inorganic solid acid. To optimise
the reaction conditions, the reaction of 4-nitrobenzoazide and
phenylacetylene was used as a model reaction to triazoles
synthesis. According to the obtained data, using the ZnO NPs
(0.0009 g) under solvent EtOH (10 mL) at room temperature is
the best condition for the triazoles formation (Scheme 1).
The stable catalyst is easily prepared (0.0009 g)32 and used
to prepare 1,4-disubstituted 1,2,3-triazoles. To confirm the
better catalytic activity of ZnO nanoparticles, initially we
studied the reaction with other catalysts at 25 °C and 20 min,
and the results are listed in Table 1 (Table 1).
Table 1 clearly demonstrates that ZnO nanoparticles is an
effective catalyst in term of yield of obtained product.
To find out the optimum quantity of ZnO nanoparticles, the
reaction of azides and acetylenes was carried out at 25 °C
using different quantities of ZnO nanoparticles (Table 2).
ZnO nanoparticles of 0.0009 g gave excellent yield in 20 min
(Table 2, entry 4).
The above reaction was also examined in various solvents
(Table 3).
Scheme 1 Reaction between azides and acetylenes catalysed by ZnO nanoparticles.
* Correspondent. E-mail: bsadeghia@gmail.com

10 JOURNAL OF CHEMICAL RESEARCH 2012
Table 1 Reaction between azides and acetylenes in different
The results indicated that different solvents affected the
efficiency of the reaction. dichloromethane, water and under
solvent-free condition at 100 and 25 ºC afforded moderate
yields, while when ethanol was used as solvent, better results
were obtained (Table 3, entry 2).
catalytic conditions at 25 °C
Entry
Catalyst
Time/min
Yielda/%
1
2
3
4
SSA NPsb
Cu(I)
20
20
20
20
24
47
32
85
To study the scope of the reaction, a series of azides and
acetylenes catalysed by ZnO nanoparticles were applied. The
results are shown in Table 4. In all cases, azides substituted
with either electron-donating or electron-withdrawing groups
underwent the reaction smoothly and gave the products in
excellent yields.
Ag(I)
ZnO NPs
a Isolated yield.
b Silica supported sulfuric acid nanoparticles.
1
The compounds 3a–p were characterised by m.p. H, 13C
NMR and IR spectroscopy and elemental analyses.20,29,33–37
Compound 3q was known and our IR and 1H NMR spectro-
scopic data of compound is in agreement with previously
reported spectral data.29
Table 2 Optimisation amount of ZnO nanoparticles on the
reaction of azides and acetylenes at 25 °C
Entry
Catalyst
Time/min
Yielda/%
Compounds 3r–u were new and their structures were
deduced by elemental and spectral analysis. The mass spec-
trum of compound 3r showed the molecular ion peak at 266.
1
2
3
4
0.001
0.004
0.008
0.0009
20
20
20
20
59
72
75
82
1
The H NMR spectrum of compound 3r exhibited protons of
the aromatic groups in the aromatic region of the spectrum.
The 13C NMR spectrum of compound 3r showed 10 signals in
agreement with the proposed structure. The IR spectrum of
compound 3r also supported the suggested structure.
In summary, we have developed a mild, new, high efficient,
simple work-up, one-pot selective method for the synthesis
of 1,4-disubstituted 1,2,3-triazoles in the presence of ZnO
nanoparticles as the solid phase acidic catalyst with excellent
yields.
a Isolated yield.
Table 3 Solvent effect on the reaction between azides and
acetylenes catalysed by ZnO nanoparticles (0.0009 g)
Entry Solvent
Temperature
/°C
Time
/min
Yielda
/%
1
2
3
4
5
Dichloromethane
Reflux
25
20
20
20
20
20
60
74
30
62
38
Ethanol
water
Neat
Experimental
25
Melting points were determined with an Electrothermal 9100 appara-
tus. Elemental analyses were performed at the analytical laboratory
of Science and Research Unit of the Islamic Azad University. Mass
spectra were recorded on a FINNIGAN-MAT 8430 mass spectrometer
180
25
Neat
a Isolated yield.
Table 4 Reaction between azides and acetylenes catalysed by ZnO nanoparticles (0.0009 g) at 25 °C
Entry
R
R1
R2
Product
Yielda/%
M.p./°C
Reported
Found
1
2
C6H5
H
C6H5
3a
3b
3c
3d
3e
3f
3g
3h
3i
3j
3k
3l
3m
3n
3o
3p
3q
3r
86
87
90
87
89
96
90
91
93
94
91
90
92
85
95
88
95
79
72
92
95
165–167
72–74
165–17120
73–7536
97–9920
105–10720
100–10236
126–13029
160–16137
140–14229
130–13137
76–7729
78–8029
187–18935
103–10434
144–14534
129–13134
123–12733
Ref. 29
–
n-C5H11
H
4-MeC6H4
4-MeOC6H4OCH2
4-ClC6H4OCH2
4-MeOC6H4
C6H5
3
C6H5
C6H5
n-C5H11
H
100–101
103–105
103–104
126–128
162–164
142–144
128–130
76–78
4
H
5
H
6
CH2C6H5
CH2C6H5
4-NO2CH2C6H4
CH2C6H5
n-C8H17
H
7
H
4-NH2C6H4
C6H5
3-OHC6H4
C6H5
CO2CH3
CO2CH3
4-MeOC6H4OCH2
4-NO2C6H4
4-BrC6H4
CO2CH3
8
H
9
H
10
11
12
13
14
15
16
17
18
19
20
21
H
n-C8H17
H
76–78
4-NO2C6H4
CH2CO2Et
CH2CO2Et
CH2CO2Et
C6H5
H
188–190
163–164
141–143
130–132
125–126
Oil
H
H
H
CO2CH3
CO2CH2CH3
H
CH2C6H5
4-NO2C6H4
2-Me- 4-NO2 C6H3
4-ClC6H4
2-Me- 4-NO2C6H3
CO2CH2CH3
C6H5
163–164
174–175
138–139
177–178
H
C6H5
3s
3t
3u
–
CO2CH3
CO2CH3
CO2CH3
–
–
CO2CH3
a Pure isolated product.

JOURNAL OF CHEMICAL RESEARCH 2012 11
operating at an ionisation potential of 70 eV. IR spectra were recorded
Received 5 October 2011; accepted 18 December 2011
Paper 1100917 doi: 10.3184/174751912X13247429490396
Published online: 31 January 2012
1
on a Shimadzu IR-470 spectrometer. H and 13C NMR spectra were
recorded on a Bruker DRX-250 Avance spectrometer at solution
in d6-DMSO using TMS as internal standard. The chemicals used in
this work were purchased from Fluka (Buchs, Switzerland) and were
used without further purification. ZnO nanoparticles (ZnO NPs) was
prepared as previously described in the literature.32
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General procedure
3
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9
Azides (1 mmol), acetylenes (1 mmol) and solvent EtOH (10 mL) in
the presence of ZnO NPs (0.0009 g) were placed in a round-bottomed
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724 cm–1. H NMR (CDCl3): d = 7.37 (m, 5 H), 5.80 (s, 2 H), 4.45
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