Ultrasound-promoted one-pot three component synthesis of tetrazoles catalyzed by zinc sulfide nanoparticles as a recyclable heterogeneous catalyst

Article abstract of DOI:10.1016/j.ultsonch.2015.06.008

Ultrasound irradiation was applied for the appropriate and rapid synthesis of 1-substituted tetrazoles through cyclization reaction of various primary amines, sodium azide and triethyl orthoformate. This reaction was effectively catalyzed by ZnS nanoparti

Full text of DOI:10.1016/j.ultsonch.2015.06.008

Ultrasonics Sonochemistry 27 (2015) 408–415
Contents lists available at ScienceDirect
Ultrasonics Sonochemistry
journal homepage: www.elsevier.com/locate/ultson
Ultrasound-promoted one-pot three component synthesis of tetrazoles
catalyzed by zinc sulfide nanoparticles as a recyclable heterogeneous
catalyst
⇑
Hossein Naeimi , Fatemeh Kiani
Department of Organic Chemistry, Faculty of Chemistry, University of Kashan, Kashan 87317, Islamic Republic of Iran
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 19 May 2015
Received in revised form 13 June 2015
Accepted 14 June 2015
Available online 15 June 2015
Ultrasound irradiation was applied for the appropriate and rapid synthesis of 1-substituted tetrazoles
through cyclization reaction of various primary amines, sodium azide and triethyl orthoformate. This
reaction was effectively catalyzed by ZnS nanoparticles as an efficient, recoverable and reusable catalyst.
Compared with conventional methods, this method has the considerable advantages such as shorter reac-
tion times, easier work-up, purer products with high yields and mild conditions. The ZnS nanoparticles
catalyst is an excellent instance to replace Brønsted acids for the preparation of 1-substituted tetrazole
derivatives in very short reaction times with excellent yields. The catalyst can be recovered and reused
several times without significant loss of its catalytic activity.
Keywords:
Ultrasonic irradiation
Tetrazoles
Zinc sulfide nanoparticles
Cyclization
Ó 2015 Elsevier B.V. All rights reserved.
Primary amines
1
. Introduction
Tetrazoles and their derivatives have gained considerable atten-
acid [4] have catalyzed cyclization of an amine, triethyl orthofor-
mate and sodium azide to afford tetrazoles. Unfortunately, all of
these methods have some drawbacks such as long reaction times,
use of expensive and toxic reagents and high boiling solvents,
harsh reaction conditions, low yield, tedious work-up, and even
the need for excess amounts of highly toxic and explosive hydra-
zoic acid [2]. Therefore, in order to overcome these drawbacks, it
is necessary to develop a simple, convenient and more efficient
method for the synthesis of tetrazoles.
Recently, nanostructured materials have attracted much atten-
tion because of their unique properties that distinguish them from
the bulk materials [20]. ZnS is one of the very important materials
applied in organic synthesis with excellent catalytic activity [3]. In
2010, Lang et al. have been used mesoporous ZnS nanospheres as a
new heterogeneous catalyst for the synthesis of 5-substituted
1H-tetrazole derivatives from various nitriles and sodium azide
in DMF as a solvent [3].
In recent years, ultrasound has been extensively applied as a
fantastic tool for different types of chemical reactions [21].
Acoustic cavitation is a physical phenomenon that promotes chem-
ical reactions under ultrasound irradiation. This phenomenon
includes the formation, growth, and implosive collapse of bubbles
in a liquid during a very short period of the time. Precipitate
implosion of these bubbles in the liquids generates localized hot
spots with very short lifetimes. The hot spot has an equivalent
temperature of 5000 °C and pressure of about 2000 atmospheres.
tion because they have a wide range of applications in information
recording systems in material science [1], medicinal chemistry [2],
photography [3] and agriculture [4]. Pharmaceutical applications
of tetrazoles include antiallergic, antimicrobial, sedatives [5],
anti-inflammatory [6], anti-HIV [7], hormonal [8], lipophilic spac-
ers [9] and diuretics activity [10]. Furthermore, a range of proline
derived tetrazoles have been reported as an enantioselective cata-
lyst in asymmetric synthesis; additionally, they play a very impor-
tant role as ligands in coordination chemistry [11]. Tetrazole
derivatives can be prepared by different methods. Generally, the
most convenient and versatile procedure for the preparation of
tetrazoles is the cycloaddition between nitriles, cyanates, cyana-
mides and azides [4]. Several methods have been reported for
the synthesis of 1-substituted tetrazoles involve acid-catalyzed
cycloaddition between hydrazoic acid and isocyanides [12].
Acid-catalyzed cycloaddition between isocyanides and trimethyl
azide [13], acetic acid or trifluoroacetic acid have catalyzed cycliza-
tion between primary amines or their salts, and an orthocarboxylic
acid ester and sodium azide [14,15]. Acidic ionic liquid [16], ytter-
bium triflate [17], zeolites [18], indium triflate [19], silica sulfuric
⇑
Corresponding author.
E-mail address: naeimi@kashanu.ac.ir (H. Naeimi).
http://dx.doi.org/10.1016/j.ultsonch.2015.06.008
350-4177/Ó 2015 Elsevier B.V. All rights reserved.
1

H. Naeimi, F. Kiani / Ultrasonics Sonochemistry 27 (2015) 408–415
409
These transient, localized hot spots run high energy chemical
transformations [22,23].
oven followed a working cycle of 50 s. (on) and 100 s. (off) at
350 W. After completion of the reaction, the mixture was slowly
cooled to room temperature. The precipitate was filtered and con-
secutively washed with deionized water (5 ꢀ 50 ml) and absolute
ethanol (3 ꢀ 10 ml) and was dried at room temperature.
In continuation of ongoing to our work on the application of
ultrasound in the organic reactions [24–26], we decided to carry
out the ultrasonication reaction of primary amines, sodium azide
and triethyl orthoformate catalyzed by ZnS NPs as a recyclable
catalyst.
2.4. General procedure for synthesis of 1-substituted
1H-1,2,3,4-tetrazoles
2
. Experimental
A mixture of selected primary amine (1 mmol), triethyl ortho-
formate (1.2 mmol) and sodium azide (1 mmol) in the presence
of 0.01 g ZnS nanoparticles was added to N,N-dimethylformamide
as solvent and the reaction mixture was irradiated in ultrasonic
apparatus with the power 50 W. The progress of the reaction was
monitored by thin layer chromatography (TLC). After completion
2
.1. Materials
All commercially available reagents were used without further
purification and purchased from the Merck Chemical Company in
high purity. The used solvents were purified by standard procedure
as followed; DMF: drying over CaSo
reduced pressure, EtOAc: washing with aqueous 5% Na
with saturated aqueous NaCl and drying with MgSO , MeOH: by
fractional distillation, EtOH: drying over CaO and distillation under
of the reaction, the mixture was diluted by 1:1 H
2
O:ethylacetate
4
and distillation under
(
10 ml), stirred at ambient temperature (20 min) and centrifuged
2
CO , then
3
to separate the solid catalyst. The organic layer of the solution
was separated, dried over sodium sulfate, and the organic solvent
and other residues were stripped in a vacuum evaporator. The pro-
duct was purified by recrystallization in a mixture of EtOAc:MeOH
4
reduced pressure, and acetonitrile: drying over
distillation.
P
2
O
5
and
(
3:1) to yield pure product. The obtained pure tetrazoles were
characterized by spectroscopic data and melting points.
2.2. Apparatus
2
2
.5. Spectral data for 1-substituted 1H-1,2,3,4-tetrazoles derivatives
IR spectra were recorded as KBr pellets on a Nicolet FT-IR spec-
trophotometer. H and C NMR spectra were recorded in CDCl on
3
a Bruker DRX-400 spectrometer with tetramethylsilane as internal
reference. A BANDELIN ultrasonic HD 3200 with probe model KE
6, with the diameter of 6 mm, was used to produce ultrasonic
irradiation and homogenizing the reaction mixture. Piezoelectric
crystal of this kind of probe normally works in the range of
00 kHz, but by using some proper clamps, the output frequency
of piezoelectric crystal have controlled and reduced to 20 kHz.
Therefore, the induced frequency of probe to the reaction mixture
is equal to 20 kHz. By changing the power of Tip the cavitations
rate is displaced so that the Tip frequency under various amounts
of power is constant. A thermal method was used for the calibra-
tion of ultrasonic power. XRD patterns were recorded by an
X’PertPro (Philips) instrument with 1.54 Ångström wavelengths
of X-ray beam and Cu anode material. Scanning electron micro-
scope (SEM) of nanoparticles was performed on a FESEM Hitachi
S4160. Transmission electron microscopy (TEM) was performed
with a Jeol JEM 2100UHR, operated at 200 kV. Melting points
obtained with a Yanagimoto micro melting point apparatus are
uncorrected. The purity determination of the substrates and reac-
tion monitoring were accomplished by TLC on silicagel polygram
SILG/UV 254 plates (from Merck Company).
1
13
.5.1. 1-phenyl-1H-1,2,3,4-tetrazole
Yellow solid. m.p = 63–65 °C; IR (KBr)/
ꢁ
1
m
(cm 1): 3 051 (C–H, sp2
stretch Ar), 1677 (C@N), 1588, 1488 (C@C); H NMR (400 MHz,
CDCl ) d ppm = 7.07–7.34 (m, 5H, ArH), 8.20 (s, 1H tetrazole).
3
7
2
.5.2. 1-(4-Boromophenyl)-1H-1,2,3,4-tetrazole
White solid. m.p = 183–185 °C; IR (KBr)/
sp2 stretch, Ar), 1659 (C@N), 1576, 1481 (C@C);
7
ꢁ
1
m
(cm ): 3151 (C–H,
1
H
NMR
(
400 MHz, CDCl ) d ppm = 6.92–6.94 (d, 2H, ArH), 7.40–7.42 (d,
3
1
3
2
3
H, ArH), 8.09 (s, 1H tetrazole); C NMR (100 MHz, CDCl ) d
ppm = 116.43, 120.76, 132.03, 143.99, 149.29.
2.5.3. 1-(4-Methylphenyl)-1H-1,2,3,4-tetrazole
ꢁ
Light yellow solid. m.p = 93–94 °C; IR (KBr)/
m
(cm 1): 3022
2
3
(C–H, sp stretch, Ar), 2918 (C–H, sp stretch), 1664 (C@N), 1607,
1506 (C@C); H NMR (400 MHz, CDCl
1
3
) d ppm = 2.34 (s, 3H, Me),
6.94–6.96 (d, 2H, ArH), 7.11–7.13 (d, 2H, ArH), 8.17 (s, 1H tetrazole);
1
3
3
C NMR (100 MHz, CDCl ) d ppm = 20.79, 119.08, 129.63, 130.17,
142.95, 149.77.
2.5.4. 1-(3-Methylphenyl)-1H-1,2,3,4-tetrazole
White solid. m.p = 112–114 °C; IR (KBr)/m
(cmꢁ1): 3066 (C–H,
sp2 stretch, Ar), 2920 (C–H, sp stretch), 1680 (C@N), 1598, 1483
3
2
.3. Synthesis of ZnS nanoparticles
1
(
C@C); H NMR (400 MHz, CDCl
3
) d ppm = 2.33 (s, 3H, Me), 6.86
ZnS nanoparticles were synthesized according to the previously
reported method [27]. Zinc nitrate hexahydrate (0.01 mol) was dis-
solved in 20 ml of propylene glycol under intensive stirring at
(s, 1H, ArH), 6.89–6.91 (d, 2H, ArH), 7.18–7.22 (t, 1H, ArH), 8.21
1
3
(s, 1H tetrazole);
3
C NMR (100 MHz, CDCl ) d ppm = 21.43,
115.93, 119.97, 124.06, 129.19, 139.26, 145.28, 149.23.
9
0 °C. Then, 10 ml of thioacetamide solution (1 M) was previously
prepared and added dropwise to the solution over 10 min.
Afterward, the solution was exposed to irradiate at microwave
2.5.5. 1-(2-Methylphenyl)-1H-1,2,3,4-tetrazole
White solid. m.p = 153–155 °C; IR (KBr)/m
(cmꢁ1): 3015 (C–H,
sp2 stretch, Ar), 2870 (C–H, sp stretch), 1664 (C@N), 1488, 1590
3
1
(
C@C); H NMR (400 MHz, CDCl
3
) d ppm = 2.33 (s, 3H, Me), 7.02–
N
N
7.03 (d, 1H, ArH), 7.05–7.07 (d, 1H, ArH), 7.18–7.22 (t, 2H, ArH),
NH2
N
13
N
8.08 (s, 1H tetrazole); C NMR (100 MHz, CDCl
3
) d ppm = 17.94,
Nano ZnS
HC(OEt)3
NaN3
117.68, 123.43, 127, 128.71, 130.72, 144.10, 147.78.
U.S / r.t.,DMF
R
R
2
.5.6. 1-[4-(1H-tetrazol-1-yl)phenyl]ethanone
Yellow solid. m.p = 148–150 °C; IR (KBr)/
m
(cmꢁ1): 3075 (C–H,
Scheme 1. Synthesis of 1-substituted 1H-1,2,3,4-tetrazoles by ultrasound irradia-
tion and ZnS nanoparticles.
sp2 stretch, Ar), 2995 (C–H, sp stretch), 1669 (C@N), 1499, 1585
3

4
10
H. Naeimi, F. Kiani / Ultrasonics Sonochemistry 27 (2015) 408–415
Fig. 1. The XRD pattern of zinc sulfide nanoparticles.
Table 1
Calculated structural parameters of ZnS nanoparticles from XRD data.
Parameters
Values
Position (°2h)
Plane (hkl)
FWHM (°2h)
e
str
D (nm)
d (lines/m)
d
hkl (Å)
45 ꢀ 10ꢁ
3
17.03
8.25 ꢀ 10
16
5.40
28.8566
111
220
311
1.4170
2.3616
2.8800
4
5
8.7168
7.0200
(
7
C@C); 1H NMR (400 MHz, CDCl
3
) d ppm = 2.60 (S, 3H, Me),
.13–7.15 (d, 2H, ArH), 7.95–7.97 (d, 2H, ArH), 8.30 (s, 1H tetrazole).
2.5.11. 1-(2-Chlorophenyl)-1H-1,2,3,4-tetrazole
White solid. m.p = 129–131 °C; IR (KBr)/
sp2 stretch, Ar), 1664 (C@N), 1470, 1582 (C@C);
400 MHz, CDCl ) d ppm = 7.03–7.50 (m, 4H, ArH), 8.10 (s, 1H
tetrazole).
ꢁ
1
m (cm ): 3047 (C–H,
1
H
NMR
(
3
2
.5.7. 1-(2,4-Dimethylphenyl)-1H-1,2,3,4-tetrazole
(cm 1): 3069 (C–H,
ꢁ
White solid. m.p = 133–135 °C; IR (KBr)/
m
sp stretch, Ar), 2914 (C–H, sp3 stretch), 1663 (C@N), 1495, 1607
2
2
.5.12. 1-(3-Chlorophenyl)-1H-1,2,3,4-tetrazole
White solid. m.p = 137–139 °C; IR (KBr)/
sp2 stretch, Ar), 1670 (C@N), 1469, 1589 (C@C);
(
(
(
C@C); 1H NMR (400 MHz, CDCl
3
) d ppm = 2.29 (s, 3H, Me), 2.30
ꢁ
1
m
(cm ): 3065 (C–H,
s, 3H, Me), 6.94–6.96 (d, 1H, ArH), 6.98–7.00 (d, 1H, ArH), 7.02
s, 1H, ArH), 8.00 (s, 1H tetrazole).
1
H
NMR
(
2
400 MHz, CDCl ) d ppm = 6.92–6.94 (d, 1H, ArH), 7.07–7.09 (d,
H, ArH), 7.26–7.27 (t, 1H, ArH), 8.14 (s-1H tetrazole); C NMR
3
13
2
.5.8. 1-(Naphthalene-1-yl)-1H-1,2,3,4-tetrazole
(100 MHz, CDCl
146.14, 149.72.
3
) d ppm = 117.45, 119.23, 123.73, 130.34, 135.12,
(cm 1): 3048 (C–H,
ꢁ
White solid. m.p = 181–183 °C; IR (KBr)/
m
sp2 stretch, Ar), 1658 (C@N), 1574, 1432 (C@C);
1
H NMR
(
400 MHz, CDCl
3
) d ppm = 7.23–8.27 (m, 7H, ArH), 8.36 (s, 1H
3. Results and discussion
tetrazole).
As a part of our growing interest in sonochemistry, with the
purpose of improving the synthesis of 1-substituted tetrazole
derivatives, we decided to perform a systematic investigation on
the synthesis of these heterocycles under significantly milder
conditions.
In continuation of our recent studies on application of ZnS
nanoparticles, we hereby report a new protocol for the synthesis
of 1-substituted 1H-1,2,3,4-tetrazoles in the presence of ZnS
nanoparticles as a stable heterogeneous catalyst under ultrasound
irradiation at room temperature (Scheme 1).
2
.5.9. 1-[2-(1H-tetrazol-1-yl)phenyl]-1H-1,2,3,4-tetrazole
ꢁ1
White solid. m.p = 167–169 °C; IR (KBr)/
sp2 stretch, Ar), 1619 (C@N), 1458, 1588 (C@C);
400 MHz, CDCl ) d ppm = 7.30–7.70 (m, 4H, ArH), 8.11 (s, 1H tetra-
zole); C NMR (100 MHz, CDCl ) d ppm = 115.76, 122.37, 138.50,
m (cm ): 3062 (C–H,
1
H
NMR
(
3
1
3
3
1
42.40.
2.5.10. 1-(4-Chlorophenyl)-1H-1,2,3,4-tetrazole
ꢁ
White solid. m.p = 153–155 °C; IR (KBr)/
m
(cm 1): 3052 (C–H,
sp2 stretch, Ar), 1661 (C@N), 1485, 1581 (C@C);
1
H
NMR
3.1. Characterization of the ZnS nanocrystals
(
2
3
400 MHz, CDCl ) d ppm = 6.98–7.00 (d-2H, ArH), 7.27–7.29 (d,
13
H, ArH), 8.09 (s, 1H tetrazole); C NMR (100 MHz, CDCl
3
) d
The microstructures of the synthesized zinc sulfide nanoparti-
cles were confirmed by X-ray diffractometer (XRD), Diffuse
ppm = 120.35, 128.85, 129.47, 143.52, 149.50.

H. Naeimi, F. Kiani / Ultrasonics Sonochemistry 27 (2015) 408–415
411
Fig. 2. SEM images of ZnS nanoparticles with two magnification (a and b) and TEM image of these nanoparticles materials (c).
Fig. 4. Energy dispersive X-ray (EDX) spectra of ZnS nanoparticles.
Fig. 3. Particle size distribution histogram of ZnS nanoparticles.
2h values of 28.8, 48.7, and 57.0 corresponds to (111), (220), and
(
311) diffraction planes of cubic ZnS, respectively. The average
crystallite sizes of the zinc sulfide were estimated by Debye–
Scherrer’s equation; D = 0.9k/bCosh, where D is the crystallite size,
b is the full width at half maximum (FWHM) in radians of the
diffraction peaks, h is the Bragg’s diffraction angle, and k is
the X-ray wave length (1.54056 Å). According to the FWHM of
Reflectance Spectroscopy (DRS), scanning electron microscope
(
SEM) and transmission electron microscope (TEM).
As revealed in Fig. 1, there are three broad peaks in the XRD pat-
tern of the synthesized ZnS nanoparticles. The diffraction peaks at

4
12
H. Naeimi, F. Kiani / Ultrasonics Sonochemistry 27 (2015) 408–415
distribution histogram in Fig. 3, the mean value and standard devi-
ation of nanoparticles size can be estimated as 27 ± 5 nm.
An Energy Dispersive X-ray Analyzer (EDX or EDA) was also
used to check the elemental identification and quantitative
compositional information of ZnS nanoparticles (Fig. 4). EDX was
provided elemental analysis on areas as small as nanometers in
diameter. The impact of the electron beam on the sample produces
X-rays that are characteristic of the elements present on the
sample. As shown in this figure, the presence of Zn L
.002 keV, Zn K peak at 1.560 keV, S L peak at 5.005 keV and S
peak at 1.560 keV could be observed. Also, no oxygen and other
a
peak at
1
a
a
K
a
peaks (except Zn and S) for any other element have been found in
the spectrum which confirmed that the ZnS nanoparticles are pure.
UV–visible diffuse reflectance spectrum of ZnS nanoparticles in
the wavelength range of 200–900 nm was shown in Fig. 5. The
band gap energy from UV-DRS was revealed the shift of band edge
at shorter wavelength compared to the bulk ZnS (337 nm) due to
the particle size of nano ZnS. The optical absorption edge of the
ZnS nanoparticles at 307 nm (3.80 eV), is slightly blue shifted from
g
that of the bulk ZnS (337 nm, E = 3.65 eV) [29]. This nearness of
Fig. 5. UV–visible diffuse reflectance spectrum of ZnS nanoparticles.
the absorption peak to the bulk ZnS crystals is attributed to the
near band edge emission [30]. The broadening of the absorption
spectrum could be due to the quantum confinement of the
nanoparticles [31].
the most intense (111) plane, the calculated crystallite size is
found to be 17 nm. Additionally, the broadening of XRD peaks
due to the FWHM is also related to the micro strain (lattice strain)
that can be calculated by Stokes–Wilson equation;
estr = bCosh/4
3.2. Optimization of the reaction conditions
[
28], where the values of b and h are explained above. The pattern
of the ZnS nanoparticles was indexed as a cubic phase which is
very close to the values in the literature (JCPDS No. 80-0020 with
cell constant a = 5.3450 Å). The amount of defects in the sample
that naming as dislocation density (d) was calculated by equation;
d = 1/D , where D is the average crystallite size. Also, inter planer
spacing was calculated using the relation dhkl = nk/2Sinh. The cal-
culated structural parameters are given in Table 1.
In the present work, we investigated the effect of ultrasound
irradiation on the model reaction of aniline, sodium azide and tri-
ethyl orthoformate in the presence of ZnS nanoparticles at room
temperature (Table 2). Firstly, the effect of different solvents and
various amounts of catalyst on the model reaction was conducted.
2
2
Several organic solvents such as acetonitrile, ethanol, DMF and H O
were examined. According to data given in (Table 2, entry 4), DMF
was the most efficient solvent for this reaction. No reaction was
observed in the absence of catalyst without ultrasonic irradiation
The very strong reflection peaks in the XRD pattern were shown
that the ZnS nanoparticles were well crystallized. Also, there was
detected any peaks in this pattern from other impurities such as
ZnO or other compounds that confirmed the nanoparticles having
pure phase.
As can be seen in Fig. 2, the images of both scanning electron
and transmission electron microscopes were confirmed by the size
of nanoparticles as 24–28 nm.
(Table 3, entry 1). When the reaction was performed at room tem-
perature in the presence of ZnS nanoparticles and in the absence of
ultrasonic irradiation, the product was obtained in lower yield and
longer reaction time (Table 3, entry 2), while in the presence of
ultrasonic irradiation and 0.05 g of the catalyst, the yield increased
to 92% and the reaction time is reduced to 20 min (Table 3, entry
Fig. 3 shows the particle size distribution histogram from TEM
image of the ZnS nanoparticles. As can be observed, the dispersed
ZnS nanoparticles were formed with uniform size. From the size
6
). It was demonstrated that combination method (ultrasound
Table 3
a
Optimization of the various amount of catalyst .
Table 2
a
NH2
+
Optimization in the presence of different solvents .
N
ZnS nanoparticles
U.S/r.t., DMF
N
N
NaN3
+
HC(OEt)3
N
NH2
+
N
ZnS nanoparticles
U.S/r.t., DMF
N
N
NaN3
+
HC(OEt)3
N
Entry
Condition
Nano ZnS (g)
Time (min)
Yield (%)b
1
2
3
4
5
6
7
Silent
Silent
US
US
US
–
120
120
85
50
35
0
12
45
61
78
92
92
0.01
0.01
0.03
0.04
0.05
0.07
Entry
Solvent
Time (min)
Yield (%)b
1
2
3
4
Acetonitrile
EtOH
30
45
45
20
62
58
63
92
H
2
O
US
US
20
20
DMF
a
a
Reaction conditions: aniline 1.0 mmol, triethyl orthoformate 1.2 mmol and
Reaction conditions: aniline 1.0 mmol, triethyl orthoformate 1.2 mmol and
sodium azide 1.0 mmol.
sodium azide 1.0 mmol.
b
b
Isolated yields.
Isolated yields.

H. Naeimi, F. Kiani / Ultrasonics Sonochemistry 27 (2015) 408–415
413
Table 4
Table 5
a
a
Study of the effect of ultrasonic irradiation on the formation of tetrazole .
Synthesis of different tetrazoles from several amines .
NH2
+
NH2
+
N
N
ZnS nanoparticles
N
N
ZnS nanoparticles
U.S/r.t., DMF
N
N
NaN3
+
HC(OEt)3
N
NaN3
+
HC(OEt)3
N
U.S/r.t., DMF
Entry
Power (W)
Time (min)
Yieldb (%)
Entry Primary amine
1
Product
Time
(min)
Yield
(%)
Refs.
[17]
b
Nonec
1
2
3
4
5
6
120
85
65
40
20
20
12
54
68
83
92
92
30
40
45
50
55
N
20
92
NH
2
N
N
N
2
3
4
N
15
20
20
88
92
89
[17]
[36]
[17]
N
N
H
3
C
NH
2
H
3
C
N
a
Reaction conditions: aniline 1.0 mmol, triethyl orthoformate 1.2 mmol and
sodium azide 1.0 mmol.
N
N
b
Br
NH
2
Br
N
Isolated yields.
The reaction without ultrasonic irradiation.
N
c
N
NH
2
N
N
N
3
H C
irradiation and ZnS nanoparticles) can be played an important role
on the product yield and reaction time.
H C
3
5
NH2
CH3
N
25
77
[17]
N
N
In continuation of this method, the role of ultrasonic irradiation
and the effect of various powers of ultrasonic irradiation on the
reaction were investigated. The reaction was performed in the
presence of ZnS nanoparticles (0.05 g) as a catalyst in DMF, under
silent condition and ultrasound irradiation (Table 4). The results
illustrated that the sonication positively affected the reaction sys-
tem. It could be reduce the reaction time and increase the yield of
the products (Table 4, entry 2). While the reaction in the presence
of ZnS nanoparticles without ultrasonic irradiation was carried out
in low yield and long reaction time (Table 4, entry 1). Also, it was
observed that the reaction in the presence of ZnS nanoparticles and
ultrasonic irradiation with the power of 50 W gave the best result
as the obtained product with 92% isolated yield during 20 min
N
CH3
6
7
O
O
N
N
20
25
86
76
[16]
[36]
N
NH
2
N
N
N
H
3
C
3
H C
H C
3
NH2
CH3
N
N
H C
3
CH
3
8
9
NH2
N
25
20
76
78
[17]
[37]
N
N
N
Cl
Cl
(Table 4, entry 5).
Ultrasonic irradiation differs from conventional energy sources.
N
N
N
N
NH
2
This incidence may be explained based on betterment of sorption
on the catalyst surface and the better mass transport of organic
compounds among the liquid phase and the catalyst surface under
ultrasonic condition. These are ascribed to the shock wave and
microjet manufactured by the cavitations. In term of sonication,
dispersed ZnS nanoparticles in solution affords extra nucleation
sites for acoustic cavity formation on its surface and gain the num-
ber of micro bubbles in the solution [32–35]. The quick implosion
of these bubbles in the liquids generates localized hot spots with
very short lifetimes. The high local temperature and pressures pro-
vide desirable conditions for driving a large number of chemical
reactions. Thus, a wide variety of organic reactions can be per-
formed in shorter reaction times with higher yields and milder
conditions under ultrasound irradiation than with traditional
methods.
N
Cl
Cl
Cl
Cl
1
0
1
N
20
25
82
74
[17]
[17]
N
N
NH
2
1
NH2
N
N
N
N
12
NH2
N
30
70
–
N
N
N
NH2
N
N
N
N
After optimization of the reaction conditions, the limitation and
generality of this work was investigated. For this aim, a variety of
primary aromatic amines (1.0 mmol) containing electron donating
and electron withdrawing substituents were reacted with triethyl
orthoformate (1.2 mmol) and sodium azide (1.0 mmol) in the
presence of ZnS nanoparticles optimum amount (0.05 g) under
ultrasonic irradiation (50 W) and the desired 1-substituted-1H-
tetrazole derivatives were obtained (Table 5). The results were
shown that a wide range of aromatic amine derivatives containing
electron withdrawing as well as electron donating groups
produced corresponding tetrazoles in excellent isolated yields
a
Reaction conditions: aniline 1.0 mmol, triethyl orthoformate 1.2 mmol, sodium
azide 1.0 mmol and ZnS nanoparticles 50 mol% (0.05 g).
b
Isolated yields.
The comparison of results related to ultrasound irradiation with
thermal conditions was indicated that, the reaction of various pri-
mary amines with triethyl orthoformate and sodium azide would
be catalyzed by ultrasonic irradiation. As shown in Table 4, in the
presence of ZnS nanoparticles, the excellent product yields were
achieved in shorter reaction time under ultrasound irradiation. In
(Table 5).

4
14
H. Naeimi, F. Kiani / Ultrasonics Sonochemistry 27 (2015) 408–415
N
OEt
OEt
N
N
H
H
ArNH2
N
OEt
Ar
-
EtOH
N
N
N
OEt
OEt
NHAr
H
H
N
Fig. 6. Reusability of ZnS nanoparticles as catalyst toward synthesis of tetrazoles.
Ar
NaN3
applicable processes. Therefore, we studied the recycling of the
catalyst for synthesis of 1-substituted 1H-tetrazoles under opti-
mized conditions. The aniline (1.0 mmol), triethyl orthoformate
-
EtOH
-NaOEt
)
)
)
OEt
N3
)
)
)
H
(
1.2 mmol), sodium azide 1.0 mmol were sonicated in the presence
of ZnS nanoparticles 50 mol% (0.05 g) in DMF as solvent (20 min).
After completion of the reaction, the mixture was diluted by 1:1
NHAr
H
2
O/EtOAc (10 ml), stirred at ambient temperature (20 min) and
centrifuged to separate catalyst. The solid catalyst was dried at
0 °C under reduced pressure to obtain almost quantitatively of
6
=
ZnS nanoparticles
)))))) = Ultrasound irradiation
the crude ZnS nanoparticles. After seven cycles, the catalyst was
shown almost the same activity and gave the corresponding pro-
duct in high yields Fig. 6.
Scheme 2. The proposed reaction mechanism.
the previously reported work [27], the reaction of triethyl orthofor-
mate and sodium azide with aniline or 4-chloro aniline catalyzed
by ZnS nanoparticles in thermal conditions for 4.5 h and 4.7 h
afforded 1-phenyl-1H-1,2,3,4-tetrazole and 1-(4-chlorophenyl)-1
H-1,2,3,4-tetrazole in 78% and 68% yields respectively (Table 3,
entries 1 and 10) [27]. Whereas the present procedure needed only
4
. Conclusion
In summary, we have described a mild, clean, fast, novel and
safe sonochemical method for the synthesis of 1-substituted
H-tetrazole derivatives by ZnS nanoparticles as a reusable and
1
recoverable catalyst at room temperature. This novel protocol have
significant advantages such as; high yields of desired products
without side reactions, no elimination of hydrazoic acid as a toxic
and explosive volatile gas, easy work-up and reusable catalyst. The
catalyst can be separated by simple filtration and reuse several
times without any significant loss of activity which is an additional
sustainable characteristic of this method. The products have been
confirmed by spectroscopic and physical data such as; IR,
NMR, C NMR and melting point.
2
0 min to result 1-phenyl-1H-1,2,3,4-tetrazole in 92% yield
(Table 5, entry 1) and 20 min to result 1-(4-chlorophenyl)-1
H-1,2,3,4-tetrazole in 82% yield (Table 5, entry 10).
This method offered several advantages including simple reac-
tion conditions, excellent yields, short reaction times, high purity,
and the easy work up procedures. These results indicated that
the ultrasound irradiation was an efficient method for the
one-pot synthesis of 1-substituted tetrazoles as considerable and
useful heterocycles.
1
H
1
3
Acknowledgment
3.3. The proposed reaction mechanism
The authors are grateful to University of Kashan for supporting
this work by Grant No. 159148/56.
The possible mechanism for the synthesis of 1-substituted
H-tetrazol through catalyzed cyclization of aniline, sodium azide
1
and triethyl orthoformate under ultrasonic irradiation in the pres-
ence of ZnS nanoparticles as catalyst is shown in Scheme 2. It is
clear adsorption of triethyl orthoformate is improved on the ZnS
nanoparticles surface by the effects of nano catalyst surface and
also ultrasonic irradiation. Additionally, ultrasound can increases
mass transfer of triethyl orthoformate between primary amine
and sodium azide via the acoustic cavitation effect. The role of cat-
alyst is activation of ethoxy groups and cleavage of C–O bonds.
Generated carbonium ions can be stable through resonance by
neighboring oxygen heteroatom or sequential nucleophilic dis-
placements by amine and cyclization with azide.
Appendix A. Supplementary data
Supplementary data associated with this article can be found, in
the online version, at http://dx.doi.org/10.1016/j.ultsonch.2015.06.
0
08.
References
[
[
3 4
1] G. Qi, W. Liu, Z. Bei, Fe O /ZnS hollow nanospheres: a highly efficient magnetic
heterogeneous catalyst for synthesis of 5-substituted 1H-tetrazoles from
nitriles and sodium azide, Chin. J. Chem. 29 (2011) 131–134.
2] M. Esmaeilpour, J. Javidi, F. Nowroozi Dodeji, M. Mokhtari Abarghoui, Facile
synthesis of 1- and 5-substituted 1H-tetrazoles catalyzed by recyclable ligand
In continuation of this research, the reusability and recyclability
of the catalyst was investigated. The possibility of recovering
and recycling of the catalyst is an important process from different
aspects such as environmental concerns, and commercial
complex of copper(II) supported on superparamagnetic Fe
nanoparticles, J. Mol. Catal. A: Chem. 393 (2014) 18–29.
3 4 2
O @SiO

H. Naeimi, F. Kiani / Ultrasonics Sonochemistry 27 (2015) 408–415
415
[
[
[
3] L. Lang, B. Li, W. Liu, L. Jiang, Z. Xu, G. Yin, Mesoporous ZnS nanospheres: a high
activity heterogeneous catalyst for synthesis of 5-substituted 1H-tetrazoles
from nitriles and sodium azide, Chem. Commun. 46 (2010) 448–450.
4] D. Habibi, H. Nabavi, M. Nasrollahzadeh, Silica sulfuric acid as an efficient
heterogeneous catalyst for the solvent-free synthesis of 1-substituted 1H-
[21] D. Habibi, M. Nasrollahzadeh, L. Mehrabi, S. Mostafaee, P
2
O
5
–SiO
2
as an
efficient heterogeneous catalyst for the solvent-free synthesis of 1-substituted
1H-1,2,3,4-tetrazoles under conventional and ultrasound irradiation
conditions, Monatsh. Chem. 144 (2013) 725–728.
[22] T.J. Mason, Ultrasound in synthetic organic chemistry, Chem. Soc. Rev. 26
(1997) 443–451.
[23] M. Nasrollahzadeh, A. Ehsani, A. Rostami-Vartouni, Ultrasound-promoted
green approach for the synthesis of sulfonamides using natural, stable and
reusable natrolite nanozeolite catalyst at room temperature, Ultrason.
Sonochem. 21 (2014) 275–282.
[24] H. Naeimi, K. Rabiei, Sonocatalyzed facile and mild one pot synthesis of gem-
dichloroaziridine derivatives under alkaline conditions, Ultrason. Sonochem.
19 (2012) 130–135.
1
,2,3,4-tetrazoles, J. Chem. 2013 (2013) 4.
5] S. Nag, S. Bhowmik, H.M. Gauniyal, S. Batra, Application of primary allylamines
from Morita–Baylis–Hillman adducts: cyanogen azide mediated synthesis of
substituted 5-aminotetrazoles and their attempted transformation into
tetrazolo[1,5-a]pyrimidinones, Eur. J. Org. Chem. 2010 (2010) 4705–4712.
6] S. Bepary, B.K. Das, S.C. Bachar, J.K. Kundu, A.S. Shamsur Rouf, B.K. Datta, Anti-
inflammatory activity of indanyltetrazole derivatives, Pak. J. Pharm. Sci. 21
[
[
(
2008) 295–298.
7] E. Muraglia, O.D. Kinzel, R. Laufer, M.D. Miller, G. Moyer, V. Munshi, F. Orvieto,
M.C. Palumbi, G. Pescatore, M. Rowley, P.D. Williams, V. Summa, Tetrazole
thioacetanilides: potent non-nucleoside inhibitors of WT HIV reverse
transcriptase and its K103N mutant, Bioorg. Med. Chem. Lett. 16 (2006)
[25] R. Ghahremanzadeh, Z. Rashid, A.-H. Zarnani, H. Naeimi, A facile one-pot
ultrasound assisted for an efficient synthesis of 1H-spiro[furo[3,4-b]pyridine-
0
4,3 -indoline]-3-carbonitriles, Ultrason. Sonochem. 21 (2014) 1451–1460.
[26] H. Naeimi, Z.S. Nazifi, A facile one-pot ultrasound assisted synthesis of 1,8-
dioxo-octahydroxanthene derivatives catalyzed by Brønsted acidic ionic liquid
(BAIL) under green conditions, J. Ind. Eng. Chem. 20 (2014) 1043–1049.
[27] H. Naeimi, F. Kiani, M. Moradian, ZnS nanoparticles as an efficient and reusable
heterogeneous catalyst for synthesis of 1-substituted-1H-tetrazoles under
solvent-free conditions, J. Nanopart. Res. 16 (2014) 1–9.
2
748–2752.
[
[
8] J. Li, S.Y. Chen, S. Tao, H. Wang, J.J. Li, S. Swartz, C. Musial, A.A. Hernandez, N.
Flynn, B.J. Murphy, B. Beehler, K.E. Dickinson, L. Giupponi, G. Grover, R.
Seethala, P. Sleph, D. Slusarchyk, M. Yan, W.G. Humphreys, H. Zhang, W.R.
Ewing, J.A. Robl, D. Gordon, J.A. Tino, Design and synthesis of tetrazole-based
growth hormone secretagogue: the SAR studies of the O-benzyl serine side
chain, Bioorg. Med. Chem. Lett. 18 (2008) 1825–1829.
[28] A. Khorsand Zak, W.H.A. Majid, M. Ebrahimizadeh Abrishami, R. Yousefi, R.
0.03
Parvizi, Synthesis, magnetic properties and X-ray analysis of Zn0.97X O
nanoparticles (X = Mn, Ni, and Co) using Scherrer and size–strain plot
methods, Solid State Sci. 14 (2012) 488–494.
9] M. Nasrollahzadeh, Y. Bayat, D. Habibi, S. Moshaee, FeCl
heterogeneous catalyst for the synthesis of 5-substituted 1H-tetrazoles via
2+3] cycloaddition of nitriles and sodium azide, Tetrahedron Lett. 50 (2009)
435–4438.
3
–SiO
2
as a reusable
[
4
[29] S. Suresh, Synthesis, structural and dielectric properties of zinc sulfide
nanoparticles, Int. J. Phys. Sci. 8 (2013) 1121–1127.
[
10] R.J. Nachman, G.M. Coast, K. Kaczmarek, H.J. Williams, J. Zabrocki,
Stereochemistry of insect kinin tetrazole analogues and their diuretic
activity in crickets, Acta Biochim. Pol. 51 (2004) 121–127.
11] V. Rama, K. Kanagaraj, K. Pitchumani, Syntheses of 5-substituted 1H-tetrazoles
catalyzed by reusable CoY zeolite, J. Org. Chem. 76 (2011) 9090–9095.
12] D.M. Zimmerman, R.A. Olofson, The rapid synthesis of 1-substituted tetrazoles,
Tetrahedron Lett. 10 (1969) 5081–5084.
13] T. Jin, F. Kitahara, S. Kamijo, Y. Yamamoto, Copper-catalyzed synthesis of 5-
substituted 1H-tetrazoles via the [3+2] cycloaddition of nitriles and
trimethylsilyl azide, Tetrahedron Lett. 49 (2008) 2824–2827.
[30] M. Wang, L. Sun, X. Fu, C. Liao, C. Yan, Synthesis and optical properties of
ZnS:Cu(II) nanoparticles, Solid State Commun. 115 (2000) 493–496.
[31] M. Ebrahimizadeh Abrishami, A. Kompany, S.M. Hosseini, N. Ghajari Bardar,
Preparing undoped and Mn-doped ZnO nanoparticles: a comparison between
sol–gel and gel-combustion methods, J. Sol–Gel. Sci. Technol. 62 (2012) 153–
159.
[32] P. Gunasekaran, S. Perumal, P. Yogeeswari, D. Sriram, A facile four-component
sequential protocol in the expedient synthesis of novel 2-aryl-5-methyl-2,3-
dihydro-1H-3-pyrazolones in water and their antitubercular evaluation, Eur. J.
Med. Chem. 46 (2011) 4530–4536.
[
[
[
[
[
[
14] Y. Satoh, N. Marcopulos, Application of 5-lithiotetrazoles in organic synthesis,
Tetrahedron Lett. 36 (1995) 1759–1762.
[33] X. Wang, Y. Wei, J. Wang, W. Guo, C. Wang, The kinetics and mechanism of
ultrasonic degradation of p-nitrophenol in aqueous solution with CCl
enhancement, Ultrason. Sonochem. 19 (2012) 32–37.
4
15] A.K. Gupta, C.H. Song, C.H. Oh, 1-(2-Iodophenyl)-1H-tetrazole as a ligand for
Pd(II) catalyzed Heck reaction, Tetrahedron Lett. 45 (2004) 4113–4116.
16] T.M. Potewar, S.A. Siddiqui, R.J. Lahoti, K.V. Srinivasan, Efficient and rapid
synthesis of 1-substituted-1H-1,2,3,4-tetrazoles in the acidic ionic liquid 1-n-
butylimidazolium tetrafluoroborate, Tetrahedron Lett. 48 (2007) 1721–1724.
17] W.-K. Su, Z. Hong, W.-G. Shan, X.-X. Zhang, A facile synthesis of 1-substituted-
[34] D. Nagargoje, P. Mandhane, S. Shingote, P. Badadhe, C. Gill, Ultrasound assisted
one pot synthesis of imidazole derivatives using diethyl bromophosphate as
an oxidant, Ultrason. Sonochem. 19 (2012) 94–96.
[35] A. Javidan, A. Ziarati, J. Safaei-Ghomi, Simultaneous sonication assistance for
[
[
[
[
the synthesis of tetrahydropyridines and its efficient catalyst ZrP
2 7
O
1
2
H-1,2,3,4-tetrazoles catalyzed by ytterbium triflate hydrate, Eur. J. Org. Chem.
006 (2006) 2723–2726.
nanoparticles, Ultrason. Sonochem. 21 (2014) 1150–1154.
[36] A. Khalafi-Nezhad, S. Mohammadi, Highly efficient synthesis of 1- and 5-
substituted 1H-tetrazoles using chitosan derived magnetic ionic liquid as a
recyclable biopolymer-supported catalyst, RSC Adv. 3 (2013) 4362–4371.
[37] S.N. Dighe, K.S. Jain, K.V. Srinivasan, A novel synthesis of 1-aryl tetrazoles
promoted by employing the synergy of the combined use of DMSO and an
ionic liquid as the solvent system at ambient temperature, Tetrahedron Lett.
50 (2009) 6139–6142.
18] D. Habibi, M. Nasrollahzadeh, T.A. Kamali, Green synthesis of the 1-substituted
H-1,2,3,4-tetrazoles by application of the natrolite zeolite as a new and
1
reusable heterogeneous catalyst, Green Chem. 13 (2011) 3499–3504.
19] D. Kundu, A. Majee, A. Hajra, Indium triflate-catalyzed one-pot synthesis of 1-
substituted-1H-1,2,3,4-tetrazoles under solvent-free conditions, Tetrahedron
Lett. 50 (2009) 2668–2670.
20] M. Muruganandham, R. Amutha, M. Sillanpää, Reagents for ZnS hierarchical
and non-hierarchical porous self-assembly, ACS Appl. Mater. Interfaces 2
(
2010) 1817–1823.