Easy single-step preparation of ZnO nano-particles by sedimentation method and studying their catalytic performance in the synthesis of 2-aminothiophenes via Gewald reaction

Article abstract of DOI:10.1016/j.molcata.2012.11.011

Zinc oxide is a multi-purpose active material with important catalytic applications. In this study, nano-sized ZnO particles were easily synthesized through sedimentation of zinc acetate di-hydrate in absolute ethanol and were characterized by XRD and SEM. The XRD results indicated pure wurtzite structure with the average particle size of 26.9 nm for the nano-particles. It was observed that size of ZnO nano-particles was decreased while solution concentration was increased. This observation would be explained considering enhancing nucleation processes of nano-particles at high concentration of zinc acetate. The prepared nano-particles (2.5 mol%) were used as catalyst for the fast and efficient synthesis of 2-aminothiophenes under solvent free conditions. The three-component mixture of a carbonyl compound, malonodinitrile, and elemental sulfur was converted into the corresponding 2-aminothiophene in moderate to high yields with excellent selectivity.

Full text of DOI:10.1016/j.molcata.2012.11.011

Journal of Molecular Catalysis A: Chemical 368–369 (2013) 16–23
Contents lists available at SciVerse ScienceDirect
Journal of Molecular Catalysis A: Chemical
journal homepage: www.elsevier.com/locate/molcata
Easy single-step preparation of ZnO nano-particles by sedimentation method and
studying their catalytic performance in the synthesis of 2-aminothiophenes via
Gewald reaction
Reza Tayebee∗, Farzad Javadi, Gholamreza Argi
Department of Chemistry, School of Sciences, Hakim Sabzevari University, Sabzevar 96179-76487, Iran
a r t i c l e i n f o
a b s t r a c t
Article history:
Zinc oxide is a multi-purpose active material with important catalytic applications. In this study, nano-
sized ZnO particles were easily synthesized through sedimentation of zinc acetate di-hydrate in absolute
ethanol and were characterized by XRD and SEM. The XRD results indicated pure wurtzite structure with
the average particle size of 26.9 nm for the nano-particles. It was observed that size of ZnO nano-particles
was decreased while solution concentration was increased. This observation would be explained consid-
ering enhancing nucleation processes of nano-particles at high concentration of zinc acetate. The prepared
nano-particles (2.5 mol%) were used as catalyst for the fast and efficient synthesis of 2-aminothiophenes
under solvent free conditions. The three-component mixture of a carbonyl compound, malonodinitrile,
and elemental sulfur was converted into the corresponding 2-aminothiophene in moderate to high yields
with excellent selectivity.
Received 8 October 2012
Received in revised form
15 November 2012
Accepted 16 November 2012
Available online 29 November 2012
Keywords:
Gewald
2-Aminothiophenes
Zinc oxide
© 2012 Elsevier B.V. All rights reserved.
Nano-particle
Catalytic
Solvent free
1. Introduction
2-Aminothiophenes have demonstrated a broad spectrum of
uses, including antibacterial, antioxidant, antifungal, antitumor,
Recently, nano-crystalline inorganic oxides exhibited enormous
opportunities and attracted the interest of several research groups,
because of their different topical characteristics and vide range
of particle sizes [1]. Zinc oxide as a non-toxic, inexpensive, and
non-hygroscopic white powder is very economical, safe, and easily
available Lewis acid catalyst, which has gained much interest in var-
ious organic transformations, sensors, piezoelectrics, transparent
conductors, and surface-acoustic-wave devices [2–8].
Zinc oxide nano-particles have very different physical and
chemical properties compared to the bulk material [5]. The induced
catalytic performance of nano-sized ZnO with reference to the com-
mercial analog in catalysis would be as a result of the increased
surface area and changes occurred in surface properties. These
nano-particles have been prepared using several physical and
chemical techniques, such as thermal decomposition, thermal
evaporation, chemical vapor deposition, sol–gel, spray pyroly-
sis, hydrothermal techniques, and precipitation methods [9–13].
Among these techniques, the well-known sol–gel route is more
routine [14].
pharmaceuticals, dyes, and agrochemical applications [15–18].
Conceptually, the simplest and the most convergent method for
the preparation of this class of compounds includes condensation
of ketones with an activated nitrile and elemental sulfur, which was
first described in 1960s by Gewald et al. [19].
A number of protocols have been announced for the synthe-
sis of substituted 2-aminothiophenes [20–24]. However, most of
these methods are generally unsuitable because they involve dif-
ficult preparation of the starting materials, multistep synthesis,
and low yields. Although, the Gewald reaction represents the
best way to the multi-component preparation of substituted 2-
aminothiophenes, however, it needs specific expensive organic
bases such as secondary or tertiary amines (diethylamine, mor-
pholine, triethylamine, pyridine, and proline) [22] in stoichiometric
amounts which produce wastes and increase production expenses
because of corrosion and environmental impacts. Moreover, polar
solvents like DMF, alcohols, and 1,4-dioxane is essential in the
Gewald method for enhancing condensation of intermediates.
Recently, we reported the catalytic role of commercial zinc
oxide in the preparation of substituted 2-aminothiophenes [23].
Now, in continuation of our ongoing research in studying effect of
particle size on catalytic activity, we carried out Gewald reaction
in the presence of nano-ZnO (2.5%) as catalyst. This methodology
was carried out in solvent-free condition at 100 ◦C (Scheme 1). The
∗
Corresponding author.
E-mail address: rtayebee@yahoo.com (R. Tayebee).
1381-1169/$ – see front matter © 2012 Elsevier B.V. All rights reserved.
http://dx.doi.org/10.1016/j.molcata.2012.11.011

R. Tayebee et al. / Journal of Molecular Catalysis A: Chemical 368–369 (2013) 16–23
17
O
2.4.2. 2-Amino-5-methylthiophene-3-carbonitrile
R1
CN
IR (KBr): 3420, 3332, 3227, 2916, 2199, 1626, 1519, 1385, 1276,
CN
CN
1106, 897, 812, 505 cm−1 1H NMR (400 MHz, CDCl3): ı6.34 (s, 1H),
;
nano ZnO(2.5 mol%)
100oC, 6h
S8
R1
4.72 (brs, 2H), 2.27 (s, 3H); 13C NMR (100 MHz, CDCl3): ı161.4,
124.4, 122.0, 115.9, 86.8, 14.8.
NH2
R2
R2
S
Scheme 1. General formulation for the synthesis of 2-aminothiophene derivatives.
2.4.3. 2-Amino-5-ethylthiophene-3-carbonitrile
IR (KBr): 3440, 3360, 3220, 2960, 2220, 1650, 1560, 1460, 1380,
1080, 840 cm−1 1H NMR (400 MHz, CDCl3): ı6.34 (s, 1H), 4.73
.
experimental procedure was remarkably simple, high yielding,
and required no toxic organic solvent or inert atmosphere.
(brs, 2H), 2.60 (q, J¼7.2 Hz, 2H), 1.20 (t, J¼7.2 Hz, 3H); 13C NMR
(100 MHz, CDCl3): ı 161.0, 132.0, 120.2, 115.9, 86.7, 23.0, 15.2.
2. Experimental
2.4.4. 2-Amino-4,5,6,7-tetrahydro-1-benzothiophene-3-
carbonitrile
2.1. Materials and methods
IR (KBr): 3440, 3340, 3200, 2910, 2840, 2200, 1650, 1640, 1520,
1320, 1120, 680 cm−1 1H NMR (250 MHz, CDCl3): ı1.78 (t, 4H,
;
Reagents and starting materials were purchased from com-
mercial resources and were used as received. ZnO nano-particles
were prepared by sedimentation method and were used as cata-
lyst in the reactions. All products were identified by comparison
of their spectral and physical data with those previously reported
[22–27]. Infrared spectra were recorded (KBr pellets) on a 8400
Shimadzu Fourier transform spectrophotometer. 1H and 13C NMR
spectra were recorded on a Bruker AVANCE instrument using TMS
as an internal reference. Data for 1H NMR are reported as chemical
shift (ı) and multiplicity (s: singlet, d: doublet, t: triplet, q: quar-
tet, m: multiplet, qt: quintuple, dq: doublet of quartets, and br:
broad). Melting points were determined in open capillary tubes
in a Stuart BI Branstead Electrothermal Cat No: IA9200 appara-
tus and uncorrected. Reaction progress was followed using thin
layer chromatography on Silufol PF254 TLC aluminum sheets. Col-
umn chromatography was carried out using Merck Kieselgel 60
(0.040–0.063 mm) with n-hexane/ethyl acetate as the eluent.
2xCH2), 4.64 (s, 2H, NH2), 2.49 (m, 4H, 2xCH2); 13C NMR (100 MHz,
CDCl3): ı22.10, 23.34, 23.72, 24.10, 88.45, 115.59, 120.50, 132.27,
160.15.
2.4.5. 2-Amino-4-phenylthiophene-3-carbonitrile
IR (KBr): 3420, 3320, 3200, 2220, 1630, 1570, 1430, 1300, 1190,
940, 768, 715 cm−1 1H NMR (400 MHz, CDCl3): ı7.60 (m, 2H), 7.44
;
(m, 2H), 7.38 (m, 1H), 6.32 (s, 1H), 5.02 (brs, 2H); 13C NMR (100 MHz,
CDCl3): ı164.1, 139.9, 134.2, 128.8, 128.2, 127.2, 116.2, 105.9, 88.0.
2.4.6. 2-Amino-4-(4-methylphenyl)thiophene-3-carbonitrile
IR (KBr): 3340, 3210, 2895, 2205, 1610, 1560, 1520, 1430, 1305,
1190, 824, 720, 475 cm−1 1H NMR (400 MHz, CDCl3): ı7.48 (d,
;
J¼8.0 Hz, 2H), 7.23 (d, J¼8.4 Hz, 2H), 6.31 (s, 1H), 4.85 (brs, 2H),
2.38 (s, 3H); 13C NMR (100 MHz, CDCl3): ı163.6, 140.0, 138.1,
131.4,129.4, 127.0, 116.0, 105.3, 88.4, 21.2.
2.4.7. 2-Amino-4-(4-nitrophenyl)thiophene-3-carbonitrile
2.2. Catalyst preparation
IR (KBr): 3320, 3450, 2200, 2930, 3200, 1660, 1730, 1130, 1320,
1520, 680 cm−1 1H NMR (400 MHz, DMSO-d6): ı8.27 (d, J¼9.1 Hz,
;
Zinc acetate di-hydrate was used for the synthesis of ZnO nano-
particles. In the first step, zinc acetate was dissolved in absolute
ethanol (0.022 M). Then, this solution was refluxed for 6 h at 80 ◦C
under stirring. Thereafter, ethanol was separated and the precip-
itate was dried at room temperature and then was calcined in a
furnace at 450 ◦C for 15 h.
2H), 7.80 (d, J¼8.9 Hz), 7.40 (s, 2H), 6.82 (s, 1H) ppm; 13C NMR
(100 MHz, DMSO-d6): ı166.2, 146.0, 140.0, 135.5, 127.3, 123.5,
115.8, 108.0, 82.0.
3. Results and discussion
3.1. Structural characterization of ZnO nano-particles
2.3. General procedure for the synthesis of 2-aminothiophenes
derivatives
Structural characterization of ZnO nano-particles was per-
formed by X-ray diffraction (XRD) and transmission and scanning
electron microscopy (TEM and SEM) [28]. Fig. 2a shows the XRD
patterns of ZnO nano-particles. The particles were highly crys-
talline, and all peaks matched well with the hexagonal structure
of ZnO. No characteristic peaks for any other phases of ZnO were
observed, therefore, the nano-particles would be formed as a pure
material.
The mean particle size was calculated for the crystallized ZnO
using the Scherrer’s equation. The crystallite size of the particles
was calculated to be about 26.9 nm. The morphology of the nano-
ZnO was also studied by SEM. Fig. 1 represents SEM and TEM
micrographs of the nano-ZnO prepared with the above method.
These findings revealed that the ZnO nano-particles were approx-
imately spherical and the mean average diameter of the particles
was calculated about 37 nm.
10 mmol of ketone or aldehyde, 10 mmol of malonodinitrile,
and 10 mmol of sulfur powder were mixed. Then, 0.02 g (2.5 mol%)
of ZnO nano-particles was added and the mixture was heated to
100 ◦C with good stirring for the required time. After 6 h, the reac-
tion was stopped and the corresponding product was worked up
by 10 ml of ethanol and ZnO was separated by a simple filtration.
Thereafter, the reaction mixture was cooled to room temperature
and poured into 150 ml of ice-water. The precipitate was filtered
off, washed with cold water and dried. To further purification, the
crude product was purified by silica gel column chromatography
with 10:1 hexane:ethyl acetate as eluent.
2.4. Spectral data of some selected compounds
2.4.1. 2-Amino-4-ethyl-5-methylthiophene-3-carbonitrile
IR (KBr): 3420, 3340, 3214, 3050, 2936, 2874, 2200, 1600, 1515,
3.2. Effect of zinc acetate concentration on the size of ZnO
nano-particles
1390,1310,1240,1160, 845, 495 cm−1 1H NMR (400 MHz, CDCl3):
;
ı4.0 (brs, 2H), 2.49 (q, J¼7.6 Hz, 2H), 2.18 (s, 3H), 1.16 (t, J¼7.6 Hz,
3H); 13C NMR (100 MHz, CDCl3): ı160.0, 136.1, 116.6, 116.0, 89.1,
20.9, 14.3, 12.1.
Different methods based on aerosol formation, micro-emulsion,
ultrasonic, sol–gel, and evaporation techniques have been reported

18
R. Tayebee et al. / Journal of Molecular Catalysis A: Chemical 368–369 (2013) 16–23
Fig. 1. SEM (a) and TEM (b) images of the prepared ZnO nano-particles.
for the preparation of ZnO nano-particles [29,30]. It is found that
concentration of the initial zinc acetate solution obviously affect
size of the ZnO nano-particles in the present precipitation method.
Fig. 2 describes XRD patterns of the prepared zinc oxides at dif-
ferent concentrations of zinc acetate in ethanol as solvent. The XRD
patterns agree well with the previously reported results [29,31].
Clearly, purity of XRD patterns and intensities of the peaks were
decreased with enhancing zinc acetate concentration. Average par-
ticle sizes of 26.9, 22.9 and 21.8 nm were calculated by using
Scherrer equation for Zn(OAc)2 concentrations of 0.022, 0.027 and
0.0303 M, respectively [32,33]. Fig. 3 shows SEM images of ZnO
nano-particles prepared under different zinc acetate concentra-
tions. Average particle sizes obtained from SEM analysis for 0.022,
0.027 and 0.0303 M solutions of zinc acetate were 37, 31 and 25 nm,
respectively.
Fig. 2. XRD patterns of ZnO nano-particles prepared in (a) 0.022 M, (b) 0.027 M, and
(c) 0.0303 M solutions of zinc acetate.
the presence of a catalytic amount of nano-ZnO under solvent free
conditions. Initially, the amount of catalyst necessary to promote
the reaction efficiently was examined. Therefore, to optimize the
reaction condition, condensation of cyclohexanone, malonodini-
trile and elemental sulfur under solvent free conditions at 100 ◦C
and after 6 h was used as a model reaction in the presence of
0–5 mol% of nano-ZnO. The obtained results are summarized in
Table 1. It was observed that yield% was increased with enhanc-
ing catalyst concentration. The yield% was increased from 34 to
77% by enhancing the catalyst amount from 0.5 to 2.5 mol%. Fur-
ther increase in the catalyst concentration from 2.5 to 5 mol%, led
to only 4% increase in yield%, 77–81%. Therefore, 2.5 mol% of the
catalyst was enough to reach the maximum conversion. Compar-
ing the above results with our previous report [23] revealed that
only 2.5 mol% of nano-sized zinc oxide have provided nearly the
same yields as obtained with 5 mol% of the commercial analog.
3.3. Effect of zinc acetate concentration on band gap energy of
the prepared ZnO nano-particles
UV–vis spectra of the obtained nano-particles are depicted in
Fig. 4. It was found that the absorption edge of the prepared nano-
particles was observed at lower wavelength compared to bulk
ZnO. Absorption edge wavelengths of 370.5, 369 and 368 nm were
observed for the prepared ZnO nano-particle in 0.022, 0.027 and
0.0303 M of ethanolic solutions, respectively. Band gap energy for
these wavelengths were 3.34, 3.36 and 3.37 eV which were greater
than the energy band gap of bulk ZnO particles.
3.5. Effect of time reaction on the three-component condensation
reaction
Table 2 shows the effect of reaction time on the yield% under the
standard reaction condition (reaction temperature 100 ◦C and cat-
alyst amount 2.5 mol%). It was observed that yield% was increased
with enlarging the reaction time. According to the obtained results,
the reaction time 6 h was selected as the suitable time for all
reactions. Comparing the results obtained with nano-ZnO with its
3.4. Studying catalytic activity of ZnO nano-particles
A simple, eco-friendly, and efficient procedure is described for
the synthesis of 2-amino-3-thiopohenecarbonitrile derivatives in

R. Tayebee et al. / Journal of Molecular Catalysis A: Chemical 368–369 (2013) 16–23
19
Fig. 3. SEM images of ZnO nano-particles prepared in (a) 0.022 M, (b) 0.027 M, and (c) 0.0303 M solutions of zinc acetate.
Fig. 4. UV–vis spectra of ZnO nano-particles prepared in different ethanolic solutions of (a) 0.022, (b) 0.027, and (c) 0.0303 M.

20
R. Tayebee et al. / Journal of Molecular Catalysis A: Chemical 368–369 (2013) 16–23
Table 1
Effect of nano-ZnO (mol%) on the condensation of cyclohexanone, malonodinitrile, and elemental sulfur.
O
CN
Nano ZnO (2.5%mol)
S8
NC
CN
NH2
°
100 C
S
Entry
Nano-ZnO (mol%)
Yield (%)
1
2
3
4
5
0
0.5
1
2.5
5
12
34
47
77
81
Reaction conditions: Cyclohexanone (10 mmol), malonodinitrile (10 mmol), and sulfur powder (10 mmol) were mixed in the presence of nano-ZnO and the reaction mixture
was heated to 100 ◦C for 6 h.
Table 2
reaction increases with enhancing carbonyl chain [34]. Moreover,
six- and seven-membered cyclic ketones such as cyclohexanone
and cycloheptanone showed higher reactivity than cyclopentanone
[22,35].
Effect of time reaction on the condensation of cyclohexanone, malonodinitrile, and
elemental sulfur.
Entry
Time (h)
Yield (%)
6
7
8
9
10
11
4
6
8
10
12
14
50
77
82
85
88
89
3.7. Studying superiority of the present protocol over some
reported catalysts
Up to now, a number of protocols have been proposed for the
synthesis of 2-amino-thiophenes under different reaction condi-
tions [20–23]. However, it seems that the present methodology
is a unique case among them, which offers an easy strategy for
one pot single step preparation of 2-amino-thiophenes under sim-
ple, aerobic, and solvent free conditions, without using expensive
strong organic Lewis bases. The superiority of the present method-
ology was studied by comparing the obtained results with those
reported previously (Table 4). Comparison was performed in terms
of catalyst mol%, reaction time, and yield%. Apparently, the present
methodology offers several advantages such as environmentally
benign nature of the catalyst, mol% of the additive, reaction condi-
tion, generality, and economical aspects of the protocol over all
reported methodologies. Comparison of the results obtained in
the presence of nano-ZnO with respect to the commercial ana-
log revealed that higher conversions (5–10%) are obtained in the
presence of fewer amount of zinc oxide as catalyst.
Reaction conditions: Cyclohexanone (10 mmol), malonodinitrile (10 mmol), sulfur
powder (10 mmol) were mixed in the presence of 2.5 mol% nano-ZnO.
commercial analog, resulted in >40% reduction in the reaction time
[23].
3.6. Synthesis of different 2-aminothiophenes catalyzed by
nano-ZnO (2.5 mol%)
To study the generality of this protocol, a range of ketones
and aldehydes were examined in the desired Gewald reaction.
Aliphatic and aromatic aldehydes and ketones bearing different
electron-withdrawing and electron-donating substituents success-
fully generated the desired products with good yields and excellent
selectivities (Table 3). It seems that efficiency of the condensation
Zn2+O2-
R2
NC
H
NC
R1
OH
CN
O2-
O2-
-O2
2+ O2-
Zn
Zn2+
H
O
CN
CN
CN
H
R1
Catalyst Surface
R2
-H+
R1 CN
NC
R1
OH
R1
H
CN
CN
-H+
S8
-H2O
R2
CN
R2
NC
S S
S
S
S
S
R2
S S
CN
CN
N
C
R1
R2
H
R1
Amino-imino
tautomerism
NH
NC
S
(s6)
s
S
S
NH2
-s7
S
S
R2
R1
R2
S
S
S
S
S
Fig. 5. Proposed mechanism for the Gewald condensation reaction.

R. Tayebee et al. / Journal of Molecular Catalysis A: Chemical 368–369 (2013) 16–23
21
Table 3
Synthesis of different 2-aminothiophenes with 2.5 mol% nano-ZnO.
Entry
Ketone or aldehyde
Product
M.P.
Yield% (this protocol)
Yield% (literature)
Reaction condition
(literature)
Ref.
CN
O
12
148–149
47
51
(A)
[20]
NH2
S
CN
O
13
104–105
56a
55
(A)
[20]
NH2
H
S
CN
O
14
15
16
17
105–106
120–121
145–146
146–147
62a
70a
49
37
75
55
86
(B)
(C)
(D)
(A)
[22]
[22]
[35]
[25]
NH2
H
S
CN
O
NH2
H
S
CN
O
NH2
S
CN
O
77
NH2
S
CN
O
18
19
128–129
136–137
67
30
86
40
(E)
(F)
[25]
[25]
NH
2
S
NC
O
NH2
S
CH3
NC
O
NH
2
20
21
142–144
120–122
50
75
42
80
(G)
(F)
[22]
[18]
S
CH
O
O N
CH
(A) Amine, 50 ◦C, in solvent, 12 h; (B) imidazole, 50 ◦C, DMF, 12 h; (C) imidazole, 60 ◦C, DMF, 10 h; (D) MW, KF-alumina, 8 min; (E) MW, KF-alumina, 6 min; (F) (1) HN(TMS)2,
HOAc, 65 ◦C, toluene, (2) S8, NaHCO3, THF, water; (G) imidazole, 60 ◦C, DMF, 15 h.
In absolute ethanol at 85 ◦C.
a

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R. Tayebee et al. / Journal of Molecular Catalysis A: Chemical 368–369 (2013) 16–23
Table 4
Comparison of the catalytic activity of nano-ZnO with some reported catalysts used for the synthesis of 2-aminothiophene derivatives.
X
X
S8
O
CN
NH2
S
X= CN, COOEt
Entry
Catalyst
Mol%
Time (h)
Yield (%)
Condition
Ref.
22
23
24
25
26
27
28
Nano-ZnO
ZnO
Imidazole
l-Proline
Morpholine
Diethylamine
KF-alumina
2.5
5
10
10
10
10
6
10
10
10
11
77
65
75
64
49
43
55
Solvent-free
Solvent-free
In DMF
In DMF
In DMF
This work
[23]
[22]
[22]
[22]
10
6 min
In DMF
MW X = COOEt
[22]
[35]
0.2 g
3.8. Proposed reaction pathway for the condensation reaction
3.9. Reusability of the catalyst nano-ZnO
A mechanistic route is suggested for the generation of 2-
aminothiophenes from the reaction of carbonyl compounds and
malononitrile in the presence of sulfur and role of nano-ZnO is
shown as the catalyst in this proposed mechanism (Fig. 5). This
mechanism involves a three-step process and nano-ZnO has dual
characters of Lewis acidic (Zn2+) in one hand and Lewis basic sites
(O2−). In the first step, Lewis acid sites of ZnO (Zn2+) coordinates
to the oxygen of the carbonyl group, hence reactivity of carbonyl
group increases. Moreover, we believe that the Lewis basic sites
of nano-ZnO (O2−) coordinates to the malononitrile and then a
nucleophilic attack to the activated carbonyl group proceeds the
reaction forward.
Although, several reviews and papers on the Gewald reaction
and its improvements have been reported in the literature [6] the
mechanism of this reaction is not fully characterized. As it is pre-
sented in Fig. 5, the substituted 2-aminothiophene ring is formed
from the aliphatic starting substrates during the multi step reac-
tion sequences of (a) condensation, (b) addition of sulfur and (c)
ring-closure. At first, the methylene group of appropriate ␣,␤-
unsaturated nitrile is being deprotonated and then sulfur addition
takes place. The ring closure step is the most crucial step which
is performed as an intra-molecular nucleophilic attack of the sul-
fur anion to triple bond of the cyano group (Fig. 5). It should be
noted that the target 2-aminothiophene in principle exists in equi-
librium with the tautomeric form of cyclic imine formed during the
cyclization. However, it is proved, that the parent aminothiophene
occurs exclusively in the amino form and it is sure that S8 has to be
activated to react with Knoevenagel–Cope product. Zinc oxide may
help this crucial step.
To study the reusability of the desired nano-catalyst, it was sep-
arated from the reaction mixture and washed with ethanol. The
catalyst was dried and activated in a vacuum oven at 150 ◦C for 4 h.
The recycled catalyst was reused for another condensation reaction
with cyclohexanone. Findings declared that the catalyst is reusable
for at least 7 cycles without considerable loss of activity (Fig. 6).
4. Conclusion
An easy and facile methodology is described for the selective
preparation of 2-aminothiophene derivatives in moderate to high
yields through condensation of different ketones and/or aldehydes
with malonodinitrile and elemental sulfur by the mediation of a
catalytic amount of nano-sized zinc oxide under solvent-free con-
dition. We found that the nano-sized zinc oxide would be prepared
under very similar conditions and revealed much better catalytic
activity than commercial analog considering reaction time, catalyst
mol%, and yield% in the Gewald reaction.
Acknowledgements
Partial financial support from the Research Council of Hakim
Sabzevari University is greatly appreciated. Special thanks to Vahid
Tayebee for English editing of the manuscript.
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