TiO2/nanoclinoptilolite as an efficient nanocatalyst in the synthesis of substituted 2-aminothiophenes

Article abstract of DOI:10.1002/aoc.3779

TiO₂/nanoclinoptilolite (TiO₂/NCP) was prepared by the mediation of hexadecyltrimethylammonium (HDTMA) as surfactant and used as an effective heterogeneous nanocatalyst for the preparation of substituted 2-aminotiophenes. The modified HDTMA/NCP was impregnated with titanium(IV) chloride solution followed by calcination at 500?°C for 20?h. The obtained nanocomposite was characterized using Fourier transform infrared spectroscopy, field emission scanning electron microscopy, inductively coupled plasma optical emission spectroscopy and X-ray diffraction. Moreover, the prepared nanocomposite had high stability and recoverability under mild and solvent-free conditions.

Full text of DOI:10.1002/aoc.3779

Received: 20 December 2016
DOI 10.1002/aoc.3779
Revised: 29 January 2017
Accepted: 2 February 2017
F U L L PA P E R
TiO /nanoclinoptilolite as an efficient nanocatalyst in the synthesis
2
of substituted 2‐aminothiophenes
1
1
2
Farzad Javadi
| Reza Tayebee | Bahram Bahramian
1
Department of Chemistry, School of
Sciences, Hakim Sabzevari University,
Sabzevar 96179‐76487, Iran
TiO /nanoclinoptilolite (TiO /NCP) was prepared by the mediation of
2
2
hexadecyltrimethylammonium (HDTMA) as surfactant and used as an effective
heterogeneous nanocatalyst for the preparation of substituted 2‐aminotiophenes.
The modified HDTMA/NCP was impregnated with titanium(IV) chloride solution
followed by calcination at 500 °C for 20 h. The obtained nanocomposite was
characterized using Fourier transform infrared spectroscopy, field emission
scanning electron microscopy, inductively coupled plasma optical emission
spectroscopy and X‐ray diffraction. Moreover, the prepared nanocomposite had
high stability and recoverability under mild and solvent‐free conditions.
2
Faculty of Chemistry, Shahrood University
of Technology, Shahrood, Iran
Correspondence
Reza Tayebee, Department of Chemistry,
School of Sciences, Hakim Sabzevari
University, Sabzevar 96179‐76487, Iran.
Email: rtayebee@hsu.ac.ir
KEYWORDS
2
2‐aminothiophenes, Gewald reaction, HDTMA, nanocomposite, TiO /NCP
1
| INTRODUCTION
recycling catalyst, long reaction times and numerous
environmental impacts provoked us to modify the Gewald
strategy by introducing a new productive, straightforward
and eco‐friendly catalytic system for the synthesis of
Expansion of new green procedures in chemical synthesis
has attracted much attention because of increasing worries
about environmental contamination. In this regard, green
solvents and heterogeneous catalysis are critical keys to the
[
9,11]
2‐aminothiophene derivatives.
Titanium dioxide (TiO ) is technically an important
2
[1]
successful development of green synthesis. Substituted
‐aminothiophenes are important starting frameworks of
numerous natural and synthetic chemicals and biologically
compound that has been widely considered. This compound
has useful features, such as low cost, commercial
2
accessibility, chemical stability, biocompatibility and non‐
[
2,3]
[13,14]
active molecules.
Moreover, 2‐aminothiophenes are
toxicity.
The productivity of TiO2 is influenced by
generally applied in industry due to their widespread
applications in modern drug design, dye chemistry,
agriculture, pharmaceuticals, antioxidants, antibacterial
numerous factors, such as crystalline structure, particle size,
specific surface area, porosity and preparation strate-
[
15,16]
gies.
Nonetheless, its practical applications in aqueous
[4–7]
agents and electronic and optoelectronic devices.
media are confined, because of the troublesome filtration
[
17]
The Gewald reaction is one of the most prevalent,
facile and flexible methodologies for the syntheses of
and recovery of ultrafine TiO particles.
Strong tendency
2
for accumulation and agglomeration leads to a decrease in
the active surface area of the catalyst and reduction or even
[
4,8–10]
2‐aminothiophenes.
This reaction incorporates a
[
16–18]
three‐component condensation reaction of ketone and/or
aldehyde with an α‐methylene moiety, sulfur and an activated
nitrile in organic solvents such as methanol, ethanol and
complete loss of catalytic activity.
In order to overcome
this problem, immobilization of TiO2 nanoparticles on
various supports such as zeolite, fibreglass, silica and clay
[
17,19–21]
1
,4‐dioxane in the presence of a strong organic base such as
is recommended.
Furthermore, these endeavours
[4,10–12]
diethylamine and morpholine as catalyst.
However,
can also improve the surface area by distributing the
the established reported protocols based on the use of
expensive catalysts and poisonous solvents, the trouble of
nanoparticles of TiO onto the surface of solid support
2
[
15]
materials.
Among the various supports, zeolites are
Appl Organometal Chem. 2017;e3779.
wileyonlinelibrary.com/journal/aoc
Copyright © 2017 John Wiley & Sons, Ltd.
1 of 11
https://doi.org/10.1002/aoc.3779

2
of 11
JAVADI ET AL.
favourable candidates for the support of TiO2 particles,
because of their extraordinary structures, uniform pores
and channels, high ion exchange capacity and excellent
NCP, a planetary ball mill in the dry state was applied.
Planetary ball milling was performed in dry conditions for
60 min, with 10 balls of 20 mm per 30 g of powder and
a milling speed of 350 rpm. The examinations were
performed in a 250 ml stainless steel jar with a protective
jacket of zirconium oxide. Zirconium oxide balls were
utilized for dry milling. In the majority of the experiments
a CP powder with average particle size of 75 μm was used
[
17,22,23]
adsorption ability.
Clinoptilolite, with the general formula Na [(AlO )
6
2 6
(
SiO ) ]⋅24H O, is the most plentiful and beneficial zeolite
2
30
2
[
24]
in nature which belongs to the class of aluminosilicates.
It has a monoclinic structure comprising a ten‐membered
and two eight‐membered rings with water molecules and
replaceable metal cations in the internal crystalline cages.
Clinoptilolite with extensive surface area and numerous
active sites has been utilized as a molecular sieve, nutriment
and food additive, odour and gas adsorbent, and as catalyst
[
34]
as the starting material.
All products were known
samples and were recognized by comparison of their
[
4,11,12]
spectral and physical data with those reported.
Melting points were recorded with a Bumstead electrother-
mal type 9200 melting point apparatus. X‐ray diffraction
(XRD) patterns were acquired using an Xpert MPD diffrac-
[25–27]
in a variety of organic transformations.
Recently, zeo-
lites modified with transition metal ions have received wide
consideration as favourable catalysts for various important
organic reactions.
tometer with Cu K radiation at 40 keV and 30 mA. The
α
−1
scanning rate was set to 3° min in the 2θ range from 5°
to 80°. The morphology and distribution of particles were
studied using scanning electron microscopy (SEM) and
field emission SEM (FESEM) with a KYKY‐EM3200 with
an accelerating voltage of 26 kV and a Hitachi S‐4160,
respectively. Fourier transform Infrared (FT‐IR) spectra
were recorded (KBr pellets) with a Shimadzu 8400 FT‐IR
spectrophotometer. A freeze dryer (model FD‐10, Pishtaz
Equipment Engineering Co., Iran) was used for drying the
prepared nanocomposite. Titanium content in the nanocom-
posite was determined using inductivity coupled plasma
optical emission spectroscopy (ICP‐OES) with a Varial
Australia, model Vista‐pro.
[
28]
Manufacturing of metal oxide‐loaded zeolitic systems is
known as a typical procedure but frequently with little
loading (<10%) of metal oxide in the pores or on the
[29,30]
surface of the zeolite structure.
In the present work,
an easily altered methodology is introduced to improve
loading of TiO2 on the surface of nanoclinoptilolite
(NCP) nanoparticles via a preliminary modification of
NCP with hexadecyltrimethylammonium (HDTMA) before
addition of titanium tetrachloride solution. Up to now,
metal oxide/NCP composites have been limitedly employed
as photocatalysts to degrade or eliminate toxic metal
[27,31–33]
ions and other toxins from wastewaters,
but there
are no reports of the use of TiO /NCP nanocomposite as
2
a catalyst for the preparation of organic compounds.
2
.2 | Preparation of TiO /NCP nanocomposite
2
The productivity of the newly prepared TiO /NCP
2
using HDTMA as surfactant
nanocomposite is evaluated as a useful, low‐cost and
recyclable nanocatalyst for the synthesis of substituted
TiO /NCP nanocomposite was obtained through the in situ
2
2
‐aminothiophenes under solvent‐free conditions at 100 °C
synthesis of TiO2 nanoparticles immobilized on the
surface of NCP. Accordingly, TiCl4 (0.5 M) solution
prepared in 30 ml of deionized water was mixed for
(Scheme 1).
3
0 min. Sodium hydroxide solution (2 M) was added
2
| EXPERIMENTAL
.1 | Materials
dropwise to the obtained solution to pH = 12. At the
same time, NCP (1 g) was homogeneously dispersed in
10 ml of HDTMA (0.1 M) solution and mixed at 75 °C
for 24 h to afford HDTMA/NCP. Afterward, the aqueous
mixture of titanium tetrachloride and sodium hydroxide
solution was added dropwise to the suspension of
HDTMA/NCP with continuous stirring at 75 °C and the
final mixture was permitted to react for 24 h. The
subsequent precipitate was isolated by filtration, washed
a few times with deionized water, and dried at 50 °C
for 3 days in an oven. Finally, the accumulated solid
product was calcined at 500 °C in a furnace for 20 h to
2
All reagents and starting materials were provided by Merck
and Fluka and were applied without further purification.
Natural clinoptilolite‐rich tuffs (CP) were obtained from
Sabzevar region in northeast Iran. For the preparation of
achieve TiO /NCP nanocomposite. A schematic of the
2
SCHEME
1
General formulation for the synthesis of 2‐
preparation of TiO /NCP using HDTMA surfactant is
2
aminothiophene derivatives
shown in Figure S1 (supporting information).

JAVADI ET AL.
3 of 11
2
.3 | Preparation of TiO /NCP nanocomposite
2.6 | Determination of micro‐strain and
2
without use of HDTMA
crystallite size using XRD
In this strategy, to prepare TiO /NCP nanocomposite, Ti/
An ideal crystal would expand immeasurably in all direc-
tions; therefore, no crystals are perfect due to their finite
size. This deviation from perfect crystallinity leads to a
broadening of the diffraction peaks. The crystallite size and
lattice strain are two principal properties that can be
extracted from peak width analysis and influence the Bragg
peak in different ways which increase the peak width and
2
NCP was initially obtained by adding 1 g of NCP into a
4+
polyethylene bottle containing 30 ml of 0.5 M Ti (as
chloride salt) aqueous solution and the suspension was
agitated at 75 °C for 24 h. Then, Ti/NCP nanoparticles were
filtered, washed thoroughly with deionized water and dried at
50 °C for 3 days in an oven. The obtained solid product was
[
36]
calcined at 500 °C in a furnace for 20 h to form TiO /NCP
intensity, and shift the 2θ peak position accordingly.
2
nanocomposite.
Micro‐strain and particle size of TiO2(32%)/NCP nanocom-
posite were determined using Scherrer and Williamson–Hall
equations as follows.
2
.4 | General method for syntheses of
2.6.1 | Debye–Scherrer method
substituted 2‐Aminothiophenes
The particle size of the prepared TiO2(32%)/NCP nanocom-
posite was computed using the X‐ray line broadening method
with the Debye–Scherrer equation:
Amounts of 5 mmol of ketone or aldehyde, 5 mmol of
malononitrile and 0.03 g of TiO /NCP nanocomposite were
2
stirred. Then, 5 mmol of sulfur powder was added and the
mixture was heated to 100 °C under stirring for the required
time. After completion, the reaction was worked up with 5 ml
of ethanol and the nanocatalyst was separated by simple
filtration. Afterwards, the reaction was cooled to room
temperature and poured into 50 ml of ice–water. The
precipitate was filtered off, washed with cold water and dried.
For further purification, the crude product was refined using
silica gel column chromatography with hexane–ethyl acetate
0
:94λ
D ¼
(1)
βD cosθ
where D is the particle size in nanometres, λ is the wave-
length of the radiation (1.54056 Å for Cu K radiation), θ is
the peak position and β is the peak width at half‐maximum
α
D
[
36]
intensity.
(10:1) as an eluent.
2.6.2 | Williamson–hall method
The Williamson–Hall method is a simplified integral breadth
2
.5 | Characterization and properties of NCP
method for deconvoluting size and strain contributions to line
[
36]
and TiO /NCP nanocomposite
2
broadening as a function of 2θ.
Broadening originating
from crystal imperfection and distortion is given by
The quantity of titanium in the TiO /NCP nanocomposite
2
was measured using ICP‐OES. For this purpose, 5 ml of
βs
HNO was added to an accurately known amount of the
3
εs ¼
(2)
tanθ
nanocomposite in a polyethylene beaker and heated at 150 °C
for 15 min. Then, 5 ml of HF was added and the mixture was
heated at 150 °C to destroy the zeolitic framework.
From equations 1 and 2, it is proved that the peak width
from crystallite size varies as 1/cos θ, whereas strain varies
as tan θ. The Williamson–Hall method is suitable for
calculating the crystallite size and the strain. Thus, the
Subsequently, 5 ml of HClO was added to the mixture and
4
heated at 150 °C for 15 min. Finally, 5 ml of diluted HCl
was added and the mixture was heated as described above.
The solution obtained was filtered and diluted in a 250 ml
volumetric flask and used for the determination of titanium.
The contents of TiO in TiO /NCP produced using HDTMA
strain‐induced line broadening β is given by
s
2
2
βs ¼ 4εs tanθ
(3)
(4)
and TiO /NCP produced without HDTMA were 32 and 27%,
2
respectively, determined using ICP‐OES analysis. This
observation obviously showed that TiO content in TiO /
2
2
βhkl ¼ β þ βs
D
NCP was somewhat enhanced in the presence of HDTMA
modifier. This finding could probably be explained by con-
sidering enhanced interactions of HDTMA with the anionic
0:94λ
βhkl
¼
þ 4εs tanθ
D cosθ
(5)
[
35]
precursor.

4
of 11
JAVADI ET AL.
1
Rearranging equation 6 gives
400–1200 cm− and (iv) bands associated with lattice
−1 [35,38]
vibrations appearing at <400 cm .
In the spectrum of
NCP a quite wide band at about 1070 cm− relating to the
asymmetric stretching vibrations of ─Si─O─Si─ is observed
which overlaps with the stretching vibrations of Al─O─Si
1
0
:94λ
D
βhkl cosθ ¼
þ 4εs sinθ
(6)
[
24]
According to the Williamson–Hall method, the individual
contribution to the broadening of reflection can be expressed
as equation 6. Wherein, βhkl is the FWHM of the Bragg peaks
in radians), λ is the wavelength of the X‐rays (0.154056 nm
and Al─O bonds.
The bands observed at 1629 and
3614 cm− are related to the OH stretching vibrations of
water molecules in the NCP framework. As seen in the spec-
tra of HDTMA/NCP and Ti/HDTMA/NCP, two new bands
appear, which are due to the HDTMA along with the C─H
stretching vibrations of the hydrocarbon chains around
1
(
for Cu K ), θ is the Bragg angle of the analysed peak, D is the
α
[37]
average crystallite size and ε is the strain.
s
−
1
2
858 and 2923 cm . Breck affirmed that transition metal
cations entering into the zeolitic structures during the ion
exchange process or by forming their oxides during
calcination process causes slight shifts in the position of the
absorption bands, especially for the bands on the right side
of the Si(Al)─O band, which indicates high stability of the
3
| RESULTS AND DISCUSSION
.1 | FT‐IR investigations
3
NCP, HDTMA/NCP, Ti/HDTMA/NCP, TiO2(32%)/NCP and
TiO2(27%)/NCP were characterized using FT‐IR spectroscopy,
and the corresponding spectra are shown in Figure 1. In
general, in the FT‐IR spectrum of zeolitic structure,
obviously four bands are observed: (i) bands related to the
zeolitic water situated in the range 1600–3700 cm , (ii)
bands due to the pseudo‐lattice vibrations of structural units
[
38]
original NCP structure.
Our findings are in good agree-
ment with Breck's results, confirming adequate loading of
TiO into the surface or channels of NCP structure. Based
2
on the FT‐IR spectral analysis, it is concluded that during
−
1
the synthesis process, a certain amount of TiO reacts with
2
the surface ─OH groups of the raw zeolite and creates new
bonds like Ti─O─Si and Ti─O─Al. Thus, the torsions of
Ti─O─ are confined by the solid surface bonding and the
energy of the torsion vibration of such bonds becomes
−
1
observed in the range 500–700 cm , (iii) bands correspond-
ing to the internal Si─O(Si) and Si─O(Al) bonds in the range
[
39]
weaker.
It seems that the peaks of TiO nanoparticles are
2
weak in TiO /NCP due to the limited ion exchange capacity
2
of nanozeolite to accept titanium cations. Accordingly, they
overlap with peaks corresponding to the vibration modes of
[
35]
NCP in these locations.
3.2 | XRD analysis
The XRD patterns of the prepared NCP and TiO2(32%)/NCP
nanocomposite are shown in Figure 2. The parent
clinoptilolite shows a pattern similar to that of the crystalline
structure, which has been reported in the X‐ray data file
[
40]
(JCPDS no. 39–1383),
proving that the utilized zeolite
has a principal zeolite clinoptilolite structure as the
significant phase. This pattern demonstrates a strong and
major diffraction peak at a 2θ value of 22.5°, relating to the
d004 reflection and the crystalline structure of NCP is
[
34]
identified.
(32%)/NCP, new diffraction peaks at 2θ values from 25° to
0° belong to TiO nanoparticles.
It seems that, in the XRD pattern of TiO2
[
41]
7
Moreover, changes of
2
peak intensities for NCP in the pattern of the nanocomposite
can be related to the immobilization of TiO on the surface of
2
[
41]
NCP.
It is established that when metal oxides are situated
in the channels of zeolite or mesoporous materials, the corre-
sponding diffraction peaks nearly become invisible, due to
[
35,42,43]
FIGURE 1 FT‐IR spectra of NCP, HDTMA/NCP, Ti/HDTMA/NCP,
the shielding effects of the surrounding matrix.
Thus,
TiO2(27%)/NCP and TiO2(32%)/NCP
the good diffraction peaks of TiO in the pattern of TiO2(32%)/
2

JAVADI ET AL.
5 of 11
FIGURE 2 XRD patterns of (a) NCP and
(
B) TiO2(32%)/NCP (b). Pattern (a) is
[
34]
reproduced from Tayebee et al.
NCP nanocomposite indicate that the greater amount of the
TiO nanoparticles are immobilized on the outer surface of
2
the NCP structure. The similarity of XRD patterns of raw
NCP and the TiO2(32%)/NCP nanocomposite proves that the
structure of NCP remains intact during the ion exchange
[44]
and calcination processes.
3
.2.1 | Determination of crystallite size and
micro‐strain of TiO /NCP
2
FIGURE 3 Williamson–hall plot for TiO2(32%)/NCP nanocomposite
The average crystallite size of TiO2(32%)/NCP nanocomposite
was determined as 45.6 nm using Scherrer's equation. But,
the reflection broadening in the XRD pattern is ascribed to
the contributions of micro‐strain, crystallite size and the
3
.3 | SEM and FESEM investigations
The morphology and particle sizes of raw NCP and TiO
2
[
45]
instrument itself.
Thus, to remove these contributions,
(32%)/NCP were studied using SEM as depicted in Figure 4.
Although the ball milling procedure reduces the zeolite crys-
tallinity, the applied optimized conditions lead to the produc-
tion of NCP with favourable crystalline structure. The
monoclinic crystallites of NCP demonstrate ‘elliptical‐like’
particles which confirms the alteration of the layered struc-
ture of the bulk CP particles during the ball‐milling pro-
the particle sizes were analysed using the Williamson–Hall
equation as described in Section 1.6.2. All reflection peaks
in the pattern of TiO2(32%)/NCP nanocomposite within the
2θ range 24–68° were used to construct a linear plot of βcos
θ versus 4sin θ, as shown in Figure 3. Strain and particle
sizes were obtained from the slope and y‐intercept of the
fitted line, respectively. The estimated values of the strain
[
34]
cess.
According to the SEM image of NCP (Figure 4a),
and the crystallite sizes of the TiO /NCP nanocomposite
homogenous individual particles and agglomerates have
dimensions close to the nanometric range. Comparing
SEM image of NCP (Figure 4a) with FESEM images of
TiO2(32%)/NCP (Figure 4b–d) confirms that immobilization
2
are 7.50 × 10− and 63 nm, respectively. From Figure 3, it
seems that the Williamson–Hall equation is a suitable
approach for the computation of lattice strain because of less
scatter of data points from the linear fit. The good fit of the
experimental data points indicates the uniformity of the
3
of TiO nanoparticles on the surface of NCP successfully
2
occurs. According to the FESEM images of the prepared
nanocomposite, it seems that the pores of NCP are blocked
[
46]
lattice strain.

6
of 11
JAVADI ET AL.
by fine TiO particles and the porosity of the prepared nano-
2
[
35,47]
composite is reduced.
Also, these images show that the
dimension of NCP particles remains unchanged after treating
with TiO nanoparticles. The major particles have dimen-
2
sions in the range 43 to 62 nm. Results obtained from
XRD and SEM studies establish that the chosen method
for the preparation of the nanocomposite is acceptable.
3
.4 | Catalytic performance of TiO /NCP
2
nanocomposite in synthesis of substituted 2‐
Aminothiophenes
A straightforward, productive and environmentally friendly
strategy was achieved for the synthesis of substituted
2‐aminothiopohenes trough the Gewald reaction in the pres-
ence of a catalytic amount of TiO /NCP under solvent‐free
2
conditions. At first, the catalytic activity of TiO2(32%)/NCP
and TiO2(27%)/NCP for the synthesis of 2‐amino‐4,5,6,7‐
tetrahydro‐1‐benzothiophene‐3‐carbonitrile was compared
using the multi‐component condensation of cyclohexanone,
malononitrile and S under solvent‐free conditions at 100 °
8
C. The obtained results indicate higher yield (90%) with
TiO2(32%)/NCP than with TiO2(27%)/NCP (60%) under similar
conditions. Consequently, TiO2(32%)/NCP was chosen as a
more active nanocatalyst compared with TiO2(27%)/NCP for
the synthesis of substituted 2‐aminothiophenes. Initially, the
optimum quantity of the nanocatalyst was determined.
3
.4.1 | Influence of catalyst concentration on
three‐component reaction
In order to determine the optimum amount of nanocatalyst,
the condensation of cyclohexanone, malononitrile and S in
8
the presence of 0–0.1 g of TiO2(32%)/NCP was selected as a
model reaction to evaluate the catalyst activity in the
synthesis of 2‐amino‐4,5,6,7‐tetrahydro‐1‐benzothiophene‐
3‐carbonitrile (Figure S2, supporting information). Results
show that only a trace amount of the desired product is
obtained in the catalyst‐free condition after 2 h; while, in
the presence of 0.01 g of the nanocatalyst, the yield is
increased from 2 to 50%. The enhanced quantity of the
nanocatalyst improves the yield on account of the increase
in the number of active sites, and furthermore, the improved
contact opportunity between the nanocomposite surface with
the molecules of the starting material. However, further
enhancement in the catalyst quantity from 0.03 to 0.1 g leads
to a decrease in yield, from 90 to 77%. This result can be
explained considering agglomeration of the nanocatalyst
active sites with increasing catalyst dosage, resulting in a
decrease in concentration of the starting material molecules
at the active sites and a decrease in yield. Therefore, 0.03 g
of the catalyst is sufficient to achieve maximum conversion.
FIGURE 4 (a) SEM images of raw NCP. (b–d) FESEM images of
TiO2(32%)/NCP

JAVADI ET AL.
7 of 11
3
.4.2 | Catalytic efficiency of the nanocom-
posite ingredients
The catalytic efficiency of TiO2(27%)/NCP and TiO2(32%)
/
NCP with NCP, bulk TiO , HDTMA, HDTMA/NCP and
2
Ti‐HDTMA/NCP in the syntheses of 2‐amino‐4,5,6,7‐
tetrahydro‐1‐benzothiophene‐3‐carbonitrile was studied
under the optimum reaction conditions. The obtained results
are summarized in Table 1. As indicated, 0.03 g of NCP and
bulk TiO lead to 7 and 15% of product, individually, after
2
2
h (entries 1 and 2). However, HDTMA surfactant is solely
ineffective (entry 4). Modified zeolite (HDTMA/NCP)
demonstrates moderate efficiency and results in 18% yield.
Albeit, the components of the nanocomposite material
provide some level of catalytic efficiency, TiO2(32%)/NCP
give the best result in the three‐component condensation
FIGURE 5 Influence of reaction time on yield of the reaction of
cyclohexanone, malononitrile and S
TiO2(32%)/NCP
8
in the presence of 0.03 g of
provide the expected products with acceptable yields
Table 2). Due to the low boiling point of butyraldehyde,
reaction (entry 8). Obviously, by improving TiO dosage on
2
(
the external surface of NCP, its catalytic performance is
improved towards the condensation reaction.
propionaldehyde and acetaldehyde, reactions were conducted
in absolute ethanol under reflux. The results obtained show
that productivity of the condensation reaction is improved
with increasing carbonyl chain length. Furthermore, six‐
and seven‐membered cyclic ketones, such as cycloheptanone
and cyclohexanone, give higher yields than cyclopentanone
under similar conditions. The obtained results are in good
3
.4.3 | Influence of reaction time on conden-
sation reaction
The impact of reaction time on the reaction of cyclohexa-
[
11]
none, malononitrile and S in the presence of 0.03 g of
8
agreement with reported findings.
TiO2(32%)/NCP was investigated at 100 °C (Figure 5). The
results obtained show that yield is enhanced with increasing
reaction time up to 120 min. Thus, a reaction time of 2 h
was chosen as the optimum time for all reactions.
3
.5 | Comparison of catalytic performance of
TiO /NCP with other catalysts
2(32%)
Some methods have been introduced for the preparation of 2‐
[
8,12]
aminothiophenes under various reaction conditions.
3
.4.4 | Preparation of substituted 2‐
Anyway, it seems that the present method is valuable and
suggests a simple procedure for the preparation of substituted
2‐aminothiophenes without expensive strong organic Lewis
bases and harmful solvents. To show the value of the present
work, in comparison with results reported in the literature, we
compared the results for TiO2(32%)/NCP nanocomposite with
aminothiophenes catalysed by TiO2(32%)/NCP
To investigate the generality and scope of the present
protocol, a range of linear aldehydes and linear and cyclic
ketones were examined in the Gewald reaction. In all cases,
aliphatic aldehydes along with aromatic ketones effectively
TABLE 1 Catalytic performance of ingredients comprising the nanocatalyst in syntheses of 2‐amino‐4,5,6,7‐tetrahydro‐1‐benzothiophene‐3‐
a
carbonitrile
Entry
Catalyst
NCP
Bulk TiO
Catalyst amount (g)
Time (h)
Yield (%)
1
2
3
4
5
6
7
8
0.03
0.03
0.03
0.03
0.03
0.03
0.03
0.03
2
2
2
2
2
2
2
2
7
15
50
0
2
Nano TiO
HDTMA
2
HDTMA/NCP
Ti‐HDTMA/NCP
TiO2(27%)/NCP
TiO2(32%)/NCP
18
77
61
90
a
Reaction conditions: cyclohexanone (5 mmol), malononitrile (5 mmol) and S
for 2 h.
8
(5 mmol) were stirred in the presence of each catalyst and the reaction was heated to 100 °C

8
of 11
JAVADI ET AL.
TABLE 2 Preparation of substituted 2‐aminothiophenes catalysed by TiO2(32%)/NCP under optimum conditions
M.P. (°C)
Ketone/
Ref.
Entry
aldehyde
Product
Yield (%)
Found
Reported
[48]
1
75
143–145
147–148
[
7]
2
3
90
80
146–147
127–130
147
125
[2]
a
[49]
[11]
4
5
45
104–106
104–106
102
a
52
105–106
a
[11]
6
7
8
60
120–123
147–150
132–135
120–121
153
[
[
49]
11]
40
27
136–137
a
In absolute ethanol.
those for other catalyst in the synthesis of 2‐amino‐4,5,6,7‐
tetrahydro‐1‐benzothiophene‐3‐carbonitrile. The obtained
results with respect to the reaction time, temperature and
yield of products are summarized in Table 3. Clearly, the
present procedure offers a few merits such as short reaction
time, easy workup, eco‐friendly nature, low cost of the
nanocatalyst and economic protocol over the other reported
methods.
3.6 | E‐factor
Sheldon introduced the idea of the E‐factor to measure the
value of the environmental impact of chemical pro-
[
54,55]
cesses.
The E‐factor is the actual amount of waste
created in a process, defined as the weight of waste generated
per weight of product and waste and is defined as everything
except for the desired product. It takes into account the
TABLE 3 Comparison of catalytic efficiency of TiO2(32%)/NCP with that of other reported catalysts in preparation of 2‐amino‐4,5,6,7‐tetrahydro‐1‐
benzothiophene‐3‐carbonitrile
Entry
Catalyst
Time (h)
Temp. (°C)
Yield (%)
Condition
E‐factor (g)
Ref.
1
2
3
4
5
6
7
8
9
TiO2(32%)/NCP
ZnO34%/NCP
2
4
100
100
100
100
100
60
90
76
74
65
70
91
91
91
89
Solvent‐free
Solvent‐free
Solvent‐free
Solvent‐free
Solvent‐free
In ethanol
5.16
6.30
6.52
7.60
6.95
17.04
49
This work
[
[
[
[
[
[
[
[
35]
9]
Bulk TiO
2
10
10
6
9]
Bulk ZnO
Nano ZnO
11]
50]
51]
52]
53]
MgO/Al
NaAlO
KF/Al
Cs CO
2
O
3
8
2
10
3.5
2.20
60
In ethanol
2
O
3
78
In ethanol
15.84
99
2
3
78
In ethanol

JAVADI ET AL.
9 of 11
chemical yield and includes reagents, solvent losses and even
fuel. There is one exception: water is generally excluded from
3.8 | Plausible reaction pathway for
condensation reaction
[56]
the calculation of the E‐factor.
Sheldon reported that a
As far as we know, several papers have reported the synthesis
higher E‐factor implies more waste and, consequently, more
negative environmental impact. The perfect E‐factor is
of 2‐aminothiophenes by the Gewald reaction, but the
[
8,10]
[
57]
reaction mechanism is not fully clear.
Based on these
zero.
In this work, we also measured the E‐factor of our
observations, a mechanism pathway (Figure S3, supporting
information) can be proposed. First, α,β‐unsaturated nitrile
intermediate is formed via a Knoevenagel condensation. In
the next step, elemental sulfur reacts with the intermediate
compound formed in the first step to complete the cycliza-
tion. Based on the literature, the ring closure step is the most
crucial in this mechanism that occurs by an intramolecular
procedure to demonstrate that this method reduces environ-
mental impacts. For this goal, data involved in the E‐factor
calculation, such as number of reactants and volume of
solvents used in the workup, were considered. The E‐factor
for the condensation of cyclohexanone (5 mmol),
malononitrile (5 mmol) and sulfur powder (5 mmol) in the
presence of TiO /NCP was calculated from the equation
2
−
nucleophilic attack of S to the cyano carbon to deliver the
described by Sheldon as follows:
final intermediate. Finally, an aromatization rearrangement
affords the desired 2‐aminothiophene. Dual catalytic roles
are suggested for the prepared nanocomposite in this
E‐factor
= [0.49 g (cyclohexanone) + 0.33 g
(
(
malononitrile) + 0.16 g (sulfur) + 3.95 g (ethanol) − 0.80 g
product)]/0.80 g (product) = 5.16 g.
pathway. Firstly, TiO , on the surface of NCP, would activate
2
To investigate the merits and efficiency of our catalyst,
the carbonyl group by linking to the oxygen atom and
from the green chemistry point of view, with respect to
reported catalysts for the synthesis of 2‐amino‐4,5,6,7‐
tetrahydro‐1‐benzothiophene‐3‐carbonitrile, E‐factor values
for some catalysts are presented in Table 3. The results show
that a lower E‐factor is obtained with TiO2(32%)/NCP as a
catalyst.
[
11]
increasing the activity of the carbonyl group.
Secondly,
2−
the Lewis basic sites of the nanocomposite (O ) would
activate malononitrile by deprotonation; then, the
nucleophilic attack to the activated carbonyl group pushes
the reaction forward.
3
.7 | Reusability of TiO /NCP Nanocatalyst
2
4
| CONCLUSIONS
A key variable for considering potential utility and practical
application of a solid catalyst is its capacity to be recycled.
In order to investigate the reusability of the intended
nanocatalyst, hot ethanol was added to the reaction mixture
and afterwards the nanocatalyst was separated by simple
filtration and washed with hot ethanol. The nanocatalyst
was dried and activated in a vacuum oven at 100 °C for
In this work, an environmentally friendly strategy for the
Gewald transformation is presented without the mediation
of organic solvent. This study established that the nanocom-
posite prepared with the inclusion of HDTMA surfactant
has a greater content of TiO nanoparticles in the surface
2
or pores of NCP than the nanocomposite prepared without
the mediation of HDTMA. Additionally, the results showed
that the catalytic efficiency of the nanocomposite was
10 h. The recovered catalyst was reused for another
condensation reaction with cyclohexanone, malononitrile
and S under the optimum conditions. The obtained results
improved with increasing content of TiO onto NCP in
2
8
show that the nanocatalyst is reusable for at least four cycles
without considerable loss of activity; nonetheless, the yield is
decreased by ca 10% after the fifth cycle (Figure 6).
the syntheses of substituted 2‐aminothiophenes. Further-
more, this method offers the benefits of high yield, easy
work‐up, short reaction time, recoverability of catalyst,
inexpensive catalyst, low E‐factor and green reaction
conditions without formation of any by‐products. To study
the effect of drying conditions on the catalytic performance
of the nanocomposite, the freeze‐drying technique was
compared with the usual classic drying. Results showed
no measurable improvements in the catalytic efficiency of
the prepared nanocomposite obtained under the freeze‐drying
conditions.
ACKNOWLEDGEMENTS
FIGURE 6 Reusability of the nanocatalyst: yield as a function of
number of reaction cycles
Partial financial support from the Research Council of Hakim
Sabzevari University is greatly appreciated.

1
0 of 11
JAVADI ET AL.
REFERENCES
[28] M. Dalconi, A. Alberti, G. Cruciani, P. Ciambelli, E. Fonda,
Microporous Mesoporous Mater. 2003, 62, 191.
[1] S. M. George, Chem. Rev. 1995, 95, 475.
[
[
[
[
[
[
[
[
29] J. Hrenovic, J. Milenkovic, N. Daneu, R. M. Kepcija, N. Rajic,
[2] M. M. Mojtahedi, M. S. Abaee, P. Mahmoodi, M. Adib, Synth.
Commun. 2010, 40, 2067.
Chemosphere 2012, 88, 1103.
30] A. Nezamzadeh‐Ejhieh, M. Amiri, Powder Technol. 2013,
[
[
[
[
[
[
[
3] K. Koike, Z. Jia, T. Nikaido, Y. Liu, Y. Zhao, D. Guo, Org. Lett.
2
35, 279.
1
999, 1, 197.
4] M. Feroci, I. Chiarotto, L. Rossi, A. Inesi, Adv. Synth. Catal. 2008,
50, 2740.
31] M. Bahrami, A. Nezamzadeh‐Ejhieh, Mater. Sci. Semicond.
Process. 2014, 27, 833.
3
32] E. Sanatgar‐Delshade, A. Habibi‐Yangjeh, M. Khodadadi‐
Moghaddam, Monatsh. Chem. 2011, 142, 119.
5] S. Gobbi, A. Rampa, A. Bisi, F. Belluti, L. Piazzi, P. Valenti, A.
Caputo, A. Zampiron, M. Carrara, J. Med. Chem. 2003, 46, 3662.
33] H. Faghihian, S. Naeemi, Iran. J. Chem. Chem. Eng. 2013,
6] D. M. Barnes, A. R. Haight, T. Hameury, M. A. McLaughlin, J.
Mei, J. S. Tedrow, J. D. R. Toma, Tetrahedron 2006, 62, 11311.
3
2, 9.
34] R. Tayebee, M. Jarrahi, B. Maleki, M. K. Razi, Z. Mokhtari, S.
7] F. Moeinpour, N. Dorostkar, M. Vafaei, Synth. Commun. 2012,
Baghbanian, RSC Adv. 2015, 5, 10869.
4
2, 2367.
8] R. Sabnis, D. Rangnekar, N. Sonawane, J. Heterocycl. Chem. 1999,
6, 333.
35] F. Javadi, R. Tayebee, Microporous Mesoporous Mater. 2016,
2
31, 100.
3
36] A. K. Zak, W. A. Majid, M. E. Abrishami, R. Yousefi, Solid State
Sci. 2011, 13, 251.
9] R. Tayebee, S. J. Ahmadi, E. Rezaei Seresht, F. Javadi, M. A.
Yasemi, M. Hosseinpour, B. Maleki, Ind. Eng. Chem. Res. 2012,
[
[
37] G. Williamson, W. Hall, Acta Metall. 1953, 1, 22.
5
1, 14577.
38] D. W. Breck, Zeolite Molecular Sieves: Structure, Chemistry and
Use, Wiley, New York 1974 636.
[
[
[
10] Z. Puterová, A. Krutošíková, D. Végh, ARKIVOC 2010, 1, 209.
11] R. Tayebee, F. Javadi, G. Argi, J. Mol. Catal. A 2013, 368, 16.
[
[
[
39] B. Jaleh, M. S. Madad, M. F. Tabrizi, S. Habibi, R. Golbedaghi, M.
12] X.‐G. Huang, J. Liu, J. Ren, T. Wang, W. Chen, B.‐B. Zeng,
Tetrahedron 2011, 67, 6202.
Keymanesh, J. Iran. Chem. Soc. 2011, 8, 161.
40] M. M. Treacy, J. B. Higgins, Collection of Simulated XRD Powder
Patterns for Zeolites, 5th revised ed., Elsevier Science 2007.
[13] V. Vaiano, O. Sacco, D. Sannino, P. Ciambelli, Appl Catal B 2015,
1
70, 153.
41] H. Zabihi‐Mobarakeh, A. Nezamzadeh‐Ejhieh, J. Ind. Eng. Chem.
2015, 26, 315.
[
[
[
14] V. Gurylev, C.‐Y. Su, T.‐P. Perng, J. Catal. 2015, 330, 177.
15] E. Amereh, S. Afshar, Mater. Chem. Phys. 2010, 120, 356.
[42] Y. Ren, F. Zhang, W. Hua, Y. Yue, Z. Gao, Catal. Today 2009,
48, 316.
1
16] E. Rossetto, D. I. Petkowicz, J. H. dos Santos, S. B. Pergher, F. G.
Penha, Appl. Clay Sci. 2010, 48, 602.
[43] F. Iacomi, Surf. Sci. 2003, 532, 816.
[
[
[
[
[
17] C. Wang, Y. Li, H. Shi, J. Huang, Surf. Interface Anal. 2015,
[44] M. Brazlauskas, S. Kitrys, Chin. J. Catal. 2008, 29, 25.
4
7, 142.
18] B. Dou, V. Dupont, W. Pan, B. Chen, Chem. Eng. J. 2011,
66, 631.
[
[
[
45] H. Klug, L. Alexander, XRD from Polycrystalline, Amorphous
Materials, John Wiley, New York 1974.
1
46] K. Venkateswarlu, A. C. Bose, N. Rameshbabu, Phys. B 2010,
405, 4256.
19] V. A. Ganesh, A. S. Nair, H. K. Raut, T. M. Walsh, S. Ramakrishna,
RSC Adv. 2012, 2, 2067.
47] A. Nezamzadeh‐Ejhieh, F. Khodabakhshi‐Chermahini, J. Ind. Eng.
Chem. 2014, 20, 695.
20] D. I. Petkowicz, S. B. Pergher, C. D. S. Da Silva, Z. N. Da Rocha, J.
H. Dos Santos, Chem. Eng. J. 2010, 158, 505.
[48] M. S. Abaee, S. Cheraghi, Turk. J. Chem. 2014, 38, 650.
21] R. Djellabi, M. Ghorab, G. Cerrato, S. Morandi, S. Gatto, V.
[49] E. Rezaei‐Seresht, R. Tayebee, M. Yasemi, Synth. Commun. 2013,
Oldani, A. Di Michele, C. Bianchi, J. Photochem. Photobiol. A
4
3, 1859.
2
014, 295, 57.
[50] R. Rajagopal, T. Jyothi, T. Daniel, K. Srinivasan, B. Rao, Synth.
[22] C. Wang, H. Shi, Y. Li, Appl. Surf. Sci. 2011, 257, 6873.
Commun. 2001, 31, 3113.
[
23] A. Nezamzadeh‐Ejhieh, S. Hushmandrad, Appl. Catal. A 2010,
[51] R. Bai, P. Liu, J. Yang, C. Liu, Y. Gu, ACS Sustain. Chem. Eng.
2015, 3, 1292.
3
88, 149.
[
[
[
[
24] M. Bahrami, A. Nezamzadeh‐Ejhieh, Mater. Sci. Semicond.
Process. 2015, 30, 275.
[52] M. Sridhar, R. M. Rao, N. H. Baba, R. M. Kumbhare, Tetrahedron
Lett. 2007, 48, 3171.
25] A. Godelitsas, T. Armbruster, Microporous Mesoporous Mater.
[53] F. Moeinpour, R. Omidinia, N. Dorostkar, B. Khoshdeli, Bull.
Korean Chem. Soc. 2011, 32, 2091.
2
003, 61, 3.
26] S. M. Baghbanian, N. Rezaei, H. Tashakkorian, Green Chem.
013, 15, 3446.
[54] A. Hasaninejed, M. R. Kazerooni, A. Zare, Catal. Today 2012,
196, 148.
2
27] N. Rajic, D. Stojakovic, N. Daneu, A. Recnik, J. Phys. Chem.
Solids 2011, 72, 800.
[55] G. Papadogianakis, L. Maat, R. A. Sheldon, J. Chem. Technol.
Biotechnol. 1997, 70, 83.

JAVADI ET AL.
11 of 11
[
56] R. A. Sheldon, Green Chem. 2005, 7, 267.
57] R. A. Sheldon, Green Chem. 2007, 9, 1273.
How to cite this article: Javadi F, Tayebee R,
[
Bahramian B. TiO /nanoclinoptilolite as an efficient
2
nanocatalyst in the synthesis of substituted 2‐
aminothiophenes. Appl Organometal Chem. 2017;
e3779. https://doi.org/10.1002/aoc.3779
SUPPORTING INFORMATION
Additional Supporting Information may be found online in
the supporting information tab for this article.