Molybdenum oxide nanoparticles as recyclable heterogeneous catalyst for synthesis of arylidene ethyl cyanoacetates

Article abstract of DOI:10.1166/jnn.2019.16571

This work reports an adapted route to the highly efficient synthesis of arylidene ethyl cyanoacetate derivatives in the presence of catalytic amounts of molybdenum oxide nanoparticles (MoO₃ NPs) under green conditions at ambient temperature. From the reaction, a wide range of novel arylidene ethyl cyanoacetates was successfully synthesized with high yields from the Knoevenagel condensation reaction between various aryl aldehydes and ethyl cyanoacetate in the presence of MoO₃ nanoparticles. The capability of catalyst to separate from the reaction mixture and then reuse is another advantage of this reaction. Furthermore, obtained products belong to analogous of organic compounds that have shown biological activity, and can be used pharmaceutics.

Full text of DOI:10.1166/jnn.2019.16571

Article
Journal of
Nanoscience and Nanotechnology
Vol. 19, 5965–5973, 2019
Copyright © 2019 American Scientific Publishers
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Printed in the United States of America
Molybdenum Oxide Nanoparticles as Recyclable
Heterogeneous Catalyst for Synthesis of
Arylidene Ethyl Cyanoacetates
Yaghoub Pourshojaei1ꢀ2ꢀ∗, Khalil Eskandari2ꢀ∗, Elaheh Elhami2, and Ali Asadipour2
1Student Research Committee, Kerman University of Medical Sciences, Kerman, 7616913555, Iran
2Department of Medicinal Chemistry, Faculty of Pharmacy & Pharmaceutics Research Center,
Kerman University of Medical Sciences, Kerman, 7616911319, Iran
This work reports an adapted route to the highly efficient synthesis of arylidene ethyl cyanoacetate
derivatives in the presence of catalytic amounts of molybdenum oxide nanoparticles (MoO3 NPs)
under green conditions at ambient temperature. From the reaction, a wide range of novel arylidene
ethyl cyanoacetates was successfully synthesized with high yields from the Knoevenagel conden-
sation reaction between various aryl aldehydes and ethyl cyanoacetate in the presence of MoO3
nanoparticles. The capability of catalyst to separate from the reaction mixture and then reuse is
another advantage of this reaction. Furthermore, obtained products belong to analogous of organic
compounds that have shown biological activity, and can be used pharmaceutics.
IP: 46.148.115.154 On: Thu, 16 May 2019 02:07:53
Keywords: Nano-MoO , Knoevenagel Condensation, Arylidene Ethyl Cyanoacetate, Green
Copyright: American Scientific Publishers
3
Procedure, Recyclable Catalyst.
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1. INTRODUCTION
Furthermore, there are reports that Knoevenagel conden-
sation was performed under continuous flow synthesis18
or fluorous biphasic system.19 Because of all above men-
tioned techniques tolerate some drawbacks such as use of
expensive and non-recyclable catalysts, harsh thermal con-
ditions, use of toxic solvents and catalysts, non-compatible
with green chemistry aspects, not economically viable, and
long reaction times, the attempts to develop and modify
new and efficient protocols to Knoevenagel condensation
reaction have been continued by chemists.2
Arylidene ethyl cyanoacetate derivatives are one of
important ꢂꢀꢁ-unsaturated compounds which obtain via
the Knoevenagel condensation reaction between ethyl
cyanoacetate and aryl aldehydes. So far a broad range
of works on biological and pharmaceutical activities of
arylidene ethyl cyanoacetate and its derivatives is pub-
lished. For example they have been recognized as anti-
nociceptive agents modulating the TREK-1 channel,20
inhibitors of 12-Lipoxygenase,21 new group of fungici-
dal and acaricidal agents,22 a new class of antagonists
at the glycine site of the NMDA receptor,23 an ingre-
dient in sunscreens and cosmetics,24 herbicidally active
compounds,25 and also a therapeutic agent for diseases of
the circulatory system.26 Also these molecules have seen
One of the most familiar and important routes to the for-
mation of carbon–carbon double bond is obtaining from
the condensation reaction between carbonyl compounds
and activated methylene compounds that is well known
as Knoevenagel condensation.1–2 Up to date this reaction
widely used to the synthesis of a broad range of organic
and biologically active compounds.3ꢀ4 Also, this reaction
occasionally has been used to examine the activity of var-
ious solid basic catalysts with considering the fact that
pKa value of CH-acidic compounds in ꢁ-dicarbonyl com-
pounds are in the range of 9–11.5
Because of the importance of this reaction in organic
synthesis and chemical industries, so far numerous
methods for Knoevenagel condensations with various
techniques have been reported. For instance, running
reaction in the presence of Lewis acids or bases,6ꢀ7
Brönsted acids,8 ionic liquids,9 green medium,10
microwave assistance,11 ultrasound irradiation,12 solid-
phase reactions,13 grinding methods,14 solvent-free
microwave assisted conditions,15 and using biocatalysts,10
organocatalysts16 or polyoxometalates17 can be countered.
∗Authors to whom correspondence should be addressed.
J. Nanosci. Nanotechnol. 2019, Vol. 19, No. 9
1533-4880/2019/19/5965/009
doi:10.1166/jnn.2019.16571
5965

MoO3 NPs as Recyclable Heterogeneous Catalyst for Synthesis of Arylidene Ethyl Cyanoacetates
Pourshojaei et al.
in molecular rotors motifs.27 These revealed properties
encourage chemists and pharmacologists designing syn-
thetic protocols to synthesize newly prepared molecules
exhibiting pharmacological and biological activities which
may be applied in the treatment of human disease as new
medicine in the future.28ꢀ29
Considering the green chemistry principles, using recy-
clable green catalysts and replacement of toxic organic
solvents by safe and clean ones have increasingly attracted
the interest of chemists and industrialists to avoid waste
production in chemical reactions.30ꢀ31
Nanoscience and nanotechnology are very important
topics in the word and have been applied in a wide
range spanning from science to engineering to medicine.32
Nowadays, nanocatalysts have also attracted much atten-
tion from chemists because of their specific, consider-
able, and efficient role in chemical reactions. For instance,
nano-sized catalysts dramatically increase the contact
between functional groups of reactants with the surface
of the catalyst.33 Among efficient and green nanocata-
lysts, molybdenum oxide nanoparticles (MoO3 NPs) have
emerged as green, highly efficient, and recyclable catalyst
in chemical reactions.34 Furthermore, MoO3 NPs in the
orthorhombic phase has been successfully applied as the
efficient catalyst for condensation reaction between aryl
aldehydes and cyclohexanone as a CH-acidic precursor.34
Based on above, and in connection with our recent
2. EXPERIMENTAL DETAILS
Chemicals were purchased from Merck and Sigma-Aldrich
chemical companies. Melting points were measured on
an electrothermal IA9100 melting point apparatus fixed
at 1 ꢀC/min. IR spectra were recorded by Brucker FT-
IR Tensor 27 infrared spectrophotometer with KBr as the
1
matrix. H NMR and 13C NMR spectra were recorded on
an FT-NMR Bruker Avance Ultra Shield Spectrometer at
frequencies of 300 and 75 MHz respectively in CHCl3 as
the solvent. Elemental analyses (C, H, N, S) were per-
formed on a Heraeus Rapid analyzer and the results were
found in good agreement ( 0.3%) with the calculated val-
ues. Scanning electron microscopy (SEM) evaluations of
the nano-catalyst were performed on a JEOL JEM 3010
instrument operating at an accelerating voltage of 300 kV.
An X-ray diffraction pattern to the characterization of the
heterogeneous nano-catalyst was studied with XRD, D8,
Advance, Bruker, AXS. Transmission electron microscopy
(TEM) investigations of the nano-catalyst were performed
on a JEOL JEM 3010 instrument operating at an accelerat-
ing voltage of 300 kV. TLC was performed on TLC-Grade
silica gel-G/UV 254 nm plates EtOAc/n-hexane (1:1) as
eluent. All products were isolated, purified and deduced
1
from their FT-IR, H NMR, and 13C NMR spectral data
along with elemental analyses (C, H, N).
2.1. Typical Procedure for the Preparation MoO3 NPs
For the synthesize of MoO3 NPs, to the stirred
mixture of ammonium heptamolybdate tetrahydrate
((NH4ꢃ6Mo7O24 × 4H2O) (2 g, 1.6 mmol) dissolved in
5 mL ethanol, and 15 mL of deionized water, at room
temperature for 20 min, HNO3 (2 M) was added dropwise
until the pH of the mixture achieved to 1. Then, formed
IP: 46.148.115.154 On: Thu, 16 May 2019 02:07:53
works to the catalytic synthesis of newly prepared poten-
35–42
Copyright: American Scientific Publishers
tially interesting biological active organic compounds,
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herein we wish to report a green one-pot catalytic reac-
tion between a broad range of aryl aldehydes 1, and ethyl
cyanoacetate (2) in the presence of catalytic amounts of
molybdenum oxide nanoparticle (MoO3 NPs) (Scheme 1).
By this reaction, we found that MoO3 NPs plays a
significant role as a key factor in the synthesis of aryli-
dene ethyl cyanoacetate derivatives via a convenient and
environmentally friendly work-up. The structures of all
products 3 were deduced from their FT-IR, FT-1H and FT-
13C NMR spectroscopies and (C, H, N, S) analyses. Also,
herein, preparation, high activation, and regeneration of
MoO3 NPs as an environmentally benign and reusable cat-
alyst in the synthesis of some medicinally important aryli-
dene ethyl cyanoacetate derivatives have been explained.
As well as, the efficiency of catalyst on reaction progress
with others to the synthesis of a model reaction was
compared.
ꢀ
clear solution was stirred under reflux conditions at 90 C
for 5 h. Afterwards, obtained light-blue precipitates were
separated by filtration, washed several times with deion-
ized water until the washing solution being neutral, and
dried in an oven at 90 ꢀC for 12 h. In the final step,
ꢀ
the catalyst was calcined at 450 C for 6 h in an electric
furnace.
2.2. General Procedure for the Preparation of
Corresponding Aldehydes 1
Corresponding aldehydes containing alkylamine ethers
was synthesized according to the procedure reported
in the literature,43 and all their structures were con-
firmed by the comparison of their physical and chem-
ical properties with those reported in the literature.43
Also, 4-(benzyloxy)benzaldehyde derivatives were pre-
pared by treating with 4-hydroxybenzaldehyde with appro-
priate benzyl chloride/bromide derivatives in the presence
of K2CO3 as the catalyst. The physical and chemical
properties of all obtained substrates were compared with
the ones reported in the literature and all of their structures
were confirmed.43
O
O
H
O
G
O
H
MoO3 NPs (3 mol%)
N
N
EtOH/H2O (4:1)
r.t.
O
G
1
2
3
Scheme 1. Knoevenagel condensation reaction between aryl aldehydes
with ethyl cyanoacetate by the use of MoO3 NPs in aqueous medium.
5966
J. Nanosci. Nanotechnol. 19, 5965–5973, 2019

Pourshojaei et al.
MoO3 NPs as Recyclable Heterogeneous Catalyst for Synthesis of Arylidene Ethyl Cyanoacetates
Figure 1. (A) FT-IR spectrum of MoO3 NPs; (B) X-ray diffraction pattern of the MoO3 NPs.
2.3. Typical Procedure for the Synthesis of 3l
65.6, 62.6, 56.7, 53.5, 14.5; Anal. calcd for C18H22N2O4:
C, 65.44; H, 6.71; N, 8.48; Found: C, 65.49; H, 6.68;
N, 8.50%.
4-(morpholinoethoxy)benzaldehyde (1 mmol, 0.235 g)
was added to a stirring mixture of ethyl cyanoacetate
(1.5 mmol, 0.170 g), and the catalytic amount of MoO3
NPs (0.004 g, 3 mol%) in EtOH/H2O (4:1). It was allowed
to the mixture to stir at room temperature for the time
indicated in Table II. After compilation of the reaction (the
reaction progress was controlled by TLC EtOAc/n-hexane
(1:1) as eluent), the reaction mixture was filtered to sepa-
rate precipitate. Next, the precipitate was dissolved in boil-
ing ethanol and filtrated to separate catalyst. In the end,
formed crystalline product was filtrated to obtain the crys-
talline pure product.
2.4.2. Ethyl (E)-3-(4-(4-benzylpiperidin-1-yl)phenyl)-2-
Cyanoacrylate (3m)
Orange crystals; FT-IR spectrum, ꢄ, cm−1: 3021, 2992,
2933, 2208, 1727, 1609, 1563, 1510, 1274, 1226, 1172,
1
964, 812, 751, 705, 517; H NMR spectrum (300 MHz,
DMSO-d6ꢃ, ꢅ, ppm (J, Hz): 8.10 (s, 1H, CHVinylicꢃ, 7.96
(d, 2H, J = 9.0, CHArꢃ, 7.36–7.18 (m, 5H, CHPhꢃ, 6.89
(d, J = 9.0, 2H, CHArꢃ, 4.38 (q, J = 6.0, 2H, OCH2ꢃ,
1
2
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3.99 (d, J = 9.0, 2H, CHArꢃ, 2.93 (d.t, 2H, J = 9.0, J =
Copyright: American Scientific Publishers
3.0, 2CH), 2.61 (d, J = 6.0, 2H, CH2ꢃ 1.92–1.86 (m, 1H,
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CH), 1.81 (d, J = 12.0, 2H, 2CH), 1.41 (t, J = 6.0, 3H,
CH3ꢃ, 1.35 (d, J = 3.0, 2H, 2CH); 13C NMR spectrum
(75 MHz, DMSO-d6ꢃ, ꢅ, ppm: 164.2, 154.3, 153.9, 139.9,
134.1, 129.1, 128.4, 126.1, 120.3, 117.4, 113.4, 94.9, 81.9,
47.5, 42.9, 38.1. 31.5, 14.3; Anal. calcd for C24H26N2O2:
C, 76.98; H, 7.00; N, 7.48; Found: C, 77.01; H, 7.13;
N, 7.51%.
2.4. Representative Spectral Data
2.4.1. Ethyl (E)-2-Cyano-3-(4-(2-morpholinoethoxy)
phenyl)acrylate (3l)
White powder; FT-IR spectrum, ꢄ, cm−1: 3033, 2996,
2938, 2217, 1718, 1588, 1514, 1263, 1185, 940, 834, 517;
1H NMR spectrum (300 MHz, DMSO-d6ꢃ, ꢅ, ppm (J, Hz):
8.32 (s, 1H, CHvinylicꢃ, 8.09 (d, J = 9.0, 2H, CHArꢃ, 7.18
(d, J = 9.0, 2H, CHArꢃ, 4.31 (q, J = 6.0, 2H, OCH2ꢃ,
4.30 (brs, 2H, CH2ꢃ, 3.66 (brs, 4H, 2CH2ꢃ, 2.92 (brs,
2H, CH2ꢃ, 2.68 (brs, 4H, 2CH2ꢃ, 1.32 (3H, t, J = 6.0,
CH3ꢃ; 13C NMR spectrum (75 MHz, DMSO-d6ꢃ, ꢅ, ppm:
163.0, 162.8, 154.9, 133.9, 124.6, 116.7, 115.9, 99.2, 65.9,
2.4.3. Ethyl (E)-3-(4-((4-chlorobenzyl)oxy)phenyl)-2-
Cyanoacrylate (3o)
White crystals; FT-IR spectrum, ꢄ, cm−1: 3028, 2951,
2925, 2219, 1725, 1590, 1515, 1433, 1387, 1311, 1267,
1
1214, 1184, 1093, 1005, 831, 760, 563, 515; H NMR
spectrum (300 MHz, CDCl3ꢃ, ꢅ, ppm (J, Hz): 8.20 (s, 1H,
CHVinylicꢃ, 8.04 (d, J = 9.0, 2H, CHArꢃ, 7.41 (brs, 4H,
Figure 3. (A) Scanning electron microscopy of MoO3 NPs; (B) TEM
Figure 2. X-ray analysis spectrum of MoO3 NPs.
image of MoO3 NPs.
J. Nanosci. Nanotechnol. 19, 5965–5973, 2019
5967

MoO3 NPs as Recyclable Heterogeneous Catalyst for Synthesis of Arylidene Ethyl Cyanoacetates
Pourshojaei et al.
CHPhꢃ, 7.08 (d, J = 9.0, 2H, CHArꢃ, 5.15 (s, 2H, OCH2ꢃ,
4.40 (q, 2H, J = 6.0, OCH2ꢃ, 1.43 (t, J = 6.0, 3H,
CH3ꢃ; 13C NMR spectrum (75 MHz, DMSO-d6ꢃ, ꢅ, ppm:
163.0, 162.5, 154.2, 134.3, 134.2, 133.6, 128.9, 128.8,
124.7, 116.1, 115.5, 99.8, 69.5, 62.5, 14.2; Anal. calcd
for C19H16ClNO3: C, 66.77; H, 4.72; N, 4.10; Found:
C, 66.81; H, 4.69; N, 4.16%.
2.4.4. Ethyl (E)-3-(3-((4-chlorobenzyl)oxy)phenyl)-2-
Cyanoacrylate (3p)
White powder; FT-IR spectrum, ꢄ, cm−1: 3061, 2949,
Figure 4. TGA analysis of MoO3 NPs.
2220, 1726, 1609, 1577, 1491, 1440, 1397, 1258, 1171,
3. RESULTS AND DISCUSSION
1085, 1044, 851, 777, 682; 1H NMR spectrum (300 MHz,
CDCl3ꢃ, ꢅ, ppm (J, Hz): 8.24 (s, 1H, CHVinylicꢃ, 7.70
(s, 1H, CHArꢃ, 7.54 (d, J = 6.0, 1H, CHArꢃ, 7.47–7.38
Molybdenum (VI) oxide nanoparticles were synthe-
sized by a slight modification of the solvothermal
reported method (Iranian Nanomaterials Pioneers Com-
pany, Mashhad).44 The functional groups of the MoO3
with the best crystalline degree were identified by FT-IR
spectrum (Fig. 1(A)). As can be seen from Figure 1, the
spectrum shows three strong peaks at 990 cm−1 attributed
to the stretching vibration of terminal M O bond with
an indicator of the layered orthorhombic MoO3 lattice,
855 cm−1 to the stretching vibration of Mo–O–Mo bonds,
and a broad band at 558 cm−1 corresponding to the
bending-stretching vibration of oxygen atom linked to
three Mo atoms.45 In FT-IR spectrum, not appearing of
peaks at 1620 and 1400 cm−1 demonstrates that MoO3
1
2
(m, 5H, CHArꢃ, 7.19 (dd, J = 6.0, J = 3.0, CHArꢃ, 5.13
(s, 2H, OCH2ꢃ, 4.43 (q, J = 6.0, 2H, OCH2ꢃ, 1.44 (t, J =
6.0, 3H, CH3ꢃ; 13C NMR spectrum (75 MHz, DMSO-d6ꢃ,
ꢅ, ppm: 162.4, 158.8, 154.8, 134.7, 134.0, 132.7, 130.3,
128.9, 128.8, 124.8, 120.9, 115.5, 115.2, 103.2, 69.4, 62.8,
14.1; Anal. calcd for C19H16ClNO3: C, 66.77; H, 4.72;
N, 4.10; Found: C, 66.81; H, 4.65; N, 4.13%.
2.4.5. Ehyl (E)-3-(4-((4-bromobenzyl)oxy)phenyl)-2-
Cyanoacrylate (3q)
−1
White crystals; FT-IR spectrumIP, :ꢄ4,6c.1m48.:11350.2175,42O94n8:,Thu, 16 May 2019 02:07:53
2218, 1724, 1590, 1514, 1434, 1381, 1311, 1268, 1214,
NPs are not in hexagonal phase, and appearing of peaks
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−1
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only at 990, 855, 558 cm strongly confirms that MoO3
1183, 1093, 1069, 1002, 832, 804, 759, 554, 515; 1H NMR
spectrum (300 MHz, CDCl3ꢃ, ꢅ, ppm (J, Hz): 8.20 (s, 1H,
CHVinylicꢃ, 8.03 (d, J = 9.0, 2H, CHArꢃ, 7.57 (d, J = 9.0,
2H, CHArꢃ, 7.34 (d, J = 9.0, 2H, CHArꢃ, 7.08 (d, J = 9.0,
2H, CHArꢃ, 5.13 (s, 2H, OCH2ꢃ, 4.40 (q, J = 6.0, 2H,
OCH2ꢃ, 1.42 (t, J = 6.0, 3H, CH3ꢃ; 13C NMR spectrum
(75 MHz, DMSO-d6ꢃ, ꢅ, ppm: 163.0, 162.5, 154.2, 134.8,
133.6, 131.9, 129.1, 124.8, 122.3, 116.1, 115.5, 99.8,
69.5, 62.5, 14.2; Anal. calcd for C19H16BrNO3: C, 59.08;
H, 4.18; N, 3.63; Found: C, 59.12; H, 4.11; N, 3.67%.
NPs are in orthorhombic phase.44
X-ray diffraction pattern (XRD) of the MoO3 NPs was
shown in Figure 1(B). In the XRD pattern of MoO3 NPs,
the distinguished diffraction peaks centered at 2ꢆ ∼ 23ꢇ7ꢀ,
25.9ꢀ, 27.1ꢀ, 33.7ꢀ, 33.9ꢀ, 35.8ꢀ, 39.1ꢀ, and 49.2ꢀ related
respectively to the (001), (011), (021), (101), (111), (121),
(051) and (002) plane of the MoO3 with an rutile phase
Table I. Examination of different conditions on model reaction.a
Entry
Catalyst
Solvent/temp.
Yieldb
1
2
3
4
5
6
7
8
None
None
EtOH, Reflux
Solvent-free, 80 ꢀC
CH2Cl2, Reflux
CH3CN, 50 ꢀC
35
30
43
45
48
45
51
78
85
86
90
91
95
96
96
91
2.4.6. Ethyl (E)-3-(3-((4-bromobenzyl)oxy)phenyl)-2-
Cyanoacrylate (3r)
Na2HPO4 (5 mol%)
Na2CO3 (5 mol%)
p-TSA (5 mol%)
Piperidine (5 mol%)
Et3N (5 mol%)
MoO3 NPs (5 mol%)
MoO3 NPs (5 mol%)
MoO3 NPs (5 mol%)
MoO3 NPs (5 mol%)
MoO3 NPs (5 mol%)
MoO3 NPs (5 mol%)
MoO3 NPs (4 mol%)
MoO3 NPs (3 mol%)
MoO3 NPs (2 mol%)
White powder; FT-IR spectrum, ꢄ, cm−1: 3045, 3028,
2955, 2225, 1732, 1614, 1574, 1486, 1430, 1378, 1254,
1166, 1056, 1011, 980, 871, 798, 776, 680, 476; 1H NMR
spectrum (300 MHz, CDCl3ꢃ, ꢅ, ppm (J, Hz): 8.24 (s, 1H,
CHVinylicꢃ, 7.70 (t, J = 3.0, 1H, CHArꢃ, 7.57–7.35 (m, 6H,
CHArꢃ, 7.21–7.17 (m, 1H, CHArꢃ, 5.12 (s, 2H, OCH2ꢃ,
4.43 (q, J = 6.0, 2H, OCH2ꢃ, 1.44 (t, J = 6.0, 3H, CH3ꢃ;
13C NMR spectrum (75 MHz, CDCl3ꢃ, ꢅ, ppm: 162.4,
158.8, 154.8, 135.3, 132.7, 131.8, 130.3, 129.2, 124.8,
122.1, 120.9, 115.5, 115.2, 130.3, 69.4, 62.8, 14.1. Anal.
calcd for C19H16BrNO3: C, 59.08; H, 4.18; Br, 20.69;
N, 3.63; Found: C, 59.15; H, 4.23; N, 3.65%.
MeOH, 50 ꢀC
H2O, 50 ꢀC
EtOH, 50 ꢀC
H2O, 50 ꢀC
9
EtOH, r.t.
10
11
12
13
14
15
16
EtOH/H2O (1:1), r.t.
EtOH/H2O (2:1), r.t.
EtOH/H2O (3:1), r.t.
EtOH/H2O (4:1), r.t.
EtOH/H2O (4:1), r.t.
EtOH/H2O (4:1), r.t.
EtOH/H2O (4:1), r.t.
Notes: aReaction time: 60 min; bisolated yield.
5968
J. Nanosci. Nanotechnol. 19, 5965–5973, 2019

Pourshojaei et al.
MoO3 NPs as Recyclable Heterogeneous Catalyst for Synthesis of Arylidene Ethyl Cyanoacetates
Table II. Highly efficient and green synthesis of arylidene ethyl cyanoacetate derivatives.a
Entry
1
Aryl aldehyde 1
Product 3
Time (min)
40
Yieldb (%)/(lit).
96/86
m.p. (lit)
H
48–49 (47–48)46
O
H
O
O
N
1a
3a
2
3
H
40
40
99/94
98/91
170–171 (169–170)46
O
O
O
N
O
O
N
N
3b
O
O
O
H
1b
91–92 (91–92)46
Cl
O
O
N
3c
Cl
1c
4
5
6
H
40
40
97/99
96/95
45–46 (43–45)47
81–82 (80–81)48
93–94 (92–93)46ꢀ 49
O
Cl
Cl
O
O
N
1d
3d
H
O
Br
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O
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Br
O
N
1e
3e
H
50
60
95/90
95/86
O
H
3C
O
O
N
3f
CH3
1f
7
155–157 (not reported)50
H
O
O
O
O
N
N
3j
N
O
1j
8
60
94/90
90–92 (not reported)50
H
O
N
O
O
N
3k
N
1k
J. Nanosci. Nanotechnol. 19, 5965–5973, 2019
5969

MoO3 NPs as Recyclable Heterogeneous Catalyst for Synthesis of Arylidene Ethyl Cyanoacetates
Pourshojaei et al.
Table II. Continued.
Entry
9
Aryl aldehyde 1
Product 3
Time (min)
60
Yieldb (%)/(lit).
92
m.p. (lit)
217–218c
H
O
O
N
O
O
N
N
O
O
O
1l
3l
10
60
95
115–116c
H
O
N
N
N
O
O
1m
3m
127–129 (123–125)51
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97/96
H
3C
11
12
H
60
O
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N
O
H
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3C
O
N
3n
N
H
3C
CH3
1n
60
98
147–149c
Cl
H
O
O
O
N
Cl
O
O
1o
3o
13
60
96
88–90c
H
O
O
O
N
O
Cl
O
1p
Cl
3p
5970
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Pourshojaei et al.
MoO3 NPs as Recyclable Heterogeneous Catalyst for Synthesis of Arylidene Ethyl Cyanoacetates
Table II. Continued.
Entry
14
Aryl aldehyde 1
Product 3
Br
Time (min)
60
Yieldb (%)/(lit).
98
m.p. (lit)
140–142c
H
O
O
O
N
Br
1q
O
O
3q
15
60
95
109–111c
H
O
O
O
N
O
Br
O
1r
Br
3r
Notes: aReaction conditions: MoO3 NPs (3 mol%), EtOH/H2O (4:1), room temperature; bisolated yields; cnovel product.
which is in agreement with the standard data for the MoO3
was studied for more investigation of MoO3 NPs morphol-
ogy (Fig. 3(B)). TEM image of MoO NPs clearly demon-
strated the MoO3 NPs have a homogeneous diameter size
IP: 46.148.115.154 On: Thu, 16 May 2019 02:07:53
orthorhombic lattice structure (JCPDS: 05-0506).34 These
Copyright: American Scientific Publishers
3
Delivered by Ingenta
peaks also strongly confirm the orthorhombic phase of
MoO3 NPs with no impurity detection.44
about 40 nm.
In addition, to determine catalyst purity, energy disper-
sive X-ray analysis (EDAX) on the molybdenum triox-
ide nanoparticles (MoO3 NPs) was performed. The results
obtained from taken pattern disclosed peaks correlated to
molybdenum and oxygen only that proves the high purity
of catalyst (Fig. 2).
The morphology of MoO3 NPs was studied by scan-
ning electron microscopy (SEM) (Fig. 3(A)). SEM images
of MoO3 NPs show the molybdenum (VI) oxide nanopar-
ticles have a diameter of about 40 nm without any
amorphous or other kinds of crystallized phase parti-
cles. In addition, the transmission electron microscopy
(TEM) image of molybdenum (VI) oxide nanoparticles
Also, to investigate the thermal stability of catalyst at
high temperatures, thermo-gravimetric analysis (TGA) of
molybdenum trioxide nanoparticles was taken (Fig. 4).
Thermo-gravimetric analysis showed that weight percent
of the catalyst remains constant up to about 780 ꢀC. From
this investigation, it was concluded that the structure of the
ꢀ
catalyst is constant in temperatures downwards 780 C.
Previous to start loading different reactions to expand
and develop of reaction scope, compound 3a was selected
as a model to find the best conditions for running reaction
(Table I).
First of all, the reaction was run in catalyst-free con-
ditions. It was observed that no remarkable product was
G
H
H2O
O
O
N
N
G
O
O
1
O
O
O
Mo
H
H
O
O
H
N
O
O
Mo
O
H
O
O
2
3
4
G
Scheme 2. Suggested mechanism to MoO3 NPs-catalyzed synthesis of arylidene ethyl cyanoacetates.
J. Nanosci. Nanotechnol. 19, 5965–5973, 2019
5971

MoO3 NPs as Recyclable Heterogeneous Catalyst for Synthesis of Arylidene Ethyl Cyanoacetates
Pourshojaei et al.
active organic compounds was described by the use of
MoO3 NPs as a highly efficient nano-catalyst and also the
scope of potentially biologically active compounds was
developed. By this procedure some novel products were
obtained which can candidate as medicinally important
compounds or even important drugs in the future. It is
believed that this methodology would attract the interest
of chemists, biologists, and pharmacologists in the future.
As well as, a new application of MoO3 NPs as an eco-
friendly, highly efficient, recyclable, and easily handled
nano-catalyst to the synthesis of organic compounds was
introduced. The merit of this protocol is the synthesis of
new kind of organic compounds by the use of an efficient
nano-Lewis acid catalyst and environmentally benign con-
ditions with good to excellent yields.
Figure 5. Recyclability results of MoO3 NPs for the synthesis of com-
pound 3o over six runs.
obtained. From this experiment, it was understood that
among different catalysts and conditions, MoO3 NPs
(3 mol%) in aqueous medium [EtOH/H2O (4:1)] at room
temperature disclosed best efficiency to synthesis of prod-
uct and under these conditions highest yield of product
was obtained in the same reaction times (Table I).
When the optimum conditions for reaction performance
were found (see above), it was tried to examine the gener-
ality of the reaction by the use of a wide range of aryl alde-
hydes and in the presence of optimum amounts of MoO3
NPs as green, highly efficient and recyclable nano-catalyst,
and the results were summarized in Table II.46–51
Acknowledgments: The authors gratefully acknowl-
edge from Pharmaceutics Research Center, Institute of
Neuropharmacology, and Research Central Labratory,
Kerman University of Medical Sciences for supporting of
this work.
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