A practical and highly efficient synthesis of densely functionalized nicotinonitrile derivatives catalyzed by zinc oxide-decorated superparamagnetic silica attached to graphene oxide nanocomposite

Article abstract of DOI:10.1002/aoc.4735

Zinc oxide-decorated superparamagnetic silica attached to graphene oxide (Fe₃O₄/SiO₂/PTS-GO-ZnO), as a novel nanocomposite, was designed, and its core-shell structure was appropriately characterized by different spectroscopy or microscopy methods and thermal techniques as well as measuring of its porosity and magnetic properties. The catalytic activity of Fe₃O₄/SiO₂/PTS-GO-ZnO, as a reusable heterogeneous catalyst, was investigated for efficient one-pot multi-component synthesis of medicinally important functionalized 2-amino-6-(2-oxo-2H-chromen-3-yl)-4-arylnicotinonitrile derivatives. The significant features of the present procedure are mild reaction conditions, low loading of the catalyst, high to quantitative yields of the desired products, avoiding the use of toxic heavy metals or solvents, simple isolation and purification of the products, and stability as well as reusability of the catalyst after at least six consecutive runs.

Full text of DOI:10.1002/aoc.4735

Received: 27 March 2018
DOI: 10.1002/aoc.4735
Revised: 12 October 2018
Accepted: 4 November 2018
F U L L P A P E R
A practical and highly efficient synthesis of densely
functionalized nicotinonitrile derivatives catalyzed by zinc
oxide‐decorated superparamagnetic silica attached to
graphene oxide nanocomposite
Farahnaz Davoodi | Mohammad G. Dekamin
| Zahra Alirezvani
Pharmaceutical and Heterocyclic
Zinc oxide‐decorated superparamagnetic silica attached to graphene oxide
(Fe3O4/SiO2/PTS‐GO‐ZnO), as a novel nanocomposite, was designed, and its
core‐shell structure was appropriately characterized by different spectroscopy
or microscopy methods and thermal techniques as well as measuring of its
porosity and magnetic properties. The catalytic activity of Fe3O4/SiO2/PTS‐
GO‐ZnO, as a reusable heterogeneous catalyst, was investigated for efficient
one‐pot multi‐component synthesis of medicinally important functionalized
2‐amino‐6‐(2‐oxo‐2H‐chromen‐3‐yl)‐4‐arylnicotinonitrile derivatives. The sig-
nificant features of the present procedure are mild reaction conditions, low
loading of the catalyst, high to quantitative yields of the desired products,
avoiding the use of toxic heavy metals or solvents, simple isolation and purifi-
cation of the products, and stability as well as reusability of the catalyst after at
least six consecutive runs.
Compounds Research Laboratory,
Department of Chemistry, Iran University
of Science and Technology, Tehran 16846‐
13114, Iran
Correspondence
Mohammad G. Dekamin, Pharmaceutical
and Heterocyclic Compounds Research
Laboratory, Department of Chemistry,
Iran University of Science and
Technology, Tehran, 16846‐13114, Iran.
Email: mdekamin@iust.ac.ir
Funding information
The Research Council of Iran University
of Science and Technology (IUST), Teh-
ran, Iran, Grant/Award Numbers: 160/
289, Iran Nanotechnology Initiative
Council, Iran
KEYWORDS
aminocyanopyridines, hybrid nanocomposite, multi‐component reactions, supermagnetic silica core‐
shell catalyst, zinc oxide‐decorated graphene oxide
1 | INTRODUCTION
Due to the importance of aminocyanopyridines, dif-
ferent strategies or techniques have been reported for
In view of the pharmacological importance of heterocy-
clic compounds, pyridine moieties have attracted signifi-
cant attention because of their widespread biological
activities and medicinal applications.[1] Noticeably,
cyanopyridines and aminocyanopyridines with different
alkyl or aryl groups have been identified to show wide-
spread biological activities such as antimicrobial,[2–6]
antitumor[7] and antihistaminic[8] agents as well as
1KK‐β and MK‐2 inhibitors,[9–12] respectively (Figure 1).
Furthermore, polysubstituted pyridine derivatives are
used as chromophores with two tunable functions and
metal chelating agents.
their synthesis from appropriate substrates.[12–17] Indeed,
the strategy of multi‐component reactions (MCRs) is
unique among the alternative synthetic paths in terms
of atom economy, straightforward procedures, and the
chance to prepare diverse target compounds by
introduction of different components in a single reaction
vessel.[14,15,18–24] Hence, MCRs have found growing
importance in modern synthetic organic chemistry,
especially for preparation of medicinally important het-
erocyclic scaffolds, by simultaneous addressing of
environmental and economic concerns.[25] However,
MCRs are often accelerated by appropriate catalytic
Appl Organometal Chem. 2019;e4735.
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© 2019 John Wiley & Sons, Ltd.
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https://doi.org/10.1002/aoc.4735

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DAVOODI ET AL.
FIGURE 1 Representative examples of biologically active aminocyanopyridine derivatives: (a) antimicrobial agents; (b,c) antitumor
agents; (d) antihistaminic agents; (e,f) IKK‐β and MK‐2 inhibitors
systems depending on the electrophilic or nucleophilic
nature of substrates.[26,27] Hence, different homogeneous
or heterogeneous catalytic systems have been developed
for MCRs.[19,20]
Graphene oxide plays a vital role in materials science
because of its individual structural and morphological
characteristics, easy chemical modification, and excel-
lent mechanical, thermal and electrical properties.[40–49]
The noticeable characteristic of GO is the addition of
oxygen atoms bound with the carbon framework
compared to the parent graphene. Therefore, GO is
hydrophilic which makes it simply dispersible in water.
Moreover, GO simultaneously contains both aromatic
and aliphatic domains that further expand the types of
interactions that can occur with its surface.[50–52] In par-
ticular, the carboxylic groups that are found at the edges
of the GO layers can exchange their proton with metal
cations or positively charged organic molecules.[53–55]
Primary efforts for the use of GO to immobilize different
metal nanoparticles have been previously reviewed
elsewhere.[56–58]
Recently, the fields of nanoscience and catalysis
simultaneously have been associated to each other to
afford more efficient and reusable heterogeneous catalytic
systems; reducing very strong economic and environmen-
tal impact of the homogeneous catalysis.[28–30] In this
regard, magnetic nanoparticles (MNPs) have received
great attention due to simple magnetic recoverability
and recyclability. However, the surface area of MNPs
such as Fe3O4 is very low.[31–33] Hence, the use of other
supports for appropriate dispersion of the active catalytic
species and maximum durability of the obtained nano-
composite is necessary.[31,34,35] Consequently, the cata-
lytic activity of the final magnetic nanocomposite is
extremely dependent on the nature of modifying supports
and linkers. Large surface area, strong metal‐support
interactions and the presence of active sites that can par-
ticipate in the consecutive reaction steps are the essential
requirements for an appropriate support.[36,37] Inorganic
metal oxides, especially SiO2, as well as organic polymers
or active carbons that display large surface areas are
typically used insoluble solid supports for the magnetic
heterogeneous catalysts.[31,38,39] Among others, the
unique features of suspensions of graphene oxide (GO)
have provided a new horizon for the expansion of sup-
ported MNPs as heterogeneous catalysts.
Among different metal oxides,[59] pure or combined
zinc oxide (ZnO) nanoparticles have been commonly
used in pigments, cosmetics, chemical sensors, solar cells,
lithium ion batteries or catalysts.[60–65] ZnO is an eco-
nomical, reusable, commercially available, air‐ and
moisture‐stable, and environmentally benign material.
ZnO is probably the richest family of nanostructures
among all materials in terms of structure and property.
ZnO is a unique material that shows piezoelectric and
semiconducting dual properties. Indeed, nanobelts,
nanorings, nanohelixes/nanosprings, nanowires and
nanocages of ZnO have been produced under specific

DAVOODI ET AL.
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growth conditions.[66,67] Therefore, introducing new
nanocomposites having both GO and ZnO components
for different applications including heterogeneous
catalysis is in great demand. In continuation of our ongo-
ing efforts towards developing efficient catalysts for dif-
ferent MCRs,[22,68–73] we report herein the catalytic
application of ZnO‐decorated superparamagnetic silica
attached to GO (Fe3O4/SiO2/PTS‐GO‐ZnO, 1), as a new,
highly efficient and recoverable core‐shell catalyst, for
the synthesis of 2‐amino‐6‐(2‐oxo‐2H‐chromen‐3‐yl)‐4‐
diffraction (XRD) pattern of the catalyst was obtained
using TW 1800 diffractometer with Cu Ka radiation (λ
= 1.54050 Å). Magnetic susceptibility measurements were
taken using a vibrating sample magnetometer (BHV‐55,
Riken, Japan) at room temperature. Analytical thin‐layer
chromatography (TLC) was performed using Merck 0.2‐
mm silica gel 60F‐254Al‐plates. All products are known,
and their structures were established from their spectral
data and melting points as compared with authentic sam-
ples or literature values.
arylnicotinonitrile
derivatives
under
solvent‐free
conditions at 100°C (Scheme 1). To the best of our
knowledge, there is no report in the literature about the
use of Fe3O4/SiO2/PTS‐GO‐ZnO for the synthesis of
2.2 | Preparation of ZnO‐decorated Fe3O4/
SiO2 core‐shell hybrid covalently attached
to GO (Fe3O4/SiO2/PTS‐GO‐ZnO)
nanocomposite
densely
functionalized
2‐aminocyanopyridine
derivatives.[74,75]
As we described before, magnetic Fe3O4/SiO2 core‐shell
hybrid covalently attached to GO (Fe3O4/SiO2/PTS‐GO)
was prepared successfully at the first step.[65] To prepare
Fe3O4/SiO2/PTS‐GO‐ZnO nanocomposite, Fe3O4/SiO2/
PTS‐GO (1.0 g) was dispersed in 100 mL of deionized
water to form a suspension by ultrasonication for 1 hr
in which a further exfoliation of GO layers was achieved.
Then, zinc acetate [(Zn (OAc)₂·(H₂O)₂, 1.0 g] and sodium
hydroxide (0.4 g) were added slowly under stirring
followed by ultrasonication for 1 hr. The obtained mix-
ture was refluxed at 100°C for 14 hr. Finally, the obtained
solid was magnetically collected, washed several times
with deionized water and dried at 100°C for 24 hr.
2 | EXPERIMENTAL
2.1 | Materials and methods
All solvents and reagents were obtained from Merck and
used without further purifications, except for benzalde-
hyde, which was used as a fresh distilled sample. Fourier
transform‐infrared (FT‐IR) spectra were acquired on a
1
Shimadzu FT‐IR‐8400S spectrometer as KBr pellets. H‐
NMR (500 MHz) and 13C‐NMR (125 MHz) spectra were
recorded on a Bruker DRX‐500 Avance spectrometers.
Microanalysis of the products was carried out by a
CHNS/O analyzer (Perkin–Elmer Series II, 2400). Scan-
ning electron microscopy (SEM) images were obtained
using a Sigma instrument from Zeiss, Germany. The mor-
phology and structure of the nanocatalyst were examined
by transmission electron microscopy (TEM; Philips
CM30). Thermal gravimetric analysis (TGA) was per-
formed by means of Bahr STA 504 instrument. Chemical
analysis of the catalyst was performed using Philips PW
1480 X‐ray fluorescence and Philips energy‐dispersive X‐
ray (EDX) XL30 model. The specific surface area determi-
nation as well as pore volume and size analysis were per-
formed by Brunauer–Emmett–Teller (BET) and Barrett–
Joyner–Halenda (BJH) methods, respectively, using a
ASAP™ Micromeritics 2020. The X‐ray powder
2.3 | General procedure for the synthesis
of 2‐amino‐6‐(2‐oxo‐2H‐chromen‐3‐yl)‐4‐
arylnicotinonitrile derivatives (6a–w)
To a mixture of 3‐acetylcoumarin (2, 1 mmol), aldehyde
(3a–w, 1 mmol), NH4OAc (4, 1.5 mmol, 0.115 g) and
malononitrile (5, 1 mmol, 0.066 g) in a round‐bottomed
flask, 50 mg of Fe3O4/SiO2/PTS‐GO‐ZnO (1) was added.
The resulting mixture was stirred under solvent‐free
conditions at 100°C for the appropriate time indicated
in Scheme 2. The reaction progress was monitored using
TLC with a mixture of EtOAc and n‐hexane (1:3) as the
eluent. After completion of the reaction, the mixture
SCHEME 1 One‐pot four‐component synthesis of 2‐amino‐6‐(2‐oxo‐2H‐chromen‐3‐yl)‐4‐arylnicotinonitrile derivatives catalyzed by zinc
oxide (ZnO)‐decorated superparamagnetic silica attached to graphene oxide (Fe3O4/SiO2/PTS‐GO‐ZnO, 1)

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DAVOODI ET AL.
SCHEME 2 Scope of different 2‐amino‐6‐(2‐oxo‐2H‐chromen‐3‐yl)‐4‐arylnicotinonitrile derivatives 6a–w catalyzed by zinc oxide (ZnO)‐
decorated superparamagnetic silica attached to graphene oxide (Fe3O4/SiO2/PTS‐GO‐ZnO, 1) through four‐component reaction strategy.
aReaction conditions: 3‐acetylcoumarin (2, 1 mmol), aldehyde derivatives (3a–w, 1 mmol), NH4OAc (4, 1.5 mmol, 0.115 g) and malononitrile
(5, 1 mmol, 0.066 g), 50 mg Fe3O4/SiO2/PTS‐GO‐ZnO (1).bKnown structure compounds were established from their spectral data and melting
points as compared with authentic samples or literature values.cYields refer to isolated yields of purified products.
was cooled to ambient temperature. Then, EtOAc (5
mL) was added to the reaction mixture and heated.
The Fe3O4/SiO2/PTS‐GO‐ZnO heterogeneous catalyst
was separated using an external magnet and kept for
the next runs. Finally, the desired products were
obtained by recrystallization from EtOAc in good to
high yields.
2.4 | Selected spectral data
2.4.1 | 2‐Amino‐4‐(4‐chlorophenyl)‐6‐(2‐
oxo‐2H‐chromen‐3‐yl) nicotinonitrile (3a)
Light yellow solid, mp 244–246°C; IR (KBr): ν 3458 and
3433 (NH2), 3047 (C−Harom.), 2923 (C−Haliph.), 2216

DAVOODI ET AL.
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(CN), 1728 (COester), 1647, 1610, 1577, 1544, 1396, 1274,
7.43–7.46 (dt, 1H, J = 7.5 Hz, Ar‐H), 7.51–7.53 (d, 1H, J
= 8.3 Hz, Ar‐H), 7.63–7.64 (dd, 2H, J = 4.4 Hz, J' = 1.7
Hz, Pyr‐H), 7.71–7.75 (t, 1H, J = 7.4 Hz, J' = 1.6 Hz, Ar‐
H), 7.80–7.82 (dd, 1H, J = 7.9 Hz, J' = 1.6 Hz, Ar‐H),
8.41 (s, 1H, coumarin 4‐H), 8.75–8.77 (dd, 2H, J = 4.4
Hz, J' = 1.7 Hz, Pry‐H) ppm; 13C‐NMR (500 MHz,
DMSO‐d6): δ 97.02, 115.77, 116.77, 118.98, 119.33,
123.52, 125.10, 125.55, 129.67, 133.58, 144.63, 144.80,
145.10, 147.59, 150.55, 153.99, 153.83, 158.84 ppm; CHN
analysis calcd for C21H12N3O2: C, 71.59; H, 3.43; N,
15.53; found: C, 70.80; H, 3.94; N, 15.53.
1
1176, 1037, 757 cm−1; H‐NMR (500 MHz, DMSO‐d6): δ
6.40 (br s, 2H, NH2), 6.97 (s, 1H, PryH), 7.42–7.45 (t,
1H, J = 7.5 Hz, Ar‐H), 7.50–7.52 (d, 2H, J = 10.0 Hz, Ar‐
H), 7.61–7.70 (m, 3H, ArH), 7.79–7.81 (d, 2H, J = 10.0
Hz, Ar‐H), 8.39 (s, 1H, coumarin 4‐H) ppm.
2.4.2 | 2‐Amino‐4‐(4‐fluorophenyl)‐6‐(2‐
oxo‐2H‐chromen‐3‐yl) nicotinonitrile (3c)
Yellow solid, mp 241–243°C; IR (KBr): ν 3415 and 3423
(NH2), 3047 (C−Harom.), 2956 (C−Haliph.), 2225 (CN),
1730 (COester), 1700, 1610, 1577, 1544, 1400, 1274, 1129,
3 | RESULTS AND DISCUSSION
820, 764 cm−1 1H‐NMR (500 MHz, DMSO‐d6): δ 6.96
;
(br s, 2H, NH2), 6.97 (s, 1H, PyrH), 7.37–7.39 (d, 3H, J
= 10 Hz, Ar‐H), 7.41–7.43 (d, 1H, J = 10.0 Hz, Ar‐H),
7.68–7.69 (d, 1H, J = 5 Hz, ArH), 7.49–7.51 (d, 2H, J =
10.0 Hz, Ar‐H), 8.39 (s, 1H, coumarin 4‐H) ppm.
3.1 | Characterization of the Fe3O4/SiO2/
PTS‐GO‐ZnO catalyst (1)
Characterization of the ZnO‐decorated Fe3O4/SiO2 core‐
shell hybrid covalently attached to GO (Fe3O4/SiO2/PTS‐
GO‐ZnO, 1), as a new magnetic nanocomposite, was
appropriately performed using various methods such as
FT‐IR spectroscopy, TGA, BET and BJH methods,
vibrating‐sample magnetometer (VSM), X‐ray powder dif-
fraction (XRD), field emission scanning electron micros-
copy (FESEM), transmission electron microscopy (TEM)
and energy‐dispersive X‐ray (EDX) spectroscopy. The FT‐
IR spectrum of the Fe3O4/SiO2/PTS‐GO‐ZnO catalyst (1)
has been compared with those of its various precursors in
Figure 2. Absorption signals at 580 and 1105 cm−1 were
assigned to the stretching vibrations of Fe‐O and Si‐O‐Si
bonds, whereas the signals at about 1620 and 3400 cm−1
were attributed to the absorbed water and hydroxy groups.
After modification with GO, new signals were detected for
the Fe3O4/SiO2/PTS‐GO at 1326 cm−1 which can be
2.4.3 | 2‐Amino‐4‐(3‐hydroxyphenyl)‐6‐(2‐
oxo‐2H‐chromen‐3‐yl) nicotinonitrile (3h)
Yellow solid, mp 232–234°C; IR (KBr): ν 3500 and 3321
(NH2), 3030 (C−Harom.), 2956 (C−Haliph.), 2225 (CN),
1700 (COester), 1621, 1600, 1554, 1484, 1229, 1129, 880,
764, 700 cm−1 1H‐NMR (500 MHz, DMSO‐d6): δ 6.91
;
(br s, 2H, NH2), 6.92 (S, 1H, PyrH), 6.97–6.99 (t, 2H, J
= 10 Hz, Ar‐H), 7.31–7.32 (t, 1H, J = 7.8 Hz, Ar‐H),
7.41–7.42 (t, 1H, J = 7 Hz, Ar‐H), 7.50–7.51 (d, 1H, J =
8.2 Hz, Ar‐H), 7.70–7.72 (t, 1H, J = 7.7 Hz, Ar‐H), 7.80
(s, 1H, coumarin 4‐H), 8.38 (S, 1H, OH) ppm.
2.4.4 | 2‐Amino‐4‐(4‐cyanophenyl)‐6‐(2‐
oxo‐2H‐chromen‐3‐yl) nicotinonitrile (3n)
Pale green olive solid, mp 320–322°C; IR (KBr): ν 3473
and 3321 (NH2), 2225 (CN), 1735 (COester), 1680, 1669,
1
1600, 820, 764 cm−1; H‐NMR (500 MHz, DMSO‐d6): δ
7.00 (s, 1H, PyrH), 7.06 (br s, 2H, NH2), 7.43–7.45 (t,
1H, J = 7.75 Hz, Ar‐H), 7.50–7.52 (d, 1H, J = 8.15 Hz,
Ar‐H), 7.70–7.71 (t, 1H, J = 6.4 Hz, Ar‐H), 7.82–7.83 (dd,
2H, J = 7.3 Hz, Ar‐H), 8.03–8.04 (dd, 2H, J = 7.3 Hz, Ar‐
H), 8.40 (S, 1H, coumarin 4‐H) ppm.
2.4.5 | 2‐Amino‐6‐(2‐oxo‐2H‐chromen‐3‐
yl)‐[4,4′‐bipyridine]‐3‐carbonitrile (3v)
Yellow solid, mp 244–246°C; IR (KBr): ν 3373 and 3328
(NH2), 3072 (C−Harom.), 2217 (CN), 1735 (COester), 1666,
FIGURE 2 Fourier transform‐infrared (FTIR) spectra of (a)
graphene oxide (GO), (b) Fe3O4, (c) Fe3O4/SiO2, (d) Fe3O4/SiO2/
PTS‐GO and (e) Fe3O4/SiO2/PTS‐GO‐ZnO core‐shell
nanocomposite (1)
1639, 1608, 1579, 1294 cm−1
;
1H‐NMR (500 MHz,
DMSO‐d6): δ 7.02 (s, 1H, PyrH), 7.09 (br s, 2H, NH2),

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DAVOODI ET AL.
assigned to the stretching of C–O bonds. On the other
hand, the broadand intense band at 2400–3600 cm−1 is
attributed to the stretching of the O–H bonds. Further-
more, the XRD patterns of Fe3O4/SiO2/PTS‐GO‐ZnO com-
posite are presented in Figure 3. The characteristic peak of
graphite at 2θ = 26.4° disappears after strong oxidation.
These data suggest that graphite is successfully converted
to GO after oxidation by the Hummers’ method.[76] The
diffraction signals (2θ) of the as‐synthesized Fe3O4 parti-
cles at 18.0°, 31.0°, 36.2°, 44.0°, 54.5° and 57.0° are in accor-
dance with the pure spinel Fe3O4 (JCPDS no. 89–3854).
On the other hand, the magnetic properties of the pre-
pared nanocatalyst 1 were investigated using a VSM.
Figure 4 shows that the magnetization hysteresis loop
appears S‐like and the magnetic remanence is nearly
zero, representing superparamagnetic behavior of the
Fe3O4/SiO2/PTS‐GO‐ZnO nanocomposite (1). The mag-
netization values were measured to be 68, 63, 30 and 30
emug−1 for Fe3O4, Fe3O4/SiO2, Fe3O4/SiO2/PTS‐GO and
Fe3O4/SiO2/PTS‐GO‐ZnO (1), respectively. The TEM
image shown as inset in Figure 5b clearly reveals that
FIGURE 3 X‐ray powder diffraction (XRD) pattern of the Fe3O4/
SiO2/PTS‐GO‐ZnO core‐shell nanocomposite (1)
FIGURE 5 (a) Field emission scanning electron microscopy
(FESEM) and (b) transmission electron microscopy (TEM) images
of the Fe3O4/SiO2/PTS‐GO‐ZnO core‐shell nanocomposite (1)
Fe3O4 is coated by a silica layer completely to form a
Fe3O4/SiO2 core‐shell structure that is inconsistent with
the magnetization values. This experiment also indicates
that Fe3O4/SiO2 core‐shell was successfully grafted on
two‐dimensional transparent GO sheets. The average par-
ticle size of the prepared Fe3O4/SiO2 core‐shell by the
TEM observations is about 20 nm. Also, SEM images
were obtained to investigate the size and surface mor-
phology of Fe3O4/SiO2/PTS‐GO‐ZnO (1), as shown in
Figure 5a. The resulting image indicated that the ZnO
FIGURE
4
Magnetic hysteresis loops [vibrating‐sample
magnetometer (VSM) curves] of the prepared (a) Fe3O4, (b)
Fe3O4/SiO2, (c) Fe3O4/SiO2/PTS‐GO and (d) Fe3O4/SiO2/PTS‐GO‐
ZnO core‐shell nanocomposite (1)

DAVOODI ET AL.
7 of 12
nanoparticles have almost been distributed uniformly on
the surface of sheet‐like structure of GO. Furthermore,
EDX analysis of this nanocatalyst verifies the presence
of all the expected elements, including, iron, silicon, zinc,
oxygen and carbon, in its structure as illustrated in
Figure 6. The elemental distribution mapping of this
analysis shows signals of carbon:oxygen:silicon:iron:zinc
in the ratio of 29.17:35.10:2.35:18.48:14.90 wt%, respec-
tively. These findings also confirm successful fabrication
of expected ZnO‐decorated superparamagnetic silica
attached to GO (1, Fe3O4/SiO2/PTS‐GO‐ZnO).
The thermal behaviors of Fe3O4/SiO2/PTS‐GO‐ZnO
nanocomposite (1) were further investigated by
TGA/differential thermal analysis (DTA) with heating
from room temperature to 800°C under an air flow (See
ESI). The GO powders show two steps of mass loss at about
200 and 500°C, which are attributed to the removal of
oxygen‐containing groups and carbon oxidation,
FIGURE 6 Energy‐dispersive X‐ray spectroscopy (EDX) analysis
of the Fe3O4/SiO2/PTS‐GO‐ZnO core‐shell nanocomposite (1)
TABLE 1 Optimization of conditions in the reaction of 3‐acetylcoumarin (2), 4‐chlorobenzaldehyde (3a), malononitrile (5) and NH4OAc
(4) under different conditionsa
Entry
Catalyst
Catalyst loading (mg)
Solvent
Temperature (°C)
Time (min)
Yieldb(%)
1
Fe3O4/SiO2/PTS‐GO‐ZnO
Fe3O4/SiO2/PTS‐GO‐ZnO
Fe3O4/SiO2/PTS‐GO‐ZnO
Fe3O4/SiO2/PTS‐GO‐ZnO
Fe3O4/SiO2/PTS‐GO‐ZnO
Fe3O4/SiO2/PTS‐GO‐ZnO
Fe3O4/SiO2/PTS‐GO‐ZnO
Fe3O4/SiO2/PTS‐GO‐ZnO
Fe3O4/SiO2/PTS‐GO‐ZnO
Fe3O4/SiO2/PTS‐GO‐ZnO
Fe3O4/SiO2/PTS‐GO‐ZnO
Fe3O4/SiO2/PTS‐GO‐ZnO
Fe3O4/SiO2/PTS‐GO‐ZnO
Fe3O4
0
–
100
100
100
100
100
100
100
100
r.t.
180
45
35
20
20
12
10
10
140
45
50
50
60
120
85
80
80
–
53
57
74
79
84
97
97
40
94
–
2
5
–
3
10
20
30
40
50
60
50
50
50
50
50
50
50
50
50
–
4
–
6
–
7
–
8
–
9
–
10
11
12
13
14
15
16
17
18
EtOH
EtOH
H2O
CH3CN
THF
–
Reflux
Reflux
100
100
100
100
100
100
32
28
38
44
63
40
Fe3O4/SiO2
–
Fe3O4/SiO2/PTS‐GO
GO
–
–
aReaction conditions: 3‐acetylcoumarin (1 mmol), 4‐chlorobenzaldehyde (1 mmol), malononitrile (1 mmol) and NH4OAc (1.5 mmol).
bIsolated yields.

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DAVOODI ET AL.
respectively.[77] The first peak centered at about 80–100°C
can be related to weight loss due to the evaporation of
physically adsorbed water. Indeed, Fe3O4/SiO2/PTS‐GO‐
ZnO (1) demonstrates a much higher thermal stability
than GO by a total mass loss of 25% when the temperature
reaches 800°C. This mass loss confirmed that ZnO had
been successfully supported on the superparamagnetic sil-
ica attached to GO. On the other hand, the N2‐sorption iso-
therm indicated that the pore sizes of Fe3O4/SiO2/PTS‐
GO‐ZnO (1) are in the mesoporous range (See ESI). The
magnetic material 1 exhibited the type IV isotherm pattern
that is characteristic of the mesoporous structure with rel-
atively broad pore size distributions. The calculated BET
specific surface area of Fe3O4/SiO2/PTS‐GO‐ZnO (1) is
close to 60.48 m2·g−1, and it exhibits a BJH average pore
diameter of 16.5581 nm and total pore volume of 0.2709
3.2 | Investigation of the catalytic activity
of the Fe3O4/SiO2/PTS‐GO‐ZnO catalyst (1)
After characterization, the catalytic activity of ZnO‐
decorated superparamagnetic silica attached to GO
(Fe3O4/SiO2/PTS‐GO‐ZnO, 1) was investigated for the
synthesis of 2‐amino‐6‐(2 oxo‐2H‐chromen‐3‐yl)‐4‐
arylnicotinonitrile derivatives 6 through a systematic
study. In this approach, appropriate reactants were
selected to afford 2‐amino‐4‐(4‐chlorophenyl)‐6‐(2‐oxo‐
2H‐chromen‐3‐yl) nicotinonitrile (6a) via four‐component
reactions of 3‐acetylcoumarin (2), 4‐chlorobenzaldehyde
(3a), ammonium acetate (4) and malononitrile (5) as a
model reaction. The reaction conditions were optimized
by considering different aspects such as appropriate
catalyst loading, different solvents and temperature. The
results are summarized in Table 1. The preliminary
cm3·g−1
.
SCHEME 3 Plausible mechanism for the one‐pot synthesis of 2‐amino‐6‐(2‐oxo‐2H‐chromen‐3‐yl)‐4‐arylnicotinonitrile derivatives 6
catalyzed by Fe3O4/SiO2/PTS‐GO‐ZnO (1)

DAVOODI ET AL.
9 of 12
optimization experiment indicated that the desired prod-
uct 6a was not obtained in the absence of any catalyst even
at 100°C after 180 min (Table 1, entry 1). However, the
yield of desired product 6a was significantly improved in
shorter reaction times at 5 up to 50 mg of the Fe3O4/
SiO2/PTS‐GO‐ZnO (1) loadings under the same reaction
conditions (Table 1, entries 2–8). Interestingly, a quantita-
tive yield of the desired product 6a was obtained when 50
mg of Fe3O4/SiO2/PTS‐GO‐ZnO (1) was used at 100°C
under solvent‐free conditions (Table 1, entry 8).
In the next steps, the model reaction was also investi-
gated in different solvents and temperatures to evaluate
their effects. All of the studied conditions afforded lower
yield of the desired product 6a even in longer reaction
times (Table 1, entries 10–14).[16] On the other hand,
when hydroxylamine hydrochloride (NH2OH·HCl) was
used instead of NH4OAc in the presence of the catalyst
1, the obtained mixture was sticky, and isolation of the
desired product 6a was difficult and laborious.
Encouraged by these results, the catalytic activity of
Fe3O4/SiO2/PTS‐GO‐ZnO (1) was further investigated
for the synthesis of a wide range of 2‐amino‐6‐(2 oxo‐
2H‐chromen‐3‐yl)‐4‐arylnicotinonitrile derivatives (6a–
w) under the optimized conditions [50 mg Fe3O4/SiO2/
PTS‐GO‐ZnO (1) loading, solvent‐free conditions at
100°C. Indeed, both aromatic and aliphatic aldehydes
(3a–w) were involved smoothly in the synthesis of
nicotinonitrile derivatives to afford the corresponding
products (6a–w). From the resulting data in Scheme 2,
it can be concluded that the reaction times for aromatic
aldehydes bearing electron‐withdrawing groups are faster
and with somewhat higher yields than those for electron‐
releasing groups. As it can be seen, high to quantitative
yields of the desired products (6a–w) were obtained
under the optimized solvent‐free conditions in very short
reaction times. After completion of the reaction (moni-
tored by TLC), EtOAc was added and the catalyst 1 was
simply separated from the reaction mixture by an
external magnet.
According to the depicted mechanistic pathway in
Scheme 3, it can be proposed that the chelated zinc cat-
ions by the carboxylate and hydroxyl groups on the edge
or surface of GO as well as free carboxylic acid and
hydroxyl groups of Fe3O4/SiO2/PTS‐GO‐ZnO (1) are
responsible for the initial activation of the carbonyl group
of 3‐acetylcoumarin (2) to facilitate nucleophilic addition
of ammonia source to afford corresponding imine (II)
and enamine intermediates (II'), respectively. Simulta-
neously, aldehydes (3) are activated with Fe3O4/SiO2/
PTS‐GO‐ZnO (1) to undergo condensation with
malononitrile, and form Knovenagel intermediate (III).
In the second step, enamine intermediate (II') reacts with
FIGURE
7
Reusability of Fe3O4/SiO2/PTS‐GO‐ZnO (1)
nanocatalyst for the synthesis of 2‐amino‐4‐(4‐chlorophenyl)‐6‐(2‐
oxo‐2H‐chromen‐3 yl) nicotinonitrile (6a)
TABLE 2 Comparison of the catalytic efficiency of Fe3O4/SiO2/PTS‐GO‐ZnO nanocatalyst (1) vs. other reported catalysts
Entry
Catalyst
Catalyst loading
Conditions
Time (min)
Yield (%)
1
Magnetic cellulose/Ag
150 mg
EtOH/Reflux
90
91[16]
2
Iron (III) phosphate
10 mol%
EtOH/Reflux
120
93[81]
3
4
Trifluoroethanol
Acetic acid
Excess
Excess
Reflux
360
10
90[82]
Microwave irradiation
79[17]
5
Fe3O4/SiO2/PTS‐GO‐ZnO
50 mg
100°C‐Solvent‐free
15
97[This work]

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DAVOODI ET AL.
the intermediate (III) to form Michael adduct (IV). Then,
the intermediate (IV) undergoes cycloaddition, isomeri-
zation and air oxidation facilitated by anomeric oxida-
tion, respectively, in the presence of the magnetic
catalyst 1 to afford the final product (6).[15,78–80]
The authors would also like to acknowledge the support
of Iran Nanotechnology Initiative Council (INIC), Iran.
ORCID
Another key characteristic of this active and efficient
heterogeneous nanocatalyst is its high degree of recycla-
bility. In this part of our study, it has been demonstrated
that Fe3O4/SiO2/PTS‐GO‐ZnO (1) could be recovered and
reused at least six times in the subsequent runs for the
model reaction using the same recovered nanocatalyst
without a considerable loss of its catalytic activity
(Figure 7). Also, FT‐IR, FESEM and TEM analysis from
the recovered catalyst obviously confirm that no substan-
tial changes in the morphology and structure were
observed after seven consecutive runs.
Mohammad G. Dekamin
7018-7363
https://orcid.org/0000-0002-
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How to cite this article: Davoodi F, Dekamin
MG, Alirezvani Z. A practical and highly efficient
synthesis of densely functionalized nicotinonitrile
derivatives catalyzed by zinc oxide‐decorated
superparamagnetic silica attached to graphene
oxide nanocomposite. Appl Organometal Chem.
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SUPPORTING INFORMATION
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article.