Fe3O4?urea/HITh-SO3H as an efficient and reusable catalyst for the solvent-free synthesis of 7-aryl-8H-benzo[h]indeno[1,2-b]quinoline-8-one and indeno[2′,1′:5,6]pyrido[2,3-d]pyrimidine derivatives

Article abstract of DOI:10.1515/chem-2020-0063

In this study, Fe3O4?urea/HITh-SO3H MNPs as a new, efficient, and recyclable solid acid magnetic nanocatalyst was synthesized and characterized using various methods including Fourier transform infrared spectroscopy, thermogravimetric analysis, scanning electron microscopy, transmission electron microscopy, vibrating sample magnetometry, energy-dispersive X-ray spectroscopy, and X-ray powder diffraction. After the characterization of this new magnetic nanocatalyst, it was efficiently utilized for the promotion of the one-pot synthesis of 7-aryl-8H-benzo[h]indeno[1,2-b]quinoline-8-one and indeno[2′,1′:5,6]pyrido[2,3-d]pyrimidine derivatives via three-component reaction of the 1,3-indanedione, aldehyde, and 1-naphthylamine/1,3-dimethyl-6-aminouracil under solvent-free conditions at 80°C. The procedure gave the desired heterocyclic structures in high-to-excellent yields and short reaction times. Also because of the magnetic nature of the nanocatalyst, it can be separated with an external magnetic field and reused at least six runs without any considerable decrease in the catalytic behavior.

Full text of DOI:10.1515/chem-2020-0063

Open Chemistry 2020; 18: 648–662
Research Article
Shenghao Jiang*, Macheng Shen, Fatima Rashid Sheykhahmad
Fe3O4@urea/HITh-SO3H as an efficient and reusable catalyst
for the solvent-free synthesis of 7-aryl-8H-benzo[h]indeno-
[1,2-b]quinoline-8-one and indeno[2′,1′:5,6]pyrido[2,3-d]
pyrimidine derivatives
https://doi.org/10.1515/chem-2020-0063
received October 21, 2019; accepted March 18, 2020
1 Introduction
The use of magnetic nanoparticles (Fe3O4 MNPs) as a
Abstract: In this study, Fe3O4@urea/HITh-SO3H MNPs as
core to support the catalyst in organic transformation
a new, efficient, and recyclable solid acid magnetic
has become quite popular in chemistry. Because they
nanocatalyst was synthesized and characterized using
include unique features such as high dispersion and
various methods including Fourier transform infrared
reactivity, easy separation under external permanent
spectroscopy, thermogravimetric analysis, scanning
electron microscopy, transmission electron microscopy,
magnetic fields and reusability, pairing with two or
multidentate ligands or inorganic structures [1–6]. The
use of magnetic nanoparticles may be restricted for
vibrating sample magnetometry, energy-dispersive X-ray
spectroscopy, and X-ray powder diffraction. After the
reasons such as deformation and aggregation during the
characterization of this new magnetic nanocatalyst, it
chemical process [7]. To remove this restriction and
was efficiently utilized for the promotion of the one-pot
reclaim their features for the specific application, these
synthesis of 7-aryl-8H-benzo[h]indeno[1,2-b]quinoline-
particles need to be modified by functionalizing their
8-one and indeno[2′,1′:5,6]pyrido[2,3-d]pyrimidine deri-
surface via organic or inorganic groups.
vatives via three-component reaction of the 1,3-indane-
Pyrimidine cores are important classes of bioactive
and heterocyclic molecules that have received signifi-
dione, aldehyde, and 1-naphthylamine/1,3-dimethyl-6-
aminouracil under solvent-free conditions at 80°C. The
cant importance in the pharmaceutical studies over
procedure gave the desired heterocyclic structures in
recent years due to their wide range of therapeutic and
high-to-excellent yields and short reaction times. Also
because of the magnetic nature of the nanocatalyst, it
can be separated with an external magnetic field and
reused at least six runs without any considerable
pharmacological features such as anticancer [8], anti-
inflammatory [9], antimicrobial [10], or antihistaminic
activity [11]. Among these compounds, pyrido[2,3-d]
pyrimidine is one of the main groups of heterocyclic
decrease in the catalytic behavior.
compounds annulated uracil; due to their wide range of
Keywords: Fe3O4@urea/HITh-SO3H MNPs, magnetic
nanocatalyst, three-component reaction, solvent free
medicinal activities such as antibacterial, anticonvul-
sants, antiaggressive activity, antifolate, antileishma-
nial, antimicrobial, anti-inflammatory, and inhibitors of
cyclin-dependent kinases [12,13]. Thus it is important to
prepare the pyrido[2,3-d]pyrimidine derivatives. For the
one-pot multicomponent preparation, the most common
types of compounds are as follow: the reaction of 1,3-
indanedione (1 mmol), aryl aldehyde (1 mmol) and 1,3-
dimethyl-6-aminouracil (1 mmol) for preparing indeno
[2′,1′:5,6]pyrido[2,3-d]pyrimidine.
The indenoquinoline derivatives, such as ubiquitous
nitrogen-containing heterocycles, play important roles
in medicinal chemistry by possessing a diverse spectrum
of pharmacological activities such as steroid reductase
inhibitors [14], acetylcholinesterase inhibitors [15], anti-
tumor [16,17], and antimalarial activities [18]. Therefore,

* Corresponding author: Shenghao Jiang, School of Engineering
and Applied Sciences, Harvard University, 29 Oxford Street,
Cambridge, MA 02318, United States of America,
e-mail: ckchangkunck@163.com
Macheng Shen: Department of Mechanical Engineering,
Massachusetts Institute of Technology, 77, Massachusetts Ave,
Cambridge, MA 02139, United States of America
Fatima Rashid Sheykhahmad: Young Researchers and Elite club,
Ardabil Branch, Islamic Azad University, Ardabil, Iran
Open Access. © 2020 Shenghao Jiang et al., published by De Gruyter.
This work is licensed under the Creative Commons Attribution 4.0
Public License.

Fe3O4@urea/HITh-SO3H as an efficient and reusable catalyst for the solvent-free synthesis

649
the synthesis of these heterocyclic compounds is 2.2 Preparation of silica-coated magnetic
significant for both organic and medicinal chemists.
Several applications of quinoline-fused frameworks have
nanoparticles (Fe3O4@SiO2 MNPs)
already been highlighted in the literature as scaffolds of
biological substances, such as ligands for preparing
OLED phosphorescent complexes and intermediates in
the dyestuffs industry [19–25]. The most common
process for synthesizing indeno [1,2-b]quinoline diones
have been reported via the condensation of 1-naphthy-
lamine (1 mmol), aldehyde (1 mmol), and 2H-indene-1,3-
dione (1 mmol).
One gram of Fe3O4 MNPs was added to a mixture
including 10 ml deionized water, 45 ml ethanol, and 7 ml
of aqueous ammonia solution (25 wt%) and agitated at
ambient temperature for about 30 min. After the time
required, 6 ml of tetraethylorthosilicate (TEOS) was
added dropwise to the reaction vessel and stirred for
24 h under mechanical agitation to afford silica-coated
magnetic nanoparticles (Fe3O4@SiO2). Finally, the resulting
solid material was isolated using a permanent magnetic
field, washed thoroughly with ethanol, and then dried in
vacuum at 50°C for 24 h.
2 Experimental
2.2.1 Preparation of chloropropyl-functionalized
magnetic nanoparticles (Fe3O4@CPTES MNPs)
2.1 General
The chemicals used in this work were obtained from Merck,
Fluka, and Aldrich chemical companies and were utilized
with any further purification. All melting points were
achieved on an Electrothermal 9100 instrument. Fourier
transform infrared spectroscopy (FTIR) spectroscopy was
Three grams of the above-synthesized Fe3O4@SiO2 was
modified with 6 ml of 3-chloropropyltriethoxysilane (CPTES)
in dry toluene (80 ml), and the reaction solution was refluxed
under nitrogen atmosphere for 12 h. The obtained Fe3O4@
CPTES MNPs were filtered with the help of a permanent
magnetic field, rinsed thoroughly with dry toluene and
diethyl ether, and then dried in vacuum at 80°C for 8 h.
done as KBr discs with
a Shimadzu spectrometer.
Thermogravimetric analysis (TGA) spectra were recorded
using a TGA thermoanalyzer (PerkinElmer) instrument.
Scanning electron microscopy (SEM) images were obtained
using a Tescanvega II XMU Digital Scanning Microscope.
Vibrating sample magnetometry (VSM) analyses were
performed in a Lakeshore 7407 at ambient temperature.
Energy dispersive X-ray spectroscopy (EDX) measurement
was performed using ESEM, Philips, and XL30. X-ray
powder diffraction (XRD) patterns of samples were obtained
using a Siemens D-5000 X-ray diffractometer. Transmission
electron microscope (TEM) images were recorded with a
TEM Philips EM 208S instrument.
2.2.2 Preparation of urea-functionalized magnetic
nanoparticles (Fe3O4@CPTES/urea MNPs)
About 2.5 g of Fe3O4@CPTES and 10 mmol of urea were
added to 50 ml dry toluene and refluxed for 12 h. The
resulting black sediment (Fe3O4@CPTES/urea MNPs) was
filtered with the help of a permanent magnetic field, washed
three times with 30 ml of ethanol to remove the unreacted
chemicals and dried in vacuum at 50°C for 24 h.
2.1.1 Catalyst synthesis
2.2.3 Preparation of Fe3O4@urea/HITh MNPs
2.1.1.1 Preparation of the magnetite nanoparticles Two grams of Fe3O4@CPTES/urea MNPs was dispersed
(Fe3O4 MNPs) in 25 ml dry toluene by ultrasonication for half an hour.
About 4.8 g of FeCl3·6H2O and 1.7 g of FeCl2·4H2O were Subsequently, 0.65 g of 4,5-dihydroxyimidazolidine-2-
dispersed in 100 ml of deionized water by ultrasonica- thione (HITh) and 0.1 ml of trifluoroacetic acid (TFA)
tion. Then, 10 ml of aqueous ammonia (25%) was added were added into the reaction flask, and the mixture was
dropwise to the reaction solution under Ar atmosphere agitated for 1 h at ambient temperature. Then, the
by stirring about 30 min with a magnetic stirrer. After resulting solid product was separated by magnetic
the time taken to advance the reaction, the black decantation, washed twice with distilled water (20 ml)
magnetite precipitate (Fe3O4) was rinsed three times and acetone (10 ml) to eliminate the unreacted chemi-
with deionized water and dried in vacuum at 60°C.
cals, and dried in vacuum at 70°C for 18 h.

650
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Shenghao Jiang et al.
2.2.4 Preparation of Fe3O4@urea/HITh-SO3H MNPs
2.2.6 General process for the preparation of indeno
[2′,1′:5,6]pyrido[2,3-d]pyrimidine derivatives 6
At the end of work, 1 g of Fe3O4@urea/HPITh MNPs was
dispersed in 25 ml dry dichloromethane by ultrasonica- A mixture containing 1,3-indanedione (1 mmol), alde-
tion for 30 min and then 10 mmol of 1,4-butane sulfonate hyde (1 mmol), 1,3-dimethyl-6-aminouracil (1 mmol),
was added to the reaction vessel. The reaction mixture and Fe3O4@urea/HITh-SO3H MNPs magnetic nanocata-
was refluxed for 8 h; after this, the resulting solid lyst (15 mg) reacted with each other in a one-pot
product was isolated using magnetic decantation. The condensation at 80°C under solvent-free conditions. To
obtained solid catalyst was rinsed three times with 30 ml ensure the completion of the reaction, the reaction
of distilled water and dried overnight in vacuum oven at mixture was monitored using TLC. After viewing a single
60°C. This synthesis is exhibited in Scheme 1.
spot on the TLC for the desired product, the catalyst was
separated by a permanent magnetic field, and the
desired pure products were achieved from the reaction
2.2.5 General process for the preparation of 7-aryl-8H- container by recrystallization from the hot ethanol.
benzo[h]indeno[1,2-b]quinoline-8-one
derivatives 4
Ethical approval: The conducted research is not related
to human or animal use.
A mixture containing 1,3-indanedione (1 mmol), aldehyde
(1 mmol), 1-naphthylamine (1 mmol), and Fe3O4@urea/
HITh-SO3H MNPs magnetic nanocatalyst (10 mg) reacted
with each other in a one-pot condensation at 80 °C under
solvent-free conditions. To ensure the completion of the
reaction, thin layer chromatography (TLC) was used to
monitor the reaction mixture. After viewing a single spot
on the TLC for the final product, the catalyst was isolated
using an external magnet, and the desired pure products
were attained from the reaction container by recrystalli-
zation from the hot ethanol.
3 Results and discussion
3.1 Catalyst characterization
3.1.1 FTIR analysis of Fe3O4@urea/HITh-SO3H MNPs
Figure 1 exhibits FTIR spectra for Fe3O4@CPTES MNPs,
Fe3O4@urea/HITh MNPs, Fe3O4@urea/HITh-SO3H MNPs,
Scheme 1: Synthesis of Fe3O4@urea/HITh-SO3H MNPs.

Fe3O4@urea/HITh-SO3H as an efficient and reusable catalyst for the solvent-free synthesis

651
Figure 1: FTIR spectra of Fe3O4@CPTES MNPs, Fe3O4@urea/HITh MNPs, Fe3O4@urea/HITh-SO3H MNPs, and recovered Fe3O4@urea/HITh-
SO3H MNPs.
and recovered Fe3O4@urea/HPITh-SO3H MNPs. The FTIR 3.1.2 Thermal analysis of Fe3O4@urea/HITh-SO3H MNPs
spectrum for the Fe3O4@CPTES MNPs shows a broad
peak at 3,436 cm−1 that can be attributed to the The TGA corresponding to the Fe3O4@CPTES MNPs,
stretching vibration of the O–H bands, which are linked Fe3O4@urea/HPITh MNPs, and Fe3O4@urea/HITh-SO3H
to the surface of Fe3O4 nanoparticles. Two typical MNPs exhibited information about functional organic
absorption peaks at 578 and 465 cm−1 can be attributed groups bonded on the magnetic nanoparticles’ surface
to the stretching vibration of the Fe–O band of the Fe3O4
lattice, while the characteristic peak at 1,087 cm−1
corresponds to the Si–O–Si stretching vibration. The
existence of a weak peak at 1,621 cm−1 comes from
vibrations of O–H stretching and twisting bonds of
Si–O–H and H–O–H in the silica shell, respectively. The
absorption band at 2,968 cm−1 is associated with the C–H
stretching vibration of 3-chloropropyltriethoxysilane
(CPTES) group. The weak absorption peak at 1,633 cm−1
is attributable to the C]O stretching vibrations of the
amidic group in Fe3O4@CPTES/urea MNPs. Moreover,
the absorption correlated to C]S peak vibration appears
at 2,325 cm−1. The existence of SO3H groups in the
Fe3O4@urea/HITh-SO3H MNPs are claimed with 3,405
and 1,239 cm−1 peaks relating to the O–H and O–SO2
stretching vibration, respectively. It is worth explaining
that the FTIR spectra for recovered Fe3O4@urea/HITh-
SO3H MNPs after the third recovery and reuse do not
show any significant change.
Figure 2: TGA curves of Fe3O4@CPTES MNPs, Fe3O4@urea/HITh
MNPs, and Fe3O4@urea/HITh-SO3H MNPs.

652
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Shenghao Jiang et al.
and the thermal stability through the primary loss of
mass (Figure 2). TGA data for all cases showed about 4%
loss of mass below 150°C because of the loss of the
surface O–H groups as well as desorption of a small
quantity of adsorbed solvents. From the TGA curve of
Fe3O4@CPTES MNPs, it can be inferred that the loss of
mass was about 7%, which can be chiefly attributed to
the CPTES organic functional group on the core–shell
structure surface. With further increase in temperature,
the TGA curve corresponding to Fe3O4@urea/HITh MNPs
indicated a more remarkable loss of mass compared with
that found in Fe3O4@CPTES MNPs. This change in the
slope of the curve can be attributed to the decomposition
of propyl groups, urea, and HITh on the surface of
core–shell structure. Besides the similar loss of mass for
all three samples, Fe3O4@urea/HITh-SO3H MNPs have
two weight loss steps that are associated with the
decomposition of organic functional groups and SO3H
molecules.
Figure 4: TEM image of Fe3O4@urea/HITh-SO3H MNPs.
3.1.4 TEM analysis of Fe3O4@urea/HITh-SO3H MNPs
3.1.3 SEM analysis of Fe3O4@urea/HITh-SO3H MNPs
TEM image of Fe3O4@urea/HITh-SO3H MNPs is depicted
in Figure 4. According to this image, the particle size of
Figure 3 shows the morphology and structure of the synthesized heterogeneous magnetic nanocatalyst is
Fe3O4@CPTES MNPs and Fe3O4@urea/HITh-SO3H using found to be approximately 17 nm.
SEM. Fe3O4@CPTES MNPs have a mean particle dimen-
sion of about 40 nm (Figure 3a). The SEM micrograph
shown in Figure 3b demonstrates clear and vivid 3.1.5 VSM analysis of Fe3O4@urea/HITh-SO3H MNPs
changes in the morphology of the Fe3O4@urea/HITh-
SO3H, which can be mainly associated with the bonding To study the magnetic feature of Fe3O4 MNPs and
of acidic groups to the catalyst surface. The particle Fe3O4@urea/HITh-SO3H MNPs, magnetic measurements
dimension of Fe3O4@urea/HITh-SO3H MNPs was were carried out by a room temperature VSM under
about 50 nm.
applied magnetic field (Figure 5). The obtained values
Figure 3: SEM image of (a) Fe3O4@CPTES MNPs and (b) Fe3O4@urea/HITh-SO3H MNPs.

Fe3O4@urea/HITh-SO3H as an efficient and reusable catalyst for the solvent-free synthesis

653
for the saturation magnetizations of Fe3O4 MNPs and
Fe3O4@urea/HITh-SO3H MNPs were 60.29 and
29.35 emu/g, respectively. These values indicate that
the magnetic saturation of the catalyst has been
reduced. Despite this decline in the magnetic saturation,
the heterogeneous magnetic nanocatalyst can still be
efficiently isolated from the reaction mixture using a
powerful magnet.
3.1.6 EDX analysis of Fe3O4@urea/HITh-SO3H MNPs
The elemental composition of Fe3O4@urea/HITh-SO3H
MNPs was obtained using EDX (Figure 6). The EDX
spectrum exhibits the characteristic peaks (Fe, O, N, Si,
and S) of the catalyst.
Figure 5: Magnetic curves of Fe3O4 MNPs and Fe3O4@urea/HITh-
SO3H MNPs.
3.1.7 XRD analysis of Fe3O4@urea/HITh-SO3H MNPs
The structure of Fe3O4 (a) and Fe3O4@urea/HITh-SO3H
MNPs (b) was analyzed using the XRD spectroscopy in
the 2θ range of 10°–80°. As shown in Figure 7, XRD of
the Fe3O4 MNPs displayed six reflections at 2θ values:
30.08, 35.91, 43.96, 53.78, 57.84, and 63.05, which were
marked by the diffractions of (220), (311), (400), (422),
(511), and (440), respectively. The same sets of reflec-
tions were also obtained for Fe3O4@urea/HITh-SO3H
MNPs, indicating the retention of the crystalline struc-
ture of Fe3O4 MNPs during surface modification.
This study aimed to publish the rapid and effective pre-
paration of 7-aryl-8H-benzo[h]indeno[1,2-b]quinoline-8-one
Figure 6: EDX of Fe3O4@urea/HITh-SO3H MNPs.
Figure 7: XRD for Fe3O4 MNPs (a) and Fe3O4@urea/HITh-SO3H MNPs (b).

654
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Shenghao Jiang et al.
R
O
NH2
80oC
N
solvent-free
O
O
CHO
4
3
O
Fe3O4@urea/HITh-SO3H MNPs
R
Me
R
N
1
2
O
O
solvent-free
80oC
N
Me
5
O
H2N
Me
N
N
N
O
Me
6
Scheme 2: Production of 7-aryl-8H-benzo[h]indeno[1,2-b]quinoline-8-one 4 and indeno[2′,1′:5,6]pyrido[2,3-d]pyrimidine 6 derivatives
using Fe3O4@urea/HITh-SO3H MNPs.
and indeno[2′,1′:5,6]pyrido[2,3-d]pyrimidine derivatives
To screen the reaction conditions to produce 7-aryl-
with lower loading of the new, efficient, and recycl- 8H-benzo[h]indeno[1,2-b]quinoline-8-one derivatives,
able solid acid magnetic nanocatalyst (e.g., Fe3O4@ the effect of the solvents, the concentrations of catalyst,
urea/HITh-SO3H MNPs) under solvent-free conditions and the reaction temperature were explored via the
(Scheme 2).
three-component reaction of 1,3-indanedione 1 (1 mmol),
Table 1: Optimizing the three-component reaction of 1,3-indanedione (1), 4-chlorobenzaldehyde (2d), and 1-naphthylamine (3) under
different conditionsa
Cl
NH2
O
O
CHO
Cl
solvent-free
Fe3O4@urea/HITh-SO3H MNPs
80oC
O
N
1
2d
3
4d
Entry
Solvent
Catalyst (mg)
Temp. (°C)
Time (min)
Yieldb (%)
1
2
3
4
5
6
7
8
9
H2O
EtOH
10
10
10
—
15
5
10
10
10
10
10
10
Reflux
Reflux
80
80
80
80
25
50
60
60
35
4
60
4
35
85
98
Trace
95
83
45
78
85
91
96
93
Solvent free
Solvent free
Solvent free
Solvent free
Solvent free
Solvent free
Solvent free
Solvent free
Solvent free
Solvent free
4
60
15
10
8
4
4
10
11
12
70
90
100
a Reaction conditions: 1,3-indanedione (1 mmol), 4-chlorobenzaldehyde (1 mmol), 1-naphthylamine (1 mmol), and needed concentration of
the catalysts. b The yields refer to the isolated product.

Fe3O4@urea/HITh-SO3H as an efficient and reusable catalyst for the solvent-free synthesis

655
Table 2: Fe3O4@urea/HITh-SO3H MNPs-catalyzed synthesis of 7-aryl-8H-benzo[h]indeno[1,2-b]quinoline-8-one derivativesa
Entry
RCHO (2)
Product
Yield
(%)/time (min)
M.P. (obsd) (°C)
201–203
M.P. (°C) [lit.]
202–204 [26]
1
O
H
94/6
96/4
95/5
O
N
4a
4b
4c
Cl
O
2
3
290–292
229–231
289–291 [27]
230–232 [26]
Cl
Cl
H
O
O
N
O
O
Cl
H
H
N
4
Cl
98/4
95/7
91/8
253–256
209–212
218–221
259–261 [27]
212–214 [26]
220–222 [26]
Cl
Cl
O
N
4d
4e
5
Cl
O
Cl
H
Cl
O
N
O
Cl
6
Cl
Cl
Cl
H
O
N
4f
O
O
Br
7
96/6
97/5
233–235
216–219
236–238 [26]
218–220 [26]
Br
H
H
O
O
N
4g
Br
8
Br
N
4h

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Shenghao Jiang et al.
Table 2: continued
Entry
RCHO (2)
Product
Yield
(%)/time (min)
M.P. (obsd) (°C)
225–227
M.P. (°C) [lit.]
222–224 [26]
O
NO2
9
96/6
O2N
H
O
N
4i
O
NO2
10
97/5
225–227
210–212 [26]
H
O2N
O
N
F
4j
4k
O
11
98/6
98/8
238–240
243–245
231–235 [27]
H
F
O
N
O
CN
12
240–241 [28]
H
NC
HO
O
N
4l
13
14
O
O
OH
89/12
93/10
230–232
251–253
228–229 [27]
256–260 [27]
H
H
O
N
4m
Me
Me
O
N
4n
15
O
OMe
91/10
89/12
231–234
231–234
233–235 [26]
H
MeO
O
O
N
4o
4p
OMeO
16
233–235 [26]
OMe
H
N
a Reaction conditions: 1,3-indanedione (1 mmol), aldehyde (1 mmol), 1-naphthylamine (1 mmol), and Fe3O4@urea/HITh-SO3H MNPs (10 mg).

Fe3O4@urea/HITh-SO3H as an efficient and reusable catalyst for the solvent-free synthesis

657
Table 3: Optimization of the three-component reaction of 1,3-indanedione (1), 4-nitrobenzaldehyde (2), and 1,3-dimethyl-6-aminouracil
(5) under different conditionsa
NO2
O
O
O
CHO
solvent-free
Me
O
O
O
N
Fe3O4@urea/HITh-SO3H MNPs
Me
N
N
H2N
80oC
N
N
O
Me
NO2
Me
1
2j
5
6j
Entry
Solvent
Catalyst (mg)
Temp. (°C)
Time (min)
Yieldb (%)
1
2
3
4
5
6
7
8
9
H2O
EtOH
15
15
15
—
20
10
15
15
15
15
15
15
Reflux
Reflux
80
80
80
80
25
50
60
60
35
15
60
15
35
85
Solvent free
Solvent free
Solvent free
Solvent free
Solvent free
Solvent free
Solvent free
Solvent free
Solvent free
Solvent free
96
Trace
93
85
42
75
83
90
94
92
15
60
25
20
20
15
10
11
12
70
90
100
15
a Reaction conditions: 1,3-indanedione (1 mmol), 4-nitrobenzaldehyde (1 mmol), 1,3-dimethyl-6-aminouracil (1 mmol), and needed
concentration of the catalysts. b The yields refer to the isolated product.
4-chlorobenzaldehyde 2d (1 mmol), and 1-naphthyl- decreased yield (Table 1, entry 6). Moreover, when the
amine 3 (1 mmol). The results are listed in Table 1. To reaction was conducted in the absence of a catalyst, the
attain the optimum reaction solvent, different solvents product yields decreased remarkably and only a trace
(e.g., water, ethanol, and solvent-free conditions) were level of the desired product was found on TLC, even after
examined in the presence of a certain concentration of the reaction time was prolonged to 60 min (Table 1,
catalyst (Table 1, entries 1–3). The reaction gave lower entry 4). Also, the effect of temperature was checked on
yields when water was utilized as the solvent (Table 1, the reaction yield (Table 1, entries 3 and 7–12). It is clear
entry 1). According to the results, the highest reaction that a low yield of the product was achieved without
yield was obtained when using ethanol as the solvent heating (Table 1, entry 7). The yield of the product was
(Table 1, entry 2). However, the optimal rate and yield increased at higher temperatures (entries 3 and 8–10).
were achieved in the absence of solvent for the reaction However, a further increase in temperature did not
(Table 1, entry 3). Moreover, the conditions regarding the improve the yield of reaction (Table 1, entries 11 and 12).
concentration of catalyst were evaluated on the reaction
After optimizing the reaction conditions, the generality
yield. After numerous screening experiments with of these conditions was studied via multifarious aromatic
different levels of the nanocatalyst, it was observed aldehydes, the outcomes of which are listed in Table 2.
that using 10 mg of the Fe3O4@urea/HITh-SO3H MNPs It was observed that aromatic aldehydes carrying both
was applicable to complete the reaction at the short different electron-donating and electron-withdrawing groups
reaction time (Table 1, entry 3). Enhancing the concen- were subjected to the condensation and in all cases, the
tration of catalyst beyond 10–15 mg did not increase the relating 7-aryl-8H-benzo[h]indeno[1,2-b]quinoline-8-one
yield (Table 1, entry 5). A low amount of the catalyst derivatives (4a–p) were obtained in high-to-excellent
required for the reaction from 10 to 5 mg resulted in a yields after the appropriate reaction times.

658

Shenghao Jiang et al.
Table 4: Fe3O4@urea/HITh-SO3H MNPs-catalyzed synthesis of indeno[2′,1′:5,6]pyrido[2,3-d]pyrimidine derivativesa
Entry
RCHO (2)
Product
Yield
(%)/time (min)
M.P. (obsd) (°C)
>300
M.P. (°C) [lit.]
>300 [34]
1
O
H
91/15
O
N
O
Me
N
N
O
Me
6a
Cl
O
2
3
94/15
93/18
>300
>300
>300 [33]
>300 [35]
Cl
O
H
O
Me
N
N
N
Me
O
6b
6c
Cl
O
O
Cl
H
H
O
O
Me
N
N
N
Me
O
Cl
4
5
96/15
96/18
95/20
>300
>300 [32]
O
Cl
Cl
O
Me
N
N
N
Me
O
6d
6e
Cl
Cl
O
295–297
252–255
297–298 [35]
253–256 [35]
H
Cl
O
O
Me
N
N
N
Me
O
Cl
O
6
Cl
Cl
Cl
H
O
O
Me
N
N
N
Me
O
6f
Br
7
O
O
92/15
95/12
>300
>300
>300 [33]
>300 [35]
Br
H
H
O
O
Me
N
N
N
Me
O
6g
Br
8
O
Br
O
Me
N
N
N
Me
O
6h
6i
NO2
O
9
93/15
>300
>300 [32]
O2N
H
O
N
O
Me
N
N
Me
O

Fe3O4@urea/HITh-SO3H as an efficient and reusable catalyst for the solvent-free synthesis

659
Table 4: continued
Entry
RCHO (2)
Product
Yield
(%)/time (min)
M.P. (obsd) (°C)
256–259
M.P. (°C) [lit.]
258–260 [34]
NO2
O
10
96/15
H
O2N
O
N
O
Me
N
N
F
O
Me
6j
O
11
94/12
291–295
294–297 [35]
H
O
N
F
O
Me
N
N
O
Me
6k
6l
CN
O
12
13
93/10
92/20
>300
>300
>300 [33]
>300 [33]
H
O
N
O
NC
Me
Me
N
N
O
Me
Me
O
H
O
O
O
Me
N
N
N
Me
O
6m
MeO
14
92/22
>300
>300 [35]
OMe
MeO
MeO
H
O
N
O
Me
N
N
Me
O
6n
a Reaction conditions: 1,3-indanedione (1 mmol), aldehyde (1 mmol), 1,3-dimethyl-6-aminouracil (1 mmol), and Fe3O4@urea/HITh-SO3H
MNPs (15 mg).
Also, we reported a fast and effective one-pot three- aromatic aldehydes comprising electron-withdrawing
component production of indeno[2′,1′:5,6]pyrido[2,3-d] and electron-donating groups in the existence of 15 mg
pyrimidine derivatives through the reaction of 1,3- of Fe3O4@urea/HITh-SO3H MNPs were investigated to
indanedione, aldehyde, 1,3-dimethyl-6-aminouracil in react with 1,3-indanedione and 1,3-dimethyl-6-aminour-
the existence of Fe3O4@urea/HITh-SO3H MNPs (Table 3). acil, and the outcomes are listed in Table 4. It was
To determine the best optimal conditions, we performed observed that the above-mentioned aromatic aldehydes
the reaction between 1,3-indanedione
1 (1 mmol), produced a high percentage of products in reaction with
4-nitrobenzaldehyde 2j (1 mmol), and 1,3-dimethyl-6- two other components.
aminouracil 5 (1 mmol), in the existence of 15 mg of
Scheme 3 presents a reasonable pathway for the
Fe3O4@urea/HITh-SO3H MNPs at 80°C under solvent- one-pot three-component condensation of 1,3-indane-
free conditions. The final product 6j was achieved with dione 1, various aldehyde 2, 1-naphthylamine 3/1,3-
an excellent yield (96%) within 15 min (Table 3, entry 3). dimethyl-6-aminouracil 5, and Fe3O4@urea/HITh-SO3H
Under optimum conditions, the scope and generality MNPs. Initially, 1,3-indanedione 1 and carbonyl group of
of this procedure were explored. To synthesize indeno activated aldehyde 2 as the reactant materials react with
[2′,1′:5,6]pyrido[2,3-d]pyrimidine derivatives, a variety of each other through
a Knoevenagel condensation

660

Shenghao Jiang et al.
cat-SO3H
cat-SO3H
O
O
O
H
R
2
1
H2O
O
O
H
N
R
7
4, 6
O
R
NH2
H2O
3, 5
OH
H
N
NH2
8
O
9
H
O
R
O
R
cat-SO3H
Scheme 3: A probable mechanism corresponding to the one-pot three-component reaction of 1,3-indanedione, aldehyde, and
1-naphthylamine/1,3-dimethyl-6-aminouracil, catalyzed by Fe3O4@urea/HITh-SO3H MNPs under solvent-free conditions.
reaction to obtain intermediate 7. Then, the polar
Recyclability is an important merit of any catalysts,
transition state 8 is obtained by adding 1-naphthylamine therefore, studying the recyclability of the Fe3O4@urea/
3/1,3-dimethyl-6-aminouracil 5, as the C–H-activated HITh-SO3H MNPs was necessary (Figure 8). To this end,
acid, via Michael addition to the intermediate 7. This the reaction was performed using the three-component
material is not stable and is converted through cycliza- condensation of 1,3-indanedione (1 mmol), 4-chloroben-
tion, dehydration, and oxidation to desired products zaldehyde (1 mmol), and 1-naphthylamine/1,3-dimethyl-
4, 6.
6-aminouracil (1 mmol) in the existence of the catalytic
Figure 8: The recycling of Fe3O4@urea/HITh-SO3H MNPs in the preparation of 7-(4-chlorophenyl)-8H-benzo[h]indeno[1,2-b]quinolin-8-one
4d (a) and 5-(4-chlorophenyl)-1,3-dimethyl-1H-indeno[2′,1′:5,6]pyrido[2,3-d]pyrimidine-2,4,6(3H)-trione 6d (b) derivatives.

Fe3O4@urea/HITh-SO3H as an efficient and reusable catalyst for the solvent-free synthesis

661
Table 5: Comparison of the outcomes of the production of 7-aryl-8H-benzo[h]indeno[1,2-b]quinoline-8-one and indeno[2′,1′:5,6]pyrido
[2,3-d]pyrimidine derivatives by means of different catalysts
Entry
Catalyst and conditions
Reaction time (min)
Yield (%)
Ref.
Cl
1
Fe3O4@cellulose-OSO3H/solvent‐free/40°C
[Fe(HSO4)3]/DMSO/90°C
5
210
120
360
45
40
90
86
96
94
98
28
30
29
31
26
This work
2
3
4
5
7
P(4-VPH)HSO4/EtOH/reflux
O
H6P2W18O62 18H2O/acetic acid/reflux
TBM/solvent‐free/80°C
Fe3O4@urea/HITh-SO3H MNPs/solvent‐free/80°C
N
4
NO2
1
InCl3/H2O/reflux
60
30
25
210
30
15
90
92
94
91
95
96
32
33
34
35
36
This work
2
3
4
5
7
Co3O4-CS-HPA/EtOH/ultrasound
Nano-Fe3O4@SiO2-SO3H/H2O/70°C
[bmim]Br/solvent‐free/95°C
Nano-Fe3O4@cellulose-SO3H/H2O/80°C
Fe3O4@urea/HITh-SO3H MNPs/solvent‐free/80°C
O
O
N
N
N
O
level of Fe3O4@urea/HITh-SO3H MNPs at 80°C. At the end Conflict of interest: Authors declare no conflict of
of the reaction, the catalyst was isolated from the reaction interest.
solution using an external magnet and rinsed with ethanol
several times, dried under reduced pressure, and reused in
subsequent reactions at least 6 runs without any consider-
able reduction in the yield of the products.
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