Ferric (III) complex supported on superparamagnetic Fe3O4@SiO2 as a reusable Lewis acid catalyst: a new highly efficient protocol for the synthesis of acridinedione and spiroquinazolin-4(3H)-one derivatives

Article abstract of DOI:10.1007/s11164-019-03942-w

Nano-Fe₃O₄@SiO₂-3,4-dihydroxybenzaldehyde/barbituric acid/phthalhydrazide-FeCl₃ (nano-Fe₃O₄@SiO₂-HBP-FeCl₃) was prepared and authenticated by usual analytical and spectroscopic techniques. The prepared nano-Fe₃O₄@SiO₂-HBP-FeCl₃ was applied to acridinedione and spiroquinazolin-4(3H)-one derivatives under green conditions. In addition, this research offers several advantages such as very easy reaction conditions, simple work-up, excellent yields, high purity of the desired product, short reaction time and one-pot reaction to synthesize Fe₃O₄@SiO₂-HBP-FeCl₃. The recycling studies revealed that catalyst could be easily recovered using an external magnet and reused five times without significant loss of its catalytic activity.

Full text of DOI:10.1007/s11164-019-03942-w

Research on Chemical Intermediates
https://doi.org/10.1007/s11164-019-03942-w
Ferric (III) complex supported on superparamagnetic
Fe3O4@SiO2 as a reusable Lewis acid catalyst: a new
highly efcient protocol for the synthesis of acridinedione
and spiroquinazolin‑4(3H)‑one derivatives
Hadi Mohammadi1 · Hamid Reza Shaterian1
Received: 9 May 2019 / Accepted: 27 July 2019
© Springer Nature B.V. 2019
Abstract
Nano-Fe3O4@SiO2-3,4-dihydroxybenzaldehyde/barbituric
acid/phthalhydrazide-
FeCl3 (nano-Fe3O4@SiO2-HBP-FeCl3) was prepared and authenticated by usual
analytical and spectroscopic techniques. The prepared nano-Fe3O4@SiO2-HBP-
FeCl3 was applied to acridinedione and spiroquinazolin-4(3H)-one derivatives under
green conditions. In addition, this research ofers several advantages such as very
easy reaction conditions, simple work-up, excellent yields, high purity of the desired
product, short reaction time and one-pot reaction to synthesize Fe3O4@SiO2-HBP-
FeCl3. The recycling studies revealed that catalyst could be easily recovered using
an external magnet and reused fve times without signifcant loss of its catalytic
activity.
Keywords Nano-Fe3O4@SiO2-HBP-FeCl3 · Superparamagnetic nanocatalyst ·
Green synthesis · Acridinediones · Spiroquinazolin-4(3H)-ones
Introduction
The objective of science is recently shifted toward preserving environment; thus,
catalyst recovery and reusability are important properties in catalytic processes [1,
2]. Nanosized metal particles are readily used and intrinsically have a high surface
area that provides an excellent accessibility of the surface-bound active catalytic
sites [3–9]. One of the important and signifcant groups of nanoparticles is magnetic
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s1116
4-019-03942-w) contains supplementary material, which is available to authorized users.
*
Hadi Mohammadi
mohammadi_hadi84@yahoo.com
1
Department of Chemistry, Faculty of Sciences, University of Sistan and Baluchestan, PO
Box 98135-674, Zahedan, Iran
Vol.:(0123456789)
1 3

H. Mohammadi, H. R. Shaterian
nanoparticles (MNPs). Magnetic nanoparticles are of great importance to research-
ers because of their applications for catalysis [10], and MNPs-based magnetically
retrievable catalysis has received considerable attention in synthetic chemistry
[11–14]. However, despite substantial progress, research is toward applications of
MNPs in the synthesis of magnetically retrievable organocatalysts. MNPs have ten-
dency to form agglomerates to reduce the energy associated with the high surface
area-to-volume ratio of the nanosized particles [15], because they are chemically
highly active [16]. A solution for this problem is to protect the magnetic core with
an outer sell such as silica [17] or polymers [18]. Mostly, silica is used to protect
the magnetic core providing appropriate properties, including preventing aggrega-
tion, which increases their stability and invariant catalytic activity. Also, the surface
silanol groups can be covalently grafted to diferent organocatalysts [19, 20]. Mag-
netic core–shell structures of silica such as Fe3O4@SiO2 can be easily functional-
ized by linker groups which can fctionalized by a range of diferent organocatalysts
[21]. In recent years, magnetic nanoparticles (MNPs) (e.g., Fe3O4) have been exten-
sively investigated as inorganic catalyst supports the synthesis of organic–inorganic
hybrid catalysts [22–24], because of their good stability, easy synthesis, function-
alization and high surface area, as well as low toxicity and price [25–27]. Recently,
much attention has been focused on the surface modifcation with appropriate cap-
ping agents onto the MNPs surface to anchor the catalytically active complexes.
Iron is of considerable interest because of its inexpensive and natural abundance.
Iron-based heterogeneous catalyst can promote a variety of organic reactions due to
their unique characteristics and properties. Additionally, iron-based heterogeneous
catalyst due to high boiling point can be compatible with high-temperature and pres-
sure chemical reactions. Such unique properties of iron further advance the appli-
cations of iron as catalyst in many organic transformations [18, 28, 29]. Literature
survey showed us that the synthesis of 1,8-dioxo-decahydroacridines is important
for researchers because of several activities and applications [30–33]. In the present
research, Fe3O4@SiO2-HBP-FeCl3 as novel nanocatalyst was prepared. All stages
from modifcation and complexion of the surface Fe3O4@SiO2 were done in one-
pot reaction (Scheme 2). The preparation of 1,8-dioxo-decahydroacridine and spir-
oquinazolin-4(3H)-one derivatives with multi-component condensation reaction of
aromatic aldehydes (1.0 mmol), dimedone (2.0 mmol), cyclic ketones (1.2 mmol),
isatoic anhydride (1.0 mmol) and primary amines (1.0 mmol) in the presence of
nano-Fe3O4@SiO2-HBP-FeCl3 as nanocatalyst under green conditions was reported
for the frst time (Scheme 1).
Experimental
Chemicals, instrumentation and analysis
1
All materials were purchased from Merck and Aldrich companies. H NMR spec-
tra were recorded on a Varian Mercury Plus (300 MHz), a Bruker Avance 300
MHz instruments in DMSO-d6 as deuterated solvents. Melting points were deter-
mined in open capillaries using a BUCHI510 melting point apparatus. Thin-layer
1 3

Ferric (III) complex supported on superparamagnetic…
R
O
H
O
NH2
O
O
R1
R2
Fe3O4@SiO2-HBP-FeCl3
Solvent-Free,
2
80 oC
N
R4
O
R
4a-p
R1
R2
R3
1
2
3
R4
O
R3
O
O
O
R'
Fe3O4@SiO2-HBP-FeCl3
Solvent-Free, 70oC
+
+
N
R'
NH2
N
H
O
N
H
8a-j
5
6
7
Scheme 1 Synthesis of 1,8-dioxo-decahydroacridine and spiroquinazolin-4(3H)-one derivatives in the
presence of nano-Fe3O4@SiO2-HBP-FeCl3
O
O
O
O
FeCl3.6H2O
70 oC
NH
NH
NH
O
N
H
O
HO
OH
H
O
N
O
O
O
Fe O @SiO
FeCl3.6H2O(excess)
2
,
3
4
Fe3O4
Cl
Cl
EtOH, 70 oC, 24 h
N
Fe
SiO2
N
Cl
O
N
O
Scheme 2 Synthesis of Fe3O4@SiO2-HBP-FeCl3 nanocatalyst
chromatography (TLC) was performed on silica-gel Poly Gram SIL G/UV 254
plates, and progress of reactions was monitored by TLC. FT-IR spectra were recorded
1
using KBr disks on a JASCO FT-IR 460 plus spectrophotometer. H and 13C-NMR
were recorded on an Agilent 300 and 75 MHz spectrometers using TMS as inter-
nal standard. Chemical shifts (δ) are reported in ppm. Elemental compositions were
determined with a Leo 1450 VP scanning electron microscope equipped with an
SC7620 energy-dispersive spectrometer (SEM–EDS) presenting a 133 eV resolution
at 20 kV. Power X-ray difraction (XRD) was performed on a Bruker D8-advance
1 3

H. Mohammadi, H. R. Shaterian
X-ray difractometer with Cu Kα (λ=0.154 nm) radiation. The magnetic property
was measured by VSM. TGA was done on a thermal analyzer with a heating rate of
10 °C min−1 over a temperature range of 25–800 °C under fowing compressed N2.
Preparation of Fe3O4@SiO2‑HBP‑FeCl3 nanoparticles (Scheme 2)
Fe3O4 MNPs were prepared by chemical co-precipitation of Fe3+ and Fe2+ ions
as described in the literature [34]. In a round bottom fask, FeCl3·6H2O (25 mg)
was added to a mixture of barbituric acid (1.5 mmol), 3,4-dihydroxybenzaldehyde
(1.5 mmol) and phthalhydrazide (1.5 mmol) and the reaction mixture was stirred at
70 °C in an oil bath for 3 h, according to the literature [35]. After the completion of
reaction and formation of product, in this point, solution of Fe3O4@SiO2 (500 mg)
dispersed in ethanol (50 mL) was added to this reaction mixture and stirred at 70 °C
for another 12 h, whose product loaded onto the surface of the nanoparticles with
hydroxyl groups on the aromatic ring. In the following, FeCl3·6H2O (1.5 mmol) was
charged to the reaction vessel and the mixture was continuously stirred for 12 h at
70 °C. Finally, Fe3O4@SiO2-HBP-FeCl3 nanoparticles were removed from solution
reaction by using an external magnet and washed several times with ethanol and
dried at 60 °C, that Fe complex grafted onto magnetic nanoparticles confrmed by
using EDX. And also, superparamagnetic nano-heterogeneous catalyst was charac-
terized by the several techniques such as XRD, FT-IR, VSM, FE-SEM, EDS and
TGA. All results confrmed the structure of the Fe3O4@SiO2-HBP-FeCl3.
General procedure for the direct synthesis 1,8‑dioxo‑decahydroacridine
derivatives using Fe3O4@SiO2‑HBP‑FeCl3 nanoparticles as catalyst
Fe3O4@SiO2-HBP-FeCl3 NMPs (9 mg) was added to a mixture of dimedone
(2.0 mmol), aniline derivatives (1.0 mmol) and aromatic aldehydes (1.0 mmol)
under solvent-free conditions. The reaction mixture was stirred at 80 °C in an oil
bath. The reaction was monitored by TLC. After the completion of reaction, etha-
nol was added to reaction mixture to remove the catalyst by an external magnet and
purifed by crystallization in EtOH. The pure known products were characterized
and their physical data were compared with those of known compounds and new
products are presented in supplementary information data.
General procedure for the synthesis of spiroquinazolin‑4(3H)‑one derivatives
Isatoic anhydride (1.0 mmol), primary amine (1.2 mmol), cyclic ketones (1.2 mmol)
and Fe3O4@SiO2-HBP-FeCl3 nanoparticles (7 mg) were stirred at 70 °C. After the
completion of the reaction (monitored by TLC), 5 mL CH2Cl2 was added and the
catalyst was separated by the use of external magnet. Then, CH2Cl2 was evaporated.
The crude product was purifed only by washing with ethanol.
9‑(4‑Chloro‑phenyl)‑10‑(3,5‑dichloro‑phenyl)‑3,3,6,6‑tetrame ‑
thyl‑3,4,6,7,9,10‑hexahydro‑2H,5H‑acridine‑1,8‑dione (4r) White solid: yield
1 3

Ferric (III) complex supported on superparamagnetic…
95%; m.p. 271–273 °C. FT‐IR (KBr, ν, cm−1): 3064, 2962, 2890, 1643, 1570, 1485,
1362, 1221, 1009, 841. 1 H NMR (300 MHz, DMSO-d6, δ, ppm): 7.28–7.97(m, 7H,
2Ar-H), 4.99 (s, 1H, CH), 1.81–2.31 (m, 8H, 4CH2), 0.75 (s, 6H, 2CH3), 0.93 (s, 6H,
13
2CH3). C NMR (75 MHz, DMSO-d6, δ, ppm):195.54, 150.29, 145.46, 140.95,
135.45, 130.72, 130.25, 129.64,128.28, 113.29, 50.00, 41.27, 32.54, 29.70, 26.56.
9‑(4‑Bromo‑phenyl)‑10‑(3,5‑dichloro‑phenyl)‑3,3,6,6‑tetrame ‑
thyl‑3,4,6,7,9,10‑hexahydro‑2H,5H‑acridine‑1,8‑dione (4s) White solid: yield
95%; m.p. 277–279 °C. FT‐IR (KBr, ν, cm−1): 3054, 2962, 2889, 1643, 1483, 1361,
1222, 1006, 910, 839. 1 H NMR (400 MHz, DMSO-d6, δ, ppm): 7.29–7.90 (m, 7H,
2Ar-H), 4.98 (s, 1H, CH), 1.81–2.34 (m, 8H, 4CH2), 0.75 (s, 6H, 2CH3), 0.92 (s, 6H,
13
2CH3). C NMR (75 MHz, DMSO-d6, δ, ppm):195.54, 150.31, 145.88, 140.94,
135.46, 131.21, 130.68, 130.24,119.26, 113.22, 50.00, 41.26, 32.55, 29.70, 26.57.
Results and discussion
Characterization of catalyst
Fe3O4@SiO2-HBP-FeCl3 nanoparticles were characterized by infrared (FT-IR)
spectroscopy, X-ray difraction (XRD), EDX, feld emission scanning electron
microscopy (FE-SEM), thermogravimetric analysis (TGA) and vibrating sample
magnetometry (VSM).
In XRD, six difraction peaks have a good concordance with the cubic structure
of maghemite (Fe3O4) (JCPDS fle No. 04-0755). The positions of all the peaks indi-
cated retention of the crystalline structure during functionalization of the Fe3O4, and
the grafting process did not change phase of the Fe3O4 nanoparticles. The XRD pat-
tern of Fe3O4@SiO2-HBP-FeCl3 showed that SiO2 and HBP-FeCl3 formed amor-
phous phase in which their patterns showed only patterns of crystalline Fe3O4 nano-
particles (Fig. 1).
We provided FE-SEM image which illustrates the catalyst surface morphology
that the morphology of the catalyst observed on the SEM micrographs points to
Fig. 1 XRD pattern of Fe3O4@SiO2-HBP-FeCl3
1 3

H. Mohammadi, H. R. Shaterian
crystalline phase and an average nanoparticles size of 18 nm using a histogram
curve from surface morphology of nano-Fe3O4@SiO2-HBP-FeCl3 (Fig. 2).
The components of the Fe3O4@SiO2-HBP-FeCl3 were also analyzed using
energy-dispersive X-ray spectroscopy (EDS). The EDS spectrum in Fig. 3 impli-
cates the presence of atoms Fe, O, Si, C, Cl and N in the catalyst which confrms
the structure of organometallic compound.
The thermal stability of the Fe3O4@SiO2-HBP-FeCl3 was investigated by
TGA analysis (Fig. 4). Small weight loss occurs below 180 °C, which is due to
physically adsorbed solvent and water. A mass loss of 12.5% in the temperature
range of 180–520 °C in the TGA curve of Fe3O4@SiO2-HBP-FeCl3 is mainly
Fig. 2 SEM images of Fe3O4@SiO2-HBP-FeCl3 (a) and particle size distribution histogram of nanocata-
lyst (b)
1 3

Ferric (III) complex supported on superparamagnetic…
Fig. 3 EDS spectrum of Fe3O4@SiO2-HBP-FeCl3
Fig. 4 Thermogravimetric
analysis of Fe3O4@SiO2-HBP-
FeCl3
attributed to the decomposition of organic groups and FeCl3 grafted to the
Fe3O4@SiO2 surface.
The VSM diagram shows the magnetic properties of synthesized catalyst
(Fig. 5). The hysteresis loop of Fe3O4@SiO2-HBP-FeCl3 is measured. Superpar-
amagnetic behavior of the Fe3O4@SiO2-HBP-FeCl3 illustrates small nanoparti-
cles size of the catalyst. As it can be observed, saturation magnetization value of
Fe3O4@SiO2-HBP-FeCl3 is 47 amu g−1
.
The characterization of Fe3O4@SiO2-HBP-FeCl3 as nanocatalyst was also
confrmed by FT-IR spectrum. The peak at 3000–3400 cm−1 was probably attrib-
uted to the NH groups, which is overlapped by the O–H stretching vibration.
C–H stretching vibrations appear at 2990 cm−1. The Fe–O stretching vibration
was observed at 550–650 cm−1, and stretching mode of Si–O-Si showed a strong
broad peak at about 1099–1220 cm−1 (Fig. 6).
1 3

H. Mohammadi, H. R. Shaterian
Fig. 5 VSM diagrams of Fe3O4@SiO2-HBP-FeCl3
Fig. 6 FT-IR spectra: (a) Fe3O4, (b) Fe3O4@SiO2, (c) Fe3O4@SiO2-HBP-FeCl3
Reaction optimization
After the characterization of the nanocatalyst, in order to establish the optimal con-
ditions for synthesizing of 1,8-dioxo-decahydroacridines in the presence of Fe3O4@
SiO2-HBP-FeCl3 as nanocatalyst, initially, the reaction of dimedone (2.0 mmol),
benzaldehyde (1.0 mmol) and aniline (1.0 mmol) was selected as a model reaction.
This model reaction with various solvents, temperatures and catalyst amounts was
studied to fnd the best condition. As shown in Table 1, the nature of the solvent was
observed to have a profound efect on both the activity of the catalyst and the yield
of product.
To select the appropriate conditions for the reaction in the presence of Fe3O4@
SiO2-HBP-FeCl3 as nanocatalyst, frst, we chose water/ethanol (1:1) mixture as sol-
vent for this reaction in the presence of Fe3O4@SiO2 and Fe3O4@SiO2-HBP-FeCl3
as nanocatalyst and catalyst-free condition for model reaction (Table 1, entries 1,
2, 4). So, without catalyst, the time is long and the yield is low. Thus, the reac-
tion does not proceed completely. The yield of desired product was increased when
1 3

Ferric (III) complex supported on superparamagnetic…
Table 1 Optimization of reaction conditions for the preparation of 3,3,6,6-tetramethyl-9,10-diphenyl
3,4,6,7,9,10-hexahydroacridine-1,8 (2H, 5H)-dione
O
H
O
O
O
NH2
N
O
4a
1
2
3
Entry Catalyst (mg)
Solvent
Solvent-free
Temp. (°C) Time (min) Yield (%)a,b
1
2
3
4
Catalyst-free
Fe3O4@SiO2(10 mg)
80
5h
75
60
30
30
50
50
30
30
30
30
30
30
30
30
30
30
50
15
60
65
75
70
35
20
60
65
85
80
95
75
95
75
85
95
78
H2O/EtOH (1:1) (3 mL) 80
Fe3O4@SiO2-HBP-FeCl3 (9 mg) Solvent-free 50
Fe3O4@SiO2-HBP-FeCl3 (9 mg) H2O/EtOH (1:1) (3 mL) 80
5
6
7
8
Fe3O4@SiO2-HBP-FeCl3 (9 mg) EtOH (3 mL)
Fe3O4@SiO2-HBP-FeCl3 (9 mg) CH3CN (3 mL)
Fe3O4@SiO2-HBP-FeCl3 (9 mg) CH2Cl2 (3 mL)
Fe3O4@SiO2-HBP-FeCl3 (9 mg) H2O (3 mL)
80
80
40
80
9
Fe3O4@SiO2-HBP-FeCl3 (9 mg) H2O/EtOH (2:1) (3 mL) 80
Fe3O4@SiO2-HBP-FeCl3 (9 mg) H2O/EtOH (1:2) (3 mL) 80
Fe3O4@SiO2-HBP-FeCl3 (9 mg) H2O/EtOH (1:3) (3 mL) 80
Fe3O4@SiO2-HBP-FeCl3 (9 mg) Solvent-free
Fe3O4@SiO2-HBP-FeCl3 (9 mg) Solvent-free
Fe3O4@SiO2-HBP-FeCl3 (9 mg) Solvent-free
Fe3O4@SiO2-HBP-FeCl3 (5 mg) Solvent-free
Fe3O4@SiO2-HBP-FeCl3 (7 mg) Solvent-free
Fe3O4@SiO2-HBP-FeCl3 (11 mg) Solvent-free
10
11
12
13
14
15
16
17
18
80
70
90
80
80
80
80
Fe3O4@SiO2-HBP (10 mg)
Solvent-free
aReaction conditions: the reaction of dimedone (2.0 mmol), benzaldehyde (1.0 mmol) and aniline
(1.0 mmol)
bYields refer to isolated pure product
the reaction was done in the presence of Fe3O4@SiO2-HBP-FeCl3 as nanocatalyst
(Table 1, entry 3). This reaction was tested in water as green solvent and organic sol-
vents such as ethanol, dichloromethane, acetonitrile and water/ethanol mixture and
also in solvent-free condition. The best performance of Fe3O4@SiO2-HBP-FeCl3
was achieved at 80 °C under solvent-free condition (Table 1, entry 12). To illustrate
the efect of FeCl3 in nanocatalyst on yield of reaction, model reaction in the pres-
ences of Fe3O4@SiO2-HBP shows 75% in comparison with 95% in the presence of
Fe3O4@SiO2-HBP-FeCl3 (Table 1, entries 12, 18). In order to assess the efect of
1 3

H. Mohammadi, H. R. Shaterian
temperature on the reaction, we carried out the reactions at various temperatures as
shown in (Table 1, entries 3, 12, 13, 14). Catalytic activity increases with increasing
temperature at 80 °C. Use of a higher temperature had no signifcant efect on the
reaction rate or the isolated yield of product (Table 1, entry 14). The efect of the
catalyst amount of the reaction was also investigated (Table 1, entries 12, 15, 16,
17). Use of a higher amount of catalyst had no signifcant efect on the reaction rate
or the isolated yield of product, while a decrease in the amount of catalyst decreased
the product yield. The best result was obtained using 9 mg of catalyst. Overall, the
ideal reaction conditions for the formation of 1,8-dioxo-decahydroacridine deriva-
tives were under solvent-free condition and 9 mg of the catalyst at 80 °C (Table 1,
entry 12).
Table 2 Preparation of spiroquinazolin-4(3H)-one in the presence of Fe3O4@SiO2-HBP-FeCl3
O
NH2
O
O
O
Fe3O4@SiO2-HBP-FeCl3
N
+
+
N
H
5
O
N
H
7
6
8d
Entry Catalyst
Reaction conditions
Time (min) Yield (%)a,b
1
2
3
4
5
6
7
8
Fe3O4@SiO2-HBP-FeCl3 (7 mg) H2O (3 mL) (80 °C)
Fe3O4@SiO2-HBP-FeCl3 (7 mg) EtOH (3 mL) (80 °C)
Fe3O4@SiO2-HBP-FeCl3 (7 mg) H2O/EtOH (1:1) (3 mL) (80 °C)
60
60
60
60
60
90
120
50
75
75
65
60
50
50
50
50
50
65
70
75
65
55
35
No
92
40
25
70
80
92
70
87
92
75
Fe3O4@SiO2 (8 mg)
Solvent-free (70 °C)
Fe3O4@SiO2-HBP-FeCl3 (7 mg) CH3CN (3 mL) (80 °C)
Fe3O4@SiO2-HBP-FeCl3 (7 mg) CH2Cl2 (3 mL) (35 °C)
Catalyst-Free
Solvent-free (90 °C)
Fe3O4@SiO2-HBP-FeCl3 (7 mg) Solvent-free (70 °C)
Fe3O4@SiO2-HBP-FeCl3 (7 mg) Solvent-free (25 °C)
Fe3O4@SiO2-HBP-FeCl3 (7 mg) EtOH (3 mL) (25 °C)
Fe3O4@SiO2-HBP-FeCl3 (7 mg) Solvent-free (50 °C)
Fe3O4@SiO2-HBP-FeCl3 (7 mg) Solvent-free (60 °C)
Fe3O4@SiO2-HBP-FeCl3 (7 mg) Solvent-free (80 °C)
Fe3O4@SiO2-HBP-FeCl3 (5 mg) Solvent-free (70 °C)
Fe3O4@SiO2-HBP-FeCl3 (6 mg) Solvent-free (70 °C)
Fe3O4@SiO2-HBP-FeCl3 (8 mg) Solvent-free (70 °C)
9
10
11
12
13
14
15
16
17
Fe3O4@SiO2-HBP (7 mg)
Solvent-free (70 °C)
aReaction conditions: isatoic anhydride 1 (1.0 mmol), aniline 2 (1.2 mmol) and cyclohexanone 4
(1.2 mmol) in diferent conditions
bYield refers to isolated pure products
1 3

Ferric (III) complex supported on superparamagnetic…
Optimization of diferent parameters in synthesis of spiroquinazolin‑4(3H)‑one
derivatives
At the onset of this research, we investigated the model one-pot three-component
cyclocondensation reaction using stirring between isatoic anhydride (1 mmol), ani-
line (1.2 mmol) and cyclohexanone (1.2 mmol) to optimize the reaction parameters.
We investigated the reaction without using any solvent in the absence of cata-
lyst, and no reaction occurred (Table 2, entry 7). After that, we investigated the
reaction in the presence of Fe3O4@SiO2-HBP-FeCl3 under solvent-free condition
at 25 °C (Table 2, entry 9). Then, we studied the model reaction in the presences
of Fe3O4@SiO2-HBP-FeCl3 catalyst in the EtOH solvent at 25 °C. The yield was
lower for ethanol (Table 2, entry 10); diferent solvents were studied such as H2O,
EtOH, H2O/EtOH, CH3CN, CH2Cl2 and solvent-free condition in the presence of
Fe3O4@SiO2-HBP-FeCl3 catalyst (Table 2, entries 1–8). Among all the solvents and
solvent-free condition, Fe3O4@SiO2-HBP-FeCl3 gives the best result under solvent-
free condition at 70 °C (Table 2, entry 8). The efect of temperature was also inves-
tigated. The model reaction was conducted in three diferent temperatures (Table 2,
entry 8, 9, 11, 12, 13), as can be seen, the highest yield was attained at 70 °C. The
efect of amount of catalyst was studied by using the model reaction. As the amount
Table 3 Synthesis of 1,8-dioxo-decahydroacridines catalyzed by Fe3O4@SiO2-HBP-FeCl3 (9 mg) nano-
particles at 80 °C under solvent-free condition
Entry
R
R1, R2, R3, R4 Product Time (min) Yield
Observed M.p
(°C)
Lit. M.p (°C)
(%)a,b
[References]
1
2
3
4
5
6
7
8
H
H, H, H, H
4a
4b
4c
4d
4e
4f
4g
4h
4i
30
35
35
25
30
25
35
25
30
35
35
25
25
40
35
40
30
30
95
94
93
95
92
90
91
90
93
92
93
95
95
92
94
90
95
95
203–205
201–203
205–207
206–208
244–246
159–161
194–196
219–221
214–216
247–249
216–218
263–265
301–303
296–298
295–297
>300
252–254 [36]
216–218 [36]
259–261 [36]
253–255 [36]
250–252 [36]
259–261 [36]
262–264 [37]
301–303 [36]
285–287 [37]
255–257 [37]
262–265 [37]
304–300 [37]
303–305 [37]
296–298 [37]
296–298 [38]
352–354 [38]
New compound
New compound
4-OMe H, H, H, H
4-Me
4-Br
3- Br
H
H
H
H, H, H, H
H, H, H, H
H, H, H, H
H, H, Me, H
H, Me, H, H
H, H, Cl, H
H, H, Cl, H
9
3-NO2
4-OCH3 H, H, Cl, H
10
11
12
13
14
15
16
17
18
4j
4k
4l
4-Me
4-Br
H
4-NO2
4-Me
OH
H, H, Cl, H
H, H, Cl, H
H, H, Br, H
4m
OH, H, H, H 4n
H, H, Me, H
H, H, Me, H
H, Cl, H, Cl
H, Cl, H, Cl
4o
4p
4q
4r
4-Cl
4-Br
271–273
277–279
aReaction conditions: the reaction of dimedone (2.0 mmol), aromatic aldehydes (1.0 mmol) and aniline
derivatives (1.0 mmol)
bYields refer to isolated pure product
1 3

H. Mohammadi, H. R. Shaterian
1 3

Ferric (III) complex supported on superparamagnetic…
Table 5 Comparison of the efciency of various catalysts with the Fe3O4@SiO2-HBP-FeCl3 in the syn-
thesis of 1,8-dioxo-decahydroacridines(a) and spiroquinazolin-4(3H)-one(b)
Entry Catalyst
Conditions
Time (min) Yield (%) References
1
2
3
4
5
6
7
8
9
Pt NPs@rGO
(PVP-SO3H) HSO4
Proline
Amberlyst-15
[Hmim]TFA
Silica-bonded S-sulfuric acid
cobalt–alanine metal complex EtOH, Refux
Fe3O4@SiO2-HBP-FeCl3
Fe3O4@SiO2@TiO2-OSO3 H
Fe3O4@SiO2-HBP-FeCl3
EtOH/H2O, 90 °C
EtOH/H2O, refux
EtOH: H2O, refux
CH3CN, refux
Solvent-free, 80 °C 270
EtOH, refux
60
30
360
300
94
95
79
81
86
94
96
95
90
92
[37](a)
[38](a)
[41](a)
[42](a)
[43](a)
120
60
30
60
50
[44](a)
[45](a)
Solvent-free, 80 °C
DES, 60 °C
Solvent-free, 70 °C
This work(a)
[39](b)
10
This work(b)
of catalyst increased, the time of the reaction decreased and the yield of reaction
increased. As can be seen, the highest yield (92%) belonged to the use of 7 mg of
catalyst.
According to optimal considered conditions, some 1,8-dioxo-decahydroacridines
and spiroquinazolin-4(3H)-ones were synthesized and results are shown in Tables 3,
4. The obtained results indicate that the reactions can proceed well enough with a
relatively wide range of aromatic substituted benzaldehydes or cyclic ketones and
anilines containing electron-donating and electron-withdrawing groups.
The results shown in Table 5 demonstrated that our present method is more ef-
cient than that of the reported methods. Additionally, the present catalyst seems to
be more benefcial from a green chemistry and commercial point of view.
Mechanism
According to the literature [36], the proposed mechanism is for the synthesis of
1,8-dioxo-decahydroacridine derivatives in the presence of Fe3O4@SiO2-HBP-
FeCl3 nanocatalyst (Scheme 3a). First, the intermediate (A) was formed via con-
densation reaction of aromatic aldehydes (1) with dimedone (2) in the presence
of Fe3O4@SiO2-HBP-FeCl3 nanocatalyst and then intermediate (A) with the
removal of group water converted to intermediate (B) and then, with Michael
addition another molecule dimedone to intermediate (B) to form intermediate
(C). Then, the intermediate (D) was obtained from the reaction of aniline deriva-
tives (3) with intermediate (C). Subsequently, intermediate (D) with tautomeri-
zation converted to intermediate (E), in which the intramolecular nucleophilic
attack by the enolic NH group (H) leads to the formation of the intermediate
(F); now this intermediate with removal of molecule water was converted to fnal
products (4a–r).
The mechanism for the formation of the desired product was suggested accord-
ing to the literature [39]. First, iron of catalyst is coordinated to the oxygen atom
of the carbonyl group on isatoic anhydride to activate them for the nucleophilic
1 3

H. Mohammadi, H. R. Shaterian
R
Cl
Cl
O
O
Fe
Cl
O
H
O
OH
N
OH
4a-r
H
O
R
R1
R2
1
-H2O
R
(A)
R4
O
Cl
2
R3
Cl
-H2O
O
Fe
FeCl
R
Cl
Cl
O
(B)
Cl
R
Fe
Cl
Cl
OH
Cl
FeCl
O
O
H
Cl
O
2
Cl
Cl
Fe
Cl
N
HO
R
(F)R
1
O
O
R4
Cl
R2
R3
R
O
O
OH
R
O
O
(C)
O
O
NH2
tautomerism
N
R1
R2
HO
R1
R2
R4
NH
Cl
O
(D)
(E)
R3
(a)
R4
R1
R2
Fe
Cl
R3
Cl
R4
R3
=Fe3O4@SiO2-HBP-FeCl3
FeCl3
Scheme 3 The proposed mechanism for the synthesis of 1,8-dioxo-decahydroacridine and spiroquinazo-
lin-4(3H)-one derivatives catalyzed by Fe3O4@SiO2-HBP-FeCl3 as Lewis acid nanocatalyst
attack of the amines to produce an intermediate I which in turn afords inter-
mediate II through decarboxylation. The proton transfer of intermediate II
afords 2-amino-N-substituted-amide III. The tautomerization of amide group
in intermediate III could be catalyzed in the presence of the supported metal.
Subsequently, the reaction of activated aldehydes or cyclic ketones with 2-amino-
N-substituted-amide III proceeds to aford the imine intermediates IV, V. The
imine moiety in intermediate IV, V is also activated by catalyst. Cyclization of
IV, V to intermediate VI, VII occurs via intramolecular nucleophilic attack of
nitrogen on imine carbon. Then, 1,5-proton shift gives the fnal desired products
(Scheme 3b).
1 3

Ferric (III) complex supported on superparamagnetic…
Cl
Cl
Cl
Fe
O
R'
NH2
7
Cl
Cl
O
O
Fe
N
H
O
Cl
O
O
5
R'
N
H
O
O
N
H
5
H
NH
I
O
Cl
Cl
O
R'
N
Fe
-CO2
Cl
N
H
8a-j
Cl
Cl
O
R'
Fe
N
Cl
H
H
NH
II
OH
R'
N
Cl
Cl
N
Fe
Cl
Cl
VI
Cl
Fe
H
N
O
O
Cl
R'
R'
N
O
(b)
H
NH2
N
III
6
V
Cl
Cl
Fe
Cl
FeCl
Cl
Fe O @SiO -HBP-FeCl
3
=
3
4
2
Cl
Scheme 3 (continued)
Recycling and reusing of the catalyst
The reusability of the Fe3O4@SiO2-HBP-FeCl3 was studied via the synthesis of
5,3,3,6,6-tetramethyl-9,10-diphenyl-3,4,6,7,9,10-hexahydroacridine-1,8 (2H, 5H)-
dione (4a, reaction model) under optimized conditions. It was concluded that the
Fe3O4@SiO2-HBP-FeCl3 nanocatalyst could be reused fve times without any sig-
nifcant reduction in product yield (Fig. 7).
1 3

H. Mohammadi, H. R. Shaterian
Fig. 7 Reusability of Fe3O4@SiO2-HBP-FeCl3 as Lewis acid nanocatalyst
Conclusion
We use a simple and efective method for synthesizing organometallic compound
supported on nanoparticles surface in which preparation of the ligand, supporting
and formation of the complex at the surface of the nanoparticles were carried out in
one-pot reaction for the preparation of Fe3O4@SiO2-HBP-FeCl3 nanocatalyst. And
also, we have developed a simple, facile, green and efcient protocol for multi-com-
ponent synthesis of 1,8-dioxo-decahydroacridine and spiroquinazolin-4(3H)-one
derivatives by using Fe3O4@SiO2-HBP-FeCl3 as a novel organometallic heterogene-
ous nanomagnetic catalyst. The products were obtained with easy reaction condi-
tions, excellent yields within short reaction time, simple work-up and avoidance of
toxic organic solvents. The nanocatalyst can be conveniently separated and recov-
ered from the reaction system by magnet and can be reused fve times without sub-
stantial loss in catalytic activity.
Acknowledgements We gratefully appreciate the University of Sistan and Baluchestan Research Coun-
cils for the fnancial support of this work.
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