Applications of a novel nano magnetic catalyst in the synthesis of 1,8-dioxo-octahydroxanthene and dihydropyrano[2,3-c]pyrazole derivatives

Article abstract of DOI:10.1016/j.molcata.2016.03.027

Imidazole-based ionic liquid-stabilized on silica coated Fe₃O₄ magnetic nano particles [nano-Fe₃O₄SiO₂(CH₂)₃-Imidazole-SO₃H]Cl as a novel heterogeneous acidic catalyst

Full text of DOI:10.1016/j.molcata.2016.03.027

Accepted Manuscript
Title: Applications of a novel nano magnetic catalyst in the
synthesis of 1,8-dioxo-octahydroxanthene and
dihydropyrano[2][2,3-c]pyrazole derivatives
Author: Mohammad Ali Zolfigol Roya Ayazi-Nasrabadi
Saeed Baghery Vahid Khakyzadeh Saeid Azizian
PII:
S1381-1169(16)30094-2
DOI:
Reference:
http://dx.doi.org/doi:10.1016/j.molcata.2016.03.027
MOLCAA 9826
To appear in:
Journal of Molecular Catalysis A: Chemical
Received date:
Revised date:
Accepted date:
2-12-2015
29-2-2016
15-3-2016
Please cite this article as: Mohammad Ali Zolfigol, Roya Ayazi-Nasrabadi,
Saeed Baghery, Vahid Khakyzadeh, Saeid Azizian, Applications of a novel
nano magnetic catalyst in the synthesis of 1,8-dioxo-octahydroxanthene and
dihydropyrano[2][2,3-c]pyrazole derivatives, Journal of Molecular Catalysis A:
Chemical http://dx.doi.org/10.1016/j.molcata.2016.03.027
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Applications of a novel nano magnetic catalyst in the synthesis of 1,8-
dioxo-octahydroxanthene and dihydropyrano[2,3-c]pyrazole derivatives
Mohammad Ali Zolfigol,*,a Roya Ayazi-Nasrabadi,a Saeed Baghery,a Vahid Khakyzadeh,b Saeid Azizianc
aDepartment of Organic Chemistry, Faculty of Chemistry, Bu-Ali Sina University, Hamedan 6517838683, Iran
bFaculty of Science, Department of Chemistry, K. N.Toosi University, P.O. Box 15875-4416, Tehran, I. R. Iran
cDepartment of Physical Chemistry, Faculty of Chemistry, Bu-Ali Sina University, Hamedan 6517838683, Iran
*Corresponding Author: Fax: +988138380709
E-mail: zolfi@basu.ac.ir and mzolfigol@yahoo.com (M.A. Zolfigol).
1

Graphical Abstract
2

Highlights

Novel magnetic nano particles with ionic liquid tag: [nano-Fe3O4@SiO2@(CH2)3-Imidazole-
SO3H]Cl or [MNP-PIm-SO3H]Cl as a heterogeneous catalyst.

Synthesis of 1,8-dioxo-octahydroxanthenes and dihydropyrano[2,3-c]pyrazole derivatives
catalyzed by {[MNP-PIm-SO3H]Cl under solvent-free conditions.
This method has the ability to tolerate a good range of substitutions.
This procedure has the shorter reaction times, high yield and agreement with the green
chemistry protocols.



Easy recovery and reusability of heterogeneous nano magnetic catalyst.
3

Abstract
Imidazole-based ionic liquid-stabilized on silica coated Fe3O4 magnetic nano particles [nano-
Fe3O4@SiO2@(CH2)3-Imidazole-SO3H]Cl as a novel heterogeneous acidic catalyst was
designed, synthesized and fully characterized by FT-IR, thermo gravimetric analysis (TGA),
differential thermal analysis (DTA), energy-dispersive x-ray spectroscopy (EDX), X-ray
diffraction patterns (XRD), scanning electron microscopy (SEM), transmission electron
microscopy (TEM), atomic force microscopy (AFM), Brunauer-Emmett-Teller (BET) and
inductively coupled plasma (ICP) analysis. The nano-structured organo solid catalyst as a novel,
mild and full-fledged catalyst was used for the cascade synthesis of 1,8-dioxo-octahydroxanthene
o
derivatives by the condensation reaction between dimedone and various aldehydes at 80 C
under solvent-free conditions. Similarly, dihydropyrano[2,3-c]pyrazole derivatives were
synthesized by the one-pot three-component condensation reaction of aldehydes, malononitrile
and 3-methyl-1-phenyl-2-pyrazoline-5-one under solvent-free conditions at room temperature.
To the knowledge of our science, this is the main investigation on the synthesis of [nano-
Fe3O4@SiO2@(CH2)3-Imidazole-SO3H]Cl as a worthy heterogeneous nano magnetic solid acid
for acid catalyzed organic reactions.
Keywords: Imidazole-based ionic liquid-stabilized magnetic nano-structured particles, [nano-
Fe3O4@SiO2@(CH2)3-Imidazole-SO3H]Cl, 1,8-dioxo-octahydroxanthenes, dihydropyrano[2,3-
c]pyrazoles, solvent-free conditions.
4

1.
Introduction
Nowadays, there is a more demand for development of ecologically sustainable approaches
in fine chemical processes, pharmaceutical industries, design, synthesis and applications of
various kinds of catalysts because catalysis plays a major role in the prevention of pollution in
our environment [1]. The catalytic reaction is a cyclic system and separation of heterogeneous
catalyst from reaction mixture is easier than homogenous one [2]. Usual heterogeneous solid acid
catalysts are inorganic or hybrid of organic and inorganic materials. Solid acid catalyst should
have great pores, many active acidic sites, high stability with good selectivity, recyclability and
reusability, high TON and TOF and also should be economically and environmentally
sustainable [3].
Magnetic nano particles (MNPs) with acidic tags have above mentioned properties. On the
other hand, MNPs can be separated into four types: metals (Fe, Co, Ni), alloys (FePt, FePd),
metal oxides (FeO, Fe2O3, Fe3O4), and ferrites (CoFe2O4, CuFe2O4). Between the four types of
magnetic nanoparticles, iron oxides have attracted the most attention, for the reason that they can
be produced effortlessly via co-precipitation and also they have stronger magnetic properties [4-
6].
1,8-Dioxo-octahydroxanthenes displays beneficial biological activities for instance
pigments and cosmetics [7], luminescent sensors [8], fluorescent materials [9], photodynamic
therapy [10], finds use in biodegradable agrochemicals [11, 12], antibacterial, antiviral activities,
anti-inflammatory [13] and in laser technologies [14]. Additionally, these compounds have been
applied in photodynamic therapy [15] and as antagonists for paralyzing the action of
zoxazolamine [16, 17].
5

Numerous processes are presented for the creation for xanthenes and benzoxanthenes
including the trapping of benzynes by phenols [18], cyclocondensation reaction between 2-
hydroxyaromatic aldehydes and 2-tetralone [19], cycloacylation of carbamates [20],
intramolecular phenylcarbonyl coupling reaction of benzaldehydes and acetophenones [21],
aryloxymagnesium halides with triethylorthoformate [22], form amide [23] and carbon
monoxide [24].
Pyrano[2,3-c]pyrazoles are very desirable as a type of heterocycles due to their potential
uses in pharmaceutical field. They display a varied range of biological activities like anti-
inflammatory [25], anticancer [26, 27], inhibitors of human Chk1 kinase [28], antimicrobial [29]
and also as biodegradable agrochemicals [30]. Moreover, they play a main role as essential
synthetic intermediates [31]. The first method has been reported by using the base-catalyzed
cyclization of 4-aryliden-5-pyrazolone [32]. New approaches for the production of pyrazole
include synthesis based process of β-cyclodextrin [33], cinchona alkaloid derivatives [34],
Sc(OTf)3 [35], triethylamine [36], water or ethanol media [37, 38], imidazole [39], CuO/ZrO2
[40] and triethylbenzylammonium chloride [41].
In continuance of our researches on the design, synthesis and use of solid acids [42],
inorganic acidic salts [43], nano magnetic catalysts [44] and science-based development of task-
specific ionic liquids (TSILs) [45], we decided to link all of the above mentioned experiences to
design and synthesis of imidazole-based ionic liquid-stabilized on silica coated Fe3O4 magnetic
nano particles [nano-Fe3O4@SiO2@(CH2)3-Imidazole-SO3H]Cl or [MNP-PIm-SO3H]Cl. Then
the described catalyst was used in the synthesis of 1,8-dioxo-octahydroxanthene and
dihydropyrano[2,3-c]pyrazole derivatives under solvent-free conditions (Scheme 1).
6

Scheme 1. The synthesis of 1,8-dioxo-octahydroxanthenes and dihydropyrano[2,3-c]pyrazole derivatives using
[nano-Fe3O4@SiO2@(CH2)3-Imidazole-SO3H]Cl as MNPs catalyst.
2.
Experimental
2.1.
General procedure for the preparation of [nano-Fe3O4@SiO2@(CH2)3-Imidazole-
SO3H]Cl as a heterogeneous acidic catalyst.
At first, magnetite phase Fe3O4 was produced by adding 3 mL FeCl3 (2 M dissolved in 2 M
HCl) to 10.33 mL double distilled water followed via drop wise addition of 2 mLNa2SO3 (1 M)
for 3 min under magnetic stirring. After the solution color changed from red to light yellow, 80
mL of an NH3·H2O solution (0.85 M) were added under vigorous stirring. After 15 min, the
magnetite precipitate (Fe3O4) was washed to pH < 7.5 by distilled water and separated with a
magnet [46]. 3 mL tetraethylorthosilicate (TEOS) was added to a mixture of 1 g of Fe3O4, 20 mL
water, 80 mL ethanol and 3 mL ammonia under reflux to attain Fe3O4-silica coated
(Fe3O4@SiO2) [47]. Thus, 3 g of Fe3O4-silica coated (Fe3O4@SiO2) and (3-chloropropyl)
triethoxysilane (2.408 g, 10 mmol) in 80 mL of dry toluene were refluxed under nitrogen for 12
h. The treated Fe3O4@SiO2@(CH2)3Cl (grafted with chloropropyl group) was filtered, washed
o
twice with dry toluene and anhydrous diethyl ether, and dried at 80 C for 6 h in vacuum.
Subsequently imidazole (0.681 g, 10 mmol) in 50 mL of dry toluene was added to the
7

Fe3O4@SiO2@(CH2)3Cl and the mixture was refluxed for 12 h [48]. The resulting solid was
filtered, washed and dried in a same procedure to create the Fe3O4@SiO2@(CH2)3-Imidazole. At
last, a solution of chlorosulfonic acid (0.666 mL, 1.165g, 10 mmol) in dry dichloromethane (10
mL) was added drop wise to the suspension of Fe3O4@SiO2@(CH2)3-Imidazole and the reaction
mixture was stirred for 6 h. Finally, the imidazole-based ionic liquid-stabilized on silica coated
Fe3O4 magnetic nano particles [nano-Fe3O4@SiO2@(CH2)3-Imidazole-SO3H]Cl was obtained
after filtering, washing and drying (Scheme 2).
Scheme 2. The synthesis of imidazole-based ionic liquid-stabilized on silica coated Fe3O4 magnetic nano particles
[nano-Fe3O4@SiO2@(CH2)3-Imidazole-SO3H]Cl as a MNPs catalyst.
2.2.
General procedure for the synthesis of 1,8-dioxo-octahydroxanthene derivatives.
[nano-Fe3O4@SiO2@(CH2)3-Imidazole-SO3H]Cl as a MNPs catalyst (10 mg) was added
and mixed to a mixture of aromatic aldehyde (1 mmol) and dimedone (0.280 g, 2 mmol) under
o
solvent-free conditions at 80 C for the suitable time described in Table 3. After completion of
the reaction which was identified with TLC (n-hexane/ethyl acetate: 5/3), the MNPs catalyst was
recovered magnetically by adding 5 ml ethanol and the mixture was purified by recrystallization
from ethanol-water (10:1), which resulted in precipitation of the expected 1,8-dioxo-
octahydroxanthene derivatives. All of the obtained product(s) are known and were identified by
comparison of their physical data with those of reported in the literature (see Table 3).
8

2.3.
General procedure for the synthesis of dihydropyrano[2,3-c]pyrazole derivatives.
[nano-Fe3O4@SiO2@(CH2)3-Imidazole-SO3H]Cl as a MNPs catalyst (7 mg) was added
and mixed to a mixture of aromatic aldehyde (1 mmol), malononitrile (0.066 g, 1 mmol) and 3-
methyl-1-phenyl-2-pyrazoline-5-one (0.174 g, 1 mmol) under solvent-free conditions at room
temperature for the suitable time defined in Table 5. After completion of the reaction which was
identified by TLC (n-hexane/ethyl acetate: 5/2), The MNPs catalyst was recovered magnetically
by adding 5 ml ethanol and the product was purified via recrystallization from ethanol-water
(10:1), which resulted in precipitation of the desired dihydropyrano[2,3-c]pyrazole derivatives.
All of the obtained product(s) are known and were identified by comparison of their physical
data with those of reported in the literature (see Table 5).
2.4.
Spectral data analysis for compounds
9-(3,5-Dichloro-2-hydroxyphenyl)-3,3,6,6-tetramethyl-3,4,5,6,7,9-hexahydro-1H-
xanthene-1,8(2H)-dione (Table 3, entry 18): White solid; M.p. 230-232 C; Yield: 94%; IR
1
(KBr, cm-1): 3182, 2961, 1665, 1648,1602, 1458, 1377, 1314, 1259, 1207, 1027, 854, 561; H
NMR (300 MHz, DMSO-d6): δ 0.89 (s, 6H, –CH3), 1.06 (s, 6H, –CH3), 2.41 (d, 4H, J = 7.8 Hz,
–CH2), 2.63 (d, 4H, J = 8.8 Hz, –CH2), 5.05 (s, 1H, –CH aliphatic), 6.85 (s, 1H, ArH), 7.44 (s,
13
1H, ArH), 10.78 (s, 1H, –OH); C NMR (DMSO-d6): δ (ppm) 26.4, 29.6, 32.1, 32.2, 50.7,
111.1, 113.0, 121.2, 127.0, 127.4, 127.9, 129.7, 145.1, 164.5, 196.1; Mass: m/z (%) = 434 (M+).
6-Amino-4-(3,5-dichloro-2-hydroxyphenyl)-3-methyl-1-phenyl-1,4-dihydropyrano[2,3-
c]pyrazole-5-carbonitrile (Table 5, entry 16): White solid; M.p. 223-225 C; Yield: 93%; IR
1
(KBr, cm-1): 3417, 3322, 3191, 3081, 2194, 1652, 1622, 1572, 1399; H NMR (300 MHz,
DMSO-d6): δ 2.26 (s, 3H, –CH3), 4.70 (s, 1H, –CH aliphatic), 7.04 (d, 2H, J = 9.8 Hz, ArH),
7.14 (t, 2H, J = 7.9 Hz, ArH), 7.42 (s, 2H, ArH), 7.55 (t, 1H, J = 7.8 Hz, ArH), 7.70 (s, 2H, –
9

NH2), 11.16 (s, 1H, –OH); 13C NMR (DMSO-d6): δ (ppm) 11.1, 30.0, 54.1, 108.8, 109.0, 118.5,
120.5, 121.3, 124.8, 125.5, 126.5, 127.4, 128.2, 129.3, 137.3, 144.5, 147.5, 147.7, 150.0, 160.2,
162.4; Mass: m/z (%) = 413 (M+).
3.
Results and discussion
3.1.
Characterization of imidazole-based ionic liquid-stabilized on silica coated Fe3O4
magnetic nano particles [nano-Fe3O4@SiO2@(CH2)3-Imidazole-SO3H]Cl as a heterogeneous
acidic catalyst.
Recently, Gu and coworkers reported a good range of sulfonyl-containing ammonium-
based Bronsted acid ILs as efficient liquid heterogeneous catalysts for the synthesis of a wide
range of organic compounds under solvent-free conditions [49]. In the same way, our research
group has also reported nano-sphere silica containing of imidazole linker with sulfonic acid tag
and its applications in various multi component reactions [50]. Herein, we wish to report a novel
core-shell nano magnetic silica coated with imidazole spacer and sulfonic acid tag [MNP-PIm-
SO3H]Cl.
The structure of imidazole-based ionic liquid-stabilized on silica coated Fe3O4 magnetic
nano particles [MNP-PIm-SO3H]Cl as a heterogeneous acidic catalyst was studied and fully
characterized by FT-IR, thermo gravimetric analysis (TGA), differential thermal analysis (DTA),
EDX, XRD, SEM, TEM and AFM analysis.
The FT-IR spectroscopy was engaged to compare the produced blank Fe3O4 magnetic nano
particles, Fe3O4@SiO2 core-shell MNPs and the further core-shell surface modified samples (Fig.
1). FT-IR spectroscopy of the bare magnetic Fe3O4 nano particles presented a characteristic
absorption peak of Fe–O bond at about 575 cm−1. The absorption peaks of the silica shell in the
Fe3O4@SiO2 core-shell MNPs about 1090 and 780 cm−1 are linked to the anti-symmetric and
10

symmetric stretching vibrations of Si–O–Si bond in oxygen-silica tetrahedral, respectively.
Individually, absorption peak of the Fe3O4@SiO2-Prop core-shell MNPs at 2987 cm−1 is related
to the stretching vibration of C–H groups. Absorption peak at 3180 cm−1 is also linked with the
stretching vibration of aromatic C–H groups on imidazole ring and the absorption peak at 1635
cm−1 is also correlated to the stretching vibration of C=N bond on imidazole ring. Additionally,
the absorption band at 3400 cm-1 illustrates stretching vibration of O–H in the SO3H group and
the peaks at 1220 cm-1 and 1073 cm-1 are linked to vibrational modes of O–SO2 bonds. The
absorption associated to S=O bond vibration is observed at 1024 cm-1.
11

Fig. 1. The IR spectrum of (a) Fe3O4; (b) Fe3O4@SiO2; (c) Fe3O4@SiO2@(CH2)3Cl; (d) Fe3O4@SiO2@(CH2)3-
Imidazole; (e) [nano-Fe3O4@SiO2@(CH2)3-Imidazole-SO3H]Cl.
The thermo gravimetric analysis (TGA) and differential thermal analysis (DTA) of [MNP-
PIm-SO3H]Cl as a worthy heterogeneous acidic MNPs catalyst shows the mass loss of organic
material as they decompose upon heating (Figures 2 and 3). The major weight loss from the
MNPs catalyst (room temperature to 110 °C) is due to the removal of physically adsorbed water
and organic solvents, which were applied in the catalyst preparing. The weight loss is about 3 %.
The weight loss (7 %) between 110 and 400 °C is linked mainly to the thermal decomposition
imidazole functionalized via chlorosulfonic acid on the surface of silica-coated. [MNP-PIm-
SO3H]Cl shows three-step weight loss behavior. Weight loss of MNPs catalyst seems about 2 %
at 510–550 °C, which is contributed to the thermal decomposition of the MNPs catalyst. As a
consequence, the thermal gravimetric analysis of the MNPs catalyst presented significant loss in
three steps, and decomposed above 510 °C.
Fig. 2. The thermal gravimetric analysis (TGA) of [MNP-PIm-SO3H]Cl.
12

Fig. 3. The differential thermal analysis (DTA) of [MNP-PIm-SO3H]Cl.
Energy-dispersive X-ray spectroscopy (EDX) from the achieved [MNP-PIm-SO3H]Cl as a
novel heterogeneous catalyst introduced the presence of the expected elements in the structure of
the MNPs catalyst, for instance Fe, Si, O, N, S, C and Cl (Fig. 4).
13

Fig. 4. The energy-dispersive X-ray spectroscopy (EDX) of [nano-Fe3O4@SiO2@(CH2)3-Imidazole-SO3H]Cl as a
MNPs catalyst.
The size, shape and morphology of [MNP-PIm-SO3H]Cl as a heterogeneous MNPs
catalyst were studied by X-ray diffraction (XRD) pattern, scanning electron microscopy (SEM),
transmission electron microscopy (TEM) and atomic force microscopy (AFM) analysis. The
XRD pattern of the MNPs catalyst was considered in a range of 5–90° (Fig. 5). As exposed in
Fig. 5, the XRD pattern displays diffraction lines of high crystalline nature at 2θ = 12.90°,
20.40°, 20.90°, 24.60°, 25.50°, 26.00°, 28.30°, 30.80°, 37.70° and 81.70°. The peak width
(FWHM), size and inter planar distance from the XRD pattern of [MNP-PIm-SO3H]Cl were
investigated in the 12.90° to 81.70° range and the achieved results are summarized in Table 1.
For instance, assignments for the highest diffraction line, 20.90°, exposed an FWHM of 0.20 and
a crystalline size for the catalyst of ca. 40.39 nm by the Debye–Scherrer’s equation [D =
Kλ/(βcosθ)] (Where D is the crystalline size, K is the shape factor, being corresponding to 0.9 , λ
is the X-ray wavelength, β is the full width at half maximum of the diffraction peak, and θ is the
Bragg diffraction angle in degree). An inter planar distance of 0.424530 nm (using the highest
diffraction line at 20.90°) was found via the Bragg equation: dhkl = λ/(2sinθ), (λ : Cu radiation
(0.154178 nm) was achieved. Crystallite sizes achieved from several diffraction lines by the
Debye–Scherrer’s equation were found to be in the nanometer range (12.42–57.12 nm), which is
mainly in a good accordance with the SEM and TEM (Fig. 6).
14

Fig. 5. The X-ray diffraction (XRD) pattern of {nano-Fe3O4} (a); {nano-Fe3O4@SiO2} (b); {nano-
Fe3O4@SiO2@(CH2)3Cl} (c); {nano-Fe3O4@SiO2@(CH2)3-Imidazole} (d); [nano-Fe3O4@SiO2@(CH2)3-Imidazole-
SO3H]Cl (e) as a MNPs catalyst.
Table 1. X-ray diffraction (XRD) data for [nano-Fe3O4@SiO2@(CH2)3-Imidazole-SO3H]Cl as a MNPs catalyst.
Entry
2θ
Peak width [FWHM] (degree)
Size [nm]
Inter planer distance [nm]
1
2
3
4
12.90
20.40
20.90
24.60
0.14
0.65
0.20
0.17
57.12
12.42
40.39
47.83
0.685444
0.434819
0.424530
0.361451
15

5
6
25.50
26.00
28.30
30.80
37.70
81.70
0.60
0.20
0.22
0.28
0.18
0.19
13.58
40.77
37.24
29.44
46.64
25.93
0.348889
0.342297
0.314979
0.289958
0.288322
0.117722
7
8
9
10
Fig. 6. The scanning electron microscopy (SEM) (a and b) and transmission electron microscopy (TEM) (c and d) of
[nano-Fe3O4@SiO2@(CH2)3-Imidazole-SO3H]Cl as a MNPs catalyst.
16

Atomic force microscopy (AFM) is a technique that lets us find and analyze surfaces with
high resolution and accuracy. AFM gives numerous advantages; for instance hard surfaces like
the surface of a ceramic material, or the dispersal of metallic nano composite; or very soft ones,
such as molecules of proteins or plastic materials. Fig. 7 shows the two- and three-dimensional
AFM images of [MNP-PIm-SO3H]Cl as a heterogeneous acidic MNPs catalyst. No important
partition area in size is identified in the illustrations. By attaining the three-dimensional 2.1 µm2
× 2.1 µm2 frameworks, we can know that the achieved MNPs catalyst approves an interrupted
structure with a desirable outside planarity. The surface of the coat on the MNPs catalyst was
obviously exposed to be less than 60 nm.
17

Fig. 7. A two- (a and b) and three-dimensional (c and d) atomic force microscopy (AFM) of [nano-
Fe3O4@SiO2@(CH2)3-Imidazole-SO3H]Cl as a MNPs catalyst.
3.2.
Application of [nano-Fe3O4@SiO2@(CH2)3-Imidazole-SO3H]Cl as a MNPs catalyst in
the synthesis of 1,8-dioxo-octahydroxanthene derivatives.
At first, to optimize the reaction conditions, the condensation reaction between 4-
chlorobenzaldehyde and dimedone was chosen as a typical and different amounts of [MNP-PIm-
SO3H]Cl as a heterogeneous catalyst at range of room temperature upto 80 °C were studied
under solvent-free conditions (Table 2). As showed in Table 2, the best results were achieved
when the reaction was attained in the presence of 10 mg of MNPs catalyst at 80 °C (Table 2,
entry 8). No improvement was known in the yield of reaction by increasing the amount of the
MNPs catalyst and temperature (Table 2, entries 9 and 10). Table 2 obviously exhibits that in the
absence of MNPs catalyst, the product was not created (Table 2, entry 1). Furthermore, to
compare the result of the solution in comparison with solvent-free conditions, a mixture of 4-
chlorobenzaldehyde and dimedone as a model reaction, by 10 mg of MNPs catalyst in different
solvents for instance water, C2H5OH, CH3CN, CH3CO2Et, benzene and toluene was investigated
at 80 °C. Solvent-free condition was the foremost condition in this reaction. In Table 2 (entries 9
and 10) with regard to the reaction mechanism, it can be said that an increase in amount of
catalyst protonate the carbonyl group of dimedone compound and the nucleophilic properties
decrease. Therefore, the products are attained in lower yield.
Table 2. Result of amount of the catalyst and temperature in the synthesis of 1,8-dioxo-octahydroxanthene
derivatives under solvent-free conditions.a
Entry
Catalyst loading (mg)
Reaction temperature (oC)
Reaction time (min)
Yieldb (%)
1
2
Catalyst-free
1
80
80
120
60
N.R
60
18

3
4
3
80
80
80
r.t.
60
80
80
80
60
40
25
180
60
15
15
10
75
90
5
5
7
95
6
10
10
10
15
20
N.R
70
7
8
98
9
97
10
97
Reaction conditions: a4-Chlorobenzaldehyde (1 mmol), dimedone (2 mmol); bIsolated yield.
After detecting the optimized reaction conditions, the investigation was followed by
performing the reaction among aromatic aldehydes with dimedone. To display the overall
applicability of this procedure, numerous aldehydes were capably reacted with two equivalents
of dimedone under the same conditions. These results encouraged us to study the scope and the
overview of this process for various aldehydes under optimized conditions. As showed in Table
3, a series of aromatic aldehydes underwent electrophilic substitution reaction with dimedone to
afford a different series of substituted 1,8-dioxo-octahydroxanthene in high to superb yields. The
nature and electronic properties of the substituents on the aromatic ring affect the conversion
rate, and aromatic aldehydes having electron-withdrawing groups on the aromatic ring react
faster than electron-donating groups do.
Table 3. The synthesis of 1,8-dioxo-octahydroxanthene derivatives in the presence of 0.01 g of of [nano-
Fe3O4@SiO2@(CH2)3-Imidazole-SO3H]Cl as a MNPs catalyst under solvent-free conditions at 80 oC.a
Entry
Aldehyde
Time (min) Yieldb (%)
M.p (oC) (Lit) [Ref.]
1
2
3
Benzaldehyde
25
20
20
92
93
94
205-206 (203-205) [51a]
204-205 (203-205) [51a]
170-172 (170-171) [51b]
2-Nitrobenzaldehyde
3-Nitrobenzaldehyde
19

4
5
4-Nitrobenzaldehyde
4-Chlorobenzaldehyde
15
15
20
20
10
10
15
10
20
40
40
20
20
30
20
96
98
95
96
95
94
90
97
95
91
89
96
92
89
94
226-228 (224-226) [51c]
238-240 (233-235) [51a]
185-187 (185-187) [51b]
226-227 (225-227) [51a]
251-252 (254-255) [51d]
233-234 (235-236) [51e]
227-229 (231-232) [51f]
239-241 (241-243) [51g]
226-228 (221-223) [51g]
210-211 (210-213) [51h]
249-251 (257-258) [51h]
216-217 (234-235) [51f]
237-238 (236-238) [51i]
223-225 (224-226) [51j]
230-232
6
3-Chlorobenzaldehyde
7
2-Chlorobenzaldehyde
8
2,4-Dichlorobenzaldehyde
4-Fluorobenzaldehyde
9
10
11
12
13
14
15
16
17
18
3-Fluorobenzaldehyde
4-Bromobenzaldehyde
2-Bromobenzaldehyde
4-Methylbenzaldehyde
4-Methoxybenzaldehyde
Naphthalene-2-carbaldehyde
Naphthalene-1-carbaldehyde
4-N,N-Dimethylaminobenzaldehyde
2-Hydroxy-3,5-dichlorobenzaldehyde
Reaction conditions: aAldehyde (1 mmol), dimedone (2 mmol); bIsolated yield.
In a probable mechanism (Scheme 3) [51], initially, aldehyde (2) is activated using the
MNPs catalyst to provide 7. At that time, dimedone (1) attacks to the carbonyl group of the
activated aldehyde (7), and gives intermediate (8). Subsequently, through removing one water
molecule from (8), intermediate (9) is prepared. Reaction is followed via activation of
intermediate (9) to provide (10) as a Michael acceptor. Then, Michael addition of dimedone (1)
to intermediate (9) affords (10). Intermediate (10) converts to (11) via tautomerization. Finally,
1,8-dioxo-octahydroxanthene will be produced by eliminating one water molecule from (11).
20

Scheme 3. The plausible mechanism for the synthesis of 1,8-dioxo-octahydroxanthene derivatives in the presence of
[nano-Fe3O4@SiO2@(CH2)3-Imidazole-SO3H]Cl as a MNPs catalyst.
Furthermore, from the magnetic separation and isolation of the MNPs catalyst on reaction
completion (the reaction between 4-chlorobenzaldehyde and dimedone), the additional
probability to reuse and recycle the MNPs catalyst for several runs was also studied. Results
displayed in Fig. 8 approve that the magnetically separable [MNP-PIm-SO3H]Cl as a MNPs
catalyst could be reused and recycled six runs without any remarkable loss of its first catalytic
activity. The deactivation of the MNPs catalyst is low. The reaction was scaled up to 10 mmol of
o
4-chlorobenzaldehyde and dimedone by 0.1 g of MNPs catalyst at 80 C. The yield of the
reaction was 98% after 15 minutes and 93% after the sixth run. The results are summarized in
Fig. 8.
21

Fig. 8. Reusability of the [nano-Fe3O4@SiO2@(CH2)3-Imidazole-SO3H]Cl as a MNPs catalyst on the synthesis of
1,8-dioxo-octahydroxanthene in 15 minutes.
3.3.
Application of [nano-Fe3O4@SiO2@(CH2)3-Imidazole-SO3H]Cl as a MNPs catalyst in
the synthesis of dihydropyrano[2,3-c]pyrazole derivatives.
In another study, to optimize the reaction conditions, the condensation reaction of 4-
chlorobenzaldehyde with malononitrile and 3-methyl-1-phenyl-2-pyrazoline-5-one was selected
as a typical and different amounts of MNPs catalyst at range of room temperature up to 70 °C
were confirmed under solvent-free conditions (Table 4). As displayed in Table 4, the best results
were attained when the reaction was achieved using 7 mg of MNPs catalyst at room temperature
(Table 4, entry 5). No improvement was detected in the yield of reaction by increasing the
amount of the MNPs catalyst and temperature (Table 4, entries 6-8). Table 4 clearly presents that
in the absence of MNPs catalyst, the product was not produced (Table 4, entry 1). To compare
the result of the solution with solvent-free conditions, a mixture of 4-chlorobenzaldehyde,
malononitrile and 3-methyl-1-phenyl-2-pyrazoline-5-one as a model reaction, using 7 mg of
22

MNPs catalyst in various solvents for instance water, CH3CN, C2H5OH, CH3CO2Et and toluene
was considered at room temperature. Solvent-free condition was the best condition in this
reaction.
Table 4. Result of amount of the catalyst and temperature in the synthesis of dihydropyrano[2,3-c]pyrazole
derivatives under solvent-free conditions.a
Entry
Catalyst loading (mg)
Reaction temperature (oC)
Reaction time (min)
Yieldb (%)
1
2
3
4
5
6
7
8
Catalyst-free
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
50
70
180
60
45
30
20
20
20
20
N.R
80
90
94
98
98
98
98
1
3
5
7
10
7
7
a
Reaction conditions: 4-Chlorobenzaldehyde (1 mmol), malononitrile (1 mmol); 3-methyl-1-phenyl-2-pyrazoline-5-
one (1 mmol); bIsolated yield.
After optimization of the reaction conditions, to investigate the efficiency and the scope of
the showed procedure, numerous dihydropyrano[2,3-c]pyrazole derivatives were produced by
the one-pot three-component condensation reaction between aromatic aldehydes with
malononitrile and 3-methyl-1-phenyl-2-pyrazoline-5-one using catalytic amounts of [MNP-PIm-
SO3H]Cl as an acidic MNPs catalyst under solvent-free reaction conditions. The results are
displayed in Table 5. The effect of substituents on the aromatic ring was assessed strong in terms
of yields under these reaction conditions. Both categories of aromatic aldehydes counting
electron-releasing and electron-withdrawing substituents on their aromatic ring gained the
appropriate products in high to excellent yields in short reaction time. The reaction time of
23

aromatic aldehydes having electron withdrawing groups was rather faster than that of electron
donating groups. Moreover, recyclability and reusability of the catalyst was also considered on
the condensation of 4-chlorobenzaldehyde with malononitrile and 3-methyl-1-phenyl-2-
pyrazoline-5-one. Similarly, MNPs catalyst was separated and reused for alternative reaction.
Table 5. The synthesis of dihydropyrano[2,3-c]pyrazole derivatives using 7 mg of [nano-Fe3O4@SiO2@(CH2)3-
Imidazole-SO3H]Cl as a MNPs catalyst under solvent-free conditions at room temperature.a
Entry
Aldehyde
Time (min) Yieldb (%) M.p (oC) (Lit) [Ref.]
1
2
Benzaldehyde
3-Nitrobenzaldehyde
30
20
15
20
30
15
60
30
45
60
45
30
60
30
70
20
90
60
91
95
97
98
93
97
92
96
94
92
89
90
93
91
89
93
85
85
176-177 (169-171) [52a]
197-199 (189-191) [52b]
197-198 (197-198) [52b]
186-187 (175-178) [52a]
141-142 (140-142) [52a]
176-178 (169-171) [52a]
210-212 (206-208) [45b]
163-165 (169-170) [52c]
173-175 (170-171) [52b]
176-178 (174-176) [52c]
193-195 (187-189) [52d]
207-208 (205) [52e]
3
4-Nitrobenzaldehyde
4
4-Chlorobenzaldehyde
5
2-Chlorobenzaldehyde
6
2,4-Dichlorobenzaldehyde
Naphthalene-2-carbaldehyde
3-Bromobenzaldehyde
7
8
9
4-Methylbenzaldehyde
10
11
12
13
14
15
16
17
18
4-Methoxybenzaldehyde
4-Hydroxy-3-ethoxybenzaldehyde
Pyridine-4-carbaldehyde
Naphthalene-1-carbaldehyde
Thiophen-2-carbaldehyde
4-Hydroxybenzaldehyde
2-Hydroxy-3,5-dichlorobenzaldehyde
Terephthalaldehyde
244-245 (235-237) [45b]
167-168 (168-169) [52f]
208-210 (213-215) [52f]
223-224
240-242 (235-236) [52d]
301-303 (297-299) [45b]
2-Hydroxy-3-methoxybenzaldehyde
a
Reaction conditions: Aldehyde (1 mmol), malononitrile (1 mmol); 3-methyl-1-phenyl-2-pyrazoline-5-one (1
mmol); bIsolated yield.
24

The suggested catalytic processes mentioned in Scheme 4 [52], are in accordance with
literature studies [40, 41]. Initially arylidene malononitrile (14) was formed in quantitative yield
by the Knoevenagel addition of activated malononitrile (4) to the activated aromatic aldehyde (7)
through loss of one water molecule. The creation of the dihydropyrano-[2,3-c]-pyrazole (6) is
proposed to contain the following tandem reactions: pyrazolone (13) creation after
tautomerization of 3-methyl-1-phenyl-2-pyrazoline-5-one (5), Michael addition of pyrazolone
(13) to arylidene malononitrile (14), followed by cyclization and tautomerization.
Scheme 4. The probable mechanism for the synthesis of dihydropyrano-[2,3-c]-pyrazole derivatives using [nano-
Fe3O4@SiO2@(CH2)3-Imidazole-SO3H]Cl as a MNPs catalyst.
Also, from the magnetic separation and isolation of the MNPs catalyst on reaction
completion (the reaction between 4-chlorobenzaldehyde, malononitrile and 3-methyl-1-phenyl-2-
25

pyrazoline-5-one), the additional possibility to reuse and recycle the MNPs catalyst for various
runs was too investigated. Results showed in Fig. 9 cofirm that the magnetically separable MNPs
catalyst could be reused and recycled six runs without any significant loss of its first catalytic
activity. The deactivation of the MNPs catalyst is low. The reaction was scaled up to 10 mmol of
reactants by 0.07 g of MNPs catalyst at room temperature. The yield of the reaction was 98%
after 20 minutes and 91% after the sixth run. The results are summarized in Fig. 9.
Fig. 9. Reusability of the [nano-Fe3O4@SiO2@(CH2)3-Imidazole-SO3H]Cl as a MNPs catalyst on the synthesis of
dihydropyrano-[2,3-c]-pyrazole in 20 minutes.
N2 adsorption-desorption measurements were studied to investigate the Brunauer-Emmett-
Teller (BET) analysis specific surface area of the materials (Fig. 10, I). The BET surface area of
MNPs catalyst is 128.2 m2/g (total pore volume = 0.281 cm3g-1; mean pore diameter = 8.77 nm)
and its pore size distribution to plotted in Fig. 10, II. The obtained surface area for Fe3O4 NPs is
34.2 m2/g (total pore volume = 0.159 cm3g-1; mean pore diameter = 18.56 nm) and its pore size
distribution to plotted in Fig. 10, II. In comparison to Fe3O4 NPs the BET surface area of the
MNPs catalyst increased. Specific surface area in MNPs catalyst increases due to coating of
26

Fe3O4 NPs with grafting organic tags (Fig. 10, I and II ). The higher surface area of the prepared
catalyst in comparison to Fe3O4 NPs core can be considered as one of the advantages of this
catalyst. The pore sizes of both samples are mainly between 1 to 10 nm which indicates that the
samples contain both microspores and mesopores.
Fig. 10. N2 adsorption-desorption isotherms (BET) of Fe3O4 NPs (a and c) and MNPs catalyst (b and d).
The general approaches to test for the presence or absence of leached soluble Fe in the
reaction solution are a hot filtration test or elemental analysis of Fe in the solution. Finally, the
full heterogeneous character of the catalytically active species as well as the recyclability and
reusability of the MNPs catalyst were approved by hot-filtration test and via multiple reuses (six
run) of the MNPs catalyst in further 1,8-dioxo-octahydroxanthene. A typical reaction between 4-
chlorobenzaldehyde and dimedone was carried out using 0.01 g under solvent-free conditions at
o
80 C. A hot filtration test is applied after 30-35% conversion of 1,8-dioxo-octahydroxanthene
had been attained to ensure that any leached soluble Fe in the filtrate would be enough to
continue a homogeneous reaction after removing the MNPs catalyst. The results were sumarized
in Fig. 11.
27

Fig. 11. The inductively coupled plasma (ICP) analysis via hot filtration test to determinate of Fe in the recycled
MNPs catalyst.
To compare the efficacy of our catalyst with some reported catalysts for the synthesis of
1,8-dioxo-octahydroxanthenes and dihydropyrano[2,3-c]pyrazoles, we have presented the results
of these catalysts to attain the condensation of 4-nitrobenzaldehyde and dimedone (in the
synthesis of 1,8-dioxo-octahydroxanthene) or 4-chlorobenzaldehyde, malononitrile and 3-
methyl-1-phenyl-2-pyrazoline-5-one (in the synthesis of 1 dihydropyrano[2,3-c]pyrazoles) in
Table 6. As Table 6 displays, MNPs catalyst has extraordinarily improved the synthesis of
compounds in different terms (reaction time, yield and amount of catalyst).
Table 6. Comparison of the results our studies with reported works.a
Entry
Reaction condition
Catalyst loading Time (min) Isolated yields (%)
[Ref.]
1
2
3
4
5
DABCO-Br
SmCl3
0.015 g
20 mol%
10 mol%
10 mol%
0.01 g
150
480
210
180
15
83
97
94
95
96
[53a]
[53b]
TBAHS
[53c]
EPZ 10
[53d]
[MNP-PIm-SO3H]Cl
This work
28

6
7
[Sipim]HSO4
TEBA
0.1 g
0.15 g
0.05 g
1 mol%
0.007 g
90
360
50
95
99
95
95
98
[54a]
[41]
8
PTSA
[54b]
9
H14[NaP5W30O110
]
50
[54c]
10
[MNP-PIm-SO3H]Cl
20
This work
4.
Conclusion
In summary, a novel heterogeneous, recycle and reusable organosilica imidazole-based
ionic liquid-stabilized on silica coated Fe3O4 magnetic nano particles [MNP-PIm-SO3H]Cl was
designed, produced and fully characterized by using FT-IR, thermo gravimetric analysis (TGA),
differential thermal analysis (DTA), EDX, XRD, SEM, TEM, AFM, BET and ICP analysis.
Catalytic applications of described catalyst was investigated in the synthesis of 1,8-dioxo-
octahydroxanthenes and dihydropyrano[2,3-c]pyrazole derivatives under mild and solvent-free
conditions. Noteworthy advantages of this study are relatively simplicity of product isolation,
cleaner reaction profile, eco-friendly benign, high yield, short reaction time, recycle and
reusability of the [MNP-PIm-SO3H]Cl catalyst.
Acknowledgements
We thank Bu-Ali Sina University and Iran National Science Foundation (INSF) for
financial support (The Grant of Allameh Tabataba'i's Award, Grant Number: BN093) to our
research group.
29