Chitosan synergistically enhanced by successive Fe3O4 and silver nanoparticles as a novel green catalyst in one-pot, three-component synthesis of tetrahydrobenzo[α]xanthene-11-ones

Article abstract of DOI:10.1016/j.molcata.2014.06.005

Chitosan (CS) is modified with Fe₃O₄ nanoparticles composite through in situ co-precipitation of Fe³⁺ and Fe ²⁺ ions via NH₄OH in an aqueous solution, resulting in magnetic Fe₃O₄

Full text of DOI:10.1016/j.molcata.2014.06.005

Accepted Manuscript
Title: Chitosan synergistically enhanced by successive Fe3O4
and silver nanoparticles as a novel green catalyst in one-pot,
three-component synthesis of
tetrahydrobenzo[α]xanthene-11-ones
Author: Reza Mohammadi Esmaiel Eidi Monireh Ghavami
Mohammad Zaman Kassaee
PII:
S1381-1169(14)00256-8
DOI:
Reference:
http://dx.doi.org/doi:10.1016/j.molcata.2014.06.005
MOLCAA 9146
To appear in:
Journal of Molecular Catalysis A: Chemical
Received date:
Revised date:
Accepted date:
16-4-2014
31-5-2014
3-6-2014
Please cite this article as: R. Mohammadi, E. Eidi, M. Ghavami, M.Z.
Kassaee, Chitosan synergistically enhanced by successive Fe3O4 and silver
nanoparticles as a novel green catalyst in one-pot, three-component synthesis
of tetrahydrobenzo[rmalpha]xanthene-11-ones, Journal of Molecular Catalysis A:
Chemical (2014), http://dx.doi.org/10.1016/j.molcata.2014.06.005
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Graphical abstract
Chitosan synergistically enhanced by successive Fe3O4 and silver nanoparticles as a novel
green catalyst in one-pot, three-component synthesis of tetrahydrobenzo[α]xanthene-11-ones
Reza Mohammadi, Esmaiel Eidi, Monireh Ghavami, Mohammad Zaman Kassaee
Department of Chemistry, Tarbiat Modares University, P.O. Box 14155-4838, Tehran, Iran
Tel.: +98 912 1000392; fax: +98 21 88006544
E-mail address: Kassaeem@Modares.ac.ir (M.Z. Kassaee)
 Corresponding author. Tel.: +98-912-1000392; Fax: +98-21-88006544;
E-mail: kassaeem@modares.ac.ir and drkassaee@yahoo.com
Page 1 of 37






Silver NPs are implanted on nontoxic, biocompatible magnetic chitosan.
The resulting Fe3O4/CS-Ag NPs is a “green” heterogeneous and reusable catalyst.
It proves efficient in synthesis of 12-aryl-8,9,10,12-tetrahydrobenzo[α]xanthene-11-ones.
The reaction is fast, one-pot, three-component, with green solvent and excellent yields.
The catalyst is removed by a magnet and recycled without significant loss of its activity.
Page 2 of 37

Chitosan synergistically enhanced by successive Fe3O4 and silver nanoparticles as a novel
green catalyst in one-pot, three-component synthesis of tetrahydrobenzo[α]xanthene-11-ones
Reza Mohammadi, Esmaiel Eidi, Monireh Ghavami, Mohammad Zaman Kassaee
Department of Chemistry, Tarbiat Modares University, P.O. Box 14155-4838, Tehran, Iran
Abstract
Chitosan (CS) is modified with Fe3O4 nanoparticles composite through in situ co-
precipitation of Fe3+ and Fe2+ ions via NH4OH in an aqueous solution, resulting in magnetic
Fe3O4/CS NPs. Adsorption of Ag+ ions on the surface of the latter, followed by green reduction
of Ag+ via ascorbic acid, renders Fe3O4/CS-Ag NPs which shows an excellent catalytic activity
toward one-pot, three-component synthesis of 12-aryl-8,9,10,12-tetrahydrobenzo[α]xanthene-
11-one derivatives. The composition of the nanocatalyst is analyzed by FT-IR, XRD, TGA,
VSM, ICP, SEM and TEM. Hence unique heterogeneous Fe3O4/CS-Ag NPs acts as an excellent
green catalyst giving high yield product with good recyclability and without significant loss of
the activity.
Keywords: Silver NPs; Chitosan; Fe3O4 NPs; Synergistic; 12-aryl-8,9,10,12-
tetrahydrobenzo[α]xanthene-11-ones.
Corresponding author. Tel.: +98-912-1000392; Fax: +98-21-88006544;
E-mail: kassaeem@modares.ac.ir and drkassaee@yahoo.com
1
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Introduction
Fabrication of nanoparticles with desired properties through their surface modifications have
attracted growing attention in recent years [1-2]. As such an ever increasing interest is
generated in the synthesis, characterization and surface modification of magnetic nanoparticles
because of their potential applications in biotechnology, biomedicine, environmental, material
science and catalysis [3-5]. Intriguing feature of these nanoparticles is the possibility to tune
their properties through a molecular-level design by varying the size of the core and by surface
modification with suitable functionalities. Polysaccharides are among the various stabilizing
agents used to prevent nanoparticles from aggregating, and represent an attractive choice for
preparation of functional materials [6-7]. In particular, an increasing attention has recently been
focused on the synthesis of CS coated Fe3O4 NPs [8-10]. As an ideal support material, CS has
its special set of properties including availability, safety, non-toxicity, biocompatibility,
biodegradability, low immunogenicity, and antibacterial properties [11-13]. Owing to these
fascinating properties, CS has found a wide application in a variety of areas such as industry,
biomedicine, pharmaceuticals, metal chelating, food processing, etc [14-16].
On the other hand metallic nanoparticles have been a topic of intense research mainly
because of their unique physical and chemical properties compared with their bulk counterparts.
They have many excellent properties such as unique optical, electronic, magnetic, chemical,
and thermal behaviors as well as the large surface to volume ratio [17-19]. The literature is rich
with examples of metallic nanoparticles exhibiting excellent catalytic activities. Many metallic
nanoparticles can be employed as heterogeneous catalyst and most likely be recycled [20-21].
Ag NPs are of particular interest due to their role as substrates in the studies of catalysis,
surface enhancement, Raman spectroscopy, and in the biomedical fields [22-25]. Because of
2
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their vast applications, many techniques for synthesizing Ag NPs have been reported including:
microemulsion, chemical, electrochemical, and photochemical reductions; as well as gamma-
ray, UV, ultrasonic and microwave methods [26-32].
Here we report synthesis of Fe3O4/CS-Ag NPs, which is applied as a green, effective, clean,
and recoverable magnetic nanocatalyst for the synthesis of important 12-aryl-8,9,10,12-
tetrahydrobenzo[α]xanthene-11-one derivatives. The latter are of importance for having various
biological and pharmaceutical activities such as antibacterial, anti-inflammatory, antiviral,
antimalaria, and antitumor properties [33-35]. Some xanthene based compounds have found
both applications as antagonists for inhibiting the activity of zoxalamine, and in photodynamic
therapy [36]. In addition, they can be used as dyes, in laser technology, and pH sensitive
fluorescent materials for visualization of biomolecular assemblies [37-39]. These make
syntheses of xanthene derivatives of great importance. In the past decade, various methods have
been developed for the synthesis of tetrahydrobenzo(α)xanthenes. Generally they are
synthesized by the three-component condensation of a cyclic 1,3-diketones with an aldehyde
and 2-naphthol. It entails the use of PTSA in ionic liquid, sulfonic acid functionalized
imidazolium salts, tetrabutyl ammonium fluoride, strontium triflate, methanesulfonic acid,
glucose sulfonic acid along with proline triflate, etc [40-50]. Here we have made an effort
toward development of a new synthetic protocol involving Fe3O4/CS-Ag NPs in one-pot, tree-
component reactions of benzaldehydes, 2-naphtol and 1,3-cyclohexadiones in water. Again,
The Fe3O4/CS-Ag NPs catalyst is produced from environmentally green compounds. It's most
basic part is CS, which as a biopolymer has its special set of properties including safety, non-
toxicity, biocompatibility, biodegradability, low immunogenicity, and antibacterial properties.
Catalytic activity of CS is synergistically enhanced by the green silver nanoparticles which
3
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have shown promising antibacterial properties [51-52]. Furthermore, our catalyst contains
magnetic NPs of an iron oxide nature that is at the forefront of the current research, owing to its
non-toxicity, biocompatibility, biodegradability, etc. [53-54]. Finally, Fe3O4/CS-Ag NPs can
easily and efficiently be removed away from the product and none of it parts contaminates the
environment.
2. Experimental
2.1. Preparation of chitosan-coated magnetic nanoparticles: Fe3O4/CS NPs
Fe3O4 nanoparticles are prepared by chemical co-precipitation of Fe3+ and Fe2+ ions with
molar ratio of 2:1, in the presence of CS, followed by the hydrothermal treatment. Specifically,
FeCl3·6H2O (1.76 g, 0.0065 mol) and FeCl2·4H2O (0.65 g, 0.0033 mol) are added to 1.5 g of CS
(average molecular weight: 100,000-300,000) dissolved in 100 mL of 0.05 M acetic acid
solution. The resulting solution is mechanically stirred for 6 h at 80 ºC, under N2 atmosphere.
Then 6 mL of 25% NH4OH is injected drop wise into the reaction mixture with constant
stirring. After 30 min, the mixture is cooled to room temperature and magnetic nanoparticles
coated over chitosan are separated by an external magnet, washed first with distilled water, then
ethanol, and finally dried under vacuum at room temperature.
2.2. Synthesis of silver nanoparticles coated magnetic chitosan: Fe3O4/CS-Ag NPs
500 mg of Fe3O4/CS NPs is dispersed in water (30 mL) in an ultrasonic bath for 30 min, then
an aqueous solution of AgNO3 (300 mg in 5 mL) is added drop-wise over a period of 10 min, at
room temperature. The mixture is mechanically stirred for 4 h. Subsequently, 2 mL of 0.1 M
4
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ascorbic acid is gradually added to the mixed solution of chitosan magnetic nanoparticles and
AgNO3, then continued stirring for 3 h. The solution changes from colorless to gray green,
indicating the completion of the reaction. Finally, Fe3O4/CS-Ag NPs is separated by an external
magnet, washed several times with water and dried under vacuum at room temperature (Scheme
1).
Scheme 1. Fabrication of heterogeneous catalyst: Fe3O4/CS-Ag NPs.
2.3. General procedure for synthesis of 12-aryl-8,9,10,12-tetrahydrobenzo[α]xanthene-11-ones
Fe3O4/CS-Ag NPs (15 mg) is added to a mixture of a benzaldehyde (1 mmol), 2-naphtol (1
mmol), and a 1,3-cyclohexadione (1 mmol) in water (5 mL), and the reaction mixture is stirred
at 80 ⁰C (Scheme 2). The progress of the reaction is monitored by TLC. After the reaction is
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completed, the catalyst is separated by an external magnet and reused as such for the next
experiment. The crude product is extracted from the aqueous phase by EtOAc, and then the
organic layer is washed with saturated brine and dried over anhydrous MgSO4. Finally, the
combined organic layers are evaporated under reduced pressure and the resulting crude product
is recrystallized from hot ethanol.
Spectroscopic data of some of the representative products:
9,9-Dimethyl-12-(4-methoxyphenyl)-8,9,10,12-tetrahydrobenzo[α]xanthene-11-one (4e): White
crystalline solid: M.p. 204-206 ⁰C; IR (KBr, cm-1): 3059, 2933,2922, 2860, 1654, 1594, 1512,
1
1463, 1369, 1226, 1189, 1035, 954. H NMR (300 MHz, CDCl3): δ = 1.08 (3H, s, CH3), 1.14
(3H, s, CH3), 1.83-1.86 (2 H, m, CH2), 2.27-2.30 (2 H, s, CH2), 3.73 (3 H, s, CH3), 6.24 (s, 1H,
CH), 6.83-6.87 (2 H, m, 2CH), 6.89-6.95 (2 H, m, 2CH), 7.34-7.36 (3 H, m, 3CH), 7.42-7.43 (2
H, m, 2CH), 7.81-8.0 (1 H, s, 1CH) ppm. 13C NMR (75 MHz, CDCl3): δ = 26.2, 27.4, 31.8,
32.6, 39.4, 50.2, 54.1, 111.4, 113.1, 115.2, 115.9, 116.3, 121.7, 122.8, 125.9, 126.1, 127.0,
128.1, 129.5, 129.7, 132.5, 135.3, 145.8, 155.2, 163.4, 198.2 ppm; EI-MS: 384 (17, M+), 326
(18), 277 (25), 165 (43), 112 (67), 77 (100), 65 (45).
12-(3-Nitrophenyl)-8,9,10,12-tetrahydrobenzo[α]xanthene-11-one (4r): White crystalline solid:
M.p. 234-236 ⁰C; IR (KBr, cm-1): 3059, 2933, 2860, 1650, 1594, 1530, 1369, 1226, 1189,
1035, 954; 1H NMR (300 MHz, CDCl3): δ = 1.89-1.92 (2 H, m, CH2), 2.24-2.28 (2 H, m, CH2),
2.45-2.47 (2 H, m, CH2), 6.47 (s, 1H, CH), 6.83 (1 H, m, 1CH), 7.08-7.12 (2 H, m, 2CH), 7.34-
13
7.36 (3 H, m, 3CH), 7.42-7.43 (2 H, m, 2CH), 7.81-8.0 (2 H, m, 2CH) ppm. C NMR (75
MHz, CDCl3): δ = 19.9, 26.4, 31.9, 37.6, 114.2, 115.1, 117.5, 124.6, 124.9, 125.1, 126.8, 127.3,
128.1, 128.6, 130.5, 132.7, 132.1, 134.5, 140.6, 149.2, 149.4, 166.4, 198.3 ppm; EI-MS: 371
(82, M+), 354 (90), 324 (85), 249 (100), 193 (45), 165 (55), 76 (30).
6
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Scheme 2. Preparation of 12-aryl-8,9,10,12-tetrahydrobenzo[α]xanthene-11-ones (4) over Fe3O4/CS-Ag NPs.
3. Results and discussion
Here we discuss the green synthesis of Fe3O4/CS-Ag NPs as a catalyst in one-pot, three-
component synthesis of 12-aryl-8,9,10,12-tetrahydrobenzo[α]xanthene-11-ones. The
heterogeneous catalyst is fully characterized by FT-IR (Fig. 1), XRD (Fig. 2), TGA (Fig. 3),
VSM (Fig. 4), SEM (Fig. 5), TEM (Fig. 6) and ICP-OES.
3.1. FT-IR analysis
Spectral scrutiny of CS, Fe3O4/CS NPs, and Fe3O4/CS-Ag NPs are instructive (Fig. 1). The
FT-IR spectrum of CS shows a broad band at 3427 cm-1 which corresponds to the stretching
vibrations of −N−H and −O−H groups. Peaks appearing at 2922 and 2856 cm-1 are
characteristic of C−H stretching vibrations. The band at 1649 cm-1 is assigned to −N−H bending
vibration and that of 1424 cm-1 to C−O stretching of primary alcoholic groups in CS. The bio-
sorption bands around 1093 and 1027 cm-1 display the stretching vibrations of the C−O bonds.
In Fe3O4/CS NPs, absorptions of CS appear along with a peak at 594 cm-1 which corresponds to
the stretching vibration of Fe−O groups. This indicates that magnetic Fe3O4 NPs is coated by
CS. Possible bindings of silver with −NH2 and −OH group in Fe3O4/CS-Ag NPs have decreased
the combined intensity of amine and hydroxyl peaks at 3426 cm-1. Splitting of the bending
7
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peaks of amine and hydroxyl at 1604 cm-1 and 1416 cm-1 also indicate the bonding of Ag with
−OH and −NH2 groups. Changes in the region 1350 cm-1 and 1000 cm-1 may be attributed to the
perturbation in C−N vibrations induced Ag complex with CS.
Fig. 1. FT-IR Spectra of CS (a); Fe3O4/CS NPs (b); and Fe3O4/CS-Ag NPs (c).
3.2. X-ray diffraction (XRD) analyses
The XRD patterns help determine the crystal structures of green synthesized Fe3O4/CS NPs
and Fe3O4/CS-Ag NPs. Sharp peaks confirm the good crystallinity of the prepared samples (Fig
2). For Fe3O4/CS NPs the results are in agreement with standard patterns of inverse cubic spinel
magnetite (Fe3O4) crystal structure, showing six diffraction peaks at 2θ about 35.3°, 41.6°,
50.7°, 63.1°, 67.7° and 74.5°marked by their indices (2 2 0), (3 1 1), (4 0 0), (4 2 2), (5 1 1), and
8
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(4 4 0), respectively. The small and weak broad bands in the range of 21-29° indicate the
existence of CS. Diffraction patterns of the Fe3O4/CS-Ag NPs exhibit three additional peaks at
2θ about 44.7°, 52.0° and 76.6°; corresponding to (1 1 1), (2 0 0) and (2 2 0) planes of face
centered cubic (fcc) silver crystal structure. In addition Fe3O4 NPs and CS are shown in the
Fe3O4/CS-Ag NPs with a decreased intensity. No impurities in the XRD patterns suggest
formation of pure Fe3O4 and Ag nanoparticles.
Fig. 2. XRD Patterns of Fe3O4/CS NPs (a); Fe3O4/CS-Ag NPs (b).
3.3. Thermogravimetric analysis (TGA)
In order to probe thermal stability, TGA experiments are carried out by heating CS,
Fe3O4/CS NPs, and Fe3O4/CS-Ag NPs in air up to 600 ºC (Fig. 3). Pure CS shows a 5-10%
weight loss at 110 ºC, due to the evaporation of adsorbed moisture. Another sharp down fall
appears at 320 ºC, which could be attributed to the degradation of chitosan chains. The weight
losses of CS, Fe3O4/CS NPs, and Fe3O4/CS-Ag NPs at 600 ºC are 66%, 43%, and 25%,
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respectively. Hence, the incorporation of Fe3O4 in Fe3O4/CS is about 23% (57%-34%), while
the incorporation of Ag in Fe3O4/CS-Ag NPs is 18% (75%-57%).
Fig. 3. TGA Diagram for CS (a), Fe3O4/CS NPs (b), and Fe3O4/CS-Ag NPs.
3.4. Magnetic properties
The magnetic properties of the as-synthesized Fe3O4/CS NPs and Fe3O4/CS-Ag NPs are
measured at room temperature. The negligible coercivity and remanence in the magnetization
curves indicate that they are super paramagnetic (Fig. 4). The saturation magnetization (MS)
value of Fe3O4/CS-Ag NPs is 21.96 emu g-1, that is lower than that for Fe3O4/CS NPs (25.08
emu g-1). It may be ascribed to the existence of Ag NPs on Fe3O4/CS NPs. Both particles show
high permeability in magnetization which facilitates magnetic separation with a conventional
magnet (Fig. 4).
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Fig. 4. VSM Curve for Fe3O4/CS NPs and Fe3O4/CS-Ag NPs at room temperature.
Also, the content of Fe3O4 NPs, and Ag, in the synthesized catalyst (Fe3O4/CS-Ag NPs) is
measured by inductively coupled plasma optical emission spectroscopy (ICP-OES). The
catalyst content of 27% for Fe3O4, and 21% for Ag appear consistent with TGA observations.
3.5. Scanning electron microscopy (SEM) and transmission electron microscopy (TEM)
The size and structures of the Fe3O4/CS NPs and Fe3O4/CS-Ag NPs are estimated using
SEM and TEM. SEM shows uniformly dispersed spherical particles, along with weak
agglomerations (Fig. 5). Comparison between TEM images of the above mentioned
nanoparticles, shows Ag NPs embedded on the magnetic CS, forming the desired composite
structure (Fig. 6).
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Fig. 5. SEM Images of Fe3O4/CS NPs (a); and Fe3O4/CS-Ag NPs (b).
Fig. 6. TEM Images of Fe3O4/CS NPs (a); and Fe3O4/CS-Ag NPs (b).
Multi-component facile synthesis of 12-aryl-8,9,10,12-tetrahydrobenzo[α]xanthene-11-ones
is carried out in the presence of catalytic amounts of Fe3O4/CS-Ag NPs, in aqueous media. To
establish the feasibility of the strategy and optimize the conditions, reaction of benzaldehyde, 2-
naphtol, and 5,5-dimethyl-1,3-cyclohexanedione is adopted as a simple model (Scheme 2,
Table 1). In order to probe the catalyst role, the model reaction is implemented in the presence
of CS, Fe3O4 NPs, Ag NPs, Fe3O4/CS NPs, CS-Ag NPs, or Fe3O4/CS-Ag NPs. In addition, as
the reaction is highly related with the synergistic effect between Ag, Fe3O4, and CS, their ratio
in the catalyst is varied in order to see how it affects the catalytic activity. As anticipated, in the
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absence of the catalyst no product is produced. The reaction is highly related with the
synergistic effect between Ag and CS and about 25% of Ag and 50% of CS in catalyst is
sufficient. Fe3O4/CS-Ag NPs demonstrates the highest catalytic activity. The use of just 15 mg
of Fe3O4/CS-Ag NPs is sufficient to push the reaction forward. A catalyst amount higher than
50 mg does not improve the yield to an appreciable extent (Table 1, entries 1-13). The model
reaction is examined in a solvent free condition, as well as in H2O, EtOH, toluene, MeCN,
CH2Cl2, and MeOH (Table 1, entries 14-19). Among them, water appears to be the solvent of
choice.
Table 1.
Optimization of the model reaction by variation of the catalyst, solvent, and reaction time, as a function of
the yield of 12-aryl-8,9,10,12-tetrahydrobenzo[α]xanthene-11-ones.a
Entry
Catalyst (mg)
CS (15 mg)
Solvent
H2O
Time (min)
Yield (%)b
60
60
60
30
30
25
40
53
1
2
3
4
Fe3O4 NPs (15 mg)
Ag NPs (15 mg)
Fe3O4/CS NPs (15 mg)
(25%-75%)c
H2O
H2O
H2O
Fe3O4/CS NPs (15 mg)
(50%-50%)c
H2O
H2O
H2O
H2O
30
30
30
30
58
50
86
88
5
6
7
8
Fe3O4/CS NPs (15 mg)
(75%-25%)c
CS-Ag NPs (15 mg)
(75%-25%)d
CS-Ag NPs (15 mg)
(50%-50%)d
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9
CS-Ag NPs (15 mg)
(25%-75%)d
H2O
30
82
–
H2O
H2O
360
30
–
10
11
12
13
14
15
16
17
18
19
Fe3O4/CS-Ag NPs (15 mg)
Fe3O4/CS-Ag NPs (10 mg)
Fe3O4/CS-Ag NPs (50 mg)
Fe3O4/CS-Ag NPs (15 mg)
Fe3O4/CS-Ag NPs (15 mg)
Fe3O4/CS-Ag NPs (15 mg)
Fe3O4/CS-Ag NPs (15 mg)
Fe3O4/CS-Ag NPs (15 mg)
Fe3O4/CS-Ag NPs (15 mg)
94
85
95
85
35
55
48
37
60
H2O
30
H2O
30
EtOH
Toluene
MeCN
CH2Cl2
MeOH
–
50
120
90
120
120
60
a
Reaction conditions: benzaldehyde (1 mmol), 2-naphtol (1 mmol), 5,5-dimethyl-1,3-
cyclohexanedione (1 mmol), catalyst, solvent (5 mL), 80 ⁰C.
b Isolated yields.
c (Fe3O4% - CS%)
d (CS% - Ag%)
A plausible provisional mechanism is presented for formation of 12-aryl-8,9,10,12-
tetrahydrobenzo[α]xanthene-11-ones (4) over our catalyst (Fe3O4/CS-Ag NPs) (Scheme 3).
Accordingly, activation of the carbonyl group of benzaldehyde (1) by the Ag NPs Lewis acid
portion of Fe3O4/CS-Ag NPs, leads to 5 which is attacked by nucleophile 2-naphthol (2) that is
already activated through deprotonation via the −NH2 groups present on the CS portion of
catalyst. This results in the formation of the adduct 6 which gives orthoquinone methide (7)
upon dehydration. In turn, Fe3O4/CS-Ag NPs activates intermediate 7, as a Michael acceptor,
which is attacked by nucleuphile 8 that has already been activated through deprotonation of 1,3-
cyclohexanediones (3) via the −NH2 groups. The result of this condensation reaction is
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To investigate the efficiency of our method, a series of differently substituted benzaldehydes
are employed (Scheme 2). The results clearly demonstrate high tolerance for a wide range of
differently substituted benzaldehydes (Table 2).
Table 2.
One-pot aqueous synthesis of 12-aryl-8,9,10,12-tetrahydrobenzo[α]xanthene-11-ones over Fe3O4/CS-Ag NPs
catalyst.a
Mp (°C)
Entry
R1
R2
Time (min) Yield (%)b
Found
149-152
190-192
175-177
206-208
204-206
180-182
177-178
207-209
166-168
245-247
186-188
206-208
175-177
194-197
178-180
236-238
170-172
234-236
Reported
H
H
CH3
H
30
30
40
45
45
45
25
25
35
35
30
30
30
35
25
25
30
30
94
94
88
87
85
85
95
94
89
88
92
90
90
90
96
96
91
90
148-151 [41]
190-191 [44]
175-176 [44]
205-206 [44]
205-206 [44]
180-181 [44]
178-179 [41]
208-210 [44]
164-166 [48]
244-246 [44]
185-187 [41]
208-209 [47]
173-175 [49]
192-194 [50]
175-178 [41]
236-237 [44]
167-170 [41]
235-236 [44]
4a
4b
4c
4d
4e
4f
4-CH3
4-CH3
4-OCH3
4-OCH3
4-Cl
CH3
H
CH3
H
CH3
H
4g
4h
4i
4-Cl
2-Cl
CH3
H
2-Cl
4j
4-Br
CH3
H
4k
4l
4-Br
3-Br
CH3
H
4m
4n
4o
4p
4q
4r
3-Br
4-NO2
4-NO2
3-NO2
3-NO2
CH3
H
CH3
H
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2-CH3
2-CH3
4-OH
4-OH
CH3
H
45
45
50
50
82
82
80
80
161-163
237-239
211-213
268-270
158-160 [41]
158-160 [41]
209-211 [44]
269-270 [47]
4s
4t
CH3
H
4u
4v
a
Reaction conditions: benzaldehydes (1 mmol), 2-naphtol (1 mmol), 1,3-cyclohexanediones (1 mmol),
Fe3O4/CS-Ag NPs (15 mg), water (5 mL), 80 ⁰C.
b Isolated yields.
In a typical procedure, after completion of the reaction, the magnetic catalyst is easily and
efficiently removed away from the product by attaching an external magnet to the reaction
vessel, followed by simple decantation of the solution (Fig. 7).
Fig. 7. Separation of the catalyst from the reaction mixture by an external magnet.
To determine possible leaching of the Ag NPs, 100 mg of Fe3O4/CS-Ag NPs is dispersed in
water for 1 h, them the catalyst is removed by an external magnet. The resulting solution is
tested by atomic absorption spectroscopy which shows no trace of silver. In addition the filtrate
is tested after a standard reaction and no silver is detected.
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The recovered catalyst is washed with EtOH and dried for 4 h at room temperature to ready
for a later run. The percentage of the recovery step in most cases is more than 96%, without
altering the physicochemical properties (Fig. 8). Moreover, the recovered catalyst is recycled in
subsequent runs without any significant loss of its activity. For instance, using the same model
reaction, the average isolated yield for seven successive runs is 91%, which demonstrates the
practical recyclability of the prepared catalyst (Fig. 8).
Fig. 8. Reusability of Fe3O4/CS-Ag NPs, as a magnetically recyclable heterogeneous catalyst ( ); and the yield of
the product 12-aryl-8,9,10,12-tetrahydrobenzo[α]xanthene-11-ones for each run ( ).
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4. Conclusion
Silver NPs are implanted on nontoxic, biocompatible magnetic chitosan (CS). The resulting
Fe3O4/CS-Ag NPs acts as a “green” heterogeneous, highly efficient and recyclable novel
catalyst for preparation of 12-aryl-8,9,10,12-tetrahydrobenzo[α]xanthene-11-ones through one-
pot, tree-component reactions of a benzaldehyde, 2-naphtol, and a 1,3-dicarbonyl compound in
water. Green solvent, high yields, short reaction time, operational simplicity, practicability,
applicability to various substrates and product purity are among the advantages of this protocol.
References
[1] K.M. Ho, P. Li, Langmuir 24 (2008) 1801-1807.
[2] D. Qi, J. Lu, C. Deng, X. Zhan, J. Phys. Chem. C 113 (2009) 15854-15861.
[3] T. Gelbrich, M. Feyen, A. M. Schmidt, Macromolecules 39 (2006) 3469-3472.
[4] A.H. Lu, E.L. Salabas, F. Schuth, Angew. Chem. Int. Ed. 46 (2007) 1222-1244.
[5] R. Mohammadi, M.Z. Kassaee, J. Mol. Catal. A: Chem. 380 (2013) 152-158.
[6] G.D. Carlo, A. Curulli, R.G. Toro, C. Bianchini, T.D. Caro, G. Padeletti, D. Zane, G.M.
Ingo, Langmuir 28 (2012) 5471-5479.
[7] A. Primo, F. Quignard, Chem. Commun. 46 (2010) 5593-5595.
[8] K.H. Bae, M. Park, M.J. Do, N. Lee, J.H. Ryu, G.W. Kim, C. Kim, T.G. Park, T. Hyeon,
ACS Nano 6 (2012) 5266-5273.
[9] X. Zhang, H. Niu, Y. Pan, Y. Shi, Y. Cai, Anal. Chem. 82 (2010) 2363-2371.
[10] N.A. Frey, S. Peng, K. Cheng, S. Sun, Chem. Soc. Rev. 38 (2009) 2532-2542.
[11] E. Guibal, Prog. Polym. Sci. 30 (2005) 71-109.
[12] M. Bodnar, J.F. Hartmann, J. Borbely, Biomacromolecules 6 (2005) 2521-2527.
19
Page 20 of 37

[13] S.H. Lim, S.M. Hudson, Carbohydr. Res. 339 (2004) 313-319.
[14] A.J. Varma, S.V. Deshpande, J.F. Kennedy, Carbohydr. Polym. 55 (2004) 77-93.
[15] E.R. Welsh, C.L. Schauer, S.B. Qadri, R.R. Price, Biomacromolecules 3 (2002) 1370-
1374.
[16] M.R. Kasaai, J. Agric. Food Chem. 57 (2009) 1667-1676.
[17] A. Henglein, Chem. Rev. 89 (1989) 1861-1873.
[18] W. Cheng, S. Dong, E.Wang, J. Phys. Chem. B 108 (2004) 19146-19154.
[19] C.C. Huang, Z. Yang, K.H. Lee, H.T. Chang, Angew. Chem. Int. Ed. 46 (2007) 6824-
6828.
[20] K. Shimizu, Y. Miyamoto, A. Satsuma, ChemCatChem 2 (2010) 84-91.
[21] W. Yan, R. Wang, Z. Xu, J. Xu, L. Lin, Z. Shen, Y. Zhou, J. Mol. Catal. A: Chem. 255
(2006) 81-85.
[22] A. Debarre, R. Jaffiol, C. Julien, P. Tchenio, M. Mostafavi, Chem. Phys. Lett. 386 (2004)
244-247.
[23] X. Xu, Q. Yang, Y. Wang, H. Yu, X. Chen, X. Jing, Eur. Polym. J. 42 (2006) 2081-2087.
[24] I. Liu, D.A. Sonshine, S. Shervani, R.H. Hurt, ACS Nano 4 (2010) 6903-6913.
[25] K.S.V. Krishna Rao, P. Ramasubba Reddy, Y. Lee, C. Kim, Carbohydr. Polym. 87 (2012)
920-925.
[26] D.K Bhui, A. Misra, Carbohydr. Polym. 89 (2012) 830-835.
[27] M. Starowicz, B. Stypula, J. Banas, Electrochem. Commun. 8 (2006) 227-230.
[28] M. Hosseini, M.M. Momeni, J. Mater. Sci. 45 (2010) 3304-3310.
[29] D. Zhang, X. Liu, X. Wang, X. Yang, L. Lu, Phys. B: Condens. Matter. 406 (2011) 1389-
1394.
20
Page 21 of 37

[30] Y.N. Rao, D. Banerjee, A. Datta, S.K. Das, R. Guin, A. Saha, Radiat. Phys. Chem. 79
(2010) 1240-1246.
[31] D. Spadaro, E. Barletta, F. Barreca, O.G. Curr, F. Neri, Appl. Surf. Sci. 256 (2010) 3812-
3816.
[32] M.N. Nadagouda, T.F Speth, R.S. Varma, Acc. Chem. Res. 44 (2011) 469-478.
[33] K. Chibale, M. Visser, D.V. Schalkwyk, P.S. Smith, A. Saravanamuthu, A.H. Fairlamb,
Tetrahedron 59 (2003) 2289-2296.
[34] N. Sato, M. Jitsuoka, T. Shibata, T. Hirohashi, K. Nonoshita, M. Moriya, Y. Haga, A.
Sakuraba, M. Ando, T. Ohe, H. Iwaasa, A. Gomori, A. Ishihara, A. Kanatani, T. Fukami, J.
Med. Chem. 51 (2008) 4765-4770.
[35] A.J. Kesel, Curr. Med. Chem. 12 (2005) 2095-2162.
[36] T. Lazarides, T. McCormick, P. Du, G. Luo, B. Lindley, R. Eisenberg, J. Am. Chem. Soc.
131 (2009) 9192-9194.
[37] R.D. Combes, R.B. Haveland-Smith, Mutation Res. 98 (1982) 101–243.
[38] M. Ahmad, T.A. King, D.K. Ko, B.H. Cha, J. Lee, J. Phys. D: Appl. Phys. 35 (2002) 1473-
1476.
[39] J. Liu, Z. Diwu, J. W.Y. Leung, Bioorg. Med. Chem. Lett. 11 (2001) 2903-2905.
[40] J. M Khurana, D. Magoo, Tetrahedron Lett. 50 (2009) 4777-4780.
[41] M.A. Zolfigola, V. Khakyzadeh, A.R. Moosavi-Zare, A. Zare, S.B. Azimi, Z. Asgari , A.
Hasaninejad, C. R. Chimie. 15 (2012) 719–736.
[42] S. Gao, C.H. Tsai, C.F. Yao, Synlett (2009) 949-954.
[43] J. Li, W. Tang, L. Lu, W. Su, Tetrahedron Lett. 49 (2008) 7117-7120.
[44] Y.H. Liua, L. Li, J. Heterocyclic Chem. 49 (2012) 861-864.
21
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formation of 9 which cyclyzes to 10 and subsequently renders 12-aryl-8,9,10,12-
tetrahydrobenzo[α]xanthene-11-ones (4) upon dehydration.
Scheme 3. A plausible mechanism for Fe3O4/CS-Ag NPs catalytic synthesis of 12-aryl-8,9,10,12-
tetrahydrobenzo[α]xanthene-11-ones.
15
Page 23 of 37

[45] Y. Wan, X Zhang, C. Wang, L. Zhao, L. Chen, G. Liu, S. Huang, S. Yue, W. Zhang, H.
Wu, Tetrahedron 69 (2013) 3947-3950.
[46] J. Li, L. Lu, W. Su, Tetrahedron Lett. 51 (2010) 2434-2437.
[47] Z.H. Zhang, P. Zhang, S.H. Yang, H.J. Wang, J. Deng, J. Chem. Sci. 122 (2010) 427-432.
[48] A. Sethukumar, M. M. Chandy, A. Prakasam, R. Pallepogu, Struct. Chem. 22 (2011) 671-
680.
[49] B. Maleki, S. Barzegar, Z. Sepehr, M. Kermanian, R. Tayebee, J. Iran. Chem. Soc. 9
(2012) 757-765.
[50] A. Sethukumar, V. Vithya, C.U. Kumar, B.A. Prakasam, J. Mol. Struct 1008 (2012) 8-16.
[51] R. Yoksan, S. Chirachanchaic, Mat. Chem. Phys. 115 (2009) 296-302.
[52] P. Sanpui, A. Murugadoss, P.V. Durga Prasad, S.S. Ghosh, A. Chattopadhyay, Int.
J. Food Microbiol. 124 (2008) 142-146.
[53] S. Laurent, D. Forge, M. Port, A. Roch, C. Robic, L.V. Elst, R.N. Muller, Chem. Rev. 108
(2008) 2064-2110.
[54] A.K. Gupta, M. Gupta, Biomaterials 26 (2005) 3995-4021.
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Scheme 1
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Figure 1
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Figure 2
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Figure 3
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Figure 4
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