Synthesis and Characterization of Fe3O4@SiO2 NPs as an Effective Catalyst for the Synthesis of Tetrahydrobenzo[a]xanthen-11-ones

In this research, the significant application of Fe3O4@SiO2 core-shell nanoparticles as efficient, green, robust, cost-effective and recoverable nanocatalyst for the multi-component reaction of aldehydes, 2-naphthol and dimedone has been developed in aqueous ethanol media under reflux conditions. In the presented procedure we had avoided to use of hazardous reagents and solvents and therefore this method can be considered as a green alternative pathway in comparison with the previous method. Simple procedure, environmentally benign, excellent yields, short reaction times, simple purification and facile catalyst separation are advantages of this protocol. Characterization and structural elucidation of the prepared products have been done on the basis of chemical, analytical and spectral analysis. In addition, the heterogeneous nanoparticles were fully characterized by FT-IR, XRD, EDX, VSM and SEM analysis.


Introduction
Core-shell nanostructures have aroused considerable interest in the various fields because of their functional attributes, such as great scattering and stability.Core-shell nanoparticles are perfect complex systems that involve the benefits of both core and shell to improve chemical and physical properties.Surface modification of nanoparticles has certainly attracted great attention in the multidisciplinary areas of organic chemistry and nanotechnology. 1,2ecently, magnetite Fe 3 O 4 nanoparticles, (Fe 3 O 4 NPs) have been used extensively as inorganic cores for the preparation of inorganic/organic core/shell nanocomposites, due to their significant applications in various chemical, biomedical and industrial scopes. 3n particular, functionalized magnetite nanocatalysts show not only excellent catalytic performance but also have a good grade of high chemical stability in the many organic transformations. 4In addition, magnetite-supported nanocatalysts can be easily separated using an external magnet and their catalytic activity remains after several reaction cycles. 5lica-coating of nanoparticles is an ideal surface modifier, due to its high stability, bio-adaptability, being non-poisonous, and easily attached to diverse functional groups.The nanostructures involving silica-coated magnetite nanoparticles (Fe 3 O 4 @SiO 2 core-shell nanoparticles) as catalyst with many reactive portions, acidic features and high surface area do not only supply high chemical stability but are also appropriate for the many functionalizations. 6,7ecently, functionalized magnetite nanoparticles were used as efficient catalytic systems in many chemical transformations including synthesis of α-amino nitriles, 8 1,1-diacetates from aldehydes, 9 diazepine derivatives, 10 indazolo[2,1-b]phthalazine-triones and pyrazolo [1,2-b]phthalazine-diones, 11 3,4-dihydropyrimidin-2(1H)ones, 12 2-amino-4H-chromen-4-yl phosphonates, 13 1,4dihydropyridines 14 and pyrrole synthesis. 15In addition, a series of organic reactions such as Knoevenagel condensation/Michael addition, 16 Suzuki/Heck cross-coupling, 17 asymmetric aldol reaction, 18 Suzuki coupling, 19 asymmetric hydrogenation of aromatic ketones, 20 acetalization reaction, 21 Ritter reaction, 22 cyanosilylation of carbonyl Ghasemzadeh: Synthesis and Characterization of Fe 3 O 4 @SiO 2 ... compounds, 23 Henry reaction, 24 enantioselective directaddition of terminal alkynes to imines 25 have been done using functionalized nanostructures.
The multi-component reactions (MCRs) are appearing as valuable tools to produce compound libraries of small molecules for potential applications in medicinal and pharmaceutical chemistry. 26MCRs often conform to the aims of green chemistry related to economy of the reaction steps as well as the many precise principles of desirable organic synthesis. 27Because of their advantages, including facile performance, being environmentally benign, fast and atom economic, MCRs have caused a great interest in relation to combinatorial chemistry.
Benzoxanthens are known, due to their numerous occurence in nature and extensive range of pharmacological and therapeutic properties, including antiviral, 28 antibacterial, 29 anti-inflammatory, 30 and other bioorganic characteristics. 31In addition, these compounds are applied widely in laser technologies, 32 dyes, 33 and as pHsensitive fluorescent materials for visualization of biomolecules. 342-Aryl-8,9,10,12-tetrahydrobenzo[a]xanthen-11ones are a class of benzoxanthen derivatives which can be prepared via three-component reaction of aldehydes, 2naphthol and cyclic 1,3-dicarbonyl compounds.Because of the importance of the structures of these compounds we observe a lot of approaches in the literature for the preparation of benzo[a]xanthen-11-one derivatives.

Results and Discussion
In the preliminary experiments Fe 3 O 4 and Fe 3 O 4 @SiO 2 nanoparticles were prepared and characterized by EDX, XRD, SEM, IR and VSM analysis.The chemical purity of the samples as well as their stoichiometry was tested by energy dispersive X-ray spectroscopy (EDAX) studies.The EDAX spectrum given in Figure 1a shows the presence of Fe and O as the only elementary components of Fe 3 O 4 NPs.In addition, as shown in Figure 1b, the Si peak clearly confirms the presence of SiO 2 groups on the Fe 3 O 4 @SiO 2 core-shell nanoparticles.
The X-ray diffraction patterns of Fe Figure 4 shows the FT-IR spectra for the samples of Fe 3 O 4 NPs and Fe 3 O 4 @SiO 2 microspheres catalysts.For the bare magnetic nanoparticles (Figure 4a), the vibration band at 575 cm -1 is the typical IR absorbance induced by structure Fe-O vibration.The absorption band at 1072 cm -1 observed on Fe 3 O 4 @SiO 2 nanoparticles can be ascribed to the stretching and deformation vibrations of Si-O 2 , reflecting the coating of silica on the magnetite surfaces (Figure 4b).
The magnetic properties of the samples containing a magnetite component were studied by a vibrating sample magnetometer (VSM) at 300 K. Figure 5  Ghasemzadeh: Synthesis and Characterization of Fe 3 O 4 @SiO 2 ...
In the preliminary experiments, in order to determine the optimized reaction conditions the reaction of 4-nitrobenzaldehyde (1 mmol), 2-naphthol (1 mmol) and dimedone (1 mmol) was selected as a model reaction and the reaction conditions were optimized on the base of solvent and catalyst (Scheme 1).
This model study was carried out in the presence of non-polar (  The model reaction was also investigated in the absence of the catalyst as well as in the presence of different catalysts (Table 2,   The summarized results in Table 2 show that most of the Brønsted and Lewis acids could carry out the model reaction.However, we found that Fe 3 O 4 @SiO 2 NPs (Table 2, entry 12) gave the best results in comparison with other catalysts in three-component reaction of 4-nitrobenzaldehyde, 2-naphthol and dimedone.
The increased catalytic activity of silica-coated magnetite nanoparticles in regard to the other catalysts is related to a high surface-area-to-volume ratio of supported magnetite nanoparticles which provide enormous driving force for diffusion.
Next, the effect of different concentrations of catalyst was evaluated using various amounts of Fe 3 O 4 @SiO 2 NPs including 2 mol%, 5 mol%, 8 mol%, 10 mol% and15 mol%.We observed that 5 mol% of Fe 3 O 4 @SiO 2 NPs afforded product with the best results and it was enough for a complete progress of the reaction (Table 2).
We investigated the scope and limitations of threecomponent reactions of aldehydes, 2-naphthol and dimedone under the optimized conditions.So we carried out synthesis of 12-aryl-8,9,10,12-tetrahydrobenzo[a]xant-hen-11-one derivatives by use of various structures of aldehydes in the presence of Fe 3 O 4 @SiO 2 core shell NPs (Scheme 2, Table 3).
A number of experiments have been performed and therefore we synthesized a series of tetrahydrobenzo[a]xanthen-11-ones in excellent yields and un short reaction times.As can be seen from Table 3, aromatic aldehydes bearing electron-withdrawing groups, such as F and Cl (Table 3, Entries 3, 4) reacted easier and faster than those with electron-releasing groups, such as Me and OMe as expected.Also the synthesis of 12-aryl-8,9,10,12tetrahydrobenzo[a]xanthen-11-one derivatives using sterically hindered aromatic aldehydes required longer reaction times.
A plausible mechanism for the synthesis of 12aryl-8,9,10,12-tetrahydrobenzo[a]xanthen-11-ones using Fe 3 O 4 @SiO 2 NPs is shown in Scheme 3. It is likely that Fe 3 O 4 @SiO 2 NPs act as a Lewis acid and increase the electrophilicity of the carbonyl groups on the

1. General
Chemicals were of commercial reagent grade and obtained from Merck or Fluka and used without further purification.All products were characterized by comparison of their FT-IR and NMR spectra and physical data with those reported in the literature.All yields refer to the

2. Preparation of Fe 3 O 4 Nanoparticles
Fe 3 O 4 MNPs were prepared according to a previously reported procedure by Hu et al. 53 using the chemical co-precipitation method.Typically, FeCl 3 × 6H 2 O (2.7 g) and FeCl 2 × 4H 2 O (1 g) were dissolved in 100 mL of 1.2 mmol/L aqueous HCl followed by ultrasonic bath for 30 min.Then, 1.25 mol/L aqueous NaOH (150 mL) was added under vigorous stirring and a black precipitate was immediately formed.The resulting transparent solution was heated at 80 °C with rapid mechanical stirring under N 2 atmosphere (scheme 2).After vigorous stirring for 2 h, the black products were centrifuged, filtered out and washed with deionized water and alcohol for several times, and finally dried at 60 °C for 12 h.

Preparation of Fe 3 O 4 @SiO 2 Nanoparticles
Fe 3 O 4 @SiO 2 core-shell particles were prepared via modified Stöber sol-gel process. 5430 mg as-prepared Fe 3 O 4 submicrospheres were ultrasonically dispersed in a solution containing 160 mL ethanol, 40 mL water and 10 mL concentrated ammonia (28 wt%).Then, 0.4 mL TEOS was added dropwise to the solution under sonication, followed by mechanical stirring for 3 h at room temperature.
Subsequently, the resulting particles were separated using a magnet and washed with deionized water and ethanol.This step was repeated several times before drying at 60 °C for 12 h (Scheme 4).A mixture of aldehyde (1 mmol), 2-naphthol (1 mmol), dimedone (1 mmol) and Fe 3 O 4 @SiO 2 NPs (0.014 g, 0.5 mmol, 5 mol%) in 2.5 mL ethanol and 2.5 mL water was refluxed at 80 °C.After completion of the reaction as indicated by TLC, the reaction mixture was cooled to room temperature and then diluted with chloroform (10 mL), the catalyst was recovered by using an external magnet.The solvent was evaporated and the solid obtained was recrystallized using ethanol.

4. General
All of the products were characterized and identified with m.p., 1 H NMR, 13 C NMR and FT-IR spectroscopy techniques.Spectral data of some of the products are given below.

5. Recycling and Reusing of the Catalyst
After completion of the reaction, the reaction mixture was dissolved in chloroform and then the catalyst was separated magnetically.The Fe 3 O 4 @SiO 2 NPs were washed three to four times with chloroform and ethylacetate and dried at 60 °C for 8 h.The separated catalyst was used for six cycles with a slight decrease in activity as shown in Table 4. a Reaction conditions: molar ratio of 4-nitrobenzaldehyde, 2-naphthol, dimedone (1:1:1); in water/ethanol under reflux conditions using recycled Fe 3 O 4 @SiO 2 ; b Isolated yield.

Conclusions
In summary, we have developed a novel and highly efficient method for the one-pot preparation of 14-aryl-14H-dibenzo[a]xanthene-8,13-dione derivatives by the reaction of β-naphthol, aromatic aldehydes and dimedone in the presence of Fe 3 O 4 @SiO 2 core-shell nanoparticles as the catalyst.The significant advantages of this methodology are high yields, a cleaner reaction, simple work-up procedure, short reaction times and easy preparation, reusability and handling of the catalyst.In addition, the onepot nature and the use of heterogeneous solid acid as an eco-friendly catalyst make it an interesting alternative to multi-step approaches.

Acknowledgements
The author gratefully acknowledges the financial support of this work by the Research Affairs Office of the Islamic Azad University, Qom Branch, Qom, I. R. Iran.

Figure 2 .Figure 3 .
Figure 2. XRD patterns of Fe 3 O 4 NPs (a) and Fe 3 O 4 @SiO 2 NPs (b) entries 2-12).Although in the absence of the catalyst only a trace amount of the product was obtained after 8 h.Many homogenous and heterogeneous catalysts, such as CH 3 COOH, MgSO 4 , NaOH, piperidine, Et 3 N, MgO NPs, CaO NPs, CuO NPs, AgI a) b)

Scheme 1 .
Scheme 1.The model reaction for the prepatation of tetrahydrobenzo[a]xanthen-11-one (4h) aldehyde and dimedone by means of a strong coordination bond.Initially, the nucleophilic addition of aldehydes and 2-naphthol in the presence of Fe 3 O 4 @SiO 2 NPs as catalyst leads to ortho-quinone methides (o-QMs) intermediate A. Subsequent Michael addition of dimedone with o-QM forms intermediate B which coordinates to the catalyst to cyclized accompanied by loss of H 2 O to afford product 4.

Table 1 ,
entries 3, 4)and protic solvents (Table1, entries 5-8) using 15 mol% of Fe 3 O 4 @SiO 2 nanoparticles.As shown in Table1the best result was obtained in H 2 O/EtOH (Table 1, entry 8) as the solvent for this multi-component reaction.It seems that the nucleophilic attack of the reactants can proceed smoothly by hydrogen bonding between water/ethanol and substrates.Next, we carried out the model reaction in H 2 O/Et-OH at various temperatures (Table1, entries 9, 10).As can be seen maximum yield was obtained under reflux conditions (Table1, entry 8).
a Isolated yield; b New Products.

Table 4 .
Reusability of the Fe 3 O 4 @SiO 2 nanoparticles a