Solvent-free synthesis of 1-amidoalkyl-2-naphthol and 3-amino-1-phenyl-1H benzo[f]chromene-2-carbonitrile derivatives by Fe3O4@enamine-B(OSO3H)2 as an efficient and novel heterogeneous magnetic nanostructure catalyst

Abstract A green procedure for the one-pot three-component synthesis of 1-amidoalkyl-2-naphthol and 3-amino-1-phenyl-1H benzo[f]chromene-2-carbonitrile derivatives from the reaction of 2-naphtol, aldehydes, and malononitrile/acetamide in the presence of a catalytic amount of Fe3O4@enamine-B(OSO3H)2 as an efficient and novel heterogeneous magnetic nanostructure catalyst is described. The catalyst was characterized using Fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), vibrating sample magnetometry (VSM), energy dispersive X-ray spectroscopy (EDX), and X-ray diffraction (XRD). These strategies possess some merits such as simple work-up method, easy preparation of the catalyst, short reaction times, good-to-high yields, and non-use of hazardous solvents during all steps of the reactions. Moreover, due to the magnetic nature of the catalyst, it was readily recovered by magnetic decantation and can be recycled at least six runs with no considerable decrease in catalytic activity.


INTRODUCTION
Energy sources have been used for various processes and systems because this source has played a major role in preventing pollution in our environment 1-2 . Nano small-sized catalysts due to their high surface area can be enhanced the chemical synthesis expediency 3-6 . Among the many efforts to fi nd the appropriate support used for the synthesis of heterogeneous catalysis, functionalization of the Fe 3 O 4 magnetic nanoparticles (MNPs) due to the ability to adjoin to functional groups with strong connection, high stability and availability have emerged as a thoughtfully route to bridge the gap between homogeneous catalysis and them 7-9 . Some features of MNPs, such as a tendency to agglomeration due to the strong dipole-dipole attraction and deform during the reaction period will limit their utilization 10- 11 . Thus, in order to increase the effi ciency of this kind of nanoparticles in the various special process, functionalization and modification of their surfaces are necessary. Surface modifi cation of the magnetic nanoparticles by silica layers improves their capability to interact with organic compounds through OH groups on the silica surfaces 12-14 . Due to the magnetic nature of the iron oxide nanoparticles, they can provide a variety of potential usages such as drug delivery, MRI contrast agents, hyper thermal agents, and cell sorting [15][16][17][18][19][20] . Also, in the catalysts synthesized using these magnetic supports, the fi nal product can be readily isolated from the reaction medium by an external magnet.
The synthesis of 1-amidoalkyl-2-naphthol and its derivatives have attracted much attention of synthetic researchers because of their important biological and pharmacological features such as bradycardia and depressor effects in humans 21 3 in ionic liquid 31 , p-toluenesulfonic acid 32 , 2,4,6-trichloro-1,3,5-triazine 33 , HPMo 34 , Sr(OTf) 2 35 , and montmorillonite K 10 36 are examples. Aminochromene structure moiety has also been successfully employed for the synthesis a variety of derivatives with remarkable biological and pharmacological properties. In addition, Aminochromene derivatives have been introduced to have antimicrobial 37-38 , anticancer 39-41 , antiviral 42-43 , antibacterial 44 , and central nervous system (CNS) 45 activities. The synthetic method for the synthesis of substituted 3-amino-1H-chromenes is one of the aminochromene derivatives involve: the condensation reaction of 2-naphthol, aldehyde, and malononitrile. There are some methods, such as using CuO-CeO 2 46 , basic ionic liquids 47-48 , K 2 CO 3 49 , Rochelle salt 50 , and DABCO 51 as homogeneous or heterogeneous catalysts which have been presented to the synthesis of 3-amino-1H-chromenes derivatives. Some of the above--mentioned catalysts suffer from disadvantages such as Hazardous organic solvents, tedious work-up, long reaction times, low yields of the product, drastic reaction conditions, toxic and corrosive reagent, and use of microwave or ultrasonic irradiation. Therefore, to overcome these drawbacks, there is still much demand to expand an effi cient and simple heterogeneous catalytic system for the preparation of amidoalkyl naphthols derivatives. spectra were obtained using a Fourier-transform infrared spectrometer (PerkinElmer PXI spectrometer in KBr wafers). A VSM (VSM; Lake Shore 7200 at 300 K VSM) was used to analyze magnetic susceptibility measurements. The energy dispersive X-ray spectroscopy (EDX) was applied to the chemical composition of synthesized nanoparticles with an (ESEM, Philips, and XL30). The structure of MNPs was examined using a scanning electron microscope (SEM-LEO 1430VP analyzer). Analysis of the crystalline phase was carried out with an X-ray diffraction XRD-6100 Shimadzu, Japan. The thermal stability of the magnetic nanoparticles was accomplished with a TG209 F1; Netzsch, Germany.

Synthesis of Magnetic Nanoparticles (Fe 3 O 4 ).
In this way, 2.2 g of FeCl 2 . 4H 2 O and 5.7 g of FeCl 3 . 6H 2 O were dissolved in 60 ml of deionized water in a beaker under vigorous stirring and nitrogen gas protection for 1h. Then 5 ml of ammonium hydroxide solution was added slowly into the reaction mixture until the content of the reaction vessel reached pH 11.0 and the black precipitate was achieved. The reaction was at continued at ambient temperature under agitation for another 1 h. After completion of the reaction, the precipitate was isolated by an appropriate external magnetic fi eld and rinsed three times with deionized water to remove any unreacted chemicals. Finally, the magnetic nanoparticles dried under vacuum oven at 50 o C for 18 h and stored in airtight containers.

Synthesis of silica coated magnetic nanoparticles (Fe 3 O 4 @SiO 2 ).
First, 0.1 g of fabricated Fe 3 O 4 MNPs was dispersed in a mixture of 50 mL ethanol, 8 mL deionized water and 4 mL of aqueous ammonia (28 wt%) under mechanical stirring for 30 min. The next step was followed by the dropwise addition of 0.5 mL TEOS to the above solution under vigorous sonication for another 30 min. After continuous stirring at 400 rpm for 24 h at room temperatures, the silica coated magnetic nanoparticles were isolated by magnetic decantation and then rinsed several times with the equal values of ethanol and distilled water to remove nonmagnetic byproduct, and fi nally dried at vacuum conditions at 50 o C for 15 h.

Synthesis of Fe 3 O 4 bonded aminopropyltriethoxysilane (Fe 3 O 4 @APTES).
About 1 g of the Fe 3 O 4 @SiO 2 was dispersed in a reaction fl ask containing 40 mL of dry toluene by ultrasonication vibration for 30 min, followed by the addition of 2 mL of aminopropyltriethoxysilane (APTES). The achieved solution was mechanically stirred at 400 rpm for 24 h under refl ux conditions. After reaching the desired product, the precipitates of core-shell Fe 3 O 4 @APTES nanoparticles were isolated by magnetic decantation, rinsed three times with deionized water and anhydrous ethanol, and dried under vacuum oven at 50 o C for 15 h.

Synthesis of Fe 3 O 4 @APTES bonded aspartic acid (Fe 3 O 4 @APTES/ASA).
1 g of Fe 3 O 4 @APTES nanoparticles was poured in 40 mL ethanol and dispersed by ultrasonic vibration; then, 0.5 g of aspartic acid (ASA) was added, and the achieved solution was mechanically stirred for 24 h under refl ux conditions. At the end of the reaction, the Fe 3 O 4 @APTES/ASA nanoparticles were extracted from the reaction vessel using an external magnetic fi eld, washed three times with equal amounts of deionized water and anhydrous ethanol to remove any unreacted organic groups, and dried under vacuum oven at 50 o C for 15 h.

Synthesis of Fe 3 O 4 @enamine-B(OH) 2 .
About, 1 g of Fe 3 O 4 @APTES/ASA nanoparticles were dispersed in 50 mL dry ethanol and sonicated for 30 min. Then, 4 mmol of 2-formylbenzeneboronic acid was added into the reaction fl ask and the solution was refl uxed and mechanically stirred for 24 h under a continuous fl ow of nitrogen gas. Finally, the resultant was collected using an appropriate magnetic fi eld and rinsed three times with equal amounts of distilled water and ethanol to eliminate any unreacted chemicals, and dried under vacuum oven at 50 o C for 15 h.

Synthesis of Fe 3 O 4 @enamine-B(OSO 3 H) 2 .
To prepare Fe 3 O 4 @enamine-B(OSO 3 H) 2 , 2 g of Fe 3 O 4 @enamine-B(OH) 2 was dispersed in 20 mL of dry dichloromethane for 30 min using ultrasonication. After that, 10 mmol of chlorosulfonic acid was added dropwise to the reaction solution and the obtained mixture was stirred at 0 o C for 6 h. Finally, these precipitates were separated with an external magnetic fi eld, rinsed three times with 30 mL of with water and ethanol to eliminate the unreacted residue of the chemicals, and next dried in a vacuum oven at 60 o C for 12 h. All stages of the Fe 3 O 4 @enamine-B(OSO 3 H) 2 synthesis are exhibited in Scheme 1.

FTIR analysis of Fe 3 O 4 @enamine-B(OSO 3 H) 2 .
The FT-IR spectra of the can see that the catalyst after the third recovery and reuse do not exhibit any difference.

TGA analysis of Fe 3 O 4 @enamine-B(OSO 3 H) 2 .
As observed in Fig. 2, thermogravimetric analysis (TGA) was applied for measuring the thermal constancy of the As can be seen in all of the samples, the weight loss in the temperature range below 240 o C was observed due to evaporation of physically adsorbed H 2 O molecules and dehydration of the surface OH groups. In the curve of

VSM analysis of Fe 3 O 4 @enamine-B(OSO 3 H) 2 .
The magnetization measurements of the Fe 3 O 4 , Fe 3 O 4 @SiO 2 , and Fe 3 O 4 @enamine-B(OSO 3 H) 2 were surveyed by vibrating sample magnetometer (VSM) at room temperature. As shown on Fig. 4, the saturation magnetization of Fe 3 O 4 , Fe 3 O 4 @SiO 2 , and Fe 3 O 4 @ enamine-B(OSO 3 H) 2 were found to be at about 61.82, 51.34, and 32.56 emu/g, respectively. The decrease in value of the saturation magnetization can be assigned to the presence of silica-layers, organic groups, and sulfuric acid groups on the surface of the magnetic nanoparticles.

RESULTS AND DISCUSSION
In continuation of our investigations and on the basis of the achieved information, Fe 3 O 4 @enamine-B(OSO 3 H) 2 was tested as a separable heterogeneous magnetic nanocatalyst for the synthesis of 1-amidoalkyl-2-naphthol and 3-amino-1-phenyl-1H-benzo[f]chromene-2-carbonitrile derivatives under solvent-free conditions (Scheme 2).  To fi nd the optimal conditions, the reaction between 2-naphtol, 4-chlorobenzaldehyde, and acetamide with 1:1:1 molar ratios and the reaction between 2-naphtol, 4-chlorobenzaldehyde and malononitrile with 1:1:1.1 molar ratios were selected as the model reactions, respectively. The effects of various factors such as amounts of the catalyst, solvents, and temperatures were studied on the rate and yield of the 1-amidoalkyl--2-naphthol and 3-amino-1-phenyl-1H-benzo[f]chromene-2-carbonitrile synthesis reaction ( Table 1). As can be seen, in the presence of the catalyst, with different solvents such as H 2 O, EtOH, CH 3 CN, CHCl 3 , DMF, and toluene, under refl ux conditions, the yields of the desired products were low-to-moderate (Table 1, entries 1-6). The outcomes showed that the model reactions using 15 mg of the Fe 3 O 4 @enamine-B(OSO 3 H) 2 as the heterogeneous magnetic nanocatalyst at 90 o C in the absence of solvent proceeded with the highest yields of the products (Table 1, entry 7). The effect of temperature on the reactions times and products yields are well proved. As can be seen from this table (Table 1, entries 7 and 11-13), the reactions times of the model are signifi cantly reduced and subsequently products yields also increase Table 1. Optimization one-pot three-component reaction between 2-naphtol, acetamide and 4-chlorobenzaldehyde, and the reaction between 2-naphtol, malononitrile, and 4-chlorobenzaldehyde under different conditions Scheme 3. A suggested mechanism for the synthesis of 1-amidoalkyl-2-naphthol (4) and 3-amino-  Table 2, to further explore the effi ciency of the heterogeneous magnetic nanocatalyst using these optimized reaction conditions, a range of 1-amidoalkyl-2-naphthols were synthesized by the one-pot three-component condensation of 2-naphtol, acetamide, and aldehydes having electron-donating as well as electron-withdrawing groups, using 15 mg of the Fe 3 O 4 @ enamine-B(OSO 3 H) 2 under solvent-free conditions at 90 o C in high-to-excellent yields with short reaction times.
After the successful preparation of a series of 1-amidoalkyl-2-naphthols, we decided to explore the effectiveness of the Fe 3 O 4 @enamine-B(OSO 3 H) 2 in the synthesis of 3-amino-1-phenyl-1H-benzo[f]chromene-2-carbonitriles by the one-pot three-component condensation of 2-naphtol, malononitrile and aldehydes having electron-donating as well as electron-withdrawing groups using 15 mg of the Fe 3 O 4 @enamine-B(OSO 3 H) 2 under solvent--free conditions at 90 o C. As shown in Table 3, the fi nal products were achieved in high-to-excellent yields under the above-mentioned conditions.
Reusability of Fe 3 O 4 @enamine-B(OSO 3 H) 2 as a novel and effi cient heterogeneous magnetic nanocatalyst was confirmed in the preparation of 1-amidoalkyl-2-naphthol 4 (a) and 3-amino-1-phenyl-1H-benzo[f]chromene-2-carbonitrile 6 (b) derivatives. Thus, after completion of the reaction, ethyl acetate as a polar solvent was added to the backer, and the reaction mixture was heated for 10 min. Extraction with magnetic decantation was achieved the corresponding product and the catalyst remained in the beaker. The recovered magnetic catalyst was rinsed with distilled water and reused with the negligible decrease in catalytic activity for six runs (Fig. 6). A comparison between the previously reported methods and our procedure could highlight the effi ciency of the synthesized catalyst Fe 3 O 4 @enamine-B(OSO 3 H) 2 for the preparation of 1-amidoalkyl-2-naphthol (4) and 3-amino-1-phenyl-1H-benzo[f]chromene-2-carbonitrile (6) derivatives. To ensure the safety, cleanliness and simplicity of classical strategies, solvent-free procedures from the perspective of green chemistry are important. The outcomes tabulated in Table 4 show that our pro- Table 3. Preparation of 3-amino-1-phenyl-1H-benzo[ ]chromene-2-carbonitrile (6) derivatives using Fe 3 O 4 @enamine-B(OSO 3 H) 2 as a catalysta cedure, utilizing Fe 3 O 4 @enamine-B(OSO 3 H) 2 , provided the highest yields of the products in low reaction times.

CONCLUSIONS
The prepared magnetic nanocatalyst was characterized by several techniques such as FTIR, TGA, VSM, EDX and XRD analysis. Magnetic recovery of the catalyst Fe 3 O 4 @enamine-B(OSO 3 H) 2 was discovered to be a highly effective and economically sustainable catalyst for the synthesis of a wide range of substituted 1-amidoalkyl-2-naphthol and 3-amino-1-phenyl-1H benzo[f] chromene-2-carbonitrile derivatives through a one-pot three component condensation reaction. The main properties of these procedures are a simple work-up method, easy preparation of the catalyst, short reaction times, good-to-high yields, and non-use of hazardous solvents during all steps of the reactions.