A simple synthesis of magnetic nanoparticles-supported 4-aminomethylbenzoic acid as a highly efficient and reusable catalyst for synthesis of 2-amino-4H-chromene derivatives

A new 4-aminomethylbenzoic acid-functionalized Fe3O4 magnetic nanoparticles as a hybrid heterogeneous catalyst was synthesised and characterized by FT-IR, XRD, TGA, TEM, SEM and VSM techniques. The catalytic activity of this nanocatalyst was probed through one-pot synthesis of 2-amino-4H-chromene derivatives from three component reactions of various aldehydes, malononitrile and dimedone. The chemically and thermally stable catalyst was easily recovered using an external magnet and reused for at least five successive runs without significant loss of its activity. The simplicity of the method, high yields of the products, mild reaction conditions and low reaction times are the other advantages of this procedure.


Introduction
Synthesis of new magnetic nanoparticles-supported catalyst has attracted considerable attention due to their facile separation from the reaction mixture using an external magnet and providing improved reusability of the catalyst by sustaining their catalytic efficiency after several repeated reactions [1]. This type of catalyst support is now growing and finds a powerful position in catalytic reactions. The gap between homogeneous and heterogeneous catalysis is bridged by surface functionalization of magnetic nanoparticles. These catalysts are widely used in biotechnology since they have good biocompatibility and biodegradability characteristics which could be important for functional organic materials grafted to Fe 3 O 4 nanoparticles [2,3]. The use of magnetic nanoparticles without surface functionalization as catalysts is not promising, since their surface is highly active and leads to the agglomeration of the catalyst particles; coating the catalyst surface with shell as prevents this deficiency [4][5][6][7][8]. It is important to note that organic catalystfunctionalized magnetic nanoparticles indicate not only a high degree of chemical and thermal stability but also high catalytic activity [9][10][11].
Compounds containing 2-amino-4H-chromene are found in a number of natural products such as tannins and polyphenols which are commonly found in a variety of fruits, vegetables, teas and red wines [12]. The interest in these compounds is increasing because of their reported benefit to health. In addition, the 2-amino-4Hchromene moiety is present in a variety of naturally occurring compounds that have anticoagulant, anticancer, anti-ancaphylactia, antibacterial and fungicidal activities [13][14][15][16][17][18].
In the present study, we present our results on the preparation and characterization of 4-aminomethylbenzoic acid (AMBA)-functionalized Fe 3 O 4 magnetic nanoparticles (AMBA-Fe 3 O 4 ) as an active and stable magnetically separable basic nanocatalyst and its catalytic application for the one-pot synthesis of 2-amino-4Hchromene derivatives from dimedone, various arylaldehydes and malononitrile in ethanol under mild conditions (Scheme 1). Melting points were measured on an Electrothermal 9100 apparatus. The X-ray powder diffraction (XRD) of the catalyst was carried out on a Philips PW 1830 X-ray diffractometer using a CuKa source (k = 1.542 Å ) in a range of Bragg's angle (10°-80°) at room temperature. Scanning electron microscopy (SEM) analyses were taken using VEGA//TESCAN KYKY-EM 3200 microscope (acceleration voltage 26 kV). Transmission electron microscopy (TEM) experiments were conducted on a Philips EM 208 electron microscope. Thermogravimetric analysis (TGA) was recorded on a Stanton Red craft STA-780 (London, UK). NMR spectra were recorded on a Bruker DRX-400 AVANCE instrument (300 MHz for 1 H, 75 MHz for 13 C). The spectra were measured in DMSO-d 6 as the solvent. FT-IR spectra were recorded on an FT-IR Bruker vector 22 spectrophotometer. Magnetic measurements were performed using a vibration sample magnetometer (VSM, MDK, and Model 7400) analysis.

Preparation of 4-aminomethylbenzoic acid functionalized Fe 3 O 4 nanoparticles
FeCl 3 Á6H 2 O (2.43 g, 0.09 mol) and FeCl 2 Á4H 2 O (0.89 g, 0.0045 mol) were dispersed in 100 mL distilled water by sonication until the salts dissolved completely. Then, 0.3 g of AMBA in 10 ml NH 4 OH solution was added to the above mixture under constant nitrogen flow, and, as a result, a black suspension was formed. This suspension was refluxed at 100°C for 12 h. AMBA-Fe 3 O 4 nanoparticles were separated from the aqueous solution by a magnetic field, washed with distilled water four times and then dried in an oven overnight (Scheme 2).

Scheme 2 Preparation of AMBA-Fe 3 O 4 nanoparticles
General procedure for the synthesis of 2-amino-4H-chromene derivatives To a 3 mL mixture of ethanol, aldehyde (1 mmol), malononitrile (1 mmol, 0.066 g), dimedone (1 mmol, 0.141 g) and AMBA-Fe 3 O 4 magnetic nanoparticles (0.05 g) as a catalyst were added and the mixture was stirred at 60°C for a specific time. When the reaction was complete (monitored by TLC), the solvent was evaporated. Then, the reaction mixture was dissolved in CH 2 Cl 2 (15 mL), and subsequently AMBA-Fe 3 O 4 was separated by a magnetic field and washed with dry CH 2 Cl 2 three times and checked for its reusability. The solvent of the solution containing the product was evaporated, the solid residue was recrystallized using ethanol and the product obtained as a white powder. All of the desired products were characterized by comparison of their physical data with those reported in the literature. Table 2,

Results and discussion
Characterization of the prepared AMBA-Fe 3 O 4 magnetic nanoparticles X-ray diffraction (XRD) analysis X-ray diffraction was used to identify phases of the synthesized AMBA-Fe 3 O 4 magnetic nanoparticles. The result shown in Fig. 1 was fitted for the observed six peaks with the following Miller indices: (2 2 0), (3 1 1), (4 0 0), (4 2 2), (5 1 1) and (4 4 0) that identified them as Fe 3 O 4 nanoparticles. The XRD peaks are broad indicating the small nanoparticles. Applying the Scherrer equation [19,20], the calculated size was estimated to be about 15 nm which is in a good agreement with the TEM observations.

Fourier transform infrared (FT-IR) analysis
The peak around 3428 cm -1 is referred to the N-H stretching vibration. The peaks around 2923 and 2854 cm -1 are ascribed to the asymmetric and symmetric vibrations of C-H stretching. The adsorption peaks at 1632, 1398 and 1028 cm -1 correspond to the asymmetric and symmetric stretching vibrations of the carboxylate group of the 4-aminomethylbenzoic acid moiety. The characteristic absorbing peak of Fe 3 O 4 appeared at 584 cm -1 , which can be ascribed to the vibration of the Fe-O group. Therefore, the obtained data from FT-IR spectroscopy can confirm the existence of the magnetic nanoparticles and aromatic ligand moiety in the structure of the AMBA-Fe 3 O 4 nanoparticles (Fig. 2). Thermogravimetric analysis (TGA) Thermal gravimetric analysis (TGA) was implemented at the range of 25-900°C under N 2 atmosphere in order to define the loading of organic groups coated on the Fe 3 O 4 magnetic nanoparticles (Fig. 3). The TGA curve of the AMBA-Fe 3 O 4 nanoparticles shows the mass loss of the organic functional group as it decomposes upon heating (volatile components disappeared before a temperature of about 100°C were ignored). The curve shows a weight loss of about 9.37% between 100

Morphological characteristic
Surface morphology, particle shape, fundamental physical properties and size details of the prepared AMBA-Fe 3 O 4 magnetic nanoparticles were investigated through SEM and TEM microscopies (Fig. 4a, b). As can be seen from the TEM and SEM images, the average particle size is estimated to be 15-30 nm while AMBA-Fe 3 O 4 showed a sphere-like structure. As shown in Fig. 4b, a basically core-shell structure (dark-colored core for Fe 3 O 4 magnetic nanoparticles and light-colored shell for AMBA) was obtained.

Vibrating sample magnetometer (VSM)
The VSM data for the  Table 1 show that an optimal condition was 20 mol% of AMBA-Fe 3 O 4 magnetic nanocatalyst at 60°C (Table 1, entry 8).
Next, various aldehydes were used in the reactions that led to the corresponding products in high to excellent yields ( Table 2). As shown in Table 2, the reactions with arylaldehydes, including electron-donating groups or electron-withdrawing groups substituents, afforded the desired products in high to excellent yields. Natural aldehydes such as vanillin and cinnamaldehyde also gave the corresponding products in high yields. Isonicotincarboxaldehyde as a hetero-aromatic aldehyde  afforded a satisfactory result. However, butyraldehyde as an aliphatic aldehydes did not proceed further this reaction.
The mechanism of the formation of 2-amino-4H-chromene derivatives in the presence of AMBA-Fe 3 O 4 as a catalyst via a three-component coupling strategy is proposed to begin with a Knoevenagel condensation between malononitile and the aromatic aldehyde, followed by the Michael addition of dimedone to the Knoevenagel product, and finally an intramolecular ring closure (Scheme 3) [28].
We also investigated the recyclability of the AMBA-Fe 3 O 4 as a magnetic nanocatalyst using the model reaction of benzaldehyde, malononitrile and dimedone ( Table 2, entry 1). The results showed that AMBA-Fe 3 O 4 is a stable catalyst in reaction media and can be reused five times without any significant loss of its activity (Fig. 6). To show the efficiency of this method, the results of the synthesis of 2-amino-4Hchromene derivatives by our method was compared with those reported in the literature. The results show that this nanocatalyst is very efficient with respect to the reaction times and yields (Table 3).

Conclusions
We have developed a new 4-aminomethylbenzoic acid functionalized Fe 3 O 4 magnetic nanoparticles as an active and reusable base hybrid heterogeneous catalyst. This basic nanocatalyst was characterized by different methods and its applicability for the preparation of 2-amino-4H-chromene derivatives from arylaldehyde, malonitrile and dimedone was investigated. This heterogeneous catalyst is highly active and has a very high surface area, and its thermal stability was confirmed by different characteristic techniques. The recoverability and reusability of this inexpensive catalyst are other advantages of the protocol.