Magnetic amine-functionalized graphene oxide as a novel and recyclable bifunctional nanocatalyst for solvent-free synthesis of pyrano[3,2-c]pyridine derivatives

Document Type: Research Paper

Authors

1 Department of Chemistry, Faculty of Science, K.N.Toosi University of Technology, Tehran, Iran

2 Faculty of Chemistry and Chemical Engineering, Malek-Ashtar University of Technology, Tehran, Iran

Abstract

The new magnetic amine-functionalized graphene oxide (Fe3O4-GO-NH2) nanocatalyst was prepared through the reaction of 3-aminopropyltriethoxysilane (APTES) with magnetic graphene oxide (Fe3O4-GO). It was characterized by XRD, TEM, SEM, FT-IR and EDX techniques. The intrinsic carboxylic acids on the edges of Fe3O4-GO along with the amine groups post grafted to the surface of Fe3O4-GO led to preparation of an acid-base bifunctional magnetically recyclable nanocatalyst. It proved to be efficient nanocatalyst for solvent-free synthesis of pyrano[3,2-c]pyridine derivatives under mild reaction conditions with good to excellent yields. This heterogeneous catalyst also exhibited higher activities than acid or base functionalized mesoporous silica, magnetic GO or basic Al2O3 an even higher than some basic homogeneous catalysts such as triethylamine and piperazine. More importantly, due to the loaded iron oxide nanoparticles, this catalyst could be easily recovered from the reaction mixture using an external magnet and reused without significant decrease in activity even after 7 runs.
 

Keywords


INTRODUCTION

Pyrano[3,2-c]pyridine derivatives are important heterocyclic compounds with a vast range of biological, medicinal and pharmacological properties. They are constituents of antitumor, anti-flammatory, antifungal and antitubercular compounds [1-6]. In view of these useful properties, several methods have been reported for the synthesis of these interesting compounds. In the reported methods several catalysts such as sodium ethoxide [4], sodium [7], hexadecyltrimethylammonium bromide [8], KF-AL2O3 [9], sodium hydroxide, piperidine [10], organocatalyst [11], quinine [12], MCM-41-SO3H [13], [BMIM]OH [14] and also different solvents such as BuOH [1,5,15], DMF [16,17], MeOH [7], H2O [8], toluene [11,12], EtOH [18] have been used for the synthesis of pyrano[3,2-c]pyridines. These compounds also have been synthesized under catalyst-free [18] and solvent-free conditions [4,13]. Although these methods are quite satisfactory, they have one or more of drawbacks such as use of hazardous organic solvents, low yields of the products, extended reaction times and high temperatures.

Therefore, it is still desirable to seek a green and efficient protocol for preparation of these compounds. In recent years, most studies have been focused on homogeneous catalysts because of their high activity and selectivity [19,20]. The difficulty of recycling and reusing of these catalysts increases the cost and even pollution of the environment and/or final product [21,22]. An efficient method to overcome the problem of homogeneous catalysts is the heterogenization of active catalytic molecules and creating a heterogeneous catalytic system. However, the recovery of the heterogeneous catalysts from the final reaction mixture requires a filtration or centrifugation step and/or tedious work up. By using magnetic catalysts, they can be easily recovered by an external magnet. Among magnetic particles, Fe3O4 magnetic nanoparticles (MNPs) have received more attention due to their large specific surface area and good super paramagnetic property, which allows them to be separated simply by applying a magnetic field.

Recently, magnetic nanoparticles have been used as reusable catalysts in many organic transformations such as oxidation of alcohols [23,24], oxidation of cyclohexene [25], reduction of 4-nitrophenol [26,27] and synthesis of 4H-chromenes [28]. Magnetic nanocomposites have also some potential applications in different fields such as batteries, electrochemical display devices, magnetic evaporations, enzyme immunoassay, drug delivery [29-33] lipase immobilization [34] and synthesis of pyrano[3,2-c]chromenes, chromenes and spiro-oxindoles [35].

GO has attracted tremendous interest owing to its unique structural and surface properties [36,37]. The abundant oxygen containing surface functionalities, such as epoxide, hydroxyl and carboxylic acid groups make GO a potential starting material for immobilization of a large number of substances including a wide range of metals, biomolecules, fluorescent molecules, drugs, and inorganic nanoparticles [38-44]. Moreover, the presence of these functional groups makes GO sheets strongly hydrophilic, causing them to readily disperse in water [45-47]. Accordingly, these properties along with the large specific surface area have provided a desirable platform for loading magnetic nanoparticles onto GO [47-50]. In addition, GO could be an ideal carbocatalyst for using in a variety of chemical transformations, such as hydration, oxidation, C-H activation and polymerization [51]. However, GO has been used as a monofunctional catalyst based on its either high acidity or strong oxidization properties [52].

Due to the importance of Pyrano[3,2-c]pyridines and following of our interest towards the development of new catalysts for the synthesis of various organic compounds [13,18,52-61], herein we report the synthesis of a magnetic acid-base bifunctional catalyst by loading Fe3O4 nanoparticles onto the surface of GO sheets which have exhibited high activity for the synthesis of pyrano[3,2-c]pyridine derivatives through the reaction between malononitrile and 3,5-bis(benzylidene)-4-piperidone (Scheme 1).

 

EXPERIMENTAL

All chemicals were purchased from the Merck chemical company. Melting points were recorded on a Buchi B-540 apparatus. IR spectra were recorded on an ABB Bomem Model FTLA 200-100 instrument. 1HNMR and 13CNMR spectra were measured on a Bruker DRX-300 spectrometer at 300 and 75 MHz, using TMS as an internal standard and DMSO-d6 as solvent. Chemical shifts (δ) were reported relative to TMS, and coupling constants (J) were reported in hertz (Hz). Mass spectra were recorded on a Shimadzu QP 1100 EX mass spectrometer with70 eV ionization potential. Elemental analyses for C, H and N were performed using a Heraeus CHN Rapid analyzer. X-ray powder diffraction (XRD) was carried out on a Philips X’Pert diffractometer with Cu Kα radiation. The structure and morphology of the products were characterized by transmission electron microscopy (TEM) and was recorded on a Philips CM-30 instrument on an accelerating voltage of 150 kV and scanning electron microscopy (SEM) analyses were performed by a Philips XL-30 instrument operating at an accelerating voltage of 7.0 kV. The chemical compositions of the samples were evaluated by scanning electron microscopy (SEM, SAMX) equipped with an energy dispersive X-ray (EDX).

 

Preparation of Fe3O4-GO-NH2

At first, Fe3O4-GO was prepared according to the previously reported method in the literature [62]. Then, a mixture of Fe3O4-GO (3g), 3-aminopropyltriethoxysilane (ATPES) (3.16 mL) in dry toluene (50 mL) was refluxed for 12 h. The catalyst was collected by an external magnet, washed with dichloromethane and diethyl ether and dried at 80ºC for 2 h.

 

Preparation of 3,5-dibenzylidenepiperidin-4-ones

In a 50 mL reaction vial, a mixture of the 4-piperidone (10 mmol), an appropriate amount of aldehyde (20 mmol), 10% NaOH (1 mL) and 95% EtOH (30 mL) was stirred at room temperature for 0.5–2 h. The separated solid was collected by filtration and was recrystallized from ethanol for further purification [1].

 

General procedure for the synthesis of pyrano[3,2-c]pyridine derivatives in the presence of Fe3O4-GO-NH2 under solvent-free conditions

A mixture of 3,5-dibenzylidenepiperidin-4-one (1mmol), malononitrile (2mmol) and Fe3O4-GO-NH2 (30 mg) was ground thoroughly. It was then transferred into a reaction vessel and stirred at 80°C for an appropriate period of time. After completion of the reaction (monitored by TLC; petroleum ether and EtOAc, 2:1), the mixture was cooled down to room temperature and poured into the water (20 mL). The catalyst was then collected with an external magnet and the crude product was recrystallized from 95% EtOH to give the pure product.

 

Spectral data of some new and known synthesized compounds

(8E)-2-Amino-8-(2,3-dichlorobenzylidene)-4-(2,3-dichlorophenyl)-5,6,7,8-tetrahydro-6-methyl-4H-pyrano[3,2-c] pyridine-3-carbonitrile (Table 4, entry 1, compound 3a, C23H17Cl4N3O)

M.P: 215-217°C; IR (KBr) (ν cm-1): 3332, 3260, 2202, 1678, 1637, 1601; 1H NMR (300 MHz, DMSO-d6), δ (ppm): 2.09 (3H, s, N-CH3), 2.51 (1H, d, H-Pyridine, J=14.0 Hz), 3.02 (1H, d, H-Pyridine, J=16.2 Hz), 3.15 (1H, d, H-Pyridine, J=14.0 Hz), 3.31 (1H, d, H-Pyridine, J=14.8 Hz), 4.70 (1H, s, H-Pyran), 6.94 (1H, s, C=CH), 7.05 (2H, s, NH2), 7.24-7.44 (4H, m, Ar-H), 7.58 (2H, d, Ar-H4, J=8.0 Hz); 13C NMR (75 MHz, DMSO-d6), δ (ppm): 44.2, 53.7, 54.2, 118.8, 119.9, 128.0, 128.9, 129.2, 129.4, 129.6, 130.3, 130.6, 132.0, 136.3, 139.5, 142. 7, 160.1; MS (EI), m/z (%): 42 (100), 81 (47), 113 (30), 149 (70), 181 (61), 216 (54), 250 (91), 293 (12), 346 (11), 390 (14), 449 (19), 492 (22); Anal. Calcd for C23H17Cl4N3O: C, 56 %; H, 3.45 %; N, 8.52 %. Found: C, 56.03 %; H, 3.44 %; N, 8.55 %.

(8E)-2-Amino-8-(2-chlorobenzylidene)-4-(2-chlorophenyl)-5,6,7,8-tetrahydro-6-methyl-4H-pyrano[3,2-c] pyridine-3-carbonitrile (Table 4, entry 2, compound 3b, C23H19Cl2N3O)

M.p: 212-214 ºC; 1HNMR (300 MHz; DMSO-d6), δ (ppm): 2.09 (3H, s, N-CH3), 2.48-2.53 (1H, d, H-Pyridine, J= 14.6 Hz), 2.99 (1H, d, H-Pyridine, J = 16.1 Hz), 3.18 (1H, d, H-Pyridine, J= 14.0 Hz), 3.31 (1H, d, H-Pyridine, J= 17.0 Hz), 4.60 (1H, s, H-Pyran), 6.95 (1H, s, C=CH), 6.98 (2H, s, NH2), 7.25-7.52 (8H, m, Ar-H); 13CNMR(75 MHz, DMSO-d6), δ (ppm): 44.3, 53.9, 54.3, 54.5, 56.0, 127.1, 128.1, 128.9, 129.0, 129.2, 129.4, 129.6, 130.5, 130.8, 131.0, 132.3, 132.8, 133.3, 133.9, 134.0, 139.4, 140.1,

159.5; MS (EI), m/z (%): 51 (36), 81 (62), 115 (66), 182 (100), 216 (89), 379 (53), 422 (74), 423 (45); Anal. Calcd for C23H19Cl2N3O: C, 65.1 %; H, 4.48 %; N, 9.90 %. Found: C, 65.07 %; H, 4.46 %; N, 9.91%.

(8E)-2-Amino-8-(4-chlorobenzylidene)-4-(4-chlorophenyl)-5,6,7,8-tetrahydro-6-methyl-4H-pyrano[3,2-c] pyridine-3-carbonitrile (Table 4, entry 4, compound 3d, C23H19Cl2N3O)

M.p: 239-242 ºC; 1HNMR (300 MHz; DMSO-d6), δ (ppm): 2.16 (3H, s, N-CH3), 2.98 (1H, d, H-Pyridine, J= 16.0 Hz), 3.20 (1H, d, H-Pyridine, J= 14.3 Hz), 3.28 (1H, d, H-Pyridine, J= 14.0 Hz), 3.46 (1H, d, H-Pyridine, J= 14.0 Hz), 4.16 (1H, s, H-Pyran), 6.87 (1H, s, C=CH), 6.88 (2H, s, NH2), 7.25 (4H, d, Ar-H1,5, J= 8.0 Hz), 7.43 (4H, d, Ar-H2,4, J= 8.0 Hz); Anal. Calcd for C23H19Cl2N3O: C, 65.1 %; H, 4.48 %; N, 9.90 %. Found: C, 65.09 %; H, 4.49 %; N, 9.88%.

(8E)-2-Amino-8-(4-(benzyloxy)benzylidene)-4-(4-(benzyloxy)phenyl)-5,6,7,8-tetrahydro-6-methyl-4H-pyrano[3,2-c] pyridine-3-carbonitrile (Table 4, entry 12, compound 3l, C37H33N3O3)

M.p: 195-197 ºC; 1HNMR (300 MHz; DMSO-d6), δ (ppm): 2.13 (3H, s, N-CH3), 2.54 (1H, d, H-Pyridine, J = 14.4 Hz), 2.94 (1H, d, H-Pyridine, J= 14.0 Hz), 3.25 (1H, d, H-Pyridine, J= 14.4 Hz), 3.45 (1H, d, H-Pyridine, J= 14.0 Hz), 3.97 (1H, s, H-Pyran), 5.06 (2H, s, OCH2), 5.10 (2H, s, OCH2), 6.75 (2H, s, NH2), 6.83 (1H, s, C=CH), 7.00 (2H, d, Ar-H, J= 8.7 Hz), 7.03 (2H, d, Ar-H, J= 8.7 Hz), 7.12 (2H, d, Ar-H, J= 8.7 Hz), 7.18 (2H, d, Ar-H, J= 8.7 Hz), 7.29-7.46 (10 H, m, Ar-H): 13CNMR (75 MHz, DMSO-d6), δ (ppm): 44.4, 53.9, 54.4, 55.7, 113.0, 115.3, 115.5, 120.3, 120.4, 127.4, 129.4, 129.5, 130.9, 131.0, 132.3, 132.4, 139.1, 139.6, 139.7, 159.5, 159.6, 159.7, 162.8; MS (EI), m/z (%): 42 (16), 65 (63), 91 (100), 131 (40), 174 (44), 198 (19), 222 (23), 250 (63), 382 (86), 410 (54), 473 (30), 501 (75), 567 (16); Anal. Calcd for C37H33N3O3: C, 78.3 %; H, 5.82 %; N, 7.41 %. Found: C, 78.33 %; H, 5.80 %; N, 7.39 %.

(8E)-2-Amino-8-(naphthalen-1-yl-2-methylidene)-6-methyl-4-(naphthalen-1-yl)-5,6,7,8-tetrahydro-6-methyl-4H-pyrano[3,2-c]pyridine-3-carbonitrile (Table 4, entry 13, compound 3m, C31H25N3O)

M.p.: 190-192 °C; IR (KBr) (ν cm-1): 3329, 3182, 3052, 2933, 2189, 1684, 1638, 1497; 1HNMR (300 MHz, DMSO-d6), δ (ppm): 1.95 (3H, s, N-CH3), 2.40 (1H, d, H-Pyridine, J= 15.7 Hz), 3.03 (1H, d, H-Pyridine, J= 15.8 Hz), 3.16 (1H, d, H-Pyridine, J= 13.7 Hz), 3.43 (1H, d, H-Pyridine, J= 14.0 Hz), 4.37 (1H, s, H-Pyran), 5.05 (1H, s, C=CH), 6.96 (2H, s, NH2), 7.32 (1H, d, J= 6.5 Hz, Ar-H), 7.53 (7H, d, J= 8.3 Hz, Ar-H), 7.86 (2H, s, Ar-H), 7.96 (2H, d, Ar-H), 8.05 (1H, d, Ar-H), 8.37 (1H, s, Ar-H); 13CNMR (75 MHz, DMSO-d6), δ (ppm): 38.6, 38.9, 39.2, 39.5, 39.7, 40.0, 40.3, 44.3, 54.4, 54.7, 56.0, 56.3, 114.1, 119.0, 120.4, 123.1, 124.4, 125.4, 125.8, 126.2, 126.4, 126.8, 127.8, 128.5, 128.9, 131.3, 132.6, 133.2, 133.6, 139.5; MS (EI), m/z (%): 42(30.05), 128 (43.35), 141 (35.8), 152 (47.39), 165 (100), 232 (91.17), 283 (23.12), 388 (33.5), 411 (90.17), 455 (60.11); Anal. Calcd for C31H25N3O: C, 81.76 %; H, 5.49 %; N, 9.23 %. Found: C, 81.78 %; H, 5.48 %; N, 9.20 %.

(8E)-2-Amino-8-(3-hydroxybenzylidene)-4-(3-hydroxyphenyl)-5,6,7,8-tetrahydro-6-methyl-4H-pyrano[3,2-c] pyridine-3-carbonitrile (Table 4, entry 14, compound 3n, C23H21N3O3)

M.P.: 245-247 °C; IR (KBr) (ν cm-1): 3516, 2996, 2909, 2099, 1995, 1658, 1432; 1H NMR (300 MHz, DMSO-d6), δ (ppm): 2.14 (3H, s, CH3), 2.59 (1H, s, H-Pyridine), 2.96 (1H, d, H-Pyridine, J= 15.9 Hz), 3.24 (1H, s, H-Pyridine), 3.45 (1H, d, H-Pyridine, J= 15.0 Hz), 3.9 (1H, s, H-Pyran), 6.61-6.64 (7H, m, C=CH, Ar-H), 6.80 (2H, s, NH2), 7.14 (2H, m, Ar-H), 9.40 (1H, s, OH), 9.48 (1H, s, OH); 13C NMR (75 MHZ, DMSO-d6), δ (ppm): 39.50, 39.8, 40.0, 40.3, 41.0, 44.5, 54.3, 54.5, 55.9, 113.3, 114.2, 115.5, 118.3, 119.9, 121.5, 127.3, 129.5, 137.2, 139.0, 145.0, 157.3, 157.6, 159.7; MS (EI), m/z (%): 42 (46.11), 77 (41.1), 107 (82.2), 131 (60.5), 160 (36.1), 172 (30.5), 216 (35), 292 (41.1), 321(100), 387 (10); Anal. Calcd for C23H21N3O3: C, 71.32 %; H, 5.43 %; N, 10.85 %. Found: C, 71.30 %; H, 5.41 %; N, 10.86 %.

 

RESULT AND DISCUSSION

At the beginning, the prepared magnetic graphene oxide was reacted with 3-aminopropyltriethoxysilane (ATPES) to obtain the Fe3O4-GO-NH2 (Scheme 2). This catalyst (Fe3O4-GO-NH2) was characterized by IR, XRD, SEM, TEM, EDX techniques and acid-base titration. Density of acidic groups in Fe3O4-GO-NH2 determined by acid-base titration showed that the amount of H+ in the catalyst is 2.5 mmol. g−1.

 

FT–IR spectra of the catalyst

The functionalization of GO with magnetic Fe3O4 and –NH2 was confirmed by Fourier-transform infrared (FT–IR). The FT-IR spectra of Go (a), Fe3O4-GO (b) and Fe3O4-GO-NH2 (c) are shown in Fig. 1. The peak at 1738 cm-1 (Fig. 1.a) referred to the stretching band of C=O in carboxylic acid on the GO. The bands at 3364 and 1225 cm-1 were assigned to the stretching and bending of the O–H, respectively. The peak at 1624 cm-1 (aromatic C=C) could be attributed to the skeletal vibrations of unoxidized graphitic domains. The FT-IR spectrum of Fe3O4-GO samples differed from that of GO. The weakening of the peaks of C=O and O–H at 1738 and 3364 cm-1 respectively, are the evidences of this claim. The band around 587 cm-1 is indicative of Fe–O stretching vibrations, confirming the existence of Fe3O4.

In FT-IR spectra of Fe3O4-GO-NH2, the bands in region of 3363-3404 cm-1 were attributed to the stretching vibration of  (-NH2) and two peaks at 2859 and 2924 cm-1, indicative of symmetric and asymmetric stretching vibrations of C-H bands of CH2-CH2 groups connecting with the NH2 group. Also, the band at 446 cm-1 was referred to the Fe-O stretching vibrations. Besides, the appearance of two peaks at 1041 and 1106 cm-1 was assigned to the O-Si-O asymmetric stretching and Si-O-C stretching vibration.

 

The XRD spectra of the catalyst

The X-ray powder diffraction (XRD) patterns of the synthesized nanocatalyst are presented in Fig. 2. The XRD analysis was performed from 1.0° (2θ) to 80.0° (2θ) in which the broad peaks at 1.0 (2θ) to 29 (2θ) are attributed to the amorphous state. Two peaks at 30° and 43° are due to the crystalline state of carbon of graphene and four peaks at 35°, 53.5°, 57°, and 62.5° are indexed to the crystalline state of cubic Fe3O4 nanoparticles. The XRD profile of Fe3O4-GO-NH2 is consistent with the reported ones for the related compounds [62-64]. This confirms the structure of the synthesized catalyst (Fe3O4-GO-NH2).

 

The SEM and TEM of the catalyst

The presence of Fe3O4 nanoparticles was confirmed by scanning electron microscopy (SEM) and transmission electron microscopy (TEM). The SEM showed that the bright dots of Fe3O4 nanoparticles were uniformly spread on the surface of  GO. Also, in the TEM images, the black dots confirm the presence of Fe3O4 nanoparticles. The Fe3O4 nanoparticles with an average size of 13.6 nm are well decorated on the surfaces of the catalyst (Fig. 3).

The EDX of the catalyst

The energy dispersive X-ray (EDX) spectrum of the catalyst was also recorded. All of the expected elements and embedded nanoparticles are observed according to relative peak surfaces (Fig. 4).

 

Synthesis of pyrano[3,2-c]pyridine derivatives catalyzed by Fe3O4-GO-NH2 under solvent-free conditions

Fe3O4-GO-NH2 was investigated in the synthesis of pyrano[3,2-c]pyridines. First, the reaction parameters such as malononitrile amount, catalyst amount ,solvent and temperature were optimized in the synthesis of (8E)-2-Amino-8-(4-chlorobenzylidene)-4-(4-chlorophenyl)-5,6,7,8-tetrahydro-6-methyl-4H-pyrano[3,2-c]pyridine-3-carbonitrile (3d) as a model reaction (Scheme 3).

In order to optimize the amount of malononitrile, different amounts of malononitrile were used (Table 1). As indicated in Table 1, when 2 mmol of the malononitrile was used for each mmol of 3,5-bis-(4-chlorobenzylidene)-1-methyl-piperidin-4-one, the best yield of 3d was obtained.

A comparison of the catalyst performance in the synthesis of 3din various solvents is shown in Table 2. Among the solvents tested (MeOH, EtOH, PrOH, CH3CN, H2O, CHCl3, H2O/DMF) and solvent-free conditions, the best yield was obtained under solvent-free condition (Table 2). Finally, the reaction was performed at different temperatures under solvent-free conditions in which 80 ºC was found to be the best.

In order to show the efficiency of Fe3O4-GO-NH2 and compare its activity with other catalysts, the model reaction was performed in the presence of (α-Fe2O3)-MCM-41-SO3H, (α-Fe2O3)-MCM-41-NH2, KF/Al2O3, triethylamine, piperazine and GO-Fe3O4 (Table 3). The results show that the presence of amine groups in Fe3O4-GO-NH2 catalyst (Table 3, entry 8), causes the reaction to complete faster as well as giving a higher yield of products than Fe3O4-GO (Table 3, entry 7). Although, the methods reported by our research group [13,18] show that running the reaction in the presence of (α-Fe2O3)-MCM-41-SO3H under solvent-free conditions and also in the catalyst-free condition in EtOH, seem appealing at the first glance (Table 3, entry 1,2), yet such a procedure suffers from using higher temperature (115ºC) along with lower yield of products for the first case [13] and also longer reaction times for the latter [18]. Hence, it is concluded that Fe3O4-GO-NH2 is the most effective catalyst for the synthesis of pyrano[3,2-c]pyridine derivatives. The efficiency of this catalyst is due to the synergetic effects of –CO2H as Brönsted acid, Fe3+ as Lewis acid and–NH2 as base.

We then explored the synthesis of various pyrano[3,2-c]pyridine derivatives under optimized reaction conditions. In order to examine the scope and generality of the process, a variety of 3,5-bis-(benzylidene)-1-methyl-piperidin-4-ones possessing both electron-donating and electron-withdrawing groups were used. The results indicated that 3,5-bis-(benzylidene)-1-methyl-piperidin-4-ones with electron-withdrawing groups afforded shorter reaction times with higher yields (5a-5f, 5j, 5k). In contrast, those with electron-donating groups led to longer reaction times and lower yields (5h, 5i, 5l-5n).

A plausible mechanism is demonstrated in Scheme 4. Because of the two-dimensional structure and the large specific surface area of Fe3O4-GO-NH2, the reactants easily gain contact with the nanocatalyst. It should be mentioned that the process is facilitated by the assistance of Brönsted acidity of the intrinsic carboxylic acids on the edges of GO and Lewis acidity of Fe3+, both of which are capable of bonding with the carbonyl oxygen of the 3,5-dibenzylidenepiperidin-4-one moiety. Afterwards, the amine groups at the surface of GO, remove the acidic hydrogen from malononitrile and make it facile for Michael addition to occurs between activated 3,5-dibenzylidenepiperidin-4-one (1) and malononitrile. Subsequently, intramolecular nucleophilic addition of hydroxyl (-OH) to one of the cyano groups in the intermediate (2), resulted in formation of the intermediate (3). Finally, through 1,3-H shift in the intermediate (3), the desired product is formed (4).

 

Reusability and stability of the catalyst

The recovery and reusability of the catalyst is an important benefit especially for commercial applications. Thus, the reusability of the prepared nanocatalyst was investigated in the model reaction under optimized reaction conditions. To do this, the Fe3O4-GO-NH2 was collected by an external magnet. Then, the recovered catalyst was washed with ethyl acetate (3*10 mL), dried at 80°C and used in subsequent runs without observation of any significant decrease in activity even after 7 runs (Fig. 5). The ease of recovery of the reused catalyst by an external magnet, indicates that there is no considerable leaching of magnetic nanoparticles in the recovered catalyst even after seven times of reusing.

CONCLUSION

In this research a new bifunctional magnetically recyclable nanocatalyst (Fe3O4-GO-NH2) has been prepared and characterized by XRD, TEM, SEM, FT-IR, EDX and acid-base titration. It has shown a remarkable catalytic activity in the synthesis of pyrano[3,2-c]pyridine derivatives. This activity is due to combination of acidic functions (carboxylic acid groups on the edges of GO as Brönsted acid and Lewis acidity of the Fe3+) to activate the oxygen moiety and basic function (the amine groups) to remove acidic hydrogen as well as large surface area of the catalyst. High yield of the desired product, short reaction time, ease of recovery and reusability of the catalyst, solvent-free and mild reaction condition are some advantages of the present work.

 

ACKNOWLEDGEMENTS

We gratefully acknowledge the support of this work from the K. N. Toosi University of Technology.

 

CONFLICT OF INTERESTS

The authors declare that there is no conflict of interests regarding the publication of this paper.