Multi-walled carbon nanotube supported Fe₃O₄NPs: an efficient and reusable catalyst for the one-pot synthesis of 4H-pyran derivatives

Abstract

Multi-walled carbon nanotube supported Fe₃O₄ nanoparticles have been prepared and characterized by Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), vibrating sample magnetometry (VSM), and transmission and scanning electron microscopy (TEM and SEM). This superparamagnetic nanocomposite, which could be conveniently separated by using an external magnet, can be used as an efficient catalyst for the promotion of the synthesis of 4H-pyran derivatives via a one-pot multicomponent reaction of an aldehyde, malononitrile and β-diketones. Some of the advantages of this work are that it is environmentally benign, has an easy work-up procedure, saves energy and uses mild reaction conditions.

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1 Introduction

In recent years, nanotechnology has rapidly progressed in chemistry, physics, materials science and biotechnology to create magnetic nanoparticles (MNPs) that have unique physical and chemical properties such as a large surface area to act either as heterogeneous promoters for catalytic reactions or as a support for homogeneous catalysts.^1,2 MNPs are commonly composed of magnetic elements such as iron, nickel, cobalt and their oxides.³ Among them, Fe₃O₄ MNPs have attracted much attention because of their inherent properties such as their fast response under an applied external magnetic field, high coercivity, environmental friendliness and high surface area per weight, which causes their higher reactivity, greater selectivity, operational simplicity, non-corrosive nature, moisture insensitivity, low toxicity, superparamagnetic behavior and ease of separation from the reaction medium by using external magnets, which minimizes the loss of catalyst during separation.^4–9

However, due to their large specific surface area and high surface energy, MNPs tend to aggregate and exhibit negligible dispersion in water and organic solvents.^10,11 Furthermore, Fe₃O₄ contains Fe²⁺ which is easily oxidized, thus decreasing the magnetism of MNPs.¹² In order to enhance the dispersion and oxidation resistance of MNPs, adjustment and a surface coating of Fe₃O₄ MNPs is essential.

Nowadays, graphitized carbon structures, such as multi-walled carbon nanotubes (MWCNTs) are receiving more attention due to their exceptional mechanical, thermal and electrical properties. Decoration of the external surface of the CNTs provides an effective barrier against oxidation and acid erosion. These facts indicate that it is possible to synthesize carbon-coated magnetic nanoparticles, which are thermally stable and have a high stability against oxidation and acid leaching, which is crucial for some applications.¹³ CNTs loaded with Fe₃O₄ nanoparticles on their external surface show an exceptional performance and have potential applications in various fields such as catalysis,^14,15 reinforcing materials,¹⁶ electrodes,¹⁷ and wastewater treatment.¹⁸ Also, Fe₃O₄-supported catalysts can be easily separated from the reaction mixture by an external permanent magnet.^19–22

The synthesis of 4H-pyran and its derivatives has attracted much attention from synthetic chemists due to their useful biological and pharmacological properties. Most of them can be used as anticoagulant, anticancer, diuretic, spasmolytic and antianaphylactic agents.^23,24 A series of natural products contains substituted 4H-pyrans in their structural units.²⁵

A variety of reagents such as sodium bromide,²⁶ hexadecyldimethyl benzyl ammonium bromide,²⁷ tetramethyl ammonium hydroxide,²⁸ sodium selenate,²⁹ iodine,³⁰ tetrabutylammonium bromide,³¹ cerium(III) chloride,³² lithium bromide,³³ Amberlite IRA-40 (OH⁻),³⁴ acidic ionic liquids,³⁵ L-proline,³⁶ nano-ZnO,³⁷ nano-SiO₂,³⁸ phenylboronic acid,³⁹ triethylenetetraammoniumtrifluoroacetate [TETA]TFA,⁴⁰ ZnO-beta zeolite,⁴¹ trisodium citrate,⁴² basic ionic liquids,⁴³ high surface area MgO,^44,45 nanosized MgO,⁴⁶ solid acids,^47,48 and organic solvents such as DMF and acetic acid,^49,50 have been used to catalyze these reactions. Pyrans have also been synthesized under microwave⁵¹ and ultrasound⁵² irradiation. Recently, some two-component⁵³ and three-component^54,55 condensations have been introduced for the synthesis of 4H-chromenes.

However, each of the above methods suffers from disadvantages such as low yields, unavailability or toxicity of the reagents, long reaction times, hazardous organic solvents, vigorous reaction conditions and a tedious work-up. Therefore, to overcome these drawbacks, there is still a great demand to develop a simple and efficient catalytic system for the synthesis of pyrans.

With regard to the importance of this topic and due to the advantages of multicomponent reactions (MCRs) such as atom economy, high selectivity and greater efficiency, we decided to demonstrate a simple, rapid and effective one-pot MCR for the synthesis of 4H-pyran derivatives using Fe₃O₄NPs/MWCNTs as a supermagnetic and reusable catalyst. To the best of our knowledge, our work is the first report using a catalytic amount of this reagent to catalyze the synthesis of 4H-pyran derivatives.

2 Results and discussions

2.1 Catalyst characterization

2.1.1 XRD analysis. Fig. 1 shows the XRD patterns of the pure MWCNTs (green) and Fe₃O₄ NPs/MWCNTs (pink). The peaks at 2θ = 26° and 42° are assigned to the (002) and (100) planes of the hexagonal graphite structure of the MWCNTs, which indicates that the deposition of the iron oxide nanoparticles did not damage the hexagonal graphite structure of the MWCNTs. Also, additional diffraction peaks at 2θ = 30.1°, 37.5°, 44.1°, 55.4°, 58.5° and 64.1° correspond to the standard XRD data for the cubic Fe₃O₄ phase of the inverse spinel crystal structure (JCPDS file no. 19–0629).⁵⁶ No peaks corresponding to impurities are present. By using the Scherrer equation, the crystallite size of the captured nanoparticles on the nanotube sidewall was found to be 18 nm, which confirms the TEM results for the particle diameter.

Fig. 1 XRD patterns of pure MWCNTs (green) and Fe₃O₄NP decorated carbon nanotubes (Fe₃O₄ NPs/MWCNTs) (pink).

2.1.2 SEM and TEM analysis. In order to investigate the morphology and particle size of the catalyst, SEM and TEM images of magnetic Fe₃O₄ NPs/MWCNTs are displayed in Fig. 2. These results show that the magnetite microspheres are randomly adhered to the outer surface of the MWCNTs (Fig. 2a). As shown, the TEM image indicates that the structure of the MWCNTs (Fig. 2b) was not destroyed during the catalyst preparation and the iron oxide nanoparticles are decorated on the outer surface of the MWCNTs in a relatively uniform fashion, with a particle size of about 10–20 nm (Fig. 2c).

Fig. 2 (a) SEM image of Fe₃O₄ NPs/MWCNTs. (b) TEM image of MWCNTs. (c) TEM image of Fe₃O₄ NPs/MWCNTs.

2.1.3 IR analysis. The IR spectrum of the prepared Fe₃O₄ NPs/MWCNTs is shown in Fig. 3. The peaks at 3434 and 1736 cm⁻¹ could be assigned to the O–H and C=O stretch mode of the carboxylic acid in the CNTs. Other peaks at 1133 and 1165 cm⁻¹ are attributed to the stretch bonds of the phenyl-carbonyl C–C and a strong peak at around 565 cm⁻¹ is related to the Fe–O–Fe interactions in Fe₃O₄.

Fig. 3 FTIR spectra of Fe₃O₄ NPs/MWCNTs.

Moreover, peaks at 1358, 2847 and 2917 cm⁻¹ are ascribed to the in-plane bending vibration of the C–H stretch vibration originating from the surface of tubes.

2.1.4 Vibrating sample magnetometer analysis. We investigated the magnetic properties of HOOC-MWCNTs and Fe₃O₄ nanoparticle decorated MWCNTs using vibrating sample magnetometry (VSM). In Fig. 4, typical magnetization curves as a function of the applied magnetic field at 300 K are shown. The lack of a hysteresis loop demonstrates that both the coercivity and retentivity of this compound are zero and the sample exhibits superparamagnetic behavior. An increase in the saturation magnetization of HOOC-MWCNTs from about 10 emu g⁻¹ (a) and to greater than 31 emu g⁻¹ for MWCNT/Fe₃O₄ (b) illustrated that a high weight ratio of Fe₃O₄ nanoparticles was loaded on HOOC-MWCNTs.⁵⁷

Fig. 4 Hysteresis curves of MWCNTs (a) and Fe₃O₄ NPs/MWCNTs (b) measured at 300 K.

After preparation and characterization of Fe₃O₄ NPs/MWCNTs, the catalytic activity of this catalyst was examined in a three component reaction between aromatic aldehydes, malononitrile, and 1,3-diketones. Initially, 4-chlorobenzaldehyde, malononitrile and dimedone in an equimolar ratio were employed as the model reactants and the effect of solvent, catalyst and temperature was investigated in the presence of various amounts of Fe₃O₄ NPs/MWCNTs (2 to 10 mg) in different solvents at temperatures ranging from 25 °C to reflux (Table 1) (Scheme 1).

Table 1 Optimization of the amount of catalyst, solvent and temperature in a one-pot synthesis of the model reaction^a

Entry	Fe3O4 NPs/MWCNTs (mg)	Solvent	Temp. (°C)	Time (min)	Yield^b (%)
a All reactions were run with 4-chlorobenzaldehyde (1.0 mmol), dimedone (1.0 mmol), and malononitrile (1.0 mmol).b Isolated yields.c Pure Fe3O4 NPs is used as a catalyst.
1	10	Water	Reflux	60	61
2	10	n-Hexane	Reflux	180	—
3	10	Acetonitrile	Reflux	60	31
4	10	Ethanol	Reflux	10	94
5	10^c	Ethanol	Reflux	30	78
6	7	Ethanol	Reflux	10	95
7	5	Ethanol	Reflux	8	97
8	3	Ethanol	Reflux	60	82
9	—	Ethanol	Reflux	180	Trace
10	5	None	80	60	Trace
11	5	Ethanol	r.t.	180	Trace
12	5	Ethanol	50	60	52

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Scheme 1 Synthesis of 2-amino-4-(4-chlorophenyl)-3-cyano-7,7-dimethyl-5-oxo-4H-5,6,7,8 tetrahydrobenzo[b]pyran as a model reaction.

The reaction was carried out in the presence of several solvents such as EtOH, MeCN, n-hexane, H₂O and also in the absence of solvent using 10 mg of catalyst. As shown in Table 1, the best result was obtained when the reaction was carried out in EtOH (Table 1, entry 4). Then, the effect of catalyst loading was studied and condensation of reactants in an equimolar ratio (1 : 1 : 1) was performed in the presence of various amounts of the catalyst under reflux conditions. No product was observed in the absence of the catalyst. The yields of the product (Table 1) indicate that 5 mg of Fe₃O₄ NPs/MWCNTs is the optimum amount of the catalyst for this reaction (Table 1, entry 6). The use of higher amounts of the catalyst neither improved the yield nor the reaction time. The effect of temperature on the reaction was monitored and reflux conditions were chosen for all further reactions. No reaction was detected after stirring the reaction mixture at room temperature for 180 min.

Furthermore, in order to show the excellent catalytic activity of this catalyst, we carried out the synthesis of the model reaction catalyzed by pure Fe₃O₄ NPs under the same reaction conditions. It was shown that the yield of the desired product in the presence of the pure Fe₃O₄ NPs was lower than that in the presence of Fe₃O₄ NPs/MWCNTs.

This could be due to the fact that Fe₃O₄ nanoparticles tend to aggregate, because of their high surface area to volume ratio and the strong dipole–dipole attraction between the particles.^10,11 Also, the magnetic properties of nano-Fe₃O₄ decrease upon the oxidation of Fe²⁺in the catalyst structure.¹²

According to the outcomes in Table 1, it can be concluded that the best yield of the products was achieved by using the 1 : 1 : 1 ratio of reactants and 5 mg of Fe₃O₄ NPs/MWCNTs, under reflux conditions in EtOH.

After optimization, the applicability of the method was studied by synthesis of several types of substituted 4H-pyrans using a series of aldehydes (Table 2) (Scheme 2). As can be seen in Table 2, the aromatic aldehydes with different substituents at the ortho-, meta- or para-positions were examined and in all cases gave corresponding products in good to excellent yields. Notably, the aromatic aldehydes with electron-withdrawing groups (such as nitro and halide) reacted faster with slightly improved yields than their electron donating counterparts (such as hydroxyl and methoxy). The pure products were identified by their melting points, IR, ¹H and ¹³C NMR, which are in agreement with those reported in the literature.

Table 2 Synthesis of 4H-chromene derivatives using Fe₃O₄ NPs/MWCNTs as the catalyst^a

Entry	R	Product^b	MW		Reflux		MP (°C)
			Time (s)	Yield^c (%)	Time (min)	Yield^c (%)	Found	Reported [References]
a Reaction conditions: aldehyde (1 mmol), malononitrile (1 mmol), cyclic-1,3-diketones (1 mmol), catalyst (5 mg), ethanol (5 mL), reflux or MW.b Melting points, IR, ^1H NMR and ^13C NMR were in accordance with those of authentic samples.c Isolated yield.
1	4-Chloro	1a	25	98	8	97	212–214	212–214 [38]
2	3-Nitro	2a	40	96	10	95	209–210	210–211 [38]
3	4-Cyano	3a	20	97	5	98	224–227	224–226 [58]
4	2-Chloro-6-fluoro	4a	20	97	8	95	202–204	—
5	2,4-Dichloro	5a	20	96	7	95	119–122	114–116 [40]
6	4-Nitro	6a	30	96	8	96	176–178	177–178 [38]
7	4-Methoxy	7a	90	87	20	85	197–200	198–200 [38]
8	3-Phenoxy	8a	180	85	40	87	181–183	182–184 [38]
9	4-Isopropyl	9a	300	86	50	84	199–201	198–200 [38]
10	4-Nitro	1b	60	91	15	90	237–239	240–241 [39]
11	2-Chloro-6-fluoro	2b	40	92	10	90	228–230	—
12	2,4-Dichloro	3b	35	90	8	88	221–223	222–224 [40]
13	4-Chloro	4b	120	89	20	87	227–229	229–230 [39]
14	4-Methoxy	5b	180	81	22	80	197–199	198–200 [39]

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Scheme 2 Fe₃O₄ NPs/MWCNTs catalyzed synthesis of 4H-chromene derivatives.

In order to develop the scope of this method, we found that when ethyl acetoacetate was used instead of a cyclic-1,3-diketone (e.g., dimedone or 1,3-cyclohexanedione) under the same reaction conditions, 6-amino-5-cyano-2-methyl-4-aryl-4H-pyran-3-carboxylic acid ethyl ester derivatives were prepared in high yields and short reaction times (Scheme 3). The results are presented in Table 3.

Scheme 3 Fe₃O₄ NPs/MWCNTs catalyzed synthesis of 6-amino-5-cyano-2-methyl-4-aryl-4H-pyran-3-carboxylic acid ethyl ester derivatives.

Table 3 Synthesis of 6-amino-5-cyano-2-methyl-4-aryl-4H-pyran-3-carboxylic acid ethyl ester derivatives using Fe₃O₄ NPs/MWCNTs as a catalyst^a

Entry	R	Product^b	MW		Reflux		MP (°C)
			Time (min)	Yield^c (%)	Time (min)	Yield^c (%)	Found	Reported [References]
a Reaction conditions: aldehyde (1 mmol), malononitrile (1 mmol), ethyl acetoacetate (1 mmol), catalyst (5 mg), ethanol (5 mL), reflux or MW (40 °C).b Melting points, IR, ^1H NMR and ^13C NMR were in accordance with those of authentic samples.c Isolated yield.
1	3-Nitro	1c	3	90	25	89	173–175	171–173 [38]
2	3,4-Difluoro	2c	1.5	94	15	93	166–168	—
3	4-Methoxy	3c	6	83	50	82	137–140	137–139 [38]
4	Phenyl	4c	4	83	35	80	113–115	112–114 [38]
5	4-Chloro	5c	2	93	20	92	174–176	175–177 [38]
6	4-Nitro	6c	2	92	20	90	176–177	176–178 [38]

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Due to the benefits of microwave-assisted reactions such as high product yields, a faster and cleaner approach and an environmentally benign source of energy, we investigated the effect of MW irradiation on the synthesis of target compounds. After optimization of the reaction conditions, using a 1 : 1 : 1 ratio of reactants, 3 mg of Fe₃O₄ NPs/MWCNTs as the catalyst, 3 mL ethanol as the solvent and MW irradiation at a power level of 40% at 40 °C, we examined the generality of the reaction. As expected in all cases, enhancement in the reaction speed and reaction times were observed (Tables 2 and 3). It seems that the absorbing characteristics of carbon nanotubes could improve the reaction time and the yield of products.^59–61

Furthermore, the efficiency of this catalyst was demonstrated by the comparison between different catalysts and the synthesis of 4H-pyran (1a) was considered as a representative example. It is noteworthy that the reaction time and the yield in the present method is better in comparison with those of others (Table 4).

Table 4 Comparison of the catalytic activity of Fe₃O₄ NPs/MWCNTs with other catalysts reported in the literature for the synthesis of 4H-chromene^a

Entry	Catalyst amount	Solvent	Time (min)	Yield^b (%)	References
a All reactions were run with 4-chlorobenzaldehyde (1.0 mmol), dimedone (1.0 mmol), and malononitrile (1.0 mmol) at reflux conditions.b Isolated yield.
1	ZrO2 (200 mg)	EtOH	90	20	[62]
2	MgO (200 mg)	EtOH	85	45	[62]
3	[TETA]TFA (0.1 mmol)	EtOH	30	93	[40]
4	ZnO (3 mg)	EtOH	10	80	[37]
5	PhB(OH)2 (5 mol%)	H2O : EtOH (1 : 1)	30	84	[39]
6	Na2SeO4 (100 mg)	H2O : EtOH (1 : 1)	180	90	[29]
7	Fe3O4 NPs/MWCNTs (5 mg)	EtOH	8	97	—

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Finally, the recycling performance of the catalyst in the model reaction was studied. For this reason, the catalyst was separated by use of an external magnet. The magnetic Fe₃O₄NPs/MWCNTs were washed three to four times with water and ethanol and dried at room temperature for 5 h. Fig. 5 shows that this catalyst could be used five times with only a slight decrease in its catalytic activity. The stability of the catalyst is confirmed via determination of Fe ion leaching by atomic absorption spectroscopy. Trace metal ions were detected in the filtrate of this reaction.

Fig. 5 Reusability of Fe₃O₄ NPs/MWCNTs in the model reaction (Table 1, entry 7).

A possible mechanism for the synthesis of 4H-pyran derivatives has been proposed in Scheme 4. Based on this mechanism, Fe₃O₄ NPs/MWCNTs is an effective catalyst for the formation of cyanoolefin A which is the Knoevenagel condensation product of arylaldehyde 1 and the active anion of malononitrile compound 2. Dimedone, after proton transfer and tautomerization, is in its enolic form, which in the presence of Fe₃O₄ NPs/MWCNTs could easily react with cyanoolefin A, resulting in the formation of intermediate B which converts to product 3.

Scheme 4 Proposed mechanism for the formation of the 4H-chromene derivative.

In summary, this is the first report of the synthesis of substituted 4H-chromene derivatives catalyzed by magnetic Fe₃O₄ NPs/MWCNTs as a novel, effective and easily reusable catalyst, which provided excellent yields (80–97%) in short reaction times.

3 Experimental

3.1 General

All materials and solvents were purchased from Merck and Fluka, and used without further purification. Yields refer to the isolated products. Products were characterized by their physical constants, comparison with authentic samples, and IR and NMR spectroscopy.

3.2 Instrumentation

IR spectra were obtained with KBr discs on a Perkin-Elmer model Spectrum one FT-IR Spectrometer. The structure of the synthesized catalysts was characterized by X-ray diffraction (XRD-Equinox-3000, INEL, France). The XRD patterns were obtained using Cu Kα radiation (the wavelength was 1.54056 Å) at a current of 200 mA and a voltage of 40 kV in the 2θ range of 10–100 with a scanning rate of 8° per min. The surface microscopic morphology of MWCNTs and Fe₃O₄ NP decorated MWCNTs was visualized by a scanning electron microscope (SEM-MIRAII TESCAN). The size of the Fe₃O₄ NPs was investigated by a transmission electron microscope (TEM-PHILIPS MC 10) with an acceleration voltage of 80 kV. Magnetic study was performed by a vibrating sample magnetometer at room temperature (VSM JDM-13). A Perkin Elmer Analyst 100 Atomic Absorption Spectrophotometer was used. The reaction progress was checked by thin-layer chromatography (TLC) with detection by UV light. ¹H NMR spectra were obtained on a Bruker DRX-400 Avance spectrometer and ¹³C NMR spectra were obtained on a Bruker DRX-100 Avance spectrometer. Samples were analyzed in DMSO-d₆, and chemical shift values are reported in ppm relative to tetramethylsilane (TMS) as the internal reference. Melting points were measured on an electrothermal apparatus. Elemental analyses were made by a Carlo-Erba EA1110 CNNO-S analyzer and agreed with the calculated values. Microwave experiments were conducted in a Milestone Microwave (Microwave Labstation-MLS GmbH-ATC-FO 300) apparatus.

3.3 Preparation of the catalyst (Fe₃O₄ NPs/MWCNTs)

Firstly, 96 mg of functionalized MWCNTs (carboxylic acid functionalized MWCNTs with a purity of more than 95% were purified by using sulfuric acid and a heat treatment method) were well dispersed in 30 mL of distilled water in a two necked round bottom flask (100 mL) by ultrasonic irradiation for 30 min. After adding 81 mg of FeCl₃·6H₂O, the solution was stirred vigorously for 30 min. Afterward, 120 mg FeCl₂·4H₂O was slowly added into the mixture under stirring for 30 min. The whole process was performed under Argon atmosphere. Then 8 mL of concentrated aqueous solution of NH₃ was added into the solution drop wise for 1 h. Thereafter, the mixture was stirred at 60 °C for 2 h. After cooling the solution to room temperature, the black magnetic Fe₃O₄NPs/MWCNTs were centrifuged at 6000 rpm and rinsed several times with deionized water and dried at 100 °C for 12 h. Measuring the amount of residual Fe ions in the filtrate by spectrophotometry showed that more than 95% of the iron is stabilized on the surface of the MWCNTs. Scheme 5 illustrates the preparation process of the Fe₃O₄ nanoparticles decorated on the outer surface of functionalized MWCNTs. As can be seen, positive ferrous and ferric ions are in close proximity with the carboxylic groups of the MWCNTs and they are converted to Fe₃O₄ NPs after the addition of a concentrated aqueous solution of NH₃ into the solution drop by drop.

Scheme 5 Simplified schematic showing the synthesis of Fe₃O₄ NPs/MWCNTs.

3.4 General procedure for the synthesis of 4H-pyran catalyzed by Fe₃O₄ NPs/MWCNTs

Fe₃O₄ NPs/MWCNTs (5 mg) was added to a mixture of aldehyde (1.0 mmol), malononitrile (1.0 mmol), and cyclic 1,3-diketone or ethyl acetoacetate (1.0 mmol) in ethanol (5 mL). The reaction mixture was stirred magnetically under refluxing conditions for the appropriate time. In the case of the microwave assisted reactions, the mixture was irradiated at 800 W at 40 °C for a few minutes depending on the reactants. After completion of the reaction as indicated by TLC, the catalyst was collected by magnetic separation using an external magnet and washed repeatedly with warm ethanol. The aqueous phase was filtered and cooled to room temperature. Then, the solid product was collected and washed with warm ethanol to afford the pure product. For further purification, products were recrystallized from ethanol.

Except for some compounds (Table 2, entries 4, 11 and Table 3, entry 2), all products are known compounds. The spectroscopic and physical data for all known compounds were found to be identical to those described in the literature.

The spectral (IR, ¹H and ¹³C NMR) data of the new compounds are presented below:

Table 2, entry 4. White solid, mp 202–204 °C; IR (KBr): υ_max 3410, 3331, 3214, 3070, 2964, 2931, 2198, 1684, 1600, 1540, 1452, 1369, 1215, 1159, 1037, 898, 781, 682, 562 cm⁻¹. ¹H NMR (400 MHz, DMSO-d₆): δ 0.95 (s, 3H, CH₃), 1.05 (s, 3H, CH₃), 2.07 (d, 1H, J = 16.4 Hz, –CH₂), 2.28 (d, 1H, J = 16 Hz, –CH₂), 2.37 (d, 1H, J = 17.6 Hz, –CH₂), 2.56 (d, 1H, J = 18 Hz, –CH₂), 4.89 (s, 1H, CH), 7.116 (s, 2H, NH₂), 7.13 (br, 1H, ArH),7.26–7.29 (m, 2H, ArH) ppm; ¹³C NMR (100 MHz, DMSO-d₆): δ 195.68, 163.55, 159.31, 154.44, 133.64, 129.17, 129.07, 125.52, 119.21, 115.11, 115.04, 55.99, 49.84, 49.82, 31.67, 26.31, 26.23, 18.53 ppm; Anal. Calc. for C₁₈H₁₆ClFN₂O₂: C, 62.34; H, 4.65; N, 8.08. Found: C, 62.54; H, 4.71; N, 8.16.

Table 2, entry 11. White solid, mp 228–230 °C; IR (KBr): υ_max 3506, 3376, 3175, 2190, 1681, 1648, 1600, 1509, 1454, 1363, 1243, 1211, 1168, 1067, 1003, 898, 780, 703, 590 cm⁻¹. ¹H NMR (400 MHz, DMSO-d₆): δ 1.88–1.94 (m, 1H, –CH₂), 1.99–2.05 (m, 1H, –CH₂), 2.24–2.40 (m, 2H, 1–CH₂), 2.59–2.65 (m, 2H, –CH₂), 4.94 (s, 1H, CH), 7.16 (s, 2H, NH₂), 7.21 (d, 1H, J = 9.2 Hz, ArH), 7.29–7.33 (m, 1H, ArH), 7.36 (d, 1H, J = 8 Hz, ArH) ppm; ¹³C NMR (100 MHz, DMSO-d₆): δ 195.81, 165.36, 159.24, 159.16, 133.65, 128.99, 126.20, 125.64, 119.21, 115.01, 114.76, 53.95, 36.19, 30.67, 26.40, 19.88 ppm; Anal. Calc. for C₁₆H₁₂ClFN₂O₂: C, 60.29; H, 3.79; N, 8.79. Found: C, 60.34; H, 3.85; N, 8.71.

Table 3, entry 2. White solid, mp 166–168 °C; IR (KBr): υ_max 3406, 3333, 3205, 2989, 2193, 1692, 1649, 1518, 1466, 1341, 1270, 1210, 1174, 1060, 957, 865, 814, 751, 650 cm⁻¹. ¹H NMR (400 MHz, DMSO-d₆): δ 1.03 (t, 3H, CH₃), 2.32 (s, 3H, CH₃), 3.98 (q, 2H, CH₂), 4.35 (s, 1H, CH), 7.00 (s, 2H, NH₂),7.01 (br, 1H, ArH), 7.17–7.22 (m, 1H, ArH), 7.34–7.41 (m, 1H, ArH) ppm; ¹³C NMR (100 MHz, DMSO-d₆): δ 165.19, 158.39, 157.32, 149.39, 146.96, 142.84, 123.94, 119.45, 117.51, 116.22, 106.31, 60.19, 59.55, 38.05, 18.21, 13.67 ppm; Anal. Calc. for C₁₆H₁₄F₂N₂O₃: C, 60.00; H, 4.41; N, 8.75. Found: C, 60.14; H, 4.50; N, 8.70.

4 Conclusions

In conclusion, we have reported an easy, convenient and novel method for the synthesis of a series of biologically and pharmacologically active 4H-pyran derivatives catalyzed by Fe₃O₄ NPs/MWCNTs using a three-component condensation in ethanol as a green solvent. In this regard, we have prepared the catalyst and confirmed the nanostructure of the Fe₃O₄ NPs on the surface of the MWNTs by XRD, SEM and TEM images. We found that Fe₃O₄ NPs/MWCNTs can be easily separated from the reaction mixture by an external permanent magnet. The key advantages of this procedure include high yields, operational simplicity, a reusable catalyst, a non-toxic solvent, short reaction times, minimum pollution of the environment and purification of the compounds by nonchromatographic methods which makes it a useful and attractive process for the preparation of the desired compounds.

Acknowledgements

The authors are grateful to the Research Council of the University of Guilan for partial support of this study.

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Footnote

† Electronic supplementary information (ESI) available. See DOI: 10.1039/c3ra46598e

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