Synthesis of pyridone derivatives using 2D rod like bifunctional Fe based MOF and CuO nanocomposites as a novel heterogeneous catalyst

In this study, a new and efficient Rod-like bifunctional Fe-based MOF@CuO nanocomposites (RL BF Fe-based MOF@CuO NC) were synthesized as new and efficient heterogeneous catalyst through a simple method from easily available 1,3,5-benzenetricarbocylic acid linker, nitrate ferric as a source of iron and copper oxide (CuO) nanoparticles under microwave irradiation. The synthesized nanocatalysts were characterized with different techniques such as Brunauer–Emmett–Teller (BET), energy dispersive spectroscopy (EDS), field emission scanning electron microscopy (FE-SEM), mapping, transmission electron microscopy (TEM), X-ray diffraction (XRD), vibrating sample magnetometer (VSM), thermogravimetric analysis (TGA) and Fourier transform infrared spectroscopy (FT-IR). The RL BF Fe-based MOF@CuO NC had relatively high specific surface area (203 m2 g−1) while exhibiting superparamagnetic properties. The catalytic activity of RL BF Fe-based MOF@CuO NC was explored in a facile and green methodology to prepare diverse N‑amino-2-pyridones by one-pot four component reactions comprising aromatic aldehyde, malononitrile, methyl cyanoacetate and hydrazine hydrate within mild and solvent-free conditions. This protocol enjoys features like providing the final products during low reaction times in excellent yields under solvent-free conditions. The use of easily available and inexpensive reactants for the synthesis of the catalyst, environmental compatibility, low catalyst loading, fast and clean work-up and reusability of catalyst for several cycles with consistent activity are counted as the outstanding features of this procedure.


Materials and apparatus
High-purity chemical substances were bought from Sigma Aldrich and used with no additional purification.Physical constants of the products were compared with the authentic samples and FT-IR spectroscopy for threir characterization.Thin layer chromatography (TLC) on Silica G60 F254 (Merck) TLC plates was used to monitor the reaction progress and determine the substrate purity.An Electrotermal 9100 device in open capillary tubes was employed to measure melting points, the values of which were left uncorrected.FTIR spectra were recorded for KBr pellets of the samples using a JASCO FT-IR-4000 spectrophotometer.NMR spectroscopy ( 1 H NMR) was obtained using a Bruker Avance 400 MHz NMR spectrometer in d 6 -DMSO at ambient temperature.The crystallinity, phase structure, and crystallite size of RL TF Fe-based MOF@CuO NC were determined by a PC-APD X-ray diffractometer and Kα radiation (α 2 , λ 2 = 1.54439Å) and graphite mono-chromatic Cu radiation (α 1 , λ 1 = 1.54056Å) (Philips, the Netherlands).The X'Pert HighScore Plus software was used for data analysis.The XRD pattern was obtained in the range 2°-80° 2θ, with a step size of 0.016°.Then, SEM and EDS (KYKY & EM 3200) were applied to investigate RL TF Fe-based MOF@CuO NC.Thermal behavior analysis was carried out in N 2 atmosphere in the temperature range of room temperature to 350 °C using a STA-1500 thermoanalyzer.A Lakeshore (model 7407) was employed to evaluate magnetization within magnetic fields under room temperature.

Synthesis of CuO nanoparticles
First, 0.1 M copper (II) sulfate pentahydrate (CuSO 4 •5H 2 O) was dissolved in deionized water.Then, saturated NaOH solution was added until the pH of the solution reached 8.0; where the resulting precipitates were collected.

Results and discussion
After preparing metal-organic framework nanostructures (Fe-MOF) via co-precipitation method using Fe (NO 3 ) 3 •9H 2 O as iron precursor and 1,3,5-benzenetricarboxylic acid as organic ligand CuO nanostructures were added to modify the surface of metal-organic nano-framework.The mentioned nanostructures were placed on the metal-organic nano-framework by co-precipitation method to achieve Rod-like trifunctional Fe-based MOF@CuO nanocomposites (RL TF Fe-based MOF@CuO NC) as nano-catalyst.

Characterization of RL BF Fe-based MOF@CuO NC
Different procedures, including XRD, FE-SEM, EDX, TGA, BET, and VSM, were used to characterize RL TF Fe-based MOF@CuO NC.
The XRD pattern of the RL TF Fe-based MOF@CuO NC is shown in Fig. 1.Accordingly, the CuO diffraction peaks are covered by TF Fe-based MOF diffraction peaks.Debye-Scherrer formula (Eq. 1) was employed to estimate the crystallite size of the obtained RL TF Fe-based MOF@CuO NC.
In which, λ, θ, and β represent the X-ray wavelength (1.54056 Å for Cu lamp), half of the Bragg diffraction angle, and half of the width of maximum intensity diffraction peak, respectively.RL TF Fe-based MOF@CuO NC had a mean crystallite size of 83.4 nm.
Figure 2a indicates a low-magnification FE-SEM image of the produced RL TF Fe-based MOF@CuO NC.The TF Fe-based MOF@CuO NC showed a rod-like structure.Based on Fig. 2b, the rods have a length and diameter of nearly 1-3 μm and 10-30 nm, respectively.Uniform coverage of the study area by the nanorods was evident.Morphologically, the RL TF Fe-based MOF@CuO NC showed a straight rod characteristic, as well as a smooth surface (Fig. 2b).
(1) D = 0.9 βcosθ  Figure 5 indicates the N 2 adsorption-desorption isotherm of the RL TF Fe-based MOF@CuO NC.Physical characteristics, such as the surface area, pore size, and volume, and distribution, were determined through N 2 sorption estimations.Type IV isotherm can be recognized in the case of RL TF Fe-based MOF@CuO NC with a distinct hysteresis loop.The surface area, the pore volume, and pore size of RL TF Fe-based MOF@CuO NC were 8.4228 m 2 g −1 , 0.031269 cm 3 g −1 , and 17.346 nm, respectively.
The VSM analysis was utilized at room temperature to characterize the magnetic properties of the RL TF Febased MOF@CuO NC. Figure 6 presents the M-H curve of the nanocomposite at room temperature.Accordingly, the semiconductor materials show magnetic characteristics with strong dependence on structural, morphological, and crystal geometric factors.Typical M-H curves represent a weak paramagnetic due to limited spin orientation at the maximum applied field (0.012 Oe).Nanocomposite has a coercivity of Hc, 75.0 Oe, suggesting their magnetic behavior with saturation magnetism of Ms, 0.17 emu.g −1 .
The FT-IR spectra of CuO, TF Fe-based MOF, and RL TF Fe-based MOF@CuO NC are shown in Fig. 7. FTIR spectroscopy can be employed for identifying molecule functional groups as each chemical bond has a distinct energy absorption band, through which the structural and bond information of compounds can be obtained.The IR spectrum of 6c shows that the addition of iron nitrate to the linker and formation Fe-MOF led to a rise in the absorption of carbonyl group due to the coordination of Fe metal with acidic OH.Also, according to the IR spectrum of 6d addition of of Fe-MOF to the CuO nanoparticles and the formation of Fe-MOF@CuO decreased the absorption of carbonyl due to the coordination of the CuO nanoparticle with the oxygen of the carbonyl group.
Thermal analysis of a representative sample of the synthesized compound, RL BF Fe-based MOF@CuO NC, is shown in Table 1.The weight losses started at 50 °C and ended at 500 °C, approximately.The 1st and 2st temperatures are 67 °C and 92 °C, where minor weight losses result from the vanished solvent and evaporated trapping solvent, respectively.Proportionate to temperature ascent from 273 to 315 °C was observed.That probably corresponds to decomposing linker on the skeleton.The weight loss of dissociation of coordinated water for nanocomposite was estimated in the range of 420-462 °C.Therefore, obtained data show high thermal stability in elevated temperatures.

Synhtesis of N-amino-2-pyridones in the presence of RL BF Fe-based MOF@CuO NC as catalyst
After successful preparation and characterization of nano organo-catalyst by SEM, EDS, mapping, XRD, BET, TGA and VSM, it was applied in prominent organic reactions to prepare N-amino-2-pyridones through one-pot four-component reaction among methyl cyanoacetate, Hydrazine hydrate, malononitrile and aromatic aldehydes to examine the catalytic function of RL BF Fe-based MOF@CuO NC as effective Lewis acid catalyst (Fig. 8).
The effects of various parameters were initially studied by testing a model reaction of methyl cyanoacetate (1 mmol), Hydrazine hydrate (1 mmol), malononitrile (1 mmol) and 4-methoxybenzaldehyde (1 mmol) to achieve optimal reaction conditions.Investigations were primarily performed to determine the contribution of the solvent to the reactions through the model reaction.Hence, this step was carried out using different solvents, including water, ethanol, methanol, acetonitrile and n-hexane solvents.Besides, solvent-free conditions were also examined in the presence of 10 w% of catalytic of RL TF Fe-based MOF@CuO NC at reflux conditions.According to the results, the solvent-free condition was the most appropriate to prepare Namino-2-pyridones, and the reaction time gradually decreased by using highly polar to less polar solvents (Table 2).
In the next step, the effect of reaction temperature was tested considering room temperature, 50 and reflux conditions.Temperature decline below 50 ºC decremented the yield of the product and increased the reaction time.Moreover, increasing temperature from 50 °C to reflux conditions was improved the progress of the reaction (Table 2, entries 6-8).www.nature.com/scientificreports/ The catalyst amount was optimized through the model reaction in solvent-free conditions in the absence and presence of various catalyst amounts.The yield was 76%, 98%, 98%, and 98% when using 5, 10, 15, 20 w% of RL BF Fe-based MOF@CuO NC, respectively (Table 2).The results indicate the RL BF Fe-based MOF@CuO NC catalyst contributes significantly to achieving the response so that reaction produced trace product in the absence of catalyst after prolonged reaction time while 10 w% catalyst seemed to be enough for the reaction to  proceed, leading to considerably high yields while requiring shorter reaction times.Hence, a decrease in the catalyst amount resulted in the efficiency reduction, while higher catalyst amounts led to no significant efficiency improvements (Table 2, entry 6 and entries 9-12).Under optimal reaction conditions, the scope, generality, and applicability of newly introduced protocol were checked by various aromatic aldehydes, with substituents that withdraw or donate electrons (Table 3), malononitrile, methylcyanoacetate and hydrazine hydrate were used to perform the reaction in the presence of 10 w%  www.nature.com/scientificreports/RL BF Fe-based MOF@CuO NC under solvent-free and reflux conditions.As Table 3 indicates, aldehydes with electron-withdrawing or electron-donating groups offer corresponding N-amino-2-pyridones with considerably high product yield (87-99%) while requiring shorter reaction times (2-5 min) with no side reactions.To examine the advantages of this methodology, new synthesized catalyst was compared with recently introduced catalysts to synthesize N-amino-2-pyridones (Table 4).According to the results, the proposed protocol was highly efficient due to the solvent-free conditions and excellent catalytic effects within short reaction time.
The catalyst reusability was examined through the reaction among 4-methoxybenzaldehyde (3 mmol), methyl cyanoacetate (3 mmol), hydrazine hydrate (3 mmol) and malononitrile (3 mmol), conducted as a model reaction in optimized reaction conditions.Noteworthy, the product yield was constant after recycling (run1, 98%; run 2, 98%; run 3, 98%).It is possible to reuse RL BF Fe-based MOF@CuO NC until three runs with no significant decline in its catalytic function.In the recycling procedure, hot acetone addition aimed at diluting the model reaction mixture following the reaction completion and stirring the mixture over a 5-min period.The catalyst was insoluble in acetone and underwent several washings with acetone for its separation by filtration.The above steps were followed by drying at 40 °C within an 8-h period and reusing the catalyst with no considerable decline in its catalytic effects (Fig. 9).
In order to indicate the stability of RL BF Fe-based MOF@CuO NC after recovering and reusing, recovered catalyst was characterized.The morphology and particle size of RL BF Fe-based MOF@CuO NC after recycling has been studied by SEM technique.The SEM image of reused RL BF Fe-based MOF@CuO NC is shown in Fig. 10.As shown in this Figure, the size and morphology of catalyst after reusing is shown a good agreement to fresh catalyst, which is about 10-30 nm in diameters.Also, the shape of the recycled catalyst was the same as the fresh catalyst, indicating its good mechanical strength.
The XRD of the recovered RL BF Fe-based MOF@CuO NC after the three cycle shows clear peaks corresponding to the composite at 8.43°, 13.92° and 20.57° (Fig. 11).It clearly indicates that the catalyst remains unchanged even after the reaction.
The proposed mechanisms were used to prepare N-amino-2-pyridones in the presence of RL BF Fe-based MOF@CuO NC as shown in Fig. 12.Firstly, arylidenemalononitrile (A) formation was done from the Knoevenagel condensation aromatic aldehydes and malononitrile when RL BF Fe-based MOF@CuO NC was present.Meantime, methyl cyanoacetate reacts with hydrazine hydrate to form intermediate (B).Then, interaction of the enolizable cyanoacetic acid hydrazide (C) with arylidenemalononitrile (A) through Michael addition, followed by booting of the intermediate's intramolecular cyclization by nano-catalyst result in the final product yields.

Conclusion
In summary, an effective technique was reported for the generation of useful RL TF Fe-based MOF@CuO NC nano-catalyst using 1,3,5-Benzenetricarboxylic acid linker via microwave irradiation.The catalytic activity of RL TF Fe-based MOF@CuO NC was explored in one-pot synthesis of N-amino-2-pyridones by facile, rapid and versatile multi-component reaction of malononitrile, diverse aromatic aldehydes, hydrazine hydrate and ethyl cyanoacetate under mild and solvent-free conditions.The procedure offers several advantages including environmentally friendly, excellent yields with short reaction times, simple work up procedure and the ability of recyclability catalyst for three times with no considerable functional loss.

Figure 4
Figure3shows a TEM image of RL BF Fe-based MOF@CuO NC.It can be observed that the diameter of Fe-based MOF nanorods is about 30 nm.The surface of Fe-based MOF nanorods is homogeneously covered with well-dispersed spherical CuO nanoparticles.The particle size of the CuO nanoparticles is different.It can be found that the diameter of CuO nanoparticles is mostly distributed between 2 and 7 nm.Figure4shows EDX results of RL TF Fe-based MOF@CuO NC.The RL TF Fe-based MOF@CuO NC, contain C, O, Cu, and Fe with the atomic ratio of C: O: Cu: Fe ≈ 33.14: 12.55: 3.76: 50.55, with no other impurity peaks.Figure5indicates the N 2 adsorption-desorption isotherm of the RL TF Fe-based MOF@CuO NC.Physical characteristics, such as the surface area, pore size, and volume, and distribution, were determined through N 2 sorption estimations.Type IV isotherm can be recognized in the case of RL TF Fe-based MOF@CuO NC with a distinct hysteresis loop.The surface area, the pore volume, and pore size of RL TF Fe-based MOF@CuO NC were 8.4228 m 2 g −1 , 0.031269 cm 3 g −1 , and 17.346 nm, respectively.The VSM analysis was utilized at room temperature to characterize the magnetic properties of the RL TF Febased MOF@CuO NC.Figure6presents the M-H curve of the nanocomposite at room temperature.Accordingly, the semiconductor materials show magnetic characteristics with strong dependence on structural, morphological, and crystal geometric factors.Typical M-H curves represent a weak paramagnetic due to limited spin orientation at the maximum applied field (0.012 Oe).Nanocomposite has a coercivity of Hc, 75.0 Oe, suggesting their magnetic behavior with saturation magnetism of Ms, 0.17 emu.g −1 .The FT-IR spectra of CuO, TF Fe-based MOF, and RL TF Fe-based MOF@CuO NC are shown in Fig.7.FTIR spectroscopy can be employed for identifying molecule functional groups as each chemical bond has a distinct energy absorption band, through which the structural and bond information of compounds can be obtained.

Figure 2 .
Figure 2. (a) SEM image and (b) high-resolution SEM image of RL BF Fe-based MOF@CuO NC.

Figure 8 .
Figure 8. Four-component synthesis of N-amino-2-pyridones catalyzed by RL BF Fe-based MOF@CuO NC under solvent-free and reflux conditions.

Figure 9 .
Figure 9. Reusability of the RL BF Fe-based MOF@CuO NC in the synthesis of 5a.

Table 1 .
TGA data of RL BF Fe-based MOF@CuO NC.

Table 2 .
Optimization of the reaction conditions for the synthesis of N-amino-2-pyridones derivatives using RL BF Fe-based MOF@CuO NC.

Table 4 .
The comparison of the catalytic activity of RL BF Fe-based MOF@CuO NC with previously reported catalysts.