Poly(acrylic acid)/Fe3O4 supported on MIL-100(Cr) MOF as a novel and magnetic nanocatalyst for the synthesis of Pyrido[2,3-d]Pyrimidines.

In the current work, a convenient and simple approach for preparing poly (acrylic acid)/Fe3O4 supported on MIL-100(Cr) for the synthesis of pyrido [2,3-d]pyrimidine derivatives via the three-component one-pot reaction of 1,3-indandione, 6-amino uracil, and aromatic aldehydes is reported. The effectiveness of this new magnetic nanocatalyst was proved. The results showed this nanocatalyst's moderate to high yield under reflux conditions. SEM, TEM, IR, EDX, XRD, BET, and TGA were used to characterize the structure of the synthesized nanocatalyst. This synthetic protocol offers various advantages, including cost-saving, excellent yields in short reaction times (67-98%), low catalyst loading, and catalyst reusability.

Introduction

Metal-organic frameworks (MOFs) as a unique class of porous materials, are used as catalysts, heavy-metal adsorption, and gas storage and separation [1, 2, 3, 4]. MOFs present various properties depending on the type of their ligands and their surface functional groups. Functional groups in these frameworks could be firstly available in organic ligand structures, or functional groups could be created within the MOFs structure after their synthesis [5]. To obtain the following objectives, Cr-based MOFs should have improved adsorption, water, thermal stability, and larger surface area in the reaction processes [6, 7].

Multicomponent reactions (MCRs) and related one-pot synthesis (such as tandem, cascade, and domino reactions) are vital in developing novel methodologies in organic catalysis and synthesis because of their countless applications, especially in pharmaceutical works [8, 9, 10, 11, 12, 13]. Hence, complex purification phases are avoided, and time and reagents and solvents are saved [14, 15]. Pyrimidine cores, as main categories of heterocyclic and bioactive molecules, have been recently the subject of intense research in pharmaceutical studies. This great attention is attributed to their broad pharmacological and therapeutic properties, including anti-inflammatory [16], anticancer [17], antimicrobial [18], or antihistaminic activities [19].

One of these materials is pyrido [2,3-d] pyrimidine. This compound is considered an important group of heterocyclic compounds annulated uracil because of their various medicinal applications, like anticonvulsants, antibacterials, and anti-aggressive activities, antileishmanial, antifolate, anti-inflammatory, antimicrobial, and inhibition of cyclin-dependent kinases [20, 21].

We review the studies on synthetic approaches to produce these compounds in the following. Shi et al. (2008) presented pyrimidine derivative synthesis in ionic liquid [bmim]Br, and they obtained 75–93% of yields [22]. Khurana et al. (2012) reported an approach for synthesizing these systems. They used 20 mol% InCl3 (20 mol%) as a catalyst in water and gained 87–90% of product yields [23]. We recently presented various synthesis methods for many products that utilize nanocatalysts [24, 25, 26, 27, 28]. The current work presents a simple method for fabricating Poly (acrylic acid)/Fe3O4 Supported on MIL-100(Cr) (Fe3O4@PAA@MIL-100(Cr)) as an efficient and robust catalyst. It is an environmentally benign, highly reusable, and heterogeneous catalyst with high catalytic activity for synthesizing pyrido [2,3-d]pyrimidine derivatives through a one-pot three-component condensation reaction of aromatic aldehydes, 1,3-indandione, and 6-amino uracil in EtOH under reflux conditions (Scheme 1).

Scheme 1

Synthesis of pyrido [2,3-d]pyrimidines using Fe3O4@PAA@MIL-100(Cr).

Experimental

Preparation of Fe3O4-PAA

Fe3O4@PAA nanocomposite was prepared according to a method reported by Tian Jin et al [29]. Typically, we added 0.6 g PAA to a mix of 0.75 g FeCl3.6H2O in 40 mL ethylene glycol, followed by stirring the solution at ambient temperature for 30 min. Afterward, NaOAc (2.5 g) was added to the solution and it was placed in a 50 mL Teflon-lined stainless steel autoclave at of 200 °C for 24 h. Then, the resulting residue was rinsed three times using ethanol and deionized water and dispersed in ethanol (40 mL).

Synthesis of Fe3O4@PAA@MIL-100(Cr)

Briefly, trimesic acid (1.05 g) and CrO3 (0.5 g) were dissolved in H2O (2 mL) and HF (0.2 g). In the next step, it was mixed with an as-prepared Fe3O4@PAA solution (10 mL). The obtained solution was stirred for 2 h at 80 °C. Lastly, the synthesized Fe3O4@PAA@MIL-100(Cr) was rinsed using ethanol, and dried at 100 °C (Scheme 2).

Scheme 2

Preparation of Fe3O4@PAA@MIL-100(Cr).

General procedure for the synthesis of indeno [2′,1′:5,6]pyrido [2,3-d]pyrimidines (4a-p) using Fe3O4@PAA@MIL-100(Cr) nanocatalyst

The mixture of Fe3O4@PAA@MIL-100(Cr) (0.008 g), 1,3-indandione (1 mmol), aromatic aldehyde (1 mmol), and 6-amino uracil (1 mmol) in ethanol (5 mL) was refluxed for 30 min. The mixture was cooled to room temperature when the reaction (which was TLC-monitored) was completed, and the resulting solid was subsequently dissolved in dichloromethane. A straightforward filtering was used to isolate the catalyst, which was insoluble in CH2Cl2. M. p., FT-IR, 1H NMR and 13C NMR spectroscopy methods were performed to characterize and identify of all the products.

The spectral data of some products are provided, as below.

5-(4-chlorophenyl)-5,11-dihydro-1H-indeno[2′,1′:5,6]pyrido[2,3-d]pyrimidine-2,4,6-trione (4d): Yellow solid; m. p. >300 °C °C. IR spectrum ν, cm−1: 3362, 3285, 3073, 2815, 1714, 1646, 1633, 1544, 1511, 1023, 1H NMR (250 MHz, DMSO-d6) δ: 4.74 (s, 1H, CH),7.12 (d, 2H, J = 8.1 Hz, Ar–H), 7.25 (d, 2H, J = 8.2 Hz, Ar–H), 7.46–7.49 (m, 4H, Ar–H), 8.45 (s, br. 1H, NH), 10.28 (s, br. 1H, NH), 10.84 (s, br. 1H, NH); 13C NMR (62.9 MHz, DMSO-d6) δ: 38.5, 78.6, 104.5, 123.2, 124.5, 126.3, 127.8, 128.5, 128.9, 133.3, 135.4, 136.7, 144.5, 145.8, 153.4, 161.6, 163.5, 191.4; Anal. Calcd. for C20H12ClN3O3: C 63.59, H 3.20, N 11.12. Found: C, 63.54, H 3.17, N 11.09; MS (EI) (m/z): 377.06 (M+).

5-(4-methylphenyl)-5,11-dihydro-1H-indeno[2′,1′:5,6]pyrido[2,3-d]pyrimidine-2,4,6-trione (4e): Yellow solid; m. p. >300 °C °C. IR spectrum ν, cm−1: 3365, 3276, 3078, 2811, 1709, 1653, 1632, 1546, 1516, 1025, 1H NMR (250 MHz, DMSO-d6) δ: 2.25 (s, 3H, CH3), 4.76 (s, 1H, CH), 7.08 (d, 2H, J = 8.2 Hz, Ar–H), 7.26 (d, 2H, J = 8.1 Hz, Ar–H), 7.55–7.59 (m, 4H, Ar–H), 8.49 (s, 1H, NH), 10.35 (s, 1H, NH), 10.82 (s, 1H, NH); 13C NMR (62.9 MHz, DMSO-d6) δ: 17.8. 39.3, 78.7, 105.9, 123.6, 125.8, 126.3, 127.2, 128.1, 128.3, 132.1, 135.3, 136.5, 144.1, 146.7, 152.7, 162.8, 164.5, 193.1; Anal. Calcd. for C21H15N3O3: C 70.58, H 4.23, N 11.76. Found: C, 70.54, H 4.21, N 11.74; MS (EI) (m/z): 357.11 (M+).

5-(4-fluorophenyl)-5,11-dihydro-1H-indeno[2′,1′:5,6]pyrido[2,3-d]pyrimidine-2,4,6-trione (4f): Yellow solid; m. p. >300 °C °C. IR spectrum ν, cm−1: 3364, 3283, 3072, 2814, 1715, 1643, 1635, 1546, 1513, 1024, 1H NMR (250 MHz, DMSO-d6) δ: 4.75 (s, 1H, CH),7.16 (d, 2H, J = 8.2 Hz, Ar–H), 7.23 (d, 2H, J = 8.4 Hz, Ar–H), 7.43–7.46 (m, 4H, Ar–H), 9.04 (s, br. 1H, NH), 10.65 (s, br. 1H, NH), 10.94 (s, br. 1H, NH); 13C NMR (62.9 MHz, DMSO-d6) δ: 39.5, 79.6, 102.5, 123.3, 125.5, 126.2, 127.1, 128.4, 128.7, 133.2, 135.2, 136.8, 144.2, 146.5, 153.2 (1JC-F = 158 Hz), 161.4, 163.2, 191.5; Anal. Calcd. for C20H12FN3O3: C 66.48, H 3.35, N 11.63. Found: C, 66.45, H 3.38, N 11.65; MS (EI) (m/z): 361.09 (M+).

5-(2-fluorophenyl)-5,11-dihydro-1H-indeno[2′,1′:5,6]pyrido[2,3-d]pyrimidine-2,4,6-trione (4n): Yellow solid; m. p. >300 °C °C. IR spectrum ν, cm−1: 3368, 3288, 3077, 2811, 1714, 1641, 1633, 1543, 1512, 1021, 1H NMR (250 MHz, DMSO-d6) δ: 4.77 (s, 1H, CH),7.17 (d, 2H, J = 8.6 Hz, Ar–H), 7.26 (d, 2H, J = 8.2 Hz, Ar–H), 7.41–7.43 (m, 4H, Ar–H), 9.08 (s, br. 1H, NH), 10.69 (s, br. 1H, NH), 10.91 (s, br. 1H, NH); 13C NMR (62.9 MHz, DMSO-d6) δ: 39.6, 79.5, 102.7, 123.8, 125.1, 126.4, 127.2, 128.3, 128.8, 133.1, 135.5, 136.7, 144.6, 146.7, 153.5, 161.3 (1JC-F = 148 Hz), 163.5, 191.4; Anal. Calcd. for C20H12FN3O3: C 66.48, H 3.35, N 11.63. Found: C, 66.46, H 3.37, N 11.66; MS (EI) (m/z): 361.09 (M+).

4-(2,4,6-trioxo-2,3,4,5,6,11-hexahydro-1H-indeno[2′,1':5,6]pyrido[2,3-d]pyrimidin-5-yl)benzonitrile (4o): Yellow solid; m. p. >300 °C. IR spectrum ν, cm−1: 3365, 3172, 3051, 2932, 1705,1674, 1591, 1458, 1205; 1H NMR (250 MHz, DMSO-d6) δ: 4.33 (s, 1H, CH), 6.74–7.05 (d, 2H, J = 8.6 Hz, ArH), 7.28–7.32 (d, 2H, J = 8.3 Hz, ArH), 7.62–7.78 (m, 4H, ArH), 9.45 (s, 1H, NH), 10.12 (s, 1H, NH), 10.50 (s, 1H, NH); 13C NMR (62.9 MHz, DMSO-d6) δ: 27.33, 31.39, 68.62, 76.82, 87.26, 101.03, 112.53, 123.45, 131.34, 133.43, 134.25, 138.56, 144.43, 146.33, 148.62, 156.47, 165.38, 168.28, 170.21, 183.31, 188.22; Anal. Calcd. for C21H12N4O3: C 68.48, H 3.28, N 15.21; Found: C, 68.46, H 3.25, N 15.18; MS (EI) (m/z): 368.35 (M+).

5-(4-(methylthio)phenyl)-5,11-dihydro-1H-indeno[2′,1':5,6]pyrido[2,3-d]pyrimidine-2,4,6(3H)-trione (4p): Yellow solid; m. p. >300 °C. IR spectrum ν, cm−1: 3365, 3172, 3051, 1705, 1674, 1591, 1500, 1485, 1375, 1205; 1H NMR (250 MHz, DMSO-d6) δ: 2.73 (s, 3H, CH3), 4.64 (s, 1H, CH), 6.76–7.04 (d, 2H, J = 8.2 Hz, ArH), 7.28–7.36 (d, 2H, J = 8.3 Hz, ArH), 7.65–7.77 (m, 4H, ArH), 9.85 (s, 1H, NH), 10.51 (s, 1H, NH), 10.83 (s, 1H, NH); 13C NMR (62.9 MHz, DMSO-d6) δ: 28.39, 32.33, 67.62, 77.82, 86.26, 102.03, 113.52, 125.44, 132.34, 134.43, 136.26, 139.56, 146.44, 148.33, 149.69, 154.47, 162.34, 164.28, 171.21, 181.32, 187.21; Anal. Calcd. for C21H15N3O3S: C 64.77, H 3.88, N 10.79; Found: C, 64.75, H 3.86, N 10.75; MS (EI) (m/z): 389.08 (M+).

Results and discussion

Using EDX, FE-SEM, TEM, FT-IR, BET, TGA, and XRD techniques, the Fe3O4@PAA@MIL-100(Cr) nanostructure was studied in the main experiments. A magnetic core with a strong inclination between the ligand and the receptor and through the specific gravity absorption of the tissue is provided by Fe3O4 in the generated heterogeneous nanocomposite. Additionally, when placed in an acidic environment, polyacrylic acid acts as a polymer layer between Fe3O4 and MOF to conduct Fe3O4 magnetic and produce a cleft in the MIL-100(Cr) structure. The polyacrylic acid (PAA) chains in this composite served as a bridge to connect the MIL-100(Cr) layer outside and the magnetite nanoparticles Fe3O4 inside.

Scanning electron microscopy was used to visualize the results of the SEM examination for each stage of the catalyst synthesis. This examination appeared that Fe3O4 is composed of moderately uniform circular particles (Figure 1a). [30]. According to literature, the SEM image of MIL-100(Cr) showed that this structure has a typical octahedral shape (Figure 1b) [31]. The Fe3O4@PAA composite dispersity worsens as a result of the coated PAA ease of coating, as demonstrated by the SEM picture of the Fe3O4@PAA in Figure 1c [32]. Because of the connection between MIL-100(Cr) and Fe3O4 created by polyacrylic acid, the particles in the SEM image of Fe3O4@PAA@MIL-100(Cr) have a cloudy appearance (Figure 1d).

Figure 1

FE-SEM images of Fe3O4 (a), MIL-100(Cr) (b), Fe3O4@PAA (c), and Fe3O4@PAA@MIL-100(Cr) (d).

Transmission electron microscopy (TEM) analysis of the Fe3O4@PAA@MIL-100(Cr) are shown in Figure 2. The morphology and the topology of the nanocatalyst were confirmed to be cloudy structures. The particles of Fe3O4@PAA@MIL-100(Cr) were observed of nano-sized (approximately 25–35 nm) with proper dispersion.

Figure 2

TEM images of Fe3O4@PAA@MIL-100(Cr).

Chemical characterization and structural investigation of the sample were carried out using energy-dispersive X-ray (EDX) spectroscopy as an analytical technique. C, Fe, F, Cr, and O are the only elementary components in Fe3O4@PAA@MIL-100(Cr), as shown in the EDX spectrum (Figure 3).

Figure 3

The EDX spectrum of Fe3O4@PAA@MIL-100(Cr).

Figure 4 represents the FT-IR spectrum of Fe3O4@PAA@MIL-100(Cr). The absorption band at 550 cm−1 is due to the Fe–O stretching vibration [33]. The peaks in 1412 and 1566 cm−1 are due to C–O and C=O stretching vibrations of PAA, respectively. Besides, the stretching vibration of OH groups of PAA was observed at 3460 cm−1. The vibration bands as characteristics of framework (O–C–O) groups appeared near 1709 and 1383 cm−1, confirming the tricarboxylate coordination in the MIL-100(Cr) framework. The peak at 1452 cm−1 is attributed to the C=C bond vibration in tricarboxylate rings. Intense bands at about 3282 and 1641 cm−1 proved the presence of water molecules in the Fe3O4@PAA@MIL-100(Cr) [34].

Figure 4

FT-IR spectrum of Fe3O4@PAA@MIL-100(Cr).

Thermal gravimetric analysis (TGA) was used to measure the mass reduction caused by heating under a nitrogen gas stream (Figure 5). Fe3O4@PAA@MIL-100(Cr) structure depicts two stages of weight loss. At temperatures between 300 and 400 °C, organic molecules from the composite including PAA are destroyed. The second case is in the 400–850 °C range, which is attributed to destructing metal-organic framework (MIL-100(Cr)) in the Fe3O4@PAA@MIL-100(Cr) structure.

Figure 5

TGA curve of Fe3O4@PAA@MIL-100(Cr).

To determine the crystaline structure of the nanocomposite, X-ray diffraction pattern (XRD) was used. Figure 6 displays the XRD patterns for Fe3O4 nanoparticles and Fe3O4@PAA@MIL-100(Cr). The indices of the typical peaks for Fe3O4 are (220) (311) (222) (400) (422) (511) and (440). All of the peaks locations and relative intensities match up well with the Fe3O4 with P63mc group standard XRD pattern (JCDPS No. 75–0449), demonstrating that the crystalline cubic spinel was retained during the functionalization of MNPs [35]. Figure 6b indicates the diffraction peaks for Fe3O4@PAA@MIl-100(Cr), confirming the Fe3O4 crystallinity following functionalization with MIL-100(Cr) and polyacrylic acid.

Figure 6

XRD patterns of Fe3O4 (a), and Fe3O4@PAA@MIl-100(Cr) (b).

Nitrogen adsorption using the BET technique was applied to determine the surface area of the Fe3O4@PAA@MIl-100(Cr). As shown by BET analysis for Fe3O4@PAA@MIL-100(Cr), the available surface area was 1248 m2 g−1. The cavity volume in the Fe3O4@PAA@MIL-100(Cr) was 0.8112 cm3gr−1 (Figure 7a). Figure 7b indicates the desorption-adsorption isotherm for Fe3O4@PAA@MIL-100(Cr) as a type I sorption isotherm. The average pore diameter of the nanocarrier, as determined by the findings of the BJH study, was 1.23 nm, confirming the presence of porosity in the MOF (Figure 7c).

Figure 7

BET-plot of Fe3O4@PAA@MIL-100(Cr) (a), adsorption/desorption of Fe3O4@PAA@MIL-100(Cr) (b), and BJH-plot of Fe3O4@PAA@MIL-100(Cr) (c).

In continue, the condensation reaction of 4-chlorobenzaldehyde, 1,3-indandione, and 6-amino uracil was chosen as a model study to optimize the reaction and examine the effects of the catalyst, reactants, and solvent on the of synthesis of pyrido [2,3-d]pyrimidine derivatives (Scheme 3).

Scheme 3

The model reaction for the synthesis of pyrido [2,3-d]pyrimidine 4d.

Initially, the effect of various solvents and solvent-free conditions were examined when we used Fe3O4@PAA@MIL-100(Cr) as a catalyst in the preparation of pyrido [2,3-d]pyrimidine 4d. As can be observed, the solvent significantly affects the reaction rate (Figure 8). Ethanol afforded the best results (98% of yield) under reflux conditions for this multi-component reaction.

Figure 8

The influence of various solvents in model study.

In continue, the significance of the prepared catalyst in comparison to other catalysts was studied. Existing catalysts such as MgO, CuI, Fe3O4, MIL-100(Cr), and Fe3O4@PAA@MIL-100(Cr) were all applied under reflux conditions while utilizing ethanol as a solvent. According to Figure 9, Fe3O4@PAA@MIL-100(Cr) was the best catalyst regarding the reaction time and obtained product yield.

Figure 9

The effect of various catalysts on model reaction.

The study model was discussed in the following using various quantities of Fe3O4@PAA@MIL-100(Cr) nanocatalyst. The optimal concentration of Fe3O4@PAA@MIL-100(Cr) was found at 0.008 g (Figure 10). As indicated, the reaction duration and yield were not altered by a quantity greater than 0.008 g.

Figure 10

The effect of catalyst amount on the model reaction.

We studied the scope of this research by synthesizing pyrido [2,3-d]pyrimidine derivatives using various aromatic aldehydes comprising electron-donating and electron-withdrawing groups in the presence of 0.008 g of Fe3O4@PAA@MIL-100(Cr) nanocomposite. According to Table 1, prolonged reaction time is required by aryl aldehydes with electron-donating groups to afford the corresponding products. However, the aryl aldehydes with withdrawing groups reacted faster to produce pyrido [2,3-d]pyrimidines. According to the mechanism pathway (Scheme 4), the first step of the mechanism is the Knoevenagel condensation between 1,3-indandione and aromatic aldehyde. Obliviously, the presence of electron-withdrawing groups on the benzaldehydes leads to a faster reaction due to more electrophilicity of the carbon group of the carbonyl. While using Fe3O4@PAA@MIL-100(Cr) as a catalyst serves as a Lewis acid catalyst and causes to increase in electrophilicity of the carbonyl groups of aldehydes. The synergic effects of both electron-withdrawing groups and Lewis acidity of Fe3O4@PAA@MIL-100(Cr) increase the rate of the reaction. However, against the electron-withdrawing groups, the existence of electron-donating groups causes to decrease in the speed of the reaction, because of a slower nucleophilic attack on carbonyl groups of aldehydes.

Table 1

Synthesis of pyrido [2,3-d]pyrimidine derivatives using Fe3O4@PAA@MIL-100(Cr)

Entry	ArCHO	Product	Time (min)	Yield (%)a	M.p. oC	Lit. M.p. oC
1	Image 1	Image 2	45	76	>300 °C	>300 °C [36]
2	Image 3	Image 4	35	95	>300 °C	>300 °C [36]
3	Image 5	Image 6	40	87	>300 °C	>300 °C [36]
4	Image 7	Image 8	30	98	>300 °C	>300 °C [36]
5	Image 9	Image 10	50	75	>300 °C	>300 °C [36]
6	Image 11	Image 12	30	94	>300 °C	>300 °C [36]
7	Image 13	Image 14	45	78	>300 °C	>300 °C [36]
8	Image 15	Image 16	35	96	>300 °C	>300 °C [36]
9	Image 17	Image 18	40	80	>300 °C	>300 °C [36]
10	Image 19	Image 20	45	79	>300 °C	>300 °C [22]
11	Image 21	Image 22	50	83	>300 °C	>300 °C [22]
12	Image 23	Image 24	45	67	>300 °C	>300 °C [36]
13	Image 25	Image 26	40	63	>300 °C	>300 °C [36]
14	Image 27	Image 28	35	85	>300 °C	>300 °C [22]
15	Image 29	Image 30	30	92	>300 °C	------b
16	Image 31	Image 32	40	86	>300 °C	------b

Isolated yield.

New Products.

Scheme 4

Proposed reaction mechanism for preparation of pyrido [2,3-d]pyrimidines using Fe3O4@PAA@MIL-100(Cr).

We compared the usability and efficiency of our catalyst to synthesize pyrido [2,3-d]pyrimidine derivatives and other catalysts reported previously. According to Table 2, Fe3O4@PAA@MIL-100(Cr) outperformed other catalysts in saving energy, time, and superior yields of the products (Table 2).

Table 2

The comparison of the outcomes of the production of pyrido [2,3-d]pyrimidines by means of different catalystsa.

Entry	Catalyst	Conditions	Time/yield (%)	References
1	[bmim]Br	Solvent-free/95 °C	210 min/89-91	[22]
2	InCl3	H2O/Reflux	60 min/87-90	[23]
3	[DMBSI]HSO4	Ethylene glyco 1/Reflux	4h/87-95	[36]
4	Nano-Fe3O4@SiO2–SO3H	H2O/Stir. (70 °C)	25 min/90-94	[37]
5	Nano-Fe3O4@cellulose-SO3H	H2O/Stir.80 °C	30 min/85-95	[38]
6	Fe3O4@PAA@MIL-100(Cr)	EtOH/Reflux	30 min/75-98	This work

Based on the three-component reaction of 4-chlorobenzaldehyde, 1,3-indandione, and 6-amino uracil.

Reuse of catalyst

The catalyst reusability is well known as the key characteristic feature. Here, we assessed the retrievability of the Fe3O4@PAA@MIL-100(Cr) on the reaction of 4-chlorobenzaldehyde 1,3-indandione, and 6-amino uracil. As shown in Figure 11, the catalytic activity of Fe3O4@PAA@MIL-100(Cr) reduced from 98% in the fresh run to 85% after 7 runs.

Figure 11

Reusability of the Fe3O4@PAA@MIL-100(Cr) catalyst.

Scheme 4 shows the plausible mechanism to prepare pyrido [2,3-d]pyrimidines in the presence of Fe3O4@PAA@MIL-100(Cr) nanostructure as the catalyst. When there are Lewis acidic sites over the catalyst surface, the reactants may undergo reaction within a shorter time. The results were examined experimentally based on the literature [37, 38]. Fe3O4 and MIL-101(Cr) are thought to function as Lewis acids that, through a potent coordination bond, boost the electrophilicity of the carbonyl groups of 1,3-indandione and aldehyde [39, 40]. In the first step, it is assumed that, electron pairs of the carbonyl groups of the 1,3-indandione and aryl aldehydes were interacted with the catalyst to improve the electrophilicity features of the functional groups (formation of intermediates A and B). In addition, the intermediate (C) was obtained via the Knoevenogel condensation between intermediate A and B. Then, by the 6-aminouracil attacks to the intermediate (C), the intermediate (D) formed through the Michael addition. Next, tautomerization of intermediate D led to the formation of intermediate E, by intramolecular cyclization and dehydration to produce 5-aryl-5,11-dihydro-1H-indeno [2′,1′:5,6]pyrido [2,3-d]pyrimidine-2,4,6-trione 4.

Conclusio

In summary, we prepared and characterized Fe3O4@PAA@MIL-100(Cr) magnetic nano-catalyst as a magnetically recyclable, green and bio-friendly catalyst. This catalyst was applied to synthesize pyrido [2,3-d]pyrimidine derivatives via a three-component reaction of 1,3-indandione, 6-amino uracil, and aromatic aldehydes. By this approach, some benefits including great yields in short reaction time, high atom economy, and mild reaction conditions were provided.

Declarations

Author contribution statement

Mohammad Ali Ghasemzadeh: Conceived and designed the experiments; Analyzed and interpreted the data; Contributed reagents, materials, analysis tools or data; Wrote the paper.

Boshra Mirhosseini-Eshkevari: Performed the experiments; Analyzed and interpreted the data; Contributed reagents, materials, analysis tools or data; Wrote the paper.

Funding statement

This work was supported by the Research Affairs Office of the Islamic Azad University, Qom Branch, Qom, I. R. Iran (grant number 2019-2898).

Data availability statement

Data will be made available on request.

Declaration of interests statement

The authors declare no conflict of interest.

Additional information

No additional information is available for this paper.