Synthesis of benzo[a]furo[2, 3-c]phenazine derivatives through an efficient, rapid and via microwave irradiation under solvent-free conditions catalyzed by H₃PW₁₂O₄₀@Fe₃O₄-ZnO for high-performance removal of methylene blue

Abstract

A rapid, one-pot synthesis of eight benzo[a]furo[2,3-c]phenazine derivatives has been achieved in moderate to good yields in good yields via a multi-component of 2-hydroxynaphthalene-1,4-dione, arylglyoxal, indole (H, CH₃) in the presence of H₃PW₁₂O₄₀@Fe₃O₄-ZnO magnetic core-shell nanoparticles (MCNPs) under solvent-free conditions using microwave irradiation. The catalyst was synthesised and characterised by X-ray diffraction, EDX, TEM, FESEM, TGA, VSM and atomic force microscope. As an application for the synthesised nanocatalyst, degradation of methylene blue as heavy-mass organic pollution was measured. These results showed advantages for synthesis, such as mild reaction conditions, low energy consumption and economically affordable.

Graphical Abstract

Keywords:

• Multi-component
• magnetic core-shell nanoparticles
• microwave-assisted
• solvent-free conditions
• green synthesis

Introduction

Multi-component reactions are one of the most successful methods in increasing structural diversity and molecular complexity using a simple process [1,2]. This method, like an evolving process for the preparation of pharmaceutical compounds, allows the expansion of many chemical compounds, with greater structural diversity. The advantages of this method compared to other methods are the use of available raw materials, low expensive, easy working method, a wide range of goods, creating a high variety in several stages [3–5].

Organic reactions under microwave radiation have attracted the attention of scientists due to their high reaction rate and clean products. Microwave-assisted reactions required short reaction times hence become a more popular route for organic chemists [6–8]. Mild reaction conditions, shorter reaction time, and excellent yields are the main advantages of this method [9,10].

Recently, semiconductor heterogeneous photocatalysts such as TiO₂ and ZnO have attracted a lot of attention due to their excellent performance in destroying organic compounds and purifying water. Among them, pure nano-ZnO has important research and application value because of its bandgap width of 3.2 eV [11,12]. Also, due to the recyclability of the catalyst, Fe₃O₄ has been considered by many researchers as a ferromagnetic material due to its good ability [13,14]. Based on the above study, we completed the effective combination of ZnO and Fe₃O₄–ZnO and designed an H₃PW₁₂O₄₀@Fe₃O₄–ZnO core-shell photocatalyst with magnetic separation capability. Core-shell nanoparticles are used for medical applications, and due to their high stability, this magnetic nanoparticle can be useful for hyperthermia magnetic therapy (MHT) for the treatment of cancer [15,16]. Furthermore, nanomaterial applications as a heterogeneous catalyst in place of homogeneous catalysts in MCRs make the process greener due to easy handling, non-corrosiveness, high surface area, surface modification ability, excellent thermal and chemical stability, simple work-up procedures, environmentally benign nature, reusability, low cost and ease of synthesis and isolation [17,18]. Among them, non-toxic ZnO and ZnO nanoparticles catalyzed organic processes are often considered to follow the principles of green chemistry, that is, these catalyzed processes consume a minimum of energy and reagents or auxiliaries and minimize waste [19].

Phenazine-based compounds are nitrogen-containing heterocycles that have been illustrated to possess numerous biological functions including antimicrobial [20], antimycobacterial [21], antifungal [22] and antitumor [23] activities. Phenazines such as XR-5944 and XR-11576 (Figure 1) have been reported to exhibit anti-cancer effects [24]. Benzo[a]phenazine derivatives are widely used in photodynamic therapy; which selectively target tumours [25].

Figure 1. Biological activity of phenazine derivatives.

Herein, we report a very green synthesis of functionalized benzo[a]furo[2, 03-c]phenazine derivatives catalyzed by H₃PW₁₂O₄₀@Fe₃O₄–ZnO magnetic core-shell nanoparticles (MCNPs) under solvent-free conditions via microwave irradiation (Scheme 1). Degradation of methylene blue was studied as a sample of organic pollutants by the core-shell structure of H₃PW₁₂O₄₀@Fe₃O₄–ZnO.

Scheme 1. Synthesis of benzo[a]furo[2, 3-c]phenazine derivatives in the presence of H₃PW₁₂O₄₀@Fe₃O₄-ZnO as heterogeneous catalyst.

Experimental

General

All melting points were determined on an Electrothermal 9100 apparatus and are uncorrected. IR spectra were recorded on a Shimadzu IR-470 spectrometer. Elemental analyses for C, H, and N were performed using a Costech ECS 4010 CHNS-O analyzer. Mass spectra were recorded on an Agilent Technology (HP) spectrometer operating at an ionization potential of 70 eV. The ¹H nuclear magnetic resonance (NMR) and ¹³C NMR spectra were recorded on Bruker DRX-400 Advance instruments with DMSO as a solvent. All reactions were carried out using a laboratory microwave oven (MicroSYNTH, Milestone Company, Italy). Thin-layer chromatography (TLC) was performed on silica-gel Polygram SILG/UV 254 plates.

All reagents and solvent were purchased from Merck and Aldrich and used without further purification. Scanning electron microscope (SEM) micrographs were taken using a VPLEO–Germany 1450 microscope. TEM measurements were performed on a Philips 120 CM electronic microscope. Atomic force microscope (AFM) was taken using an Easy scan 2 Nanosurf microscopes. Thermal analysis (TGA-DTA) was carried out using a Bahr STA-503 instrument at a heating rate of 10 °C min⁻¹ in the air. Powder X-ray diffraction (XRD) patterns were obtained on an STOE diffract metre using Cu K radiation (=0.15418 nm).

Preparation of nano-Fe3O4

To prepare the iron nanoparticles, 2 g of ferric chloride II (FeCl₂·4H₂O) were dissolved with 5.4 g of ferric chloride III (FeCl₃·6H₂O) in 522 ml of deionized water, and then 62 ml of ammonia was added dropwise under mechanical stirring. The colour of the solution immediately changed to black. The resulting solution is stirred at 72 °C for 92 min and then rinsed with deionised water. Due to the high saturation magnetization of the nanoparticles, Fe₃O₄ absorbs the magnet well after each washing step and facilitates the washing operation. When rinsed by placing a magnet under the fuzzy separator, the transparent solution is discarded and discarded. After three rinses, the precipitates were dried under a vacuum (Figure 2).

Figure 2. Phase separation of Fe₃O₄ sediments from solution using a conventional magnet.

Preparation of ZnO nanoparticle

First, 0.1 mol of zinc nitrate was dissolved in 0.15 mol of oxalic acid in 100 cc of deionized water and stirred for 30 min at 45 °C with a magnetic stirrer. The obtained solution was then transferred to a two-way balloon for reflux and homogenization. The reflux lasted for 15 h at 75 °C. The solution was then centrifuged for 10 h at 90 °C in the oil bath and then placed directly on the hot plate at 130 °C for two hours. It was then incubated in the oven at 500 °C for 1 h.

Preparation of Fe₃O₄/ZnO core/shell MNPs

Fe₃O₄ superparamagnetic cores were synthesized by co-precipitation of FeCl₃⋅6H₂O and FeCl₂·4H₂O at the 2:1 molar ratio of Fe³⁺ and Fe²⁺, and they were dissolved in deionized water. After stirring for 10 min, the calculated amount of NH₄OH was added to the solution. The Fe3O4 precipitates were separated using a centrifuge and washed rigorously with deionized water. Fe₃O₄/ZnO core/shell nanoparticles were synthesized using a previously reported method with minor modifications. The as-prepared magnetite sample was dispersed into deionized water and the pH value was regulated to 5.0. Then, Zn(NO₃)₂ dissolved in deionized water was dripped into the solution with a molar ratio of magnetite to zinc source adjusted to 1:2. After 1 h of contact, the pH value was increased up to 9.0 at 80 °C to promote the dehydration and atomic rearrangement involved with the formation of ZnO on the surface of the magnetite. At the end of the contact stage, the solids were magnetically collected, washed with ethanol and abundant deionized water, and dried (Scheme 2).

Scheme 2. Synthesis process of Fe₃O₄@ZnO nanoparticles.

Preparation of H₃PW₁₂O₄₀@Fe₃O₄–ZnO nanoparticles

1.0 g Fe₃O₄–ZnO nanoparticles were suspended in a methanolic solution of phosphotungstic acid (1.0 g in 50 ml), and the mixture briefly sonicated and microwave irradiation then stirred at ambient temperature for 9 h. The resulting solid was separated and repeatedly washed with ethanol and water, then dried under reduced pressure and designated PTA@Fe₃O₄–ZnO. The bulk W loading from ICP-OES was 12.9 wt% (equivalent to 16.9 wt% PTA), with loadings of other elements as follows: Fe 29.1 wt%.

General experimental procedure for the synthesis of benzo[a]furo[2, 3-c]phenazine derivatives (6a–h)

Initially, 2-hydroxynaphthalene-1,4-dione 1 (1 mmol), aromatic 1,2-diamines 2 (1 mmol) were mixed at 80 °C until an orange solid of benzo[a]phenazine 3 was formed within 3-5 min [13].

The microwave was programmed to give a maximum internal temperature of 100 °C. Then, arylglyoxal (1 mmol), indole (1 mmol), and 0.03 g of 60% H₃PW₁₂O₄₀@Fe₃O₄–ZnO nanoparticles were added to the above reaction mixture which was irradiated further at the same temperature (300 W, max. 100 °C) for an appropriate time as shown in Table 1. Upon completion of the reaction, monitored by TLC, the reaction mixture was allowed to cool to room temperature. Then, 5 ml of water was added to the mixture and washed several times. The catalyst was separated from the solvent by a magnet and finally dried under vacuum overnight. The separated product was washed twice with ethanol (2 × 5 ml). The crude solid product gives pure product 6 after washing and filtration (Table 2).

Table 1. Optimization of reaction conditions of compound 6a.

^aReaction conditions: 2-hydroxynaphthalene-1,4-dione (1 mmol), arylglyoxal (1 mmol), indole (1 mmol) in the presence of different catalytic systems under various conditions.

Table 2. Sequential one-pot four-component synthesis of benzo[a]furo[2, 3-c]phenazine derivatives.

^aYields refer to the pure isolated products.

The analytical and spectroscopic data for the unknown compounds

1-(1h-indol-3-yl)-2-(4-methoxyphenyl)-10-nitrobenzo[a]furo[2,3-c]phenazine (6a)

Red powder; yield 0.51 g (97%), m.p 232 − 234 °C; IR (KBr): ν_max= 3315, 3030, 2850, 1661, 1606, 1573, 1521, 1471, 1445, 1326, 1211, 1148, 1113, 1025, 1000, 945, 808, 755 cm⁻¹; ¹H NMR (500 MHz, DMSO-d₆) δ 3.79 (s, 3H), 7.06 − 7.13 (m, 2H), 7.23 − 7.32 (m, 2H), 7.44 − 7.55 (m, 2H), 7.63 (td, J=7.8, 1.2 Hz, 1H), 7.75 − 7.81 (m, 2H), 8.03 (d, J=2.5 Hz, 1H), 8.06 − 8.13 (m, 1H), 8.30 − 8.41 (m, 3H), 8.61 (dd, J=7.8, 1.3 Hz, 1H), 9.21 (d, J=2.0 Hz, 1H), 9.46 (s, 1H) ppm; ¹³C NMR (125 MHz, DMSO-d₆) δ 55.3, 107.0, 112.2, 114.3, 120.4, 120.9, 121.7, 122.3, 122.5, 123.3, 124.1, 124.9, 125.6, 125.8, 126.1, 126.5, 128.1, 128.6, 128.6, 129.1, 129.2, 129.4, 136.8, 137.7, 138.2, 141.4, 143.2, 148.2, 151.4, 155.9, 160.2; MS (m/z, %): 536 (M⁺, 83); Anal. Calcd for C₃₃H₂₀N₄O₄: C, 73.87; H, 3.76; N, 10.44%. Found: C, 73.89; H, 3.74; N, 10.42%.

1-(1h-indol-3-yl)-10-nitro-2-(p-tolyl)benzo[a]furo[2,3-c]phenazine (6 b)

Orange powder; yield 0.48 g (94%), m.p 292 − 294 °C; IR (KBr): ν_max=3245, 3135, 2675, 2340, 1673, 1629, 1576, 1510, 1478, 1434, 1404, 1317, 1210, 1165, 1116, 1084, 1002, 952, 834, 755 cm⁻¹; ¹H NMR (500 MHz, DMSO-d₆) δ 2.36 (s, 3H), 7.21 − 7.32 (m, 4H), 7.45 − 7.56 (m, 2H), 7.63 (td, J = 7.7, 1.5 Hz, 1H), 7.74 − 7.81 (m, 2H), 8.05 − 8.12 (m, 2H), 8.30 − 8.41 (m, 2H), 8.42 (d, J = 8.4 Hz, 1H), 8.61 (dd, J=7.8, 1.2 Hz, 1H), 9.21 (d, J=2.1 Hz, 1H), 9.47 (s, 1H) ppm; ¹³C NMR (125 MHz, DMSO-d₆) δ 21.2, 107.0, 112.2, 120.5, 120.8, 121.7, 122.3, 123.2, 124.0, 124.9, 125.5, 125.6, 125.7, 126.1, 126.5, 127.7, 128.1, 128.6, 129.2, 129.7, 136.8, 137.7, 138.2, 140.0, 141.3, 143.3, 148.2, 151.4, 155.7; MS (m/z, %): 520 (M⁺, 86); Anal. Calcd for C₃₃H₂₀N₄O₃: C, 76.14; H, 3.87; N, 10.76%. Found: C, 76.15; H, 3.85; N, 10.74%.

1-(1h-indol-3-yl)-2-(p-tolyl)benzo[a]furo[2,3-c]phenazine (6c)

Brown powder; yield 0.40 g (85%), m.p 251 − 253 °C; IR (KBr): ν_max=3420, 3250, 3030, 2875, 2695, 2340, 1617, 1582, 1528, 1481, 1443, 1404, 1348, 1312, 1222, 1130, 1063, 1001, 814, 761, 734, 706 cm⁻¹; ¹H NMR (500 MHz, DMSO-d₆) δ 2.37 (d, J=0.8 Hz, 3H), 7.22 − 7.32 (m, 4H), 7.46 − 7.55 (m, 2H), 7.55 − 7.62 (m, 1H), 7.58 − 7.69 (m, 2H), 7.75 − 7.82 (m, 2H), 8.01 − 8.13 (m, 3H), 8.14 − 8.22 (m, 1H), 8.36 (dd, J=8.1, 1.5 Hz, 1H), 8.58 − 8.64 (m, 1H), 9.47 (s, 1H) ppm; ¹³C NMR (125 MHz, DMSO-d₆) δ 21.2, 107.0, 112.1, 120.4, 120.9, 121.7, 122.3, 123.2, 124.1, 125.0, 125.5, 125.7, 126.0, 127.7, 128.0, 128.6, 128.7, 128.9, 129.2, 129.2, 129.5, 129.7, 136.7, 136.9, 139.8, 141.7, 142.4, 142.5, 151.5, 155.0; MS (m/z, %): 475 (M⁺, 90); Anal. Calcd for C₃₃H₂₁N₃O: C, 83.35; H, 4.45; N, 8.84%. Found: C, 83.33; H, 4.42; N, 8.82%.

1-(1h-indol-3-yl)-2-phenylbenzo[a]furo[2,3-c]phenazine (6d)

Brown powder; yield 0.42 g (93%), m.p 249 − 251 °C; IR (KBr): ν_max= 3440, 3240, 3050, 2890, 1612, 1581, 1518, 1484, 1444, 1400, 1327, 1200, 1161, 1111, 1084, 1025, 1002, 943, 821, 734 cm⁻¹; ¹H NMR (500 MHz, DMSO-d₆) δ 7.23 − 7.32 (m, 2H), 7.40 − 7.48 (m, 1H), 7.46 − 7.56 (m, 4H), 7.58 (dd, J=7.2, 5.7 Hz, 1H), 7.58 − 7.68 (m, 2H), 7.83 − 7.90 (m, 2H), 8.01 − 8.13 (m, 3H), 8.14 − 8.21 (m, 1H), 8.36 (dd, J=7.9, 1.3 Hz, 1H), 8.61 (dd, J=8.1, 1.3 Hz, 1H), 9.46 (s, 1H) ppm; ¹³C NMR (125 MHz, DMSO-d₆) δ 107.0, 112.1, 120.4, 120.9, 121.7, 122.3, 123.2, 124.1, 125.0, 125.7, 126.0, 127.3, 127.9, 128.0, 128.6, 128.7, 128.9, 129.1, 129.3, 129.4, 129.5, 129.6, 136.8, 136.9, 141.8, 142.4, 142.5, 151.5, 155.2; MS (m/z, %): 461 (M⁺, 91); Anal. Calcd for C₃₂H₁₉N₃O: C, 83.28; H, 4.15; N, 9.10%. Found: C, 83.30; H, 4.12; N, 9.12%.

1-(2-Methyl-1H-indol-3-yl)-2-(p-tolyl)benzo[a]furo[2,3-c]phenazine (6e)

Brown powder; yield 0.44 g (91%), m.p 240–242 °C; IR (KBr): ν_max= 3460, 3280, 3160, 3045, 1583, 1515, 1483, 1443, 1402, 1328, 1269, 1227, 1201, 1169, 1112, 1025, 1002, 944, 826, 736, 690 cm⁻¹; ¹H NMR (500 MHz, DMSO-d₆) δ 2.37 (s, 3H), 2.70 (s, 3H), 7.14 (td, J=7.4, 1.2 Hz, 1H), 7.21 (td, J=7.5, 1.9 Hz, 1H), 7.26 (d, J=8.3 Hz, 2H), 7.51 (ddd, J=9.3, 7.8, 1.6 Hz, 2H), 7.55 − 7.65 (m, 2H), 7.65 (td, J=7.8, 1.2 Hz, 1H), 7.73 − 7.79 (m, 2H), 7.89 (dd, J=7.8, 1.4 Hz, 1H), 8.02 − 8.10 (m, 1H), 8.13 − 8.22 (m, 1H), 8.31 (dd, J=7.8, 1.4 Hz, 1H), 8.62 (dd, J=7.8, 1.3 Hz, 1H), 9.47 (s, 1H) ppm; ¹³C NMR (125 MHz, DMSO-d₆) δ 12.3, 21.2, 105.5, 112.3, 120.9, 121.7, 121.8, 123.2, 124.5, 124.9, 125.0, 125.4, 126.4, 126.9, 127.7, 128.1, 128.6, 128.7, 128.8, 128.9, 128.9, 129.5, 129.67, 135.7, 136.5, 136.7, 137.5, 140.0, 142.4, 142.5, 151.0, 160.1; MS (m/z, %): 489 (M⁺, 79); Anal. Calcd for C₃₄H₂₃N₃O: C, 83.41; H, 4.74; N, 8.58%. Found: C, 83.38; H, 4.76; N, 8.56%.

2-(4-Ethoxyphenyl)-1-(2-methyl-1H-indol-3-yl)benzo[a]furo[2,3-c]phenazine (6f)

Brown powder; yield 0.45 g (90%), m.p 255 − 257 °C; IR (KBr): ν_max= 3425, 3185, 3045, 2865, 1668, 1606, 1582, 1517, 1482, 1440, 1325, 1274, 1199, 1169, 1114, 1065, 1002, 942, 890, 810, 744, 675 cm⁻¹; ¹H NMR (500 MHz, DMSO-d₆) δ 1.44 (t, J=6.6 Hz, 3H), 2.70 (s, 3H), 4.02 (q, J=6.6 Hz, 2H), 7.00 − 7.06 (m, 2H), 7.14 (td, J=7.5, 1.4 Hz, 1H), 7.21 (td, J=7.6, 1.9 Hz, 1H), 7.51 (ddd, J=7.6, 6.3, 1.5 Hz, 2H), 7.55 − 7.67 (m, 3H), 7.74 − 7.80 (m, 2H), 7.90 (dd, J=8.0, 1.5 Hz, 1H), 8.02 − 8.11 (m, 1H), 8.16 − 8.22 (m, 1H), 8.34 (dd, J=7.9, 1.4 Hz, 1H), 8.62 (dd, J=7.8, 1.3 Hz, 1H), 9.47 (s, 1H) ppm; ¹³C NMR (125 MHz, DMSO-d₆) δ 12.3, 14.6, 63.5, 105.5, 112.2, 114.4, 120.7, 121.7, 121.8, 122.2, 123.2, 124.6, 124.9, 125.3, 126.4, 127.0, 128.1, 128.6, 128.6, 128.7, 128.9, 129.2, 129.3, 129.5, 129.5, 135.7, 136.6, 136.7, 137.6, 142.4, 142.5, 150.9, 159.6, 160.3; MS (m/z, %): 505 (M⁺, 73); Anal. Calcd for C₃₄H₂₃N₃O₂: C, 80.77; H, 4.59; N, 8.31%. Found: C, 80.72; H, 4.61; N, 8.34%.

1-(2-Methyl-1H-indol-3-yl)-10-nitro-2-(p-tolyl)benzo[a]furo[2,3-c]phenazine (6 g)

Brown powder; yield 0.46 g (87%), m.p 279 − 281 °C; IR (KBr): ν_max= 3425, 3185, 3045, 2865, 1668, 1606, 1582, 1517, 1482, 1440, 1325, 1274, 1199, 1169, 1114, 1065, 1002, 942, 890, 810, 744, 675 cm⁻¹; ¹H NMR (500 MHz, DMSO-d₆) δ 2.36 (d, J=0.9 Hz, 3H), 2.70 (s, 3H), 7.13 (td, J=7.4, 1.3 Hz, 1H), 7.17 − 7.29 (m, 3H), 7.52 (ddd, J=7.7, 6.2, 1.6 Hz, 2H), 7.63 (td, J=7.8, 1.2 Hz, 1H), 7.74 − 7.80 (m, 2H), 7.90 (dd, J=8.0, 1.6 Hz, 1H), 8.32 (d, J=8.4 Hz, 1H), 8.41 − 8.33 (m, 2H), 8.59 − 8.65 (m, 1H), 9.21 (d, J=1.9 Hz, 1H), 9.47 (s, 1H) ppm; ¹³C NMR (125 MHz, DMSO-d₆) δ 12.3, 21.2, 108.3, 112.3, 120.9, 121.7, 121.7, 123.2, 124.8, 124.9, 125.0, 125.4, 125.7, 126.4, 126.5, 127.0, 127.6, 128.1, 128.6, 129.2, 129.3, 129.7, 135.7, 136.5, 137.5, 138.1, 140.0, 141.3, 143.3, 148.2, 150.9, 160.3; MS (m/z, %): 534 (M⁺, 73); Anal. Calcd for C₃₄H₂₂N₄O₃: C, 76.39; H, 4.15; N, 10.48%. Found: C, 76.36; H, 4.12; N, 10.45%.

2-(4-Methoxyphenyl)-1-(2-methyl-1H-indol-3-yl)-12-nitrobenzo[a]furo[2,3-c]phenazine (6 h)

Brown powder; yield 0.51 g (93%), m.p 253 − 255 °C; IR (KBr): ν_max= 3425, 3185, 3045, 2865, 1668, 1606, 1582, 1517, 1482, 1440, 1325, 1274, 1199, 1169, 1114, 1065, 1002, 942, 890, 810, 744, 675 cm⁻¹; ¹H NMR (500 MHz, DMSO-d₆) δ 1.43 (t, J=6.6 Hz, 3H), 2.70 (s, 3H), 4.02 (q, J=6.6 Hz, 2H), 7.00 − 7.06 (m, 2H), 7.13 (td, J=7.5, 1.4 Hz, 1H), 7.21 (td, J=7.6, 2.0 Hz, 1H), 7.47 − 7.55 (m, 2H), 7.63 (td, J=7.8, 1.2 Hz, 1H), 7.74 − 7.80 (m, 2H), 7.90 (dd, J=7.8, 1.4 Hz, 1H), 8.30 − 8.42 (m, 3H), 8.61 (dd, J=7.7, 1.5 Hz, 1H), 8.72 (d, J=1.9 Hz, 1H), 9.47 (s, 1H) ppm; ¹³C NMR (125 MHz, DMSO-d₆) δ 12.3, 14.6, 63.5, 109.0, 112.1, 114.5, 120.9, 121.7, 121.7, 122.2, 123.3, 124.9, 125.3, 125.4, 125.5, 126.4, 126.5, 127.0, 128.1, 128.6, 129.2, 129.5, 135.7, 136.5, 137.5, 138.1, 141.3, 143.3, 148.2, 150.9, 159.6, 160.4; MS (m/z, %): 550 (M⁺, 81); Anal. Calcd for C₃₄H₂₂N₄O₄: C, 74.17; H, 4.03; N, 10.18%. Found: C, 74.15; H, 4.06; N, 10.08%.

To optimise the catalytic system, the reaction of benzo[a]phenazine (1 mmol), arylglyoxal (1 mmol), indole (1 mmol) under solvent-free was used as a model reaction for the synthesis of compound 6a. We studied the type of catalyst, catalyst amount, solvent, and the influence of microwave irradiation. The results are summarised in Table 1. The reaction gave the highest yield using 60% of H₃PW₁₂O₄₀@Fe₃O₄–ZnO under microwave irradiation (300 W, max. 100 °C) (Table 1, entry 7). Increasing the amount of 60% H₃PW₁₂O₄₀@Fe₃O₄–ZnO to more than 0.06 g showed no substantial improvement in the yield, whereas the yield decreased by decreasing the amount of the catalyst to 0.015 g. The IR spectrum of compound 6a exhibits two absorption bands, one at 1648 cm⁻¹ for the (O=C) and the other at 1331 and 1506 cm⁻¹ for the (2NO₂) groups. The 500 MHz ¹H NMR spectrum of 6a exhibits multiplets at δ 7.08–9.21 ppm for aromatic protons. The ¹³C NMR spectrum of compound 6a shows 27 distinct resonances, in agreement with the proposed structure.

As shown in Figure 3, employing magnetic separation of the catalyst and subsequent ethanol washing and drying at 90 °C for 4 h in between each reaction. We found that the catalyst could be used at least five times with only slight reduction inactivity, for example, the yield (6a) typically declined from 88 to 85%. It can be seen that the activity of the recovered catalyst with the same function is very appropriate during the two stages. In the later stages, the activity of the magnetic catalyst is reduced, which can be expressed due to the weight of the catalyst in the later stages of synthesis during the recovery process. This proper performance of the catalyst indicates its excellent performance in the reaction under solvent-free conditions and microwave radiation.

Figure 3. The investigation of the recycling of nano H₃PW₁₂O₄₀@Fe₃O₄–ZnO.

With the optimised conditions in hand, the scope and efficiency of the reaction were explored for the synthesis of benzo[a]furo[2,3-c]phenazine derivatives. Thus, 2-hydroxynaphthalene-1,4-dione, arylglyoxal, indole in the presence of a catalyst (60 mol%) at microwave irradiation. The results are shown in Table 2.

To show the merit of the present work in comparison with the reported results in the literature, we compared the results of SiO₂–SO₃H as catalyst with PTSA [26], H₂SO₄ [27], phosphotungstic acid [27], [NMP]H₂PO₄ [27] and SiO₂–SO₃H [28] in the synthesis benzo[a]furo[2,3-c] phenazine derivatives from 2-hydroxynaphthalene-1,4-dione 1, aromatic 1,2-diamines 2, arylglyoxal and indole. As shown in Table 3, entry 7, this new catalytic system compared to previous similar works has a number of advantages such as: very shorter reaction time, higher yields, catalyst recovery, and most importantly, avoidance of hazardous or toxic catalysts and organic solvents. In all these cases, our work has introduced green and more economically cost-effective relative to previous similar works.

Table 3. Comparison of results obtained using H₃PW₁₂O₄₀@Fe₃O₄–ZnO with results obtained using other catalyst reported in the literature for the synthesis.

Entry	Catalyst (mol %)	Condition	Time (min)	Yield (%)^a, b	Ref.
1	PTSA (10)	PEG-400	120	88	[26]
2	H2SO4 (20)	EtOH/H2O	300	87	[27]
3	HPA (20)	EtOH/H2O	300	99	[27]
4	[NMP]H2PO4 (20)	Solvent-free	150	81	[27]
5	SiO2–SO3H (20)	Solvent-free	60	86	[28]
6	SiO2–SO3H (20)	Solvent-free (MW)	7	93	[28]
7	H3PW12O40@Fe3O4–ZnO (10)	Solvent-free (MW)	6	97	This work

^a Isolated yields.

^b The reaction was carried out under microwave irradiation (MW) conditions.

Thermal analysis of H₃PW₁₂O₄₀@Fe₃O₄–ZnO nanoparticles is given in Figure 4. According to Figure 4, the TGA curve of naked Fe₃O₄ nanoparticles showed a weight loss of 5.05% from 25 to 900 °C. While the H₃PW₁₂O₄₀@Fe₃O₄–ZnO nanoparticles showed a weight loss of 12.76%. The reason was possible that compared with naked Fe₃O₄ nanoparticles there was the release of hydroxyl ions and decomposition of aminopropyl groups on the H₃PW₁₂O₄₀@Fe₃O₄–ZnO nanoparticles except for water thermo-desorption. It was also confirmed that the Fe₃O₄ nanoparticles were successfully decorated by APTMS. Also, it could be easily concluded that the magnetic content of H₃PW₁₂O₄₀@Fe₃O₄–ZnO nanoparticles was 8.12% less than that of naked Fe₃O₄ nanoparticles.

Figure 4. Thermogravimetric (TG) nano H₃PW₁₂O₄₀@Fe₃O₄–ZnO.

Results and discussion

Structural characterization

The X-ray diffraction pattern for the samples of Fe₃O₄, ZnO, and H₃PW₁₂O₄₀@Fe₃O₄–ZnO is shown in Figure 5. Structural characterization of X-ray diffraction patterns of samples including crystal structure type, spatial band, and cellular parameter calculation was performed by Xpert High Score and Fullprof software. The results show that the best fit is done with the least possible difference. As you can see in Figure 4, the characteristic diffraction peaks for Fe₃O₄ at angles 2θ (30.2, 35.3, 43.4, 53.1, 57.2 and 74.6) corresponding to the plates (220), (311), (400), (400), (511) and (533), respectively. Structural investigations using the Xpert commercial package confirm the formation of a cubic spinel structure with the Fd-3m space group without the presence of the impure phase, which is consistent with the values recorded in standard JCPDS cards number 0206-79. As can be seen, most of the diffraction is from the plate (311).

Figure 5. X-ray diffraction pattern of Fe₃O₄, ZnO, and H₃PW₁₂O₄₀@Fe₃O₄–ZnO samples.

The SEM and TEM images of the Fe₃O₄ and H₃PW₁₂O₄₀@Fe₃O₄–ZnO were shown in Figure 6. Fe₃O₄ nanoparticles have a spherical shape and have a smooth surface without porosity. Magnetite particles also have a very strong tendency to accumulate plasma and form larger particles. Core-shell particles tend to accumulate plasma, which is an expected event. Because the zinc oxide particles, which are located in the outermost part of the core-shell structure, tend to shrink. The diameter of the H₃PW₁₂O₄₀@Fe₃O₄–ZnO core-shell particle varies in the range of 75 to 89 nm.

Figure 6. FESEM and TEM images of Fe₃O₄ (a, c) and H₃PW₁₂O₄₀@Fe₃O₄–ZnO (b, d, e).

A hot filtration test was performed by separating the H₃PW₁₂O₄₀@Fe₃O₄–ZnO catalyst from the reaction mixture after 5 min in the first cycle of reaction. The recovered nanocatalyst was collected and then dried at 100 °C. This may lead to a slight increase of the yield to 59% from 55% after the hot filtration test. Furthermore, disruptions, such as hot filtration, may deactivate an existing active dissolved metal, leading to the incorrect conclusion that there are no active homogeneous catalytic species before the filtration (Figure 7).

Figure 7. Hot filtration test for H₃PW₁₂O₄₀@Fe₃O₄–ZnO catalyzed.

Magnetic Properties of Fe₃O₄, H₃PW₁₂O₄₀@Fe₃O₄–ZnO nano-particles by the vibrating sample magnetometer was examined. Magnetization diagram in terms of the magnetic field applied to each specimen in Figure 8. As you can see in all three samples, there is a very narrow residual loop and a sudden increase in magnetization with a slight increase in field magnetically, thereby having a paramagnetic cloud property. For all three samples, the magnetization in the fields does not reach saturation and still has a slight increase.

Figure 8. VSM curves of Fe₃O₄, Fe₃O₄–ZnO, H₃PW₁₂O₄₀@Fe₃O₄–ZnO.

As can be seen in Figure 9, the slope of the magnetization diagrams at large magnetic fields decreases for the samples of Fe₃O₄, Fe₃O₄/EN-MIL-101 and nano TiO₂-PTA@Fe₃O₄/EN-MIL-101(Cr), respectively, which is another evidence of increasing size. Particles. The values obtained for the forcing field, saturation magnetization, and residual magnetization are reported in Table 4.

Figure 9. Comparison of the slope of the magnetization curve at high fields.

Table 4. Coercion field values, saturation magnetization and residual magnetization.

Sample	Ms (emu/g)	Hc (G)	Mr (emu/g)	Mr/Ms
Fe3O4	62.55	1.07	0.054	0.0008
Fe3O4–ZnO	58.1	3.4	0.199	0.0034
H3PW12O40@Fe3O4–ZnO	28.81	11	0.332	0.0301

To further characterize the H₃PW₁₂O₄₀@Fe₃O₄-ZnO nanocomposite, the AFM analysis was applied. AFM is a beneficial instrument for investigating various structural features and parameters and has the advantage of probing in deep insights of surface topography qualitatively due to its both straight and vertical nanometer-scale spatial resolution. Figure 10 shows an AFM image of the Nano H₃PW₁₂O₄₀@Fe₃O₄-ZnO and its surface morphology. As observed in Figure 10(a), AFM image revealed the presence of sphere-like nanoparticles and their respective particle size and morphology were close to those determined by the SEM images. In Figure 10(b), the surface of the composite showed an approximately uniform structure indicating that the size (height) of the particles on the nanocomposite sheet was 75 nm.

Figure 10. AFM 3D and 2D images of H₃PW₁₂O₄₀@Fe₃O₄–ZnO nanocomposite.

The energy gaps of H₃PW₁₂O₄₀@Fe₃O₄–ZnO sample are shown in Figure 11, respectively. As can be seen, the energy gap of the catalyst nanostructure was 2.33 electron volts, respectively. The reason for the decrease in the bandgap is the increase in particle size, which is consistent with TEM images.

Figure 11. Curve (αhυ)² by hυ for Fe₃O₄–ZnO (left) and H₃PW₁₂O₄₀@Fe₃O₄–ZnO (right) sample.

In photocatalytic activity, by receiving the necessary energy from ultraviolet light, an electron-hole pair is formed in ZnO nanoparticles. The formed cavity reacts with the water present in the medium to produce OH radicals. The OH radical produced attacks on the coloured organic compounds and breaks down their bonds and breaks down the composition into lighter organic compounds. This phenomenon is known as photocatalytic degradation. The electrons produced in ZnO are reduced in the graphene oxide conduction band and from there to the conduction band of Fe₃O₄ nanoparticles. Iron III in Fe₃O₄ structure by electron conversion to iron II and iron II reacts with oxygenated oxygen in the environment, producing ion and OH radicals and again iron III. The created OH radical destroys the organic compound. This phenomenon is called the Fenton process. As the concentration of oxygenated water increases, the rate of production of OH radicals from the Fenton canal increases, and there is an increase in degradation. After a certain concentration, the degradation process will be reduced.

The reason for this is that after a certain concentration with increasing oxygenated water, the OH radicals produced with H₂O₂ present in the environment not yet reacted with Fe II react, and the rate of the Fenton process decreases with the conversion of H₂O₂ to ordinary water (Figure 12). The optimum conditions for the degradation of methylene blue with a concentration of 1.61 g L⁻¹ catalyst and 0.0779 mol L⁻¹ of H₂O₂ was obtained and, under the above conditions, methylene blue was degraded by 97% in 120 min.

Figure 12. Diagram of effect of H₂O₂ concentration on photon fenton methylene blue degradation.

Based on this mechanism, at first, 2-hydroxynaphthalene-1,4-dione 1 tautomerizes to intermediate 6. The primary condensation of 4-hydroxy-1,2-naphthoquinone 6 with benzene-1,2-diamine 2 obtains benzo[a]phenazin-5-ol 3. A reaction pathway involves the formation of an intermediate (II) medium when reacted with the indole group after being added to the carbonyl group or upon the replacement of the side-chain hydroxy group. Based on the second route, arylglyoxal and indole developed the open shaft (III) or the OH group electron pair. This, then forms intermediate III informing the C–C and C-–N bonds through the intermolecular [3 + 2] ring reaction, which is made after reacting with the intermediate middle (I) benzo[a] phenazine-5-ol, caused by the loss of water during the ring formation process before the desired product is obtained (Figure 13).

Figure 13. Proposed mechanism for the synthesis of benzo[a]furo[2, 3-c]phenazine derivatives.

Conclusions

In conclusion, the reaction of 2-hydroxynaphthalene-1,4-dione, arylglyoxal, indoles in the presence H₃PW₁₂O₄₀@Fe₃O₄-ZnO MCNPs afforded benzo[a]furo[2, 3-c]phenazine derivatives in excellent yields. The present procedure has the advantage that the reaction is performed under solvent-free conditions using microwave irradiation and the starting material can be used without any activation or modification. In conclusion, a simple and efficient method for the synthesis of phenazines derivatives has been explored. Mild reaction conditions, shorter reaction time, easy and quick isolation of the products, low power consumption, and excellent yields are the main advantages of this method, which makes it an attractive and useful contribution to the present methodologies. The morphology and particle size were investigated using XRD, FESEM, TEM, AFM and VSM analysis reveals the functional compounds present in the nanoparticles. Photocatalytic degradation results show 97% methylene blue degradation under conditions has the best.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

We gratefully acknowledge financial support from the Research Council of the Islamic Azad University of Yazd.