Rational design and fabrication of g-C₃N₄/CS/MOF-5 nanocomposite as a green, recyclable and efficient catalyst for the rapid synthesis of novel benzo[a]pyrano[2,3-c]phenazine derivatives

Abstract

The efficient synthesis of high-yield organic compounds continues to represent a central challenge in the field of synthetic chemistry. In the present study, a novel nanocomposite (g-C₃N₄/CS/MOF-5) was rationally designed and synthesized to serve as a heterogeneous catalyst. Comprehensive characterization techniques, including SEM, EDS, elemental mapping, TGA, BET, FT-IR and XRD, were employed to elucidate the morphological, structural, compositional, thermal and surface characteristics of the prepared catalyst. The obtained results confirmed the successful preparation and structural integrity of the nanocomposite. Benefiting from the synergistic integration of g-C₃N₄, MOF-5, and chitosan, the catalyst demonstrated exceptional catalytic performance in the synthesis of benzo[a]pyrano[2,3-c]phenazine derivatives via a one-pot, four-component reaction involving thiobarbituric acid, o-phenylenediamine, benzaldehyde derivatives, and 2-hydroxy-1,4-naphthoquinone. The reactions were efficiently carried out in an ethanol–water (1:1) medium at 90 °C, affording the desired products in high yields (77–96%) within relatively short reaction times (30–120 min). Notably, the catalyst exhibited high surface area (15.84 m².g^-1) and excellent reusability, maintaining its catalytic activity over six consecutive cycles without appreciable loss in performance (96–89%).

Supplementary Information

The online version contains supplementary material available at 10.1038/s41598-025-32332-z.

Introduction

Green chemistry represents a progressive and human-centered approach aimed at developing chemical processes and materials which provide the environmental and human safety. It emphasizes designing reactions whit maximum efficiency and yield and minimize the formation and release of hazardous substances^1–3. By advocating the use of renewable resources, eco-friendly raw materials, efficient catalysts, and mild reaction conditions, green chemistry reduces energy consumption and waste generation. This approach, fosters sustainable chemical production and supports the development of environmentally responsible technologies, offering valuable opportunities for scientific and industrial advancement^4,5.

Multicomponent reactions (MCRs), first introduced with the Strecker synthesis in 1850, have long been recognized as efficient, green and environmentally friendly methods for constructing organic molecules^5,6. In recent years, various advancements, including the use of nanostructured and recyclable catalysts, have significantly improved the efficiency, selectivity, and sustainability of MCRs. These developments have established MCRs as essential tools in drug discovery, heterocyclic compound synthesis, combinatorial chemistry, and green processes by enhancing atom economy and reducing energy consumption^7–11.

Benzopyrano-phenazines are tricyclic nitrogen-containing heterocycles formed by the fusion of benzopyran and phenazine moieties, representing a significant class in medicinal chemistry. Their synthesis typically involves multistep reactions between 2-hydroxy-1,4-naphthoquinone and ortho-phenylenediamine, yielding fused phenalazine and benzopyran frameworks. These methods enable the creation of diverse derivatives that possess improved physicochemical and biological properties^12,13. Notably, benzopyrano-phenazines demonstrate potent antimicrobial, anticancer, and antioxidant activities by inhibiting enzymes, inducing oxidative stress, and modulating cellular signaling pathways (Scheme 1). Their unique tricyclic structure and nitrogen content facilitate strong interactions with DNA and proteins, underscoring their potential as anticancer agents^14–18.

Scheme 1.

Phenazine-based molecules with pharmacological effects.

Catalysts are required to accelerate chemical reactions, contributing significantly to industrial efficiency and environmental sustainability¹⁹. Heterogeneous catalysts are valuable for their ease of separation, stability, and recyclability, find broad applications in chemical synthesis and environmental processes^20–23.

Chitosan, a natural polymer derived from chitin, has gained prominence in heterogeneous catalysis due to its high chemical modifiability and abundant active amino groups. Its high surface area and mechanical strength, make it an excellent scaffold for preparation of advanced nanocomposites with notable efficacy in organic transformations and pollutant removal^24–26. Functionalization with various groups such as metal organic frameworks (MOFs), sulfonic, carboxylic, and amide moieties enhances its catalytic activity, selectivity, and stability, broadening its relevance, particularly in environmental and synthetic applications. These capabilities reinforce the role of chitosan as an effective and eco-friendly support in catalytic applications^25,27,28.

Graphitic carbon nitride (g-C₃N₄) is a two-dimensional layered semiconductor composed of triazine and heptazine units. Due to the strong covalent bonds between carbon and nitrogen atoms, it exhibits remarkable thermal and chemical stability^29,30. This nitrogen-rich framework, with its modifiable surface, provides an effective platform for a wide range of applications, including heterogeneous catalysis, nanocomposite design, and pollutant removal^31,32. It is typically synthesized via pyrolysis of simple nitrogen-containing precursors at temperatures ranging from 500 to 600 °C³³. Characteristics such as its porous structure, high surface activity, and environmental compatibility, make g-C₃N₄ a cost-effective and multifunctional material for emerging technologies³⁴.

Metal–organic frameworks (MOFs) are a class of nanoporous crystalline materials composed of metal ions or clusters coordinated to organic ligands. Owing to their high surface area, uniform porosity and tunable chemical functionality, MOFs have found widespread applications in areas such as gas storage, catalysis, drug delivery, and sensing^35–39. Among the well-known members of this family is MOF-5 (also known as IRMOF-1), which is constructed from Zn (II) ions and benzene-1,4-dicarboxylate (BDC) ligand. MOF-5 features a three-dimensional structure with well-defined cavities and a high specific surface area⁴⁰. Its ability to undergo functionalization, post-synthetic modification, and incorporation with nanoparticles or polymers makes it a promising candidate for the design of nanocomposites and catalytic systems. The effectiveness of MOF-5 in heterogeneous catalysis is attributed to the accessibility of active metal sites, its porous architecture facilitating molecular transport, and the potential for surface engineering to enhance catalytic activity and selectivity^41–43. Although recently g-C₃N₄-MOF or MOF-biopolymer composites were used as catalyst in chemical reactions^28,32,44,45, herein, we design a new composite with synergistic effect of g-C₃N₄, chitosan and MOF for catalyzing the synthesis of benzo[a]pyrano-[2,3-c]phenazines under green conditions (Scheme 2). The reactions were carried out under mild conditions, in water–ethanol (1:1) media at 90 °C and 0.015 g of the catalyst, yielding the desired products with high efficiency and short reaction times.

Scheme 2.

Synthesis of benzo[a]pyrano-[2,3-c]phenazine derivatives catalyzed by g-C₃N₄/CS/MOF-5.

Experimental section

Chemicals and instrumentation

Reagents and solvents were purchased from Merck, Aldrich and Fluka companies. The progression of the reaction was monitored by periodically analyzing using thin-layer chromatography (TLC) on silica gel plates (Silica sheets FG₂₄₅), enabling observation of reactant consumption and product formation under UV light. Melting points were determined using a Scientific Thermo MK3IA 9300 (England) apparatus, with phase transitions visually observed under controlled manual conditions. The catalyst and synthesized products were comprehensively characterized by FT-IR spectroscopy using a Magna 550 (Nicolet) spectrometer. Structural characterization was conducted using a Bruker Avance DRX NMR spectrometer operating at 400 MHz for ¹H and 100 MHz for ¹³C nuclei, with spectra acquired in deuterated DMSO. Chemical shifts (δ) were referenced to tetramethylsilane (TMS) as the internal standard and coupling constants (J) were reported in Hertz. X-ray diffraction (XRD) patterns of the samples were systematically acquired using a Bruker D8 Advance diffractometer operating at 40 kV and 40 mA, with Cu Kα radiation (λ = 0.154 nm) as the X-ray source. The morphology, composition and elemental dispersion in g-C₃N₄/CS/MOF-5 were comprehensively investigated using field emission scanning electron microscopy (FE-SEM) on a TESCAN MIRA3 instrument. Specific surface area and pore characteristics were determined by nitrogen adsorption–desorption at 77 K using a Micromeritics ASAP 2020 BET analyzer. Thermogravimetric analysis (TGA) was recorded in air with heating rate of 10 °C/min using a METLER-810 instrument.

Preparation of catalyst

Preparation of g-C₃N₄ nanosheets

In the initial stage, melamine powder (3 g) was subjected to an annealing process at 500 °C for 4 h, resulting in the formation of g-C₃N₄ structure as yellow color. To prepare g-C₃N₄ nanosheets, a significant portion of the powder obtained from this step was sonicated in ethanol for 2 h. Finally, the synthesized nanostructures were separated by centrifugation and dried at 100 °C for 5 h.

Preparation of CS/MOF-5 composite

To prepare the CS/MOF-5 hybrid structure, 1.95 g (7.5 mmol) of Zinc nitrate tetrahydrate (Zn(NO₃)₂0.4H₂O) was dissolved in 20 mL of DMF to form a clear solution. Simultaneously, 1.62 g of terephthalic acid (TPA) was dissolved in 25 mL of DMF in a separate vessel. Two prepared solutions were then combined and vigorously stirred using a magnetic stirrer for 15 min to achieve homogenous solution. In the subsequent step of the process, 0.70 g of chitosan (CS) was dispersed in 20 mL of DMF using ultrasonication to yield a fully homogeneous suspension. Thereafter, the MOF-5 precursor solution was gradually added to the chitosan suspension, followed by an additional 20 min of ultrasonication to enhance the initial interactions between the MOF components and the polymer matrix. The resulting reaction mixture was transferred into a Teflon-lined autoclave and subjected to hydrothermal treatment at 120 °C for 12 h, facilitating the complete formation of the MOF-5 structure within the chitosan frameworks. Upon completion, the solid precipitate was washed three times with 10 mL portions of DMF, followed by three additional washes with dichloromethane to eliminate the residual solvents and reactants. Finally, the product was dried at 100 °C for 5 h, yielding the CS/MOF-5 hybrid structure.

Preparation of g-C₃N₄/CS/MOF-5

To functionalize the g-C₃N₄ nanosheets with the CS/MOF-5 nanocomposite, initially, 0.3 g of g-C₃N₄ were dispersed in a mixture of 3.2 mL of epichlorohydrin (ECH) and 6 mL of ethanol and stirred at 60 °C for 8 h to chemically attachment of ECH to the surfaces of g-C₃N₄ nanosheets. After the time, 0.6 g of the CS/MOF-5 nanocomposite was added to the suspension and the resulting mixture was stirred at 60 °C for 24 h. Subsequently, the suspension was gradually cooled to room temperature and then centrifuged. The obtained precipitate was washed with deionized water and ethanol and finally, dried in an oven at 60 °C for 24 h.

General procedure for the preparation of benzo[a]pyrano-[2,3-c]phenazine derivatives

To synthesize benzo[a]pyrano-[2,3-c]phenazine derivatives, a mixture comprising 3 mL of H₂O/EtOH (1:1) was prepared. Subsequently, 1 mmol (0.11 g) of ortho-phenylenediamine and 1 mmol (0.18 g) of 2-hydroxy-1,4-naphthoquinone were added to the mixture. The solution was stirred continuously at 90 °C for about 5 min to produce the 6H-benzo[a]phenazin-5-one intermediate, which was confirmed within thin-layer chromatography (TLC). In the subsequent step, 1 mmol (0.144 g) of thiobarbituric acid, 1 mmol of benzaldehyde derivatives, and 0.015 g of the g-C₃N₄/CS/MOF-5 were introduced into the reaction mixture. The reaction was maintained at 90 °C with constant stirring for a specified duration, with progress monitoring periodically via TLC. Upon completion, the catalyst was separated from the reaction mixture through simple filtration. Thereafter, the resulting solution was subjected to liquid–liquid extraction with ethyl acetate to isolate the product. The organic phase was dried and the solvent was evaporated to yield the crude product. Finally, to achieve high purity, the crude product was purified through recrystallization from ethanol.

Spectral data

16-(4-chlorophenyl)-3-thioxo-2,3,4,10,15,16-hexahydro-1H-benzo[a]pyrimido[5',4':5,6]pyrano[2,3-c]phenazin-1-one (5a)

M.P.: 290–293 °C; FT-IR (KBr) ῡ (cm⁻¹): 3349 (NH, stretch), 2924 (C–H sp², stretch), 1635 (C = O), 1611, 1583 (C = C aromatic), 1511 (NH, bending), 1124 (C–O), 1008 (C = S), 767 (C–Cl); ¹H NMR (400 MHz, DMSO, d₆) δ (ppm): 12.33 (s, 2H), 9.10 (d, J = 8.0 Hz, 1H), 8.34 (d, J = 8.0 Hz, 1H), 8.28 (t, J = 8.0 Hz, 1H), 7.99–7.86 (m, 6H), 7.29–7.18 (m, 5H), 6.48 (s, 1H); ¹³C NMR (100 MHz, DMSO, d₆) δ (ppm): 170.6, 166.4, 150.6, 148.6, 146.6, 134.5, 134.1, 131.3, 130.9, 130.1, 129.9, 127.9, 127.6, 125.7, 124.2, 116.0, 113.9, 111.5, 32.6.

16-(4-nitrophenyl)-3-thioxo-2,3,4,10,15,16-hexahydro-1H-benzo[a]pyrimido[5',4':5,6]pyrano[2,3-c]phenazin-1-one (5b)

M.P.: 250–252 °C; FT-IR (KBr) ῡ (cm⁻¹) = 3354 (NH, stretch), 3028 (C–H sp², stretch), 1650 (C = O), 1614, 1585 (C = C aromatic), 1519 (NH, bending), 1445 (NO₂ asymmetrical stretch), 1346 (NO₂ symmetrical stretch), 1238 (C–O), 1201 (C = S); ¹H NMR (400 MHz, DMSO, d₆) δ (ppm): 12.20 (s, 2H), 9.16 (d, J = 8.0 Hz, 1H), 8.36 (d, J = 8.0 Hz, 1H), 8.30 (d, J = 8.0 Hz, 1H), 8.10 (d, J = 8.0 Hz, 2.0H), 8.00–7.86 (m, 7H), 7.47 (d, J = 8.0 Hz, 2H), 6.79 (s, 1H); ¹³C NMR (100 MHz, DMSO, d₆) δ (ppm): 166.8, 166.7, 150.9, 148.9, 147.0, 134.9, 134.6, 131.3, 130.5, 130.3, 130.0, 128.3, 128.0, 126.1, 124.6, 116.4, 114.3, 111.9, 33.0.

16-(4-bromophenyl)-3-thioxo-2,3,4,10,15,16-hexahydro-1H-benzo[a]pyrimido[5',4':5,6]pyrano[2,3-c]phenazin-1-one (5c)

M.P.: 285–287 °C; FT-IR (KBr) ῡ (cm⁻¹): 3348 (NH, stretch), 2921 (C–H sp², stretch), 1623 (C = O), 1600, 1590 (C = C aromatic), 1442 (NH, bending), 1122 (C–O), 1006 (C = S), 604 (C–Br); ¹H NMR (400 MHz, DMSO, d₆) δ (ppm): 12.35 (s, 2H), 9.08 (d, J = 8.0 Hz, 1H), 8.33 (d, J = 8.0 Hz, 1H), 8.30–8.25 (m, 1H), 7.98–7.79 (m, 7H), 7.41 (d, J = 8.0 Hz, 2H), 7.16 (t, J = 8.0 Hz, 2H), 6.45 (s, 1H); ¹³C NMR (100 MHz, DMSO, d₆) δ (ppm): 168.5, 167.1, 150.1, 149.6, 148.4, 146.6, 144.9, 139.1, 133.5, 130.9, 128.9, 127.4, 126.3, 124.1, 123.3, 116.0, 114.2, 111.6, 32.7.

16-(4-hydroxyphenyl)-3-thioxo-2,3,4,10,15,16-hexahydro-1H-benzo[a]pyrimido[5',4':5,6]pyrano[2,3-c]phenazin-1-one (5d)

M.P.: 280–282 °C; FT-IR (KBr) ῡ (cm⁻¹): 3169 (NH, stretch), 3062 (C–H sp², stretch), 1644 (C = O), 1600, 1594 (C = C aromatic), 1500 (NH, bending), 1403 (OH, bending), 1215 (C–O), 1141 (C = S); ¹H NMR (400 MHz, DMSO, d₆) δ (ppm): 12.36 (s, 1H), 12.26 (s, 1H), 10.98 (s, 1H), 9.27 (s, 1H), 8.39 (d, J = 8.0 Hz, 2H), 8.34–8.28 (m, 2H), 8.23 (s, 1H), 8.15 (d, J = 8.0 Hz, 1H), 8.02–7.83 (m, 5H), 7.19 (s, 1H), 6.90 (d, J = 8.0 Hz, 2H); ¹³C NMR (100 MHz, DMSO, d₆) δ (ppm): 166.8, 166.2, 150.3, 148.2, 146.8, 144.2, 138.9, 134.2, 133.5, 130.6, 130.0, 124.2, 122.7, 122.2, 121.3, 116.0, 113.9, 111.6, 32.6.

16-(4-(dimethylamino)phenyl)-3-thioxo-2,3,4,10,15,16-hexahydro-1H-benzo[a]pyrimido[5',4':5,6]pyrano[2,3-c]phenazin-1-one (5e)

M.P.: 268–270°C; FT-IR (KBr) ῡ (cm⁻¹): 3061 (NH, stretch), 2909 (C–H sp², stretch), 2806 (C–H sp³, stretch), 1664 (C = O), 1648, 1595 (C = C aromatic), 1508 (NH, bending), 1204 (C–O), 1193 (C = S); ¹H NMR (400 MHz, DMSO, d₆) δ (ppm):12.14 (s, 1H), 12.04 (s, 1H), 9.27 (s, 1H), 8.47 (d, J = 12.0 Hz, 2H), 8.34–8.28 (m, 2H), 8.15 (d, J = 8.0 Hz, 2H), 7.93–7-83 (m, 5H), 7.19 (s, 1H), 6.82 (d, J = 12.0 Hz, 2H), 3.16 (s, 6H, 2NCH₃); ¹³C NMR (100 MHz, DMSO, d₆) δ (ppm): 166.6, 166.1, 151.1, 150.5, 148.5, 147.9, 146.9, 144.0, 140.6, 131.1, 128.7, 125.7, 124.8, 124.2, 124.1, 116.0, 113.8, 111.6, 48.3, 32.5.

16-(4-methoxyphenyl)-3-thioxo-2,3,4,10,15,16-hexahydro-1H-benzo[a]pyrimido[5',4':5,6]pyrano[2,3-c]phenazin-1-one (5f)

M.P.: 260–262 °C; FT-IR (KBr) ῡ (cm⁻¹): 3060 (C–H sp², stretch), 2905 (C–H sp³, stretch), 1694 (C = O), 1651, 1591 (C = C aromatic), 1528 (NH, bending), 1212 (C–O), 1000 (C = S); ¹H NMR (400 MHz, DMSO, d₆) δ (ppm): 12.43 (s, 1H), 11.59 (s, 1H), 9.08 (s, 1H), 8.35–8.26 (m, 3H), 7.93–7.86 (m, 4H), 7.14–7.06 (m, 3H), 6.89–6.72 (m, 3H), 6.32 (s, 1H), 3.69 (s, 3H); ¹³C NMR (100 MHz, DMSO, d₆) δ (ppm): 169.9, 166.1, 150.4, 148.5, 146.9, 135.8, 134.3, 133.2, 131.3, 130.3, 129.5, 128.9, 125.8, 125.3, 124.2, 116.0, 113.8, 111.6, 56.1, 32.5.

16-(2,5-dimethoxyphenyl)-3-thioxo-2,3,4,10,15,16-hexahydro-1H-benzo[a]pyrimido[5',4':5,6]pyrano[2,3-c]phenazin-1-one (5g)

M.P.: 286–288 °C; FT-IR (KBr) ῡ (cm⁻¹): 3066 (NH, stretch), 2923 (C–H sp², stretch), 2834 (C–H sp³, stretch), 1625 (C = O), 1599, 1534 (C = C aromatic), 1415 (NH, bending), 1230 (C–O), 1028 (C = S); ¹H NMR (400 MHz, DMSO, d₆) δ (ppm) = 12.37 (s, 1H), 11.52 (s, 1H), 9.09 (s, 1H), 7.69 (d, J = 8.0 Hz, 2H), 7.45 (d, J = 4.0 Hz, 1H), 7.23 – 7.08 (m, 5H), 6.95 (d, J = 8.0 Hz, 2H), 6.85 (d, J = 8.0 Hz, 2H), 6.52 (s, 1H), 3.84 (s, 3H), 3.69 (s, 3H); ¹³C NMR (100 MHz, DMSO, d₆) δ (ppm): 171.2, 167.3, 149.0, 146.8, 145.9, 141.0, 135.9, 133.5, 132.3, 129.5, 128.9, 128.8, 128.4, 124.6, 124.0, 116.3, 112.6, 111.4, 56.1, 32.7.

16-(3-nitrophenyl)-3-thioxo-2,3,4,10,15,16-hexahydro-1H-benzo[a]pyrimido[5',4':5,6]pyrano[2,3-c]phenazin-1-one (5h)

M.P.: 266–268 °C; FT-IR (KBr) ῡ (cm⁻¹): 3370 (NH, stretch), 3075 (C–H sp², stretch), 1618 (C = O), 1595, 1538 (C = C aromatic), 1500 (NH, bending), 1442 (NO₂ asymmetrical stretch), 1344 (NO₂ symmetrical stretch), 1168 (C–O), 1117 (C = S); ¹H NMR (400 MHz, DMSO, d₆) δ (ppm): 12.11 (s, 1H), 11.24 (s, 1H), 8.21–8.18 (m, 1H), 7.76–7.73 (m, 3H), 7.65–7.60 (m, 3H), 7.51–7.49 (m, 1H), 7.37–7.34 (m, 1H), 7.30–7.27 (m, 3H), 7.01 (d, J = 8.0 Hz, 2H), 6.60 (s, 1H); ¹³C NMR (100 MHz, DMSO, d₆) δ (ppm): 169.9, 166.7, 158.2, 157.9, 150.6, 149.4, 148.9, 148.7, 146.7, 138.4, 130.1, 129.6, 123.0, 118.8, 118.1, 116.4, 115.1, 114.4, 33.2.

16-(3-bromophenyl)-3-thioxo-2,3,4,10,15,16-hexahydro-1H-benzo[a]pyrimido[5',4':5,6]pyrano[2,3-c]phenazin-1-one (5i)

M.P.: 248–250 °C; FT-IR (KBr) ῡ (cm⁻¹): 3359 (NH, stretch), 3072 (C–H sp², stretch), 1673 (C = O), 1648, 1563 (C = C aromatic), 1435 (NH, bending), 1342 (C–O), 1171 (C = S), 604 (C–Br); ¹H NMR (400 MHz, DMSO, d₆) δ (ppm): 12.30 (s, 1H), 9.12 (s, 1H), 8.35 (d, J = 8.0 Hz, 1H), 8.28 (d, J = 8.0 Hz, 1H), 8.13–7.83 (m, 7H), 7.70 (dd, J = 20.0, 8.0 Hz, 1H), 7.37 (s, 2H), 7.20 (s, 2H), 6.56 (s, 1H); ¹³C NMR (100 MHz, DMSO, d₆) δ (ppm): 167.9, 167.3, 151.4, 149.6, 149.3, 140.0, 135.3, 134.6, 131.7, 127.0, 125.3, 125.0, 123.9, 123.3, 122.4, 117.1, 115.1, 112.7, 33.8.

16-(3,4-dimethoxyphenyl)-3-thioxo-2,3,4,10,15,16-hexahydro-1H-benzo[a]pyrimido[5',4':5,6]pyrano[2,3-c]phenazin-1-one (5j)

M.P.: 285–287 °C; FT-IR (KBr) ῡ (cm⁻¹): 3488 (NH, stretch), 3000 (C–H sp², stretch), 2853 (C–H sp³, stretch), 1620 (C = O), 1594, 1514 (C = C aromatic), 1444 (NH, bending), 1345 (C–O), 1197 (C = S); ¹H NMR (400 MHz, DMSO, d₆) δ (ppm): 12.06 (s, 1H), 11.69 (s, 1H), 9.40 (s, 1H), 9.05 (s, 1H), 7.68 (d, J = 8.0 Hz, 1H), 7.37 (d, J = 8.0 Hz, 1H), 7.20 (ddd, J = 8.0, 7.1, 3.6 Hz, 3H), 7.13 (dd, J = 8.0, 2.1 Hz, 1H), 7.05 (d, J = 8.0 Hz, 1H), 6.84 (d, J = 8.0 Hz, 2H), 6.45 (t, J = 8.0 Hz, 2H), 6.19 (s, 1H), 3.83 (s, 3H), 3.71 (s, 3H); ¹³C NMR (100 MHz, DMSO, d₆) δ (ppm): 168.9, 167.4, 150.5, 149.9, 148.8, 147.0, 145.3, 139.5, 133.8, 131.2, 129.3, 126.6, 124.5, 123.7, 116.6, 116.4, 114.6, 111.9, 56.5, 33.1.

Results and discussion

Following the synthesis of the g-C₃N₄/CS/MOF-5 nanocomposite (Scheme 3), its structural and functional properties were investigated using an array of advanced analytical techniques including FE-SEM, XRD, EDS, BET-BJH, TGA and FT-IR. Subsequently, the optimization of reaction conditions for the synthesis of benzo[a]pyrano[2,3-c]phenazine derivatives in the presence of this catalyst was meticulously studied. Furthermore, catalyst recovery was comprehensively evaluated to assess its reusability potential.

Scheme 3.

Preparation steps of g-C₃N₄/CS/MOF-5.

Characterization of catalyst

Figure 1 presents the FT-IR spectra of g-C₃N₄ nanosheets (a), chitosan (b), CS/MOF-5 composite (c) and g-C₃N₄/CS/MOF-5 composite (d). In spectrum (a), the absorption bands observed in the range of 1241–1638 cm⁻¹ are attributed to the stretching vibrations of C-N and C = N bonds, confirming the heterocyclic structure and triazine rings arrangement in g-C₃N₄. The characteristic absorption band at 806 cm⁻¹ is correspond to triazine units in graphitic frameworks. The broad absorption band around 3190 cm⁻¹ is assigned to the N–H stretching vibration. Spectrum (b), related to chitosan, displays a broad band around 3437 cm⁻¹, from the stretching vibrations of N–H and O–H groups. The absorption bands at 2920 and 1381 cm⁻¹ are associated with the stretching vibrations of C–H bonds. The presence of N-acetyl groups is confirmed by the absorption bands at 1649 cm⁻¹ and 1424 cm⁻¹. Additionally, the absorption band at 1093 cm⁻¹ corresponds to C–O stretching, indicating the polysaccharide structure of chitosan. In spectrum (c) of the CS/MOF-5 composite, in addition to the characteristic bands of chitosan, absorption bands at 1600 and 1668 cm⁻¹ are assigned to the stretching vibrations of carboxylate (COO⁻) groups from the terephthalic acid ligand. The peak at 738 cm⁻¹ proves that the benzene rings are 1,4-substituted. Moreover, the absorption band at 532 cm⁻¹ corresponds to the Zn–O tensile vibration in the Zn₄O cluster of MOF-5 into the composite. Spectrum (d), corresponding to the g-C₃N₄/CS/MOF-5 nanocomposite, contains all the characteristic absorption bands of g-C₃N₄, chitosan, and MOF-5, verifying the successful integration and effective structural synergy among the three constituents in the final composite^46,47.

Fig. 1.

FT-IR spectra of g-C₃N₄ nanosheets (a), Chitosan (CS) (b), CS/MOF-5 composite (c) and g-C₃N₄/CS/MOF-5 composite (d).

Figure 2 presents the XRD patterns of g-C₃N₄ nanosheets (a), Chitosan (b), CS/MOF-5 composite (c) and g-C₃N₄/CS/MOF-5 (d). In Fig. 2a, two distinct diffraction peaks are observed at 2θ ≈ 13.2° and 27.3°, corresponding to the (100) and (002) crystal planes, respectively. These peaks indicate the in-plane ordering of tri-s-triazine units and the interlayer π–π stacking in the graphitic structure (according to JCPDS card No. 87–1526). In Fig. 2b, the XRD pattern of chitosan (CS) shows a relatively broad and sharp peak at around 2θ ≈ 20°, which is indicative of its amorphous nature. This broad peak arises from short-range order and the lack of long-range crystalline structure in this natural polymer. In Fig. 2c, distinct peaks appear at 2θ ≈ 8.4°, 10.6°, 13.7°, 16.9°, 21.1°, and 25.2°, which are in good agreement with the crystalline structure of MOF-5 (based on JCPDS card No. 50–0667). However, compared to pure MOF-5, a slight reduction in the intensity of some peaks is observed, which is attributed to the presence of chitosan and its physical or chemical interactions with the MOF-5 crystalline framework. In Fig. 2d, the characteristic peaks of g-C₃N₄, MOF-5, and chitosan are distinguishable, indicating the successful integration of all three components (g-C₃N₄, chitosan, and MOF-5) and the relative preservation of the crystalline structure in the final composite. Furthermore, the slight decrease in peak intensities and the distortion of certain peaks, compared to the pure materials, suggest interactions among the components and the formation of a stable composite structure⁴⁶. Overall, the XRD results in Fig. 2 confirm that the ternary composite has been successfully synthesized and that favorable structural interactions have been established among g-C₃N₄, chitosan, and MOF-5.

Fig. 2.

XRD pattern of g-C₃N₄ nanosheets (a), Chitosan (CS) (b), CS/MOF-5 composite (c), g-C₃N₄/CS/MOF-5 (d).

Scanning Electron Microscopy (SEM) images were prepared to investigate the morphology of four samples, including g-C₃N₄, CS, CS/MOF-5, and g-C₃N₄/CS/MOF-5 (Fig. 3). In the case of g-C₃N₄, Figs. 3a and b display thin and sheet-like structures, indicating the layered nature of this material. The smooth and continuous surfaces, without prominent roughness, confirm the formation of a planar structure with a graphitic arrangement. In the chitosan sample (Figs. 3c and d), an amorphous and uneven surface is observed. Figure 3c reveals an irregular texture with shallow surface depressions. Figure 3d also indicates the presence of clustered and semi-spherical particles, likely formed due to the aggregation of polymer chains or the formation of micro-particles in solution. In the CS/MOF-5 sample (Figs. 3e and f), the presence of well-defined crystals with polyhedral shapes and distinct boundaries is noticeable. These crystals are well distributed within the chitosan matrix, indicating the successful formation of crystalline structures within the amorphous polymeric background. Finally, Fig. 3g and h related to the g-C₃N₄/CS/MOF-5 nanocomposite exhibit a complex and multiphase structure. In Fig. 3g, bulk agglomerations are observed, lacking clear boundaries between phases, suggesting the integration of the components. Figure 3h also reveals dispersed particles with a relatively spherical morphology, indicating the distribution of MOF-5 within the layered-polymeric matrix of the composite.

Fig. 3.

FE-SEM images of g-C₃N₄ (a, b), chitosan (CS) (c, d), CS/MOF-5 (e, f), and g-C₃N₄/CS/MOF-5 (g, h).

In this study, Energy Dispersive X-ray Spectroscopy (EDS) analysis was employed as a precise and efficient method for qualitative and quantitative identification of the elemental composition in g-C₃N₄ and the novel g-C₃N₄/CS/MOF-5 nanocomposite. The results presented in Fig. 4, clearly confirm the accuracy of the synthesis and the purity of samples, as well as demonstrate the successful structural design of the advanced composite. In the EDS analysis of the pure g-C₃N₄ sample (Fig. 4a), the weight percentages of Carbon (33.75%) and Nitrogen (66.25%) are fully consistent with the structure of the material. In the EDS analysis of the g-C₃N₄/CS/MOF composite (Fig. 4b), Carbon (30.45%), Nitrogen (14.32%), Oxygen (49.75%) and Zinc (5.48%) were detected. The presence of Zinc signifies the successful deposition of the MOF-5 in catalyst structure. Overall, the presented EDS analysis, with remarkable accuracy and comprehensiveness, verifies the optimal integration of g-C₃N₄ and chitosan/MOF-5 components within the final composite structure and confirms the success of the synthesis strategy and structural design of this novel system.

Fig. 4.

EDS spectra of g-C₃N₄ (a), and the g-C₃N₄/CS/MOF-5 composite (b).

The elemental mapping results for the g-C₃N₄/CS/MOF-5 composite is presented in Fig. 5. The obtained results demonstrate the uniform distribution of C, N, O, and Zn elements in catalyst structure. Elemental mapping images confirm the presence and successful incorporation of chitosan/MOF-5 in the final composite structure. Furthermore, the homogeneity in the distribution of elements confirms the formation of a well-mixed and multicomponent composite structure.

Fig. 5.

Elemental mapping images of the g-C₃N₄/CS/MOF composite.

In order to evaluate the thermal stability of g-C₃N₄/CS/MOF-5, Chitosan (CS), MOF-5, and g- C₃N₄, the TGA analysis was used. As shown in Fig. 6, The TGA curve of g-C₃N₄ exhibits a good stability to about 700 ºC. A weight loss about 90% at 700–790 ºC demonstrate the decomposition of g-C₃N₄ nanosheets. The TGA graph of CS show a low weight loss below 180 ºC due to removal of adsorbed water or remained solvents through CS structure also, a 75% weigh loss is occurred between 310 and 600 ºC from decomposition of chitosan’s polysaccharide chains. In MOF-5 TGA curve, a weight loss about 7% below 200 ºC attributed to the removal of physically adsorbed solvent molecules within the porous structure and a 40% weight loss at 450–510 ºC is mainly due to the thermal decomposition of organic groups of MOF-5. TGA graph of g-C₃N₄/CS/MOF-5 show three distinct weight loss stages. In the first stage (310–450 °C), approximately 10% weight loss occurs, which corresponds to the thermal decomposition of chitosan attached on g-C₃N₄ chains. The second stage (450–510 °C) involves a 20% weight loss, associated with the collapse of the MOF-5 frameworks. At third step, degradation of g-C₃N₄ (40%) is occurred at 700–790 ºC.

Fig. 6.

TGA analysis diagram of g-C₃N₄, MOF-5, Chitosan (CS) and g-C₃N₄/CS/MOF-5 catalyst.

According to the surface characterization results illustrated in Fig. 7a–d, the textural properties of g-C₃N₄ and g-C₃N₄/CS/MOF-5 were examined using BET and BJH analyses. The obtained results were collected in Table 1. As can be seen in Table 1, the specific surface area, total pore volume and the average pore diameter of catalyst were enhanced when g-C₃N₄ was modified with CS/MOF-5 due to porous structure of CS/MOF-5. Also, the nitrogen adsorption–desorption isotherm exhibits a type IV profile, which is indicative of a mesoporous structure for both g-C₃N₄ and g-C₃N₄/CS/MOF-5. Furthermore, the hysteresis loop observed corresponds to type H3, suggesting the presence of wedge-shaped pores that are typically associated with slit-like or aggregated particle morphologies. These characteristics collectively confirm the mesostructured and open porous nature of the synthesized nanomaterials.

Fig. 7.

The N₂ adsorption–desorption (ADE & DES) isotherms and Pore Size distribution of g-C₃N₄ (a, b) and g-C₃N₄/CS/MOF-5 (c, d).

Table 1.

BET analysis results for g-C₃N₄ and g-C₃N₄/CS/MOF-5.

Material	Specific surface area (m2.g-1)	Average pore diameter (nm)	Total pore volume (cm3.g-1)
g-C₃N₄	6.32	18.52	0.0536
g-C₃N₄/CS/MOF-5	15.84	22.719	0.093

Optimization of reaction conditions

To enhance the reaction yield and reduce the synthesis time of target products, a comprehensive optimization of key parameters including solvent type, catalyst amount, and reaction temperature was performed using 1 mmol of each primary reactant for the synthesis of 4b, as model reaction (Table 2). This process aimed to precisely assess the influence of each parameter on both the efficiency and rate of the reaction. In the initial step, the solvent type was investigated as a critical factor affecting the reaction’s progression. The results revealed that a mixture of H₂O:EtOH (1:1) exhibited superior performance compared to other solvents (Table 2, Entry 5). In contrast, the use of solvents such as CHCl₃, CH₃CN, H₂O, and EtOH led to lower yields and longer reaction times (Table 2, Entries 1–4). The superior performance of the EtOH/H₂O mixture can be attributed to its optimal balance of polarity and solvation capacity, which facilitates improved solubility of the reactants and enhances mass transfer within the reaction system. Following the identification of the optimal solvent, the effect of the catalyst amount was examined. The absence of catalyst resulted in a markedly slower reaction rate and negligible yield (Table 2, Entry 6). The highest yield was achieved with 0.015 g of the g-C₃N₄/CS/MOF-5 catalyst (Table 2, Entry 5). Lower catalyst amounts, such as 0.005 g (Entry 7) and 0.01 g (Entry 8), led to reduced yields. Additionally, increasing the catalyst amount to 0.02 g (Entry 9) did not result in any significant improvement in reaction performance. Finally, reaction temperature was optimized as the third influential parameter. The results showed that the temperature of 90 °C yielded the highest product efficiency (96%) within the shortest reaction time (30 min) (Table 2, Entry 5). At lower temperatures namely, room temperature, 50 °C, and 80 °C (Entries 10–12), the reaction exhibited reduced efficiency and longer durations. Based on these findings, it can be concluded that the optimal conditions were EtOH/H₂O (1:1) as solvent, 0.015 g of the g-C₃N₄/CS/MOF catalyst under temperature of 90 °C.

Table 2.

Optimization of reaction parameters for the synthesis of Benzo[a]pyrano[2,3-c]phenazine derivatives^a.

Entry	Solvent	Catalyst (g)	Temp. (°C)	Time (min)	Yieldb (%)
1	CHCl3	0.015	Reflux	200	80
2	CH3CN	0.015	Reflux	50	90
3	H2O	0.015	Reflux	120	78
4	EtOH	0.015	Reflux	40	94
5	EtOH/H2Oc	0.015	90	30	96
6	EtOH/H2O	–	90	30	–
7	EtOH/H2O	0.005	90	30	32
8	EtOH/H2O	0.01	90	30	71
9	EtOH/H2O	0.02	90	30	96
10	EtOH/H2O	0.015	r.t	30	15
11	EtOH/H2O	0.015	50	30	45
12	EtOH/H2O	0.015	80	30	88

^a Reaction conditions: Thiobarbituric acid (1 mmol), o-phenylenediamine (1 mmol), 4-nitrobenzaldehyde (1 mmol), 2-hydroxy-1,4-naphthoquinone (1 mmol), solvent (3 mL), under thermal condition.

^b Product yield obtained after purification.

^c volume ratio: (1:1).

To assess the generalizability of this method, a diverse array of benzaldehydes bearing electron-withdrawing and electron-donating substituents was evaluated under optimized reaction conditions. The resulting data, presented in Table 3, indicate substantial yields with no detectable by-products. Notably, compounds derived from benzaldehydes with electron-withdrawing groups exhibited significantly superior performance compared to those with electron-donating groups. These findings underscore the pivotal role of substituents in enhancing reaction efficiency.

Table 3.

Efficient Synthesis of Benzo[a]pyrano[3,2-c]phenazines using g-C₃N₄/CS/MOF-5.

Entry	product	R	Time (min)	Yield (%)	m.p. (°C)
1	5a	4-Cl	40	95	290–293
2	5b	4-NO2	33	96	250–252
3	5c	4-Br	45	94	285–287
4	5d	4-OH	60	80	280–282
5	5e	4-N(Me)2	45	94	268–270
6	5f.	4-OMe	80	80	260–262
7	5g	2,5-di OMe	120	77	286–288
8	5h	3-NO2	30	96	266–268
9	5i	3-Br	35	95	248–250
10	5j	3,4-di OMe	125	75	285–287

^aReaction conditions: Thiobarbituric acid (1 mmol), o-phenylenediamine (1 mmol), 4-nitrobenzaldehyde (1 mmol), 2-hydroxy-1,4-naphthoquinone (1 mmol), g-C₃N₄/CS/MOF-5 composite (0.015 g), 3 mL of EtOH/H₂O (1:1) at 90 °C.

^b Product yield obtained after purification.

Reusability of nanocatalyst

The recovery of nanocatalysts is of superior significance of catalyst. Recovery of catalyst reduces the consumption of materials but also plays a pivotal role in promoting the sustainability of synthetic processes aligned with the principles of green chemistry. To evaluate the recyclability and operational stability of the g-C₃N₄/CS/MOF-5 nanocomposite, the synthesis of compound 5b was selected as a model reaction, utilizing 15 mg of the nanocatalyst in 3 mL of EtOH/H₂O (1:1) at 90 °C. After each cycle, the catalyst was easily separated from the reaction medium by centrifugation, washed with water and ethanol, and, after drying at 80 °C, reused directly in the subsequent reaction. This recycling and reuse protocol was repeated over six consecutive cycles. As depicted in Fig. 8a, the nanocomposite demonstrated no significant loss in catalytic activity even after six successive uses, and the reaction proceeded with consistently high yields. Moreover, FT-IR spectrum, XRD pattern and scanning electron microscopy (SEM) analysis of the recovered catalyst after the sixth cycle (Fig. 8b–d), confirmed the preservation of the functionality, crystality, surface and morphological integrity of reused catalyst. For further evaluation, ICP analysis was performed, which showed 6.85% Zn²⁺ in the recycled catalyst compared to 7.48% Zn²⁺ in the fresh catalyst. These results indicate that the catalyst exhibits high stability with negligible leaching.

Fig. 8.

Recycling chart of the g-C₃N₄/CS/MOF-5 (a), SEM (b), XRD (c) and FT-IR (d) of catalyst after six cycles.

Leaching test

To illustrate the heterogeneous characteristics and surface activity of g-C₃N₄/CS/MOF-5, a control experiment was conducted. A mixture containing g-C₃N₄/CS/MOF-5 (0.015 mg) in water (7 mL) was stirred at 90°C for 33 min. The catalyst was then separated by filtration. The resulting filtrate was used as reaction medium for the synthesis of 4b involving Thiobarbituric acid (1 mmol), o-phenylenediamine (1 mmol), 4-nitrobenzaldehyde (1 mmol), 2-hydroxy-1,4-naphthoquinone (1 mmol) at 90 °C for 33 min. After the time, the product yielded 11%, confirming that g-C₃N₄/CS/MOF-5 effectively catalyzes the reaction heterogeneously, exhibiting significant surface activity.

Reaction mechanism

Scheme 4 proposes a rational synthetic strategy for the attainment of benzopyranophenazines utilizing the heterogeneous catalyst g-C₃N₄/CS/MOF-5. The proposed reaction pathway performs with the initial step of tautomerization of 2-hydroxy-1,4-naphthoquinone, leading to the formation of an active species capable of participating in subsequent condensation reaction with o-phenylenediamine, yielding the intermediate I after removal of H₂O (2 eq). On the other hand, intermediate II is formed via a Knoevenagel reaction between thiobarbituric acid and benzaldehyde (which activated by Zn⁺² as active site of catalyst). The subsequent step involves a Michael addition reaction between intermediates I and II, resulting the formation of intermediate III in the presence of g-C₃N₄/CS/MOF-5. Ultimately, the final benzopyranophenazine product is obtained through an intramolecular cyclization process accompanied by the elimination of a water molecule.

Scheme 4.

The suggested reaction mechanism for the synthesis of benzo[a]pyrano[3,2-c]phenazine.

Conclusion

In this study, a biocompatible g-C₃N₄/CS/MOF-5 nanocomposite was meticulously designed and synthesized utilizing the bio-based polymer chitosan. Highly efficiency of prepared heterogeneous catalyst, show the synergistic interplay of its constituents, exhibited remarkable chemical stability, recyclability and environmental compatibility. Comprehensive characterization through techniques such as SEM, EDS, TGA, BET, FT-IR, and XRD, confirmed the structural integrity and functional properties of the nanocomposite. The catalyst demonstrated exceptional performance in the synthesis of novel benzo[a]pyrano[2,3-c]phenazine derivatives via a one-pot, four-component reaction in a 1:1 aqueous-ethanolic medium at 90 °C with high yields (75–96%) within short reaction times (30–125 min). Key advantages of this method include biocompatibility, high efficiency, adherence to green chemistry principles, recyclability for up to six consecutive cycles without performance loss, and facile separation from the reaction medium.

Author contributions

Atefeh Zeinali: Methodology, Investigation. Leila Moradi: Supervision, Review & editing.

Funding

There was no funding for the manuscript.

Data availability

The data that supports the findings of this study are available in the ESI† of this article.

Declarations

Competing interests

The authors declare no competing interests.