Abstract

The present study reports a green and effective photocatalytic procedure for synthesizing Benzochromenoquinoline derivatives under visible green LED irradiation. The synthesized compounds were characterized using 1H-NMR, 13C-NMR, and HRMS to ensure their structural integrity. Photophysical properties were investigated using UV-vis spectroscopy, and all derivatives were examined in a THF solvent. Selected derivatives (4a, 4d, 4f, and 4m) were further analyzed at varying concentrations in THF to elucidate their concentration-dependent spectroscopic behavior. Antioxidant activity was assessed at various concentrations. In silico ADMET predictions were made, demonstrating conformity with Lipinski’s rule of five and emphasizing their drug-like features.

Keywords:Sulfanilic acid, Coumarins, Photo redox, Green LED lights, Uv-vis spectra, Biological evaluation

Abbreviations:MCR: Multicomponent Reactions; SET: Single-Electron Transfer; TLC: Thin-layer Chromatography; TMS: Tetramethylsilane; PC: Photo-Redox Catalyst; ISC: Intersystem Crossing; BBB: Blood-Brain Barrier, MR: Molar Refractive; HBD: hydrogen Bond Donors, TPSA: Topological Polar Surface Area; HBA: Hydrogen Bond Acceptors

Introduction

Multicomponent reactions (MCRs) are an important family of convergent reactions that include the simultaneous interaction of three or more reactants to generate a single product, with significant molecular contributions from each reactant [1]. These reactions allow for the efficient synthesis of structurally intricate molecules in a single step, avoiding the need for expensive purification methods and reducing reagent and solvent use. MCRs are an environmentally friendly synthetic process due to their inherent sustainability, manifested through lower chemical waste emergence as compared to conventional bicomponent reactions [2]. This novel technique has emerged as a popular alternative to standard multi-step synthetic protocols, with numerous applications in synthetic organic chemistry, biological scaffold development, and pharmaceutical discovery [3]. The reaction outcome, notably in terms of selectivity, pliability, and environmental compatibility, is heavily impacted by key operational factors such as reaction temperature, catalyst loading and solvent system composition. The coumarin scaffold (Figure 1), a privileged heterocyclic structural motif, is abundantly found in a wide range of therapeutically relevant natural compounds. These compounds have shown significant therapeutic potential due to their broad range of pharmacological actions, which include antibacterial, antiviral, anti-HIV, anticoagulant, and cytotoxic characteristics [4-6]. Aside from its therapeutic applications, coumarin derivatives have found considerable industrial use as agrochemicals (herbicides), food and cosmetic additives (flavouring agents, perfumes, and colourants) [7]. Furthermore, their distinctive photophysical properties have led to their use in optical applications such as laser dyes, fluorescent brighteners, nonlinear optical chromophores, and photovoltaic energy collectors [8].

Over the past decade, visible light-mediated reactions have emerged as an effective technique in sustainable chemistry, allowing for a wide range of chemical transformations under mild conditions [9,10]. Photoredox catalysis is a key achievement in this discipline, as it provides an efficient route to radical cyclisation as well as unique approaches for C-C/C-X bond production in heterocyclic synthesis. Photocatalysts, both transition metalbased and organic variants (Figure 2), are exceptionally useful due to their enhanced reducing/oxidizing capabilities in their photoexcited states compared to their ground states, allowing them to function as efficient single-electron transfer (SET) mediators in mild reaction conditions. This catalytic platform has numerous applications in various fields, including photochemistry, radical chemistry, and environmentally friendly synthesis [11]. Photocatalysts use visible light as a renewable energy source to facilitate chemical transformations via SET reactions, activating low-energy organic substrates [12].

Sulfanilic acid is a cost-effective, environmentally friendly, and flexible chemical usually appearing as grayish-white crystals or powder. It is highly stable but interacts with strong oxidizing chemicals. It has been used extensively as a catalyst in producing several heterocyclic compounds [13,14]. Sulfanilic acid is a zwitterion in its solid state due to its amphiprotic character, which includes both amine (-NH₂) and sulfonic acid (-SO3H) functional groups (Figure 3). The sulfonic acid group can undergo deprotonation to form sulfonate (–SO₃−), while the amine group can be protonated to yield an ammonium ion (–NH₃⁺), underscoring its dual reactivity. Sulfanilic acid has recently emerged as a photocatalyst in visible light-mediated photoredox organic reactions. As an organic photocatalyst, it absorbs visible light to become excited and can initiate single-electron transfer (SET) reactions with substrates [15]. The amine group acts as an electron donor, while the sulfonic acid moiety stabilizes radical intermediates, altering redox potentials and increasing reactivity. Unlike traditional photocatalysts such as transition metal complexes (e.g., Ru(bpy)₃s2+, Ir(ppy)₃) or organic dyes (e.g., Eosin Y, rhodamine B, methylene blue and Rose Bengal, etc), sulfanilic acid has distinct advantages: it is metal-free, inexpensive, non-poisonous, and easily separable or recyclable, which aligns with green chemistry concepts. However, to the best of our knowledge, the literature reveals [16] no specific research on the sulfanilic acid-catalyzed visible light-driven synthesis of benzo[f]chromeno[4,3-b] quinolin-6-one derivatives. To address this gap, herein, we report a unique, one-pot multicomponent methodology for synthesizing these compound and its derivatives, employing sulfanilic acid as a photoredox catalyst under green LED irradiation. At ambient temperatures, 2-naphthylamine, substituted aryl/heteroaryl aldehydes, and 4-hydroxycoumarin are combined in THF (Scheme 1), emphasizing environmental sustainability. TLC was used to monitor the reaction, and the products were characterized using FT-IR, NMR (¹H and ¹³C), mass spectrometry, and elemental analysis. Furthermore, the photophysical and antioxidant characteristics of the synthesized compounds were studied.

Experimental

Material and Methods

All the solvents were purchased and used without further purification. 4-Hydroxycoumarin (Spectrochem Pvt. Ltd., Mumbai, >99.8%) and arylaldehyde (Molychem Pvt Ltd., India, >98%). 2-Napthylamine (CDH Pvt. Ltd., Gujarat, >97%). Solvents were purchased from Loba Chemie Pvt. Ltd. Mumbai, India, and the Sulfanilic acid was purchased from E. MERCK Ltd. Mumbai 98–99%. The progress of reactions was carefully monitored using thin-layer chromatography (TLC) with pre-coated silica gel 60 F₂₅₄ plates. The green LEDs used were commercial, and no cutoff filter was used. 1, 1-Diphenyl-2-picrylhydrazyl (DPPH*) was purchased from Hi Media Pvt. Ltd. Mumbai, India. A UV-visible spectrophotometer (Systronic, Model No. 118) was used for quantitative estimation of molecular absorption. Melting points are uncorrected. ¹H NMR and ¹³C NMR spectra were determined on Bruker Av III HD DRX 300 (^{1H NMR: 300 MHz, 13C NMR: 75 MHz) spectrometer in DMSO-d6 solution. Coupling constants (J) are specified in hertz (Hz). Signals are abbreviated as follows: singlet. s; doublet. d; doublet-doublet. dd; doublet-triplet dt; triplet. t; multiplet. m.Chemical changes (δ) are measured in parts per million (ppm) compared to the internal standard, tetramethylsilane (TMS). Signal multiplicities are denoted by standard abbreviations: singlet (s), doublet (d), doublet of doublets (dd), triplet (t), and multiplet (m). Coupling constants (J) are expressed in hertz (Hz) to provide precise structural information about the synthesized compounds.}

General route for the synthesis of Benzochromenoquinolines

The synthetic technique was carried out in an oven-dried round bottom flask using visible light photoredox conditions. In the reaction vessel, 4-hydroxycoumarin (1; 1 equivalent), substituted aryl/heteroaryl-aldehyde (2; 1 equivalent), and 2-naphthylamine (3; 1.2 equivalents) were added successively, with sulfanilic acid (20 mol%) functioning as the photoredox catalyst. 5 mL of anhydrous tetrahydrofuran (THF) was used for solvent-mediated processes. The reaction mixture was exposed to a visible green light-emitting diode (18W LED, λmax = 535 nm) at room temperature and open-air atmospheric conditions. The progress of the reaction was monitored at scheduled time intervals via thin-layer chromatography (TLC) using silica gel 60 F₂₅₄ pre-coated plates. This analytical technique monitored starting material consumption and product creation throughout the reaction process. Following TLC confirmation of the reaction complete, the crude mixture was quenched with 3 mL of distilled water, resulting in product precipitation. The precipitate was separated and then dissolved in pure ethanol. Insoluble contaminants were removed from this solution using the filtration method, and the pure product was gained by evaporating the solvent. Systematic optimization studies revealed that using 20 mol% sulfanilic acids as a photocatalyst in THF under green LED irradiation produced the target Benzochromenoquinoline derivatives with an exceptional isolated yield of 98%, indicating the optimal conditions for this transformation. The synthesized chemicals underwent comprehensive analytical characterization. Nuclear magnetic resonance spectroscopy (¹H and ¹³C NMR) confirmed structural details and established the synthesis success. Compound purity and elemental composition were confirmed using analytical elemental analysis techniques. Additional characterization includes photophysical property tests, antioxidant activity assessments, computational in-silico research for mechanistic understanding, and kinetic investigations to clarify reaction pathways. Compounds 4a, 4c, and 4i had already been described in the literature, and compound 4a spectrum data was directly matched to published values [16] for comparison. All novel compounds were thoroughly characterized using the above analytical techniques to determine their structural identity and purity. This rigorous characterization validated both our synthetic methodology and the quality of the resulting products.

Results and Discussions

To test the feasibility of our protocol, 4-hydroxycoumarin (1), aryl aldehyde (2), and 2-napthylamine (3) were selected as model substrate for the designed product. Initially, when we used THF as a solvent in the presence of sulfanilic acid as a photocatalyst under the irradiation of green LED light (18 W; λmax = 535 nm), Benzochromenoquinolines (4) was obtained in 36% yield (Table 1, entry 1). A control experiment without the photocatalyst, which gave only a trace amount of product under the irradiation of green LEDs (Table 1, entry 10), confirmed the catalytic role of sulfanilic acid. A satisfactory product yield of 98% (Table 1, entry 12) was obtained in the presence of THF, sulfanilic acid (20 mol%). Therefore, Sulfanilic acid (0.6 mmol) in the presence of a THF solvent system was chosen as the most suitable photocatalyst for our present study. A slight excess of 2-napthylamine was found to be advantageous. Hence, the aromatic aldehyde and 2-napthylamine ratio were kept at 1:1.2 eq. Encouraged by these results, a wide variety of aryl aldehydes, 2-napthylamine, and 4-hydroxycoumarin were treated using sulfanilic acid under the optimized conditions in the presence of THF solvent to afford the corresponding Benzochromenoquinolines (Table 2) in good to excellent yields. This approach reduces waste, tedious workup, and process costs.

After optimizing the reaction conditions, we investigated the substrate scope for the green LED visible-light-mediated sulfanilic acid-catalyzed synthesis of Benzochromenoquinolines. A range of substituted arylaldehydes was studied, and it was found that substituted arylaldehyde with different groups created the desired products with acceptable yields. The position and type of substituents on the aryl ring did not significantly affect the reaction. Instead, they provided a satisfactory yield of the desired products (84.51-98.39%) with an uncorrected melting point of ≤430 ℃. However, as expected, the aryl aldehydes bearing electron-withdrawing groups reacted slightly better than those with electron-donating groups.

^aReaction condition: 1 (1eq.), 2 (1 eq.) and 3 (1.2 eq.), in presence of sulfanilic acid (20 mol%) in THF (5 ml) as solvent and green LED (535 nm) irradiation under air atmosphere at room temperature.
^bIsolated yield of product.
^cReaction was carried out without photo-catalyst.

^aReaction condition: 1 (1eq.), 2 (1 eq.) and 3 (1.2 eq.), in presence of sulfanilic acid (20 mol%) catalyst, THF (5 ml) as solvent and green LED (18W; λ_max = 535 nm) as a visible light source for 3-5 h.
^bIsolated yield of product.

Suggesting a plausible reaction pathway

Despite the fact that the precise reaction mechanism is unknown, a potential mechanistic route incorporating visiblelight- mediated catalysis is constructed as a plausible mechanism proposed in (Scheme 2). Upon irradiation with visible light, photoredox catalyst (PC) is stimulated to its singlet excited state (1PC*) and then undergoes intersystem crossing (ISC) to reach its most stable triplet state (3PC*). This 3PC* converted 4-hydroxycoumarin into a radical cation by oxidation of one electron through a single electron transfer (SET) path. Alternatively, (e) is obtained from the reaction of substituted aryl aldehyde and 2-napthylamine, and intramolecular cyclization occurs via the elimination of water molecules. Now this radical cation (a) reacts with (d) to form compound (e). Further, (PC*) undergoes its ground state by donating an electron from intermediate (e) to (f) via a single electron transfer (SET) route, and (g), followed by (f), forms a compound. Finally, (g) undergoes a simple dehydration reaction and leads to the desired product.

Spectral data

i. 7 - p h e n y l - 7 , 1 4 - d i h y d r o - 6 H - b e n z o [ f ] chromeno[4,3-b] quinoline-6-one (Entry 4a)

Yield: 90.83%; 1H NMR (DMSO-d6): δ 11.63 (s, 1H, NH), 8.27 (d, 1H, ArH), 7.83-7.76 (m, 2H, ArH), 7.70 (m, 2H, ArH), 7.65 (t, 2H, ArH, J = 7.5 Hz), 7.43-7.35 (m, 2H, ArH), 7.37-7.21 (m, 3H, ArH), 7.03 (t, 2H, ArH, J = 7.5 Hz), 4.73 (s, 1H, CH) ppm; 13C NMR: δ 161.8, 153.5, 146.7, 143.5, 132.7, 129.1, 120.9, 116.8, 40.2 ppm; m/z calculated for [C₂₆H₁₇NO₂]: 375.4270; found: 375.4263; Anal. Calcd. for C₂₆H₁₇NO₂: C 83.28, H 4.53, N 3.72; Found: C 82.78, H 3.86, N 3.23.

ii. 7-(naphthalen-2-yl)-7,14-dihydro-6H-benzo[f ] chromeno[4,3-b] quinoline-6-one (4b)

Yield: 91.40%; 1H NMR (DMSO- d6): δ11.64 (s, 1H, NH), 8.31 (d, 1H, ArH), 7.98-7.83 (m, 2H, ArH), 7.77 (m, 2H, ArH), 7.60 (t, 2H, ArH, J = 7.5 Hz), 7.51-7.40 (m, 2H, ArH), 7.47-7.35 (m, 3H, ArH), 7.05 (t, 2H, ArH, J = 7.5 Hz), 4.72 (s, 1H, CH) ppm; 13C NMR: δ 161.8, 152.4, 145.1, 135.1, 127.1, 122.1, 116.7, 96.4, 40.6 ppm; m/z calculated for [C₃₀H₁₉NO₂]: 425.4871; found: 425.4860; Anal. Calcd. for C₃₀H₁₉NO₂: C 84.64, H 4.52, N 3.28; Found: C 84.57, H 4.48, N 3.21.

iii. 7-(4-(dimethylamino)phenyl)-7,14-dihydro-6Hbenzo[ f]chromeno[4,3-b]quinoline-6-one (4d)

Yield: 84.51%; 1H NMR (DMSO- d6): δ 11.65 (s, 1H, NH), 8.37 (d, 1H, ArH), 7.85-7.80 (m, 2H, ArH), 7.71 (m, 2H, ArH), 7.69 (t, 2H, ArH, J = 7.5 Hz), 7.43-7.38 (m, 2H, ArH), 7.28-6.69 (m, 3H, ArH), 4.78 (s, 1H, CH), 3.03 (s, 3H, CH3) ppm; 13C NMR: δ 162.8, 152.6, 148.7, 145.2, 143.0, 137.3, 129.3, 120.9, 116.9, 113.3, 96.5, 41.4 ppm; m/z calculated for [C₂₈H₂₂N₂O₂]: 418.4961; found: 418.4954; Anal. Calcd. for C₂₈H₂₂N₂O₂: C 80.37, H 5.34, N 6.70; Found: C 80.26, H 5.11, N 6.63.

iv. 7-(4-chlorophenyl)-7,14-dihydro-6H-benzo[f ] chromeno[4,3-b] quinoline-6-one (4e)

Yield: 95.23%; 1H NMR (DMSO- d6): δ 11.67 (s, 1H, NH), 8.34 (d, 1H, ArH), 7.89 (m, 2H, ArH), 7.76 (m, 2H, ArH), 7.72 (t, 2H, ArH, J = 7.5 Hz), 7.66-7.43 (m, 2H, ArH), 7.39 (m, 3H, ArH), 4.76 (s, 1H, CH) ppm; 13C NMR: δ 153.5, 145.6, 144.8, 143.3, 132.7, 131.6, 126.4, 117.6, 113.5, 96.6, 40.3 ppm; m/z calculated for [C₂₆H₁₆ClNO₂]: 409.8691; found: 409.8685; Anal. Calcd. for C₂₆H₁₆ClNO₂: C 76.20, H 3.91, Cl 8.67, N 3.43; Found: C 76.16, H 3.86, Cl 8.54, N 6.63.

v. 7-(3-nitrophenyl)-7,14-dihydro-6H-benzo[f ] chromeno[4,3-b] quinoline-6-one (4f)

Yield: 98.39%; 1H NMR (DMSO- d6): δ 11.61 (s, 1H, NH), 8.39 (d, 1H, ArH), 8.33-8.18 (m, 2H, ArH), 7.85 (m, 2H, ArH), 7.79 (t, 2H, ArH, J = 7.5 Hz), 7.71-7.68 (m, 2H, ArH), 7.43-7.35 (m, 3H, ArH), 4.74 (s, 1H, CH) ppm; 13C NMR: δ 162.1, 153.4, 148.5, 132.6, 121.2, 113.6, 96.4, 40.1 ppm; m/z calculated for [C₂₆H₁₆N₂O₄]: 420.4243; found: 420.4236; Anal. Calcd. for C₂₆H₁₆N₂O₄: C 74.29, H 3.89, N 6.68; Found: C 74.21, H 3.75, N 6.54.

vi. 7-(2,5-dimethoxyphenyl)-7,14-dihydro-6H-benzo[f] chromeno[4,3-b] quinoline-6-one (4g)

Yield: 85.60%; 1H NMR (DMSO- d6): δ 11.54 (s, 1H, NH), 8.36 (d, 1H, ArH), 7.79-7.72 (m, 2H, ArH), 7.64 (m, 2H, ArH), 7.43 (t, 2H, ArH, J = 7.5 Hz), 7.37-7.15 (m, 2H, ArH), 6.97-6.94 (m, 2H, ArH), 4.71 (s, 1H, CH) , 3.72 (s, 3H, CH3) ppm; 13C NMR: δ 164.8, 153.6, 145.2, 132.6, 128.4, 124.7, 117.4, 116.6, 113.6, 96.4, 55.9, 56.2, 34.6 ppm; m/z calculated for [C₂₈H₂₁NO₄]: 435.4791; found: 435.4783; Anal. Calcd. for C₂₈H₂₁NO₄: C 77.24, H 4.87, N 3.24; Found: C 77.18, H 4.41, N 3.01.

vii. 7-(2-chloro-6-fluorophenyl)-7,14-dihydro-6Hbenzo[ f]chromeno[4,3-b]quinoline-6-one (4h)

Yield: 97.61%; 1H NMR (DMSO- d6): δ 11.57 (s, 1H, NH), 8.33-7.84 (d, 1H, ArH), 7.65 (m, 2H, ArH), 7.49 (d, 2H, ArH, J = 7.5 Hz), 7.42-7.36 (m, 2H, ArH), 7.27 (m, 2H, ArH), 7.04 (m, 2H, ArH), 4.76 (s, 1H, CH) ppm; 13C NMR: δ 162.3, 153.5, 143.2, 135.3, 132.6, 130.5, 126.4, 120.7, 113.5, 97.8, 28.5 ppm; m/z calculated for [C₂₆H₁₅ClFNO₂]: 427.0776; found: 427.0763; Anal. Calcd. for C₂₆H₁₅ClFNO₂: C 73.11, H 3.56, Cl 8.28, F 4.46, N 3.28; Found: C 72.98, H 3.42, Cl 8.19, F 4.32, N 3.11.

viii. 7-(3-methoxyphenyl)-7,14-dihydro-6H-benzo[f ] chromeno[4,3-b] quinoline-6-one (4j)

Yield: 87.10%; 1H NMR (DMSO- d6): δ 11.63 (s, 1H, NH), 8.29- 7.84 (d, 1H, ArH), 7.75-7.72 (m, 2H, ArH), 7.68 (d, 2H, ArH, J = 7.5 Hz), 7.42-7.31 (m, 2H, ArH), 7.06 (m, 2H, ArH), 6.94-6.89 (m, 2H, ArH), 4.74 (s, 1H, CH), 3.72 (s, 3H, CH3) ppm; 13C NMR: δ 162.9, 143.8, 132.6, 125.4, 122.1, 121.6, 116.7, 96.5, 56.7, 40.1 ppm; m/z calculated for [C₂₇H₁₉NO₃]: 405.4531; found: 405.4526; Anal. Calcd. for C₂₇H₁₉NO₃: C 80.11, H 4.76, N 3.49; Found: C 79.96, H 4.72, N 3.40.

ix. 7-(4-fluorophenyl)-7,14-dihydro-6H-benzo[f ] chromeno[4,3-b] quinoline-6-one (4k)

Yield: 93.42%; 1H NMR (DMSO- d6): δ 11.56 (s, 1H, NH), 8.35 (d, 1H, ArH), 7.86 (m, 2H, ArH), 7.79 (m, 2H, ArH), 7.70 (t, 2H, ArH, J = 7.5 Hz), 7.67-7.46 (m, 2H, ArH), 7.31-7.16 (m, 3H, ArH), 4.74 (s, 1H, CH) ppm; 13C NMR: δ 162.1, 160.3, 153.3, 145.1, 145.0, 143.1, 132.5, 128.4, 125.3, 117.8, 113.7, 96.5, 40.1 ppm; m/z calculated for [C₂₆H₁₆FNO₂]: 409.8691; found: 409.8685; Anal. Calcd. for C₂₆H₁₆FNO₂: C 79.39, H 4.12, F 4.85, N 3.57; Found: C 79.32, H 3.98, F 4.73, N 3.46.

x. 7- (m- to lyl ) - 7 , 14- d ihydro - 6 H - b e n z o [ f ] chromeno[4,3-b] quinoline-6-one (4l)

Yield: 89.93%; 1H NMR (DMSO- d6): δ 11.61 (s, 1H, NH), 8.34 (d, 1H, ArH), 7.84-7.76 (m, 2H, ArH), 7.71 (m, 2H, ArH), 7.66 (t, 2H, ArH, J = 7.5 Hz), 7.41-7.42 (m, 2H, ArH), 7.41-7.39 (m, 3H, ArH), 7.04 (t, 2H, ArH, J = 7.5 Hz), 4.74 (s, 1H, CH), 2.32 (s, 3H, CH3) ppm; 13C NMR: δ 153.4, 145.3, 144.7, 142.4, 136.2, 131.4, 127.9, 125.4, 113.6, 96.3, 40.4, 21.5 ppm; m/z calculated for [C₂₇H₁₉NO₂]: 390.1448; found: 389.4532; Anal. Calcd. for C₂₇H₁₉NO₂: C 83.29, H 4.91, N 3.61; Found: C 83.20, H 4.84, N 3.55.

xi. 7-(furan-2-yl)-7,14-dihydro-6H-benzo[f ] chromeno[4,3-b] quinoline-6-one (4m)

Yield: 92.59%; 1H NMR (DMSO- d6): δ 11.61 (s, 1H, NH), 8.39 (d, 1H, ArH), 7.86-7.73 (m, 2H, ArH), 7.71-7.66 (m, 2H, ArH), 7.50- 7.32 (m, 2H, ArH), 6.34-6.12 (m,, 2H, ArH), 4.98 (s, 1H, CH) ppm; 13C NMR: δ 162.4, 152.8, 145.3, 143.2, 142.3, 132.4,, 127.4, 126.3, 122.6, 110.7, 106.8, 96.4, 32.3 ppm; m/z calculated for [C₂₄H₁₅NO₃]: 365.3881; found: 365.3862; Anal. Calcd. for C₂₄H₁₅NO₃: C 80.31, H 4.16, N 3.89; Found: C 80.01, H 3.96, N 3.62.

Drug likeness/Analysis of pharmacokinetic properties

The structural property of the molecule, referred to as druglikeness, is a key factor in determining guidelines that lead to effective and productive results in drug discovery. Various rules are used in the calculations, such as QED, Lipinski’s rule, MDDR-like rule, Ghose filter, Veber rule, BBB rule, and CMC- 50 rule [17]. The wide variety of actions exhibited by benzo[f] chromeno[4,3-b] quinoline-6-one derivatives are necessary for applying the drug-likeness rule and achieving efficacy. All ADME parameters, including skin permeability (log kp), blood-brain barrier (BBB), molar refractive index (MR), hydrogen bond donors (HBD), topological polar surface area (TPSA), and hydrogen bond acceptors (HBA), as well as their bioavailability score, were summarized for the synthesized compounds in (Table 3). Less than five HBD and HBA atoms should be present. These values are within Lipinski’s rule of Five, suggesting good oral bioavailability potential.

The consistency in HBD and similarity in HBA indicate these compounds likely have comparable hydrogen bonding capabilities, which can affect solubility, protein binding, and permeability. TPSA is a good predictor of drug absorption, including intestinal absorption and blood-brain barrier penetration. Values <140 Å2 are generally associated with good oral bioavailability. The range suggests these compounds should have good oral absorption, with some variation among derivatives. The qualifying range for molar refractivity (MR) is 40 to 130 [18], with an average value of 97.52. MR is related to the total polarizability of a mole of a substance. Molecular polarization testing shows higher-value molecules have more distinct interactions and a more substantial polarization potential. This property significantly impacts how these chemicals interact with protein targets, ultimately affecting the therapeutic potential. When assessing these molecules as potential medications, it is critical to consider their polarization and medicinal efficacy. The majority of compounds in this series had favorable absorption profiles, according to gastrointestinal absorption characteristics, except derivatives 4b, 4f, and 4h. This encouraging absorption behavior is beneficial for possible oral drug delivery applications because it indicates sufficient bioavailability via this mode of administration. According to blood-brain barrier penetration experiments, only compounds 4a and 4d had the structural properties required for potential CNS activity. The series has a consistent bioavailability score of 0.55, indicating modest absorption characteristics.

HBD – Hydrogen Bond Donor, HBA – Hydrogen bond acceptor, MR – Molar refractivity, TPSA – Topological polar surface area, GI – Gastrointestinal, BBB – blood-brain barrier penetration, log k_p – skin permeability.

The metabolic stability study examined CYP1A2 interactions, critical phase I metabolic enzymes that play a role in drug metabolism, and potential drug-drug interactions. Inhibition could lead to drug-drug interactions, potentially affecting the metabolism of other drugs. All compounds except 4b are predicted to be CYP1A2 inhibitors. The skin permeability (log kp) lies between -4.99 to -3.83 cm/s. Lipinski’s Rule of Five predicts the likelihood of oral bioavailability. Having 0-1 violations suggests these compounds are likely to have good oral bioavailability, with 4f, 4g, and 4m potentially superior in these aspects. The above discussion showed that the titled compound and its derivatives were beneficial building blocks frequently used in synthesizing numerous bioactive components and medicines.

In-vitro Antioxidant activity

1, 1-Diphenyl-2-picrylhydrazyl (DPPH* Assay) A strong dose-dependent diamagnetic DPPH* quenching ability was examined to determine the compound’s (4a-4m) shielding profile. DPPH* is produced in the methanolic solution (2) by 2-diphenyl-1-picrylhydrazyl (DPPH). The majority of the substances under analysis exhibited exceptional efficacy against DPPH*. DPPH* was utilized as a radical scavenger; because of its odd electron, it has a maximum absorption at 517 nm. The process monitors the decline in absorption and demonstrates the compound’s antioxidant activity.

The formula used for the calculation is: -
% Inhibition of DPPH* activity =
Where Ac = absorbance value of the control sample, As = absorbance value of the tested sample.

A stock solution (1.0 mg in 10mL−1) of compounds was prepared in methanol. The stock solution of DPPH* was also prepared at the concentration of 1mg in 50 mL-1 in methanol. Different concentrations, such as 2 mL, 1.5 mL, 1 mL, 0.5 mL, 0.25 mL, and 0.125 mL of compounds, were taken out in the test tube separately and made up the volume up to 2 mL by adding methanol, respectively. Now add 2 mL DPPH* solution in each test tube, increase the volume to 4 mL, and keep the solutions for 30 minutes in the dark at room temperature for incubation. After the incubation, the UV-spectrophotometer recorded the samples’ absorbance at λ = 517 nm. By either hydrogen or electron donation, antioxidant compounds scavenge DPPH radicals. As a result, the purple color of the DPPH assay solution turns yellow, which can be determined by a decrease in absorbance at wavelength 517 nm. As illustrated in (Figure 4), all the synthesized compounds exhibited moderate to good antioxidant activity (55.14 - 94.76%). The results depicted in (Table 4) indicated that the presence of substituents (electron-withdrawing or electron-donating) on the aromatic ring could play an essential role in its antioxidant activity Kadhum et al. [19]. The 4d, 4g, 4j, and 4i showed antioxidant potential with 94.76, 88.02, 84.23, and 81.32% DPPH* inhibition compared to gallic acid (standard;97.66%).

Photophysical Evaluation

The chemo-sensing properties of 4a-4m were further investigated by UV-vis spectroscopy. The UV-vis absorption spectra of the synthesized compounds were recorded in THF solvent at room temperature to characterize their electronic transitions within the wavelength range of 300-650 nm (Figure 5). The spectra exhibited strong absorption bands in the 300–500 nm region, attributed to π→π* transitions of the conjugated molecular framework. Weaker, broader absorption spectra extending to a longer wavelength, 550 nm, were also observed, likely due to n→π* transitions involving heteroatoms in the structure [20].

To assess the effect of the concentration on the absorption spectra of compounds 4a, 4d, 4f, and 4m, compounds were employed at different concentrations in THF solvent at room temperature. The selection of compounds 4a, 4d, 4f, and 4m for concentrationdependent UV-vis studies was based on their representative structural diversity within the synthesized series. Compound 4a is the baseline reference with its simple phenolic hydroxyl group, whereas 4d has an electron-donating dimethylamino group that considerably changes π-conjugation. Compound 4f, which contains a strong electron-drawing nitro group, was chosen to study the effect of electron-deficient systems on absorbance activity. Compound 4m, with its thiophene heterocycle, exhibits the impact of a characteristic aromatic sulfur-containing system. Among the series, these four selected compounds efficiently representing the entire electronic spectrum, from electron-rich to electron-poor frameworks, enabling for a thorough assessment of concentration effects on absorption profiles.

The spectra of Benzochromenoquinolines (4a, 4d, 4f, and 4m) were recorded in four different concentrations (1.25 mL, 1.5 mL, 2 mL, 10 mL) in the range of 350-650 nm to study the concentration effect on electronic spectra of compounds. The spectra of compounds recorded in different concentrations are given in (Figure 6). The spectral result displayed that the Benzochromenoquinoline derivative 4a exhibits a characteristic absorption band between 370-380 nm, with a decline observed beyond 400nm, which is probably due to π-π* and/or n- π* transition characteristic of aromatic or conjugated systems, with minimal absorption occurring in the visible region 450-650 nm. Derivative 4d displays distinct spectra, characterized by a broad absorption band with a maximum of approximately 400- 410 nm and a higher absorbance intensity (⁓2.0 a.u.) for 10 mL concentration. Compared to 4a, this bathochromic shift indicates extended conjugation or additional auxochromic groups that enhance electron delocalization. The lower concentrations (2 mL, 1.5 mL, and 1.25 mL) exhibit well-defined peaks around 400 nm with proportionally reduced intensities, maintaining the spectral profile of the parent compound. Derivative 4f has the most assertive absorption profile, with maximum absorbance at the most significant concentration, indicating the existence of strong chromophoric groups and substantial π-electron delocalization. This derivative has a strong absorption that begins at about 350 nm and steadily diminishes with increasing wavelength without any distinguishable secondary peaks. The steep absorption curve suggests intense electronic transitions occur primarily in the near-UV region. Derivative 4m has a modest absorption intensity at its greatest concentration. The spectrum reveals a reasonably prominent peak near 390 nm, followed by a quick fall in absorption above 430 nm. This spectral pattern shows a more localized electronic transition than 4f but retains significant chromophoric features.

Arrhenius plot and calculation of energy of activation (Ea)

The activation energy is the lowest kinetic energy needed by reactants to generate products. Thus, high activation energy activities are slower, whereas low activation energy processes occur faster. Energy of activation (Ea) is a process parameter that indicates how quickly a particular reaction will progress. The chemical reaction will occur gradually when the value of Ea is high. The synthesis of 7-phenyl-7,14-dihydro-6H-benzo[f] chromeno[4,3-b] quinoline-6-one (4a) as target compound has been studied kinetically, and the Arrhenius equation is used to calculate the energy of activation (Ea).

Where: k is rate constant (min^-1); A is a pre-exponential factor; Ea is the activation energy (kJmol^-1); R is the gas constant (8.314 Jmol^-1K^-1 or 1.987 cal mol^-1 K^-1); and T is temperature (K).

Different rate constants (k) were calculated at different temperatures (K) and a plot was made between ln k and (1/T), where a straight line is obtained. Slope of the straight line gives the value of energy of activation (Ea) and found as 34.626 KJmol^-1 (or 8.275 kcal mol^-1) represented in (Table 5) and (Figure 7). This Ea suggests a typical single-step reaction or a rate-determining step in a multi-step process. It provides insight into the energy barrier of the reaction, which is important for understanding the reaction’s feasibility and spontaneity. In synthesis, this Ea suggests that moderate heating would significantly increase the reaction rate of (4a), which could be useful for optimizing yield and reaction time. Overall, this activation energy suggests that the reaction proceeds at a reasonable rate.

Conclusion

In conclusion, we have developed an efficient one-pot, three-component synthetic methodology for the production of Benzochromenoquinolines using 2-naphthylamine, substituted aryl aldehydes, and 4-hydroxycoumarin catalyzed by sulfanilic acid under mild conditions. Notably, our findings differ from those of Martinez et al., as this specific synthetic method for the target molecules has not been published in the scientific literature before. all the synthesized compounds showed moderate to good antioxidant activity (55.14 - 94.76%). Photophysical investigations on the target molecule and its derivatives revealed consistent absorbance indicating stable optical characteristics. The UV-Vis spectroscopic analysis of derivatives 4a, 4d, 4f, and 4m revealed a unique absorption intensity trend (4f > 4d > 4m > 4a), with all compounds having typical absorption peaks in the near-UV region (350-450 nm) and displaying apparent concentration-dependent behavior. Temperature variation experiments were used to calculate activation energy (8.275 kcal mol-1) and drug-likeness assessments were carried out. The devised approach has various advantages, including the use of an economical and environmentally friendly organocatalyst, a simple operational process, and high product yields. These findings lay the groundwork for future research into these Benzochromenoquinolines compounds and their prospective applications in antioxidant and medicinal research.

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