Catalytic application of non-toxic Persia americana metabolite entrapped SnO₂ nanoparticles towards the synthesis of 3,4-dihydroacridin-1(2H)-ones

Abstract

Eco-friendly methods in organic synthesis are dynamic prerequisites for environmental safety. In general, metal nanoparticles displayed various levels of toxicity, photocatalytic activity and catalytic activity. Due to their diverse properties, recent work has been focused towards the exploitation of plant sources in nanoparticle synthesis. Herein, we have highlighted the non-toxic studies of green synthesized SnO₂ nanoparticles (SnO₂ NPs) using Persia americana seed. The catalytic effects of SnO₂ NPs were investigated on the synthesis of 3,4-dihydroacridin-1(2H)-ones. Synthesized compounds were confirmed using ¹H NMR, ¹³C NMR and LCMS analysis. We proved that SnO₂ NPs are non-toxic towards aquatic organisms.

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Introduction

Throughout the globe, environmental pollutants constitute a major recent threat and cause an adverse effect on human health.¹ Several organic pollutants are discarded directly into the environment by the pharmaceutical, chemical and textile industries.¹ The explosion of different types of organic toxic effluent has led to severe environmental damage. To overcome these toxic effects most researchers have focused on nanoparticle synthesis by various methodologies which help in catalytic reactions. Nanotechnology is a rapidly growing field among the various interdisciplinary sciences. Even though they show potent applications, nanomaterials have a high negative impact on human health and the environment.¹ It was identified that metal nanoparticles are exposed to the environment after their utilization. These airborne metals may settle in the environment for longer durations. They may cause short- and long-term effects to the environment and human health.^2,3 Metal oxide nanoparticles are small in size but have a large surface, hence they can be easily bind to toxic chemicals and transport toxic chemical pollutants.^4,5 The SnO₂ NPs have wide application in various fields but have their own disadvantage of inducing acute toxic effects. Inhalation of SnO₂ NPs may irritate the upper respiratory tract, skin and eyes. When SnO₂ NPs bind to a metal like indium they cause adverse effects on human health such as chronic toxicity,⁶ pulmonary toxicity,⁷ testicular toxicity,⁸ etc.; although metal oxide nanoparticles are utilized in various applications such as solid state gas sensors, solar cells, rechargeable Li batteries and optical electronic devices.^9,10 SnO₂ NPs have been considered as one of the best photocatalysts, with an n-type tetragonal crystal structure and a band gap of around 3.6 eV.¹¹ Several methods have been adopted for the synthesis of SnO₂ NPs such as sol–gel processes, spray pyrolysis, solvothermal methods, micro emulsion, homogenous precipitation, sonochemical methods, the polymerized complex citrate route and non-aqueous approaches.^12–14 But these methods lead to toxic effects to the environment and human health due to the usage of toxic solvents and chemicals.^15–17 Various biological heterocycles have been reported with chemical methods but they may be toxic.¹⁸ To overcome these toxicity effects we have focused our research towards the environmentally friendly synthesis of SnO₂ NPs using Persia americana seed methanolic extract; furthermore, we have employed these for organic synthesis, i.e. SnO₂-nanoparticle-catalysed synthesis of 3,4-dihydroacridin-1(2H)-ones under solvent free conditions.

Results and discussion

The percentage natality in test and control samples of the surveyed nauplii was counted after 24 h with the aid of a 3× magnifying glass. The LC₅₀ values of the tests were obtained from a best-fit line graph plotted between the concentrations versus percentage natality. The statistical data obtained from the natality percentage and survival of nauplii by this best-fit line method using Origin software are clearly illustrated in (Fig. 1).

Fig. 1 Toxicity profiling of SnO₂ NPs against A. salina.

By using the graph, we have obtained the interesting result of an LC₅₀ value which is less than 0.5 μg mL⁻¹; this supports the idea that the green synthesized SnO₂ NPs have less toxic effects on aquatic species. To optimize the effect of SnO₂ NPs in organic synthesis we have used them as catalyst in various amounts (0, 5, 10, 15, 20 mol%). When the reaction was carried out in the absence of catalyst we found, unfortunately, that the yield of the reaction is a very low 22% (Table 1).

Table 1 Optimization of amount of SnO₂ NPs for the synthesis of compound, 3a

Sl. no.	Solvents	Time/min	Isolated yield (%)
1	MeOH	120	84
2	DCM	60	64
3	Chloroform	60	71
4	Toluene	120	81
5	Water	120	70
6	No solvent	15	93

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Effect of solvent for the synthesis of 7-nitro-9-phenyl-3,4-dihydroacridin-1(2H)-one 3a was employed (Table 2, Fig. 2).

Table 2 Effect of solvent for the synthesis of compound, 3a

Catalyst loading (mol%)	0	5	10	15	20
Isolated yield (%)	22	56	93	92	90

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Fig. 2 Effect of solvent.

Among these, the solvent free conditions provided about 93% isolated yield when compared to other settings. We also found that the optimized quantity of catalyst for the formation of the product 3a is 10 mol%. By fine-tuning the reaction conditions, we have synthesized successfully seven acridone analogues with a good to excellent yield ratio.

The synthesized compounds were confirmed using ¹H NMR, ¹³C NMR and LCMS analysis. In the ¹H NMR spectra of the compound 3a, there is one quartet in the range from δ 2.28–2.34 and it corresponds to H-3 (one –CH₂). Two triplets appear at δ 2.77 and 3.45 which were assigned to H-2 and H-4, respectively. Then, 8 aromatic protons appear in the range of δ 7.19–8.54. In the ¹³C NMR spectrum of compound, 3a there are 3 signals at δ 21.0, 34.8, and 40.4, which are assigned to C-03, C-04, and C-02, respectively. The signal δ 197.0 is assigned to C-1 (carbonyl carbon). The remaining signals correspond to 15 aromatic carbons which include both protonated and non-protonated carbons. The catalyst has been reused several times without significant variation in the yield. This clearly shows that the catalyst can be used multiple times (Fig. 3).

Fig. 3 Reusability of the SnO₂ NPs.

Conclusion

SnO₂ NPs were synthesized using Persia americana methanolic extract seed without introducing any toxic elements to the environment, providing one of the cheapest methods for the synthesis of SnO₂ nanoparticles. The synthesized SnO₂ NPs were characterized by UV, XRD, and TEM. The SnO₂ NPs provide promising results towards the organic synthesis of 3,4-dihydroacridin-1(2H)-ones, 3(a–g) under solvent-free conditions. The synthesized compounds were purified without column chromatography techniques.

Experimental

Synthesis of SnO₂ NPs

The preparation of SnO₂ NPs was achieved using Persia americana as a green source. The synthesised SnO₂ NPs were characterised by UV, XRD and SEM are reported in our earlier publication.¹⁹ The green synthesis of SnO₂ NPs is illustrated in Fig. 4.

Fig. 4 Eco-friendly synthesis of SnO₂ nanoparticles.

Toxicity studies

For the toxicity assays the samples were prepared with an overall concentration of 500 μg mL⁻¹ by mixing a 10 mg mL⁻¹ stock solution of SnO₂ NPs and 19 mL of sea water. The experimental process was done using a 6-well plate technique which contains various concentrations like 2.5, 2, 1.75, 1.5, 1.25, 1, 0.75, 0.5, 0.25, 0.2, 0.175, 0.075, 0.05, 0.025 μg mL⁻¹ and a blank with 5 mL of sea water with 10 Artemia salina (A. salina) nauplii. In each well 10 nauplii were introduced by mixing with sea water and SnO₂ NPs to attain a final quantity of 5 mL in each well. After introducing 10 nauplii to each well, the plate was placed for incubation at room temperature under dark conditions for 24 h and the experiment was ran in triplicate. The LC₅₀ value and percentage natality were calculated from the experimental data.²⁰ The percentage of natality of A. salina was calculated by the given formula,

% NT = (A_N/P_T) × 100

where: % NT = % of natality; A_N = number of living Artemia nauplii; P_T = total number of population.

SnO₂ NPs in organic synthesis

General procedure for the synthesis of 3,4-dihydroacridin-1(2H)-ones. A mixture of amine, 1 (3 mmol), diketone, 2 (3 mmol) and SnO₂ NPs (10 mol%) was heated at 150 °C for 15 min. The reaction progress was monitored by TLC and on completion of the reaction, the mixture was cooled to room temperature and further ethyl acetate was added to the reaction mixture. Then the mixture was centrifuged at 4000 rpm for 15 min, the organic layer was then removed, and it was evaporated. The residue was washed with hexane to afford the product as a solid (Scheme 1). By using this methodology we have synthesized seven derivatives, named 3a–g, which were well characterized by spectroscopic techniques.

Scheme 1 Synthesis of 3,4-dihydroacridin-1(2H)-ones, 3. ^a Reaction conditions: amine (1 mmol), diketone (1 mmol), catalyst (10 mol %), heated to 90 °C for the respective time. ^b Reaction time. ^c Isolated yield.

Characterization of compound of 3a–g

7-Nitro-9-phenyl-3,4-dihydroacridin-1(2H)-one (3a). Brown solid; yield 93%; mp: 195–197 °C; ¹H NMR (400 MHz, CDCl₃) δ 8.54–8.51 (m, 1H), 8.45 (d, J = 2.4 Hz, 1H), 8.21 (d, J = 9.2 Hz, 1H), 7.59–7.57 (m, 3H), 7.22–7.19 (m, 2H), 3.45 (t, J = 6.4 Hz, 2H), 2.77 (t, J = 6.4 Hz, 2H), 2.34–2.28 (m, 2H); ¹³C NMR (100 MHz, CDCl₃) δ 21.0, 34.8, 40.4, 124.9, 125.0, 125.3, 126.8, 128.0, 128.5, 130.4, 135.7, 145.5, 150.3, 153, 166.1, 197.0. LCMS: m/z calcd for C₁₉H₁₄N₂O₃ 318.3 found 319.1 [M + 1].

7-Chloro-9-phenyl-3,4-dihydroacridin-1(2H)-one (3b). Brown solid; yield 91%; mp: 183–185 °C; ¹H NMR (400 MHz, CDCl₃) δ 8.00 (d, J = 9.2 Hz, 1H), 7.70–7.68 (m, 1H), 7.52–7.50 (m, 3H), 7.41 (d, J = 1.6 Hz, 1H), 7.17–7.15 (m, 2H), 3.36 (t, J = 6.4 Hz, 2H), 2.71 (t, J = 6.4 Hz, 2H), 2.28–2.22 (m, 2H); ¹³C NMR (100 MHz, CDCl₃) δ 21.2, 34.5, 40.6, 124.4, 126.7, 127.9, 128.0, 128.3, 128.4, 130.1, 132.4, 132.6, 136.8, 147.0, 150.5, 162.5, 197.7.

9-Phenyl-3,4-dihydroacridin-1(2H)-one (3c). Off-white solid; yield 90%; mp: 157–159 °C; ¹H NMR (400 MHz, CDCl₃) δ 8.12 (d, J = 8.4 Hz, 1H), 7.81 (t, J = 7.2 Hz, 1H), 7.58–7.38 (m, 5H), 7.22–7.19 (m, 2H), 3.42 (t, J = 6.4 Hz, 2H), 2.73 (t, J = 6.8 Hz, 2H), 2.31–2.25 (m, 2H). ¹³C NMR (100 MHz, CDCl₃) δ 21.3, 34.4, 40.6, 123.9, 126.5, 127.5, 127.6, 128.0, 128.1, 128, 128.3, 131.8, 137.5, 148.4, 151.7, 162.2, 197.8.

3,4-Dihydroacridin-1(2H)-one (3d). Off-white solid; yield 90%; mp: 109–111 °C; ¹H NMR (400 MHz, CDCl₃) δ 8.75 (s, 1H), 7.97–7.95 (m, 1H), 7.84 (d, J = 8.0 Hz, 1H), 7.74–7.70 (m, 1H), 7.48–7.44 (m, 1H), 3.23 (t, J = 6.0 Hz, 2H), 2.71 (t, J = 6.4 Hz, 2H), 2.22–2.16 (m, 2H); ¹³C NMR (100 MHz, CDCl₃) δ 21.7, 33.4, 39.0, 126.3, 126.6, 126.8, 128.5, 129.7, 132.3, 137.0, 149.6, 161.9, 197.8.

3,3,9-Trimethyl-3,4-dihydroacridin-1(2H)-one (3e). Off-white solid; yield 84%; mp: 108–110 °C; ¹H NMR (400 MHz, CDCl₃) δ 8.58 (d, J = 8.0 Hz, 1H), 8.32 (d, J = 8.4 Hz, 1H), 7.93 (t, J = 7.6 Hz, 1H), 7.73 (t, J = 8.0 Hz, 1H), 3.50 (s, 2H), 3.18 (s, 3H), 2.70 (s, 2H), 1.16 (s, 6H); ¹³C NMR (100 MHz, CDCl₃) δ 16.8, 28.1, 32.3, 45.0, 54.4, 124.2, 125.4, 125.9, 127.8, 128.3, 134.0, 159.8, 198.2.

3,3-Dimethyl-3,4-dihydroacridin-1(2H)-one (3f). Off-white solid; yield 89%; mp: 101–102 °C; ¹H NMR (400 MHz, CDCl₃) δ 8.83 (s, 1H), 8.05 (d, J = 8.4 Hz, 1H), 7.94 (d, J = 8.0 Hz, 1H), 7.80 (t, J = 7.6 Hz, 1H), 7.55 (t, J = 7.6 Hz, 1H), 3.20 (s, 2H), 2.65 (s, 2H), 1.15 (s, 6H); ¹³C NMR (100 MHz, CDCl₃) δ 28.3, 32.7, 47.2, 52.5, 125.3, 126.7, 126.8, 128.6, 129.7, 132.2, 136.5, 150.0, 160.8, 197.9.

9-Methyl-3,4-dihydroacridin-1(2H)-one (3g). Off-white solid; yield 91%; mp: 68–70 °C; ¹H NMR (400 MHz, CDCl₃) δ 8.19 (d, J = 8.4 Hz, 1H), 8.00 (d, J = 8.4 Hz, 1H), 7.76 (t, J = 7.6 Hz, 1H), 7.55 (t, J = 8.0 Hz, 1H), 3.26 (t, J = 6.4 Hz, 2H), 3.03 (s, 3H), 2.80 (t, J = 6.8 Hz, 2H), 2.22–2.18 (m, 2H); ¹³C NMR (100 MHz, CDCl₃) δ 16.0, 21.3, 34.7, 41.0, 125.3, 125.4, 126.3, 127.6, 129.1, 131.5, 147.9, 149.9, 162.1, 200.6.

Acknowledgements

We thank the management of VIT University for providing all research facilities to carry out this work. Mainly we also thank VIT-SIF-DST-FIST for providing NMR facilities, IIT Chennai and Gandhigram Rural University for characterization of the nanoparticles. This study was supported by the Deanship of Scientific Research, College of Science Research Centre, King Saud University, Saudi Arabia.

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Footnote

† Electronic supplementary information (ESI) available. See DOI: 10.1039/c5ra25975d

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