Biosynthesized Silver Nanoparticles Catalyzed Aqueous-Phase Synthesis of Isoxazol-5(4H)-One Derivatives

Abhimanyu Pawar¹*, Kishor Naktode¹, Arvind Mungole², Dalesh Parshuramkar³

¹Department of Chemistry, Nevjabai Hitkarini College, Bramhapuri, Maharashtra 441206, India.

²Department of Botany, Nevjabai Hitkarini College, Bramhapuri, Maharashtra 441206, India.

³Department of Physics, Nevjabai Hitkarini College, Bramhapuri, Maharashtra 441206, India.

*Corresponding Author E-mail: abhaypawar1988@gmail.com

ABSTRACT:

We developed a sustainable and efficient protocol for synthesizing isoxazol-5(4H)-one derivatives using green synthesized silver nanoparticles as a green nonocatalyst. The one-pot, three-component reaction of aromatic aldehydes, ethyl acetoacetate, and hydroxylamine hydrochloride proceeded smoothly in aqueous phase at room temperature, affording the target compounds in high to excellent yields with short reaction times. The plant-derived silver nanoparticles demonstrated exceptional catalytic activity while offering advantages such as low toxicity, cost-effectiveness, and easy handling. Notably, electron-donating substituents on the aromatic aldehydes enhanced reactivity, whereas steric and electronic factors influenced reaction efficiency. This method aligns with green chemistry principles by eliminating organic solvents, minimizing energy consumption, and utilizing a biodegradable catalyst. The protocol provides a practical, eco-friendly, and scalable approach to heterocyclic synthesis, making it a valuable addition to sustainable organic transformations.

KEYWORDS: Isoxazol-5(4H)-one, Silver nanoparticle, Benzaldehyde, Green synthesis, Mild conditions.

INTRODUCTION:

A catalyst is a chemical entity that facilitates the acceleration of a chemical transformation by offering an energetically favorable alternative reaction pathway, thereby reducing the activation energy barrier, without undergoing net chemical change in the overall reaction cycle¹. Although it may transiently engage in intermediate complex formation during the reaction mechanism, the catalyst is regenerated at the end of the catalytic cycle and thus remains stoichiometrically unaltered.

Catalysis functions through the provision of active sites that promote the stabilization of high-energy transition states or facilitate the generation of reactive intermediates, enabling an enhanced reaction rate for both the forward and reverse processes, while preserving the equilibrium position of the system.

Catalysts are characterized by three principal physicochemical properties such as catalytic activity, referring to their ability to accelerate reaction kinetics; selectivity, which determines the preferential formation of specific products; and, in the context of heterogeneous catalysis, recyclability and stability, which are essential for long-term operational viability. Catalysis constitutes a foundational pillar in modern chemical science, addressing a broad spectrum of global challenges, particularly in the realms of sustainable energy production, green chemical manufacturing, and environmental remediation. In synthetic organic chemistry, the deployment of catalytic systems is indispensable for enabling atom-economic, regioselective, and stereoselective transformations under mild and environmentally benign conditions². Catalytic systems are conventionally bifurcated into two distinct categories: homogeneous and heterogeneous catalysts³^,⁴. Homogeneous catalysts, residing in the same phase as the reactants (typically in solution), afford uniform distribution of active sites and often exhibit superior selectivity and molecular-level tunability. However, their widespread application is hindered by practical limitations, including laborious separation procedures, limited recyclability, and potential leaching or contamination of the final product. Conversely, heterogeneous catalysts—operating in a distinct phase from the reactants—exhibit several operational advantages, such as facile separation, enhanced thermal and mechanical stability, and reusability across multiple catalytic cycles. These features render heterogeneous catalysis particularly amenable to integration within continuous-flow processes and align closely with the core principles of green chemistry, including waste minimization, resource efficiency, and process intensification. The advent of nanotechnology has revolutionized, giving rise to nano-catalysis, where nanoparticles (NPs) serve as highly efficient catalytic platforms. Nano-catalysts exhibit exceptional properties, such as enhanced surface reactivity and high surface area-to-volume ratios, which confer superior activity, selectivity, and stability compared to bulk materials⁵. These attributes facilitate reactions under milder conditions, with reduced energy consumption and improved yields, making them indispensable in sustainable synthetic methodologies^6,7. Among metal-based nano-catalysts, silver nanoparticles have emerged as particularly promising due to their cost-effectiveness, ease of synthesis, high atom economy, recyclability, and robust catalytic performance^8,9,10,11.

Leveraging these advancements, our prior work established a green synthesis protocol for silver nanoparticles^12,13 as nano-catalyst using plant-derived reductants, offering an eco-friendly and scalable preparation method^14,15,16. In the present study, we employ these biosynthesized or green synthesized silver nanoparticles as heterogeneous catalysts for the synthesis of isoxazol-5(4H)-one derivatives a pharmacologically significant heterocyclic scaffold^17,18. This methodology operates under ambient conditions in aqueous media, ensuring sustainability while maintaining high efficiency. The catalytic system demonstrates excellent reactivity, recyclability, and compatibility with diverse substrates, underscoring the potential of green synthesized silver nanoparticles in advancing green and sustainable organic synthesis.

MATERIALS AND METHODS:

All starting materials and solvents were procured from SD Fine Chemicals Ltd., Mumbai, and used without further purification. Prior to use, all glassware and equipment were thoroughly cleaned and sterilized to ensure optimal hygiene and prevent contamination. The melting points of the synthesized compounds were determined using an electrothermal melting point apparatus and are reported as uncorrected values. Reaction progress was monitored by thin-layer chromatography (TLC) on pre-coated silica gel plates, with visualization under UV light. Purification of the synthesized compounds was achieved through recrystallization from ethanol to ensure high purity. The preferred plant Rumex nepalensis (Spreng.) was collected from the Bramhapuri area of Chandrapur district in Maharashtra state, India, and used to prepare silver nanoparticles. Silver nitrate (AgNO3) was procured from Sigma-Aldrich chemical.

GENERAL PROCEDURE:

A mixture of ethyl acetoacetate (1 mmol), aryl aldehyde (1 mmol), hydroxylamine hydrochloride (1 mmol), and biosynthesized silver nanoparticles (15 mol%) was suspended in distilled water in a Schlenk tube¹⁹. The reaction mixture was stirred at room temperature, and the progress was monitored by thin-layer chromatography (TLC). Upon completion (reaction times summarized in Table 2), the mixture was filtered, and the residue was dissolved in hot ethanol. The catalyst was recovered by filtration and reused for subsequent reactions. The filtrate was allowed to cool, and the product was isolated via recrystallization from hot ethanol, yielding the pure isoxazol-5(4H)-one derivatives in high yields. The identity of known compounds was confirmed by comparing their melting points with literature values.

RESULTS AND DISCUSSIONS:

The investigation commenced with the physicochemical characterization of green-synthesized silver nanoparticles as Nano-catalyst employing standard analytical techniques, as outlined in our previously published literature²⁰. After analysis revealed that the silver nanoparticles were highly dispersed, predominantly spherical in shape, and had an average size ranging from 19 to 28 nm. For the model reaction, we employed a multicomponent condensation system comprising benzaldehyde, hydroxylamine hydrochloride, and ethyl acetoacetate in water as solvent, nanocatalyzed by 15 mol% of the synthesized silver nanoparticles (Scheme 1).

Scheme 1: Model Reaction

1. Effect of solvent

Initial optimization studies focused on solvent effects, where various solvents including n-hexane, acetone, ethanol, methanol, and water were systematically evaluated (Table 1). Remarkably, the aqueous system demonstrated superior catalytic performance, exhibiting both accelerated reaction kinetics and enhanced product yields compared to organic solvents. This pronounced aqueous-phase enhancement likely stems from improved mass transfer and effective interactions between the polar reactants and the silver nanoparticles catalyst surface. Furthermore, the use of water as a green solvent aligns with sustainable chemistry principles while maintaining excellent reaction efficiency. These findings highlight the critical importance of solvent selection in heterogeneous catalytic systems, particularly emphasizing the advantages of aqueous media for this transformation.

Table 1: Model reaction using different solvents.

Sr. No.	Solvent	Catalyst (Mol %)	Time (Min)	% Yields
1	Ethanol	15	90	40
2	Methanol	15	90	43
3	n-hexane	15	90	29
4	Acetone	15	90	61
5	Water	3	90	40
6	Water	6	90	52
7	Water	9	90	71
8	Water	12	90	88
9	Water	15	90	92 (Present Work)
10	Water	18	90	92
11	Water	21	90	93

2. Effect of concentration:

The graph (Fig. 1) shows how the amount of silver nanoparticle catalyst affects the reaction yield. When we increase the catalyst from 5% to 15%, the yield improves significantly from 66% to 93%. This means more catalyst provides more active sites, helping the reaction happen faster and more efficiently. However, adding even more catalyst (20% or 25%) does not increase the yield further it stays around 94%. This suggests that beyond 15%, the reaction doesn’t benefit from extra catalyst, likely because all the necessary active sites are already being used. Experiments without any silver nanoparticles gave almost no product, proving that these nanoparticles are crucial for the reaction. The best balance is 15% catalyst, which gives the highest yield without wasting extra material.

Fig.1: The influence of catalyst loading on the model reaction’s efficiency was investigated.

3. Effect of substituent:

The results revealed pronounced electronic effects, with electron-donating groups such as hydroxygroup, Methoxy group, methyl group significantly enhancing reaction kinetics and product yields. This acceleration can be attributed to increased electron density at the carbonyl carbon of the aldehyde moiety, which facilitates the rate-determining nucleophilic attack by hydroxylamine. Particularly noteworthy was the enhanced reactivity of para- and meta-substituted aldehydes, which afforded products in more than 90% yield within less time. These observations align with previous reports demonstrating the superior reactivity of electron-rich benzaldehydes in analogous heterocyclic formations^21,22.

Conversely, substrates bearing electron-withdrawing substituents such as chloro group, nitro group etc exhibited markedly reduced reactivity, with several cases failing to reach completion even after extended reaction times. This electronic deactivation results from decreased electrophilicity of the carbonyl carbon, as established in prior mechanistic studies. A particularly instructive comparison emerged from the positional isomers of hydroxy-benzaldehydes, where steric constraints in ortho-substituted derivatives led to both prolonged reaction times and diminished yield compared to their para- and meta-counterparts. This steric hindrance effect, quantified for the first time in this catalytic system, demonstrates the delicate balance between electronic and steric factors in governing reaction efficiency^23,24.

The robust performance of this silver nanoparticles catalysed system, particularly with electron-rich substrates, establishes a practical and sustainable protocol for isoxazolone synthesis. The comprehensive substituent effects documented in this study provide valuable insights for predicting reactivity patterns in related heterocyclic formations. (as shown the Table-2)

Table 2: Silver nanoparticles as noncatalyzed synthesis of various synthesis of isoxazole-5(4H)-one derivatives.

Sr. No.	Aldehyde	Products	Time (Min)	Isolated % Yield	M.P (^0C) Found                   Reported [Ref]
1	m-OHC6H4CHO	4a	90	92	200-203	202 – 203^25
2	p-OMeC6H4CHO	4b	75	90	173 - 176	173 -175^26
3	p-MeC6H4CHO	4c	70	93	126 -129	129 -131^27
4	C6H5CHO	4d	80	92	140–143	142–144^28
5	p-ClC6H5CHO	4e	200	-	-	Rare^29
6	C6H5CH=CHCHO	4f	75	91	170–173	173–178^30
7	3-OH-4-OCH3C6H3CHO	4g	70	92	185–187	185–187^31
8	C4H3SCHO	4h	85	91	145–147	144–146^32
9	p-OHC6H4CHO	4i	70	92	212 – 215	212 – 215^33
10	C6H5CHO2N	4j	150	-	-	Rare^34
11	C4H3OCHO	4k	85	91	238–241	238–241^35
12	p-OHC8H7O2CHO	4l	70	92	214–217	211–214^36
13	o-OHC6H4CHO	4m	95	89	195 - 197	195 – 197^37
14	o-OMe-C6H4CHO	4n	85	91	159 -162	162 -164^38
15	4-N(CH3)2 -C6H4CHO	4o	65	93	207-210	206-209^39

4. Effect of Recycling the catalyst:

An intriguing aspect of this method is that the silver nanoparticles, used as nano-catalysts, can be recovered and reused multiple times without any loss in their catalytic efficiency during the model reaction. To recover the catalyst after finishing the reaction, the mixture was filtered, and the catalyst was cleansed with chloroform. After drying, it was employed in the same reaction. This process was reiterated for four cycles, and the yield of product remained relatively constant (Table 3). These outcomes strongly indicate the stability of silver nanoparticles in the reaction medium, as well as their ability to be recovered and reused without a significant decline in their activity (fig. 2).

Table 3: Recycling the catalyst in the experiment involving the reaction was performed.

Entry	No. of repetition	%Yield	Time (Min)
1	1(Fresh)	92	90
2	2	90	90
3	3	90	90
4	4	85	90

Fig. 2. Recycling of the catalyst used in the experiment.

Table 4: Overview of various catalysts employed for the synthesis of isoxazol-5(4H)-one derivatives and their corresponding evaluation parameters.

Sr. No.	Mol. %	Catalyst	Condition	Minutes	% Yield R
1	30	Cetyltrimethylammonium chloride	Water, 90 0C	240	8940
2	30	γ-Alumina	Water, reflux		8041
3	100	Pyridine	Water, Ultrasound	90	6742
4	22	Antimony trichloride	Water, rt	120	8543
5	100	Pyridine	EtOH, reflux	120	52.544
6	15	Silver nanocatalyst	Water, rt	90	92 Present work

5. Effect of different catalysts:

Further, conducted a comparative analysis to evaluate the catalytic efficiency of synthesized silver nanoparticles, as outlined in Table 4. The results unequivocally showcased the remarkable catalytic activity of these nanoparticles, leading to significantly enhanced yields of the desired product. This improved catalytic performance can be ascribed to the substantial surface area of the synthesized silver nanoparticles, facilitating heightened adsorption of reactants on their surfaces. These encouraging outcomes prompted the adoption of synthesized silver nanoparticles in subsequent test reactions, resulting in a notable reduction in reaction times. This enhancement in catalytic activity is primarily attributed to the nanoparticles' expanded surface area and their improved dispersion within the reaction mixture. These findings underscore the potential of synthesized silver nanoparticles as highly effective catalysts for various chemical reactions, holding promise for applications in diverse fields. This methodology presents safety, a recyclable, cost-effectiveness, atom economy catalyst, and exceptional tolerance for various functional groups in the synthesis of diverse isoxazol-5(4H)-one derivatives. Consequently, the significance and versatility of isoxazol-5(4H)-one derivatives are extensive and multifaceted.

6. Possible mechanism:

The product formation follows a well-established reaction mechanism, illustrated in Figure 5. Initially, silver nanoparticles as nanocatalyse the activation of the carbonyl carbon in ethyl acetoacetate. Subsequently, the hydroxyl (-OH) and amino (-NH₂) groups in hydroxylamine hydrochloride act as nucleophiles, attacking both carbonyl carbons in ethyl acetoacetate, facilitated by the presence of silver nanoparticles. This leads to the formation of a cyclic adduct. The adduct then reacts with an aldehyde, initiating a condensation reaction. This reaction not only yields the desired product but also eliminates a water molecule and removes silver nanoparticles from the reaction, ensuring the purity of the final product.

Fig. 5. Possible mechanism for all the synthesized compounds.

CONCLUSIONS:

To recap, we have presented an efficient methodology for the one-pot synthesis of isoxazol-5(4H)-one derivatives utilizing silver nanoparticles as nano-catalyst. These nanoparticles exhibit reusability and are non-toxic. The primary merits of this approach encompass high product yields, straightforward experimental protocols, brief reaction durations, compatibility with various substrates, facile work-up procedures, avoidance of hazardous organic solvents, and the convenience of catalyst recovery and recycling. These attributes render it a valuable, appealing, and environmentally benign strategy for the preparation of isoxazol-5(4H)-one derivatives. This has promising prospects in materials science, agrochemicals, medicinal chemistry, pharmaceutical intermediates, photo stabilizers, photodynamic therapy, and biochemical research. Consequently, these derivatives maintain considerable appeal across various scientific and industrial domains, offering substantial potential for future progress and creativity.

CONFLICT OF INTEREST:

The authors have no conflicts of interest regarding this investigation.

ACKNOWLEDGMENTS:

The authors gratefully acknowledge the Principal of Nevjabai Hitkarini College, Bramhapuri, District Chandrapur (Maharashtra), for their valuable support and for providing the necessary laboratory facilities to carry out this research work.

REFERENCES:

1. Anna Pratima Nikalje, Amogh C. Tathe, Mangesh S. Ghodke. Biocatalysis: A Brief Review. Asian J. Research Chem. 2011; 4(9): 1355-1360.

2. Afewerki S, Cordova A. Combinations of aminocatalysts and metal catalysts: a powerful cooperative approach in selective organic synthesis. Chemical Reviews. 2016; 116(22): 13512–13570. doi: 10.1021/acs.chemrev.6b00226

3. Ch. V. Subbarao, K.V. Dharma Rao, T. Srinivas, Sumana V.S, Krishna Prasad K.M.M. Review on Heterogeneous Catalysis for Biodiesel Production. Asian J. Research Chem. 2011; 4(4):   524-536.

4. Raghu Ram G., Rohit K., Srikanth P., Subbarao Ch. V., Krishn Prasad K. M. M. Homogeneous Catalysis for Biodiesel Production- A Review. Asian J. Research Chem. 2011; 4(6):  873-878.

5. Sharma N, Ojha H, Bharadwaj A, Pathak DP, Sharma RK. Preparation and catalytic applications of nanomaterials: a review. RSC Advances. 2015; 5(66): 53381–53403. doi: 10.1039/C5RA06778B.

6. Abady MM, Mohammed DM, Soliman TN, Shalaby RA, Sakr FA. Sustainable synthesis of nanomaterials using different renewable sources. Bulletin of the National Research Centre. 2025; 49(1): 24. doi: 10.1186/s42269-025-01316-4.

7. Raviraj M. Kulkarni, Manjunath S. Hanagadakar, Ramesh S. Malladi. Silver (I) catalyzed and uncatalyzed oxidation of levofloxacin with aqueous chlorine: A comparative kinetic and mechanistic approach. Asian J. Research Chem. 2013; 6(12): 1124-1132.

8. Athar Jamal, Ayesha Maqsood. Review of Synthesis of Silver Nanoparticles from different Medicinal Plants and their Pharmacological Activities. Asian J. Pharm. Tech. 2021; 11(1): 88-93.

9. Jain K, Takuli A, Gupta TK, Gupta D. Rethinking nanoparticle synthesis: a sustainable approach vs. traditional methods. Chemistry–An Asian Journal. 2024; 19(21): e202400701. doi: 10.1002/asia.202400701.

10. Shahzadi S, Fatima S, Shafiq Z, Janjua MRSA. A review on green synthesis of silver nanoparticles (SNPs) using plant extracts: a multifaceted approach in photocatalysis, environmental remediation, and biomedicine. RSC Advances. 2025; 15(5): 3858–3903. doi: 10.1039/D4RA07519F.

11. Dawle J. K., Mathapati S. R., Bondge A. S., Momin K. I.. Green Synthesis of Novel Heterocycles Carrying Triazole Derivatives of Dihydropyrimidine. Asian J. Research Chem. 2012; 5(6): 707-711.

12. Sonali P. Mahaparale, Reshma S. Kore. Silver Nanoparticles: Synthesis, Characterization, Application, Future Outlook. Asian J. Pharm. Res. 2019; 9(3): 181-189.

13. S. Sathish Kumar, G. Melchias, P. Ravikumar, R. Chandrasekar, P. Kumaravel. Bioinspired synthesis of silver nanoparticles using Euphorbia hirta leaf extracts and their antibacterial activity. Asian J. Pharm. Res. 2014; 4(1): 39-43.

14. Manohar V Lokhande, Priyaka R. Kokate, Khushi M. Sapkale, Mitali M. Tendulkar. Bio-Synthesis of AgNPs and MnNPs of Philodendron giganteum Herbal Extract and catalysis’s activity. Asian Journal of Research in Pharmaceutical Sciences. 2024; 14(2): 122-8.

15. C. Thiruppathi, P. Kumaravel, R. Duraisamy, AK. Prabhakaran, T. Jeyanthi, R. Sivaperumal, P.A. Karthick. Biofabrication of Silver nanoparticles using Cocculus hirsutus leaf extract and their antimicrobial efficacy. Silver nanoparticles, Cocculus hirsutus, Antimicrobial activity. Asian J. Pharm. Tech. 2013; 3(3): 93-97. .

16. Chowdhury SS, Ibnat N, Hasan M, Ghosh A. Medicinal Plant-Based nanoparticle synthesis and their diverse applications. In: Ethnopharmacology and OMICS Advances in Medicinal Plants Volume 2: Revealing the Secrets of Medicinal Plants. Singapore: Springer Nature Singapore; 2024:213–250. doi: 10.1007/978-981-97-4292-9_10.

17. Manohar V Lokhande, Priyaka R. Kokate, Khushi M. Sapkale, Mitali M. Tendulkar. Bio-Synthesis of AgNPs and MnNPs of Philodendron giganteum Herbal Extract and catalysis’s activity. Asian Journal of Research in Pharmaceutical Sciences. 2024; 14(2): 122-8.

18. Pandhurnekar CP, Pandhurnekar HC, Mungole AJ, Butoliya SS, Yadao BG. A review of recent synthetic strategies and biological activities of isoxazole. Journal of Heterocyclic Chemistry. 2023; 60(4): 537–565. doi: 10.1002/jhet.4586.

19. Pawar A, Mungole AJ, Naktode KS. Biosynthesized ZnO nanoparticles from Rumex nepalensis (Spreng.) plant extract serve as efficient catalysts for the aqueous synthesis of 4H-isoxazol-5-one derivatives. The Bioscan. 2023; 18(1): 21–28. https://thebioscan.com/index.php/pub/article/view/485

20. Pawar AP, Naktode KS, Mungole AJ. Green synthesis of silver nanoparticles from whole plant extract analyzed for characterization, antioxidant, and antibacterial properties. Physics and Chemistry of Solid State. 2023; 24(4): 640–649. doi: 10.15330/pcss.24.4.640-649.

21. Mosallanezhad A, Kiyani H. Green synthesis of arylideneisoxazol-5-ones catalyzed by silicon dioxide nanoparticles. Polycyclic Aromatic Compounds. 2024; 44(8): 5022–5037. doi: 10.1080/10406638.2023.2259564.

22. Maleki B, Chahkandi M, Tayebee R, Kahrobaei S, Alinezhad H, Hemmati S. Synthesis and characterization of nanocrystalline hydroxyapatite and its catalytic behavior towards synthesis of 3,4-disubstituted isoxazole-5(4H)-ones in water. Applied Organometallic Chemistry. 2019; 33(10): e5118. doi: 10.1002/aoc.5118.

23. Kiyani H, Mosallanezhad A. Sulfanilic acid-catalyzed synthesis of 4-arylidene-3-substituted isoxazole-5(4H)-ones. Current Organic Synthesis. 2018; 15(5): 715–722. doi: 10.2174/1570179415666180423150259.

24. Maleki B, Chahkandi M, Tayebee R, Kahrobaei S, Alinezhad H, Hemmati S. Synthesis and characterization of nanocrystalline hydroxyapatite and its catalytic behavior towards synthesis of 3,4-disubstituted isoxazole-5(4H)-ones in water. Applied Organometallic Chemistry. 2019; 33(10): e5118. doi: 10.1002/aoc.5118.

25. Safari J, Ahmadzadeh M, Zarnegar Z. Sonochemical synthesis of 3-methyl-4-arylmethylene isoxazole-5(4H)-ones by amine-modified montmorillonite nanoclay. Catalysis Communications. 2016; 86: 91–95. doi: 10.1016/j.catcom.2016.08.018.

26. Shitre GV, Patel AR, Ghogare RS. Green synthesis of 3,4-disubstituted isoxazol-5(4H)-one using gluconic acid aqueous solution as an efficient recyclable medium. 2023. http://doi.org/10.25135/acg.oc.151.2304.2762

27. Bashash Rikani A, Setamdideh D. One-pot and three-component synthesis of isoxazol-5(4H)-one derivatives in the presence of citric acid. Oriental Journal of Chemistry. 2016; 32: 1433–1437. doi: 10.13005/ojc/320317.

28. Liu Q, Hou X. One-pot three-component synthesis of 3-methyl-4-arylmethylene-isoxazol-5(4H)-ones catalyzed by sodium sulfide. Phosphorus, Sulfur, and Silicon and the Related Elements. 2012; 187: 448–453. doi: 10.1080/10426507.2011.621003.

29. Pawar AP, Naktode KS, Mungole AJ. Efficiently synthesize isoxazol-5(4H)-one derivatives in aqueous medium using CuO nanoparticles catalysis with a biosynthesized approach. Heterocyclic Letters. 2025; 15(2): 377–393. http://heteroletters.org

30. Cheng Q. One-pot synthesis of 3-methyl-4-arylmethylene-isoxazol-5(4H)-ones in aqueous media under ultrasonic irradiation. Chinese Journal of Organic Chemistry. 2009; 29(8): 1267.

31. Vekariya RH, Patel KD, Patel HD. Fruit juice of Citrus limon as a biodegradable and reusable catalyst for facile, eco-friendly and green synthesis of 3,4-disubstituted isoxazol-5(4H)-ones and dihydropyrano[2,3-c]pyrazole derivatives. Research on Chemical Intermediates. 2016; 42: 7559–7579. doi: 10.1007/s11164-016-2553-4.

32. Kiyani H, Darbandi H, Mosallanezhad A, Ghorbani F. Research on Chemical Intermediates. 2015; 41: 7561. doi: 10.1007/s11164-014-1844-x.

33. Khandebharad AU, Sarda SR, Gill CH, Agrawal BR. Synthesis of 3-methyl-4-arylmethylene-isoxazol-5(4H)-ones catalyzed by tartaric acid in aqueous media. Research Journal of Chemical Sciences. 2015.

34. Pawar AP, Naktode KS, Mungole AJ. Efficiently synthesize isoxazol-5(4H)-one derivatives in aqueous medium using CuO nanoparticles catalysis with a biosynthesized approach. Heterocyclic Letters. 2025; 15(2): 377–393. http://heteroletters.org

35. Setamdideh D. Dowex® 50WX4/H₂O: A green system for a one-pot and three-component synthesis of isoxazol-5(4H)-one derivatives. Journal of the Mexican Chemical Society. 2015; 59: 191–197.

36. Kiyani H, Samimi HA. Nickel-catalyzed one-pot, three-component synthesis of 3,4-disubstituted isoxazole-5(4H)-ones in aqueous medium. Chiang Mai Journal of Science. 2017; 44: 1011–1121.

37. Kalhor M, Samiei S, Mirshokraie SA. MnO₂@Zeolite-Y nanoporous: preparation and application as a highly efficient catalyst for multi-component synthesis of 4-arylidene-isoxazolidinones. Silicon. 2021; 13: 201–210. doi: 10.1007/s12633-020-00413-5.

38. Mirzazadeh M, Mahdavinia GH. Fast and efficient synthesis of 4-arylidene-3-phenylisoxazol-5-ones. E-Journal of Chemistry. 2012; 9: 425–429. doi: 10.1155/2012/562138.

39. Setamdideh D. Dowex® 50WX4/H₂O: A green system for a one-pot and three-component synthesis of isoxazol-5(4H)-one derivatives. Journal of the Mexican Chemical Society. 2015; 59(3): 191–197.

40. Wu M, Feng Q, Wan D, Ma J. CTACl as catalyst for four-component, one-pot synthesis of pyranopyrazole derivatives in aqueous medium. Synthetic Communications. 2013; 43(12): 1721–1726. doi: 10.1080/00397911.2012.666315.

41. Mecadon H, Rohman MR, Rajbangshi M, Myrboh B. γ-Alumina as a recyclable catalyst for the four-component synthesis of 6-amino-4-alkyl/aryl-3-methyl-2,4-dihydropyrano[2,3-c]pyrazole-5-carbonitriles in aqueous medium. Tetrahedron Letters. 2011; 52(19): 2523–2525. doi: 10.1016/j.tetlet.2011.03.036.

42. Cheng Q. One-pot synthesis of 3-methyl-4-arylmethylene-isoxazol-5(4H)-ones in aqueous media under ultrasonic irradiation. Chinese Journal of Organic Chemistry. 2009; 29(8): 1267.

43. Pourmousavi SA, Fattahi HR, Ghorbani F, Kanaani A, Ajloo D. A green and efficient synthesis of isoxazol-5(4H)-one derivatives in water and a DFT study. Journal of the Iranian Chemical Society. 2018; 15: 455–469. doi: 10.1007/s13738-017-1246-2.

44. Zhang YQ, Ma JJ, Wang C, Li JC, Zhang DN, Zang XH, Li J. Chinese Journal of Organic Chemistry. 2008; 28: 141. doi: 10.3184/174751911X13176501108975.

Received on 19.07.2025      Revised on 11.08.2025

Accepted on 30.08.2025      Published on 30.09.2025

Available online from October 07, 2025

Asian J. Research Chem.2025; 18(5):311-318.

DOI: 10.52711/0974-4150.2025.00047

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