Plant mediated synthesis of flower-like Cu2O microbeads from Artimisia campestris L. extract for the catalyzed synthesis of 1,4-disubstituted 1,2,3-triazole derivatives

This study presents a novel method for synthesizing 1,4-disubstituted 1,2,3-triazole derivatives through a one-pot, multi-component addition reaction using flower-like Cu2O microbeads as a catalyst. The flower-like Cu2O microbeads were synthesized using an aqueous extract of Artimisia Campestris L. This extract demonstrated the capability to reduce and stabilize Cu2O particles during their initial formation, resulting in the formation of a porous flower-like morphology. These Cu2O microbeads exhibit distinctive features, including a cubic close-packed (ccp) crystal structure with an average crystallite size of 22.8 nm, bandgap energy of 2.7 eV and a particle size of 6 µm. Their catalytic activity in synthesizing 1,4-disubstituted 1,2,3-triazole derivatives was investigated through systematic exploration of key parameters such as catalyst quantity (1, 5, 10, 15, 20, and 30 mg/mL), solvent type (dimethylformamide/H2O, ethanol/H2O, dichloromethane/H2O, chloroform, acetone, and dimethyl sulfoxide), and catalyst reusability (four cycles). The Cu2O microbeads significantly increased the product yield from 20% to 85.3%. The green synthesis and outstanding catalytic attributes make these flower-like Cu2O microbeads promising, efficient, and recyclable catalysts for sustainable and effective chemical transformations.

Cuprous oxide (Cu 2 O) has emerged as a versatile and efficient heterogenous catalyst for a wide range of organic synthesis reactions, offering greener and more sustainable alternatives to traditional methods (Yadav et al., 2019).Cu 2 O proves effective in C-H arylation reactions, facilitating the introduction of aryl groups into organic compounds, and it plays a role in carbon-carbon coupling reactions.Its unique properties make it particularly well-suited for catalyzing diverse transformations (click reactions, redox reactions, crosscoupling reactions, hydrolyzation, C-H activation) in organic chemistry (Ojha et al., 2017).For instance, Cu 2 O micro/ nanoparticles facilitates controlled oxidation, converting alcohols to carbonyl compounds, and is involved in reduction reactions, reducing nitro compounds to amino compounds (Yadav et al., 2019).They have been also employed as catalysts for the copper(I)-catalyzedazide-alkyne cycloaddition (CuAAC) reaction (Varzi et al., 2021), which provides an efficient and eco-friendly route tosynthesize1,2,3-triazole derivatives (Moeini-Eghbali and Eshghi, 2023).This method eliminates the need for toxic and moisture-sensitive reagents often used in traditional approaches, showcasing the green chemistry aspect of Cu 2 O catalysis (Moeini-Eghbali and Eshghi, 2023).Another remarkable example is the synthesis of arylamines via the reduction of nitro compounds, and the use of Cu 2 O nanoparticles as a catalyst which minimizes the use of hazardous reagents and reduces waste production (Sasmal et al., 2016;Roemer et al., 2022).
Traditionally, Cu 2 O micro/nanoparticles have been synthesized using various techniques such as microwave irradiation, vapor deposition, thermal decomposition, and electrochemical methods (Mallik et al., 2020).However, these methods come with some limitations, encompassing challenges related to scalability and purification, substantial energy consumption, and the use of hazardous chemicals (Le et al., 2021).To overcome these challenges, green synthesis methods using plant extracts and microorganisms have been developed for producing Cu 2 O particles.Plant extracts are often preferred for their simplicity and rapid reduction capabilities, whereas microorganisms offer versatility and the potential for controlled synthesis under specific conditions (Varghese et al., 2020).Numerous studies have reported successful synthesis of Cu 2 O particles using plant extracts, including banana pulp waste (Torres-Arellano et al., 2021), Aloe vera (Kerour et al., 2018), Piper longum (Murphin Kumar et al., 2020), and Cressa leaf (Hui et al., 2022) extracts.These methods not only align with sustainable and eco-friendly principles but also contribute to the expansion of green nanotechnology in the production of Cu 2 O NPs for diverse applications (Waris et al., 2021).
This study explores the synthesis of flower-like Cu 2 O microbeads using an aqueous extract of Artimisia Campestris L., which are subsequently employed as catalysts in the synthesis of 1,4disubstituted 1,2,3-triazole derivatives.The approach not only leverages natural resources from the Artimisia Campestris L. extract, presenting a sustainable and eco-friendly method for producing catalytic Cu 2 O microbeads but also demonstrates their application in the synthesis of 1,4-disubstituted 1,2,3-triazole derivatives.Characterization of 1,4-disubstituted 1,2,3-triazole derivatives were performed by thin-layer chromatography (TLC), hydrogen nuclear magnetic resonance (H-NMR), carbon-13 nuclear magnetic resonance (C-NMR), Fourier transform infrared red spectroscopy (FTIR), and for Cu 2 O microbeads, X-ray diffraction (XRD), UV-Vis spectroscopy, Infra-Red (FTIR) spectroscopy, and scanning electron microscopy (SEM) are employed.The study extended to discuss the crucial factors to producing 1,4disubstituted 1,2,3-triazole derivatives such as catalyst quantity, solvent choice, and catalyst reusability.Overall, this research holds significant promise in advancing green chemistry principles and contributing to drug discovery.

Plant-mediated synthesis of Cu 2 O microbeads
Fresh leaves of Artimisia Campestris L. were meticulously washed with tap water, followed by a drying at room temperature for 15 days.Subsequently, the dried leaves were ground into a fine powder.The extraction process was carried out through the maceration method.Specifically, 10 g of the powdered leaves were dispersed in 100 mL of hot deionized water (100 °C) in Erlenmeyer flask for duration at 1 h.The resultant extract was subsequently filtered and stored at a temperature of 4 °C for subsequent utilization.About 10 mL of aqueous plant extract mixed with 10 mL a 1 M CuSO 4 .5H 2 O solution.Subsequently, these two solutions were mixed in a suitable ratio under magnetic stirring for 30 min at 70 °C.During the reaction, the initial blue color, attributed to the presence of Cu 2+ ions, transformed into a persistent reddish-brown suspension, signifying the formation of Cu 2 O microbeads as a dispersed phase.The Cu 2 O microbeads were then collected through a centrifugation process, and the resultant particles were dried in an electric oven at 80 °C for duration of 2 h to obtain the Cu 2 O powder sample.
For the synthesis of 1,4-disubstituted 1,2,3-triazoles, a reaction was carried out involving benzyl chloride derivatives (1.0 mmol), sodium azide (3.0 mmol), and alkynes (1.0 mmol) in a DMF:water mixture (8:2).Next, the Cu 2 O microbeads were added into the reaction at a concentration of 20 mg/mL.The reaction mixture was kept under vigorous stirring for duration of 3-4 h at a temperature of 90 °C, and the progression of the reaction was monitored using the TLC.Upon the completion of the reaction, the addition of ice-cold water led to the precipitation of the product.The precipitate was subsequently filtered, washed with water, and subjected to recrystallization from ethanol to obtain 1,4-disubstituted 1,2,3triazoles (Figures 2D-K).To assess the catalyst's reusability, it was recovered from the reaction mixture through centrifugation, followed by filtration and washing with acetone, chloroform, and hot ethanol.Subsequently, it was reused in the next three cycles after drying under the same reaction conditions.

Characterization
UV-vis spectrophotometer (UV-vis, SP-UV 500DB/VDB, Spectrum Instruments, Shanghai) was used to determine the light absorbance and bandgap energy of Cu 2 O microbeads within the wavelength range of 220-600 nm.To assess the crystallinity and crystal structure of Cu 2 O microbeads, X-ray diffraction (XRD, Miniflex 600 Rigaku, Tokyo, Japan) was performed with CuKα radiation (40 kV and 30 mA) at a wavelength of 1.5418 Å, utilizing a scanning speed of 0.5 °.
Chemical bonding in the Cu 2 O microbeads were analyzed using Fourier transform infrared spectroscopy (FTIR, Spectrometer Agilent Cary, 630) covering a spectral range of 4,000-500 cm -1 .The particle size and morphology of Cu 2 O microbeads were examined using scanning electron microscopy (SEM, Thermo Scientific, Quatro, Thermo Fisher Scientific, Germany), and energy-dispersive X-ray (EDX) analysis was used to determine the elemental composition.

Results and discussion
3.1 Characteristics of the Cu 2 O microbeads XRD, FTIR, and UV-Vis spectroscopy plays a crucial role in distinguishing between different copper oxide compounds, such as Cu 2 O and CuO, by observing distinct patterns associated with their crystal structure and functional groups.
The XRD pattern of the Cu 2 O microbeads sample is presented in Figure 3A.The XRD analysis results provided, with intense and sharp peaks at 34.21 °, 36.50 °, 43.28 °, and 51.40 °corresponding to the (111), ( 111), ( 200), and (211) planes, respectively, indicates the presence of the Cu 2 O phase.These peaks are consistent with the The reactions were conducted under vigorous stirring using K 2 CO 3 as a catalyst, DMF as the solvent, with a reaction time of 2 h at a temperature of 80 °C.
The chemical synthesis utilizes 20 mg/mL Cu 2 O microbeads as a catalyst, a DMF:H 2 O mixture as the solvent, with a reaction time of 3 h under reflux conditions at 90 °C.cubic close-packed (ccp) structure of Cu 2 O (JCPDS, card no: 05-0667), no other phases like CuO are detected which indicating the purity of the prepared particles.The average crystallite size of the Cu 2 O microbeads was calculated using the Debye-Scherer formula (D = K λ/β cos θ), resulting in a size of 22.81 nm.Where, λ represents the X-ray wavelength (0.1541 nm), ß is the full width half maximum (in radians), and θ is the diffraction angle.
FTIR spectrum in Figure 3B exhibits several characteristic peaks associated both the inorganic (Cu-O) elements and the phytochemicals within the extract.This indicates that the Cu 2 O microbeads indeed incorporate phytochemicals, as results of the interactions occurring between the organic extract and copper ions throughout the synthesis process.The absorption peak at 610 cm -1 corresponds to Cu-O stretching vibrations in the Cu 2 O microbeads (Mannarmannan and Biswas, 2021), while the absorption peak at 3,100 cm -1 attributed to O-H stretching vibrations.The reduced intensity of this O-H peak is linked to the oxidation of certain O-H groups during the reduction of Cu ions to Cu(I) (Lermontova et al., 2018).The broadened shape of the O-H peak may result from overlap with stretching vibrations of C-H bonds at 2,890 and 2,656 cm -1 , contributing to reduced intensity in the C-H group.This broadening might also come from interactions between O-H groups in organic compounds from the organic extract and Cu + ions, impacting the overall vibrational pattern (Maulana et al., 2022).The presence of atmospheric CO 2 during measurement is shown as peak at 2,120 cm -1 associated with CO 2 stretching vibrations (Kumar et al., 2018).Furthermore, the peaks at 1,608 cm -1 and 1,512 cm -1 correspond to stretching vibrations of C=C and C=O bonds in the ketone (C=O) group, respectively (Maulana et al., 2022).The peak at 1,034 cm -1 is attributed to the C-O stretching vibrations (Dou et al., 2021), and the bending modes of vibration for C-H bonds are indicated by the peak at 685 cm -1 .
UV-Vis spectra in Figure 4A shows a significant absorption peak at 220 nm, providing strong evidence for the successful formation of Cu 2 O rather than CuO.This distinction is supported by previous studies, which note that Cu 2 O and CuO phases exhibit unique absorption patterns in the UV-Vis spectrum due to differences in their electronic structures and bandgap energies.Specifically, CuO is characterized by a distinct absorption peak at around 640 nm, while Cu 2 O displays a primary absorption peak within the 200-270 nm range, corresponding to a red shift in the visible spectrum (Bhardwaj et al., 2019).The bandgap of Cu 2 O microbeads is typically around 2.7 eV (Figure 4B), which places it in the category of a direct bandgap semiconductor (Srinivasan et al., 2021).This further confirms that the prepared microbeads are Cu 2 O and not CuO.The bandgap of CuO is smaller, typically around 1.3-1.7 eV (Jeong et al., 2022).The absorption and bandgap energy values can vary slightly based on factors such as crystal structure, size of the particles, and specific experimental conditions (Djamila et al., 2022).
Several factors exert a significant influence on the shape and particle size of Cu 2 O microbeads, including solution pH, temperature, the quantity of plant extract utilized, and the concentrations of CuSO 4 .5H 2 O applied (Chokkareddy and Redhi, 2018).SEM images in Figure 5A (Pakzad et al., 2019).These findings align with the results obtained from FTIR analysis.
Formation of flower-like Cu 2 O microbeads proposes a comprehensive three-stage growth process (Figure 6).This process undergoes multiple stages as follows: Initial Stage: The

Effect of the amount of the catalyst
The amount of catalyst (measured in mg/mL) plays a key role in the synthesis of 4-((1-benzyl-1H-1,2,3-triazol-4-yl)oxy)-3methoxybenzaldehyde (Figure 7A).The data presented in Table 2   distinctly demonstrates the significant impact of the quantity of the Cu 2 O catalyst on the final product yield.In the DMF: H 2 O solvent system, the increase of the catalyst dosage from 1 mg/mL to 20 mg/ mL, resulting in an increase in product yield: 5.26% ± 2.0%, 15% ± 2.0%, 52% ± 2.0%, 57.9% ± 2.0%, and reaching a maximum of 85.3% ± 2.0% at 20 mg/mL.However, with a further increase in the catalyst dosage to 25 and 30 mg/mL, the yield experienced a slight decrease to 74.6% ± 2.0% and 70% ± 2.0%, respectively.This indicates a clear correlation between the amount of catalyst and the yield of the product.

Effect of the type of solvent
The choice of solvent significantly influences the product yield in the synthesis of 4-((1-benzyl-1H-1,2,3-triazol-4-yl)oxy)-3methoxybenzaldehyde (Figure 7B).The data in Table 2 indicates varied yields for different solvents, demonstrating the critical role of solvent selection in this chemical process.The DMF:H 2 O system exhibited a direct correlation between the amount of catalyst (Cu 2 O microbeads) and product yield, peaking at 85.3% ± 2.0% with 20 mg/ mL of the Cu 2 O microbeads.This combination proved most effective among the solvents tested.Conversely, other solvents, such as EtOH: H 2 O, CHCl 3 , CH 2 Cl 2 :H 2 O, acetone, and DMSO, showed lower yields, ranging from 20% ± 2.0% to 56% ± 2.0% at the same Cu 2 O microbeads dosage (20 mg/mL).The variance in yields underscores the significant impact of different solvents on reaction efficiency, affecting factors like solubility, reactivity, and stability of reactants and catalyst.The DMF: H 2 O system stands out for enabling high yields, highlighting the critical role of solvent selection in optimizing the outcomes of this work.

Effect of the reusability of the Cu 2 O microbeads
Figure 7C shows the effect of the reusability of the Cu 2 O microbeads (initially at 20 mg/mL) on the yield of the organic product across multiple cycles.The initial yield in the first cycle is observed at 85.3% ± 2.0%.However, as the catalyst is reused in subsequent cycles, there is a notable decline in the yield.In the second cycle, the yield drops to 75% ± 2.0%, signifying a reduction from the initial yield despite the catalyst's reuse.This decreasing trend continues in the subsequent cycles, with yields of 50% in the third cycle and a further decrease to 25% ± 2.0% in the fourth cycle.The reduction in product yield over the four cycles indicates a decreasing the catalyst efficiency, likely due to the loss of catalyst during the recovery process (centrifuging) and potential deactivation or alteration of the Cu 2 O microbeads' surface through repeated use.This indicates the need for of implementing strategies for catalyst recovery or regeneration to maintain consistent or improved yields in repeated usage.

Evaluation in the context of prior research
Plant-mediated synthesis of Cu 2 O microbeads involves utilizing plant extracts as reducing and stabilizing agents (Figure 6).Bale et al. (Bale and Reddy, 2022) synthesized face-centered cubic (FCC) Cu 2 O nanoparticles using aqueous extracts of Allium Cepa and Raphanus Sativus, exhibiting average grain sizes ranging from 15 to 30 nm and 12-25 nm, respectively.In a similar vein, Chowdhury et al. (Chowdhury et al., 2021) used Sechium edule extract to synthesize Cu 2 O nanoparticles with a face-centered cubic (fcc) lattice structure and an average crystallite size of 23.2 nm.Kumar et al. (Kumar et al., 2021) synthesized spherical and crystalline Cu 2 O nanoparticles using Andean Capuli Cherry, with an average particle size of approximately 49 nm.Rai et al. (Rai and Chand, 2020) employed rice as a source of reducing and stabilizing agent to synthesize Cu 2 O nanoparticles with homogeneous particle size of 9-10 nm.There is a scarcity of data regarding the synthesis of Cu 2 O microbeads using Artemisia Campestris L. extract, emphasizing the unique contribution of our research.While previous research has showcased Cu 2 O synthesis using plant extracts, the novelty of this work centers on the synthesis of flower-like Cu 2 O microbeads, with unique morphology not reported before.This underscores the originality and potential innovation of this study in the realm of catalyst synthesis via plant-mediated methods.
The recyclability of Cu 2 O microbeads stands out when compared to other catalysts in the synthesis of 4-((1-Benzyl-1H-1,2,3-triazol-4-yl)oxy) benzaldehyde (Table 3).Unlike traditional catalysts that may suffer decreased activity, Cu 2 O microbeads provide an environmentally friendly and sustainable alternative with notable recyclability.In various reactions, including those using Cu(OAc).H 2 O and CuSO 4 .5H 2 O, Cu 2 O microbeads maintain a high yield (70.0%) even after multiple cycles.This underscores their efficiency and stability, making them an economically viable and environmentally friendly option.The recyclability of Cu 2 O microbeads enhances organic synthesis efficiency, aligning with green chemistry principles by reducing waste and minimizing environmental impact.These characteristics emphasize the importance of Cu 2 O microbeads as a sustainable catalyst in organic synthesis.

Conclusion
This study introduces an environmentally conscious approach to fabricate porous flower-like Cu 2 O microbeads, serving as an ecofriendly alternative to conventional physicochemical synthesis methods.Leveraging the unique attributes of Artimisia Campestris L. extract as a dual reducing and stabilizing agent, the study achieved the production of flower-like Cu 2 O microbeads characterized by exceptional catalytic properties.These biogenic porous flower-like Cu 2 O microbeads demonstrated high efficiency as catalyst in the synthesis of 1,4-disubstituted 1,2,3-triazole derivatives through a one-pot, multi-component addition reaction.The outcomes underscore the remarkable capability of Artimisia Campestris L. extract to efficiently reduce, stabilize, and combine the primary formed Cu 2 O particles, resulting in 6 µm microbeads exhibiting a flower-like morphology, an average crystallite size of 22.8 nm.These microbeads exhibit noteworthy catalytic activity, facilitating the synthesis of 1,4-disubstituted 1,2,3triazole derivatives.Systematic investigations into key parameters, including catalyst quantity, solvent type, and catalyst reusability, revealed the catalyst's ability to enhance product's yield from 20% to 85.3%.This exceptional performance underscores the potential of these Cu 2 O microbeads for sustainable and efficient chemical transformations.This study plays a key role in moving towards a greener and more sustainable future.It contributes significantly to the field of catalysis and environmentally friendly materials, offering a promising direction for more eco-conscious chemical processes.
-cclearly show spherical flower-like structures dominating the Cu 2 O microbead morphology.The histogram in Figure 5D illustrates a uniform particle size distribution, indicating that the prepared Cu 2 O microbeads fall within the range of 6 ± 3 µm.To gain further insights into the elemental composition, energy dispersive X-ray spectroscopy (EDX) was employed.The SEM-EDX analysis in Figure 5E reveals a composition predominantly comprised of copper (Cu) at 54.91% and oxygen (O) at 23.73%, aligning with the expected elemental composition of Cu 2 O phase.Notably, the presence of carbon (C) at 21.72% is observed, suggesting adsorption of the phytochemicals from the extract during the synthesis of the Cu 2 O microbes

FIGURE 5 SEM
FIGURE 5 SEM analysis of Cu 2 O microbeads synthesized using Artimisia Campestris L. extract (A-C) SEM images using different magnification, (D) histography showing particle size distribution, and (E) EDX elemental analysis.

FIGURE 6
FIGURE 6Plant extract-mediated synthesis of flower-like Cu 2 O microbeads from aqueous CuSO 4 .5H 2 O and Artemisia Campestris L. Leaf extract without using a reducing or capping agent.

FIGURE 7
FIGURE 7 Effect of the catalyst on the synthesis of 4-((1-benzyl-1H-1,2,3triazol-4-yl)oxy)-3-methoxybenzaldehyde.(A) Effect of the catalyst dose (Cu 2 O microbeads mg/mL) in DMF:H 2 Oas solvent and 3 h reflux; (B) Effect of the type of solvent at Cu 2 O microbeads catalyst dose of 20 mg/mL for 3 h reflux at 90 °C; (C) Effect of catalyst reusability at Cu 2 O microbeads catalyst dose of 20 mg/mL in DMF:H 2 O as solvent and 3 h reflux at 90 °C.All the synthesized products in these tests were confirmed by their melting points and TLC.

TABLE 3
2,oxy)benzaldehyde and some derivatives in different reaction conditions from previous works (Figure2D).