Silver nanoparticles-decorated Preyssler functionalized cellulose biocomposite as a novel and efficient catalyst for the synthesis of 2-amino-4H-pyrans and spirochromenes

Silver nanoparticles-decorated Preyssler functionalized cellulose biocomposite (PC/AgNPs) was prepared and fully characterized by FTIR, UV–vis, SEM, and TEM techniques. The preparation of PC/AgNPs was studied systematically to optimize the processing parameters by Taguchi method using the amount of PC, reaction temperature, concentration of silver nitrate and pH of medium. Taguchi’s L9 orthogonal (4 parameters, 4 level) was used for the experimental design. The SEM analysis confirmed the presence of the Preyssler as a white cloud as well as spherical AgNPs on the surface of cellulose. The formation of AgNPs on the surface was observed by changing of the color from yellow to deep brown and confirmed by UV–vis spectroscopy. The best yield of AgNPs forming was obtained in pH 12.5 at 80 ºC in 20 min. TEM analysis confirmed the formation of spherical AgNPs with a size of 50 nm, at the 1% wt. loading of Preyssler. This easily prepared PC/AgNPs was successfully employed as an efficient, green, and reusable catalyst in the synthesis of a wide range of 2-amino-4H-pyran and functionalized spirochromene derivatives via a one-pot, multicomponent reaction. The chief merits realized for this protocol were the utilization of commercially available or easily accessible starting materials, operational simplicity, facile work-up procedure, obtaining of high to excellent yields of the products and being done under green conditions. The catalyst could be easily separated from the reaction mixture and reused several times without observing any appreciable loss in its efficiency.

Scientific RepoRtS | (2020) 10:14540 | https://doi.org/10.1038/s41598-020-70738-z www.nature.com/scientificreports/ of synthetic organic chemists 94 . Accordingly, there have been a few reports 95 concerning MCRs for the synthesis of spirooxindole derivatives in aqueous media, using a plethora of different catalyst, for example L-proline 96 , TEBA 97 , and NH 4 Cl 96 have been employed in these reactions, enhancing the difficulty of purifications. We are interested in heterocyclic chemistry [98][99][100][101][102][103][104][105][106][107][108] especially in the synthesis of heterocycles via MCR 109,110 being synthesized in the presence of heterogeneous catalysis in water [111][112][113] . In last few decades, our research group has focused on the heteopolyacids and their polyoxmetalates-catalyzed reactions. The results of these achievements have been collected in several review articles, useful to those synthetic organic chemists who are interested in HPAs-catalyzed reactions 114 . We have also recently reported the preparation and applications of immobilized AgNPs [115][116][117][118][119][120] . Based on the points mentioned above and in continuation of our interest in exploring green heterogeneous catalysts for organic transformations resulting in the construction of the heterocyclic systems 111,121,122 , herein we wish to report our successful attempt to apply our novel and fully characterized PC/ AgNPs as an efficient and reusable catalyst in the synthesis of 4H-pyrans and spirochromenes via a one-pot threecomponent cyclocondensation reactions. A wide range of substrates including differently substituted benzaldehydes, isatin derivatives, and acenaphthenequinone are condensed with enolizable C-H activated compounds and alkylmalonates to afford a wide range of the desired products in good high yields (Scheme 1).
Instruments. The Scanning Electron Microscope (SEM) model VP-1450 (LEO, Co., Germany), was used for SEM analysis. For transmission electron microscopy (TEM) analysis, an LEO 912 AB instrument was used. The formation of AgNPs was studied by UV-vis spectra using Milton Roy, Spectvonic 1,001 plus spectrophotometer. Using the ATR method, infrared absorption spectra were recorded in KBr pellets on a VERTEX-70 infrared spectrometer.
Melting points were measured by an electro thermal 9,200 apparatus. IR spectra were recorded on a FT-IR Tensor 27 Spectrophotometer. All products were already known and identified by comparison of their physical (melting points) and spectral (FTIR spectra) data with those of authentic samples and found being identical.
Preparation of PC/AgNPs. In a typical reaction, 5 mL of AgNO 3 solution (1.5 mM) and PC (1.0 g in 10 mL H 2 O), as a catalyst, were stirred at 50-80 °C, during vigorous stirring, hydrochloric acid or sodium hydroxide was added dropwise into the reaction mixture to adjust an appropriate pHs. After 5 min. silver nanoparticles (AgNPs) were precipitated as brown particles at pH = 6-12.5. At equal time intervals, the solutions were analyzed by a UV-vis spectroscopy to monitor the progress of the reaction.
Experimental design by Taguchi method. For experiential design, the Taguchi orthogonal array was applied. All parameters that had important impact on the preparation of AgNPs were selected as well as their levels. The amount of silver nitrate, temperature (°C), the amount of PC and pH were chosen as parameters at four levels. The concentration of silver nitrate was varied from 1.5-6 mM, the synthesis temperature was varied from 50 to 80 °C, the amount of PC was selected 0.13, 0.26, 0.52, 1 gr and the pH adjusted was between 5.5-12.5. Table 1 summarizes all of the parameters and levels used in this experiment.   Tables 4, 5, 6, 7, and 8. The progress of the reaction was monitored by TLC (7:3 n-hexance/ethylacetate). Upon completion of the reaction (indicated by TLC), the mixture was filtered off under reduced pressure. The filtrate was cooled to room temperature and the precipitated solid was separated by filtration under reduced pressure. The respective product was pure enough but was further purified by crystallization from a mixture of EtOH/H 2 O to afford the respective desired product. The products were identified by comparison of their physical properties (melting points) as well as their FTIR spectral with those of already reported authentic compounds and found being identical.

Results and discussion
The interrelationship between the existed parameters for synthesis of nanoparticles to optimize the factors is a time and labor consuming work. Therefore, using statistical experimental design and the Taguchi method, in particular, have been performed by many researchers. Taguchi method can determine the experimental conditions having the least variability as the optimum condition. Not only, it is economical for characterizing a complicated process, but also it uses fewer experiments required in order to study all levels of all input parameters.
In this research, we performed statistical experimental design and Taguchi's robust design concurrently. The statistical experimental design can be well-thought-out as the fresh data analysis, and the Taguchi's robust design can be considered as the signal to noise (S/N) data analysis. The changeability can be conveyed by signal to noise (S/N) ratio.
The effects of silver nitrate concentration, temperature, pH and different loadings PC on the UV-Vis analysis of silver nanoparticles at four different levels (1, 2, 3 and 4) were investigated in Fig. 2 and "plot" is a verb in this context.
Control factors are those design and process parameters that can be controlled in Taguchi method. Noise factors cannot be controlled during production or product use, but can be controlled during experimentation. In a Taguchi designed experiment, we manipulate noise factors to force variability to occur and from the results, identify optimal control factor settings that make the process or product robust, or resistant to variation from the noise factors. Higher values of the signal-to-noise ratio (S/N) identify control factor settings that minimize the effects of the noise factors. Main effects plot in Fig. 2 shows how each factor affects the response characteristic. A main effect exists when different levels of a factor affect the characteristic differently. In Fig. 2, the main effects plot for S/N ratio indicates that pH has the largest effect on the signal-to-noise ratio and after that, temperature shows the largest effect. The amount of PC and AgNO 3 had the same effect on the signal-to-noise ratio. Table 2 in the experimental section, shows the structure of Taguchi orthogonal robust design as well as the mean of S/N ratio for each level along with the UV-vis analysis measurements. In Fig. 2, higher values of the signal-to-noise response variable of one level, indicates a higher utility of that level than the other levels. (Table 2), including in situ one-pot synthesis of AgNPs without additional reducing agents was checked, showing a promising green catalyst with different loading of preyssler to prepare a new nanobiocomposite to catalyze the synthesis of 4H-pyrans. The formation of AgNPs on the surface of PC was observed by color change from white to deep brown in solution and confirmed by UV-vis spectroscopy. Figure 3 exhibits the UV-vis spectra of AgNPs development showing a role of pH.

UV-visible results. With Taguchi experimental conditions
The absorption band at 440 nm is appeared as the result of formation of silver nanoparticles. The increase of the absorption band alongside with an optical color variation clearly showed the Ag + ions were reduced to Ag (0). Ag + can fully be subjected to reduction mediated by biocomposite PC and as a result a nanobiocomposite created www.nature.com/scientificreports/ in brown color at the bottom of the reaction pot. As it can be realized, the generation of AgNPs is related to the pH of the solution, so the best pH for preparation of AgNPs is obtained 12.5 in loading of 1 gr and AgNO 3 6 mM at 70-80 °C. The Preyssler anion make available extremely dispersed charged surfaces, that is perfect for being bounded to the metal ions through their aqueous predecessor solutions. These results suggest that Preyssler acts as reductant and stabilizer, which can lead to releasing the Preyssler in the solution and stabilizing of the AgNPs. This phenomenon strongly inhibited the deposition of AgNPs on the surface of the cellulose biocomposite. This is a common occurrence in the polyoxometalate catalysis when immobilized on different supports.
SeM analysis. Figure  ftiR results. Figure 6a shows the FT-IR spectrum of the microcrystalline cellulose. A strong band at approximately 3,500 cm −1 , is related to the stretching vibration of O-H groups. The characteristic peak around 2,800 cm −1 is attributed to the symmetric C-H vibrations. An adsorption band around 1,700 cm −1 is due to the absorbed water. Additionally, the peaks at around 1,200, and 670 cm −1 are related to the stretching vibration intermolecular ester bonding, and C-OH out-of-plane bending mode, respectively. The existence of the Preyssler on the surface was confirmed by Fig. 6b, as we can see the existed peaks corresponds to Preyssler. Preyssler's contains four kinds of oxygen that are in charge for the bands appeared in fingerprint region (between 1,200 and 600 cm −1 ) in the IR spectrum of Preyssler anion. The distinctive bands of the Preyssler anion, [NaP 5 W 30 O 110 ] 14− are three different bands at 1,163 cm −1 , 1,079 cm −1 , and 1,022 cm −1 , due to P-O stretching, respectively. In addition, two other bands at 941 cm −1 and 913 cm −1 can be ascribed to W-O-W a band at 757 cm −1 is attributed to W=O and a band at 536 cm −1 can be assigned to P-O bending. Interestingly, the above-mentioned bands can be weakly, strongly shifted, or oven covered in changed conditions. In the spectrum of PC, an addition to band appeared at 788 cm −1 , assigned to (Si-O-Si), the band expected at about 1,080 cm −1 (Si-O-Si) was overlapped with the bands of cellulose in the same spectral region. In addition, the sharp band at 1,480 cm −1 is due to nitrate anions. Most of the absorption bands of Preyssler HPA were masked by functionalized cellulose matrix in 600-1,200 cm −1 .
After definite determination structure of the PC/AgNPs catalyst, it was tested as heterogeneous nanocatalyst for the preparation of 2-amino-4H-pyrans through MCR in under green conditions (Table 3).
To find the secured optimal reaction conditions, the consequence of various factors such as catalyst loading, kind of solvent and reaction temperature were examined in a model reaction comprising 4-chlorobenzaldehyde, malononitrile and barbituric acid (Table 3). Among an unalike solvent the mixture of EtOH/H 2 O (1:1, 5 mL) the above reaction was found being proceeded more smoothly, completed in shorter time and giving better yield. As outlined in Table 3, for examining the influence of the catalyst on the progress of the reaction, the above mentioned model reaction was performed in the absence of the PC/AgNPs catalyst under reflux condition in    www.nature.com/scientificreports/ Accordingly, the best result was obtained by employing of 0.025 gr of PC/AgNPs as catalyst in refluxing EtOH/H 2 O. Relied on the optimized reaction conditions, the catalytic activity of PC/AgNPs was examined in the synthesis of various 7-amino-tetrahydro-2H-pyrano[2,3-d] pyrimidines (4a-j) via the three-component reaction of substituted aromatic aldehydes, malononitrile or ethylcyanoacetate and barbituric acid. Differently substituted benzaldehydes involving electron-releasing groups such as (4-methoxybenzaldehyde, 4-methyl benzaldehyde) and electron-with drawing groups such as (4-nitrobenzaldehyde) were utilized successfully in this protocol to provide the desired products (4a-j) in satisfactory yields. In addition, when ethylcyanoacetate was utilized instead of malononitrile the corresponding 2-amino-4H-pyrans (4f.-4j) were obtained. Delightfully, the expected products were obtained in good to excellent yields as exhibited in Table 4.
In order to extend the substrate scope of this approach, we employed dimedone instead of barbituric acid. Three-component reaction of substituted aromatic aldehydes, malononitrile or ethylcyanoacetate and dimedone mediated by PC/AgNPs refluxing EtOH/H 2 O was successfully giving the expected corresponding products in satisfactory yields. The results are underlined in Table 5. As exhibited in the aforementioned table, the reaction of both electron-releasing on benzaldehydes such as 4-methylbenzaldehyde, 2-methoxybenzaldehyde, 3-methoxybenzaldehyde and 4-methoxybenzaldehyde and electron-withdrawing group on bezaldehydes such as 4-nitrobenzaldehyde, 4-chlorobenzaldehyde, 4-hydroxybenzaldehyde proceeded smoothly resulting in the construction of the corresponding products, substituted 2-amino-7,7-dimethyl-5-oxotetrahydro-4H-chromenes (5a-n) in satisfactory yield in relatively short reaction times.
A reasonable mechanism for the synthesis of pyrano [2,3-d] pyrimidinones was proposed as depicted in Scheme 2. It is presumed that, at first the PC/Ag NPs activates the carbonyl group of the aromatic aldehyde by H protonation. Next, the Knoevenagel condensation of activated aromatic aldehyde with malononitrile (2) occurs by the loss of one H 2 O molecule forming arylidenemalononitrile (13). In the second step, the nucleophilic (Michael) addition of the enolizable 1,3-dicarbonyl to arylidenemalononitrile generates intermediates (14). To end, tautomerization gives the corresponding products (tetrahydrobenzo[b]pyrans and pyrano [2,3-d] pyrimidinones) (15).
Pleasantly, it was found that the expected products (10a-u) were provided in excellent yields. Furthermore, we successfully examined the other derivative of isatin namely 4-chloroisatin.
The three-component reaction of isatin, and malononitrile/ethylcyanoacetate with dimedone/ barbituric acid/ ethyl acetoacetate or 4-hydroxycoumarin/3-methyl-1H-pyrazol-5(4H)-one or α-naphtol/β-naphtol in which gave the expected desired products (10a-u) in satisfactory yields ( Table 9). Irrespective of the influence of nature of substituent on the isatin, the desired products were provided in high yields. When acenaphthenequinone (11) was used the desired spiro-4H-pyrans (12a-j) were also produced in good yield (Table 10). Noticeably, the reaction with ethylcyanoacetate required longer reaction times than those with malononitrile, which was perhaps because of their lower reactivity (Table 10).
The process represents a typical sequential cascade reaction in which the isatin (9), at first, condenses with malononitrile (2) to give isatylidene malononitrile (16) in the presence of PC/Ag NPs in refluxing EtOH/water. This step was considered as a rapid Knoevenagel condensation. Next, intermediate (17) is attacked via Michael addition of 1,3-dicarbonyl compound (3) to afford the intermediate (18) with subsequent cycloaddition of hydroxyl group to the cyano moiety to give the desired product (19) (Scheme 3). Indeed, the reaction is a cascade reaction via combination of two famous name reactions so called Knoevenagel condensation/Michael addition.
To present the advantages of our novel catalyst, its catalytic activity was compared with the other catalysts reported for the aforementioned MCRs, hitherto (Table 11). The catalytic potency of our novel catalyst (PC/ AgNPs) was compared with the same recently reported MCR, involving acenaphthenequinone, malononitrile and dimedone for the preparation of 2′-amino-tetrahydro-2H-spiro[acenaphthylene-1,4′-chromene]-3′carbonitrile (12b) with various catalysts such as CaCl 2 , 164      After first run, the catalyst was separated by simple filtration under reduced pressure, washed with ethanol. Next, the recovered catalyst was reused in the next run under the same reaction conditions in the model reaction. This investigation showed that the catalyst could be recovered and reused at least three times whiteout significant loss of its catalytic activity (Fig. 7). Worthy to mention that Fig. 8 shows the comparison between the FT-IR PC/AgNPs and reused catalyst.

conclusions
In conclusion, the above-presented research opened a gateway to a facile and rapid in situ preparation of Ag nanoparticles immobilized onto the functionalized microcrystalline cellulose/Preyssler heteropolyacid. It was tested as an eco-friendly, benign, and green nanobiocomposite heterogeneous catalyst. The opportunity of collecting three green materials including inorganic polymers, cellulose matrices and nanoparticles can open a green gateway in forthcoming requests such as the design and engineering of green and eco-friendly catalysts based on poly-functionalized polymers. The Taguchi robust design strategy was also employed for the optimization www.nature.com/scientificreports/ of the experimental parameters for the first time to obtain nanoparticle. The operating factors involved in this process were the concentration of silver nitrate, different loadings PC, pH, and temperature. Absorption spectra of AgNPs showed peak at 440 nm and broadening of peak showed that the particles are poly dispersed. Optimal conditions involved in this study were: performing the reaction in 80 °C, concentration of silver nitrate = 6 mM, pH = 12.5 and loading PC = 1gr. The results obtained under the aforementioned conditions were in good agreement with the data analyzed by Taguchi robust design method. The results of UV-vis absorption undoubtedly confirm the above findings. Novel PC/AgNPs was successfully employed as catalyst in the synthesis of biologically active 2-amino-4Hpyran and spirochromenes. The PC/AgNPs were fully characterization by using standard techniques. The above mentioned catalyst was used in refluxing EtOH/H 2 O providing the corresponding products in good to high yield. The catalyst was recovered and reused for three times without a significant decrease in its efficiency. Other advantages of this catalytic system were that reactions could be performed under mild reaction conditions and in very short reaction times, along with easy product and catalyst separation. This catalyst showed high stability and durability under optimal reaction conditions. The leaching of the AgNPS from the heterogenized catalyst was also found being minimal.