Utilizing magnetic xanthan gum nanocatalyst for the synthesis of acridindion derivatives via functionalized macrocycle Thiacalix[4]arene

An effective method for synthesizing acridinedione derivatives using a xanthan gum (XG), Thiacalix[4]arene (TC4A), and iron oxide nanoparticles (IONP) have been employed to construct a stable composition, which is named Thiacalix[4]arene-Xanthan Gum@ Iron Oxide Nanoparticles (TC4A-XG@IONP). The process used to fabricate this nanocatalyst includes the in-situ magnetization of XG, its amine modification by APTES to get NH2-XG@IONP hydrogel, the synthesis of TC4A, its functionalization with epichlorohydrine, and eventually its covalent attachment onto the NH2-XG@IONP hydrogel. The structure of the TC4A-XG@IONP was characterized by different analytical methods including Fourier-transform infrared spectroscopy, X-Ray diffraction analysis (XRD), Energy Dispersive X-Ray, Thermal Gravimetry analysis, Brunauer–Emmett–Teller, Field Emission Scanning Electron Microscope and Vibration Sample Magnetomete. With magnetic saturation of 9.10 emu g−1 and ~ 73% char yields, the TC4As-XG@IONP catalytic system demonstrated superparamagnetic property and high thermal stability. The magnetic properties of the TC4A-XG@IONP nanocatalyst system imparted by IONP enable it to be conveniently isolated from the reaction mixture by using an external magnet. In the XRD pattern of the TC4As-XG@IONP nanocatalyst, characteristic peaks were observed. This nanocatalyst is used as an eco-friendly, heterogeneous, and green magnetic catalyst in the synthesis of acridinedione derivatives through the one-pot pseudo-four component reaction of dimedone, various aromatic aldehydes, and ammonium acetate or aniline/substituted aniline. A combination of 10 mg of catalyst (TC4A-XG@IONP), 2 mmol of dimedone, and 1 mmol of aldehyde at 80 °C in a ethanol at 25 mL round bottom flask, the greatest output of acridinedione was 92% in 20 min.This can be attributed to using TC4A-XG@IONP catalyst with several merits as follows: high porosity (pore volume 0.038 cm3 g−1 and Pore size 9.309 nm), large surface area (17.306 m2 g−1), three dimensional structures, and many catalytic sites to active the reactants. Additionally, the presented catalyst could be reused at least four times (92–71%) with little activity loss, suggesting its excellent stability in this multicomponent reaction. Nanocatalysts based on natural biopolymers in combination with magnetic nanoparticles and macrocycles may open up new horizons for researchers in the field.


Catalyst preparation
Preparation of IONP@XG For preparing magnetic XG by co-precipitation method, 0.4 g XG was added to 85 ml d.w. in a double-mouthed flask.The temperature was raised to 45 °C until it was completely dissolved.FeCl 2 .4H 2 O (0.396 g, 2 mmol), FeCl 3 .6H 2 O (0.54 g, 4 mmol), and 10 ml d.w. were added to the mixture and stirred for 30 min to dissolve.Then, it was placed under a N 2 atmosphere, and the temperature was raised and fixed at 80 °C.The mixture was stirred for 1 h after adding 8 ml of ammonia dropwise.After that, it was washed 10 times with d.w. and ethanol after that dried in an oven over 65 °C.Finally, a brown powder (IONP@XG) was obtained.
Preparation of IONP@XG-NH 2 0.5 g IONP@XG, 2 ml APTES, and 20 ml ethanol were poured into a round bottom flask and refluxed for 48 h.Then, it was washed seven times with ethanol, dried in an oven, and a brown powder (IONP@XG-NH 2 ) was obtained.
Preparation of TC4A-XG@IONP 0.36 g prepared thiacalix [4]arene (TC4A was synthesized based on the reported procedure in literature 41 ) and 35 ml ethanol were added to a 250 ml round bottom flask with a solution of NaOH (1 M) (to make the mixture basic) and stirred for 20 min.Next, 0.1 ml epichlorohydrin was added to the mixture, and litmus paper was used to check the basic of the mix.Then, the temperature was raised to 60 °C, and the mixture was stirred for 3 h.After that, 0.5 g IONP@XG-NH 2 and 25 ml distilled water were added and stirred for 16 h.Then, the mixture was filtered, washed with distilled water and ethanol, and dried in an oven.Finally, a dark brown powder (TC4A-XG@IONP) was obtained.The preparation route of the TC4A-XG@IONP nanocatalyst is illustrated in Fig. 2.
General procedure for the synthesis of acridinedione derivatives A 25 ml round bottom flask was filled with a combination of aldehyde (1 mmol), dimedone (2 mmol), ammonium acetate/aniline/substituted aniline (1 mmol), TC4A-XG@IONP catalyst (0.01 g), and ethanol (5 ml), and the liquid was refluxed at 80 °C for 20 min.TLC kept track of the reaction's development.The combination was

Field emission scanning electron microscope analysis
The Field Emission Scanning Electron Microscope imaging (FE-SEM) was used to observe the particle size distribution and surface morphology of nanocatalysts XG, IONP@XG, TC4A , TC4A-XG@IONP and shown in (Fig. 4a,b) The XG image illustrate a relatively uniform matrix and non-porous structure provide a relatively smooth and regular surface, in contrast the image of IONP@XG (Fig. 4c,d) spherical nanoparticles of iron oxide are completely visible in networks without aggregation in XG polymers 46 .Also, The TC4A images (Fig. 4e,f) have an average diameter of 50 nm found in the nanoparticle structure, which consists exclusively of rod-like structures.Graph of TC4A-XG@IONP (Fig. 4g,h) exhibited the presence of TC4A on the hydrogel network of TC4A-XG@IONP by chemical attachment.

Thermal gravimetry analysis
Thermal Gravimetry Analysis (TGA) evaluation of thermal resistance was performed on the samples XG, IONP@ XG, IONP@XG-NH 2 , and TC4A-XG@IONP as shown in Fig. 5. TGA analysis of Fe 3 O 4 was studied in detail to determine the thermal behavior of synthesized samples 47 .The reported thermal profile of iron oxide nanoparticles showed that its weight loss was about 5-6% up to 800 °C is related to the evaporation of surface absorbed water 9 .This weight loss continued with increasing temperature, up to 300 °C, and after it went downhill 48 .About 50% of its weight is reduced between temperatures of 200-300 °C and its residuals weight at 800 °C is about 14%.The thermal profile of IONP@XG hydrogel (Illustrated in Fig. 5b) exhibited considerably elevated residual weight (73%) than unmodified XG over the studied range of temperature.This indicates the formation of iron oxide nanoparticles within the XG matrix and its effective interaction with chains of XG limits the mobility of chain of this natural polymer.Based on IONP@XG hydrogel thermogram, the first weight loss began at 270 °C which continued up to 400 °C and the second thermal decomposition observed between 400 and 800 °C.These are related to the surface dehydrogenation and dehydroxylation, dissociation of site chain and functional groups and decomposition of glycosidic bridge of XG.Thermal degradation of IONP@XG-NH 2 as illustrated in Fig. 5c, showed similar trend with slightly decreased resudial weight (68%) as compared to IONP@XG 48 .The thermal degradation of the TC4A-XG@IONP showed three step decomposition (Fig. 5d).The initial weight loss in the temperature range of 50-200 °C caused by evaporation of adsorbed water in its cavities, the next one started at 250 °C and stained up to 300 °C which can be related to the breakdown the linkage between IONP@XG-NH 2 and TC4A and thermal dissociation of XG functional groups.The last weight loss in the temperature range of 350-450 °C might be caused by thermal degradation of TC4A and depolymerization of XG.Modifying IONP@ XG-NH 2 with TC4A supermolecule increased its thermal resistance by 5%.Accordingly, TC4A-XG@IONP had relatively high thermal resistance with ~ 73% residual weight unto 800 °C.

Vibration sample magnetometer analysis
The vibrating Sample Magnetometer (VSM) analysis measured the synthesized nanocatalyst magnetic properties.According to (Fig. 6a), the property magnetic coercivity and the magnetic reluctance of TC4A-XG@IONP is zero.Therefore, the synthesized samples have superparamagnetic properties.The magnetic saturation value of IONP nanoparticles is 58 emu g −1 , and saturation magnetization of IONP@XG and TC4A-XG@IONP are decreased to 30.060 emu g −1 and 9.300 emu g −1 as illustrated in Fig. 6b,c respectively.The decrease in magnetic saturation is related to XG and TC4A, a natural polysaccharide, and a macrocyclic compound, which none of them have a magnetic nature.However, the magnetic saturation of TC4A-XG@IONP nanocatalyst is sufficient to separate it using a magnet in the experiments.

Brunauer-Emmett-Teller analysis
We conducted a nitrogen adsorption-desorption analysis by Brunauer-Emmett-Teller (BET) to determine the specific surface area, porosity, and textural properties of the synthesized nanocatalyst.Based on BJH theory, Table 1 summarizes IONP@XG and TC4As-XG@Fe 3 O 4 specific surface areas, pore volumes, and average pore diameters.Figure 7 illustrates type-IV isotherm profiles (with H4 hysteresis loops) for both nanocatalyst materials.Mesoporous materials are classified by IUPAC based on type-IV isotherm profiles.In contrast to neat XG, IONP@XG (Fig. 7a) showed a BET surface area of 45.317 m 2 g −1 , much higher than the 0.676 m 2 g −1 previously reported for neat XG.For explanation of this observation can be said that, during the in-situ fabrication of magnetic iron oxide nanoparticles in XG natural polymer matrix, the inherent coordination potential of Fe 3+ (trivalent metal ion) in alkaline reaction media leads to the coordination bonding between hydroxylate and carboxylate functional groups of polymeric chains of XG natural and formation of three-dimention hydrogel network with improved surface area 49 .In the case of TC4A-XG@IONP nanocatalyst (Fig. 7b), the BET surface area was measured 17.3065 m 2 g −1 , which was satisfactory compared to IONP@XG.The surface area and size of TC4A-XG@ IONP were decreased following, amine-functionalization, and then covalent bonding to funtionalized TC4A.A nanocatalyst fabricated with favorable textural properties, a porous structure, and a high specific surface area may be considered as a desired catalytic system.

X-Ray diffraction analysis
The crystallinity of the produced materials in the range of 5-80° was investigated using X-Ray diffraction analysis (XRD) analysis 50 .According to earlier research, a distinctive peak (at 2θ = 18°-25°) was seen in the XRD pattern of XG, indicating that it is an amorphous material (Fig. 8b).As shown in Fig. 8a, the acceptable IONP pattern with card number JCPDS, 01-77-0010 fits the XRD pattern for LONP, which includes diffraction peaks at 2θ = 30.61°35.99°, 43.27°, 54.18°, 57.53° and 63.35°.The same peaks as those associated with IONP have been identified for IONP@XG, but since XG is an amorphous material, their pitch is less intense (Fig. 8c).According to studies in the literature, TC4A has a crystalline structure in Fig. 8d.Additionally, the typical IONP peak can be seen in the Table 1.BET Surface area, pore volume and pore size of IONP@XG and TC4A-XG@IONP nanocatalyst.a The surface area parameter was acquired via BET analysis.b The pore volume and pore size parameters were acquired via BJH analysis.XRD pattern of the TC4A-XG@IONP nanocatalyst, confirming the existence of IONP MNPs there.Finally, it can be said that compared to pristine XG, in-situ magnetization,amine modification and functionalization with TC4As produced better crystallinity(Fig.8e).

Energy dispersive X-ray
The detection and identification of organic and inorganic elements in the manufactured compounds was done by the Energy Dispersive X-Ray (EDX) qualitative analysis method 51,52 .Therefore, the constituent elements of the prepared samples can be examined in the EDX spectrum.As shown in Fig. 9a-e, the EDX spectrum of neat XG was illustrated in Fig. 9a

Catalytic study
The green and eco-friendly TC4A-XG@IONP was applied as a catalyst in organic reaction.For this purpose, it was used as a catalyst in synthesizing acridinedione derivatives.The one-pot reaction between dimedone, 4-chlorobenzaldehyde, ammonium acetate/aniline/substituted aniline, and ethanol as solvent was carried out as a model reaction.Different conditions like temperature, amount of catalyst, solvent, and reaction time were investigated and shown in Table 2. First, the reaction was performed without a catalyst at room temperature (rt) and 80 °C and observed there was no product, which shows the essential role of the catalyst (Table 2, Entry 1 and 2).Then, the reaction was applied at rt, 40 °C, and 80 °C, it was observed at 80 °C, the product yield was the highest (Table 2, Entry 3-5).Other green solvents including water, methanol, and acetonitrile were investigated, and ethanol as a solvent has the highest yield (Table 2, Entry 6-8).Also, the amount of catalyst was investigated, which observed that 20 mg catalyst is the optimized amount, and the extra amount does not affect yield (Table 2, Entry 9 and 10).The reaction time was also investigated at 10, 20, and 30 min.It was found that the optimized reaction time is 20 min, and more than, does not affect the yield of the intended product (Table 2, Entry 11-13).
Moreover, the reaction performed by XG and TC4A.The results showed that the TC4A-XG@IONP nanocatalyst has more yield, which shows the merits of its catalytic activity (Table 2, Entry 14 and 15).After obtaining the optimized reaction conditions, various aldehyde and amine derivatives were used to show the TC4A-XG@IONP nanocatalytic merits, and the intended products were obtained with high yields (Table 3).
In addition, the catalytic activity of TC4A-XG@IONP nanocatalyst comparisons was made with some other catalysts reported (Table 4) and observed that using the synthesized nanocatalyst has a higher yield than the others.Based on this, it can be concluded that TC4A-XG@IONP nanocatalyst is an efficient catalyst in synthesizing acridinedione derivatives.

Proposed mechanism
The green and multifunctional TC4A-XG@IONP nanocatalyst can perfectly accelerate organic reactions due to the desired physicochemical properties as follows; large surface area, high porosity, three-dimentional network, and abundantly OH and NH 2 groups.The plausible mechanism for synthesizing acridinedione derivatives with TC4A-XG@IONP as a nanocatalyst.First, the catalyst makes a hydrogen bonding with dimedone and makes the alpha hydrogen highly acidic.Then, aromatic aldehyde was activated by TC4A-XG@IONP nanocatalyst, and dimedone made a nucleophilic attack and a knovenagel product was obtained.By dehydration, a Michael reaction would occur with another dimedone with acidic hydrogen through hydrogen bonding with TC4A-XG@IONP nanocatalyst.Then ammonium acetate would react with the carbonyl group, and the intended product would be obtained with the help of a nanocatalyst by intramolecular cyclization and dehydration (Fig. S5).

Reusability
In green chemistry, the ability to reuse the catalyst is one of the main principles.So, the reusability of TC4A-XG@ IONP nanocatalyst was investigated in synthesizing the acridinedione derivatives.This process involved extracting the TC4A-XG@IONP nanocatalyst from a mixture with an external magnet, washing it several times with ethanol and water, drying it in an oven, and reusing it for the reaction.As shown in Fig. 10a, the TC4A-XG@ IONP nanocatalyst was reused four times with no apparent diminish in the product yield.Also, the FT-IR of reused TC4A-XG@IONP is shown in Fig. 10b, and it is clear that the structure maintained its stability.

Conclusion
In the present work, we constructed a composition of XG and TC4A via covalent bonding in the presence of IONP and by using organosilane, and epichlorohydrine.The next step, the employed characterization methods have confirmed well the construction of TC4A-XG@IONP nanocatalyst.We then used that nanocatalyst to synthesize the acridinedione derivatives through one-pot multicomponent reaction of dimedone, various aromatic aldehydes, and different amines (ammonium acetate or aniline/substituted aniline).The corresponding products were synthesized with good to high yields (92-72%).The presented eco-friendly catalytic system has great textural and structural characteristics which originated from its constituent components, (i.e., XG, IONP, and TC4A) and their synergistic effects such as high porosity and presence of cavity shaped structure, high surface area, abundant reactive functional groups as catalytic sites, high thermal stability, and great retrievability, considering the great advantages that this nanocatalyst has for the acridinedione derivatives, still has challenges such as scalability challenge researchers could explore innovative approaches for producing the nanocatalyst on a larger scale while maintaining its catalytic activity and stability.This could involve investigating alternative synthesis methods or www.nature.com/scientificreports/optimizing the current synthesis process to reduce production costs and increase yield.To evaluate the potential environmental impact of the nanocatalyst, researchers could conduct comprehensive toxicity studies to assess its effects on human health and the environment.They could also investigate methods for safely disposing of or recycling the nanocatalyst after use to minimize any negative environmental impacts.Overall, addressing these challenges will be crucial for advancing the development and application of the TC4A_XG@IONP nanocatalyst as a sustainable and efficient alternative for organic transformations in various industrial sectors.

Figure 7 .
Figure 7.The left panel is the isotherms of N 2 adsorption-desorption, and the right panel demonstrates the pore size distribution of (a) IONP@XG and (b) TC4A-XG@IONP.