Immobilization of Lewis acidic ionic liquid on perlite nanoparticle surfaces as a highly efficient solid acid catalyst for the solvent-free synthesis of xanthene derivatives

In this study, perlite nanoparticles were prepared through a simple method and then modified with Lewis acidic ionic liquid (perlite NP@IL/ZrCl4) through a two step procedure. The prepared solid acid catalyst was characterized by Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), X-ray diffraction (XRD), energy-dispersive X-ray spectroscopy (EDX) and thermo gravimetric analysis (TGA). Perlite NP@IL/ZrCl4 was used as a new solid acid, reusable and green heterogeneous nanocatalyst for the one-pot synthesis of xanthene derivatives. Synthesis of xanthenes was performed under solvent free conditions using a catalytic amount (0.005 g, 0.4 mol%) of the prepared catalyst with simple work-up and high to excellent yield of products. The reusability and high efficiency of this catalyst makes this method attractive for large scale environment-friendly operations.


Introduction
Xanthene and its derivatives are pharmaceutically and biologically active compounds. 1,2 Because of the widespread use of this class of heterocyclic compounds in the preparation of dyes, 3 laser technologies 4 and pH-sensitive uorescent materials for visualization of biomolecules, 5 they have received signicant attention in recent years. On the other hand, fused pyran ring systems especially pyranopyrimidines have biological activities including antimicrobial, 6 anticonvulsant, 7 antiplatelet, 8 antibacterial, 9 antiphlogistic, 10 analgesic, 11 anti-inammatory, 11 antigenotoxic 12 and antifungal activities. 7,[13][14][15] These unique properties, led to intensive research on the synthesis of xanthene and naphthopyranopyrimidine derivatives in the presence of various catalysts such as CoPy 2 Cl 2 , 16 I 2 , 17 choline chloride, 18 Y(NO 3 ) 3 $6H 2 O and SnCl 2 $2H 2 O, 19 ZnO NPs, 20 Al(HSO 4 ) 3 , 21 sulfamic acid, 22 perlite-SO 3 H, 23 LiBr, 24 silica sulfuric acid, 25 (nBu) 4 NBr, 26 TfOH, 27 cellulose sulfamic acid, 28 molecular iodine, 29 heteropolyacid, 30 phosphoric acid supported on alumina, 31 37 and sulfonyl-functionalized acidic ionic liquids. 38 In recent years, the application of supported catalysts was developed for the synthesis of organic compounds. In this way, using low cost and readily available supports has been considered for the preparation of this class of heterogeneous catalysts. Perlite is an amorphous volcanic glass containing SiO 2 (70-75%), Al 2 O 3 (12-15%), Na 2 O (3-4%), K 2 O (3-5%), Fe 2 O 3 (0.5-2%), MgO (0.2-0.7%) and CaO (0.5-1.5%). 39,40 Because of its low density and relatively low price, many commercial applications for perlite have been developed in the construction and manufacturing elds. It is used in lightweight plasters, concrete, insulation and ceiling tiles. 41 In horticulture, perlite can be used as a soil amendment or alone as a medium for hydroponics or starting cuttings. 42 Small quantities of perlite are also used in foundries, cryogenic insulation and in ceramics as a clay additive. It is also used by the explosives industry. 42 It was found to be an excellent support for immobilization of catalysts and biocatalysts such as enzymes for bioremediation and sensing applications. 24,43,44 To avoid of using the toxic organic solvents and due to the advantages of multicomponent reactions including low response time, high efficiency, clean work-up and easy purication, we have designed environmentally benign procedures for the one-pot synthesis of xanthene and naphthopyranopyrimidine derivatives under thermal and solvent free conditions using perlite NPS@IL/ZrCl 4 as a new efficient and reusable solid acid catalyst (Scheme 1).

Results and discussion
FT-IR spectra of perlite nanoparticles and perlite NPs@IL/ZrCl 4 were presented in Fig. 1 to prove the catalyst structure. FTIR of perlite nanoparticles (Fig. 1a) TGA curve of perlite NPs@IL/ZrCl 4 at the range of 25 to 800 C is shown in Fig. 2. The weight loss at the range of 100 to 200 C was only 5%. This can be attributed to the removal of moisture from nanoparticle surfaces. A weight loss about 21% in the range of 300 to 350 C is related to the separation of ionic liquid from the surface of catalyst. Finally, by removing the hydroxyl groups from perlite nanoparticle surfaces, a weight loss about 4% in the range of 480 to 520 C is observed. Obtained results from TGA graph conrmed the chemical attachment of organic groups to the perlite NPs surfaces.
X-ray diffraction analysis was used for investigating the structure of perlite nanoparticles and perlite NPs@IL/ZrCl 4 . The obtained diffractograms are displayed in Fig. 3. As shown in this Figure, XRD patterns of primary and modied perlite nanoparticles exhibit the same characteristic peaks which shows that the peaks and relative intensities match well with the X-ray diffraction pattern of amorphous particles and the structure of the primary perlite NPS preserved in the prepared catalyst. These graphs also show that the presence of organic species has no effect on the structure of perlite NPs. The peaks related to ZrCl 4 are recorded at 2q ¼ 30, 33, 50.5 and 60 . In the XRD pattern of perlite NPs@IL/ZrCl 4 , the peaks of 2q ¼ 33 and 50.5 are distinguishable and two other peaks are covered by other broad peaks.
The scanning electron microscope (SEM) images of the perlite NPs and perlite NPs@IL/ZrCl 4 were displayed in Fig. 4(a  and b). These images clearly show the nanosize structure of perlite NPs and modied sample. As can be seen from Fig. 4b, the morphology of the perlite NPs@IL/ZrCl 4 was quite similar to the raw nanoparticles and there are no changes in nanoparticle morphology aer modication process.
The composition of perlite nanoparticles and synthesized catalyst was investigated by energy-dispersive X-ray spectroscopy (EDX). Results clearly conrmed the existence of Zr, Cl and N elements in the prepared catalyst structure (Fig. 5) and consequently proved that ionic liquid and ZrCl 4 were attached successfully to the perlite nanoparticle surfaces.
As can be seen, the Zr and N content was 6.9% and 2.5% respectively. It concluded that the percentage of ionic liquid immobilized on perlite surfaces was about 1.25%. Further amount of Zr demonstrated the chelating of Zr to OH groups    existed on the perlite surfaces (addition to be as zwitterion for imidazolium ion). Furthermore, the mol% of catalyst based on Zr ration was about 0.4 mol%.
Aer the preparation and characterization of catalyst, reaction conditions including the amount of catalyst and temperature were optimized. Firstly, optimum amount of catalyst was determined using the reaction between dimedone (2 mmol) and 3-nitrobenzaldehyde (1 mmol) in the presence of various amounts of catalyst at 80 C. Results in Table 1 show that the best yield of product was obtained in the presence of 0.005 g (0.4 mol%) of catalyst (entry 2); also when the reaction was carried out in the absence of catalyst, the yield of product was only 5% aer 100 min (entry 5).
For evaluation the temperature effect on the yield of product, the model reaction was done in the presence of 0.005 g (0.4 mol%) of catalyst at different temperatures ( Table 2). Obtained results show that 80 C was the best temperature (entry 3). Furthermore, the yield of product at 100 C was decreased due to decomposition of products aer 100 min (entry 5).
Aer the determination of optimized conditions, appraisal of the catalyst efficiency was estimated using the reaction of a variety of aryl aldehydes, 2-naphthol and 1,3-dicarbonyl compounds such as dimedone and barbituric acid for preparation of xanthene derivatives in the presence of catalytic amount of perlite NPs@IL/ZrCl 4 . Obtained results in Table 3 show that aldehydes bearing electron withdrawing groups lead to products with higher yields aer shorter times. Also in case of aldehydes with electron donating groups, it was observed that yield of reaction was lower aer longer times.
Further study was done using the reaction of terephthaldehyde with 2 mmol of dimedone (2) and 2 mmol of 2naphthol (3) for the preparation of 4e. Symmetric dimer product was prepared with the reaction of terephthaldehyde with 4 mmol of dimedone (2) for preparation of 5e (Scheme 2). The  yield of products was excellent and the spectroscopic data of these products demonstrated the structure of prepared compounds.
In continue, the efficiency of prepared catalyst was compared with some of other reported catalyst applied for the synthesis of 4c, 5a and 7c (as examples of three types of synthesized xanthene derivatives). The results are summarized in Table 4. As shown in this table, best yields were obtained using 0.005 g (0.4 mol%) of perlite-NPs@IL/ZrCl 4 at 80 C in the absence of solvent (Entry 6, 18 and 27). Catalyst amount in presented method is less than most of catalysts depicted in Table 4 demonstrated the high efficiency of solid acid catalyst.
On the other hand, in most reaction conditions (16 cases) the temperature is higher than 80 C (applied temperature in presented method) and the yield of products is lower. As a result, Lewis acidic ionic liquid supported catalyst is more active than others in term of time, catalyst amount and temperature. In fact, Zr atoms (as Lewis acid sites) loaded in catalyst surfaces, can be activated the reactants (as shown in reaction mechanism) and catalyzed the solvent-free synthesis of xanthenes. Results collected in Table 4 shown that prepared catalyst improved the yield of products compare with other catalysts.
Furthermore, easy available and very low cost material of catalyst support (perlite), facile procedure for preparation of perlite nanoparticles as well as easy functionalization process, reusability and easy work up are some of the advantageous of proposed method. As can be seen in Table 4, most of catalysts are expensive, homogeneous, toxic and without facile availability.
Consequently, presented method has proved to be very effective, green, eco-friendly, safe and easy to operate and also the scale up of this method is easy.
Suggested mechanism for the synthesis of xanthene derivatives is shown in Scheme 3. As can be seen, in the initial step, Lewis acidic ionic liquid catalyzed the conversion of keto to enol form of 1,3 dicarbonyl; on the other hand, catalyst activated the carbonyl group of aldehyde and the nucleophilic addition of 1,3 dicarbonyl compound to activated aldehyde lead to formation of (I). Removal of H 2 O and nucleophilic addition of second mole of 1,3 dicarbonyl compound to I, created the intermediate II.
Finally, cyclization and H 2 O removal from (II), give subsequent xanthene.
One of the outstanding advantages of the catalysts is their reusability and stability which makes them valuable for commercial applications. Study on the reusability of prepared catalyst was done using model reaction. Aer completion of the reaction, the catalyst was separated. The recovered catalyst was washed with chloroform (3 Â 5 ml) and dried to use for the next run in current reaction under equal conditions. It was found that the catalyst could be reused for four times without considerable loss of its activity (Fig. 6).
The characterization of recovered catalyst by FTIR and SEM methods was shown in Fig. 7. As can be seen, no changes were occurred on morphology and particle size of recycled catalyst; also, the main peaks are identical in both of the fresh and recycled catalyst. Consequently, the prepared catalyst has high stability and high efficiency in solvent-free synthesis of xanthenes.

Preparation of perlite nanoparticles
To make perlite from a crystalline to nanosize structure, 5 g of perlite was heated in 500 C for 1 hour. Then HCl (150 ml, 2 M) was added and reuxed for 24 hours. Aer that, the mixture was ltered, washed and pH was controlled to neutralize. Finally,   the precipitate was dried in 100 C for 4 hours and then calcinated in 700 C for 2 hours 23 (Scheme 4).

Preparation of perlite NPs@IL/ZrCl 4
In rst step for preparation of catalyst, 1-(3-triethoxysilyl)propyl-3-methylimidazolium chloride (Si[pmim]Cl) was synthesized according to Kumar method. 65 A mixture of methyl imidazole (1 mmol) and 3-chloropropyltriethoxysilane (1 mmol) was reuxed in 5 ml anhydrous toluene for 2 hours under N 2 atmosphere. Aer the reaction time, obtained viscous ionic liquid was extracted by diethyl ether. In order to attach the ionic liquid to perlite nanoparticle surfaces, 1 g of perlite nanoparticles was added to 0.6 g of Si[pmim]Cl and stirred for 16 hours at 90 C. Aer the time, the mixture was washed with 10 ml of boiling dichloromethane and dried. Then, 0.7 g ZrCl 4 dissolved in anhydrous toluene was added to obtained precipitate and stirred at room temperature for 12 hours. Finally, prepared catalyst was dried at 80 C and characterized by FT-IR, XRD, SEM, EDX and TGA techniques (Scheme 2).

General procedure for the preparation of xanthene derivatives
In order to achieve satisfactory results, in a general procedure, a mixture of 1 mmol benzaldehyde derivative, 2 mmol dimedone or (1 mmol 2-naphthol and 1 mmol dimedone) in the presence of optimized amount of perlite@IL/ZrCl 4 nanoparticles (0.005 g, 0.4 mol%) was stirred for adequate times under conventional heating conditions at 80 C. Aer completion of the reaction, the mixture was resolved in hot ethanol and catalyst was separated by simple ltration. The crude product was obtained aer evaporation and for further purication, recrystallized from ethanol. In case of naphthopyranopyrimidines, a mixture of 1 mmol benzaldehyde derivative, 1 mmol dimedone and 1 mmol N,N-dimethylbarbituric acid was stirred in the presence of 0.005 g, (0.4 mol%) of catalyst at 80 C. Separation and purication of reaction products was done according to xanthene route.

Conclusions
In this study, perlite nanoparticles was prepared and modied with Lewis acidic ionic liquid (perlite NPs@IL/ZrCl 4 ) and characterized with FTIR, XRD, SEM, EDX and TGA techniques. We presented a new efficient and environmental friendly pathway for one pot synthesis of xanthene and naphthopyranopyrimidine derivatives via multicomponent reactions using perlite NPs@IL/ZrCl 4 as a recyclable effective solid acid catalyst. This simple procedure is solvent free and it's easy and clean work up, high yield of products and reusability of catalyst as well as low cost and very little amounts of catalyst (0.005 g, 0.4 mol%), make this method considerable for the synthesis of other organic compounds.

Conflicts of interest
There are no conicts to declare.