Synthesis and Characterization of a Novel Nanosilica Supported Bipyridinium Chloride Nanocomposite and its Application as a Basic Catalyst in the One-pot Preparation of Tetrahydrobenzo[b]pyran, Dihydropyrano[3,2-c]chromene and Dihydropyrano[4,3-b]pyran Derivatives

Document Type : Research Paper


1 Chemistry Department, Faculty of Sciences, Shahid Chamran University of Ahvaz, Ahvaz, Iran

2 ACECR-Production Technology Research Institute, Ahvaz, Iran


A novel rice-husk-silica supported n-propyl bipyridinium chloride (RHPrBPCl) has been prepared. Due to the basicity of RHPrBPCl, it was decided to evaluate its catalytic activity in the one-pot preparation of tetrahydrobenzo[b]pyran, dihydropyrano[3,2-c]chromene and dihydropyrano[4,3-b]pyran derivatives. The catalyst was characterized by FT-IR, SEM and TGA analyses. This methodology offers several advantages including easy work-up procedure, high yields of the products, short reaction times, recyclable catalyst and green reaction medium.



Multi-component reactions (MCRs) are defined as one-pot processes which three or more substrates combine either simultaneously, or through a sequential addition procedure that does not require any change of solvent. Quite recently MCRs have gained importance especially in the total synthesis of natural products, and medicinal heterocyclic compounds, because of their simplicity, higher yield of the products, and lower reaction times [1,2].

4H-pyran derivatives as an important class of heterocycles, have attracted strong attention to their useful biological and pharmacological properties such as anticoagulant, spasmolytic, diutretic, anticancer and antianaphylactin characteristics [3]. 4H-Pyrans also occur in various natural products [4]. It has also reported that some of benzopyran derivatives have photochemical activities [5]. Development of 4H-pyrans synthesis has been of considerable interest in organic synthesis, because of their wide biological and pharmaceutical activities. Consequently numerous methods have been reported for the synthesis of 4H-pyrans [6].

Dihydropyrano[3,2-c]chromenes derivatives are also a class of important heterocycles with a wide range of biological properties such as spasmolytic, diuretic, anticoagulant, anti-cancer and anti-anaphylactic activity [7]. Despite their importance from pharmacological, industrial and synthetic point of views, comparatively few methods have been reported for the preparation of pyrano[3,2-c] chromene derivatives [8].

Some of the reported procedures require long reaction times, multi-step reactions and complex synthetic pathways, afford products with only modest yields, and non-reusability of the catalyst. Therefore, the development of more effective methods for their preparation is still necessary.

It is well known that fused pyran derivatives possess a variety of pharmacological and biological properties, such as fungicidal, insecticidal, acaricidal [9], antiviral, antileishmanial [10] and anticonvulsant activity [11]. Moreover, they have been introduced as non-peptide human immunodeficiency virus (HIV) protease inhibitors [12]. Despite their wide range of pharmacological, industrial and synthetic applications, the synthesis of pyrano[4,3-b]pyrans has received little attention [13].

In continuation of our interest to introduce organic units into the skeleton framework of the ordered mesoporous silica [14-18], herein we would like to introduce a novel nanocomposite, rice-husk-silica supported n-propyl bipyridinium chloride (RHPrBPCl), for the one-pot preparation of tetrahydrobenzo[b]pyran, dihydropyrano[3,2-c]chromene and dihydropyrano[4,3-b]pyran derivatives (Scheme 1).




All commercially available chemicals were purchased from Fluka and Merck companies and used without further purification. Products were characterized by their physical constant and comparison with authentic samples. Reaction monitoring was accomplished by TLC on silica gel polygram SILG/UV 254 plates. The IR spectra were recorded on a BOMEM MB-Series 1998 FT-IR spectro-photometer using KBr pellets for the samples and catalyst in the range of 4000-400 cm-1. 1H and 13C NMR spectra were recorded in CDCl3 and DMSO-d6 on a Bruker Advanced DPX 400 MHz spectrometer using TMS as internal standard. The SEM analyses were carried out using a LEO 1455VP Scanning Electron Microscope, operating at 1-30 KV. Thermal stability of the supported catalyst was examined by BÄHR, SPA 503 Thermo-gravimetric Analyzer (TGA) at heating rate of 10 °C min-1 over the temperature range of 40-700 °C.


 Scheme 1. Preparation of tetrahydrobenzo[b]pyrans (6a-i), dihydropyrano[3,2-c]chromenes (7a-h) and dihydropyrano[4,3-b]pyrans (8a-h) in the presence of RHPrBPCl


General Procedure for the Preparation of (n-Prpyl-trimethoxy silane)-4,4’-bipyridinium Chloride (PTBPCl)

PTBPCl was prepared according to Arenas et al. [21] with some modification. In a 50 ml RBF, 1.24 g (8 mmol) 4,4’-bipyridine was dissolved in 5 ml of DMF, afterwards 8 mmol 3-chloropropyl trimethoxy silane was added dropwise. The mixture was stirred at 90 °C under Argon atmosphere for 72 h. Finally, the precipitate was filtered and washed with methanol and dried at 90 °C for 2 h.


General Procedure for the Preparation of RHPrBPCl

In a 500 ml RBF, 3 g of rice-husk nanosilica, was dissolved in 350 ml of 1 M NaOH for 24 h. Afterwards the mixture was filtered to remove any residue. Then 2 g of PTBPCl was added to the filterate. The pH of this solution was adjusted to pH = 5.0 by addition of 3.0 M HNO3 solution. In this case, the solution was aged for 24 h. Subsequently the precipitate was filtered and washed repeatedly with water and at last with acetone. The obtained silica was dried at 60 °C for 24 h.


General Procedure for the Preparation of Benzopyran Derivatives in the Presence of RHPrBPCl in Water

A 50 ml RBF was charged with aromatic aldehydes (1 mmol), malononitrile (1.2 mmol), 1,3-dicarbonyl compound, (dimedone, 4-hydroxy coumarine and 4-hydroxy-6-methyl-2-pyrone) (1 mmol), RHPrBPCl (0.01 g) and 10 ml deionized water. The mixture was in an oil-bath for specific time (7-45 min). Completion of the reaction was indicated by TLC [TLC n-hexane/ethyl acetate (7:3)]. After completion of the reaction (as indicated in Table 2), the mixture was filtered. The solid was washed with 15 ml hot ethanol to dissolve the product. The products were recrystallized in ethanol again.


General Procedure for the Recovery of RHPrBPCl

A 50 ml RBF was charged with 4-methyl benzaldehyde (1 mmol), malononitrile (1.2 mmol), dimedone (1 mmol), RHPrBPCl (0.01 g) and 10 ml deionized water. The mixture was placed in an oil-bath for specific time. Completion of the reaction was indicated by TLC [TLC n-hexane/ethyl acetate (7:3)]. After completion of the reaction, the mixture was filtered. The solid was washed with 15 ml hot ethanol to dissolve the product (the yield was calculated). The residue (RHPrBPCl) was washed with hot ethanol twice, dried at 60 °C for 2 h and used for the next run (Fig. 6).



In the first step, nanosilica was extracted from rice husk according to Adam et al. [19]. In the second step, n-propyl trimethoxy silane-4,4’-bipyridinium chloride (SiBP) was prepared via nucleophilic substitution of 4,4’-bipyrinine and (n-propyl)trimethoxy silane. In the last step, nanosilica was converted to sodium silicate in NaOH solution, and subsequently SiBP was added to prepare RHPrBPCl in acidic medium via sol-gel process (Scheme 2).


Scheme 2. General procedure for the preparation of RHPrBPCl


The obtained nanocomposite was characterized via FT-IR, SEM and TGA techniques. The FT-IR spectra of rice husk silica (Fig. 1) and the nanocomposite (RHPrBPCl) were recorded. A broad peak in 3200-3600 cm-1 is related to stretching vibration of OH groups of silica surface and absorbed water molecules in silica. The presence of water in silica is further confirmed by characteristic bending vibration at 1640 cm-1. The strong stretching vibration of Si-O-Si is observed at 1099 cm-1. Further peaks at 446 and 800 cm-1 are due to Si-O vibrations.

In FT-IR spectrum of RHPrBPCl, other than RH-SiO2 peaks, characteristic peaks of propyl bipyridinium chloride moiety is observed at 1400, 1480 and 1545 cm-1 (Fig. 2).


 Fig. 1. FT-IR spectrum of RH-SiO2



 Fig. 2. FT-IR spectrum of RHPrBPCl


Qualification of a catalyst for promoting a specific reaction needs further analyses, including inspection of surface morphology and thermal stability. Accordingly after initial confirmation of nanocomposite with FT-IR, it was decided to inspect the surface morphology via SEM and thermal stability via TGA.

In SEM images of the nanocomposite, the agglomerated nanoparticles are observed which with further dispersion can efficiently sprea’/kjmd throughout the reaction vessel (Fig. 3).

Inspection of the thermal stability of the RHPrBPCl nanocomposite via TGA indicated that there are two weight reduction steps in thermogram. The first weight reduction (20%) is occurred up to 190 °C which is related to the evaporation of absorbed water molecules from silica. The second weight reduction (40%) is occurred in the range of 280-450 °C, which can be attributed to the decomposition of organic moiety of the composite. According to this analysis, we can say that 40% of the composite is organic and 40% is inorganic which is stable up to 700 °C in this thermogram (Fig. 4).


Fig. 3. SEM images of RHPrBPCl nanocomposite


Fig. 4. TGA diagram of RHPrBPCl nanocomposite


After qualification of catalyst with FT-IR, SEM and TGA analyses, it was decided to explore the catalytic activity of this catalyst in the one-pot preparation of benzopyran derivatives in aqueous medium. In this regard, the three-component reaction of aromatic aldehydes, malononitile and 1,3-dicarbonyl compounds (dimedone, 4-hydroxy coumarine and 4-hydroxy-6-methyl-2-pyrone) in the presence of RHPrBPCl as the catalyst was investigated (Scheme 1).

Fig. 5. Postulated mechanism for the synthesis of dihydro pyrano chromenes


Fig. 6. Recyclability of RHPrBPCl in the reaction of 4-methyl benzaldehyde, malononitrile and dimedone


In the first step, the reaction conditions, including temperature, solvent and amount of catalyst were optimized for the reaction of 4-methyl benzaldehyde, malononitrile and dimedone (Scheme 2, Table 1). With optimized conditions in hand, the MCRs were performed in water at reflux conditions and in the presence of 0.01 g of the catalyst.

Delighted with these results, we decided to synthesize a library of benzopyran derivatives via the three-component reaction of aromatic aldehydes, malononitile and 1,3-dicarbonyl compounds (dimedone, 4-hydroxy coumarine and 4-hydroxy-6-methyl-2-pyrone) in the presence of RHPrBPCl as a dual ionic liquid-basic catalyst.


Table 1. Optimization of the Reaction of 4-Methyl Benzaldehyde, Malononitrile and Dimedone


Table 2. One-pot preparation of  Tetrahydrobenzo[b]pyran (6a-i), Dihydropyrano[3,2-c]chromenes  
(7a-h), and Dihydropyrano[4,3-b]pyranes (8a-h) in the Presence of RHPrBPCl


According to the obtained results (Table 2), RHPrBPCl has efficiently catalyzed the reaction as a phase transfer catalyst and the corresponding products were obtained with good to excellent yield. Furthermore electron-donating or electron-withdrawing groups did not have any significant effect on the reaction yield, albeit electron-withdrawing groups lower the reaction time. The postulated mechanism has been shown (Fig. 5) [20].

To validate the structure of the desired products, FT-IR, 1H NMR and 13C NMR of these products were obtained. In the FT-IR spectra, a sharp characteristic peak at about 2200 cm-1 is due to stretching vibration of the CN group. Also, a sharp peak at 1715 cm-1 corresponds to 1,3-dicarbonyl moiety. Moreover, two bands in the region of 3200-3450 cm-1 are related to NH2 group. It is noteworthy that the presence of CN group in the products is confirmed by a peak at 110-120 ppm in 13C NMR.

Due to importance of green chemistry and recycling the solvents and catalysts, the recyclability of nanocomposite was assessed in the reaction of 4-methyl benzaldehyde, malononitrile, and dimedone. The result is shown in Fig. 6. The activity of nanocomposite is slightly decreased after 6 times of reuse.



A novel rice-husk-silica supported n-propyl bipyridinium chloride (RHPrBPCl) with dual feature of being ionic liquid and basic catalyst, was prepared and utilized in the one-pot preparation of tetrahydrobenzo[b] pyran, dihydropyrano[3,2-c]chromene and dihydropyrano[4, 3-b]pyran derivatives. The catalyst was characterized by FT-IR, SEM and TGA analyses. This methodology offers several advantages including easy work-up procedure, high yields of the products, short reaction times, recyclable catalyst, and green reaction medium.



We are grateful to the Research Council of Shahid Chamran University for financial support.

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