Arash Mouradzadegun*,
Somayeh Elahi and
Fatemeh Abadast
Department of Chemistry, Faculty of Science, Shahid Chamran University, Ahvaz, Iran. E-mail: arash_m@scu.ac.ir; Fax: +98(611)3337009; Tel: +98(611)3331042
First published on 17th June 2014
In this work, for the first time, a 3D-network polymer-supported Bronsted acid ionic liquid was synthesized via two post-functionalization steps. Initially, the active homogeneous catalyst was chemically immobilized onto a polymeric support based on calix[4]resorcinarene by silylation of the hydroxyl groups to form a cationic polymer that contains imidazolium moieties. The formation of this cationic polymer was confirmed by elemental analysis, scanning electron microscopy (SEM), thermal gravimetric analysis (TGA) and derivative thermogravimetric (DTG) analysis. Subsequently, HSO4 anion was incorporated into the polymer along the imidazolium pendant groups via a well-known ion exchange reaction. Elemental analysis data revealed that the cationic polymer was conveniently loaded with the desired Bronsted acid anion; therefore, it provides a novel heterogeneous acid catalyst for achieving synthetic goals. The immobilized acidic ionic liquid effectively catalyzed the one-pot synthesis of symmetrical bisamides by the multicomponent condensation of two moles of amides with aldehydes. Interestingly, the catalyst exhibited a high turnover number (TON) and turnover frequency (TOF), which were even comparable with that of H2SO4. The unique features of this catalyst, such as superior thermal stability, recyclability, excellent catalytic activity in terms of yield and reaction time, high turnover number and turnover frequency, are potentially important for the applications of this catalyst in the industry.
In this context, the grafting of strong acidic ionic liquids (ILs) onto inorganic materials, such as mesoporous silicas and zeolites, has received considerable attention.4 However, the hydrophilic inorganic networks of the supports largely affect their catalytic activities due to the presence of water, which is usually a by-product in many acid catalyzed reactions; moreover, water easily co-adsorbs near the acidic sites, further leading to the partial deactivation or leaching of the active sites.5 Furthermore, the presence of organic halides containing cations usually results in the destruction of the inorganic supports, which largely constrains their wide application.6
Compared with inorganic supports, polymers have shown adjustable hydrophobicity and good stability for various acids. These features, coupled with their biodegradability and green nature, make polymeric supports attractive materials to organic and industrial chemists.
However, some of these polymeric supports suffer from one or more defects in their synthetic or functionalization routes and properties, including long reaction times, multiple steps for synthesis, functionalization via copolymerization or further post-polymerization under harsh reaction conditions, the use of expensive catalysts, solubility in various solvents, and low thermal and/or chemical stability. Hence, at present, developing and applying new supports for heterogeneous-type catalytic systems, which may quickly move from the laboratory to green industrial plants, have received increased attention.
It seems that the 3D-network polymer based on calix[4]resorcinarene may be a good candidate as a support material for heterogeneous catalysis because of its ease of preparation and unique properties such as good dispersion of active sites, versatile chemical modification (acylation, alkylation and silylation of hydroxyl group and nucleophilic aromatic substitution on the aromatic ring), its straightforward functionalization route via post-functionalization without undergoing copolymerization or further post-polymerization, porous surface (pore radius from approximately 100 to 500 nm), and high thermal and chemical stability.7
To the best of our knowledge, despite its convenient properties and significant potential for functionalization under mild reaction conditions without the use of acidic or basic catalysts, there have been no reports to date on the immobilization of acidic ionic liquid onto this polymeric structure.
Thus far, some immobilization processes for acidic ILs onto solid support have been designed. Among them, the synthesis of functionalized cationic polymers via covalently anchored ILs onto a polymeric backbone, which could then be converted to the acidic form by a facile ion exchange reaction, has generated much interest.
Quaternary ammoniums (QAs) have been most widely studied as cationic groups for the functionalization of various polymers. However, environmental issues concerning the use of highly volatile reagents, such as the trimethyl amine, which is used for the introduction of these QAs, limits their large scale synthesis and application.
To overcome this limitation, alkyl imidazolium has recently been incorporated into polymers as a cationic moiety due to its low volatility, and excellent thermal and chemical stabilities.8
Hence, it would be reasonable to consider the immobilization of acidic ionic liquids containing imidazolium moieties onto a 3D-network polymer based on calix[4]resorcinarene as a promising solid support, which could then be used as an efficient acidic catalyst in chemical reactions for the construction of valuable target molecules.
Because of the exceptional properties of the amide bond, it plays an important role in amide derivatives, such as biochemicals, structural subunit of polymers, and stable synthetic intermediates in chemistry and materials science.9 Among a large variety of compounds containing amide bonds, bisamides are one of the more important amide derivatives, which have been used as versatile intermediates in the synthesis of biologically active compounds such as amidoalkyl.10 They have also been applied as ligands in Ullmann coupling reactions;11 moreover, they are of considerable interest in the synthesis of pharmacological materials such as peptidomimetic compounds.12
Due to the aforementioned chemical and pharmacological significance, a great deal of effort has been focused on developing new and efficient synthetic routes to generate bisamide derivatives in recent years. Although these methods are effective, they suffer from some drawbacks such as long reaction time, multiple reaction steps, the use of expensive catalysts, special care in handling and storing the catalyst, and laborious work-up and purification steps. Consequently, the development of more convenient, economical and eco-friendly protocols that use an efficient and reusable catalyst is highly desired.
With the above points in mind, as part of our continuing efforts to develop high performance and environmentally friendly procedures for various important reactions and transformations13 and due to our new interest in the application of the 3D-network porous polymer based on calix[4]resorcinarene for the preparation of biologically important molecules,7 herein, we report for the first time, the functionalization of polymeric calix[4]resorcinarene via a covalently anchored acidic ionic liquid and the investigation of its efficiency as a solid acid for the synthesis of bisamide derivatives through the one-pot reaction of various aldehydes with aliphatic and aromatic amides.
Monitoring of the reactions and the purity determination of the products were accomplished by TLC on silica gel PolyGram SILG/UV 254 plates.
To achieve this objective, the 3D-network polymer 2 was prepared by the reaction of resorcinol and acetaldehyde, followed by the polycondensation of calix[4]resorcinarene 1 with formaldehyde,14,15 and the synthesis steps are shown in Scheme 1.
The structure of compound 1 was established unambiguously from the spectroscopic (IR, 1H NMR, 13C NMR) data (see ESI†). The formation of polymer 2 was also confirmed and characterized by atomic force microscopy (AFM), X-ray diffraction (XRD) and scanning electron microscope (SEM)7 (available in the ESI†).
Subsequently, in the first step of post-functionalization, the prepared polymer 2 was treated with 1-methyl imidazole and (3-chloropropyl) trimethoxysilane in water/ethanol to undergo a condensation reaction, yielding cationic polymer 3 in a one-step modification reaction (Scheme 2). The loading amount of the cationic moieties on the polymer was determined by elemental analysis. The nitrogen analysis of supported IL 3 (N, 7%) indicates that 2.5 mmol of the imidazolium moieties were grafted onto the surface per 1 g of the polymer. The formation of 3 was also confirmed by SEM, TG and DTG analyses.
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Scheme 2 Synthesis of cationic polymer (3) containing imidazolium moieties through the one-step chemical modification of (2). |
In order to gain an insight into the morphology of the synthesized polymer 3, scanning electron microscopy was used (Fig. 1).
Since the cationic polymer 3 shows smaller pores (about 97 nm in diameter) than polymer 2 (300 nm in diameter, see ESI†), it can be concluded that the ILs are successfully grafted onto the polymeric backbones.
The stability of the functionalized polymer 3 was determined by thermo gravimetric analysis at a heating rate of 10 °C per minute under a nitrogen atmosphere (Fig. 2). The TG curve indicates an initial weight loss of 8.46% up to 100 °C due to the adsorbed water and organic solvent in the polymeric support, which is common in the cases of immobilized catalysts onto organic or inorganic supports.16 A complete loss of the IL chains is seen in the range of 300–469 °C. The weight loss in the temperature range of 500–1100 °C can be assigned to the decomposition of the polymeric support. Moreover, the peak in the DTG curve shows that decomposition of the IL chains mainly occurred in two steps at 395 and 430 °C, which can be attributed to the decomposition of the imidazolium moieties and propylsilane linkers, respectively. Thus, the TGA and DTG curves also convey the clear information that IL chains are successfully grafted onto the polymeric backbones.
After the characterization of 3, in the second step of post-functionalization, the resultant cationic polymer was further reacted with H2SO4 in dichloromethane to form the corresponding 3D-network polymer-supported acidic catalyst 4 (Scheme 3).
The sulfur content of the catalyst, measured by CHNS analysis, showed the value of about 2.9%. Based on this value, the amount of HSO4 anions, which were supported on the polymer, is about 0.906 mmol per gram polymer. This result gave us confidence that the imidazolium side-chains and polymeric backbones are completely stable under acidic conditions.
It is noteworthy that this polymeric support showed more potential for covalently anchored acidic ionic liquids in comparison with some previous solid supports reported in literature.17 Moreover, the synthesized polymer supported acid catalyst (4) is effectively insoluble in various solvents, including H2O, CH3OH, EtOH, DMSO, DMF, CH3CN, CH2Cl2, and CHCl3. These features render it suitable for conducting chemical transformations in various reaction media as an efficient heterogeneous acid catalyst.
In this regard, owing to the widespread applications of bisamide derivatives, we decided to investigate the synthetic applicability of 4 as an acid catalyst for the rapid and efficient construction of bisamide derivatives through a multicomponent reaction.
To develop suitable reaction conditions, the reaction of 2 mmol benzamide with 1 mmol benzaldehyde was chosen as a model reaction (Scheme 4) and parameters such as solvent and amount of catalyst (4) were examined in detail.
The solvent optimization revealed that the solubility of both the substrate and product play an important role in the process. It was found that when the substrate was highly soluble and the product precipitated the process came together with the increased ease of work-up using filtration, the high yield and the purity of product.18 Thus, tetrahydrofuran, acetone, acetonitrile and ethyl acetate failed to afford a homogeneous solution at the first stage, which diminished the yield and purity of the final product (entries 2–5, Table 1). To our surprise, among the solvents investigated, boiling toluene boosted the yield to 80% (entry 6, Table 1), due to its perfect solubility for the substrate and insolubility for the product.
Entry | Solvent | Catalyst | Amount of catalyst (g)/mmol H+ | Time | Yield (%) |
---|---|---|---|---|---|
1 | None | 4 | 0.1/0.092 | 6 h | 0 |
2 | THF | 4 | 0.1/0.092 | 6 h | 5 |
3 | Acetone | 4 | 0.1/0.092 | 6 h | 15 |
4 | Acetonitrile | 4 | 0.1/0.092 | 6 h | 13 |
5 | Ethyl acetate | 4 | 0.1/0.092 | 6 h | 20 |
6 | Toluene | 4 | 0.1/0.092 | 30 min | 80 |
7 | Toluene | 4 | 0.08/0.074 | 30 min | 85 |
8 | Toluene | 4 | 0.07/0.065 | 30 min | 78 |
9 | Toluene | None | — | 6 h | 10 |
10 | Toluene | H2SO4 | 0.004/0.074 | 60 min | 50 |
The reaction was also evaluated in the presence of various amounts of catalyst. The results showed that 0.08 g of catalyst efficiently catalyzed the reaction to give the desired product (5) (entry 7, Table 1). It was also found that increasing or decreasing the amount of catalyst not only improves the reaction times but also reduces the yield of the desired product significantly (entries 6 and 8, respectively, Table 1). This may be rationalized by considering the fact that small amounts of acidic catalyst could not activate the aldehyde effectively, but large amounts of it inactivate the amide via its protonation. Thus, the reaction of 2 mmol benzamide with 1 mmol benzaldehyde in the presence of 0.08 g catalyst in refluxing toluene was chosen as the optimized reaction condition.
To confirm the catalyst efficiency, further experiments were carried out. Initially, in a control experiment, we carried out the model reaction in the absence of any catalyst. In this case, only a trace amount of product was detected after 6 h (entry 9, Table 1).
Next, the model reaction was examined in the presence of H2SO4. As shown in Table 1, the yield of N,N′-phenylidene bisamide (5) was much higher with solid protic acid (4) compared with sulfuric acid (entries 7 and 10, respectively, Table 1).
The superiority of this solid analog of sulfuric acid to commercial sulfuric acid is attributed to its porosity. The adsorption of substrate onto the surface of the functionalized polymer based on hydrophobic interaction between the substrates and polymeric backbone could increase the local concentration of substrates around the active sites of the polymer and effectively promote the reaction. These observations clearly highlight the existence of a synergistic effect between the cavities of the polymeric support and the immobilized acidic ILs, which leads to high catalytic activities.
These results encouraged us to demonstrate the efficiency and the applicability of the present acid-catalyzed multicomponent reaction. For this purpose, the optimized reaction conditions were applied to a variety of aldehydes containing electron-withdrawing or electron-donating groups. Representative results of this synthetic modification are listed in Table 2.
Both electron-rich and electron-deficient aldehydes gave the N,N′-arylidene bisamide in good to excellent yields (entries A–F, Table 2).
In order to further expand the scope of this catalytic system, acetamide was treated with a variety of aldehydes and successfully converted to their corresponding bisamide (entries G–L, Table 2).
All products were identified by comparing their physical and spectral data with those of authentic samples.19
It is noteworthy that the formation of 5A–F by this method are of considerable interest, since this is the first attempt at the synthesis of these privileged compounds in the presence of polymer supported Bronsted acid ionic liquid as an efficient solid acid catalyst.
On the basis of the results obtained above, a possible mechanism for the sequence of events is shown in Scheme 5. It seems that initially, the solid acid catalyst 4 activates the carbonyl group of the aldehyde for reaction with the amide to form a hemiamidal intermediate (6). Subsequently, elimination of water from 6, forms N-acyliminium intermediate (7), which is then converted to the desired product 5 by a nucleophilic reaction with another molecule of amide.
It is well known that the reusability, turnover numbers (TON) and turnover frequencies (TOF) of a catalytic system are the key factors that identify whether it has potential applications in industry.
Considering this fact, in order to test the catalyst reusability, the reaction of 2 mmol benzamide with 1 mmol benzaldehyde was carried out under optimal reaction conditions. After completion of each reaction, hot ethanol was added, and the catalyst was then filtered. The recovered catalyst was washed with ethanol, dried and reused. The results illustrated in Fig. 3 show that the catalyst can be reused for up to five cycles without significant loss in its activity. This result indicates that the catalyst was very stable and could endure this reaction's conditions without decomposition or leaching of the active species in the reaction media.
Next, the catalytic performances as TON and TOF of this reusable analog of sulfuric acid were compared with commercially available sulfuric acid for the model reaction under optimized conditions (entries 1 and 2, Table 3). The results show a greater superiority of catalyst 4 to H2SO4.
Entry | Catalyst | Acid capacity | Yield (%) | Time (min) | TON | TOF | References |
---|---|---|---|---|---|---|---|
a Molybdate sulfuric acid.b Silica sulfuric acid.c Silica-bonded S-sulfonic acid nanoparticles. | |||||||
1 | 4 | 0.074 mmol H+ per 0.08 g | 85 | 30 | 1148 | 38.26 | Present work |
2 | H2SO4 | 0.074 mmol H+ per 0.004 g | 50 | 60 | 676 | 11.26 | Present work |
3 | MSA | 0.2 mmol H+ per 0.029 g | 91 | 30 | 455 | 15.2 | 19d |
4 | SSA | 0.125 mmol H+ per 0.05 g | 90 | 30 | 720 | 24 | 19d |
5 | SBSSANPs | 0.096 mmol H+ per 0.08 g | 93 | 240 | 969 | 4.04 | 19a |
In order to show the merit of this novel catalyst, Table 3 compares our results obtained from the model reaction in the presence of catalyst 4 with the results reported in literature. It can be seen that the heterogeneous catalyst 4 exhibited a significantly higher turnover number and turnover frequency than those reported for other catalytic systems (entries 3–5, Table 3).
Based on these results, we expect that this catalyst 4 will be a suitable alternative to the existing acid catalyst in laboratory and industrial applications.
Catalyst 4 possesses a combination of a stable and hydrophobic polymeric support, strong acid strength, excellent catalytic activity and good recyclability in acid catalyzed reactions, and may open up a new route for the synthesis of novel and efficient heterogeneous acid catalysts via modification of the 3D-network polymer based on calix[4]resorcinarene. Unique properties, such as uniform reaction site and significant potential for functionalization, will allow researchers to optimize the properties of this polymer for immobilization of the desired catalyst via post-functionalizations without undergoing copolymerizations or further post-polymerization modifications.
Thus, this study suggests that the 3D-network polymer based on calix[4]resorcinarene can be used as an important and versatile green solid support for a variety of acid catalysts.
Footnote |
† Electronic supplementary information (ESI) available. See DOI: 10.1039/c4ra03463e |
This journal is © The Royal Society of Chemistry 2014 |