Mesoporous KIT-6 Supported Ionic Liquids as New and Highly Effective Heterogeneous Catalysts for Three-component Synthesis of 2-Amino-3-cyano-4H-pyrans

: A series of mesoporous KIT-6 supported ionic liquids were prepared and tested as effective and practical catalysts for the synthesis of 2-amino-3-cyano-4H-pyrans. The effects of type of catalysts, catalyst amount, and catalyst stability have also been investigated in detail, the catalyst KIT-6@ILMoO 4 exhibited excellent activity in good to excellent yields of 88 % – 98 %, may be attributed to the synergetic effect between hydroxyl groups of support beta and molybdate from the ionic liquid. In addition, the supported catalyst can be easily recovered and reused for six times still with satisfactory catalytic activity. Furthermore, a general synergetic catalytic mechanism for the reaction was proposed. Maybe this work employing KIT-6@ILMoO 4 as highly efficient and stable catalyst for the synthesis of 2-amino-3-cyano-4H-pyrans has potential commercial applications.

Ionic liquids (ILs), as a charming functional material, have found various industrial applications in synthesis and catalysis due to their negligible vapour pressure, thermal and chemical stability, non-flammable, nonvolatile and strong structural design prospects. [18][19][20][21][22][23][24] Through the functional design of anions and cations of ionic liquids, the use of ILs as catalysts in the efficient synthesis of 4H-pyrans and their derivatives have been devoleped. [25][26][27] However, the isolation of pure ILs from products and reusability has been the major issue in these processes in view of eco-sustainability. Therefore, the immobilization of these functionalized ILs over different solid supports to explore heterogeneous supported ILs has made the process easier through their easy handling, thermal stability, facile isolation and reusability. [28][29][30][31][32] Among these soild supports, mesoporous materials offer significant advantages of large surface area, highly ordered structure, thermal and chemical stabilities. These materials can be used as a platform for the loading 4H and dispersion of active components such as ILs or transition metals, thereby increasing their catalytic activities and have been widely utilized as supports in the case of heterogeneous catalysis. [33][34][35][36][37][38] In this work, we wish to report the design and synthesis of a series of mesoporous KIT-6 supported ionic liquids. These supported ionic liquids have been employed as recyclable and high-efficient heterogeneous catalysts for the product of 2-amino-3-cyano-4Hpyrans under mild conditions (Scheme 1). Furthermore, the recycling performance of catalyst and possible catalytic mechanism were explored.

General
Pluronic 123 (EO20PO70EO20) was purchased from Sigma-Aldrich, and other reagents were of analytical grade and used without any further purication. Scanning electron microscopy (SEM) and energy dispersive X-ray spectroscopy (EDX) were carried out on a JSM-7500F electron microscope. FT-IR spectra were recorded on a PE Fourier Transform spectrometer. Powder X-ray diffraction (XRD) data were obtained using Ultima IV diffractometer. The thermogravimetric analysis (TGA) was carried out on a NETZSCH STA 449 F5 at a heating rate of 10 °C min -1 under nitrogen. UV-Vis spectra were recorded on a Shimadzu UV-2450 spectrophotometer. N2 adsorption-desorption isotherms were recorded using a BELSORP-max instrument and pore size distribution curves were calculated from the analysis of desorption branch of the isotherm by the BJH (Barrett-Joyner-Halenda). NMR spectra were recorded on a Bruker 400 MHz spectrometer. Elemental analysis was recorded on a Vario Micro cube Elemental Analyzer. Melting points were measured by an electro-thermal IA 9100 apparatus.

Synthesis of Supported Ionic Liquids
KIT-6 was synthesized as described in literatures. [34][35][36][37] The supported ILs catalysts were synthesized according to literatures (Scheme 2). [18,19,[28][29][30] A typical procedure was as follows: Sodium ethoxide (0.5 mol), ethanol (300 mL) and 2-methylimidazole (0.5 mol) were stirred at 80 °C for 5 h to give a. Then (3-chloropropyl) triethoxysilane (0.5 mol) was added, and the reaction mixture was refluxed for 24 h. After evaporating the solvent, the mixture was washed with ethanol-water (v / v = 1 / 1, 60 mL) and dried under vacuum to afford b. Subsequently, 1-bromobutane (0.3 mol), and b (0.3 mol) were added to a 500 mL roundbottomed flask in the presence of toluene (250 mL). The reaction mixture was heated to 90 °C under nitrogen for 24 h, thereafter, the solvent was isolated and dried to give c. Next, c (0.1 mol), sodium vanadate or sodium molybdate or sodium ethoxide or sodium hydroxide (0.1 mol), ethanol (80 mL) were stirred at 80 °C for 24 h, then the solvent was evaporated, the obtained residue was washed with ethyl acetate and then dried at 50 °C under vacuum to give ionic liquid d ILVO4 or ILMoO4 or ILOC2H5 or ILOH. Finally, KIT-6 (1.0 g) and d (0.4 g) were added into a solution of dry toluene (120 mL), and the mixture was stirred and refluxed for 24 h under nitrogen. Then the resulting solid was filtered, cleansed twice with diethyl ether and dried under vacuum under the temperature of 60 °C for obtaining the supported ILs e.

KIT-6
Scheme 2. Schematic diagram of supported ionic liquids fabrications. typical procedure, aldehyde (0.01 mol), malononitrile (0.01 mol), ethyl acetoacetate (0.01 mol), EtOH/H2O (v / v = 1 / 1, 15 mL) and KIT-6@ILMoO4 (0.5 g) were put into the reactor. And then, the reaction mixture was stirred at 80 °C for a period of time. After completion (by TLC, ethyl acetate / petroleum ether = 1 / 3 solvent system), the mixture was filtered to separate the catalyst and washed with ethanol. The filtrate was concentrated and the crude product purified with ethanol to afford the final product. Fresh substrates were then recharged to the recovered catalyst and then recycled under identical reaction conditions.

RESULTS AND DISCUSSION
Initially, the catalytic synthesis of ethyl 6-amino-5-cyano-2methyl-4-phenyl-4H-pyran-3-carboxylate from benzaldehyde, malononitrile, and ethyl acetoacetate was chose as the model reaction to vary the reaction parameters (Table  1). It can be observed that all the bulk ionic liquids ILVO4, ILMoO4, ILOC2H5, ILOH and mesoporous support KIT-6 as catalysts have only 23-81 % product yields after 10-12 h, which suggested that bulk ionic liquids and KIT-6 showed bad catalytic activities (Table 1, entries 5-9). In addition, when catalyst was inexistence, no product was found even at longer reaction time of 24 h (Table 1, entry 10). However, the as-prepared supported ionic liquids could promote the catalytic process significantly, and drastic increase in the product yields were achieved within shorter reaction times of 3-5 h ( Table 1, entries 1-4). It was found that the two supported ionic liquids KIT-6@ILMoO4 and KIT-6@ILOC2H5 demonstrated the better performance, especially KIT-6@ILMoO4 demonstrated the highest catalytic perfor mance with 93 % product yield (Table 1, entry 2). Next, the effect of amount of best catalyst KIT-6@ILMoO4 was studied. The product yield increased significantly when the catalyst amount was increased, moderate to excellent yields were obtained from 0.1g to 0.5 g (Table 1, entries 11-13 and 2), which means that increase of the amount of catalyst is conductive for the condensation reaction. However, the amount of catalyst was further increased to 0.6 g, no obvious enhancement of product yield was observed (Table 1, entry 14). The results showed that KIT-6@ILMoO4 has the highest catalytic activity with 0.5 g catalyst amount.
The effect of solvents was performed in the presence of KIT-6@ILMoO4 at 80 °C (Figure 1). Solvent variations indicated that ethanol were generally better than other solvents such as water, acetonitrile, tetrahydrofuran, trichloromethane, and toluene, with ethyl 6-amino-5-cyano-2-methyl-4-phenyl-4H-pyran-3-carboxylate being the best yield. A control experiment showed that solvent-free condition was indispensable for the reaction. It clearly illustrated that ethanol is a more effective solvent. The important indicator to measure the pros and cons for the design of catalyst is the stability evaluation of the catalyst KIT-6@ILMoO4. As shown in Figure 2, recycling catalytic experiments over KIT-6@ILMoO4 were carried out using the model reaction under the optimized conditions. The catalyst KIT-6@ILMoO4 was easily isolated by filtration and can be used directly for consecutive runs. Remarkably, KIT-6@ILMoO4 possessed a good reusability and maintained high catalytic performance at least six times without considerable reduction in catalytic activity. The product yield in the six run was 88 %, showing merely a 5 % decrease in performance compared to the fresh catalyst. The recovered catalyst after six times has no obvious change in morphology ( Figure S3f). The recovered catalyst after six times has no obvious change in crystalline structure, referring to the XRD pattern in comparison with the fresh catalyst ( Figure 3). Furthermore, a hot-filtration test was carried out to investigate the stability of catalyst. The reaction was performed for first 1.5 h with 68 % yield and then the catalyst was filtered off from the reaction mixture. The above filtrate was continued for another 3.5 h, and no progress for the reaction was monitored by HPLC ( Figure 4). This observation indicated that nearly no active species leach into the reaction mixture and also confirmed the good stability of the catalyst examined by thermogravimetric analysis ( Figure  S7). Hence, the excellent stability and reusability of KIT-6@ILMoO4 made it possible for commercial applications.
After having the optimized conditions in hand, we explored the generality of our developed protocol by employing other aldehydes and the corresponding catalytic activities were showed in Table 2. The corresponding 2-amino-3-cyano-4H-pyrans were obtained in good to excellent yields (88 % -98 %) and conversions (90 % -99 %) within 4 h. The catalytic activities of aldehydes that contained electron donating groups (Table 2, entries 2-4) were higher than those of other aldehydes. When the structure of substitute containing electron withdrawing groups, it took longer time to satisfy the good yields (Table 2, entries 5-10).
Based on the above results and relevant literatures, [8][9][10][11][12] a possible catalytic mechanism is proposed for this reaction (Scheme 2). The first step involves the Knoevenagel condensation of aldehyde and malononitrile for the formation of the intermediate olefin I. The MoO4 anion of KIT-6@ILMoO4 actives malononitrile and hydroxyl groups on the SBA-15 support actives aldehyde, which could helps to activate the condensation and improves the reaction efficiency. At the same time, the multifunctional catalyst helps to activate ethyl acetoacetate to for the formation of the intermediate enolate II. Subsequently, the intermediate II adds to I by Michael addition to give the intermediate III, followed by the intramolecular cyclization to give the target compound IV. The synergistic effect of Mo O4 and hydroxyl hydroxyl active species is helpful to the reaction and can greatly accelerates the catalytic performance.

CONCLUSIONS
In conclusion, a series of mesoporous KIT-6 supported ionic liquids were prepared and tested as catalysts for the synthesis of 2-amino-3-cyano-4H-pyrans. The experiment demonstrated that the catalyst KIT-6@ILMoO4 possessing abundant active sites exhibited excellent activity in good to excellent yields (88 % -98 %), may be attributed to the synergetic effect between hydroxyl groups of support beta and molybdate from the ionic liquid greatly accelerates the reaction. The catalyst having full utilization of active sites can be easily recovered and reused for six times without considerable reduction in catalytic activity. The protocol was found to be advantageous in terms of good to excellent yields, ease of isolation and reusability of the catalyst. This study confirmed that the the construction of synergistic catalytic active sites of mesoporous material supported lLs was a cost effective way that not only markedly enhanced the catalytic activity but also facilitated the operation and transport, which offered a broad application prospect in the practical application of green and high efficient catalytic heterogeneous process.