Application of Sulfonic Acid Functionalized Nanoporous Silica ( SBA-PrSO 3 H ) for One-Pot Synthesis of Quinoxaline Derivatives

Sulfonic acid functionalized SBA-15 (SBA-Pr-SO3H) with pore size 6 nm was proved to be an efficient heterogeneous nanoporous solid acid catalyst in the synthesis of quinoxaline derivatives from the reaction of o-Phenylenediamines with 1, 2-diketone compounds in very good yields.


Introduction
Quinoxalines exhibit a wide range of biological activities.In the core part of many agrochemicals and pharmaceuticals were found quinoxaline ring.(Sakata et al. 1988;Sato et al. 1996;Seitz et al. 2002;Gazit et al. 1996) Similarly, it was found that quinoxaline ring also exists in antibiotics, such as actinomycin, levomycin, and echinomycin (Brown et al. 2004) .Its derivatives have been used as anti-viral (Lindsley et al. 2005) and anticancer agents (Loriga et al. 1997).
The high ordered nanoporous silica, such as MCM-41 (Beck et al. 1992), LUS-1 (Reinert et al. 2003, Bonneviot et al. 2001) and SBA-15 (Zhao et al. 1998) are unique inorganic solid supports that have very high surface area with controllable pore sizes between 2 to 30 nm.They can be used as catalysts (Trong On et al. 2001, Mohammadi et al. 2007), for the preconcentration of metals (Ganjali et al. 2006(Ganjali et al. , 2004(Ganjali et al. , 2006)), and as modified carbon electrodes (Badiei et al. 2005, Zhang et al. 2006, Walcarius et al. 1999).The SBA-15 is new nanoporous silica with hexagonal structure, large pore, high surface area, high thermal stability and also diffusion free due to thicker pore walls and larger pore size respectively.This can be prepared by using commercially available triblock copolymer Pluronic P126 as a structure directing agent (Zhao et al. 1998).Integration of acidic functional groups (e.g., -SO 3 H) into SBA-15 has been explored to produce promising solid acids.The sulfonic acid functionalized SBA-15 were usually synthesized through direct synthesis or post-grafting (Lim et al. 1998, Wight et al. 2002).

Characterization
IR spectra were recorded from KBr disk using a FT-IR Bruker Tensor 27 instrument.Melting points were measured by using the capillary tube method with an electro thermal 9200 apparatus.The 1 H NMR (250 MHz) was run on a Bruker DPX, 250 MHz.Weight change curve in nitrogen was measured on a TA instrument of TGA Q50 V6.3 with maximum heating rate of 20˚C/min.Nitrogen adsorption and desorption isotherms were measured at -196C using a Japan Belsorb II system after the samples were vacuum dried at 150°C overnight.

Preparation of SBA-15
The synthesis of SBA-15 was carried out in accordance to the earlier reports (Zhao et al. 1998).In a typical synthesis batch, triblock copolymer surfactant as a template (P123 = EO 20 PO 70 EO 20 , M ac =5800) (4.0 g) was dissolved in 30 g of water and 120 g of 2 M HCl solution.Then, TEOS (tetraethylorthosilicate) (8.50 g) was added to reaction mixture which was stirred for 8 h at 40 C.The resulting mixture was transferred into a Teflon-lined stainless steel autoclave and kept at 100 C for 20 h without stirring.The gel composition P123: HCl: H 2 O: TEOS was 0.0168 : 5.854 : 162.681: 1 in molar ratio.After cooling down to room temperature, the product was filtered, washed with distilled water and dried overnight at 60 C in air.The as-synthesized sample was calcinated at 550 C for 6 h in air atmosphere to remove the template.

Functionalization of the SBA-15 by organic groups
Functionalization of the SBA-15 catalyst was schematically shown in Fig. 1.The calcinated SBA-15 (2 g) and (3-mercaptopropyl)trimethoxysilane (10 ml) in dry toluene (20 ml) were refluxed for 24 h.The product was filtered and extracted for 6h in CH 2 Cl 2 using a soxhlet apparatus, then dried under vacuum.The solid product was oxidized with H 2 O 2 (excess) and one drop of H 2 SO 4 in methanol (20 ml) for 24 h at rt and then the mixture was filtered and washed with H 2 O, and acetone.The modified SBA-15-Pr-SO 3 H was dried and used as nanoporous solid acid catalyst in the following reaction.

Results and Discussion
At the beginning of this work, the condensation reaction of o-Phenylenediamines with benzil in the presence of nanoporous acid catalyst of SBA-Pr-SO 3 H was employed as the model reaction to screen the suitable reaction conditions (scheme 1).A plausible mechanism was shown in scheme 2. Among different conditions, we found using CH 2 Cl 2 as solvent in room temperature give the best result on the yields and time of the reaction (Table 1) and then these conditions were chosen as the optimized condition.Thus, under the optimized reaction conditions, this reaction was effected using various 1,2-diamines and 1,2-dicarbonyl compounds, and the results were summarized in Table 2.It can be seen when the electron-donating substituents present in diamine part, increased yields of products were observed, whereas the effect was reverse with the electron withdrawing substituent.On the other hand, substituents on aromatic 1, 2-diketone had no significant effect on the product yields.
The efficiency of various catalysts in synthesis of quinoxalines derivatives has been compared in Table 3.The best yield and short reaction time is attributed to the high efficiency of the nano-catalyst of SBA-Pr-SO 3 H.
The TGA analysis of SBA-Pr-SO 3 H confirmed the amount of organic groups on SBA-15.The weight reduction in the temperature range between 200-600C (about 15%) indicated that the amount of organic group was 1.2 mmol/g.The nitrogen adsorption-desorption isotherm SBA-Pr-SO 3 H (Fig. 2) shows type-IV adsorption behavior with the hysteresis loops appearing at relatively high pressure, suggesting that the prepared samples have regular mesoporous framework structures.The surface area, average pore diameter calculated by the BET method and pore volume of SBA-Pr-SO 3 H are 440 m 2 g -1 , 6.0 nm and 0.660 cm 3 g -1 , respectively, which are smaller than those of SBA-15 due to the immobilization of sulfonosilane groups into the pores.Table 4 shows the obtained results from the nitrogen adsorption studies at -196 °C.

Figure 1 .
Figure 1.Schematic illustration for the preparation of SBA-Pr-SO 3 H

Table 3 .
Comparison of efficiency of various catalysts in synthesis of quinoxaline derivatives 3c