untitled European Journal of Chemistry 3 (3) (2012) 279‐282 European Journal of Chemistry ISSN 2153‐2249 (Print) / ISSN 2153‐2257 (Online)  2012 EURJCHEM DOI:10.5155/eurjchem.3.3.279‐282.630 European Journal of Chemistry Journal homepage: www.eurjchem.com Application of sulfonic acid functionalized nanoporous silica (SBA‐Pr‐SO3H) in the solvent free synthesis of (E)‐arylidene‐1,3‐dihydroindole‐2‐ones Parisa Gholamzadeha, Ghodsi Mohammadi Ziarania,*, Alireza Badieib, and Zohreh Bahramib a Department of Chemistry, Alzahra University, Vanak Square, 199389‐1176, Tehran, Iran b School of Chemistry, College of Science, University of Tehran, 14155‐6455, Tehran, Iran *Corresponding author at: Department of Chemistry, Alzahra University, Vanak Square, 199389‐1176, Tehran, Iran. Tel.: +98.21.88044040; fax: +98.21.88035187. E‐mail address: gmziarani@hotmail.com (G.M. Ziarani). ARTICLE INFORMATION ABSTRACT Received: 05 May 2012 Received in revised form: 02 June 2012 Accepted: 02 June 2012 Online: 30 September 2012 KEYWORDS An efficient and green condensation reaction is developed for the synthesis of (E)‐arylidene‐ 1,3‐dihydroindole‐2‐ones; (1), using heterogeneous nanoporous acid catalyst of SBA‐Pr‐SO3H with pore size, 6 nm in solvent free condition. Arylidene‐1,3‐dihydroindole‐2‐ones have many pharmaceutical properties such as Tyrosin kinase inhibiton. This method has the advantages of short reaction time, isolation ease of the products, excellent yields and recyclable catalyst. Oxindole SBA‐Pr‐SO3H Green synthesis Solvent free reaction Tyrosin kinase inhibitor Arylidene‐1,3‐dihydroindole‐2‐ones 1. Introduction Mesoporous silica SBA‐15 was first synthesized by Zhao et al. in 1998 [1,2]. These materials have attracted vast interest since then due to their potential applications as catalyst support [3], adsorbents as well as nanoreactors for making an ordered crystalline alumina molecular sieves [4,5]. SBA‐15 is nanoporous silica with a hexagonal structure, excellent stability (chemical and thermal), good accessibility due to high surface areas, large pore size, high selectivity, and isolation ease of the products [6,7]. Sulfonic acid functionalized nanoporous silica (SBA‐Pr‐SO3H) as a green and heterogeneous nano catalyst with noncorrosive properties was prepared by the functionalization of SBA‐15 [8,9]. Homogenous acid catalysts such as H2SO4, HF, and AlCl3 have serious hazards in handling, corrosiveness, difficult separation, and production of toxic waste [7]. SBA‐Pr‐SO3H has applied in the synthesis of triazoloquinazolinones and benzimidazoquinazolinones [9], polyhydroquinolines [10], Etherification of benzyl alcohols [7], quinoxaline derivatives [11] and esterification of glyceroles for monoglycride production, oxidation of sulfides into sulfoxides [6]. (Z)‐ and (E)‐arylidene‐1,3‐dihydroindole‐2‐ones, 1, have many pharmaceutical properties such as tyrosin kinase inhibition [12‐16], phosphodiesteras inhibition [17], anti‐ rhematic agent [18], and are also selective inhibitors of Plasmodium falciparum cyclin dependent protein kinase [19]. In the literature, some methods for the synthesis of these compounds have been reported using different conditions such as microwave radiation [20], Brønsted acidic ionic liquid [21], piperidine in ethanol [12,14,22,23], and pyrrolidine in benzene [24]. We decided to report the application of SBA‐Pr‐SO3H as a highly active nano‐acid catalyst in the efficient and green synthesis of arylidene‐1,3‐dihydroindole‐2‐ones. 2. Experimental 2.1. Instrumentation The chemicals employed in this work were obtained from Merck Company and were used with no purifications. 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 1H NMR (500 MHz) was run on a Bruker DPX. GC‐Mass analysis was performed on a GC‐Mass model: 5973 network mass selective detector, GC 6890 Agilent. Weight change curve in nitrogen was measured on a TA instrument of TGA Q50 V6.3 with maximum heating rate of 20 oC/min. Nitrogen adsorption and desorption isotherms were measured at ‐196 oC using a Japan Belsorb II system after the samples were vacuum dried at 150 oC overnight. SEM analysis was performed on a PhilipsXL‐30 field‐emission scanning electron microscope operated at 16 kV while TEM was carried out on a Tecnai G2 F30 at 300 kV. 2.2. Preparation of SBA‐15 The synthesis of SBA‐15 was carried out in accordance to the earlier reports [1,2]. In a typical synthesis batch, triblock copolymer surfactant as a template (P123 = EO20PO70EO20, Mac = 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 oC. The resulting mixture was transferred into a Teflon‐lined stainless steel autoclave and kept at 100 oC for 20 h without stirring. The gel composition P123:HCl:H2O:TEOS was 0.0168:5.854:162.681:1 in molar ratio. 280 Gholamzadeh et al. / European Journal of Chemistry 3 (3) (2012) 279‐282 Table 1. SBA‐Pr‐SO3H catalyzed the synthesis of (E)‐arylidene‐1,3‐dihydroindole‐2‐ones under solvent free condition. No Product R Time (h) Temp (oC) Yield (%) M.p. (oC) M.p. Lit. (oC) 1 1a H 1.0 120 90 178‐180 175‐176 [21,25] 2 1b 2´‐OCH3 1.5 120 65 221‐224 221‐222 [22] 3 1c 3´‐OCH3 6.0 120 40 150‐152 151‐152 [22] 4 1d 4´‐OCH3 1.0 120 86 162‐165 159‐160 [25] 5 1e 2´,3´‐(OCH3)2 2.0 120 81 184‐186 New 6 1f 4´‐OH 1.0 120 71 295‐297 299 [26] 7 1g 4´‐N(CH3)2 1.5 120 50 225‐227 230‐233 [27] 8 1h 4´‐Cl 1.5 120 58 178‐181 188‐190 [25] 9 1i 2´,3´‐(Cl)2 1.0 120 77 220‐224 New 10 1j 3´‐NO2 0.5 120 90 203‐204 209‐210 [21] Table 2. The optimization of reaction conditions in the synthesis of 1j. No Solvent Time (h) Temp (oC) Yield (%) 1 EtOH 9 80 60 2 H2O N.R. 100 ‐ 3 CH3CN 24 80 27 4 Solvent free 0.5 120 90 N.R. = No Reaction. After cooling down to room temperature, the product was filtered, washed with distilled water and dried overnight at 60 oC in air. The as‐synthesized sample was calcinated at 550 oC for 6 h in air atmosphere to remove the template. 2.2.1. Functionalization of SBA‐15 with organic group 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 6 h in CH2Cl2 using a soxhlet apparatus, then dried under vacuum. The solid product was oxidized with H2O2 (excess) and one drop of H2SO4 in methanol (20 mL) for 24 h at room temperature and then the mixture was filtered and washed with H2O, and acetone. The modified SBA‐15‐Pr‐SO3H was dried and used as nanoporous solid acid catalyst in the following reactions. 2.2.2. General procedure for the preparation of (E)‐ arylidene‐1,3‐dihydroindole‐2‐ones The SBA‐Pr‐SO3H (0.02 gr) was activated in vacuum at 100 oC and then after cooling of catalyst to room temperature, oxindole (0.133 g, 1 mmol) and aryl aldehydes (1 mmol) were added to it. The mixture was heated in oil bath (120 oC) in appropriate time as shown in Table 1. After completion of the reaction which monitored by Thin layer chromatography (TLC), the crude product was dissolved in hot ethanol and then filtered for removing the solid catalyst. Filtrate was cooled to give the pure product. The solid acid catalyst subsequently was washed with diluted acid solution, distilled water and then acetone, dried under vacuum that it can be used for several times without loss of significant activity. E‐3‐benzylideneindolin‐2‐one (1a): Color: Yellow. Yield: 90%. M.p.: 178‐180 oC. FT‐IR (KBr, , cm‐1): 3150 and 3078 (NH) (amide), 1707 (C=O) (amide), 1614, 1462 and 1361 (C=C). 1H NMR (500 MHz, CDCl3, δ, ppm): 6.89 (m, 2H, Ar‐H), 7.22 (t, J = 7.7 Hz, 1H, Ar‐H), 7.48 (m, 3H, Ar‐H), 7.65 (dd, J = 7.70 Hz, 6.95 Hz, 3H, Ar‐H), 7.86 (s, 1H, C=CH‐), 8.3 (bs, 1H, NH). MS (EI, m/z (%)): 221 (M+, 100), 220 (75), 193 (30), 165 (25). E‐3‐(2‐methoxybenzylidene)indolin‐2‐one (1b): Color: Yellow. Yield: 65%. M.p.: 221‐224 oC. FT‐IR (KBr, , cm‐1): 3139 and 3073 (NH) (amide), 2950 and 2834 (CH3‐O), 1699 (C=O) (amide), 1609 and 1461 (C=C), 1228 (C‐O‐C). 1H NMR (500 MHz, CDCl3, δ, ppm): 3.89 (s, 3H, CH3), 6.85 (d, J = 0.95 Hz, 1H, Ar‐H), 6.87 (d, J = 0.95 Hz, 1H, Ar‐H), 7.00 (d, J = 8.5 Hz, 1H, Ar‐ H), 7.04 (t, J = 7.4 Hz, 1H, Ar‐H), 7.2 (td, J = 1.0 Hz, 7.6 Hz, 1H, Ar‐H), 7.27 (s, 1H, C=CH‐), 7.44 (td, J = 1.8 Hz, 7.8 Hz, 1H, Ar‐H), 7.58 (d, J = 7.7 Hz, 1H Ar‐H), 7.74 (dd, J = 7.5 Hz, 1H Ar‐H), 7.99 (s, 1H, NH). MS (IE, m/z (%)): 252 (15), 251 (M+, 90), 221(40), 220 (100). E‐3‐(2,3‐dimethoxybenzylidene)indolin‐2‐one (1e): Color: Yellow. Yield: 81%. M.p.: 184‐186 oC. FT‐IR (KBr, , cm‐1): 3183 and 3079 (NH) (amide), 2955 and, 2834 (CH3‐O), 1705 (C=O) (amide), 1611, 1580, 1462 (C=C). 1H NMR (500 MHz, CDCl3, δ, ppm): 3.9 (d, 6H, CH3), 6.85 (t, J = 7.4 Hz, 1H, Ar‐H), 7.0 (dd, J = 34.7 Hz, 7.65 Hz, 2H, Ar‐H), 7.14 (t, J =7.8 Hz, 1H, Ar‐H), 7.21 (t, J = 7.55 Hz, 1H, Ar‐H), 7.31 (d, J = 7.55 Hz, 1H, Ar‐H), 7.53 (d, J = 7.5 Hz, 1H, Ar‐H), 7.98 (s, 1H, C=CH‐), 9.34 (s, 1H, NH). MS (IE, m/z (%)): 281 (M+, 20), 251 (30%), 250 (100), 235 (15). E‐3‐(2,3‐dichlorobenzylidene)indolin‐2‐one (1i): Color: Yellow. Yield: 77%. M.p.: 220‐224 oC. FT‐IR (KBr, , cm‐1): 3447 and 3182 (NH) (amide), 1709 (C=O) (amide), 1617, 1553, 1466, 1409 (C=C). 1H NMR (500 MHz, CDCl3, δ, ppm): 6.85 (t, J = 7.75 Hz, 1H, Ar‐H), 6.90 (d, J = 7.65 Hz, 1H, Ar‐H), 7.3 (m, 3H, Ar‐H), 7.6 (dd, J = 7.65 Hz, 7.45 Hz, 2H, Ar‐H), 7.82 (s, 1H, C=CH‐), 8.2 (bs, 1H, NH). MS (IE, m/z (%)): 290(M+2, 2), 289 (M+, 5), 256 (30), 254 (100), 219 (5), 190 (8). 3. Result and discussion In this paper, the condensation of aromatic aldehydes, 2, with oxindole, 3, in the presence of nanoporous solid acid catalyst (SBA‐Pr‐SO3H) has been studied (Scheme 1). As shown results in Table 2, among the tested solvents such as CH3CH2OH, H2O, CH3CN and solvent free system, the best results were obtained after 0.5 hour in the solvent free condition in excellent yield. The high yields of reactions are attributed to the effect of nanopore size about 6 nm of solid acid catalyst, which could act as nano‐reactor (Figure 1). Therefore, this reaction was developed with different aldehydes and the results were summarized in the Table 1. The reaction time was 0.5‐2.0 h and high yields of products were obtained. The acid catalyst was separated from the crude products and reactivated by simple washing subsequently with diluted acid solution, water and acetone, and then reused without noticeable loss of reactivity. The new products were characterized by IR and NMR spectroscopy data. Melting points are compared with reported values in the literature as shown in Table 1. Scheme 1 Gholamzadeh et al. / European Journal of Chemistry 3 (3) (2012) 279‐282 281 Scheme 2 Figure 1. SBA‐Pr‐SO3H acts as a nano‐reactor. The suggested mechanism for the SBA‐Pr‐SO3H catalyzed condensation was shown in Scheme 2. Concerning the reaction 3 mechanism, we suggest that initially, the solid acid catalyst protonates the carbonyl group of aldehydes, 2, and then condenses with oxindole 3 to give the adduct product which is converted to target molecule 1 by losing of H2O. After finishing of reaction, the filtrated solid acid catalyst was subsequently washed with diluted acid solution, distilled water and then acetone, dried under vacuum. As it is shown in Table 3, after recycling of SBA‐Pr‐SO3H, no significant decrease in its activity up to five runs was observed. Table 3. Reusability of the catalysts in the synthesis of 1j. Entry Number of recycle Yield (%) 1 First 90 2 Second 90 3 Third 88 5 Forth 86 6 Fifth 86 The synthesis of arylidene‐1,3‐dihydroindole‐2‐ones, 1, have been studied in several conditions in literature as shown in Table 4. In comparison with other existing methods, the present methodology has several advantages such as a greener conditions, simple synthesis, short reaction time, easy work‐up, and excellent yields with high purity of products. 3.1. Preparation of catalyst New nanoporous silica SBA‐15 can be obtained by using commercially available triblock copolymer Pluronic P126 as a structure directing agent [1,2]. Functionalizing of SBA‐15 with ‐ SO3H group was usually performed though direct synthesis or post‐grafting. As shown in Figure 2, the SBA‐15 silica was functionalized with (3‐mercaptopropyl)trimethoxysilane (MPTS) then the thiol groups of the product were oxidized to sulfonic acid by hydrogen peroxide. Analyzing of the catalyst surface was performed by various methods such as TGA, BET and CHN methods which demonstrated that the propyl sulfonic acids were immobilized into the pores. Calculating average pore diameter of the surface area was performed by the BET method and pore volume of SBA‐Pr‐SO3H are 440 m2/g, 6.0 nm and 0.660 cm3/g, respectively, which are smaller than those of SBA‐15 due to the immobilization of sulfonosilane groups into the pores [10]. SEM image of SBA‐Pr‐SO3H (Figure 3a) shows uniform particles about 1 μm. The same morphology was observed for SBA‐15. It can be concluded that morphology of solid was saved without change during the surface modifications. On the other hand, the TEM image (Figure 3b) reveals the parallel channels, which resemble the pores configuration of SBA‐15. This indicates that the pore of SBA‐Pr‐ SO3H was not collapsed during two steps reactions [28]. Figure 2. Schematic illustration for the preparation of SBA‐Pr‐SO3H. (a) (b) Figure 3. SEM (a) and TEM (b) image of SBA‐Pr‐SO3H. 282 Gholamzadeh et al. / European Journal of Chemistry 3 (3) (2012) 279‐282 Table 4. Comparison of different condition in the synthesis of arylidene‐1,3‐dihydroindole‐2‐ones. Entry Catalyst Solvent Condition Time Yield (%) Year 1 Piperidine Ethanol Reflux 18 h 44‐88 2009 [22] 3 Piperidine Ethanol Reflux 3‐5 h 80 1998 [12] 4 [(CH2)3SO3Hmim]HSO4 ‐ 80 °C 20‐120 min 86‐97 2008 [21] 5 KF‐Al2O3 ‐ MW 3‐10 min 69‐94 1998 [20] 6 SBA‐Pr‐SO3H ‐ 120 °C 0.5‐2 h 31‐90 This work 7 No catalyst ‐ 120 °C 5 h 50 This work 4. Conclusions A novel and highly efficient method for the synthesis of arylidene‐1,3‐dihydroindole‐2‐ones has been developed in the solvent free reaction of aromatic aldehydes and oxindole using recyclable and environmentally benign SBA‐Pr‐SO3H as a nano and green solid acid catalyst. Acknowledgement We gratefully acknowledge the financial support from the Research Council of Alzahra University and the University of Tehran. References [1]. 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