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A simple and one pot process for the synthesis of flavanones in the presence of SO 2A 4 =ZrO 2, a reusable, heterogeneous catalyst has been described. Reactions were conducted both with and without solvent (using toluene as solvent) at 140 degC with reaction times of 3-4 h. The catalyst was easily recycled and reused without loss of its catalytic activity.
A simple and one pot process for the synthesis of flavanones in the presence of SO 2A 4 =ZrO 2, a reusable, heterogeneous catalyst has been described. Reactions were conducted both with and without solvent (using toluene as solvent) at 140 degC with reaction times of 3-4 h. The catalyst was easily recycled and reused without loss of its catalytic activity.
A simple and one pot process for the synthesis of flavanones in the presence of SO 2A 4 =ZrO 2, a reusable, heterogeneous catalyst has been described. Reactions were conducted both with and without solvent (using toluene as solvent) at 140 degC with reaction times of 3-4 h. The catalyst was easily recycled and reused without loss of its catalytic activity.
reusable catalyst for one pot synthesis of avanones Bashir A. Dar a , Nisar Ahmad b , Jyoti Patial a , Parveen Sharma a , Kushal Bindu c , Sudip Maity d , Baldev Singh a, * a NPC and Catalysis Lab., Indian Institute of Integrative Medicine (CSIR), Canal Road, Jammu 180 001, India b Quality Control Lab., Indian Institute of Integrative Medicine (CSIR), Canal Road, Jammu 180 001, India c Analytical Division, Indian Institute of Integrative Medicine (CSIR), Canal Road, Jammu 180 001, India d CIMFR, Dhanbad, Jharkhand, India Received 30 June 2011; accepted 27 September 2011 Available online 5 October 2011 KEYWORDS Flavonoids; Impregnation; Strong acid; Aldehydes; Catalyst; One pot synthesis; Sulfated zirconia Abstract A simple and one pot process for the synthesis of avanones in the presence of SO 2 4 =ZrO 2 , a reusable, heterogeneous catalyst has been described. The reactions were conducted both with and without solvent (using toluene as solvent) at 140 C with reaction times of 34 h. Under these conditions several examples were found with very good yields (7387%) and up to 83% selectivity. The catalyst was easily recycled and reused without loss of its catalytic activity. The present synthetic method is a simple, clean and environment friendly alternative for synthesiz- ing substituted avanones. 2011 Production and hosting by Elsevier B.V. on behalf of King Saud University. 1. Introduction The avanones are a class of naturally occurring polypheno- lic compounds which are extensively distributed in vascular plants (Lee et al., 2007). These are minor ingredients of the human diet, (Kabalka and Mereddy, 2005; Bennardi et al., 2007) the most abundant being the avanones. Members of this class have been shown to display a wide variety of biological activities, (Viuda-Martoz et al., 2008) such as antioxidant effect, inhibition of HIV-1 proteinase, and anticancer (Yanling et al., 2007), vasodilator, antiviral and antiallergenic (Alan and Miller, 1996), in addition to antimicrobial (Cushnie and Lamb, 2005; Young et al., 2007), anti-inammatory (Pan et al., 2010) activities. The curiosity in the biological properties of avanones has resulted extreme synthetic efforts toward the synthesis of dif- ferent avanones. There are number of methods available for the synthesis of avanones and their analogs. The gen- eral methods to obtain avanones are the cyclization of 1,3-diphenylpropane-1, 3-diones or o-hydroxychalcones (Lee et al., 2007; Pathak et al., 2008) and Baker and Venkatar- aman rearrangement wherein o-hydroxyacetophenone is ben- zoylated to form the benzoyl ester (Diana et al., 2000; * Corresponding author. Tel.: +91 2572002/2579117/2578206/ 2547493; fax: +91 2548607/2548329/2546383. E-mail address: drbaldevsingh@yahoo.co.in (B. Singh). Peer review under responsibility of King Saud University. Production and hosting by Elsevier Journal of Saudi Chemical Society (2014) 18, 464468 King Saud University Journal of Saudi Chemical Society www.ksu.edu.sa www.sciencedirect.com http://dx.doi.org/10.1016/j.jscs.2011.09.015 1319-6103 2011 Production and hosting by Elsevier B.V. on behalf of King Saud University. Balogh and Laszlo, 1993; Chisem et al., 1997). Other meth- ods include AllanRobinson synthesis and intramolecular Wittig strategy (Huang et al., 2003; Ganguly et al., 2005). But these methods are not environment friendly because of using homogeneous catalysts, such as FeCl 3 (Kumar and Perumal, 2007), sodium acetate (Wu et al., 1989), H 2 SO 4 (Zembower and Zhang, 1998), PalladiumThiourea (Miao and Yang, 2000), SeO 2 (Ballesteros et al., 1995), acetic acid (Kalinin et al., 1990), DMSO (Makrandi and Kumari, 1989; Agrawal and Soni, 2005) NiCl 2 /Zn/KI (Miyake et al., 2003), Br 2 /CHCl 3 , NaOAc/AcOH, EtOH/HCl, clay (Varma et al., 1998). Chemical and pharmaceutical industries are always in search of environment friendly methodologies for organic transformations. To overcome these problems different solid acid catalysts, such as zeolites, clays, Al-MCM-41, oxides like alumina (Varma et al., 1985), magnesium oxide (Drexler and Amiridis, 2003), and supported reagents like supported triuoromethanesulfonic acid have been used in this transformation (Parvulescu et al., 2005). These heteroge- neous catalysts are not only recyclable and easier to separate from the reaction mixture, but also show better selectivity than homogeneous catalysts. However most of them require tedious preparation methods and the use of expensive and toxic solvents (Wang et al., 2005; Drexler and Amiridis, 2003). It is known that sulfated zirconia an extraordinarily acidic material that exhibits greater catalytic activity than that of 100% sulfuric acid in several catalytic reactions (Reddy et al., 2006) is an efcient catalyst for different func- tional group transformations under heterogeneous conditions and has received much attention in organic synthesis (Singh et al., 2011). But nobody has reported this catalyst for the synthesis of avanones to the best of our knowledge. So herein we report the catalytic efciency of sulfated zirconia for one pot synthesis of avanones from substituted benzal- dehydes and substituted 2-hydroxyacetophenones (Scheme 1). 2. Experimental 2.1. Catalyst preparation Zirconium oxychloride ZrOCl 2 8H 2 O (Loba Chemie), ammo- nia (25 wt%) (Loba Chemie), ammonium sulfate (NH 4 ) 2 SO 4 (Loba Chemie), and sodium sulfate Na 2 SO 4 (Loba Chemie) were of analytical grade. About 25 g of ZrOCl 2 8H 2 O was dis- solved in 500 ml double distilled water. To this clear solution, dilute aqueous ammonia was added drop-wise from a burette with vigorous stirring until the pH of the solution reached 7.58. The gel mixture was stirred continuously for 30 min and the resulting gel was washed with distilled water until free from chloride ions and dried at 120 C for 24 h. To a ne pow- der of zirconium hydroxide calculated amount of ammonium sulfate was introduced by implementing the impregnation method. The product was dried at 95 C and calcined at 550 C in air atmosphere and stored in vacuum desiccator. 2.2. Catalyst characterization The surface and bulk properties of zirconia and sulfated zir- conia catalyst were examined by different techniques namely X-ray powder diffraction (Fig. 1) BET surface area and ammonia-TPD reported elsewhere (Singh et al., 2011). XRD patterns were recorded at room temperature on a D8 ADVANCE (BRUKER AXS, Germany) diffractometer using CuKa (k = 0.15418 nm) parallel beam (Gobel Mirror) radiation which illustrates that the catalysts include two types of zirconia phases (ZrO 2 ) namely tetragonal phases and monoclinic phases (beddeleyite). Crystallite sizes of tetragonal and monoclinic phases are determined using (111) planes at 2h value of 30.283 and 28.175, respectively. The acidity of catalyst was determined by CHEMBET-3000 TPR/TPD/TPO instrument, containing a quartz reactor (i.d. = 4 mm) and a T.C.D. detector. Prior to TPD studies; sample was pretreated at 250 C for 2 h with continuous ow of pure nitrogen (99.9%) then cooled to room temper- ature. After pretreatment, the sample was saturated with 10% anhydrous ammonia gas until saturated adsorption. The temperature was increased to 80 C and kept there for 2 h to remove the physisorbed ammonia. Finally the system was heated from 80 to 1200 C at the rate of 10 C/min and the desorbed gas was monitored with a T.C.D. detector. All the ow rates were maintained at normal temperature and pressure (NTP). All the chemicals used in this synthesis of avanones were purchased from Sigma Aldrich; the proce- dure for the catalytic reactions was followed from those ear- lier reported (Wang et al., 2005). 2.3. Reaction in toluene as solvent In a typical experiment avanone synthesis was carried out under N 2 in a round bottomed ask equipped with a reux condenser immersed in a thermostatted bath and stirred magnetically. Model avanone was prepared by mixing in 15 mmol of benzaldehyde derivative and 10 mmol of substi- tuted o-hydroxyacetophenone and heated to 140 C, 5 ml toluene and SO 2 4 =ZrO 2 catalyst (1% mmol) was reuxed with stirring for the indicated time (see Table 1). The reac- tion was monitored by TLC. After completion of the reac- tion, the catalyst was ltered and washed twice with toluene then with dichloromethane and recycled. The extracts were combined and washed with 1 M NaOH, then with H 2 O, and dried with anhydrous sodium sulfate. The R H O + O CATALYST OH R' OH R' O R O O R R' intermediate Scheme 1 Sulfated zirconia as an efcient heterogeneous and reusable catalyst for one pot synthesis of avanones 465 organic solution was concentrated in vacuum. The crude product thus obtained was dissolved in ethyl acetate and analyzed by GCmass spectrometry (GCMS/MS), Varian 4000 gas chromatograph (GC) FID detector and compared with authentic samples. 2.4. Solvent-free reaction Model avanone was prepared by mixing in 15 mmol of benz- aldehyde derivative and 10 mmol of substituted 2-hydroxyace- tophenone and heated to 140 C, and SO 2 4 =ZrO 2 catalyst (1% mmol) was reuxed with stirring for the indicated time (see Table 1). The reaction was monitored by TLC. After comple- tion of the reaction, the catalyst was ltered and washed twice with toluene, then with dichloromethane and recycled to check the reusability of the catalyst. No appreciable change in the reactivity was observed for the successive ve runs (Fig. 2). The extracts were combined and washed with 1 M NaOH, then with H 2 O, and dried with anhydrous sodium sulfate. The organic solution was concentrated in vacuum. The crude prod- uct thus obtained was dissolved in ethyl acetate for analysis by GCmass spectrometry (GCMS/MS), Varian 4000 gas chro- matograph (GC) FID detector and compared with authentic samples. The products were isolated by column chromatogra- phy and were analyzed by 1 H NMR and GC comparison with authentic compounds. 3. 1 H NMR data of the products ((CDCl 3 ) d (ppm)) 3.1. 2,3-Dihydro-2-phenylchromen-4-one 3.5 (d, 2H, OCCH 2 ), 5.6 (t, 1H, OCH), 7.07.9 (m, 4H, 5, 6, 7, 8-Ar-H), 7.3 (s, 5H, 2 0 , 3 0 , 4 0 , 5 0 , 6 0 -Ar-H). 3.2. 2,3-Dihydro-6-methoxy-2-phenylchromen-4-one 3.5 (d, 2H, OCCH 2 ), 3.8 (s, 3H, OCH 3 ), 5.6 (t, 1H, OCH), 6.87.5 (m, 3H, 5, 7, 8-Ar-H), 7.3 (s, 5H, 2 0 , 3 0 , 4 0 , 5 0 , 6 0 -Ar-H). 3.3. 6-Chloro-2,3-dihydro-2-phenylchromen-4-one 3.5 (d, 2H, OCCH 2 ), 5.6 (t, 1H, OCH), 6.97.9 (m, 3H, 5, 7, 8-Ar-H), 7.3 (s, 5H, 2 0 , 3 0 , 4 0 , 5 0 , 6 0 -Ar-H). Figure 1 XRD of SO 2 4 =ZrO 2 . Table 1 Sulfated zirconia catalyzed synthesis of avanones in the absence of solvents at 140 C. Reaction R R 0 Isolated yield (%) Selectivity of avanone wrt. intermediate (%) 1 H H 80 71 2 H CH 3 O 78 69 3 H Cl 83 77 4 CH 3 O CH 3 O 73 69 5 CH 3 O Cl 81 78 6 Cl CH 3 O 82 78 7 Cl H 84 81 8 NO 2 CH 3 O 84 79 9 NO 2 H 87 83 Figure 2 Recyclability of catalyst (SO 2 4 =ZrO 2 ). 466 B.A. Dar et al. 3.4. 2,3-Dihydro-6-methoxy-2-(4-methoxyphenyl) chromen-4- one 3.5 (d, 2H, OCCH 2 ), 3.8 (s, 6H, OCH 3 ), 5.6 (t, 1H, OCH), 6.87.5 (m, 3H, 5, 7, 8-Ar-H), 6.57.1 (s, 4H, 2 0 , 3 0 , 5 0 , 6 0 -Ar-H). 3.5. 2-(4-Chlorophenyl)-2,3-dihydro-6-methoxychromen-4-one 3.4 (d, 2H, OCCH 2 ), 3.8 (s, 3H, OCH 3 ), 5.6 (t, 1H, OCH), 6.87.5 (m, 3H, 5, 7, 8-Ar-H), 7.17.3 (s, 4H, 2 0 , 3 0 , 5 0 , 6 0 -Ar-H). 3.6. 6-Chloro-2,3-dihydro-2-(4-methoxyphenyl) chromen-4-one 3.4 (d, 2H, OCCH 2 ), 3.8 (s, 3H, OCH 3 ), 5.6 (t, 1H, OCH), 6.97.9 (m, 3H, 5, 7, 8-Ar-H), 6.87.3 (s, 4H, 2 0 , 3 0 , 5 0 , 6 0 -Ar-H). 3.7. 6-Chloro-2,3-dihydro-2-phenylchromen-4-one 3.4 (d, 2H, OCCH 2 ), 5.6 (t, 1H, OCH), 6.97.9 (m, 3H, 5, 7, 8-Ar-H), 7.3 (s, 5H, 2 0 , 3 0 , 4 0 , 5 0 , 6 0 -Ar-H). 3.8. 2-(4-Chlorophenyl)-2,3-dihydro-6-nitrochromen-4-one 3.4 (d, 2H, OCCH 2 ), 5.6 (t, 1H, OCH), 3.8 (s, 3H, OCH 3 ), 7.38.9 (m, 3H, 5, 7, 8-Ar-H), 6.97.2 (m, 4H, 2 0 , 3 0 , 5 0 , 6 0 -Ar-H). 3.9. 2,3-Dihydro-6-nitro-2-phenylchromen-4-one 3.4 (d, 2H, OCCH 2 ), 5.6 (t, 1H, OCH), 7.38.9 (m, 3H, 5, 7, 8-Ar-H), 7.3 (s, 5H, 2 0 , 3 0 , 4 0 , 5 0 , 6 0 -Ar-H). 4. Results and discussion In view of emerging importance of avanone synthesis we have found that SO 2 4 =ZrO 2 is an effective, convenient and practical catalyst (Scheme 1) with excellent yields. The reac- tion was optimized by taking entry 1 (Table 1) as a model reaction. In addition to atmospheric conditions the reaction was also tried in nitrogen atmosphere where better results were obtained. It is because of the oxidation of aldehydes to the corresponding acid in the presence of air which was also conrmed by GCMS. However the reported results are all under atmospheric conditions. To optimize tempera- ture, the model reaction was carried at different temperatures starting from room temperature up to 140 C 5. Only 4 5% yield was observed at room temperature and the yield increases with increase in temperature, 140 C found to be optimum beyond which there was no signicant increase in yield. Reactions 1 and 2 (Table 1) gave better yield even at 90 C. Optimum reaction time was found between 3 and 4 h. No conversion was observed without the catalyst hence it is concluded that for good yields the catalyst as well as the high temperature (140 C or above) is essential which provides the reaction sufcient energy to cross the activation barrier to form the product. Catalyst recyclability was scru- tinized for ve cycles without any considerable decrease of its activity. It is evident from (Table 1) that on substituting R with electron releasing groups there is a decrease in the yield as well as the selectivity of the product where as reverse is the case with electron withdrawing groups, this is because of decrease and increase in electrophilicity and thus reactivity of the carbonyl carbon. 5. Conclusion In conclusion, here we report a simple, one pot and efcient method for the synthesis of avanones using SO 2 4 =ZrO 2 a recyclable, cheap, non-toxic and environment friendly catalyst. 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