A Green chemical method for the synthesis of chalcones using Amberlite Resin.

Transcription

1 A Green chemical method for the synthesis of chalcones using Amberlite Resin. 1 R.M.Ezhilarasi, 2 N.Jayachandramani, 3 S.Mahalakshmi 1 Department of chemistry, Guru Nanak College, Velachery, Chennai-42. 2,3 Department of chemistry, Pachiyappa s College, Chennai-30,Tamil Nadu, India. 1 ezhilarchana@gmail.com [Received: 20 th Feb.2015; Revised:1 st March 2015; Accepted:17 th April 2015] Abstract : Chalcones exhibit a number of biological activities. They are well known intermediates for synthesizing various heterocyclic compounds. Among the methods reported for the synthesis of chalcones, Claisen- Schmidt condensation and aldol condensation are important. Claisen - Schmidt condensation of an appropriate acetophenone with substituted benzaldehyde in the presence of nucleophilic and non-nucleophilic bases has been reported for the synthesis of various chalcones. An eco friendly method of synthesis of chalcone is reported here. It involves the condensation of acetophenone with substituted benzaldehyde in the presence of anion exchange resin at ambient temperature. The advantages of this method are good yield of the reaction and easier recovery of the product and recyclability of the resin. Reactions were carried out in the presence of solvent as well as under solvent free condition. Key Words : Chalcone, Amberlite resin, benzaldehyde, acetophenone I. INTRODUCTION Chalcones and its derivatives have been reported to possess a number of biological activitivities like antimicrobial (1), anti-inflammatory (2), analgesic (3), antiplatelet (4), antiulcerative (5), antimalarial (6), anticancer (7), antiviral (8), antileishmanial (9), antioxidant (10) and antitubercular (11) activities. 1,3-diphenyl-2- propene-1-one skeletal system was recognized as the main pharmacophore for chalcones. It is also an important intermediate for the synthesis of flavones (12,13) and pyrazoloines (14,15). Chalcones can be synthesized by many methods. Generally chalcones were prepared by Claisen-Schmidt condensation of electrophilic substituted benzaldehyde with substituted acetophenone as nucleophile in the presence of bases like NaOH, KOH,Ba(OH) 2, hydrotalcites, Zeolites, LiHMDS, Na 2 CO 3, K 2 CO 3, magnesium t-butoxide, alumina, MgO,KF/natural phosphate, calcined NaNO 3 -natural phosphates and piperidine. They can also be prepared by acid-catalysed methods using AlCl 3, dry HCl, Zn(bpy)(OAC) 2, TiCl 4, Cp 2 ZrH 2 -NiCl 2, RuCl 3, BF 3.Et 2 O, SOCl 2 -EtOH, bronsted acidic ionic liquid catalyst and iodine (16,17,23,24).Chalcones are also prepared by ultrasonic (18,19) and microwave irradiation (20,21) techniques. Green chemistry is the need of the day and hence it was planned to synthesize chalcones in an ecofriendly way without using solvents and air sensitive, corrosive bases. Thus the synthesis involves the Claisen-Schmidt reaction between acetophenone derivatives and substituted benzaldehydes in presence of basic anion exchange resin at ambient temperature. Easier recovery of the product and recyclability of the resin are the added advantages of this synthesis. Ion exchange resins (22-25) are polymers that are capable of exchanging or providing either cations or anions under experimental conditions. Commercially available Amberlite IRA-400 chloride resin can be modified to a basic resin by simple methods and hence chosen for the synthesis of chalcones by Claisen-Schmidt reaction. Chalcones synthesized were characterized using Mass spectrometry, Fourier Transformed Infrared Spectroscopy (FTIR) and 1 HNMR & 13 CNMR. Preparation of Reagent II. EXPERIMENTAL The basic anion exchange resin was prepared from the commercially available Amberlite IRA 400 (Chloride form).it was taken in a RB flask. A solution of (2N) sodium hydroxide was added until the yellow color of the resin turned brown. It was stirred for about an hour. The hydroxylated resin beads were collected and dried in vacuum. Estimation of hydroxide ion content of resin The amount of hydroxide present in the Amberlite IRA chloride resin was determined by a simple volumetric titration. 10 ml of water was added to the known amount of hydroxylated resin, stirred and it was titrated against 0.01N hydrochloric acid using phenolphthalein as an indicator. From the titre value, the amount of hydroxide present in the resin was calculated.from the 5

2 results of Table 1 it is seen that about 1g of Amberlite resin can be hydroxylated to an extent of 0.24 mmol. S. No Table 1 : Hydroxide content of the Resin Weight of Hydroxide resin (g) Hydroxide content from titre values (mmol) Optimization of reaction condition for synthesis of chalcone using the reagent To arrive at optimum stoichiometry, acetophenone(1mmol) and substituted benzaldehyde (1mmol) were allowed to react with 15,30,45 and 60 mmol of the resin. The yield of the chalcone obtained was maximum with 30 mmol. of the resin per 1mmol of acetophenone. Synthesis of chalcone using ion exchange resin (R= H, 3-NO 2, 4-NO 2, 3-CN, 4-CH 3 ) General procedure for the preparation of chalcones: a. Solution phase conventional method: A mixture of acetophenone (1 equivalent) and substituted aryl aldehyde (1 eq) was stirred in ethanol (10 vol) and then hydroxide ion resin (W/W) was added. The mixture was stirred at room temperature. On completion of reaction (monitored by TLC at an interval of every 15 minutes), it was poured in to crushed ice and acidified with HCl. The solid separated was filtered and recrystallized from ethanol. b. Solid phase synthesis: To a mixture of acetophenone (1 eq) and substituted aromatic aldehyde (1eq) taken in 50mL borosil flask, hydroxide ion resin (W/W) was added and the mixture was stirred at room temperature. The reaction was monitored by TLC at an interval of 15 minutes and after the completion of reaction, product was obtained through extraction in organic solvents. The product was recovered after distilling off the solvent under reduced pressure and purified by recrystallization. Table 2 : Reaction conditions and Yield S. Acetophenone Substituted Hydroxy resin Time % Yield No. Benzaldehyde (hour) 1. 1 g (R= H) 0.883g 1 g g (R=3-NO 2 ) g 1 g g (R=4-NO 2 ) g 1 g g (R=3-CN) g 1 g g (R= 4-CH 3 ) 1g 1 g 7 75 III. RESULTS AND DISCUSSION Claisen-Schmidt reactions carried out between acetophenone and substituted benzaldehydes in presence of basic amberlite resin gave higher yield of the respective chalcones (75%-85%).The structure of the synthesized compounds were confirmed by IR, Mass and NMR. All the compounds gave the characteristic IR peak for α,β unsaturated carbonyl group in the range cm -1 corresponding to c=o stretching and c=c stretching in the range cm -1. The chalcone derivatives showed that the molecular ion peak corresponds to the molecular mass of the proposed compound. Hence m/z value confirms the molecular weight of the respective chalcone. Proton NMR and C-13 NMR also supported structure proposed for the respective chalcone Table 3 : Synthesis of chalcones the 6

3 Table-3 presents the structure of the product formed in the respective reactions along with yield of the reaction and time taken for the completion of the reaction both in the presence and absence of solvent. The presence of electron withdrawing groups like nitro and cyano increases the rate of reaction and also the yield due to higher electron deficiency developed at the electrophilic carbonyl carbon. However, lesser yield is obtained when electron releasing groups are present in benzaldehyde. Spectral Data: (1)1, 3-Diphenyl-propenone. It was obtained from the reaction of acetophenone with benzaldehyde. Yellow needles. M.P C, IR (KBr cm -1 ): (Ar=CH stretching), 1608 (C=C conjugation with C=O stretching), 1661(CH=CH stretching); (Aromatic C-C vibration); ( aromatic five adjacent hydrogen wagging) 1 HNMR (CDCl 3 -d, 300MHz, δ, ppm): (8H, m), (1H, d, J=15.75Hz), (2H, dd, J=9.51Hz, 1.47Hz); 13 C NMR (CDCl 3, 100 MHz): , , , , , , , , , , MS (ES+APCI): m/z [M+H] +. (2) 3-(3-Nitro-phenyl)-1-phenyl-propenone: It was obtained from the reaction of acetophenone with 3-nitro benzaldehyde. Pale yellow solid. M. P. 162 C IR (KBr cm -1): (Ar-CH stretching), 1658 (C=C conjugation with C=O stretching), 1608(CH=CH stretching); 1597(C-NO 2 asymmetry stretching);1515 (Aromatic C-C vibration);1318(symmetry stretching) 746,854 (aromatic five, four, one adjacent hydrogen wagging) 1HNMR (CDCl3-d, 400 MHz, δ, ppm): (3H, d, J=6.52Hz), (2H, m), (1H, m), (2H, dd, J= 9.28Hz, 1.96Hz), (1H, d, J=15.72Hz), (2H, t, J=9.16Hz) 13 C NMR (CDCl 3, 100 MHz): , , , , , ,128.9, 130.5, 132.8, 134.9, 138.2,144.8, MS (ES+APCI): m/z [M+H] +. (3) 3-(4-Nitro-phenyl)-1-phenyl-propenone: It was obtained from the reaction of acetophenonewith 4-Nitro benzaldehyde.pale yellow solid. M. P. 177 C IR (KBr cm -1 ): 3057 (Ar-CH stretching), 1667 (C=C conjugation with C=O stretching), 1608(CH=CH stretching); 1577(C-NO 2 asymmetry stretching); 1445 (Aromatic C-C vibration); 1318(C-NO 2 symmetry stretching) 698,860 (aromatic five, two adjacent hydrogen wagging) 1HNMR (CDCl3-d, 300 MHz, δ, ppm): (2H, m), (2H, m), (3H, m), (2H, d, J=7.74 Hz), (2H, d, J=8.52Hz) 13 C NMR (CDCl 3, 100 MHz): , , , , , , , , , ,

4 MS (ES+APCI): m/z [M+H] +. (4) 3-(3-Cyano-phenyl)-1-phenyl-propenone:It was obtained from the reaction of acetophenonewith 3- cyanobenzaldehyde.yellowish white. M. P. 53 C IR(KBcm -1 ): 3061 (Ar-CH stretching),2212(cn stretching),1665(c=nstretching),1608(ch=ch stretching), 1607 (C=C conjugation with C=O stretching), 1441 (Aromatic C-C vibration); 1050 (C-N stretching), 746,854 (aromatic five,four,one adjacent hydrogen wagging) 1 HNMR (CDCl3-d, 400 MHz, δ, ppm): (m, 5H), 7.78 (d, J = Hz, 1H), 7.86 (d, J = 6.68 Hz, 1H), 7.87 (s, 1H), 7.94 (d, J = 1.52 Hz, 1H), 8.03 (d, J = 1.48 Hz, 2H). 13 C NMR (CDCl3, 100 MHz): , , , 128.8, , , , , , , 137.6, 141.7,189.7). MS (ES+APCI): m/z [M+1] +. (5) 3-(4-methyl-phenyl)-1-phenyl-propenone: It was obtained from the reaction of acetophenone with 4- methyl benzaldehyde. White solid.m. P. 68 C IR (KBr cm -1 ): 3065 (Ar-CH stretching), 1655 (C=C conjugation with C=O stretching), 1599 (CH=CH stretching); 1449 (Aromatic C-C vibration); 693,843 (aromatic five, two adjacent hydrogen wagging) 1 HNMR (CDCl3-d, 400 MHz, δ, ppm): (t,8.48 Hz, 2H) (d, 15.6 Hz, 1H), (d, 8 Hz, 2H), (m, 2 H), (m, 2H), (d, 7.96 Hz, 2H), 2.35 (s, 3H). 13 C NMR (CDCl3, 100 MHz): 21.3, 124.1, 128.3,131.1,134.5,137.8,145.1, MS (ES+APCI): m/z [M+1] +. IV. CONCLUSION A simple and solvent free, ecofriendly method was used for the synthesis of chalcone using basic amberlite resin at room temperature. This method is an alternative method for the synthesis of chalcone with electron withdrawing groups in benzaldehyde in higher yield at ambient temperature involving lesser reaction time.the resin utilized in this work can be regenerated and reused. V. ACKNOWLEDGEMENT Financial assistance from University Grants Commission, Hyderabad, India is greatly acknowledged. VI. REFERENCES [1]. S.S.Mokele, M A Sayeed, Kothawar and Chopde, Synthesis and antimicrobial activity of some chalcone derivatives, Int.J.Chem.Sci., vol.2, issue 1, pp. 96,( 2004). J.Pharm.pharmacol, vol.52, issue.2, pp , (2000). [3]. L.M. Zhao, H.S. Jin ; L.P. Sun, H.R. Piao and Z.S. Quan Z, Synthesis and evaluation of antiplatelet activity of trihydroxychalcone derivatives, Bio org. Med. Chem.Lett, vol.15,issue 22,. pp , (2005). [4]. G.S.Viana, M.A. Bandeira and F Matos Analgesic and antiinflammatory effects of chalcones isolated from Myracrodruonurundeuvaallemão,.J.Phytomedicine, vol. 10, issue 2-3, pp , (2003). [5]. S. Mukarami, M Muramatsu, H Aihara and S. Otomo Inhibition of gastric H +, K+-ATPase by the anti-ulcer agent, Sofalcone Biochem, pharmacol, vol. 42, issue 7, pp , (1991). [6]. M. Liu, P.Wilairat and LM Go, Antimalarialalkoxylated and hydroxylatedchalcones, J.Med.Chem. vol. 44, issue 25, pp , (2001). [7]. E. Francesco, G. Salvatore, M. Luigi and C. Massimo Chemistry and pharmacology of oxyprenylated secondary plant metabolics, Phytochem, vol. 68, issue 7,pp , (2007). [8]. B A Bhat, K L Dhar, S C Puri, A K Saxena, M Shanmugavel, G N Qazi Synthesis and biological evolution of chalcones and their derived pyrazoles as potential cytotoxic agents Bioorg. Med. Chem.Lett, vol. 15, issue 12, pp , (2005). [9]. S.F. Nielsen, M Chen, T.G. Theander, A. Kharazmi and S.B. Christensen, Synthesis of antiparasitic licorice chalcones, Bioorg. Med. Chem.Lett, vol. 5, issue 5, pp , (1995). [10]. C L Miranda, GLM Aponso, J F Stevens, ML Deinzer and D.R. Buhler, Antioxidant and prooxidant actions of prenylatedand nonprenylatedchalcones and flavanones in vitro J. Agric. Food Chem, vol.48,issue 9, pp , (2000). [11]. PM Siva Kumar, SK GeethaBasu and D Mukesh, QSAR studies on chalcones and flavonoids as anti-tuberculosis agents using genetic function approximation GFA method, Chem. Pharm. Bull. vol. 55, issue 1, pp , (2007). [12]. L Tang, S Zhang, J Yang, W Gao, J Gui, and T Shag, A novel approach to the synthesis of 6-Amino-7-hydroxy-flavone Molecules, vol. 9, issue 10, pp , (2004). [13]. J I Lee, H S Son and M G Jong, A novel [2]. L T Hsiesh,H.K,Tsao and JP. Wang, Synthesis synthesis of flavones from 2-methoxy benzoic and anti-inflammatory effect of chalcones, acids, Bull. Korean Chem. Soc, vol. 26,issue9, pp , (2005). 8

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