J.

Atoms and Molecules / 3(1); 2013 / 463468 Research Article

Rajashree AM et al

Journal of Atoms and Molecules

An International Online Journal
ISSN 2277 1247

GREEN CHEMISTRY APPROACH TO NOVEL CHALCONES AND THEIR ANTIOXIDANT PROPERTIES Rajashree A Markandewar*1, Kendre N.M2, S.Shah N.N2, M. A. Baseer2 Department of Applied Chemistry, Ballarpur Institute of Technology, Ballarpur-442605, Maharashtra, India. 2 Organic Chemistry Research Laboratory, Yeshwant Mahavidyalaya, Nanded-431602, Maharashtra, India. Received on: 12-02-2013 Revised on: 21-02-2013 Accepted on: 27022013
1

ABSTRACT: A series of some novel 2Hydroxy Chalcone using inert Silica Gel (Mesh 230-400)by Microwave irradiation is reported. These newly synthesized compounds were screened for their antioxidant potential using DPPH screening method. The promising feature of this reaction is solvent free synthesis and excellent yield with high purity of compounds synthesized/targeted. All the synthesized compounds were confirmed by IR, 1HNMR and MS data. Synthesized compounds exhibited potent antioxidant activity, which is close to/ comparative to standard flavonoid quercetin. KEY WORDS: 2HydroxyChalcones, inert silica gel, Antioxidants, Microwave irradiation.

INTRODUCTION: In recent years, microwave accelerated organic synthesis has attracted much attention as it offers several advantages such as simple procedure, fast reaction rate, mild reaction conditions, eco-friendly and improved yields as compared to the conventional methods.1 * Corresponding author Rajashree Markandewar, Email: rajashree.markandewar@gmail.com Tel: +91 9970379816 Prompted by the varied biological activities of chalcones2, their derivatives3and increasing application of Microwave irradiation in Organic synthesis4 it was thought of interest to synthesize various substituted chalcones by Microwave irradiation. The combination of supported reagents and Microwave irradiation has gained much interest to carry out wide range of reactions in short time and with high conversion and All rights reserved 2011 www.jamonline.in 463

J. Atoms and Molecules / 3(1); 2013 / 463468 selectivity, without the need of 5,6 solvent Recently various modified methods have been reported for the solvent free synthesis of chalcones, using different catalyst Natural phosphate like SOCl27, 8 LithiumNitrate , KF/Natural Phosphate9, Na2CO310,NaOH-Al2O311, Silica Sulfuric acid 12,13 ,anhydrous K2CO314and Silica Chloride15. Chalcone an important intermediate of Flavonoid synthetic pathway exhibits pharmacological effects like anticancer, antioxidant, anti-inflammatory, antimicrobial, antiallergic and antimalarial16,. Antioxidants are the compounds that prevent oxidative damage due to free radical scavenging ability17.Chalcones with antioxidant activity have been demonstrated to have anticancer, anti-cardiovascular, and anti-inflammatory& many other activities18. Prompted by perusal of literature survey and lack of reported method for the targeted molecule, we report here in the synthesis of Novel chalcones by solvent free microwave irradiation using inert Silica gel (Mesh 230400) and study of its antioxidant potential. MATERIALS & METHODS: Experimental: All the melting points are uncorrected and were recorded using open ended capillaries. Thin Layer Chromatography of synthesized compounds was performed on Silica Gel G plates using (n-Hexane: Ethyl Acetate 7:3) solvent system and Iodine vapors as visualizing agent. IR spectra were recorded on KBr spectometer.1HNMR spectra on a Bruker Advance DPX 400 MHz spectrometer with DMSO as a solvent and TMS internal standard. The chemical shift values are expressed in part per million (ppm) downfield from the internal standard and signals are quoted as s (singlet), d (doublet), t All rights reserved 2011

Rajashree AM et al (triplet) and m (multiplet). Mass Spectra were recorded on VG7070 H Mass spectrometer at 70eV. All the reactions were carried out in Domestic Microwave Oven (Kenstar, Output Energy 1200W, frequency 2400 Mhz, Model No. M69706) General procedure Chalcones: for Synthesis of

A mixture of aromatic aldehyde (0.01mol) and substituted ortho-hydroxy acetophenone (0.01mol) along with solid NaOH (0.02mol) were homogenized in a mortar. The reaction mixture was poured onto Inert Silica Gel (230-400) 2.5gms. The reaction mix was irradiated in a domestic Microwave Oven for 2-5 mins with a regular interval of 30 sec. After completion of reaction (monitored by TLC) the content of the flaks was cooled to RT. Acetone (10ml) was added to the reaction mixture and filtered through filter paper to separate solid catalyst(i.e Silica). The filtrate was poured onto crushed ice HCl to afford solid product i.e chalcones. The Chalcones were recrystallized from glacial acetic acid. The physical data of synthesized compounds are presented in Table-1 Antioxidant Activity. All the Synthesized Compound were assigned for in vitro antioxidant activity using 1,1Diphenyl-2- picrylhydrazyl (DPPH) radical scavenging method19. The aliquot of different concentrations (50 to 100 g/ml)of the test sample was added to 0.5ml of 0.003M DPPH in methanol. Final volume was adjusted to 3ml .Quercetin was used as a positive control. Negative control was prepared by using the same amount of DPPH mixed with only methanol devoid of samples. Absorbance values were measured at 517nm using Ultraviolet Visible spectrophotometer. Absorbance was www.jamonline.in 464

J. Atoms and Molecules / 3(1); 2013 / 463468 converted into % Antioxidant activity using the following equation20.The antioxidant activity data is summarized in Table 02 S (%) =

Rajashree AM et al Where A0 = Absorbance of control (Containing all reagents except the test compound) AS= Absorbance of the test Compound

Scheme - I

Table 1 Physical data of Synthesized chalcones. Sr.No Entry 1 2 3 3a 3b 3c R1 H H I R2 H H H R3 H Cl CH3 R4

N

Mol. formula C19 H19NO2 C19 H18ClNO2 C20 H20INO2

Yield (%) 94 92 89

M.P. 0C 196 182 158

Literature 198 180 --

CH3

3d

N N

C20H22N2O2

92

126

125

CH3 N

3e

Cl
N
CH3

C20 H21ClN2O2

90

138

138

6 7 8 9

3f 3g 3h 3i

I H H I

H H H H

CH3 H Cl CH3

N N

C21 H23IN2O2 C20H21NO2 C20 H20ClNO2 C21 H22INO2

88 92 89 90

198 154 176 108

-----

All rights reserved 2011

www.jamonline.in 465

J. Atoms and Molecules / 3(1); 2013 / 463468

Rajashree AM et al

Table 2: Antioxidant activity of synthesized chalcones (3a-i) and standard flavonoid quercetin represented as % DPPH inhibition. Concentration (g/ml) 50 75 100 3a 45.68 3b 44.8 3c Series name/Products and Standard 3d 3e 3f 3g 3h 3i 44.92 56.81 69.82 Quercetin 56.73 74.96 89.96

43.29 45.37 47.51 44.31 46.18 46.37

52.84 58.92 52.17 58.93 57.48 53.71 60.32 61.42 68.82 70.39 67.34 71.62 73.77 70.18 71.46 72.48

All the above values are representative of three independent replicates and calculated from as mean + SEM of individual samples.

RESULTS & DISCUSSION: The structures of all synthesized compounds were elucidated on the basis of IR, 1HNMR and MS. IR spectra of synthesized chalcones showed characteristic band near region15901680 cm-1 due to >C=O stretching vibrations. A broad peak in between 3000-3400 cm-1 was observed due to the phenolic OH group. The1HNMR spectra of compounds were studied in DMSO-d6 showed characteristic doublets signals near 7.40-7.80 due to olefinic , unsaturated protons. Phenolic proton (2 OH) appeared as a singlet at 11.00-13.00 was observed and aromatic protons as multiplet around 7.40-7.80. The mass spectra of corresponding chalcones confirm their molecular formulae and were at respectively weights. It is found to be in agreement with the literature. Spectral data of selected compounds: 3-(-4-Pyrrolidin-1-yl-phenyl)-1-phenylpropenone):(3a) IR (KBr); 3290 [Ar--OH], 1644 [ C=O] 1613[C=C],cm-1 1 H NMR; 2.0 (t, 4H,-(CH2), 3.3(t,4H,CH2), 6.57 (d, 1H, Ethylenic), 8.1

(d,1H, Ethylenic ), 7.5-7.8 (m,8H,Ar-H), 11.70 (s, 1H,phenolic ) ppm, Mass (m/z); 294 (m+ ion) 3-[4-(4-methyl-piperazine-1-phenyl)-1phenyl]-propenone :(3d) IR (KBr); 3129[Ar-OH], 1646 [C=O], 1566[C=C], cm-1 1 H NMR; 2.2 (s, 3H, CH3), 2.4(t, 4H, CH2), 3.2 (t, 4H, CH2) 3.2 (t ,4H, (CH2), 6.9 (d, 2H ,Ethylenic ) 8.1 (d, 2H, Ethylenic, ), 7.0-8.2 (m,6H,Ar-H), 11.70 (s, 1H,phenolic) ppm Mass (m/z); 323 (m+ ion). 1-[(5-chloro-2-methyl-phenyl)-3-(4piperidine-1-phenyl)]-propenone:(3h) IR (KBr); 3433.41 [Ar-OH], 1597.11[ C=O], 1550.82 [C=C], cm-1 1 H NMR; 2.6 (s, 2H, CH2), 3.2 (d, 4H, CH2), 3.4 (d, 4H, CH2), 6.8-7.9 (m, 6H, Ar-H), 8.1 (m, 6H,Aromatic), 12.70 (s, 1H,phenolic) ppm Mass (m/z); 341 (m+ ion).

All rights reserved 2011

www.jamonline.in 466

J. Atoms and Molecules / 3(1); 2013 / 463468 CONCLUSION To conclude, novel 2Hydroxy Chalcones and its derivatives were synthesized using inert silica gel (Mesh 230-400) by Microwave irradiation and characterized by spectral data. When evaluated these compounds for antioxidant potential using in vitro DPPH method, it has been observed that, synthesized compounds exhibited potent antioxidant activity, which is close to standard flavonoid quercetin .Amongst all the derivatives, compound 3d, 3g and 3hexhibited maximum potency as compared to other derivatives ACKNOWLEDGEMENT: The authors are thankful to Principal Yeshwant Mahavidyalaya, Nanded for providing necessary facilities. Authors are thankful to Director SAIF, Chandigarh for providing spectral analysis facilities for the research work and Principal, National Pharmacy College, Nanded for anti oxidant activity. REFERENCES: (1).K. L. Ameta. Nitu S. Rathore and Brijesh Kumar,Synthesis of some novel Chalcones and their facile one pot conversion to 2aminobenzoyl 1-3 Dichloronitriles using Malonitrite ,Chimia (Series Nova) ,20(1) , 15 24(2011). (2)(a) Dim mock J.R, Elias D.W.,Beazley M. A. ,Bioactivities of Chalcones,Curr Med. Chem, 6 : 1125 (1999) . (b) DuckiS. The development of Chalcones as anticancer agents . Anticancer Med. Chem, 9 :336(2009). (c) TomarV, Bhattacharjee G, Kamluddin S, Synthesis of new Chalcones derivatives containing acryla moiety with potential antimalarial activity,Eur. J. Med Chem.45;745 (2010).

Rajashree AM et al (3). (a) Ohkatsu Y, Satoh Antioxidant and photo antioxidant activities of Chalcone derivatives, J Ipn. Petro Inst. 51; 298(2008) (b) KaramI, Gezegen H ,Gurdere M. B., Screening of biological activities of a series of Chalcone derivatives against human pathogenic microorganisms ,Chem Biodivers 7 (2),400 8 , (2010). (4) RaoS.S.,Gahlot V.S.,Pulavat S.S.,Vyas R.,Solvent free improved synthesis of some substituted 3 diaryl propene and 3,5 diaryl 6 Carboxyl cyclohexanones under microwave irradiation, Indian J. of chem.,45(B),469.(2006). (5) Rajendra V R, Solvent free organic synthesis using supported reagent and microwave irradiation,Green Chem.I,-43-55 (1999). (6) SrivastavaY.K, Ecofreindly microwave assisted synthesis of come Chalcone, Rasayan J. chem. I; 884-886(2008). (7) Petro,Iranova Y, Gerova M,SOCl2/EtOH catalytic system for synthesis of Chalcones, Catalysis Communication. 9; 315 317 (2008). (8) Sebti S, Sloshy A, Somabh A, Kossir A, Dramatic activity enhancement of natural phosphate catalyst by Lithium Nitrate:Am efficient synthesis of Chalcones,Catalysis Communication; 3; 335-339 (2009). (9) Macquarie D J,Nazih R, Sebti S, KF/Natural phosphate as an efficient catalyst for synthesis of 2hydroxy Chalcones and flavonones, Green chemistry;4 ; 56 59. (2002). (10) Zhang Z, Dong Y W, Wang G W, Efficient and clean aldol condensation catalyzed by sodium carbonate in water, Chemistry Letters,32 : 966 967 (2003). (11) SardaS R, Jadhav W N, Wasemaker S K, Dake S A, Pawar R P, Solvent free Naohwww.jamonline.in 467

All rights reserved 2011

J. Atoms and Molecules / 3(1); 2013 / 463468 Al2O3 supported synthesis of 1,3 diaryl -2propene-1-ones.Retal.International Journal of Chem Tech Research .2; 265 269,(2009). (12) Jayapal M R.Sreedhar N Y, Synthesis of 2,4dihydroxy substituted Chalcones using silica sulfuric acid reagent under solvent free condition .Asian journal of pharmaceutical and clinical research,4(1),2011,106-108 (2011). (13) Thiru Narayanan G, Vanagamudi G, Synthesis of some 4 Bromo 1-napthyl Chalcones using silica sulfuric acid reagent under solvent free conditions,,Arkivoc, XII; 58-64 (2006). (14) Jayant P Singh,Mangalshree Dulawat, Microwave enhanced claisen-schmidt condensation: A green route to chalcones.,Ind J. ChemVol 51B pp 1623-1627 (2012). (15) Hazarkhani H, Kumar P, Kondiram K S, Shafi Godwal I M,Highly selective claisenschmidt condensation catalysed by silica chloride under solvent free conditions Synthetic Communications, 40 ; 2887 289 6.5 (2010). (16) Y.M. Lin, Y Zhou, M Flavin,L M Zhou, W Nie and F C Chem,Chalcones and flavonoids as anti-tuberculosis agents., Bioorganic & Medicinal Chemistry,10(8), 2795 2802 ,(2002) (17) Z Nowakowska,A review of anti infective and anti inflammatory chalcones.,European Journal of Medicinal Chemistry., 42(2),125-137,(2007). (18) E. Cadenas and L. Packer, Handbook of Antioxidants Marcel Dekker, New York 1996. (19) K Kato,S Terao, N Shimamoto and M hirata, Studies on scavengers of active oxygen species: A synthesis and biological activity of 2-O-Alkyl ascorbic acids Journal of Medicinal chemistry.,31 (4),493- 798. (1988)

Rajashree AM et al (20) Milan Mladenovic et Sci.;12(3):2822-2841,(2011). al .IntMol

(21) S.Shah N.N ,Hanfi M Ziauddin, Mohammed Zameer, Kendre M M, Dhole J A, M A Baseer, Der Chemica Sinica,2(1), ,3337, (2011). (22) S.Shah N.N, Hanfi Md. Ziauddin, Mohammed Zameer, Kendre, Dhole J A,Tauseef Khan, M A Baseer, Der Pharmacia Sinica,3(1),180-184, (2011).

All rights reserved 2011

www.jamonline.in 468