International Journal of Pharmacy and Pharmaceutical Sciences ISSN- 0975-1491
Vol 3, Issue 3, 2011
Research Article
SYNTHESIS OF CHALCONE AND THEIR DERIVATIVES AS ANTIMICROBIAL AGENTS
ALKA N CHOUDHARYa*, VIJAY JUYALa a
Medicinal Chemistry Research Laboratory, Department of Pharmaceutical Sciences, Bhimtal campus, Kumaun University, Bhimtal 263136, Nainital, Uttarkhand, India. Email:
[email protected] Received: 14 March 2011, Revised and Accepted: 11 April 2011
ABSTRACT In a wide search program towards new and efficient antimicrobial agents, substituted chalcones have been synthesized by condensing benzaldehyde derivatives with acetophenone derivatives in dilute ethanolic sodium hydroxide solution at room temperature according to Claisen – Schmidt condensation. The structures of these compounds have been investigated by infra red spectroscopy, nuclear magnetic resonance spectroscopy and mass spectrometry. The antimicrobial activity of the novel products was evaluated by Filter Paper Disc diffusion Method. The compound 1b showed excellent activity against S. aureus at both concentration i.e. 500μg/ml and1000 μg/ml. Keywords: Chalcone derivates, Antimicrobial agents. INTRODUCTION There is growing interest in the pharmacological potential of natural products is chalcones constitute an important group of natural products. Chemically, they consist of open chain flavanoids in which the two aromatic rings are joined by a three carbon α .β unsaturated carbonyl system The presence of a reactive α, β unsaturated keto function in chalcones is found to be responsible for their antimicrobial activity1 In recent years a variety of chalcones have been reviewed for their cytotoxic, anticancer chemoprevenive and mutagenic as well as antiviral, insecticidal and enzyme inhibitory properties2,3. A number of chalcones having hydroxy, alkoxy groups in different position have been reported to possess anti‐bacterial4, antiulcer5, 7, vasodilatory8, antimitotic9, antimalarial 10, antifungal6, antioxidant antileshmanial11 and inhibition of chemical mediators release, inhibition of leukotriene B412, inhibition of tyrosinase 13,14 and inhibition of aldose reductase15 activities. Appreciation of these findings motivated us to synthesize chalcones as a potential template for antimicrobial agents. It must be noted that this scaffold provides substitution pattern on benzylidenacetophenones nucleus. EXPERIMENTAL. The melting points were recorded in open sulphuric acid or oil bath using thermometer and were uncorrected. IR spectra were recorded using Perkin‐Elmer FTIR‐RX1 spectrophotometer. A 1HNMR spectrum was recorded using CDCl3 on Bruker Avance (400 MHz) and their chemical shifts are recorded in δ (parts per million) units with respect to tetramethyl silane (TMS) as internal standard. Mass spectra were recorded on a Waters Q‐T of micro MS. All the reagents and solvents used were of analytical grade and were used as supplied unless otherwise stated. Progress of the reactions was monitored using TLC, performed on aluminium plates precoated with silica gel‐G, using chloroform: methanol (92:8) as the solvent systems and the spots were visualized by exposure to iodine vapors. General Procedure Chalcones were synthesized by base catalyzed Claisen‐Schmidt condensation reaction of appropriately substituted acetophenones and aldehydes by known literature method16. A mixture of benzaldehyde derivatives (0.01 mol) and acetophenone derivatives (0.01 mol) was dissolved in 10 ml rectified spirit in a 250 ml round‐bottomed flask equipped with a magnetic stirrer. Then 10 ml NaOH solution (1g in 10ml H2O) was added drop wise to the reaction mixture on vigorous stirring for 30 minutes when solution became turbid. The reaction temperature was maintained between 20‐25˚ C using a cold water bath on the magnetic stirrer. After vigorous stirring for 4‐5 hours the reaction mixture was neutralized by 0.1‐0.2N HCl whereby the precipitation occurred. On filtering off, the crude chalcones were dried in air and recrystallized by rectified
spirit. The residue was purified on column chromatography (silica gel with 10% ethyl acetate in hexane) to afford pure chalcones (Scheme 1). The chemical profile of the compounds is as shown in Table 1. 3(4methoxy phenyl)1(4bromophenyl)2propen1one (1a) To a stirred mixture of p‐bromo acetophenone (10mmol) and p‐ methoxy benzaldehyde (10mmol) in rectified spirit (10mL), sodium hydroxide (10.0 mL) was added drop wise and treated as in the general procedure to give 1a. Recrystalization from rectified spirit.. IR (nujol) cm‐1: 1658 (>C=O in conjugation with C=C), 1596,1540 (>C=CC=O in conjugation with C=C), 1599,1528 (>C=CC=O in conjugation with C=C), 1576,1534(>C=CC=O in conjugation with C=C), 1552,1498 (>C=C
