Synthesis, Characterization and Antiinflammatory Activity of Chalcone Derivatives Linked with Apocynin and 5-Nitrofuran Moiety

Abstract

The present paper describes the synthesis of some new chalcone derivatives i.e. 1-[3-methoxy-4-(5-nitro-furan-2-ylmethoxy)-phenyl]-3-(substituted phenyl)-propenone derivatives (9A-9K) from furfural and apocynin as starting materials. Claisen-Schmidt reaction of 1-(4-((5-nitrofuran-2-yl)methoxy)-3-methoxyphenyl)ethanone (7) with aromatic aldehydes (8A-K) under solvent free conditions using solid NaOH as catalyst at room temperature resulted in the formation of chalcone derivatives (9A-9K) in 86-96 % yield. These compounds were characterized by 1 H NMR, Mass and IR spectroscopy and were evaluated for their anti-inflammatory activity.Keywords: Anti-inflammatory activity, Apocynin, Chalcones, Furfural, Synthesis.Asian Journal of Chemistry; Vol. 30, No. 2 (2018), 312-316 Merck pre-coated plates (silica gel 60 F254) were used and spots were visualized under UV light. Merck silica gel 60 (230-400 mesh) was used for flash column chromatography and the eluting solvents are indicated in the procedures. Melting point determinations were performed by using Mel-temp apparatus and are uncorrected. 1H NMR spectra were recorded in Varian MR-400 MHz instrument. The mass spectra were recorded on Agilent ion trap MS and infrared spectra were recorded on a Perkin Elmer FT-IR spectrometer. 5-Nitrofurfural diacetate (2):A premixed solution of concentrated nitric acid (8.6 mL, 12.2 g, 193.62 mmol) and concentrated sulphuric acid (0.06 mL, 1.1 g, 11.2 mmol) was added drop-wise into acetic anhydride (90 mL) at 0 °C with stirring. To the above reaction mixture, furfural (1) (freshly distilled, 10.4 mL, 12.06 g, 125.5 mmol) was added dropwise over a period of 45 min and stirred for 1 h at 0 °C. Water (100 mL) was added to the mixture and stirred at room temperature for 30 min to obtain a white precipitate. To the reaction contents, 10 % NaOH solution was added until the pH of the mixture reached about 2.5 and the mixture was heated at 50°C for 1 h. After cooling to room temperature, the white precipitate formed was filtered, washed with water, recrystallized from anhydrous ethanol and dried to obtain diacetate compound 2. Yield: 24.84 g, 82 %. 5-Nitrofurfural (3):A mixture of 5-nitrofurfural diacetate (2) (10 g, 41.12 mmol) and 50 % aqueous sulphuric acid (100 mL) was heated to 100 °C for 10 min. After completion of the reaction, checked by TLC, the reaction mixture was cooled to room temperature and extracted with ethyl acetate (2 × 100 mL) and the organic layer was washed with water, brine solution and dried over anhydrous sodium sulphate, filtered and concentrated under reduced pressure to obtain 5-nitrofurfural 3. Yield: 5.10 g, 88 %. m.p.: 35-36 °C.(5-Nitrofuran-2-yl)methanol (4): To a stirred solution of 5-nitrofurfural (3) (5 g, 35.44 mmol) in methanol (100 mL), cooled to 0 °C, was added sodium borohydride (1.47 g, 38.98 mmol) portion-wise and continued to stirred for additional 30 min. After completion of the reaction, checked by TLC, the solvent was concentrated under reduced pressure and the residue was quenched with water (2...

Chalcones: A review on synthesis and pharmacological activities

“…It is a commonly employed and easy method (Scheme 1). In the method, chalcones are synthesize by condensing substituted or unsubstituted benzaldehyde with substituted or unsubstituted acetophenone with the use of bases or acids as catalysts in an appropriate solvent at about 50°C-100°C for few hours (Kaur and Narasimhan, 2018;Khanapure et al, 2018;Monga et al, 2014;Özdemir et al, 2017;Rahman et al, 2007;Reddy and Kathale, 2018). It is normally carried out in the liquid phase, but some syntheses occur in the solid phase, like resin was bound with acetophenone compounds and then reacted with benzaldehyde compounds (Mahapatra et al, 2015) or under solvent-free conditions such as catalytic condensation in the presence of triazabicyclodecene (Fringuelli et al, 2004).…”

“…In a recent study, a new series of chalcone analogs containing Apocynin and 5-Nitrofuran group have been reported. Compounds CD-CN were prepared by Claisen-Schmidt's condensation, which was carried out under solvent-free conditions and was evaluated as active anti-inflammatory agents (Reddy and Kathale, 2018).…”