EDTA-catalyzed fast and efficient eco-friendly synthesis of ...

Maddela Prabhakar J. Chem. Pharm. Res., 2013, 5(5):89-93______________________________________________________________________________dangerous, and environmentally friendly reactions, such as Diels–Alder reactions [25], Claisen rearrangementreactions [26], Reformatsky reactions [27], and pinacol-coupling reactions [28].Presently, EDTA (ethylene diamine tetraacetic acid) have gained special attention as catalyst in organic synthesisbecause many advantages such as excellent solubility in water, uncomplicated handling, inexpensiveness and ecofriendlynature. To the best of our knowledge, there is no report of the application of EDTA catalyst for thesynthesis of dicoumarol derivatives in aqueous media, and we hope that this will be a very useful, simple, fast andscalable green protocol for the preparation of dicoumarol derivatives in water.EXPERIMENTAL SECTIONAll reagents and solvents were of the highest commercial quality purchased from Aldrich & Merk and were usedwithout further purification. 1 H NMR spectra were recorded on a Bruker AC 400 ( 1 H NMR, 400 MHz) spectrometerwith tetramethylsilane (TMS) as an internal standard. Chemical shifts are reported in parts per million (ppm, δ).Infrared Spectra (IR) was recorded on JASCO IR-A-302 Spectrometer. CHN analysis was performed on a CarloErba Strumentazion-Mod-1106 Italy. Purities of assayed compounds are, in all cases, greater than 96%, asdetermined by reverse-phase HPLC analysis. Thin layer chromatography (TLC) was performed on pre-coated silicagel glass plates (Kieselgel 60, 254, E. Merck, Germany). Chromatograms were visualized by, UV at 254 and 365nm, followed by iodine vapors. Melting points were determined on a Kofler hot-stage apparatus and are uncorrected.SynthesisGeneral procedure for the synthesis of dicoumarol derivatives (3a-p): A mixture of 4-hydroxycoumarin (1) (2mmol) and aromatic/heteroaromatic aldehydes (2a-p) (1 mmol) in 15 mL of water was added EDTA-catalyst (10mol%) and stirred at room temperature for the appropriate time mentioned in Table 1. The completion of reactionwas monitored by Thin Layer Chromatography system. After completion of the reaction, the solid products werecollected by filtration methods and washed with hot water. Finally the products were recrystallized from ethanol togive the desired pure products (3a-p).Table 1. EDTA-catalyzed synthesis of dicoumarol derivatives (3a-p) in water aOH+ R CHOO O1 2a-pEDTAWater / rt, 20-40 min.OHOR HOO O O3a-pEntry R Product Time (min) Yield (%)1 C 6H 5 3a 30 962 4-CH 3OC 6H 4 3b 25 933 4-ClC 6H 4 3c 25 954 4-HOC 6H 4 3d 30 945 2-NO 2C 6H 4 3e 25 906 2-C 5H 4N 3f 30 857 2-C 4H 3O 3g 25 908 2,5-(OCH 3) 2C 6H 3 3h 20 989 4-N(CH 3) 2C 6H 4 3i 20 9610 H 3j 40 8511 CH 3 3k 35 8012 2-OHC 6H 4 3l 25 9213 3-ClC 6H 4 3m 20 9414 -CH=CH-C 6H 5 3n 30 9315 1-Naphthyl 3o 25 9016 2,4,5-(OCH 3) 3C 6H 2 3p 20 98a Reaction conditions: EDTA (10 mol %), 4-hydroxycoumarin (2.0 mmol); Benzaldehyde (1.0 mmol); 15 mL water at RT.All synthesized compounds were characterized with 1 H-NMR and mass spectrometry. Also the melting pointsrecorded were compared with the corresponding literature melting points and found to be matching.RESULTS AND DISCUSSIONIn this paper, we wish to report a EDTA-catalyzed green approach for the synthesis of dicoumarol derivatives inwater at room temperature (Scheme 1). In our initial study, 4-hydroxycoumarin was reacted with benzaldehyde inthe presence of NH 4 OAc in water solution under refluxing temperature for 1 h and the expected product was90