Journal of the Korean Chemical Society 2012, Vol. 56, No. 4 Printed in the Republic of Korea http://dx.doi.org/10.5012/jkcs.2012.56.4.459 -459- Synthesis of New 8-Formyl-4-methyl-7-hydroxy Coumarin Derivatives D. M. Manidhar, K. Uma Maheswara Rao, N. Bakthavatchala Reddy, Ch. Syama Sundar, and C. Suresh Reddy* Department of Chemistry, S.V. University, Tirupati, A.P, India. * E-mail: csrsvu@gmail.com (Received January 13, 2012; Accepted June 13, 2012) ABSTRACT. 8-Formyl-4-Methyl-7-Hydroxy Coumarin Derivatives were synthesized via Penchem condensation followed by Duffs reaction. Treatment of this with N,N-di substituted cyano acetamides in the presence of piperdine afforded New 8- Formyl-4-Methyl-7-Hydroxy Coumarin Derivatives (7a-o). Their structures were characterized by IR, 1 H and 13 C NMR and Mass spectral and elemental analysis data. Key words: N,N-di substituted cyano acetamides, Piperdine, Coumarin derivatives INTRODUCTION Coumarin is a pleasanty fragrant benzopyrone com- pound, found in many plants, notably in high concentra- tion in the tonka bean (Dipteryx odorata), vanilla grass (Anthoxanthum odoratum), sweet woodruff (Galium odo- ratum), mullein (Verbascum spp.), sweet grass (Hiero- chloe odorata), Cassia cinnamon (Cinnamomum aromaticum) and sweet clover. Natural products with coumarin moiety and have wide range of biological activity. They are used as drugs, intermediates and pesticides. 1 They are found to have anti-coagulant, inflammatory microbial, 2 oxidant, 3 HIV, allergic, cancer, 4 proliferative and viral 5 properties. 4-methyl-7-hysroxy coumarin has similar structure of Scopoletin, an alkaloid which is isolated from medicinal plant (Gelsemium Seperiven) has an anti-cancer activity. Recently 4-methyl-7-hydroxy coumarin has been reported to have anti skin-cancer activity. 6 Coumarin has clinical medical value by itself, as an edema modifier. Coumarin and other benzopyrones, such as 5,6 benzopyrone, 1,2 benzopyrone, diosmin and others stimulate macrophages and degrade extracellular albu- men, allowing faster resorption of edematous fluids. Coumarin itself has no anticoagulant activity but is transformed into the natural anticoagulant called dicou- marol by a number of fungi species. This occurs as the result of the production of 4-hydroxycoumarin, then fur- ther (in the presence of naturally occurring formaldehyde) into the actual anticoagulant dicoumarol, a fermentation product and mycotoxin. This substance was responsible for the bleeding disease known historically as “sweet clo- ver disease” in cattle eating moldy sweet clover silage. EXPERIMENTAL Materials and Methods Melting points were determined on Buchi-540 melting point apparatus and are un-corrected. FT-IR spectra were recorded as KBr pellet on Nicolet-380 FT-IR instrument (Model Thermo Electron corporation-Spectrum one), 1 H and 13 C NMR (proton decoupled) spectra were recorded on Varian 300 MHz spectrometer using DMSO-d 6 and CDCl 3 as solvent. Mass spectra were recorded on Agilent triple quadrapole mass spectrometer equipped with turbo ion spray interface at 360 o C. Synthesis of 4-Methyl-7-hydroxy Coumarin of 2 7 Concentrated sulfuric acid (20 mL) was added to a 100 mL round bottom flask and cooled to 0-5 o C in an ice bath. A solution of resorcinol (0.001 mol) in ethyl ace- toacetate (0.0015 mol) was added to sulfuric acid under constant stirring at 0-5 o C. The reaction mass was stirred over night at room temperature and poured in to crushed ice under vigorous stirring. An off-white solid obtained was filtered and recrystallised in ethanol. m.p: 180-182 o C; 1 H NMR (300MHz, CDCl 3 ): δ 2.49 (s, 3H, C4-CH 3 ), 6.31 (s, 1H, C3-H), 6.92 (d, 1H, C6-H, J=9.0 Hz), 6.94 (s, 1H, C8- H), 7.57 (d, 1H, C5-H, J=9.0 Hz); IR (KBr, ν max): 3423 (-OH), 1733 (-CO), 1555 (-C=C-) cm -1 . Synthesis of 4-Methyl-7-hydroxy-8-formyl Coumarin 3 8 7-hydroxy-4-methyl-coumarin (2) (0.001 mol) was dis- solved in glacial acetic acid (20 mL) and hexamethylene tetramine (0.003 mol) was added to the reaction mixture. Heated to 80-85 o C in a water bath for 6.0 hr. A hot mix-