Unexpected Dimer from Demethylization Reaction of Eugenol under Acidic Conditions
Keywords:Eugenol, demethylation, dimerization, natural products, clove essential oil
Eugenol is an alkenyl phenol compound obtained as an essential oil from different parts of the clove such as its leaves and flowers. The essential oil from cloves can contain up to 90% eugenol, which is mainly responsible for its aroma. Eugenol is an interesting compound due to its simplicity and richness in functionalities, making it a valuable building block in synthesis. One of the key steps in eugenol transformation is demethylation to produce a hydroxycavicol. Demethylation is commonly carried out using a nucleophilic or an acidic method. In this study, a simple yet reliable nucleophilic method for demethylation using lithium chloride (LiCl) was attempted. The product was characterized by NMR, FTIR and HRMS spectroscopy. The absence of a methoxy signal at 3.5-4 ppm in the 1H NMR spectrum suggests that demethylation was successful. The HRMS result showed m/z 149.0596, confirming the formation of product. The demethylation reaction under acidic conditions formed a dimer of eugenol with the methoxy group still intact. This was supported by the 1H NMR data, which showed methoxy signals at 3.85 and 3.82 ppm and integration in the aromatic region, which suggests a dimer structure.
Chaieb, K., Hajlaoui, H., Zmantar, T., Nakbi, A.B.K., Rouabhia, M., Mahdouani, K. & Bakhrouf, A., The Chemical Composition and Biological Activity of Clove Essential Oil, Eugenia Caryophyllata (Syzigium Aromaticum L. Myrtaceae), Phytotherapy Res., 21(6), pp. 501-506, 2007.
Hansel, R., Schulz, J. & Pelter, A., Structure of Silibinin: Synthetic Studies, Chem. Comm, 3, pp. 195-196, 1972.
Lampman, G.M., Andrews, J., Bratz, W., Hanssen, O., Kelley, K., Perry, D. & Ridgeway, A., Preparation of Vanillin from Eugenol and Sawdust, J. Chem. Edu., 54(12), pp. 776, 1977.
Denmark, S.E. & Werner, N.S., Cross Coupling Metathesis of Aromatics Bromides with Allylic Silanolate Salts, J. Am. Chem. Soc., 130, pp. 16382-16393, 2008.
Maharramov, A.M., Bayramov, M.R., Agayeva, M.A., Mehdiyeva, G.M. & Mamedov, I.G., Alkenylphenols: Preparations, Transformations and Applications, Russian Chemical Reviews, 84(12), pp. 1258-1278, 2015.
Satyal, P. & Setzer, W.N., Chemical Composition and Biological Activities of Nepalese Piper Betle L, IJPHA, 1, pp. 23-26, 2012.
Dwivedi, V., Tripathi, S. & Sheldon, R.A., Review Study on Potential Activity of Piper Betle, J. Pharm. Phytochemistry, 3(4), pp. 93-98, 1995.
Node, M., Nishide, K., Fuji, K & Fujita, E., Hard Acid and Soft Nucleophile System. 2.' Demethylation of Methyl Ethers (of Alcohol and Phenol with An Aluminum Halide-Thiol System. J. Org. Chem., 45, pp. 4275-4277, 1980.
Fang, Z., Zhou. G.C., Zheng, S.L., Li, G., Li, J.L., He. L. & Bei, D., Lithium Chloride-Catalyzed Selective Demethylation of Aryl Methyl Ethers under Microwave Irradiation, J. Mol. Cat. A., 274(1), pp. 16-23, 2007.
Mc Omie., J.F.W., Watts., M.L. & West, D.E., Demethylation of Aryl Methyl Ethers by Boron Tribromide, Tetrahedron, 24(5), 2289-2292, 1968.
Wilhelm, H. & Wessjohann, L.A., An Efficient Synthesis of the Phytoestrogen 8-Prenylnaringenin from Xanthohumol by A Novel Demethylation Process, Tetrahedron, 62(29), pp. 6961-6966, 2006.
Ogata, M., Hoshi, M., Urano, S. & Endo, T., Antioxidant Activity of Eugenol and Related Monomeric and Dimeric Compounds, Chem. Pharm. Bull. (Tokyo), 48, pp. 1467-1469, 2000.
Kharasch, M.S. & Mayo, F.R., The Peroxide Effect in the Addition of Reagents to Unsaturated Compounds. I. The Addition of Hydrogen Bromide to Allyl Bromide, J. Am. Chem. Soc., 55(6), pp. 2468-2496, 1993.