ORIGINAL PAPER Ferric perchlorate as an efficient and useful catalyst for the selective benzylation and methylation of alcohols with benzyl chloride and methyl iodide Farahnaz K. Behbahani Æ Majid M. Heravi Æ Hossien A. Oskooie Received: 6 August 2008 / Accepted: 15 August 2008 / Published online: 7 October 2008 Ó Springer-Verlag 2008 Abstract A mild and efficient method was developed for selective benzylation and methylation of hydroxyl com- pounds in the presence of a catalytic amount of ferric perchlorate. We showed that ferric perchlorate was very effective in selectively promoting the benzylation and methylation of primary aliphatic and benzylic alcohols versus secondary aliphatic alcohols and phenolic hydroxy groups. Keywords Benzylation Á Hydroxy compounds Á Alcohols Á Ferric perchlorate Á Etherification Á Methylation Introduction Hydroxyl groups are present in a number of compounds of biological and synthetic interest, including nucleosides, carbohydrates, steroids, macrolides, polyethers, and the side chain of some amino acids. In some oxidation reac- tions, such as acylation, halogenation with phosphorus, hydrogen halides, or dehydration of these compounds, a hydroxyl group must be protected. In polyfunctional mol- ecules, selective protection becomes an issue that has been addressed by the development of a number of new meth- ods. Ethers are among the most used protective groups in organic synthesis and vary from the simplest, the most stable methyl ether to the more elaborate, substituted trityl ethers developed for use in nucleotide synthesis. Ethers are formed and removed under a wide variety of conditions. There have been many reports on the formation of the ether linkage, but a few are presented from hydroxyl compounds and halides [1]. Numerous methods are available for pro- tecting an alcohol moiety. Conversion into corresponding ethers has been recognized as a common and useful method for the protection of hydroxyl groups. Most commonly used protecting groups are the tetrahydropyranyl (THP), t- butyldimethylsilyl (TBDMS), and benzyl (Bn) groups. Benzyl ethers are widely utilized as alcohol protecting groups. They are easily installed, but with poor selectivity between primary and secondary alcohol groups [2, 3], e.g., in carbohydrates, are stable to a wide range of reagents, and are readily removed in the presence of many common functionalities via catalytic hydrogenolysis, dissolving metals, or Lewis/Brønsted acids [4]. In other words, selectivity of reaction pathways is extremely important in organic reactions, such as etherification [5–7]. Recently, we have reported etherification of allylic and benzylic alcohols with aliphatic alcohols in the presence of ferric perchlorate [8] and the ability of ferric perchlorate as a catalyst for some kinds of transformations in organic synthesis [9–12]. In continuation of our works to develop new synthetic methodologies [13–23], we wish to report an effective, inexpensive, and selective benzylation and methylation of hydroxyl groups using ferric perchlorate (Scheme 1). Results and discussion Initially, a systematic study was carried out for catalytic evaluation of ferric perchlorate for benzylation and M. M. Heravi (&) Á H. A. Oskooie Department of Chemistry, School of Sciences, Azzahra University, Vanak, Tehran, Iran e-mail: mmh1331@yahoo.com F. K. Behbahani Department of Chemistry, School of Sciences, Islamic Azad University, Karaj branch, Karaj, Iran e-mail: farahnazkargar@yahoo.com 123 Monatsh Chem (2009) 140:181–184 DOI 10.1007/s00706-008-0054-x