Protection of Alcohols Bull. Korean Chem. Soc. 2009, Vol. 30, No. 12 2899 DOI 10.5012/bkcs.2009.30.12.2899 Efficient Protection of Alcohols with Carboxylic Acids Using a V ariety of Heteropolyoxometallates as Catalysts, Studying Effective Reaction Parameters Reza Tayebee * and Fatemeh Cheravi Department of Chemistry, Sabzevar Tarbiat Moallem University, Sabzevar 397, Iran. * E-mail: rtayebee@sttu.ac.ir Received July 7, 2009, Accepted September 14, 2009 Esterification is an important class of reactions in the preparation of perfumery and flavor chemicals, wherein homogeneous, solid acidic, and superacidic catalysts are normally used. Now, an efficient and selective protocol for protection of various functionalized alcohols employing carboxylic acids as protecting agents is realized through the catalytic mediation of simple heteropolyoxometallates. In this methodology, water is the only by-product and notably the aspect of effluent treatments does not arise. The advantages include the operational simplicity, recycle ability of the catalyst and mild reaction conditions. The present catalytic system may be a potential candidate not only for laboratory practice but also for commercial applications and offers an environmentally safer alternative to the existing processes. Key Words: Acetylation, Heteropolyoxometallate, Catalytic, Alcohol, Formylation Introduction The protection of hydroxyl functional groups is an impor- tant and widely used transformation and is often necessary during the course of various organic synthesis sequences, in particular in the construction of polyfunctional molecules such as nucleosides, carbohydrates, steroids, natural products, and drugs. A number of reagents coupled with different catalysts have been put forth for the protection of alcohols. Protection of alcohols is usually performed employing acid anhydrides or acyl chlorides in the presence of stoichiometric amounts of protonic and Lewis acids, such as p-toluenesulfonic acid, 1 scandium trifluromethanesulfonate, 2 trimethylsilyl triflouro- methanesulfonate, 3 zinc chloride, 4 and cobalt chloride. 5 The above options employing acetic anhydride as acetylating agent and soluble acids as reagents or catalysts presents achieve less than 50% atom economy in the consumption of acetic an- hydride by utilizing only the acetyl group. Moreover, acid halides and acid anhydrides are usually employed as the acetylating agents in the presence of an acid or base catalyst such as H2SO4, 6 PTSA, 7 Shvo’s catalyst, 8 distannoxane catalyst 9 and lipase. 10 Most of the above procedures can be applied for the protection of various acid/base sensitive substrates. However, limitations in terms of reagent availability, prolonged reaction times, formation of unwanted side products, and need for halogenated solvents are of drawbacks of these common methods. Considering the importance of environmental aware- ness in chemical technology, it is important to minimize the prevalence of undesirable hazardous chemical substances that are dangerous to human health and the environment. Heteropolyoxometallates of the Keggin series have been proven to be good catalysts in many homogenous organic transformations and for the synthesis of fine and specialty chemicals. 11-14 Due to their acidic nature, redox properties, catalytic activity, selectivity, thermal resistance, and reusa- bility, heteropoly compounds are useful and versatile catalysts in a number of transformations. 15-16 These interesting com- pounds generally exhibit higher catalytic activities than con- ventional catalysts, such as mineral acids, ion-exchange resins, zeolites, etc. in both heterogeneous and homogeneous sys- tems. 11 Furthermore, heteropoly catalysis lacks side react- ions, such as sulfonation, chlorination, etc. that frequently occur with mineral acids. Most of usual Keggin-type hetero- polyoxometallates are soluble in water and polar organic solvents, such as lower alcohols and carboxylic acids, but insoluble in hydrocarbons. This provides an opportunity for the easy recovery of catalysts from liquid-phase reaction systems without neutralization, simply by precipitating with a hydrocarbon solvent. 11 In continuation of our ongoing research program on using heteropolypolyoxometallates in organic synthesis, 17-27 herein, we wish to report a simple, efficient, selective, and general method for the protection of some alcohols by the mediation of some heteropoly compounds at room temperature or under reflux conditions. The reactions were carried out in good yields within quite short reaction times. Results and Discussion Functional group protection is the heart and soul of multi- functional and multi step syntheses of target molecules. The protection of alcohol moieties represents one of the most ubiquitous steps in chemistry. Organic esters are a very impor- tant class of chemicals having applications in pharmaceuticals. Since, acetyl is the most common group in view of easy intro- duction, being stable under acidic conditions, and being easily removable by mild alkaline hydrolysis, the protection of alcohol functional groups is usually achieved through acetyl- ation and obviously different approaches have been employed on both laboratory and commercial scales to prepare esters. As mentioned in the introduction, research has been directed to overcome the drawbacks of conventional methods and insurmountable problems in the recovery of the catalysts and by-products and there is a need to develop a reusable and economic solid acid catalyst for acetylation using carboxylic acids as acetylating agents to achieve high atom economy.