DOI: 10.1002/adsc.200700292 Part 148 in the Series “Studies on Novel Synthetic Methodolo- gies:” Selective Acetylation of Alcohols, Phenols and Amines and Selective Deprotection of Aromatic Acetates using Silica-Supported Phosphomolybdic Acid Biswanath Das, a, * Ponnaboina Thirupathi, a Rathod Aravind Kumar, a and Keetha Laxminarayana a a Organic Chemistry Division-I, Indian Institute of Chemical Technology, Hyderabad – 500007, India Fax:(+ 91)-40-2716-0512; e-mail: biswanathdas@yahoo.com Received: June 15, 2007; Published online: November 27, 2007 Abstract: An environmentally friendly silica-sup- ported phosphomolybdic acid was found to be a highly efficient catalyst for the selective acetylation of alcohols, phenols and amines in the absence of any solvent and also for the chemoselective depro- tection of aromatic acetates under very mild condi- tions. This method has been used for the protection of the hydroxy groups as well as for the deprotec- tion of the acetates of several naturally occurring bioactive phenolic compounds. The catalyst can be easily recovered and reused. Keywords: alcohols; amines; heterogeneous cata- lysts; protecting groups; silica-supported phospho- molybdic acid; solvent-free conditions Protection of functional groups is highly essential in organic synthesis. Alcohols, phenols and amines are frequently protected as acetates, which are generally prepared by reaction with Ac 2 O in the presence of pyridine. [1] 4-(Dimethylamino)pyridine (DMAP) and 4-pyrrolidinopyridine (PPY) are also known to cata- lyze the acetylation of alcohols. [2] Several Lewis acids, such as metal halides, [3] metal triflates [4] and micro- wave irradiation [5] have recently been introduced for the preparation of acetates from alcohols and phenols. However, many of these methods are associated with one or more drawbacks such as non-availability of the reagents, harsh reaction conditions, long reaction times, unsatisfactory yields and disturbance to other functional groups. Moreover, the selectivity of acety- lation is also important in multistep syntheses. Thus, a suitable, efficient and selective method for the acety- lation of alcohols, phenols and amines would be highly useful. In recent years, heterogeneous catalysts have gained considerable importance due to environmental and economic considerations. In continuation of our work [6] on the application of the heterogeneous cata- lysts for the development of useful synthetic method- ologies, we have observed that silica-supported phos- phomolybdic acid [7] is very suitable to catalyze the acetylation of alcohols and phenols with acetic anhy- dride to form the corresponding acetates at room temperature (Scheme1).This catalyst is important from an environmental point of view as it possesses excellent activity, low toxicity and high stability to- wards humidity. It can be recovered from the reaction mixture and reused. The catalytic activity of silica-supported phospho- molybdic acid was determined initially by preparing acetyl-3-methoxyphenol in high yield (78%) from the reaction of 3-methoxyphenol and acetic anhydride using the catalyst in CH 2 Cl 2 at room temperature within 3.0h. (Table 1, entry 1). We used different sol- vents such as CHCl 3 , CH 2 Cl 2 , THF, MeCN or Et 2 O for the reaction but the conversion proceeded best Scheme 1. Adv. Synth. Catal. 2007, 349,2677–2683 # 2007 Wiley-VCH Verlag GmbH&Co. KGaA, Weinheim 2677 COMMUNICATIONS