Fe-exchanged montmorillonite K10––the first heterogeneous catalyst for acylation of sulfonamides with carboxylic acid anhydrides Devendrapratap U. Singh, Pankajkumar R. Singh and Shriniwas D. Samant * Organic Chemistry Research Laboratory, University Institute of Chemical Technology, N.M. Parekh Marg, Matunga, Mumbai 400 019, India Received 26 January 2004; revised 1 April 2004; accepted 8 April 2004 Abstract—Fe-exchanged montmorillonite K10 catalyzes a highly efficient reaction between sterically and electronically diverse sulfonamides and carboxylic acid anhydrides to furnish N-acylsulfonamides in excellent yield and high selectivity. The catalyst can also be reused several times. Ó 2004 Elsevier Ltd. All rights reserved. In drug synthesis, the N-acyl sulfonamide moiety has emerged as an important feature for biological activity. Several recently developed drugs, including therapeutic agents for Alzheimer’s disease, 1 inhibitors for tRNA synthetase as antibacterial agents 2 and prostaglandin Fla sulfonamides for the potential treatment of osteo- porosis, 3 incorporate this moiety. In addition, N-acyl- N-(2,3,4,5,6-pentafluorophenyl)methane sulfonamides function as chemoselective N-acylating reagents. 4 The majority of reports describe the preparation of the N-acyl derivatives using basic reaction media. For in- stance, the target compounds have been obtained by coupling sulfonamides with acid chlorides or anhydrides in the presence of trialkylamines or pyridine, 4;5 or alkali hydroxides. 6 Another approach utilizes carboxylic acids along with coupling agents like EDC, DCC or carbonyl diimidazole, 2;3 the by-product of which must subse- quently be removed from the reaction mixture. Moris- awa et al. has used concd H 2 SO 4 in the carboxylic acid anhydride itself taken as a solvent; whereas Martin et al. has used concd H 2 SO 4 in acetonitrile. 7 In recent years, the use of solid acidic catalysts, such as clays and zeolites, has received considerable attention in different areas of organic synthesis, because of their environmental compatibility, reusability, greater selec- tivity, operational simplicity, nontoxicity, noncorro- siveness, low cost and ease of isolation. In particular, clay catalysts make a reaction convenient, more economic and environmentally benign. They act as both Brønsted and Lewis acids in their natural and ion-exchanged for- ms. 8 We have recently reported the high activity of Fe-exchanged montmorillonite clays for the Friedel– Crafts benzylation of arenes with benzyl chlorides, 9a;b;c the Beckmann rearrangement 9d and nitrile formation. 9e The present paper describes a selective and highly effi- cient procedure for the synthesis of N-acyl sulfonamides using an inexpensive and reusable Fe-exchanged mont- morillonite K10 catalyst (K10-FeO) (Scheme 1). R S O O N H O R' R SO 2 NH 2 R' O O O R' R = CH 3 ,C 6 H 5 , p-CH 3 C 6 H 4 , p-MeOC 6 H 4 , p-ClC 6 H 4 R' = CH 3 ,C 6 H 5 , CF 3 CH 3 CN, 60 ˚C K10-FeO + Scheme 1. N-acylation of sulfonamides with carboxylic acid anhy- drides. Keywords: Fe-exchanged montmorillonite; Sulfonamides; Carboxylic acid anhydrides. * Corresponding author. Tel.: +91-22-24145616; fax: +91-22-241456- 14; e-mail: samantsd@udct.org 0040-4039/$ - see front matter Ó 2004 Elsevier Ltd. All rights reserved. doi:10.1016/j.tetlet.2004.04.077 Tetrahedron Letters 45 (2004) 4805–4807 Tetrahedron Letters