Zinc oxide as a new, highly efficient, green, and reusable catalyst for microwave-assisted Michael addition of sulfonamides to ,  -unsaturated esters in ionic liquids Abdolkarim Zare, Alireza Hasaninejad, Ahmad Reza Moosavi Zare, Abolfath Parhami, Hashem Sharghi, and Ali Khalafi-Nezhad Abstract: A simple, clean, and efficient procedure for the green synthesis of some N-alkyl derivatives of sulfonamides is described. Microwave-assisted Michael addition of sulfonamides to α, β-unsaturated esters, in the presence of cata- lytic amount of zinc oxide (ZnO) in 1-butyl-3-methylimidazolium bromide ([bmim]Br), affords the title compounds in high yields and short reaction times. Key words: zinc oxide, green chemistry, microwave, Michael addition, sulfonamide, ionic liquid. Résumé : On décrit une méthode simple, propre et efficace pour la synthèse verte de quelques dérivés N-alkyles des sulfonamides. L’addition de Michael assistée par micro-ondes de sulfonamides sur des esters α, β-insaturés, en présence d’une quantité catalytique d’oxyde de zinc (ZnO) dans le bromure de 1-butyl-3-méthylimidazolium ([bmim]Br) conduit à la formation des produits mentionnés dans le titre, avec des rendements élevés et de courts temps de réaction. Mots-clés : oxyde de zinc, chimie verte, micro-onde, addition de Michael, sulfonamide, liquide ionique. [Traduit par la Rédaction] Zare et al. 444 Introduction Currently, ionic liquids are the subject of considerable in- terest as benign reaction media in organic synthesis because of their unique properties, such as non-volatility, non- flammability, recyclability, and ability to dissolve a wide range of materials (1). During the past decade, a variety of ionic liquids have been demonstrated as efficient and practi- cal alternatives to organic solvents for many important or- ganic transformations (1). Catalytic activity has been also reported for these green solvents (2). Together with the sub- stitution of common molecular solvents, non-conventional activation methods, mainly microwave irradiation (MWI), have emerged as powerful techniques to reduce reaction times and to enhance reaction rates (3). As part of our drive to avoid the use of volatile organic solvents in reactions (4), we have initiated a program to explore the use of ionic liq- uids as efficient reaction media for useful organic transfor- mations at room temperature. N-Alkyl derivatives of sulfonamides are important be- cause they have various biological activities, including their antidepressant, psychostimulant, analgesic, anti-ulcer, anti- emetic, and anti-inflammatory properties (5). These com- pounds can be prepared via aza-conjugate addition of sulfonamides to α, β -unsaturated compounds (6). Michael re- action of sulfonamides with α, β -unsaturated esters also af- fords protected β -amino acids. This class of compounds ( β - amino acids) are essential components in many bioactive compounds and drugs scaffolds, such as β -peptides (7), imeriamine (hypoglycemic and antiketogenic agent, Fig. 1) (8), vitamin B 3 (Fig. 1) (9), cryptophycin (antitumor) (10), and TAN-1057 A (antibiotic) (11). Indeed, to the best of our knowledge, there are only a few reports of Michael addition of sulfonamides. Reitz et. al have used alumina to carry out this reaction (6). However, in their report, the reaction times are long, and the yields are moderate. Moreover, they ap- plied more reactive α, β -unsaturated ketones. In aza-conjugate reactions, the nucleophilic nitrogen is usually among the powerful nucleophiles, such as amines (12), which, if used in the reaction, can lead to side prod- ucts, e.g., amides via nucleophilic attack of amine to car- bonyl group of α, β -unsaturated esters (12a). Furthermore, 1,2- and 1,4-condensation of a β -amino residue to α, β - unsaturated esters caused polymerization or tar formation (12a). Moreover, some procedures often require a large ex- cess of reagents (12b). Therefore, in this context, using sulfonamides instead of amines in Michael reaction with Can. J. Chem. 85: 438–444 (2007) doi:10.1139/V07-050 © 2007 NRC Canada 438 Received 6 March 2007. Accepted 9 May 2007. Published on the NRC Research Press Web site at canjchem.nrc.ca on 12 June 2007. A. Zare. 1 Department of Chemistry, Payam Noor University of Bushehr, Bushehr 1698, Iran. A. Hasaninejad. 2 Department of Chemistry, Faculty of Sciences, Persian Gulf University, Bushehr 75169, Iran. A.R. Moosavi Zare, A. Parhami, H. Sharghi, and A. Khalafi-Nezhad. Department of Chemistry, College of Sciences, Shiraz University, Shiraz 71454, Iran. 1 Corresponding author (e-mail: abdolkarimzare@yahoo.com). 2 Corresponding author (e-mail: ahassaninejad@yahoo.com). Can. J. Chem. Downloaded from www.nrcresearchpress.com by 202.46.129.17 on 05/06/11 For personal use only.