1296 Simple and Clean Procedure for Three-Component Syntheses of Spiro{pyrido[2,1-b]benzothiazole-3,3 0 -indolines} and Spiro{thiazolo[3,2-a]pyridine-7,3 0 -indolines} in Aqueous Medium Vol 49 Essam M. Hussein* and Ahmed M. El-Khawaga Department of Chemistry, Faculty of Science, Assiut University, Assiut 71516, Egypt *E-mail: essam.hussein78@yahoo.com Received January 27, 2011 DOI 10.1002/jhet.908 View this article online at wileyonlinelibrary.com. A simple and efficient one-pot three component synthesis of spiro{pyrido[2,1-b]benzothiazole-3,3 0 -indoline} and/or spiro{thiazolo[3,2-a]pyridine-7,3 0 -indoline} derivatives were carried out by the reaction of 2-mercaptoaniline and/or mercaptoacetic acid, malononitrile, and a series of 2-oxoindoline-3-ylidines in aqueous medium. This method is of great value because of its environmentally benign character, high yield processing, and easy handling. J. Heterocyclic Chem., 49, 1296 (2012). INTRODUCTION The need to reduce the amount of toxic waste and byproducts arising from chemical processes requires increasing emphasis on the use of less toxic and more environmentally compatible materials in the design of new synthetic methods [1]. One of the most promising approaches uses water as reaction medium [2]. In recent years, there has been increasing recognition that water is an attractive medium for many organic reactions [3,4]. The aqueous medium with respect to organic solvents is less expensive, less dangerous, and more environ- mentally friendly. The indole nucleus is probably the most well known heterocycle, a common and important feature of a variety of natural products and medicinal agents [5]. Compounds carrying the indole moiety exhibit antibacterial and antifungal activities [6]. Furthermore, it has been reported that sharing of the indole 3-carbon atom in the formation of spiroindoline derivatives highly enhances biological activity [7–11]. As a consequence of our interest in the aqueous medium organic synthesis of spirohetero- cycles containing indoline moiety [12–16], we investigated a three-component reaction of 2-mercaptoaniline and/or mercaptoacetic acid, malononitrile, and 2-oxoindoline- 3-ylidines to afford a series of some new spiro{pyrido [2,1-b]benzothiazole-3,3 0 -indoline} and/or spiro{thia- zolo[3,2-a]pyridine-7,3 0 -indoline} derivatives in water mediated by the surfactant TEBACl (triethylbenzylam- monium chloride). RESULTS AND DISCUSSION In recent years, many surfactants have been used as phase transfer catalysts in number of organic reactions having unique capabilities to dissolve both organic and aqueous solutions to enhance the reaction rate. After some preliminary experiments, it was found that an equimolar mixture of 2-mercaptoaniline 1, malononitrile 2, and 2-oxoindoline-3-ylidines (3a-f), were stirred for 3–6 h at 80  C in aqueous medium in the presence of TEBACl (20 mol %) could afford spiro{pyrido[2,1-b] benzothiazole-3,3 0 -indoline} derivatives (4a-f) in excel- lent yields (93–98%) (Scheme 1). To optimize the reaction temperature, the reactions were carried out at different temperatures ranging from room temperature to 100  C. We found that the yield of product (4e) was improved and the reaction time was shortened as the temperature was increased to 80  C. Surprising, the yield decreased when temperature was further increased © 2012 HeteroCorporation