Highly efficient synthesis of triazolo[1,2-a]indazole-triones and novel spiro triazolo[1,2-a]indazole-tetraones under solvent-free conditions Alireza Hasaninejad a, * , Abdolkarim Zare b, * , Mohsen Shekouhy a a Department of Chemistry, Faculty of Sciences, Persian Gulf University, Bushehr 75169, Iran b Department of Chemistry, Payame Noor University (PNU), Bushehr 1698, Iran article info Article history: Received 26 June 2010 Received in revised form 21 October 2010 Accepted 8 November 2010 Available online 12 November 2010 Keywords: Combinatorial chemistry Multi-component reaction PEG-SO 3 H Urazole Triazolo[1,2-a]indazole-triones Spiro triazolo[1,2-a]indazole-tetraone abstract A new, convenient, and high yielding procedure for the synthesis of triazolo[1,2-a]indazole-triones by the condensation reaction between dimedone, aryl aldehydes, and ueazoles in the presence of a catalytic amount of sulfonated polyethylene glycol (PEG-SO 3 H) as a highly stable and reusable eco-friendly de- gradable polymeric catalyst is described under solvent-free conditions. This procedure has also been applied successfully for the synthesis of novel spiro triazolo[1,2-a]indazole-tetraones. Ó 2010 Elsevier Ltd. All rights reserved. 1. Introduction Heterocyclic compounds occur very widely in nature and are essential to life. Nitrogen-containing heterocyclic molecules con- stitute the largest portion of chemical entities, which are part of many natural products, fine chemicals, and biologically active pharmaceuticals vital for enhancing the quality of life. 1 Amongst them, urazole derivatives are very interesting compounds, found to have some biological as well as pharmaceutical activity, such as anti-cancer and hypolipidemic. 2 These compounds are also used in the preparation of herbicides, 3 pesticides, 4 insecticides, 5 and polymeric materials with unique properties, such as heat-resistant coatings, 6 tyre rubbers with high gripability, 7 and melamine resins. 8 One of the most important biologically active compound containing a urazole moiety in its structure is compound a, that has been shown to have HSP inhibitory 9 (Fig. 1). Beside this several indolines, spiro-annulated with heterocycles at the 3-position, have shown good biological activities. 10,11 These compounds are the core structure of many pharmacological agents and natural alka- loids. 12e14 For example, spirotryprostatins (b), natural alkaloids isolated from the fermentation broth of Aspergillus fumigatus, have been identified as novel inhibitors of microtubule assembly. 14 Moreover, Compound (c) has shown antimicrobial activity 10 (Fig. 1). Multi-component reactions (MCRs), have many advantages over conventional synthetic methodologies, such as higher productivity, simple procedures, and facile execution, and play an important role in combinatorial chemistry. 15 Despite the spectacular investment in, and organic growth of, combinatorial chemistry as a platform tech- nology within the pharmaceutical industry during two past decades, few new MCRs were discovered or developed. Typical examples are Biginelli, 16 Passerini, 17 Ugi, 15b,18 and Mannich 19 reactions that used successfully in many organic syntheses. Upon these facts, great efforts have been and still are being made to find and develop new MCRs. The utility of polymer catalysts is now well-recognized because of their ease of workup and of separation of products and catalysts, from the economical point of view, and in application to industrial processes, etc. 20 In general, catalysts are immobilized on polymers N H O MeO N N O O (b) N H O O O N H N N H 2 N (c) N N N O O Ph O O H OH (a) Fig. 1. Biological active compounds base on urazole and/or spirooxindole derivatives. * Corresponding authors. Tel.: þ98 771 4222319; fax: þ98 771 4541494 (A.H.); tel.: þ98 771 559486; fax: þ98 771 5559489 (A.Z.); e-mail addresses: ahassani- nejad@yahoo.com (A. Hasaninejad), abdolkarimzare@yahoo.com (A. Zare). Contents lists available at ScienceDirect Tetrahedron journal homepage: www.elsevier.com/locate/tet 0040-4020/$ e see front matter Ó 2010 Elsevier Ltd. All rights reserved. doi:10.1016/j.tet.2010.11.029 Tetrahedron 67 (2011) 390e400