Heteroatom Chemistry Volume 16, Number 2, 2005 Solvent-Free Neat Synthetic Route to Tetrahydroacridinones M. Kidwai and S. Rastogi Department of Chemistry, University of Delhi, Delhi 110007, India Received 7 June 2004; revised 15 October 2004 ABSTRACT: An environmentally benign approach for the synthesis of acridines using inorganic solid supports and “neat reaction” technology is described. These methodologies completely eliminate the use of solvent during the course of reaction. More- over, microwave-assisted reactions reduce the reac- tion time from hours to minutes with improved yield. C  2005 Wiley Periodicals, Inc. Heteroatom Chem 16:138–141, 2005; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.20080 INTRODUCTION Acridines and its derivatives inhibit HIV-1 reverse transcriptase by intercalating the template–primer hybrid [1]. They are also well known as antimicro- bials [2,3] and antitumor agents [4,5] and are used for the treatment of urinary incontinence [6]. The title compounds under investigation are also asso- ciated with the structural aspects of dihydropyri- dine (DHP) and quinoline moieties. The chemical modifications carried out on the DHP ring [7] such as the presence of different substituents [8] or het- eroatoms [9] have allowed expansion of the structure activity relationship and afforded some insights into the molecular interactions at the receptor level. 1,4- DHPs are well known because of their pharmacolog- ical profiles [10,11]. Furthermore, hexahydroquino- lines play an important role in medicinal chemistry as anxiolytic [12] and memory enhancers [13] and Correspondence to: M. Kidwai; e-mail: kidwai chemistry@ yahoo.co.uk. c  2005 Wiley Periodicals, Inc. show marked positive inotropic effect [14]. An es- sential prerequisite for the therapeutic application prompted us to undertake the title investigation. We herein report a method that allows the rapid, facile synthesis of acridines-related structures and does not rely on the conventional procedure [15]. Instead, our procedure involves a microwave- promoted solvent-free variation of acridine syn- thesis. The application of microwave irradiations (MWI) in organic synthesis has been the focus of con- siderable interest in recent years. Chemical technol- ogy is increasingly facing eco-environmental pres- sure and is thus obliged to re-examine, conventional methodologies to seek ways of developing and ap- plying more efficient eco-friendly strategies. One of the areas wherein substantial progress has been seen in our laboratory [16,17] is the microwave-assisted solid support synthesis. These heterogeneous reac- tions are facilitated by reagents immobilized on porous solid supports (alumina, montmorillonite, bentonite, etc.). These dry media reactions [18] have advantages over conventional solution phase reac- tions owing to dispersion of active reagent sites, catalysis, associated selectivity, and recyclability. The other one is the “neat reaction” technology. “Neat Re- action” [7] is an alternative solvent-free approach in which a mixture of reactants without any solvent is irradiated under microwaves. This technique is fur- ther beneficial as it obviates the requirement of the solvent for the adsorption of reactants and elution of product in pre- and post-reaction stages. Such solvent-free synthesis is advantageous for environ- mental reasons and offers the benefits of shorter reaction time along with enhanced yield especially when coupled with microwaves [19]. 138