Current Organocatalysis   Send Orders for Reprints to reprints@benthamscience.net 124 Current Organocatalysis, 2020, 7, 124-133 RESEARCH ARTICLE Bisindolization Reaction Employing Phthalimide-N-sulfonic Acid as an Efficient Catalyst Hoda Banari 1 , Hamzeh Kiyani 1,* and Ali Reza Pourali 1 1 School of Chemistry, Damghan University, Damghan, Iran Abstract: Background: Bis(indolyl) methanes (BIMs) have a wide spectrum of applications in bio- medicine and agriculture as well as are present in natural products. These bisheterocyclic compounds possess vast pharmacological, including antifungal, antitubercular, anti-inflammatory, antibacterial, anticancer, anticonvulsant, antibiotic, antiviral, antimalarial, analgesic, and antidiabetic properties. BIMs scaffolds have also been employed as selective optical chemosensors for detection of some ani- ons and cations with the naked eye. Because of the importance of these bisheterocycles, various meth- ods have been reported for their synthesis through reaction of indole derivatives and aldehydes or ke- tones. Therefore, the synthesis of BIMs through different methodologies has received widespread atten- tion in the field of organic synthesis and medicinal chemistry. Objective: In this study, the catalytic activity of phthalimide-N-sulfonic acid (PISA) as an efficient and safe solid acidic organocatalyst toward the synthesis of BIMs derivatives in ethanol is described. Methods: Indole derivatives (2 mmol), aryl/heteroaryl aldehydes (1 mmol), and PISA (10 mol%) were mixture in ethanol. The reaction mixture was stirred at room temperature for the appropriate times. After workup and separation of catalyst, the corresponding heterocyclic products were obtained through recrystallization from hot ethanol. Results: The BIMs derivatives were easily obtained via Bisindolization Reaction (BIR) of two indoles (2-methylindole and indole) with a series of aryl and heteroaryl aldehydes. The BIR was efficiently catalyzed at room temperature using PISA as an excellent organocatalyst under optimized reaction conditions. Conclusion: The reactions were implemented in simple manner and were completed within acceptable reaction times. The expected BIM products were obtained in satisfactory yields. The catalyst can be recovered and reused several times in the template reaction. This approach provides the benefits of convenience, simple operational procedure, no use of hazardous organic solvents, cheapness and ease of preparation of catalyst. A R T I C L E H I S T O R Y Received: August 1, 2019 Revised: September 27, 2019 Accepted: October 4, 2019 DOI: 10.2174/2213337206666191022110730 Keywords: Bis(indolyl)methanes, green synthesis, indole, phthalimide-N-sulfonic acid, aryl aldehyde, organocatalyst. 1. INTRODUCTION The chemistry of bis(indolyl)methanes (BIMs) continues to be of attention due to their applications in industry, and the biological importance of these attractive classes of N- containing heterocyclic compounds [1, 2]. BIMs are widely distributed as key structural units in various biologically ac- tive natural substances and natural-like molecules (Fig. 1). In addition, it has been reported that they show a wide range of biological activities, including antimicrobial [3], antioxidant [3b-3c], antifungal [4], anti-inflammatory [5], analgesic [6], DNA damaging [7], antihyperlipidemic [8], anticancer *Address correspondence to this author at the School of Chemistry, Damghan University, P.O. Box: 36716-41167, Damghan, Iran; Tel/Fax: ++98-233-522-0095, E-mails: hkiyani@du.ac.ir; hakiyani@gmail.com [9], cytotoxic [10], HIV-1 integrase inhibitory [11], an- titubercular [12], anti-methicillin-resistant Staphylococcus aureus (MRSA) [13], topoisomerase IIa inhibitory [14], an- tileishmanial, and anti-diabetic properties [15]. Furthermore, they have also served as the dietary supplements [16], solar cells [17], corrosion inhibitor for mild steel [18] as well as the oxidized form, efficiently utilized as colorimetric chemo sensors [19] and pH indicators [20]. Some BIMs were ap- plied as chemosensors for Hg 2+ and Cu 2+ ions [21]. Thus, the development of new catalytic strategies to achieve the BIMs remains to be explored. Frequently, BIMs are synthesized by the pseudo-3- component bisindolization reaction (3CBIR) of indoles with various aldehydes or ketones. In recent years, because of wide-ranging applications of these valuable bisheterocycles 2213-3380/20 $65.00+.00 © 2020 Bentham Science Publishers