Molecular iodine: An efficient catalyst for the synthesis of both symmetrical and unsymmetrical triindolylmethanes (TRIM) Abhijit Hazra, Priyankar Paira, Krishnendu B. Sahu, Sukdeb Banerjee, Nirup B. Mondal * Indian Institute of Chemical Biology, 4 Raja S C Mullick Road, Jadavpur, Kolkata 700 032, India Received 20 June 2007; received in revised form 29 January 2008; accepted 31 January 2008 Available online 7 February 2008 Abstract Lewis acid catalyzed synthesis of triindolylmethanes from indole-3-carboxaldehyde and several other indole derivatives is described. A systematic study was carried out to evaluate the catalytic activity of seven Lewis acids and molecular iodine. Iodine appeared to be the most efficient in affording symmetrical and unsymmetrical triindolylmethanes in high yield. Ó 2008 Elsevier B.V. All rights reserved. Keywords: Lewis acid; Molecular iodine; Triindolylmethane 1. Introduction Triindolylmethanes (TRIM) have attracted the attention of synthetic organic chemists for their biological activities [1,2] and industrial applications [3]. Protic acids as well as Lewis acids are known to promote dimerization and polymerization of indoles [4]. In 1970’s for the first time, Bergman et al. prepared triindolylmethanes (TRIM) by the treatment of substituted indoles with acetic-formic anhydride at moderate temperature [5]. Akgu ¨n et al. [6] also reported the preparation of the same by condensation of indoles with orthoformate. Thereafter, several other methods have appeared in the literature [7–9]. Recently, Chakrabarty et al. [10] described the synthesis of TRIM by reacting indoles with 3-formyl indole using acid washed montmorillonite K-10 clay. However, these methods suffer due to poor yield, difficulty in isolation, requirement of expensive reagents and undesired precursors as well as harsh reaction conditions that limit their use. Moreover, the reported methods bear the deficiency of identifying the most effective one, as these are not conglomerated in the same report. In recent years, molecular iodine has gained consider- able attention in organic synthesis as an inexpensive, non-toxic, readily available catalyst for organic transfor- mations like dehydration of tertiary alcohols to alkenes [11], synthesis of benzo-thiophenes [12], bis-indoles [13], deprotection of acetals [14], esterification [15], transesterifi- cation [16], acylation [17] and Michael addition [18,19]. As a part of our continued search for efficient methodologies for the synthesis of bioactive molecules from indoles and quinolines [20–23], we investigated the use of molecular iodine and commonly used Lewis acids for the synthesis of triindolylmethanes. The present communication reports the effectiveness of molecular iodine over different Lewis acids, and the effect of solvent in the synthesis of TRIM. 2. Results and discussion Indole-3-carboxaldehyde (1) along with indole or substituted indoles were chosen as the two reactants, and iodine as well as various Lewis acids as the catalyst. In each case two equivalents of indole derivatives were added to the mixture of one equivalent of indole-3-caboxalde- hyde and the catalyst (5 mmol%, with respect to indole- 3-carboxaldehyde). The progress of the reactions was monitored at an interval of 5 min by thin layer chromat- ography (TLC). 1566-7367/$ - see front matter Ó 2008 Elsevier B.V. All rights reserved. doi:10.1016/j.catcom.2008.01.028 * Corresponding author. Tel.: +91 33 2473 3491; fax: +91 33 2473 5197. E-mail address: nirup@iicb.res.in (N.B. Mondal). www.elsevier.com/locate/catcom Available online at www.sciencedirect.com Catalysis Communications 9 (2008) 1681–1684