Potassium carbonate catalyzed one pot four-component synthesis of rhodanine derivatives Sarangthem Joychandra Singh, S. M. S. Chauhan ⇑ Bio-organic Laboratory, Department of Chemistry, University of Delhi, Delhi 110007, India article info Article history: Received 22 December 2012 Revised 27 February 2013 Accepted 2 March 2013 Available online 13 March 2013 Keywords: Rhodanine Potassium carbonate Multicomponent reactions Ketene dithioacetal Amines abstract A novel multicomponent synthesis of ketene dithioacetal rhodanines has been reported by reactions of primary amine, carbon disulfide, ethyl chloroacetate, and alkyl halide in DMF. The catalytic effects of dif- ferent bases have been investigated and potassium carbonate can efficiently catalyze the reaction in moderate to good yields at room temperature. Ó 2013 Elsevier Ltd. All rights reserved. Multicomponent reactions (MCRs) are one of the most impor- tant methods for the synthesis of natural products, medicinal, and combinatorial chemistry in recent years. 1 These reactions avoid time consuming and costly processes for the purification of various precursors and isolation of intermediates. 2 Multicompo- nent reactions are often accompanied by significant increases in molecular complexity and impressive selectivity. 3 Therefore, the development of new methodology for multicomponent reactions is very important in the fields of organic and medicinal chemistry. Rhodanine-based molecules are known to possess diverse bio- logical activities 4a through the inhibition of numerous targets such as HIV-1, 4b Alzheimer’s deseases, 4c HCV NS3 protease, 4d b-lacta- mase, 4e PMT1 mannosyl transferase, 4f PRL-3, and JSP-1 phospha- tases. 4g Additionally, they have been reported to possess antimicrobial, 5a antiviral, 5b anticonvulsant, 5c antidiabetic, 5d and antitumor activities. 5e The unusual biological activity displayed by many rhodanine-based molecules have made them attractive synthetic targets. Rhodanine derivatives have been synthesized so far by assem- bling the functionalized heterocycles through the reaction of a- halogencarboxylic acid and maleic acid derivatives with carbon disulfide and amines or that of isothiocyanates with thioglico- lates. 6 Recently, three-component, one-flask preparation of 5-ary- lidene rhodanines, 7 5-hydrazinoalkylidene rhodanines, 8 5-acyl rhodanines, 9 5-carboxymethyl rhodanines, 10 5-alkylidene rhoda- nine, 11 and 2-amino 4-thiazolones 12 have been reported. Besides these, highly functionalized two-component rhodanine deriva- tives 13 and four-component rhodanine derivatives have been achieved. 14 A careful literature survey reveals that there have been no re- ports on the synthesis of ketene dithioacetal rhodanines via one pot four-component reactions. However, there are a few reports 0040-4039/$ - see front matter Ó 2013 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.tetlet.2013.03.004 ⇑ Corresponding author. Tel./fax: +91 11 27666845. E-mail address: smschauhan@chemistry.du.ac.in (S.M.S. Chauhan). S N O S R K 2 CO 3 /DMF 8 h, r..t + Cl O O CS 2 + 1 2 3 R NH 2 Br Br S S CH 3 I K 2 CO 3 /DMF 8 h, r..t S N O S R SCH 3 H 3 CS (1eq.) (2 eq.) (1eq.) (1eq.) (2 eq.) 4 4 5 5 Scheme 1. Synthesis of ketene dithioacetal rhodanines. Tetrahedron Letters 54 (2013) 2484–2488 Contents lists available at SciVerse ScienceDirect Tetrahedron Letters journal homepage: www.elsevier.com/locate/tetlet