Microwave-assisted polystyrene sulfonate-catalyzed synthesis of novel pyrroles
© Cárdenas et al.; licensee Springer. 2012
Received: 3 January 2012
Accepted: 20 April 2012
Published: 22 June 2012
Pyrroles are widely distributed in nature and important biologically active molecules. The reaction of amines with 2,5-dimethoxytetrahydrofuran is a promising pathway for the synthesis of pharmacologically active pyrroles under microwave irradiation.
Microwave-induced polystyrenesulfonate-catalyzed synthesis of pyrroles from amines and 2,5-diemthoxytetrahydrofuran has been accomplished with excellent yield. This method produces pyrroles with polyaromatic amines.
The present procedure for the synthesis of N-aromatic substituted pyrroles will find useful application in the area of pharmacologically active molecules.
KeywordsPyrrole Polystyrene sulfonate Microwave 2,5-dimethoxytetrahydrofuran
FT-IR spectra were registered on a Bruker IFS 55 Equinox FTIR spectrophotometer (Bruker Corporation, Billerica, MA, USA) as KBr discs.1 H-NMR (600 MHz) and13 C-NMR (150 MHz) spectra were obtained at room temperature with Bruker-600 equipment (Bruker Corporation) using TMS as internal standard and CDCl3 as solvent. Analytical grade chemicals (Sigma-Aldrich Corporation, St. Louis, MO, USA) were used throughout the project. Deionized water was used for the preparation of all aqueous solutions.
Results and discussion
General procedure for the synthesis of pyrroles (3)
Amine (1.0 mmol), 2, 5-dimethoxytetrahydrofuran (1.2 mmol) and polystyrene sulfonate (18 wt% solution in water) in ethanol/water (1:1) mixture was stirred at room temperature, and the progress of the reaction was monitored by TLC every 30 min. After completion of the reaction (Table 2), the reaction mixture was basified with saturated aqueous sodium bicarbonate solution and extracted with dichloromethane. The organic layer was then washed with brine, dried with sodium sulfate and evaporated to isolate the pure product.
Alternatively, amine (1.0 mmol), 2, 5-dimethoxytetrahydrofuran (1.2 mmol) and polystyrene sulfonate (18 wt% solution in water) in ethanol/water (1:1) were irradiated in an automated microwave oven (CEM Corporation, Matthews City, NC, USA). The reaction was monitored by TLC every 5 min. Depending upon the nature of the amines, the reaction was completed in different time. The result of the procedure was shown in Table 1. All the products have demonstrated satisfactory spectral and mp data with our reported compounds .
A new and simple method for the synthesis of N-substituted pyrroles in aqueous solution has been investigated with success. Based on our previous studies in this series, the compounds as reported herein may demonstrate anticancer activities.
We gratefully acknowledge the funding support from the Kleberg Foundation, Texas.
- Fan H, Peng J, Hamann MT, Hu J-F: Lamellarins and related pyrrole-derived alkaloids from marine organisms. Chem Rev 2008, 108: 264–287. 10.1021/cr078199mView ArticleGoogle Scholar
- Walsh CT, Garneau-Tsodikova S, Howard-Jones AR: Biological formation of pyrroles: nature's logic and enzymic machinery. Nat Prod Rep 2006, 23: 517–531. 10.1039/b605245mView ArticleGoogle Scholar
- Aiello A, D'Esposito M, Fattorusso E, Menna M, Mueller WEG, Perovic-Ottstadt S, Schroeder HC: Novel bioactive bromopyrrole alkaloids from the Mediterranean sponge Axinella verrucosa. Bioorg Med Chem 2006, 14: 17–24. 10.1016/j.bmc.2005.07.057View ArticleGoogle Scholar
- Domingo VM, Aleman C, Brillas E, Julia L: Diradical dications of m- and p-phenylenebis[2,5-di(2-thienyl)-1-pyrrole]: weakly coupled diradicals. J Org Chem 2001, 66: 4058–4061. 10.1021/jo001656dView ArticleGoogle Scholar
- Knorr L: Synthesis of pyrroline-derivatives II. Chem Ber 1884, 17: 1635–1642. 10.1002/cber.18840170220View ArticleGoogle Scholar
- Paal C: Synthesis of thiophen and pyrolline derivatives. Chem Ber 1885, 18: 367–371. 10.1002/cber.18850180175View ArticleGoogle Scholar
- Cardoso AL, Nunes RMD, Arnaut LG, Pinho M, Teresa MVD: Synthesis of pyrroles in supercritical carbon dioxide: formal [3 + 2] cycloaddition of 2-benzoyl-aziridines and allenoates. Synthesis 2011, 21: 3516–3522.Google Scholar
- Zeng J, Bai Y, Cai S, Ma J, Liu X-W: Direct synthesis of pyrroles via a silver-promoted three-component reaction involving unusual imidazole ring opening. Chem Commun 2011, 47: 12855–12857. 10.1039/c1cc14716aView ArticleGoogle Scholar
- Ng EPJ, Wang Y-F, Chiba S: Manganese(III)-catalyzed formal [3 + 2] annulation of vinyl azides and β-keto acids for synthesis of pyrroles. Synlett 2011, 6: 783–786.Google Scholar
- Stuart DR, Alsabeh P, Kuhn M, Fagnou K: Rhodium(III)-catalyzed arene and alkene c-h bond functionalization leading to indoles and pyrroles. J Am Chem Soc 2010, 132: 18326–18339. 10.1021/ja1082624View ArticleGoogle Scholar
- Lamande-Langle S, Abarbri M, Thibonnet J, Duchene A, Parrain J-L: Domino allylic amination/Sonogashira/heterocyclisation reactions: palladium-catalysed three-component synthesis of pyrroles. Chem Commun 2010, 46: 5157–5159. 10.1039/c0cc00500bView ArticleGoogle Scholar
- Saito A, Konishi T, Hanzawa Y: Synthesis of pyrroles by gold(I)-catalyzed amino-Claisen rearrangement of N-propargyl enaminone derivatives. Org Lett 2010, 12: 372–374. 10.1021/ol902716nView ArticleGoogle Scholar
- Wyrebek P, Sniady A, Bewick N, Li Y, Mikus A, Wheeler KA, Dembinski R: Microwave-assisted zinc chloride-catalyzed synthesis of substituted pyrroles from homopropargyl azides. Tetrahedron 2009, 65: 1268–1275. 10.1016/j.tet.2008.11.094View ArticleGoogle Scholar
- Banik BK, Samajdar S, Banik I: Simple synthesis of substituted pyrroles. J Org Chem 2004, 69: 213–216. 10.1021/jo035200iView ArticleGoogle Scholar
- Banik BK, Banik I, Renteria M, Dasgupta SK: A straightforward highly efficient Paal–Knorr synthesis of pyrroles. Tetrahedron Lett 2005, 46: 2643–2645. 10.1016/j.tetlet.2005.02.103View ArticleGoogle Scholar
- Bandyopadhyay D, Mukherjee S, Banik BK: An expeditious synthesis of N-substituted pyrroles via microwave-induced iodine-catalyzed reaction under solventless conditions. Molecules 2010, 15: 2520–2525. 10.3390/molecules15042520View ArticleGoogle Scholar
- Andoh-Baidoo R, Danso R, Mukherjee S, Bandyopadhyay D, Banik BK: Microwave-induced N-bromosuccinimide-mediated novel synthesis of pyrroles via Paal-Knorr reaction. Heterocycl Lett 2011, 1: 107–109.Google Scholar
- Abrego D, Bandyopadhyay D, Banik BK: Microwave-induced indium-catalyzed synthesis of pyrrole fused with indolinone in water. Heterocycl Lett 2011, 1: 94–95.Google Scholar
- Rivera S, Bandyopadhyay D, Banik BK: Facile synthesis of N via microwave-induced bismuth nitrate-catalyzed reaction under solventless conditions.-substituted pyrroles. Tetrahedron Lett 2009, 50: 5445–5448. 10.1016/j.tetlet.2009.06.002View ArticleGoogle Scholar
- Banik I, Becker FF, Banik BK: Stereoselective synthesis of β-lactams with polyaromatic imines: entry to new and novel anticancer agents. J Med Chem 2003, 46: 12–15. 10.1021/jm0255825View ArticleGoogle Scholar
- Becker FF, Banik BK: Polycyclic aromatic compounds as anticancer agents: synthesis and biological evaluation of some chrysene derivatives. Bioorg Med Chem Lett 1998, 8: 2877–2880. 10.1016/S0960-894X(98)00520-4View ArticleGoogle Scholar
- Becker FF, Mukhopadhyay C, Hackfeld L, Banik I, Banik BK: Polycyclic aromatic compounds as anticancer agents: synthesis and biological evaluation of dibenzofluorene derivatives. Bioorg Med Chem 2000, 8: 2693–2699. 10.1016/S0968-0896(00)00213-3View ArticleGoogle Scholar
- Banik BK, Becker FF: Polycyclic aromatic compounds as anticancer agents. 4. Structure-activity relationships of chrysene and pyrene derivatives. Bioorg Med Chem 2001, 9: 593–605. 10.1016/S0968-0896(00)00297-2View ArticleGoogle Scholar
- Banik BK, Becker FF: Synthesis, electrophilic substitution and structure-activity relationship studies of polycyclic aromatic compounds towards the development of anticancer agents. Curr Med Chem 2001, 8: 1513–1533. 10.2174/0929867013372120View ArticleGoogle Scholar
- Banik BK, Becker FF, Banik I: Synthesis of anticancer β-lactams: mechanism of action. Bioorg Med Chem 2004, 12: 2523–2528. 10.1016/j.bmc.2004.03.033View ArticleGoogle Scholar
- Bandyopadhyay D, Granados JC, Short JD, Banik BK: Polycyclic aromatic compounds as anticancer agents: evaluation of synthesis and in vitro cytotoxicity. Oncol Lett 2012, 3: 45–49.Google Scholar
This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.