Research Journal of Chemical Sciences__________________________________________________Vol. 1 (2) May (2011) Res.J.Chem.Sci.120 Synthesis of 2-Cyclopentene-1-one Derivatives by Aldol Condensation CAI Xiao-hua and XIE Bing College of Chemistry and environmental Science, Guizhou University for Nationalites, Guiyang, CHINA Available online at: www.isca.in (Received 16th April 2011, revised 21st April 2011, accepted 21st April 2011) Abstract Aldol condensation of benzil and ketone with -hydrogen atom in the presence of a solution of sodium hydroxide was carried out to afford some valuable 2-cyclopentene-1-one derivatives in 35~85 yield. Keywords: 2-cyclopentene -1-one derivatives, benzil, aldol condensation, synthesis Introduction 2-Cyclopenten-1-ones derivatives (1) are key and valuable intermediates in organic synthesis, and are widely applied as precursors for preparation of anti-viral, insecticides and antitumour drugs 2. 2-Cyclopenten-1-ones derivatives comprising the cyclopentenone nucleus as inhibitors of the NF-B factor, with anti-inflammatory, anti-proliferative, immunosuppressive, cytoprotective and antiviral activity. It is also found that the a,ß-unsatured carbonyl group in the cyclopentenone ring is the key structure necessary for NF-kB inhibition. However, some of the reported the synthesis of 2-cyclopenten-1-one derivatives suffer from certain drawbacks such as prolonged reaction time, unsatisfactory yield and complex product not to be separated easily. Therefore, the discovery of simple and efficient procedures for the synthesis of 2-cyclopentene-1-one derivatives has gained considerable attention. A useful carbon-carbon bond-forming reaction was known as the Aldol reaction or Aldol condensation5,6.The reaction may occur between two molecules of aldehyde, two molecules of ketones or one molecule of aldehyde and a molecule of ketone7,8. In some cases, the products obtained from the Aldol addition can easily be converted (in situ) to important -unsaturated carbonyl compounds, either thermally or under acidic or basic catalysis. Here we wish to develop a simple and inexpensive procedure for the synthesis of 2-cyclopentene-1-one derivatives by Aldol condensation of benzil (2) and ketone with hydrogen atom in the presence of a solution of sodium hydroxide (Scheme 1). Our initial attempts to Aldol condensation of 4, 4´dibromo-benzil (, 1.5 mmol) and acetone (, 10 mmol) in the presence of a solution of 10% sodium hydroxide in methanol (30 ml), and produced 2-cyclopentene-1-one in 85% yield. The success of this reaction prompted us to examine the Aldol condensation of other benzils and ketones instead of4, 4´-dibromo-benzilandacetone under the similar reaction conditions, and the results exhibited that the reaction can carry out smoothly and give the corresponding 2-cyclopentene-1-one derivatives in moderate to good yields (table 1). Table 1 shows the reactions of methyl isopropyl ketone and with benzil derivatives which have electron-donating groups (1j and 1m) have higher yield than reactions with electron-withdrawing Research Journal of Chemical Sciences__________________________________________________Vol. 1 (2) May (2011) Res.J.Chem.Sci.121 groups on Para-position of benzil (1c and 1g). These electron withdrawing groups accelerate benzil-benzilic acid rearrangement more than electron-donor groups,which lower the yield of aldol condensation reaction. Material and Methods In a typical procedure, a solution of 10% sodium hydroxide in methanol (30 ml) was dropwise added into a mixture of benzil (, 1.5 mmol) and ketone (, 10 mmol), then the reaction mixture was maintained under room temperture for the appropriate time (Table 1). After completion of the reaction (monitored by TLC), the reaction mixture was diluted with water, and the resulting solid product was collected by filtration. The crude product was washed with water and ether, respectively, then gave the corresponding 2-cyclopentene-1-one derivatives 1. 3,4-bis(-bromophenyl)-4-hydroxy-2-cyclopentetne-1-one (1a): mp 234~236 °C, IR (KBr) (max, cm-1): 3363 (OH), 1685 (CO); H NMR (400 MHz, CDCl): 2.77~2.96 (2H, CH), 5.92 (1H, s, OH), 6.83 (1H, s, CH), 7.43~7.52 (6H, dd, C), 7.70~7.76 (2H, d, C); ESI-MS m/z(%): 406 (M, 100), 408 (M+2, 100), 405 (M-H, 100), 407 (M+2-H, 100). 3,4-bis(-bromophenyl)-4-hydroxy-2-methyl-2-cyclopentetne-1-one (1b): mp 172~175 °C; IR (KBr) (max, cm-1): 3425 (OH), 1689 (CO); H NMR (400 MHz, CDCl): 1.87 (3H, s, CH), 2.86-2.95 (2H, dd, CH), 5.62 (1H, s, OH), 7.35~7.60 (8H, m, C); ESI-MS m/z (%): 420 (M, 65), 64 (M+2, 66). 3,4-bis(-bromophenyl)-5,5-dimethyl-4-hydroxy-2-cyclopentetne-1-one (1c): mp 199~201 °C; IR (KBr) (max, cm-1): 3272 (OH), 1693 (CO); H NMR (400 MHz, CDCl): 0.58 (3H, s, CH), 1.23 (3H, s, CH), 5.43 (1H, s, OH), 6.78 (1H, s, CH), 7.50-7.68 (8H, dd, C); ESI-MS m/z (%): 419 (M-CH, 100), 421(M-CH+2, 99), 3,4-bis(-chlorophenyl)-5,5-dimethyl-4-hydroxy-2-cyclopentetne-1-one(1g): mp: 165~167 °C; IR (KBr) (max, cm-1): 3355 (OH), 1692 (CO); 1H NMR (400 MHz, CDCl): 0.60 (3H, s, CH), 1.25 (3H, s, CH), 7.30~7.34 (4H, d, ). 7.68~7.73 (4H, d, C); ESI-MS m/z (%): 331(M-15,19). 3,4-bis(-methylphenyl)-4-hydroxy-2-methyl-2-cyclopentetne-1-one 1i): mp 105~107 °C; IR (KBr) (max, cm-1): 3406 (OH), 1695 (CO); H NMR (400 MHz, CDCl): 1.85 (3H, s, CH), 2.23 (6H, s, CH), 2.73~2.90 (2H, CH), 5.10 (1H, s, OH), 7.10-7.13 (4H, d, C), 7.28-7.31 (2H, d, ESI-MS m/z (%): 292 (M, 80). 3,4-bis(p-methoxyphenyl)-4-hydroxy-2-cyclopentetne-1-one (1k): mp 220-222 °C; IR (KBr)(max, cm-1): 3401 (OH), 1685 (CO); 1H NMR (400 MHz, CDCl): 2.88 (1H, d, CH), 2.92(1H, d, CH), 3.72 (3H, s, OCH), 3.75 (3H, s, OCH), 5.29 (1H, s, OH), 6.65 (1H, s, CH), 6.85-6.88 (4H, d, C), 7.43-7.46 (2H, d, C), 7.82-7.84 (2H, d, C); Calcd. forC1918: C, 73.55; H, 5.81 Found: C, 73.56; H, 5.78. Conclusion In conclusion, a simple, inexpensive and efficient methodology for the synthesis of 2-cyclopentene-1-one derivatives by Aldol condensation of benzil and ketone with -hydrogen atom in the presence of sodium hydroxide was developed. Acknowledgment The authors thank the National Natural Science Foundation of China (No. 20962006) and the Natural Science Foundation of the Guizhou Education Department (No. 2007051) for financial support. Research Journal of Chemical Sciences__________________________________________________Vol. 1 (2) May (2011) Res.J.Chem.Sci.122 References 1. Roberts S. M., Santoro M. G. and Guyot T., J.Chem. Soc., Perkin Trans. 1, 2437, (1999) 2. Tian J., Li D. L., Zhai, F. Y., Wang, X. H., and Li, R., Med. Chem. Res., 19, 1162,(2009) 3. Gabriella S. M., Antonio R., Giuliano E., EP 1704855 A2, 09-27 (2006)4. Zhang L. M. and Wang, S. Z., J. Am. Chem. Soc., 128, 1442, (2006) 5. Wade L. 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