Standard Reflux Method Preparation and characterization of several N-aryl enamino ketones Shannon R. Woodruff,* Kristie A. LaGrone, Laura J. Moore, and Dr. Darrell G. Watson University of Mary Hardin-Baylor, Department of Chemistry Abstract Reaction Results Several N-aryl enamino ketones have shown significant pharmacological activity in past studies. The synthesis and characterization of several N-aryl enamino ketones were investigated during this study. Aniline derivatives were reacted with several different β-diketones. The resulting N-aryl enamino ketones were isolated and characterized using basic spectroscopic techniques. Identifications of the compounds of interest were made on the basis of the following spectral data: Compound I: 1H NMR (CDCl3, 500 MHz) δ 7.296 – 7.121 (5H, m), 5.559 (1H, s), 2.347 (1H, s), 2.192 (1H, s), 1.073 (6H, s); 13C NMR (CDCl3, 125 MHz) δ 197.972, 160.862, 138.259, 129.208, 125.366, 123.811, 98.161, 50.308, 43.356, 32.739, 28.231; EIMS m/z 215 (M+, 33), 159 (100), 130 (56), 92 (22), 77 (27) Compound II: 1H NMR (CDCl3, 500 MHz) δ 7.427 – 7.130 (5H, m), 5.334 (1H, s), 3.254 (3H, s), 2.172 (2H, s), 2.076 (2H, s), 0.995 (6H, s); 13C NMR (CDCl3, 125 MHz) δ 197.203, 163.842, 144.978, 129.560, 127.358, 126.891, 98.772, 67.659, 49.339, 41.828, 32.906, 28.035; EIMS m/z 229 (M+, 39), 212 (56), 173 (100), 144 (50), 82 (99) Compound III: 1H NMR (CDCl3, 500 MHz) δ 7.983 – 7.456 (5H, m), 2.694 (4H, s), 2.584 (3H, s), 2.381 (3H, s); 13C NMR (CDCl3, 125 MHz) δ 158.300, 145.729, 140.424, 128.982, 127.842, 125.306, 123.411, 24.751, 15.714, 14.330; EIMS m/z 189 (M+, 20), 171 (100), 156 (24), 118 (54), 77 (39) Compound IV: 1H NMR (CDCl3, 500 MHz) δ 7.120 – 6.978 (5H, m), 5.194 (1H, s), 2.367 (2H, q), 2.312 (3H, s), 2.282 (2H, q), 1.147 (3H, t), 1.039 (3H, t); 13C NMR (CDCl3, 125 MHz) δ 199.630, 166.114, 135.301, 129.441, 125.828, 124.980, 93.763, 34.934, 24.858, 20.638, 12.205, 9.703; EIMS m/z 217 (M+, 26), 188 (100), 173 (26) Introduction Several N-aryl enamino ketones have been found to have pharmacological activity in past studies. In addition to their pharmacological properties, several of these compounds are known to react photochemically to yield substituted indoles and indolines, some of which are also known to have pharmacological activity. With the need for new pharmaceutical compounds on the rise, a study has been undertaken on the synthesis and characterization of N-aryl enamino ketones. The results of this study are described below. Table 1: R Group Values Compound R1 R2 R3 R4 I H H3C CH3 C H2C CH2 II CH3 III IV CH2CH3 Procedure Standard Reflux Method A sample of either aniline or N-methylaniline (0.1 moles) was weighed and added to 250 mL of an aromatic hydrocarbon (either toluene or xylene). One of several different β-diketones (0.1 moles) was then slowly added to the mixture along with a catalytic amount (0.05 moles) of glacial acetic acid. The resulting solution was equipped with a Dean Stark trap, condenser, and drying tube. The reaction was refluxed for at least 24 hours. After reflux, the solution was allowed to cool to room temperature and concentrated by rotary evaporation and analyzed by GC/MS. Purification Methods The solution resulting from the standard reflux method above was further concentrated in vacuo. If a significant amount of starting material was still present, the mixture was then purified by a short path vacuum distillation. Resulting products were also recrystallized by creating a supersaturated solution of product and solvent (either THF or hexane). Analysis Methods GC/MS analysis was carried out on a Hewlett Packard, model G-1800C GCD Series II (GC-EID), equipped with a 30 m × 0.25 mm, HP-5ms capillary column; carrier gas He (1.0 mL/min) and temperature program 110°-220°C at a rate of 7°C/min, final hold time 3.0 min, injector temperature of 250°C, detector temperature of 280°C. Electron impact mass spectra (70 eV) were acquired in m/z range 45-450. Nuclear magnetic resonance (NMR) spectra were recorded using a Varian 500 MHz NMR spectrometer. 1H and 13C nucleus probes were used. Conclusion This method seems to be a satisfactory method of preparing N-aryl enamino ketones. Additional work is needed to refine this method and maximize yield of these products. Further investigations are also needed to better determine methods of isolation and purification. Literature Cited Table 2: Percent Yield Compound Percent Yield I 68.9501% II 10.2165% III 12.9158% IV 53.51% O.L. Chapman, G.L. Eian, A. Bloom, and J. Clardy, J. Amer. Chem. Soc. 93, 2918 (1971). K.P. Zeller and G. Gauglitz, A. Naturfrosch 32b, 285 (1977). A.G. Schultz and M.B De Tar, J. Amer. Chem. Soc. 96, 296 (1974). Darrell Watson and Dennis R. Dillin, Tet. Letters, 3969 (1980). Darrell Watson and Dennis R. Dillin, Texas Journal of Science, XXXII, 357 (1980). I.C. Paul and D.Y. Curtin, Acc. Chem. Res., 6, 217 (1973) H. Morawetz, Science, 152, 705 (1966). Donald F. Mullica, Dennis R. Dillin, Darrell G. Watson, Michael Angel, J. Matt Farmer, and Jason Kautz, Journal of Chemical Crystallography, 28, 899 (1998). Acknowledgments We would like to express our appreciation to Brenton McKinney and Dr. Charles Garner for their help in this research. This work was made possible by the Robert A. Welch Foundation, grant number AY0033.