Synthesis
General procedure: Cyanoacetamide (2.35 g, 28 mmol) was added to a pre-prepared ethanol solution of sodium ethanolate (50 mL, prepared by dissolving 0.87 g of sodium metal (38 mmol) in anhydrous ethanol at 0°C), and the reaction mixture was subsequently heated to 60°C and maintained for 30 minutes. After the reaction mixture was cooled to room temperature, 4-butoxy-1,1,1-trifluoro-3-buten-2-one (5.0 g, 25 mmol) was slowly added dropwise for 20 minutes. After completion of the dropwise addition, the reaction mixture was refluxed for 5 h, during which the reaction process was monitored by thin layer chromatography (TLC). Upon completion of the reaction, the reaction mixture was neutralized with 15% hydrochloric acid solution, the residue was extracted with ethyl acetate and the organic phase was dried with anhydrous sodium sulfate followed by distillation under reduced pressure to remove the solvent. The resulting crude product was purified by chromatography on a 60-120 mesh silica gel column, using a n-hexane solution of 25% ethyl acetate (1:3, v/v) as eluent. The final yellowish solid product was obtained in 70.4% yield with a melting point of 210-211 °C. The product was purified by chromatography on a 60-120 mesh silica gel column. The structure of the product was confirmed by Fourier transform infrared spectroscopy (FTIR, KBr pressed): 2230 cm-1 (CN stretching vibration), 1672 cm-1 (C=O stretching vibration); nuclear magnetic resonance hydrogen spectrum (1H NMR, DMSO-d6, 300 MHz): δ 7.26 (d, J = 7.74 Hz, 1H, =CH-), 8.18 (d, J = 7.55 Hz, 1H, =CH-); NMR carbon spectrum (13C NMR, DMSO-d6, 75 MHz): δ 99.20 (C-CN), 110.06 (Ar-C), 113.70 (CN), 119.52 (q, J = 275.09 Hz, CF3), 144.58 (Ar-C), 146.81 (q, J = 35.21 Hz, C-CF3), 163.58 (C=O); electrospray mass spectrometry (ESI-MS): m/z 189 ([M+H]+), 211 ([M+Na]+).
References
[1] Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 2016, vol. 55B, # 11, p. 1361 - 1375
[2] Journal of Heterocyclic Chemistry, 2015, vol. 51, # 5, p. 1531 - 1535
[3] Bioorganic and Medicinal Chemistry Letters, 2016, vol. 26, # 18, p. 4427 - 4432
