All materials and solvents were purchased from Merck and Aldrich and were used without any additional purification. The melting points of the products were determined in open capillary tubes using BAMSTEAB Electrothermal apparatus model 9002. The 1H NMR spectra were recorded at 300 MHz. The 13C-NMR spectra were recorded at 75 MHz. The 19F-NMR spectra were recorded at 282 MHz. In the 19F-NMR spectra, up field shifts were quoted as negative and referenced to CFCl3. Mass spectra were taken by a Micro mass Platform II: EI mode (70 eV). Silica plates (Merck) were used for TLC analysis.
Preparation of 2-(perfluoropyridin-4-yl)malononitrile 6a
Pentafluoropyridine 1 (0.1 g, 0.6 mmol), malononitrile 2a (0.04 g, 0.6 mmol) and potassium carbonate (0.11 g, 1.0 mmol) were stirred together in DMF (5 mL) at reflux temperature for 3 h. The reaction mixture was evaporated to dryness than the solid product was recrystallisation from acetonitrile to give 2-(perfluoropyridin-4-yl)malononitrile (0.22 g, 86 %) as a red crystals; mp 260 °C dec, 19F NMR (acetone): 1H NMR (acetone): δ (ppm) 7.79 (s, 1H, CH); δ (ppm) −83.5 (m, 2F, F-2,6), −84.4 (m, 2F, F-2′,6′), −135.4 (m, 2F, F-3,5), −139.4 (m, 2F, F-3′,5′). MS (EI), m/z (%) = 508 (M+), 440, 364, 291, 180, 147, 121, 105, 91, 77, 57, 43.
Preparation of 2-ethoxy-3,5,6-trifluoro-4-((1-methyl-1H-tetrazol-5-yl)thio)pyridine 5b
Pentafluoropyridine 1 (0.1 g, 0.6 mmol), 1-methyl-1H-tetrazole-5-thiol 2b (0.09 g, 0.6 mmol) and sodium hydrogencarbonate (0.11 g, 1.0 mmol) were stirred together in CH3CN (5 mL) at reflux temperature for 4 h (monitored by TLC). The solvent was evaporated; water (5 mL) was added and extracted with dichloromethane and ethyl acetate (3 × 5 mL). Solvent evaporation and recrystallisation from ethanol gave 2-ethoxy-3,5,6-trifluoro-4-((1-methyl-1H-tetrazol-5-yl)thio)pyridine 5b (0.2 g, 75 %) as a white crystal; mp 130 °C dec. 1H NMR (acetone): δ (ppm) 1.37 (3H, m, CH3), 3.90 (3H, s, N-CH3), 4.3 (2H, m, CH2); 19F NMR (acetone): δ (ppm) −88.6 (1F, m, F-2), −131.4 (1F, m, F-3), −154.8 (1F, m, F-5); 13C NMR (acetone): δ (ppm) 14.6, 35.5, 63.2, 64.4, 139.2, 140.5, 142.6, 143.7, 145.9 ppm. MS (EI), m/z (%) = 292 (M+), 263, 235, 219, 180, 132, 100, 83, 43.
Preparation of 1,4-bis(perfluoropyridin-4-yl)piperazine 3c
Pentafluoropyridine 1 (0.1 g, 0.6 mmol), piperazine 2c (0.03 g, 0.5 mmol) and sodium hydrogencarbonate (0.11 g, 1.0 mmol) were stirred together in CH3CN (5 mL) at reflux temperature for 5 h. After complicated reaction, the solvent was evaporated; water (5 mL) was added and extracted with dichloromethane and ethyl acetate (3 × 5 mL). Solvent evaporation and recrystallization from CH3CN gave 1,4-bis(perfluoropyridin-4-yl)piperazine 3c (0.2 g, 52 %) as a white crystal; mp 288 °C dec. 1H NMR (acetone): δ (ppm) 4.30 (8H, s, CH2); 19F NMR (acetone): δ (ppm) −97.3 (4F, m, F-2,6), −160.5 (4F, m, F-3,5). 13C-NMR (acetone): δ (ppm) 60.3, 123.7, 127.1, 131.3 ppm. MS (EI), m/z (%) = 384 (M+), 317, 292, 263, 235, 219, 180, 152, 132, 116, 100, 83, 63, 43.