4-Chloro-5-fluoro-1,2-phenylenediamine → 5-Fluorobenzimidazole

関与物質

反応手順

4-Chloro-5-fluoro-1,2-phenylenediamine (12a, 3.212 g, 20 mmol) was dissolved in 40 mL of MeOH and then added dropwise to a stirred solution of 4.4 mL of 5M BrCN/MeCN in 40 mL of H2O over 30 min. After the addition, stirring was continued at room temperature for 3 hr. The reaction mixture was concentrated to ~40 mL and then was washed with EtOAc (100 mL). The EtOAc phase was extracted with H2O (60 mL). The combined H2O phase was neutralized with sat. NaHCO3 solution to ~pH 8 and the resulting suspension was extracted with EtOAc (200 mL). The EtOAc phase was washed with a mixture of sat. NaHCO3 /sat. NaCl solution (20 mL/180 mL), dried (Na2SO4), and evaporated. The residue was coevaporated with CHCl3 (20 mL×2) and then was suspended in 50 mL of CHCl3. The suspension was filtered to give 3.340 g of 12b as a grey solid. The filtrate was evaporated and coevaporated with CHCl3. The resulting solid was again suspended in a small amount of CHCl3 and the suspension was filtered to give an additional 0.235 g of 12b. The total yield of 12b was 3.575 g (96%). This product showed a single spot on TLC. MP: 194°-196° C. MS: (El) m/e 185.0156 (100%, M+ =185.0156). 1H NMR (DMSO-d6): d 10.85, (br s, 1, 1-NH), 7.16 (d, 1, 4-H, 4JF-H =7.0 Hz), 7.06 (d, 1, 7-H, 3JF-H =10.0 Hz), 6.43 (br s, 2, 2-NH2). Anal. Calcd. for C7H5ClFN3 ; C, 45.30; H, 2.72; N, 22.64. Found: C, 45.14; H, 2.67; N, 22.44.

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