General procedure for the synthesis of 2-chloro-5-cyanobenzimidazole from 2-oxo-2,3-dihydro-1H-benzo[d]imidazole-5-carbonitrile: First, a solution was prepared by dissolving 3,4-diaminobenzonitrile (2.60 g, 18.2 mmol) and pyridine (2 mL, 25 mmol) in DMF (20 mL). This solution was slowly added dropwise to a tetrahydrofuran solution (20 mL) of bis(trichloromethyl)carbonate (2.12 g, 7.14 mmol) under ice bath cooling conditions. After the dropwise addition was completed, the reaction mixture was stirred at room temperature for 18 hours. Upon completion of the reaction, the mixture was acidified by adding dilute hydrochloric acid to the mixture and subsequently extracted with ethyl acetate. The organic phase was washed with brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure to remove the solvent. To the concentrated residue was added ethyl acetate and the precipitate precipitated was collected by filtration to afford 2-hydroxybenzimidazole-5-carbonitrile (896 mg, 29% yield) as a purple solid. Next, 2-hydroxybenzimidazole-5-carbonitrile (894 mg, 5.62 mmol) obtained above was mixed with phosphorus trichloride (12 mL) and the reaction was heated to reflux for 3 hours. At the end of the reaction, the reaction mixture was quenched by pouring it into ice water and extracted with ethyl acetate. The organic phase was sequentially washed with brine, dried with anhydrous sodium sulfate, concentrated under reduced pressure and purified by silica gel column chromatography with hexane/ethyl acetate (2:3, v/v) as eluent to afford the target compound, 2-chloro-5-cyanobenzimidazole (322 mg, 32% yield), as a white powder.LC-MS (ESI) m/z 178.0 [M + H]+.
