1H-Benzimidazole-5-carboxylic acid

• 1H-benzoimidazole-5-carboxylic acid benzotriazol-1-yl ester
• piperidin-1-yl(1-m-tolyl-1H-benzo[d]imidazol-5-yl)methanone

124-38-9

4887-88-1

15788-16-6

To a solution of 5-bromo-1H-benzimidazole (0.87 g, 4.4 mmol, 1.0 eq.) in anhydrous THF (20 mL) was slowly added 2 M isopropylmagnesium chloride (i-PrMgCl) in a solution of THF (2.2 mL, 4.4 mmol, 1.0 eq.) at 0 °C, keeping the reaction temperature not more than 20 °C. After addition, the clarified solution was continued to be stirred at 0 °C for 5 min. Subsequently, 2.5 M hexane solution (3.5 mL, 8.8 mmol, 2.0 eq.) of n-butyllithium (n-BuLi) was added dropwise over 5 min, controlling the temperature below 20 °C. The reaction mixture was stirred at the same temperature for 30 min. Then, dry carbon dioxide (0.20 g, 4.4 mmol, 1.0 eq.) was added to the reaction system and the mixture was slowly warmed to 20 °C over 30 min. Upon completion of the reaction, the reaction was quenched with deionized water (6 mL). After stirring at 20 °C for 10 min, the organic and aqueous phases were separated. The aqueous phase was extracted once with ethyl acetate (10 mL). The organic phases were combined, filtered through a 0.51 cm silica gel pad and eluted with ethyl acetate (10 mL). The filtrate was concentrated and the residue was purified by silica gel column chromatography (eluent: petroleum ether/ethyl acetate = 3:1) to afford 1H-benzimidazole-5-carboxylic acid (0.5 g, 71% yield) as a brown solid. The product was structurally confirmed by 1H-NMR (600 MHz, DMSO-d6) and 13C-NMR (151 MHz, DMSO-d6).