Benzothiophene-4-carboxylic acid

5118-13-8

124-38-9

10134-95-9

Benzo[b]thiophene-4-carboxylic acid was prepared as follows: a small amount of iodine crystals was added as initiator to a stirring suspension of magnesium (Mg, 4.79 g, 197 mmol) in anhydrous tetrahydrofuran (THF, 100 mL) under nitrogen protection. Subsequently, a solution of 4-bromobenzo[b]thiophene (40.0 g, 188 mmol) in anhydrous THF (150 mL) was added slowly and dropwise. Initially, only 5% of the total amount (~1 mL) was added to initiate the reaction, after which the remaining solution was added at a rate that maintained the reaction temperature at 50-55 °C, a process that took about 30 min. After addition, the reaction mixture was continued to be stirred at 50°C for 1 hour. After most of the magnesium has been consumed, the reaction is cooled to 23°C and carbon dioxide (CO2) gas produced from dry ice is passed into the solution. The reaction is exothermic and the solution temperature needs to be maintained at about 23°C by an ice bath. The gas is continuously vented for 15-20 minutes until a large amount of precipitate generation is observed. Upon completion of the reaction, the reaction is carefully quenched with 10% aqueous hydrochloric acid (HCl) solution at 0°C. Saturated aqueous sodium chloride solution was added and the mixture was extracted with ethyl acetate (EtOAc). The organic phase was extracted with 2 M aqueous sodium hydroxide (NaOH) and subsequently the aqueous phase was acidified to pH 1 with 37% aqueous HCl to form a suspension. After filtration and drying, benzo[b]thiophene-4-carboxylic acid was obtained as a white solid (24.9 g, 74% yield).