4-Chloro-3-cyanobenzoic acid

544-92-3

151-50-8

117738-76-8

The general procedure for the synthesis of 4-chloro-3-cyanobenzoic acid from cuprous cyanide and potassium cyanide was as follows: sodium nitrite (10.0 g, 145 mmol) was added to a mixed solution of sulfuric acid (60 mL) and water (95 mL) containing 3-amino-4-chlorobenzoic acid (10.0 g, 57.1 mmol) at 0 °C. The reaction mixture was kept stirred at 0 °C for 2 hours. Subsequently, the mixture was slowly added to a pre-stirred solvent mixture of water (250 mL) and benzene (175 mL) in which cuprous cyanide (7.1 g, 79.3 mmol), potassium cyanide (21.7 g, 333 mmol), and potassium carbonate (285 g, 2.06 mmol) were dissolved, taking care to control the temperature to no higher than 15 °C. The reaction system was heated to 80 °C and stirred for 1 h, after which it was cooled to room temperature. The insoluble material was collected by filtration through diatomaceous earth and washed with benzene (100 mL) and ether (100 mL) under cooling in an ice bath. The aqueous phase was separated and the pH was adjusted to 2 with concentrated hydrochloric acid while stirring under ice bath cooling. The aqueous phase was extracted with ether (200 mL x 2), the organic phases were combined and dried over anhydrous sodium sulfate. The solvent was removed by distillation under reduced pressure, and the resulting residue was purified by silica gel column chromatography (eluent: ethyl acetate/hexane), resulting in 2.0 g of the light yellow crystalline target product 4-chloro-3-cyanobenzoic acid in 19% yield. The structure of the product was confirmed by 1H-NMR (CDCl3/CD3OD = 20/1, 400 MHz): δ 7.61 (1H, d, J = 9Hz), 8.20 (1H, dd, J = 2Hz, 9Hz), 8.36 (1H, d, J = 2Hz).