[Synthesis]
An aqueous solution (10 mL) of NaNO2 (2.21 g, 32 mmol) was slowly added to an aqueous solution (40 mL) of 5-amino-2-chlorobenzoic acid (5.0 g, 29.14 mmol) at 0 °C, followed by the addition of concentrated HCl (10 mL). The reaction mixture was kept at -5 °C and stirring was continued for 1 hour. The resulting diazonium salt solution was added dropwise to a pre-prepared solution of potassium copper tetracyanide [prepared from an aqueous solution of KCN (10 g, 15.38 mmol) (18 mL) with an aqueous solution of Cu (7 g, 43.8 mmol) (12 mL) stirred for 1 h at 50 °C]. Upon completion of the reaction, the reaction mixture was acidified with 1.5 N HCl solution, followed by extraction of the target product with EtOAc. The organic phases were combined, washed sequentially with water and brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The crude product was purified by column chromatography (silica gel 60-120 mesh, eluent 1-2% MeOH in CHCl3 solution) to afford 2-chloro-5-cyanobenzoic acid (1.8 g, 34% yield).1H NMR (400 MHz, DMSO-d6) δ 13.92 (br s, 1H), 8.24 (d, J = 2.1 Hz, 1H), 8.02- 7.99 (dd, J = 8.4 Hz, 2.1 Hz, 1H), 7.80-7.78 (d, J = 8.2 Hz, 1H).MS (ESI) m/z: calculated value for C8H4ClNO2: 180.99; measured value: 179.6 (M-H)-. |