56961-30-9

89-54-3

56961-30-9

General procedure for the synthesis of 2-chloro-5-hydroxybenzoic acid from 5-amino-2-chlorobenzoic acid: aqueous sodium nitrite (90 mL, 0.5 M) was slowly added to a stirring suspension of 5-amino-2-chlorobenzoic acid (16) (5.01 g, 29.6 mmol) and sulfuric acid (6.00 mL, 0.167 mol) at 0 °C. During addition, the reaction temperature was maintained between 0 and 5 °C. After addition, stirring was continued in an ice bath for 1 hour. Subsequently, the reaction mixture was diluted with water (900 mL) and stirred under reflux conditions for 30 minutes. Upon completion of the reaction, the mixture was cooled to room temperature and extracted with ethyl acetate (3 x 500 mL). The organic phases were combined, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure to give the light brown solid product 17 (4.97 g, 98% yield). The melting point of the product was 165-168 °C; IR (ZnSe) showed absorption peaks located at 3311, 2920, 2598, 1676, 1599, 1573, 1474, 1447, 1228, 826 cm-1 ; 1H NMR (300 MHz, MeOD) chemical shifts were δ 7.26 (1H, d, J = 8.7 Hz), 7.23 (1H, d, J = 3.0 Hz), 6.89 (1H, dd, J = 3.0 and 8.7 Hz) ppm, no 2xOH signal observed; 13C NMR (75 MHz, MeOD) chemical shifts were δ169.1, 157.4, 132.7, 132.8, 123.8, 120.7, 116.2 ppm; LRMS (-) ESI) showed m/z 171 ([M-H]-, 100%), 127 ([M-CO2H]-, 36%).