4-amino-3,5-dimethyl-benzoic acid

3095-38-3

4919-40-8

3,5-Dimethyl-4-nitrobenzoic acid (976 mg, 5 mmol) was suspended in water (20 mL) under vigorous stirring for 30 min until the mixture was homogeneously dispersed. Sodium carbonate (Na2CO3, 300 mg, 2.8 mmol) and zinc powder (3 g, 30 mmol) were sequentially added to the suspension and the reaction mixture was subsequently heated to 30 °C. Concentrated hydrochloric acid (HCl, 10 mL) was added slowly and dropwise over a period of 20 min. After completion of the reaction, the mixture was filtered and the filter cake was washed twice with water (2 x 7 mL). To remove unreacted 3,5-dimethyl-4-nitrobenzoic acid, the filtrate was washed twice with ethyl acetate (2 × 40 mL). The pH of the aqueous layer was adjusted to 9.35 by adding saturated sodium carbonate solution (35 mL) and the precipitated zinc hydroxide (Zn(OH)2) was filtered. The filter cake was again washed twice with 5% sodium bicarbonate solution (2 x 10 mL). To remove the by-products, the filtrate was washed twice with ethyl acetate (2 × 80 mL). Subsequently, the pH of the aqueous layer was adjusted to 3.5 with 1N hydrochloric acid (~120 mL).Finally, the aqueous layer was extracted five times with ethyl acetate (5 × 80 mL). The organic layers were combined, dried over anhydrous magnesium sulfate (MgSO4) and concentrated under reduced pressure. 4-Amino-3,5-dimethylbenzoic acid was obtained as a clear brown solid in 76% yield (629 mg).1H NMR (500 MHz, CD3CN): δ 8.94 (br s, 1H, OH), 7.55 (s, 2H, H3', H5'), 4.52 (br s, 2H, NH2), 2.15 (s, 6H, H7'). 13C NMR (126 MHz, CD3CN): δ 168.5 (C8'), 149.9 (C1'), 131.0 (C3', C5'), 122.4 (C4'), 121.4 (C2', C6'), 17.9 (C7'). MS (ESI+): m/z 166 [M + H]+.