General procedure for the synthesis of 4-hydroxy-3-nitrophenylacetic acid from p-hydroxyphenylacetic acid:
(a) Nitration reaction: fuming nitric acid (1.36 mL) was slowly added dropwise to a solution of 4-hydroxyphenylacetic acid (4.00 g, 26.3 mmol) in acetic acid (25 mL) under cooling in an ice bath. After the dropwise addition was completed, the reaction mixture was slowly warmed up to room temperature and reacted for 1 hour, during which time the solution gradually changed from yellow to brown color, accompanied by the formation of a precipitate. After completion of the reaction, the solid product was collected by filtration and recrystallized from ethyl acetate/hexane mixed solvent to obtain yellow needle-like crystals of 4-hydroxy-3-nitrophenylacetic acid (3.61 g, 70% yield). The structure of the product was confirmed by 1H-NMR: δ (CDCl3-d4/DMSO, 4:1) 3.50 (2H, s), 7.04 (1H, d, J = 9 Hz), 7.46 (1H, dd, J = 9, 3 Hz), 7.94 (1H, d, J = 3 Hz).
