Example 24A Synthesis of 4-formyl-3-hydroxybenzonitrile: 100 mL of a dichloromethane solution of boron tribromide (1M, 100 mmol) was slowly added dropwise to 80 mL of anhydrous dichloromethane solution containing 8 g (49.64 mmol) of 4-formyl-3-methoxybenzonitrile, protected by argon gas and at -78 °C. The reaction mixture was stirred continuously at room temperature until complete reaction of the raw material was confirmed by TLC detection (about 5 days). Subsequently, the reaction system was cooled to 0 °C and minimally neutralized with saturated sodium bicarbonate solution. The organic and aqueous phases were separated and the organic phase was further washed with saturated sodium chloride solution, dried over anhydrous magnesium sulfate and concentrated under reduced pressure to remove the solvent. The crude product was purified by silica gel column chromatography using cyclohexane/ethyl acetate (3:1, v/v) as mobile phase. Finally, 4.5 g of the target product 3-hydroxy-4-formylbenzonitrile in yellow solid form was obtained in 61% yield. The product was analyzed by LC-MS (Method 1) showing Rt = 1.38 min; [MH]- = 146. 1H-NMR (300 MHz, CDCl3) data were as follows: δ = 7.38 (d, 1H), 7.38 (s, 1H), 7.77 (d, 1H), 10.33 (s, 1H), 11.38 (s, 1H).
