Example 2: Preparation of isochroman-1,4-dione (compound of formula (III))
Under stirring conditions, 2-acetylbenzoic acid (compound of formula (XI), 1.00 kg, 6.09 mol) was mixed with chlorobenzene (10.0 L), followed by the addition of a 55% hydrobromic acid solution of acetic acid (55 mL) and bromine (310 mL) sequentially. The reaction mixture was slowly warmed to 30 °C and maintained for 3 hours. After that, water (10.0 L) was added and the reaction system was heated to reflux. After continuing the reaction for 3 hours, the reaction solution was cooled to 60 °C and the organic layer was separated and removed. The aqueous layer was extracted with chlorobenzene (2.0 L), and all organic layers were combined and concentrated under reduced pressure to about 3.0 L. Isopropanol (5.0 L) was added to the concentrate, and the resulting slurry was cooled to 0 °C, followed by filtration and washing of the solid with isopropanol (2.0 L). Finally, the resulting solid was dried under vacuum at 50 °C to afford isochroman-1,4-dione (736 g, 75% yield).
Product characterization data:
1H NMR (400 MHz, CDCl3): δ 5.14 (2H, s, H-9), 7.82-7.91 (2H, m, H-2 and H-3), 8.08-8.10 (1H, m, H-1), 8.28-8.30 (1H, m, H-4).
13C NMR (100 MHz, CDCl3): δ 73.4, 125.6, 128.0, 130.9, 131.8, 134.7, 135.9, 161.4, 189.5.
