3-Bromophthalide is a major intermediate in the synthesis of drugs such as tannic acid ester and phthalimide. Further hydrolysis of 3-bromophthalide can yield o-sylbenzaldehyde, which is an important intermediate in the synthesis of antipyretic analgesics.
3-Bromophthalide is produced by reacting phthalide with N-bromosuccinimide in carbon tetrachloride solution.
Ten grams (0.075 mole) of phthalide (Note 1), 13.3 g. (0.075 mole) of N-bromosuccinimide, and 200 ml. of dry carbon tetrachloride are refluxed for 30 minutes in a 500-ml. flask carrying a reflux condenser equipped with a drying tube containing Drierite. The reaction mixture is exposed to the light of an ordinary 100-watt unfrosted light bulb placed 6–8 in. from the flask. The end of the reaction is indicated by the disappearance of N-bromosuccinimide from the bottom of the flask and accumulation of succinimide at the top of the reaction mixture. The succinimide is removed by filtration and the filtrate concentrated under atmospheric pressure to 15–20 ml. Cooling of this concentrate followed by filtration gives 12–13 g. (75–81%) of crude 3-bromophthalide, m.p. 74–80°. The crude material, when recrystallized from cyclohexane, gives colorless plates, m.p. 78–80°.
[1] Patent: US4960902, 1990, A
[2] Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 1999, vol. 38, # 7, p. 810 - 813
[3] Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 2000, vol. 39, # 6, p. 455 - 457
[4] Synlett, 2003, # 5, p. 702 - 704
[5] Chemical and Pharmaceutical Bulletin, 1983, vol. 31, # 8, p. 2698 - 2707
