Description
6-fluoro-4-nitro-3H-isobenzofuran-1-one is a kind of benzofuran
derivative. As a kind of isobenzofuranone, it can be used to enhance
aroma in perfumery. It also has certain pharmacological effects such
as antioxidant activity and antiplatelet activity.
6-Fluoro-4-nitro-1(3H)-isobenzofuranone appeared as a reactant in the synthesis of a Poly(ADP-ribose) Polymerase-1/2 Inhibitor, which is a proposed anticancer agent.
Uses
6-Fluoro-4-nitro-1(3H)-isobenzofuranone appeared as a reactant in the synthesis of a Poly(ADP-ribose) Polymerase-1/2 Inhibitor, which is a proposed anticancer agent.
Synthesis
The general procedure for the synthesis of 6-fluoro-4-nitroisobenzofuran-1(3H)-ones from methyl 2-(bromomethyl)-5-fluoro-3-nitrobenzoate was as follows: methyl 5-fluoro-2-methyl-3-nitrobenzoate (28 g, 130.5 mmol), N-bromosuccinimide (NBS, 27.8 g, 156.6 mmol) and benzoyl peroxide ( BPO, 3.13 g, 13.1 mmol) in carbon tetrachloride (CCl4, 400 mL) were heated to reflux and reacted overnight. The reaction was monitored by thin layer chromatography (TLC, unfolding agent ratio of petroleum ether/ethyl acetate = 15:1) to confirm complete consumption of the feedstock. Upon completion of the reaction, water (200 mL) was added and carbon tetrachloride was removed by distillation under reduced pressure. The residue was extracted with dichloromethane (DCM, 200 mL x 3). The organic layers were combined, washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated to give the crude product methyl 2-(bromomethyl)-5-fluoro-3-nitrobenzoate (36 g, 94% yield) as a brown oil. The resulting methyl 2-(bromomethyl)-5-fluoro-3-nitrobenzoate (36 g, 123 mmol) was dissolved in 1,4-dioxane (250 mL) and water (62.5 mL) and heated to reflux for 4 days. Complete consumption of the raw material was confirmed by TLC (unfolding agent ratio petroleum ether/ethyl acetate = 15:1). Upon completion of the reaction, 1,4-dioxane was removed by distillation under reduced pressure. The residue was extracted with ethyl acetate (EtOAc, 300 mL x 4). The organic layers were combined, washed with saturated saline, dried over anhydrous sodium sulfate and concentrated to give the crude product. The crude product was purified by silica gel column chromatography (eluent tapered from petroleum ether to petroleum ether/ethyl acetate=5:1) to afford 6-fluoro-4-nitroisobenzofuran-1(3H)-one (19.2 g, yield 79%) as a white solid. The structure of the product was confirmed by 1H-NMR (400 MHz, CDCl3) and LC-MS (ESI): 1H-NMR δ (ppm): 5.74 (s, 2H), 7.97-7.98 (dd, 1H), 8.24-8.27 (dd, 1H); LC-MS (ESI) m/z: 198 (M+1)+.
References
Boden, Richard M, and W. L. Schreiber. "Use of 1 (3H)- isobenzofuranone in perfumery." US, US 5665697 A. 1997.
Ma, F., et al. "Antiplatelet activity of 3-butyl-6-bromo-1 (3H)- isobenzofuranone on rat platelet aggregation. " Journal of Thrombosis & Thrombolysis 33.1(2012): 64-73.
Pahari, Pallab, B. Senapati, and D. Mal. "Regiospecific Synthesis of Isopestacin, a Naturally Occurring Isobenzofuranone Antioxidant." Cheminform 45.26(2004): 5109-5112.
