6-Nitrophthalide

pale yellow crystalline powder

Step A: Synthesis of 6-nitrobenzofuran-l(3H)-one[0086] To an ice-cold stirred solution of phthalide (40.0 g, 298 mmol) in sulfuric acid (50.0 mL) was added potassium nitrate (30.4 g, 300 mmol) dissolved in sulfuric acid (80 mL) via dropwise addition. The reaction was stirred and allowed to warm to room temperature over 5 h. The resulting mixture was poured into ice-water, and the precipitate collected was recrystallized from ethanol (3 L) to afford 6-nirobenzofuran-l(3H)-one (50.4 g, 94percent) as an off-white solid (98percent of the desired regioisomer by NMR): 1H NMR (500 MHz, CDC1Step a: 6-Nitroisobenzofuran-1(3H)-one 3H-Isobenzofuran-1-one (4.00 g, 29.8 mmol) was dissolved in concentrated sulfuric acid (5.0 ml) at 0° C., and a solution of potassium nitrate (3.0 g, 30 mmol) in concentrated sulfuric acid (8.0 ml) was added dropwise thereto. After stirring at room temperature for 5 hours, the reaction solution was diluted with water. The precipitated solid was filtered and recrystallized from ethanol (20 ml) to obtain the title compound (2.0 g, 37percent). [1323] 1H NMR (400 MHz, DMSO-dTo a solution of phthalide (2.5 g, 18.65 mmol) in conc.HStep A: Synthesis of 6-nitrobenzofuran-l(3H)-one[0086] To an ice-cold stirred solution of phthalide (40.0 g, 298 mmol) in sulfuric acid (50.0 mL) was added potassium nitrate (30.4 g, 300 mmol) dissolved in sulfuric acid (80 mL) via dropwise addition. The reaction was stirred and allowed to warm to room temperature over 5 h. The resulting mixture was poured into ice-water, and the precipitate collected was recrystallized from ethanol (3 L) to afford 6-nirobenzofuran-l(3H)-one (50.4 g, 94%) as an off-white solid (98% of the desired regioisomer by NMR): 1H NMR (500 MHz, CDC13) delta 8.77 (d, J= 1.5 Hz, 1H), 8.58 (dd, J= 8.5, 2.0 Hz, 1H), 7.72 (d, J- 8.5 Hz, 1H), 5.45 (s, 2H).A solution of phthalide 1 (1 eq, 22 mmol, 3.0 g) in 30 mL ofH2SO4 (95e98%) was added dropwise at 0 C to a solution of KNO3(1.2 eq, 26.0 mmol, 2.63 g) in 12 mL of H2SO4 (95e98%). The reaction mixture was stirred at room temperature for 2h30 and then poured on ice. The resulting precipitate was filtered under reducedpressure and washed with distilled water. The filtrate was onceagain filtered under reduced pressure and the remaining solid waswashed with distilled water. The combined solids were dried under reduced pressure to give Step a: 6-Nitroisobenzofuran-1(3H)-one To a stirred solution of 3H-isobenzofuran-1-one (30.0 g, 0.220 mol) in H2SO4 (38 mL) was added KNO3 (28.0 g, 0.290 mol) in H2SO4 (60 mL) at 0 C. The mixture was stirred at 20 C. for 1 h. The reaction mixture was poured into ice and the resulting precipitate was filtered off. The solid was recrystallized from ethanol to give Step a: 6-Nitroisobenzofuran-1(3H)-one To a stirred solution of 3H-isobenzofuran-1-one (30.0 g, 0.220 mol) in H2SO4 (38 mL) was added KNO3 (28.0 g, 0.290 mol) in H2SO4 (60 mL) at 0 C. The mixture was stirred at 20 C. for 1 h. The reaction mixture was poured into ice and the resulting precipitate was filtered off. The solid was recrystallized from ethanol to give 6-Nitroisobenzofuran-1(3H)-one To a stirred solution of 3H-isobenzofuran-1-one (30.0 g, 0.220 mol) in H2SO4 (38 mL) was added KNO3 (28.0 g, 0.290 mol) in H2SO4 (60 mL) at 0 C. The mixture was stirred at 20 C. for 1 h. The reaction mixture was poured into ice and the resulting precipitate was filtered off. The solid was recrystallized from ethanol to give 3H-Isobenzofuran-1-one (4.00 g, 29.8 mmol) was dissolved in concentrated sulfuric acid (5.0 ml) at 0 C., and a solution of potassium nitrate (3.0 g, 30 mmol) in concentrated sulfuric acid (8.0 ml) was added dropwise thereto. After stirring at room temperature for 5 hours, the reaction solution was diluted with water. The precipitated solid was filtered and recrystallized from ethanol (20 ml) to obtain the title compound (2.0 g, 37%). [1323] 1H NMR (400 MHz, DMSO-d6): delta 8.62-8.59 (m, 1H), 8.53 (d, J=2.8 Hz, 1H), 7.72 (d, J=8.0 Hz, 1H), 5.57 (s, 2H)To a solution of phthalide (2.5 g, 18.65 mmol) in conc.H2S04 was added a solution of potassium nitrate (2.22 g, 18.65 mmol) in cone. H2S04. The reaction mixture was stirred at 0C for 30 minutes and quenched with water and filtered. The filtrate was concentrated and purified by column chromatography to afford 1.00 g of the title product. 1H NMR (300 MHz, DMSO-Je): delta 5.45 (s, 2H), 7.72 (d, / = 8.4 Hz, 1H), 8.58 (d, / = 8.1 Hz, 1H), 8.78 (s, 1H).a. Preparation of

Molecular Weight:179.13
XLogP3:0.6
Hydrogen Bond Acceptor Count:4
Exact Mass:179.02185764
Monoisotopic Mass:179.02185764
Topological Polar Surface Area:72.1
Heavy Atom Count:13
Complexity:247
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes