6-Bromo-2(3H)-benzoxazolone

White solidChEBI: A member of the class of benzoxazoles that is 2-benzoxazolinone substituted at position 6 by a bromo group.

Cincreasin is a member of the class of benzoxazoles that is 2-benzoxazolinone substituted at position 6 by a bromo group. It is a benzoxazole and an organobromine compound.

3H-1, 3-Benzoxazol-2-one (5.00 g, 37.00 mmol) was dissolved in acetic acid (50 mL) and bromine (1.9 mL, 37.0 mmol) was added dropwise. The reaction mixture was stirred at 20 °C for 4 h.The reaction mixture was poured onto ice and the precipitate was collected by filtration, washed with water and air-dried to give a pink powder (7.48 g, 34.8 mmol, 94percent). Mp 191.6-192.3 °C. To a mixture of 3H-benzooxazol-2-one (20 g, 0.15 mol) in DCM (500 mL) was added bromine (8.34 mL, 0.16 mol). After stirring at room temperature for 19.5 h, the orange precipitate that had formed was filtered off and washed with DCM until the orange color was washed out. The filtrate was concentrated to approximately 33percent of its original volume and filtered and washed as before. The combined solids weighed 28.36 g. Step 1: N-Bromosuccinimide (26.6 g, 0.15 mol) was added to a stirred solution of 2-benzoxazolinone (20.0 g, 0.15 mol) in glacial acetic acid (220 mL), and the mixture was stirred at room temperature for 3 days. The reaction mixture was poured into H2O (1.2 L), and the white solid that formed was collected. Recrystallization from hot EtOH (300 mL) gave bromide 1 (22.1 g, 70percent) as an off-white solid: mp 190-195 C.; IR (KBr): 3278, 1779, 1736, 1623 cm'1; 1H NMR (300 MHz, CD3OD): '7.41 (d, J=2 Hz, 1H), 7.32 (dd, J=5, 2 Hz, 1H), 6.99 (d, J=5 Hz, 1H); CI MS (methane) (m/z): 215 [M+H]+.Preparation of 6-Bromo-3H-benzoxazol-2-one. [0950] To a solution of XXXV-1 (3 g, 16 mmol) in dry DCM (50 mL) was added TEA (3.2 g, 32 mmol). The reaction mixture was cooled to 0°C, triphosgene (1.6 g, 5.3 mmol) was added slowly. The mixture was stuffed overnight at rt, then quenched with water, extracted with DCM (80 mLx3). The combined organic layer was washed with brine, dried over anhydrous Na2SO4 and concentrated. The residue was purified by column chromatography on silica gel (PE/EA=10/1) to afford XXXV-2b (2.7g, 79percent yield).3H-1, 3-Benzoxazol-2-one (5.00'g, 37.00'mmol) was dissolved in acetic acid (50'mL) and bromine (1.9'mL, 37.0'mmol) was added dropwise. The reaction mixture was stirred at 20'C for 4'h.The reaction mixture was poured onto ice and the precipitate was collected by filtration, washed with water and air-dried to give a pink powder (7.48'g, 34.8'mmol, 94%). Mp 191.6-192.3'C. 1H NMR (300'MHz, DMSOd6): delta 11.81 (s, 1H), 7.57 (dd, J?=?1.9'Hz, J?=?0.3'Hz, 1H), 7.30 (dd, J?=?8.3'Hz, J?=?1.9'Hz, 1H), 7.04 (dd, J?=?8.3'Hz, J?=?0.3'Hz, 1H). 13C NMR (75'MHz, DMSOd6): delta 154.5, 144.5, 130.3, 126.9, 113.5, 113.2, 111.7. LCMS m/z calc for [M?-?H]+: 211.9, 213.9, found: 211.8, 213.8.To a mixture of 3H-benzooxazol-2-one (20 g, 0.15 mol) in DCM (500 mL) was added bromine (8.34 mL, 0.16 mol). After stirring at room temperature for 19.5 h, the orange precipitate that had formed was filtered off and washed with DCM until the orange color was washed out. The filtrate was concentrated to approximately 33% of its original volume and filtered and washed as before. The combined solids weighed 28.36 g. 1H NMR indicated the product was clean albeit contained ca. 8-9% starting material meaning the true yield of product was 26.72 g, 84%.Step 1: N-Bromosuccinimide (26.6 g, 0.15 mol) was added to a stirred solution of 2-benzoxazolinone (20.0 g, 0.15 mol) in glacial acetic acid (220 mL), and the mixture was stirred at room temperature for 3 days. The reaction mixture was poured into H2O (1.2 L), and the white solid that formed was collected. Recrystallization from hot EtOH (300 mL) gave bromide 1 (22.1 g, 70%) as an off-white solid: mp 190-195 C.; IR (KBr): 3278, 1779, 1736, 1623 cm'1; 1H NMR (300 MHz, CD3OD): '7.41 (d, J=2 Hz, 1H), 7.32 (dd, J=5, 2 Hz, 1H), 6.99 (d, J=5 Hz, 1H); CI MS (methane) (m/z): 215 [M+H]+.Preparation of 6-Bromo-3H-benzoxazol-2-one. To a stirred suspension of 3H-benzoxazol-2-one (1.35 g, 10 mmol) in acetonitrile (23 ML) at -15 C. was added portionwise NBS (2.00 g, 11.0 mmol).Following complete addition of NBS the mixture was stirred at -15 to 0 C. for 3 h then allowed to warm to ambient temperature and stirred overnight.The solvent was evaporated in vacuo and the residue was partitioned between CH2Cl2/H2O precipitating the intermediate title compound, 6-bromo-3H-benzoxazol-2-one, (0.67 g, 31%) as a brown solid. 1HNMR(CDCl3) delta 7.0 (1H, d), 7.15 (1H., d), 7.3 (1H, s), 11.9 (1H, s).To a mixture of 3H-benzooxazol-2-one (20 g, 0.15 mol) in DCM (500 mL) was added bromine (8.34 mL, 0.16 mol). After stirring at room temperature for 19.5 h, the orange precipitate that had formed was filtered off and washed with DCM until the orange color was washed out. The filtrate was concentrated to approximately 33% of its original volume and filtered and washed as before. The combined solids weighed 28.36 g and contained ca. 8-9% starting material.Step 1: To a solution of benzoxazolinone (20 g, 0.148 mol) in 220 mL glacial acetic acid was added N-bromosuccinimide (NBS, 26.36 g, 0.148 mol), and the reaction mixture was stirred at room temperature for 63 hours before pouring into 1500 mL water. The precipitated product was washed thoroughly with water upon collection and recrystallized from EtOH to give 6-bromo-3H-benzoxazol-2-one (9) (25.09 g, 79%): Theory: C, 39.28; H, 1.88; N, 6.54; Br, 37.33. Found: C, 39.36; H, 2.02; N, 6.36; Br, 37.43. MP 192-194 C.

Molecular Weight:214.02
XLogP3:1.9
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:2
Exact Mass:212.94254
Monoisotopic Mass:212.94254
Topological Polar Surface Area:38.3
Heavy Atom Count:11
Complexity:185
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes