3-Bromo-4-nitrophenol

Brown Solid

Sulfuric acid (98percent, 20 ml_, 375 mmol) was added dropwise to a solution of sodium nitrate (27 g, 318 mmol) in water (60 ml_) keeping the temperature between 20 and 30 °C. A solution of 3-bromophenol (24 g, 140 mmoL) dissolved in ethanol (50 ml_) was then added dropwise, keeping the temperature close to room temperature. The mixture was stirred overnight at room temperature, then poured into ice water (600 ml_) and extracted with dichloromethane (3 x 200 ml_). The combined organic fractions were dried over magnesium sulfate, filtered, and concentrated onto silica gel. Purification by column chromatography (isocratic, dichloromethane) provided 11.0 g (36percent) of the title compound as brown solid. 3-Bromophenol (32.9 g, 0.19 mol) was added slowly to a cold (10° C.) solution of sodium nitrate (29.0 g, 0.34 mol) in conc. sulfuric acid; (40.0 g) and water (70.0 mL) and the resulting mixture was allowed to stir at room temperature for 2 h. Water (200 mL) was added and the resulting mixture was extracted with diethyl ether and the extract was dried (MgSO4), filtered and concentrated. The residue was purified by flash chromatography (silica gel, 10percent ethyl acetate/hexanes) to afford first the title compound (8.1 g, 20percent), mp 40-42° C., then the undesired isomer, 3-bromo-4-nitrophenol, as a yellow solid (12.7 g, 31percent). mp 125-127° C.3-bromo-4-nitrophenol and 3-bromo-6-nitrophenol. 3.8 ml of fuming nitric acid (89 mmole) in 12 ml glacial acetic acid was added over 35 minutes to a solution of 15.2 grams (87.9 mmole) of 3- bromophenol in 60 ml of glacial acetic acid in a flask with a surrounding ice bath. The reaction was stirred at room temperature for an additional 30 minutes and the reaction was then poured on ice. This was then concentrated in vacuo. Medium pressure chromatography on silica gel (1: 2 ethyl acetate: hexanes as eluent) allowed separation of products 3-bromo-4-nitrophenol (3.47 grams, 15.9 mmole, 18percent yield); m. p. 130-131C following recrystallization from ether/hexanes (reported m. p. 130- 131C (Wright, C et al., 1987) and 131 C (Hodgson, HH et al., 1926);'H NMR (DMSO-d6, 500 MHz) 8 7.99 (d, 1H, J= 9 Hz), 7.18 (d, 1H, J= 3 Hz), 6.91 (dd, 1H, J= 9, 3 Hz, ); and 3-bromo-6-nitrophenol (1.94 grams, 8.90 mmole, 10percent yield, following recrystallization from ether/hexanes); m. p. 41.5-42. 5C (reported m. p. 42-45 C (Hanzlik, RP et al., 1990) and 42 C (Hodson et al., ) ;'H NMR (CDCl3, 500 MHz) 8 10.60 (s, 1H), 7.95 (d, 1H, J= 9 Hz), 7.35 (d, 1H, J= 2 Hz), 7.11 (dd, 1H, J= 9, 2 Hz, ) ; 13C NMR (CDCl3 ; assignments aided by HMQC) 8 122.9 (C-2), 123.8 (C-4), 126.0 (C-5), 132.2 (C-3), 132.7 (C-6), 155.2 (C-1) ; IR (KBr) 3450 (broad), 1612, 1578, 1527, 1475, 1311, 1235, 1186, 900 cm'').4-(Benzyloxy)-2-bromo-1-nitrobenzene (Compound 15) Compound 4 (930 mg, 4.29 mmol) was dissolved in DMF (40 mL), then K2CO3 (890 mg, 6.44 mmol) was added. The reaction mixture was stirred at room temperature for 20 min, at which point benzyl bromide (407 muL, 3.43 mmol) was added. After stirring overnight at room temperature, the reaction was quenched by adding H2O (100 mL), and partitioned with Et2O (200 mL). The organic layer was washed with H2O (3*50 mL) and brine (50 mL). The organic layer was collected, dried over anhydrous Na2SO4, filtered, concentrated, and purified by silica column chromatography (15percent EtOAc in hexanes) to afford compound 15 in 99.5percent (1.05 g) yield as a brown solid. 1H-NMR (CDCl3, 400 MHz) delta 7.99 (1H, d, J=8.4 Hz, Ar), 7.41 (5H, m, Ar), 7.31 (1H, s, Ar), 6.99 (1H, d, J=8.4 Hz, Ar), 5.13 (2H, s, OCH2); 13C-NMR (CDCl3, 100 MHz) delta 161.7, 142.5, 134.9, 128.8, 128.6, 127.9, 127.5, 121.0, 116.8, 114.1, 70.9; MS (ESI) m/z Calcd for C13H10BrNO3 (M+): 307.0, Found: 308.1 (M+H+).

Molecular Weight:218.00
XLogP3:1.9
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:3
Exact Mass:216.93746
Monoisotopic Mass:216.93746
Topological Polar Surface Area:66
Heavy Atom Count:11
Complexity:158
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes