2-Bromo-7-hydroxynaphthalene

White powder

A synthetic procedure was based on the literature method [12]. To a vigorously stirred mixture of triphenylphosphine (31.5g, 120mmol) in acetonitrile (50.0mL), bromine (19.2g, 120mmol) was added dropwise at 0°C. The reaction mixture was allowed to reach room temperature, and 2, 7-dihydroxynaphthalene 1 (16.0g, 100mmol) was added in one portion. The mixture was heated to 70°C for 30min, after which the solvent was removed by rotary evaporation. The flask was equipped with a gas trap, and the black residue was heated to 250°C for 1h. After cooling to room temperature, the mixture was dissolved in 200mL of dichloromethane and the viscous liquid was obtained after column chromatography (silica gel, petroleum ether/dichloromethane 1:1). The crude product was purified by column chromatography (silica gel, petroleum ether/dichloromethane 3:2) to give the compound 2 (18.8g, 84.3mmol, 84percent) as a beige powder. To a stirring suspension of Triphenyl phosphine (31.5 g) in Acetonitrile (50 mL) in a 250 mL10 Schlenk-flaskwas added carefully Bromine (6.2 mL) at 0 00 with a syringe over 30 mm. The yellow solution was warmed to room temperature and 2, 7-Dihydroxynaphthalene (16 g) was added in one portion. The reaction was refluxed at 70 00 for one hour. After cooling to room temperature, the solvent was removed under reduced pressure. The reaction flask was connected to a gas-washing bottle filled with a concentrated sodium hydroxide solution. The flask was heatedto 250 00 for two hours and the black residue dissolved in 100 mL Dichloromethane and purified via column chromatography (DCM:Pentan 1:1 to pure DCM). Product 101 was received as a beige powder (14.7 g, 66percent)DC: Dichloromethane:Pentane, 1:1, R=0, 21H-NMR: (300 MHz, ODd3) = 7.76 (d, 1 H), 7.63 (d, 1 H), 7.54 (d, 1 H), 7.32 (dd, 1 H), 7.03 (dd, 1H), 6.98 (d, 1H), 4.98 (b, 1H)Preparation 2 [0100] Preparation of 2-Bromo-7-methoxy-naphthalene. [CHEMMOL-00021] [0101] Preparation of 7-Bromo-2-naphthalenol. [0102] Triphenyl phosphine (89.7 g, 0.342 mol) and acetonitrile (350 mL) were combined in a 1-L flask under N2 atmosphere. The mixture was cooled to 10° C. Bromine (17.6 mL, 0.342 mol) was added dropwise over 10 minutes. The cooling bath was removed and 2, 7-dihydroxynaphthalene (50.0 g, 0.312 mol) was added along with 350 mL of CH3CN rinse. The resulting yellow tan mixture was heated at reflux for 3 hours. Acetonitrile was distilled off under a water aspirator pressure over 2 hours, resulting in a grayish white solid. The solid was heated to 280° C. over 30 minutes giving a black liquid. The liquid was heated to 310° C. over 20 minutes and the temperature was maintained at 310° C. for an additional 15 minutes until gas evolution ceased. The black mixture was cooled to room temperature. Chromatography yielded 34.5 g of the intermediate title compound as an off-white solid which was 87percent pure by HPLC (43percent yield).Triphenyl phosphine (89.7 g, 0.342 mol) and acetonitrile (350 mL) were combined in a 1-L flask under N2 atmosphere. The mixture was cooled to 10° C. Bromine (17.6 mL, 0.342 mol) was added dropwise over 10 minutes. The cooling bath was removed and 2, 7-dihydroxynaphthalene (50.0 g, 0.312 mol) was added along with 350 mL of CH3CN rinse. The resulting yellow tan mixture was heated at reflux for 3 hours. Acetonitrile was distilled off using a water aspirator over 2 hours resulting in a grayish white solid. The solid was heated to 280° C. over 30 minutes giving a black liquid. The liquid was heated to 310° C. over 20 minutes and the temperature was maintained at 310° C. for an additional 15 minutes until gas evolution ceased. The black mixture was cooled to room temperature. Chromatography yielded 34.5 g of the intermediate title compound as an off-white solid which was 87percent pure by HPLC (43percent yield).Triphenyl phosphine (89.7 g, 0.342 mol) and acetonitrile (350 mL) were combined in a 1-L flask under N2 atmosphere. The mixture was cooled to 10 C. Bromine (17.6 mL, 0.342 mol) was added dropwise over 10 minutes. The cooling bath was removed and 2, 7-dihydroxynaphthalene (50.0 g, 0.312 mol) was added along with 350 mL of CH3CN rinse. The resulting yellow tan mixture was heated at reflux for 3 hours. Acetonitrile was distilled off using a water aspirator over 2 hours resulting in a grayish white solid. The solid was heated to 280 C. over 30 minutes giving a black liquid. The liquid was heated to 310 C. over 20 minutes and the temperature was maintained at 310 C. for an additional 15 minutes until gas evolution ceased. The black mixture was cooled to room temperature. Chromatography yielded 34.5 g of the intermediate title compound as an off-white solid which was 87percent pure by HPLC (43percent yield).  Triphenylphosphine (500 mg, 2.9 mmol) was dissolved in MeCN (5 mL), and bromine (0.15 mL, 2.9 mmol) was added at 0 °C whilst stirring. The solution was allowed to warm up to rt, and 7-methoxy-naphthalen-2-ol, 44 (490 mg, 2.8 mmol) was added portionwise. The solution was refluxed for 2 h, and the solvent removed in vacuo. The residue was heated to 250 °C in a sealed tube overnight. After cooling to rt, the residue was purified by chromatography using a stepped gradient of 10–20percent EtOAc in heptane to yield 45 as a beige solid. Yield: 120 mg (19percent).

Molecular Weight:223.07
XLogP3:3.4
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:1
Exact Mass:221.96803
Monoisotopic Mass:221.96803
Topological Polar Surface Area:20.2
Heavy Atom Count:12
Complexity:160
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes