2,6-dibromophenol

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 2,6-Dibromophenol (14.5 g, 0.058 mole) was treated with sodium methoxide (from 10.3 g sodium, 0.45 g atom) in methanol (100 ml) and dimethylformamide (100 ml) in the presence of cuprous iodide (2 g) in the same way as described in detail for 2,6-dibromo-4-t-butylphenol in Example 9. The crude yield of title product was 5.4 g (60%), m.p. 53°-6° C. (literature gives 55°-6° C.). The lower yield may be explained by incomplete extraction, 2,6-dimethoxyphenol being to some extent water soluble.

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 4-Acetamido-2,6-dibromophenol (used as starting material in Example 54) was prepared from 2,6-dibromophenol and acetic anhydride, using the method described above for the preparation of 4-acetamido-2,6-dichlorophenol, as a solid, m.p. 155°-156° C.

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In 5 ml of acetic anhydride was dissolved 5.0 g of 2,6-dibromophenol and, one drop of conc. sulfuric acid was added to the solution. While sometimes manually shaking, the mixture was stirred. When generation of heat stopped, the solution was poured onto 50 ml of ice water and the precipitated crystals of acetic acid-2,6-dibromophenyl were taken by filtration. The crystals were washed with chilled water and dried under reduced pressure. Next, this acetic acid-2,6-dibromophenyl was dissolved in 20 ml of nitrobenzene and 4.0 g of powdery aluminum chloride was gradually added to the solution. The reaction was carried out at 60° to 70° C. for 50 hours to effect Fries rearrangement. After completion of the reaction, the reaction solution was poured onto 100 ml of cold dil. hydrochloric acid. After allowing to stand at 5° C. overnight, the precipitated crystals were taken out by filtration, washed with n-hexane and dried under reduced pressure to give 3.87 g of 2,6-dibromo-4-acetylphenol as crude crystals. The crystals were recrystallized from hot ethyl acetate to give 2.42 g of pure 2,6-dibromo-4-acetylphenol as light brown crystals. 2,6-Dibromo-4-acetylphenol (3,5-dibromo-4-hydroxyacetophenone): C8H6Br2O2 was added to the solution the mixture was stirred When generation of heat the precipitated crystals of acetic acid-2,6-dibromophenyl were taken by filtration The crystals were washed with chilled water dried under reduced pressure Next, this acetic acid-2,6-dibromophenyl was dissolved in 20 ml of nitrobenzene 4.0 g of powdery aluminum chloride was gradually added to the solution After completion of the reaction to stand at 5° C. overnight the precipitated crystals were taken out by filtration washed with n-hexane dried under reduced pressure

Conditions: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A flame-dried 500 mL flask was charged with 2,6-dibromophenol (1.20 g, 4.76 mmol), tungsten oxychloride (0.813 g, 2.38 mmol), and anhydrous toluene (25 mL). The resulting suspension was heated at reflux under nitrogen for 1 h, and then the solvent was evaporated in vacuo. The solid residue was broken up with a spatula and dried in vacuo for 30 min. To the residue were added toluene (160 mL), Et4Pb (1.54 g, 4.76 mL), and 702 (22 g, 131.0 mmol). The mixture was heated at 90° C. under nitrogen for 1.5 h. After being cooled to r.t., the mixture was filtered through a celite, and the celite was rinsed with t-BuOMe. The combined filtrates were washed with 1% NaOH soln, water, and brine, and concentrated by evaporation at reduced pressure. The residue was distilled (37-38° C./1 Torr) to give 13.06 g (71%) of 703 as a colorless liquid. 1H NMR (400 MHz, CDCl3) δ 5.67 (s, 2H, CH═CH), 4.14 (q, 2H, J=7.2 Hz, OCH2), 3.11 (pentuplet, J=7.6 Hz, 1H, CH), 2.65 (d, J=7.6 Hz, 4H, 2 CH2), 1.27 (t, J=7.2 Hz, 3 H, CH3). The resulting suspension was heated at reflux under nitrogen for 1 h the solvent was evaporated in vacuo dried in vacuo for 30 min After being cooled to r.t. the mixture was filtered through a celite the celite was rinsed with t-BuOMe The combined filtrates were washed with 1% NaOH soln water, and brine, and concentrated by evaporation at reduced pressure The residue was distilled (37-38° C./1 Torr)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 2,6-dibromophenol (25 g, 0.099 mol), powder potassium carbonate (28 g, 0.2 mol, 2 equiv) and dimethyl sulfate (12.6 g, 0.099 mol) in acetonitrile (400 mL) was kept at reflux with good stirring for 4 hr. After cooling, the solids were removed by filtration and the solvent was removed in a rotary evaporator. The residue was taken in 2:1 heptane/ethyl acetate mixture (800 mL) and washed with water (2×400 mL). The organic layer was dried over sodium sulfate, filtered and the solvent was removed in a rotary evaporator, leaving almost pure 1 (15.5 g, 96%). at reflux After cooling the solids were removed by filtration the solvent was removed in a rotary evaporator washed with water (2×400 mL) The organic layer was dried over sodium sulfate filtered the solvent was removed in a rotary evaporator

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 2,6-dibromophenol (25 g, 0.099 mol), powder potassium carbonate (28 g, 0.2 mol, 2 equiv) and dimethyl sulfate (12.6 g, 0.099 mol) in acetonitrile (400 mL) was kept at reflux with good stirring for 4 hr. After cooling, the solids were removed by filtration and the solvent was removed in a rotary evaporator. The residue was taken in 2:1 heptane/ethyl acetate mixture (800 mL) and washed with water (2×400 mL). The organic layer was dried over sodium sulfate, filtered and the solvent was removed in a rotary evaporator, leaving almost pure 1 (15.5 g, 96%). at reflux After cooling the solids were removed by filtration the solvent was removed in a rotary evaporator washed with water (2×400 mL) The organic layer was dried over sodium sulfate filtered the solvent was removed in a rotary evaporator

Conditions: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A flame-dried 500 mL flask was charged with 2,6-dibromophenol (1.20 g, 4.76 mmol), tungsten oxychloride (0.813 g, 2.38 mmol), and anhydrous toluene (25 mL). The resulting suspension was heated at reflux under nitrogen for 1 h, and then the solvent was evaporated in vacuo. The solid residue was broken up with a spatula and dried in vacuo for 30 min. To the residue were added toluene (160 mL), Et4Pb (1.54 g, 4.76 mL), and 702 (22 g, 131.0 mmol). The mixture was heated at 90° C. under nitrogen for 1.5 h. After being cooled to r.t., the mixture was filtered through a celite, and the celite was rinsed with t-BuOMe. The combined filtrates were washed with 1% NaOH soln, water, and brine, and concentrated by evaporation at reduced pressure. The residue was distilled (37-38° C./1 Torr) to give 13-06 g (71%) of 703 as a colorless liquid. 1H NMR (400 MHz, CDCl3) δ 5.67 (s, 2H, CH═CH), 4.14 (q, 2H, J=7.2 Hz, OCH2), 3.11 (pentuplet, J=7.6 Hz, 1H, CH), 2.65 (d, J=7.6 Hz, 4H, 2 CH2), 1.27 (t, J=7.2 Hz, 3H, CH3). The resulting suspension was heated at reflux under nitrogen for 1 h the solvent was evaporated in vacuo dried in vacuo for 30 min After being cooled to r.t. the mixture was filtered through a celite the celite was rinsed with t-BuOMe The combined filtrates were washed with 1% NaOH soln water, and brine, and concentrated by evaporation at reduced pressure The residue was distilled (37-38° C./1 Torr)