4-bromo-2-prop-2-enylphenol

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

Procedure: A solution of 4-bromophenol (1 mol) in tetrahydrofuran (500 mL) was added to a slurry of sodium hydride (1.17 mol) in dimethylformamide (1.2 L) at 25° C. After complete reaction allylchloride (1.32 mol) was added and after stirring for a further 3 h at 45° the product was isolated with water and hexane. Distillation gave allyl-(4-bromophenyl(ether. bp. 65°-67° at 0.1 mm (82%). This material was heated at 195° with dimethylanaline for 4 hours and then distilled to yield 2-allyl-4-bromophenol (0.81 mol). A solution of this material (0.81 mol) in tetrahydrofuran (200 mL) was added to a mixture of 1-bromononane (0.8 mol). sodium hydride (0.92 mol) potassium iodide (1 g) in dimethylformamide (1 L) at 25° C. After hydrogen evaluation was complete the mixture was heated at 50° for 14 h. cooled, added to an excess of water and extracted with hexane. Distillation furnished nonyl-(2-allyl-4-bromophenyl)ether (256 g): b.p. 147°-156° at 0.1 mm. This material (255 g) in dimethylsulfoxide (1 L) and tetrahydrofuran (0.5 L) was heated at 35°-40° with potassium tert. butoxide (2 g) for 2 h and then quenched with acetic acid (5 mL) and water. Isolation of the reaction products with hexane yielded pure 1-[2-(nonyloxy)-5-(bromo)phenyl]propene (234 g): b.p. 145°-155° at 0.1 mm. A solution of the above material (0.56 mol) in tetrahydrofuran (600 mL) was converted to the Grignard reagent with magnesium (1 mol) at 55° C. for 3 h. After complete reaction the mixture was cooled to 0° C. and treated with trimethylborate (0.75 mol) in ether (200 mL). After stirring for a further 30 min. at 25° C. the mixture was cooled to 0° and exposed to a mixture of ammonium chloride (10%) and hydrogen peroxide (10%, 500 mL) and stirred for a further 1 h at 25° C. Addition of water and hexane gave the crude material after removal of the hexane in vacuo. The crude product was passed through a plug of silica gel to yield para [2-(1-propenyl-4-(nonyloxy)phenyl]phenol (73 g). Acetylation of this material (0.8 g) with acetylchloride and triethylamine in dichloromethane gave the [2-(1-propenyl)-4-(nonyloxy)-1-(acetoxy)]benzene (89%). This material (99 g) was dissolved in a mixture of methanol (150 mL) and dichloromethane (1.5 L) and treated with ozone at -40° C. until all the starting material had been consumed. Dimethylsulfide (50 mL) and water 500 mL) were then added and after vigorous stirring for 30 min. at 25° the organic phase was dried (MgSO4 and concentrated to yield [2-(nonyloxy)-5-(acetoxy)]benzaldehyde (83 g). Reduction of this material (80 g) with sodium borohydride (6 g) in ethanol (1 L) at 20° C. for 2 h gave the crude [2-(nonyloxy)-5-(acetoxy)]benzenemethanol which was immediately exposed to aqueous potassium hydroxide (300 mL, 40%) in ethanol (1 L) for 30 min at 60° C. Acidification with aqueous acid (6 Molar hydrogen chloride) and extraction with chloroform yielded the crude product on concentration. Digestion of the residue with hexane gave pure [3-(hydroxymethyl)-4-(nonyloxy)]phenol (63 g) as a solid. A solution of this material (62 g) in a mixture of acetonitrile (0.5 L) and trihenylphosphine hydrobromide (86 g) was heated at reflux for 14 h and concentrated to dryness at 50° to yield [[2-(nonyloxy)-5(hydroxy)phenyl]methyl]triphenylphosphonium bromide as a glass. was added Distillation gave allyl-(4-bromophenyl(ether This material was heated at 195° with dimethylanaline for 4 hours distilled

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

Procedure: Ethyl bromoacetate (1.68 g) was added to a stirred suspension of 2-allyl-4-bromophenol (2.13 g) and potassium carbonate (1.50 g) in butan-2-one (15 ml). The mixture was heated at reflux for 16 hours. The reaction mixture was cooled to ambient temperature and filtered. Water (100 ml) was added to the filtrate and the aqueous phase was extracted with ethyl acetate (3×50 ml). The ethyl acetate extracts were combined, washed with brine (2×25 ml), dried (MgSO4) and evaporated to give a solid which crystallised from hexane to give ethyl 2-allyl-4-bromophenoxyacetate (2.10 g), mp 70.5° C.; microanalysis, found: C, 52.0; H, 5.10%; C13H15BrO3 requires: C, 52.2; H, 5.05%; NMR (CDCl3) 1.29 (3H, t), 3.42 (2H, d), 4.25 (2H, q), 4.58 (2H, s), 5.07-5.17 (2H, m), 5.88-6.18 (1H, m), 6.60 (1H, d) and 7.20-7.27 (2H, m); m/z 300 (M+H). The mixture was heated at reflux for 16 hours filtered Water (100 ml) was added to the filtrate the aqueous phase was extracted with ethyl acetate (3×50 ml) washed with brine (2×25 ml) dried (MgSO4) evaporated to give a solid which crystallised from hexane

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

Procedure: A solution of 4-bromophenol (1 mol) in tetrahydrofuran (500 mL) was added to a slurry of sodium hydride (1.17 mol) in dimethylformamide (1.2 L) at 25° C. After complete reaction allylchloride (1.32 mol) was added and after stirring for a further 3 h at 45° the product was isolated with water and hexane. Distillation gave allyl-(4-bromophenyl(ether. bp. 65°-67° at 0.1 mm (82%). This material was heated at 195° with dimethylanaline for 4 hours and then distilled to yield 2-allyl-4-bromophenol (0.81 mol). A solution of this material (0.81 mol) in tetrahydrofuran (200 mL) was added to a mixture of 1-bromononane (0.8 mol). sodium hydride (0.92 mol) potassium iodide (1 g) in dimethylformamide (1 L) at 25° C. After hydrogen evaluation was complete the mixture was heated at 50° for 14 h. cooled, added to an excess of water and extracted with hexane. Distillation furnished nonyl-(2-allyl-4-bromophenyl)ether (256 g): b.p. 147°-156° at 0.1 mm. This material (255 g) in dimethylsulfoxide (1 L) and tetrahydrofuran (0.5 L) was heated at 35°-40° with potassium tert. butoxide (2 g) for 2 h and then quenched with acetic acid (5 mL) and water. Isolation of the reaction products with hexane yielded pure 1-[2-(nonyloxy)-5-(bromo)phenyl]propene (234 g): b.p. 145°-155° at 0.1 mm. A solution of the above material (0.56 mol) in tetrahydrofuran (600 mL) was converted to the Grignard reagent with magnesium (1 mol) at 55° C. for 3 h. After complete reaction the mixture was cooled to 0° C. and treated with trimethylborate (0.75 mol) in ether (200 mL). After stirring for a further 30 min. at 25° C. the mixture was cooled to 0° and exposed to a mixture of ammonium chloride (10%) and hydrogen peroxide (10%, 500 mL) and stirred for a further 1 h at 25° C. Addition of water and hexane gave the crude material after removal of the hexane in vacuo. The crude product was passed through a plug of silica gel to yield para [2-(1-propenyl-4-(nonyloxy)phenyl]phenol (73 g). Acetylation of this material (0.8 g) with acetylchloride and triethylamine in dichloromethane gave the [2-(1-propenyl)-4-(nonyloxy)-1-(acetoxy)]benzene (89%). This material (99 g) was dissolved in a mixture of methanol (150 mL) and dichloromethane (1.5 L) and treated with ozone at -40° C. until all the starting material had been consumed. Dimethylsulfide (50 mL) and water 500 mL) were then added and after vigorous stirring for 30 min. at 25° the organic phase was dried (MgSO4 and concentrated to yield [2-(nonyloxy)-5-(acetoxy)]benzaldehyde (83 g). Reduction of this material (80 g) with sodium borohydride (6 g) in ethanol (1 L) at 20° C. for 2 h gave the crude [2-(nonyloxy)-5-(acetoxy)]benzenemethanol which was immediately exposed to aqueous potassium hydroxide (300 mL, 40%) in ethanol (1 L) for 30 min at 60° C. Acidification with aqueous acid (6 Molar hydrogen chloride) and extraction with chloroform yielded the crude product on concentration. Digestion of the residue with hexane gave pure [3-(hydroxymethyl)-4-(nonyloxy)]phenol (63 g) as a solid. A solution of this material (62 g) in a mixture of acetonitrile (0.5 L) and trihenylphosphine hydrobromide (86 g) was heated at reflux for 14 h and concentrated to dryness at 50° to yield [[2-(nonyloxy)-5(hydroxy)phenyl]methyl]triphenylphosphonium bromide as a glass. was added Distillation gave allyl-(4-bromophenyl(ether This material was heated at 195° with dimethylanaline for 4 hours distilled

Conditions: temp:2.51; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 21.3 g (100 mmol) of 2-allyl-4-bromophenol, 12.1 g (120 mmol) of triethylamine (hereinafter referred to as “TEA”), and 120 ml of distilled tetra hydrofuran (hereinafter referred to as “THF”) were loaded into a 300-ml four-necked flask equipped with a reflux pipe with a calcium chloride dry pipe, a dropping funnel, a nitrogen gas introducing pipe, and a mechanical stirring device. The mixture was placed under nitrogen, and was stirred at 0 to 5° C. During the stirring, 11.0 g (120 mmol) of chlorotrimethylsilane were slowly added to the mixture from the dropping funnel. After the completion of the dropping, the resultant was subjected to a reaction at the temperature for 1 hour and then at room temperature for 6 hours. After that, the solvent, excessive trimethylamine, and excessive chlorotrimethylsilane were removed by condensation under reduced pressure, and the residue was washed with water and dried. Thus, 2-allyl-4-bromo-1-trimethylsiloxybenzene was quantitatively obtained. were loaded into a 300-ml four-necked flask dry pipe, a dropping funnel a nitrogen gas introducing pipe After the completion of the dropping, the resultant was subjected to a reaction at the temperature for 1 hour After that, the solvent, excessive trimethylamine, and excessive chlorotrimethylsilane were removed by condensation under reduced pressure the residue was washed with water dried

Conditions: temp:2.51; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 21.3 g (100 mmol) of 2-allyl-4-bromophenol, 12.1 g (120 mmol) of triethylamine (hereinafter referred to as “TEA”), and 120 ml of distilled tetra hydrofuran (hereinafter referred to as “THF”) were loaded into a 300-ml four-necked flask equipped with a reflux pipe with a calcium chloride dry pipe, a dropping funnel, a nitrogen gas introducing pipe, and a mechanical stirring device. The mixture was placed under nitrogen, and was stirred at 0 to 5° C. During the stirring, 11.0 g (120 mmol) of chlorotrimethylsilane were slowly added to the mixture from the dropping funnel. After the completion of the dropping, the resultant was subjected to a reaction at the temperature for 1 hour and then at room temperature for 6 hours. After that, the solvent, excessive trimethylamine, and excessive chlorotrimethylsilane were removed by condensation under reduced pressure, and the residue was washed with water and dried. Thus, 2-allyl-4-bromo-1-trimethylsiloxybenzene was quantitatively obtained. were loaded into a 300-ml four-necked flask dry pipe, a dropping funnel a nitrogen gas introducing pipe After the completion of the dropping, the resultant was subjected to a reaction at the temperature for 1 hour After that, the solvent, excessive trimethylamine, and excessive chlorotrimethylsilane were removed by condensation under reduced pressure the residue was washed with water dried

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

Procedure: Under an atmosphere replaced with argon, 2-allyl-4-bromophenol (compound 3), potassium carbonate and benzyloxy-benzylchloride (BnBr) were dissolved in dimethylformamide (DMF), and stirred at room temperature for 3 hours. After confirming that the starting materials were disappeared using thin-layer chromatography (TLC) (with a developer of n-hexane:ethyl acetate=4:1), the reaction liquid was subjected to extraction using 20 mL of water and 20 mL of ethyl acetate. The organic phase was washed with 20 mL of water twice, dried using magnesium sulfate, and then subjected to filtration. The filtrate was concentrated under reduced pressure using an evaporator. The resultant residue was subjected to purification using silica gel flash chromatography (silica gel flash c.c.) (with a developer of n-hexane:ethyl acetate×4:1), to thereby obtain 2-allyl-1-(4-benzyloxy-benzyloxy)-4-bromobenzene (compound 4) as light brown solid. was subjected to extraction The organic phase was washed with 20 mL of water twice dried subjected to filtration The filtrate was concentrated under reduced pressure an evaporator The resultant residue was subjected to purification

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

Procedure: Ethyl bromoacetate (1.68 g) was added to a stirred suspension of 2-allyl-4-bromophenol (2.13 g) and potassium carbonate (1.50 g) in butan-2-one (15 ml). The mixture was heated at reflux for 16 hours. The reaction mixture was cooled to ambient temperature and filtered. Water (100 ml) was added to the filtrate and the aqueous phase was extracted with ethyl acetate (3×50 ml). The ethyl acetate extracts were combined, washed with brine (2×25 ml), dried (MgSO4) and evaporated to give a solid which crystallised from hexane to give ethyl 2-allyl-4-bromophenoxyacetate (2.10 g), mp 70.5° C.; microanalysis, found: C, 52.0; H, 5.10%; C13H15BrO3 requires: C, 52.2; H, 5.05%; NMR (CDCl3) 1.29 (3H, t), 3.42 (2H, d), 4.25 (2H, q), 4.58 (2H, s), 5.07-5.17 (2H, m), 5.88-6.18 (1H, m), 6.60 (1H, d) and 7.20-7.27 (2H, m); m/z 300 (M+H). The mixture was heated at reflux for 16 hours filtered Water (100 ml) was added to the filtrate the aqueous phase was extracted with ethyl acetate (3×50 ml) washed with brine (2×25 ml) dried (MgSO4) evaporated to give a solid which crystallised from hexane

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

Procedure: A solution of 4-bromophenol (1 mol) in tetrahydrofuran (500 mL) was added to a slurry of sodium hydride (1.17 mol) in dimethylformamide (1.2 L) at 25° C. After complete reaction allylchloride (1.32 mol) was added and after stirring for a further 3 h at 45° the product was isolated with water and hexane. Distillation gave allyl-(4-bromophenyl(ether. bp. 65°-67° at 0.1 mm (82%). This material was heated at 195° with dimethylanaline for 4 hours and then distilled to yield 2-allyl-4-bromophenol (0.81 mol). A solution of this material (0.81 mol) in tetrahydrofuran (200 mL) was added to a mixture of 1-bromononane (0.8 mol). sodium hydride (0.92 mol) potassium iodide (1 g) in dimethylformamide (1 L) at 25° C. After hydrogen evaluation was complete the mixture was heated at 50° for 14 h. cooled, added to an excess of water and extracted with hexane. Distillation furnished nonyl-(2-allyl-4-bromophenyl)ether (256 g): b.p. 147°-156° at 0.1 mm. This material (255 g) in dimethylsulfoxide (1 L) and tetrahydrofuran (0.5 L) was heated at 35°-40° with potassium tert. butoxide (2 g) for 2 h and then quenched with acetic acid (5 mL) and water. Isolation of the reaction products with hexane yielded pure 1-[2-(nonyloxy)-5-(bromo)phenyl]propene (234 g): b.p. 145°-155° at 0.1 mm. A solution of the above material (0.56 mol) in tetrahydrofuran (600 mL) was converted to the Grignard reagent with magnesium (1 mol) at 55° C. for 3 h. After complete reaction the mixture was cooled to 0° C. and treated with trimethylborate (0.75 mol) in ether (200 mL). After stirring for a further 30 min. at 25° C. the mixture was cooled to 0° and exposed to a mixture of ammonium chloride (10%) and hydrogen peroxide (10%, 500 mL) and stirred for a further 1 h at 25° C. Addition of water and hexane gave the crude material after removal of the hexane in vacuo. The crude product was passed through a plug of silica gel to yield para [2-(1-propenyl-4-(nonyloxy)phenyl]phenol (73 g). Acetylation of this material (0.8 g) with acetylchloride and triethylamine in dichloromethane gave the [2-(1-propenyl)-4-(nonyloxy)-1-(acetoxy)]benzene (89%). This material (99 g) was dissolved in a mixture of methanol (150 mL) and dichloromethane (1.5 L) and treated with ozone at -40° C. until all the starting material had been consumed. Dimethylsulfide (50 mL) and water 500 mL) were then added and after vigorous stirring for 30 min. at 25° the organic phase was dried (MgSO4 and concentrated to yield [2-(nonyloxy)-5-(acetoxy)]benzaldehyde (83 g). Reduction of this material (80 g) with sodium borohydride (6 g) in ethanol (1 L) at 20° C. for 2 h gave the crude [2-(nonyloxy)-5-(acetoxy)]benzenemethanol which was immediately exposed to aqueous potassium hydroxide (300 mL, 40%) in ethanol (1 L) for 30 min at 60° C. Acidification with aqueous acid (6 Molar hydrogen chloride) and extraction with chloroform yielded the crude product on concentration. Digestion of the residue with hexane gave pure [3-(hydroxymethyl)-4-(nonyloxy)]phenol (63 g) as a solid. A solution of this material (62 g) in a mixture of acetonitrile (0.5 L) and trihenylphosphine hydrobromide (86 g) was heated at reflux for 14 h and concentrated to dryness at 50° to yield [[2-(nonyloxy)-5(hydroxy)phenyl]methyl]triphenylphosphonium bromide as a glass. was added Distillation gave allyl-(4-bromophenyl(ether This material was heated at 195° with dimethylanaline for 4 hours distilled

Conditions: temp:2.51; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 21.3 g (100 mmol) of 2-allyl-4-bromophenol, 12.1 g (120 mmol) of triethylamine (hereinafter referred to as “TEA”), and 120 ml of distilled tetra hydrofuran (hereinafter referred to as “THF”) were loaded into a 300-ml four-necked flask equipped with a reflux pipe with a calcium chloride dry pipe, a dropping funnel, a nitrogen gas introducing pipe, and a mechanical stirring device. The mixture was placed under nitrogen, and was stirred at 0 to 5° C. During the stirring, 11.0 g (120 mmol) of chlorotrimethylsilane were slowly added to the mixture from the dropping funnel. After the completion of the dropping, the resultant was subjected to a reaction at the temperature for 1 hour and then at room temperature for 6 hours. After that, the solvent, excessive trimethylamine, and excessive chlorotrimethylsilane were removed by condensation under reduced pressure, and the residue was washed with water and dried. Thus, 2-allyl-4-bromo-1-trimethylsiloxybenzene was quantitatively obtained. were loaded into a 300-ml four-necked flask dry pipe, a dropping funnel a nitrogen gas introducing pipe After the completion of the dropping, the resultant was subjected to a reaction at the temperature for 1 hour After that, the solvent, excessive trimethylamine, and excessive chlorotrimethylsilane were removed by condensation under reduced pressure the residue was washed with water dried