5-bromo-2-ethylaniline

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a stirred mixture of 5-bromo-2-ethylaniline (3.39 g, 200 mmol) in distilled water (110 ml) is added concentrated sulfuric acid (5.60 ml), followed by brief heating at reflux until dissolution. The mixture is allowed to cool to room temperature, producing a fine precipitate, then further cooled to approximately 0° C. in an ice/salt bath. To this slurry is added an aqueous solution of sodium nitrite (1.17 g, 16.94 mmol) in distilled water (10 ml) dropwise over 15 minutes, maintaining a temperature below 5° C., followed by additional stirring for 30 minutes. The reaction mixture is next filtered then added to a second solution of aqueous potassium iodide (8.44 g, 50.83 mmol) in distilled water (45 ml) dropwise at room temperature. After the addition is complete the solution is briefly heated to 80° C. then allowed to cool to room temperature again. The reaction mixture is extracted with ethyl acetate (3×50 ml), and the organic phase is washed with 1M aqueous hydrochloric acid (30 ml) and aqueous sodium thiosulfate (2×30 ml). After drying over anhydrous magnesium sulfate and concentration in vacuo 4-bromo-1-ethyl-2-iodobenzene (4.90 g) is furnished as an orange liquid. by brief heating at reflux until dissolution producing a fine precipitate further cooled to approximately 0° C. in an ice/salt bath maintaining a temperature below 5° C. The reaction mixture is next filtered After the addition is briefly heated to 80° C. to cool to room temperature again The reaction mixture is extracted with ethyl acetate (3×50 ml) the organic phase is washed with 1M aqueous hydrochloric acid (30 ml) and aqueous sodium thiosulfate (2×30 ml) After drying over anhydrous magnesium sulfate and concentration in vacuo 4-bromo-1-ethyl-2-iodobenzene (4.90 g) is furnished as an orange liquid

反応条件: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 2-ethyl-5-bromo nitrobenzene (9.71 g, 230 mmol) in ethanol (125 ml) is added tin(II) chloride dihydrate (35.72 g, 225.71 mmol), followed by heating at 70° C. for 2 hours. After cooling to room temperature the solution is poured into crushed ice (1 liter) then diluted with ethyl acetate (200 ml). Solid sodium carbonate is cautiously added until pH 7 is achieved, at which stage the viscous mixture is filtered through diatomaceous earth (further washing with ethyl acetate/aqueous sodium carbonate) and the phases separated. After additional extraction of the aqueous phase, all organic phases are combined, dried over anhydrous magnesium sulfate then concentrated in vacuo. The crude oil is purified by flash column chromatography on silica gel (hexane/ethyl acetate 8:2 ratio) to afford 5-bromo-2-ethylaniline (7.89 g) as a brown oil. After cooling to room temperature the solution is poured is filtered through diatomaceous earth ( further washing with ethyl acetate/aqueous sodium carbonate) and the phases separated After additional extraction of the aqueous phase dried over anhydrous magnesium sulfate then concentrated in vacuo The crude oil is purified by flash column chromatography on silica gel (hexane/ethyl acetate 8:2 ratio)

反応条件: temp:20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 4-Chlorophenylboronic acid (13.2 g, 0.08 mol) and tetrakis(triphenylphosphine) palladium (0) (2.4 g, 0.002 mol) are added to a solution of 5-bromo-2-ethylaniline (14.1 g, 0.07 mol) in 1,2-dimethoxyethane (140 ml). After stirring the reaction mixture for 15 minutes at 20° C., a solution of 20% aqueous sodium carbonate (300 ml) is added to the mixture, and the resulting mixture is refluxed for 24 hours. The reaction mixture is cooled to room temperature, diluted with water and extracted using ethyl acetate. The combined organic extracts are dried over anhydrous sodium sulfate, filtered and the filtrate evaporated in vacuo. The residue is further purified by column chromatography on silica gel, eluting with 5% ethyl acetate in hexane to give 5-(4-chlorophenyl)-2-ethylaniline (14.3 g). the resulting mixture is refluxed for 24 hours The reaction mixture is cooled to room temperature extracted The combined organic extracts are dried over anhydrous sodium sulfate filtered the filtrate evaporated in vacuo The residue is further purified by column chromatography on silica gel eluting with 5% ethyl acetate in hexane

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of ammonium chloride (12.5 g, 0.2 mol) in water (30 ml) is added to a mixture of zinc dust (35.7 g, 0.5 mol) and 4-bromo-1-ethyl-2-nitrobenzene (18 g, 0.07 mol) in methanol (720 ml) and water (180 ml). The reaction mixture is refluxed for one hour, then cooled to room temperature and filtered through a plug of diatomaceous earth. The filtrate is concentrated in vacuo, then diluted with water and extracted with ethyl acetate. The combined organic extracts are washed with water and brine, dried over anhydrous sodium sulfate, filtered and the filtrate concentrated in vacuo to yield 5-bromo-2-ethylaniline (14 g), used without further purification in the next step. The reaction mixture is refluxed for one hour filtered through a plug of diatomaceous earth The filtrate is concentrated in vacuo diluted with water extracted with ethyl acetate The combined organic extracts are washed with water and brine dried over anhydrous sodium sulfate filtered the filtrate concentrated in vacuo

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of ammonium chloride (12.5 g, 0.2 mol) in water (30 ml) is added to a mixture of zinc dust (35.7 g, 0.5 mol) and 4-bromo-1-ethyl-2-nitrobenzene (18 g, 0.07 mol) in methanol (720 ml) and water (180 ml). The reaction mixture is refluxed for one hour, then cooled to room temperature and filtered through a plug of diatomaceous earth. The filtrate is concentrated in vacuo, then diluted with water and extracted with ethyl acetate. The combined organic extracts are washed with water and brine, dried over anhydrous sodium sulfate, filtered and the filtrate concentrated in vacuo to yield 5-bromo-2-ethylaniline (14 g), used without further purification in the next step. The reaction mixture is refluxed for one hour filtered through a plug of diatomaceous earth The filtrate is concentrated in vacuo diluted with water extracted with ethyl acetate The combined organic extracts are washed with water and brine dried over anhydrous sodium sulfate filtered the filtrate concentrated in vacuo

反応条件: temp:20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 4-Chlorophenylboronic acid (13.2 g, 0.08 mol) and tetrakis(triphenylphosphine) palladium (0) (2.4 g, 0.002 mol) are added to a solution of 5-bromo-2-ethylaniline (14.1 g, 0.07 mol) in 1,2-dimethoxyethane (140 ml). After stirring the reaction mixture for 15 minutes at 20° C., a solution of 20% aqueous sodium carbonate (300 ml) is added to the mixture, and the resulting mixture is refluxed for 24 hours. The reaction mixture is cooled to room temperature, diluted with water and extracted using ethyl acetate. The combined organic extracts are dried over anhydrous sodium sulfate, filtered and the filtrate evaporated in vacuo. The residue is further purified by column chromatography on silica gel, eluting with 5% ethyl acetate in hexane to give 5-(4-chlorophenyl)-2-ethylaniline (14.3 g). the resulting mixture is refluxed for 24 hours The reaction mixture is cooled to room temperature extracted The combined organic extracts are dried over anhydrous sodium sulfate filtered the filtrate evaporated in vacuo The residue is further purified by column chromatography on silica gel eluting with 5% ethyl acetate in hexane

反応条件: temp:20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 4-Chlorophenylboronic acid (13.2 g, 0.08 mol) and tetrakis(triphenylphosphine) palladium (0) (2.4 g, 0.002 mol) are added to a solution of 5-bromo-2-ethylaniline (14.1 g, 0.07 mol) in 1,2-dimethoxyethane (140 ml). After stirring the reaction mixture for 15 minutes at 20° C., a solution of 20% aqueous sodium carbonate (300 ml) is added to the mixture, and the resulting mixture is refluxed for 24 hours. The reaction mixture is cooled to room temperature, diluted with water and extracted using ethyl acetate. The combined organic extracts are dried over anhydrous sodium sulfate, filtered and the filtrate evaporated in vacuo. The residue is further purified by column chromatography on silica gel, eluting with 5% ethyl acetate in hexane to give 5-(4-chlorophenyl)-2-ethylaniline (14.3 g). the resulting mixture is refluxed for 24 hours The reaction mixture is cooled to room temperature extracted The combined organic extracts are dried over anhydrous sodium sulfate filtered the filtrate evaporated in vacuo The residue is further purified by column chromatography on silica gel eluting with 5% ethyl acetate in hexane

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of ammonium chloride (12.5 g, 0.2 mol) in water (30 ml) is added to a mixture of zinc dust (35.7 g, 0.5 mol) and 4-bromo-1-ethyl-2-nitrobenzene (18 g, 0.07 mol) in methanol (720 ml) and water (180 ml). The reaction mixture is refluxed for one hour, then cooled to room temperature and filtered through a plug of diatomaceous earth. The filtrate is concentrated in vacuo, then diluted with water and extracted with ethyl acetate. The combined organic extracts are washed with water and brine, dried over anhydrous sodium sulfate, filtered and the filtrate concentrated in vacuo to yield 5-bromo-2-ethylaniline (14 g), used without further purification in the next step. The reaction mixture is refluxed for one hour filtered through a plug of diatomaceous earth The filtrate is concentrated in vacuo diluted with water extracted with ethyl acetate The combined organic extracts are washed with water and brine dried over anhydrous sodium sulfate filtered the filtrate concentrated in vacuo

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a stirred mixture of 5-bromo-2-ethylaniline (3.39 g, 200 mmol) in distilled water (110 ml) is added concentrated sulfuric acid (5.60 ml), followed by brief heating at reflux until dissolution. The mixture is allowed to cool to room temperature, producing a fine precipitate, then further cooled to approximately 0° C. in an ice/salt bath. To this slurry is added an aqueous solution of sodium nitrite (1.17 g, 16.94 mmol) in distilled water (10 ml) dropwise over 15 minutes, maintaining a temperature below 5° C., followed by additional stirring for 30 minutes. The reaction mixture is next filtered then added to a second solution of aqueous potassium iodide (8.44 g, 50.83 mmol) in distilled water (45 ml) dropwise at room temperature. After the addition is complete the solution is briefly heated to 80° C. then allowed to cool to room temperature again. The reaction mixture is extracted with ethyl acetate (3×50 ml), and the organic phase is washed with 1M aqueous hydrochloric acid (30 ml) and aqueous sodium thiosulfate (2×30 ml). After drying over anhydrous magnesium sulfate and concentration in vacuo 4-bromo-1-ethyl-2-iodobenzene (4.90 g) is furnished as an orange liquid. by brief heating at reflux until dissolution producing a fine precipitate further cooled to approximately 0° C. in an ice/salt bath maintaining a temperature below 5° C. The reaction mixture is next filtered After the addition is briefly heated to 80° C. to cool to room temperature again The reaction mixture is extracted with ethyl acetate (3×50 ml) the organic phase is washed with 1M aqueous hydrochloric acid (30 ml) and aqueous sodium thiosulfate (2×30 ml) After drying over anhydrous magnesium sulfate and concentration in vacuo 4-bromo-1-ethyl-2-iodobenzene (4.90 g) is furnished as an orange liquid

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a stirred mixture of 5-bromo-2-ethylaniline (3.39 g, 200 mmol) in distilled water (110 ml) is added concentrated sulfuric acid (5.60 ml), followed by brief heating at reflux until dissolution. The mixture is allowed to cool to room temperature, producing a fine precipitate, then further cooled to approximately 0° C. in an ice/salt bath. To this slurry is added an aqueous solution of sodium nitrite (1.17 g, 16.94 mmol) in distilled water (10 ml) dropwise over 15 minutes, maintaining a temperature below 5° C., followed by additional stirring for 30 minutes. The reaction mixture is next filtered then added to a second solution of aqueous potassium iodide (8.44 g, 50.83 mmol) in distilled water (45 ml) dropwise at room temperature. After the addition is complete the solution is briefly heated to 80° C. then allowed to cool to room temperature again. The reaction mixture is extracted with ethyl acetate (3×50 ml), and the organic phase is washed with 1M aqueous hydrochloric acid (30 ml) and aqueous sodium thiosulfate (2×30 ml). After drying over anhydrous magnesium sulfate and concentration in vacuo 4-bromo-1-ethyl-2-iodobenzene (4.90 g) is furnished as an orange liquid. by brief heating at reflux until dissolution producing a fine precipitate further cooled to approximately 0° C. in an ice/salt bath maintaining a temperature below 5° C. The reaction mixture is next filtered After the addition is briefly heated to 80° C. to cool to room temperature again The reaction mixture is extracted with ethyl acetate (3×50 ml) the organic phase is washed with 1M aqueous hydrochloric acid (30 ml) and aqueous sodium thiosulfate (2×30 ml) After drying over anhydrous magnesium sulfate and concentration in vacuo 4-bromo-1-ethyl-2-iodobenzene (4.90 g) is furnished as an orange liquid

反応条件: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 2-ethyl-5-bromo-1-nitrobenzene (9.71 g, 230 mmol) in ethanol (125 ml) is added tin(II) chloride dihydrate (35.72 g, 225.71 mmol), followed by heating at 70° C. for 2 hours. After cooling to room temperature the solution is poured into crushed ice (1 liter) then diluted with ethyl acetate (200 ml). Solid sodium carbonate is cautiously added until pH 7 is achieved, at which stage the viscous mixture is filtered through diatomaceous earth (further washing with ethyl acetate/aqueous sodium carbonate) and the phases separated. After additional extraction of the aqueous phase, all organic phases are combined, dried over anhydrous magnesium sulfate then concentrated in vacuo. The crude oil is purified by flash column chromatography on silica gel (hexane/ethyl acetate 8:2 ratio) to afford 5-bromo-2-ethylaniline (7.89 g) as a brown oil. After cooling to room temperature the solution is poured is filtered through diatomaceous earth ( further washing with ethyl acetate/aqueous sodium carbonate) and the phases separated After additional extraction of the aqueous phase dried over anhydrous magnesium sulfate then concentrated in vacuo The crude oil is purified by flash column chromatography on silica gel (hexane/ethyl acetate 8:2 ratio)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a stirred mixture of 5-bromo-2-ethylaniline (3.39 g, 200 mmol) in distilled water (110 ml) is added concentrated sulfuric acid (5.60 ml), followed by brief heating at reflux until dissolution. The mixture is allowed to cool to room temperature, producing a fine precipitate, then further cooled to approximately 0° C. in an ice/salt bath. To this slurry is added an aqueous solution of sodium nitrite (1.17 g, 16.94 mmol) in distilled water (10 ml) dropwise over 15 minutes, maintaining a temperature below 5° C., followed by additional stirring for 30 minutes. The reaction mixture is next filtered then added to a second solution of aqueous potassium iodide (8.44 g, 50.83 mmol) in distilled water (45 ml) dropwise at room temperature. After the addition is complete the solution is briefly heated to 80° C. then allowed to cool to room temperature again. The reaction mixture is extracted with ethyl acetate (3×50 ml), and the organic phase is washed with 1M aqueous hydrochloric acid (30 ml) and aqueous sodium thiosulfate (2×30 ml). After drying over anhydrous magnesium sulfate and concentration in vacuo 4-bromo-1-ethyl-2-iodobenzene (4.90 g) is furnished as an orange liquid. by brief heating at reflux until dissolution producing a fine precipitate further cooled to approximately 0° C. in an ice/salt bath maintaining a temperature below 5° C. The reaction mixture is next filtered After the addition is briefly heated to 80° C. to cool to room temperature again The reaction mixture is extracted with ethyl acetate (3×50 ml) the organic phase is washed with 1M aqueous hydrochloric acid (30 ml) and aqueous sodium thiosulfate (2×30 ml) After drying over anhydrous magnesium sulfate and concentration in vacuo 4-bromo-1-ethyl-2-iodobenzene (4.90 g) is furnished as an orange liquid