4-bromo-2,6-dimethylbenzenecarbonitrile

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 4-Bromo-2,6dimethylaniline (4.49 g, 22.4 mmol) was taken up in water (25 ml) and concentrated hydrochloric acid (8.0 ml) was added. The mixture was sonicated to form a fine suspension and then cooled to 0° C. A solution of sodium nitrite (1.67 g, 24.2 mmol) in water (5 ml) was then added dropwise so as to maintain the temperature of the reaction between 0–5° C. The mixture was stirred at 0–5° C. for ½ h and then neutralised by addition of solid sodium carbonate. The resulting solution was then added portionwise to a solution of copper cyanide (2.42 g, 27.0 mmol) and potassium cyanide (3.65 g, 56.1 mmol) in water (25 ml) at 70° C. The mixture was stirred at 70° C. for ½ h, allowed to cool and then extracted with toluene (2 times). The combined extracts were washed with water and brine, dried over MgSO4, and concentrated in vacuo. The residue was purified by flash chromatography on silica (eluant EtOAc:pet. ether 5:95) to give an orange solid; yield 3.2 g (68%). The mixture was sonicated to form a fine suspension to maintain the temperature of the reaction between 0–5° C The mixture was stirred at 70° C. for ½ h to cool extracted with toluene (2 times) The combined extracts were washed with water and brine dried over MgSO4 concentrated in vacuo The residue was purified by flash chromatography on silica (eluant EtOAc:pet. ether 5:95) to give an orange solid

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 4-Bromo-2,6dimethylaniline (4.49 g, 22.4 mmol) was taken up in water (25 ml) and concentrated hydrochloric acid (8.0 ml) was added. The mixture was sonicated to form a fine suspension and then cooled to 0° C. A solution of sodium nitrite (1.67 g, 24.2 mmol) in water (5 ml) was then added dropwise so as to maintain the temperature of the reaction between 0–5° C. The mixture was stirred at 0–5° C. for ½ h and then neutralised by addition of solid sodium carbonate. The resulting solution was then added portionwise to a solution of copper cyanide (2.42 g, 27.0 mmol) and potassium cyanide (3.65 g, 56.1 mmol) in water (25 ml) at 70° C. The mixture was stirred at 70° C. for ½ h, allowed to cool and then extracted with toluene (2 times). The combined extracts were washed with water and brine, dried over MgSO4, and concentrated in vacuo. The residue was purified by flash chromatography on silica (eluant EtOAc:pet. ether 5:95) to give an orange solid; yield 3.2 g (68%). The mixture was sonicated to form a fine suspension to maintain the temperature of the reaction between 0–5° C The mixture was stirred at 70° C. for ½ h to cool extracted with toluene (2 times) The combined extracts were washed with water and brine dried over MgSO4 concentrated in vacuo The residue was purified by flash chromatography on silica (eluant EtOAc:pet. ether 5:95) to give an orange solid

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 4-Bromo-2,6dimethylaniline (4.49 g, 22.4 mmol) was taken up in water (25 ml) and concentrated hydrochloric acid (8.0 ml) was added. The mixture was sonicated to form a fine suspension and then cooled to 0° C. A solution of sodium nitrite (1.67 g, 24.2 mmol) in water (5 ml) was then added dropwise so as to maintain the temperature of the reaction between 0–5° C. The mixture was stirred at 0–5° C. for ½ h and then neutralised by addition of solid sodium carbonate. The resulting solution was then added portionwise to a solution of copper cyanide (2.42 g, 27.0 mmol) and potassium cyanide (3.65 g, 56.1 mmol) in water (25 ml) at 70° C. The mixture was stirred at 70° C. for ½ h, allowed to cool and then extracted with toluene (2 times). The combined extracts were washed with water and brine, dried over MgSO4, and concentrated in vacuo. The residue was purified by flash chromatography on silica (eluant EtOAc:pet. ether 5:95) to give an orange solid; yield 3.2 g (68%). The mixture was sonicated to form a fine suspension to maintain the temperature of the reaction between 0–5° C The mixture was stirred at 70° C. for ½ h to cool extracted with toluene (2 times) The combined extracts were washed with water and brine dried over MgSO4 concentrated in vacuo The residue was purified by flash chromatography on silica (eluant EtOAc:pet. ether 5:95) to give an orange solid

反応条件: temp:0.00; pressure:0.00; stir:

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

実験手順: A solution of 4-bromo-2,6-dimethyl-benzonitrile (8.0 g, 38 mmol), 5N NaOH (60 mL), and MeOH (60 mL) was stirred at 80° C. for 17 h. The reaction mixture was cooled to ambient temperature and the methanol evaporated. The resulting solution was extracted with dichloromethane (2×200 mL). The combined organic extracts were dried over anhydrous MgSO4, filtered, and concentrated. GC-MS indicated that 70% of benzonitrile was converted to benzamide derivative. This material (7.0 g) was treated with 85% phosphoric acid (20 mL) and stirred at 150° C. for 18 h. After this time, the reaction mixture was cooled to ambient temperature and treated with water (30 mL). The resulting solution was extracted with ethyl acetate (2×200 mL). The combined organic extracts were dried over anhydrous MgSO4, filtered, and concentrated to afford 4-bromo-2,6-dimethyl-benzoic acid. The material was used without further purification. the methanol evaporated The resulting solution was extracted with dichloromethane (2×200 mL) The combined organic extracts were dried over anhydrous MgSO4 filtered concentrated This material (7.0 g) was treated with 85% phosphoric acid (20 mL) After this time, the reaction mixture was cooled to ambient temperature treated with water (30 mL) The resulting solution was extracted with ethyl acetate (2×200 mL) The combined organic extracts were dried over anhydrous MgSO4 filtered concentrated

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

実験手順: A solution of 4-bromo-2,6-dimethyl-benzonitrile (8.0 g, 38 mmol), 5N NaOH (60 mL), and MeOH (60 mL) was stirred at 80° C. for 17 h. The reaction mixture was cooled to ambient temperature and the methanol evaporated. The resulting solution was extracted with dichloromethane (2×200 mL). The combined organic extracts were dried over anhydrous MgSO4, filtered, and concentrated. GC-MS indicated that 70% of benzonitrile was converted to benzamide derivative. This material (7.0 g) was treated with 85% phosphoric acid (20 mL) and stirred at 150° C. for 18 h. After this time, the reaction mixture was cooled to ambient temperature and treated with water (30 mL). The resulting solution was extracted with ethyl acetate (2×200 mL). The combined organic extracts were dried over anhydrous MgSO4, filtered, and concentrated to afford 4-bromo-2,6-dimethyl-benzoic acid. The material was used without further purification. the methanol evaporated The resulting solution was extracted with dichloromethane (2×200 mL) The combined organic extracts were dried over anhydrous MgSO4 filtered concentrated This material (7.0 g) was treated with 85% phosphoric acid (20 mL) After this time, the reaction mixture was cooled to ambient temperature treated with water (30 mL) The resulting solution was extracted with ethyl acetate (2×200 mL) The combined organic extracts were dried over anhydrous MgSO4 filtered concentrated

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

実験手順: 4-Bromo-2,6-dimethylbenzonitrile (4.0 g, 19 mmol) was stirred in MeOH (100 mL) and 5N NaOH (100 mL) at 100° C. for 12 hours. The reaction was cooled to room temperature and partitioned between CH2Cl2 and water and the organic layer was dried over anhydrous Na2SO4. The solvent was removed under reduced pressure and the resulting product was stirred in H2PO3 (20 mL) for 6 hours at 150° C. The reaction mixture was basified with 6M KOH, filtered and then acidified with 12M HCl. The reaction was partitioned between CH2Cl2 and water and the organic layer was dried over anhydrous Na2-SO4. The solvent was removed under reduced pressure to afford the product (2.81 g). 1H NMR (300 MHz, CDCl3): δ 7.22 (s, 2H), 6.17 (s, 1H), 5.67 (s, 1H), 2.36 (s, 6H). partitioned between CH2Cl2 and water the organic layer was dried over anhydrous Na2SO4 The solvent was removed under reduced pressure filtered The reaction was partitioned between CH2Cl2 and water the organic layer was dried over anhydrous Na2-SO4 The solvent was removed under reduced pressure

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

実験手順: 4-Bromo-2,6-dimethylbenzonitrile (4.0 g, 19 mmol) was stirred in MeOH (100 mL) and 5N NaOH (100 mL) at 100° C. for 12 hours. The reaction was cooled to room temperature and partitioned between CH2Cl2 and water and the organic layer was dried over anhydrous Na2SO4. The solvent was removed under reduced pressure and the resulting product was stirred in H2PO3 (20 mL) for 6 hours at 150° C. The reaction mixture was basified with 6M KOH, filtered and then acidified with 12M HCl. The reaction was partitioned between CH2Cl2 and water and the organic layer was dried over anhydrous Na2-SO4. The solvent was removed under reduced pressure to afford the product (2.81 g). 1H NMR (300 MHz, CDCl3): δ 7.22 (s, 2H), 6.17 (s, 1H), 5.67 (s, 1H), 2.36 (s, 6H). partitioned between CH2Cl2 and water the organic layer was dried over anhydrous Na2SO4 The solvent was removed under reduced pressure filtered The reaction was partitioned between CH2Cl2 and water the organic layer was dried over anhydrous Na2-SO4 The solvent was removed under reduced pressure

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 4-Bromo-2,6-dimethylphenylamine (10 g, 500 mmol) was suspended in concentrated HCl (10 mL) and crushed ice (41 g) and cooled to 0° C. NaNO2 (3.52 g, 51 mmol) in water (10 mL) was added, maintaining a temperature of 0° C. and the reaction was stirred for 30 minutes. A solution of copper cyanide (5.60 g, 62.5 mmol) in water (25 mL) and sodium cyanide (7.79 g, 159 mmol) in water (12 mL) were cooled to 0° C. in a separate flask. The concentrated HCl mixture was neutralized with sodium carbonate and the resulting diazonium salt mixture was added to the copper cyanide and sodium cyanide solution along with toluene (100 mL) under vigorous stirring, maintaining a temperature of 0° C. for 1 hour, followed by stirring at room temperature for 4 hours. The reaction mixture was heated to 50° C. and then cooled to room temperature. The reaction was partitioned between water and toluene and the organic layers were combined and washed with water and dried over anhydrous Na2SO4. The product was purified by column chromatography on silica (20% EtOAc/Hexanes) to afford a brown solid (8.10 g). 1H NMR (300 MHz, CDCl3): δ 7.33 (s, 2H), 2.53 (s, 6H). maintaining a temperature of 0° C. maintaining a temperature of 0° C. for 1 hour by stirring at room temperature for 4 hours The reaction mixture was heated to 50° C. cooled to room temperature The reaction was partitioned between water and toluene washed with water dried over anhydrous Na2SO4 The product was purified by column chromatography on silica (20% EtOAc/Hexanes)

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

実験手順: 4.55 ml of n-butyllithium solution (1.6M in hexane) are added dropwise to a solution of 1.39 g of 4-bromo-2,6-dimethylbenzonitrile in 25 ml of dry tetrahydrofuran at −78° C. After stirring at this temperature for 20 minutes, 1.88 ml of triisopropyl borate are added. After 45 minutes, 15 ml of 1N aqueous HCl are added to the reaction mixture, which is warmed to room temperature. The phases are separated and the aqueous phase is extracted three more times with 100 ml of diethyl ether/tetrahydrofuran (1:1) each time. The combined organic phases are dried with sodium sulphate, filtered and concentrated to 4 ml in vacuo. The remaining oil is mixed with 50 ml of pentane, and the precipitate which has separated out is filtered off with suction and washed twice with pentane. Drying under high vacuum results in the title compound as a beige solid. Rt=3.20. After 45 minutes The phases are separated the aqueous phase is extracted three more times with 100 ml of diethyl ether/tetrahydrofuran (1:1) each time The combined organic phases are dried with sodium sulphate filtered concentrated to 4 ml in vacuo The remaining oil is mixed with 50 ml of pentane the precipitate which has separated out is filtered off with suction washed twice with pentane Drying under high vacuum