4-bromo-2,6-di(propan-2-yl)aniline

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: With stirring, 21 g (0.15 mol) of potassium carbonate are initially added to 141 g (1.5 mol) of phenol in 500 g of toluene, followed by the addition of 168 g (1.5 mol) of a 50% aqueous solution of potassium hydroxide. The entire water of reaction is then separated under reflux, and then ca. 400 g of toluene are removed by distillation. The residue is dissolved in 700 g of dimethyl formamide. After addition of 6 g (0.05 mol) of copper carbonate, solvent is distilled off until the temperature of the reaction mixture is 140° C. Then 256 g (1 mol) of 4-bromo-2,6-diisopropylaniline are added at 140° C. and the mixture is kept for 10 hours at 140° C. The dimethyl formamide is then removed by vacuum distillation, the residue is extracted with water, and the product is taken up in toluene. After stripping off the toluene, the crude product is purified by vacuum distillation, giving 215 g (80% of theory) of 4-phenoxy-2,6-diisopropylaniline with a boiling point of 142°-145° C./0.04 mbar and a melting point of 69°-71° C., in the form of a bright red product. Conversion to the hydrochloride is effected by dissolving the product in 300 g of butyl acetate, adding 115 g of a 37% solution of hydrochloric acid, and removing the water of reaction by vacuum distillation. The hydrochloride is isolated by filtration, washed with butyl acetate and dried under vacuum, giving 235 g (96% of theory, based on 4-phenoxy-2,6-diisopropylaniline) of 4-phenoxy-2,6-diisopropylaniline hydrochloride in the form of white crystals which melt at 247°-249° C. is then separated under reflux ca. 400 g of toluene are removed by distillation The residue is dissolved in 700 g of dimethyl formamide is distilled off until the temperature of the reaction mixture is 140° C The dimethyl formamide is then removed by vacuum distillation the residue is extracted with water the crude product is purified by vacuum distillation

Conditions: temp:5.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a 2 L 3-neck flask, equipped with mechanical stirrer, thermometer, and additional funnel, added 300 g of ice and 300 mL of H2SO4. 2,6-diisopropyl-4-bromoaniline (46.0 g, 0.18 mol) in 200 mL of CH3CN was added dropwise to this mixture while the temperature was maintained under 5° C. Then sodium nitrite (22.5 g, 0.32 mol) in 180 mL of ice cold water was added dropwise while the temperature was maintained around 0° C. The resulting clear solution was slowly poured into the solution of potassium iodide (105 g, 0.63 mol) in 300 ml of water at room temperature. The mixture was stirred for 1 h. After regular work up, the crude product was distilled at 170° C. under vacuum to afford 1-iodo-2,6-diisopropyl-4-bromobenzene (60 g) as light brown soft solid upon cooling. To a 2 L 3-neck flask, equipped with mechanical stirrer was maintained around 0° C After regular work up, the crude product was distilled at 170° C. under vacuum

Conditions: temp:5.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a 2 L 3-neck flask, equipped with mechanical stirrer, thermometer, and additional funnel, added 300 g of ice and 300 mL of H2SO4. 2,6-diisopropyl-4-bromoaniline (46.0 g, 0.18 mol) in 200 mL of CH3CN was added dropwise to this mixture while the temperature was maintained under 5° C. Then sodium nitrite (22.5 g, 0.32 mol) in 180 mL of ice cold water was added dropwise while the temperature was maintained around 0° C. The resulting clear solution was slowly poured into the solution of potassium iodide (105 g, 0.63 mol) in 300 ml of water at room temperature. The mixture was stirred for 1 h. After regular work up, the crude product was distilled at 170° C. under vacuum to afford 1-iodo-2,6-diisopropyl-4-bromobenzene (60 g) as light brown soft solid upon cooling. To a 2 L 3-neck flask, equipped with mechanical stirrer was maintained around 0° C After regular work up, the crude product was distilled at 170° C. under vacuum

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

Procedure: 48.9 g of phenol are dissolved in 500 ml of xylene, and to this solution are added 30.2 g of pulverised potassium hydroxide in an atmosphere of nitrogen. The reaction mixture is stirred and heated to boiling point, while continuously distilling off the water that is formed. After addition of 0.6 g of copper chloride and 100 g of 2,6-diisopropyl-4-bromoaniline, the mixture is stirred for 8 hours at 150°-155° C., then cooled, and filtered with suction. The filtrate is washed with 15% sodium hydroxide solution (150 ml) and with two 150 ml portions of water. The organic phase is separated and dried over sodium sulfate. The solvent is removed by distillation and the product is distilled, affording the compound of the formula ##STR5## with a boiling point of 103°-104° C./0.01 torr and a melting point of 71°-72° C. (after recrystallisation from hexane). heated while continuously distilling off the water that is formed the mixture is stirred for 8 hours at 150°-155° C. cooled filtered with suction The filtrate is washed with 15% sodium hydroxide solution (150 ml) and with two 150 ml portions of water The organic phase is separated dried over sodium sulfate The solvent is removed by distillation the product is distilled affording the compound of the formula ##STR5## with a boiling point of 103°-104° C./0.01 torr a melting point of 71°-72° C. (after recrystallisation from hexane)

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

Procedure: Under an argon atmosphere, to a solution of 18.9 g (73.8 mmol) of 4-bromo-2,6-diisopropylaniline in 200 ml of THF, 29.5 ml of 2.5 M (73.8 mmol) nBuLi in hexanes was added at −80° C. This mixture was warmed for ca. 1 hour to ambient temperature. Then, the resulting solution was added dropwise over ca. 1 hour, while vigorously stirring, to a solution of 17.9 g (73.8 mmol) of chloro(4,5-dimethyl-6H-cyclopenta[b]thien-6-yl)dimethylsilane in 100 ml of THF. The resulting mixture was stirred overnight at ambient temperature, and then, evaporated to dryness. To the residue, 150 ml of toluene was added. This mixture was filtered through a glass frit (G4). The filtrate was evaporated to dryness. Fractional distillation gave a yellow liquid, bp 180° C./0.1 mm Hg. The product crystallizes slowly at ambient temperature. Yield 11.9 g (35%). This mixture was warmed for ca. 1 hour to ambient temperature Then, the resulting solution was added dropwise over ca. 1 hour evaporated to dryness To the residue, 150 ml of toluene was added This mixture was filtered through a glass frit (G4) The filtrate was evaporated to dryness Fractional distillation gave a yellow liquid, bp 180° C./0.1 mm Hg The product crystallizes slowly at ambient temperature

Conditions: temp:5.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a 2 L 3-neck flask, equipped with mechanical stirrer, thermometer, and additional funnel, added 300 g of ice and 300 mL of H2SO4. 2,6-diisopropyl-4-bromoaniline (46.0 g, 0.18 mol) in 200 mL of CH3CN was added dropwise to this mixture while the temperature was maintained under 5° C. Then sodium nitrite (22.5 g, 0.32 mol) in 180 mL of ice cold water was added dropwise while the temperature was maintained around 0° C. The resulting clear solution was slowly poured into the solution of potassium iodide (105 g, 0.63 mol) in 300 ml of water at room temperature. The mixture was stirred for 1 h. After regular work up, the crude product was distilled at 170° C. under vacuum to afford 1-iodo-2,6-diisopropyl-4-bromobenzene (60 g) as light brown soft solid upon cooling. To a 2 L 3-neck flask, equipped with mechanical stirrer was maintained around 0° C After regular work up, the crude product was distilled at 170° C. under vacuum

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

Procedure: A solution of 2,6-diisopropylaniline (2.0 mL, 11 mmol) in methanol (80 mL) was treated dropwise with bromine (543 μL, 10.6 mmol). The solution was stirred at room temperature for 15 min. Chloroform and 0.1 N NaOH were added and the organic layer was dried (Na2SO4), filtered and concentrated to an orange liquid. Kugelrohr distillation (110° C. @ 0.06 Torr) afforded a colorless liquid (2.22 g 79%): 1H NMR (400 MHz) δ1.25 (d, J=6.4 Hz, 12H), 2.88 (m, 2H), 3.70 (brs, 2H), 7.11 (s, 2H); 13C NMR δ22.1, 27.9, 111.0, 125.6, 134.5, 139.3; Anal calcd for C12H19BrN: C, 56.26; H, 7.08; Br, 31.19; Found, C, 56.24; H, 7.07; Br, 30.98. the organic layer was dried (Na2SO4) filtered concentrated to an orange liquid Kugelrohr distillation (110° C. @ 0.06 Torr) afforded a colorless liquid (2.22 g 79%)

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

Procedure: To a solution of 2,6-diisopropylaniline (25 g, 0.141 moL) in toluene (25 mL) was added dimethyl sulfoxide (12.1 g, 1.1 equivalents), and the mixture was heated to 90° C. 48% Aqueous hydrobromic acid solution (26.1 g, 1.1 equivalents) was added dropwise to the mixture at the same temperature over 30 min. Then, the mixture was stirred at 86° C. for 3 hr and at 100° C. for 2 hr. Water (20 mL) was added to the mixture at 0° C., and 1M aqueous sodium hydroxide solution (30 mL) was added dropwise to the mixture. The mixture was partitioned, and the organic layer was washed with 1M aqueous sodium hydroxide solution (50 mL). The organic layer was dried over anhydrous magnesium sulfate and filtered naturally, and the filtrate was concentrated under reduced pressure. The residue was distilled under reduced pressure to give 4-bromo-2,6-diisopropylaniline (29.4 g, pale-yellow liquid). 37% Formaldehyde (23.1 g, 2.5 equivalents) was added to a solution of 4-bromo-2,6-diisopropylaniline synthesized as mentioned above in formic acid (189 g, 4.11 moL) at 32° C., and the mixture was stirred under refluxing for 2 hr. Toluene (100 mL) and 8M aqueous sodium hydroxide solution (150 mL) were added to the mixture at 0° C., the mixture was partitioned, and the organic layer was successively washed with 1M aqueous sodium hydroxide solution (50 mL) and water (50 mL). The organic layer was dried over anhydrous magnesium sulfate and filtered naturally, and the filtrate was concentrated under reduced pressure. The residue was purified by column chromatography to give the title compound (35.0 g, colorless solid). yield 95%. The mixture was partitioned the organic layer was washed with 1M aqueous sodium hydroxide solution (50 mL) The organic layer was dried over anhydrous magnesium sulfate filtered naturally the filtrate was concentrated under reduced pressure The residue was distilled under reduced pressure

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

Procedure: To a solution of 2,6-diisopropylaniline (25 g, 0.141 moL) in toluene (25 mL) was added dimethyl sulfoxide (12.1 g, 1.1 equivalents), and the mixture was heated to 90° C. 48% Aqueous hydrobromic acid solution (26.1 g, 1.1 equivalents) was added dropwise to the mixture at the same temperature over 30 min. Then, the mixture was stirred at 86° C. for 3 hr and at 100° C. for 2 hr. Water (20 mL) was added to the mixture at 0° C., and 1M aqueous sodium hydroxide solution (30 mL) was added dropwise to the mixture. The mixture was partitioned, and the organic layer was washed with 1M aqueous sodium hydroxide solution (50 mL). The organic layer was dried over anhydrous magnesium sulfate and filtered naturally, and the filtrate was concentrated under reduced pressure. The residue was distilled under reduced pressure to give 4-bromo-2,6-diisopropylaniline (29.4 g, pale-yellow liquid). 37% Formaldehyde (23.1 g, 2.5 equivalents) was added to a solution of 4-bromo-2,6-diisopropylaniline synthesized as mentioned above in formic acid (189 g, 4.11 moL) at 32° C., and the mixture was stirred under refluxing for 2 hr. Toluene (100 mL) and 8M aqueous sodium hydroxide solution (150 mL) were added to the mixture at 0° C., the mixture was partitioned, and the organic layer was successively washed with 1M aqueous sodium hydroxide solution (50 mL) and water (50 mL). The organic layer was dried over anhydrous magnesium sulfate and filtered naturally, and the filtrate was concentrated under reduced pressure. The residue was purified by column chromatography to give the title compound (35.0 g, colorless solid). yield 95%. The mixture was partitioned the organic layer was washed with 1M aqueous sodium hydroxide solution (50 mL) The organic layer was dried over anhydrous magnesium sulfate filtered naturally the filtrate was concentrated under reduced pressure The residue was distilled under reduced pressure

Conditions: temp:5.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a 2 L 3-neck flask, equipped with mechanical stirrer, thermometer, and additional funnel, added 300 g of ice and 300 mL of H2SO4. 2,6-diisopropyl-4-bromoaniline (46.0 g, 0.18 mol) in 200 mL of CH3CN was added dropwise to this mixture while the temperature was maintained under 5° C. Then sodium nitrite (22.5 g, 0.32 mol) in 180 mL of ice cold water was added dropwise while the temperature was maintained around 0° C. The resulting clear solution was slowly poured into the solution of potassium iodide (105 g, 0.63 mol) in 300 ml of water at room temperature. The mixture was stirred for 1 h. After regular work up, the crude product was distilled at 170° C. under vacuum to afford 1-iodo-2,6-diisopropyl-4-bromobenzene (60 g) as light brown soft solid upon cooling. To a 2 L 3-neck flask, equipped with mechanical stirrer was maintained around 0° C After regular work up, the crude product was distilled at 170° C. under vacuum