4-chloro-2-methylbenzonitrile

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:0.00; pressure:0.00; stir:

反応条件: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Toluene (30 mL) and ice was added to the above copper cyanide solution and then the reaction mixture was stirred vigorously. The above diazonium salt solution was then slowly added to the reaction mixture. After the addition was complete, the reaction mixture was stirred at 0° C. for 30 minutes. The reaction mixture was then allowed to warm to room temperature (25° C.), and then stirred for another hour. The reaction mixture was then heated to 50° C. for 2 hours without stirring. The toluene phase and precipitate were then separated from the aqueous phase. To the toluene phase was added 10 mL concentrated HCl, 40 mL hot H2O, and FeCl3.6H2O (32 g, 0.118 mol) and this reaction mixture was then stirred overnight. The reaction mixture was then added to 200 mL H2O. The organic phase was then extracted with toluene, dried and evaporated under reduced pressure to produce 4-chloro-2-methylbenzonitrile as a dark brown oil. After the addition the reaction mixture was stirred at 0° C. for 30 minutes stirred for another hour The reaction mixture was then heated to 50° C. for 2 hours without stirring The toluene phase and precipitate were then separated from the aqueous phase this reaction mixture was then stirred overnight The organic phase was then extracted with toluene dried evaporated under reduced pressure

反応条件: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Toluene (30 mL) and ice was added to the above copper cyanide solution and then the reaction mixture was stirred vigorously. The above diazonium salt solution was then slowly added to the reaction mixture. After the addition was complete, the reaction mixture was stirred at 0° C. for 30 minutes. The reaction mixture was then allowed to warm to room temperature (25° C.), and then stirred for another hour. The reaction mixture was then heated to 50° C. for 2 hours without stirring. The toluene phase and precipitate were then separated from the aqueous phase. To the toluene phase was added 10 mL concentrated HCl, 40 mL hot H2O, and FeCl3.6H2O (32 g, 0.118 mol) and this reaction mixture was then stirred overnight. The reaction mixture was then added to 200 mL H2O. The organic phase was then extracted with toluene, dried and evaporated under reduced pressure to produce 4-chloro-2-methylbenzonitrile as a dark brown oil. After the addition the reaction mixture was stirred at 0° C. for 30 minutes stirred for another hour The reaction mixture was then heated to 50° C. for 2 hours without stirring The toluene phase and precipitate were then separated from the aqueous phase this reaction mixture was then stirred overnight The organic phase was then extracted with toluene dried evaporated under reduced pressure

反応条件: temp:40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Methylmagnesium bromide (6.29 g, 52.8 mmol) was added to a stirred solution of 4-chloro-2-methyl-benzonitrile (5.00 g, 33.0 mmol) in diethyl ether (44 mL). The mixture was heated to 40° C. After 72 h the mixture was cooled to room temperature and poured into a stirred mixture of anhydrous diethyl ether (120 mL), ice water (100 mL), and 10% aqueous HCl (100 mL). The aqueous layer was separated, stirred at reflux for 1 h, then was cooled to room temperature and was extracted into diethyl ether (4×50 mL). The organic layers were combined, washed with saturated NaHCO3 and brine, dried (Na2SO4) and concentrated in vacuo. 1-(4-Chloro-2-methylphenyl)ethanone was obtained as an oil. 1H NMR (CDCl3, 400 MHz) δ 2.52 (s, 3H), 2.56 (d, J=0.7 Hz, 3H), 7.24 (m, 2H), 7.65 (d, J=8.8 Hz, 1H). After 72 h the mixture was cooled to room temperature The aqueous layer was separated at reflux for 1 h was cooled to room temperature was extracted into diethyl ether (4×50 mL) washed with saturated NaHCO3 and brine dried (Na2SO4) concentrated in vacuo

反応条件: temp:40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Methylmagnesium bromide (6.29 g, 52.8 mmol) was added to a stirred solution of 4-chloro-2-methyl-benzonitrile (5.00 g, 33.0 mmol) in diethyl ether (44 mL). The mixture was heated to 40° C. After 72 h the mixture was cooled to room temperature and poured into a stirred mixture of anhydrous diethyl ether (120 mL), ice water (100 mL), and 10% aqueous HCl (100 mL). The aqueous layer was separated, stirred at reflux for 1 h, then was cooled to room temperature and was extracted into diethyl ether (4×50 mL). The organic layers were combined, washed with saturated NaHCO3 and brine, dried (Na2SO4) and concentrated in vacuo. 1-(4-Chloro-2-methylphenyl)ethanone was obtained as an oil. 1H NMR (CDCl3, 400 MHz) δ 2.52 (s, 3H), 2.56 (d, J=0.7 Hz, 3H), 7.24 (m, 2H), 7.65 (d, J=8.8 Hz, 1H). After 72 h the mixture was cooled to room temperature The aqueous layer was separated at reflux for 1 h was cooled to room temperature was extracted into diethyl ether (4×50 mL) washed with saturated NaHCO3 and brine dried (Na2SO4) 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 −78° C. solution of 4-chloro-2-methylbenzonitrile (5.00 g, 32.98 mmol) in Et2O (190 mL) was added 1 M DIBAL in THF (66.0 mL) over 10 min. After 5 h additional 1M DIBAL in THF (3.30 mL) was added dropwise and the solution was stirred for 1 hour. The reaction was quenched with water followed by concentrated H2SO4 and stirred at ambient temperature for 16 h. The solution was extracted into Et2O, dried (Na2SO4) and reduced in vacuo. 4-Chloro-2-methylbenzaldehyde was isolated as a yellow oil. 1H NMR (CDCl3, 400 MHz) δ 2.59 (s, 3H), 7.19 (s, 1H), 7.26 (d, J=8.2 Hz, 1H), 7.66 (d, J=8.2 Hz, 1H), 10.15 (s, 1H). The reaction was quenched with water stirred at ambient temperature for 16 h The solution was extracted into Et2O dried (Na2SO4)

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

実験手順: To a stirred −78° C. solution of 4-chloro-2-methylbenzonitrile (5.00 g, 32.98 mmol) in Et2O (190 mL) was added 1 M DIBAL in THF (66.0 mL) over 10 min. After 5 h additional 1M DIBAL in THF (3.30 mL) was added dropwise and the solution was stirred for 1 hour. The reaction was quenched with water followed by concentrated H2SO4 and stirred at ambient temperature for 16 h. The solution was extracted into Et2O, dried (Na2SO4) and reduced in vacuo. 4-Chloro-2-methylbenzaldehyde was isolated as a yellow oil. 1H NMR (CDCl3, 400 MHz) δ 2.59 (s, 3H), 7.19 (s, 1H), 7.26 (d, J=8.2 Hz, 1H), 7.66 (d, J=8.2 Hz, 1H), 10.15 (s, 1H). The reaction was quenched with water stirred at ambient temperature for 16 h The solution was extracted into Et2O dried (Na2SO4)

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

実験手順: To a stirred solution 4-Chloro-2-methyl-benzonitrile 1(5.0 g, 33.0 mmol) in carbon tetrachloride (150 mL) was added N-bromosuccinamide (7.6 g, 42.9 mmol) and 2,2′-azobisisobutyronitrile (cat.). The reaction mixture was refluxed 6 hrs, filtered, concentrated, and partitioned between ether and water. The ether layer was dried, concentrated, and purified by silica gel chromatography (10% ether/hexanes) to yield a white solid (40%). 1H NMR (400 MHz, CDCl3) δ7.61 (d, J=8.3 Hz, 1 H, Ar), 7.57 (d, J=2.2 Hz, 1 H, Ar), 7.41 (dd, J=8.3, 2.0 Hz, 1 H, Ar), 4.59 (s, 2 H, CH2). The reaction mixture was refluxed 6 hrs filtered concentrated partitioned between ether and water The ether layer was dried concentrated purified by silica gel chromatography (10% ether/hexanes)

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

実験手順: To a solution of 4-chloro-2-methylbenzonitrile (10 g, 66 mmol) in conc. H2SO4 was added KNO3 (7.0 g, 69.3 mmol) at 0° C. in small portions, and then the reaction mixture was stirred overnight at ambient temperature. It was then poured into ice and extracted with AcOEt. The combined extracts were washed by sat. NaHCO3 aq., dried over MgSO4 and concentrated. The resulting precipitates were collected by filtration, washed with ether, and dried under reduced pressure to give 5.5 g (42%) of the title compound. It was then poured into ice extracted with AcOEt The combined extracts were washed by sat. NaHCO3 aq. dried over MgSO4 concentrated The resulting precipitates were collected by filtration washed with ether dried under reduced pressure

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

実験手順: To a solution of 4-chloro-2-methylbenzonitrile (10 g, 66 mmol) in conc. H2SO4 was added KNO3 (7.0 g, 69.3 mmol) at 0° C. in small portions, and then the reaction mixture was stirred overnight at ambient temperature. It was then poured into ice and extracted with AcOEt. The combined extracts were washed by sat. NaHCO3 aq., dried over MgSO4 and concentrated. The resulting precipitates were collected by filtration, washed with ether, and dried under reduced pressure to give 5.5 g (42%) of the title compound. It was then poured into ice extracted with AcOEt The combined extracts were washed by sat. NaHCO3 aq. dried over MgSO4 concentrated The resulting precipitates were collected by filtration washed with ether dried under reduced pressure