2,4,6-Trichlorobenzaldehyde

反応条件: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Add 2,4,6-trichlorobenzonitrile (206 mg, 1.0 mmol) to 96% formic acid (5 mL, 96%) and water (1 mL). Add nichol/aluminum alloy (206 mg) to the mixture. Heat at 100° C. for 4 hours. Dilute with ethyl acetate and filter through Celite®. Extract the filtrate with 1 N sodium hydroxide and saturated aqueous sodium chloride, dry (sodium sulfate), filter, and concentrate to give 2,4,6-trichlorobenzaldehyde (195 mg, 93%). 1H NMR (400 MHz, CDCl3) δ 10.36 (s, 1H), 7.99 (s, 1H), 7.61 (s, 1H). filter through Celite® Extract the filtrate with 1 N sodium hydroxide and saturated aqueous sodium chloride dry (sodium sulfate) filter concentrate

反応条件: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Add 2,4,6-trichlorobenzonitrile (206 mg, 1.0 mmol) to 96% formic acid (5 mL, 96%) and water (1 mL). Add nichol/aluminum alloy (206 mg) to the mixture. Heat at 100° C. for 4 hours. Dilute with ethyl acetate and filter through Celite®. Extract the filtrate with 1 N sodium hydroxide and saturated aqueous sodium chloride, dry (sodium sulfate), filter, and concentrate to give 2,4,6-trichlorobenzaldehyde (195 mg, 93%). 1H NMR (400 MHz, CDCl3) δ 10.36 (s, 1H), 7.99 (s, 1H), 7.61 (s, 1H). filter through Celite® Extract the filtrate with 1 N sodium hydroxide and saturated aqueous sodium chloride dry (sodium sulfate) filter concentrate

反応条件: temp:160.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: In a microwave vial 2,4,6-trichlorobenzaldehyde (4.0 g, 19.1 mmol) was dissolved in 1,4-dioxane (8 mL) and hydrazine (7.2 mL, 229 mmol) was added. The vial was sealed and heated under microwave irradiation at 160° C. for 30 min. The reaction was quenched with water and extracted with EtOAc. The organic layer was washed with brine then dried over MgSO4 and concentrated. The residue was purified by silica gel chromatography with 50% to 100% EtOAc/heptane to provide 1.38 g (38%) of 4,6-dichloro-1H-indazole as a white solid. 1H NMR (CDCl3, 300 MHz): δ (ppm) 8.14 (s, 1H), 7.44 (s, 1H), 7.20 (d, J=1.5 Hz, 15H). The vial was sealed The reaction was quenched with water extracted with EtOAc The organic layer was washed with brine then dried over MgSO4 concentrated The residue was purified by silica gel chromatography with 50% to 100% EtOAc/heptane

反応条件: temp:160.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: In a microwave vial 2,4,6-trichlorobenzaldehyde (4.0 g, 19.1 mmol) was dissolved in 1,4-dioxane (8 mL) and hydrazine (7.2 mL, 229 mmol) was added. The vial was sealed and heated under microwave irradiation at 160° C. for 30 min. The reaction was quenched with water and extracted with EtOAc. The organic layer was washed with brine then dried over MgSO4 and concentrated. The residue was purified by silica gel chromatography with 50% to 100% EtOAc/heptane to provide 1.38 g (38%) of 4,6-dichloro-1H-indazole as a white solid. 1H NMR (CDCl3, 300 MHz): δ (ppm) 8.14 (s, 1H), 7.44 (s, 1H), 7.20 (d, J=1.5 Hz, 15H). The vial was sealed The reaction was quenched with water extracted with EtOAc The organic layer was washed with brine then dried over MgSO4 concentrated The residue was purified by silica gel chromatography with 50% to 100% EtOAc/heptane

反応条件: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 2,4,6-Trichlorobenzaldehyde was prepared according to the procedure outlined in Synthesis 2008, 279. To a solution of 1,3,5-trichlorobenzene (10.0 g, 55.1 mmol) in THF (200 ml) at −78° C. was slowly added n-BuLi (1.6 M in hexanes, 34.4 ml, 55.1 mmol) over 20 min. The reaction mixture was stirred at −78° C. for 30 min then DMF (7.5 ml, 96.4 mmol) was added dropwise. The reaction was stirred at −78° C. for an additional 1.5 h then quenched with 3 N HCl (200 ml) and warmed to room temperature. The mixture was extracted with EtOAc. The organic layer was washed with sat NaHCO3 and brine then dried over MgSO4 and concentrated to afford 10.7 g (93%) of 2,4,6-trichlorobenzaldehyde as a white solid. 2,4,6-Trichlorobenzaldehyde was prepared outlined in Synthesis 2008, 279 at −78° C. over 20 min The reaction was stirred at −78° C. for an additional 1.5 h then quenched with 3 N HCl (200 ml) warmed to room temperature The mixture was extracted with EtOAc The organic layer was washed with sat NaHCO3 and brine then dried over MgSO4 concentrated

反応条件: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 2,4,6-Trichlorobenzaldehyde was prepared according to the procedure outlined in Synthesis 2008, 279. To a solution of 1,3,5-trichlorobenzene (10.0 g, 55.1 mmol) in THF (200 ml) at −78° C. was slowly added n-BuLi (1.6 M in hexanes, 34.4 ml, 55.1 mmol) over 20 min. The reaction mixture was stirred at −78° C. for 30 min then DMF (7.5 ml, 96.4 mmol) was added dropwise. The reaction was stirred at −78° C. for an additional 1.5 h then quenched with 3 N HCl (200 ml) and warmed to room temperature. The mixture was extracted with EtOAc. The organic layer was washed with sat NaHCO3 and brine then dried over MgSO4 and concentrated to afford 10.7 g (93%) of 2,4,6-trichlorobenzaldehyde as a white solid. 2,4,6-Trichlorobenzaldehyde was prepared outlined in Synthesis 2008, 279 at −78° C. over 20 min The reaction was stirred at −78° C. for an additional 1.5 h then quenched with 3 N HCl (200 ml) warmed to room temperature The mixture was extracted with EtOAc The organic layer was washed with sat NaHCO3 and brine then dried over MgSO4 concentrated

反応条件: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Add 2,4,6-trichlorobenzonitrile (206 mg, 1.0 mmol) to 96% formic acid (5 mL, 96%) and water (1 mL). Add nichol/aluminum alloy (206 mg) to the mixture. Heat at 100° C. for 4 hours. Dilute with ethyl acetate and filter through Celite®. Extract the filtrate with 1 N sodium hydroxide and saturated aqueous sodium chloride, dry (sodium sulfate), filter, and concentrate to give 2,4,6-trichlorobenzaldehyde (195 mg, 93%). 1H NMR (400 MHz, CDCl3) δ 10.36 (s, 1H), 7.99 (s, 1H), 7.61 (s, 1H). filter through Celite® Extract the filtrate with 1 N sodium hydroxide and saturated aqueous sodium chloride dry (sodium sulfate) filter concentrate

反応条件: temp:160.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: In a microwave vial 2,4,6-trichlorobenzaldehyde (4.0 g, 19.1 mmol) was dissolved in 1,4-dioxane (8 mL) and hydrazine (7.2 mL, 229 mmol) was added. The vial was sealed and heated under microwave irradiation at 160° C. for 30 min. The reaction was quenched with water and extracted with EtOAc. The organic layer was washed with brine then dried over MgSO4 and concentrated. The residue was purified by silica gel chromatography with 50% to 100% EtOAc/heptane to provide 1.38 g (38%) of 4,6-dichloro-1H-indazole as a white solid. 1H NMR (CDCl3, 300 MHz): δ (ppm) 8.14 (s, 1H), 7.44 (s, 1H), 7.20 (d, J=1.5 Hz, 15H). The vial was sealed The reaction was quenched with water extracted with EtOAc The organic layer was washed with brine then dried over MgSO4 concentrated The residue was purified by silica gel chromatography with 50% to 100% EtOAc/heptane

反応条件: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 2,4,6-Trichlorobenzaldehyde was prepared according to the procedure outlined in Synthesis 2008, 279. To a solution of 1,3,5-trichlorobenzene (10.0 g, 55.1 mmol) in THF (200 ml) at −78° C. was slowly added n-BuLi (1.6 M in hexanes, 34.4 ml, 55.1 mmol) over 20 min. The reaction mixture was stirred at −78° C. for 30 min then DMF (7.5 ml, 96.4 mmol) was added dropwise. The reaction was stirred at −78° C. for an additional 1.5 h then quenched with 3 N HCl (200 ml) and warmed to room temperature. The mixture was extracted with EtOAc. The organic layer was washed with sat NaHCO3 and brine then dried over MgSO4 and concentrated to afford 10.7 g (93%) of 2,4,6-trichlorobenzaldehyde as a white solid. 2,4,6-Trichlorobenzaldehyde was prepared outlined in Synthesis 2008, 279 at −78° C. over 20 min The reaction was stirred at −78° C. for an additional 1.5 h then quenched with 3 N HCl (200 ml) warmed to room temperature The mixture was extracted with EtOAc The organic layer was washed with sat NaHCO3 and brine then dried over MgSO4 concentrated

反応条件: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Meldrum's acid (2.06 g, 14.32 mmoles) was added to TEAF (7.05 ml) at ambient temperature under stirring and the reaction mixture was kept under nitrogen atmosphere. After 10 min 2,4,6-trichloro benzaldehyde (3 g, 14.32 mmoles) was added to the reaction mixture. It was then refluxed at 120° C. for 3 hrs. On completion of the reaction, the mixture was cooled at ambient and was poured into ice water (50 ml). Then aq. layer was extracted with ethyl acetate (3×80 ml), the combined organic layer was washed with brine (40 ml) and dried over sodium sulphate. Organic layer was concentrated under vacuum. 3.10 g (86.0% of theory) of 3-(2,4,6-trichloro-phenyl)-propionic acid was obtained in form of a white solid. On completion of the reaction the mixture was cooled at ambient and Then aq. layer was extracted with ethyl acetate (3×80 ml) the combined organic layer was washed with brine (40 ml) dried over sodium sulphate Organic layer was concentrated under vacuum

反応条件: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a stirred solution of 2,4,6-trichloro-benzaldehyde (19 g, 90.69 mmol) and ammonium acetate (16.75 g, 217 mmol) in acetic acid (76 ml, 4 Vol.), nitroethane (45.1 ml, 625 mmol) was added in drops at a temperature of 0° C. The reaction mass was stirred at a temperature of 100° C. for 90 minutes. When the TLC confirmed the completion of the reaction, the reaction mass was allowed to attain ambient temperature and was diluted with ice cold water (700 ml), further aqueous layer was then extracted with ethyl acetate (3×50 ml). Combined ethyl acetate layer was washed with saturated sodium bicarbonate solution to neutral pH, then with water, followed by brine wash and dried under anhydrous Na2SO4 before the complete evaporation of solvents. The resulting crude mass was purified by column chromatography using 60-120μ mesh silica gel and product collected at 1% ethyl acetate in hexane as elution system to give 1,3,5-trichloro-2-((E)-2-nitro-propenyl)-benzene (15 g, 61%) the completion of the reaction to attain ambient temperature was then extracted with ethyl acetate (3×50 ml) Combined ethyl acetate layer was washed with saturated sodium bicarbonate solution to neutral pH wash dried under anhydrous Na2SO4 before the complete evaporation of solvents The resulting crude mass was purified by column chromatography collected at 1% ethyl acetate in hexane as elution system

反応条件: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a stirred solution of 2,4,6-trichloro-benzaldehyde (19 g, 90.69 mmol) and ammonium acetate (16.75 g, 217 mmol) in acetic acid (76 ml, 4 Vol.), nitroethane (45.1 ml, 625 mmol) was added in drops at a temperature of 0° C. The reaction mass was stirred at a temperature of 100° C. for 90 minutes. When the TLC confirmed the completion of the reaction, the reaction mass was allowed to attain ambient temperature and was diluted with ice cold water (700 ml), further aqueous layer was then extracted with ethyl acetate (3×50 ml). Combined ethyl acetate layer was washed with saturated sodium bicarbonate solution to neutral pH, then with water, followed by brine wash and dried under anhydrous Na2SO4 before the complete evaporation of solvents. The resulting crude mass was purified by column chromatography using 60-120μ mesh silica gel and product collected at 1% ethyl acetate in hexane as elution system to give 1,3,5-trichloro-2-((E)-2-nitro-propenyl)-benzene (15 g, 61%) the completion of the reaction to attain ambient temperature was then extracted with ethyl acetate (3×50 ml) Combined ethyl acetate layer was washed with saturated sodium bicarbonate solution to neutral pH wash dried under anhydrous Na2SO4 before the complete evaporation of solvents The resulting crude mass was purified by column chromatography collected at 1% ethyl acetate in hexane as elution system