(4-bromophenyl)hydrazine

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: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:; See reaction.notes.procedure_details.

実験手順: To a 500 mL flask were added p-bromophenylhydrazine 1 (50.3 g, 0.27 mol) glacial acetic acid (300 mL) and 3-methylbutanone (40 mL, 0.37 mol). The mixture was heated at reflux for 4 h and then cooled to rt. The volatile components were removed in vacuo and the residue was partitioned between petroleum ether (350 mL) and water (100 mL). The aqueous phase was washed again with petroleum ether (2×100 mL). The combined organic solutions were dried (MgSO4) and filtered and the solvent was evaporated in vacuo to afford 5-bromo-2,3,3-trimethyl-3H-indole 2 (56.3 g, 87%). The mixture was heated at reflux for 4 h The volatile components were removed in vacuo the residue was partitioned between petroleum ether (350 mL) and water (100 mL) The aqueous phase was washed again with petroleum ether (2×100 mL) The combined organic solutions were dried (MgSO4) filtered the solvent was evaporated in vacuo

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

実験手順: To a 500 mL flask were added p-bromophenylhydrazine 1 (50.3 g, 0.27 mol) glacial acetic acid (300 mL) and 3-methylbutanone (40 mL, 0.37 mol). The mixture was heated at reflux for 4 h and then cooled to rt. The volatile components were removed in vacuo and the residue was partitioned between petroleum ether (350 mL) and water (100 mL). The aqueous phase was washed again with petroleum ether (2×100 mL). The combined organic solutions were dried (MgSO4) and filtered and the solvent was evaporated in vacuo to afford 5-bromo-2,3,3-trimethyl-3H-indole 2 (56.3 g, 87%). The mixture was heated at reflux for 4 h The volatile components were removed in vacuo the residue was partitioned between petroleum ether (350 mL) and water (100 mL) The aqueous phase was washed again with petroleum ether (2×100 mL) The combined organic solutions were dried (MgSO4) filtered the solvent was evaporated in vacuo

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

実験手順: To a 1 L flask were added finely powdered p-bromoaniline (69 g, 0.4 mol), water (200 mL) and conc. HCl (100 mL, 1.2 mol). The mixture was cooled in an ice bath to less than 5° C. A solution of sodium nitrite (30 g, 0.43 mol) in water (90 mL) was added dropwise to the aniline suspension over approx. 1 h, while maintaining the temperature at less than 5° C. The mixture was stirred for a further 30 min and then was gravity filtered through a No. 1 paper into a chilled flask. The solution was added in small portions to a solution of 92% ammonium sulfite (118 g, 0.8 mol) in water (250 mL), which had been chilled to 0° C., at a rate such that the temperature remained at less than 5° C. (approx. 1 h). During the addition a yellow solid formed in the mixture. After the addition was completed, stirring was continued for 1 h at 0° C. and the mixture was then allowed to warm to rt. The solid was filtered off and the filtrate was treated with conc. HCl (120 mL). The solution was heated to reflux during which time a solid formed and then mostly dissolved. The hot solution was filtered and then allowed to cool to rt before chilling in a refrigerator overnight. The crystals were filtered off and were washed with 1 M HCl (60 mL). The solid was added to a mixture of DCM (1 L) and 1N sodium hydroxide (600 mL) and the suspension was shaken until the solid dissolved. The layers were separated and the aqueous phase was washed again with DCM (2×400 mL). The combined organic solutions were dried (MgSO4), filtered and the solvent was evaporated in vacuo to afford p-bromophenylhydrazine (50.3 g, 67%). The mixture was cooled in an ice bath to less than 5° C while maintaining the temperature at less than 5° C filtered through a No remained at less than 5° C. (approx. 1 h) During the addition a yellow solid formed in the mixture After the addition stirring was continued for 1 h at 0° C. to warm to rt The solid was filtered off the filtrate was treated with conc. HCl (120 mL) The solution was heated to reflux during which time a solid formed mostly dissolved The hot solution was filtered to cool to rt before chilling in a refrigerator overnight The crystals were filtered off were washed with 1 M HCl (60 mL) The solid was added to a mixture of DCM (1 L) and 1N sodium hydroxide (600 mL) the suspension was shaken until the solid dissolved The layers were separated the aqueous phase was washed again with DCM (2×400 mL) The combined organic solutions were dried (MgSO4) filtered the solvent was evaporated in vacuo

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

実験手順: To a 1 L flask were added finely powdered p-bromoaniline (69 g, 0.4 mol), water (200 mL) and conc. HCl (100 mL, 1.2 mol). The mixture was cooled in an ice bath to less than 5° C. A solution of sodium nitrite (30 g, 0.43 mol) in water (90 mL) was added dropwise to the aniline suspension over approx. 1 h, while maintaining the temperature at less than 5° C. The mixture was stirred for a further 30 min and then was gravity filtered through a No. 1 paper into a chilled flask. The solution was added in small portions to a solution of 92% ammonium sulfite (118 g, 0.8 mol) in water (250 mL), which had been chilled to 0° C., at a rate such that the temperature remained at less than 5° C. (approx. 1 h). During the addition a yellow solid formed in the mixture. After the addition was completed, stirring was continued for 1 h at 0° C. and the mixture was then allowed to warm to rt. The solid was filtered off and the filtrate was treated with conc. HCl (120 mL). The solution was heated to reflux during which time a solid formed and then mostly dissolved. The hot solution was filtered and then allowed to cool to rt before chilling in a refrigerator overnight. The crystals were filtered off and were washed with 1 M HCl (60 mL). The solid was added to a mixture of DCM (1 L) and 1N sodium hydroxide (600 mL) and the suspension was shaken until the solid dissolved. The layers were separated and the aqueous phase was washed again with DCM (2×400 mL). The combined organic solutions were dried (MgSO4), filtered and the solvent was evaporated in vacuo to afford p-bromophenylhydrazine (50.3 g, 67%). The mixture was cooled in an ice bath to less than 5° C while maintaining the temperature at less than 5° C filtered through a No remained at less than 5° C. (approx. 1 h) During the addition a yellow solid formed in the mixture After the addition stirring was continued for 1 h at 0° C. to warm to rt The solid was filtered off the filtrate was treated with conc. HCl (120 mL) The solution was heated to reflux during which time a solid formed mostly dissolved The hot solution was filtered to cool to rt before chilling in a refrigerator overnight The crystals were filtered off were washed with 1 M HCl (60 mL) The solid was added to a mixture of DCM (1 L) and 1N sodium hydroxide (600 mL) the suspension was shaken until the solid dissolved The layers were separated the aqueous phase was washed again with DCM (2×400 mL) The combined organic solutions were dried (MgSO4) filtered the solvent was evaporated in vacuo

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

実験手順: 3-Methylbutanal (0.921 g, 10.69 mmol) was added to a solution of (4-bromophenyl)hydrazine (2 g, 10.69 mmol) in acetic acid (100 mL) at 80° C., and the mixture was stirred for 3 h at 120° C. The reaction mixture was concentrated to get the residue, and the residue was partitioned between ethyl acetate and water. Organic layer was separated, washed with saturated bicarbonate solution and brine, dried over sodium sulphate and filtered. The filtrate was concentrated in vacuo and purified by flash chromatography using 2% ethyl acetate in pet ether to afford title compound (1.1 g, 38.4%) as an oil. 1H NMR (400 MHz, CDCl3): δ 7.91 (bs, 1H), 7.76 (m, 1H), 7.25-7.20 (m, 2H), 6.95 (d, J=2.4 Hz, 1H), 3.18-3.11 (m, 1H), 1.35 (d, J=6.8 Hz, 6H). The reaction mixture was concentrated to get the residue the residue was partitioned between ethyl acetate and water Organic layer was separated washed with saturated bicarbonate solution and brine dried over sodium sulphate filtered The filtrate was concentrated in vacuo purified by flash chromatography

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

実験手順: The title compound was prepared by the reaction of 4-bromophenylhydrazine with acrylonitrile in the presence of a suitable base such as sodium ethoxide in refluxing ethanol followed by oxidation with N-bromosuccinimide; 1H NMR (300 MHz, DMSO-d6) δ 3.81 (br s, 2H), 5.84 (s, 1H), 7.41 (d, J=8.7 Hz, 2H), 7.47 (d, J=8.7 Hz, 2H), 7.63 (s, 1H).

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

実験手順: Water (20 ml) was added to a flask containing glyoxal (2.0 g, 14 mmmol). Hydroxylamine.HCl (958 mg, 13.8 mmol) and sodium carbonate (1.53 g, 14.5 mmmol) were added in one portion to the glyoxal flask (CO2 evolution observed). The reaction mixture was stirred at RT for 20 minutes (reaction mixture turned yellow). Methanol (40 ml) was added to the reaction mixture and 4-bromophenyl hydrazine.HCl (3.1 g, 13.8 mmole) was added portionwise under ice cooling. The reaction mixture was then stirred at rt for 30 min. Copper (II) sulfate.hexahydrate (20 g, 78 mmol) was was added to the reaction mixture. A water: pyridine (1:1) mixture (200 ml) was added then heated at 90° C. for 16 hours. The reaction mixture was cooled and adjusted to pH=3 with 6N HCl (approx 200 ml). The mixture was filtered through celite to remove insolubles. The celite was washed with additional ethyl acetate (1000 ml). The organic layer was separated and the product extracted additionally from the aqueous layer with EtOAc (3×250). The organic phases were combined, dried over potassium carbonate, filtered and concentrated to approximately half the volume. This material was then filtered through a silica pad (approx 6 in). Silica was washed with an additional 300 ml of ethyl acetate. The solvent was then concentrated in vacuo. The crude material was purified by chromatography on silica gel (4:1 heptane: EtOAc to 3:1 heptane: EtOAc). Concentrated fractions furnished a light tan solid (1.0 g, 30% TY). MS (LC/MS) m/z 240.1 (M+1). 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 7.47 (d, J=0.98 Hz, 1H) 7.65-7.69 (m, 2H) 7.73 (d, J=0.78 Hz, 1H) 7.86-7.90 (m, 2H) (reaction mixture turned yellow) The reaction mixture was then stirred at rt for 30 min then heated at 90° C. for 16 hours The reaction mixture was cooled The mixture was filtered through celite to remove insolubles The celite was washed with additional ethyl acetate (1000 ml) The organic layer was separated the product extracted additionally from the aqueous layer with EtOAc (3×250) dried over potassium carbonate filtered concentrated to approximately half the volume This material was then filtered through a silica pad (approx 6 in) Silica was washed with an additional 300 ml of ethyl acetate The solvent was then concentrated in vacuo The crude material was purified by chromatography on silica gel (4:1 heptane: EtOAc to 3:1 heptane: EtOAc) Concentrated fractions furnished a light tan solid (1.0 g, 30% TY)