(4-chloro-2-fluorophenyl)hydrazine

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: 8.0 Parts of 4-chloro-2-fluorophenylhydrazine and 9.2 parts of ethyl 2-cyclohexanoneacetate [bp 92°-93°, 0.5 mm Hg; prepared by the method described by A. Sergre, et al., J. Amer. Chem. Soc., 79 3503 (1957)] were dissolved in 75 parts of glacial acetic acid, and the resulting solution was refluxed for 16 hours. The reaction solvent was removed under a reduced pressure of 300 mm Hg, and the residual brown oil was dissolved in 150 parts of methylene chloride. The organic solution was washed with saturated aqueous sodium bicarbonate solution, dried with anhydrous magnesium sulfate and the solvent was removed under a reduced pressure of 300 mm Hg to give 2-(4-chloro-2-fluorophenyl)-4,4a,5,6,7,8-hexahydro-3(2H)-cinnolinone as a brown oil that solidified on scratching. Purification was achieved by recrystallization from cyclohexane to yield 5.9 parts of tan solid, mp 110°-112°. prepared by the method the resulting solution was refluxed for 16 hours The reaction solvent was removed under a reduced pressure of 300 mm Hg the residual brown oil was dissolved in 150 parts of methylene chloride The organic solution was washed with saturated aqueous sodium bicarbonate solution dried with anhydrous magnesium sulfate the solvent was removed under a reduced pressure of 300 mm Hg

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

実験手順: 8.0 Parts of 4-chloro-2-fluorophenylhydrazine and 9.2 parts of ethyl 2-cyclohexanoneacetate [bp 92°-93°, 0.5 mm Hg; prepared by the method described by A. Sergre, et al., J. Amer. Chem. Soc., 79 3503 (1957)] were dissolved in 75 parts of glacial acetic acid, and the resulting solution was refluxed for 16 hours. The reaction solvent was removed under a reduced pressure of 300 mm Hg, and the residual brown oil was dissolved in 150 parts of methylene chloride. The organic solution was washed with saturated aqueous sodium bicarbonate solution, dried with anhydrous magnesium sulfate and the solvent was removed under a reduced pressure of 300 mm Hg to give 2-(4-chloro-2-fluorophenyl)-4,4a,5,6,7,8-hexahydro-3(2H)-cinnolinone as a brown oil that solidified on scratching. Purification was achieved by recrystallization from cyclohexane to yield 5.9 parts of tan solid, mp 110°-112°. prepared by the method the resulting solution was refluxed for 16 hours The reaction solvent was removed under a reduced pressure of 300 mm Hg the residual brown oil was dissolved in 150 parts of methylene chloride The organic solution was washed with saturated aqueous sodium bicarbonate solution dried with anhydrous magnesium sulfate the solvent was removed under a reduced pressure of 300 mm Hg

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

実験手順: Alternatively, 4-chloro-2-fluorophenyl hydrazine is prepared by the following method. 43.7 parts of 4-chloro-2-fluoroaniline was dissolved in 735 parts of concentrated hydrochloric acid. The solution was cooled to 0°-5° C. and a solution of 22.8 parts of sodium nitrite in 187 parts water was added dropwise maintaining the temperature of the reaction between 0°-5°. The excess nitrite was destroyed by the addition of small amounts of sulfamic acid until a negative test with sulfone reagent was obtained. To the solution of the diazonium salt was added, as rapidly as possible, a solution of 170 parts stannous chloride dihydrate in 275 parts of concentrated hydrochloric acid, precooled to -50°. When the addition was complete, a heavy white precipitate formed. The reaction mixture was allowed to warm to ambient temperature over one hour. The precipitate was collected by filtration, then suspended in 750 parts ice-water. The pH of the solution was adjusted to 11 by the addition of 50% aqueous sodium hydroxide. The resulting aqueous suspension was extracted three times; 200 parts of methylene chloride was used for each extraction. The combined organic extracts were dried with anhydrous magnesium sulfate, and the solvent removed under reduced pressure of 300 mm Hg to leave 38.5 parts of pinkish-tan crystalline 4-chloro-2-fluoro-phenylhydrazine, mp 51°-63°. Alternatively, 4-chloro-2-fluorophenyl hydrazine is prepared by the following method The solution was cooled to 0°-5° C. maintaining the temperature of the reaction between 0°-5° The excess nitrite was destroyed by the addition of small amounts of sulfamic acid until a negative test with sulfone reagent was obtained precooled to -50° When the addition a heavy white precipitate formed The precipitate was collected by filtration The pH of the solution was adjusted to 11 by the addition of 50% aqueous sodium hydroxide The resulting aqueous suspension was extracted three times 200 parts of methylene chloride was used for each extraction The combined organic extracts were dried with anhydrous magnesium sulfate the solvent removed under reduced pressure of 300 mm Hg

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

実験手順: Six parts of 4-chloro-2-fluorophenyl hydrazine hydrochloride was shaken with 100 parts of methylene chloride and 100 parts of 1-molar aqueous sodium hydroxide for one to two minutes until a clear two-phase solution was obtained. The organic phase was washed three times with 60 parts of water, dried with anhydrous magnesium sulfate, and evaporated under a reduced pressure of 50 to 300 mm Hg. to give 3.8 parts of pale tan 4-chloro-2-fluorophenyl hydrazine, m.p. 57°-63° C. was obtained The organic phase was washed three times with 60 parts of water dried with anhydrous magnesium sulfate evaporated under a reduced pressure of 50 to 300 mm Hg

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

実験手順: Six parts of 4-chloro-2-fluorophenyl hydrazine hydrochloride was shaken with 100 parts of methylene chloride and 100 parts of 1-molar aqueous sodium hydroxide for one to two minutes until a clear two-phase solution was obtained. The organic phase was washed three times with 60 parts of water, dried with anhydrous magnesium sulfate, and evaporated under a reduced pressure of 50 to 300 mm Hg. to give 3.8 parts of pale tan 4-chloro-2-fluorophenyl hydrazine, m.p. 57°-63° C. was obtained The organic phase was washed three times with 60 parts of water dried with anhydrous magnesium sulfate evaporated under a reduced pressure of 50 to 300 mm Hg

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

実験手順: 8.0 Parts of 4-chloro-2-fluorophenylhydrazine and 9.2 parts of ethyl 2-cyclohexanoneacetate [bp 92°-93°, 0.5 mm Hg; prepared by the method described by A. Sergre, et al., J. Amer. Chem. Soc., 79 3503 (1957)] were dissolved in 75 parts of glacial acetic acid, and the resulting solution was refluxed for 16 hours. The reaction solvent was removed under a reduced pressure of 300 mm Hg, and the residual brown oil was dissolved in 150 parts of methylene chloride. The organic solution was washed with saturated aqueous sodium bicarbonate solution, dried with anhydrous magnesium sulfate and the solvent was removed under a reduced pressure of 300 mm Hg to give 2-(4-chloro-2-fluorophenyl)-4,4a,5,6,7,8-hexahydro-3(2H)-cinnolinone as a brown oil that solidified on scratching. Purification was achieved by recrystallization from cyclohexane to yield 5.9 parts of tan solid, mp 110°-112°. prepared by the method the resulting solution was refluxed for 16 hours The reaction solvent was removed under a reduced pressure of 300 mm Hg the residual brown oil was dissolved in 150 parts of methylene chloride The organic solution was washed with saturated aqueous sodium bicarbonate solution dried with anhydrous magnesium sulfate the solvent was removed under a reduced pressure of 300 mm Hg

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

実験手順: Alternatively, 4-chloro-2-fluorophenyl hydrazine is prepared by the following method. 43.7 parts of 4-chloro-2-fluoroaniline was dissolved in 735 parts of concentrated hydrochloric acid. The solution was cooled to 0°-5° C. and a solution of 22.8 parts of sodium nitrite in 187 parts water was added dropwise maintaining the temperature of the reaction between 0°-5°. The excess nitrite was destroyed by the addition of small amounts of sulfamic acid until a negative test with sulfone reagent was obtained. To the solution of the diazonium salt was added, as rapidly as possible, a solution of 170 parts stannous chloride dihydrate in 275 parts of concentrated hydrochloric acid, precooled to -50°. When the addition was complete, a heavy white precipitate formed. The reaction mixture was allowed to warm to ambient temperature over one hour. The precipitate was collected by filtration, then suspended in 750 parts ice-water. The pH of the solution was adjusted to 11 by the addition of 50% aqueous sodium hydroxide. The resulting aqueous suspension was extracted three times; 200 parts of methylene chloride was used for each extraction. The combined organic extracts were dried with anhydrous magnesium sulfate, and the solvent removed under reduced pressure of 300 mm Hg to leave 38.5 parts of pinkish-tan crystalline 4-chloro-2-fluoro-phenylhydrazine, mp 51°-63°. Alternatively, 4-chloro-2-fluorophenyl hydrazine is prepared by the following method The solution was cooled to 0°-5° C. maintaining the temperature of the reaction between 0°-5° The excess nitrite was destroyed by the addition of small amounts of sulfamic acid until a negative test with sulfone reagent was obtained precooled to -50° When the addition a heavy white precipitate formed The precipitate was collected by filtration The pH of the solution was adjusted to 11 by the addition of 50% aqueous sodium hydroxide The resulting aqueous suspension was extracted three times 200 parts of methylene chloride was used for each extraction The combined organic extracts were dried with anhydrous magnesium sulfate the solvent removed under reduced pressure of 300 mm Hg

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: By substituting 4-chlorophenylhydrazine in the former procedure for 4-chloro-2-fluorophenylhydrazine, 2-(4-chlorophenyl)-1,4,5,6-tetrahydrocyclopentapyrazol-3(2H)-one was prepared, m.p. 193.5°-195°. was prepared

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

実験手順: By substituting 4-chlorophenylhydrazine in the former procedure for 4-chloro-2-fluorophenylhydrazine, 2-(4-chlorophenyl)-1,4,5,6-tetrahydrocyclopentapyrazol-3(2H)-one was prepared, m.p. 193.5°-195°. was prepared

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

実験手順: A mixture of 9.3 parts of 2-carbethoxycycloheptanone [prepared by the method of G. Stork, et al., J. Am. Chem. Soc., 85, 207 (1963)], 8.1 parts of 4-chloro-2-fluorophenyl hydrazine, 100 parts of toluene and 0.5 parts of acetic acid was refluxed for 4 hours until all water was evolved. The resulting solution was cooled to -50° and filtered to yield 12 parts of 2-(4-chloro-2-fluorophenyl)-1,4,5,6,7,8-hexahydrocycloheptapyrazol-3(2H)-one melting at 197°-201°. Four parts of the pyrazolone was mixed with 4.4 parts of phosphorous oxybromide and 2.2 parts of N,N-diethylaniline in 200 parts of xylene and the mixture refluxed for 3 hours. 0.5 Part of N,N-dimethyl formamide was added and the mixture refluxed for 1 hour. The mixture was poured over 100 parts of ice and the phases separated. The organic phase was evaporated under reduced pressure of 50 mm. Hg at 70° to a crude product. The product was dissolved in 100 parts of chloroform, washed with 100 parts of 10% aqueous sodium carbonate, dried with anhydrous magnesium sulfate and evaporated to an oil under reduced pressure of 500 mm. Hg at 40°. Purification by chromatography on alumina using 3% ether in hexane as the eluent gave 0.8 parts of 3-bromo-2-(4-chloro-2-fluorophenyl)-2,4,5,6,7,8-hexahydrocycloheptapyrazole melting at 59°-60°. prepared by the method of G The resulting solution was cooled to -50° filtered