ethyl 2-chloro-2-[(4-chlorophenyl)hydrazinylidene]acetate

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: Part B: To a stirred boiling solution of ethyl 2-chloro[(4-chlorophenyl) hydrazono]acetate (22.95 gram, 0.088 mol) and styrene (30.3 ml, 0.264 mol) in benzene (140 ml) is added triethylamine (34.3 ml, 0.247 mol) and the resulting solution is heated at reflux temperature for 1 hour. The resulting solution is cooled to room temperature and the formed precipitate is removed by filtration and washed with toluene. The filtrate is concentrated in vacuo and purified by flash chromatography (silica gel, dichloromethane) to give ethyl 1-(4-chlorophenyl)-5-phenyl-4,5-dihydro-(1H)-pyrazole-3-carboxylate (27.2 gram, 94% yield) as a syrup which slowly solidifies on standing. 1H-NMR (200 MHz, CDCl3): 1.38 (t, J=7 Hz, 3H), 3.06 (dd, J=18 and 7 Hz, 1H), 3.73 (dd, J=18 and 13 Hz, 1H), 4.33 (q, J=7 Hz, 2H), 5.38 (dd, J=13 and 7 Hz, 1H), 7.02 (br d, J=8 Hz, 2H), 7.08-7.40 (m, 7H). the resulting solution is heated at reflux temperature for 1 hour the formed precipitate is removed by filtration washed with toluene The filtrate is concentrated in vacuo purified by flash chromatography (silica gel, dichloromethane)

反応条件: temp:2.51; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Part A: To a stirred solution of 4-chloroaniline (15.68 gram, 0.123 mol) in ice (30 ml) and concentrated hydrochloric acid (30 ml) is slowly added a solution of NaNO2 (9.0 gram, 0.13 mol) in water (16 ml) and the resulting solution is stirred for 1Hour at 0-5° C. and subsequently added to a cold mixture of NaOAc (32 gram, 0.39 mol), ethanol (520 ml) and ethyl 2-chloro-3-oxobutanoate (16.6 ml, 0.12 mol). After stirring the resulting mixture for 1 hour the formed precipitate is collected by filtration, washed with ethanol and dried in vacuo to give ethyl 2-chloro[(4-chlorophenyl)hydrazono]acetate (22.99 gram, 73% yield). Melting point: 147.5-149.5° C. 1H-NMR (200 MHz, CDCl3): 1.40 (t, J=7 Hz, 3H), 4.39 (q, J=7 Hz, 2H), 7.16 (br d, J=8 Hz, 2H), 7.30 (br d, J=8 Hz, 2H), 8.31 (br s, 1H). After stirring the resulting mixture for 1 hour the formed precipitate is collected by filtration washed with ethanol dried in vacuo

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: Part B: To a stirred boiling solution of ethyl 2-chloro[(4-chlorophenyl) hydrazono]acetate (22.95 gram, 0.088 mol) and styrene (30.3 ml, 0.264 mol) in benzene (140 ml) is added triethylamine (34.3 ml, 0.247 mol) and the resulting solution is heated at reflux temperature for 1 hour. The resulting solution is cooled to room temperature and the formed precipitate is removed by filtration and washed with toluene. The filtrate is concentrated in vacuo and purified by flash chromatography (silica gel, dichloromethane) to give ethyl 1-(4-chlorophenyl)-5-phenyl-4,5-dihydro-(1H)-pyrazole-3-carboxylate (27.2 gram, 94% yield) as a syrup which slowly solidifies on standing. 1H-NMR (200 MHz, CDCl3): 1.38 (t, J=7 Hz, 3H), 3.06 (dd, J=18 and 7 Hz, 1H), 3.73 (dd, J=18 and 13 Hz, 1H), 4.33 (q, J=7 Hz, 2H), 5.38 (dd, J=13 and 7 Hz, 1H), 7.02 (br d, J=8 Hz, 2H), 7.08-7.40 (m, 7H). the resulting solution is heated at reflux temperature for 1 hour the formed precipitate is removed by filtration washed with toluene The filtrate is concentrated in vacuo purified by flash chromatography (silica gel, dichloromethane)

反応条件: temp:2.51; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Part A: To a stirred solution of 4-chloroaniline (15.68 gram, 0.123 mol) in ice (30 ml) and concentrated hydrochloric acid (30 ml) is slowly added a solution of NaNO2 (9.0 gram, 0.13 mol) in water (16 ml) and the resulting solution is stirred for 1Hour at 0-5° C. and subsequently added to a cold mixture of NaOAc (32 gram, 0.39 mol), ethanol (520 ml) and ethyl 2-chloro-3-oxobutanoate (16.6 ml, 0.12 mol). After stirring the resulting mixture for 1 hour the formed precipitate is collected by filtration, washed with ethanol and dried in vacuo to give ethyl 2-chloro[(4-chlorophenyl)hydrazono]acetate (22.99 gram, 73% yield). Melting point: 147.5-149.5° C. 1H-NMR (200 MHz, CDCl3): 1.40 (t, J=7 Hz, 3H), 4.39 (q, J=7 Hz, 2H), 7.16 (br d, J=8 Hz, 2H), 7.30 (br d, J=8 Hz, 2H), 8.31 (br s, 1H). After stirring the resulting mixture for 1 hour the formed precipitate is collected by filtration washed with ethanol dried in vacuo

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

実験手順: The compound of Example 6 (1.0 gm) was converted to the title compound (0.6 gm) by adaptation of the procedure of Example 9 to 4-chloro-α-methyl styrene (2.5 ml). The product was a yellow oil. NMR (CDCl3) 7.3-6.8 (m, ArH, 8H), 4.3 (q, 2H, CH2), 3.3 (m, 2H, CH2), 1.8 (s, 3H, CH3), 1.3 (t, 3H, CH3).

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

実験手順: The compound of Example 6 (5.0 gm) was heated in refluxing benzene (30 ml) containing 4-chlorostyrene (7.0 ml). Addition of a benzene (10 ml) solution of triethylamine(7.5 ml) was followed by one hour of continued heating. The cooled mixture was filtered, rotovapped, and dried on the vacuum pump to remove excess styrene. The residual solid was recrystallized from hexane/benzene (charcoal) to give the title compound (6.3 gm); m.p.: 128° to 130° C. NMR (CDCl3) 7.3-6.9 (m, 8H, ArH), 5.4 (dd, 1H, CH), 4.3 (q, 2H, OCH2), 3.8 (m, 1H, CH), 3.0 (m, 1H, CH), 1.38 (t, 3H, CH3). The cooled mixture was filtered dried on the vacuum pump to remove excess styrene The residual solid was recrystallized from hexane/benzene (charcoal)

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: Part B: To a stirred boiling solution of ethyl 2-chloro[(4-chlorophenyl) hydrazono]acetate (22.95 gram, 0.088 mol) and styrene (30.3 ml, 0.264 mol) in benzene (140 ml) is added triethylamine (34.3 ml, 0.247 mol) and the resulting solution is heated at reflux temperature for 1 hour. The resulting solution is cooled to room temperature and the formed precipitate is removed by filtration and washed with toluene. The filtrate is concentrated in vacuo and purified by flash chromatography (silica gel, dichloromethane) to give ethyl 1-(4-chlorophenyl)-5-phenyl-4,5-dihydro-(1H)-pyrazole-3-carboxylate (27.2 gram, 94% yield) as a syrup which slowly solidifies on standing. 1H-NMR (200 MHz, CDCl3): 1.38 (t, J=7 Hz, 3H), 3.06 (dd, J=18 and 7 Hz, 1H), 3.73 (dd, J=18 and 13 Hz, 1H), 4.33 (q, J=7 Hz, 2H), 5.38 (dd, J=13 and 7 Hz, 1H), 7.02 (br d, J=8 Hz, 2H), 7.08-7.40 (m, 7H). the resulting solution is heated at reflux temperature for 1 hour the formed precipitate is removed by filtration washed with toluene The filtrate is concentrated in vacuo purified by flash chromatography (silica gel, dichloromethane)

反応条件: temp:2.51; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Part A: To a stirred solution of 4-chloroaniline (15.68 gram, 0.123 mol) in ice (30 ml) and concentrated hydrochloric acid (30 ml) is slowly added a solution of NaNO2 (9.0 gram, 0.13 mol) in water (16 ml) and the resulting solution is stirred for 1Hour at 0-5° C. and subsequently added to a cold mixture of NaOAc (32 gram, 0.39 mol), ethanol (520 ml) and ethyl 2-chloro-3-oxobutanoate (16.6 ml, 0.12 mol). After stirring the resulting mixture for 1 hour the formed precipitate is collected by filtration, washed with ethanol and dried in vacuo to give ethyl 2-chloro[(4-chlorophenyl)hydrazono]acetate (22.99 gram, 73% yield). Melting point: 147.5-149.5° C. 1H-NMR (200 MHz, CDCl3): 1.40 (t, J=7 Hz, 3H), 4.39 (q, J=7 Hz, 2H), 7.16 (br d, J=8 Hz, 2H), 7.30 (br d, J=8 Hz, 2H), 8.31 (br s, 1H). After stirring the resulting mixture for 1 hour the formed precipitate is collected by filtration washed with ethanol dried in vacuo