(2,4,6-trichlorophenyl)hydrazine

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Part A: To a stirred solution of 106 g (500 mmol) of 2,4,6-trichlorophenyl hydrazine in 600 mL of absolute ethanol was added 48.1 mL (530 mmol) of isobutyraldehyde. The solution was stirred 2 h at RT and concentrated under reduced pressure to afford an oil. The crude oil was dissolved in 450 mL of dry DMF and cooled to 0° C. This solution was treated with 94.3 g (530 mmol) of NBS in four portions over 10 min. The solution was stirred 1 h at 0° C. and poured onto ice. The mixture was diluted with water and extracted with 800 mL of ether. The organic extract was washed twice with water and once with brine, dried (MgSO4), and concentrated under reduced pressure to afford an oil. In a separate flask, 44.3 g (670 mmol) of malononitrile in 140 mL of EtOH was cooled to 0° C. and treated with 252 mL (670 mmol) of 2.66 M NaOEt in EtOH over 6 min. This solution was added in four portions over 5 min. to a rapidly stirred solution of the crude bromohydrazone in 350 mL of absolute EtOH. Using a heat pistol, this solution was maintained at reflux for 10 min. further. The reaction was cooled, quenched with 5% aq. HOAc, and extracted twice with ether. The combined organic extracts were washed (brine), dried (MgSO4) and filtered over activated charcoal and celite, and concentrated under reduced pressure. The product was chromatographed on silica gel (gradient elution with 1:3 ether-hexanes and 2:1 ether-CH2Cl2) to afford 93.5 g (57%) of 5-amino-4-cyano-3-isopropyl-1-(2,4,6-trichlorophenyl)pyrazole as a white solid. 1H NMR(CDCl3, 300 MHz) δ 7.51(s, 2H); 4.28(br. s, 2H); 3.05(septet, 1H, J=7.0 Hz); 1.36(d, 6H, J=7.0 Hz). concentrated under reduced pressure to afford an oil cooled to 0° C The solution was stirred 1 h at 0° C. poured onto ice extracted with 800 mL of ether The organic extract was washed twice with water and once with brine dried (MgSO4) concentrated under reduced pressure to afford an oil this solution was maintained at reflux for 10 min. further The reaction was cooled quenched with 5% aq. HOAc extracted twice with ether The combined organic extracts were washed (brine) dried (MgSO4) filtered over activated charcoal and celite concentrated under reduced pressure The product was chromatographed on silica gel (gradient elution with 1:3 ether-hexanes and 2:1 ether-CH2Cl2)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Part A: To a stirred solution of 320 mg (1.9 mmol) of 2-cyano-3-ethoxypentenamide in 7 mL of MeOH was added 465 mg (2.2 mmol) of 2,4,6-trichlorophenylhydrazine. The solution was stirred 3 h at reflux, treated with 2 mL of water, and allowed to stir an additional 1 h, cooling to RT. The white solid which precipitated was filtered, washed with 2:1 MeOH-water, and air-dried to afford 520 mg (82%) of 5-amino-3-ethyl-1-(2,4,6-trichlorophenyl) pyrazole-4-carboxamide, mp 186-188° C., Mass Spec(CI+): 331.9989(M)+. at reflux to stir an additional 1 h The white solid which precipitated was filtered washed with 2:1 MeOH-water air-dried

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The title compound was prepared as an orange solid, m.p. 208.5-209.5° C. by the procedure of Preparation A starting with ethoxymethylenemalononitrile and 2,4,6-trichlorophenylhydrazine.

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of bis(methythio)methylenecyanoacetamide (7.800 g, 50 mmol) and 2,4,6-trichlorophenylhydrazine (10.575 g, 50 mmol) in 250 ml of methanol was heated at reflux for 2.5 hours. The mixture was cooled and water was added. Precipitate formed and filtered to give 14.323 g (81.5% yield) of the title compound as a white solid. 1H NMR(CDCl3): 2.6 (s,3H), 5.5(brs, 2H), 7.5(s,2H) ppm. Recrystallization of a small portion of the solid from chloroform gave white crystals; m. p. 198-199° C. Anal. Calc. for C11H9Cl3N4OS: C, 37.57; H, 2.58; N, 15.93; Found: C, 37.54; H, 2.51; N, 15.73. was heated at reflux for 2.5 hours The mixture was cooled Precipitate formed filtered

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: By the method of Example 3, Step C, 25.9 g (0.122 mole) of 2,4,6-trichlorophenylhydrazine and 22.7 g (0.123 mole) of ethyl 2-dimethylaminomethyleneacetoacetate were reacted in ethanol, yielding 1-(2,4,6-trichlorophenyl)-4-ethoxycarbonyl-5-methyl-1H-pyrazole as tan solid; mp 112.5°-113° C. The NMR spectrum was consistent with the proposed structure.

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 2,4,6-trichlorophenylhydrazine (21.1 g) and tetracyanoethylene (13.3 g) in ethanol (100 ml) was heated at reflux for 15 minutes. The reaction mixture was cooled and the solid precipitate was filtered off and washed with diethyl ether to give 5-amino-3,4-dicyano-1-(2,4,6-trichlorophenyl)pyrazole (13 g), as a buff colored solid, m.p. 267°-271° C. was heated at reflux for 15 minutes The reaction mixture was cooled the solid precipitate was filtered off washed with diethyl ether

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 2,4,6-trichlorophenylhydrazine (21.1 g) and tetracyanoethylene (13.3 g) in ethanol (100 ml) was heated at reflux for 15 minutes. The reaction mixture was cooled and the solid precipitate was filtered off and washed with diethyl ether to give 5-amino-3,4-dicyano-1-(2,4,6-trichlorophenyl)pyrazole (13 g), as a buff colored solid, m.p. 267°-271° C. was heated at reflux for 15 minutes The reaction mixture was cooled the solid precipitate was filtered off washed with diethyl ether

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To 280 g of 2,4,6-trichlorophenylhydrazine was added 180 ml of ethyl acetoacetate, and the resulting mixture was stirred at room temperature for 30 minutes. After adding thereto a solution prepared by dissolving 215 g of potassium hydroxide in 7 l of ethanol, the reaction solution was refluxed with heating for 1 hour. The reaction solution was poured into 6 l of water and neutralized with conc. hydrochloric acid. After being cooled to room temperature, a precipitate thus formed was filtered off, washed with water, and then dried under reduced pressure to obtain the titled compound. Yield: 300 g. Melting point: 178° to 180° C. After adding a solution prepared the reaction solution was refluxed with heating for 1 hour After being cooled to room temperature a precipitate thus formed was filtered off washed with water dried under reduced pressure

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To 280 g of 2,4,6-trichlorophenylhydrazine was added 180 ml of ethyl acetoacetate, and the resulting mixture was stirred at room temperature for 30 minutes. After adding thereto a solution prepared by dissolving 215 g of potassium hydroxide in 7 l of ethanol, the reaction solution was refluxed with heating for 1 hour. The reaction solution was poured into 6 l of water and neutralized with conc. hydrochloric acid. After being cooled to room temperature, a precipitate thus formed was filtered off, washed with water, and then dried under reduced pressure to obtain the titled compound. Yield: 300 g. Melting point: 178° to 180° C. After adding a solution prepared the reaction solution was refluxed with heating for 1 hour After being cooled to room temperature a precipitate thus formed was filtered off washed with water dried under reduced pressure

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 2,4,6-trichlorophenylhydrazine (21.1 g) and tetracyanoethylene (13.3 g) in ethanol (100 ml) was heated at reflux for 15 minutes. The reaction mixture was cooled and the solid precipitate was filtered off and washed with diethyl ether to give 5-amino-3,4-dicyano-1-(2,4,6-trichlorophenyl) pyrazole (13 g), as a buff colored solid, m.p. 267°-271° C. was heated at reflux for 15 minutes The reaction mixture was cooled the solid precipitate was filtered off washed with diethyl ether

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 2,4,6-trichlorophenylhydrazine (21.1 g) and tetracyanoethylene (13.3 g) in ethanol (100 ml) was heated at reflux for 15 minutes. The reaction mixture was cooled and the solid precipitate was filtered off and washed with diethyl ether to give 5-amino-3,4-dicyano-1-(2,4,6-trichlorophenyl)pyrazole (13 g), as a buff colored solid, m.p. 267°-271° C. was heated at reflux for 15 minutes The reaction mixture was cooled the solid precipitate was filtered off washed with diethyl ether

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 2,4,6-trichlorophenyl hydrazine (21.1 g) and tetracyanoethylene (13.3 g) in ethanol (100 ml) was heated at reflux for 15 minutes. The reaction mixture was cooled and the solid precipitate was filtered off and washed with diethyl ether to give 5-amino-3,4-dicyano-1-(2,4,6-trichlorophenyl)pyrazole (13 g), as a buff colored solid, m.p. 267-271° C. was heated at reflux for 15 minutes The reaction mixture was cooled the solid precipitate was filtered off washed with diethyl ether