(2,5-dichlorophenyl)hydrazine;hydrochloride

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: (2,5-Dichlorophenyl)hydrazine hydrochloride (0.3 g, 1.40 mmol) was dissolved in MeOH (3 mL) and 1,2-cyclo hexadione (0.15 g, 1.40 mmol) was added and the mixture heated to 60° C. for 24 h. The reaction mixture was cooled to room temperature and the volatiles were removed in vacuo. The residue was diluted with water, neutralized with NaHCO3 solution and extracted with EtOAc (3×15 mL). The combined organic extracts were concentrated in vacuo to give the crude compound which was purified by silica gel chromatography [EtOAc-hexane (3:17) as eluant] to provide the title compound (0.35 g, 11.8%). 1H NMR (200 MHz, CDCl3, δ in ppm) 8.92 (bs, 1H), 7.26 (d, J=8.2 Hz, 1H), 7.06 (d, J=8.0 Hz, 1H), 3.36 (t, J=6.2 Hz, 2H), 2.69 (t, J=6.0 Hz, 2H), 2.34-2.21 (m, 2H). The reaction mixture was cooled to room temperature the volatiles were removed in vacuo The residue was diluted with water extracted with EtOAc (3×15 mL) The combined organic extracts were concentrated in vacuo to give the crude compound which was purified by silica gel chromatography [EtOAc-hexane (3:17) as eluant]

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: (2,5-Dichlorophenyl)hydrazine hydrochloride (0.3 g, 1.40 mmol) was dissolved in MeOH (3 mL) and 1,2-cyclo hexadione (0.15 g, 1.40 mmol) was added and the mixture heated to 60° C. for 24 h. The reaction mixture was cooled to room temperature and the volatiles were removed in vacuo. The residue was diluted with water, neutralized with NaHCO3 solution and extracted with EtOAc (3×15 mL). The combined organic extracts were concentrated in vacuo to give the crude compound which was purified by silica gel chromatography [EtOAc-hexane (3:17) as eluant] to provide the title compound (0.35 g, 11.8%). 1H NMR (200 MHz, CDCl3, δ in ppm) 8.92 (bs, 1H), 7.26 (d, J=8.2 Hz, 1H), 7.06 (d, J=8.0 Hz, 1H), 3.36 (t, J=6.2 Hz, 2H), 2.69 (t, J=6.0 Hz, 2H), 2.34-2.21 (m, 2H). The reaction mixture was cooled to room temperature the volatiles were removed in vacuo The residue was diluted with water extracted with EtOAc (3×15 mL) The combined organic extracts were concentrated in vacuo to give the crude compound which was purified by silica gel chromatography [EtOAc-hexane (3:17) as eluant]

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

Procedure: 2,5-Dichlorophenylhydrazine hydrochloride (240 g, 1.1 mol) and acrylamide (100 g, 1.4 mol) is refluxed in a solution of sodium (56 g, 2.4 mol) in ethanol (1000 ml) and toluene (1000 ml) for 3 hours. Evaporation of the solvents, acidification with acetic acid dilution with water, filtration and drying (high vacuum, +100° C.) gives the 1-(2,5-dichlorophenyl)-3-pyrazolidone. Evaporation of the solvents, acidification with acetic acid dilution with water, filtration drying (high vacuum, +100° C.)

Conditions: temp:102.51; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Into an 8 mL vial was weighed 202.7 mg (539 μmol) of (Z)-1,1,1-trifluoro-4-hydroxy-4-(5-(3-(methylsulfonyl)phenyl)thiophen-2-yl)but-3-en-2-one, 117.4 mg (550 μmol) of 2,5-dichlorophenylhydrazine hydrochloride, 3 mL of acetic acid, and 1 mL of DMF. The resulting reaction was stirred at 100-105° C. for 3 h then was concentrated to dryness in vacuo. The residue was purified by silica gel flash chromatography (3×23 cm, 1:1 ethyl acetate-hexanes) and was dried affording the product as a faintly yellow solid, yield: 89 mg (55%). 1H NMR (400 MHz, CDCl3): δ 8.08 (s, 1H), 7.87 (d, J=9 Hz, 1H), 7.75 (d, J=9 Hz, 1H), 7.6 (m, 2H), 7.5 (m, 2H), 7.27 (d, J=4 Hz, 1H), 6.90 (s, 1H), 6.87 (d, J=4 Hz, 1H), 3.09 (s, 3H). The resulting reaction then was concentrated to dryness in vacuo The residue was purified by silica gel flash chromatography (3×23 cm, 1:1 ethyl acetate-hexanes) was dried affording the product as a faintly yellow solid, yield: 89 mg (55%)

Conditions: temp:102.51; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Into an 8 mL vial was weighed 202.7 mg (539 μmol) of (Z)-1,1,1-trifluoro-4-hydroxy-4-(5-(3-(methylsulfonyl)phenyl)thiophen-2-yl)but-3-en-2-one, 117.4 mg (550 μmol) of 2,5-dichlorophenylhydrazine hydrochloride, 3 mL of acetic acid, and 1 mL of DMF. The resulting reaction was stirred at 100-105° C. for 3 h then was concentrated to dryness in vacuo. The residue was purified by silica gel flash chromatography (3×23 cm, 1:1 ethyl acetate-hexanes) and was dried affording the product as a faintly yellow solid, yield: 89 mg (55%). 1H NMR (400 MHz, CDCl3): δ 8.08 (s, 1H), 7.87 (d, J=9 Hz, 1H), 7.75 (d, J=9 Hz, 1H), 7.6 (m, 2H), 7.5 (m, 2H), 7.27 (d, J=4 Hz, 1H), 6.90 (s, 1H), 6.87 (d, J=4 Hz, 1H), 3.09 (s, 3H). The resulting reaction then was concentrated to dryness in vacuo The residue was purified by silica gel flash chromatography (3×23 cm, 1:1 ethyl acetate-hexanes) was dried affording the product as a faintly yellow solid, yield: 89 mg (55%)

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

Procedure: Prepared according to Method B from 2,2′,4,4′-tetrahydroxybenzophenone (0.4 g, 1.6 mmol), sodium acetate (0.27 g, 3 mmol) and 2,5-dichlorophenylhydrazine hydrochloride (0.45 g, 2.5 mmol) to give 0.127 g of product as a beige solid (mp 78–80° C.). Prepared

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: (2,5-Dichlorophenyl)hydrazine hydrochloride (0.3 g, 1.40 mmol) was dissolved in MeOH (3 mL) and 1,2-cyclo hexadione (0.15 g, 1.40 mmol) was added and the mixture heated to 60° C. for 24 h. The reaction mixture was cooled to room temperature and the volatiles were removed in vacuo. The residue was diluted with water, neutralized with NaHCO3 solution and extracted with EtOAc (3×15 mL). The combined organic extracts were concentrated in vacuo to give the crude compound which was purified by silica gel chromatography [EtOAc-hexane (3:17) as eluant] to provide the title compound (0.35 g, 11.8%). 1H NMR (200 MHz, CDCl3, δ in ppm) 8.92 (bs, 1H), 7.26 (d, J=8.2 Hz, 1H), 7.06 (d, J=8.0 Hz, 1H), 3.36 (t, J=6.2 Hz, 2H), 2.69 (t, J=6.0 Hz, 2H), 2.34-2.21 (m, 2H). The reaction mixture was cooled to room temperature the volatiles were removed in vacuo The residue was diluted with water extracted with EtOAc (3×15 mL) The combined organic extracts were concentrated in vacuo to give the crude compound which was purified by silica gel chromatography [EtOAc-hexane (3:17) as eluant]