1-(2,6-dichlorophenyl)ethanone

Conditions: temp:0.00; pressure:0.00; stir:

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

Procedure: (32) To a solution of the 2,6-dichlorobenzaldehyde (438 mg, 2.50 mmol) and 2,6-dichloroacetophenone (473 mg, 2.50 mmol) in 3.7 ml of ethanol was added 0.1 ml of 40% sodium hydroxide in water at 10° C. After stirring for 2 hours at room temperature, a solid appeared and was filtered. The precipitate was recrystallized from methanol to afford 465 mg (53.8%) of white, cottony needles: mp 130-130.4° C. (lit. mp 124-125° C., Kaiser, et al., Monatshefte fur Chemie, 1997, 128, 1247-1254). 1H NMR (250 MHz) δ 7.43-7.17 (m, 7 H), 7.10-7.03 (d, 1 H); 13C NMR (62.7 MHz) 193.0, 141.7, 137.5, 135.3 134.4, 132.1, 131.8, 131.0, 130.6, 129.0, 128.3 ppm. was filtered The precipitate was recrystallized from methanol to afford 465 mg (53.8%) of white, cottony needles

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

Procedure: (32) To a solution of the 2,6-dichlorobenzaldehyde (438 mg, 2.50 mmol) and 2,6-dichloroacetophenone (473 mg, 2.50 mmol) in 3.7 ml of ethanol was added 0.1 ml of 40% sodium hydroxide in water at 10° C. After stirring for 2 hours at room temperature, a solid appeared and was filtered. The precipitate was recrystallized from methanol to afford 465 mg (53.8%) of white, cottony needles: mp 130-130.4° C. (lit. mp 124-125° C., Kaiser, et al., Monatshefte fur Chemie, 1997, 128, 1247-1254). 1H NMR (250 MHz) δ 7.43-7.17 (m, 7H), 7.10-7.03 (d, 1H); 13C NMR (62.7 MHz) 193.0, 141.7, 137.5, 135.3 134.4, 132.1, 131.8, 131.0, 130.6, 129.0, 128.3 ppm. was filtered The precipitate was recrystallized from methanol to afford 465 mg (53.8%) of white, cottony needles

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

Procedure: (32) To a solution of the 2,6-dichlorobenzaldehyde (438 mg, 2.50 mmol) and 2,6-dichloroacetophenone (473 mg, 2.50 mmol) in 3.7 ml of ethanol was added 0.1 ml of 40% sodium hydroxide in water at 10° C. After stirring for 2 hours at room temperature, a solid appeared and was filtered. The precipitate was recrystallized from methanol to afford 465 mg (53.8%) of white, cottony needles: mp 130-130.4° C. (lit. mp 124-125° C., Kaiser, et al., Monatshefte fur Chemie, 1997, 128, 1247-1254). 1H NMR (250 MHz) δ 7.43-7.17 (m, 7H), 7.10-7.03 (d, 1H); 13C NMR (62.7 MHz) 193.0, 141.7, 137.5, 135.3 134.4, 132.1, 131.8, 131.0, 130.6, 129.0, 128.3 ppm. was filtered The precipitate was recrystallized from methanol to afford 465 mg (53.8%) of white, cottony needles

Conditions: temp:-20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred solution of lithium bis(trimethylsilyl)amide (1.0 molar in tetrahydrofuran, 11 mL, 1.1 mole equivalent) cooled at −70 under nitrogen was added dropwise a solution of 2,6 dichloroacetophenone (965 mg, 1.0 molar equivalent) in anhydrous tetrahydrofuran. The resulting mixture was stirred at −20° C. for 2 h. The reaction mixture was re-cooled to −70° C., and a solution of 3-nitrobenzoylcyanide (900 mg, 1.0 molar equivalent) in tetrahydrofuran was added dropwise. The 3-nitrobenzoylcyanide was prepared according to the procedures of S. Yamaguchi et. al. in, Bull. Chem. Soc. Jpn. 1989, 62,3036–3037. The mixture was allowed to warm to room temp over 1 h and was stirred at room temperature for 2 h. The reaction was quenched by the addition of saturated aqueous ammonium chloride. The reaction mixture was extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to dryness. The crude solid product was purified by column chromatography over silica gel using hexanes and ethyl acetate to give the desired 1-(2,6-dichlorophenyl)-3-(3-nitrophenyl)-1,3 propanedione. NMR 300 MHz (CDCL3) 8.75 (m, 1H), 8.40 (m, 1H), 8.28 (m, 1H), 7.69 (t, 1H), 7.39 (m, 2H), 6.43 (s, 2H) The reaction mixture was re-cooled to −70° C. to warm to room temp over 1 h was stirred at room temperature for 2 h The reaction was quenched by the addition of saturated aqueous ammonium chloride The reaction mixture was extracted with ethyl acetate The organic layer was dried over anhydrous sodium sulfate filtered concentrated under reduced pressure to dryness The crude solid product was purified by column chromatography over silica gel

Conditions: temp:0.00; pressure:0.00; stir:

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

Procedure: To a solution of 2′,6′-dichloroacetophenone (12.5 g, 66 mmol) and diethyl oxalate (14.6 g, 100 mmol) in 450 mL of anhydrous toluene, cautiously add sodium hydride (60% dispersion in mineral oil, 2.8 g, 70 mmol). Cautiously heat the reaction mixture to reflux under N2 for 1 h, cool to ambient temperature and pour onto ice-cold 1M HCl. Separate the layers and extract the aqueous phase with EtOAc (2×200 mL). Wash the combined organic extracts with brine, dry over MgSO4 and evaporate to obtain the title compound which is used in the next step without further purification. Cautiously heat the reaction mixture to reflux under N2 for 1 h pour onto ice-cold 1M HCl Separate the layers extract the aqueous phase with EtOAc (2×200 mL) Wash the combined organic extracts with brine dry over MgSO4 evaporate

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

Procedure: (32) To a solution of the 2,6-dichlorobenzaldehyde (438 mg, 2.50 mmol) and 2,6-dichloroacetophenone (473 mg, 2.50 mmol) in 3.7 ml of ethanol was added 0.1 ml of 40% sodium hydroxide in water at 10° C. After stirring for 2 hours at room temperature, a solid appeared and was filtered. The precipitate was recrystallized from methanol to afford 465 mg (53.8%) of white, cottony needles: mp 130-130.4° C. (lit. mp 124-125° C., Kaiser, et al., Monatshefte fur Chemie, 1997, 128, 1247-1254). 1H NMR (250 MHz) δ 7.43-7.17 (m, 7 H), 7.10-7.03 (d, 1 H); 13C NMR (62.7 MHz) 193.0, 141.7, 137.5, 135.3 134.4, 132.1, 131.8, 131.0, 130.6, 129.0, 128.3 ppm. was filtered The precipitate was recrystallized from methanol to afford 465 mg (53.8%) of white, cottony needles

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

Procedure: 4-Nitrobenzonitrile and 2,6-dichlorophenyl methyl ketone can be reacted with phenyliodine (III) diacetate and trifluoromethylsulfonic acid by the method of R. S. Varma, et al, J. Heterocyclic Chem., 1998, 35(6), 1533-1534 to give 5-(2,6-dichlorophenyl)-2-(4-nitrophenyl)-1,3-oxazole. The nitrophenyl group can be reduced to the corresponding aniline with tin (II) dichloride or iron powder and ammonium chloride. Reaction of this aniline with 2,2-dichloroacetyl chloride and triethylamine can then give 2,2-dichloro-N-[4-[5-(2,6-dichlorophenyl)-2-(1,3-oxazolyl)]phenyl]acetamide.

Conditions: temp:-20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred solution of lithium bis(trimethylsilyl)amide (1.0 molar in tetrahydrofuran, 11 mL, 1.1 mole equivalent) cooled at −70 under nitrogen was added dropwise a solution of 2,6 dichloroacetophenone (965 mg, 1.0 molar equivalent) in anhydrous tetrahydrofuran. The resulting mixture was stirred at −20° C. for 2 h. The reaction mixture was re-cooled to −70° C., and a solution of 3-nitrobenzoylcyanide (900 mg, 1.0 molar equivalent) in tetrahydrofuran was added dropwise. The 3-nitrobenzoylcyanide was prepared according to the procedures of S. Yamaguchi et. al. in, Bull. Chem. Soc. Jpn. 1989, 62,3036-3037. The mixture was allowed to warm to room temp over 1 h and was stirred at room temperature for 2 h. The reaction was quenched by the addition of saturated aqueous ammonium chloride. The reaction mixture was extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to dryness. The crude solid product was purified by column chromatography over silica gel using hexanes and ethyl acetate to give the desired 1-(2,6-dichlorophenyl)-3-(3-nitrophenyl)-1,3 propanedione. NMR 300 MHz (CDCL3) 8.75 (m, 1H), 8.40 (m, 1H), 8.28 (m, 1H), 7.69 (t, 1H), 7.39 (m, 2H), 6.43 (s, 2H) The reaction mixture was re-cooled to −70° C. to warm to room temp over 1 h was stirred at room temperature for 2 h The reaction was quenched by the addition of saturated aqueous ammonium chloride The reaction mixture was extracted with ethyl acetate The organic layer was dried over anhydrous sodium sulfate filtered concentrated under reduced pressure to dryness The crude solid product was purified by column chromatography over silica gel

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

Procedure: To a solution of 2′,6′-dichloroacetophenone (12.5 g, 66 mmol) and diethyl oxalate (14.6 g, 100 mmol) in 450 mL of anhydrous toluene, cautiously add sodium hydride (60% dispersion in mineral oil, 2.8 g, 70 mmol). Cautiously heat the reaction mixture to reflux under N2 for 1 h, cool to ambient temperature and pour onto ice-cold 1M HCl. Separate the layers and extract the aqueous phase with EtOAc (2×200 mL). Wash the combined organic extracts with brine, dry over MgSO4 and evaporate to obtain the title compound which is used in the next step without further purification. Cautiously heat the reaction mixture to reflux under N2 for 1 h pour onto ice-cold 1M HCl Separate the layers extract the aqueous phase with EtOAc (2×200 mL) Wash the combined organic extracts with brine dry over MgSO4 evaporate

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

Procedure: To a solution of 2′,6′-dichloroacetophenone (12.5 g, 66 mmol) and diethyl oxalate (14.6 g, 100 mmol) in 450 mL of anhydrous toluene, cautiously add sodium hydride (60% dispersion in mineral oil, 2.8 g, 70 mmol). Cautiously heat the reaction mixture to reflux under N2 for 1 h, cool to ambient temperature and pow onto ice-cold 1M HCl. Separate the layers and extract the aqueous phase with EtOAc (2×200 mL). Wash the combined organic extracts with brine, dry over MgSO4 and evaporate to obtain the title compound which is used in the next step without further purification. Cautiously heat the reaction mixture to reflux under N2 for 1 h Separate the layers extract the aqueous phase with EtOAc (2×200 mL) Wash the combined organic extracts with brine dry over MgSO4 evaporate