N-(3-hydroxyiminobutan-2-ylidene)hydroxylamine

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

Procedure: A mixture containing 70 ml of dioxane, 2.3 g (0.02 mole) of dimethylglyoxime, 3.8 g (0.02 mole) of p-toluenesulfonyl chloride and 2.0 g (0.02 mole) of triethylamine was stirred for several days at room temperature. Dioxane was then removed by evaporation under reduced pressure and the solid residue stirred in ice water. The slurry was filtered and the solid material (4.1 g) was dried in a vacuum oven. The solid had no definite melting point. Dioxane was then removed by evaporation under reduced pressure the solid residue stirred in ice water The slurry was filtered the solid material (4.1 g) was dried in a vacuum oven

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

Procedure: A mixture containing 70 ml of dioxane, 2.3 g (0.02 mole) of dimethylglyoxime, 3.8 g (0.02 mole) of p-toluenesulfonyl chloride and 2.0 g (0.02 mole) of triethylamine was stirred for several days at room temperature. Dioxane was then removed by evaporation under reduced pressure and the solid residue stirred in ice water. The slurry was filtered and the solid material (4.1 g) was dried in a vacuum oven. The solid had no definite melting point. Dioxane was then removed by evaporation under reduced pressure the solid residue stirred in ice water The slurry was filtered the solid material (4.1 g) was dried in a vacuum oven

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

Procedure: To 300 ml of 1,4 dioxane in a round-bottom flask was added 11.6 g (0.1 mole) of dimethylglyoxime. When the solid had completely dissolved, 22.9 g (0.2 mole) of methanesulfonyl chloride was added. The mixture was stirred and 20.2 g (0.2 mole) triethylamine was added dropwise. The reaction mixture was stirred for 51/2 hours during which time a precipitate was formed. The dioxane was removed by evaporation under reduced pressure. The residue was stirred in ice water, then filtered. The solid product was dissolved in dichloromethane and dried over anhydrous sodium sulfate. The slurry was filtered and the solvent was removed in a rotary evaporator. The solid residue was stirred in cold ethanol, then filtered and dried in a vacuum oven, giving 21.05 g (77% yield) of di-(methanesulfonyl)-dimethylglyoxime with mp 169-172° C. When the solid had completely dissolved The reaction mixture was stirred for 51/2 hours during which time a precipitate was formed The dioxane was removed by evaporation under reduced pressure The residue was stirred in ice water filtered The solid product was dissolved in dichloromethane dried over anhydrous sodium sulfate The slurry was filtered the solvent was removed in a rotary evaporator The solid residue was stirred in cold ethanol filtered dried in a vacuum oven

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

Procedure: To 300 ml of 1,4 dioxane in a round-bottom flask was added 11.6 g (0.1 mole) of dimethylglyoxime. When the solid had completely dissolved, 22.9 g (0.2 mole) of methanesulfonyl chloride was added. The mixture was stirred and 20.2 g (0.2 mole) triethylamine was added dropwise. The reaction mixture was stirred for 51/2 hours during which time a precipitate was formed. The dioxane was removed by evaporation under reduced pressure. The residue was stirred in ice water, then filtered. The solid product was dissolved in dichloromethane and dried over anhydrous sodium sulfate. The slurry was filtered and the solvent was removed in a rotary evaporator. The solid residue was stirred in cold ethanol, then filtered and dried in a vacuum oven, giving 21.05 g (77% yield) of di-(methanesulfonyl)-dimethylglyoxime with mp 169-172° C. When the solid had completely dissolved The reaction mixture was stirred for 51/2 hours during which time a precipitate was formed The dioxane was removed by evaporation under reduced pressure The residue was stirred in ice water filtered The solid product was dissolved in dichloromethane dried over anhydrous sodium sulfate The slurry was filtered the solvent was removed in a rotary evaporator The solid residue was stirred in cold ethanol filtered dried in a vacuum oven

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

Procedure: 50 mg of 1-(4-bromobenzyl)-5-(4-oxo-2-thioxothiazolidine-5-ylidenemethyl)-3,4-dihydro-1H-quinolin-2-one was suspended in a mixed solvent of 0.15 ml of methanol, 0.1 ml of water, 0.08 ml of an aqueous 1 N-sodium hydroxide solution, and 0.1 ml of THF. 0.03 ml of a DMF (5 ml) solution of 42 mg of cobalt chloride 6-hydrate and 250 mg of dimethylglyoxime was further added to the suspension, and the mixture was heated to 30° C. to 40° C. An aqueous solution (0.1 ml) of 15 mg of sodium borohydride was added, followed by stirring for 30 minutes. A saturated aqueous potassium hydrogensulfate solution was added, the mixture was extracted with ethyl acetate, and the extract was washed with water. The extract was dried over anhydrous magnesium sulfate and concentrated. The residue was purified by preparative silica gel thin layer chromatography (ethyl acetate:n-hexane=1:1) to give 44.7 mg (89% yield) of 1-(4-bromobenzyl)-5-(4-oxo-2-thioxothiazolidin-5-ylmethyl)-3,4-dihydro-1H-quinolin-2-one as a colorless amorphous solid, and further recrystallized from ethyl acetate-diethyl ether, giving a white powder. the mixture was heated to 30° C. to 40° C the mixture was extracted with ethyl acetate the extract was washed with water The extract was dried over anhydrous magnesium sulfate concentrated The residue was purified by preparative silica gel thin layer chromatography (ethyl acetate:n-hexane=1:1)

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

Procedure: 50 mg of 1-(4-bromobenzyl)-5-(4-oxo-2-thioxothiazolidine-5-ylidenemethyl)-3,4-dihydro-1H-quinolin-2-one was suspended in a mixed solvent of 0.15 ml of methanol, 0.1 ml of water, 0.08 ml of an aqueous 1 N-sodium hydroxide solution, and 0.1 ml of THF. 0.03 ml of a DMF (5 ml) solution of 42 mg of cobalt chloride 6-hydrate and 250 mg of dimethylglyoxime was further added to the suspension, and the mixture was heated to 30° C. to 40° C. An aqueous solution (0.1 ml) of 15 mg of sodium borohydride was added, followed by stirring for 30 minutes. A saturated aqueous potassium hydrogensulfate solution was added, the mixture was extracted with ethyl acetate, and the extract was washed with water. The extract was dried over anhydrous magnesium sulfate and concentrated. The residue was purified by preparative silica gel thin layer chromatography (ethyl acetate:n-hexane=1:1) to give 44.7 mg (89% yield) of 1-(4-bromobenzyl)-5-(4-oxo-2-thioxothiazolidin-5-ylmethyl)-3,4-dihydro-1H-quinolin-2-one as a colorless amorphous solid, and further recrystallized from ethyl acetate-diethyl ether, giving a white powder. the mixture was heated to 30° C. to 40° C the mixture was extracted with ethyl acetate the extract was washed with water The extract was dried over anhydrous magnesium sulfate concentrated The residue was purified by preparative silica gel thin layer chromatography (ethyl acetate:n-hexane=1:1)

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To the suspension containing CoCl2.6H2O (3.83 mg, 0.014 mmol) and dimethylglyoxime (63.56 mg, 0.54 mmol) in 10 ml of water, 4 drops of 1.0N NaOH and NaBH4 (355.43 mg, 9.24 mmol) were subsequently added. The mixture was cooled to 0° C., and 5-(3-chloro-4-(2-cyclohexylethoxy)benzylidene)thiazolidine-2,4-dione (1 g, 2.72 mmol) in 15 ml of THF-DMF (2:1) was added thereto over 20 minutes. The mixture was stirred at room temperature for 18 hours, to which acetic acid was then added until the pH thereof reached about 6. The mixture was diluted with water and extracted with ethyl acetate and water. The organic layer was washed with water several times, dried with anhydrous magnesium sulfate, filtered and solvent-evaporated. The residual oil was chromatographed on silica gel to afford 5-(3-chloro-4-(2-cyclohexylethoxy)benzyl)thiazolidine-2,4-dione (Derivative 120 of the above formula) as white solid (0.8 g, yield: 79%). were subsequently added was then added until the pH extracted with ethyl acetate and water The organic layer was washed with water several times dried with anhydrous magnesium sulfate filtered solvent-evaporated The residual oil was chromatographed on silica gel

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To the suspension containing CoCl2.6H2O (4.77 mg, 0.016 mmol) and dimethylglyoxime (73.14 mg, 0.63 mmol) in 10 ml of water, 4 drops of 1.0N NaOH and NaBH4 (409.4 mg, 10.65 mmol) were subsequently added. The mixture was cooled to 0° C., and 5-(4-(2-cyclopentylethoxy)benzylidene)thiazolidine-2,4-dione (1 g, 3.13 mmol) in 15 ml of THF-DMF (2:1) was added thereto over 20 minutes. The mixture was stirred at room temperature for 18 hours, to which acetic acid was then added until the pH thereof reached about 6. The mixture was diluted with water and extracted with ethyl acetate and water. The organic layer was washed with water several times, dried with anhydrous magnesium sulfate, filtered and solvent-evaporated. The residual oil was chromatographed on silica gel to afford 5-(4-(2-cyclopentylethoxy)benzyl)thiazolidine-2,4-dione (Derivative 118 of the above formula) as white solid (0.8 g, yield: 79%). were subsequently added was then added until the pH extracted with ethyl acetate and water The organic layer was washed with water several times dried with anhydrous magnesium sulfate filtered solvent-evaporated The residual oil was chromatographed on silica gel

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To the suspension containing CoCl2.6H2O (3.98 mg, 0.014 mmol) and dimethylglyoxime (66.13 mg, 0.57 mmol) in 10 ml of water, 4 drops of 1.0N NaOH and NaBH4 (370.06 mg, 9.62 mmol) were subsequently added. The mixture was cooled to 0° C., and 5-(3-chloro-4-(cyclohexylmethoxy)benzylidene)thiazolidine-2,4-dione (1 g, 2.83 mmol) in 15 ml of THF-DMF (2:1) was added thereto over 20 minutes. The mixture was stirred at room temperature for 18 hours, to which acetic acid was then added until the pH thereof reached about 6. The mixture was diluted with water and extracted with ethyl acetate and water. The organic layer was washed with water several times, dried with anhydrous magnesium sulfate, filtered and solvent-evaporated. The residual oil was chromatographed on silica gel to afford 5-(3-chloro-4-(cyclohexylmethoxy)benzyl)thiazolidine-2,4-dione (Derivative 117 of the above formula) as white solid (0.8 g, yield: 79%). were subsequently added was then added until the pH extracted with ethyl acetate and water The organic layer was washed with water several times dried with anhydrous magnesium sulfate filtered solvent-evaporated The residual oil was chromatographed on silica gel

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To the suspension containing CoCl2.6H2O (3.98 mg, 0.014 mmol) and dimethylglyoxime (66.13 mg, 0.57 mmol) in 10 ml of water, 4 drops of 1.0N NaOH and NaBH4 (370.06 mg, 9.62 mmol) were subsequently added. The mixture was cooled to 0° C., and 5-(3-chloro-4-(cyclohexylmethoxy)benzylidene)thiazolidine-2,4-dione (1 g, 2.83 mmol) in 15 ml of THF-DMF (2:1) was added thereto over 20 minutes. The mixture was stirred at room temperature for 18 hours, to which acetic acid was then added until the pH thereof reached about 6. The mixture was diluted with water and extracted with ethyl acetate and water. The organic layer was washed with water several times, dried with anhydrous magnesium sulfate, filtered and solvent-evaporated. The residual oil was chromatographed on silica gel to afford 5-(3-chloro-4-(cyclohexylmethoxy)benzyl)thiazolidine-2,4-dione (Derivative 117 of the above formula) as white solid (0.8 g, yield: 79%). were subsequently added was then added until the pH extracted with ethyl acetate and water The organic layer was washed with water several times dried with anhydrous magnesium sulfate filtered solvent-evaporated The residual oil was chromatographed on silica gel

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To the suspension containing CoCl2.6H2O (4.49 mg, 0.016 mmol) and dimethylglyoxime (74.54 mg, 0.64 mmol) in 10 ml of water, 4 drops of 1.0N NaOH and NaBH4 (417.1 mg, 10.85 mmol) were subsequently added. The mixture was cooled to 0° C., and 5-(4-(benzyloxy)benzylidene)thiazolidine-2,4-dione (1 g, 3.27 mmol) in 15 ml of THF-DMF (2:1) was added thereto over 20 minutes. The mixture was stirred at room temperature for 18 hours, to which acetic acid was then added until the pH thereof reached about 6. The mixture was diluted with water and extracted with ethyl acetate and water. The organic layer was washed with water several times, dried with anhydrous magnesium sulfate, filtered and solvent-evaporated. The residual oil was chromatographed on silica gel to afford 5-(4-(benzyloxy)benzyl)thiazolidine-2,4-dione (Derivative 116 of the above formula) as white solid (0.8 g, yield: 79%). were subsequently added was then added until the pH extracted with ethyl acetate and water The organic layer was washed with water several times dried with anhydrous magnesium sulfate filtered solvent-evaporated The residual oil was chromatographed on silica gel

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To the suspension containing CoCl2.6H2O (4.6 mg, 0.016 mmol) and dimethylglyoxime (76.4 mg, 0.65 mmol) in 10 ml of water, 4 drops of 1.0N NaOH and NaBH4 (427.6 mg, 11.12 mmol) were subsequently added. The mixture was cooled to 0° C., and 5-(4-(cyclopentylmethoxy)benzylidene)thiazolidine-2,4-dione (1 g, 3.27 mmol) in 15 ml of THF-DMF (2:1) was added thereto over 20 minutes. The mixture was stirred at room temperature for 18 hours, to which acetic acid was then added until the pH thereof reached about 6. The mixture was diluted with water and extracted with ethyl acetate and water. The organic layer was washed with water several times, dried with anhydrous magnesium sulfate, filtered and solvent-evaporated. The residual oil was chromatographed on silica gel to afford 5-(4-(cyclopentylmethoxy)benzyl)thiazolidine-2,4-dione (Derivative 115 of the above formula) as white solid (0.8 g, yield: 79%). were subsequently added was then added until the pH extracted with ethyl acetate and water The organic layer was washed with water several times dried with anhydrous magnesium sulfate filtered solvent-evaporated The residual oil was chromatographed on silica gel