3H-1-benzothiophen-2-one

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

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: A mixture of benzo[b]thiophen-2(3H)-one (11.2 g) aqueous sodium hydroxide (5.58 g in 100 ml water) and tetrahydrofuran (10 ml) was heated under reflux for two hours. A solution of 2,5-difluorobenzyl bromide (15.5 g) in tetrahydrofuran (10 ml) was added and the mixture refluxed for a further 2 hours and allowed to cool. The aqueous layer was clarified by ether extraction and then acidified with concentrated hydrochloric acid. The precipitate was collected, washed with water and dried. The solid was recrystallised from dipropyl ether/hexane to give [2-(2,5-difluorobenzylthio)phenyl]acetic acid, mp 106.5°-107.5°. A solution of this product (14.4 g) in methanol (150 ml) containing concentrated sulphuric acid (0.5 ml) was heated under reflux for 4 hours, cooled and evaporated. The residue was dissolved in ethyl acetate/ether and washed with water and aqueous sodium bicarbonate, dried and evaporated to give methyl [2-(2,5-difluorobenzylthio)phenyl]acetate, as a light brown oil. was heated under reflux for two hours the mixture refluxed for a further 2 hours to cool The aqueous layer was clarified by ether extraction The precipitate was collected washed with water dried The solid was recrystallised from dipropyl ether/hexane

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

実験手順: A mixture of benzo[b]thiophen-2(3H)-one (11.2 g) aqueous sodium hydroxide (5.58 g in 100 ml water) and tetrahydrofuran (10 ml) was heated under reflux for two hours. A solution of 2,5-difluorobenzyl bromide (15.5 g) in tetrahydrofuran (10 ml) was added and the mixture refluxed for a further 2 hours and allowed to cool. The aqueous layer was clarified by ether extraction and then acidified with concentrated hydrochloric acid. The precipitate was collected, washed with water and dried. The solid was recrystallised from dipropyl ether/hexane to give [2-(2,5-difluorobenzylthio)phenyl]acetic acid, mp 106.5°-107.5°. A solution of this product (14.4 g) in methanol (150 ml) containing concentrated sulphuric acid (0.5 ml) was heated under reflux for 4 hours, cooled and evaporated. The residue was dissolved in ethyl acetate/ether and washed with water and aqueous sodium bicarbonate, dried and evaporated to give methyl [2-(2,5-difluorobenzylthio)phenyl]acetate, as a light brown oil. was heated under reflux for two hours the mixture refluxed for a further 2 hours to cool The aqueous layer was clarified by ether extraction The precipitate was collected washed with water dried The solid was recrystallised from dipropyl ether/hexane

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

実験手順: In a sulfonating flask under a nitrogen atmosphere, 15 g of benzo[b]thiophene-2(3H)-one (100 mmol) are dissolved in 150 ml of distilled hexametapol. The light-yellow solution is cooled to 5°. 8.9 g of a sodium hydride suspension (55%) that has been de-oiled with n-hexane are then added in portions while stirring. The resulting suspension is stirred for 15 minutes at 20°, during which time the evolution of gas is observed. The suspension is then cooled to -10°and 17.65 g of 2-(2-thienyl)-acetic acid chloride are added, the internal temperature being maintained at below 0°. After the cooling has been removed, the mixture is stirred for 1 hour. The reaction mixture is poured onto 2 liters of ice-water and 60 ml of 2N hydrochloric acid, and then 500 ml of toluene are added. The separated organic phase is extractedtwice with water and then three times using 200 ml of 5% soda solution eachtime. The alkaline phase is filtered and poured onto ice and 2N hydrochloric acid, and the crystals that are formed are filtered off and dried. Chromatography over silica gel and recrystallisation from methanol yield 2-hydroxy-3-[2-(2-thienyl)-acetyl]-benzo[b]thiophene, ##STR7## The light-yellow solution is cooled to 5° are then added in portions The resulting suspension is stirred for 15 minutes at 20°, during which time the evolution of gas are added the internal temperature being maintained at below 0° After the cooling has been removed the mixture is stirred for 1 hour The reaction mixture is poured onto 2 liters of ice-water and 60 ml of 2N hydrochloric acid 500 ml of toluene are added The alkaline phase is filtered poured onto ice and 2N hydrochloric acid the crystals that are formed are filtered off dried Chromatography over silica gel and recrystallisation from methanol

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

実験手順: In a sulfonating flask under a nitrogen atmosphere, 15 g of benzo[b]thiophene-2(3H)-one (100 mmol) are dissolved in 150 ml of distilled hexametapol. The light-yellow solution is cooled to 5°. 8.9 g of a sodium hydride suspension (55%) that has been de-oiled with n-hexane are then added in portions while stirring. The resulting suspension is stirred for 15 minutes at 20°, during which time the evolution of gas is observed. The suspension is then cooled to -10°and 17.65 g of 2-(2-thienyl)-acetic acid chloride are added, the internal temperature being maintained at below 0°. After the cooling has been removed, the mixture is stirred for 1 hour. The reaction mixture is poured onto 2 liters of ice-water and 60 ml of 2N hydrochloric acid, and then 500 ml of toluene are added. The separated organic phase is extractedtwice with water and then three times using 200 ml of 5% soda solution eachtime. The alkaline phase is filtered and poured onto ice and 2N hydrochloric acid, and the crystals that are formed are filtered off and dried. Chromatography over silica gel and recrystallisation from methanol yield 2-hydroxy-3-[2-(2-thienyl)-acetyl]-benzo[b]thiophene, ##STR7## The light-yellow solution is cooled to 5° are then added in portions The resulting suspension is stirred for 15 minutes at 20°, during which time the evolution of gas are added the internal temperature being maintained at below 0° After the cooling has been removed the mixture is stirred for 1 hour The reaction mixture is poured onto 2 liters of ice-water and 60 ml of 2N hydrochloric acid 500 ml of toluene are added The alkaline phase is filtered poured onto ice and 2N hydrochloric acid the crystals that are formed are filtered off dried Chromatography over silica gel and recrystallisation from methanol

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

実験手順: A solution of 6 g of 2,3-dihydro-2-oxo-benzo[b]thiophene in 40 ml of tetrahydrofuran is added dropwise, at 10° to 20°, to a stirred suspension of 1.93 g of a 50% strength sodium hydride/mineral oil suspension in 50 ml of tetrahydrofurane. The mixture is stirred for a further 30 minutes at room temperature and 5.5 g of 3-fluoro-phenyl isocyanate are then added slowly dropwise, an exothermic reaction taking place. The reaction mixture is then stirred for a further one hour at room temperature and for one hour at 40° and is poured into a mixture of 500 ml of ice water and 50 ml of 2 N hydrochloric acid and the precipitate, which at first is oily but immediately crystallises, is filtered off and recrystallised from acetone/petroleum ether. N-(3-Fluorophenyl)-2-oxo-2,3-dihydro-3-benzo[b]thiophenecarboxamide with a melting point of 169°-171° is obtained. an exothermic reaction The reaction mixture is then stirred for a further one hour at room temperature and for one hour at 40° immediately crystallises is filtered off recrystallised from acetone/petroleum ether

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

実験手順: A solution of 18.2 g of 2,3-dihydro-2-oxo-benzo[b]thiophene in 60 ml of hexamethylphosphoric acid triamide is added dropwise to a suspension of 5.9 g of a 50% strength sodium hydride/mineral oil suspension in 180 ml of hexamethylphosphoric acid triamide whilst cooling, the reaction temperature being kept below 15°. After stirring for one hour at room temperature, 30.4 g of phenyl N-(3-chlorophenyl)-carbamate are added in portions, with external cooling. The mixture is stirred for a further 16 hours at room temperature and poured onto a mixture of 100 ml of 2 N hydrochloric acid and 1,000 g of ice, whereupon an oil separates out; this oil crystallises on leaving to stand for several hours. The crystals are collected and dissolved in 300 ml of diethyl ether. The solution is washed with water and the organic phase is separated off, dried over sodium sulphate and evaporated to dryness. The residue is recrystallised from ether and gives N-(3-chlorophenyl)-2-oxo-2,3-dihydro-3-benzo[b]thiophenecarboxamide with a melting point of 175°-177°. whilst cooling being kept below 15° The mixture is stirred for a further 16 hours at room temperature this oil crystallises on leaving to stand for several hours The crystals are collected dissolved in 300 ml of diethyl ether The solution is washed with water the organic phase is separated off dried over sodium sulphate evaporated to dryness The residue is recrystallised from ether

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

実験手順: A solution of 18.2 g of 2,3-dihydro-2-oxo-benzo[b]thiophene in 60 ml of hexamethylphosphoric acid triamide is added dropwise to a suspension of 5.9 g of a 50% strength sodium hydride/mineral oil suspension in 180 ml of hexamethylphosphoric acid triamide whilst cooling, the reaction temperature being kept below 15°. After stirring for one hour at room temperature, 30.4 g of phenyl N-(3-chlorophenyl)-carbamate are added in portions, with external cooling. The mixture is stirred for a further 16 hours at room temperature and poured onto a mixture of 100 ml of 2 N hydrochloric acid and 1,000 g of ice, whereupon an oil separates out; this oil crystallises on leaving to stand for several hours. The crystals are collected and dissolved in 300 ml of diethyl ether. The solution is washed with water and the organic phase is separated off, dried over sodium sulphate and evaporated to dryness. The residue is recrystallised from ether and gives N-(3-chlorophenyl)-2-oxo-2,3-dihydro-3-benzo[b]thiophenecarboxamide with a melting point of 175°-177°. whilst cooling being kept below 15° The mixture is stirred for a further 16 hours at room temperature this oil crystallises on leaving to stand for several hours The crystals are collected dissolved in 300 ml of diethyl ether The solution is washed with water the organic phase is separated off dried over sodium sulphate evaporated to dryness The residue is recrystallised from ether

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

実験手順: A solution of 50 g of 2,3-dihydro-2-oxo-benzo[b]thiophene in 200 ml of hexamethylphosphoric acid triamide is added dropwise to a suspension of 16 g of a 50% strength sodium hydride/mineral oil dispersion in 500 ml of hexamethylphosphoric acid triamide, whilst cooling, the temperature being kept below 15°. After stirring for one hour at room temperature, 77 g of phenyl N-(2-fluorophenyl)-carbamate are added in portions, with external cooling. The reaction mixture is stirred for a further 16 hours at room temperature and poured into a mixture of 300 ml of 2 N hydrochloric acid and 3,000 ml of ice water. An oil separates out and this crystallises after about 2 hours. The crystalline product, in which solvent is incorporated, is dissolved in 1,000 ml of diethyl ether and the solution is washed with water. The organic phase is separated off, dried over sodium sulphate and evaporated to dryness. The crude product is recrystallised from diethyl ether and gives N-(2-fluorophenyl)-2-oxo-2,3-dihydro-3-benzo[b]thiophenecarboxamide, melting point 155°-156°. whilst cooling being kept below 15° The reaction mixture is stirred for a further 16 hours at room temperature this crystallises after about 2 hours is dissolved in 1,000 ml of diethyl ether the solution is washed with water The organic phase is separated off dried over sodium sulphate evaporated to dryness The crude product is recrystallised from diethyl ether

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

実験手順: A solution of 7.5 g of 2,3-dihydro-2-oxo-benzo[b]thiophen in 50 ml of hexamethylphosphoric acid triamide is added dropwise, with cooling, to a suspension of 2.4 g of a 50% sodium hydride/mineral oil dispersion in 100 ml of hexamethylphosphoric acid triamide, the temperature being kept below 15° during the addition. After stirring for half an hour at room temperature, 52 g of phenyl N-(2-thienyl)-carbamate, dissolved in 50 ml of hexamethylphosphoric acid triamide, are added dropwise, with external cooling. The reaction mixture is stirred for a further 16 hours at room temperature and is poured into a mixture of 200 ml of 2 N hydrochloric acid and 1000 ml of ice-water. An oil separates out and this crystallises after about 2 hours. The crystalline product, which contains solvent, is dissolved in 2 N sodium hydroxide solution and the solution is washed four times with ethyl acetate. The organic phase is washed with water, the aqueous phases are combined and acidified to a pH of 1 and the crude product is filtered off with suction and recrystallised from tetrahydrofuran/ether. N-(2-Thienyl)-2-oxo-2,3-dihydro-3-benzo[b]thiophen-carboxamide with a melting point of 142°-144° (decomposition) is obtained. the temperature being kept below 15° during the addition are added dropwise, with external cooling The reaction mixture is stirred for a further 16 hours at room temperature this crystallises after about 2 hours is dissolved in 2 N sodium hydroxide solution the solution is washed four times with ethyl acetate The organic phase is washed with water the crude product is filtered off with suction recrystallised from tetrahydrofuran/ether