4-bromo-3-methyl-2,3-dihydroinden-1-one

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 116 g (0.52 mol) of 4-bromo-3-methylindan-1-one in 950 ml of a mixture of THF-methanol (2:1, vol.) 38.3 g (1.02 mol) of NaBH4 was added in small portions, while vigorously stirring, over 2 h at 0° C. This mixture was stirred for 12 h at room temperature and then added to 1000 ml of cold water. The organic layer was separated, the aqueous layer was extracted with 3×300 ml of methyl-tert-butyl ether. The combined organic fractions were dried over K2CO3 and then evaporated to dryness. The residue was dissolved in 1500 ml of toluene, and 2.0 g of p-TosOH was added. The resulting solution was refluxed for 2 h using a Dean-Stark trap to remove the water formed, and then it was passed through a short Silica Gel 60 column (40-63 um, d 100 mm, l 80 mm, eluent: hexanes). This column was additionally washed with 250 ml of toluene. The combined organic extract was evaporated to dryness. The product was isolated by vacuum distillation (bp 104-108° C./5 mm Hg). Yield 100 g (93%). This mixture was stirred for 12 h at room temperature The organic layer was separated the aqueous layer was extracted with 3×300 ml of methyl-tert-butyl ether The combined organic fractions were dried over K2CO3 evaporated to dryness The residue was dissolved in 1500 ml of toluene 2.0 g of p-TosOH was added The resulting solution was refluxed for 2 h to remove the water formed This column was additionally washed with 250 ml of toluene The combined organic extract was evaporated to dryness The product was isolated by vacuum distillation (bp 104-108° C./5 mm Hg)

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 116 g (0.52 mol) of 4-bromo-3-methylindan-1-one in 950 ml of a mixture of THF-methanol (2:1, vol.) 38.3 g (1.02 mol) of NaBH4 was added in small portions, while vigorously stirring, over 2 h at 0° C. This mixture was stirred for 12 h at room temperature and then added to 1000 ml of cold water. The organic layer was separated, the aqueous layer was extracted with 3×300 ml of methyl-tert-butyl ether. The combined organic fractions were dried over K2CO3 and then evaporated to dryness. The residue was dissolved in 1500 ml of toluene, and 2.0 g of p-TosOH was added. The resulting solution was refluxed for 2 h using a Dean-Stark trap to remove the water formed, and then it was passed through a short Silica Gel 60 column (40-63 um, d 100 mm, l 80 mm, eluent: hexanes). This column was additionally washed with 250 ml of toluene. The combined organic extract was evaporated to dryness. The product was isolated by vacuum distillation (bp 104-108° C./5 mm Hg). Yield 100 g (93%). This mixture was stirred for 12 h at room temperature The organic layer was separated the aqueous layer was extracted with 3×300 ml of methyl-tert-butyl ether The combined organic fractions were dried over K2CO3 evaporated to dryness The residue was dissolved in 1500 ml of toluene 2.0 g of p-TosOH was added The resulting solution was refluxed for 2 h to remove the water formed This column was additionally washed with 250 ml of toluene The combined organic extract was evaporated to dryness The product was isolated by vacuum distillation (bp 104-108° C./5 mm Hg)

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

実験手順: To a solution of sodium ethoxide in ethanol obtained from 15.4 g (0.67 mmol) of sodium and 360 ml of anhydrous ethanol, a solution of 215 g (1.34 mmol) of diethyl malonate in 240 ml of ethanol was added dropwise, while vigorously stirring, over 15 min. Then, 137 g (0.52 mmol) of 1-bromo-2-(1-bromoethyl)benzene in 50 ml of ethanol was added dropwise with such a rate, so the reaction mixture would be slowly refluxing. The resulting mixture was additionally refluxed for 4 h, then cooled to room temperature, and a solution of 105 g of potassium hydroxide in 280 ml of water was added. This mixture was refluxed for 3 h, and then ethanol was distilled off at atmospheric pressure. The solution obtained was cooled to ambient temperature and acidified by saturated hydrochloric acid to pH 1. The precipitate formed was filtered off, washed with 2×200 ml of cold water, and dried in air. The dibacic acid obtained was then dehcarboxylated by heating it at 160° C. for 2 h. To the viscous oil obtained, 130 ml of SOCl2 was added, and the resulting mixture was stirred for 24 h at room temperature. The excess of SOCl2 was distilled off, and the residue was dissolved in 160 ml of anhydrous dichloromethane. The solution obtained was added dropwise to a suspension of 80.0 g (0.60 mmol) of AlCl3 in 800 ml of dichloromethane for 1 h at 0° C. The reaction mixture was refluxed for 3 h, then cooled to room temperature, poured on 500 cm3 of ice, and finally acidified by saturated HCl to pH 3. The organic layer was separated, and the aqueous layer was washed with 3×300 ml of methyl-tert-butyl ether. The combined organic extract was dried over K2CO3 and then evaporated to dryness. The title product was isolated fractional distillation in vacuum, bp 108-112° C./3 mm Hg. Yield 101 g (86%). so the reaction mixture would be slowly refluxing The resulting mixture was additionally refluxed for 4 h This mixture was refluxed for 3 h ethanol was distilled off at atmospheric pressure The solution obtained was cooled to ambient temperature The precipitate formed was filtered off washed with 2×200 ml of cold water dried in air The dibacic acid obtained by heating it at 160° C. for 2 h To the viscous oil obtained the resulting mixture was stirred for 24 h at room temperature The excess of SOCl2 was distilled off the residue was dissolved in 160 ml of anhydrous dichloromethane The solution obtained The reaction mixture was refluxed for 3 h cooled to room temperature The organic layer was separated the aqueous layer was washed with 3×300 ml of methyl-tert-butyl ether The combined organic extract was dried over K2CO3 evaporated to dryness

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

実験手順: To a solution of sodium ethoxide in ethanol obtained from 15.4 g (0.67 mmol) of sodium and 360 ml of anhydrous ethanol, a solution of 215 g (1.34 mmol) of diethyl malonate in 240 ml of ethanol was added dropwise, while vigorously stirring, over 15 min. Then, 137 g (0.52 mmol) of 1-bromo-2-(1-bromoethyl)benzene in 50 ml of ethanol was added dropwise with such a rate, so the reaction mixture would be slowly refluxing. The resulting mixture was additionally refluxed for 4 h, then cooled to room temperature, and a solution of 105 g of potassium hydroxide in 280 ml of water was added. This mixture was refluxed for 3 h, and then ethanol was distilled off at atmospheric pressure. The solution obtained was cooled to ambient temperature and acidified by saturated hydrochloric acid to pH 1. The precipitate formed was filtered off, washed with 2×200 ml of cold water, and dried in air. The dibacic acid obtained was then dehcarboxylated by heating it at 160° C. for 2 h. To the viscous oil obtained, 130 ml of SOCl2 was added, and the resulting mixture was stirred for 24 h at room temperature. The excess of SOCl2 was distilled off, and the residue was dissolved in 160 ml of anhydrous dichloromethane. The solution obtained was added dropwise to a suspension of 80.0 g (0.60 mmol) of AlCl3 in 800 ml of dichloromethane for 1 h at 0° C. The reaction mixture was refluxed for 3 h, then cooled to room temperature, poured on 500 cm3 of ice, and finally acidified by saturated HCl to pH 3. The organic layer was separated, and the aqueous layer was washed with 3×300 ml of methyl-tert-butyl ether. The combined organic extract was dried over K2CO3 and then evaporated to dryness. The title product was isolated fractional distillation in vacuum, bp 108-112° C./3 mm Hg. Yield 101 g (86%). so the reaction mixture would be slowly refluxing The resulting mixture was additionally refluxed for 4 h This mixture was refluxed for 3 h ethanol was distilled off at atmospheric pressure The solution obtained was cooled to ambient temperature The precipitate formed was filtered off washed with 2×200 ml of cold water dried in air The dibacic acid obtained by heating it at 160° C. for 2 h To the viscous oil obtained the resulting mixture was stirred for 24 h at room temperature The excess of SOCl2 was distilled off the residue was dissolved in 160 ml of anhydrous dichloromethane The solution obtained The reaction mixture was refluxed for 3 h cooled to room temperature The organic layer was separated the aqueous layer was washed with 3×300 ml of methyl-tert-butyl ether The combined organic extract was dried over K2CO3 evaporated to dryness

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 116 g (0.52 mol) of 4-bromo-3-methylindan-1-one in 950 ml of a mixture of THF-methanol (2:1, vol.) 38.3 g (1.02 mol) of NaBH4 was added in small portions, while vigorously stirring, over 2 h at 0° C. This mixture was stirred for 12 h at room temperature and then added to 1000 ml of cold water. The organic layer was separated, the aqueous layer was extracted with 3×300 ml of methyl-tert-butyl ether. The combined organic fractions were dried over K2CO3 and then evaporated to dryness. The residue was dissolved in 1500 ml of toluene, and 2.0 g of p-TosOH was added. The resulting solution was refluxed for 2 h using a Dean-Stark trap to remove the water formed, and then it was passed through a short Silica Gel 60 column (40-63 um, d 100 mm, l 80 mm, eluent: hexanes). This column was additionally washed with 250 ml of toluene. The combined organic extract was evaporated to dryness. The product was isolated by vacuum distillation (bp 104-108° C./5 mm Hg). Yield 100 g (93%). This mixture was stirred for 12 h at room temperature The organic layer was separated the aqueous layer was extracted with 3×300 ml of methyl-tert-butyl ether The combined organic fractions were dried over K2CO3 evaporated to dryness The residue was dissolved in 1500 ml of toluene 2.0 g of p-TosOH was added The resulting solution was refluxed for 2 h to remove the water formed This column was additionally washed with 250 ml of toluene The combined organic extract was evaporated to dryness The product was isolated by vacuum distillation (bp 104-108° C./5 mm Hg)

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

実験手順: To a solution of sodium ethoxide in ethanol obtained from 15.4 g (0.67 mmol) of sodium and 360 ml of anhydrous ethanol, a solution of 215 g (1.34 mmol) of diethyl malonate in 240 ml of ethanol was added dropwise, while vigorously stirring, over 15 min. Then, 137 g (0.52 mmol) of 1-bromo-2-(1-bromoethyl)benzene in 50 ml of ethanol was added dropwise with such a rate, so the reaction mixture would be slowly refluxing. The resulting mixture was additionally refluxed for 4 h, then cooled to room temperature, and a solution of 105 g of potassium hydroxide in 280 ml of water was added. This mixture was refluxed for 3 h, and then ethanol was distilled off at atmospheric pressure. The solution obtained was cooled to ambient temperature and acidified by saturated hydrochloric acid to pH 1. The precipitate formed was filtered off, washed with 2×200 ml of cold water, and dried in air. The dibacic acid obtained was then dehcarboxylated by heating it at 160° C. for 2 h. To the viscous oil obtained, 130 ml of SOCl2 was added, and the resulting mixture was stirred for 24 h at room temperature. The excess of SOCl2 was distilled off, and the residue was dissolved in 160 ml of anhydrous dichloromethane. The solution obtained was added dropwise to a suspension of 80.0 g (0.60 mmol) of AlCl3 in 800 ml of dichloromethane for 1 h at 0° C. The reaction mixture was refluxed for 3 h, then cooled to room temperature, poured on 500 cm3 of ice, and finally acidified by saturated HCl to pH 3. The organic layer was separated, and the aqueous layer was washed with 3×300 ml of methyl-tert-butyl ether. The combined organic extract was dried over K2CO3 and then evaporated to dryness. The title product was isolated fractional distillation in vacuum, bp 108-112° C./3 mm Hg. Yield 101 g (86%). so the reaction mixture would be slowly refluxing The resulting mixture was additionally refluxed for 4 h This mixture was refluxed for 3 h ethanol was distilled off at atmospheric pressure The solution obtained was cooled to ambient temperature The precipitate formed was filtered off washed with 2×200 ml of cold water dried in air The dibacic acid obtained by heating it at 160° C. for 2 h To the viscous oil obtained the resulting mixture was stirred for 24 h at room temperature The excess of SOCl2 was distilled off the residue was dissolved in 160 ml of anhydrous dichloromethane The solution obtained The reaction mixture was refluxed for 3 h cooled to room temperature The organic layer was separated the aqueous layer was washed with 3×300 ml of methyl-tert-butyl ether The combined organic extract was dried over K2CO3 evaporated to dryness

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

実験手順: To a solution of sodium ethoxide in ethanol obtained from 15.4 g (0.67 mmol) of sodium and 360 ml of anhydrous ethanol, a solution of 215 g (1.34 mmol) of diethyl malonate in 240 ml of ethanol was added dropwise, while vigorously stirring, over 15 min. Then, 137 g (0.52 mmol) of 1-bromo-2-(1-bromoethyl)benzene in 50 ml of ethanol was added dropwise with such a rate, so the reaction mixture would be slowly refluxing. The resulting mixture was additionally refluxed for 4 h, then cooled to room temperature, and a solution of 105 g of potassium hydroxide in 280 ml of water was added. This mixture was refluxed for 3 h, and then ethanol was distilled off at atmospheric pressure. The solution obtained was cooled to ambient temperature and acidified by saturated hydrochloric acid to pH 1. The precipitate formed was filtered off, washed with 2×200 ml of cold water, and dried in air. The dibacic acid obtained was then dehcarboxylated by heating it at 160° C. for 2 h. To the viscous oil obtained, 130 ml of SOCl2 was added, and the resulting mixture was stirred for 24 h at room temperature. The excess of SOCl2 was distilled off, and the residue was dissolved in 160 ml of anhydrous dichloromethane. The solution obtained was added dropwise to a suspension of 80.0 g (0.60 mmol) of AlCl3 in 800 ml of dichloromethane for 1 h at 0° C. The reaction mixture was refluxed for 3 h, then cooled to room temperature, poured on 500 cm3 of ice, and finally acidified by saturated HCl to pH 3. The organic layer was separated, and the aqueous layer was washed with 3×300 ml of methyl-tert-butyl ether. The combined organic extract was dried over K2CO3 and then evaporated to dryness. The title product was isolated fractional distillation in vacuum, bp 108-112° C./3 mm Hg. Yield 101 g (86%). so the reaction mixture would be slowly refluxing The resulting mixture was additionally refluxed for 4 h This mixture was refluxed for 3 h ethanol was distilled off at atmospheric pressure The solution obtained was cooled to ambient temperature The precipitate formed was filtered off washed with 2×200 ml of cold water dried in air The dibacic acid obtained by heating it at 160° C. for 2 h To the viscous oil obtained the resulting mixture was stirred for 24 h at room temperature The excess of SOCl2 was distilled off the residue was dissolved in 160 ml of anhydrous dichloromethane The solution obtained The reaction mixture was refluxed for 3 h cooled to room temperature The organic layer was separated the aqueous layer was washed with 3×300 ml of methyl-tert-butyl ether The combined organic extract was dried over K2CO3 evaporated to dryness

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 2.6 g (11.5 mmol) of 4-bromo-3-methyl-1-indanone [J. Org. Chem. 22, 1019 (1957)] and 1.14 g (12.7 mmol) of copper(I) cyanide in 2.5 ml of DMF is stirred for 6 hours at 170°. The reaction mixture is then cooled to 100°, and 50 ml of toluene and a solution of 4.5 g (16.5 mmol) of iron(III) chloride hexahydrate in 7 ml of water and 1.7 ml of concentrated hydrochloric acid are added in succession thereto. The reaction mixture is stirred for 20 minutes at 70°, cooled and diluted with toluene and water. The organic phase is separated off, washed with water, a semi-saturated sodium hydrogen carbonate solution and again with water, dried and concentrated by evaporation. The residue is distilled at 100°-120°/0.05 mbar in a bulb tube still and corresponds to starting compound (a), m.p. 109°-111°; IR (CH2Cl2): 2220, 1710 cm-1 ; 1H-NMR (CDCl3): δ=7.92 (m,2H); 7.52 (t,1H); 3.73 (m,1H); 3.03 (q,1H); 2.40 (q,1H); 1.55 (d,3H). The reaction mixture is then cooled to 100° The reaction mixture is stirred for 20 minutes at 70° cooled The organic phase is separated off washed with water a semi-saturated sodium hydrogen carbonate solution and again with water, dried concentrated by evaporation The residue is distilled at 100°-120°/0.05 mbar in a bulb tube still

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

実験手順: A mixture of 2.6 g (11.5 mmol) of 4-bromo-3-methyl-1-indanone [J. Org. Chem. 22, 1019 (1957)] and 1.14 g (12.7 mmol) of copper(I) cyanide in 2.5 ml of DMF is stirred for 6 hours at 170°. The reaction mixture is then cooled to 100°, and 50 ml of toluene and a solution of 4.5 g (16.5 mmol) of iron(III) chloride hexahydrate in 7 ml of water and 1.7 ml of concentrated hydrochloric acid are added in succession thereto. The reaction mixture is stirred for 20 minutes at 70°, cooled and diluted with toluene and water. The organic phase is separated off, washed with water, a semi-saturated sodium hydrogen carbonate solution and again with water, dried and concentrated by evaporation. The residue is distilled at 100°-120°/0.05 mbar in a bulb tube still and corresponds to starting compound (a), m.p. 109°-111°; IR (CH2Cl2): 2220, 1710 cm-1 ; 1H-NMR (CDCl3): δ=7.92 (m,2H); 7.52 (t,1H); 3.73 (m,1H); 3.03 (q,1H); 2.40 (q,1H); 1.55 (d,3H). The reaction mixture is then cooled to 100° The reaction mixture is stirred for 20 minutes at 70° cooled The organic phase is separated off washed with water a semi-saturated sodium hydrogen carbonate solution and again with water, dried concentrated by evaporation The residue is distilled at 100°-120°/0.05 mbar in a bulb tube still

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 116 g (0.52 mol) of 4-bromo-3-methylindan-1-one in 950 ml of a mixture of THF-methanol (2:1, vol.) 38.3 g (1.02 mol) of NaBH4 was added in small portions, while vigorously stirring, over 2 h at 0° C. This mixture was stirred for 12 h at room temperature and then added to 1000 ml of cold water. The organic layer was separated, the aqueous layer was extracted with 3×300 ml of methyl-tert-butyl ether. The combined organic fractions were dried over K2CO3 and then evaporated to dryness. The residue was dissolved in 1500 ml of toluene, and 2.0 g of p-TosOH was added. The resulting solution was refluxed for 2 h using a Dean-Stark trap to remove the water formed, and then it was passed through a short Silica Gel 60 column (40-63 um, d 100 mm, l 80 mm, eluent: hexanes). This column was additionally washed with 250 ml of toluene. The combined organic extract was evaporated to dryness. The product was isolated by vacuum distillation (bp 104-108° C./5 mm Hg). Yield 100 g (93%). This mixture was stirred for 12 h at room temperature The organic layer was separated the aqueous layer was extracted with 3×300 ml of methyl-tert-butyl ether The combined organic fractions were dried over K2CO3 evaporated to dryness The residue was dissolved in 1500 ml of toluene 2.0 g of p-TosOH was added The resulting solution was refluxed for 2 h to remove the water formed This column was additionally washed with 250 ml of toluene The combined organic extract was evaporated to dryness The product was isolated by vacuum distillation (bp 104-108° C./5 mm Hg)