4-methyl-3,4-dihydro-2H-naphthalen-1-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:; See reaction.notes.procedure_details.

実験手順: The 3,4-dihydro-2-(dimethylaminomethylene)-4-methyl-1(2H)-naphthalenone starting material was prepared from 4-methyl-1-tetralone (4.0 g, 25 mmol) and N,N-dimethylformamide diethyl acetal (17 ml, 100 mmol) to give the desired product as a thick yellow oil (4.53 g). δH (CDCl3) 8.03 (1H, dd, J 7.7, 1.5 Hz), 7.77 (1H, s), 7.39 (1H, td, J 7.4, 1.5 Hz), 7.29 (1H, td, J 7.5, 1.3 Hz), 7.20 (1H, dm, J 7.5 Hz), 3.12 (6H, s), 3.10-2.90 (2H, m), 2.75 (1H, apparent q, 6.9 Hz) and 1.30 (3H, d, J 6.9 Hz). MS (ES+) 216 (MH+, 100%).

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

実験手順: The 3,4-dihydro-2-(dimethylaminomethylene)-4-methyl-1(2H)-naphthalenone starting material was prepared from 4-methyl-1-tetralone (4.0 g, 25 mmol) and N,N-dimethylformamide diethyl acetal (17 ml, 100 mmol) to give the desired product as a thick yellow oil (4.53 g). δH (CDCl3) 8.03 (1H, dd, J 7.7, 1.5 Hz), 7.77 (1H, s), 7.39 (1H, td, J 7.4, 1.5 Hz), 7.29 (1H, td, J 7.5, 1.3 Hz), 7.20 (1H, dm, J 7.5 Hz), 3.12 (6H, s), 3.10-2.90 (2H, m), 2.75 (1H, apparent q, 6.9 Hz) and 1.30 (3H, d, J 6.9 Hz). MS (ES+) 216 (MH+, 100%).

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

実験手順: Commercially available 4-methyl-1-tetralone, 32.0 grams, contained in 250 ml. of chloroform and 50 ml. of ethyl acetate is heated to boiling. A mixture of 98.3 grams of cupric bromide and 50 ml. of ethyl acetate is heated to its reflux temperature. After all of the hydrogen bromide is evolved, the mixture is maintained at its reflux temperature for an additional hour. The reaction mixture is filtered while hot, the residue washed with boiling chloroform and the combined filtrates evaporated to dryness in vacuo. The residue is dissolved in a minimum of methylene chloride, placed upon an alumina column and eluted with methylene chloride. The eluate is concentrated and the desired 2-bromo-4-methyl-1-tetralone obtained as a dark oil. reflux temperature the mixture is maintained at its reflux temperature for an additional hour The reaction mixture is filtered while hot, the residue washed with boiling chloroform the combined filtrates evaporated to dryness in vacuo The residue is dissolved in a minimum of methylene chloride eluted with methylene chloride The eluate is concentrated

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

実験手順: A solution of 801 mg (5.0 mmol) of 4-methyl-1-tetralone in 20 mL of dry methanol was treated with 417 mg of hydroxylamine hydrochloride (6.0 mmol, 1.2 eq) and 504 mg (6.0 mmol, 1.2 eq) of sodium bicarbonate and the resulting mixture was stirred at room temperature for 16 hours. The solid was filtered off and the solvent was removed under vacuum. The white residue was redissolved in 10 mL of methylene chloride and filtered. The filtrate was evaporated to dryness under vacuum to give the product in quantitative yield. 1H NMR (400 MHz, CDCl3): 1.30 (d, 8 Hz, 3H), 1.69 (m, 1H), 2.45 (m, 1H), 2.88 (m, 3H), 7.15-7.35 (m, 3H), 7.86 (d, 8 Hz, 1H). The solid was filtered off the solvent was removed under vacuum The white residue was redissolved in 10 mL of methylene chloride filtered The filtrate was evaporated to dryness under vacuum to give the product in quantitative yield

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

実験手順: Following a similar procedure to that reported in Ferraz, which is hereby incorporated by reference, to a stirred solution of 4-methyl-α-tetralone (0.867 g, 4.98 mmol) in methanol (20 mL) was added NaBH4 (0.56 g, 14.9 mmol) portionwise. The reaction mixture was followed by TLC and, after complete consumption of the starting material (about 2 h), was quenched with saturated NaHCO3. The aqueous layer was extracted with diethyl ether, dried with magnesium sulfate (MgSO4), and filtered; and the solvent was removed under reduced pressure. The crude alcohol was dissolved in toluene (25 mL) and a few crystals of p-TsOH were added. The reaction mixture was stirred overnight, then neutralized by slow addition of saturated sodium bicarbonate (NaHCO3) and extracted with diethyl ether. The combined organic layers where washed with brine, dried with magnesium sulfate (MgSO4), and filtered; and the solvent was removed under reduced pressure. The product was purified by flash chromatography (SiO2, hexanes) to give 1,2-dihydro-1,6-dimethylnaphthalene ((±)-4) as a clear oil (0.479 g, 61% yield). This compound is volatile and cannot be dried for long periods (>30 min) under high vacuum. The spectroscopic data are consistent with previously reported data (Adachi et al., Bull. Chem. Soc. Jpn., 56:651ff (1983), which is hereby incorporated by reference). after complete consumption of the starting material (about 2 h) was quenched with saturated NaHCO3 The aqueous layer was extracted with diethyl ether dried with magnesium sulfate (MgSO4) filtered and the solvent was removed under reduced pressure The crude alcohol was dissolved in toluene (25 mL) a few crystals of p-TsOH were added neutralized by slow addition of saturated sodium bicarbonate (NaHCO3) extracted with diethyl ether The combined organic layers where washed with brine dried with magnesium sulfate (MgSO4) filtered and the solvent was removed under reduced pressure The product was purified by flash chromatography (SiO2, hexanes)

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

実験手順: 1,2-Dihydro-1-methylnaphthalene ((±)-8) was prepared using a similar procedure to that reported in Ferraz et al., Tetrahedron, 57:1709ff (2001) (“Ferraz”), which is hereby incorporated by reference). The scheme is set forth in FIG. 7C. To a stirred solution of commercially available 4-methyl-α-tetralone (0.50 g, 3.12 mmol) in methanol (50 mL) was added NaBH4 (0.35 g, 9.36 mmol) portionwise. The reaction mixture was followed by TLC and, after complete consumption of the starting material (approx. 2 h), was quenched with saturated NaHCO3. The aqueous layer was extracted with diethyl ether, dried with magnesium sulfate (MgSO4), filtered, and the solvent was removed under reduced pressure. The crude alcohol was dissolved in toluene (15 mL), and a few crystals of p-TsOH were added. The reaction mixture was stirred overnight, then neutralized by slow addition of saturated sodium bicarbonate (NaHCO3) and extracted with diethyl ether. The combined organic layers where washed with brine, dried with magnesium sulfate (MgSO4), filtered, and the solvent was removed under reduced pressure. The product was purified by flash chromatography (SiO2, hexanes) to give 1,2-dihydro-1-methylnaphthalene ((±)-8) as a clear oil (0.35 g, 78% yield). The compound is volatile and cannot be dried for long periods (>30 min) under high vacuum. The spectroscopic data are consistent with previously reported data (Ferraz, which is hereby incorporated by reference). 1,2-Dihydro-1-methylnaphthalene ((±)-8) was prepared after complete consumption of the starting material (approx. 2 h) was quenched with saturated NaHCO3 The aqueous layer was extracted with diethyl ether dried with magnesium sulfate (MgSO4) filtered the solvent was removed under reduced pressure The crude alcohol was dissolved in toluene (15 mL) a few crystals of p-TsOH were added neutralized by slow addition of saturated sodium bicarbonate (NaHCO3) extracted with diethyl ether The combined organic layers where washed with brine dried with magnesium sulfate (MgSO4) filtered the solvent was removed under reduced pressure The product was purified by flash chromatography (SiO2, hexanes)

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

実験手順: 1,2-Dihydro-1-methylnaphthalene ((±)-8) was prepared using a similar procedure to that reported in Ferraz et al., Tetrahedron, 57:1709ff (2001) (“Ferraz”), which is hereby incorporated by reference). The scheme is set forth in FIG. 7C. To a stirred solution of commercially available 4-methyl-α-tetralone (0.50 g, 3.12 mmol) in methanol (50 mL) was added NaBH4 (0.35 g, 9.36 mmol) portionwise. The reaction mixture was followed by TLC and, after complete consumption of the starting material (approx. 2 h), was quenched with saturated NaHCO3. The aqueous layer was extracted with diethyl ether, dried with magnesium sulfate (MgSO4), filtered, and the solvent was removed under reduced pressure. The crude alcohol was dissolved in toluene (15 mL), and a few crystals of p-TsOH were added. The reaction mixture was stirred overnight, then neutralized by slow addition of saturated sodium bicarbonate (NaHCO3) and extracted with diethyl ether. The combined organic layers where washed with brine, dried with magnesium sulfate (MgSO4), filtered, and the solvent was removed under reduced pressure. The product was purified by flash chromatography (SiO2, hexanes) to give 1,2-dihydro-1-methylnaphthalene ((±)-8) as a clear oil (0.35 g, 78% yield). The compound is volatile and cannot be dried for long periods (>30 min) under high vacuum. The spectroscopic data are consistent with previously reported data (Ferraz, which is hereby incorporated by reference). 1,2-Dihydro-1-methylnaphthalene ((±)-8) was prepared after complete consumption of the starting material (approx. 2 h) was quenched with saturated NaHCO3 The aqueous layer was extracted with diethyl ether dried with magnesium sulfate (MgSO4) filtered the solvent was removed under reduced pressure The crude alcohol was dissolved in toluene (15 mL) a few crystals of p-TsOH were added neutralized by slow addition of saturated sodium bicarbonate (NaHCO3) extracted with diethyl ether The combined organic layers where washed with brine dried with magnesium sulfate (MgSO4) filtered the solvent was removed under reduced pressure The product was purified by flash chromatography (SiO2, hexanes)

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

実験手順: Tellurium dioxide (79.5 g=0.5 mole) was dissolved in concentrated hydrochloric acid (200 ml). Hydroxylamine hydrochloride (35 g=0.5 mole) was added and then ethanol to bring the total volume to 2000 ml. To the slightly turbid solution was added 4-methyl-α-tetralone (80 g=0.5 mole) and the stirred mixture heated briefly to boil. The clear deep red solution was then kept overnight at room temperature. The solid mass of crystalline product was collected, washed well with water and dried in a vacuum oven at 90° C. to give a first crop (111.1 g) of dark red needles. The filtrate was heated once again and kept at room temperature for 24 hours. A second crop of 14.3 g crude product was obtained. The well-dried product was placed into a Soxhlet thimble and extracted with methylene chloride. The majority of purified product crystallized from the solvent during the course of the extraction to give a yield of 97.0 g=58.3% of theory, m.p. 196°-198° C. Elemental analyses results were in agreement with the structural formula. The ultraviolet and visible spectra in dichloromethane showed three maxima. the stirred mixture heated briefly The solid mass of crystalline product was collected washed well with water dried in a vacuum oven at 90° C.

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

実験手順: Tellurium dioxide (79.5 g=0.5 mole) was dissolved in concentrated hydrochloric acid (200 ml). Hydroxylamine hydrochloride (35 g=0.5 mole) was added and then ethanol to bring the total volume to 2000 ml. To the slightly turbid solution was added 4-methyl-α-tetralone (80 g=0.5 mole) and the stirred mixture heated briefly to boil. The clear deep red solution was then kept overnight at room temperature. The solid mass of crystalline product was collected, washed well with water and dried in a vacuum oven at 90° C. to give a first crop (111.1 g) of dark red needles. The filtrate was heated once again and kept at room temperature for 24 hours. A second crop of 14.3 g crude product was obtained. The well-dried product was placed into a Soxhlet thimble and extracted with methylene chloride. The majority of purified product crystallized from the solvent during the course of the extraction to give a yield of 97.0 g=58.3% of theory, m.p. 196°-198° C. Elemental analyses results were in agreement with the structural formula. The ultraviolet and visible spectra in dichloromethane showed three maxima. the stirred mixture heated briefly The solid mass of crystalline product was collected washed well with water dried in a vacuum oven at 90° C.

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

実験手順: 4.8 g (0.03 mole) of 4-methyl-1-tetralone are reacted with 4.8 g (0.03 mole) of bromine in ethyl acetate, analogously to the instructions indicated in Example 29 (a), to give 2-bromo-4-methyl-1-tetralone. The oily product is further processed immediately without further purification.