2-(2,2,3-trimethylcyclopent-3-en-1-yl)acetaldehyde

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

実験手順: A solution was made of α-campholenic aldehyde (200 g) in acetone (2 liters) and cooled to 0° C. Jones reagent was prepared from 115 ml conc. sulfuric acid, 500 ml water and 134 g of chromium (VI) oxide. The reagent (400 ml) was added to the solution at 0° C. over a period of 30 minutes. After an additional 15 minutes at 0° C. the acetone was removed by decantation and the residual chromium salts were washed with an additional 200 ml acetone. The combined acetone solution was concentrated to 1 liter, diluted with 10% aqueous sodium hydroxide (1 liter) and washed with CH2Cl2 (2×1 liter). The aqueous phase was acidified with 25% sulfuric acid and extracted with CH2Cl2 (2×1 liter). Concentration of the CH2Cl2 solution yielded an oil (145 g) which was distilled under reduced pressure to give 116 g of a yellowish liquid; bp 121° C. @ 2.2 mm Hg; analysis: 98% (CW 20M fused silica column, 180° C.) α-campholenic acid. After an additional 15 minutes at 0° C. the acetone was removed by decantation the residual chromium salts were washed with an additional 200 ml acetone The combined acetone solution was concentrated to 1 liter diluted with 10% aqueous sodium hydroxide (1 liter) washed with CH2Cl2 (2×1 liter) extracted with CH2Cl2 (2×1 liter)

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

実験手順: A solution was made of α-campholenic aldehyde (200 g) in acetone (2 liters) and cooled to 0° C. Jones reagent was prepared from 115 ml conc. sulfuric acid, 500 ml water and 134 g of chromium (VI) oxide. The reagent (400 ml) was added to the solution at 0° C. over a period of 30 minutes. After an additional 15 minutes at 0° C. the acetone was removed by decantation and the residual chromium salts were washed with an additional 200 ml acetone. The combined acetone solution was concentrated to 1 liter, diluted with 10% aqueous sodium hydroxide (1 liter) and washed with CH2Cl2 (2×1 liter). The aqueous phase was acidified with 25% sulfuric acid and extracted with CH2Cl2 (2×1 liter). Concentration of the CH2Cl2 solution yielded an oil (145 g) which was distilled under reduced pressure to give 116 g of a yellowish liquid; bp 121° C. @ 2.2 mm Hg; analysis: 98% (CW 20M fused silica column, 180° C.) α-campholenic acid. After an additional 15 minutes at 0° C. the acetone was removed by decantation the residual chromium salts were washed with an additional 200 ml acetone The combined acetone solution was concentrated to 1 liter diluted with 10% aqueous sodium hydroxide (1 liter) washed with CH2Cl2 (2×1 liter) extracted with CH2Cl2 (2×1 liter)

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

実験手順: A solution was made of α-campholenic aldehyde (200 g) in acetone (2 liters) and cooled to 0° C. Jones reagent was prepared from 115 ml conc. sulfuric acid, 500 ml water and 134 g of chromium (VI) oxide. The reagent (400 ml) was added to the solution at 0° C. over a period of 30 minutes. After an additional 15 minutes at 0° C. the acetone was removed by decantation and the residual chromium salts were washed with an additional 200 ml acetone. The combined acetone solution was concentrated to 1 liter, diluted with 10% aqueous sodium hydroxide (1 liter) and washed with CH2Cl2 (2×1 liter). The aqueous phase was acidified with 25% sulfuric acid and extracted with CH2Cl2 (2×1 liter). Concentration of the CH2Cl2 solution yielded an oil (145 g) which was distilled under reduced pressure to give 116 g of a yellowish liquid; bp 121° C.@ 2.2 mm Hg; analysis: 98% (CW 20 M fused silica column, 180° C.) α-campholenic acid. After an additional 15 minutes at 0° C. the acetone was removed by decantation the residual chromium salts were washed with an additional 200 ml acetone The combined acetone solution was concentrated to 1 liter diluted with 10% aqueous sodium hydroxide (1 liter) washed with CH2Cl2 (2×1 liter) extracted with CH2Cl2 (2×1 liter)

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

実験手順: According to this article, α-pinene oxide rearranged exothermically in the presence of zinc bromide catalyst in benzene solvent to give about 80% yield of alpha-campholenic aldehyde (Scheme 1). Since then, this batch process, or variations thereof, has been described in numerous publications and patents.

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

実験手順: A mixture of campholenic aldehyde (456 g, 3.0 mol) and freshly distilled propionaldehyde (348 g, 6.0 mol) was slowly added, over a 1.0 hour period, to a stirred refluxing solution of 18 ml of 40% aqueous sodium hydroxide and 800 ml methanol. The mixture was refluxed an additional two hours, cooled to room temperature and poured into 1,000 ml of water. The resultant solution was extracted three times with 300 ml of hexane. The hexane extracts were combined, washed first with 600 ml of water and then with 600 ml of brine. The solvent was removed by distillation and the oil fractionally distilled to yield the 2-methyl-4-(2,2,3-trimethylcyclopent-3-en-1-yl)but-2-enal. Yield 323 g (56.1% theory); bp 64°-65° C (0.9 mm); mol wt. 192 (ms); ir, 3035, 2710, 1690 (s), 1640 (s), 800 cm-1 ; nmr, 0.8δ and 1.0 (6 H, 2s, geminal dimethyl groups), 1.7 (3H, broad s, olefinic methyl attached to the cyclopentenyl group), 1.9-2.2 (3H, broad multiplet), 2.3-2.6 (3H, broad multiplet), 5.3 (1H, broad multiplet, olefinic H), 6.6 (1H, t, J~7.5 Hz), 9.4 (1H, sharp s, aldehyde H). was slowly added, over a 1.0 hour period, to a stirred The mixture was refluxed an additional two hours The resultant solution was extracted three times with 300 ml of hexane washed first with 600 ml of water The solvent was removed by distillation the oil fractionally distilled

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

実験手順: A mixture of campholenic aldehyde (456 g, 3.0 mol) and freshly distilled propionaldehyde (348 g, 6.0 mol) was slowly added, over a 1.0 hour period, to a stirred refluxing solution of 18 ml of 40% aqueous sodium hydroxide and 800 ml methanol. The mixture was refluxed an additional two hours, cooled to room temperature and poured into 1,000 ml of water. The resultant solution was extracted three times with 300 ml of hexane. The hexane extracts were combined, washed first with 600 ml of water and then with 600 ml of brine. The solvent was removed by distillation and the oil fractionally distilled to yield the 2-methyl-4-(2,2,3-trimethylcyclopent-3-en-1-yl)but-2-enal. Yield 323 g (56.1% theory); bp 64°-65° C (0.9 mm); mol wt. 192 (ms); ir, 3035, 2710, 1690 (s), 1640 (s), 800 cm-1 ; nmr, 0.8δ and 1.0 (6 H, 2s, geminal dimethyl groups), 1.7 (3H, broad s, olefinic methyl attached to the cyclopentenyl group), 1.9-2.2 (3H, broad multiplet), 2.3-2.6 (3H, broad multiplet), 5.3 (1H, broad multiplet, olefinic H), 6.6 (1H, t, J~7.5 Hz), 9.4 (1H, sharp s, aldehyde H). was slowly added, over a 1.0 hour period, to a stirred The mixture was refluxed an additional two hours The resultant solution was extracted three times with 300 ml of hexane washed first with 600 ml of water The solvent was removed by distillation the oil fractionally distilled

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

実験手順: To a stirred solution of 400 g (6.1 moles) of methyl ethyl ketone, 1025 g (32 moles) of methanol, 30.5 g (0.54 mole) of potassium hydroxide and 380 g of water cooled to -5° to -10° C was added 152 g (1.0 mole) of campholenic aldehyde over 15-30 minutes. The mixture was maintained at 0° to -10° C for 24-36 hours and then at 25°-35° C for 18-24 hours. The mixture was neutralized by addition of 36.8 g of 62.5% sulfuric acid and the unreacted methyl ethyl ketone and excess methanol were removed by atmospheric distillation. The residual liquid was added to 200 ml of hexane and 200 ml of water. The aqueous layer was drawn off and the hexane layer was washed with 200 ml of brine. The hexane was removed by atmospheric distillation and the oil fractionally distilled under vacuum to give 3-methyl-5-(2,2,3-trimethylcyclopent-3-en-1-yl) pent-3-en-2-one and two other isomers in a ratio of ca. 86:6:8 by glc. Yield 140.3 g (85% theory); bp 102°-105° C (1.3 mm); nD20 1.4888; mol wt. 206 (ms); nmr, 0.8δ (3H, s), 1.0 (3H, s), 1.6 (3H, broad s), 1.8 (3H, broad s), 2.3 (3H, s, acetyl CH3), 5.3 (1H, broad multiplet, olefinic H), 6.7 (1H, complex, β-olefinic H of an α,β-unsaturated carbonyl system); ir, 3030, 1670, 1635, 790 cm-1. The mixture was maintained at 0° to -10° C for 24-36 hours the unreacted methyl ethyl ketone and excess methanol were removed by atmospheric distillation The residual liquid was added to 200 ml of hexane and 200 ml of water the hexane layer was washed with 200 ml of brine The hexane was removed by atmospheric distillation the oil fractionally distilled under vacuum

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

実験手順: To a stirred solution of 400 g (6.1 moles) of methyl ethyl ketone, 1025 g (32 moles) of methanol, 30.5 g (0.54 mole) of potassium hydroxide and 380 g of water cooled to -5° to -10° C was added 152 g (1.0 mole) of campholenic aldehyde over 15-30 minutes. The mixture was maintained at 0° to -10° C for 24-36 hours and then at 25°-35° C for 18-24 hours. The mixture was neutralized by addition of 36.8 g of 62.5% sulfuric acid and the unreacted methyl ethyl ketone and excess methanol were removed by atmospheric distillation. The residual liquid was added to 200 ml of hexane and 200 ml of water. The aqueous layer was drawn off and the hexane layer was washed with 200 ml of brine. The hexane was removed by atmospheric distillation and the oil fractionally distilled under vacuum to give 3-methyl-5-(2,2,3-trimethylcyclopent-3-en-1-yl) pent-3-en-2-one and two other isomers in a ratio of ca. 86:6:8 by glc. Yield 140.3 g (85% theory); bp 102°-105° C (1.3 mm); nD20 1.4888; mol wt. 206 (ms); nmr, 0.8δ (3H, s), 1.0 (3H, s), 1.6 (3H, broad s), 1.8 (3H, broad s), 2.3 (3H, s, acetyl CH3), 5.3 (1H, broad multiplet, olefinic H), 6.7 (1H, complex, β-olefinic H of an α,β-unsaturated carbonyl system); ir, 3030, 1670, 1635, 790 cm-1. The mixture was maintained at 0° to -10° C for 24-36 hours the unreacted methyl ethyl ketone and excess methanol were removed by atmospheric distillation The residual liquid was added to 200 ml of hexane and 200 ml of water the hexane layer was washed with 200 ml of brine The hexane was removed by atmospheric distillation the oil fractionally distilled under vacuum

反応条件: temp:86.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a rapidly stirred refluxing suspension of 7.5 g (0.055 mole) of zinc chloride (anhydrous) in 1000 ml of benzene there was added 304 g (2.0 moles) of α-pinene epoxide over 1.0-1.25 hour period. The resultant mixture was heated at reflux (86° C) for 1.0-1.5 hours, cooled to 25° C and then poured into 400 ml of 5% sodium carbonate solution. The aqueous layer was drawn off and the benzene layer washed twice with 400 ml of brine. The solvent was removed and the oil fractionally distilled to give campholenic aldehyde: 193.2 g (70.2% yield), bp 51°-52° C (1.5 mm); nD20 1.4658; mol wt. 152 (ms); nmr, 0.8δ (3H, s), 1.0 (3H, s), 1.6 (3H, broad s, olefinic CH3), 2.1-2.6 (4H, broad complex), 5.2 (1H, broad multiplet, olefinic H), 9.7 (1H, doublet of doublets, J~3.5 + 1.5 Hz, aldehyde H); ir, 3020, 2700, 1714, 790 cm-1. refluxing cooled to 25° C the benzene layer washed twice with 400 ml of brine The solvent was removed the oil fractionally distilled

反応条件: temp:10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 60.0 g (0.36 mol) of 2-(2,2,3-trimethylcyclopent-3-enyl)propionaldehyde, prepared from campholenic aldehyde as known per se, and 42.0 g (0.72 mol) of propanal was added successively during 15 min and 2 hours, respectively, to the sodium methylate solution prepared from 0.83 g of sodium and 200 ml of anhydrous methanol, at 10° C. The reaction mixture was stirred at 10° C. for 2 hours and at room temperature for the following 42 hours. After addition of 5 ml of acetic acid the solvent was evaporated in vacuo at the temperature maintained below 50° C. The residue was diluted with 500 ml of MTBE, washed with 2×200 ml of brine, dried (MgSO4), concentrated in vacuo and distilled at 76-95° C./0.1 Torr to give 28.1 g (38%) of 2-methyl-4-(2,2,3-trimethylcyclopent-3-enyl)pent-2-enal. An analytical sample was prepared by flash chromatography on silica gel (eluent: hexane/MTBE 12:1). was added successively during 15 min and 2 hours was evaporated in vacuo at the temperature maintained below 50° C The residue was diluted with 500 ml of MTBE washed with 2×200 ml of brine dried (MgSO4) concentrated in vacuo distilled at 76-95° C./0.1 Torr

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

実験手順: A solution was made of α-campholenic aldehyde (200 g) in acetone (2 liters) and cooled to 0° C. Jones reagent was prepared from 115 ml conc. sulfuric acid, 500 ml water and 134 g of chromium (VI) oxide. The reagent (400 ml) was added to the solution at 0° C. over a period of 30 minutes. After an additional 15 minutes at 0° C. the acetone was removed by decantation and the residual chromium salts were washed with an additional 200 ml acetone. The combined acetone solution was concentrated to 1 liter, diluted with 10% aqueous sodium hydroxide (1 liter) and washed with CH2Cl2 (2×1 liter). The aqueous phase was acidified with 25% sulfuric acid and extracted with CH2Cl2 (2×1 liter). Concentration of the CH2Cl2 solution yielded an oil (145 g) which was distilled under reduced pressure to give 116 g of a yellowish liquid; bp 121° C. @ 2.2 mm Hg; analysis: 98% (CW 20M fused silica column, 180° C.) α-campholenic acid. After an additional 15 minutes at 0° C. the acetone was removed by decantation the residual chromium salts were washed with an additional 200 ml acetone The combined acetone solution was concentrated to 1 liter diluted with 10% aqueous sodium hydroxide (1 liter) washed with CH2Cl2 (2×1 liter) extracted with CH2Cl2 (2×1 liter)

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

実験手順: A solution was made of α-campholenic aldehyde (200 g) in acetone (2 liters) and cooled to 0° C. Jones reagent was prepared from 115 ml conc. sulfuric acid, 500 ml water and 134 g of chromium (VI) oxide. The reagent (400 ml) was added to the solution at 0° C. over a period of 30 minutes. After an additional 15 minutes at 0° C. the acetone was removed by decantation and the residual chromium salts were washed with an additional 200 ml acetone. The combined acetone solution was concentrated to 1 liter, diluted with 10% aqueous sodium hydroxide (1 liter) and washed with CH2Cl2 (2×1 liter). The aqueous phase was acidified with 25% sulfuric acid and extracted with CH2Cl2 (2×1 liter). Concentration of the CH2Cl2 solution yielded an oil (145 g) which was distilled under reduced pressure to give 116 g of a yellowish liquid; bp 121° C. @ 2.2 mm Hg; analysis: 98% (CW 20M fused silica column, 180° C.) α-campholenic acid. After an additional 15 minutes at 0° C. the acetone was removed by decantation the residual chromium salts were washed with an additional 200 ml acetone The combined acetone solution was concentrated to 1 liter diluted with 10% aqueous sodium hydroxide (1 liter) washed with CH2Cl2 (2×1 liter) extracted with CH2Cl2 (2×1 liter)