4-(2-methylpropoxy)benzaldehyde

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:130.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A 500 mL, 1 neck, round-bottomed flask equipped with a magnetic stirrer and reflux condenser is charged with 4-(2-methylpropoxy)benzaldehyde (17.84 g, 0.100 mol, as from Example 2a), malonic acid (10.42 g, 0.100 mol), and 19 mL of pyridine. The mixture is heated with stirring in a 130° C. oil bath for 24 hours, then stirred at room temperature for 16 hours. The reaction mixture is then poured into a separatory funnel containing 300 mL of pH 12 aqueous sodium hydroxide and 300 mL of ether. The layers are separated and the aqueous phase washed with 150 mL of ether. The aqueous phase is then acidified with concentrated hydrochloric acid to bring the pH to 1 whereupon the powdery white acid precipitates out. The mixture is chilled in an ice/salt bath and the solid collected giving 5.89 g (0.027 mol, 27%) of product, m.p. 161°-164° C. A 500 mL, 1 neck, round-bottomed flask equipped with a magnetic stirrer reflux condenser The mixture is heated stirred at room temperature for 16 hours The reaction mixture is then poured into a separatory funnel The layers are separated the aqueous phase washed with 150 mL of ether precipitates out The mixture is chilled in an ice/salt bath the solid collected

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

Procedure: A 1000 mL, 1 neck, round-bottomed flask equipped with a magnetic stirrer and reflux condenser is charged with 4-hydroxybenzaldehyde (33.18 g, 0.272 mol), 100 ml of ethanol, and a solution of potassium hydroxide (20.42 g, 0.309 mol) in 100 mL of ethanol. The reaction mixture is heated with stirring for one-half hour. Next 1-iodo-2-methylpropane (100 g, 0.543 mol) is added and the mixture refluxed for 12 hours. After cooling, the solvents are removed by rotary evaporation to yield a brown solid which is added to a separatory funnel containing 500 mL ether and 500 mL of 5% aqueous sodium carbonate. The layers are separated and the aqueous phase is washed with ether (2×500 mL). The combined ether layers are washed with pH 12 sodium hydroxide solution (5×200 mL) until the washes are colorless. The organic solution is then washed with brine (100 mL) and dried over magnesium sulfate. After filtration and removal of the solvents by rotary evaporation, a viscous yellow liquid is obtained. This material is purified by Kugel-Rohr distillation to give 22.3 g (0.125 mol, 46%) of a colorless liquid. A 1000 mL, 1 neck, round-bottomed flask equipped with a magnetic stirrer reflux condenser The reaction mixture is heated the mixture refluxed for 12 hours After cooling the solvents are removed by rotary evaporation to yield a brown solid which is added to a separatory funnel The layers are separated the aqueous phase is washed with ether (2×500 mL) The combined ether layers are washed with pH 12 sodium hydroxide solution (5×200 mL) until the washes The organic solution is then washed with brine (100 mL) dried over magnesium sulfate After filtration and removal of the solvents by rotary evaporation a viscous yellow liquid is obtained This material is purified by Kugel-Rohr distillation

Conditions: temp:130.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A 500 mL, 1 neck, round-bottomed flask equipped with a magnetic stirrer and reflux condenser is charged with 4-(2-methylpropoxy)benzaldehyde (17.84 g, 0.100 mol, as from Example 2a), malonic acid (10.42 g, 0.100 mol), and 19 mL of pyridine. The mixture is heated with stirring in a 130° C. oil bath for 24 hours, then stirred at room temperature for 16 hours. The reaction mixture is then poured into a separatory funnel containing 300 mL of pH 12 aqueous sodium hydroxide and 300 mL of ether. The layers are separated and the aqueous phase washed with 150 mL of ether. The aqueous phase is then acidified with concentrated hydrochloric acid to bring the pH to 1 whereupon the powdery white acid precipitates out. The mixture is chilled in an ice/salt bath and the solid collected giving 5.89 g (0.027 mol, 27%) of product, m.p. 161°-164° C. A 500 mL, 1 neck, round-bottomed flask equipped with a magnetic stirrer reflux condenser The mixture is heated stirred at room temperature for 16 hours The reaction mixture is then poured into a separatory funnel The layers are separated the aqueous phase washed with 150 mL of ether precipitates out The mixture is chilled in an ice/salt bath the solid collected

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

Procedure: A 1000 mL, 1 neck, round-bottomed flask equipped with a magnetic stirrer and reflux condenser is charged with 4-hydroxybenzaldehyde (33.18 g, 0.272 mol), 100 ml of ethanol, and a solution of potassium hydroxide (20.42 g, 0.309 mol) in 100 mL of ethanol. The reaction mixture is heated with stirring for one-half hour. Next 1-iodo-2-methylpropane (100 g, 0.543 mol) is added and the mixture refluxed for 12 hours. After cooling, the solvents are removed by rotary evaporation to yield a brown solid which is added to a separatory funnel containing 500 mL ether and 500 mL of 5% aqueous sodium carbonate. The layers are separated and the aqueous phase is washed with ether (2×500 mL). The combined ether layers are washed with pH 12 sodium hydroxide solution (5×200 mL) until the washes are colorless. The organic solution is then washed with brine (100 mL) and dried over magnesium sulfate. After filtration and removal of the solvents by rotary evaporation, a viscous yellow liquid is obtained. This material is purified by Kugel-Rohr distillation to give 22.3 g (0.125 mol, 46%) of a colorless liquid. A 1000 mL, 1 neck, round-bottomed flask equipped with a magnetic stirrer reflux condenser The reaction mixture is heated the mixture refluxed for 12 hours After cooling the solvents are removed by rotary evaporation to yield a brown solid which is added to a separatory funnel The layers are separated the aqueous phase is washed with ether (2×500 mL) The combined ether layers are washed with pH 12 sodium hydroxide solution (5×200 mL) until the washes The organic solution is then washed with brine (100 mL) dried over magnesium sulfate After filtration and removal of the solvents by rotary evaporation a viscous yellow liquid is obtained This material is purified by Kugel-Rohr distillation

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

Procedure: The compound was synthesized as in Example 24.1, using 4-hydroxybenzaldehyde (200 mg, 1.64 mmol) and isobutyl bromide (449 mg, 1.97 mmol) in place of 1-chloro-3,3-dimethylbutane (no sodium iodide was used) to give 4-isobutoxybenzaldehyde (294 mg, quant. crude) as a yellow oil that was used without further purification or characterization. The compound was synthesized as in Example 24.1

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

Procedure: To a mixture of 4-isobutoxybenzaldehyde (6.9 g, 38.7 mmol), aluminum chloride (12.9 g, 96.8 mmol) and nitromethane (39 mL) was added methoxyacetyl chloride (4.1 mL, 44.5 mmol) under stirring at 0° C., and the mixture was stirred at the same temperature for 3 hr. After completion of the reaction, the reaction mixture was poured into ice water, and the mixture was extracted with ethyl acetate. The organic layer was dried over magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate=10/1-4/1) to give the title compound (5.22 g, yield 60%) as colorless crystals. the mixture was stirred at the same temperature for 3 hr After completion of the reaction the mixture was extracted with ethyl acetate The organic layer was dried over magnesium sulfate concentrated under reduced pressure The residue was purified by silica gel column chromatography (hexane/ethyl acetate=10/1-4/1)

Conditions: temp:130.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A 500 mL, 1 neck, round-bottomed flask equipped with a magnetic stirrer and reflux condenser is charged with 4-(2-methylpropoxy)benzaldehyde (17.84 g, 0.100 mol, as from Example 2a), malonic acid (10.42 g, 0.100 mol), and 19 mL of pyridine. The mixture is heated with stirring in a 130° C. oil bath for 24 hours, then stirred at room temperature for 16 hours. The reaction mixture is then poured into a separatory funnel containing 300 mL of pH 12 aqueous sodium hydroxide and 300 mL of ether. The layers are separated and the aqueous phase washed with 150 mL of ether. The aqueous phase is then acidified with concentrated hydrochloric acid to bring the pH to 1 whereupon the powdery white acid precipitates out. The mixture is chilled in an ice/salt bath and the solid collected giving 5.89 g (0.027 mol, 27%) of product, m.p. 161°-164° C. A 500 mL, 1 neck, round-bottomed flask equipped with a magnetic stirrer reflux condenser The mixture is heated stirred at room temperature for 16 hours The reaction mixture is then poured into a separatory funnel The layers are separated the aqueous phase washed with 150 mL of ether precipitates out The mixture is chilled in an ice/salt bath the solid collected

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

Procedure: A 1000 mL, 1 neck, round-bottomed flask equipped with a magnetic stirrer and reflux condenser is charged with 4-hydroxybenzaldehyde (33.18 g, 0.272 mol), 100 ml of ethanol, and a solution of potassium hydroxide (20.42 g, 0.309 mol) in 100 mL of ethanol. The reaction mixture is heated with stirring for one-half hour. Next 1-iodo-2-methylpropane (100 g, 0.543 mol) is added and the mixture refluxed for 12 hours. After cooling, the solvents are removed by rotary evaporation to yield a brown solid which is added to a separatory funnel containing 500 mL ether and 500 mL of 5% aqueous sodium carbonate. The layers are separated and the aqueous phase is washed with ether (2×500 mL). The combined ether layers are washed with pH 12 sodium hydroxide solution (5×200 mL) until the washes are colorless. The organic solution is then washed with brine (100 mL) and dried over magnesium sulfate. After filtration and removal of the solvents by rotary evaporation, a viscous yellow liquid is obtained. This material is purified by Kugel-Rohr distillation to give 22.3 g (0.125 mol, 46%) of a colorless liquid. A 1000 mL, 1 neck, round-bottomed flask equipped with a magnetic stirrer reflux condenser The reaction mixture is heated the mixture refluxed for 12 hours After cooling the solvents are removed by rotary evaporation to yield a brown solid which is added to a separatory funnel The layers are separated the aqueous phase is washed with ether (2×500 mL) The combined ether layers are washed with pH 12 sodium hydroxide solution (5×200 mL) until the washes The organic solution is then washed with brine (100 mL) dried over magnesium sulfate After filtration and removal of the solvents by rotary evaporation a viscous yellow liquid is obtained This material is purified by Kugel-Rohr distillation

Conditions: temp:130.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A 500 mL, 1 neck, round-bottomed flask equipped with a magnetic stirrer and reflux condenser is charged with 4-(2-methylpropoxy)benzaldehyde (17.84 g, 0.100 mol, as from Example 2a), malonic acid (10.42 g, 0.100 mol), and 19 mL of pyridine. The mixture is heated with stirring in a 130° C. oil bath for 24 hours, then stirred at room temperature for 16 hours. The reaction mixture is then poured into a separatory funnel containing 300 mL of pH 12 aqueous sodium hydroxide and 300 mL of ether. The layers are separated and the aqueous phase washed with 150 mL of ether. The aqueous phase is then acidified with concentrated hydrochloric acid to bring the pH to 1 whereupon the powdery white acid precipitates out. The mixture is chilled in an ice/salt bath and the solid collected giving 5.89 g (0.027 mol, 27%) of product, m.p. 161°-164° C. A 500 mL, 1 neck, round-bottomed flask equipped with a magnetic stirrer reflux condenser The mixture is heated stirred at room temperature for 16 hours The reaction mixture is then poured into a separatory funnel The layers are separated the aqueous phase washed with 150 mL of ether precipitates out The mixture is chilled in an ice/salt bath the solid collected

Conditions: temp:130.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A 500 mL, 1 neck, round-bottomed flask equipped with a magnetic stirrer and reflux condenser is charged with 4-(2-methylpropoxy)benzaldehyde (17.84 g, 0.100 mol, as from Example 2a), malonic acid (10.42 g, 0.100 mol), and 19 mL of pyridine. The mixture is heated with stirring in a 130° C. oil bath for 24 hours, then stirred at room temperature for 16 hours. The reaction mixture is then poured into a separatory funnel containing 300 mL of pH 12 aqueous sodium hydroxide and 300 mL of ether. The layers are separated and the aqueous phase washed with 150 mL of ether. The aqueous phase is then acidified with concentrated hydrochloric acid to bring the pH to 1 whereupon the powdery white acid precipitates out. The mixture is chilled in an ice/salt bath and the solid collected giving 5.89 g (0.027 mol, 27%) of product, m.p. 161°-164° C. A 500 mL, 1 neck, round-bottomed flask equipped with a magnetic stirrer reflux condenser The mixture is heated stirred at room temperature for 16 hours The reaction mixture is then poured into a separatory funnel The layers are separated the aqueous phase washed with 150 mL of ether precipitates out The mixture is chilled in an ice/salt bath the solid collected

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

Procedure: A 1000 mL, 1 neck, round-bottomed flask equipped with a magnetic stirrer and reflux condenser is charged with 4-hydroxybenzaldehyde (33.18 g, 0.272 mol), 100 ml of ethanol, and a solution of potassium hydroxide (20.42 g, 0.309 mol) in 100 mL of ethanol. The reaction mixture is heated with stirring for one-half hour. Next 1-iodo-2-methylpropane (100 g, 0.543 mol) is added and the mixture refluxed for 12 hours. After cooling, the solvents are removed by rotary evaporation to yield a brown solid which is added to a separatory funnel containing 500 mL ether and 500 mL of 5% aqueous sodium carbonate. The layers are separated and the aqueous phase is washed with ether (2×500 mL). The combined ether layers are washed with pH 12 sodium hydroxide solution (5×200 mL) until the washes are colorless. The organic solution is then washed with brine (100 mL) and dried over magnesium sulfate. After filtration and removal of the solvents by rotary evaporation, a viscous yellow liquid is obtained. This material is purified by Kugel-Rohr distillation to give 22.3 g (0.125 mol, 46%) of a colorless liquid. A 1000 mL, 1 neck, round-bottomed flask equipped with a magnetic stirrer reflux condenser The reaction mixture is heated the mixture refluxed for 12 hours After cooling the solvents are removed by rotary evaporation to yield a brown solid which is added to a separatory funnel The layers are separated the aqueous phase is washed with ether (2×500 mL) The combined ether layers are washed with pH 12 sodium hydroxide solution (5×200 mL) until the washes The organic solution is then washed with brine (100 mL) dried over magnesium sulfate After filtration and removal of the solvents by rotary evaporation a viscous yellow liquid is obtained This material is purified by Kugel-Rohr distillation