3-bromo-4-hydroxy-5-methoxybenzaldehyde

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

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

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

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

Procedure: 2-bromo-6-methyl-heptane was reacted with 3-methoxy-4-hydroxy-5-bromo-benzaldehyde to obtain 5-bromo-4-[(1,5-dimethyl-hexyl)-oxy]-m-anisaldehyde (boiling point = 190°-193°C/0.1 mmHg); 2-bromo-6-methyl-heptane was reacted with p-hydroxy-benzonitrile to obtain p-[(1,5-dimethyl-hexyl)-oxy]-benzonitrile (boiling point = 165°-168°C/1.0 mmHg);

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

Procedure: 2-bromo-6-methyl-heptane was reacted with 3-methoxy-4-hydroxy-5-bromo-benzaldehyde to obtain 5-bromo-4-[(1,5-dimethyl-hexyl)-oxy]-m-anisaldehyde (boiling point = 190°-193°C/0.1 mmHg); 2-bromo-6-methyl-heptane was reacted with p-hydroxy-benzonitrile to obtain p-[(1,5-dimethyl-hexyl)-oxy]-benzonitrile (boiling point = 165°-168°C/1.0 mmHg);

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

Procedure: A mixture of 23.1 g of 3-bromo-4-hydroxy-5-methoxy benzaldehyde, 9.3 g of cuprous cyanide and 140 ml of dimethyl acetamide (DMA) was refluxed for 2 hours with stirring. After cooling, the mixture was poured over ice and extracted with an ethyl acetate-methanol mixture (90-10). The organic phase was washed and dried and the solvents were eliminated to obtain 18 g of crude product, which was used as is for the following step. It melted at 180° C. was refluxed for 2 hours After cooling the mixture was poured over ice extracted with an ethyl acetate-methanol mixture (90-10) The organic phase was washed dried

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

Procedure: To a solution of 5-bromovanillin (2.00 g, 8.65 mmol) in acetone (50 mL) was added potassium carbonate (1.4 g, 10.38 mmol) and dimethylsulfate (1 mL, 10.38 mmol). The solution was stirred at room temperature for 16 hours. The reaction mixture was diluted with ethyl acetate and the organic layer was washed successively with water and brine, dried over anhydrous magnesium sulfate, filtered and evaporated to afford 1.88 g of 3-bromo-4,5-dimethoxybenzaldehyde (89%). the organic layer was washed successively with water and brine dried over anhydrous magnesium sulfate filtered evaporated

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

Procedure: A mixture of 23.1 g of 3-bromo-4-hydroxy-5-methoxy benzaldehyde, 9.3 g of cuprous cyanide and 140 ml of dimethyl acetamide (DMA) was refluxed for 2 hours with stirring. After cooling, the mixture was poured over ice and extracted with an ethyl acetate-methanol mixture (90-10). The organic phase was washed and dried and the solvents were eliminated to obtain 18 g of crude product which was used as is for the following step. It melted at 180° C. was refluxed for 2 hours After cooling the mixture was poured over ice extracted with an ethyl acetate-methanol mixture (90-10) The organic phase was washed dried

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

Procedure: A mixture of 23.1 g of 3-bromo-4-hydroxy-5-methoxy benzaldehyde, 9.3 g of cuprous cyanide and 140 ml of dimethyl acetamide (DMA) was refluxed for 2 hours with stirring. After cooling, the mixture was poured over ice and extracted with an ethyl acetate-methanol mixture (90-10). The organic phase was washed and dried and the solvents were eliminated to obtain 18 g of crude product which was used as is for the following step. It melted at 180° C. was refluxed for 2 hours After cooling the mixture was poured over ice extracted with an ethyl acetate-methanol mixture (90-10) The organic phase was washed dried

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

Procedure: To a vigorously stirred suspension of 3-bromo4-hydroxy-5-methoxy-benzaldehyde (15.20 g, 65.8 mmol), AlCl3 (9.65 g, 72.4 mmol) in CH2Cl2 (100 mL) at 0° C. with exclusion of moisture was added pyridine (22.90 g, 290 mmol, 23.4 mL) to keep the temperature below 32° C. The resulting clear dark solution was heated to reflux for 24 hours and cooled to RT. The mixture was poured into a slurry of 1 N HCl and ice. The CH2Cl2 layer was removed and the aqueous suspension was extracted with ether till clear. The combined ether layers were dried over anhydrous magnesium sulfate, filtered and evaporated to a volume of approximately 200 mL and cooled to 0° C. for 2 hours. The resulting suspension was collected by filtration and dried under high vacuum to give 10.12 g of 3-bromo-4,5-dihydroxybenzaldehyde (71%) as a tan solid. 1H NMR (500 MHz; CDCl3): δ 7.18 (s, 1H); 7.37 (d, J=2.0 Hz, 1H); 8.48 (brs, 1H); 9.40 (brs, 1H); 9.56 (s, 1H). the temperature below 32° C The resulting clear dark solution was heated to reflux for 24 hours The CH2Cl2 layer was removed the aqueous suspension was extracted with ether till clear The combined ether layers were dried over anhydrous magnesium sulfate filtered evaporated to a volume of approximately 200 mL cooled to 0° C. for 2 hours The resulting suspension was collected by filtration dried under high vacuum

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

Procedure: To a vigorously stirred suspension of 3-bromo4-hydroxy-5-methoxy-benzaldehyde (15.20 g, 65.8 mmol), AlCl3 (9.65 g, 72.4 mmol) in CH2Cl2 (100 mL) at 0° C. with exclusion of moisture was added pyridine (22.90 g, 290 mmol, 23.4 mL) to keep the temperature below 32° C. The resulting clear dark solution was heated to reflux for 24 hours and cooled to RT. The mixture was poured into a slurry of 1 N HCl and ice. The CH2Cl2 layer was removed and the aqueous suspension was extracted with ether till clear. The combined ether layers were dried over anhydrous magnesium sulfate, filtered and evaporated to a volume of approximately 200 mL and cooled to 0° C. for 2 hours. The resulting suspension was collected by filtration and dried under high vacuum to give 10.12 g of 3-bromo-4,5-dihydroxybenzaldehyde (71%) as a tan solid. 1H NMR (500 MHz; CDCl3): δ 7.18 (s, 1H); 7.37 (d, J=2.0 Hz, 1H); 8.48 (brs, 1H); 9.40 (brs, 1H); 9.56 (s, 1H). the temperature below 32° C The resulting clear dark solution was heated to reflux for 24 hours The CH2Cl2 layer was removed the aqueous suspension was extracted with ether till clear The combined ether layers were dried over anhydrous magnesium sulfate filtered evaporated to a volume of approximately 200 mL cooled to 0° C. for 2 hours The resulting suspension was collected by filtration dried under high vacuum

Conditions: temp:75.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a 500 mL round bottomed flask with a stirring bar, reflux condenser and an argon inlet was added 5-bromovanillin (10 g, 43.28 mmol), DMF (125 mL), powdered Cs2CO3 (28.2 g, 86.56 mmol) and 2-bromoethylmethyl ether (5.08 mL, 54.10 mmol). This well stirred mixture was heated at 75° C. for 24 h. The cooled mixture was filtered through a frit to remove the cesium salts and the filtrate was concentrated in vacuo. The residue was dissolved in EtOAc and washed with water and brine. Drying (MgSO4), filtration and removal of the solvent in vacuo gave an oil. 1H NMR (CDCl3): δ3.44 (s, 3H); 3.77 (t, j=4 Hz, 2H); 3.92 (s, 3H); 4.27 (t, j=4 Hz, 2H); 7.38 (d, j=2 Hz, 1H); 7.65 (d, j=2Hz, 1H); 9.84 (s, 1H). To a 500 mL round bottomed flask with a stirring bar, reflux condenser and an argon inlet The cooled mixture was filtered through a frit to remove the cesium salts the filtrate was concentrated in vacuo The residue was dissolved in EtOAc washed with water and brine Drying (MgSO4), filtration and removal of the solvent in vacuo gave an oil