4-hydroxy-3-iodo-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:

Conditions: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Vanillin (28.4 g, 200 mmole (millimole)) was dissolved in 1N NaOH (200 ml) and warmed to 90° C. to avoid precipitation of sodium vanillate. A 2 molar aqueous solution of NaI3.NaI (105 ml, 210 mmole I2) plus 3.55 molar aqueous H2SO4 (5 ml) was added over 3 hours with stirring. The iodine color was discharged, and a pale tan stirrable precipitate formed. The solution was then cooled to room temperature, acidified to pH 2-3 with 20% aqueous H2SO4, and extracted with 10% methanol/90% chloroform. The organic phase was dried (MgSO4) and the solvent stripped to yield 53 g (99%) of 5-iodovanillin, more than 95% pure as analyzed by nuclear magnetic resonance spectroscopy (NMR). precipitation of sodium vanillate a pale tan stirrable precipitate formed The solution was then cooled to room temperature extracted with 10% methanol/90% chloroform The organic phase was dried (MgSO4)

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

Procedure: 5-Iodovanillin (25 g, 0.09 mol) in DMF (100 mL) was treated with potassium carbonate (32 g, 0.23 mol) and n-propyl iodide (52 g, 0.3 mol, 31 mL) and heated for 16 hours. The solution was allowed to cool to room temperature and then poured into water (500 mL) and extracted with ether (3×250 mL). The organic layers were combined and washed with water and saturated sodium chloride solution, and then dried over magnesium sulfate. The organic layer was evaporated by distillation under diminished pressure to an oil, and then purified by column chromatography (silica, 7:3 petroleum ether-ethyl acetate), to provide an amber colored solid (26.9 g, 93%). 1H NMR (CDCl3) 1.07 (t, 3H), 1.85 (m, 2H), 3.89 (s, 3H), 4.06 (t, 3H), 7.39 (s, 1H), 7.84 (s, 1H), 9.81 (s, 1H). heated for 16 hours extracted with ether (3×250 mL) washed with water and saturated sodium chloride solution dried over magnesium sulfate The organic layer was evaporated by distillation under diminished pressure to an oil purified by column chromatography (silica, 7:3 petroleum ether-ethyl acetate)

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

Procedure: A mixture of 5-iodovanillin (7 g, 25.18 mmole), potassium carbonate (8.78 g, 63.53 mmole) and iodomethane (6.43 g, 45.30 mmole) was suspended in 60 mL of DMF and stirred at room temperature for 14 hours. The reaction mixture was quenched with water and extracted with diethyl ether. The organic layer was dried over MgSO4, filtered and evaporated in vacuo to obtain a solid which was recrystallized from hexane/ethyl acetate (2:1) (6.28 g, 85.4%). The reaction mixture was quenched with water extracted with diethyl ether The organic layer was dried over MgSO4 filtered evaporated in vacuo to obtain a solid which was recrystallized from hexane/ethyl acetate (2:1) (6.28 g, 85.4%)

Conditions: temp:40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 5-Iodovanillin (25 g, 90 mmol) in DMF (100 mL) was added to potassium carbonate (18.6 g, 135 mmol). The mixture was heated at 40° C. for 16 hours. The reaction mixture was allowed to cool to room temperature and quenched with water (500 mL) and extracted with ethyl acetate. The organic layer was washed with water and saturated NaCl solution, and dried over MgSO4, filtered and evaporated in vacuo to an oil, and then purified by column chromatography (silica, 2:1 hexane/ethyl acetate), to provide the product (16.6 g, 57%). 1H NMR (CDCl3): 2.70 (t, 1H); 3.92 (t, 2H); 3.92 (s, 3H); 3.94 (s, 3H); 4.29 (t, 2H); 7.44 (s, 1H); 7.87 (s, 1H); 9.85 (s, 1H). to cool to room temperature quenched with water (500 mL) extracted with ethyl acetate The organic layer was washed with water and saturated NaCl solution dried over MgSO4 filtered evaporated in vacuo to an oil purified by column chromatography (silica, 2:1 hexane/ethyl acetate)

Conditions: temp:40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 5-Iodovanillin (25 g, 90 mmol) in DMF (100 mL) was added to potassium carbonate (18.6 g, 135 mmol). The mixture was heated at 40° C. for 16 hours. The reaction mixture was allowed to cool to room temperature and quenched with water (500 mL) and extracted with ethyl acetate. The organic layer was washed with water and saturated NaCl solution, and dried over MgSO4, filtered and evaporated in vacuo to an oil, and then purified by column chromatography (silica, 2:1 hexane/ethyl acetate), to provide the product (16.6 g, 57%). 1H NMR (CDCl3): 2.70 (t, 1H); 3.92 (t, 2H); 3.92 (s, 3H); 3.94 (s, 3H); 4.29 (t, 2H); 7.44 (s, 1H); 7.87 (s, 1H); 9.85 (s, 1H). to cool to room temperature quenched with water (500 mL) extracted with ethyl acetate The organic layer was washed with water and saturated NaCl solution dried over MgSO4 filtered evaporated in vacuo to an oil purified by column chromatography (silica, 2:1 hexane/ethyl acetate)

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

Procedure: Rac-3,4-dihydro-2-ethynyl-2,5,7,8-tetramethyl-2H-1-benzopyran-6-ol, 2.3 g, was reacted with 4.17 g (15 mmol) of 5-iodovanilline as described in example 1, but extending the reaction time to 4.5 hours. After the usual workup, the residue was chromatographed over 150 g of silica gel using 10% (V/V) of ethyl acetate in methylene chloride. Crystallization from ether/hexane and recrystallization from ethyl acetate/hexane yielded colorless crystals with m.p. 158°-160°. to 4.5 hours After the usual workup, the residue was chromatographed over 150 g of silica gel using 10% (V/V) of ethyl acetate in methylene chloride Crystallization from ether/hexane and recrystallization from ethyl acetate/hexane yielded colorless crystals with m.p. 158°-160°

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

Procedure: Rac-3,4-dihydro-2-ethynyl-2,5,7,8-tetramethyl-2H-1-benzopyran-6-ol, 2.3 g, was reacted with 4.17 g (15 mmol) of 5-iodovanilline as described in example 1, but extending the reaction time to 4.5 hours. After the usual workup, the residue was chromatographed over 150 g of silica gel using 10% (V/V) of ethyl acetate in methylene chloride. Crystallization from ether/hexane and recrystallization from ethyl acetate/hexane yielded colorless crystals with m.p. 158°-160°. to 4.5 hours After the usual workup, the residue was chromatographed over 150 g of silica gel using 10% (V/V) of ethyl acetate in methylene chloride Crystallization from ether/hexane and recrystallization from ethyl acetate/hexane yielded colorless crystals with m.p. 158°-160°

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

Procedure: Benzyl chloride (30 g, 0.24 mol) was added to a solution of 5-iodovanillin (60g, 0.216 mol) in DMF (250 mL) containing potassium carbonate (50 g). The mixture was stirred at 80° C. for 1.5 h or until TLC (hexane ethyl acetate; 4:1, v/v; Rf 0.5) showed the reaction to be complete. The mixture was then cooled and the solvent was decanted into ice water (1 L). The product was extracted with ethyl ether and the ethereal layer was washed with water, dried, and evaporated in vacuo to an oil, which solidified upon standing: mp 53°-54° C. the reaction The mixture was then cooled the solvent was decanted into ice water (1 L) The product was extracted with ethyl ether the ethereal layer was washed with water dried evaporated in vacuo to an oil, which