4-(hydroxymethyl)-2-methoxyphenol

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

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

Procedure: This compound was synthesized by the method described in Kobata et al. (Biosci. Biotechnol. Biochem., 66(2), 319-327, 2002). Decanoic acid methyl ester (2.13 mL, 10.5 mmol), vanillyl alcohol (1.62 g, 10.5 mmol), molecular sheaves 4 Å (10 g), and Novozyme 435 (2.5 g) were added to acetone (50 mL) and stirred for 2 hours at room temperature. The reaction solution was filtered through cellite and the filtrate was concentrated under reduced pressure. The concentrated residue was purified by silica gel chromatography, yielding 2.25 g (7.30 mmol, 73.0 percent) of vanillyl decanoate in the form of a colorless oily substance. This compound was synthesized by the method The reaction solution was filtered through cellite the filtrate was concentrated under reduced pressure The concentrated residue was purified by silica gel chromatography

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

Procedure: This compound was synthesized by the method described in Kobata et al. (Biosci. Biotechnol. Biochem., 66(2), 319-327, 2002). Decanoic acid methyl ester (2.13 mL, 10.5 mmol), vanillyl alcohol (1.62 g, 10.5 mmol), molecular sheaves 4 Å (10 g), and Novozyme 435 (2.5 g) were added to acetone (50 mL) and stirred for 2 hours at room temperature. The reaction solution was filtered through cellite and the filtrate was concentrated under reduced pressure. The concentrated residue was purified by silica gel chromatography, yielding 2.25 g (7.30 mmol, 73.0 percent) of vanillyl decanoate in the form of a colorless oily substance. This compound was synthesized by the method The reaction solution was filtered through cellite the filtrate was concentrated under reduced pressure The concentrated residue was purified by silica gel chromatography

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

Procedure: 4-Hydroxy-3-methoxybenzyl alcohol (1 g, 6.49 mmol) is treated with 1.73 g (7.13 mmol) of ethyl 4-bromobutyrate, 2.69 g (19.46 mmol) of potassium carbonate and a catalytic amount (97.22 mg 0.65 mmol) of sodium iodide as described in Preparation 3 to give 821 mg of 4-[4-(hydroxymethyl)-2-methoxyphenoxy]butanoic acid, ethyl ester as a light brown oil (47%). The 1H NMR (300 MHz, CDCl3) is consistent with the desired product; IR (neat) 3500, 1730, 1620, 1600 cm-1 ; MS (CI (low res)) m/e 269 (M+H), 251, 223, 195.

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

Procedure: 4-Hydroxy-3-methoxybenzyl alcohol (1 g, 6.49 mmol) is treated with 1.73 g (7.13 mmol) of ethyl 4-bromobutyrate, 2.69 g (19.46 mmol) of potassium carbonate and a catalytic amount (97.22 mg 0.65 mmol) of sodium iodide as described in Preparation 3 to give 821 mg of 4-[4-(hydroxymethyl)-2-methoxyphenoxy]butanoic acid, ethyl ester as a light brown oil (47%). The 1H NMR (300 MHz, CDCl3) is consistent with the desired product; IR (neat) 3500, 1730, 1620, 1600 cm-1 ; MS (CI (low res)) m/e 269 (M+H), 251, 223, 195.

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

Procedure: 4-Hydroxy-3-methoxybenzyl alcohol (1 g, 6.49 mmol) is treated with 1.73 g (7.13 mmol) of ethyl 4-bromobutyrate, 2.69 g (19.46 mmol) of potassium carbonate and a catalytic amount (97.22 mg 0.65 mmol) of sodium iodide as described in Preparation 3 to give 821 mg of 4-[4-(hydroxymethyl)-2-methoxyphenoxy]butanoic acid, ethyl ester as a light brown oil (47%). The 1H NMR (300 MHz, CDCl3) is consistent with the desired product; IR (neat) 3500, 1730, 1620, 1600 cm-1 ; MS (CI (low res)) m/e 269 (M+H), 251, 223, 195.

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

Procedure: Finely powdered K2CO3, 10.4 grams (0.075 moles), and KI, 9.1 grams (0.060 moles), were placed in a 300 mL round-bottomed flask equipped with a magnetic stir bar, and 150 mL acetone was added. 3-methoxy-4-hydroxybenzyl alcohol, 7.71 grams (0.050 moles), and propargyl chloride, 4.10 grams (0.055 moles), were then added, and the mixture stirred and refluxed for approximately 48 hours. The results from thin layer chromatography showed no starting material (3-methoxy-4-hydroxybenzyl alcohol) as well as the presence of a new compound. The solution was then filtered. The acetone of the resulting filtrate was removed by rotary evaporation, leaving an oily residue. The oily residue was dissolved in 50 mL dichloromethane and washed with water (30 mL×2) and then dried over anhydrous potassium carbonate. After filtering the organic phase, the solvents were removed by rotary evaporation, leaving a liquid product. 9 grams of product was obtained, which corresponds to a 94% yield. equipped with a magnetic stir bar refluxed for approximately 48 hours The results from thin layer chromatography The solution was then filtered The acetone of the resulting filtrate was removed by rotary evaporation leaving an oily residue washed with water (30 mL×2) dried over anhydrous potassium carbonate After filtering the organic phase the solvents were removed by rotary evaporation leaving a liquid product

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

Procedure: Finely powdered K2CO3, 10.4 grams (0.075 moles), and KI, 9.1 grams (0.060 moles), were placed in a 300 mL round-bottomed flask equipped with a magnetic stir bar, and 150 mL acetone was added. 3-methoxy-4-hydroxybenzyl alcohol, 7.71 grams (0.050 moles), and propargyl chloride, 4.10 grams (0.055 moles), were then added, and the mixture stirred and refluxed for approximately 48 hours. The results from thin layer chromatography showed no starting material (3-methoxy-4-hydroxybenzyl alcohol) as well as the presence of a new compound. The solution was then filtered. The acetone of the resulting filtrate was removed by rotary evaporation, leaving an oily residue. The oily residue was dissolved in 50 mL dichloromethane and washed with water (30 mL×2) and then dried over anhydrous potassium carbonate. After filtering the organic phase, the solvents were removed by rotary evaporation, leaving a liquid product. 9 grams of product was obtained, which corresponds to a 94% yield. equipped with a magnetic stir bar refluxed for approximately 48 hours The results from thin layer chromatography The solution was then filtered The acetone of the resulting filtrate was removed by rotary evaporation leaving an oily residue washed with water (30 mL×2) dried over anhydrous potassium carbonate After filtering the organic phase the solvents were removed by rotary evaporation leaving a liquid product

Conditions: temp:65.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Vanillyl alcohol (5) (10.3 g, 66.8 mmol) was dissolved in ethyl acetate (160 ml) at room temperature, Novozym 435 (2.00 g) was added, and the mixture was stirred at 65° C. for 69 hours. Then, the reaction mixture was cooled to room temperature, the enzyme was filtered off, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (gradient; ethyl acetate:n-hexane=19:81→40:60) to give 4-acetoxymethyl-2-methoxyphenol (6) (11.8 g, 59.8 mmol, yield 89%) as a colorless solid. Then, the reaction mixture was cooled to room temperature the enzyme was filtered off the filtrate was concentrated under reduced pressure The residue was purified by silica gel column chromatography (gradient; ethyl acetate:n-hexane=19:81→40:60)

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

Procedure: Decanoic acid (10.0 g, 58.1 mmol), vanillyl alcohol (8.05 g, 52.2 mmol), and lipase PS-C “Amano” I (enzyme immobilized on ceramic: 1.44 g) were measured and placed in a flask (500 ml), and toluene (200 ml) was added. Under an argon atmosphere, the mixture was heated with stirring in an oil bath at 40° C. for 2 hours. This reaction mixture was concentrated under reduced pressure, and dehydration was promoted by azeotropic effect. Toluene (150 ml) was further added to the concentrate, and the mixture was heated with stirring in an oil bath at 40° C. for 20 hours. The reaction mixture was again concentrated under reduced pressure, and heptane (200 ml) was added. The mixture was stirred at room temperature for 2.5 hours, and immobilized enzyme and precipitated vanillyl alcohol were removed by filtration. The filtrate was concentrated under reduced pressure to give a mixture (15.8 g) of vanillyl decanoate and decanoic acid. As a result of the analysis, the yield of vanillyl decanoate was 98% and the purity was 97.9 area % by HPLC. The mixture contained 8.6 wt % of decanoic acid relative to vanillyl decanoate. placed in a flask Under an argon atmosphere, the mixture was heated This reaction mixture was concentrated under reduced pressure, and dehydration Toluene (150 ml) was further added to the concentrate the mixture was heated with stirring in an oil bath at 40° C. for 20 hours The reaction mixture was again concentrated under reduced pressure, and heptane (200 ml) was added The mixture was stirred at room temperature for 2.5 hours immobilized enzyme and precipitated vanillyl alcohol were removed by filtration The filtrate was concentrated under reduced pressure

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

Procedure: Decanoic acid (10.0 g, 58.1 mmol), vanillyl alcohol (8.05 g, 52.2 mmol), and lipase PS-C “Amano” I (enzyme immobilized on ceramic: 1.44 g) were measured and placed in a flask (500 ml), and toluene (200 ml) was added. Under an argon atmosphere, the mixture was heated with stirring in an oil bath at 40° C. for 2 hours. This reaction mixture was concentrated under reduced pressure, and dehydration was promoted by azeotropic effect. Toluene (150 ml) was further added to the concentrate, and the mixture was heated with stirring in an oil bath at 40° C. for 20 hours. The reaction mixture was again concentrated under reduced pressure, and heptane (200 ml) was added. The mixture was stirred at room temperature for 2.5 hours, and immobilized enzyme and precipitated vanillyl alcohol were removed by filtration. The filtrate was concentrated under reduced pressure to give a mixture (15.8 g) of vanillyl decanoate and decanoic acid. As a result of the analysis, the yield of vanillyl decanoate was 98% and the purity was 97.9 area % by HPLC. The mixture contained 8.6 wt % of decanoic acid relative to vanillyl decanoate. placed in a flask Under an argon atmosphere, the mixture was heated This reaction mixture was concentrated under reduced pressure, and dehydration Toluene (150 ml) was further added to the concentrate the mixture was heated with stirring in an oil bath at 40° C. for 20 hours The reaction mixture was again concentrated under reduced pressure, and heptane (200 ml) was added The mixture was stirred at room temperature for 2.5 hours immobilized enzyme and precipitated vanillyl alcohol were removed by filtration The filtrate was concentrated under reduced pressure

Conditions: temp:55.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 8-Methylnonanoic acid (1.54 g, 8.95 mmol), vanillyl alcohol (1.34 g, 8.70 mmol), and Novozym 435 (8.90 mg) were measured and placed in a flask (25 ml). The mixture in the flask free of a plug was heated with stirring in an oil bath at 55° C. for 45 hours. After 2 to 3 hours of stirring with heating, attachment of water on the wall of the upper part of the flask was observed. The flask was returned to room temperature, heptane (10 ml) was added to the reaction mixture, and the mixture was stirred for 30 minutes. Novozym 435 and a small amount of precipitated vanillyl alcohol were removed by filtration. The filtrate was concentrated under reduced pressure, and the obtained colorless oil (2.67 g) was analyzed by HPLC to find that dihydrocapsiate was contained in 97.2 area %. The mixture was partitioned with heptane (15 ml) and 10% aqueous citric acid solution (15 ml), and the aqueous layer was further extracted with heptane (15 ml). The combined heptane layer was washed with water (15 ml) and saturated brine (15 ml) and dried over anhydrous magnesium sulfate. Magnesium sulfate was removed by filtration, and the filtrate was concentrated under reduced pressure to give a mixture (2.67 g) of dihydrocapsiate and 8-methylnonanoic acid as a colorless oil. As a result of the analysis, the yield of dihydrocapsiate was 95.9%, and the purity was 99.4 area % by HPLC. The mixture contained 3.86 wt % of 8-methylnonanoic acid relative to dihydrocapsiate. placed in a flask The mixture in the flask free of a plug was heated After 2 to 3 hours of stirring with heating was returned to room temperature the mixture was stirred for 30 minutes Novozym 435 and a small amount of precipitated vanillyl alcohol were removed by filtration The filtrate was concentrated under reduced pressure The mixture was partitioned with heptane (15 ml) and 10% aqueous citric acid solution (15 ml) the aqueous layer was further extracted with heptane (15 ml) The combined heptane layer was washed with water (15 ml) and saturated brine (15 ml) dried over anhydrous magnesium sulfate Magnesium sulfate was removed by filtration the filtrate was concentrated under reduced pressure