3-ethylphenol

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:0.00; pressure:0.00; stir:

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

Procedure: To a 50 gallon glass lined reactor was added 23.07 pounds (0.769 mole--1.04 equiv.) of paraformaldehyde, followed by 92 pounds (%Wt/Wt Phenol to Solvent--100%) of acetonitrile, and then 92 pounds (0.739 mole--1.0 equiv.) of 98.0% pure m-ethylphenol. The mixture was heated to 65° C., and 66.2 pounds (0.761 mole--1.03 equiv.) of morpholine was added at a rate of 0.5 lb./min. during a two hour period. Upon completion of addition, the reaction mixture was heated to 65-70° C. where it stirred for three hours. After this time, the reaction mixture was concentrated under vacuum at 70° C., yielding 171 pounds of 89.4% pure 2-(morpholin4-ylmethyl)-5-ethylphenol (93% yield). Upon completion of addition the reaction mixture was heated to 65-70° C. where it After this time, the reaction mixture was concentrated under vacuum at 70° C.

Conditions: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred solution of 244.0 grams (1.78 moles--1.0 equiv.) of 89.1% pure m-ethylphenol in 320 mL (%Wt/Vol. Phenol to Solvent--76.3%) of acetonitrile was added 67.6 grams (2.14 moles--1.2 equiv.) of paraformaldehyde. Upon completion of addition, the mixture was stirred for ten minutes and then heated to 65° C. where 179.5 grams (2.06 moles--1.16 equiv.) of morpholine was added during a one hour period at a rate to maintain the reaction temperature below 70-75° C. Upon completion of addition, the reaction mixture was heated to 70° C. where it stirred for two hours. At this point, the reaction mixture was analyzed by GC, which indicated that 2% of the phenol starting material remained. An additional 3.5 grams (0.04 mole--0.02 equiv.) of morpholine was added. Upon completion addition, the reaction mixture was stirred at 70° C. until GC analysis indicated that 1.1% of the phenol starting material remained. The acetonitrile was removed under vacuum, yielding 446.6 grams of 89.1% pure 2-(morpholin-4-ylmethyl)-5-ethylphenol (90% yield). Upon completion of addition was added during a one hour period at a rate to maintain the reaction temperature below 70-75° C Upon completion of addition stirred for two hours Upon completion addition the reaction mixture was stirred at 70° C. until GC analysis The acetonitrile was removed under vacuum

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

Procedure: To a 25 mL round bottom flask equipped with a mechanical stirrer and a thermometer was added 4 mL (%Wt/Vol. Phenol to Solvent--50%) of isopropanol, followed by 2.0 grams (0.0164 mole--1.0 equiv.) of m-ethylphenol and then 2.22 grams (0.0197 mole--1.2 equiv.) of an aqueous 40% N,N-dimethylamine solution. The mixture was stirred at ambient temperature to effect dissolution, and 0.59 gram (0.0197 mole--1.2 equiv.) of paraformaldehyde was added. The reaction mixture began to exotherm so it was cooled to ambient temperature where it stirred for 17 hours. After this time, the reaction mixture was concentrated under reduced pressure to a residue, and the residue was taken up in heptane and water. The organic layer was separated, washed with an aqueous saturated sodium chloride solution, dried with magnesium sulfate, and filtered. The filtrate was concentrated under reduced pressure, yielding 2.8 grams of 2-[(N,N-dimethylamino)methyl]-5-ethylphenol (88.7% yield). Gas Chromatography (GC) analysis of the product indicated the presence of about 7% of an impurity. The NMR spectrum was consistent with the proposed structure. To a 25 mL round bottom flask equipped with a mechanical stirrer was added was cooled to ambient temperature where it stirred for 17 hours After this time, the reaction mixture was concentrated under reduced pressure to a residue The organic layer was separated washed with an aqueous saturated sodium chloride solution dried with magnesium sulfate filtered The filtrate was concentrated under reduced pressure

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

Procedure: To a stirred solution of 3-ethyl phenol (1.50 g, 12.28 mmol) in NaOH (1N) was added epichlorohydrin (2.07 g, 22.47 mmol). The reaction mixture was stirred at room temperature for 4 days. Excess epichlorohydrin was removed by concentration in vacuo and the two-phase mixture treated with NaOH (1N) (10 ml) after addition of THF (10 ml). The reaction mixture was heated to 55° C. for 15 minutes and then stirred at room temperature for 30 minutes. The THF was removed by concentration in vacuo and the product extracted with ethyl acetate (2×50 ml), concentrated in vacuo and purified by flash column chromatography on silica (150:10:1 dichloromethane:methanol:ammonia) to give the product as a yellow oil. Excess epichlorohydrin was removed by concentration in vacuo the two-phase mixture treated with NaOH (1N) (10 ml) after addition of THF (10 ml) The reaction mixture was heated to 55° C. for 15 minutes stirred at room temperature for 30 minutes The THF was removed by concentration in vacuo the product extracted with ethyl acetate (2×50 ml) concentrated in vacuo purified by flash column chromatography on silica (150:10:1 dichloromethane:methanol:ammonia)

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

Procedure: Employing procedures and materials similar to those described in Example 1, except that 3-ethylphenol was substituted for m-cresol, and the reaction was carried out in the presence of ethylene dichloride as solvent, there was obtained the desired product, 3-ethyl-1-hydroxy-5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthalene 66% theor., GLC purity 99%+, exhibiting the expected spectral data.

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

Procedure: A stirred solution of 200 mL (0.20 mole) of 1.0M of ethylmagnesium bromide (in tetrahydrofuran) in 100 mL of tetrahydrofuran was cooled in an ice-bath and 25.0 grams (0.21 mole) of 3-ethylphenol was added dropwise. Upon completion of addition, the reaction mixture was allowed to warm to ambient temperature where it stirred for 30 minutes. After this time, 15.4 grams (0.51 mole) of paraformaldehyde, 36.7 grams (0.21 mole) of hexamethylphosphoramide, and 350 mL of toluene were added. Upon completion of addition, the reaction mixture was heated to 80° C. where it stirred for about 18 hours. The reaction mixture was then cooled and concentrated under reduced pressure to a residue. The residue was taken up in diethyl ether and 200 mL of an aqueous 10% hydrochloric acid solution was added. The aqueous layer was separated and extracted with diethyl ether. The extract was combined with the organic layer, and the combination was washed with water. The organic layer was dried with magnesium sulfate and filtered. The filtrate was concentrated under reduce pressure to a residue. The residue was subjected to column chromatography on silica gel, using 1:1 hexane and methylene chloride as the eluant. The product-containing fractions were combined and concentrated under reduced pressure, yielding 21.8 grams of 5-ethyl-2-formylphenol. The NMR spectrum was consistent with the proposed structure. Upon completion of addition Upon completion of addition the reaction mixture was heated to 80° C. where it stirred for about 18 hours The reaction mixture was then cooled concentrated under reduced pressure to a residue 200 mL of an aqueous 10% hydrochloric acid solution was added The aqueous layer was separated extracted with diethyl ether the combination was washed with water The organic layer was dried with magnesium sulfate filtered The filtrate was concentrated concentrated under reduced pressure

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

Procedure: 3-ethylphenol (5.00 g, 41 mmol) was dissolved in methylene chloride(40 mL) followed by the addition of sodium nitrate (3.83 g, 45 mmol). The addition of sulfuric acid (50 mL/3M) was then made, followed by addition of a catalytic amount of sodium nitrite. The mixture was allowed to stir. After 24 hours, the reaction mixture was diluted with methylene chloride and extracted with water. The organic layer was dried over MgSO4 and filtered. The solvent was evaporated and chromatography of the resulting solid on silica gel (4% MeOH/CH2Cl2) gave the desired product(1.7 g, 25%). 1H NMR (CD3COCD3): d 8.02 (d,1H), 6.99 (s,1H), 6.85 (d, 1H), 2.69 (q, 2H), 1.30 (t, 3H). extracted with water The organic layer was dried over MgSO4 filtered The solvent was evaporated