Phenylacetic Acid -> Phenethylalcohol w/ NaBH4

[Rhodium]

Here I found a nifty method for a reduction of phenylacetic acids to phenylethanols using sodium borohydride (should work for any aliphatic acid, or maybe even aromatic acids). The methyl ester of the acid is first formed by dissolving it in methanol with a catalytic amount of acid (room temp, 2 hours). Then the solution is concentrated, the residue washed and the solvent is dried and evaporated. The crude ester is then reduced with aqueous sodium borohydride (room temp, 2 hours), and the crude product worked up to give the alcohol in close to quantitative yield.

The second method concerns the Pyridine*CrO₃ (PDC) oxidation of phenylethanols to phenylacetaldehydes.


2-(3-Hydroxyphenyl)ethanol

2-(3-Hydroxyphenyl)acetic acid (0.5 g) was dissolved in anhydrous methanol (50 mL) and two drops of concentrated H₂SO₄ were added. After 2 h, the reaction was concentrated in vacuo, diluted with ethyl acetate, washed with brine until the pH was neutral, dried with anhydrous sodium sulfate, and the solvent evaporated under reduced pressure. The methyl ester (0.45 g; 82%) was obtained and immediately treated with an aqueous solution of excess NaBH₄. After 2 h, the solution was acidified with 2 N HCl, extracted with ethyl acetate, and worked up as reported above. The residue obtained was purified by silica gel column chromatography, eluting with CHCl₃/MeOH (9:1), gave pure 25 (0.37 g; 98%).

Oxidation of 2-(4-Hydroxyphenyl)ethanol  to 2-(4-Hydroxyphenyl)acetaldehyde

PDC (2.05 equiv.) was added in one portion to a solution of 2-(4-Hydroxyphenyl)ethanol (100 mg) in CH₂Cl₂/EtOAc = 1:0.5 at room temperature, the mixture was allowed to stir for about 5 hours. The mixture was filtered through a short path of Celite and washed with the reaction solvent (CH₂Cl₂/EtOAc = 1:0.5; 70 mL). The pale yellow solution obtained was washed with brine and dried with anhydrous Na₂SO₄. Filtration and evaporation of the solvent yielded crude 2-(4-Hydroxyphenyl)acetaldehyde, which was used in the following reaction without purification.

Reference: Eur. J. Org. Chem. 17, 3407-3411 (2003)