(Chief Bee)
07-30-02 13:02
No 338923
      Substituted benzaldehydes to phenethylalcohols
(Rated as: excellent)


A mixture of powdered sodium hydride 60% in mineral oil (2.0 g, 0.05 mol) was washed with hexane and then suspended in anhydrous DMSO (40.0 mL) and stirred under nitrogen at 75C until evolution of hydrogen ceased (ca. 0.5 h). The solution was cooled to room temperature, diluted with anhydrous THF (40 mL), and then cooled to -5C with an ice-salt bath. A solution of trimethylsulfonium iodide (10.2 g, 0.05 mol) in anhydrous DMSO (40 mL) was added to the resulting mixture over the course of about 3 min and without stirring. After completion of the addition, the reaction mixture was stirred for 1 min and then treated dropwise with a solution of 2,3-dimethoxybenzaldehyde (6.9 g, 0.041 mol) in anhydrous DMSO (100 mL). The mixture was stirred at the same temperature for 15 min and at room temperature for 12 h and was then poured into H20 and extracted with ethyl acetate. Evaporation of the washed (H2O) and dried extracts yielded an oil consisting of (2,3-dimethoxyphenyl)oxirane (6.0 g, 81%) which was directly used in the subsequent transformation.


A stirred solution of NaBH4 (1.06 g, 28.02 mmol) in anhydrous THF (7.5 mL) was cooled in an ice bath under nitrogen and then treated with a solution of BF3*Et2O (3.45 mL, 28.02 mmol) in anhydrous THF (8.5 mL). The resulting mixture was diluted with anhydrous THF (65 mL) and then treated in succession with BF3*Et2O (3.45 mL, 28.02 mmol) and a solution of (2,3-dimethoxyphenyl)oxirane (5.05 g, 28.02 mmol) in anhydrous THF (28 mL). The reaction mixture was stirred for 1 h at the same temperature and was then hydrolyzed with water and saturated with potassium carbonate. Evaporation of the washed (H2O) and dried organic layer yielded an oil which was purified by distillation to afford 2-(2,3-Dimethoxyphenyl)ethanol (2.0 g, 40%): bp 93-95C/0.6mmHg.

Ref: Journal of Medicinal Chemistry, 1993, Vol. 36, No. 21, pp 3077-3086

The idea here is then to make the mesylate/tosylate of the alcohol and substitute it with azide for further reduction (Mg, Ca or NaBH4) to the phenetylamine, alternatively make the azide (or a protected amine) directly using Mitsunobu conditions.
(PVC-Analog Taste-Tester)
08-03-02 07:30
No 340470
      Nice !  Bookmark   

  Good find! Could this 2-(2,3-Dimethoxyphenyl)ethanol be converted to the substituted benzyl chloride via shaking with HCl acid? Do you think this could be applied to just about any benzaldehyde, including plain-old benzaldehyde. Sorry I don't have anything to add; just noticed that no one has responded, and wanted to knock this back to the top of the thread. Peace!cool

Love my country, fear my government.
(Chief Bee)
08-03-02 08:59
No 340500
      I believe the method is generally applicable to ...  Bookmark   

I believe the method is generally applicable to any benzaldehyde, however, you cannot make a benzyl chloride out of a phenethylalcohol as you probably understand.

If you want to make a phenethylchloride out of it, you need to use PCl3/SOCl2 or something like that.
08-05-02 02:27
No 341397
      as phenethyl alcohol is aliphatic in character ...  Bookmark   

as phenethyl alcohol is aliphatic in character HCl (aq) will do the business, you will probably need a catalyst though to get a decent yield and reaction rate. I think phenethyl halides are in Vogel I think one of the older editions has a hydrohalic (for want of a better term) acid and a catalyst/dehydratng agent.   any of the reactions for converting aliphatic alcohols to alkyl halides will probably work with the proviso that the reagent it doesn't substitute the ring.
08-10-02 01:13
      Preparation Of Tertiary Chloroalkanes Is
(Rated as: redundant)
(PVC-Analog Taste-Tester)
08-30-02 17:22
No 350700
      Oops!  Bookmark   

  I was confusing benzyl alcohols with phenethylalcohols.tongue

Love my country, fear my government.
(Hive Bee)
08-31-02 20:49
No 351038
      is elimination going to be a problem?  Bookmark   

I would be concerned that forming the styrene from the mesyl or tosyl -ate would be an problem