Subject: (pseudo)Ephedrine to Meth w/ Raney-Nickel
Author: Rhodium (Chief Bee)
Date: 26-Dec-2002 21:23
Post No: 393077
(Rated as: excellent)
General procedure for Raney Ni catalyzed hydrogenolysis of aromatic alcohols
Applied Catalysis A: General 219, 281-289 (2001) (http://designer-drugs.com/pte/12.162.180.114/dcd/pdf/ephedri...)
1-Phenylethanol (2g) was added to a mixture of Raney nickel (5g) in 2-propanol (30 ml). While open to the atmosphere, the
reaction mixture was vigorously stirred and refluxed (water-cooled condenser attached to flask) for 15 minutes. Isolation of the product involved
decanting the 2-propanol solution, washing the Raney nickel with 2-propanol (3×10 ml), filtering the combined 2-propanol layers through celite, and
evaporation of the 2-propanol and acetone to give ethylbenzene in 98% yield.
The yield is substantially the same with 1-Phenylethanol, 1-Phenylbutanol, 2,2-Dimethyl-1-phenyl-1-propanol and several other more or less sterically
hindered alcohols, and both Raney Nickel and Raney Cobalt can be used as catalyst. The reaction is fast, clean, and uses simple isopropanol (IPA,
2-propanol) as the sole reducing agent (it turns into acetone) in conjunction with the catalyst. It is reasonable to believe that this reaction may
work with Urushibara Nickel, and that (pseudo)ephedrine can be used as substrate to give methamphetamine.
Raney Ni catalyzed hydrogenolysis of (pseudo)Ephedrine amide to Methamphetamine amide
J. Org. Chem. 63, 7795-7804 (1998) (http://designer-drugs.com/pte/12.162.180.114/dcd/pdf/ephedri...)
To a mechanically stirred suspension of Raney Ni (wet, prepared from 200 g of aluminum-nickel alloy, Raney type Ni-Al
50:50) in ethanol (700 mL) was added 4 (29.55 g, 0.125 mol), and the mixture was heated to reflux for 2 h. After cooling to room temperature the
mixture was filtered through Celite. Concentration, flash chromatography (hexane/ethyl acetate, 2:1) on silica gel (218g), and distillation
(88°C/0.35 mmHg) gave 5 as a colorless liquid (23.80 g, 86%).
This is almost as close as it gets. In the article the authors describe that they did not have the proper licenses to synthesize methamphetamine, so
they used very similar derivatives of ephedrine and pseudoephedrine (the ethoxycarbonyl amide) and reduced them to the ethoxycarbonyl amide of
methamphetamine as the first step towards their target compound (which is completely unrelated). The yields for the ephedrine and pseudoephedrine
amides were 86% and 81%, respectively, simply by refluxing them with freshly prepared Raney Nickel (Fieser & Fieser Vol. 1, p 729) in ethanol for
two hours. Again, Urushibara Nickel might just work, and there is no glaring obstacle against using plain (pseudo)ephedrine instead of the
corresponding amides, but this has not yet been tried in practice, and has been left as an exercise to the reader. Now you have something to do next
year too, the Hive staff and elderbees always do their best to prevent you from getting bored...
Kudos to Foxy2 for finding these articles in the first place, and Happy New Year - whereever you are... |
