PNP's into amphetamines reduction on alu foil

tetraedr · Wed Feb 16, 2005 4:31 pm

Hi everybody!
My Granny had a dream, that her spirit came and told her the amazing story about cheap and easy PNP’s into amphetamines reduction without LAH. And she said me this story. I wrote it and want to give it to you for discussion.

To a 1.5 g of thin aluminium foil cut in 1 inch squares (in a 250 mL Erlenmeyer flask) there was added 200 ml of warm (not a cool) water and 50 mg of mercuric chloride. Amalgamation was allowed to proceed until there was the evolution of the fine bubbles, the formation of the light-grey precipitate and the appearance of the occasional silvery spots on the surface of the aluminium. It takes about 10-20 min, depending on the freshness of surface and temperature of the water. The water was removed by decantation and foil was washed 2x200 mL of water. Then to this flask was added the solution of 3,4-methylenedioxyphenylnitropropene (1.12 g, 5.41 mmol) in the mixture of 10 mL of IPA and 20 mL of AcOH (if necessary, this mixture should be warmed until starting material completely dissolved). Then a long tube was attached to the neck of this flask and mixture was warmed a bit to initialize the reaction. Then the exothermic reaction was occurred, mixtures was become to reflux a bit (cooling is not necessary), and aluminium foil was dissolved into the grey precipitate (using the magnet stirrer is recommended). Reaction was complete after 20-30 min. Mixture was cooled down, diluted with 50-100 mL of cool water, alkalized with KOH solution until strong base, the product was extracted with ether (or DCM), combined organic layers were washed with water, dried with sodium sulfate, concentrated under vacuum, obtained light-yellow oil was dissolved in small amount of IPA, acidified to pH 5-6 with HCl solution, concentrated under vacuum again, resulting oil was treated with ether, obtained white crystals iltered off, washed with ether and dried. Yield - 0.93 g (80%). Product has a good purity (according NMR) and can be used without additional purification.
NMR-1H (DMSO-d6) ppm: 1.11 d (3H, Me), 2.58-2.63 m (1H, CHa), 2.9-2.97 m (1H, CHb), 3.65 m (1H, CH), 5.68 c (2H, CH2), 6.68-6.70 m (1H, Ar-CH), 6.85-6.87 m (2H, Ar-CH), 8.18 bs (3H, NH3+).

Willie · Wed Feb 16, 2005 4:50 pm

The 80% yield seems to be great!
Was there any problem with extraction procedure? I means if there was some kind of emulsion or nît?
Why the dulited acid was used, why not pure HCl 37%?

woden · Wed Feb 16, 2005 5:04 pm

My congratulations, tetraedr!
You've raised the yield of MDA till 80% from 62% got before by somehive bee. Maybe because of you've used amalganation aluminium instead of mixture of every component in one pot at once...
IMHO, this method is the best for nitrostyrol's reductions.

tetraedr · Wed Feb 16, 2005 5:40 pm

I have used the DCM, and had an emulsion (foam).
But I have destroyed it after next water washing.
I mean, using the ether instead DCM can help to avoid the foam obtaining.

There are small amount of inorganic precipitates, and in this procedure is possible to avoid of any filtration. This precipitate do not disturb to extract the product

Willie · Wed Feb 16, 2005 8:58 pm

tetraedr · Wed Feb 16, 2005 10:25 pm

Willie · Thu Feb 17, 2005 3:58 pm

Thanks a million!

The last questions:
- I have Hg(NO3)2, it's less poisoness and more soluable in water. Can I use it instead of HgCl2? (I suppose the answer will be Yes, but confirmation is advisable);
- what's the reason of using KOH instead of more conventional NaOH? Is it better or the same?

tetraedr · Thu Feb 17, 2005 4:56 pm

1. You can use ANY soluble salt of Hg
2. I have only KOH - I use it. It is more easy to dissolve in water, than NaOH and probably, cheaper... I do not see the big difference between KOH and NaOH for this case.

ApprenticeCook · DILLIGAF

The wait for the amalgamation to complete before addition is the best way to run Al/Hg for most compounds, this allows the component of the reaction doing the work (the aluminum) to form without hassles in its own enviroment. Then once added the reduction takes place nice and easy... If its all added at once or the amalgum is formed at the same time as the compound is being added the yields are sometimes lower due to other shit going on in the flask, let the amalgum form first as described then after that start the addition so there is only one process trying to occur in the reaction vessel at a time, this often increases yields where it is possible.

Good work, your granny has good dreams, tell her keep them comin...
-AC

IndoleAmine · Dreamreader Deluxe

Tetraedr, sorry - but this won't work. In contrast to phenyl-nitroethenes, nitropropenes cannot be reduced directly one-pot with Al/Hg.

Reason: the double bond beetween the 1 and the 2 carbon makes it impossible without reducing the whole thing to the oxime, then a Nef reaction occurs due to acidic conditions, and immediately you have phenylacetone...
(but sadly you have no other amine in there, hm? So no schiff base wil form, and nothing will be reduced. At best you will get some hydroxylamine, but no phenylisopropylamine)

Reduce the double bond with NaBH4/aequ.IPA and make the phenyl-2-nitropropane, then reduce that with Al/Hg. Or do the nef rxn separately with Fe/GAA for example, then condense the resulting propanone with hydroxylamine to make the oxime, then reduce that with either acidic Al/Hg or sodium/EtOH or other methods. Works for sure, with good yields.

Or use urushibara Ni, but yields will be low (like 30%)...

tetraedr · Mon Feb 21, 2005 5:38 pm

woden · Mon Feb 21, 2005 7:58 pm

IndoleAmine, check this link - http://www.rhodium.moppy.net/www.rhodium.ws/chemistry/nitrostyrene.reduction.alhg.html

Willie · Mon Feb 21, 2005 9:50 pm

To IndoleAmine:
I think the Nef reaction will not occur due to acidic medium. As you know Nef reaction uses K2CO3/H2O2 thus making the Rm basic but not acid.
And if someone want to make nitropropane from nitropropene (reducting the double bond to single), do not use H2O at all! It will react with NaBH4, reducing the yield greatly; use dry IPA and not MeOH for the same reason.

IndoleAmine · Dreamreader Deluxe

bee · Wed Feb 23, 2005 7:38 am

great post tetraedr!!!

sure worth dreaming!!