(pseudo)Ephedrine to ---- w/ Raney-Nickel-Rhodium

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Rhodium
(Chief Bee)
12-26-02 15:23
No 393077




(pseudo)Ephedrine to ---- w/ Raney-Nickel
(Rated as: excellent)
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General procedure for Raney Ni catalyzed hydrogenolysis of aromatic alcohols
Applied Catalysis A: General 219, 281ñ289 (2001) (https://www.rhodium.ws/pdf/ephedrine-rani-1.pdf)

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 methedrine.

Raney Ni catalyzed hydrogenolysis of (pseudo)Ephedrine amide to methedrine amide
J. Org. Chem. 63, 7795-7804 (1998) (https://www.rhodium.ws/pdf/ephedrine-rani-2.pdf)

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 methedrine, so they used very similar derivatives of ephedrine and pseudoephedrine (the ethoxycarbonyl amide) and reduced them to the ethoxycarbonyl amide of methedrine 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...

Organikum
(Hive Addict)
12-26-02 18:25
No 393122




not only the Vatikan...
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has hidden archives.....

We will see if it holds what it promises. I have no problem looking like an idiot if something like this comes over in exchange. If it works it may help the methheads to calm down from the annie & RP madness and they can lean back and watch the MDMA cooks getting more greedy every day.....

ORG
now or never

Barium
(Hive Bee)
12-28-02 05:46
No 393460




Mmmm
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What is pretty darn interesting is that the authors used EtOH as the hydrogen source in the second hydrogenolysis described. I like that

Organikum
(Hive Addict)
12-28-02 11:13
No 393510




Very straight forward, I don¥t buy it.
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¥thatThe first article looks serious and on the point. The second article is IMHO regarding the hydrogenolysis of a benzylalcohol plain BS - just a filler in the lengthy deadly boring synth it describes.(Or a lil¥ joke? "¥hey I bet no ass sees this as no ass reads it?") Dunno. 2-propanol as hydrogen donor may be possible also I postulate that most hydrogen comes from the nickel which is charged like a hydride   and gets recharged (partly) by the IPA (thats CTH I believe) but this working with ethylalcohol? No thus I don¥t buy as this fact would have become obvious long before by some exploding laboratories. I also doubt that this works with urushibara nickel because I think the sponge-like structure of rayney is very important here.

Not to forget the insane substrate to nickel ratios, 1 to 10 seems favorable following WizardX whose earlier posted hydrogenolysis of ephedrine with nickel is much the same. Interesting is that the reference WizardX names uses Ni and Pd hydride not rayney.

So could one of those skilled in the art have some mercy on thy worthless methheads and post an easy Nickelhydride OTC synth? Pleaze?

The idea of Tengo to use NiMH in a electrosynth wasn¥t bad at all - he just never tried it in realworld.
Might doping the nickel with some noble metal be the way to go?

Just my 2 cents
ORG

now or never

Tengo
12-28-02 20:29




Organikum: I understand that christmas is a...
(Rated as: offending)
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Organikum
(Hive Addict)
12-28-02 22:41
No 393704




Tengo, I asked already ...
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and I did it here:
Post 392797 (Organikum: ""it works" is not enough...", Stimulants)
your answer:
Post 393007 (Tengo: "What could possibly be mentioned about the ...", Stimulants)

What could possibly be mentioned about the reaction, except that it bubbles H2 from the cathode, and that the silver anode turns black and white, due to the formation of Ag2O and AgCl.

(complete description of the reaction)

You can do in a sentence for what those chemists need pages over pages in journals and write whole books. And on a brandnew item also. Not disclosing how you came to the idea, no references.

You didn¥t do the reaction except in your dreams perhaps but you strongly believe that it works (whats possible) and now someone shall try it for you, do all the fucking little work and tuning here and there until it works, but you can tell: "I did it before!"

My christmas was ok, thanks for thinking on me
ORG

now or never

Tengo
(Newbee)
12-29-02 01:18
No 393739




Organikum: You are wrong about me.
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Organikum: You are wrong about me.

Organikum
(Hive Addict)
12-29-02 21:19
No 394022




nickel doped zeolithe?
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The immense amount of nickel needed makes me think that this isn¥t a surface reaction as with Pd/Pt but a reaction occuring by trapping the benzylalcohol in a nickel structure (sponge). This leads me to the question if a basic nickel doped zeolithe might be usable.

anyone knows or can point me?
ORG

now or never

PolytheneSam
(Master Searcher)
12-29-02 21:51
No 394028




How about this?
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http://www.geocities.com/dritte123/Nipat.html

Patent US3431220 Nickel is mentioned in column 4 lines 21-22.

http://www.geocities.com/dritte123/PSPF.html
The hardest thing to explain is the obvious

foxy2
(Distinctive Doe)
01-11-03 16:40
No 397318




hehehe
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Thanks for the mention Rhodium.

PrimoPyro
Remember when you asked me about this, well here it is.
foxy

SPISSHAK
(Hive Addict)
06-26-03 12:27
No 442716




What about Pd/C 10%?
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I agree that ethanol as a cth donor looks like bullshit, but swim has a good qauntity of degussa Pd/C and wants to know if you could substitute Pd/C as in the IPA CTH of benzylic alcohols?
Anyone.
I'll try it and let you know I just don't want to waste good catalyst If I can avoid it.

java
(Hive Bee)
06-26-03 15:50
No 442747




RE:General procedure for Raney Ni catalyzed hydro.
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I'm thinking phenylalanol alcohol reduction to an alkane with this method , hence would the catalyst react with the amine group? Although there are manyways to reduce the primary alcohol to the CH3, some methods are cleaner than others, I found Zinc+ HCl to be messy once the OH was halogenated and the low yields , and the silane seems a bit involved with some hard to get solvents. Ideally I would like to treat the alcohol in acid and make an alkene then hydrogenate with a Pd catalyst but I'm not sure of the action with the amine group and the H2SO4 environment.......java

We're all in this world together,
http://www.chiapaslink.ukgateway.net/

SPISSHAK
(Hive Addict)
06-26-03 22:20
No 442792




no I'm aware of acid promoted
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Palladium catalyzed reductions of benzylic alcohols, my question is this, would 10% Pd/C be a viable substitute in the reaction the Rhodium proposed, or are the catalyst's mechanics different?

Lucid_Dreamer
(Hive Bee)
07-04-03 01:08
No 444426




Isolation
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What is the importance of filtering through celite and flash chromotagraphy in the second one, if someone were to try this out what would be an easier work-up/isolation method? If the Ni catalyst stay in tact the whole time wouldn't ot be that much easier to seperate and work-up?

--Word on the street is, You Reap What You Sow

Rhodium
(Chief Bee)
07-04-03 11:09
No 444510




Skip the column, keep the rest
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Filtering through Celite is to remove the catalyst (it would just clog an ordinary filter), but careful vacuum distillation and recrystallization of the HCl salt is enough for purification, the flash column can be skipped.