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Dreamer - posted at the Hive 10-12-98

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18gr of Palladium on Carbon were prepared using following methode:

- 1,7gr PdCl2 in 2ml 31% HCl and 20ml dH2O are heated for 15min at 80�
- 20gr activated carbon are heated with 450ml H2O and 15ml 31% HCl for 2h;
the carbon is filtered off
- the PdCl2 solution is added to 30gr sodium acetat trihydrate in 200ml
dH2O in a 500ml Flask
- the washed carbon is added to this solution
- hydrogenate the mixture for 3h, using drone's hydrogen generator; set
it up to produce 1mol of H2; don't forget to stir vigorously; iron
powder works nicely (only powder works, sheet's won't)
- when the hydrogenation is complete and the carbon settles down and you
should have a colorless mixture with the catalyst at the bottom
- filter the carbon , wash it with 4-5*100ml dH2O; dry the catalyst at 50�
- I got 18gr (my filter methode wasn't good, use only glas no plastic,
easier to clean) of 5% Palladium on Carbon;

- - - - -

- 22gr highly purified Phenyl-2-nitropropene

- 300ml 99% glacial acetic acid (maybe too much)
- 38gr Ammonium Formate
- 9gr 5% Palladium on Carbon ( Pd-C)

were introduced in a 500ml Flask.

22gr P2NP were dissolved in 300ml 99% glacial acetic acid and added
to the 5% Pd-C. All was heated to 100� and vigorously stirred.
I introduced 3*~13gr Ammonium Formate; All was refluxed for 25 min;
Then everything was cooled; 100ml Chloroform were added so that it
is easier to filter the Pd-C. I used normal coffee filter paper and
vacuum, which worked. Then i added 1l of dH2O and the Chloroform
separated out. The layers were separated andi "washed" again with
additional 100ml Chloroform. But amphetamine wasn't soluble in the
glacial acetic acid, so i extracted it with the chloroform.

The chloroform was eliminated and i got 15.5gr of a yellow oil,

which was dissolved in 200ml 15% HCl, washed trhee time with 75ml
DCM, made basic with 25% NaOH and extracted with Ether. And again
i failed to make the HCl salt , i tried to dry the ether with Epsom
Salt and then to afford the salt with dry HCl. But all i got was a
slightly yellow colored layer at the bottom of my ether mixture.
I decided then to make the salt with 99% H2SO4 in Ether and Ethanol,
which worked perfectly. (first i made again everything basic...)
The salt was washed and i got 14gr of white! Amphetamine salt.

- - - - -

I didn't use any H2SO4 in the CTH because i don't know if it helps or if
it destroys everything, maybe it helps and the yields would be higher.
Maybe anhydrous ethanol works better, if anyone sends my Calcium oxide
POWDER i will try it )

Palladium on carbon is not easy to handle, i suggest to use only glas

filter funnels, my plastic funnel is still full with carbon.
Anyone knows a secure methode to form the HCl salt of an amphetamine ?
I dried with the Epsom Salt (~30gr) for 2h, is it not possible to dry
with Epsom Salt (MgSO4 * 7H2O)? already too many H2O's ?

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beagle boy:

Excellent post! Most informative. Did your info on this reaction come from
Tet Lett 29(45), 5733 (1988)? Any other refs?

I don't get this bit "But amphetamine wasn't soluble in the glacial acetic
acid, so i extracted it with the chloroform." It isn't!? And you didn't
basify the reaction mixture B4 extraction?

You had problems forming the HCl salt because it is hard to do. Much
harder than meth HCl. Early papers on amphetamine synth. always described
the HCl salt as hygroscopic, if they could even obtain it as a solid at
all. Actually, when extremely pure it is not particularly hygroscopic.

Epsom Salts are not a good drying agent. Cook in the oven for awhile to
dehydrate first.

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Cherrie Baby:

Don't skimp on the formate. Most of the dudes (below) are using 5 to 12
mole xs. of Formate, w.r.t. main reactant, in their CTHs. This will give
the best yield.

Was all the Pd homemade? I would have got hold of some of that Pd on
polymer - it should last at least 50 reductions.

Catalytic Transfer Hydrogenation Reactions are considered so easy that

J. Chem. Ed. are flogging them for new undergrad. Programs. - get your
ticket soon. Cheap, versatile - but not perfect. Ultra-cheapskates can
even substitute Ni for Pd as the catalyst (sometimes)!

Alkenes -> alkanes

ketones -> alkanes
nitroalkanes -> amines
azides -> amines
chloro-cpds -> hydrocarbons (psssst halo-ephedrine -> meth)
deprotection of peptides
deprotection of benzylic ether (to alcohol)
nitro-alkene -> oxime

Catalytic Transfer Hydrogenation Reactions for Undergraduate Practical

Programs, R Hanson, J. Chem. Ed. 74(4), p 430-1 (1997).

Catalytic Transfer Hydrogenation of Benzaldehyde in a Microwave Oven,

Gordon et al. Organometallics 12, 5020-2 (1993).

Microwave-Induced Organic Reaction Enhancement Chemistry. 2. Simplified

Techniques. Bose et al., J. Org. Chem. 56, p 6968-70 (1991). [page 6969]

Transfer Hydrogenation: A stereospecific method for the conversion of

nitro alkanes to amines, Barrett, Tetr. Lett. 29(45) p 5733-4 (1988).
Ammonium Formate in Organic Synthesis: A Versatile Agent in Catalytic
Hydrogen Transfer Reductions. R Ehrenkaufer, Synthesis 1988, p 91-95

Reduction of Aldehydes and Ketones to Methylene Derivatives using

Ammonium Formate as a Catalytic Hydrogen Transfer Agent. S Ram &
L Spicer. Tetr. Lett. 29(31), p 3741-4 (1988).

Heterogeneous Catalytic Transfer Hydrogenation and its Relation to Other

Methods for Reduction of Organic Compounds. R Johnstone, A Wilby &
I Entwistle. Chem. Rev. 85, p 129-170 (1985).

A General Procedure for the Mild and Rapid Reduction of Aliphatic and
Aromatic Nitro compounds using Ammonium Formate as a Catalytic Hydrogen
Transfer Agent. S Ram & R Ehrenkaufer, Tetr. Lett. 25(32), p 3415-8 (1984).

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Dreamer:

beagle boy, after the filtration of the Pd-C with 100ml i added 1l of
dH2O. I separeted the two layers and "washed" again with 100ml Chloroform;
Then i added enough 50% NaOH to the glacial acetic acid to make it basic
and extracted it with DCM, when i evaporated the DCM i found only 1ml of
yellow oil. When i eliminated the chloroform from the washes i got ~15gr
of a yellow oil. This oil was then converted into the sulfuric salt.

Maybe the ammonium formate didn't let the amphetamine dissolve in the 30%
acetic acid. When i made it basic i smelled ammonia too, maybe the ammonia
was present and reduced the dissolve power of glacial acetic(made it basic?),
boh, i am not a chemist, i am happy that i didn't loose my amphetamine oil.

My information source for this reaction was the internet and vogel's book
on practical organic chemistry...

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dreamer:

- 0.05mol 8gr beta nitropropene C9H9NO2 63gr/mol

- 13gr 5% Pd-C
- 100ml Methanol
- 50ml THF
- 0.15 mol NaBH4

- 8gr P2NP are dissolved in 50ml THF and 50ml Methanol and is stirred on
a magnetic stirrer
- 1.9gr NaBH4 are slowly added over a period of 30min
- the addition of nabh4 is effervscent
- after 15min of stirring 13gr 5% Pd/C in 100ml methanol is added;
- don't add the Pd/C without solvent, it will catch fire )
- the you should add slowly over a period off 1h (i did it) 4 gr NaBH4;
- reaction is continued for another 3h and 5ml of acetic acid is added
(to neutralize NaBH4 .. maybbe you don't this) and 20ml of 31% HCl and
50ml of H2O;
- the solution turns red
- Pd/c is filtered away and washed with Methanol and dH2O
- Methanol and THF is eliminated, the red color disappears
- all is washed with DCM
- make it basic with 100ml 25%NaOH and extract; you should get around 5gr
of the freebase (i did), yield ~70%; the salt is easily made with H2SO4
 in ethanol, but don't add too much H2SO4 or your salt dissolves (if
this happens make all basic and extract)

a few days bevor i tried the same thing with ethanol, yields were much
lower and the addition of NaBH4 was not so effervescent

I would like to try to isolate the nitroalkane which is formed by the

reduction with NaBH4 in methanol and reduce it with Al/Hg, i need to know
if reduction of a nitroalkane with Al/Hg is sensible to water (will it
work in 95% ethanol?) and how much Al/Hg for 0.1mol of P2NP i should use?

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