phenylpropanolamine from benzaldehyde

IndoleAmine · Dreamreader Deluxe

Of course you don't appear like being a smartass, why do you think so?
(post has been removed, hope your happy with the freed bandwith)

i_a

Hex · Sat Apr 16, 2005 2:43 pm

There is one of the Akabori reaction samples:

http://synthetikal.com/synthforum/viewtopic.php?p=3549#3549

Astrum · Wed Apr 20, 2005 5:42 pm

Well SWIM took another run at this using ethanol instead of toluene this time. SWIM added the 45% NaOH solution dropwise to the ethanol, benzaldehyde, dH2O, and l-alanine over an hour at roughly 0C. A clear yellow solution was present after the addition which was allowed to warm to room temperature with stirring. It was further stirred at room temperature for five hours where CO2 evolved. At five hours a lot of white percipitate formed quite unexpectedly. SWIM knows the HCl salt of PPA is water and alcohol soluble but SWIM isn't sure about the solubility of the base form. So the question is, is this percipitate PPA or a byproduct?

Cheers

IndoleAmine · Dreamreader Deluxe

Hm - sounds like a carbonate has formed if you ask me.

http://physchem.ox.ac.uk/MSDS/NO/l(-)-norephedrine.html

(the best I could find; but no word about solubility! Crying or Very sad

)

PPA freebase is a crystalline solid at room temp., but I would say since it has that OH and NH2 and phenyl ring, it should be very soluble in EtOH....

Carbonates OTOH have a limited solubility in EtOH, and since a lot of CO2 was evolved, I think there is a great chance that carbonates of the starting material and product are formed, as well as some sodium carbonate etc..

(Anyone know about the solubility of PPA.carbonate in EtOH? Very Happy

)

I would try and add lots of acidic H2O, remove the solvent and residual BzCHO through distillation/steam distillation, and then proceed with basifying, extraction and vacuum distillation and then you see what you are left with... Wink

Good luck!

IndoleAmine · Dreamreader Deluxe

Thanks to Shib, the following very interesting document is available here:
Schiff bases. I. Thermal decarboxylation of alpha-amino-acids in the presence of ketones. (Al-Sayyab AF, Lawson A.)
J Chem Soc [Perkin 1]. 1968;4:406-10.

Note: ketones and aldehydes share the same carbonyl moiety, so this deals with exactly what we're trying to achieve here, I would say...

Could be a good explanation why excess benzaldehyde is needed compared to alanine,..

Oh BTW Astrum: maybe the crystals are just sodium benzoate? solubility: 1g dissolves in about 75 ml alcohol, in 50 ml of a mixture of 47.5 ml alcohol and 3.7 ml water... Question

i_a

Astrum · Thu Apr 21, 2005 3:35 pm

Well SWIM did some tests. First off the percipitated crystalls were filtered off. The substance was slightly soluble in ethanol (more so than sodium benzoate). Next SWIM tested for the presence of sodium which turned out positive. This shouldn't be a suprise since NaOH should be present to some extent. It's mp was roughly that of phenylpropanolamine (base). University is taking over again so SWIM will see what he can do next week perhaps.

Anyone else running experiments? Wink

IndoleAmine · Dreamreader Deluxe

Yes - me with n-BuOH solvent (and a few percent H2O) and heating to 140°C... (and maybe KOH? better not?)

(as soon as my alanine arrives at least Sad

)

Willie · Wed Apr 27, 2005 12:51 pm

And what about the benzaldehyde and alanine condensation itself? I mean time, temperature, catalists, acid or alcaline medium. Who knows the exact conditions of this reaction?

java · Consumer

Here is a thread on the subject and enclosed some articles in japanese and one in english to help understand the problems, if any.....java

Direct Link URL: http://home.ripway.com/2005-1/247174/akaborirun.html
Alternate URL: http://host.picturewizard.com/2005-1/247174/akaborirun.html

These are articles in Japanese that deal with akabori synthesis of ephedrine and norephedrine.......

Direct Link URL: http://home.ripway.com/2004-11/211899/YakugakuZasshi.zip
Alternate URL: http://host.picturewizard.com/2004-11/211899/YakugakuZasshi.zip

java · Consumer

In the study "Studies on /reaction between aromatic Aldehydes and alpha-amino Acids.v. Results obtained by Paper chromatography" one of the papers inclosed in the post above; the only one in english, reviews the synthesis of ephedrine by mixing bezaldehyde and N-methylalanine and the result is ephedrine .

So my question is how does one get from alanine to n-methylalanine.......can it be done with formic acid then reduced either with catalytic hydrogenation or by any of the other methods mentioned in
rhodium's page on methylation of amphetamine.....

It seems to me that with the information privided by WizardX on the reducing phenylalanine to benzaldehyde by a simple procedure .....

Bumblebee · Mon May 02, 2005 4:42 am

some info i told someone not long ago about the Akabori.
ithink it belong in this thread:

when you start with:

-d,l-alanine (the racemic stuff) would give you d,l-pseudoephedrine and after reducing Benzedrine (dl-amphetamine)

-l-alanine food grade would give you l-pseudoephedrine and would end with Dexedrine (l-amphetamine)

-N-methyl-d,l-alanine would give a mixture of dl-pseudoephedrine and dl-ephedrine that is reduced to racemic chili along with some Benzedrine! Wink

I found out that N-methylalanine is nearly impossible to get anywhere. An if it is in the case of the n-methyl stuff as also as hard to dissolve the stuff in the reaction as it is with l-alanine i would forget about it.

but l-ephedrine is much easier to extraxt from the reaction mixture as the PPA is. It doesnt dissolve that good in H2O... Smile

jackoozzi · specialist

I think you will find that alanine will make PPA not pseudoephedrine and the PPA will reduce to amphetamine

java · Consumer

Bumblebee ..although you may be close but as you said it's been a while but here is a table from on of the articles I posted where you can see the end result ..... java

IndoleAmine · Dreamreader Deluxe

Do you maybe have more details about the rxn nr. three (benzaldehyde/dl-alanine/pyridine) mentioned in your table? It seems as a base catalyst would be needed in order to avoid biphenyl compnd. formation and favor phenylpropanolamine production..

java · Consumer

I've had several request for more on the exerp posted, the information has been posted and the articles are there I guess I will have to pull it out and repost it as it was included with the other articles that were in japanese.....

pdf