decomposing phenylalanine to phenethylamine

loki · guinea pig

i decided that this is an appropriate question for this forum, being that phenethylamines are the subject under study here.

I am aware of the fact that phenethylamine itself is of little use, a study i found recently, however, showed that there may be a way to make use of it. Specifically the study found that 30mg/kg of phenethylamine 'sporadically' manifested effects that drug discriminating monkeys trained to recognise methedrine. But if the monkeys were treated with deprenyl (selegiline, propargyl-methedrine) the effects of the phenethylamine came up by a factor of 30.

I thought, ok, so i'm on a regular dose of deprenyl now, let's try out this phenethylamine thing and see how it works in a human subject. A positive result was found, but the temptation to up the dose of deprenyl overtook me and, so it seems, the 'nonselective MAO' effect of deprenyl invariably results in me getting very listless and sleepy... STOOPID well just goes to show you sometimes bigger is not better...

however, an attempt to decarboxylate phenylalanine, which worked to a limited degree, provided sufficient phenethylamine hydrochloride to test its effects with a subject being treated with deprenyl, and the results were, to the subject, quite comparable to methedrine.

However, simple heat decomposition of the amino acid was not terribly good. A lot of oxidation occurred and much benzaldehyde and phenylacetaldehyde was formed in the reaction (and presumably benzoic acid too i guess). not wanting to be forced to flood the reaction with nitrogen gas (due to the inconvenience of such) while some phenethylamine was produced via simple heating (about 160 degrees C) the degree of conversion was woeful, there was not even the formation of enough phenethylamine freebase to see that it was liquid (PEA is liquid to below 60 degrees at atmospheric) Obviously it decomposes readily via oxidation, and thus it probably also keeps better, overall, as the salt, this ready oxidation must have something to do with the phenethylamine freebase dissolving oxygen readily.

I am aware of methods using high boiling ketones, but all the ones documented in patents and references are difficult to get (such as cyclohexenone) and some time back experiments with producing tryptamine with carvone (from mint oil) were less than fruitful.

I happened to stumble on a page which was saying that quicklime was an effective method of decarboxylation. The reaction primarily occurs via the sodium hydroxide however, but the quicklime has the advantage of keeping the reaction dry. I was thinking maybe this might be a possible solution.

I am posting this because I want to know if anyone can suggest an effective route to phenethylamine from phenylalanine, because i wish to study it in combination with selegiline, since monkeys thought it was similar enough to ---- to warrant pushing the lever, maybe it would constitute an effective substitute, because in this (and most) countries, methedrine has been taken off the list for medical use altogether, a move which has just kinda bulldozed right over the fact that it has been long an effective last resort when dexamphetamine and ritalin have too many side effects, for illnesses such as ADHD and narcolepsy.

thx for any advice Very Happy

IndoleAmine · Dreamreader Deluxe

"an attempt to decarboxylate phenylalanine, which worked to a limited degree, provided sufficient phenethylamine hydrochloride to test its effects with a subject" - Question

I thought it would give amphetamine upon decarbox. (removal of CO2), but noone ever achieved it under non-professional circumstances and with easy equipment/reagents? (I know one paper using some hexafluoro-something to decarbox phenylalanine, Java could surely tell you a story or two about it Wink

- but, no offense here, I doubt that you produced phenethylamine here.

OTOH: removing CO2 from phenylalanine gives indeed a terminal amine a.k.a. phenethylamine, thats right. Wonder why the discussion is all about "decarboxylation to amphetamine", but it wasn't my idea - I just mentioned what I've read.

IndoleAmine · Dreamreader Deluxe

As a side note, acetophenone gives phenethylamine in a leuckart reduction - and for this specific substrate the leuckart is a killer rxn... Wink

And benzaldehyde condensed with nitromethane/catalytic NaOH gives phenylnitrostyrene which can be reduced with Zn/HCl to give phenethylamine, for example.

Just two ideas...

Sandmeyer · Fri May 06, 2005 1:57 am

java · Consumer

There is an established fact that decarboxylation of phenylalanine will give you a reduced phenylalanine minus one carbon so phenethylamine , no amphetamine for the stated reason, also decarboxylation with NaOH will give benzaldehyde, as posted in some other thread in the other stimulus forum....java.

loki · guinea pig

One vaguely interesting fact discovered from the experiment is that the hydrochloride ion reduced the amount of oxidation that occurred (my theory is that it changes the charges surrounding the alpha carbon making them less vulnerable to oxidative cleavage), which i am thinking implies that some process along the same lines (maybe using carvone or some other benzene containing ketone to decrease oxidation and catalyse decarboxylation) would be useful for getting tryptamine out of tryptophan.

Another thought too was that, in the unlikely event of acquiring alpha methyl N methyl phenylalanine, that the material could be moderately efficiently decarboxylated as the HCl salt under the conditions in which the decarboxylated product is frequently used (ie, vapourised). I couldn't think of any likely reasons why this would be useful information, or whether one could manage to produce this phenylalanine analogue (cinnamic acid in a grignard vaguely comes to mind). Besides all this, it's likely that it would be decarboxylated after being absorbed into the blood.

IndoleAmine · Dreamreader Deluxe

loki · guinea pig

in case it wasn't transparent, the decomposition seemed to produce less oxidation products when performed with the HCl salt of the amino acid. this may or may not be useful information, and may or may not be accurate, however afaik, experiments have always involved the free amino acid. aminos can form salts with acids and bases.

IndoleAmine · Dreamreader Deluxe

Since you don't want the acid moiety but want to keep the amine moiety, it is advisable to protect the amine function.
This can indeed be accomplished by salt formation as well as amide formation, whereas the carboxyl part can be protected for example by esterification (but in this case it isn't wanted anyway).
The problem with decarboxylating amino acids is specific for tryptophane - other acids work well..

loki · guinea pig

it may be possible to improve the efficiency and specificity of the tryptophan if one could protect that delicate pyrrole ring. perhaps via a mildly excessive formylation to attach a formyl group to both nitrogens? presumably one would want to remove them after achieving the decarboxylation. also, the formyl on the nitrogen may help catalyse the decarboxylation, being that double-bonded oxygens are catalysts for decarboxylation.

mk-1 · Sun May 15, 2005 7:51 pm

an article named "Efficient Procedure for the Reduction of a-Amino Acids to Enantiomerically Pure a-Methylamines" which apeard in J. Org. Chem. 2000, 65, 5037-5042 outlines the procedure for Amino acids to amines in high yield (85-99% yield). It is a bit long, and doesnt particularly suite the clandestine chemist but here it is anyway -
http://rapidshare.de/files/1231276/J.Org.Chem._2000__65__5037-5042.pdf.html

stooge · Sat Jun 04, 2005 3:27 pm

Hey! I know the question might sound a bit dumb, but as i'm quite new to chemistry i'll ask it anyway, as this seems to be the right thread:

Swim did a first try on the Decarboxylation of l-phenylalanine to Phenetylamine following the write up with the same name from rhodiums. He changed the Cyclohexanol for Paraffin cause he wasn't able to obtain Cyclohexanol, but that's all he changed, depart from doing the whole thing with 2g Phenylalanine instead of 10g.

What he doesn't understand is: After reaction is done, does he have to proceed like with go-go (darn, is there a function that vipes out "bad words" like "----"?!? it looks like! wow! Smile

))?

I mean, after diluting with HCL, departing the solvent and so on from the watery layer and the following basification of the fluid? Swim now mixed it again with some np and is trying to salt it out with slightly acidic dh2o (+hcl)...
is this the right way to go? or are there any better possible solutions? Or did he get the whole thing completely wrong?

Would be very glad on any hint on this ...

Thanks!

stratosphere · Sat Jun 04, 2005 6:40 pm

just curious if you saw bubbling (e.g. C02 evolution)?

washing the molten parrafin with hot(hot eneough to not solidify the parrafin) dilute HCl would certainly pick up the pheylethylamine, but would also pick up any unreacted pheynlalanine or other aminated junk ctreated in the process.

if the bubbling was strong and came to a definite end then unreacted phenylalanine would probobly not be a major contaminant, but if it is, it could be seperated by by strongly basifing the aqueous solution and washing with an NP, the amino acid staying in the water layer as a carboxylate salt.
the NP being evaprated should leave you pheynethylamine freebase

stooge · Sat Jun 04, 2005 7:00 pm

Hey stratosphere - Very nice - just feared i couldn't get any hint on this anymore, i asked around already at wd and so on.

yes, i saw some bubbling, not very much, but it did buble definitely.
What i was wondering was - i thought the phenylalanine would dissolve when the solution would become hot enough, but it didn't, not even at temps over the in the write up mentioned 161C ...
The liquid turned nice yellow, but the solids where (more or less) still there ...

Thanks anyway, that hint with the pea-base in the np was very useful for me - wouldn't have got to that thought by myself!
I think it will be recommendable to wash the base after evaporation of the np, or ... ?
what would be best to wash it with (or to clean)?

Thanks a lot!!

stratosphere · Sat Jun 04, 2005 10:22 pm

parafin is probobly just to non-polar to dissolve the p-alanine, im trying to think of some common high BP semi-polar solvents. i wonder if gycerine or propylene glycol could work? that would of course change the work up procedure, youd have to base it, then wash with an NP.

without being dissolved id think alot of bad stuff like polymerization would happen to the clumps of p-alanine when heated.