DDTea
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5-HTP as a precursor to Tryptamines
I'm not sure where to put this. Biochemistry? Organic chemistry? Or even on sciencemadness at all (as it is related to a certain branch of 'illegal
chemistry' ). I had originally put it on totse, but I doubt I'll get the kind of discussion I want... So here you are!
5-Hydroxytryptophan is sold on store shelves in the herbal supplement section. I first came across it when I heard it could be used to prevent
migraines (which I get all too often).
But looking at its structure, it looks like an obvious precursor to other tryptamines, namely psychedelic ones--especially of the kind like 5-Methoxy
Dimethyl Tryptamine, which is found in toad venom.
First for a primer on Indole chemistry:
http://www.unb.br/iq/labpesq/qo/olv/olv/about.htm
Anyhow, for a theoretical synthesis of 5-MeO-DMT from 5-HTP, here's what I've come up with:
First convert 5-HTP into Serotonin by a process analogous to this: http://www.erowid.org/archive/rhodium/chemistry/tryptophan.h... . From what I can tell, the OH at the 5 position should not interfere... Please
correct me if I'm wrong--this would be the biggest stumbling block if I am. And in that article, for the reaction with Copper Acetate, is there any
reason why Diphenylmethane is used as the solvent? Can anyone tell me what kind of reaction is happening and what the requirements are for the
solvent?
Next would be methylating the Ethylamine at the 3 position. This could be done with methyl iodide in an acid scavenger like pyridine. However, I
worry that the amine would be "over methylated" into a quaternary nitrogen... But this risk could be mitigated by using an excess of Serotonin in the
reaction.
After that, should all go well, the solution would be acidified and methyl iodide added again to form the Methoxy ether at the 5 position.
But then this sounds all too easy... If it were simple, you'd think you'd hear of more high school stoner kids playing with psychedelics, right??
You'd see news reports of them breaking up families and killing the dinosaurs, etc.
Here's the structure of 5-HTP: http://z.about.com/d/headaches/1/0/U/5htp1b.gif
For Serotonin:
http://www.cem.msu.edu/~cem181h/projects/98/sleep/SEROTONIN....
And the target molecule, 5-MeO-DMT
http://upload.wikimedia.org/wikipedia/en/0/0c/5-MeO-DMT.png
[Edited on 3-11-06 by Samosa]
"In the end the proud scientist or philosopher who cannot be bothered to make his thought accessible has no choice but to retire to the heights in
which dwell the Great Misunderstood and the Great Ignored, there to rail in Olympic superiority at the folly of mankind." - Reginald Kapp.
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Flip
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As far as I can tell, you've posted your idea in the best possible forum for this.
Hopefully this will just be an initial response, as I am interested in researching your idea further, but i'm tied up between several projects right
now. First of all I have to say that this is an awesome idea, and you have no idea how happy it makes me to know that there are people here with
minds such as yours.
In answer to your question concerning the hydroxy group, it should not effect the decarboxylation.
In answer to your question concerning diphenylmethane, this is not related to the copper catalyzed decarboxylation. The reactions concerning DPM are
thermal decarboxylations, and DPM is a good choice of solvent for this due to it's extremely high boiling point (264*C).
Now, I do have concerns. The first is in regards to this: | Quote: | | The products of alkylation reactions of indole are complex because they are subject to both kinetic and equilibrium
control. With methyl iodide, eg, initial attack is on the 3-position to give first 3-methylindole then 3,3-dimethylindolenine. This is followed by
equilibration between the 2- and 3-positions to form 2,3-dimethylindole which, in turn, is attacked to give 2,3,3-trimethylindolenine and, finally,
1,2,3,3-tetramethylindoleninium iodide. The latter compound loses HI, when treated with aqueous alkali, to form 1,3,3-trimethyl-2-methyleneindolenine,
a widely used intermediate for the manufacture of cationic dyestuff. |
Of course, you thought of this
 However, I tend to think while controlling the stoichiometry will do a lot for
this method, you'll probably need additional and very specific reaction conditions to make this a high yeilding synthesis. If we knew just what the
ratio of equilibrium was between those products it might help us to diagnose how big a problem this could be. This will take a fair amount of
research but should not be insurmountable. My first suggestion might be the substitution of methyl bromide for methyl iodide, as the bromide
shouldn't attack quite so readily.
I am also curious about the alkylation of the hydroxy group. I have heard of the acid catalysed alkylation of alcohols to ethers, but the reactions
that I know don't involve an alkyl halide. Also, I can't find anything at all about the alkylation of alcohols under 'alkylation' in my copy of
March's, and I can't figure why. Do you have any information on this step of the procedure that you can share? Is there any reason you have in terms
of reaction conditions why this step is considered seperately from the alkylation of the amine? Utilizing the same conditions, you would again face
the problem of the crazy methyl-shifty weirdness. In any case, I hope that it can be done, but you might want to look into alternative methods with a
specific focus on the -OH group, as I believe the reaction may have to differ somewhat from the first procedure. Sorry I can't be of more help on
that particular issue.
So anyway, excellent idea, excellent work, you've really thought this out and I wish the world had more people like you. I'm going to check into this the next time I get some time on a good database,
because finding some references here is really going to be the key if you're ever going to make this happen.
Thanks for sharing!!
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Flip
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Bufotenin
If nothing else, you should be able to synthesize 5-OH-DMT, a compound known as bufotenin that is slightly less active than it's methoxy cousin.
Unfortunately, it is also scheduled.
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budullewraagh
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well, if one wanted to (and i don't see why they ever would) they could, say, cleave the amide with hydroxide, isolate the product amine, methylate it
and then use a strong base to pull the H off the hydroxyl group before reacting with an alkyl halide. problem is, the base would need to be pretty
strong, though the arene does contribute electron denisty to the O from OH, which would make the O-H a weaker bond and thus easier to pull off.
another problem is that alkylation of the nitrogen from from the ethyl branch would probably lead to alkylation of the ring nitrogen, which you should
probably protect before amide cleavage.
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DDTea
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Ah! The Chemistry fairies have visited my slightly loopy late night head and I see a synthesis! A possible one, involving some difficult reagents, but
it should work!
The first step is to replace the Amino group in 5-HTP with a Dimethylamino group. I don't know of a way to do this directly, but indirectly it would
involve removing the Amine...somehow. Next step would be a "Hell Vollhard Zelinski" reaction, or any other suitable reaction to place a Br or I on
the alpha position of the carboxylic acid (as the HVZ reaction calls for PBr3 and Br2).
Alternately, is it possible to do a nucleophilic substitution on the Amino group? Maybe by first "over reacting" it with say, Methyl Iodide, to make
it a better leaving group? If we can at least get the enol, doing an alpha halogenation will be easy.
This in turn is reacted with Dimethylamine. The last step is the thermal decarboxylation, leaving the desired 5-Hydroxy-DMT, or Bufotenin.
Edit: and on further thought, the Phenolic OH is, in fact, acidic. Perhaps we could form the Sodium salt and react that with an Methyl Iodide or
something to for the 5-Methoxy part of the molecule. This would have to be done BEFORE we react the alpha-halogen with Dimethylamine, so as not to
get nasty side reactions.
This would yield the desired 5-Methoxy-DMT.
[Edited on 5-23-06 by Samosa]
"In the end the proud scientist or philosopher who cannot be bothered to make his thought accessible has no choice but to retire to the heights in
which dwell the Great Misunderstood and the Great Ignored, there to rail in Olympic superiority at the folly of mankind." - Reginald Kapp.
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