Active OTC tryptamine formation with Betaine

[romiir]

While I wish I could take credit for this creative insight, the idea is not my own. I was reading a board that I regularly check in efforts of harm reduction and to sharpen my skills of my organic chemistry hobby, however I came across this most interesting post. I would like others thoughts on this synthesis method. I'm posting it here, because you folks are open minded enough to see that I am asking a purely scientific question. Especially what the resulting products would be of the reaction. The one thing that really scares me about these untested methylation methods is the possibility of forming tryptoline MPTP analogs in the unfortunate event of an ring closure. I would personally recommend staying away from anything like this unless you can verify the target structure. I don't accept any responsibility for someone attempting this foolish dream, etc, etc. Don't do this. I am asking what mechanisms are involved, and how this could work. One bee in Russia says it did.

My thoughts... If it's this simple, why does everyone else use formaldehyde? It's worth noting that many substitutions can be made to the decarboxylation reaction, the important thing is a high boiling point solvent to drive out the co2, an inert atmosphere is not necessary as long as boling speed is sufficient to flush the container/condenser with solvent vapor. A sparkless hotplate is necessary to avoid fires, explosions, that sort of thing, but other then that minor thing, this is pretty much all OTC.

I quote:

Zerol and betaine

After noticing a similarity between the chemical structures of alkylbenzenes (ie. Zerol Alkylbenzene Refrigeration Oil http://www.nucalgon.com/nucalgon/nuc...E?OpenDocument ) and diphenylmethane, SWIH decided to try using some Zerol 150 to decarboxylate tryptophan. When about a half gram of tryptophan was heated in about 50 ml of Zerol 150, it remained in powder form until the temperature went over about 250 degrees where the tryptophan changed into a black tar. The mixture was heated for about a half hour to 45 minutes (about a third of the Zerol 150 evaporated), cooled and some toluene was added. It was gassed with HCl gas (from NaCl and H2SO4) to precipitate tryptamine hydrochloride. The precipitate was filtered with suction (Buchner funnel) and dried. It was then mixed with about 3 times its weight of betaine and heated. The temperature was gradually raised over time to about 250 degrees for about 2-3 hours to methylate the tryptamine. Betaine produces trimethylamine when heated to decomposition which should convert the tryptamine to the free base before its methylated. Betaine can be used to methylate primary aromatic amines according to JCS 1942, p48-55 so I thought it might work with other amines such as tryptamine. The product was biotested (smoked) and found to produce a strong intoxication with kinesthetic distortion similar to LSD and made colors look brighter. It was a lot stronger than the product formed in some other experiments using magnesium metal and formaldehyde in methanol to methylate tryptamine.

Further, references for these processes:
http://designer-drug.com/pte/12.162....ryptophan.html

http://designer-drug.com/pte/12.162....y/betaine.html



Also see:

"The Interaction of Betaine with Primary Aromatic Amines, Organic Disulphides, and Sodium Sulphite. " by Frederick Challenger (and others)

http://www.fileden.com/files/2008/8/...42-betaine.pdf

[nshanin]

Originally Posted by romiir

The one thing that really scares me about these untested methylation methods is the possibility of forming tryptoline MPTP analogs in the unfortunate event of an ring closure.

Really? Because I'm not seeing an aldehyde anywhere in your synthesis (required for P-S closure, as anyone who has seen the thread that you take this made-up "MPTP analog" phrase from knows).

I'd be concerned about overmethylation, as always. As you said, it's quite OTC and there's no risk of carboline formation; try it out!

[romiir]

Originally Posted by nshanin

Really? Because I'm not seeing an aldehyde anywhere in your synthesis (required for P-S closure, as anyone who has seen the thread that you take this made-up "MPTP analog" phrase from knows).

I'd be concerned about overmethylation, as always. As you said, it's quite OTC and there's no risk of carboline formation; try it out!

Well yes it is OTC, but that doesn't mean its safe. I don't claim to be an expert, and I'm actually unfamiliar with the "MPTP analog" thread you speak of. (perhaps you should link it here?) However I do recall seeing a methylated tryptoline derivative which is a functional analog of MPP+ (think MPP+, but with an added N-methyl bridge joining the rings), and I've read many instances of botched synthesis's cyclizing, although as you said, usually that happens through an aldehyde condensation in the case of cyclizing tryptamine to a trypoline IIRC. The reason I urge such caution here stems from an incomplete understanding of this reaction. I plan to completely read the earlier attached JCS article soon, but I haven't had a chance to look it over yet. So until then... The aforementioned active neurotoxic analog is called 2,N-dimethylharmine. However I have been unable to find any information on the methylated analog of Harmalan which is the (possibly neurotoxic?, unsure on this) molecule that has some chance of being formed by a ring closure of tryptamine. Though in cases of over methylated species, the main effect would be to slow the metabolic degradation of the molecule, as is seen in most of the TMT series molecules documented by Shulgin. But it also may unfortunately partially (or even completely) ruin the binding at 5HTs, depending on where the extra methylation occurs.

I don't see how partial over-methylation would be an issue if ring closure is a complete non-possibility. However I would definitely seek more opinions on whether or not this reaction could produce toxic analogs before suggesting anyone try it besides the rats. I'm not a pharmacologist.


structure of 2,N-Dimethylharmine:
http://isomerdesign.com/PiHKAL/explo...ain=tk&id=5401


P.S. I intended to say functional analog of MPP+ in all mentions of 2,N-Dimethylharmine (which I earlier incorrectly posted was a functional analog of MPTP in error, although it conveys the same idea, its also important to note that MPP+ and 2,N-Dimethylharmine are both polar but many other methylated tryptolines are lipophilic, this is important, because in theory, you could be injected with MPP+ and it wouldn't cross the blood-brain barrier, the reason MPTP works, is because of MAOB turning it into MPP+ inside the serotonergic neurons, killing them directly and selectively.)