• Members of the previous forum can retrieve their temporary password here, (login and check your PM).

Decarboxylation of Tryptophan

Migrated topic.
thethinice

thethinice

Rising Star
In doing some research and reading through some articles, I have found a number of methods to decarboxylate tryptophan. I'm just trying to better understand the chemistry actually taking place. I've learned that
1. Amino acids are decarboxylated at high temperatures in the presence of a catalyst.
2. Use of certain natural oils as catalysts prove successful in the production of tryptamine, but produce tetrahydrobetacarbolines or THBCs.
3. N-bromosuccinimide (NBS) has been shown to readily decarboxylate almost all amino acids.

I also read that barium hydroxide can decarboxylate amino acids. So I suppose my questions are such:

By what mechanism does an aromatic aldehyde or ketone catalyze the decarboxylation of tryptophan?
By what mechanism does NBS decarboxylate tryptophan?
Can barium hydroxide successfully decarboxylate tryptophan?
Could cinnamaldehyde function as a catalyst?
How could one, from an aqueous mixture, successfully isolate the tryptamine and NOT any potential THBCs, BaCO3, unreacted Ba(OH)2, catalysts, etc.?

I'm thinking cinnamaldehyde would be a fine catalyst for such a reaction
I'm also thinking the use of natural oils should be avoided, considering tryptophans readiness to form a betacarboline.
NBS is available online, but not necessarily from trustworthy sources, meaning home synthesis from succinimide or even synthesis of succinimide itself may be a better option.
 
Protip:

You need a keytone catalyste, use acetophenone.. it catslyzes itself. Just dissolve and reflux, extract, crystallize in heptane.

No need to overcomplicate this.

Further protip: run a tube from the column to a water jar so you can moniter the formation and cessation of CO2.
 
If you can read German: http://www.versuchschemie.de/htopic,13652,tryptamin.html

From my experience with harmala alkaloids (betacarbolines), these are not very soluble in aliphatic hydrocarbons, whereas tryptamines generally are. You could try to exploit this to get rid of any Pictet-Spengler products.
 

Attachments

  • Analytical+characterisation+-+thermolytic+decarboxylation+from+tryptophan+to+tryptamine.pdf
    595.6 KB · Views: 0
  • Fingerprint+analysis+of+thermolytic+decarboxylation+of+tryptophan+to+tryptamine+catalyzed+by+n...pdf
    439.2 KB · Views: 0
pitubo said:
If you can read German: http://www.versuchschemie.de/htopic,13652,tryptamin.html

From my experience with harmala alkaloids (betacarbolines), these are not very soluble in aliphatic hydrocarbons, whereas tryptamines generally are. You could try to exploit this to get rid of any Pictet-Spengler products.
Click to expand...


Or you could exploit the massive temperature difference between them. Reflux it onto a column and distill it over, crystallize from boiling hexane/heptane. Distill it over directly from the post reaction acetophenone solution.

I may be wrong here but from the top of my head I want to say that cyclized compounds are soluble in chloroform as evidenced by pitubo's 2nd paper, whereas tryptamine I believe is insoluble in chloroform.

The imine should be quite stable in acetophenone, rendering inert any issues you have with cyclization.
 
1ce said:
I may be wrong here but from the top of my head I want to say that cyclized compounds are soluble in chloroform as evidenced by pitubo's 2nd paper, whereas tryptamine I believe is insoluble in chloroform.
Click to expand...
Tryptamine freebase or some tryptammonium salt? It sounds quite odd to me that the freebase would not be soluble in chloroform.

What about pH-selective precipitation from aqueous solution as a means of separation?
 
It all sounds magic and probable until you actually go about and do this. In theory, yes, adjusting ph to precipitate tryptamine sounds easy. But the liquid is thick and hard to handle and extracting it just doesn't work the way it does on paper.

Drop a distillation head on, feed your condenser with warm tap water and heat the flask in a bath of peanut oil. Use gentle heating to purify your product, reagents will make a mess.

Look at bp of:

Acetophenone
Tryptamine
Thbc
Mthbc

Phase transition will be the more effective way to go since the bp of most solvents for this decarboxylation are well over the bp for tryptamine. Acetophenone works adequetly for the distillation of DMT as well, offering an advantageous way to separate out dmt from nmt and cyclized carbolines.

Here is what I suggest,

Add acetophenone to a 500ml rbf flask, heat to 100-110C and dissolve trypophan. Reflux ~140-145C until cessation of CO2. Allow flask to cool, setup for simple distillation and distill over tryptamine freebase.
 
Pitubo: Tryptophan - Wikipedia

Sorry about that, I thought I had responded to that already. Yes trytophan is insoluble in chloroform. You could grab some basic materials from a fast-mart and synthesize chloroform easily, but if you're going to distill anyway you might as well just distill out tryptamine.

If you've never distilled before, well.. consider it much like driving a car. It may seem rather complex and intimidating at first once you're behind the wheel; and with it: freedom.

I said I may be wrong because I felt too lazy to provide a source (mobile high speed data cap) and I knew it would be questioned. If you can source dcm/chloroform without having to distill, that would be your ticket. I get that there's speculation about chloroform being carcinogenic (has this ever been demonstrated?), and I get that spengler byproduct carbolines, particularly the methylated ones are speculated to cause parkinson's disease. I personally see no merit in either speculation, but the lesser of two evils smells alot like chloroform.

Washing out impurities would be acceptable if using a combination of say.. cyclohexanol/cyclohexanone (even comes premixed, for decarbs) or cyclohexanol/spearmint oil. These post reaction solutions WILL contain spengler biproducts, so removing them with chloroform/dcm will be key.

OR

Decarboxylate using acetophenone and distill out. These routes will be your bread and butter.

Regards, 1ce
 
To further elaborate on ph assisted precipitation and purificion of tryptamine, one must understand that there is alot of speculation on the internet. In order to do this anhydrous solvents must be used always. Chloroform must be free of stabalizing ethanol (THIS CAN BE FATAL IF YOU DO NOT HANDLE IT PROPERLY!). Basic water iz used to extract the tryptamine/carbolines from the solution, impurities are removed with chloroform.

Tryptamine is extracted into a suitable solvent that is immiscible with water, and remaining moisture removed by drying over MgSO4. Dry HCL gas is passed through the solvent to precipitate out tryptamine-hcl, and separated quickly with vacuum filtration.

It is critical that tryptamine is extracted from a dry solvent to prevent formation of hydrochloric acid that will destroy tryptamine.

I feel we should avoid further discussion of this route due to the fact that both handling and producing HCL gas requires other chemicals regarded as potentially dangerous, and the gas itself can seriously harm the user while destroying property simultaneously. Maybe we can find an alternative route akin to FASA?
 
Ineresting writeups, 1ce. Do you have any references on the sensitivity of (un)substituted tryptamines to HCl(aq)? I had some doubts already about using HCl in A/B extractions of DMT, but no certainty. I would welcome more information about this.

Anhydrous HCl isn't hard to obtain, just drip sulfuric acid drain cleaner onto table salt or dishwasher salt. Anhydrous HCl is hard to contain, that is why it has no place in the kitchen.

Is not hexanes/naphtha a suitable selective solvent for the purification of the results of decarboxylation? Both tryptophan and betacarbolines are not very soluble in it, I guess.

Could CO2 be useful for the purpose of gassing out? Would it form a carbonate or a carbamate with the tryptamine?
 
Dmt should be fine in aq. Hcl, it is tryptamine you should be worried about. I tried gassing with CO2, the results were unfortunately unhelpful, I had no visible precipitate drop out of the solution which caused me a bit of extra work undoing my mistake.

The problem with gassing is that it indeed easy, which increases the risk of somebody harming themselves with a face/lung full of gas. Take into fact many here have a hard time understanding acid base chemistry, and it becomes clear that the nexus isn't the best place to talk about it publicly.

Some information of the amino acid hydrolysis of tryptophan/tryptamine:


http://www2.bioch.ox.ac.uk/immunoch/PCFWebSite/Acideffects.htm
Complete amino acid analysis of peptides and proteins after hydrolysis by a mixture of Sepharose-bound peptidases

and here.

Also the steps taken to purify tryptamine depend greatly on its indended use. If it will be used for purpose of human use then the greatest affordable extent of purification must be employed.

If it is being used for a novel synthesis or non-human/animal nutrient then impurities are far more acceptable.
 
So much great info! Thanks a lot. So these answers pose for me a few more questions, then.

Synthesis of chloroform or other halide organic solvent (dcm)?

(Di)methylation of tryptamine by iodomethane? My thinking with this is that iodomethane very well may methylate tryptamine at a variety of positions, either on the benzene ring or on one of the two nitrogens, which would be a problem.

Is acetophenone available or synthesizeable?

Again, thanks for the info, especially on those betacarbolines.
 
Also, when you say acetophenone is self-catalyzing, does that mean it will occur at lower temps or?
And I'm thinking the NH2 group on tryptamine would likely be the most readily methylated by CH3I, but the resulting N-methyltryptamine may be more likely methylated elsewhere, or evenly methylated at the indole nitrogen and the already methylated nitrogen.
 
acetophenone is both a high boiling reagent, and a ketone catalyst. decarboxylation requires a good bit of energy (probably the reason it's a rate-limiting step in tryptophan metabolism), thermolytically requiring temps >165C. the process can take up to 4 h. or more.

the scenario of the indole amine getting methylated isn't likely (probably due to the pi-bond character in pyrrole..that amine is less amenable to protonation/deprotonation in the conditions being considered here) but formation of the quat-amine (N,N,N-TMT) is.
 
thethinice said:
(Di)methylation of tryptamine by iodomethane? My thinking with this is that iodomethane very well may methylate tryptamine at a variety of positions, either on the benzene ring or on one of the two nitrogens, which would be a problem.
Click to expand...
Biggest problem with methylation is overmethylation at the amine nitrogen, creating a quaternary trimethylammonium iodide. This happens long before the indole nitrogen or the benzene ring is methylated.

Please consuklt Shulgin's DMT systhesis in TIHKAL for detail on methylation with methyl iodide.

BTW, methyl iodide is a real carcinogen, because it also likes to methylate DNA.
 
Iodomethane just makes my head hurt a bit. I learned about it in my chem book as neucleophilic substitution. But when you're talking about adding a methyl group to a compound with it, it kind of flips your thinking. Not only that, but this reaction would theoretically produce hydroiodic acid, if I'm not mistaken, which may mess up tryptamine. Are there any other compounds capable of methylating tryptamine in perhaps an easier fashion or without such reactives invloved?
 
benzyme said:
acetophenone is both a high boiling reagent, and a ketone catalyst. decarboxylation requires a good bit of energy (probably the reason it's a rate-limiting step in tryptophan metabolism), thermolytically requiring temps >165C. the process can take up to 4 h. or more.
Click to expand...
For acetophenone catalysed decarboxylation of tryptophan into tryptamine, Georges Chatelus claims that a temperature of 130 degrees Celcius for 4 hours will yield 100% product (page 8 of the first attached pdf.)
 

Attachments

  • LaDecarbI.pdf
    765.1 KB · Views: 0
  • LaDecarbII.PDF
    482.3 KB · Views: 0
I made an attempt at thermal decarboxylation of lysine in my vegetarian girlfriend's kitchen. I'm 100% never allowed to do that again.
 
Back
Top Bottom