Decarboxylating Tryptophan

[urushibara]

Some more questions and ideas from a new bee:

It seems to me that the simplest routes to synthetic DMT start with tryptamine, and tryptamine can be easily made by carboxylating tryptophan, so I am looking for ways to make decarboxylation easier.

Firstly I will explain decarboxylation as I understand it (from my searches on the web). Decarboxylation is the release of CO₂ from a carboxylic acid. According to most accounts I have read, this is a simple reaction with dicarboxylic acids, which is due to the close proximity of a double-bonded oxygen to the carboxylic acid group. Okay, so that's why all the methods thus far posted involve a ketone, as the ketone catalyses the oxidation. (just a question: does the ketone degrade or is it left untouched, just behaving like a good catalyst should).

So, having thought quite a bit about it first I want to find out whether just using a ketone as the solvent to catalyse the reaction, as opposed to dissolving the ketone in a heavy non-polar solvent (hexanol, tetralin) would work. That is to say, dissolve tryptophan in acetone and reflux. If =O is crucial to the reaction, then surely lots of it will make it go faster?

My second idea is a different one. What about using esters to dissolve the tryptophan. Esters have =O's on them, some more than others - for example, diethyl fumarate would have two on it. Esters are very easy to make, one just needs to mix an alcohol and a carboxylic acid in the presence of a strong acid (HCl, H₂SO₄) and voila. If we want a big molecule that won't boil until at least 150 C, one could use ascorbic acid and cyclohexanol (cyclohexyl ascorbate ester). It would have the prerequisite =O group on it and a nice high bp.

I would think that it would be better to use a lower bp solvent though, since ultimately at the end the best product for the next reactions is freebase (since it is hydrophobic and anhydrousness is important to most reactions involving alkylation) and a nice volatile solvent will separate from our higher mp freebase more easily, methyl formate would evap very quickly (bp: 32 C). Perhaps isopropyl citrate or tartarate? A low mp ester such as methyl formate would be useful in that the whole reaction would be self-agitated by the convection in such a light liquid. Also it would be very easy to do the workup for it (methanol oxidises--> formic acid; mix formic acid w/methanol + HCl heat--> methyl formate). Perhaps it would take a lot longer...

Still, what is the hive's advice on using esters in decarboxylation?
C₁₂H₁₆N₂

[hypo]

Okay, so that's why all the methods thus far posted involve a ketone,

wrong. see decarboxylation via the copper chelate of tryptophan.

I would think that it would be better to use a lower bp solvent

i do not understand. the point of using heavy solvents is that the reaction needs lots of heat. the only way to achieve that in a low boiling solvent is pressure => push the CO2 right back in...

[urushibara]

I saw that copper chelation method, and it seemed rather convoluted and messy when all that is needed is some way to stimulate the CO₂ to release from the amino acid.

As to the bp thing, exactly how does pressure make the CO₂ go back in? Back in where? CO₂ is pretty stable, it might make carbonate if there was water around otherwise it would just dissolve in the methanol/ester solution. Making carboxylic acids is a little more complicated than that, in fact you have to oxidise alcohols, and our hypothetical high-pressure carbon dioxide environment wouldn't allow much oxidation to go on. Also, CO₂ release from carboxylic acids is a one-way reaction. That's why it doesn't take much energy to do it.

And the temperature thing is just a time factor. Using methyl formate, as I have suggested, may take 24 hours, maybe 48. In case you didn't notice, we are not in an absolute zero environment, and room temp would prompt quite a bit of decarboxylation with the presence of the ketone group catalysis (which an ester would provide).

If a suitable reaction vessel were used, something which could handle the pressure of our solvents at about 80-90°C, (I was thinking that a champagne bottle, but maybe soda glass wouldn't like being that hot and pressurised - and if it was used a few times could be a bit liable to crack open), it could be cooked at pressure, though it would probably need to be cooled (slowly slowly unless you got borosilicate) and vented a few times to get the CO₂ outta there.

Anyway, the point is that using methyl formate would decarboxylate (via the =O group on it), and then with more time would make the formamide (it might be the opposite order - there's something to discuss). Reflux might be better, but the pressure you spoke of would keep the solvents in liquid phase, which is equivalent to higher bp solvent at reflux. There would still be a lot of kinetic energy in there making both decarboxylation and formamidisation happen at a reasonably decent rate.

You wouldn't want to do it with an ester unless you wanted the acid end of the ester on the amine tail of the tryptamine anyway. I have just such a synthesis in mind in another thread. I was just casting about to see if anyone could find any major objections to having an ester provide the =O catalyst for decarboxylation. (other than the byproduct I have already mentioned).
C₁₂H₁₆N₂

[urushibara]

Pardon me, esters wouldn't be all that good, but the question is, could you go from amino acid to formamide via a something-formate? A big acid, like ascorbic (in the aforementioned hex-something ascorbate) might be okay because there's no way that ascorbate ions could stick on the end of the tryptamine - or is there? Hmmm...

Perhaps hexanol/formic acid ester would be good for its higher bp, if one desired the formamide at the end.

I thought of a way to name the formamide at last: N,N dimethal tryptamine. al for the aldehyde thing (really it's not just formic acid groups on the N, it's aldehydes, H-CO=O). Or N,N dicarboxyl tryptamine? I'm leaning towards the methal personally, since there isn't an OH on it.
C₁₂H₁₆N₂

[hypo]

I saw that copper chelation method, and it seemed rather convoluted and messy

not so! the first step is a wonderful reaction with consistent yields. the second step is done in 10 minutes. the only problem we have to solve is the workup.

As to the bp thing, exactly how does pressure make the CO2 go back in?

now come on... don't take everything so literally. high pressure will not favor CO2 release...

And the temperature thing is just a time factor.

an exponential factor...

all in all - i don't know... tetraline is one of the cheaper solvents and you need a vacuum pump anyway.

[hest]

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And the temperature thing is just a time factor.
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No, you need a sertain amounth off energee before the reaction start to run (just as gasoline don't burn in the tank)
And why work with the decarboxylation of trypthophan, in cuclohexanol and with a ketone with a high boilingpoint the yeald is in the 90'

 
 

[terbium]

Personally, I am getting tried of urushibara's ramblings. He does not do a very good fman impersonation. Until he can improve his fman act he should move this stuff over to the Couch.

[urushibara]

I agree that reflux is better than a pressurised rxn vessel in some ways. Mainly when we try to decarboxylate our carboxylic acid in a quantity that would evolve more gas than the strength of our vessel can withstand.

22.4L of CO₂ (at 0°C and 101.3kpa) must evolve from every mole of tryptophan (204.2g). I don't see how gas pressure, which does not affect our liquid phase reaction except by limiting evaporation when the gas is saturated, and furthermore, so long as there's enough heat making things all jumpy, enough so the carboxylic acid deforms and breaks off with the help of our ketone group (in whatever form we introduce it). A reasonable amount of the CO2 will stay dissolved in the solvent, not much, but a little, and more with greater pressure, and the gas phase will just get denser and denser (higher and higher pressure).

I did some gas pressure calculations with regard to a hypothetical .048 mol of tryptophan (10g) in a 700ml (space for gas) reaction vessel, and the gas pressure of 700ml of that much CO₂ is 238kpa, or 2.3atm at 137°C, which is not all that much - you could probably generate that much pressure in that space with your breath. If you cooled the reaction mix to -18 in a freezer with the lid open, close it once it's temp is as low as the rest of the freezer, ( I imagine a champagne bottle with the pressure holding cage on the 'cork'), then put your reaction vessel into an oil bath at a steady 140°C, I think that the total gas pressure would scarcely exceed 300kpa (or about 3atm) which should be perfectly safe in my imagined vessel) Could anyone tell me what the maximum pressure that champagne bottles must withstand? I imagine it's something around 6-7 atmospheres. A buchner flask or thickwall flask should be able to handle it too. If you put the vessel in the freezer first (-18°C), the air in the bottle is at sub atmosphere pressures (like about 1/4 - I could calculate it but I'm being lazy). when that amount of gas is heated to 150 it would barely reach atmospheric, which the CO₂ will happily dissolve into the gas phase at least up to two atmospheres, but I reckon it could do it up to three. And by then we've decarbed 10g of tryptophan. If one wished to decarb more, I imagine one could cool the vessel down to below the bp of our solvent, open it and vent the CO₂, cool it right down in the freezer again, close up and do it again. Gas pressure will not stop the decaboxylation, gas pressure will just increase with the rate of the decarb. Kinetic energy powers the reaction, which relies on a ketone bumping hard into the O-H and the H on the tryptophan chain next to the carboxylic acid group, enough so the bonds can exchange, the O from the O-H double bonds with the carbon and the H bonds with the carbon on the now tryptamine (well, after it happens). Gas pressure only affects evaporation of the solvent, it does nothing to stop explosive quantities of gas evolving from the liquid through other mechanisms which involve reactions or what have you. It does affect the reaction when the gas pressure gets so high the liquid phase becomes saturated with the pressurised gas though, but again, not all that much, and with CO₂ it might actually help the reaction by providing more possibilities of an =O crashing into the carboxylic acid and releasing yet another carbon dioxide.

Yes I am rambling now. Somebody around here says that I ramble. Well, I say that I'm just verbose. Nobody suffers when verbosity enters a scientific discussion. More detail is always helpful.
C₁₂H₁₆N₂

[slappy]

Yes I am rambling now. Somebody around here says that I ramble. Well, I say that I'm just verbose. Nobody suffers when verbosity enters a scientific discussion. More detail is always helpful.

The disscussion suffers when that verbose person is talking out of thier ass. You don't understand what you are talking about well enough to be so verbose about it. You need a good dose of humility.

And I would recommend that you read up on thermodynamics and organic reaction mechanisms.

[dely72]

Wise man once say:  "Those who know the most say the least, and those who know the least say the most."

Very wise man indeed in my opinion.

Some care more about impressing others with their supposed knowledge than making the finished product. Why waste time trying to develope novel synths that are in no way easier than known ones when there are perfectly fine synths requiring perfectly easy to obtain precursers?

[urushibara]

(chastened)

Can anyone give a definite answer on the effect of pressure on decarboxylation?

I saw a thing on creating coal-like fuels from peat and other organic carbon-rich things, and the first step was cooking the stuff up at high pressure, like a pressure cooker, and one of the things that was said to happen in this high pressure environment was decarboxylation. Since aminos will not spontaneously decarboxylate, they  need a catalyst, one suitable catalyst is acetone. I feel that a test of decarboxylation at pressure needs to be performed.

Thus an experiment will be undertaken: create a pressure-chamber with galvanised steel pipe and end caps that can be removed to add and remove contents. Tyrosine extracted from tablets (using relative insolubility of tyrosine to isolate lactose binder from amino acid) added to chamber with a quantity of acetone. Chamber is placed in an oven preheated to 200°C, baked for 10-15 minutes. Allow to cool, empty contents. If successful the product will boil at a much lower temperature than the amino acid.

C₁₂H₁₆N₂

[Lilienthal]

Don't kill yourself!!! If you have no training in (high-pressure) chemistry don't do it!

Why not using published procedures with higher boiling solvents (or OTC variations)? Use the search engine for turpentine thinner (tetraline and decaline) and see

Post 175553

(element109: "Tryptophan to tryptamine: practical xperiences", Tryptamine Chemistry) for use of thujone as the ketone catalyst. Checking that out would be of great significance compared to the kamikaze-type high pressure reactions you are planning   .

[urushibara]

I don't know Lil, I think that assuming I seal the pipe with ptfe tape and really REALLY tighten it, 200°C should be okay. If it starts leaking I will find out in the water/test phase. And as you would know, water at 200°C is higher pressure than acetone at the same temp, so a water test will be conclusive. And also to add to that there is the idea of filling the pipe up so the gas space is only like 50-100ml, which will account for liquid expansion and give less gas space to build up enough pressure to make it pop. If it doesn't pop with water, it definitely won't with acetone. Oh bottom end sealed with locktite, or something similar.
C₁₂H₁₆N₂

[Lilienthal]

Add shielding, stay away, NEVER fill more than 1/3 so you have at least 2/3 gas space!!! Better don't do it!

[urushibara]

Lilienthal, I just thought you might wanna know that I dreamed I made a pipe-bomb reactor out of galvanised water piping (a 3 inch double-nipple piece with two round end-caps), sealed with teflon tape (I even did one side dodgy with the tape going anti-clockwise).

In my dream I used vice-grips and a multigrips to tighten it up, tight as hell I made it. The pipe contained about 30ml of acetone and (well, I don't know really how much) of tyrosine. Anyhow, in the dream the pipe didn't leak in boiling water at 101 (I live next to the sea, I'm guessing that my thermo is a little inaccurate), so I put it into the oven at 200°C, turned off the oven while it sat in that temp for five minutes. Opened it up and no tell-tale smell of 'tone, so I amped it up to 250, left it on for ten minutes. Still no boom. No dream about getting 3-OH phenethylamine out of it yet... soon, soon.
Disclaimer: everything I said I pulled outta my arse  

[urushibara]

In a subsequent dream I opened up the pipe, it was at room temp now, so if nothing happened there shouldn't have been gassing, but there was gassing, just a little pffft. And the most joyous thing of all was that the previously white powder that I thought was probably tyrosine, there's still a little white, probably chalk that got through the filter paper; but the solution is orange, and so is the bulk of the solids in there. It kinda looks fluorescent, but there was no handy UV light in my dream so I couldn't test that one.

Dwarfer's bin playing around with pressure pipes for ages, I wonder why no-one else dared to. No boom boom risk so long as you really REALLY tighten the hell outta the pipe. And with decarbing, as we all know you don't need much acetone mixed with the tetralin, 30ml would probably easily decarb 5g of stuff. Well, another thing I can report from the dream is that the liquid was still acetone, it doesn't change, it only encourages the carboxylic acid to go poof. Thus my dream pipe-reactor, with a total volume capacity of about 55ml, is plenty for up to about 10-15g of aminos.

I wanna get me some tryptophan goddammit. Wish I wasn't so fuckin broke. Wish I wasn't in a country with such a piss-poor exchange rate with US $. Fuck. Well, there'll be more dreams coming, involving getting this orange stuff and heating it with flames from underneath on a spoon to see if it boils easy. Don't have a thermo to do that proper either... Won't be entirely conclusive dreams, but color-change is a big deal, nonetheless.
Disclaimer: everything I said I pulled outta my arse  

[urushibara]

And I fell asleep again and had another dream. In the dream the orange stuff was dried out and scraped up. The smell is vaguely reminiscent of solder flux, but somehow different. There was also a trace of a menthol type smell, possibly residue in the acetone or from in the pressure pipe (it had some kind of grease in it, which I hadn't cleaned up properly. When placed on foil and heat from a lighter applied, it boiled violently, releasing smoke, very much reminiscent of some bad DMT extract I once smoked a few times, bubbling and letting a white looking smoke that stank the place up quite a bit.

Unfortunately in the dream I had no device to measure the bp of the stuff, but from memory lighter flames are somewhere about 300°C, so though there might have been some remaining amino acids in it, it had obviously been changed as it boiled almost immediately, and the smell had distinctly changed from the original material, though some of that element may have been contaminants in the acetone and in the pipe. Oh the other thing which suggests it to be an amine: it was bitter.

I put some of it on a piece of plastic, and magickally it appeared as a jpeg on my computer's hard disk in the real world, I discovered upon waking. I have posted a scan of it at 1200dpi, which you can find at

http://www.angelfire.com/darkside/urushibara/index.htm

This stuff smelled contaminated with the solvent, but there was no trace of the original amino acid smell either. I've never seen meth freebase, only DMT freebase, but it sure seemed a lot like freebase. And it boiled like freebase. Though there might have been traces of everything else from the tabs.

Anyway, swim's gonna be getting some pure aminos for the next experiment, cos something definitely happened.

What yas think about the picture?

Oh, sorry, that white stuff is the original stuff that underwent the change to the brownish orange (presumably tyrosine). In my dream there was no methanol for me to use, so nothing's crystalline. Next time recrystallisation will be dreamt.

Disclaimer: everything I said I pulled outta my arse  

[urushibara]

Swim did a second experiment. About 3g of lysine this time, in the same apparatus, tightened fully. Placed in boiling water, no signs of gas leaking. Placed in oven set at 250°C, oven left on until thermostat turned off the heat, then switched off oven and left overnight to cool (did not open until morning).
   Again no signs of stress, nothing to suggest the pipe was holding more pressure than it could handle.
   Inside the pipe the acetone had turned yellow. Swim'll be posting his pictures soon, the starting material, Lysine behaves very peculiarly when it's crystallising, when the water is saturated, it forms a skin around the water. It had to be baked at 200 to get it to dry properly. Weighed on a dye scale it weighed in at 24g, which was the expected quantity, it just looked a lot more bulky than the weight suggested (lysine makes very fluffy crystals obviously). Anyway the stuff put in wasn't fully crushed so lots of it didn't react. Pictures will be at the same url as the last post shortly.
    Lysine decarboxylate freebase is very different, not very soluble in acetone or water. I think part of the colour changes has been cooking the additive in the acetone, which turns it yellow and makes it smell like menthol. I was wondering if it was adulterated. Evidently the acetone cooks the additive into something else too.
   The address again:

http://www.angelfire.com/darkside/urushibara/index.htm

   Second experiment proves that the pressure pipe can withstand 250°C.
   Swim's not planning on doing another experiment until he gets some tryptophan. Possibly also he might get a bigger pipe.

An addendum: The substance which swim thought was a byproduct of contamination dried out, the menthol evaporated, and a free-base looking gum was left behind. It was still slightly contaminated with the menthol smelling stuff, as evidenced by the smell of it when boiled on foil with a lighter, but a distinct freebase type smell was also produced. Furthermore, the material had a strong bitter taste.

Swim's not entirely sure what the insoluble product was. Possibly high-pressure acetone does more than just decarboxylate. The other possiblility is that it was the remains of the tyrosine from the first experiment that had been previously baked in with the container open, and perhaps this brown stuff was the binder used to make the insoluble tyrosine stick to the chalk. Or possibly swimm did the extract wrong, and there was very little chalk and he threw away the chalky stuff, which might have been the very insoluble tyrosine.

Anyway, the decarboxylated lysine stuff, the gummy freebase looking stuff - swim's redissolved in acetone and with luck it will recrystallise, so pretty pictures can be taken... stay tuned.

Sigh. Swim had better hurry up and get tryptophan powder...

I know naaaathing.

[Student]

An Exspearmint with Tryptophan

Add 500 mg of tryptophan and 15 mg (1 drop) of spearmint oil to a 10 by 150 mm test tube and wash down the sides with 5 mL of xylene or turpentine. Add boiling stones or a stir bar and cork the tube gently. Boil the mixture at a rate sufficient to heat the tube an inch or two above the liquid until all the suspended solid has dissolved. Turn off any stirring and let the tube of clear yellow liquid cool undisturbed. The next day pour off the colorless liquid into a dish and place the hose from an aquarium air pump into the tube and let the solvent evaporate. The yield (using xylene as solvent) of yellow crystals of tryptamine in the tube is 61-87%, melting at 104-105°C (Merck 118°C). There is a small additional crop of crystals from the evaporated mother liquor.

Notes:

1. The tube is corked to prevent the solvent from evaporating. The system is not intended to be sealed.

2. If xylene is used as the solvent the reaction will require about a week to complete but all the product tends to separate as crystals. If turpentine is used the reaction takes several hours, but part of the product comes out as an oil.

3. The rate of boiling needs to be sufficient to prevent the reaction mixture from being exposed to air. Air exposure causes a dark deposit to form on the test tube walls and no product can be isolated even by acid extraction.

4. Other oils which will probably work are caraway, dill or pennyroyal oil.

Suggestions for future refinement:

1. Try using butanone instead of spearmint oil with turpentine as the solvent, giving the reaction a week to complete.

2. After a reaction using turpentine, place the test tube in boiling water to cool. After a few minutes add a seed crystal and let the water cool slowly with the tube in it. This may allow complete crystallization of the product.

3. Increasing the amount of tryptophan, or adding more tryptophan at the end of the reaction and waiting for it to react, may increase the yield or reduce the required proportion of solvent and catalyst.

4. Determine the optimum concentration of catalyst.

Bonus question:

Why does spearmint oil catalyze the reaction better than butanone?

[foxy2]

Student
Did you do this??
If so how did you boil xylene for a week in a test tube with only a cork to prevent it from evaporateing?

Something tells me that this won't work
please elaborate
Foxy
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