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Author: Subject: L-tryptophan decarboxylation
Alyosha Karamazov
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Interesting info on the distillation, I might try using short-path distillation with hot water through the condensor and a heat gun as steve did. It seems that distilled tryptamine is less prone to aerobic oxidation (eg. turning into a sticky mess)?

@ Mythrilium: I lost my notes on that but I recall it was about an hour of passing dried CO2 through the crude tryptamine dissolved in DCM. The key here may be adequate cooling, I remember doing it at room temperature. I don't have the patent with me now, but does it specify chilling the mixture in ice?

Anyway, a precipitate was formed, but it was dark coloured and very fine, seemed to pass right through the filter paper. It resembled more a collloidal suspension than a precipitate.
Mythrilium
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Okay, thank you for your information.
I also got a dark coloured very fine precipitate from acetone using CO2, even at 260K.
I just remember having done a single recrystallisation from acetone before doing it with DCM.
So the trick might be to get rid of some stuff which prohibits the T from forming the carbonate...

Anyway, distillation seems the way to succeed with less effort.
The only question that remains: first freeze it out of solvent or distill solvent of under vac, before setting up the short path distillation?
slightlyinspired
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I'm curious as to whether anyone has had success with the copper-catalyzed decarboxylation of tryptophan. In my experience, the initial copper-chelate forms beautifully with a little added heat, but that's where the beauty ended for me. I did get gas evolution around 175 degrees in DMSO; however, the resulting mixture is a mess, and I believe a rushed extraction of said mess may have been my downfall. I've been unable to find a more quantitative protocol at this point in my search. That said, I'm wondering if anyone could help steer me in the right direction.
hive3
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Interesting to see an attempt at that method, what extraction method did you use? Extracting is the trick with any decarboxylation method. Tryptamine is just difficult stuff to work with.
turd
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Indeed, the problem is the workup, therefore using a method that has such a low literature yield (40%!) to start with is irrational. Keep the Cu-chelate as an oddity and use one of the many ketone-catalyzed methods.
slightlyinspired
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It's certainly troublesome. As far as the extraction goes, I diluted the cooled DMSO solution with a nice amount of water and then basified with NaOH. I then extracted with chloroform, rotovapped and was left with a small amount of orange-ish oil. A quick proton NMR of the oil showed that essentially no tryptamine came out in the extraction. If I could get a proper extraction to work, this route would be very straightforward.
slightlyinspired
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I've thought about this extraction some more, and I've come up with the following; however, I'm not sure it would work. According to the Merck Index, tryptamine is soluble in ethanol, while DMSO is not. Would it be possible to basify the DMSO solution with an anhydrous ethanol/NaOH mix then stick the vessel in the fridge to force the tryptamine out of the freezing DMSO and into the ethanol where it can be more easily manipulated? What am I not considering?
Nicodem
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 Quote: Originally posted by slightlyinspired What am I not considering?

The more appropriate question would be: "Am I considering anything at all?"
Nothing you wrote in the above post makes sense chemically. DMSO and ethanol not being miscible!? Have you tried at all?
Just use a published isolation method. Don't try to reinvent the wheel, if you don't understand how the wheels works. Besides, you never mentioned how you monitored the reaction. How do you know the tryptophan was converted to tryptamine? It is a bit pointless attempting to isolate a product that you don't know is even there.

…there is a human touch of the cultist “believer” in every theorist that he must struggle against as being unworthy of the scientist. Some of the greatest men of science have publicly repudiated a theory which earlier they hotly defended. In this lies their scientific temper, not in the scientific defense of the theory. - Weston La Barre (Ghost Dance, 1972)

*FWOOSH*
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Distilling it from mineral oil isn't the greatest idea, the lower boiling fractions will come over with the product. I would freeze and decant first.
palico
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I performed this reaction with negative results.
I put 10g of L-tryptophan and 4,80g of cyclohexanone in 35 ml of naphta. I refluxed for 3,5 h ( 140°C circa ) and I noticed a change in color, from yellow to dark red at finish. The solution was not clear, tryptophan was still on the bottom of the flask. So I filtered, and tried to crystallize the solute in freeezer overnight. A residue precipitated
( not crystal ), the solvent decanted and the remaining evaporated. A very viscous amber - colored liquid is left, that did not crystallize in the freezer and with great probability is not tryptamine.
Which was my mistake ?
The oil is soluble in alcohol, acetone and sligthly in naphta I used to reflux, insoluble in water.
Crowfjord
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Cyclohexanone probably isn't a very good catalyst. Enones work much better, for some reason (I would love to hear a good hypothesis on this). When I tried using peppermint oil as a catalyst (predominant ketone is menthone), the yield was abysmal. Spearmint oil or purified carvone have been shown to work very well however.

I think the main problem is choice of solvent, though. Naphtha is also pretty low boiling, so reaction time of 3.5 hours at temperature is not nearly enough. 140 C is pretty close to the boiling point of xylene, which IIRC needs a reflux of a week or more to effect usable levels of decarboxylation. I highly recommend using mineral oil. It is cheap, easily available, properly high boiling, and it doesn't stink!
palico
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I used cyclohexanone becuase it was indicated on the article I look.
The solvent is high boiling naphta, with a b.p of 180° at least.
I repeated the experiment.
I put 5g of tryptophan and 2,4g of cyclohexanone in 40ml of naphta, in oil bath this time.
The temperature of the bath raised up to 200°C. Putting a thermometer inside the flask, I verified the internal temperature was pretty much 180°C.
I left refluxing for 8 h.
Once refluxing was finished the solution was brown with carbonized tryptophan on the bottom of the flask.
One night in the freezer gave me the same viscous amber oil of the last reaction.
I have some little suspicious the amber oil is simply " toasted " tryptophan !
Really, I have no idea why this reaction doesn't work. The literature speak clearly about using 0,1 molar ratio ketone \ aminoacid and 8 h refluxing.
I think what I call naphta is your mineral oil.
Crowfjord
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Why do you think it doesn't work? That amber oil likely has some tryptamine in it. Mine looked like that, too, before I performed acid/base extraction. Have you tried to do a purification at all?
palico
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Not yet, I have still left it in the freezer.
I will try to dissolve it in toluene or ether and acid base extraction.
hive3
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Placo,

Are you using a a sealed setup with tubing take off to blubber? There is really no way to determine if this reaction is occurring unless you see gas evolution. If you are performing the reaction in an O2 environment you are certainly going to oxidize the tryptamine. In a sealed environment the CO2 will quickly displace the O2 as it is heavier.

I have performed this reaction several times and have gotten the temperature to over 200C with no reaction because of omitted carvone, and even at 180C there is little gas evolution. You really need the mixture over 200C but if you hit temps over 225C the Tryptophan / tryptamine mix clearly starts to vaporize and degrade.

Good luck
palico
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Yes hive3 you are right, detect CO2 bubbles is the best way to recognize the ongoing reaction, but unfortunately I'm not able right now to perform it. I was thinking to collect CO2 bubbles in a test tube containing a water soluble calcium salt, using the carbonate formed as analyzer.
I believe there is another problem in my setup: I have no stirrer !
Maybe stirring has an important influence on decarboxylation.
What you think about it ?
lullu
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some good writeups on german boards regarding decarboxylation

bombjack @ lambdasyn did some impressive work on this
http://forum.lambdasyn.org/index.php/topic,747.0/all.html

regarding destillation:
http://forum.lambdasyn.org/index.php/topic,1057.msg5570/topicseen.html
palico
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Thank you lullu but I don't understand german.
Bot0nist
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An online translater will get you pretty far.

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palico
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I dissolved the product in toluene and I have extracted three times with 2M HCl. The aqueos phase become opalescent, the dark oil is still present attached on the glass of the sepratory funnel and in the becher. I neutralized with NaHCO3 until neutral and evaporated off the solvent. Crystal of sodium chloride mixed with a dark powder appeared. I'm waiting my thiele tube arriving for melting point determination of the dark powder.
I Like Dots
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Hello, I had a go at this. I have not finished the workup, but this is the current situation.
5g Tryptophan base was added to 40ml of acetophenone in a round bottom flask. The tryptophan would not dissolve. The mixture was heated on a oil bath to 180c. Gas evolution was smooth, starting at ~140c.

Gas was collected to determine the progress. According to theory, 5g tryptophan will produce 636ml CO2@ 24c. After 45 minutes, no more gas production was observed. 550ml of gas was collected, indicating a possible yield of 84%. Literature reports 100% yields.

Error analysis: The scale was poor resolution, only measuring grams. I did not grease the joints, CO2 may have leaked. The water may have absorbed CO2. It was Saturday. the universe was out of alignment. etc...

Setup.

140c, T+0m

180c T+30m

180c T+45m

24c T+1h

The reaction was stoppered, will purify tomorrow.
Is this color normal?

Crowfjord
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The color looks fine to me. I'm surprised you didn't get a higher conversion. I assume you used the ideal gas equation to predict the volume of carbon dioxide? The last time I did the decarboxylation, I tried to measure the volume of CO2, but the beaker I was using tipped over at about ~70% completion. So, good job there.
*FWOOSH*
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I've performed Crowjford's procedure with success (after a bit of troubleshooting).
I'd like to reinforce what has been said before about Temperature, keep it close to 200 C, if it goes too far above you will kill your yield, too far below you kill the reaction.
When performing AB CAREFULLY titrate your acetic acid solution with your base, don't put any more than you really need to in and you'll get some nice clean product.

Now for my own little contribution:

Just for kicks I tried this out with DMSO, with a similar procedure to the one found here:

It was supposed to be a quick qualitative run so here's the rough and dirty.
~20g Tryptophan suspended in 50-60ml DMSO a 250ml RBF with a liebig condenser attatched reflux style but with no coolant flow (my stove can heat an oil bath FAST, but the sink is out of reach of my hoses so I can choose between hotplate and coolant in the bathroom or try to do without on the stove).
Added ~2ml Spearmint oil and immersed in oil bath.
Flask submerged in oil bath, which was quickly brought up to 225-250 C and held somewhere around there. Flask was agitated by hand.
As the internal temperature of the flask reached ~130 C there was a LOT of bubbling and the whole contents of the flask turned a clear yellow. The bubbling stopped shortly after.
I wanted to make sure I actually achieved conversion so this time around I chose to keep on going until I had obtained an internal temp ~200 C and held it there for a while.
Yes, most of the DMSO boiled off in the process, actually kind of what I wanted, it's a bitch to seperate from your reaction mixture.
I ended up with a dark red clear mixture which I allowed to cool to RT with no visible changes, stuck er in the freezer for an hour or so and got what looked like DMSO crystals and possibly something else.
After some deliberation I decided to try something novel (to me at least), I saturated a few mls of Acetone with some Fumaric Acid I have laying around (Cheap, $<30 for 500g on ebay including shipping, and it's a food additive) and diluted a couple drops of the reaction mixture in another ml of acetone. I added some FASA (Fumaric Acid Saturated Acetone) to the diluted product and VIOLA, a milky suspension was obtained. Repeated this with ~7g Fumaric acid (somewhat) dissolved in ~250ml acetone which I poured into my reaction mixture and proceeded to stir the living hell out of. The solution was filtered and the filtrate (some white powder, some crystals, some red goo) suffered my attempts to dissolve it in water without really budging (fumaric acid sol. in H2O = 6.3g/L...). I scraped as much as I could into an xtal dish and rinsed my filter paper with water, then a little bit of 10% KOH, and then some more water. The resultant mess was made basic with 10% KOH (Potassium Fumarate = Very Sol. H2O), which made it turn milky and start dropping out presumed tryptamine freebase, and stirred heavily for a bit to make sure all fumarate salts reacted. it was then allowed to settle, resulting in yellow-white precipitate. That's currently sitting in my fridge. Will update later if y'all are interested. EDIT: I forgot to mention I flushed the suspension with argon and swirled it around a bit before heating, to try to avoid having shitloads of oxygen trapped in there. Please forgive the half-assedness of this all, I started this after midnight and it's currently 4am, G'night. Double Edit: Worked it all up and ended up with ~2.5g brown crude tryptamine, definitely not pure, and the yield has a lot to be desired. But it worked . I want to try this again but stop around when the foaming stops instead of boiling it. The color was a VERY nice yellow at that point but turned to a familiar dark red the longer I heated it. Gotta say it's not bad for the abysmal technique that was employed. [Edited on 2-4-2014 by *FWOOSH*] Arsole Hazard to Self Posts: 52 Registered: 21-1-2012 Location: USA Member Is Offline Mood: Sleepy Troubles Hey folks, I have tried this procedure a number of times and each time I am left with a large amount of solids in the flask. This is before any work up and well after decarboxilation should have finished. The reaction mixture is bright red. No inert gas was used. I attempted "students" procedure using turpentine. The mix was refluxed on a sand bath. Any idea what is going on? Thoughts, like fleas, jump from man to man, but they don't bite everybody. -Stanisław Jerzy Lec Rabodon Harmless Posts: 10 Registered: 16-6-2014 Member Is Offline Mood: No Mood Why all this fuzz about Tryptophane decarboxylation? I've done it once in terpentuine (genuine stuff, no subsitute) as solvent and spearmint oil as catalsyt. Simply reflux tryptophane in TPT with a splash of spearmint oil until CO2 evolution stops. Extract dark terpentuine layer several times with 5% acetic acid, wash the aq. layer a few times with an organic solvent of your choice to remove most catalyst (you will smell it), TPT and most color, precipiate crude tryptamine by slow addition of large excess of very strong (~50%) NaOH solution under strong stirring (might take a few moments until the tryptamine begins to crystallise, if it doesn't crystallise at all after addition of the NaOH, stop stiring, let the oil settle and cool it in a fridge - you will get one very large massive trypamine chunk), filter, wash with ammonia to remove NaOH (80-90% yield on crude slightly waxy amber-brownish trypamine) and destill under good vacuum (a cheap 100$ vacuum pump from Ebay works fine enough I think) with open flame and a few boiling stones and no water in cooler (heatgun might be helpful aswell if the condenser clogs) to get very pure trypamine freebase, suitable for any synthesis. You can do it in one afternoon with 100% OTC chemicals and simple apertures with very good yields and high purity product and it can be upscaled to ~500g batches very easily.

Where's the problem? You don't need DMF, acetophenone and other carcinogenic or expensive chemicals!

Is it because you all don't have a vacuum pump?
Buy one! It's worth it! To use it for such a workup almost always gives higher yield, much cleaner product, it saves A LOT of solvents, and it's also faster. And a cheap vacauum pump isn't even much more expensive than a large seperating funnel.

Without vacuum pump I would do a few more acid-base like extractions (dissolve in 5% acetic acid, wash with organic solvent, precipiate with NaOH, filter, wash with water or thinned aq. ammonia, and repeat) and then precipiate it as carbonate with CO2 (gassing out or using dry ice) from an non-polar organic solvent which dissolves trypamine. After that I would freebase it again and recrystallise it from EtOAc for example.
Forget trying making *HCl, sulphate or acetate salts at first, in my experience that only works nice with already quite pure educt.
Fumaric acid/acetone might be also an interesting idea to precipiate the product as fumerate (fumaric acid and tryptamine dissolves well in acetone while the tryptamine fumerate doesn't I guess).

[Edited on 18-9-2014 by Rabodon]

[Edited on 18-9-2014 by Rabodon]
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 Sciencemadness Discussion Board » Fundamentals » Organic Chemistry » L-tryptophan decarboxylation Select A Forum Fundamentals   » Chemistry in General   » Organic Chemistry   » Reagents and Apparatus Acquisition   » Beginnings   » Responsible Practices   » Miscellaneous   » The Wiki Special topics   » Technochemistry   » Energetic Materials   » Biochemistry   » Radiochemistry   » Computational Models and Techniques   » Prepublication Non-chemistry   » Forum Matters   » Legal and Societal Issues   » Detritus   » Test Forum