Sciencemadness Discussion Board

L-tryptophan decarboxylation

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L6L - 29-5-2007 at 18:05

to start off, i would like to tell you that i have no formal background or education in chemistry, aside from a basic high school chemistry course (i'm in high school). so allow myself to apologize in advance if i post some bad chemistry. i'm committed to improving however.

OK, i am following a synthesis in which L-tryptophan is decarboxylated with a ketone catalyst to yield tryptamine. what i did was this: i put 35g of L-tryptophan in a 500mL RBF with 130mL of xylene as solvent. i added about 4 grams of MEK. i then turned on the magnetic stirrer (hotplate/stirrer combo), and held this mixture at reflux for 9 hours. the temperature of the oil bath was 135 - 145 the entire time. once the 9 hours had finished, i left the temperature at what it was, but just removed the liebig condenser. during this time, i took out the spinbar and let the xylene evaporate. i was now left with (hopefully) decarboxylated product.

this is where i am having trouble. i cannot seem to find much information about the tryptamine compound! the synthesis tells me to dissolve the contents of the flask in DCM, followed by a wash with sodium bicarbonate solution and drying with MgSO4.

where can i find information on tryptamines solubility in DCM? or other similar, useful information?
it seems like the remaining flask contents will require at least a liter of DCM for it to be dissolved.

and yeah, i'm having my doubts on whether the reaction even went well. i couldn't tell if the bubbling was from the xylene evaporating or CO2 being formed. any pointers you guys can give me would be great.

Furch - 30-5-2007 at 02:48

You should've somehow tried to measure the gas evolution using hoses, plugs, water baths and water filled upside-down beakers and some other cool gadgets. That way you could at least tell for sure that the stuff has reacted.

I'm sorry to say I don't Merck at hand, but according to some site on the net it's "soluble in ethanol, acetone, insoluble in ether, benzene and chloroform", and I'd say that if it's insoluble in chloroform, it's probably insoluble in DCM as well.

Good luck!

Methyl.Magic - 30-5-2007 at 09:24

Hey !!!

I've successfully decarboxylate tryptophan !

The first tests didnt works. I refluxed Tryptophan in NMP with MEK as catalyst, dont know about yield, but tryptamine is hard to isolate.

The problem is that T is insoluble in DCM, hexane,ether or other non-polar solvant and slightly soluble in water (you get a white cream impossible to filtrate trhough a G4). Another problem is that acidic water destroy your T freebase... therefore you cant do the regular acid/base extraction.

I suggest you can add your T/tryptophan mixture into basic water (not too strong), tryptophan is (slightly) soluble into basic water. Than you must find a nonmiscible solvent wich dissolves T. MEK is a ketone and you know that T is very soluble in acetone, right ? Perhaps pentanone or MIBK are better because there are less soluble in water.
Boil your ketone to get pure T freebase.

The best methode I did is refluxing Tryptophan in a high-boiling point liquid ketone.
I refluxed 1g of T in a few ml of Acetophenone for 1 hour. Distilled the solvent off and get a >95% tryptamine freebase as cream colored solid. ;)

IPN - 30-5-2007 at 10:02

Methyl.Magic what do you mean by acidic water destroying tryptamine freebase?

I think best results could be had from using cyclohexanol as a solvent and cyclohexanone as the catalyst. This was mentioned in some references at rhodium. Then just add dry HCl in toluene to precipitate the tryptamine as the hydrochloride.

L6L - 30-5-2007 at 10:30

where did you get acetophenone from, or did you have to synthesize it yourself? that would be awesome if i had a high boiling point ketone like that.

but i'm a little confused on what you are saying about treating the tryptophan/tryptamine mix. if i were to add basic water to dissolve the tryptophan, and then acetone to dissolve the tryptamine, acetone and water are miscible. do you mean i should first get rid of the basic water with dissolved tryptophan?

i referred to the Merck index, and it only got as detailed as saying that tryptamine is soluble in acetone. does anyone have more specific information so i know how much acetone i should use?

Nicodem - 30-5-2007 at 11:36

He just says to wash the organic phase, for example with 5% aqueous NaHCO3, in order to remove the unreacted tryptophan and other potential acidic side products. You will still need to recrystallize tryptamine until proper mp is achieved. Ethyl acetate is appropriate for extracting tryptamine. CH2Cl2 will also work if enough is used. But first you will need to properly decarboxylate tryptophan. Xylene is too low boiling for the decarboxylation to finish in 9 hours.

L6L - 30-5-2007 at 11:46

thanks for all the help you guys are giving me.

so i guess i'll have to add some more xylene and MEK and let it react for longer... oh well, the weekend is coming up and i'll have time.

jon - 31-5-2007 at 00:16

I've read that mek, acetone whatever does'nt do a very good job or does'nt work at all.
In the original paper they specify the use of cyclohexeneones (not cyclohexanones) and in rhodium he uses spearmint oil which contains pulgelone an isoprenylcyclohexenone and gets the goods. something to think about.

Methyl.Magic - 31-5-2007 at 08:38

Quote:
Message original : IPN
Methyl.Magic what do you mean by acidic water destroying tryptamine freebase?

I think best results could be had from using cyclohexanol as a solvent and cyclohexanone as the catalyst. This was mentioned in some references at rhodium. Then just add dry HCl in toluene to precipitate the tryptamine as the hydrochloride.


yes, dry HCl is HCl in gas form because tryptamine is destroyed in aqueous HCl (processus of destruction preasent in the human body). Indole (?) is formed, as far as I know...
I thing he dindn't use cyclohexanone but cyclohex-èn-one wich is harder to find that acetophenone.

L6L, you should buy acetophenone, or synthetise it if you can (grignard, friedel-craft, ... ). This is the best method of decarboxylation I ever done.
Xylène dont do the job... perhaps anethole but low bp.

Yes acetone is soluble in water, therefore you must use MEK or other non-soluble ketone (MIBK, pentanones, ... ), or insoluble esters like nicodem said.

jon - 31-5-2007 at 11:29

yes cyclohexenone is hard to find but it's isoprenyl cousins are naturally occuring in spearmint oils and in others in excess of 50% and it does the same job because the neccesary functional groups are there the double bond and the carbonyl function.

L6L - 4-6-2007 at 18:04

between work, school, work, work, work, school, and work, i squeezed in some time on sunday for chemistry! (more like sunday night - monday morning...)
well, i let the solution reflux for another 11 hours, for a total of 20 hours refluxing.

however, in this time, i found a source of acetophenone. learning from methyl.man's experiences, i'll take his word that the acetophenone decarboxylation was the best method he tried :) since i want to run this reaction properly, i figured i should stop messing around with the MEK and xylene and just do what will work best. Good thing for me too, because otherwise i would have been forced doing a friedel-crafts reaction, which may have been beyond my current lab abilities :(

also in the meantime, i purchased some DMSO. it has a significantly higher boiling point. would there be any reasons why i should not substitute DMSO for the xylene?

jon - 4-6-2007 at 18:30

dmso and xylene are two totally different animals dmso has a higher dielectric constant and It might chage the dynamics of your reaction system, it's possible this reaction is done in aromatic solvents for a reason but I can't say for sure.
It's cocievable that acetophenone would work I think there has to be some kind af electron pair conjugation between a double bond Pi system and the carbonyl oxygen for the ketone to properly work and acetophenone fits the bill, benzophenone might work too but this is doubtful due to steric factors.

[Edited on 5-6-2007 by jon]

[Edited on 5-6-2007 by jon]

Methyl.Magic - 5-6-2007 at 00:26

DMSO dont do the job !

Benzophenone works but this is a solid...

Go with acetophenone !

Perhaps other solvent are usable with a keto-catalyst : diphenylmethane, phenetole, benzylic alcool, diphenylether, pure cyclohexanone, ...

Distilling acetophenone off

Grimble_Gromble - 16-6-2007 at 13:46

Quote:
Originally posted by Methyl.Magic
Hey !!!

I refluxed 1g of T in a few ml of Acetophenone for 1 hour. Distilled the solvent off and get a >95% tryptamine freebase as cream colored solid. ;)



Did you distill off acetophenone in a reduced pressure environment?
Acetophenone has a bp of about 120-150ºC, I´m not sure. My concern is to destroy the tryptamine with high temperatures.

Misanthropy - 26-6-2007 at 07:26

AFAIK, tryptamine is available without restrictions in the USA.

beheada - 6-8-2007 at 05:53

Why wouldn't the DMSO work? Perhaps because it is a slightly acidic solvent? It seems like it would work under anhydrous conditions with the appropriate ketone added (MEK, acetone, etc).

chemrox - 7-10-2007 at 11:14

This is all re-inventing the wheel. Decarboxylation of tryptophan in various media with yields are discussed in the article at Rhodium published with references. It looked like the best method was in diphenylmethane with a ketone catalyst. The refs are:

1. D. H. R. Barton, On the origin of the C-1 Fragment in Indole Alkaloids, J. Chem. Soc., 3990-3994 (1965)
2. T. Kametani, A Simple Preparation of Tryptamine, Synthesis 475 (1972)
3. T. Kametani, Synthesis 171 (1974)
4. S. Takano, Efficient Synthesis of Tryptamine, Heterocycles 6(8), 1167-1171 (1977)
5. M. Hashimoto, A Novel Decarboxylation of alpha-Amino Acids, Chem. Lett., 893-896 (1986)
6. E. J. John, Casein, Org. Syn. Coll. Vol. 2, 120-122 (1943)
7. G. J. Cox, L-Tryptophan, Org. Syn. Coll. Vol. 2, 612-616 (1943)
8. G. Laval, One-pot Sequence for the Decarboxylation of alpha-Amino Acids, Synlett 542-546 (2003)

Source: Synthesis of Tryptamine from Tryptophan
by Rhodium

Here's the purification from that article:

"A good way to purify tryptamine without having to resort to distillation under strong vacuum is to dissolve the crude tryptamine hydrochloride in water, adjust the pH to between 7.6 and 8.2 and extract the solution with chloroform. "

impurities go with ChCl3?


"The pH is then adjusted to 14 with NaOH and the pure tryptamine is filtered off with suction and air dried."

simple!



[Edited on 7-10-2007 by chemrox]

Sergei_Eisenstein - 7-10-2007 at 12:07

Quote:
simple!


No, it's not. Many people have experimented with the decarboxylation of tryptophane, and there usually are problems with the reproducibility of the experiment. Sometimes there is little or no reaction, at other times transamination is a disturbing side-reaction.

chemrox - 7-10-2007 at 19:12

and as has been pointed out, the stuff isn't even watched in the US so why not buy it. I haven't checked but I'm guessing that tryptamine is less expensive than tryptophan (US spelling).

Sergie makes a good point. I should not have said, 'simple.' I've had fits reproducing "simple" looking published procedures.

Decarboxylation of amino acids requires two things: heat and the right catalyst. Who knows what actually went into some of the published mxitures? Recall the Cooper's Blue accident.

Methyl.Magic - 10-10-2007 at 10:31

Quote:
Message original : Grimble_Gromble
Quote:
Originally posted by Methyl.Magic
Hey !!!

I refluxed 1g of T in a few ml of Acetophenone for 1 hour. Distilled the solvent off and get a >95% tryptamine freebase as cream colored solid. ;)



Did you distill off acetophenone in a reduced pressure environment?
Acetophenone has a bp of about 120-150�C, I�m not sure. My concern is to destroy the tryptamine with high temperatures.


haha !

tryptophan needs high temperature to be decarboxylated. More heat = faster decarboxylation ! I think less than min of acetophenone reflux is sufficiant !

You can evaporated the PhCOMe under vacuum but it isnt necessairy, you can evaporated acetophenone at normal pressure to get the liquid tryptamine.
Tryptamine can probably be precipited without difficulty by passing dry HCl into the solution to get Tryptamine hydrochloride. Be careful because in the presence of water, HCl destroy the T !

The tryptamine freebase can be crystalised from (perhaps) toluene.

antibody - 8-2-2011 at 09:34

You are right 2-Cyclohexen-1-one is a challenge to source. It isn't available locally and shipping it across a border means shipping costs which triple its cost . . . sigh

But cyclohexanone is readily available. Any opinions on whether this would work as well in cyclohexanol? It is also a ketone and there is only one double bond difference b/w the two. Based on this reference.

M. Hashimoto, A Novel Decarboxylation of alpha-Amino Acids, Chem. Lett., 893-896 (1986)

I was under the impression that it was a MAO that destroyed tryptamine in the body (perhaps mistakenly). I haven't been able to find any reference that says tryptamine is unstable in acidic conditions, other than possible ring closure when reacted with formaldehyde. In fact the only prohibitive condition I've seen is against oxidizers. Have I overlooked something?

Thanks in advance for any opinions/refs
Quote: Originally posted by Methyl.Magic  
Quote:
Message original : IPN
because tryptamine is destroyed in aqueous HCl (processus of destruction preasent in the human body). Indole (?) is formed, as far as I know...
I thing he dindn't use cyclohexanone but cyclohex-èn-one wich is harder to find that acetophenone.




[Edited on 8-2-2011 by antibody]

[Edited on 8-2-2011 by antibody]

turd - 8-2-2011 at 10:11

Carvone is a cyclohexenone. It can be sourced by vacuum distillation of spearmint oil (up to 60% carvone content!).

Cyclohexanol might not be the best solvent, see: https://www.sciencemadness.org/whisper/viewthread.php?tid=99...

I like the idea of using acetophenone.

[Edited on 8-2-2011 by turd]

madscientist - 8-2-2011 at 11:57

The use of a ketone catalyst will result in the formation of beta-carbolines (Pictet-Spengler), which are difficult to separate from tryptamines. They may or may not be potent neurotoxins, or toxic in other unforeseen ways, so be careful not to accidentally inhale any...

antibody - 8-2-2011 at 13:05

Quote: Originally posted by madscientist  
The use of a ketone catalyst will result in the formation of beta-carbolines (Pictet-Spengler), which are difficult to separate from tryptamines. They may or may not be potent neurotoxins, or toxic in other unforeseen ways, so be careful not to accidentally inhale any...


No kidding, I was under the impression that an acid catalyst of some sort would be necessary to effect a PS ring closure? I suppose Tryptoline would be the product that side reaction?

madscientist - 8-2-2011 at 13:15

Conditions don't have to be what we'd consider acidic in order for it to occur. I have a paper on this somewhere, I'll post it soon.

turd - 8-2-2011 at 13:27

Well, for starters you could check the paper I linked to upthread. It gives a few examples of beta-carboline side products obtained in ketone catalyzed decarboxylations. :)

antibody - 8-2-2011 at 14:02

Yes, Thanks for that Turd. I downloaded it earlier today but haven't had the time yet to delve into it yet. This evening . . . much appreciated!

madscientist - 8-2-2011 at 14:30

That's actually the same paper I was going to post! :o

ChemichaelRXN - 15-2-2011 at 08:45

I would assume methyl benzoate will work as the solvent for this reaction? (It has a high b.p. at 199.6C and also easy to make.)



madscientist - 15-2-2011 at 09:22

Esters react with amines to form amides - I would use a different solvent.

ctrlphreak - 9-3-2011 at 14:54

Glycol/Glycerine is an excellent solvent for the decarboxylation, and according to a paper I have analyzing the various solvents, and ketones, as is described all over the web, and noted the various Beta-carbolines formed from various procedures.

The interesting thing to note was that in every case, the L-Carverone I believe it was did NOT have the issue of converting the Tryptophan into a BETA-Carboline.

Glycerine has also been used alone to effect a decarboxylation thermally, but yeah, just saying.

jon - 11-3-2011 at 23:36

the reason carvenone and cylcohexenone don't cause cyclization is due to the steric bulkiness of the ketones.
a useful thing to consider are balwin's rules for cyclization when dealing with tryptamines.

http://en.wikipedia.org/wiki/Baldwin's_rules

Vogelzang - 12-3-2011 at 09:03

Here's two good articles about decarboxylation of amino acids.

Attachment: LaDecarbI.pdf (765kB)
This file has been downloaded 2737 times

Attachment: LaDecarbII.PDF (482kB)
This file has been downloaded 1818 times

12332123 - 12-4-2011 at 04:29

I have some success to report...

I refluxed 5g of tryptophan and 22g of naphthalene with 2ml of peppermint oil under a dry condensor with vigorous stirring till the reaction went clear (~1 hour). On cooling a dark amber glass was formed which was dissolved in around 300ml of DCM. The solution was filtered under gravity and then cooled in an ice bath. I then gassed it with CO2, giving a fine tan precipitate of Tryptamine carbonate which was filtered off and washed with several small portions of DCM. This was then warmed in around 200ml of anhydrous isopropanol and fumaric acid was added until no more fizzing was observed. Tryptamine fumarate was collected and washed with several small portions of isopropanol and DCM, giving a nearly white fine powder. Yield ~70%. :)

[Edited on 12-4-2011 by 12332123]

GreenD - 12-4-2011 at 06:37

WELL THERE YA GO!

Nicodem - 12-4-2011 at 09:05

Quote: Originally posted by 12332123  
...
I then gassed it with CO2, giving a fine tan precipitate of Tryptamine carbonate which was filtered off and washed with several small portions of DCM. This was then warmed in around 200ml of anhydrous isopropanol and fumaric acid was added until no more fizzing was observed. Tryptamine fumarate was collected and washed with several small portions of isopropanol and DCM, giving a nearly white fine powder. Yield ~70%. :)

Very interesting work up and good yields. And an original choice of solvent as well. Have you confirmed the product identity? The mp?

12332123 - 12-4-2011 at 09:40

I recently managed to break my thermometer so I unfortunately can't say for sure that its pure, but I'll try and
get a melting point ASAP. I thought I'd probably have problems with sublimation of the napthtalene, but this luckily turned out not to be a problem at all and the reaction went very cleanly; its a very nice OTC choice.

jon - 12-4-2011 at 09:52

i'd bet it would get even more intersting if you reacted it with isopropyl iodide in the prescence of hunig's base

GreenD - 13-4-2011 at 15:27

Interesting, Jon. I've never heard of the compound you refer too. Looks like it is worth investigating.


[Edited on 13-4-2011 by GreenD]

12332123 - 14-4-2011 at 09:19

Is my product more likely to be ditryptamine fumarate or monotryptamine fumarate?

GreenD - 14-4-2011 at 10:15

The french paper that vogal zang gives says that decarboxylation of phenylalanine (100% conversion) happens in acetophenone over 3 hours at 150°C (below reflux).

and decarboxylation of tryptophan (100%) happens in acetophenone at 130° C over 4 hours...

VERY INTERESTING.

12332123, I would assume you're going to have a mixture of both, depending on the equivalents you used... If you use less than 2 equivalents your majority is going to definitely be in the mono-region.

Why didn't you mix directly a fumaric solution. Why did you gas first?

12332123 - 14-4-2011 at 11:24

Fumaric acid is not very soluble in organic solvents, and a water soln would dissolve some of the product. Plus, I wanted to see if the patent floating around about tryptamine carbonates actually worked. Anyway, the issue of which salt I had is a little moot now, as I've made some nice white freebase crystals from it.

[Edited on 14-4-2011 by 12332123]

GreenD - 14-4-2011 at 16:24

Does that have a distinct smell ? :)

turd - 26-4-2011 at 13:06

Quote: Originally posted by 12332123  
I have some success to report...

Nice one!
I am quite happy with the workup by student (http://www.erowid.org/archive/rhodium/chemistry/tryptophan.h...). 25 % aq. NH4OH seems to be the wonder cure.

150 ml tetralin, 20 g tryptophan and 2 ml carvone, refluxed for 70 min. Cooled, filtered and tetralin removed under vacuum. Dissolved residue in 5% AcOH, washed with 20 ml CCl4 (bad choice, doesn't dissolve the solids), centrifuged off remaining solids and organic phase. Added NaHCO3 until only little foaming. Washed with 20 ml CCl4, centrifuged off remaining solids. Basified with small amount of 20% NaOH. Cooled, filtered and got a nasty sticky semi solid. Wased with 25 % ice cold NH4OH and first surprise - semi-solid crystallized. Second surprise - wonderful white crystals in the mother liquor! Filtered, dried over sicapent, got in total 9 g, overall purity propably not as good as distilled, but most of it excellent.

[Edited on 26-4-2011 by turd]

chemrox - 25-4-2012 at 15:57

Quote: Originally posted by Nicodem  
But first you will need to properly decarboxylate tryptophan. Xylene is too low boiling for the decarboxylation to finish in 9 hours.

I think so too. I'd love it if it worked. I priced some high boiling ethers and the cost of them made conversion from indole look pretty good in comparison.

rannyfash - 28-4-2012 at 08:15

well i came up with this idea http://www.sciencemadness.org/talk/viewthread.php?tid=19194#... if you replace the dimethylamine with ammonia in the final step.

but i guess you could extract enzymes produced from the yeast by macerating cells using dichloromethane/methanol and running a column chromatography on the resulting aqueous layer, testing the different separated enzymes (or a mix) to exclude the enzyme that converts the amine to an alcohol,

[Edited on 28-4-2012 by rannyfash]

GreenD - 29-4-2012 at 09:02

I attempted this decarboxylation and must say without ethyl acetate, the work up gave me <10% yields.

:\

Crowfjord - 7-5-2013 at 13:23

Hello all! I have been experimenting with this reaction for some time now, and I thought I would share the results of my latest, and so far most successful attempt.

Abstract: A facile synthesis of tryptamine may be conducted using everyday, easy to find materials; there is no need for such solvents as tetralin, diphenyl ether, acetophenone or others. Decarboxylation of tryptophan occurred in regular drugstore mineral oil with a spearmint oil catalyst, the reaction complete (cessation of effervescence) at about 45 minutes of heating at 225-230 degrees C. After workup, crude tryptamine (MP: 105-107 C) was isolated at 70% yield.

Experimental: To a 250 mL round bottom flask with egg-shaped stirbar was added 80 mL mineral oil (USP, contained ~0.1% mixed tocopherols according to MSDS), 7.58g L-tryptophan (USP grade) and 6 mL naphtha (Ronson lighter fluid)(*). the flask contents were swirled to form a cream-colored slurry, 0.75 mL of spearmint oil (Mountain Rose Herbs) was added and the flask swirled again to incorporate.
The flask was set up for reflux on an oil bath (condenser water ~14.5 *C) and heating began with medium-speed stirring. Some bubbling was observed when the bath temperature reached 209 degrees C - possible boiling of naphtha/catalyst.
Oil bath temperature was held between 225-230 degrees C for about 45 minutes(**), at which point the mixture became transparent and effervescence ceased. The solution was a golden color at this point. The flask was removed from the the oil bath and as it cooled, the solution quickly became a turbid/opaque peach color. The flask was held under running water until it reached about 30 degrees C.
The flask contents were poured into a 1000 mL separatory funnel, the flask rinsed with 100 mL 5% acetic acid (AcOH), then 50 mL ethyl acetate (EtAc, Kleen Strip MEK Substitute), then 2 X 25 mL EtAc to remove the thick red oil from the bottom of the flask. All was added to the separatory funnel and shaken together vigorously. Three layers formed - the lowermost (aqueous) layer was removed and the remaining upper two layer were extracted with4 X 30 mL 5% AcOH. 1 mL 99% AcOH and 2 mL distilled water (d. H2O) were added, shaken, separated and pooled with the rest of the aqueous extracts.
The acidic (pH = ~4) aqueous extracts were pooled and washed with 3 X 30 mL EtAc, then chilled about 15 minutes in the freezer. The chilled extract was basified with 25% NaOH (persistent cloudiness was noted at ~pH 10) to ~pH 11 and extracted with 30 mL EtAc. 3 mL 25% NaOH were added to the aq. extract to precipitate more (suspected) tryptamine, extracted again with 30 mL EtAc. This was repeated with 4 mL 25% NaOH and 30 mL EtAc. EtAc extracts were pooled and stored in the freezer for 7 days.

The golden EtAc solution was extracted with 4 X 30 mL 5% AcOH. To this aqueous solution was added 25% NaOH until it was about pH 13 (low resolution on indicator papers). An amber colored oil separated and sank top the bottom of the flask. This was removed for further inspection, and placed in the freezer. A small amount of oil remained suspended in the clear aqueous solution.

At this point I was vexed; I had expected a solid precipitate as before, but the previous solutions had not been treated with ethyl acetate as this had. It seemed that maybe some N-actyl trypamine had formed and made a mixture, causing the tryptamine to oil out. And then - a happy accident. Just to see what would happen, I added 1 mL of 25% NaOH to the remaining aqueous solution, which immediately became turbid. The suspended oil droplets coalesced and then solidified to waxy yellow globs. The previously separated oil, which had been sitting in the freezer had formed some light yellow crystals among the amber oil. The entirety of this was added back to the solution with swirling, and the remaining oil NaOH solution (about 15 mL) was added 1 mL at a time with swirling.
The rest of the oil solidified, and more white, waxy, shimmering solid crystals precipitated. The solids were vacuum filtered on a Buchner funnel and dried over NaOH. Crude yield: 4.17 g of pale yellow crystals, 70%. MP: 105-108 degrees C. (Lit. 113-116 C)

The product seems to be tryptamine, albeit still slightly contaminated by oxidation products, and possibly N-acetyl tryptamine, from the slightly depressed melting point. It shall have to be recrystallized. Does anyone have any suggestions? I was thinking of using ethyl acetate/pentane but am worried about amide formation. I also read that heptane works, but currently do not have any.

Any and all questions and/or comments are welcome. Thanks!

* Naphtha was added in an attempt to provide an inert atmosphere
**It should also be noted that mineral oil boils at a much higher temperature than 250 degrees C (as high as my thermometer reads) so careful monitoring and adjustment of the temperature is necessary.

[Edited on 7-5-2013 by Crowfjord]

[Edited on 7-5-2013 by Crowfjord]

turd - 14-5-2013 at 10:55

Cool. It's always nice to read about tryptamine chemistry.

If you write AcOH for acetic acid, then ethylacetate is AcOEt. Accordingly, AcEt is MEK.

I doubt that AcOEt is a good solvent for extracting highly basic NaOH solutions. It reacts according to AcOEt + NaOH --> NaOAc + EtOH! :o

As for recrystallization - I believe(!) both toluene and aliphatic hydrocarbons work. But be very careful and patient.

[Edited on 14-5-2013 by turd]

Crowfjord - 14-5-2013 at 12:36

@Turd: thanks for the tip. You are of course right about the basic cleavage of ethyl acetate (and other esters). I considered using methyl ethyl ketone or methyl isobutyl ketone for that reason, but the store did not have it. I believe though that the cleavage of ethyl acetate is slow enough at the temperatures I worked at (20-25 degrees C) to not be of much consequence to the goal. It worked quite well.

As for recrystallization, maybe I will try a small variety of solvents, and see what works best.

Also, for the sake of thoroughness, I should mention, since I forgot to in my previous post, that I washed the filter cake with extra strength household ammonia prior to drying.

Recrystalization

hive3 - 3-7-2013 at 09:29

I have used boiling Heptane and it works very well. It requires a lot of patience though, I only seem to get about 50mg per 25ml pull. It will really clean up the product though as it only seems to absorb the tryptamine, not the colored gunk. Be sure to run a reflux condenser while boiling, and no open flame of course.

Success with Crowfjord's mineral oil conversion

hive3 - 17-7-2013 at 11:56

I was very excited to also see beautiful Tryptamine crystals forming from the oil 24 hours later.

Experimental: To a 250 mL round bottom flask with egg-shaped stirbar was added 80 mL mineral oil 7.58g L-tryptophan (USP grade) . The flask contents were swirled to form a cream-colored slurry, 0.75 mL of Spearmint oil was added and the flask swirled again to incorporate.

Flask was capped with a 1-2 neck converter with a thermometer placed in the neck over the flask so the solution temperature could be monitored. A vacuum take off condenser elbow was added to the second neck and stoppered. The the vacuum adaptor attached to a trap and then the trap attached to a bubbler. The glassware was flushed with nitrogen instead of using naphtha to create an oxygen barrier.

The solution was slowly brought up to 225C in a mineral oil bath. The oil bath smoked mildly during the process. As the temperature came up to 200C no bubbling was noted. Earlier carvone had been distilled off this spearmint oil and it appeared there was less than 10% carvone in the oil. To compensate, 10 drops of pure carvone was added from the earlier distillation and bubbling commenced almost immediately. As the reaction heated up bubbles appeared at approximately a 1 to 2 second interval and the reaction proceeded to completion in approximately 1 hour as indicated by the solution turning a clear amber and bubbling stopped.

A deep amber oil appeared at the buttom of the flask. The solution was left for 24 hours at 30C and upon examination white crystals appeared at the bottom of the flask growing among the very viscous amber oil.

Thanks Crowfjord for this great OTC conversion. It was much cleaner, faster and less odorous than the turpentine process.


[Edited on 17-7-2013 by hive3]

[Edited on 17-7-2013 by hive3]

[Edited on 17-7-2013 by hive3]

megalodon - 26-7-2013 at 11:16

I would also like to thank Crowfjord for a much more pleasant decarboxylation technique :)

A bit of internet history: What appear to be the original Student's postings to the Hive.

http://y47ylcppnh3afqk4.onion/the-hive.ws/tryptamine/0002716...
http://y47ylcppnh3afqk4.onion/the-hive.ws/tryptamine/0002843...

Note that these are .onion pages and will require Tor or similar to access. (Don't know of any other complete Hive archives, sorry!)

solo - 26-7-2013 at 13:10

Reference Information





One-pot Sequence for the Decarboxylation of a-Amino Acids
Laval, Bernard T. Golding
Synlett
2003, No. 4, Print: 12 03 2003.



Uploaded with ImageShack.us

Abstract
Treatment of an ?-amino acid with N-bromosuccinimide
in water at pH 5 or in an alcoholic-aqueous ammonium chloride
mixture, followed by addition of nickel(II) chloride and sodium
borohydride, effected an overall decarboxylation via an intermediate
nitrile to afford the corresponding amine in good yield.


[Edited on 26-7-2013 by solo]

Attachment: one pot sequence for the decarboxylation of alpha amino acids.pdf (66kB)
This file has been downloaded 1238 times

Purification of Tryptamine from Crowfjord’s process

hive3 - 25-8-2013 at 15:54

The mineral oil and participated crystals and orange oil were heated to 80C, washed 3 times with 50ml 5% acidic acid in a separation flask and the washes combined. Ph was brought up using 25% NaOH. As I added the NaOH a white participate appeared and then went back into solution. At PH7.0-7.5 orange gunk crashed out of solution. I have no idea what it was but I vacuum filtered through fast paper and was left with a cloudy solution and a orange gunk in the filter paper. I continued adding NaOH until the PH reached 12 and then put in the freezer for ½ hour. Pure white fine crystals crashed out along with what appeared to be the same crystals in yellow orange oil. The solution was vacuum filtered again through fast paper and washed twice with 10% Ammonia at -10C. The filter paper with the filtrate was placed in a damp rid container filled with Nitrogen and allowed to dry for 1 day.

The dry filtrate was weighed at 3.34g. 1g of the filtrate was placed in 25ml of boiling heptane in a 125 ml flask with a condenser set up for reflux. Orange oil separated and fell to the bottom of the flask. White crystals formed around the boil line. The boiling heptane was transferred to a 50ml round bottom flask and white crystals immediately started to fall out. The orange oil remained in the original flask sticking to the bottom and sides. The 50ml flask containing clear heptane and no oil by products was placed in 60C water bath and roto vaped under vacuum. Final product weighed .353 g as a white sticky powder with a strong Tryptamine smell that clung to the flask. None of the tallow/orange tinting remained.

The product was left in the flask, and stored in a freezer at -10C under vacuum. Previous runs turn orange and then brown in days when stored in an oxygen environment. The conversion rate of 18% is bothersome given documented conversions of over 60% in literature.

[Edited on 26-8-2013 by hive3]

Crowfjord - 25-8-2013 at 16:36

Nice. It's good to see some practical reports on purification. I've been meaning to try some things along those lines as well, but have been too busy or tired from work to do much tinkering lately. I need to get some more melting point capillaries, too.

The visual observations are encouraging, but did you take a melting point or TLC or something to get an idea of the purity?

Also, I bet you can increase yield by doing another recrystalliztion on the orange leftover gunk.

megalodon - 25-8-2013 at 17:23

I am away from my notebook so you will have to forgive a bit of generalization and vagueness. I'll fill in any missing details later.

I generally have had good success with a modified version of Student's workup. My procedure is as follows:

1) Refrigerate the reaction vessel to solidify the dark oil which forms.
2) Pour off the mineral oil. I have never expected it to contain much product; perhaps I'm wrong?
3) Extract with 2x75 mL boiling 5% acetic acid, while heating and stirring the mixture to soften and mix the dark oil. A cloudy lemonade-yellow liquid results. This is filtered into a sep funnel. I do this in batches due to the size of my sep funnel.
4) The vinegar is extracted with a few mL chloroform. The aqueous layer is poured into a beaker and the organic layer discarded.
5) A few mL chloroform are added. With stirring, sodium bicarbonate is added by the knifetip until only mild fizzing results and the pH is 7-8. Quite a bit of nasty garbage comes out at this point, forming a sticky, hard-to-remove residue which seems to absorb the chloroform.
6) The liquid is filtered into a sep funnel and any remaining chloroform removed. The aqueous layer is poured into an Erlenmeyer flask.
7) 2 grams sodium hydroxide are dissolved in a bit of water and added. This solution is added to the flask. Immediately, the solution turns a milky white. The solution is refrigerated overnight.
8) Some combination of crystals and precipitate result. The mixture is vacuum filtered.

The product is generally some shade of tan. I haven't taken an mp yet (my thermometer doesn't go high enough) but TLC shows it to be pretty clean. I have had good results with recrystallization from boiling hexane if you desire a lily-white product.

Megalodon’s purification process

hive3 - 26-8-2013 at 04:19

Thanks for the pointers. I will definitely try the boiling acidic acid extraction in the future.

Have you computed your yields from hexane? My frustration with both the turpentine and mineral oil processes is that I have not been able to produce the tryptamine with more than a 20% conversion rate from tryptophan. (Tryptamine mw 160, Tryptophan 204 Theroretical yield = .78 of starting material. I started with 7.5g of Tryptophan so theroretical yield should be 5.85g of Tryptamine. Based on my extractions to this point, I project 3.34*.353 = 1.17g or 1.17/5.85 = 20 % yield) . From my tests:

The initial acidic acid extraction leaves behind a very dark solid oil. It still smells of Tryptamine but if there is Tryptamine left in it, subsequent extractions don’t pull anything out of it. I have saved this material by dissolving it in EtOac, and I will TLC it .
Additional gunk drops out of the extraction when brought to a PH of 7. This is a significant amount of material but I have not weighed it, or saved it.

Using Chloroform extractions to purify at the extract at this point just seems to dissolve the gunk and allow it to be separated without filtering. It has not affected my final yield in the past and since I don’t have a lot of chloroform I prefer to use filter paper.

During the heptane extraction a thick dark oil that clings to the sides of the beaker is left behind, generally 60 to 70 percent of the starting material is left behind during this step. It is similar to the material left behind during the acidic acid extraction and still smells strongly of Tryptamine.

Tryptamine seems to be very reactive with O2. Almost white Tryptamine recrystallized from heptane quickly yellows when the heptane is poured off and left to evaporate in the atmosphere. This is why I am now evaping the heptane under vacuum .I have a .25g sample that I saved from my last run that is about a month old and has turned a dark brown/grey. It was kept in a sealed 10 ml. bottle. This stuff is very unstable.

I will do a MP test tonight and let you know the results.


[Edited on 26-8-2013 by hive3]

MP's

hive3 - 26-8-2013 at 17:23

Tryptamine Melting Points


I did the MPs tonight.

MP of Filtered Tryptamine after Ammonia wash 101-105C
MP of heptane recrystallized Tryptamine 114-115 (published 113C to 116C)

I will confess that my technique was not the best, the oil bath was increasing at probably 30 seconds per degree, but I pulled it off the burner and it topped out at 115C on the second test and by that time all of the tryptamine melted at that temp.

For the first test please note that there were 2 distinct layers of the tryptamine in that sample. Some was just off white and the other the yellow slightly oily stuff. The white melted at 105C and the yellow at 101C

[Edited on 27-8-2013 by hive3]

megalodon - 28-8-2013 at 15:48

I typically get yields ~85-90% (eg, 4.5g tryptamine from 6.8 g tryptophan).

I've found that the scum that drops out upon basification seems to dissolve well in isopropyl alcohol.

Crowfjord - 3-9-2013 at 23:49

I finally got around to trying a few things to purify my tryptamine that has been busily oxidizing since I made it nearly four months ago. The pale yellow powder/chunks had since turned an orange-brown color, similar to rust. I tried recrystallizing from n-pentane, but tryptamine is very sparingly to completely not soluble in it.

Boiling in ethyl acetate (EtOAc) and triturating with pentane gave a foggy solution, but no crystals. So, I went about doing an acid/base purification, very similar to the one that I posted up thread.

1.0 g crude tryptamine was dissolved in about 20 mL EtOAc and 10 mL n-pentane, then extracted with 30 mL then 10 mL 5% acetic acid (made with 99% acetic acid and distilled water). The aqueous layer was extracted twice with a mixture of 30 mL EtOAc and 2 mL pentane*. The aqueous layer at this point was a tiny bit turbid and just ever-so-slightly yellow. It was slowly and carefully basified with 25% NaOH solution with stirring, just until cloudiness persisted. The container with the solution/suspension was capped and placed in the freezer for about 15-20 minutes. I was pleasantly surprised when I was greeted with a suspension of shimmering crystals! These were vacuum filtered, washed with ice-cold ammonia and dried over NaOH to give 0.90 g of waxy, nearly colorless crystals.

Unfortunately I am out of melting point capillaries, so no analysis until I get more in a week or two. Here's a picture, though. :D



photo (598x800).jpg - 305kB

hive3 - 4-9-2013 at 12:24

Very nice result and an excellent yield from recrystallization. Did you record the PH before recrystallation?

I have extracted again the remainder of the 1g of unpurified tryptamine using a second heptane extraction and sure enough I have more pure tryptamine. The problem for me seems to be not using enough heptane and of course not checking the solubility.

[Edited on 4-9-2013 by hive3]

Crowfjord - 4-9-2013 at 15:25

I did not check the pH, but in retrospect I should have. When I get the time I will do another run and take detailed notes. I'm really hopeful that I can make a good reproducible method.

Mythrilium - 15-10-2013 at 07:54

I often tried this with tetralin and MEK / acetone and would like to share my experiences:

All in all I never reached a yield (purified tryptamine) higher than 40%

Stripping off tetralin (or other high boiling solvent) under vaccuum always ended up with a sticky oil, which wouldn't crystallize but can be easily recrystallized from acetone in freezer, but will remain still very impure.
Further recrystallisation from hexan/heptan/petroleum is possible but needs huge amount of solvent.

Using aqueous HCl to extract the amine never led to a product, but often formed sticky mess which evolved ammonia-steam when basified.

Best way to purify the crude tryptamin was found to be percipitation of the (di-?)carbonate, simply by bubbling CO2 through a diffusor. Leads to very light yellow/white powder. Works bad from acetone, great from DCM, maybe works also directly from Cyclohexanol/Acetophenone ?!
The vaccuum filtered carbonate is then dissolved in water and brought up to about 50-60°C. Brown impuritys start to float on the surface and will stick to the walls (they can be easily extracted by a mix of EtOAc and hexan). Now aqueous NaOH is added (PH > 11) and cream-white snowflakes of pure tryptamine start to form in the aqueous solution. Let it sit for 2-3 hours in the fridge (about 5-7°C), then it can be filtered off and eventually dried on common ways.

hive3 - 15-10-2013 at 11:54

Is the 40% yield from the carbonate process? I have used the boiling heptane method and it is a time consuming process as the product of the decarbolization is in a very viscous oil even in the boiling heptane. I usually do repeated extractions and the oil gets more and more viscous. After 3 extractions I still only get about a 35% yield after crystallation and evaporation of the heptane, although very pure. Your process looks significantly faster.

Mythrilium - 15-10-2013 at 14:57

Yeah, 40% from the carbonate process
(probably limited by impure tetralin + tryptophan)

The process was my best try to be fast, whole reaction + workup done in <8h.
Heptane pulls are very time consuming, I know that experience...
(might be worth it for alkylated T) :cool:


Has anybody tried pure acetophenone for reflux?

bahamuth - 16-10-2013 at 06:28

I tried synthesis grade acetophenone a few years ago, but had great troubles recovering the tryptamine, due to not knowing an efficient extraction method and a very busy schedule so it was abandoned. Only thing I remembered was the speed and apparent total conversion in a short time.

Was actually planning a trial tomorrow and will take some pics and post my notes.

I Like Dots - 18-10-2013 at 07:37

Could you extract the tryptamine from the acetophenone with a dilute hcl solution? Maybe not because the acetophenone is slightly soluble in water.. Trying to distill the acetophenone would not be favorable either. it looks like the tryptamine might come over first!The CO2 sounds promising.

Alyosha Karamazov - 19-10-2013 at 01:18

As said here before, it's safer to use dilute acetic acid solutions instead of HCl with tryptamine for extraction. Acetophenone has a 100% conversion (search the board, the original french ref was posted too), but the literature did not provide details on the isolation of the target amine. Several problems have been encountered during several different workup approaches. Transamination was one, also the intermediate imine is said to be very stable with acetophenone.

The best results I have had is what most people seem to do now, extracting the post-decarboxylation solution multiple times with white vinegar, neutralizing with NaHCO3 until pH 7, filter off small amount of precipitate, wash with ethyl acetate or dichloromethane, and basify with ammonia or dilute NaOH.

The result is however very unreliable, sometimes an acceptable yield is obtained, more often the isolated amount is rather low. The product is also waxy and hard to handle, the initial white precipitate becomes yellow and oily within minutes.

After repeated recrystallisation attempts from hexane (which uses way too much solvent) my product will always turn yellow and resinous very quickly. But a TLC run against a commercial tryptamine sample always shows a single spot where it should be.

Passing CO2 through the post-reaction black acetophenone solution makes it cloudy but nothing seems to precipitate. Or it is so fine it goes right through filter paper. When I try making the carbonate salt of the isolated tryptamine, it also precipitates as a yellow sticky resin that is too frustrating too handle.

I think that the best option would be short-path distillation. But I wonder if my refrigerator compressor vac pump (around 20 mmHg) is enough for that job? Although sublimation is a valid option for purifying small amounts (up to a gram or so).

Flash chromatography was used in the copper chelate decarboxylation procedure:
Quote:
After distillation of the solvent, the resultant residue was purified by flash chromatography on silica gel to give tryptamine

The resultant residue from that route is an unfathomable black tarry mess, so it might hold some value. Flash chromatography could be done using a large 100ml (kitchen-type) plastic syringe packed half-way with silica gel and the solvent (chloroform?) pushed through in a crude mcgyver version.

This page has good information on how to screen the solvent combination using a TLC batch for flash chromatography:
http://www.reachdevices.com/SetUpColumn.html

[Edited on 19-10-2013 by Alyosha Karamazov]

[Edited on 19-10-2013 by Alyosha Karamazov]

Alyosha Karamazov - 19-10-2013 at 01:26

The oil that precipitates from the mineral oil in this procedure, it is probably largely tryptamine. I hope to hear the TLC result soon. Why not try short-path destillation directly from there and skip the acid/base extraction?

hive3 - 21-10-2013 at 08:09

I have not tried a distillation. Others who have tried using standard short path distillations seem to have issues with clogging of the head during the process. It seems short path ball to ball distillation would work best, but I don't have the equipment. Anyone try this with a Kugelrohr? I suspect this would be the quickest (but most expensive) workup method.

I have run a TLC on heptane extracted Tryptamine from the mineral oil process. One Dot, but I don't have a reference. After Crystallization, I did pour off the Heptane and then rotovaped under vacuum to get the final product. This prevented oxidation leaving me with an almost pure white crystals. I have it stored in a freezer under nitrogen and it has stayed white.

This product works perfectly in followup reactions.

[Edited on 21-10-2013 by hive3]

stoichiometric_steve - 21-10-2013 at 08:32

i have successfully distilled it, not using short path but with a regular Liebig condenser filled with hot water. it is a laborious process, since the head does indeed get clogged from time to time, but heating it with a heat gun takes good care of this.

and this is what it looked like afterwards:

index.jpeg - 114kB

hive3 - 21-10-2013 at 08:38

Absolutely beautiful!!!!!

palico - 21-10-2013 at 13:23

Ok, you are ready for the next step.

Mythrilium - 21-10-2013 at 14:47

What kind of heat-source would you recommend for short path distillation?
And how did you get rid of the solvent? Freezing out or also distillation?
What was the overall yield?

I'm still looking for an easy way, as i haven't tried CO2 through cyclohexanol/acetophenon yet, and want to be sure which solvent to look for.

@ Alyosha Karamazov: How long did you pass CO2 through the reaction mixture, and at which temperature was it? Tryptamincarbonate seems to be soluable in alochols and ketones, but not at low temperatures (liquid CO2 and crystalisation should cool the reaction mixture well beyond 0°C) I used to proceed CO2 bubbling for about 40-50 minutes on 600ml of Solvent (DCM) which yielded (as said before) about 35-40%

Alyosha Karamazov - 23-10-2013 at 04:26

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 - 23-10-2013 at 10:45

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 - 2-1-2014 at 20:05

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 - 3-1-2014 at 06:17

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 - 3-1-2014 at 08:36

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 - 3-1-2014 at 08:47

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 - 3-1-2014 at 16:36

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 - 4-1-2014 at 03:08

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.

*FWOOSH* - 23-1-2014 at 06:32

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 - 29-1-2014 at 15:31

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.
Please help !

Crowfjord - 29-1-2014 at 17:37

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 - 30-1-2014 at 10:11

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 - 30-1-2014 at 11:50

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 - 31-1-2014 at 11:26

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 - 4-2-2014 at 14:06

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 - 4-2-2014 at 16:40

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 - 5-2-2014 at 07:27

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 - 5-2-2014 at 10:25

Thank you lullu but I don't understand german.

Bot0nist - 5-2-2014 at 10:59

An online translater will get you pretty far.

palico - 9-2-2014 at 14:23

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 - 22-3-2014 at 14:39

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 - 23-3-2014 at 15:45

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* - 2-4-2014 at 00:02

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:
http://about.mdma.ch/000507814.html

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.:D

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 :D.
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*]

Troubles

Arsole - 5-9-2014 at 22:34

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?

Rabodon - 17-9-2014 at 17:12

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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