L-tryptophan decarboxylation

Decarboxylation of L-Tryptophan in DMF

Quote: Originally posted by HollowMan

Hi, i wanted to ask, if anyone tried this interesting decarboxylation method of tryptophan.

Quote: Originally posted by HollowMan

Of course DMF is no keton but it has the same functional group. Thas what i meant.

Quote: Originally posted by HollowMan

I already read some posts but I didn´t got something what works for sure. lets talk about this one you definitely know: http://www.sciencemadness.org/talk/viewthread.php?tid=31306

1.Did you use just paraffin oil or mixed with DMSO like in hyperlab? They mixed xylene with DMSO and turpentine/DMSO.
2. Did you heat up till boiling?
3. How about your yield?

Thanks for sharing your experience

Quote: Originally posted by HollowMan

Thanks for your extensively reply. At first I thought, this procedure should be the easiest I will ever do, but now it seems pretty tricky.

Acetophenone

Acetophenome Decarb Procedure

Quote: Originally posted by hive3

4:40 distillation head temp reads 95C and Acetophenome and a nonmisicable fluid come over.

Acetophenome Workup

Quote: Originally posted by Quatro

I don't have a Rotovap but that would be a neat piece of equipment to own!

I ordered 100 mL of 2-cyclohexenone from MP (pm me for full name -- it's a perfectly fine lab chemical supply site, kind of like an alibaba for chemical suppliers, I just don't want this route shut down). I would be willing to sell some of the catalyst in smaller batches after it arrives later today

My main issue with decarboxylation is solubility. For example, I have been able to source some carbidopa from an Indian pharmacy. As you can see, if you methylenate it (per Rhodium) with dichloromethane, tetrabutylammonium bromide PTC catalyst (I should have bought the iodide, but w/e) and sodium iodide catalyst (http://onlinelibrary.wiley.com/doi/10.1002/jccs.199100038/ab... -- I have the full text on how this enhances the reactivity of alkyl halides in PTCs), then decarboxylate it in cyclohexanol I should be able to get a certain entactogenic product.

My problem is that carbidopa, as well as its derivatives that are also amino acids, is weakly soluble in water and even less soluble in DCM. So it's hard to do a typical acid-base extraction. If I run a PTC as per Rhodium's article "the methylenation of catechol" and end up with methylenated carbidopa, I still have to worry about the zwitterionic nature of the intermediate. One patent suggests I could use extract amino acids with a ~1M PTC catalyst (like Aliquat 336, but I have TBAB) in an organic layer to exchange with a monoanionic form of the amino acid. NaBr / NaI would get left behind in the aqueous phase and/or precipitate in the organic phase, while a lipophilic dimer of tetrabutylammonium [amino acid anion] would get extracted into an organic layer. I could then back-extract into acidic water?

[Edited on 16-1-2016 by yanzi]

Quote: Originally posted by yanzi

I ordered 100 mL of 2-cyclohexenone from MP (pm me for full name -- it's a perfectly fine lab chemical supply site, kind of like an alibaba for chemical suppliers, I just don't want this route shut down). I would be willing to sell some of the catalyst in smaller batches after it arrives later today My main issue with decarboxylation is solubility. For example, I have been able to source some carbidopa from an Indian pharmacy. As you can see, if you methylenate it (per Rhodium) with dichloromethane, tetrabutylammonium bromide PTC catalyst (I should have bought the iodide, but w/e) and sodium iodide catalyst (http://onlinelibrary.wiley.com/doi/10.1002/jccs.199100038/ab... -- I have the full text on how this enhances the reactivity of alkyl halides in PTCs), then decarboxylate it in cyclohexanol I should be able to get a certain entactogenic product. My problem is that carbidopa, as well as its derivatives that are also amino acids, is weakly soluble in water and even less soluble in DCM. So it's hard to do a typical acid-base extraction. If I run a PTC as per Rhodium's article "the methylenation of catechol" and end up with methylenated carbidopa, I still have to worry about the zwitterionic nature of the intermediate. One patent suggests I could use extract amino acids with a ~1M PTC catalyst (like Aliquat 336, but I have TBAB) in an organic layer to exchange with a monoanionic form of the amino acid. NaBr / NaI would get left behind in the aqueous phase and/or precipitate in the organic phase, while a lipophilic dimer of tetrabutylammonium [amino acid anion] would get extracted into an organic layer. I could then back-extract into acidic water? [Edited on 16-1-2016 by yanzi]

Quote: Originally posted by FormicAcidAnimal

Quote: Originally posted by yanzi   I ordered 100 mL of 2-cyclohexenone from MP (pm me for full name -- it's a perfectly fine lab chemical supply site, kind of like an alibaba for chemical suppliers, I just don't want this route shut down). I would be willing to sell some of the catalyst in smaller batches after it arrives later today My main issue with decarboxylation is solubility. For example, I have been able to source some carbidopa from an Indian pharmacy. As you can see, if you methylenate it (per Rhodium) with dichloromethane, tetrabutylammonium bromide PTC catalyst (I should have bought the iodide, but w/e) and sodium iodide catalyst (http://onlinelibrary.wiley.com/doi/10.1002/jccs.199100038/ab... -- I have the full text on how this enhances the reactivity of alkyl halides in PTCs), then decarboxylate it in cyclohexanol I should be able to get a certain entactogenic product. My problem is that carbidopa, as well as its derivatives that are also amino acids, is weakly soluble in water and even less soluble in DCM. So it's hard to do a typical acid-base extraction. If I run a PTC as per Rhodium's article "the methylenation of catechol" and end up with methylenated carbidopa, I still have to worry about the zwitterionic nature of the intermediate. One patent suggests I could use extract amino acids with a ~1M PTC catalyst (like Aliquat 336, but I have TBAB) in an organic layer to exchange with a monoanionic form of the amino acid. NaBr / NaI would get left behind in the aqueous phase and/or precipitate in the organic phase, while a lipophilic dimer of tetrabutylammonium [amino acid anion] would get extracted into an organic layer. I could then back-extract into acidic water? [Edited on 16-1-2016 by yanzi] I would try to make diiodomethane first from DCM and use it as solvent (bp 181°C - should dissolve it much better and also highly increase reaction rates) or making water solouble phosphate salt from it or simply use DMF as solvent . - btw. how you do you plan to get rid of the -NH2-Group of Carbidopa?

Quote: Originally posted by clearly_not_atara

CH2I2 only reacts with the strongest nucleophiles; if you read Bonthrone and Cornforth's seminal 1964 article on methylenation it explains that the methylene halides will only react readily with the catecholate dianion (not the monoanion). Amine alkylation won' t be an issue but you may have some difficulty stabilizing the trianion (since COOH is also deprotonated) in aqueous media. You could (I think?) use NaOEt/EtOH and you won't need any PTC, but there is a side reaction creating diethoxymethane (an interesting compound, but not the goal). [Edited on 24-1-2016 by clearly_not_atara]

How do you guys prevent everything from stinking of feces?

Quote: Originally posted by Crowfjord

There will always be some smell, but if the reaction is run with proper catalyst and kept at a reasonable temperature (below ~230 C or so) the stinky byproducts should be reduced to a manageable level. Also make sure to let the mixture cool to ambient temperature or below before disassembling the setup.

Hello,

I wanted to report my results so far of decarboxylation in mineral oil and ask some advice on workup. I like detail, so sorry:

rxn:

10 g of tryptophan powder was added to 105 mL of light (fischer) mineral oil and 5 mL (R) carvone in a 250 mL round bottom flask with a metal stir bar and heated with a fiberglass insulated mantle. A claisen adapter was fitted to the flask and a thermometer placed in the center of the oil. In the other neck a nitrogen line was added and the flask flushed before heating; this was haphazardly done and some oxygen probably got through.

As the temperature increased to 90c the oil was a frothy cream color. At 135 condensation of some sort was seen on the upper layer of the flask (not hot enough to burn). At 170 the flask got slightly darker. At 200, it was noted that the tryptophan was still present, and the mixture was still foaming. It took ~30 minutes to get to this point, and the temperature was held for another 30 minutes, never rising above 205. During this time, the tryptophan disappeared and the mixture got darker. The heat was stopped after the tryptophan was consumed and the flask turned a deep red. After cooling, the flask turned back to a cream color.

a/b extraction:

After cooling in the fridge, a dark oil settled at the bottom of the flask. the mineral oil above it was tossed and dark oil mixed with a final volume of 100 mL of 5% boiling acetic acid and filtered into sep funnel. The aqueous layer was like orange juice, and the black goop was extracted in batches until further addition of acetic acid resulted in a clear aqueous layer.

5 mL chloroform was added and shaked resulting in a clear organic layer with black goop at the boundary between it and the aqueous layer. Organic layer was tossed and repeated with 2 ml chloroform.

5 mL more chloroform added to aq layer and sodium bicarbonate added until pH was 8 and fizzing was mild. **Only a little bit of stuff crashed out at this point.** When removed via sep funnel, the chloroform was black. Further washing with chloroform was less black.

2.5g of naoh was dissolved in 10 mL DI water and added resulting in a final ph of 12. The solution turned milky white and and brown stuff came out of solution. This is probably the goop that was supposed to come out with the bicarbonate.

after:

After chilling in the fridge for a few days, many white fog-like crystals formed above the brown gunk, and was filtered via buchner by simple pouring (gunk stuck to bottom as cake, soluble in acetone) and washed with cold naoh. These crystals looked white-tan until being squished with filter paper to aid dryness by me, where they became a yucky tan-brown.

MP was done on some nice looking white crystals (closeup picture attached). Some melting at 103c, a little bit of melting 103-120, and then some brown goop stayed solid.

So I now have some gross looking mash that is drying, and a bunch of pieces of filter paper that may have absorbed tryptamine via crystals or oil and I do not wish to throw away. Where to proceed from here? I have many solvents available, so I was thinking re crystallization, but I also wanted to try sublimation since it is a fun technique.

-ChemGirl














[Edited on 23-1-2017 by chemgirl]

Quote: Originally posted by Misanthropy

AFAIK, tryptamine is available without restrictions in the USA.

Quote: Originally posted by Racconized

Quote: Originally posted by Misanthropy   AFAIK, tryptamine is available without restrictions in the USA. Doubt it since (I assume) that it could easily be methylated at the amine probably with alkyl halides or some formaldehyde reaction (I recall seeing some amine methylation employing formaldehyde but I can't remember the exact procedure) Also this thread is really old, who bumped Edit: http://orgsyn.org/demo.aspx?prep=CV3P0723 I don't know if I should post it tbh but it's chemistry afterall [Edited on 26-1-2017 by Racconized]

Quote: Originally posted by alking

0.55g from 10g tryptophan is pretty abysmal.

Quote: Originally posted by alking

I've done this a few times in the past, normally I get a 50%+ yield, generally higher. I've also tried flushing the system with argon (rather haphazardly, was not totally inert) and putting an air lock on it (a step I see you omitted). With the airlock/inert atmosphere it nearly eliminated the red oil and I even had crystals forming (within the oil mind you) in the flask after the reaction cooled.

Quote: Originally posted by Corrosive Joeseph

And this thread is about L-tryptophan decarboxylation, not the methylation of tryptamine.

Quote: Originally posted by Crowfjord

advice! As for methylation, see this thread and the paper that I will post there shortly.

Thanks for the advice, I think I will try this again with more tryptophan and less carvone. And fantastic find. Have you tried it?

[Edited on 29-1-2017 by chemgirl]





[Edited on 29-1-2017 by chemgirl]

Quote: Originally posted by 12332123

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]

TA purification via oxalate

Here are my experiences about tryptophan decarboxylation and purification via oxalate

1) Decarboxylation: 40 g tryptophan (99+) + 240 mL turpentine oil + 8 mL MEK + 40 droplets of carvone. 2 x 12 hours under reflux. Color was dark-brown-red.
Used AB purification: content after decarboxylation was extracted in 60-80 mL parts by 10% HAc (at 80C), total amount HAc was 400 mL. Juicy extract was filtered.
100 mL part of HAc extract was extracted by CHCl3 (3 x 15 mL), bottom part was dark brown, almost black, which was poured out.
100 mL purified solution was cooled to 0 C and mixed with ~ 15 mL of 50% NaOH (0 C) to pH about 12. Tryptamine base (TA) precipitated and created bottom layer, put to freezer (-20C)
and after 1 hour, it started to crystallize. When all TA was solid, content was crumbled by knife, cleaned by cool water, 5% solution of NH4OH to remove rest of NaOH, filtrated and dried above silikagel.
From 40g of tryptophan was prepared 16.4 g raw tryptamine.

Purity of tryptamine varied. In first case (before), when I worked with 10g of tryptophan (250 ml flask), I obtained purity about 93% with yield 47-53%. In this case above (4000 mL flask), purity was much worse, about 82%. I just guess, I boiled tryptophan too long and burned it. Following purification was performed with this 82% tryptamine.

2) Purification of tryptamine - recrystallization
First, I tried to recrystallize from acetonitrile. Solution was dark-red-brown, used carcoal but color was still quite dark. Cooled to -20C, used small TA crystal to start. From 1g TA obtained
just 0.1 purified. That was small yield, but purpose was to obtain TA (to be assured that I have pure TA for next tests). Purity was 97.2 % by GC-MS.

3) Purification of tryptamine via oxalate
Here, some people mentioned oxalate as good method of purification, but nobody brought details. Here follows what I did:

a) 5 g of raw TA (82%) dissolved in 15 mL MeOH. In second beaker, 5 g of oxalic acid, dihydrate was dissolved in 15 mL MeOH.
Mixed. Nothing precipitated, but after freezing to -20C, it started. I let in freezer few hours to be sure that all tryptamine oxalate (TAox) was solid (and probably some extra oxalic acid too).
Filtrated and flushed by cold MeOH. Obtained about 4g dry TAox, light brownish color.

b) 4g of TAox dissolved in ~130mL of water. At 25C, there were solid parts, so heated to 40-50C, then all was dissolved, tea-like color, no solid particles observed.
At 50C, TA base was precipitated by 40% NaOH => milk like color. Cooled in freezer (-20C), but not too low, about 0-10C. Obtained nice large crystals of TA, similar to cotton wool, yellowish color.
Filtrated and carefully flushed by cold water (0 C), dried above silikagel. From 4g, obtained ~ 2g OF PURITY 99.5+% !!!

4) B.p. of TA: raw: 92-95C, ACN recrystallized: 100-102C, oxalate purified: 102-105C. Still pretty far from ideal 114-116C.
I used GC-MS. DB5 column, 30m x 0.25 mm, program 40-300 @ 10C/min, split-less injection, ion trap. Sample dissolved in EtOH.

Here I present 2 pictures:
a) TA_raw.png: GC-MS raw TA, purity 82%. 17.09 min is TA, 19.43 min is the only impurity, which I observed. Rest of the peaks are
methyl siloxanes from septum and column. Spectrum of inpurity @19.43 min is on bottom picture. Library suggests following reasonable hits:

1,7-Trimethylene-2,3-dimethylindole
10,10-Spirocyclohexanotetrahydropyrimido[1,2-a]indole
Cycloheptan[a]indole
2-Methyl-1-(4-methylamino-1,3,4,5-tetrahydrobenzo[cd]indol-5-yl)-prop-2-en-1-ol
Carbazole, 1,2,3,4-tetrahydro-3-methyl-
1H-Indole, 4-(3-methyl-2-butenyl)-
...


b) TA_purification.png:
Here you can see what changed by oxalate purification. Impurity @19.43min from raw TA (above) was (almost) completely removed.
As before, peaks like 25.79, 26.78, 27.98, 29.48... are cyclic siloxanes (m/z 207, 281 and many other with difference always 74 = Si-O-(CH3)2).

I integrated area for TA (17.09min) and rest of impurity (19.43min) => purity of TA was 99.5%


My conclusions:
1) Even very bad raw TA (82% is really shit) can be converted to excellent purity by simple reaction with cheap
oxallic acid with reasonable yield.

2) There is still space for application of charcoal. My final TA was very lightly brown. Probably in the point 3a) when TA is
dissolved in CH3OH or in 3b) when TAox is dissolved in water.

3) Yield of TA. There is still space for optimizations. In point 3b) where TAox is dissolved in ~130 mL water, it will be probably better to reduce amount of water and use higher temperature (up to 70C).



Was not successful with purification of TA via carbonate salt. And lazy to buy vacuum pump / apparatus. Hope this will help someone and you will share experiences with TAox method here.

Enjoy your pure TA




[Edited on 25-1-2018 by joe_chem]

Very well done joe_chem!

Tryptamine is trolling?

Half a year ago I was making tryptamine by decarboxylation of tryptophan in acetophenone (at 150-180° bath temp).
Tryptamine was isolated and purified via oxalate salt (~50% yield).

Since melting point of obtained product was at 103-105°C, I decided to do futher purification by extraction with boiling hexanes.
It gave product that has a look of absolutely colorless crystals but it still melts at around 105°!
$#@#$?!1!


I am very confused as the literature gives melting point for tryptamine in ranges from 111 to 118°. Definitely not 105°C.
And I have no idea how to purify this obtained product further.
Recrystallization from MTBE and various aromatic hydrocarbons didn't helped with melting point at all. And vacuum distillation is not an option for me as I have no access to good vacuum pump.



[Edited on 29-3-2019 by bipolar]