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

Microwave-assisted Tryptophan decarboxylation into Tryptamine

Migrated topic.
This tek allows synthesizing tryptamine (T) from L-Tryptophan with no deep knowledge of chemistry or expensive equipment. T should not be confused with DMT (N,N-dimethyltryptamine) - T is not psychedelic and therefore legal in most of the world. Although DMT can be made from T rather easily, doing so is outside the scope of this thread.

The spoiler below contains information about the equipment and ingredients.
Equipment
  • Goggles and gloves - for handling corrosive chemicals like lye.
  • Microwave oven - regular household microwave oven (it is better to use a portable one that you can take outdoors or place under a kitchen range hood). It has to support cooking at reduced power (usually from 10% to 100%). Ideally the reduced power is supplied continuously, but ovens that cycle on/off periodically would also do.
  • Magnetic stirrer - ideally a magnetic hotplate stirrer.
  • Reaction vessel - a round, flat-bottom, 50-100 mL, ground joint, borosilicate glass flask and an angled barb hose adapter with glass/PTFE valve are ideal. An Erlenmeyer flask will cause a volcano. A 50 mL beaker or shot glass will work, but it is best to cover it with something - if you use aluminum foil, keep it smooth around the edges to avoid sparks and glass-melting plasma.
  • Two more small flasks, milligram scales, 25 mL and 50 mL measuring cylinders, airtight flask stopper, powder funnel, filter paper (medium or slow), lab thermometer, pH papers - or kitchen-grade alternatives.
Ingredients

  • L-Tryptophan (CAS 73-22-3) is an essential amino-acid. Food-grade Tryptophan is easy to purchase as white powder, but it is sometimes contaminanated. If it has any smell at all, or releases oil upon heating, or it dissolves in hot water but becomes cloudy again as you increase the temperature to 70 °C, if, after microwaving, the reaction mixture is cloudy, then try a different brand, or purify it by recrystallization. NutriVita is a good brand.
  • L-Carvone (CAS 6485-40-1) (flammable), also known as R-(–)-carvone, is the major ingredient (~80%) of spearmint essential oil. You can use spearmint oil instead of Carvone, but you will need a bit more of it, microwaving will take more time and result in a yellow (instead of amber) transparent mixture, and the final product may not end up off-white.
Chemicals for extraction

  • AcOH - 10% acetic acid solution, can be prepared by diluting glacial acetic acid (corrosive, volatile) with distilled water, 1:9. Household vinegar (5%) may also work, but you may need more of it.
  • NaOH (corrosive) - food-grade lye, for the freebase route only.
  • NH3(aq) (corrosive, volatile) - aqueous ammonium hydroxide (ammonia), as concentrated as possible (at least 10%), for freebase washing only (optional).
  • NaCl - table salt, for the salt route only. Pickling salt is the best since it does not contain anything else, like iodine.
  • MeOH (toxic, volatile, flammable) - absolute (100%) anhydrous (dried over molecular sieves 3Å ) methyl alcohol, for salt recrystallization only (optional).
  • n-Heptane (flammable) - helps protect dissolved T from atmospheric oxygen, and is also used for freebase recrystallization (optional). For oxygen protection you can also use hexane, naphtha, or any vegetable oil.
Reaction

1) To a small boiling flask add 4.0 g Tryptophan powder and 15 mL Carvone. Stopper the flask but ensure there is a small hole for CO2 to escape through.

2) Gently microwave the flask at ~250-300 W (enough to reach the boiling point, not too much to cause an eruption) for ~3-4 minutes (longer if you are using spearmint oil). Stop immediately after the mixture becomes transparent, with little or no unreacted tryptophan at the bottom.

3) Stopper the flask airtight (keep as much CO2 inside as possible) and let the mixture cool down to room temperature. Avoid contact with air or acids while it is hot.

  • [*]Tryptophan forms an imine with Carvone, which decarboxylates into T imine, releasing carbon dioxide.
    [*]The red hue is due to decomposition products dissolved in carvone. The lighter the color, the better you have protected T from oxygen.
    [*]Low power and short reaction time are necessary to minimize the thermal decomposition of T. If the mixture is brown, opaque, and smells like feces - you have overheated it.
Extraction

4) At room temperature, add 30 mL of 10% acetic acid solution and stir the mixture for 5-10 minutes at a very high speed. The emulsion should look homogeneous and orange while mixing, but will separate into 2 layers whenever you pause: a yellow aqueous layer at the bottom, a darker organic layer at the top.

5) Pre-wet filter paper with water and pour the entire mixture through the filter into another small flask. The acidic extract will pass through the filter and should be collected, while the dark hydrophobic liquid will be retained and can be discarded.

  • [*]T imine gets protonated and dissolves in the aqueous layer.
    [*]The pre-wetted paper acts as a membrane that slows the organic liquid down. This trick only works with liquids that are poorly soluble in water. If your paper is too porous, use a pair of paper filters instead of one.
    [*]If you want to increase the yield you can perform three smaller (3 x 10 mL) extractions instead of one larger extraction (1 x 30 mL): after collecting the aqueous extract place the filter on the empty reaction flask and puncture the paper to drain the organic liquid back.
Hydrolysis (recommended)

6) Insert a thermometer into the flask with the filtered acidic extract. Optionally add a layer of heptane to shield the dissolved T from atmospheric oxygen. With very slow stirring, bring the temperature to 70-75 °C and keep it in that range for ~10 minutes. A dark layer will appear and thicken on top while the rest of the mixture will gradually become semi-transparent - you will begin to see the magnetic stir bar and the tip of the thermometer. Cool the mixture down to room temperature.

7) Filter the mixture through pre-wetted filter paper (just like you did in step 5). Sprinkle the filter with a bit of fresh acetic acid solution to push all T through. The collected filtrate should be transparent yellow.

  • [*]The elevated temperature accelerates T imine hydrolysis into T and Carvone from a day at room temperature to a few minutes at 70 °C.
    [*]A thermometer adapter with a thermometer in it can help you minimize contact with air.
    [*]With a hotplate stirrer you could try to save time by combining the extraction and hydrolysis steps: heat the reaction mixture up and stir it at 70-75 °C for 10+ minutes at maximum speed, filter through a pair of wet paper filters.
    [*]Imine formation and hydrolysis are opposite reactions in equilibrium with each other. The more water is present, the less imine remains and the more T you will recover, but some imine will remain and precipitate in subsequent steps.
Workup

Here you can either choose the salt route to obtain T as hydrochloride salt, or the freebase route to obtain T as a free amine.

Salt route (easier)

8a) With medium-speed stirring, slowly saturate the acetic acid solution with sodium chloride (about 26 g per 100 mL of 10% acetic acid solution). Only add more salt after the previous batch dissolves (when stirring becomes quiet again). If drops of Carvone appear on top, soak them out with a small piece of paper towel. Crude T hydrochloride (T·HCl) will begin to precipitate early, but you should continue to add sodium chloride. After the entire planned amount has been added, allow stirring to continue for some time to dissolve as much sodium chloride as possible.

9a) Filter the precipitate through filter paper, dry and weigh it.

10a) Optionally, recrystallize T·HCl from boiling methanol: 1 g pure T·HCl dissolves in ~9 mL boiling methanol (so you will need a bit more methanol to dissolve impure T·HCl). Filter or decant the hot solution off any undissolved solids. Add seed T·HCl crystals or scratch the inner side of the flask to promote crystallization. Stopper the flask to prevent evaporation. Allow the solution to cool down to the room temperature. After several hours move it to a refrigerator. A few hours later - to a freezer; leave it there overnight. Filter off-white T·HCl crystals (picture attached): about 79% will be recovered, 21% will remain dissolved in methanol.

11a) Wash T·HCl with fresh ice-cold methanol from the freezer, dry and weigh it.

  • [*]Sodium chloride has reverse solubility in MeOH, so it will not precipitate when cooled down.
    [*]It is possible to recrystallize T·HCl from anhydrous ethanol instead of methanol, but larger volumes of ethanol will be required. T·HCl is soluble in water, so it is possible to recrystallize it from ethanol-water mixtures, but losses will be substantial.
Freebase route (harder)

8b) In an ice bath and with continuous stirring, add sodium hydroxide pellets to the acidic solution, letting the mixture cool down before adding more. The color will change from clear yellow to cloudy yellow. Around pH 9-10 the color will change again - to pale orange, you will see dark droplets floating around - a lot of them, if you skipped the hydrolysis step above.

9b) Filter the mixture through a pre-wetted cotton ball. Squeeze the cotton to push the last drops out. The filtrate should be cloudy white.

10b) Continue to add NaOH until pH goes well above 12. Filter and dry precipitated T. Depending on your technique, its color (and purity) will vary from snow-white to off-white to pale yellow.

11b) To get rid of microscopic sodium hydroxide crystals deposited on T surface, rinse T with ice-cold concentrated ammonia.

12b) Optionally, recrystallize T freebase from very large amounts (liter per gram) of hot/boiling n-Heptane. T recrystallized from heptane is snow-white. A Soxhlet extractor (ideally with a recirculating water chiller) is a convenient device for purifying T without large amounts of heptane or manual effort.

  • [*]The residual T imine is less basic than T and precipitates first, at lower pH values, as sticky goo. Cotton fibers capture that goo, and the remaining T will precipitate clean.
    [*]You will need to develop a sense for when (at what pH) to perform the final filtering. If you filter too soon, not all imine will precipitate, and your final product will not be snow-white. If you take pH too high before filtering, too much T will precipitate and get trapped in the cotton ball.
    [*]Concentrated (10-28%) ammonia is basic enough to keep T in the freebase form, contains enough water to dissolve sodium hydroxide deposits, and will evaporate away cleanly as water vapor and ammonia gas.
----

Storage

T freebase will darken when exposed to light, heat, and oxygen. It is therefore best stored in a closed container in a freezer. T hydrochloride appears to be resilient to oxidation.

Conversion

T hydrochloride can be converted to T freebase by dissolving it in a small amount of ice-cold concentrated ammonia, filtering and drying the precipitate.

T freebase can be converted to T hydrochloride by dissolving it in diluted (5-10%) acetic acid and salting out as described in step 8a above.

Purification

T freebase can be purified by either recrystallizing it from hot heptane (step 12b above) or converting it to T hydrochloride and back. T hydrochloride can be purified by recrystallizing it from boiling methanol (step 10a above).

Characterization

TLC
Rf = 0.45 (experimental, YMMV) in methanol:conc.ammonia 7:1 v/v

Melting points (literature)

T: 118 °C
T·HCl: 254 °C

*** Photos ***

1) tryptamine hydrochloride recrystallized from boiling methanol
2) tryptamine freebase recrystallized from heptane (with a Soxhlet extractor)​
 

Attachments

  • THCl.jpg
    THCl.jpg
    90.5 KB · Views: 2
  • Tryptamine_Soxhlet.jpg
    Tryptamine_Soxhlet.jpg
    41.7 KB · Views: 2
Thanks for sharing! This is very cool info for non-chemists like myself. Would just need to figure out what to do with Mr. T then :lol:
 
Woolmer said:
Thanks for sharing! This is very cool info for non-chemists like myself. Would just need to figure out what to do with Mr. T then :lol:
You are welcome!

T is quite similar to DMT in terms of properties: T is more basic, less soluble in heptane, melts at a higher temperature, but its behavior in acidic and basic environments is quite similar to that of DMT. For example, if you want to practice making or freebasing DMT fumarate, you can perfect your FASI technique on T fumarate first (T reacts with acetone, so FASA is not recommended).
 
Would you consider this information accurate?
 
grimlid said:
Would you consider this information accurate?
It looks accurate but overly simplistic as it attempts to describe an entire family of psychedelics in one article. There are dozens of tryptamines, and they are quite different.

To see what I mean, check out TiKHAL. It is written 24 years ago so it does not describe many novel tryptamines, but I am not aware of a newer work that would be just as comprehensive. In each chapter, skip the chemistry and read the subjective comments.
 
Considering that there are so many different tryptamines, do you know of (or think there may exist) a synthesis that leads to a psychoactive tryptamine that is simple, relatively safe, and does not use watched chemicals?

I suppose since there is no common knowledge on this, that there does not exist such a synthesis. Surely it would often be discussed on forums like the nexus, or perhaps I am just being lazy in gathering info.
 
Woolmer said:
Considering that there are so many different tryptamines, do you know of (or think there may exist) a synthesis that leads to a psychoactive tryptamine that is simple, relatively safe, and does not use watched chemicals?
It depends on how you define "simple", "safe", and "watched".

"Simple" really depends on your knowledge and experience. What is simple to some folks on this forum would be beyond others' reach.

"Safe" is also very relative. Is lye safe? There is a horrific story on reddit about a NaOH particle getting stuck under someone's eyelid (he did not use goggles). Most non-polar solvents are toxic, so are most alcohols, etc.

"Watched" is a moving target that also depends on the country. Almost every compound, including tryptophan and acetone, is watched in the US - but there are different levels of "watched", so tryptophan is less likely to trigger an investigation compared to, say, iodine.

If we use the tek in this thread as a standard, then my answer will be "no, I am not yet aware of a full psychedelic synthesis that would be equally simple, safe, and legal". Both reductive amination and exhaustive methylation involve handling carcinogenic liquids and obscure lab chemicals, and therefore cannot be published and discussed here.

I suppose since there is no common knowledge on this, that there does not exist such a synthesis. Surely it would often be discussed on forums like the nexus, or perhaps I am just being lazy in gathering info.
Nexus has a "no synthesis" rule - no synthesis that involves dangerous or watched chemicals can be discussed in the open.

The rule has its merits. If you lurk around a bit, you will see posts like this by people (children?) who are likely to hurt themselves and others by doing even traditional plant extractions. They are also unprepared legally and will incriminate themselves if the law enforcement knocks. A few busts or deaths linked to DMT Nexus - and the forum will be at risk; so much for psychedelic liberty.

The door is not closed completely - the rule just raises the bar on the safety of any synthesis that can be published here. As of 2021, to the best of my knowledge, nobody has been able to clear that bar. I am aware of an ongoing effort to produce a "Nexus-friendly" DMT tek, however.
 
This is a good thread 😁
Hailstorm is correct, and made some excellent points regarding the responsibility that comes with the information.
I'll need to try this with limonene with a dash of PhAc. Microwave chemistry works best with solvents that lack a dipole, like limo, because they won't superheat. Limonene is used for microwave decarboxylation and extraction of cannabinoids, to great effect.

Tryptamine chemistry is tricky, what appears simple on paper, is not necessarily the case in practice. Transamidation reactions can occur with temps above 220 C, when decarboxylating. And that's just decarboxylating tryptophan.

Tryptamine hcl can be added to PF substrate, to boost psilocin/psilocybin content; 10-20 mM. Higher than that tends to stunt growth.

~aniracetam/pinoline
 
benzyme said:
Tryptamine hcl can be added to PF substrate, to boost psilocin/psilocybin content; 10-20 mM. Higher than that tends to stunt growth.
This is very interesting. Do you have a link to a study on this? I have only been able to find one study by Jochen Gartz done in 1989 but it seems this has not been repeated quantitatively.
 
njnx2uwykwi41.jpg


This is my typical approach; nitrogen-purged reflux, 95:5 limo:acetophenone.
 
famine said:
Microwave is very interesting! Only a few minutes :?: What yield do you get?
I got 86% (2.7 g) beige (somewhat impure) T using one 30 mL extraction, freebase route (after step 10b).

This tek forgoes best practices like multiple extractions, inert atmosphere, etc. for simplicity. I would be happy with anything north of 50% as long as it is reasonably pure.

benzyme said:
I'll need to try this with limonene with a dash of PhAc.
I was actually inspired by studying aniracetam's/pinoline's many contributions :) Invaluable was your reddit comment about T reacting with ethyl acetate, adding to the list of many gotchas.

Random notes:

Limonene's auto-ignition temperature is 237°C (for folks reading this: please be careful). I could not find the auto-ignition temperature for carvone.

I have come across an article that found isophorone to be the highest-yielding (higher than acetophenone). It is also cheap and somewhat less stinky. However, like acetophenone, isophorone is partially soluble in water, which makes the workup more tedious than just throwing everything into a piece or two of wet filter paper - one needs a sep. funnel or syringe/pipette, a wash with DCM/chloroform, etc.

Tryptophan in neat benzophenone results in a lot of decomposition products (indole, skatole), possibly from overheating due to benzophenone's high boiling point. Similar issues may arise with raspberry ketone - however, it is cheap and non-watched; there is conflicting data on whether it is soluble in water or not.

I do not know the rate of imine hydrolysis for acetophenone or isophorone. Carvone imine only begins to hydrolyze at an appreciable rate above 60°C. If acetophenone imine hydrolyzes at room temperature, during the acidic extraction step, that would be convenient. If not, then, unlike carvone, acetophenone formed via hydrolysis is going to remain dissolved in water, and a few non-polar washes may be necessary to drive the hydrolysis equilibrium.

L-Carvone has a faint, pleasant minty smell.

When I tried to pour acetic acid into the reaction mixture which was still too hot, the aqueous layer became green'ish. I'd be wary of producing beta-carbolines and therefore would not recommend heating the acidic extract above 70°C.
 
Hailstorm said:
benzyme said:
I'll need to try this with limonene with a dash of PhAc.
I was actually inspired by studying aniracetam's/pinoline's many contributions :) Invaluable was your reddit comment about T reacting with ethyl acetate, adding to the list of many gotchas.

Thanks.
Like so many others, including yourself, I'm a student of Shulgin. So enamored by the process, I had to throw analysis in the mix, since I readily have the tools to do so. TLC is a great tool for preliminary studies; I don't have plates, I use HPLC instead. And as you undoubtedly have guessed, my avatar is the same on reddit and other boards. It's the mass analyzer, quadrupole ion trap.

I'm glad my work inspired others; some have used benzyl alcohol to good effect. Pugelone is also effective, not sure if anyone has used it yet. I did also crash out tryptamine extracted with dcm, by bubbling it with carbon dioxide, to get carbamate salts. I bet the microwave treatment would convert it back to the free base.
 
Is T HCl soluble in acetone?

After step 9a, could T HCl be dissolved in minimal acetone, and then acetone saturated with benzoic acid added to be added to this mixture? I have read elsewhere with a different starting procedure that T benzoate can be washed with 1:9 Acetone:Hexane, and recrystalized with 2:8 boiling acetone:hexane for a very decently pure product.

Or could benzoic saturated acetone simply be added after the hydrolysis (step 7) to salt out the T? Are there some implications due to the presence of water? The person outlining the benzoic acid route stated that aqueous solutions could degrade the product and require more extractions for cleanup (They salted from turpentine).
 
I expect T hydrochloride to be very poorly soluble in acetone. I also doubt that adding benzoic acid to a solution of T acetate or hydrochloride can salt T benzoate out.

You can try adding molar excess benzoic acid (dissolved in carvone) to the solution of T in carvone after decarboxylation (step 3). You will be skipping hydrolysis so the yield will be low, but it could be the easiest workup ever if T benzoate crashes out.
 
Back
Top Bottom