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.
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.
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.
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.
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.
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.
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)
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.
- 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.
- 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.
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.
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.
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.
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.
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)
Invaluable was your reddit comment about T reacting with ethyl acetate, adding to the list of many gotchas.