Woolmer
Established member
@Hailstorm Have you tried this method using less carvone maybe just mixed in another solvent? Most reports I've read that do a reflux usually use way less carvone than your method.
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Microwave-assisted Tryptophan decarboxylation into Tryptamine
- Thread starter Hailstorm
- Start date
Woolmer
Established member
I wonder if old limonene can be used as some of it oxidizes into carvone after a while. This paper reports 1-2% oxidation into a mix of carvone/carveol 8 weeks after air exposure.
I've got some limonene probably at least a year old now that has changed colour. Think I will give it a go.
I've got some limonene probably at least a year old now that has changed colour. Think I will give it a go.
It's catalytic so a ketone must be present for this decarb to work efficiently.
Woolmer
Established member
Right what I meant was that maybe in old limonene enough carvone is present to act as a catalyst. I gave it a go anyways and observed a colour change from light yellow to deep amber, which I believe indicates that I ran it at too high a temperature and decomposition occurred? Barely any of the tryptophan seemed to react as there was still plenty left and I am not sure whether I was observing CO2 evolution or just bubbles from the limonene reaching near boiling. I was lazy and salted with benzoic acid instead of doing hydrolysis as recommended. Nothing crashed out.
I've ordered some spearmint oil now to make sure I do it right
I've ordered some spearmint oil now to make sure I do it right
The higher the concentration of the ketone is, the faster the reaction will proceed. If you plan to use the ketone in catalytic amounts only, the benefits of the microwave method begin to diminish – if you have to run the reaction for hours, you might as well use proper glassware, traditional heating, and inert atmosphere.
If you are just starting to experiment, use pure carvone until you are happy with the results. It is tried and true.
If you are just starting to experiment, use pure carvone until you are happy with the results. It is tried and true.
Woolmer
Established member
Success! I performed the method as outlined by @Hailstorm, scaling to 2g of tryptophan. I used spearmint oil instead of pure carvone. It was difficult to perform the microwave reaction because even at the lowest setting my microwave would heat it up too much and it would start bubbling like crazy. I realize that the wattage is fixed so it merely runs the microwave for a few seconds then stops for a few, but I think there is too little liquid that gets heated too easily. So it needed multiple heating cycles to get there and probably took about 30 min to perform.
I tried to protect it from the atmosphere by putting cling wrap over with a rubber band around the neck and poking 3 small holes with a needle.
I did 3 x 8 ml acetic acid extractions. Yielded 1.51 grams of the hydrochloride salt, though there may be a tiny bit of water that still needs to evaporate. It looks decently pure. There was never any smell of decomposition products, even though I definitely pushed the temperature to a max and the solution turned a dark red.
Does the attached picture look like pure enough tryptamine to use for other reactions? Or would it need a re-x?
I've scaled up another reaction now to 10 g of tryptophan. I tried to put some water in a bowl to absorb some microwaves but this just completely stopped the solution from heating at all.
Thanks for the write-up it could not be more concise and easy to follow.
I tried to protect it from the atmosphere by putting cling wrap over with a rubber band around the neck and poking 3 small holes with a needle.
I did 3 x 8 ml acetic acid extractions. Yielded 1.51 grams of the hydrochloride salt, though there may be a tiny bit of water that still needs to evaporate. It looks decently pure. There was never any smell of decomposition products, even though I definitely pushed the temperature to a max and the solution turned a dark red.
Does the attached picture look like pure enough tryptamine to use for other reactions? Or would it need a re-x?
I've scaled up another reaction now to 10 g of tryptophan. I tried to put some water in a bowl to absorb some microwaves but this just completely stopped the solution from heating at all.
Thanks for the write-up it could not be more concise and easy to follow.
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I have tons of spearmint in my garden - the carvone crashes out of a strong tea on cooling so I've got this reaction earmarked somewhere above the middle of my to do list 
Great to hear of this success in that respect.
Great to hear of this success in that respect.
Woolmer
Established member
I had success scaling up to 10 g of tryptophan using 30 ml of spearmint oil. It took quite a long time to microwave (~ 1 hr) with lots of stop and start. I could only microwave for 10-20 second bursts otherwise it would froth over. I used a 100 ml boiling flask but I would recommend something bigger due to it frothing over so easily. I let the hydrolysis run for 20 minutes this time. Unsure about yield yet as it is still slightly wet... But it looks decent!
It seems slightly less pure than my 2 g run but on drying it might lose some colour as my first batch did. Both of these trials still smell like spearmint.
I am going to perform a DCM wash on these, basify, and store in pet ether as I have read elsewhere it helps to resolve the tryptamine.
It seems slightly less pure than my 2 g run but on drying it might lose some colour as my first batch did. Both of these trials still smell like spearmint.
I am going to perform a DCM wash on these, basify, and store in pet ether as I have read elsewhere it helps to resolve the tryptamine.
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Hi,
I think colour is always a poor indicator of purity... especially tryptamines. It should loose colour once it dries up for sure though!
Are you able to dissolve it in pet ether easily? It should be quite insoluble even as the freebase.
I think colour is always a poor indicator of purity... especially tryptamines. It should loose colour once it dries up for sure though!
Are you able to dissolve it in pet ether easily? It should be quite insoluble even as the freebase.
Woolmer
Established member
Ok thanks good to know.
I don't plan on dissolving it as you say it should be poorly soluble in pet ether. I only want to let it sit in the pet ether to prevent it from absorbing moisture.
As per this method from a subreddit that I am not sure I can share the link to:
"Rinse the acidic layer with a nonpolar to wash out the ketone, basify with NaOH. Put in the fridge overnight. Vac filter, rinsing with cold ammonia. Air-dry, and let sit in pet ether. Can either refrigerate for later use, or distill it off. The trypamine should now be 95-97% pure."
"Storing it in pet ether helps resolve it further... I do this to recrystallize, and to keep it from absorbing ambient moisture"
I don't plan on dissolving it as you say it should be poorly soluble in pet ether. I only want to let it sit in the pet ether to prevent it from absorbing moisture.
As per this method from a subreddit that I am not sure I can share the link to:
"Rinse the acidic layer with a nonpolar to wash out the ketone, basify with NaOH. Put in the fridge overnight. Vac filter, rinsing with cold ammonia. Air-dry, and let sit in pet ether. Can either refrigerate for later use, or distill it off. The trypamine should now be 95-97% pure."
"Storing it in pet ether helps resolve it further... I do this to recrystallize, and to keep it from absorbing ambient moisture"
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Tryptamine is quite stable and I would not worry about it absorbing ambient moisture
I recommend recrystallizing tryptamines as salts whenever possible, freebasing only when needed. The extra ionic bond makes the nitrogen less reactive and more stable in air.
It is evident when you heat both above 110°C. Tryptamine freebase rapidly and irreversibly turns into brown goo (presumably tryptamine N-oxide), while the hydrochloride salt remains off-white, showing no signs of thermal degradation.
It is evident when you heat both above 110°C. Tryptamine freebase rapidly and irreversibly turns into brown goo (presumably tryptamine N-oxide), while the hydrochloride salt remains off-white, showing no signs of thermal degradation.
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Hi,
I don't believe they are this fragile... I keep disub tryptamines and 5-methoxytryptamines as freebase @ 100-120C for days before finishing workup. I don't see any thermal degradation.
I keep 5-methoxytryptamine at 130C for a few hours before we vacuum distill it.
I find impurities to be the cause of tryptamines to become goo.
I don't believe they are this fragile... I keep disub tryptamines and 5-methoxytryptamines as freebase @ 100-120C for days before finishing workup. I don't see any thermal degradation.
I keep 5-methoxytryptamine at 130C for a few hours before we vacuum distill it.
I find impurities to be the cause of tryptamines to become goo.
Woolmer
Established member
I washed my T HCl with chloroform twice. It seems like a substantial amount of carvone was removed as the filtered chloroform was quite red. The resulting T HCl was now off white.
View attachment 100530
I dissolved this in warm water, added 25% ammonia in 5 minute intervals until no more colour change was observed, then placed it in the fridge.
At first, what seemed like a brownish goo or solid crashed out, followed by beautiful long crystals on top.
I think I could have performed another wash and perhaps the avoided the brown layer
View attachment 100530
I dissolved this in warm water, added 25% ammonia in 5 minute intervals until no more colour change was observed, then placed it in the fridge.
At first, what seemed like a brownish goo or solid crashed out, followed by beautiful long crystals on top.
I think I could have performed another wash and perhaps the avoided the brown layer
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You keep substituted freebase tryptamines at 100–120°C for days before the workup? in open air, above their melting points, with no yellowing, smell of indole/skatole, or other signs of degradation? This is very surprising. Perhaps @Woolmer could run a quick experiment and heat his fresh tryptamine (freebase and HCl) to such temperatures for, say, an hour?
Likewise, mexamine, if kept at 130°C for hours, quickly becomes dark red in my experience. Oxidative degradation in air, accelerated by high pH and high temperatures, is why, for example, the classic alkaline hydrolysis of melatonin into mexamine prescribes sodium dithionite as an anti-oxidant, and why it is not required in the acidic hydrolysis of melatonin with tosylic acid since the amine gets immediately protonated.
(...By the way, what would the purpose of keeping tryptamines at 100–120°C for days be?)
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Woolmer
Established member
The freebase T crystalline layer weighed 2.51 g while the amorphous bottom layer weighed 2.34 g (= 4.85 g total). The total weight of the T HCl that I dissolved in water to turn to freebase was 8.14 g. I believe full conversion to freebase should have yielded 6.63 g freebase, so it seems a substantial amount is still dissolved in the water. I'm going to try pull with some DCM or chloroform to see if something more is yielded.
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Hi,
The sodium dithionite is actually unnecessary too. All our melatonin hydrolysis to mexamine were done in KOH/Propanol without any issues of oxidation, etc. We yield 85-90% yield. I wouldn't worry at all about unsubstituted tryptamines being oxidised.
Unless purified properly, all tryptamines freebases even in white apperance, will melt into a reddish liquid.
We extract substituted tryptamines in 2MeTHF, distill it off and let it dry at 110C usually to get rid of any trace solvent/water. After this we feed into a molecular distillation setup which keeps the whole batch warm at 110C.
One time we had issues with one of our vacuum pumps and we just left it in the feeding tank at 110C for I think was around 15 days while we had the pump serviced. We had no loss of yield or product degradataion.
Regards,
famine
The sodium dithionite is actually unnecessary too. All our melatonin hydrolysis to mexamine were done in KOH/Propanol without any issues of oxidation, etc. We yield 85-90% yield. I wouldn't worry at all about unsubstituted tryptamines being oxidised.
Unless purified properly, all tryptamines freebases even in white apperance, will melt into a reddish liquid.
We extract substituted tryptamines in 2MeTHF, distill it off and let it dry at 110C usually to get rid of any trace solvent/water. After this we feed into a molecular distillation setup which keeps the whole batch warm at 110C.
One time we had issues with one of our vacuum pumps and we just left it in the feeding tank at 110C for I think was around 15 days while we had the pump serviced. We had no loss of yield or product degradataion.
Regards,
famine