Sciencemadness Discussion Board

Tryptamine and formaline at room temperature

TheMasterOfTheInternet - 13-3-2019 at 03:12

Hi!
I've just dissolved 1g tryptamine (98% synthesis grade) in about 5-6mL MeOH (99%) and added a little splash of 1.2mol-eq of aqueous stabilized 37% formaldehyde (pharmaceutical grade)

First some tryptamine precipitated upon addition but it redissolved completly after shaking a little.
About 10s later the solution turned warm and got milky again.
Within 10min an oil with the color and consistence of caramel sauce precipitated. What is this oil?

I decanted the upper layer and tried to redissolve the Oil in MeOH, but it's is only sparingly soluble in MeOH.

Now the question - could it be already the picted spengler product without adding any acid?

Or is it possible that the imine precipitated?
Or what could it be?

Any ideas how I could test the identity without reference samples?
My target molecule is N-Monomethyl-Tryptamine

[Edited on 13-3-2019 by TheMasterOfTheInternet]

[Edited on 13-3-2019 by TheMasterOfTheInternet]

Assured Fish - 13-3-2019 at 20:41

Ive no experience with such a reaction, but i can be fairly certain that the reaction did not follow through to the tetrahydro carboline product.
At best you would have formed an imine, at worse some kind of polymerization.
To confirm you haven't got some polymerized mess i would attempt to dissolve it in something non polar such as DCM or trichlormethane (the later preferably as DCM can dissolve some polymers) if it doesn't dissolve then you have a mess.
Also try to hydrolyze it in an excess of water, since tryptamine is more or less insoluble in water it should precipitate over time.
Beyond this i can only tell you how to test for the presence of amines and given that its likely some of the imine has hydrolyzed or some amine has gone unreacted, this is rather useless, unless you want to titrate some nitrous acid, which is ill advised.

If your target is actually N-methyl tryptamine then you will need to first properly dehydrate the mixture to push the equilibrium in favor of the imine and then reduce the imine.

I think during the reaction as the solution warmed up, what you saw with the cloudiness was a small amount of precipitation due to water being formed and mixing with the methanol resulting is slightly different solubility characteristics which caused some temporary crashing out of solution.

If what you have there is in fact an imine then it will likely slowly hydrolyze back to the amine and carbonyl, as the reaction is in equilibrium.

Id honestly not even heard of this approach till today, as i had always assumed a mannich reaction was the go too approach to these kind of compounds, like so:
http://orgsyn.org/demo.aspx?prep=cv6p0965

TheMasterOfTheInternet - 13-3-2019 at 21:46

Quote: Originally posted by Assured Fish  
At best you would have formed an imine, at worse some kind of polymerization.
To confirm you haven't got some polymerized mess i would attempt to dissolve it in something non polar such as DCM or trichlormethane (the later preferably as DCM can dissolve some polymers) if it doesn't dissolve then you have a mess.
Good idea, I will try that. I have some DCM ordered anyway, I could try in a few days

Do you or anyone else has an idea how a polymer would look (structure)

Quote:

Also try to hydrolyze it in an excess of water, since tryptamine is more or less insoluble in water it should precipitate over time.

So I should try to suspend the oil in warm water and wait if solid tryptamine forms again?
Quote:

If your target is actually N-methyl tryptamine then you will need to first properly dehydrate the mixture to push the equilibrium in favor of the imine and then reduce the imine.
That was my plan (adding molsieves would have been the next step) but with an insoluble material in doesn't seem to make much sense now at this moment. If the oil (~500mg) is the imine, I will try to dissolve it in DCM and reduce it with NaBH4



[Edited on 14-3-2019 by TheMasterOfTheInternet]

Assured Fish - 14-3-2019 at 00:19
Quote:

Do you or anyone else has an idea how a polymer would look

Sadly no, it was more of a stab in the dark for potential side products, i had read about some primary amines polymerizing with formaldehyde in the production of some resins.
In reality i cannot think of any side reactions that would take place under the conditions you described.
Quote:

So I should try to suspend the oil in warm water and wait if solid tryptamine forms again?

Yes but of coarse not all the oil, it seems you don't have a lot to work with but this would work assuming your product was the imine.

Assuming you eventually end up at mono methyl tryptamine, then you should be able to do a melting point determination mp: 88*C
https://en.wikipedia.org/wiki/N-Methyltryptamine

Im also not certain as to the legality of this compound, one would think it legal given its a component of human urine but in certain parts of the world i suspect it may fall under analog restrictions.
Shulgin stated some notes about it having some activity but he didn't take it far it seems.

TheMasterOfTheInternet - 14-3-2019 at 08:46

The caramal sauce solidifed in the fridge in the meanwhile
Quote:

...i had read about some primary amines polymerizing with formaldehyde in the production of some resins...

Do you have a link for me? I only know of formaline+NH3-->hexamethylenetetramine
Quote:

Im also not certain as to the legality of this compound, one would think it legal given its a component of human urine but in certain parts of the world i suspect it may fall under analog restrictions.
Shulgin stated some notes about it having some activity but he didn't take it far it seems.

I can't imagine that it could be used as a recreational drug,
Shulgin noted that 50-100mg(!) smoked are necessary for 15s of "visuals"(!??). I rather guess these visuals were caused by DMT impurities.
For me it's "only" an interesting reaction. It's a useful as percurser for Rizatriptan-derivates (that's the direction im thinking on)



[Edited on 15-3-2019 by TheMasterOfTheInternet]

Assured Fish - 14-3-2019 at 20:08

Like I stated earlier, it was nothing more than a stab in the dark with only a hint of remembrance as to some paper mentioning some polymerization reactions with aldehydes and amines.
https://patents.google.com/patent/US2482498
Anyway, it would seem for such reactions to take place they would also require a phenol or aryl hydroxide, so unless you actually started with something like 4 or 5 hydroxytryptamine then polymerization is extremely unlikely.

With a bit more reading on the nature of the equalibrium between imines and carbonyls, acid catalysis of the hydrolysis should help to speed things along quite a bit, heating would make it even faster.
Unfortunately this will mean you will end up with the acid salt of tryptamine so you will want to then freebase this followed by filtration and a melting point determination if you want to be precise.
https://www.masterorganicchemistry.com/reaction-guide/imine-...
Id advise an equimolar ratio of acid to tryptamine, as the secondary amine on the indole ring is surprisingly acidic despite it being a secondary amine.

Bronstein - 15-3-2019 at 23:13

Primary amines can trimerize with formaldehyde into a sixmembered ring, hexahydro-1,3,5-triazines. Usually in the procedures I've seen a base is added, but maybe it reacts without base too?

https://en.m.wikipedia.org/wiki/Hexahydro-1,3,5-triazine

TheMasterOfTheInternet - 16-3-2019 at 19:18

Tryptamine is a quite strong base on its own, so a trazine I a very good guess I think

I the meanwhile I found that my caramal sauce turns into a white solid in contact with hot water, which indicates that it's simply the expected desired imine but with a much worse soloublity in MeOH than I expected.
I will try to reduce it when my DCM arrives in an MeOH/DCM system, hoping it dissolves in DCM/MeOH.

Thank you all!

TheMasterOfTheInternet - 18-3-2019 at 15:28

Update:
The product does NOT dissolve in 25% acetic acid, even when boiling for >30min.
The oily sauce becomes a brittle solid which EXACTLY looks and and feels like crispy pork rind snacks I know from thailand and denmark.


So I'm pretty sure it's not the imine or at least a mixture of the imine and a big part of another product, as the imini should hydrolyse back to tryptamine which is very solouble in acetic acid.

Triazine seems to be the best idea so far



[Edited on 18-3-2019 by TheMasterOfTheInternet]

[Edited on 18-3-2019 by TheMasterOfTheInternet]

Assured Fish - 18-3-2019 at 22:45

Do a melting point determination of both the supposed imine and the product that was produced via hydrolysis.