Psilocybin/Psilocin to N,N-DMT?

[thrdel]

I would love to hear from those chemistry savvy on the following theoretical process :
The difference between DMT and the 4-HO-DMT molecule is in fact an extra oxygen atom on the indole , hence the 4-HO - DMT. With the phenol molecule , the oxygen seems to be easy to remove by zinc dust that forms ZnO (insoluble in water). Wouldn't a similar process render DMT from Psilocin ?
I know that some heat is required for the Phenol molecule to release the oxygen and change to benzene but don't know how much heat. Is anything else other than Zinc suitable ?
Psilocin isn't water soluble but it is soluble in acidic water. Also, at about 70 - 80 ^C psilocybin (water soluble) changes to psilocin. Not hard extraction, or so it seems. Is the next step of getting rid of the extra oxygen atom feasible ?

No, this will never work.

Maybe at 100PSI under H2 at 300C, which would utterly destroy everything of course.

The only practical way to do such a transformation would be palladium hydrogenolysis of the triflate after it has been prepared from the -OH, completely expensive and ridiculous. On top of the fact that the dosage for DMT is many times higher than that of psilocin, and that psilocin is produced in much smaller amounts relative to the DMT producing plants. Not really worth pursuing. At that point, its better transform that triflate into something more valuble.

Why the 100PSI and the 300C ? Why under H2 ? Stripping on oxygen from the Phenol molecule to obtain benzene , with Zn catalyst , is just a normal reaction, no high pressure, no enormous temperatures or anything else special. Do you have a specific reason in mind ?
The most recommended dosage for psilocin is 10-30 mg and the range for DMT is about there also. Not really many times higher .
The psilocin/psilocybin in shrooms go up to about 1.2% or a bit higher in some cases. The content of DMT in plants with higher content go to probably 1.5% . Do you see such a big difference there ?
The point of this conversion of psilocin to DMT, if possible , other than that some people happen to actually like DMT , is that DMT is much more stable long term, psilocin degrades very rapid even if extracted to crystals form, degrades even faster in dried mushrooms which is a loss basically, shrooms are easier to grow and probably many other reasons.

 

[Loveall]

What if we could genetically engineer a mushroom strain that lacks the psiH enzyme?

PsiM is expected to catalyze iterative
methyl transfer to the amino group of 7 to yield
N,N-dimethyltryptamine (10).

Maybe it won't work if psiH transformation is a requirement before psiM can go to work. The paper in the link above suggests that when all enzymes are present methylation is the last step. Does anyone know what would happen if the psiH enzyme gene is deactivated? Could methylation still happen just at a slower pace?

Genetically modified DMT mushrooms would be neat if possible.

Or maybe extract mushroom proteins to water, remove psiH somehow (maybe it crashes out separetly from psiD/M with ammonium sulfate if we ate lucky), and add some Tryptophan from the vitamin shop to see what happens.

 

[Mindlusion]

Why the 100PSI and the 300C ? Why under H2 ? Stripping on oxygen from the Phenol molecule to obtain benzene , with Zn catalyst , is just a normal reaction, no high pressure, no enormous temperatures or anything else special. Do you have a specific reason in mind ?
The most recommended dosage for psilocin is 10-30 mg and the range for DMT is about there also. Not really many times higher .
The psilocin/psilocybin in shrooms go up to about 1.2% or a bit higher in some cases. The content of DMT in plants with higher content go to probably 1.5% . Do you see such a big difference there ?
The point of this conversion of psilocin to DMT, if possible , other than that some people happen to actually like DMT , is that DMT is much more stable long term, psilocin degrades very rapid even if extracted to crystals form, degrades even faster in dried mushrooms which is a loss basically, shrooms are easier to grow and probably many other reasons.

the temperatures and pressures I overstated in order to alluded to you the harsh nature of the reaction conditions, but it didn't work.

What do you think the yield of benzene is for the classical reaction with phenol you have posted?

and you know the reaction is done neat right? liqufied phenol? And with high temperatures well over 100C?

Phenol and benzene, two very thermally stable products, can take a hit. And even still, the reaction is crude and only workable since the benzene can be distilled over the the course of the reaction.

So you are trying to tell me you want to heat liquified psilocin with zinc dust and collect the DMT? I'm telling you that is a great way to make tar. Go ahead and try it out.

There is a reason the more advanced methods are used in synthesis, methods that can be applied to variety of substrates in good yield.

 

[Mindlusion]

What if we could genetically engineer a mushroom strain that lacks the psiH enzyme?

PsiM is expected to catalyze iterative
methyl transfer to the amino group of 7 to yield
N,N-dimethyltryptamine (10).

Maybe it won't work if psiH transformation is a requirement before psiM can go to work. The paper in the link above suggests that when all enzymes are present methylation is the last step. Does anyone know what would happen if the psiH enzyme gene is deactivated? Could methylation still happen just at a slower pace?

Genetically modified DMT mushrooms would be neat if possible.

Or maybe extract mushroom proteins to water, remove psiH somehow (maybe it crashes out separetly from psiD/M with ammonium sulfate if we ate lucky), and add some Tryptophan from the vitamin shop to see what happens.

Now this would be cool and worth doing

 

[Jupitor]

How about this one- 4-aco-dmt to 4-ho-dmt?

 

[benzyme]

yup, in the liver.

 

[Jupitor]

yup, in the liver.

I've heard this hypothesized, and even assumed. But has it actually been proven? Some are under the impression that maybe the 4-aco-dmt is active in its own right.

 

[Mindlusion]

yup, in the liver.

I've heard this hypothesized, and even assumed. But has it actually been proven? Some are under the impression that maybe the 4-aco-dmt is active in its own right.

You're kidding, right?

Have you heard of Asprin? Cleavage of esters (by esterases) is probably the simplest and most well known and most widely studied metabolic pathways that exist.

There's also every reason to suggest that 4-AcO-DMT is active only as a prodrug, since the group on the 4-position is far too large to fit in the receptor, similar size substitutions render the molecule inactive. And the fact that the -OH participates in hydrogen bonding that is vital for activity.. For example 4-OMe is nearly completely inactive or at least has no effects that even remotely resemble psilocin.

Especially considering the effects and the potency of 4-AcO-DMT are near identical to psilocin, it obvious.

I believe there is even a paper with in vitro assays that show little to none binding affinity with ht2a, not that anyone would have needed to check.

 

[Jupitor]

yup, in the liver.

I've heard this hypothesized, and even assumed. But has it actually been proven? Some are under the impression that maybe the 4-aco-dmt is active in its own right.

You're kidding, right?

Have you heard of Asprin? Cleavage of esters (by esterases) is probably the simplest and most well known and most widely studied metabolic pathways that exist.

Please forgive my limited understanding of both metebolic processes and chemistry. Now I know

Is there a relatively easy way to do this in a kitchen lab?

 

[Mindlusion]

yes, alkaline or acid hydrolysis

Acidic hydrolysis doesn't work well on this kind of ester, it likely will not go to completion.

Its better to use NaOH, it works well. Though then of course, you will lose yield and have some of your psilocin oxidize.

 

[benzyme]

as Mind mentioned, 4-AcO is a pro-drug. There is no benefit, pharmalogical or otherwise, to convert it to the less stable 4-HO.
and revising my previous statement, there’s a good chance deacetylation occurs before it even reaches the liver, via acidic hydrolysis in the stomach.

 

[thrdel]

the temperatures and pressures I overstated in order to alluded to you the harsh nature of the reaction conditions, but it didn't work.

What do you think the yield of benzene is for the classical reaction with phenol you have posted?

and you know the reaction is done neat right? liqufied phenol? And with high temperatures well over 100C?

Phenol and benzene, two very thermally stable products, can take a hit. And even still, the reaction is crude and only workable since the benzene can be distilled over the the course of the reaction.

So you are trying to tell me you want to heat liquified psilocin with zinc dust and collect the DMT? I'm telling you that is a great way to make tar. Go ahead and try it out.

There is a reason the more advanced methods are used in synthesis, methods that can be applied to variety of substrates in good yield.

The removal of the hydroxyl group from phenol does require heat, if you read my original post, I've mentioned that. Apparently 165-170 C. What's the yield on that ? Very high if done correctly I suppose, it is just removing an oxygen atom ,doesn't change anything else.
It is not a reaction of benzene and phenol but rather phenol and zinc. The result is benzene and zinc oxide .
"Liquified phenol ?" - FYI - Phenol melts at 40 C so liquid phenol isn't so amazing. That reaction was simply an example of stripping an oxygen atom from a benzene ring . Sure there are other similar reactions . The compound one needs to work on ,many times can be dissolved in a solvent . You don't really need to melt table salt when it can be dissolved in water, do you ? What's wrong with that ?
Psilocin Melting point 173 to 176 °C (343 to 349 °F) - it can take some heat apparently.
I'm trying to find out if it really needs 160 - 170 C or if it can be done in theory at lower temperatures. Psilocin molecule isn't exactly phenol. Maybe the bonds in phenol are much stronger and that's why it requires that much heat. In H2O2 - hydrogen peroxide - the bonds are much weaker and require almost no heat to break.
I'm not a chemist and don't have any equipment, that's why I'm discussing it on this forum.
As I said, the difference between DMT and Psilocin is only one Oxygen atom.

 

[benzyme]

I'm not a chemist and don't have any equipment, that's why I'm discussing it on this forum.
As I said, the difference between DMT and Psilocin is only one Oxygen atom.

your former statement explains why you don't grasp the concept that psilocin is far less stable than DMT, much less phenol. Psilocin has weak partial charges, as partial positive on the amine, and partial negative on the OH group (the charges are more pronounced on psilocybin). Any alterations to the stability of the molecule renders it inactive, and it readily oxidizes. I said it years ago, and I'll say it again. You're not removing anything from that benzene ring, but you can try, and I'll analyze it if you want.

position matters, regarding stability..but even the more stable 5-MeO-DMT, or serotonin, are not easily converted to DMT, due to strong covalent forces with the benzene ring. It's neither economically nor energetically favorable.

 

[thrdel]

your former statement explains why you don't grasp the concept that psilocin is far less stable than DMT, much less phenol. Psilocin has weak partial charges, as partial positive on the amine, and partial negative on the OH group (the charges are more pronounced on psilocybin). Any alterations to the stability of the molecule renders it inactive, and it readily oxidizes. I said it years ago, and I'll say it again. You're not removing anything from that benzene ring, but you can try, and I'll analyze it if you want.

position matters, regarding stability..but even the more stable 5-MeO-DMT, or serotonin, are not easily converted to DMT, due to strong covalent forces with the benzene ring. It's neither economically nor energetically favorable.

You clearly didn't bother to read my original post. I'm perfectly aware that psilocin readily degrades and that's the whole point of this discussion , to find a way to remove that Oxygen atom that makes it unstable. What is not clear there ? I'm not interested if it is possible to break the indole or the benzene ring, not interested in making DMT from phenol , none of that was actually thew purpose of this post. Yes, partial negative on the hydroxyl group is the reason why that Oxygen should react with Zinc and form Zinc Oxide and the rest of the molecule, unchanged in any other way , is DMT.
What is so hard to understand about that ?
No one's removing anything from the benzene ring , there is no oxygen in benzene ! The oxygen in the hydroxyl group of psilocin is an addition, it is attached to the indole not actually part of it.
Just saying...

 

[benzyme]

I would love to hear from those chemistry savvy on the following theoretical process :
The difference between DMT and the 4-HO-DMT molecule is in fact an extra oxygen atom on the indole , hence the 4-HO - DMT. With the phenol molecule , the oxygen seems to be easy to remove by zinc dust that forms ZnO (insoluble in water). Wouldn't a similar process render DMT from Psilocin ?
I know that some heat is required for the Phenol molecule to release the oxygen and change to benzene but don't know how much heat. Is anything else other than Zinc suitable ?
Psilocin isn't water soluble but it is soluble in acidic water. Also, at about 70 - 80 ^C psilocybin (water soluble) changes to psilocin. Not hard extraction, or so it seems. Is the next step of getting rid of the extra oxygen atom feasible ?

this is your original query. We've already answered it, several times.

It looks easy on paper, just looking at the structures. It's not, when you understand intramolecular forces.

 

[thrdel]

I would love to hear from those chemistry savvy on the following theoretical process :
The difference between DMT and the 4-HO-DMT molecule is in fact an extra oxygen atom on the indole , hence the 4-HO - DMT. With the phenol molecule , the oxygen seems to be easy to remove by zinc dust that forms ZnO (insoluble in water). Wouldn't a similar process render DMT from Psilocin ?
I know that some heat is required for the Phenol molecule to release the oxygen and change to benzene but don't know how much heat. Is anything else other than Zinc suitable ?
Psilocin isn't water soluble but it is soluble in acidic water. Also, at about 70 - 80 ^C psilocybin (water soluble) changes to psilocin. Not hard extraction, or so it seems. Is the next step of getting rid of the extra oxygen atom feasible ?

this is your original query. We've already answered it, several times.

It looks easy on paper, just looking at the structures. It's not, when you understand intramolecular forces.

I don't doubt the fact that you think you've answered my question several times, but I hope you don't mind if I don't consider what was posted so far as an actual answer.
Let's leave it there for now. I can wait for better answers.

 

[benzyme]

You're going to do a lot of waiting then, because you want an answer that you want to hear, not what's actually valid.
"Oh sure, you just add some lemon juice, a dash of zinc, heat it in a water bath, then badda boom badda bam..elf spice."

Enzymes don't even remove the OH, it's just not energetically favorable..but somehow it seems reasonable that it could be done in a kitchen/lab?

 

[Mindlusion]

You clearly didn't bother to read my original post. I'm perfectly aware that psilocin readily degrades and that's the whole point of this discussion , to find a way to remove that Oxygen atom that makes it unstable. What is not clear there ? I'm not interested if it is possible to break the indole or the benzene ring, not interested in making DMT from phenol , none of that was actually thew purpose of this post. Yes, partial negative on the hydroxyl group is the reason why that Oxygen should react with Zinc and form Zinc Oxide and the rest of the molecule, unchanged in any other way , is DMT.
What is so hard to understand about that ?
No one's removing anything from the benzene ring , there is no oxygen in benzene ! The oxygen in the hydroxyl group of psilocin is an addition, it is attached to the indole not actually part of it.
Just saying...

I'm beginning to think this guy is either trolling, since its a new account, or just willfully ignorant.

You've stated your not a chemist, and you clearly don't understand our explanations. Why are you arguing?

You found a picture online of phenol reacting with zn going to benzene. You used this to think of the idea, "can i do the same with psilocin?". Without understanding the chemistry behind it, its a reasonable suggestion.

When you DO understand the chemistry behind it, there is 100 reasons why it wouldn't work.

First of all, can you find ONE example of that reaction taking place on a molecule other than phenol? and if so, how complex is that molecule? Do you think there might be a reason that you can't find any complex molecules able to undergo this transformation?

And what is the yield for the phenol reaction? Don't assume, do your research and give me a number. How is the product recovered?

Lets say the -OH can react with zinc, but whats to stop the other parts of the molecule from reacting? The pyrrole nitrogen, the amine nitrogen, the indole c2-c3 double bond, and whats to stop the molecule from reacting with itself?

Exactly what is so special about indole with hydroxy on the 4- position that makes it so reactive? Do you know? Why is 5-ho-DMT (Bufotenine) or serotonin, not reactive in the same way?

You know the mechanism is a single electron process, are you aware of other single electron processes that indole likes to do? Do you think these could possibly get in the way?

You can go ahead and wait for 'better answers', though I can promise you won't be satisfied. Unless you don't want an answer from a chemist. Just because can't understand the explanation, doesn't mean its invalid.

 

[benzyme]

I'm beginning to think this guy is either trolling

same.

It it were a feasible reaction, there would most likely be refs. dating back to the 1950's.

 

[downwardsfromzero]

I would love to hear from those chemistry savvy on the following theoretical process :
The difference between DMT and the 4-HO-DMT molecule is in fact an extra oxygen atom on the indole , hence the 4-HO - DMT. With the phenol molecule , the oxygen seems to be easy to remove by zinc dust that forms ZnO (insoluble in water). Wouldn't a similar process render DMT from Psilocin ?
I know that some heat is required for the Phenol molecule to release the oxygen and change to benzene but don't know how much heat. Is anything else other than Zinc suitable ?
Psilocin isn't water soluble but it is soluble in acidic water. Also, at about 70 - 80 ^C psilocybin (water soluble) changes to psilocin. Not hard extraction, or so it seems. Is the next step of getting rid of the extra oxygen atom feasible ?

There's a way that works with bufotenine, linked to in this post, which might possibly work with psilocin.

Yeah the yield was a bit sucky. You can't imagine it being any better for psilocin, really.

At least there's a twist now, when every so often this question gets asked (again)...

"NO!! But...."

The zinc reduction? Not a chance. Good luck with getting the psilocin up to the required reaction temperature intact.