Sciencemadness Discussion Board - Dimethylation of tryptamine via formaldehyde/STAB

Dimethylation of tryptamine via formaldehyde/STAB

turd - 13-3-2013 at 23:16

This should have been posted a long time ago, anyway here it is:

A few years ago a preparation of DMT via aq. formaldehyde solution and STAB (sodiumtriacetoxyborohydride) with excellent yields was posted at erowid: https://www.erowid.org/experiences/exp.php?ID=61171. Some people doubted the results, since STAB is supposedly very water sensitive and there are fears of reduction to the indoline, acetylation of the indole-N or the dreaded Pictet-Spenger. The thing is: it definitely works.

Tryptamine was prepared by decarboxylation of tryptophan (cheap!) in tetraline with carvone fractionated out of spearmint oil and purifed by distilling. Works like a charm. People likewise recommend decarboxylation in neat acetophenone (search the board).

In an ice bath with good stirring 5.93 g finely powdered NaBH4 was suspended in 150 ml THF. <del>9.38</del> 28.59 g AcOH was added slowly, letting foaming subside after every addition (Practically no more foaming after addition of 2/3rd of the AcOH). The reaction was stirred for another hour. 5.00 g tryptamine and 3.75 g AcOH in 10 ml THF were added. 13.4 g 36% HCHO (prepared by heating an appropriate paraformaldehyde / water suspension in an autoclave at 150°C) was slowly dropped in and the reaction stirred for another 2.5 h. All tryptamine was gone on TLC (EtOAc/MeOH 2:1 with NH3), minor amounts of side products (tryptamine: Rf~0.1, DMT~0.2).

The reaction was made basic with 25% NaOH, extracted with toluene, washed with brine, dried over freshly dried and powdered K2CO3 and distilled. 1 g of a light yellow oil was obtained which crystallized in the freezer to a pale yellow, waxy solid with characteristic tryptamine scent. M.p: not sharp ~60°C. Bioassay: A++++ smashing success, highly recommended (smoke not nearly as bad as the lore says).

The reaction was repeated at a lower scale, this time with column chromatography (EtOAc/MeOH) as work up procedure followed by crystallization from cyclohexane/pentane - very nice pale yellow crystals, but similar low yields.

Due to the TLC I'm convinced that the reaction is not the problem, but rather the workup. This should be tried with bigger batches. And even if the yield stays as terrible - the reactants are dirt cheap. Everything is OTC; do this at home, kids.

<hr width="800" />
<b>Attention</b>: megalodon found an error in the original post (thank you!): It must read "28.59 g AcOH" instead of "9.38 g AcOH". The goal was 1 eq. tryptamine, 5 eq. NaBH4 and 15.25 eq. AcOH.

Would be great if a moderator could fix the original post. Thank you.

[Edited on 6-8-2013 by turd]

[<a href="u2u.php?action=send&username=bfesser">bfesser</a>: errata]

[Edited on 9.8.13 by bfesser]

Nicodem - 14-3-2013 at 11:39

Though there are several examples in the literature of STAB being used for the dimethylation of primary amines with formaldehyde, this one is peculiar in that the substrate is a tryptamine for which NaCNBH₃ has been traditionally applied. Its good to have a checker for that procedure as most people prefer to endlessly speculate on the validity of whats published rather than go and do some real work.

I like the idea of the in situ formation of the reagent - it makes it more amateur friendly (even though STAB become widely available in the last years).

Now, to the low yield problem.
Was there a TLC spot at the starting point? If there was, the apparent mass balance can not be judged just from the disappearance of the starting material and minor spots of the side products. Things sometimes polymerize into TLC-immobile crap.
During the vacuum distillation, was there a nonvolatile residue?
Even stranger is the loss during the column chromatography. Did you weight the crude product before the column? Does the product trail on silica when using EtOAc/MeOH only (without added ammonia)? Some could have stuck on silica.
But seeing that you tried out two very different isolations and both gave you similar results, I'm more keen to believe that the low yield is due to crap formation rather than the losses during the isolation.

turd - 14-3-2013 at 22:42

Well, all things considered you are probably right. I had conversation via U2U with another person who reports the same isolated yields. Unfortunately, to find out what really happened, the experiment will have to be repeated since this was performed quite some time ago and my memories may be tainted by wishful thinking. I will hunt the depths of my freezer for remaining tryptamine, but first I'd like to finish two other projects.

The rest of this posting is from memory with support by my notes, so it may not be 100% accurate.

What I'm sure is that yes, there was lots of residue after distillation. I attributed this to (wishful thinking) scorching - the crude product was an orange, but not very dark, oil and after distillation it was the typical dark red oil. But we all know that colours don't mean anything.

I believe(!) there was no significant amount of product at the application spot of the TLC.

The problem with chromatography was that it was ineffective - I had to apply a gradient and the resulting pale orange oil did not crystallize, therefore it had to be crystallized from cyclohexane/pentane. Unfortunately it was not weighed before crystallization. There was a very pale yellow colouration of the column which coincided with the main fraction but there was no colouration remaining at the start of the column. And yes, of course ammonia was added.

Even if the dimethyltryptamine is only a side product, I don't think the main product is undefined polymer, but rather a dimer or an indole-N-alkylated thing. But unless this is repeated all of this is idle speculation...

And hey, it's very unlikely, but maybe I even encouraged someone to do independent experimentation.

bananaman - 15-3-2013 at 00:50

Amines are known to be rather polar, and would often stick to polar silica gel. Usually, there is a need basify the column with a base such as triethylamine to minimize losses, else, use a reversed phase packing material.

Additionally, consider salting the amines out using HCl gas or ethereal HCl.

salting spice

Meakanesis - 16-3-2013 at 20:47

GAA would be better for salting HCL would work so would gassing but acetic is often used with great success with this compound, making sure your GAA is very dry will result in a crash using dilute gaa will result in a tincture that can be used to measure out dose if done correctly, the nexus is your friend on this subject and i really think they would appreciate you dropping this in there.

hive3 - 31-7-2013 at 08:01

Quote: Originally posted by turd

All tryptamine was gone on TLC (EtOAc/MeOH 2:1 with NH3), minor amounts of side products (tryptamine: Rf~0.1, DMT~0.2).

thanks turd, Its nice to see a real confirmation of this process. What was the proportion of Ammonia used in the TLC?

[<a href="u2u.php?action=send&username=bfesser">bfesser</a>: fixed BBCode]

[Edited on 31.7.13 by bfesser]

turd - 4-8-2013 at 21:41

Quote: Originally posted by hive3

What was the proportion of Ammonia used in the TLC?

Sorry, it was a long time ago and I don't have that information in my notes. But I'm quite sure it was "a few drops" conc. aq. NH3 from a Pasteur pipette.

Quote:

Believe the sodiumtriacetoxyborohydride is created in situ from NaBH4 and the acidic acid.

Yes, but if you can use commercial triacetoxyborohydride directly, this is certainly the way to go. The reasons for the low yields are not yet established and it's a good idea to exclude as many variables as possible.

Edit: grammar.

[Edited on 5-8-2013 by turd]

Nicodem - 8-8-2013 at 01:01

All the numerous off topic posts in regard to the acquisition of STAB and synthesis of NaBH₄ were split into a separate thread. Please continue that discussion there and leave this thread only for discussions about the "Dimethylation of tryptamine via formaldehyde/STAB" topic.

megalodon - 23-8-2013 at 05:54

Looking at the reaction schema for STAB given at wikipedia:

https://en.wikipedia.org/wiki/Triacetoxyborohydride

it seems that a similar procedure might be able to produce diisopropyl tryptamine, DiPT. This is an interesting compound in that its psychedelic properties are primarily aural rather than visual. Would it be as simple as replacing the formaldehyde with acetone?

Another interesting possibility is methyl isopropyl tryptamine, MiPT. Perhaps this could be synthesized via STAB and a mixture of formaldehyde and acetone. Combinatorically, I would expect a half and half mixture of formaldehyde and acetone to produce a quarter DMT, a quarter DiPT, and a half MiPT. Acetone being more sterically hindered than formaldehyde, the ratios wouldn't be exactly that, probably depleted of DiPT and enriched somewhat in the other two. The mixture could be separated by chromatography.

Does this sound reasonable?

lullu - 6-2-2014 at 05:35

It could be possible that the reaction time for the in-situ preparation of STAB-H is the problem here.
see below:

Quote:

Sodium Triacetoxyborohydride. A 100” Schlenk flask equipped
with a Schlenk filter was charged with 186 mg (4.93 mmol) of sodium
borohydride and 50 mL of anhydrous benzene. The slurry was cooled
to 10 OC and 860 pL (15.0 mmol, 3.04 equiv) of anhydrous acetic acid was added dropwise so as to maintain an internal temperature no higher
than 20 OC. Hydrogen evolution was measured with a gas buret. After
addition of acetic acid was complete the mixture was allowed to warm
to ambient temperature and stirred at that temperature for 8 h. Hy-
drogen evolution had ceased at 330 mL (theoretical for 3.00 equiv is 331
mL) after 5 h. The colorless slurry was filtered and the resultant white
powder washed with three 20-mL portions of freshly distilled, anhydrous
ether. The combined ether filtrates did not liberate hydrogen when
treated with 1 N aqueous hydrochloric acid. The powder was held under vacuum over night to afford 961 mg (92%) of analytically pure sodium
triacetoxyborohydride as a white, hygroscopic solid: IR (Nujol) 2500,
1682, 1375, 1316, 1149, 1023, 962, 845 cm-I; ‘H NMR (250 MHz
CD3CN) 6 1.88 (s, 9 H, CH,CO,B); "C NMR (75.5 MHz, CDJCN)
6 175.25, 23.36; "B NMR (96.3 MHz, CD3CN) 6 -1.47 (d, JBH 122
Hz).
Anal. Calcd for C6HloO6BNa: C, 34.00; H, 4.76. Found: C, 33.87;
H, 4.79.

Directed Reduction of @-Hydroxy Ketones Employing
Tetramethylammonium Triacetoxyborohydride

D. A. Evans,* K. T. Chapman, and E. M. Carreira

Contribution from the Department of Chemistry, Harvard University, Cambridge, Massachusetts 021 38.
Received July 10, I987

Dr.Q - 26-2-2014 at 08:05

Could be the low yields because of the water. I want to the this reaction with only difference using paraformaldhyde.
Since i have limited amount of NaBH4 i wonder will paraformladhyde rise some problems if it is used beside formalin ? any ideas ?

[Edited on 26-2-2014 by Myeou]

*FWOOSH* - 13-3-2014 at 09:59

The problem you're going to run into with paraformaldehyde is that there will likely be no or minimal reaction. Formaldehyde tends to polymerize in acidic solutions, so with the GAA catalyst around it it's probably going to be very comfortable staying that way.
I've tried using paraformaldehyde as a formalin replacement in a similar reaction and was not happy with the results.

The poor yields are, as stated before I think, most likely due to pictet-spengler cyclization. Which, with tryptamine, occurs under even mildly acidic conditions in the presence of formaldehyde. It's basically a race between the borohydride and the proton to see who gets to reduce the molecule first

The cyclization product is extremely difficult to remove from methylated tryptamine without using chromatography.
Another possible side reaction is tryptamine being reduced to an indoline.

You can likely repeat this procedure with success, but follow it closely and expect to get diddly if you don't use a column to purify.

Just my two cents.

[Edited on 13-3-2014 by *FWOOSH*]

Dr.Q - 20-3-2014 at 01:20

Quote: Originally posted by *FWOOSH*

The problem you're going to run into with paraformaldehyde is that there will likely be no or minimal reaction. Formaldehyde tends to polymerize in acidic solutions, so with the GAA catalyst around it it's probably going to be very comfortable staying that way.
I've tried using paraformaldehyde as a formalin replacement in a similar reaction and was not happy with the results.

The poor yields are, as stated before I think, most likely due to pictet-spengler cyclization. Which, with tryptamine, occurs under even mildly acidic conditions in the presence of formaldehyde. It's basically a race between the borohydride and the proton to see who gets to reduce the molecule first

if it is because of acidic conditions how it is even possible %80 yield with cyanoborohydride and with the STAB-H...
You can easily find succesive reports on scifinder with over %70 yield with cyanoborhydride in acidic conditions.
Also for STAB-H link in first post.

Yes formaldehyde polimerize under acidic conditions but that compare to the our reduction reaction this will take much longer time and i think one of the reason that to add 30 eq. formaldehyde is this.

As you said it is race between the proton and borohydride. But i think since kinetically borohydride reduction reaction is far more faster that proton , there will be no time to proton to reduce the imine

[Edited on 20-3-2014 by Myeou]

madscientist - 14-5-2014 at 21:23

I agree that the Pictet-Spengler reaction is probably tanking the yield. There's a lot of misconceptions spread far and wide about it - it does work with ketones, for example, and a proton source is unnecessary (even Na+ can suffice). Reductive amination routes to N-alkyl tryptamines are usually problematic for this reason.

lullu - 10-9-2014 at 03:44

I stumbled over this and remembered this thread.
So hopefully it resolves the ongoing pictet spengler speculations:

from miamiechin

Quote:

5-Methoxy-N,N-dimethyltryptamine, 5-MeO-DMT
5-methoxy-tryptamine freebase (12.5 g, 63 mmol, 95% pure) was dissolved in MeOH (250 mL) and the solution was cooled to 0 °C with a ice/salt bath. There was then added, while controling the temperature to not go above 5 °C, in six portions espaced by 15 min : 5 g of 36% HCHO solution in MeOH (39% m/v) followed after 10 sec by NaBH4 (1.2 g, powder). Hence in total during 1h30 there was added 6 x (5 g 36% HCHO in MeOH + 1.2 g NaBH4) = 10.8 g HCHO (360 mmol, 6 eq) and 7.2 g NaBH4 (189 mmol, 3 eq). After each addition an exothermic reaction occur and the temperature must be controlled to stay under 5 °C. The conversion of 5-MeO-T to 5-MeO-DMT was complete under these conditions. The solvent was evaporated, water was added followed by NaOH until pH 12 and the residue was extracted with CH2Cl2. Drying over Na2CO3, filtration, washing with CH2Cl2 and recrystallization from boiling hexanes yielded pale yellow crystals (8.5 g, 62%), >99% pure by NMR and HPLC.

Quote:

By using neutral conditions and several additions of formaldehyde immediately followed by NaBH4 the pictet reaction has no time to occur and the procedure is remarkably straightforward. Just be sure to cool efficiently and do not allow the temperature to go higher than 5 °C to not have side products. There is no need to use NaBH3CN for this reaction anymore now!

Crowfjord - 28-1-2017 at 10:31

Likewise, in my research into reduction of the indolene double bond, I found a paper detailing the synthesis of the migraine medicine rizatriptan using N,N-dimethyltryptamine as an intermediate. The authors synthesize this intermediate via reductive amination of formaldehyde with tryptamine and sodium borohydride in methanol/water, similar to the above quotation posted by lullu.

Attachment: Novel rizatriptan synthesis.pdf (607kB)
This file has been downloaded 1170 times

Attachment: Rizatriptan supplementary material.doc (2.8MB)
This file has been downloaded 1054 times

stoichiometric_steve - 29-1-2017 at 10:25

Quote: Originally posted by Crowfjord

Likewise, in my research into reduction of the indolene double bond, I found a paper detailing the synthesis of the migraine medicine rizatriptan using N,N-dimethyltryptamine as an intermediate.

Just how trustworthy is this paper?

Crowfjord - 29-1-2017 at 12:30

I have heard that Tetrahedron's credibility is hit and miss, but the theory seems sound to me as far as the chemistry goes in the above paper. The reductive amination is at least corroborated by the write-up quoted by lullu above.

[Edited on 29-1-2017 by Crowfjord]

HollowMan - 18-7-2017 at 05:25

Someone tried Tetrahedron´s method?

(Patent of making Rizatriptan)

chemrox - 20-7-2017 at 13:10

I propose an alternate route bypassing the reduction step. Tryptamine, MeI (1.2 eq.) in acetonitrile with 1.5 eq of DPEA. It should take a little time (monitor with TLC). The DPEA should prevent the quartenary amine formation. Also I've seen writeups using para and ZnCl2 in Ch2Cl2 and 35% formalin in MeOH both followed by NaBH4 redux.

mackolol - 13-5-2020 at 05:35

from miamiechin

Quote:

Hi, I performed the procedure as described, but with this difference, that I used aqueous formaldehyde instead of methanol solution, but I don't think it should be a problem as borohydride is not very unstable in water conditions and there are similar procedures that use aq solution of nabh4.
After evaporation of methylene chloride I was left with brown oil totally insoluble in naphtha, which means that it is not alkylated tryptamine (DMT should be soluble in hydrocarbons). What could cause the problem, maybe somebody had successfully performed such synthesis?

karlos³ - 13-5-2020 at 09:02

I read that synthesis is regularly performed in amateur labs with yields above 80%.
And they even discuss that on a forum dedicated for this specific kind of amateur chemistry, you can surely find it easily, but you need to register since said forum is not open to the public.
DMT and soluble in naphtha? It is badly soluble in hot naphtha, yes.
Did you do any test to check the composition of the brown oil?
Because it works.
I think you DMT is just really dirty, maybe distill it first?

TheMrbunGee - 13-5-2020 at 11:12

Quote: Originally posted by karlos³

I read that synthesis is regularly performed in amateur labs with yields above 80%.
And they even discuss that on a forum dedicated for this specific kind of amateur chemistry, you can surely find it easily, but you need to register since said forum is not open to the public.
DMT and soluble in naphtha? It is badly soluble in hot naphtha, yes.
Did you do any test to check the composition of the brown oil?
Because it works.
I think you DMT is just really dirty, maybe distill it first?

Are You sure those are not extractions, not synthesis. Extraction is easy, materials are available, I do not see a need for synthesis.

@ Few gram scales DMT is soluble enough, and quite selective for purification means. Trying to distill it would be enormous shot in the dark. Also, I don't think mackolol had more then few grams of final product.

And for what could the product be - Insolubility in naphtha, assuming You know Your naphtha is in fact - naphtha You think it is, confirms that it is not DMT. Guessing is not my strong side in OC.

mackolol - 13-5-2020 at 11:58

Quote: Originally posted by TheMrbunGee

Quote: Originally posted by karlos³

I just want to explore chemistry behind it. So what does the scale mean if it's less than few grams it is worse to purify? And could my product be so poor quality that it doesn't behave normally?

karlos³ - 13-5-2020 at 12:17

NaBH4 reduction of tryptamine, with formaldehyde.
But yes, it is followed by an extraction afterwards, so... both?

Reductive amination is much easier and you don't need to deal with obscenely large volumes for tiny bits of product, you can do that very convenient in a small flask instead.
And not only the dimethylated tryptamine, you can a lot of sorts of alkyl groups via reductive amination, try that with an extraction.

A few grams, are there limits for the amount below which a proper purification is not needed?
I purify everything, a few hundred mg's, or a few dozen grams, I don't understand?
Especially when it is a dirty oil like he described, wouldn't a proper purification be in order especially in such a case?

The sentence with the naphtha, I don't understand what that means.

I know many people who used that reaction successful.
Extractions, I don't see the need for, where would one even get the plant matter, and isn't that stuff expensive and illegal or controlled?
I don't know if someone I knew extracted a tryptamine lately, guess not, at least not from a natural source?

[Edited on 13-5-2020 by karlos³]

TheMrbunGee - 13-5-2020 at 13:22

Quote: Originally posted by mackolol

I just want to explore chemistry behind it. So what does the scale mean if it's less than few grams it is worse to purify? And could my product be so poor quality that it doesn't behave normally?

I meant that if it's more, than it is harder with naphtha, because solubility of DMT in 50°C is roughly 2g/100ml, which is perfect for 2g extraction, but quite a small amount if one wants to dissolve 100g of the stuff, which is one of the little reasons to do synthesis instead of extraction. But as You said, exploration is one more, which is enough on it's own. What I can say is if sugar does not dissolve in water, it ain't sugar. (or it ain't water.

)

Quote:

karlos³

It all depends on why one needs the DMT. I can't say much about synthetic DMT, but when it is extracted from a plant matter single crystallization from hot naphtha with less than a few % lost, result is really pure DMT, impurities being harmles if not introduced by solvent. There are plant matter containing close to 2% DMT. If substance is needed for personal use, a 1l scale extraction usually suffices.

If one needs it for further reactions, sure, go synthetic.

So what I am saying is, naphtha is an excellent solvent for DMT, but for small scale. And in subzero temperatures solubility of DMT in light naphtha goes negligible, which means little losses and reusability.

And plant matter is available widely, and there are many plants containing extractable DMT, but few are quite packed (2%), not legal in many places but some. Prices are about twice of NaBH4 compared with extracted DMT gram per gram. Including every other component of extraction.

And extractions are done completely house-hold. Dudes with little chemical background writing extraction write-ups like top write-ups here.

So I really don't see a reason for synth, other than being curious for chemistry or making bulk, for selling.

[Edited on 13-5-2020 by TheMrbunGee]

karlos³ - 13-5-2020 at 14:52

Preservation of nature?
Less solvent fumes given off in nature too(naphtha, yeah maybe well, but not for extraction of an already much cleaner reaction mixture, we need something effective there and not selective, don't want to throw around liters of fluid).
Also, what do you pay for NaBH4?

I think you have no accurate depiction in mind of this.

Cou - 13-5-2020 at 18:00

Weird that DMT is illegal, when it's so unimaginably horrifying that after one huge dose, you're literally physically incapable of smoking it again because the fight or flight tremors prevent you from holding the pipe to your mouth.

DMT is very serious stuff. You could be sent to your own personal hell for what feels like years.

I think people are only interested in DMT because it's illegal. A forbidden fruit thing. If hallucinogens were available on the shelf, people would try it once, go "wtf why would someone want to mess with their brain like this" and never touch it again.

[Edited on 14-5-2020 by Cou]

karlos³ - 13-5-2020 at 18:29

I have right now my shirt on where I printed a DMT molecule on.
So, I obviously have the authority as a qualified expert to say something wise and thoughtful to your reply, Cou.
People can see that because of the shirt of course.

Usually it is true that the curious but not as enthusiastic explorers of the mind have a saturation limit.
And in case of intravenous injection, I remember that there is even a consensus how many experiences are enough for a lifetime, because of the guaranteed breakthrough experience if the dosage is right.

I had a friend who made it(not from tryptamine, from indole) and as a nonsmoker he saw no other option than injection of the fumarate.
Four times.
He could describe almost nothing, you saw how he grasped for suitable words and failed, and I'm talking about a well cultured man with 2 Ph.D.'s, a skilled piano player and one of the top clinical pharmacologists at Merck in his fifties, at the time...
Barely have you ever seen him with a look of utter incomprehension, unable to explain something, unable to comprehend something himself.
Not even "was it good?", well, it definitely "was", but besides that?

I liked that look, because from my own experiences smoking that stuff I remember similar little and can't neither verbalize anything.
And, which confirms that personal limit, I think the last time I've used that stuff... must have been 7-8 years ago.
I don't feel compelled to repeat it.

But I think that everyone benefits from such an experience.
Personal hell?
I really disagree with, harmless people like us here, who have more doubts and feelings of self-guilt and what not, usually don't experience a real horrible time ever, even if those expect that most often, yet the drug won't kick them in the butt in a bad way.
But give it to one of those self confident, ever grinning politicians in a suit... it will rip them apart and throw all the pieces on a pile, leaving a broken and shattered "human".
Really for those it should be mandatory. "You want political power? Ok, smoke this stuff first, we'll ask you again after".
Corruption would be gone in no time!

TheMrbunGee - 13-5-2020 at 23:29

Quote: Originally posted by karlos³

Preservation of nature?
Less solvent fumes given off in nature too(naphtha, yeah maybe well, but not for extraction of an already much cleaner reaction mixture, we need something effective there and not selective, don't want to throw around liters of fluid).
Also, what do you pay for NaBH4?

I think you have no accurate depiction in mind of this.

In what way, I am now more confused about why would one need more than few grams of substance, as I don't think anyone should sell this on streets. (There would not be many takers anyway, and there are many other reasons not to do so.)

And for the fumes- as some of naphtha is released in atmosphere:
1) It is all extracted from earth to begin with. Literal tons of these hydrocarbons go in atmosphere by natural means, and many times more by industry.
2) The drop of solubility means one does not have to boil off the solvent.
3) For 2nd point - you can reuse the small amount.

Yes, sorry, had a different price for borohydride in mind. Anyway one can pay 20 euros for a plant matter where a gram of DMT can be extracted.

An for the friend of Karlos, IV feels like roughest RoA, one can make the DMT orally active, or vaporize it. But that is just my personal view on needles.

Syn the Sizer - 13-6-2020 at 01:46

I am curious, I do not plan on trying to synthesize any tryptamine but I am interested in a couple aspects.

1 is, melatonin is N-Acetyl-5MeO-tryptamine, you can de-acetylate it to 5-MeO-tryptsmine with NaOH.

Again this is to understand the science, I do not plan on synthesizing any drugs, but Alexander Shulgin has written some great documents in organic chemistry.

After de-acetylating the N group, would MeI methylate the N group to produce 5-MeO-DMT?

question 2 is has 5-MeO-DPeT, 5-methoxy-dipentyltryptamine been explored?

Again, I DO NOT want to synthesize these compounds, I am just curious about the science.

If you wish to U2U I am fine with that.,

mackolol - 13-6-2020 at 04:20

Quote: Originally posted by Syn the Sizer

I am curious, I do not plan on trying to synthesize any tryptamine but I am interested in a couple aspects.

1 is, melatonin is N-Acetyl-5MeO-tryptamine, you can de-acetylate it to 5-MeO-tryptsmine with NaOH.

Again this is to understand the science, I do not plan on synthesizing any drugs, but Alexander Shulgin has written some great documents in organic chemistry.

After de-acetylating the N group, would MeI methylate the N group to produce 5-MeO-DMT?

question 2 is has 5-MeO-DPeT, 5-methoxy-dipentyltryptamine been explored?

Again, I DO NOT want to synthesize these compounds, I am just curious about the science.

If you wish to U2U I am fine with that.,

5 MeO tryptamine behaves the same as regular in matter of dimethylation. There are even procedures in this thread that call for 5 MeO tryptamine, but can be used with plain tryptamine. If 5MeO could be dimethylated with just MeI, the procedure with formaldehyde/borohydride would be unnecessary and even useless.

And for the melatonin, you can make 5 MeO tryptamine from it easily here's the link: https://erowid.org/archive/rhodium/chemistry/mexamine.html

DrIronic101 - 14-6-2020 at 10:36

Quote: Originally posted by Syn the Sizer

Methyl halides are able to methylate the amine. The problem is that, unlike the Eschweilier-Clarke reaction, methyl halides usually always form the quaternary ammonium salt. In this case, N,N,N-trimethyltryptammonium halide.

If you look at TiHKAL #6, Shulgin uses methyl iodide to form the N,N,N-trimethylammonium iodide. In order to get it to the N,N-dimethyl, he uses two distinct methods:

1. Plain reduction of the iodide salt with lithium triethylborohydride.

2. A replacement-type reaction with AgCl to form the chloride salt, then pyrolysis of the chloride salt under hard vacuum. Anyone who can find another example of this sort of reaction (pyrolysis of quaternary ammonium salt) gets 12 cookie points.

njl - 14-6-2020 at 11:03

https://www.tandfonline.com/doi/abs/10.1080/0030494800935648... like this?

Syn the Sizer - 14-6-2020 at 12:21

Interesting

karlos³ - 14-6-2020 at 13:45

Eh, you can just boil the quaternary ammonium salt in ethanolamine to demethylate it.

mackolol - 15-6-2020 at 01:43

Quote: Originally posted by karlos³

Eh, you can just boil the quaternary ammonium salt in ethanolamine to demethylate it.

I doubt that it works with tryptamine. I haven't seen any successful try on it in internet. Just one or two guys who just screamed that it has worked for them and no specific data neither any reply from them. For me it didn't work, after pouring water in, I was left with unchanged quaternary salt.

Opylation - 18-5-2021 at 00:33

I’m probably going to get flack for posting this again, since I just posted it a day or so ago in another thread, but after reading the last few posts on here I felt compelled to share this paper. It’s about the demethylation of quaternary amines using sodium sulfide or potassium thioacetate

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