I wanted to make some more THH and needed a new load of Harmalas. I was using different sources on about at which pH I need to stop freebasing ... my old protocol (retrieved from somewhere here) told to stop at pH 7. That is just neutral and therefore I was wondering if indeed you can already freebase a huge load even in the acidic range (pH 6,5 -> 7). Then the VDI Protocol was not somewhat clear, but those complicated diagrams seemed to show that you should slowly freebase until 7,6 to get mostly pure Harmalin.

I used a pH electrode and calibrated with 3 points before doing the separation, but man ... even at pH 7,6 there was no precipitation.

So I went rather freestyle and just throw inside a huge load of NH3 in increments. After every load I I exchanged the pot and collected that fraction. I got 4 in total, but because I did not even dare measuring same amounts of NH3, the total amount of every fraction was completely random. To then have a chance to know which one I might use for THH conversion, 1H-NMR spectroscopy was conducted. That post here now is rather just informative as I have that data anyways.

Still it shows that at least i nmy case even at the beginning the Harmine precipitating is not completely pure. But I have to add, that this might also come because of just dropping a huge bomb of NH3 inside: In the respective volume element the amount of Harmaline might drop so fast that then freebasing of Harmaline (which only should appear later) will also occur, as there is no other Alkaloid to be freebased instead. The perfect way would have rather included stirring the solution at the absolute maximum, while only dropping NH3 inside at the absolut minimum.

So while it might be possible to precipitate the Harmine more carefully, it could still be used as a reference for kitchen chemistry, as people might also more do the ghetto method like I did, rather than titrating their Harmine with 1 ml NH3 / minute.

There are 3 ways to identify the different Harmalas and calculate the ratio from that:

I. ratio of the indolic NH-signals #1
= bad as these protons are loosely bound and their integral not to be trusted too well

II. occurence of additional 2x sp2 R-CH=R units from Harmine (position #6 + #7) at 7,80 ppm and 8,15 ppm
= better than I. in terms of reliability, but it can be even better

III. ratio of R-CH3 peak of Methyl #4 at 2,26 ppm (Harmalin) and 2,73 ppm (Harmin)
= good, but might be hidden with trance impurities

IV. ratio of MeO-R peak #14 at 3,80 ppm (Harmalin) and 3,89 ppm (Harmin)
= Signals are partially mixed, so not perfectly accurate, but well enough to give a +- 5 % ratio I just assume.

Actually I. and IV. are so remote from the actual structure unit that is changed between both, that it should have no influence on the signal anymore ... but seems like it still can have indeed, good for us.


Now all the NMRs are not posted here. I only took the time to align the signals to the structure to the first one. But just refer to this one to identify the rest. To see spectrum, just click on the name.

Fraction I
= 31 % of total precipitated Alkaloid content
= 89 % Harmin

Fraction II
= 31+16 = 47 % of total precipitated Alkaloid content
= 77 % Harmin

Fraction III
= 47+13 = 60 % of total precipitated Alkaloid content
= 25 % Harmin

Fraction IV
= 60+40 = 100 % of total precipitated Alkaloid content
= 16 % Harmin

Sidenote here:
Again no Vasicin can be seen. We would easily identify it at ~ 4,50 ppm with a Singulett, Integral = 2 which is derived from the middle ring R-CH2-N Unit. It's not here so I conclude no Vasicin present. And that is important because I did not do any Manske and just went with

1. Cook at pH 3
2. Basify to pH 11
3. Wash until neutral

That is a much faster way than doing the re-precipitations for multiple cycles and as I would say based on that spectrum are not having any benefit, when excessive washing also leads to no Vasicin present (if it was present at all ...).

Now here is just a small graph showing everything:



So what I can say is that at least in my case the separation seems not to happen in such perfect windows, but it's probably ok as a good starting material for THH conversion. Also at first these points may seem a little random, therefore I also added a sigmoidal curve fitting to illustrate what is actually happening. Now you can clearly see how the content of Harmin is high at the beginning and then quickly drops at around 54 % in favor of Harmalin. But to really identify the ratio between both the NMR of the combined extracts must be measured like here, which shows roughly a 1:1 or at maximum 1,05:1 of Harmin:Harmalin.




Now a small funny anecdote last:

I just took a look at those NMR samples again after a few days. And I saw something weird. To me Harmalas have always been a little boring in a chemical sense, bad solubility, low reactivity (Once by accident I roasted Harmalas for 10 h at 160 °C and nothing happened). It took even quite a while to dissolve 10 mg Harmalas in 400 µl DMSO at 70 °C, but now after those days I saw some precipitate again. Well not too crazy, but it was WHITE:



So I did not remove DMSO so far and maybe coloration will change a little. But I was thinking Harmalas are always tan? And that NMR does not show any major impurities, so it must be the Harmalas itself?

Would be funny if that tan colour is just some remainder from the seed extraction. Will now just throw like 100 mg Harmalas in boiling DMSO and see how it looks after several days ...



PS: THH purification is further down.

Thanks once again for sharing your data - your contributions are immeasurably important.

Now I'm looking forward to your DMSO harmala recrystallisation report

I am actually checking every day how things are going

First 2 days nothing happens but since monday these grow bigger and bigger. Sadly not that white, but instead also long needles - but Freebase and not *HCl.

Tried to wash that other stuff off with Hexane in the NMR Tubes, but seems like the DMSO still contained too much Harmalas to make it insoluble with Hexan and so it just formed a glue around those ... had to toss it and now hoping that I might still get same colour Harmala Freebase Crystals. Maybe these are darker now due to the much higher concentration used now.

Thanks for sharing!

But hey, unless I´m missing something, isn´t it the other way around, harmine precipitates at lower pH therefore would be at your earlier fractions, while harmaline would precipitate later?

That's what I was wondering too - having thought that the logical order for basicity would be H < DHH < THH. Or do effects from aromaticity somehow mean that it goes DHH < H < THH?

Not quite to do with harmalas, but relevant to DMSO and indoles such as DMT is this:

https://sci-hub.ru/10.1055/s-1979-28645
"A simple general method for the oxidation of indoles to oxindoles" Szabo-Pusztay & Szabo, Synthesis 1979 (04), 276

Indoles with DMSO and HCl oxidise in the 2-position - something worth bearing in mind generally, perhaps.

Oh no completely right!

Thanks for clarifying ... I always screw these 2 over. It went even so far that I already did the THH conversion with HARMIN

Wanted to do this as my last Harmalas sourcing and now I will have to get those again and repeat. What a bad awakening this morning

But besides inside of text now corrected.

Just switched every Harmin / Harmalin - but regarding those Signals at 6,7 ppm / 7,43 ppm it is not the new aromatic signals of Harmin, but just the same which we see for Harmin of Harmalin, just shifted a little due to different structure ...

New picture has every single signal connected to the structure so now any misconception should be not possible anymore.



Oh well ok indeed. But I am sure my stuff was washed neutral before adding anything in DMSO. Still something to keep in mind for sudden weird Harmala behaviour.

So now made a picture of these and sadly they are brown, but still crystalline. Concentration was much higher, maybe the white colour was only if much more DMSO is used? Still long needles and Freebase:

Beautiful crystals, thanks for sharing!

Now made a new *Tracking [...] with NMR*. As that whole Harmalas were just for the sake of making THH again, I tried to get towards completely white THH and checked the purity of the respective sample after each step.

Nothing great to show, more just to share data which I have now anyways. Those numbers give the order of processing from what I was left in the first post to some white THH.

1.)
Used sample from batch #4 from first post, which contained 16:100 Harmin:Harmalin - picture.
purity ~ 86 % Harmalin

--> Super annoying that I first thought Harmalin would be the first batch, now that other REAL Harmalin contained a little more of the unwanted Harmala Alkaloid. But well 16 to 100 is still not much.

2.)
Made THH conversion, 3 h of stirring at RT in Zink + Acetic Acid. Crude Product contained 16:100 Harmin:THH - picture.
purity ~ 86 % THH

--> It would be possible to quantify the ratio also with the same signal like first post (#14 at 3,8 ppm), but with THH there is a new signal at 4,0 ppm at that makes stuff less reliable here. Instead the Ratio of aromatic signals was used.

--> Interestingly the Ratio of Harmin : X did not change. As yield is mostly 70 % and 30 % of Alkaloids are always lost, I would have guessed maybe the ratio would have changed as probably 1 alkaloid would undergo stronger whatever process makes it disappear. Instead the same amount Harmin/THH "gets lost" when performing that reduction. Note that sadly it's hard to determine if any Harmin "is hiding" below the THH. As they share mostly the same signals. But combined signals (6,60 ppm / 6,81 ppm / 7,2 ppm) vs. THH-only signals (4,0 ppm) are quite 1:1 so probably only traces of Harmin present, if at all.

3.)
First re-x in boiling Ethanol. Solubility data is now added here. First checked only the composition of the remaining liquid, which should be enriched with Harmin now. So this is what you would THROW AWAY as the liquid decanted from the freezer crystals. Mixture contained 34:100 Harmin:THH - picture.
purity ~ 75 % THH

--> I was hoping for a much more enriched Harmin mix. But sadly solubility of THH at - 20 °C Ethanol is still quite high. So while you may purify your precipitates, you will still loose quite a lot of THH within the remaining EtOH at - 20 °C.

4.)
Second re-x in boiling Ethanol. Again checked the composition of the remaining liquid. Mixture contained again 16:100 Harmin:THH. So this is what you would THROW AWAY as the liquid decanted from the freezer crystals. Already less staying behind in Ethanol, due to losing most in the first step, but still a lot of THH that would go down the drain when not recovering - picture.
purity ~ 86 % THH

5.)
Second re-x in boiling Ethanol. This time also directly checked the purity of the precipitate. Precipitate was clear white crystals, which contained ~ 2:100 Harmin:THH - now shown directly here:
purity ~ 98 % THH:



--> seems like 2x re-x must be done to get rid of all the Harmin, when starting with 10+ % Harmin like in my case. Probably needed as solubility of both are not too different. Now that stuff is really white, but if you dont salvage the remaining stuff from the Ethanol, seems like not worth the whole process like in my case to just remove *16 Harmin out of 100 THH*. Moreover, THH would be broken up by MAO-A/B anyways? So it would even give a potency/duration boost, if making any interaction at all. So unless you want really white THH I guess there is no real reason to loose that much THH for nothing. Also as I wrote above that Harmala-Separation was quite freestyle and ineffective, so people might end up with only 5:100 Harmin:Harmalin for step 1.) and then final product might be already just yellow-white.




Made this THH again to just eat some more of those ... I made already some trials years ago, but just picked up some interest again. Will report soon.


Pictures attached are some microscope images of that last sample. As usual always 2x pictures per 1x crystal because of both illumination modes.

So I was always curious about the effects of THH, as it was not only told to be a mood brightener (due to SRI activity), but also some miraculous things written across the forum:



That sounds pretty epic, but it's an information from 69ron, who was known to advertise THH and then sell some 'fake THH' (Harmalas + traces of DMT) on a website, if I am not wrong with this information.



THH I ate in the past:

1. ~ 2018 ate 300 mg. Did not feel anything (but maybe it was just Harmin again due to my mistakes of interchanging the Harmalas )

2. ~ 2022 ate 400 mg. Did not feel anything (but maybe it was just Harmin again due to my mistakes of interchanging the Harmalas )

3. Now I made some new THH and prove identity first. So I ate 500 mg of the unrefined mix with 16 % Harmin. That should be

420 mg THH
80 mg Harmin

Drank that down with a 'Doppelbock' which already gave me a slight buzz. So after 1,5 h I just had the feeling that I had a little buzz from that drink ... nothing more felt.

But then this effect lasted for 4 h so I was then sure it came from the THH.

Effect was relaxed / sedated / dreamy ...

Quite enjoyable to just sit on my sofa with gentle music and do nothing.

Still ... just the same effect as drinking 3 beer No real psychedelic effect or any OEVs / CEVs at all.

Therefore as it just felt like a little alcoholized I think those 420 mg THH were not worth all that work, considering that had quite a resemblance to drinking 3x beer (which can be 1 € in Germany).

Still it was written that THH could be a strong amplifier for other psychedelics. Might try that but if taken alone that was not too interesting :/



Still will try to smoke it soon and see how it will feel with some brute-force-administration.

This matches my experience. THH is extremely gentle, feelings are very subtle. A light enhancement of a meditative state.

However, it really enhances DMT.

The combination of harmine/THH/DMT is divine. I take 20mg Harmine, 20mg THH sublingually. After 20 minutes I vape DMT citrate in e-juice (roughly at neutral pH with one part DMT and 1/3 parts citric acid). It is beautiful and heavenly in my experience ❤️

I think that 69ron claims were mostly just ads for his product.

IMO harmalas are most effective sublingually, much lower dose is needed.
Their full effect can be felt in combination with other substances, alone it is quite subtle experience (of course harmaline is quite different)

Thank you for information about ethanol re-x, it is very useful.

Still seems somewhat wasteful, as both have nearly the same solubility . So you need to overshoot with Ethanol to keep all the Harmine in solution. Therefore of course only working with excess mixtures of THH:Harmin.

But of course people could just evaporate that residual EtOH and just get

1x Mix with less Harmine
+
1x Mix with more Harmine

And not loose anything.

Also is there any information if THH is also metabolized by MAO-A/B? That constrained structure already looks suspicius of causing some different enzyme interactions, but as it is also not a MAOI itself, does it even have any interaction with those MAOs ?

Guess in any case leaving that Harmine inside will not make problems, just will always be slight yellow.






That still sounds pretty epic. So I was checking if any less-material administration might be worth a try and tried the vapor method.

50 mg THH were vaporized within ~ 10 min.

Divided that whole powder into 4x portions of ~ 12 mg.

Effect:

none ...

Sadly did not feel any real effect compared to that eaten 420 mg which was definetly very dreamy.

But have to say that even if I tried holding that vapor for at least 15 sec, there was always a HUGE cloud coming out of my mouth when exhaling. So seems like lung absorption is really poor ... probably therefore minimal efficiency when smoked. Such a pity, as it is vaporizing quite nicely.

At least my banger lid looked quite funny after vaping Quite a bunch of material stuck there, but could not vape it faster due to holding breath even longer than 'normal'. Picture attached.

PS: Of course I made the mistake again At 3. and 4. it's of course HARMIN and not HARMALIN. omg will never learn it

More pictures of crystalline semi-white Harmalas from DMSO re-x. Still some brown liquid around them, but not sure how to remove. Water does not work, because the last brown DMSO is fully saturated on Harmalas and will not mix, but form a goo in water and organic solvents might dissolve the delicate crystals. Hexane does not mix with Harmala-saturated DMSO ...

Anyways some cool crystals floating around. Quite a difference to "normal Harmalas". Check the cool geometry of the big rock in picture 4 giving some orthorhombic vibes

Mmm, almost sugary

To recap, this was harmala freebase?

I suppose if you value purity over yield you could keep repeating the process with ever-diminishing measures of fresh, hot DMSO.