Tetrahydroharmine purification struggles

[blue.magic]

Yesterday I've made some tetrahydroharmine (THH) using the zinc-acetic reduction.

I filtered the THH solution (to remove zinc), basified with 20% sodium carbonate, filtered again, washed with distilled water.

I had quite some concern about zinc carbonate contamination, so I wanted to dissolve the damp THH freebase in isopropyl alcohol and filter (since alcohol will dissolve THH but not the zinc carbonate).

To my suprise, THH freebase does not seem to dissolve at all in the alcohol (see the image) - it just sits there, not dissolving at all. No stirring or heating helps.

I think this is because of the little water in the damp THH, maybe. I am not drying the THH - it already took over 7 hours of drying and it is still damp and wet. I have absolutely no idea what happened It looks like it complexed with the alcohol, or maybe adhered to the salts somehow... I don't know.

I experimented with THH in the past, but the possible zinc impurity concerns me as it renders the compound food-unsafe. Many zinc compounds are claimed to be quite toxic.

Unfortunately, zinc behaves similarly to the alkaloid in terms of solubility. After acid treatment, it is water soluble (zinc acetate, zinc chloride etc.) and after base treatment, it is insoluble (zinc carbonate, sodium zincate etc.). The only way to remove it seems to be the use of alcohol, but so far this does not work for me either... I'll see after the drying completes though.

 

[Auxin]

Zinc chloride is highly soluble in water, a manske will crystallize out THH hydrochloride while leaving zinc acetate/chloride in solution.

 

[blue.magic]

Zinc chloride is highly soluble in water, a manske will crystallize out THH hydrochloride while leaving zinc acetate/chloride in solution.

I've read on several places that THH.HCl does not crystallize from solution like harmine/harmaline. Plus, I found nothing when trying googling this...

The problem is the crystallization adds more time to already extremely time consuming process of harmala production. The THH produced is pure enough, so it makes sense to just separate the possible zinc impurity by the means of solvents.

According to the VDS paper, they successfully recrystallized THH from ethanol, so maybe I will try ethanol instead of isopropanol. I've just read in one forum that someone used IPA to dissolve THH, but who knows ...

Another reason for me being tempted in using alcohol is that after filtering, not only zinc carbonate is removed, but I can rapidly convert THH to the HCl salt by simply adding hydrochloric acid and rotavapping off the ethanol.

 

[blue.magic]

Most of the dried THH freebase powder does not dissolve in absolute ethanol, which is really weird. It should mostly dissolve...

It might mean there is a serious zinc carbonate contamination

Maybe it would be worth making a dry run (without harmalas) and see if how much zinc carbonate gets formed by the addition of sodium carbonate into zinc acetate solution...

But now I guess I will revert to dissolving THH in water and trying to crystallize from water as was suggested even though I have not found any reference that Manske work for THH (quite the contrary).

Maybe ammonia is better for freebasing THH. But what is a reaction of ammonia with zinc acetate? Wouldn't it also create some kind of insoluble salt or complex?

 

[Elrik]

Its well established that THH hydrochloride can be crystallized in high yield by a manske style salt precip. It was examined in the VDS verification thread, among others. Its solubility parameters are very much like those of harmaline. I've always worked with my THH as mansked THH hydrochloride dihydrate to very good effect.
The only ambiguity was a single report of failure by someone using an unspecified procedure on purchased material like 15 years ago, which most likely wasn't even THH. Modern attempts to manske THH have worked.
If ammonia is slowly added to a zinc acetate solution a haze of zinc hydroxide precipitate can form before the ammonium ion concentration gets high enough to complex with the zinc and form a water soluble ammonium complex. Upon further addition of ammonia the zinc haze vanishes. If the zinc acetate solution is pre-loaded with soluble ammonium salts, like 5%+ ammonium sulfate or ammonium chloride, then the haze never forms. This is based on trials done by myself and others.
Harmalas should be precipitated with hydroxides, not carbonates. Even if there is no zinc, precipitating with carbonates can be messy.

 

[Mindlusion]

To my suprise, THH freebase does not seem to dissolve at all in the alcohol (see the image) - it just sits there, not dissolving at all. No stirring or heating helps.

I think this is because of the little water in the damp THH, maybe. I am not drying the THH - it already took over 7 hours of drying and it is still damp and wet. I have absolutely no idea what happened It looks like it complexed with the alcohol, or maybe adhered to the salts somehow... I don't know.

THH is soluble in ethanol, what you have is not THH but a mixture that is heavily contaminated with zinc salts.

Zinc salts are often difficult to remove, even by filtration and liquid liquid extraction, because many of them are easily soluble in a wide range of non-polar solvents.

This is why it is necessary to use ammonia to solubilize the zinc salts in the aqueous layer. the zinc ammine complex is very soluble in the aqueous and the freebase precipitates can be isolated free of the zinc salts, especially after washing with aqueous ammonia.

This is the reason why ammonia is used as a base, there is a reason for why its used and not other bases. All of this info is here on the nexus too

 

[blue.magic]

This is why it is necessary to use ammonia to solubilize the zinc salts in the aqueous layer. the zinc ammine complex is very soluble in the aqueous and the freebase precipitates can be isolated free of the zinc salts, especially after washing with aqueous ammonia.

Thanks! I've read just part of the threads but I suffer with an information overload. I am not much of a forum fan as the information is scattered around threads and I usually look in academic papers or websites.

I was wondering why ammonia was used in the VDS paper, especially since I believed ammonia forms precipitate with zinc (I've read on some chemistry textbook that it is actually used to detect Zn2+ ion as it forms precipitate) - but then I found exces ammonia dissolves the precipitate. Thanks for pointing that out.

Okay I will redissolve everything (water), basify with ammonia, wash with more ammonia, ten dissolve in ethanol, acidify and finally evaporate off the solvent.

 

[Mindlusion]

This is why it is necessary to use ammonia to solubilize the zinc salts in the aqueous layer. the zinc ammine complex is very soluble in the aqueous and the freebase precipitates can be isolated free of the zinc salts, especially after washing with aqueous ammonia.

Thanks! I've read just part of the threads but I suffer with an information overload. I am not much of a forum fan as the information is scattered around threads and I usually look in academic papers or websites.

I was wondering why ammonia was used in the VDS paper, especially since I believed ammonia forms precipitate with zinc (I've read on some chemistry textbook that it is actually used to detect Zn2+ ion as it forms precipitate) - but then I found exces ammonia dissolves the precipitate. Thanks for pointing that out.

Okay I will redissolve everything (water), basify with ammonia, wash with more ammonia, ten dissolve in ethanol, acidify and finally evaporate off the solvent.

Sounds good, you should be able to recrystallize the HCl in ethanol too if you want.

Yeah it is a bit of information overload, i think the VDS thread is something like 50 pages long. A bit too much for someone looking for a procedure and key details of it.

 

[blue.magic]

Yeah it is a bit of information overload, i think the VDS thread is something like 50 pages long. A bit too much for someone looking for a procedure and key details of it.

Yes this is exactly why I am making a detailed writeup on extraction from seeds to pure alkaloids. The teks in Wiki really need a refresh. I will post it soon for the community to proofread and suggest fixes, improvements etc.