Harmine, harmaline and THH from Syrian Rue. Verification and finetuning of the VDS-protocols

[An1cca]

...The conclusion is that an ammonia-free route to THH synthesis IS possible by first precipitating the Zinc-ions as carbonate with sodium BIcarbonate, filtering them off and then precipitating the THH out of solution with sodium carbonate. That is, if THH is not precipitated by sodium carbonate (as is indeed suggested by the experiments of VDS)...

The underlined should be sodium BIcarbonate I presume. I had myself edited so often, these words mingle up so easily LOL.

Exactly :d

1) a route of strict minimal fuzz, the fast way, no separation steps, reducing harmine+DHH into harmaline+THH...

I presume you mean converting harmine+DHH into harmine+THH? Apparently harmine can not get reduced by zinc-acetic acid. VDS tried this.

I think we're getting somewhere, Jees! :thumb_up:

Can any of the Nexians check the separation of harmine and DHH with sodium bicarbonate? This is a low-tech accessible technique that seems to work when repeated a few times...

 

[DreaMTripper]

Looking at it all I see no reason to use ammonia/ammonium just careful additions of NaOH to precipitate THH after the first separation of ZnCO3 (possibly cadmium carbonate too) and harmine.
Maybe I missed something, is there a problem using just NaOH to precipitate THH?

Re pka "Harmaline and harmine were found to have pKa values of 9.55 +/- 0.04 and 7.45 +/- 0.03, respectively."
Ionization processes of some harmala alkaloids - PubMed
So sodium bicarb should be able to separate I believe it can raise pH to 8-9.

Re: cadmium, it has very similar properties to Zn, the same charge, the same column on the periodic table therefore it is
likely to behave very similar and precipitate out of solution as cadmium carbonate (CCdO3) Cadmium carbonate

 

[An1cca]

DreaMTripper, I expect no troubles precipitating THH with lye after sodium bicarbonate has pulled the zinc ions out of solution. However, it just seems safer to use ammonia or sodium carbonate...

 

[Jees]

...I presume you mean converting harmine+DHH into harmine+THH?...

Yes lol, those little peskey typing errors.

 

[An1cca]

Some updates on the Zn-precipitates:

The precipitate from sodium carbonate basification was flocculent, difficult to filter (clogging but also passing the filter), gel-like and difficult to dry. At the moment, it looks like little off-white rocks. Nevertheless, it reacts with vinegar to form carbon dioxide, strongly suggesting it is (a form of) zinc carbonate: 'dry' weight: 1330mg (from 536mg of reacted zinc that should yield 1028mg). So obviously, the powder isn't really dry and by looking at it, is not likely to dry further without heating.

On the other hand, the precipitate from the bicarbonate basification was cloudy to powdery, easy to filter and drying quickly to a snow-white powder. Dry weight: 1098mg (from 520mg of reacted zinc that should yield 997mg). So perhaps my residue isn't totally dry yet, or some sodium bicarbonate wasn't dissolved after all.

Conclusion: do yourself a favor and DO NOT precipitate the zinc-ions with sodium carbonate. Get them out first with sodium bicarbonate (together with harmine if you're not going for the separation-route) or use ammonia to form hexaaqua zinc that will stay in solution.

Concerning cadmium-impurities: this web-page claims that just as for zinc, an excess ammonia will form a complex that is soluble: Cadmium

Also, if one wants an extra warranty against cadmium ingestion, THH-recrystallisation from saturated NaCl ("Manske") is worth trying, I'll look into that after I did the conversion experiments (in a few days).

 

[Jees]

Keep going
Good news about the cadmium stuff!

It has always been a question if THH would manske out as a solid.
Hopefully we can gather enough THH to do some tests and solve the riddle for good.

I'm short in spare time, have to do things slowly.

I've been washing my modest amount of harmine+THH mix with sodcarb water pH 10.
The filtrate was slightly yellow colored which let me think of redissolved alks. The pH of the filtrate was 9.5. I would regret loosing THH (that would be the first to loose) by washing. Upped the pH of the filtrate to 12.5 with NaOH and the yellow disappeared and went more white. This indicate indeed some alks that redissolved in the sodcarb pH10 water. I filtered the pH 12.5 water and some white was on the filter, that is now drying, but at first glance it would be negligible in weight.

The experiment I did the other day was basing with NaOH and yielded flocculent semi gel type ZnOH precipiate, see picture. It did turn dry though. But the filtrate had a white mist so I consider this route (NaOH) not recommendable.

I will repeat your test with the sodBIcarb and see if the filtrate has a mist or not.

Thank you, you're doing such a marvelous job :thumb_up:

 

[Jees]

See attachment: give it a boost in the microwave :twisted:
With no microwave, all you see is a bubble now and then.
Standard vinegar + Zn 99.99%

 

[Jees]

...I filtered the pH 12.5 water and some white was on the filter, that is now drying, but at first glance it would be negligible in weight...

Good news, there was some on the filter paper but so little it could not be collected. So if your washing water colors a bit, no worries :thumb_up:

 

[DreaMTripper]

DreaMTripper, I expect no troubles precipitating THH with lye after sodium bicarbonate has pulled the zinc ions out of solution. However, it just seems safer to use ammonia or sodium carbonate...

Right, with you now, not as caustic but also keeps any remaining Zn and Cd etc in solution when the alkaloids precipitate.

 

[Jees]

An1cca, we are not alone with those typing errors I believe
Page 17, fraction 13, we are now in the second pH depression and there should be only harmaline, not harmine.

 

[ijahdan]

Ijahdan, after the reduction and filtering of excess zinc, use sodium bicarbonate to precipitate all of the harmine and all of the zinc ions present as the carbonate salt.

Clean up this fraction by redissolving in vinegar and reprecipitating the harmine with ammonia. The zinc ions will stay in solution.

To the filtrate of the first paragraph, add ammonia or sodium carbonate to precipitate THH. Check protocol 4 at the end of VDS's paper but do not use sodium carbonate as the reprecipitating base for harmine.

Thanks, just realised what you meant. I was thinking the harmaline precipitated at a lower pH than harmine, but of course it's the other way round. If cadmium carbonate precipitates too, that would be a bonus.

 

[Jees]

...If cadmium carbonate precipitates too, that would be a bonus...

We prefer any metal-hydroxide or metal-carbonate to not end up in the alkaloids. We rely on ammonia to keep those liquid, not precipitated.

 

[An1cca]

Wow Jees, hell breaks loose in that little recipient! An ideal setting for some heavenly THH

That in situ recrystallized harmALine looks fascinating microscopically, I would really like to see this for myself. I might just get hold on a microscope this week...that would also help with validating the pH-metric separation.

In the meantime, the reproducible pH-curve has given me confidence in the process already. I'm separating some more for THH-conversion experiments. I have found this method to be very fast as well. It took me about 25 minutes from start to finish. The depression/time-parameter is an excellent indicator. Just go slowly from pH 7,20 on and you won't lose much as a mixed fraction. If you browse this forum again VDS, thanks a lot!

Good to know that we won't lose much THH when using sodium carbonate as a base, Jees. Yet another argument for leaving the sodium hydroxide on the shelf.

Jees, if you have some combined harmine+THH left, you could try a reprecipitation from vinegar with sodium bicarbonate to separate both alkaloids. This would validate protocol 4. If you don't have enough left, I think I will have some in a few days, no worries...

 

[An1cca]

...If cadmium carbonate precipitates too, that would be a bonus...

We prefer any metal-hydroxide or metal-carbonate to not end up in the alkaloids. We rely on ammonia to keep those liquid, not precipitated.

True, except in the case where we would use sodium bicarbonate after a pure DHH to THH conversion. In that case, we rely on sodium bicarbonate to precipitate the zinc-ions and possibly the cadmium-ions. Afterwards, sodium carbonate can be used to precipitate THH (ammonia-free route). However, ammonia will still stay the safest way to go, complexing any remaining metal-ions.

 

[ijahdan]

Thats what I meant, doing the harmine harmaline separation (after reduction with zinc) using bicarbonate, then retrieving the harmine from this first precipitate by redissolving in vinegar and then using excess ammonia to dissolve zinc and cadmium hydroxides, while leaving a harmine precipitate to filter off.

Then thh and any unreduced harmaline could be retrieved using any base you like.

Think Ill get some decent ammonia and use it for all the basing anyway.

 

[An1cca]

Thats what I meant, doing the harmine harmaline separation (after reduction with zinc) using bicarbonate...

After reduction with zinc, you separate harmine from THH. Apparently, if the article is correct, no harmaline remains unreacted. This has also been shown by Endlessness and others.

 

[An1cca]

Think Ill get some decent ammonia and use it for all the basing anyway.

You can make reagent grade by placing some store-bought ammonia in a largely open container next to one filled with an equal amount of demineralized water. Put both containers in a larger one and let this setup stand for 2 weeks. The demineralized water will be pure ammonia half the strenghth of the impure one. You can use the same procedure with hydrochloric acid in case you want to convert your alkaloids into more stable molecules without sodium chloride contamination from doing a Manske.

 

[ijahdan]

Thats what I meant, doing the harmine harmaline separation (after reduction with zinc) using bicarbonate...

After reduction with zinc, you separate harmine from THH. Apparently, if the article is correct, no harmaline remains unreacted. This has also been shown by Endlessness and others.

Yeah I meant the THH/harmine separation. Posting from work and keep getting distracted! Thanks for the ammonia purification tip. Never thought of that. And for HCL. Will do that. Cheers.

 

[pitubo]

I was wondering what forms of zinc could be precipitating. Among the possible compounds formed are:

Zinc hydroxide: Zn(OH)2
Zinc carbonate: ZnCO3
Basic zinc carbonate: [ZnCO3]2 . [Zn(OH)2]3
Zinc bicarbonate: Zn(HCO3)2

While searching, I found some interesting information regarding the bicarbonate precipitation of zinc ions:

With aqueous of sodium carbonate zinc ion solutions produce a precipitate of white zinc carbonate, but its a basic carbonate, i.e. the carbonate precipitate is mixed with the hydroxide, Zn(OH)2.

Zn2+(aq) + CO32–(aq) ==> ZnCO3(s)

better prepared using NaHCO3: Zn2+(aq) + 2HCO3–(aq) ==> ZnCO3(s) + H2O(l) + CO2(g)

(source: Zinc Zn Chemistry Zn2+ compounds oxidation state +2 complexes complex ions chemical reactions GCE AS A2 IB A level inorganic chemistry revision notes)

This could well explain why the precipitate resulting from the addition of sodium carbonate is hard to filter: instead of zinc carbonate, basic zinc carbonate is formed. Only through addition of sodium bicarbonate is actual zinc carbonate formed.

You can use the same procedure with hydrochloric acid in case you want to convert your alkaloids into more stable molecules without sodium chloride contamination from doing a Manske.

Uggh! Did you ever actually try that? I did and my chrome-plated faucet is still discolored green from the HCl vapors coming of the filter cake left drying near to it. My previously nice yellow also turned red from the procedure. I read somewhere (original Manske treatise?|) that boiling harmalas in concentrated HCl will convert them into harmol and harmalol.

 

[An1cca]

Very interesting Pitubo! It is indeed clear that both precipitates are fundamentally different...

As for the hydrochlorides: Shulgin and VDS (article) did this with their THH as well. From what I understand it is best to work stoechiometrically in alcohol so that drying and a large excess of HCl-fumes can be avoided.

There is an interesting webpage detailing conversion of harmine to its fumarate. CN103626760A - Salt of harmine derivative derivative - Google Patents. I tried it and can testify that it works. Making fumarates from water seems quite difficult giving the poor solubility of fumaric acid in water.

Actually, I keep my harmala's stored as freebases in the freezer, tightly packed in a test-tube. For THH however, I am inclined to convert it to a salt.

Suggestions welcome!