Harmaline to THH reduction with zinc and vinegar works! (GC-MS results)

[blue.magic]

added excess zinc dust

How much zinc is that for, say, a 100 mg of harmaline? 50 milligrams? A gram? Quarter the volume of solvent?

Thanks for any advice on how much "excess" actually is. I have about 250 grams of zinc dust but I don't want to unnecessarily spoil any.

As for filtering the zinc dust, I would use standard vacuum filtering with glass micro fiber and bed of Celite, which is okay right? (the "Celite" I use is simply a food-grade DE)

 

[ijahdan]

How much zinc is that for, say, a 100 mg of harmaline? 50 milligrams? A gram? Quarter the volume of solvent?

Thanks for any advice on how much "excess" actually is. I have about 250 grams of zinc dust but I don't want to unnecessarily spoil any.

As for filtering the zinc dust, I would use standard vacuum filtering with glass micro fiber and bed of Celite, which is okay right? (the "Celite" I use is simply a food-grade DE)

Check out the thread about harmaline to thh, a harm reduction approach. Cant remember exact title of thread and dont know how to link it but you could search for VDS protocol also as this method works well and all quantities of reagents used are documented. From memory, I think about a gram of zinc was used with 6g harmaline, so 50mg for 100mg should be ok. There will be losses however, so dont expect to recover much thh.

 

[blue.magic]

Thanks ijahdan!

I found the full paper here: A harm-reduction approach to the isolation of harmine and its hydrogenated derivatives from Peganum Harmala seed in low-tech settings

Here is the DHH (harmaline) to THH conversion part:

2.5 Conversion of DHH freebase to THH
2002mg of DHH was dissolved in 100ml of acetic acid 7%. To this solution, 3008mg zinc
powder was added. This mixture was left to stand at room temperature for several hours under
regular stirring. It was observed under UV-light that the solution's fluorescent color changed
from yellow-green to deep blue in the course of 3 hours. The mixture was left to react for an
additional 6 hours. Then it was filtered giving residue RA1 and the recipient was washed with
water that was poured over the unreacted zinc in the filter and was thereby added to the filtrate.
This brought the total volume of filtrate to 200ml.
Under continuous pH-measurement, a solution of ammonia 12% was added dropwise. The
starting pH was 3,88. When the pH reached 5,42 after adding 16ml of base, a very fine mist
appeared in the solution that did not augment during the further addition of base. At pH 7,25
(21,5ml of ammonia added in total), the solution was filtered again to give residue RA2.
More ammonia was added and after the total addition of 33ml of ammonia 12% (pH 8,77),
clouding once again appeared in the solution and the pH declined steadily to 8,62. At this point
the solution was filtered again and precipitate RA3 was obtained.
The addition of ammonia was continued, but no more clouding nor pH-depression was observed
up to a pH of 9,64. At that moment, 4ml of ammonia 12% were added that gave rise to clouding
at a pH of 9,76. The solution was filtered again to give residue RA4.
A small amount of RA4 was then sublimated at 1mbar and 130°C to give RA5. Another amount
of RA4 was recrystallized twice from ethanol 96% giving RA6.
Then an excess (20ml) of ammonia 12% solution was added that brought the pH to 10,02. No
precipitate formed.
The melting ranges of three consecutive samples of each residue were measured using a Thiele
tube. These results were averaged and rounded to the nearest half degree.

 

[intosamadhi]

As Mindlusion said, it seems to have worked well. And indeed do with lesser concentration of the sample, will prob help separating the spots better.
......
What surprised me is using acetone to dissolve the harmalas. How much acetone did you use ? How many pulls?

Acetone was the only solvent I had on hand, and I found an online reference saying that zinc carbonate is insoluble in acetone. I used approx 800ml in 4 pulls. +/- 5g on first, 2.5, .8,.3 if i remember correctly.

What solvent mixture did you use in TLC?

I used the bunk police separation kit. So the solvent is whatever they supply.

Could you elaborate more on the details of your conversion?
E.g. how long did you stir? How much vinegar?
Anhydrous acetone, right?
Anything heated?
etc.

Check the start of this thread for the details. The main difference between what i did and what endlessness suggested was not separating the harmine and harmaline first, and then collecting the thh + harmine mix using acetone.

I left the zinc + vinegar + harmala mix to sit over night and I just stirred it everytime i walked past (ie. many times). There was a lot of yellow foam.

I am not sure if the acetone I am using is anhydrous. I warmed up the vinegar before adding it to the mix. Quantity of vinegar was around 500ml.

Thanks for the reassurance guys. I am going to do another conversion, but rather than freebase the resulting fluid I will just reduce and keep it for oral use, since zinc acetate is safe for consumption according to online sources.

Is it possible to run a tlc on an acid liquid ? or does it need to be a freebase ?

 

[DrSeltsam]

You can run tlc on an acid or an acid solution, no problem with that. Just keep in mind that when using a basic solvent (like ammonia), this might create a different pH at the point where the solvent hits the spot of the substance you are trying to investigate. This might cause a problem as the substance might not be traveling through the stationary phase in a constant manner.

In case you are using a basic solvent, I would simply try different levels of dilution with the solvent to see if there is an effect. If you are using an acid solvent this is not a problem at all.

 

[Mindlusion]

if you run tlc in the acid phase, the spot will not rise as high as it would as a freebase, it also tends less resolved spot because of what DrSeltsam described.

with TLC generally the more dilute the better, only an extremely tiny amount is necessary to be picked up by TLC, especially with fluorescent alkaloids like harmalas.

 

[Jagube]

Another approach worth trying (and this is where I'd put my money) would be to first use any available base to precipitate the zinc salts and THH freebase, then collect precipitates and retrieve THH with vinegar or better carbonated water; All the zincs will remain insoluble and be left behind while THH will be collected as its acetate or carbonate salt, ready to be re-precipitated with base.

If the zincs are insoluble in vinegar, why weren't they discarded in the "filter out excess zinc" stage after the reduction? Everything that made it to the basic soup should still dissolve in vinegar, otherwise it wouldn't have made it that far, no?

As for carbonated water, is it the stuff sold as sparkling water at grocery stores that some people for some reason drink?

 

[blue.magic]

Another approach worth trying (and this is where I'd put my money) would be to first use any available base to precipitate the zinc salts and THH freebase, then collect precipitates and retrieve THH with vinegar or better carbonated water; All the zincs will remain insoluble and be left behind while THH will be collected as its acetate or carbonate salt, ready to be re-precipitated with base.

If the zincs are insoluble in vinegar, why weren't they discarded in the "filter out excess zinc" stage after the reduction? Everything that made it to the basic soup should still dissolve in vinegar, otherwise it wouldn't have made it that far, no?

As for carbonated water, is it the stuff sold as sparkling water at grocery stores that some people for some reason drink?

Yes that strikes me too. I am thinking about doing a clean run (without harmalas): simply basify the zinc-acetic solution, filter precipitate (presumably zinc carbonate) and place it in acidic solution (HCl or vinegar). Then observe whether it dissolves or not. I guess it either forms zinc chloride/acetate and dissolves OR it stays in carbonate form undissolved, which would be great.

After half-day of research, I still cannot find how to separate zinc carbonate from THH free base reliably. The information is inconclusive and unbased.

I've read on Shroomery that dry IPA can be used as it dissolves THH but not the zinc carbonate. I haven't had success. I would also avoid acetone as this brings more issues (getting pure acetone is hard, it could contaminate the product even more and one has to use a lot and evaporate it).

The VSD article providing DHH to THH conversion protocol uses ammonia or sodium carbonate to precipitate. Both bases form possibly nasty zinc salts? Maybe ammonia is safer?

Or was there some discovery that zinc carbonate won't make it to the final product?

We need to sort this out once and for all, since people will be making their THH according to VDS, possibly eating lots of zinc carbonate... I also don't want to poison anyone

 

[blue.magic]

Okay so I've read on my local language wikipedia, that zinc carbonate is soluble in acidic and basic aqueous solutions as well as in ammonia solution.

Well this means that zinc carbonate, though water-insoluble should not precipitate that easily from basic solution.

This might also be a reason why in VDS they washed free base harmalas with dilute ammonia. This might wash out any zinc carbonate and possibly mettalic zinc that could made it through.

 

[Jagube]

I remember reading that post-reduction zinc compounds dissolve in ammonia before the THH precipitates, but if your THH contains harmine which you want to recover, it makes things more complicated as the zinc compounds precipitate roughly at the same pH as harmine, and don't dissolve until more ammonia is added.

However, what are the consequences of this (http://www.npi.gov.au/resource/zinc-and-compounds)?:

Zinc carbonate is soluble in dilute acids, alkalies and in ammonium salt solutions. It is insoluble in water, ammonia, pyridine, alcohol and acetone.

It says soluble in alkalies (bases), but not in ammonia, which is a base...

Also what about the potential cadmium contamination of zinc? I remember someone saying they probably behave the same way as zinc as far as solubility goes. Do we have a confirmation of this?

The more recent thread Harmine, harmaline and THH from Syrian Rue. Verification and finetuning of the VDS-protocols has much more up-to-date info, but much of it is about harmine/DHH separation.

 

[blue.magic]

I remember reading that post-reduction zinc compounds dissolve in ammonia before the THH precipitates, but if your THH contains harmine which you want to recover, it makes things more complicated as the zinc compounds precipitate roughly at the same pH as harmine, and don't dissolve until more ammonia is added.

However, what are the consequences of this (http://www.npi.gov.au/resource/zinc-and-compounds)?:

Zinc carbonate is soluble in dilute acids, alkalies and in ammonium salt solutions. It is insoluble in water, ammonia, pyridine, alcohol and acetone.

It says soluble in alkalies (bases), but not in ammonia, which is a base...

Also what about the potential cadmium contamination of zinc? I remember someone saying they probably behave the same way as zinc as far as solubility goes. Do we have a confirmation of this?

The more recent thread Harmine, harmaline and THH from Syrian Rue. Verification and finetuning of the VDS-protocols has much more up-to-date info, but much of it is about harmine/DHH separation.

So therefore using sodium carbonate as a base to precipitate THH seems safer than ammonia assuming THH is synthesized from isolated DHH, not from the mix.

Also sodium hydroxide seems safe as zinc hydroxide is soluble in NaOH solution (though not in different basic solution).

Yes I still have to read through that VDS thread, unfortunately it's monstrous

 

[Jagube]

So therefore using sodium carbonate as a base to precipitate THH seems safer than ammonia assuming THH is synthesized from isolated DHH, not from the mix.

I fail to see why it would be so? And is it still true when there are no carbonate salts to begin with in the post-reduction solution?

Normally if your alks are pure and distilled water was used, your solution contains zinc, zinc acetate, THH, and possibly cadmium compounds. There is no zinc carbonate. Now what I'm not clear on is what zinc compounds are created when ammonia is added, but clearly zinc carbonate is not one of them.

On the other hand when you base it with sodium carbonate, you get zinc carbonate and sodium zincate (?). The quote I posted implies that at least the former should stay in solution.

 

[downwardsfromzero]

Chemistry footnote: the insolubility of zinc carbonate in ammonia refers to anhydrous ammonia, liquefied at -33°C or under pressure. that's why ammonia solutions are listed separately. "Soluble in alkalies" implies strong alkalies so >=pH12.

On the other hand when you base it with sodium carbonate, you get zinc carbonate and sodium zincate (?). The quote I posted implies that at least the former should stay in solution.

It's the latter that will be soluble, and that will form with an excess of sodium hydroxide, not merely with sodium carbonate.

The main safety concern is to avoid the use of zinc with a significant content of cadmium or other toxic heavy metals (e.g., lead, mercury).

 

[blue.magic]

So therefore using sodium carbonate as a base to precipitate THH seems safer than ammonia assuming THH is synthesized from isolated DHH, not from the mix.

I fail to see why it would be so? And is it still true when there are no carbonate salts to begin with in the post-reduction solution?

Normally if your alks are pure and distilled water was used, your solution contains zinc, zinc acetate, THH, and possibly cadmium compounds. There is no zinc carbonate.

Actually three possible sources of zinc carbonate I can think of:

1) zinc acetate itself - since its hydrolyzed, the zinc ion is avaliable for the carbonate ion introduced by adding base - why won't therefore some zinc ions stick to carbonate ions forming ZnCO3 ? Some of this salt can get trapped in the THH FB precipitate when filtering and won't get away unless washed with basic water as neutral water won't dissolve it.
2) metallic zinc particles passing through the filter (especially if coffee filter or paper filter is used)
3) distilled water - still not free of ions (unless de-ionized) - may form nasty salts with the unreacted residual zinc - this could form plethora of salts, making the product at least not food grade - maybe I am paranoid but...

I agree heavy metals are a bigger problem though.

Maybe leaving the filtered solution to sit for a week or so will allow the heavy metals to sit on the bottom of the container, then the bottom can be drained.

Also maybe treatment with some clarification agent (i.e. Chitosan, activated carbon) could bind the heavy metals and improve cleanup procedure.

I would really give my THH to some people but my conscience won't allow handing them anything there is even slight chance of it containing any poisons, unless in trace amounts comparable to that of drinking water.

 

[Jagube]

From Cadmium :

Aqueous ammonia reacts with cadmium ion to precipitate white cadmium hydroxide, which dissolves in excess ammonia [..]

Sodium hydroxide produces a precipitate of Cd(OH)2, but the precipitate does not dissolve in excess hydroxide

Does this mean using ammonia for freebasing solves the potential cadmium contamination issue, as long as enough ammonia is used?

 

[downwardsfromzero]

From Cadmium :

Aqueous ammonia reacts with cadmium ion to precipitate white cadmium hydroxide, which dissolves in excess ammonia [..]

Sodium hydroxide produces a precipitate of Cd(OH)2, but the precipitate does not dissolve in excess hydroxide

Does this mean using ammonia for freebasing solves the potential cadmium contamination issue, as long as enough ammonia is used?

Using cadmium-free zinc is better. Much better.

But strong aqueous ammonia will solubilize any trace of cadmium, yes. If one were to have a genuine concern about cadmium content, a further wash with fairly concentrated aqueous ammonia would probably be prudent as pure water would be capable of reprecipitating the hydroxide.

Of course, THH contains an amine nitrogen which is also (theoretically) capable of complexing to various metals. Excess ammonia would still take care of this as it's fair to assume that the equilibrium would turn out greatly in favour of the metal-ammonia complex in those circumstances.

 

[pitubo]

Downwardsfromzero is right on the mark. Don't let any toxic metals get into the mix, so you don't need to get them out again.

If you cannot find a pure enough grade metallic zinc powder, you could always buy usp grade zinc oxide and convert it to metallic zinc powder yourself using electrolysis.

Hat tip to NurdRage for the procedure:

 

[downwardsfromzero]

Downwardsfromzero is right on the mark. Don't let any toxic metals get into the mix, so you don't need to get them out again.

If you cannot find a pure enough grade metallic zinc powder, you could always buy usp grade zinc oxide and convert it to metallic zinc powder yourself using electrolysis.

Hat tip to NurdRage for the procedure:

That's exactly what I was getting at - including the (unstated) means of producing your own high-purity zinc.

 

[Jagube]

But strong aqueous ammonia will solubilize any trace of cadmium, yes. If one were to have a genuine concern about cadmium content, a further wash with fairly concentrated aqueous ammonia would probably be prudent as pure water would be capable of reprecipitating the hydroxide.

From this I take it that the concentrations we end up with after the THH crashes out (pH ~ 10) are strong enough?

If you cannot find a pure enough grade metallic zinc powder, you could always buy usp grade zinc oxide and convert it to metallic zinc powder yourself using electrolysis.

And in that case, isn't the potential contamination of the sodium hydroxide an issue?

To get rid of the heavy metals we can always do Manske as has been shown in the other thread (contrary to what has been said in this thread).

 

[downwardsfromzero]

This doesn't cover the ammine, but is still useful to read: http://www.iupac.org/publications/pac/pdf/2011/pdf/8305x1163.pdf

Note that cadmium is also solubilised by chloride ions even in slightly basic solutions in the presence of carbonate, so what you say about the Manske holds true.

And in that case, isn't the potential contamination of the sodium hydroxide an issue?

What exactly do you mean here? Contamination of the sodium hydroxide in the electrolytic process? By nickel? Or do you mean something else entirely?