Thanks for all the clarifications! This is extremely helpful to me (and hopefully others as well) as a non-chemist.

Yes I observe lowering of the pH curve. After filtering out harmine, the second pH point (7.8 ) should be reached and no base added after precipitation happens. I was not sure whether to keep adding base until we have stable pH 7.8 as to remove most of the remaining harmine/harmaline mix to get purer harmine in the end. But considering I will do a second run, that is prolly not that important.

As for the acid content, I can actually salt the hydrochlorides directly, dry it and dissolve in (distilled) water. This way no acid or salts are present and one should get even cleaner separation.

The VDS article is aimed at people in low-tech settings, who don't get access to clean HCl. I fortunately do, so this is probably an option.

Adding pH meter with USB and graphing software to the lab wishlist ...

Okay I tried the separation starting with mixed harmala hydrochlorides (20 mg/ml concentration, i.e. 50 ml distilled water per gram of harmala hydrochloride). This works much better than with freebase dissolved in vinegar.

From left: DHH, mixed fraction, harmine:



As you can see, almost nothing precipitated in the mixed fraction giving cleaner separation. The resulting powders are much lighter than the ones done from freebase/acetic approach.

The taste test works too, harmine fraction is tasteless while the DHH is bitter.

I've put the 1 gram of the DHH fraction in 50 ml 7% vinegar and added 500 mg zinc. After about hour, the solution turned blue under UV light showing successful reduction to THH.

Congratulations!

I have calculated the stoichiometry and it looks that 50 ml 1% HCl is enough to salt 1 gram of harmalas (it's actually little over 40 ml for harmine, DHH and THH).

Okay I will most probably delete this thread and add results in the VDS thread if anything useful is found. Thanks for all the help so far.

Why not ask moderators to append it to that thread?

Because most of this is redundant and will make the already monster thread even bigger. I will append just if I have something new to say.

BTW here is the THH freebase (right) made from DHH.HCl using zinc-acetic reductive synthesis:



I will make a tek going from rue to the final products and update that according to the best knowledge reached on the VDS thread.

awesome. please do.

Yeah, a tek would be great. That thh looks really clean, Ill have to try this hcl thing. Do you think it could also be used in the reduction in place of acetic acid?

Also, Ive got hcl, but dont know the exact concentration. Whats the best way to salt the alkaloids to avoid excess hcl? Is there an optimum pH reached or do you just add slowly till all freebase is dissolved?

Zinc also reacts with hydrochloric acid, forming zinc chloride. Hydrogen is released in the reaction that might hydrogenate the harmaline as well. But this depends on how strongly HCl bonds to the harmala relative to the zinc.

Maybe bubbling pure hydrogen through the solution would also work?

These are all questions for a chemist, but before knowing for sure, I would not experiment with the precious harmalas for now.

With a dissolving zinc reduction it ain't the hydrogen that does the reduction, but the electrons given off by the zinc as it dissolves. The hydrogen adds to the reduced molecule as protons from the acidic water.

To hydrogenate with gaseous hydrogen, a catalyst would be required. Nickel boride might be worth a try.

Thanks for clarifying that.

Please let me correct if I get anything wrong in the following: harmaline.HCl in water undergoes hydrolysis into harmaline and hydrochloride ions. When zinc is mixed in, it reacts with HCl forming zinc chloride and a free hydrogen (released as gas?). Electron-wise, zinc offers electrons to harmaline, it gets negative charge and hyrogenates from the hydronium ion (from H+Cl-).

The question is whether harmaline.HCl will react like that and what is the final form (freebase?). Provided the .HCl part is consumed by zinc, there is not HCl left to form a salt with harmaline. Or will zinc react only with the excess acid be it acetic or hydrochloric?

First an overview of ionic solutions and a nomenclature primer.

When harmaline.HCl dissolves in water, it forms a dissolved harmalinium (protonated harmaline) cation harmalinium+(aq) and a dissolved chloride anion Cl-(aq) . AFAICS all harmaline.HCl is dissociated in aqueous solution.

The same goes for hydrochloric acid. Being a strong acid, it is completely dissociated in aqueous solution as chloride anions Cl-(aq) and free proton cations H+(aq) , sometimes also denoted as hydronium H3O+(aq) .

With acetic acid it is a bit more complicated, because it is a weak acid and only partially dissociates into acetate anion H3COO-(aq) and proton cation H+(aq) . A certain percentage of the acetic acid will remain undissociated as H3COOH(l). I write the latter as a liquid (l), as I assume that it is mixed with water, not dissolved with a solvation shell - real chemists may want to correct me if I am wrong.

When you add zinc dust to an acidified solution of harmaline, the solution initially contains:
harmalinium+(aq);
Cl-(aq);
H+(aq);
Zn(s) and of course
H2O(l):
(For completeness, there is also a relatively minute amount of OH-(aq) anions as a result of water's spontaneous dissociation, and for the same reason there are slightly more H+(aq) cations than Cl-(aq) anions. These details are not important here.)


Now onto the reduction part.

This is quite complicated for me. I'm not sure if I really understand it, but this is what I can make of it:

A zinc dust atom Zn(s) reacts with the harmalinium+(aq) cation by donating an electron to the harmalinium cation . The result is a dissolved zinc cation Zn+(aq) and a neutralized harmalinium radical harmalinium*(aq). The latter is called a radical because it now has an unpaired electron -- in a molecule, electrons always bind as pairs. And perhaps it isn't really neutral, maybe it is a negatively charged cation with both a localized + charge (on the nitrogen) and a localized - charge (on the adjacent carbon). It's complicated.

Anyway. Next, a proton H+(aq) joins the harmalinium radical, forming a hydroharmalinium+*(aq) radical cation.

The zinc cation Zn+(aq) reacts again with the hydroharmalinium+*(aq) radical cation by donating another electron to it. This results in a dissolved zinc cation Zn2+(aq) of a higher oxidation state and a hydroharmalinium(aq) species (another negatively charged cation?)

Finally, another proton H+(aq) joins the hydroharmalinium(aq), turning it into a dihydroharmalinium+(aq) cation. Since dihydroharmaline is the same thing as tetrahydroharmine, we can also call it a tetrahydroharminium+(aq) cation.

Well, that is the simple version. In actuality, the steps can happen in a different order too. I am not going to expound on that, apart from showing this diagram of a similar reduction scheme:



Perhaps mindlusion, ulim or downwardsfromzero could draw a nice scheme with curly arrows. I don't know if it would make it more intelligible, but it would sure look better.


There are some side reactions to consider too.

HCl is a strong acid and will attack the zinc directly, generating hydrogen gas H2(g). Perhaps using acetic acid is better here because it is less vigorous in its attack on the zinc. That's just a speculation. Sometimes ammonium chloride is suggested as a proton source for zinc reductions. Could be even better.

Another possible side reaction is the linking of two harmaline molecules in various stages of reduction. That is called dimerization. I have no idea how likely that is in practice and how much of what exact sideproducts to expect.

Wow. Thanks for the detailed explanation I didn't realized there are actually two extra hydrogens added to DHH to form THH (although the nomenclature clearly says it). DHH is also "two hydrogens away" from harmine.

Short but possibly wrong breakdown

DHH + Zn(s) = DHH- + Zn+(aq)

DHH- + H3O+ = DHHH + H2O

DHHH + Zn+(aq) = DHHH- + Zn2+(aq)

DHHH- + H3O+ = THH + H2O

(DHHH as in 1 H attached to DHH)

So glad I read this thread - had the same separation issues as BM, and now will go down the same route. Using the theoretical sodium bicarb/carb pKa difference approach didn't really work for me - after the first separation, subsequent separations didn't isolate the alkaloids any further and what was initially separated definitely didn't match what I expected (ie. the supposed "harmine" was almost pure white and gritty while the small amount of "harmaline" was a finely textured tan colour). VDS paper now a staple in my reference collection

Perhaps the wiki teks need a note about the Harmine/DHH separation step using just Na2CO3 and NaHCO3 to the effect that it may not work under some conditions?

padawan, color of the extracts isn't a good way to assay for purity, it can be very misleading. Was that the only indicator for you that separation didnt work?

Btw, did anyone ever do a tlr on the vds protocol thread? If so, we can def add that to the wiki too.

Yeah, I understand where you're coming from, but I don't have access to GC and I'm a bit cagey about ordering a TLC kit (perhaps I shouldn't be). But in any case, it wasn't just the colour but also the fact that it appeared to be 95% harmine / 5% DHH and subsequent separations yielded no more harmine from the DHH extract and vice versa. Too many things didn't add up. I've recombined and am manske-ing now as a reset, then I'll try the VDS method using sodium bicarbonate (I can't get clear ammonia and I'm not inclined to distill cloudy ammonia) and finally saturating with some sodium carb.

Unless I've misunderstood VDS' method, the operative part of the process is to slowly add a base to the purified mixed harmala HCL solution until precipitation begins to occur (~ PH 7.2) and look for the PH dip as the harmine FB crashes out and slowly return to that PH and then filter the harmine. Then repeat again and look for the second precipitation/PH dip (~ PH 7.7) and do the same to precipitate and filter the harmaline. Then saturate with your base to >PH 8.5 precipitate the last of the harmaline. Repeat the whole process again on each of the harmine and harmaline to further purify each harmala.

^ is that right? Surely it could be appended to the harmala teks as an alternative process to the bicarb/carb saturation separation method (also note that it absolutely requires a PH meter to a least PH 0.1 accuracy)

About yes.
When using carbonates expect CO2 to be formed, fizzling. The CO2 that is still in the solution play part in the pH game. That's annoying, and all you can do is your best to drive that CO2 out by working very slow and stirring/spinners. What also worked fine was poring the solution trough a coffee filter, CO2 seems reluctant to pass the filter without driving off (%?), or a little cotton plush in a funnel.

We encountered a brown sticking sludge sometimes as a FB form instead of pale floating flakes. Carbonates were particulary sensitive to this effect. An1cca resolved by using VDS his used concentrations rigorous.
I gave up on using carbonates for that job


When harmine is harvested (as you wrote) then you could skip the search for a second dip (or plateau which is more realistic to encounter) and just base up to the ceiling you want, and call all that harmaline.


Nice that you want to try

In my experience, the separation is very clean if precise pH control is applied and ammonia is used.

I get only negligible amount of impurity on the second run, so the harmine or harmaline from the first run can already be used as is.

I purify it anyway, though the amount of harmaline in harmine (or harmine in harmaline) is so small I just obtain one fraction and discard the rest.

Two year old thread, yeah I know, but excuse me...



Hey blue.magic - don't wanna be a pest, but did you do this yet? I for one am waiting with baited breath. Every issue I have had with Rue extraction, and that I turn to nexus looking for answers, I stumble on another thread you started or posted in and find you had very similar experiences so I am very keen to see your tek or even some kind of summary....



Yes, this was from another thread but again, it points to much hidden knowledge and experience you have to contribute to this process! Please elaborate...

TIA