Okay I finally extracted some fairly pure harmaline (4x Manske, 2x pH separation with ammonia). Due to circumstanes, I had most of the harmaline as free base and some as HCl salt.

I therefore disoolved all the harmaline in 5% acetic acid, then added 8 grams of zinc powder (approx. 1 500 mg per gram of harmaline).

I kept this on strong stirring for 24 hours (9 hours should be enough but I got to it later). As expected, the solution changed colour slightly and the zinc formed chunks. What suprised me was tiny bubbles coming from the zinc like if it was still reacting (!):



The solution became opaque with the addition of 10% ammonia and obtained this weird burgundy color (totally unexpected):



I added more ammonia until no more precipitation took place (most precipitation formed between pH 6.0 and 9.0, which is very weird) and I filtered everything (notice the burgundy filtrate):



I remember my last THH extract was brigh white color. There was also lots of it, a thick layer, not corresponding to the amount of harmaline. I washed the powder in 3% ammonia and filtered again. Now the filtrate was yellowish and the powder lost some of the burgundy color:



I took three fractions based on pH precipitation. The left one precipitated before pH 9.0, the middle one between 9.0-10.5 and the right one when pH was pushed to 13.0-14.0 with NaOH:



Note that there should not be any metallic zinc as I used Celite to filter it out before adding base.

I marked the left one as "low ph" fraction and the right two as "high ph". I dissolved these two in 7% acetic acid and checked the UV fluorescence against control (harmine in the small ebaker).

You can see the faint blue glow of THH compared to radioactive green of harmine, indicating that we really have THH:



I combined the THH solutions and added about 200 mL of 5% sodium bicarbonate. I saw absolutely no precipitation. The pH was still acidic (excess acetic acid), but there was no reaction even when pouring in the carbonate:



Now I added lots of 25% ammonia but still no precipitation took place even at pH almost 10.0 - the solution became slightly opaque though:



I then added about 100 mL of 50% NaOH and stirred for quite some time until I finally noticed precipitation:



I filtered the solution, washed the filter with 3% ammonia and dried the powder.

I was left with about 2.25 g of tetrahydroharmine free base. I am totally confused about the weird coloring, initial early precipitation, then no precipitation later, and the loss of product.

Any theories on what could have happened? Could the chlorine ions from dissolved harmaline.HCl affect the reaction?

With dissolving metal reductions such as this one with the zinc, there's always a small chance of side-reactions leading to dimerization of the partially reduced molecule. Due to the free radicals formed during the reduction, it's also possible that oxygen is absorbed from the atmosphere, forming further side-products.

It could be that a number of uncontrolled factors have led to your reduced yield, and the unusual coloration is certainly a sign of reaction by-products. The presence of chloride in your is but one variable- and would that have increased the solubility of oxygen in your reaction mixture by a significant amount? Probably not.

I think the major variable here was the increased stirring time. You've nearly tripled the contact time with atmospheric oxygen and have probably driven a side reaction that way.

Interesting that the colour formed could be likened to Harmala Red, supposedly an oxidation product of harmala alkaloids.

All this is off the top of my head, so any meaningful criticism is gratefully received.

What would be useful to add is that having used an inert atmosphere would most probably have been of some value in improving yield in this situation. Harmala alkaloids are known to be prone to oxidation, especially in solution as it would seem.


PS - it's always a joy to see your lab reports, even a relative failure is informative. Keep up the good work!

Thanks. Actually I would be able to seal the reaction mixture in a bottle under argon.

Does the zinc react enough even if it just sits in the reaction mixture? Or is stirring essential for it to react completely? I though the stirring is needed for it to touch all molecules.

However, the VDS paper calls for 8 hours of reacting, I don't remember correctly but they might mention stirring as well ... I thought the longer and more stirring the better. There is not a word about possible side reactions or side product, which is a shame given that it's a "harm reduction" paper.

Good that I bought all that chemistry books to read through during winter... I have given up searching internet for "recipes" for anything as there are always, always too many unknowns and even the simplest reactions can go bad in so many ways

As I'm sure you're aware, there would need to be some kind of pressure relief for the excess hydrogen that develops! Or, at least use a pressure-capable vessel.


Stirring surely helps, although the hydrogen bubbles do effect some kind of stirring.

Yes it could go through a wash bottle, hence inert gas can replace the air, then excess hydrogen can escape without allowing air in. Suckback can be prevented by a second wash bottle.

It won't be sealed, that's a mistake.

I don't think the chloride is a problem. The DHH -> THH reduction can as well be done in HCl instead of acetic acid. In fact, I first dissolve my freebase in vinegar and then add HCl to bring the pH down quickly. This also results in quicker reductions and dissolves my zinc. The only reason I use vinegar is to obtain acetate salts, because HCl salts are poorly soluble and I'm not sure the reduction would be effected on undissolved harmaline HCl floating about.

I've never had my zinc clump as a result of THH synthesis, it always either remains a dust or disappears completely.

I just based out a DHH>THH zinc reduction after about 60 hours of reacting in an open beaker (occasional stirring) without any burgundy colouring or dark freebase colouration, so I'd suggest ruling out the side reactions with atmospheric oxygen theory.

Reason for such a long reduction was because I had fine zinc shavings instead of genuine powder and the reduction was slower. Although, for 1g of harmaline, the initial 1.5g of zinc fully dissolved, as did the second lot of about 1g.