Fellow Chemists,

Over the span of the past four years, each and every one of my innumerable attempts to extract and purify harmala alkaloids from Syrian Rue seed have failed miserably. I have tried nearly every single tek on this site, and have wasted kilos' of P. Harmala seed in my process/attempts. Unfortunately, I lack the financial resources ATM to purchase a vacuum filtration system in order to properly and easily isolate/separate the precipitate/alkaloids from alkaline solution.

Due to my lack of financial resources and innumerable failed attempts at extracting harmalas via the traditional teks, which involve the use of a traditional acid-base extraction with only one solvent (dihydrogen monoxide), I have turned my eyes towards designing a novel extraction tek involving the use of a non-polar solvent, such as xylene/naphtha/d-limonene, to pull the alkaloids from an alkaline solution, followed by back-salting them from the NPS, and into a fresh aqueous 4% acetic acid solution (in a manner akin to mescaline teks). The pH of this distilled white vinegar solution (pH~3), now [hopefully] impregnated with the alkaloids, would be titrated to a pH of 12-14 via addition of a 5% solution of either Na2CO3 or NaOH (please lmk which reagent would be best-suited for precipitating full spectrum harmala alkaloids from an aqueous solution). Upon re-basification, the solution would be left overnight in a dark cabinet at RT (~25 degrees centigrade, 100% humidity; assume entire experiment takes place at a pressure of ~760 mmHg) in order to ensure optimal yield of precipitate. This basified solution would then be vigorously agitated, as before, and added to a separatory funnel, followed by addition of more alkaline water and agitated as before in order to ensure that as much precipitate gets in the vessel as possible. 100-400ml of either a different NPS, or the one used in the initial pulls (please lmk which option I should use; if multiple NPS are warranted/suggested, please elaborate as to the order of solvents I should use in each run/pull in my process, and why I should do so in that order. Unfortunately I only have access to naphtha, xylene, [potentially] toluene, n-hexane/heptane/octane/pentane and d-limonene ATM) would be added to the funnel. It would be sealed and vigorously agitated, burping it every 30-ish seconds along the way, until only impurities are in the aqueous layer, with harmalas in NPS. A small aliquot of alkaline aqueous layer would then be drained into several sterilized glass test tubes, sealed, and subjected to colorimetric reagent testing in order to check for alkaloid which remains in solution; if the tests suggest that a significant fraction of the alkaloids are still in aqueo, additional pulls will be done until no significant amount of alkaloid is detected in the alkaline layer, at which point the layers would be separated. The NPS would be back-salted yet again with 4% acetic acid solution overnight.

After separating the solvents, the pH of the aqueous solution would then be slowly titrated via addition of 5% Na2CO3 to a pH of ~8 and left to sit for a few hours, followed by hot gravity filtration and/or vacuum filtration, depending on circumstance. This precipitate would consist mainly of freebase harmine, harmol, and other species with lower pKas. Upon complete filtration, the pH would be slowly titrated to 12.6 with the 5% Na2CO3 solution, and left to precipitate-out the more basic harmalas in a dark cabinet at room temperature/humidity/pressure overnight, and then filtered in the same manner as the prior precipitate. In both cases, the precipitate would be dried on a seedling warming mat at ~27 centigrade, then carefully scraped into glass containers, each of which would labelled with a sharpie marker for reference.





The above-mentioned sea of word sperm outlines my future scheme. Any and all input from professional/experienced chemists would be grately appreciated, especially so with respect to the order of non-polar solvents I should use, as well as if I should use hydroxide or carbonate to titrate the pH with. Any/all other concerns and grains of advice would be gratefully appreciated. I'm planning to attempt this extraction process in the near future, and would appreciate any/all input concerning it.

Thank You,
-Godsmacker

Freebase harmala alkaloids are not very soluble in non-polar solvents. Methylenechloride and chloroform have some solubility, which you apparently do not have access to, but naphtha is totally useless to dissolve harmalas.

Putting solids in a separation funnel is generally not a smart thing to do, and quite unnecessary, too. Usually, solids are filtered or decanted from a liquid phase. A separation funnel is used with two liquid phases. Dissolved harmalas are filtered hot, precipitated harmalas are filtered cold.

When I read the amount of detail you are proposing, while asking for guidance on the big picture, it makes me wonder if putting your efforts in debugging your implementation of the default teks wouldn't be more efficient than developing a new one, that might not even work out in the end.

Did you try to follow to the letter the initial extraction parts of the method published by Frederik Vandersypt as discussed elsewhere on the forum?

What does "fail" mean to you? What happened in your extractions that you felt you 'failed'?

You do know that until you throw things away, nothing is lost, alkaloids can always be recovered.

Fail means that, whilst decanting, I happened to be unable to successfully get all the water off of the harmalas; regardless as to how I tried to decant, I could not do so perfectly, and oftentimes lost most of my yield due to the multiple decanting steps which, in turn, make me lose more and more harmalas until there are practically none left after the second or third round. Thus, to me, 'fail' in this sense means to have lost crystals during multiple decanting steps to the point where my yield was next to none. I am sick of slowly decanting the basified solutions, only to end up either losing most of my yield as I try to decant and/or siphon-off those last few millimeters of water, or have a layer of aquatic gunk hovering over the Xtals, making it an even bigger cluster headache to deal with when it comes to purification.

I am considering using decolorizing carbon after initial filtrations from original solution post-boiling the seeds whilst still acidic, then filter further before basification in order to speed things up.

Pitubo, I looked through their solubility tables and I must concur that non-polar solvents would only make things worse... I guess I may just have to pony-up the dough for a vacuum filtration system after-all...

*sigh*
-God

If you decant over to a container that keeps the decanted liquid, you will never lose anything since you can always recover.

Also, you should only just decant the main part where you clearly notice there are no harmalas.. The rest, filter with a coffee filter / funnel (or two ).

You can improvise vacuum filtering by having a funnel, a hard plastic container, some tube, some tape and a vacuum cleaner, ive done it and works great (note, obviously only use for harmala extractions which use water, dont use it for flammable solvent filtering)

I never tilt my recipient to decant, but skim off the top layer, til nearly the bottom layer, 5 mm above at max (1/5" ). For this I use a jar with 2 tubes, one to suck on, one to skim off, see here. Watch the *.avi attachment how it goes. In this vid there's 1 inch of grounded seeds on the bottom, seed powder . The siphoned off layer is to be based in this particular case. In other applications it's the top layer that is to be removed (E.g. after basing).
I lose no alks even after 1000 decants that way, in a manner of speaking. Usually a full night goes over each settling job.

I think if you fix the decanting, then the filtering, you're there
Filtering can be hugely substituted by more a/b's + decanting/siphon-off's job's.
Main thing is to be not in a hurry, a good settling job is 12 hours imho.
Hope this helps.

I'm currently doing a standard A/B tek on 100g p.harmala seeds. The way of it has been:

1. grind seeds
2. boil in weak acid solution 3x (there appeared to be more in the seeds, more boiling would certainly increase yields)
3. filter (very tedious)
4. boil down
5. base solution with 15g NaOH in some water
6. extract with DCM

this is where I'm stuck. Apparently the free base harmala alkaloids are not incredibly soluble in DCM. The DCM layer does most certainly glow with blacklight light. There is a very thick emulsion, which settles between the layers as a light yellow powdery looking precipitate. I am thinking this must be the harmala alkaloid bases. Perhaps a better way is to skip the DCM, basify the solution and simply decant and filter afterward.

Another thing I happen to notice is that while there's no obvious stains on my hands in regular light, in the blacklight I can see my hands are covered in harmala base. Alcohol, acetone, water and soap, acidic water have all been tried and none will make this stuff budge! Any suggestions? I guess I'll just have a little harmala alkaloids in my diet until it all wipes off my hands somehow.