Thc-a Recrystallization (alex siegel method)

Just had a thought

What if we threw a sonicator at this? Or at least into the alkane portion. I’d think some agitation might get these stones to drop faster.

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I have a pentane / ethanol jar going. I’m thinking of adding it to a flask with stir bar and a dry ice cold trap and regulating vacuum to slowly saturate the mixture while keeping the solution cold

Sounds good. All of my experiments have been done at essentially room temp using warm heptane to super saturate

At the moment I’d recommend using only a few percentages of ethanol maybe 10% maximum

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10% ethanol to water correct?

10% ethanol 90% heptane. I would do this to grow seeds and then make them bigger in a heptane mixture later

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Clearly the pentane or heptane saturates with water over a weeks time course.
You mention adding EtOH to pentane 10% to enhance needle like crystals…
some sort of antisolvent?
Have you tried saturating the alkane with water first…then layer that on water?
Or are we talking layering MgSO4/Na2SO4 “dried” solvent-solution layered on water.

When THCA drops out of terp laden sauce…that is an incredibly impure solution…
so ther must be something catalyzing the crystallization step…
Here you stress “it works best for pre-purified THCA” …any thoughts about this?

but I see photos of crystalline material that looks like the Na+COO-R salt form as well.
any comments? No one seems to point out these obvious two types of preparations.
Have you ever done a LLE of the pentane solution with distilled water, let it settle
and measure the pH of the water phase?

Ion pair extraction of carboxylic acids (ionized state) paired with counter ions into
hexane (alkane solvents) is a well known phenomena. Ion-Pair Solvent Extraction of EDTA Anions with Tetraalkylammonium Ions in Various Organic Solvents | SpringerLink

So when people say they extract with butane…I am not sure what it is they are extracting
becasue no one knows the state of the of the THCA in the Trichome vacuole.

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We’ve done a trial where after setup (THCa, heptane, pentane layer on top of a water layer) then shake. Shaking mixes the two together and seemed to leave some water in the top layer. It was cloudier than normal but mono crystals formed in that solution better than any other, now that I think about it.

So those of you doing this in mason jars and also have a way to remove the water from mother liquor later, maybe try shaking the mixture before letting it sit. I would not try this with ethanol in the mixture because you’ll probably lose some of your alcohol to the water layer

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Crystallizing with terpenes and other impurities is more difficult. Slower and lower yields so I would recommend doing this as a recrystallization of already crystallized THCa or use very pure crude that was going to crystallize on its own

I think the crystal shape here is more about the geometry of the surface it’s growing on, nothing more. Are you suggesting that the THCa could be entering the water layer then recrystallizing at the interface? I think it’s far more likely we’re just seeing a physical effect nothing chemically changes

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If you can share a photo of the types of salt THCa crystals you’re talking about that would be helpful.

And if I can be proven wrong about there being no chemical changes, that would be very cool!

How would we go about doing an experiment to test if the seeds are a THCa-salt?

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AlexSiegel: Your work is thought inspiring! In no way am I trying to “prove you wrong.”
I am trying to promote general thought concerning alkane solutions of carboxylic cannabinoids and butane extractions of carboxylic cannabinoids. US20150038567A1 - Cannabinoid Carboxylic Acids, Salts of Cannabinoid Carboxylic Acids, and the Production and Uses of Same - Google Patents
Please take note of this patent which lays the ground work for my thoughts…
that and an understanding of pK values and ionization in “aqueous solutions”

(Ion-Pair Solvent Extraction of EDTA Anions with Tetraalkylammonium Ions in Various Organic Solvents | SpringerLink)
The later explains the ion pair extraction into Hexane as example.
When one has a BHO “extract” derived from plant material…
how do you know whether you have ion pairs dissolved or whether
you have the non ionized Hydrogen form dissolve, or a mixture of both?
So it is an "a prior " question.

The THCA synthase is excreted into the extracelluar lumen…that means CBGA is also
excreted. The synthase likes to work in aqueous environment at pH 5.0.
At this pH the cannabinoic acids are 99:1 ionized. So I would "assume ’ the speicies loaded into the catalytic cleft is ionized. Since the surrounding milieu is probably a monoterpene
solution of hydroxlyated terpenes acting somewhat as a detergent in some-sort of “aqueous
environment” I would expect Na+and Ca++ ions everywhere. In fact, Ca++ is known to be pumped into plant vacuoles. I do not know how butane solubilizes
THCA or what form THCA is in , in the trichrome. (read the above papers for reference)

Your post is most interesting because it brings the Cannabinoid Alkane Solution/Extract into direct contact with water!

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Example:
In their patent on CBDA methyl ester, Mechoulam et al. synthesize CBDA as a precursor to the methyl ester step. CBDA synthesis below:
Synthesis of Cannabidiolic Acid (CBDA):

A mixture of Cannabidiol (CBD, 314 mg, 1 mmol) and 2 molar solution of Magnesium Methyl Carbonate (MMC/2M, 1.5 ml, 3 mmol) in dimethylformamide (DMF) is heated at 130° C. for 3 hours. Then the reaction is cooled to 0° C., acidified with 10% hydrochloric acid and extracted with ether. The organic layer is washed with saline, dried over the drying agent magnesium sulfate (MgSO4) and then evaporated. The crude compound is then cleaned by column chromatography (20% ether-petroleum ether)."

In regards to this posting, look closely at the 1.) acidification step prior to extraction in to ether. They are using 10% HCl which is pH= -0.5. (minus emphasis)
If you want the carboxylic acid in H+ form…this is how you do it.
2.)Then in a second step they back wash the ether with sat’d NaCl before evaporation.
second step confuses me a bit, but it is possible that it is an ion exchage step.
I’m trying to look as this ??? on going.
Comments?

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Edit. Misread

Love it! Always want to play whit water. I want to try this water layer tek with my diethyl refined crude mixture, the dieth carryer a lot of water…and they act as a antisolvent. Before i dry the solution sometimes is very cloudy.
When the solution is very wet, aprox 70%crude 30% solvent, if i seed in this moment start crystalization in the moment.
Sooo lets do some test.

Thanks
Regards!

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Are you thinking we should acidify the mixture? Sorry I’m trying to keep up with where you’re taking this!

I’m not sure what the acid’s function is in the methyl ester synthesis beyond neutralizing the leftover magnesium methyl carbonate and making sure the CBDa methyl ester is protonated. The ether solvent will then be able to extract it more effectively from the mix if it is in neutral form.

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If someone could shake their THCa mix and then test the water pH that would answer the question possibly. Also run a control where no THCa is present

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the first step in their synthesis is CBD to CBDA.
They are synthesizing CBDA.
The acidification and ether is an extraction of the CBDA.
LLE of CBDA +H form into ether.
as mentioned above the saline was post that step confuses me…
but I am thinking it may result in CBDA Na+ form by ion exchange…
these salts are talked about in detail in the patent reference aways back.

There is an entire second step process to make the ester.

The salts make crystals as well when precipitated,
So it all depends on how you prepared your upper solution of THCA in Pentane/Heptane.
Becasue most people readily decarboxylate either in an oven or by smoking this is all moot.

But when you want the THCA as a product…and that is what you are doing, the question
is pertinent what form is your acid in? They all crystallize. Probably the best example
universally know to every one is Vitamin C. You either buy it as the free acid or you by it as Calcium Ascorbate. Both are pretty white crystals.
The question in Cannabinoid Chemistry is how is it that Butane is such an efficient
solvent for THCA in the biomass. It does not make sense at the pH of 6-7 especially at
-40 C. Moreover, when you crystallize as you are doing, which form are you crystallizing?
In recent years, a lot of people are washing crude with salt water and or at various pH…
I am just trying to delineate what is going on when working with Cannabinoic Acids.
This becomes very obvious if you have worked with the isolations of CBDA and THCA using
water in the pH ranges of 11.5 to 12.5 and subsequent precipitations using HCl or Acetic acid. At the higher pH , the phenolics ionize as well. THCA has a double negative charge and CBDA has a triple negative charge!

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You bet, go!
I don’t have ether…so I am very interested.

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Yes, that may give an indication. I really do not know …what it will mean…
but I often add a shot of conc. Acetic acid to either hexane or alcohol primary extracts…
just to make sure.
however here is another example: (A. Wohlfarth et al. / J. Chromatogr. B 879 (2011) 3059–3064) consider the exact same detail when describing their single column proceedure for 99% pure THCA crystal isolation:

Perhaps, they say it a little better than I have:

Pyridine is an organic base that easily dissolves in these mobile phases and possesses an optimal pKs of 5.3 to quantitatively deprotonate THCA (pKs 3.3) without setting alkaline conditions that would favour decarboxylation. This way the only difference between THCA and its main impurity THC – which is the polarity of the deprotonated carboxyl function intensifying interactions with the silica sorbent – is optimally exploited

Of course, pyridine is undesirable after that. It is therefore removed immediately after pooling all THCAfractions by extraction with 0.5 M hydrochloric acid (5 mL per 100 mL eluate). Pyridium chloride is highly soluble in aqueous medium (85 g/100 mL water). Apart from the elimination of pyridine this acidification has a beneficial side effect: it transfers THCA into its more stable protonated form. In the final analysis with NMR no pyridine was found.
Note that they go back to a very strong HCl wash…which like Mechoulam’s work noted above
certainly protonates the carboxylic acid …in addition to the ion pair extraction of pyridine
into water.
Just to make sure every one understands the known unknowns here…
extraction with butane does not change the pH of the biomass, wet or dry.
So what ever the effective pH is in the trichome-Terp-water soup, it is highly unlikely
to be below the pK of THCA. In fact is is most likely 6.5. with ratios of 100 to 1000 to 1
in favor of the ionized state. How do you get that into butane at -40C???or even room temp???
But people do it every day.

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Stir it

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Alex: thanks for the very interesting discussion and your time:
I want you to get back to your original post subject.

In leaving I want to stress the paragraph below quoted from the THCA-salt patent
noted above:
" The present invention solves this problem by providing a process for the production of amorphous and crystalline salts, in particular pure, preferably crystalline salts of cannabinoid carboxylic acids by production of synthetic cannabinoid carboxylic acids in a chemical reaction or extraction of natural cannabinoid carboxylic acids from plant materials or cell cultures of Cannabis sativa and subsequent treatment with a suitable organic base, inorganic base and/or a suitable inorganic or organic salt in a suitable solvent. Here, pure is understood to relate to substance mixtures with a salt content of >90 wt. %."

Please note they refer to two classes of THCA-x crystals:

  1. Amorphous and Crystalline

And: 2.) note the term “salts” the mean more than two !

I have previously noted how these are controlled by pH and counter ions in solution.

the mystery of butane extraction might be attributed to intramolecular hydrogen bonding
in addition to other hypotheses noted.

It does not seem that the founding father’s of 4200 have ever thought this through.

Something further to think about is decompositon (“decarbing”) with heat…
do all “salts” decompose the same way and to the same extent?

Blockquote

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