Butane works but no theory! A few dozen hints

Hash and Stuff Extraction
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That I like very much. It can be generalized to ANY salt of the THCA
redisolved in ETOH (now protic solvent all the nasty configurations
of the salicylic moiety switch over to protic form) and done in
“batch” form. Love it. Get rid of the EtOH and H20 by rotovap…
redissolve in alkane of choice…and everyone has a standard proceedure to create H form diamonds.
You will have to teach them how to wash, clean and prepare the H+ form resins …but once done…it is nice. Would you add a bit of acid to the ethanol?

let me let that sink in…I hope 4200 takes notice …
it could be the final “ion/salt form” cleanup step.
this may well get everyone on the same page.

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During elution, no. That would somewhat defeat the purpose of the principle of ion exchange. And any time you add a bit of acid, you also add a bit of the acid’s conjugate base, so now you’d have that to contend with.

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It’s not complicated. Some ions have better affinity than others for the resin functionality. That’s basically all there is to it, that and deionized water to wash off excess regeneration mixture.

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it is possible that acid washed silica or Alumina may suffice…
as it is already in use, I believe they can act as weak ion exchangers of some limited capacity.

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I don’t think so. I see the properties of alumina and silica more as general character of their surfaces, and not an ion exchange character.

Maybe with a chemical pretreatment like you suggest, one could maybe get it to work, but what about the excess chemical pretreatment, where does this end up in the process?

Flash SGC on non-treated straight out of the box Brockmann 1 alumina might work, leave the tail end on the column?

Acidic alumina will retain basic impurities and basic alumina will retain acidic impurities. But they won’t exchange and donate something in return, like an ion-exchange resin.

Ion-exchange is one-for-one, that’s the beauty of it from a chemical workup point of view, and you can control what the resin gives in return.

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something I just thought of…
I’ve bought peppermint oil, I’ve bought menthol crystals, and, I have had peppermint oil crash out the menthol crystals without trying to make it happen…

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there is a whole body of thought about such chemical interaction.
Certainly I have given thought to this concerning…how does THCA
crash out of crude bho? Seems weird does it not? Mother liquids are considered somewhat magic.
However, it might be crystal…what is the exact nature of those crystals. There is science to cyrstallization, (I am quite ignorant of it)
but in many regards it is also thought of as ART.
Someone in Madras knows how to crash out CBDA?

Yes, and earth is a liquid and you are walking on crystals that
“crash up”. assuming your note is cryptic in some manner?

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It’s weird how these kinds of conversations don’t have all the likes from all the forum members.

Shit like this, “Running 2.75k isolate to 2.75L of heptane to 27.5G of pTSA.” gets a bunch of likes.

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One and a half mol percent of catalyst would get an upvote from me. The solvent to substrate ratio seems to thick. This is a very exothermic reaction and think of the solvent as having to absorb the exotherm and mediate the heat exchange between the cooled walls of your reactor and the reactants.

I’d be surprised if pilot plant synthesis scale-up in drug development would even consider less than 3:1 (solvent/substrate).

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That’s a head scratcher if chromatography in any way isn’t going to give you an answer. Maybe figuring out new programming measures along with new chemical sops to give a reaction to a chromatography machine so it can analyze what kind of thca salt you’ve constructed. Other than that I have no direct answer.

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@GroovyOctopusLabs thank you, and Yes…agree…If you look closely at what the varian/Agilent
people were doing in the FIA HRAM section of their paper,
they are directly injecting the Cerilliant standard (diluted)
into the electrospray ionization MS (no hplc column).
their results surprised me: THCA Na salt.

but these amounts at analytical scale hardly amount to
nanograms…and are easily contaminated… so it is really
hard to say what is in the Cerilliant vial.

The proposed concept of thca solution being passed over an
ion exhange column H+ to ensure the neutral H form looks promising.
see above @mitokid and the addendum section above: weak anion exchanger.

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So in theory, you’d LLE the shit out of what you’re making as a thca solution and get it close enough before the ion exchange, right?

What do mean by a thca solution for this scenario?

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I point out a LLE acid wash that is used in preparations
of H form acids . @mitokid has suggested a clever alternative
to achieve the same result with ion exchange resins.
The solution (protic) solvent for the ion exhchage would be Ethanol although other solvents may do.

LLE is an acid wash of an immisible alkane (aprotic) with a protic
water pH less than pH 2. All dictated by the pKa of 3 for the carboxyl of THCA. (one might in a sense think of this as ion exchange).

Both steps achieve the same result…in one case you end up in Ethanol the other alkane.

You see we have two groups of extractors of cannabinoic acids.
Ethanol people and Butane people.

In a restricted sense…this blog “Butane works but no theory” is all
about the UNIQUE challenges of extracting weak anions from
plant materials utilizing an aprotic solvent. The problem is complicated by the anion being an analogue of salicylic acid.
(the later presents many varieties of form, intramolecular and intermolecular, dimers and ion pairs etc…and these forms switch
with pH and transitions from aprotic to protic solvents)

Thinking about preparing mother liquid solutions to cyrstallize specific forms by precipitation from aprotic solvent is NOT straight forward. Nor is the analysis of such cystalline salts by RP HPLC methods without problems.

Yes, Butane works as a extraction solvent, and as a mother liquid
for crystallization. Yes, you get pretty crystals (of multiple forms)
but what salt form do you have?

This present discussion has evolved into how to force your product into the H form. And, the present discussion may at some time
help to understand the now ubiquitous questions concerning “Crystal diamonds” vs “Chalk production” vs “mesomorphic glassine states.”

Or just smoke that shit and don’t think about it.
sometimes I think Willybilly “DUH” might know something as well.

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This discourse is getting a little diffuse and confused, I think.

I said that I if I was concerned that my supposed THCa-H preparation had a little THC-Na in it, I would prefer to convert the putative sodium salt contamination back to THCa-H using ion-exchange instead of repetitive acid washing.

From a conceptual point of view, I find it highly unlikely that “chalky” THCa-H preparations are due to THCa-X or (THCa)2-Y, where X could be Na or Y could be Mg, since those solids aren’t known and can be assumed to not be stable species.

Someone else (I think it was @Trippie) already hinted at different crystallization behavior in butane vs iso-butane. To me, it seems much more plausible that lower quality crystalline preparations are the results of solvent inclusion and as residual solvent is released/escapes the crystal lattice it has the overall effect of macroscopic breakdown of the crystals.

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So I guess we should just ignore the only know data where
the THCA Na adduct is detected by direct ionspray MS…?
Is it your interpretation this is an artifact?

Where do you get the idea that such salts do not exist?
Assuming you have read the Patent on Cannabinoic Salt preparation?

curious?

Actually if you made a close inspection of the literature you would find those who report the isolation of THCA H form…by using the “strong acid wash”…report it to be “chalky white powder”…I believe I have pointed this out above or else where.
So this means we are in agreement on that aspect.

sodium salicylate…buy it from Sigma…
so you have some crystal ball that says you can not prepare
the sodium salt of THCA…I assume this is your own unpublished
work with THCA preparations?
https://www.sigmaaldrich.com/US/en/search/54-21-7?focus=products&gclid=Cj0KCQiA8ICOBhDmARIsAEGI6o1GeQObQslsCQ4AUeLDuGODPwIasHsHDQWyNRZ35rfiU2vYC-m50ZEaAp2HEALw_wcB&page=1&perPage=30&sort=relevance&term=54-21-7&type=cas_number

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I am not saying that the salts cannot be detected in the gas-phase of an MS-detector.

But extrapolating that detection to surmising that the salt would be crystalline, is a stretch of my imagination.

I don’t remember if we went over this in DMs or in this thread, but there’s quite a difference between for example alkali salts and ammonium salts. In the latter, there’s a proton involved and the charge separation between the THCa anion and its counter-ion is not complete. In the former case, the charge separation is complete and I suspect the resorcinylate to not be stable. I have provided my $0.02 as to why this might be the case.

And while the patent claim these salts, no examples beyond typical ammonium salts are given.

I am not claiming to have a crystal ball, but if I had the setup, I’d do some experiments, convert THCa-H to some salts using ion exchange, evaporate those preparations to dryness and I’d communicate my findings.

Maybe the cesium and barium salts are stable?

Sodium salicylate is quite different from the putative (crystalline) sodium salt of THCa. The ring structure of THC is such that the resorcinylic oxygens exacerbate the situation.

That is why THCa decarboxylates more readily than CBDa, and I did provide a reference to a pretty comprehensive in-silico study.

Here’s an old paper of some relevance:

The Carboxylation of Resorcinol and the Separation of beta and y-Resorcylic Acid by Ion-exchange Chromatography.pdf (792.9 KB)

I interpret the relatively harsh conditions needed to carboxylate resorcinols with corresponding relative ease of decarboxylation. It’s a case of microscopic reversibility, EAS is an equilibrium, in a sense. Another piece of evidence is from Mechoulam’s lab when they studied carboxylation of cannabinoids with MMC, a related reaction to the one in the paper. They could form CBDa in decent yield, but in the case of THCa, yield was low single digit %, if I am not mistaken.

If crystalline cannabinoid acid metal salts were stable, they would have appeared in the chemical literature a long time ago.

The fact that Cerilliant’s THCa-H was supplied in MeCN may have contributed to stability of any THCa-Na contamination. The paper lack experimental section and doesn’t seem to have been peer-reviewed. Who knows where those sodium ions came from, workup artifact, syringe, sample prep?

The authors’ findings, spurious or not, does not extrapolate to extraction of THCa-Na from biomass with a LPG, resulting in downstream complications in the attempted diamond formation step.

Would it be helpful running your first crop “chalk” through Dowex and then attempt diamond formation; I cannot see why not?

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So that being said, perhaps there could be a way to find the perfect blend of Butane×Isobutane×Propane or a mix of the two to get the “Ideal” crystal growth.

Trial and Error?

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That was exactly what I was inferring. I likened a straight short-chain alkane to having an effective shorter shortest dimension than for example iso-butane, possibly being better at “wiggling” itself away from the growing crystal lattice.

A perfect crystallization solvent is a single solvent, in my opinion. In the case of diamonds, slow growth may be the more important factor attributable to crystalline quality.

Crystallization can definitely be a lot of trial and error and oftentimes it happens by accident. The fact that THCa is very crystalline is of course a good starting point.

Maybe it’d be better to pick a “bigger” alkane, and I did mention neo-pentane. Another one could be iso-octane, a cheap and pure hydrocarbon.

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So we agree about possible contamination as an explanation for ion spray data.
We agree chalk could be H form.

I think I’ll stick to the strong acid wash below pH 3 if you don’t mind.
I think your ion exchange resin proposal has great potential
as final CRC step implemented at scale…especially in protic ethanol-extraction labs. Some may already exploit this in the form of acid washed silica…(New Hampshire ?) proceedure.

I have the greatest respect for Mitokid’s advice…
but all should know there are grey areas…
“but no theory” is the point to explore ideas (grey) …
I’ve thown out at least “A few dozen hints”…these need to
be evaluated and most discredited. It is a check list. That is the whole purpose. Extraction from biomass to crystallization from mother liquid is a lot to cover, with one solvent , in this case various forms of Butane.

btw…the paper was peer-rewiewed.

“The authors’ findings, spurious or not, does not extrapolate to extraction of THCa-Na from biomass with a LPG, resulting in downstream complications in the attempted diamond formation step.”

I would agree, in caveat version: “does not necessarily extrapolate.”
nor did I say it did…from extraction only…but a lot of people run their material through CRC right off the butane extraction column…
and when it come to “dirt” for purity, not CRC (color)…I have pointed
out things are a bit more complicated. Sodium is so ubiquitous in
any type of biomass, it boggles the mind to think of any extraction of
plant or animal biomass that does not have measurable sodium ions present. And grant you Butane would be the lowest.

I’ll stick to the strong acid wash.

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I thought plants were more into potassium and magnesium. In any event, I would assume that whatever metal anions are essential to a plant are bound to negatively charged plant macromolecules and don’t necessarily suddenly decide to pair of with THC carboxylate anions just because the biomass is extracted.

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