Crystallization from Aqueous Phase

So, I’m winding down for the night and I unfortunately had an epiphany.

As we well know at this point, alkaline conditions “remove” the hydrophobicity of cannabinoids.

Edit: ima tag my favorite chemists and non-chemists I believe may have insight @Photon_noir @cyclopath @RockSteady @hambread @squig @Roguelab

Is it feasible for one to migrate cannabinoids from the non polar phase to the aqueous phase?

For instance, using the potassium tert-butoxide, you could increase the aqueous phase pH to around 17 (super fucking high) and ensure that the entirety of your cannabinoids were moved to the aqueous phase. This could potentially eliminate all color from the cannabinoids while keeping them suspended in the aqueous phase.

Then, so that you don’t co extract potassium tert-butoxide with your cannabinoids, you could resuspend in the non polar phase and then recover solvent.

Just a crazy idea before bed, but I can’t think of any reasons it won’t work…

Thoughts?

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Check this thread (my first on the forum) about the topic:

You don’t need the pH all that high and you’d likely cause reactions you don’t want if you do take it that far. It’s certainly possible to do but the efficiency is somewhat poor. We gave it one shot and I never got to give it a second go

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FutureGood Life Gang

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Jul '19

Mike from @labsociety and I had success salting out THCa, I’ll dig up the SOP and share

THCA

200 g of dried (or ca. 600 g of fresh) flowering tops and leaves of Cannabis sativa (THC type of the “white widow” variety) are extracted with 2 L of isopropanol at <40c. Next the undissolved plant components are removed by filtration. Then the alcohol volume is reduced to ~200 ml by distillation at reduced pressure. 300 ml of heptane is then added to the isopropanol solution. The organic phase is washed twice with 500 ml of 1% saline to remove the alcohol.

This first extract is stirred with 1 L of aqueous 0.1 M sodium hydroxide solution and 1% saline to stop emulsions. Test the pH of the aqueous layer. pH should equal 13.

This second, aqueous extract is separated and treated with a solution of 15 g of citric acid in 150 ml water, whereupon the cannabinoid carboxylic acids precipitate as an oil. Test the pH of the solution. pH should equal 2.

By addition of 2x200 ml heptane and stirring, a third extract is now prepared. Removal of the organic phase and evaporation under reduced pressure at 40° C. yields 15.7 g of an oily residue, which 80% consists of a mixture of the THC acids A and B.

15.7 g of a ca. 80% mixture of THC acids A and B are dissolved in 150 ml isopropanol with stirring and 8.0 g of dicyclohexylamine are added with stirring. 24 hrs stirring at 0°C. produces a thick white precipitate of the dicyclohexylamine salts of the cannabinoid carboxylic acids. Cooling to -10°C with stirring is sometimes necessary to help fully precipitate all salts out of solution. After suction filtration, washing with 50 ml cold isopropanol and drying, 18.7 g of dicyclohexylamine salt of the THC acids with a content of 91% are obtained.

18.7 g of dicyclohexylamine salt of THCA A and B with a content of 91% THC acids in the cannabinoid content are dissolved with stirring in 150 ml of boiling absolute ethanol, and cooled immediately after dissolution has occurred. Stir overnight at 0° C to crystallize out. Cooling to -10°C with stirring is sometimes necessary to help fully precipitate all salts out of solution. Suction filter the white precipitate formed and wash with 50 ml cold absolute ethanol. Yield: 15.5 g of pure white salt with a content of >97% of THC acids (A and B) in the cannabinoid content.

15.0 g of recrystallized dicyclohexylamine salt of the tetrahydrocannabinolic acids A and B are suspended in 200 ml water and over layered with 200 ml hexane. 4 g of citric acid are now added and the mixture stirred until the cannabinoid carboxylic acid salt has completely dissolved. Test the pH of the aqueous phase. pH should equal 2.

The aqueous phase, which now contains the citrate of dicyclohexylamine, is separated and discarded. The hexane phase, which now contains the free tetrahydrocannabinolic acids, is successively washed once with 50 ml of 1% citric acid and three times with 50 ml portions of water. After evaporation of the hexane phase on the water bath at 40° C. under reduced pressure, 9.8 g of amorphous residue of the two positional isomeric tetrahydrocannabinolic acids remain.

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Extremely high PH will denature and degrade your target compound

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Well, that particular base would not survive long in the presence of water, for one thing. It would probably convert to KOH and tert-butanol.

If the cannabinoids are in acid form, it is possible to LLE them (with multiple washes) from the apolar solvent with alkaline water. Unfortunately, alkaline water can also pull certain color bodies, so it is not really a viable decoloring option… Sorry, Man.

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just do multiple smaller formation crystallizations with hydrocarbons only. the colors disappear from your thca with way less work.

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Why do people insist on calling me a chemist? :rofl:

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“Chemist”

Lol but I also said my favorite chemists and non-chemists :wink:

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As mentioned, direct extraction and recrystallization using alkane solvents is much easier with much higher yields.

As a caveat, you actually can get pretty decent yields using acid/base with a straight to base(STB) style extraction on good biomass. However, scaling it uses large amounts of water and separation becomes difficult(either counter current LLE or filtration and drying) It can be done, but I haven’t seen it scaled while still being cheaper and/or more efficient than hydrocarbon extraction

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Why not go ethyl acetate - ph wash - brine wash, pull cannabanoids, then heptane wash to extracts from ethyl & recover ?

I know this is off of the direct topic, but has anyone ever tried crystallization in aqueous phase by doing a drop wise two solvent recrys? Dissolve as much THC-A into a solvent that is compatible with water, like acetone, and then setup a titration setup (Buret with compound or an empty chromatography column with a bulb reservoir) filled with the THC-A and acetone mixture (saturated).

Under the buret/column you place a Erlenmeyer flask filled with pure water, stirring enough to swirl but not make a cyclone in the flask. Drop-wise, add saturated compound solution to water flask and the acetone will dissipate and leave small fluffy crystals behind of medium-high purity THC-A flowing around the flask (for cannabis the structure would be horrible for users, it would come out as a clumpy powder.) Retrieve crystals on standard Buchner/filter paper. Put under high vac to dry. Send to analytics.

Maybe?

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you don’t need a strong base to deprotonate a weak acid, strong base will be less discriminate about what it deprotonates (strong enough base will deprotonate phenols, aka any cannabinoid). You also risk making quinones in the case of CBD/CBDA.

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In a ph environment of ph 16 for 16 hours I have had less then 2% degradation if any so I must say cbd it pretty robust

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