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FASA precipitation - Why fumaric acid?


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#1 greenskeeper

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Posted 13 April 2021 - 05:09 AM

There is a technique of precipitating alkaloids out of solution that uses Fumaric Acid Saturated Alcohol (FASA).

 

I want to try it but I can't get find fumaric acid or methanol. I've been wondering why fumaric is the chosen acid, and why methanol is the preferred solvent - Can I find substitutes?

 

I started reading about the properties of various acids and solvents (I love you PubChem) and I found that fumaric acid has the interesting property of being quite insoluble in water. On thinking a bit more I realised that there is no water involved in FASA precipitation when it's done right so it might be irrelevant.

 

It seems that acid-saturated alcohol is used to disperse the acid through the freebase-containing NP solution without introducing water. It is similar to HCl gassing in that way.

 

What about fumaric acid's solubility in alcohol, especially methanol? A bit more reading reveals that many acids are soluble in many alcohols, so I think that's not why fumaric is chosen. People are also using Fumaric Acid Saturated IsoPropyl Alcohol (FASIPA) for the same purpose.

 

I'm starting to think I could use Citric Acid Saturated Isopropyl Alcohol (CASIPA?) - citric is freely soluble in IPA and insoluble in xylene. Mescaline citrate is insoluble in xylene so it should precipitate out when CASIPA is added. Is mescaline citrate soluble in a mixture of xylene and IPA? I don't know - I'm guessing it is not.

 

Why should the alcohol solution be saturated? What happens if it only contains quite a lot of acid but has room for more? What if I put a glass of isopropanol and a glass of HCl 35% in a box together and left them for a while? Could mescaline HCl be precipitated from xylene without gassing?

 

Is there something else I'm missing about FASA precipitation?

Is it because the technique was originally used for DMT and the fumarate salt of DMT can be vapourised at about 150deg?

 

Or is it something else?


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#2 Norman

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Posted 13 April 2021 - 12:15 PM

We have our own PubChem here, his name is phineas carmichael and I’m looking forward to his answer as much as you.
Keep in mind that FASA started out using acetone not alcohol and that the alcohol versions are splinters of the original. Most DMT salts are soluble in acetone but not fumaric when the solution is saturated, hence “fumaric acid saturated”.
A deep dive over at the nexus will get you to a lot of the early discussions had during its development. Just make sure to come back here to talk about your findings.
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#3 Phineas_Carmichael

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Posted 13 April 2021 - 10:55 PM

Stop Norman, you're making me blush! Truth be told I almost always have a few PubChem tabs and a textbook or 2 open when I'm writing these things, y'all just can't see behind the scenes!

My understanding is that fumaric was used initially in the DMT precipitation because DMT fumarate is the only easily obtainable DMT salt that cryatallizes well and doesn't absorb moisture from the air. I'm not sure where I got that idea, but if the goal of the original FASA pioneers was to provide a more temperature stable form of DMT than the freebase that could still be vaporized then the fumarate salt is a good choice.

I don't see any reason why your CASIPA precipitation of mescaline wouldn't work, provided that mescaline citrate is a crystalline solid and that the solubility data available online is accurate. I can't seem to find any data whatsoever on the citrate salt from published scientific sources. Whatever solvent you use needs to be as close to anhydrous as possible, as any water in the solution will suck up the mescaline salt & keep it from precipitating. Keep in mind also that the products of an acid/base reaction are a salt and water, so the very nature of the reaction is a (statistically insignificant but non-zero quantity) loss vector. [EDIT]This is true of standard Acid/Base reactions, but not of reactions with "freebase" amines like our favorite alkaloids. Please disregard that last bit and forgive my cerebral flatulence![/EDIT]

99% IPA & Hardware Store acetone can be made anhydrous by baking Epsom salt on a sheet tray at 400°F (200°C) for 75 minutes or so, stirring every 15 minutes until the salts become a bone dry powder. Add this to your solvent, shake it up, let it settle and filter out the drying agent and you've got anhydrous solvent.

The alcohol needs to be saturated with acid because these reactions in solution are all equilibrium reactions. That is, if all the components are present in equal ratios the reaction happens forwards and backwards at an equal rate and at the same time. Essentially the reaction bounces back and forth until it settles with equal amounts of reactants & products. Packing as much acid into solution as possible forces the equilibrium to favor the right side of the equation, the products, by preventing it from bouncing backwards. [EDIT]Does that make sense to anyone but me? Feels like I could do better explaining that...[/EDIT]

Concerning HCl: at standard temperature and pressure it is a gas. The HCl we buy at the hardware store or from a chemical supply house is made by bubbling the gas through water. A glass of HCl left in a sealed box with a glass of IPA will offgass small amounts of the acid, which will then indeed disperse into the alcohol. The amount that disperses will be trivial though, as the interaction only happens on the surface of the alcohol & an equilibrium will be reached pretty quickly based on the low concentration of HCl in the atmosphere of the box. The only way to get enough HCl into an anhydrous alcohol to use it like FASA would be to bubble HCl through it. At that point you might as well just bubble the HCl through the xylene directly and cut out the middle man.

Did I get to all your questions or did I leave something out?

Edited by Phineas_Carmichael, 14 April 2021 - 12:05 AM.

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#4 greenskeeper

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Posted 14 April 2021 - 12:05 AM

Thank you, I think you covered it.

 

Anhydrous acetone: If the safety data sheet says my acetone is 100% can I assume it is anhydrous? Wikipedia says there's no azeotrope with water.

 

Epsom salts: if you preheat your oven dish to 200°C, Epsom salts crystals pop like popcorn and stick to the inside of the oven.



#5 Phineas_Carmichael

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Posted 14 April 2021 - 12:38 AM

If the SDS says 100% acetone that just means there are no other hazardous additives. It should theoretically be good to use straight out of the can. There's no azeotrope, but it is miscible with water & readily absorbs it from atmospheric humidity. A fresh can of hardware store acetone is probably anhydrous, but a half-full can from the shelf in the garage has definitely absorbed a (again statistically insignificant but non-zero) quantity of water from the atmosphere in the can.

I've never seen Epsom salts pop in the oven when sliding a cold (foil lined) quarter sheet-pan with a 1cm layer of MgSO4*7H2O into a preheated oven, but I could see it happening. Uneven heating could cause the water in the crystals deep inside the Epsom salt "cake" to boil & throw other crystals around. If that happens it is because the layer of salt on the sheet tray is too thick or the heat is too high

This sometimes happens in automotive paint when an inexperienced technician at the body shop puts the paint on too thick after a repair and/or applies too much heat. The low-boiling solvents in the paint boil so quickly that the remaining paint can't flow to fill in the holes made by the boil & you get "solvent pop" or "pinhole" defects. The solution is always less paint or less heat.

You only need a few tablespoons of anhydrous Epsom salts to dry a litre of solvent, so if you're worried about the oven try this instead. Spread a couple tablespoons on a cold foil lined rimmed baking sheet with lots of real estate between the crystals. Place it in a cold oven & slowly ramp up the heat. Bring it to your lowest oven setting and let it sit for 10 minutes before giving the tray a shake and increasing the heat 20°C or so. Repeat until your heat is well above 100°C & you've got a bone dry powder. This gentle heat with plenty of space between individual crystals will prevent any boiling that throws adjacent crystals around.

Edited by Phineas_Carmichael, 14 April 2021 - 12:45 AM.

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#6 greenskeeper

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Posted 14 April 2021 - 12:50 AM

The lesson I learned about baking epsom salt is "don't preheat the dish". If I start with epsom salt on a cold dish I have no problem.


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#7 Phineas_Carmichael

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Posted 14 April 2021 - 01:16 AM

Yes, definitely don't preheat the dish.

And keep the Epsom salt "cake" thin. Don't try & bake a 5cm thick layer in a casserole dish or cake pan. Instead use a larger rimmed baking sheet so that the same amount of Epsom salts has a larger surface area.

[EDIT]Or just use enough Epsom salt in whatever cold dish you choose so it's not more than 1cm thick. Sorry, I'm a Chemist and a Cook & have a tendency to conflate the two & overcomplicate things, especially when they combine in Kitchen Chemistry...

Edited by Phineas_Carmichael, 14 April 2021 - 01:42 AM.

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#8 Norman

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Posted 14 April 2021 - 02:27 AM

Phin, you’re right about the FASA pioneers going for fumarate salt because it’s the only common form that exists as a dry crystal. It’s also more stable than freebase so there was a lot of talk of precipitating fumarate for storage and then freebasing it back for consumption. They were also using the precipitation as a clean up process since impurities presumably wouldn’t fall out. Nobody talked about it much, but I think an injectable product was also a goal.
I really don’t see a big advantage to FASA with mescaline myself. You’re just trading a salting and drying step for a precipitating step. It’s all a lot of fun to mess around with though.
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