Purification of Mescaline HCl

[DrSeltsam]

Dear fellow members of the nexus,

during the last months I did some extraction of cacti and purified the extracts. Endlessness was so kind to offer me LC-MS testing on the results (many, many thanks!) and of course I would like to share them.

Extraction
Difference to Ron69:
I salt with 50 mL of very diluted HCl*dH2O (~ pH 3-4) a couple of times until the pH does not change any more. I used to put the 50 mL in a ceramic pot on my induction stove and got rid of the water quickly (no problem with good temperature control).
This resulted in 2250 mg of crude product (from multiple extractions. Yield was between 0.42% and 1.4%).

If you know what you are doing with HCl then I would say that this tek is faster and easier than the original tek by Ron69. The HCl salt is much more stable and can be heated up to evaporate the water quickly. Going from 500g of dried cuttings to the raw extract in 4 days as a side project is no problem.

Cleanup
(all solvents were dried over MgSO_4)

Step one:

Washed the salts:
2x 20 ml Acetone
1x with cold IPA

Dissolved the crystals in dH2O, filtered them, and evaporated the water again.

2x with 10 ml Acetone

Result: 1914 mg (85%) slightly yellow product with some smell.

Step 2:

The IPA/Acetone was evaporated without heat and collected as a brown, slightly sticky, and smelly salt.
This is sample #1
The remaining 1914 mg were taken and boiled in 25 ml Acetone:IPA 4:1. After boiling for 5-6 minutes, the mixture was cooled down and put in a freezer over night.
This resulted in 1614 mg slightly off white crystals (87%, 74% total) without a smell. This is sample #3.
The solvents were evaporated without heat and the residue collected. This is sample #2.

On Friday Endlessness send me the results and I was blown away:

#1- 72% Mescaline
Contained DMPEA (3,4-dimethoxyphenethylamine) (unquantified due to lack of ref standard)
#2 -99% mescaline
#3 - 93% mescaline

Comments:

#1: Not great that I caught so much mescaline when washing with acetone/IPA but it seemed to work.

#2: This fraction was supposed to be waste but it turns out to be more pure than the final fraction. It has a typical smell though.

#3: Good news: my final product is nice and pure. The washes seem to work nicely, although they did not remove the smell. When removing the smell with the IPA/acetone boil I seem to lower the purity of mescaline in the main fraction. Why are my left overs more pure than the main fraction?

I have some comments:

#2 might not be purer than #3 but the sample was not representative. When I evaporate the water in the ceramic pot, some spots contain more of the brown impurities than others. See an attached photo for an example.

The smell might just be a chemical that one can smell at very low concentrations and the smell or the color says nothing about the purity.

It seems to be very important to not only dry the solvents but the crystals as well. In later experiments I put the extract in a paper envelope in a jar where dry MgSO4 was at the button. Weighing confirmed that the MgSO4 removed some weight. I will post the results of these experiments in the upcoming days

 

[Quetzal7]

Thanks for sharing
I'm still researching all available info about mescaline clean up ; this is still a confusing topic isn't it? so thanks for adding to the story !
#1 and #2 are supposed to be the discarded parts... so, is this cleaning removing more unwanted material than it is removing mescaline?
Thou, you still got 74% after cleaning, i thought it would be more loss.

 

[DrSeltsam]

If you have Mescaline HCl (make sure that you do!) the cleanup is quite nice to do.

The washes are pretty straight forward and the best part is that if you fuck up you can just evaporate the solvents and you are back where you started. If you ever done column chromatography that is something that you crave for

Without a lab you have two options:

1.) Wash with acetone or IPA

2.) Recrystallise from IPA or IPA/acetone.

About the yield: It is very close to 85% as fraction #2 is essentially pure mescaline. This means that I started with nearly pure mescaline before the cleanup and the cleanup was pretty pointless

 

[Elrik]

Nice work
A shame that 1/9th of the mescaline went off with the accessory alkaloids and gunk in the initial purification stage. But at least that got the DMPEA removed.
Perhaps washing with something a touch less polar would direct it more toward the DMPEA and other alkaloids. Acetone or MEK with a few drops of toluene, perhaps.
Did you happen to bioassay the mescaline + DMPEA + gunk and compare it to 240 mg of the pure mescaline.HCl?

 

[DrSeltsam]

I would not think of a shame that I lost some mescaline. I got a nice drug without going to the black market. This was the main objective and I reached it

Xylene or tuloele might work but I don’t want to have these kind of solvents at home. They are even more toxic than limonen.

I’m really careful with bioassays. I don’t consume more often than every 6-8 weeks and refrain from anything besides caffeine in the meantime (that includes alcohol). Having said this I tried 270 mg of #3 and it gave me a very frightening ego death experience. For now I’m not sure if I ever want to go that high again. Thus, the material will last a bit for my personal use

 

[urtica]

Thank you for this! I have been thinking that I would convert my crude HCl extracts to the sulphate for purification, but maybe now I don't have to!

 

[DrSeltsam]

I did a new extraction and got 2756 mg of raw extract. The stuff was pretty smelly, brown, and a bit sticky.

In the following everything was dry and I think this is a key to reducing losses. The brown stuff in the extract is pretty hydroscopic and thus you have a lot of water present when doing washes.

The solvents where dried over MgSO_4 as usual. The solids where placed in a small paper envelope in a jar where the bottom is filled with dry MgSO_4. In my trials the solids lost 200-250 mg of weight over night. Between the steps, the solids where placed over the MgSO_4 again.

Step one:

I performed 3 washes with acetone. There are two challenges here:

a.) As the power is super fine, it will run through a coffee filter when you decant of the solvent after the washes. You will need proper filters where you let the solvent run through when decanting. See the acetone_wash pictures.

b.) After the washes it is very hard to get the powder out of the glass without losses. I simply dissolved the left overs in dH_2O (wash multiple times with dH_2O!), transfer the solution somewhere and evaporate the water. See picture evaporation_mesc1

The acetone was evaporated as well. The residues didn't crystallise but where just a sticky brown/black oil. See picture acetone_leftovers.

This step yielded 2622 mg (95%) of still brownish solids (see evaporation_mesc2).

Step two:

The solids where placed in a sealable glass jar (heat resistant!) in an oil bath (105-115 °C) and 8 ml IPA/g were added. Then adding a few ml at a time until everything was dissolved. This can take quite a bit of time. I would say that one needs about 8-9 ml IPA/mg of mescaline. If you reduce too much, the mescaline will just crash out in the heat. See the recrystallisation_ photos for details.

The solution was reduced a bit and then removed from the heat. See recrystallisation_3

Formation of the crystals was relatively quick and happened without any help within a few minutes. See recrystallisation_4. After this I added 10 ml of Acetone and placed it in a freezer for a couple of hours but nothing really changed anymore.

I think you can just recrystallise from IPA directly as seen in the literature. No need for acetone.

The crystals were directly washed with acetone and dried using medium heat. This gave 2246 mg (85%) of slightly brown crystals (see recrystallisation_5).

The solvents were evaporated but only with minor crystallisation was seen for the residues. See recrystallisation_leftovers_1.

I am not sure if I want to recrystallise again or if the result is pure enough. Probably I would need to ask Endlessness to test again

So much. Any comments?

 

[An1cca]

Hmmm, those EC-results are hard to believe. A residue that isn't even white would be 99% pure? I attach a picture of M-SO4 that was tested by EC and was reported to be 'only' 94% pure. That being said, I'm a sulfate-man, so I have no experiene in cleaning up HCL-salts....

I agree that the washing-step is lossy. I observed the same thing with M-SO4 and MgSO4-dried acetone. You can read about this in the pdf of this OP: Mescaline quantification in live cacti using TLC - Collaborative Research Project - Welcome to the DMT-Nexus . Successive recrystallizations give yields >95% (3 times). However, this process is time consuming and you'll have to be creative in your techniques when working with small sample masses. Check out the pdf for ideas on this.

I can also say that purification for the sake of dosing can be omitted by using quantitative TLC with a known reference. Takes a few minutes to make a solution of 1mg/ml and then 30 minutes for developing the plate and analyzing the ninhydrin-spots. Although I just love the looks of pure crystal, any loss of this precious gift is too much. You can read the procedure in the pdf above. Quantification of extracts tends to be very accurate and reproducible.

 

[Mindlusion]

Hmmm, those EC-results are hard to believe. A residue that isn't even white would be 99% pure? I attach a picture of M-SO4 that was tested by EC and was reported to be 'only' 94% pure. That being said, I'm a sulfate-man, so I have no experiene in cleaning up HCL-salts....

Wow, I too find that hard to believe looking at those crystals. Normally when you have long needles like that, its not even worth to run spectra, you know its >99%

Did EC send you any further information? If they do not discount water, it would definitely contain some, and that will throw off the data if not recognized. Unless it is an inorganic salt but if the crystals are uniform like that it would be pretty obvious.

perhaps even just the molecular weight was miscalculated, the formula weight for 1 mol mescaline sulfate dihydrate is 276g/mol

if you don't include the dihydrate it is 260g/mol

260/276 = 0.9356 = 94%

 

[DrSeltsam]

An1cca, thanks for commenting

Sorry if I caused confusion with the pictures. The batch which EC tested is not depicted above, this is a later batch from which I have taken the photos. The actual batch looks slightly off-white to brownish.

From the years of lab courses I can remember that color is no indicator for purity Even 0.5% impurities can make something look really dirty if the impurities have a strong color and the main component is white. Often times during my time in the lab the main impurities were left over solvents.

I would agree with Mindlusion that EC did not take into account that sulfate forms the dihydrate. If I remember your pdf right, the result should be practically pure. Additionally, the numbers from Mindilusion look suspiciously close

Also, thanks for the suggestion with the TLC quantification. As I currently don't own a TLC chamber, plates etc. this is not an option but it might be something I will look into in the future

 

[An1cca]

Wow, I too find that hard to believe looking at those crystals. Normally when you have long needles like that, its not even worth to run spectra, you know its >99%

Did EC send you any further information? If they do not discount water, it would definitely contain some, and that will throw off the data if not recognized. Unless it is an inorganic salt but if the crystals are uniform like that it would be pretty obvious.

perhaps even just the molecular weight was miscalculated, the formula weight for 1 mol mescaline sulfate dihydrate is 276g/mol

if you don't include the dihydrate it is 260g/mol

260/276 = 0.9356 = 94%

Thanks a lot for that Mindlusion! This was Endlessness's report from EC: "Results arrived, its 94% mescaline.. I asked for the mass spectra file but it seems there's nothing else in there "

That would be in complete accord with your calculation. Great, so it seems to be even purer! I used this sample to prepare a reference for TLC, so will have to adjust all results accordingly...

From the years of lab courses I can remember that color is no indicator for purity

You're absolutely right there, that statement of mine held no sense. I had the same experience when sending snow-white 'harmine' to EC for analysis, only to find out that it was only 63% pure... In those analyses as well, I frowned my eyebrows from time to time, but hey, GC/MS doesn't lie, does it :? ?

 

[endlessness]

Yeah some surprising results there TBH..

They should be doing everything correctly, they have reference standards and do quantification curves, so results should be reliable.

In any case I was thinking, we should maybe resend the most controversial samples and see if the results are consistent, what do you guys think?

And maybe next time we could send 2 of each sample labelled differently, to increase the certainty of the results

 

[DrSeltsam]

@An1cca, GC/MS is a bitch, just like the truth.

@endlessness, I don't see any reason to not trust the results from EC Quantifying attached water is super hard in LS-MS or GC-MS. To do this, the method of choice would be the good old fashion elemental analysis/thermogravimetric analysis which one would run complementary to a LC-MS/GC-MS.

 

[Elrik]

Has it been determined whether the accessory alkaloids are being removed best by acetone or IPA?
On the subject of washing or recrystallizing mescaline.HCl, people tend to evaluate success most by the color change in the product. I like pure white sexy crystals as much as the next person but ultimately I intend to swallow the stuff and I havent seen any direct comparisons between cleaning method and change in drug effects in the forums here.
I started gearing up to recrystallize 3 grams in IPA, wash 3 grams in acetone, and wash 3 grams in acetone followed by recrystallizing in IPA so I could compare the effects but figured I should ask so I'm not needlessly duplicating effort.
Basically I hope to reduce body load and make it more clear headed with the decolorizing of the product being a secondary consideration that I wouldnt sacrifice much yield for.
I'm never going to sell the stuff so it doesnt really matter if it looks like tang powder :lol:

 

[Biawak]

Going the FASA route produces nice white mesc without all the fiddling around and losses.

 

[DrSeltsam]

Elrik, this is my hunch:

If you have a low concentration of the amber coloured impurities, I would do as I did with the fist batch and use acetone and IPA. It is rather quick to do and it seems like removing the smell by boiling in IPA is a waste of material.

If your extract is rather brown, sticky, and hydroscopic I would go for re-crystallisation from IPA. When I did this in the second batch, I was surprised how much of the oily, brown substance was in the mother liquid although I washed with Acetone before.

Once, I performed a dual solvent re-crystallisation of MDMA. The MDMA rapidly dissolved in boiling IPA before adding acetone while for the mescaline HCl it took 10-15 minutes to dissolve in boiling IPA. The difference being that MDMA HCl is the salt of a secondary amine, which is less polar than the salt of a primary amine.

My hypothesis is that the waches are rather ineffective for the oily substance as the kinetics is very slow and it takes heat to get it into solution. Does this make sense to you?

 

[endlessness]

Going the FASA route produces nice white mesc without all the fiddling around and losses.

agreed

 

[An1cca]

Going the FASA route produces nice white mesc without all the fiddling around and losses.

agreed

So to the freebase dissolved in xylene/toluene you add FASA until no more M-fumarate precipitates out?

Do you wash with anhydrous acetone afterwards or do you make abstraction of potential residues...?

Is this method specific for 3,4,5-TMPEA? Any known GC/MS of extracts thus purified?

Can you recycle your solvent in any way?

 

[DrSeltsam]

I would also be very interested in the results of the FASA route. Sorry for my directness but this sounds like the poor mans version of what you usually do to get clean salts. Shlugin describes this in PIHKAL after the reduction step with LAH and the workup:

There was then added 50 g potassium sodium tartrate, followed by sufficient NaOH to bring the pH >9. This was then extracted with 3x75 mL CH2Cl2, and the solvent from the pooled extracts was removed under vacuum. The residue was distilled at 120-130 °C at 0.3 mm/Hg giving a white oil that was dissolved in 10 mL IPA and neutralized with concentrated HCl. The white crystals that formed were diluted with 25 mL Et2O, removed by filtration, and air dried to provide 2.1 g 3,4,5-trimethoxyphenethylamine hydrochloride (M) as glistening white crystals.

Shulgin removes the NPS before preparing the freebase in IPA. The reason for this is twofold: the vacuum distillation is very nice for cleaning and you want to form the crystals from a solvent which you do not mind ingesting. As I can tell from my own experience, I could always see the the solvents in my NMRs when I directly crystallised from the NPS.

Perhaps I just have an anchoring bias here... MS results would always make me happy.

 

[endlessness]

So to the freebase dissolved in xylene/toluene you add FASA until no more M-fumarate precipitates out?

Exactly! (or limonene)

Add FASA (or FASI) dropwise very slowly over a few hours for larger crystals and (seemingly) extra purity

Do you wash with anhydrous acetone afterwards or do you make abstraction of potential residues...?

Yeah I do at least a quick wash to make sure I remove the non-polar from it . Can be with cold anhydrous acetone or IPA, both work fine..

Is this method specific for 3,4,5-TMPEA? Any known GC/MS of extracts thus purified?

More tests would be necessary to affirm that, in the test I did years ago I remember mesc being the only alk

Can you recycle your solvent in any way?

Easily, just wash your non-polar solvent with water several times to remove acetone or IPA and excess fumaric acid, and you can reuse it

I would also be very interested in the results of the FASA route. Sorry for my directness but this sounds like the poor mans version of what you usually do to get clean salts.

On the contrary, I find it one of the most efficient (and beautiful) ways to precipitate salts and easily clean them.

To be honest it was many years ago I did this test and I dont remember the exact results but I think it was around 90% IIRC

Id totally be willing to send to analysis if anybody did this.. It would be specially awesome to do a side-by-side to compare the FASA/FASI method vs other methods in terms of purity and yield.

If you give it a try let us know how it goes