Purification of MDMA by recrystallisation

[ThreePointCircle]

I posted this on the What is wrong... thread but it got buried. I hope making it into its own thread is ok.

I wanted to understand purification by recrystallisation a bit more - specifically when an impurity has similar solubility to the desired product.

I was reading for example here that an impurity of a similar solubility could be removed by recrystalisation if there was sufficient difference in concentrations - because their saturations are different and so one will recrystallise before the other. If you wanted to remove MDDMA HCL (for example), I note that its solubility appears to be the same as MDMA HCL, at least for the solvents listed. So could they be separated if the ratio was as high as 20:80? That article says the rule of thumb is 5 mol% or less but I was wondering if you could do it with repetitions and a tolerance for lower yield? Would the MDMA and MDDMA being closely related cause a problem?

Hopefully someone can answer, I couldn't find a lot of info online but I lack the chemistry knowledge so could have been googling the wrong thing.

 

[HOOH]

Yeah there's not really a simple way to isolate MDMA and MDDMA from each other, but most MDMA doesn't containing MDDMA anyways.

 

[ThreePointCircle]

Yeah there's not really a simple way to isolate MDMA and MDDMA from each other

So how come the procedure doesn't work if there's a difference in proportions? The more I read, the more it seems like it should, albeit with quite a bit of product lost.

but most MDMA doesn't containing MDDMA anyways

This paper would suggest otherwise. What are you basing that claim on?

 

[S.J.B.]

Yes, if you have two crystallizable components of equal solubility in an 80:20 ratio, and they do not co-crystallize, then you can increase the ratio of the major component to the minor via recrystallization. In addition, being a tertiary amine, MDDMA HCl should be somewhat more soluble than MDMA HCl in organic solvents, which will ease the purification.

This paper would suggest otherwise. What are you basing that claim on?

Note that trace impurities are being analyzed here. There isn't any quantification, but the MDDMA HCl, at least in the spectrum and graphs shown, is nowhere near 20% of the mixture (most likely far less than 1% ). Which will, of course, ease its removal by crystallization.

 

[ThreePointCircle]

Note that trace impurities are being analyzed here. There isn't any quantification, but the MDDMA HCl, at least in the spectrum and graphs shown, is nowhere near 20% of the mixture (most likely far less than 1% ). Which will, of course, ease its removal by crystallization.

Yeah true. I'm just working on a theory after Energy Control changed their mind on @indigoaura 's sample and that the author of this paper guestimated that 20% MDDMA might be enough to cause a 'meh' type of effect. So I fully accept that I'm working off some guesswork here but I thought it would be worth doing a good recrystallisation attempt. But I wanted to know if, assuming those guesses were correct (or another impurity producing a similar scenario) that this kind of procedure would have a chance of success.

I fully accept it's a bit of a stab in the dark but I'm keen to give it a go.

 

[indigoaura]

I would also attempt this if the process was straight forward. I have quite a bit of unsatisfying product that is just going to be trashed unless I figure out something to do with it to purify it.

 

[HOOH]

This paper would suggest otherwise. What are you basing that claim on?

On the fact that most MDMA is not synthesized from MDA (from which you would also get MDDMA via accidental overalkylation), rather it's synthesized from reductive amination of MD-P2P.

So how come the procedure doesn't work if there's a difference in proportions? The more I read, the more it seems like it should, albeit with quite a bit of product lost.

MDMA and MDDMA have very similar solubilities in almost everything, so there's not a simple way you could isolate them at home, although there are laboratory techniques.

 

[ThreePointCircle]

MDMA and MDDMA have very similar solubilities in almost everything, so there's not a simple way you could isolate them at home, although there are laboratory techniques.

But the quoted procedure is for when both have very similar solubilities, but different proportions. The more prevalent substance would saturate and crystallise first on cooldown so, if you tolerate the product loss and get rid of the solvent early, little of the undesired product would have had time to crystallise and will therefore be discarded.

 

[HOOH]

But the quoted procedure is for when both have very similar solubilities, but different proportions. The more prevalent substance would saturate and crystallise first on cooldown so, if you tolerate the product loss and get rid of the solvent early, little of the undesired product would have had time to crystallise and will therefore be discarded.

At first glance I don't see a necessary problem to that, so I guess it could work.
The product loss is still notable however.
And even more glaringly, why would you even mind taking the MDDMA, discarding it won't increase the MDMA high, you just have less of the powder youre going to take.

 

[ThreePointCircle]

At first glance I don't see a necessary problem to that, so I guess it could work.
The product loss is still notable however.
And even more glaringly, why would you even mind taking the MDDMA, discarding it won't increase the MDMA high, you just have less of the powder youre going to take.

MDDMA is a known inhibitor of MDMA

 

[HOOH]

MDDMA is a known inhibitor of MDMA

Really? Do you have any sources?

 

[ThreePointCircle]

Really? Do you have any sources?

Binding Mode Selection Determines the Action of Ecstasy Homologs at Monoamine Transporters

@indigoaura contacted the lead author. He was quite interested in our big discussion and guesstimated 20% MDDMA would be sufficient to cause the 'meh' effect. I don't know whether he meant 20% of the entire sample (1:4) or relative to MDMA (1:5). But it was a guess anyway. The paper also shows MDTMA inhibits also but I'm not aware of that being found in any samples.

Also see this paper for two other inhibitors that supposedly have been found in seized samples before.

 

[ThreePointCircle]

Here's my draft procedure. I'm no chemist so its been quite a bit of googling and mostly adapted from the procedure outlined here on BlueLight. I've put some questions at the end, hopefully some of you have some thoughts, and can critique any other aspects.

1. Prepare anhydrous acetone. Heat epsom salts in oven to convert into magnesium sulphate (see ). Put that in acetone, add enough until there is a snow globe effect upon agitation. See . Use later by pipetting off what is needed with minimal agitation
2. Weigh out 400 * 8 = 3.2g of source ‘MDMA’. 3 repetitions of procedure will leave 1/8th of product at the end (at least that’s the goal)
3. Ground in a mortar and pestle to powder and put in beaker
4. In a separate beaker pour 45mg 99% IPA
5. Place IPA beaker in shallow oil bath. Oil bath should have magnetic stirrer set to medium
6. Gently lay a sheet of aluminium over the beaker but not sealed/air tight. This is used to help keep moisture in the air out of the IPA
7. Heat the IPA to boiling or near boiling
8. Remove aluminium foil and reduce the volume of IPA somewhat to azeotropically remove the approx 1% H2O present in the IPA
9. Use a pipette to incrementally add the IPA to the product. This must be done quickly so the IPA doesn’t absorb too much H2O from the air. Do this until the product is completely dissolved, optionally swirling across the hotplate occasionally to keep the temperature up in the product/IPA mixture. Make a note of the amount of IPA added
10. Cover the product beaker with aluminium and pinch to seal
11. Let the beaker cool slowly to approximately room temperature (or only slightly warm to the touch).
12. Add 4 x the quantity of added IPA of freezer chilled anhydrous acetone. This is to help lower the solubility of the MDMA in the IPA. [need to wait until IPA is at room temp or otherwise acetone will flash boil]
13. Carefully (to minimise agitation and disruption to crystal formation) move to fridge. Allow to cool to fridge temperature
14. Carefully move to freezer. Crystals should start forming forming after 30mins
15. Wait until approximately half the product crystallise
16. Filter through filter paper and discard solvent
17. Repeat whole process from step 4, 2 more times (so finally there should be approximately 400mg left)
18. Spread crystals over a drying plate and let them fully air dry
19. Ground to a fine powder and allow more air drying to get rid of any solvent trapped in the crystals

Questions:

1. Do I need to do the oil bath, or is it fine to just heat the beaker of IPA on a hotplate with a stirrer? [step 5]
2. What’s that azeotropically removing the water from the IPA all about? Would it be better/ok to just add magnesium sulphate to the IPA and then heat that up?
3. Any ideas of how to approximate when half of the product has crystallised? All I can think of is eyeballing it [step 15]

Thanks

 

[HOOH]

Binding Mode Selection Determines the Action of Ecstasy Homologs at Monoamine Transporters

@indigoaura contacted the lead author. He was quite interested in our big discussion and guesstimated 20% MDDMA would be sufficient to cause the 'meh' effect. I don't know whether he meant 20% of the entire sample (1:4) or relative to MDMA (1:5). But it was a guess anyway. The paper also shows MDTMA inhibits also but I'm not aware of that being found in any samples.

Also see this paper for two other inhibitors that supposedly have been found in seized samples before.

Hmm, I see. Well, it's still unlikely for MDDMA to be found in any of street MDMA.

 

[G_Chem]

On the fact that most MDMA is not synthesized from MDA (from which you would also get MDDMA via accidental overalkylation), rather it's synthesized from reductive amination of MD-P2P.

MDMA and MDDMA have very similar solubilities in almost everything, so there's not a simple way you could isolate them at home, although there are laboratory techniques.

MDDMA will also form when an impure, often made in lab, methylamine is used. (Dimethylamine and Ammonium chloride present as impurities.). When this happens though MDA is often spotted too.

-GC

 

[HOOH]

MDDMA will also form when an impure, often made in lab, methylamine is used. (Dimethylamine and Ammonium chloride present as impurities.). When this happens though MDA is often spotted too.

-GC

Most illict MDMA is not synthesized directly from methylamine, rather the methylamine is produced via the reduction of the widely available nitromethane with Al(Hg).

 

[ThreePointCircle]

Hi, let me explain my thought process for this thread. There are several of us that think that there is something wrong with the MDMA we have access to nowadays. In the literature there are a few known inhibitors that have been found in seized samples, and Energy Control has changed their mind on a meh sample submitted thinking that it may contain MDDMA in addition to MDMA. They admit they aren't good at finding impurities or substances they don't know much about and as they, along with similar services, are our main way of finding out what's in our products we're a bit in the dark on everything. The duloxetine paper very much meets the description of meh and, although I don't think for a minute duloxetine is the cause, it demonstrates inhibition of MDMA is a worthwhile theory.

I want to be proactive and try and do something so I started this thread with the intention of doing a good recrystallisation method to try to remove any potential inhibitors (be that MDDMA, those other two cited, or something else). Will it work? Is there likely to be MDDMA present? Is actually the MDMA I'm getting pure as the driven snow and this is all in my mind? I don't know. But to me it's worth trying.

Therefore can I humbly request that the discussion on synth routes, and potential for MDDMA or anything else being there, be shifted on to the What is wrong... thread (where it will have a bigger audience and be appreciated) so my questions about recrystallisation don't get buried. I would like to get on with it and would really appreciate the advice of those who have better chemistry knowledge than me on techniques.

 

[vecktor]

So how come the procedure doesn't work if there's a difference in proportions? The more I read, the more it seems like it should, albeit with quite a bit of product lost.

This paper would suggest otherwise. What are you basing that claim on?

absolutely! recrystalisation works if there is a difference in proportions or a difference in solubility.
Of course there is nothing to stop you recrystalising the solid product from the first crystalisation and again, a process know as fractional crystalisation.

Don't bother drying the isopropanol unless you like pointlessly wasting time, commercial isopropanol is 99% even 95% isopropanol, which can be dried using the 87% IPA azeotrope (constant boiling point mixture) of ispropanol and water is fine for amine hydrochlorides. Don't bother. if you are that concerned throw activated 4a molecular sieves in it.
Isopropanol readily forms peroxides so be careful distilling old isopropanol to dryness.

anhydrous IPA doesn't quickly suck up water from the air, the author of that video is full of shit.

You can't suck up boiling liquid with a pipette, guess what it just boils as you reduce the pressure , when you suck it up and then sprays liquid out of the pipette.

just add enough hot IPA to get the solids to dissolve. if they don't dissolve heat it to boiling and stir be patient, then if they still don't dissolve add a little more. Guessing here because I have no idea about these solids, 3g of crude solids will dissolve in 6-12ml boiling IPA. Using a conical flask with foil on the top to stop the vapour escaping too much is the easy way.

cool slowlyt and collect all the crystals using a filter and then wash them very sparingly with ice cold solvent this removes the mother liquor stuck on the crystals. Then if you want you can repeat. having vacuum filtration makes washing and drying crystals much easier.

The old school chemistry method is to recrystalise the solids until the melting point stops going up and the melting point range is less than 2 degrees. That indicates the material is pure.

the MDDMA idea is an interesting one, most large scale production is using commercial methylamine or methylamine synthesised from nitromethane, only methylamine hydrochloride is closely watched so the big producers have no difficulty getting the stuff. But they are probably not wasting it and not using large excess which leads to the dimers.

the other way to separate MDMA and MDDMA is using acetic anhydride, treat with acetic anhydride the MDMA is a secondary amine and will form an amide, N-acetyl MDMA, this is not soluble in acidic water the MDDMA is a tertiary amine and does not form an amide and will go into the water. Pure mdma can then be isolated by hydrolysing the amide by heating with base. Acetyl is unfortunately a relatively difficult amide to hydrolyse. trifluoroacetyl amines and BOC amines or even TMS amines are easier to hydrolyse but BOC2O or trfluoroacetic anhydride or chlorotrimethylsilane or BSA are not chemicals amateurs should handle under any circumstances.

I think you will get pure product by careful recrystalisation from isopropanol.

good luck

 

[ThreePointCircle]

@vecktor thanks so much for replying! I got a few questions:

Of course there is nothing to stop you recrystalising the solid product from the first crystalisation and again, a process know as fractional crystalisation.

Yeah I was thinking of doing it 3 times, each time recrystallising half and chucking the rest. Fingers crossed that's enough to get rid of the impurity if it can be done via this method

Don't bother drying the isopropanol unless you like pointlessly wasting time

So 99% IPA and don't worry about drying. Cool, that's nice and straight forward

anhydrous IPA doesn't quickly suck up water from the air, the author of that video is full of shit

Yeah that comment came from the bluelight post. Looked authoritative but I wasn't in a position to judge haha

You can't suck up boiling liquid with a pipette

Right, so just poor the near boiling ipa into the 'MDMA' conical flask? I guess I've just got to do that carefully

cool slowlyt and collect all the crystals using a filter

Right. To room temperature, or after that to fridge then freezer?

And is there value in adding the freezer cooled anhydrous acetone to the mix to help the MDMA crystallise out?

One big worry I have, because I want to discard half each time, is how to judge when that amount has crystallised. If I just leave it the impurities will crystallise out as well. At the moment all I've got is eyeballing it. But visually I don't know how good my guess is going to be. Any ideas?

I think you will get pure product by careful recrystalisation from isopropanol.

good luck

Thanks, I'm going to give it my best shot. I guess some of my questions might be a bit dumb but I appreciate that if this is worth doing then only if done right.

I was thinking of getting a hot plate/stirrer. I know there's concerns about heating up IPA but I'm assuming the quantities here are not too risking. Would the magnetic stirrer in the IPA be useful while heating or unnecessary?

 

[Ambien Powered Rabbit]

Why not distillation?

MDDMA is a known inhibitor of MDMA

Really? Do you have any sources?

Binding Mode Selection Determines the Action of Ecstasy Homologs at Monoamine Transporters

can you explain what you mean by "mddm is a known inhibitor of mdma"? and simply quote the part of that text which validates it.
People here have a habit of claiming something then dropping a book on the desk of anyone who asks for clarity. Reading 100 paragraphs to find 1 (which may or may not even be there) is not an efficient way to back up claims.