Stimulants Amphetamine purification with methanol

[mutteri]

This information may be difficult to find from the internet, so posting it here.
Amphetamine sulfate is soluble in methanol, with solubility around 4g / 100ml or more. In comparison, amphetamine is only slightly soluble in ethanol at around 0.2g / 100ml. Also, methanol evaporates quickly, twice as fast as ethanol or four times as fast as water. Thus, methanol is really good solvent to purify poor quality street speed. Though, the acetone wash should still be the first purification procedure. Unlike in the acetone wash, it is not recommended to "dry" methanol with epsom salt, as dryness is totally unnecessary, and menthol additives in the epsom salt will dissolve in polar methanol.

The information that 4g amphetamine dissolves in 100ml of methanol is everything needed, techniques for filtration and evapoartion can vary. Basically mix speed into methanol, then filter out crap not dissolved, and evaporate out the methanol. This may remove the majority of the cutting agents. The procedure can be repeated to the consentrated sample with smaller amount of methanol, though it works only if the cutting agents are less soluble in methanol that amphetamine is. Handy tools in the process are glass syringe to gently suck liquids, and glass petri dish for evaporation. Note that plastic tools may dissolve in stronger solvents, and it is better to use glassware with solvents.

 

[4DQSAR]

I believe amphetamine phosphate predominates in some markets. I don't know what the solubility characteristics of the phosphate addition salt are.

I guess if you know what excipient(s) are present, it's a decent idea, but again, it does seem like the 'cuts' vary from nation to nation.

But if it works for you - that's what matters.

 

[Docta]

solubility characteristics of the phosphate

RE: Amphetamine Phosphate

Slightly Soluble in Methanol (1-10g : 1000mL)

it is not recommended to "dry" methanol

By far the most common adulterant is Glucose, powdered (amorphous) not crystal.

Thing to keep in mind, amorphous glucose is sparingly soluble in methanol and that's with reagent grade "dry" methanol.

Any amount of water such as what is found in industrial grade methanol would increase glucose solubility. Problem is you'd really need to dry using 3Å molecular sieves or better just use dry methanol.

 

[4DQSAR]

RE: Amphetamine Phosphate

Slightly Soluble in Methanol (1-10g : 1000mL)

That's one heck of a range.

I only know OF it because it turned up on Russian Hyperlab at some point in the 90s with various Russian (?) chemists saying how much easier it was to produce compared to the sulfate.

I've never knowingly come across it. That said, I've never encounted any form of non-medical amphetamine.

 

[Docta]

That's one heck of a range.

Yeah, my early Pharmacopia are kind of vague giving a generic range for the term "Slightly Soluble" not an exact value or specific temp to saturate a given solution, unlike what we take for granted today.

Russian Hyperlab at some point in the 90s with various Russian (?) chemists saying how much easier it was to produce compared to the sulfate.

That's really odd, cos when selecting an acid conjugate for salts or co-crystals a suitable acid is generally ΔpKa >3 below that of the base.
Amphetamine is pKa 9.9 therefore suitable acid must be pKa 7 or less.
Phosphoric acid (H₃PO₄) would need to disassociate to dihydrogen phosphate (H₂PO₄⁻) with pKa1 (2.15) to form a good salt, with the other disassociations outside the ΔpKa >3 rule. Resulting in a sticky mess like paste needing extra steps to cleanup, the only upside is all that extra mass gives a shit load more product as an end result.

As a comparison:
Hydrochloric acid is pKa -7 and that's fine and it disassociates fully in one step, but it's very hygroscopic making storage of the end product an issue.
Sulfuric acid is a polyprotic acid making pining down the pKa value kinda tricky, let's call it pKa -3 (for the sake of the post) so it's fine and no issues with the chemical properties of the resulting sold making it the most commonly used, the extra mass over HCl pumping up the weight of the end product a plus.

4g amphetamine dissolves in 100ml of methanol is everything needed,

FYI: that's pretty much the same solubility of glucose in methanol, mind you I doubt glucose is an adulterant worth worrying about.

 

[4DQSAR]

Well it got a patent. Specifically US2507468

But I am aware that one general rule of patent composition is that you don't need to give the optimized synthesis, merely a method that produces at least some product hence my suspicion that the workup and possibly the entire synthesis was telescoped based on experimentaton.

I SUSPECT the reasons that the phosphate is so highly prized was because not only is the (I presume telescoped) workup actually simpler but also the product isn't hygroscopic.

I'm based in the UK and I've been told that for a while at least, it was possible to obtain what was referred to as 'amphetamine base' - which I think we can agree is a ridiculous idea. By the description, it sounded like someone had found a cut that would around a reasonably stable solid form of amphetamine that is apporoximately 50% pure (making the term 'base' even sillier). Apparently it comes a a single lump of a waxy solid. Now I have no way of knowing what addition salt(s) would be in that waxy solid. Any thoughts?

Now that precludes snorting the stuff so I did wonder if was aimed at injecting users.

I'm out of touch with current data on the subject but I know that decades ago there were estimated to be three to four injecting speed users for each injecting heroin user.

As for the hydrochloride. I don't know how soluble it is. If MOST of your consumers intend to snort it, the lower the solubility, the more painful it is.

 

[4DQSAR]

BTW I only just considered the fact of HOW pKa is calculated. Is 85% phosphoric acid in 15% water a solution of the acid in water or a solution of water in the acid? I'm sure I read that one molecule of phosphoric acid interacts with something like 22 molecules of water. I'm also pretty sure above 85% phosphoric acid forms polyphosphoric acids. It's an odd one.

 

[Docta]

Well it got a patent. Specifically US2507468

Gotta say I too am somewhat skeptical of the efficacy of the patent, it refers to "amphetamine dihydrogen phosphate." as the principal invention but doesn't clarify the constraints for the H₂PO₄⁻ ion, as you state above any aqueous solution is a poor coordinating solvent with no ion selectivity. Glossing over the presence of the other two ions (HPO₄²⁻ & PO₄³⁻) in a neutralization reaction where the conjugate pairs will favor a lower energy state. The energy will need to be dissipated through vibration and rotation heating up the reaction mixture promoting unstable bonding.

I dunno maybe there's something in the patent citations covering hydrogen bonding and temperature dependencies that I'm not seeing. As you say "it's an odd one" with pKa values shooting up further with each step of deprotonation.

Now I have no way of knowing what addition salt(s) would be in that waxy solid. Any thoughts?

I'm more inclined to think of the UK's 'amphetamine base' as a product of clandestine production/importation where HCL gas is used to precipitate the amine from whatever medium it's transported in. Hydroscopic salts are quite temperature dependent so I'm thinking when cut it'd be waxy solid cold and more of a paste when warmed up. Or alternately a phosphate with all the afore mentioned "sticky mess like paste" issues discussed earlier. I'm assuming the clandestine "chemists" aren't that big on post reaction workup.

Now that precludes snorting the stuff so I did wonder if was aimed at injecting users.

My understanding is standard ROA is swallowed in a rolled-up cigarette paper, I very much doubt IV would be the target demographic.

As for the hydrochloride. I don't know how soluble it is.

According to Pharmacopia HCl salts are soluble in water, methanol and chloroform.

 

[4DQSAR]

Well amphetamine sulfate is more correctly ampetamine hydrogen sulfate. It's not one molecule of sulfuric acid is forming an addition salt with two molecules of amphetamine. So with the phosphate, it's more properly amphetamine dihydrogen phosphate.

But as I said, when you reasch 85% phosphoric acid, you get the odd situation where pyrophosphoric is being formed i.e. dehydration of the acid.

Do you mean GENERALLY HCl salts are soluble in water, methanol and chloroform? Because I can point to many examples where the hydrochloride salts are almost totally insoluble in water - it's those addition salts that retain free hydrogens that are far more soluble. I know this because I've had to find salts which were reasonably soluble in water when the hydrochloride salts proved impossible to snort.

It's been a LONG time since I was around people using amphetamine sulfate, but they were all snorting it. Yes people bomb the stuff, but it's not uncommon for people to snort it. Maybe if 'base' is now common, people would be faced with bombing it or shooting it, I guess.

 

[Docta]

Do you mean GENERALLY HCl salts are soluble in water, methanol and chloroform?

No, in this instance I'm refiring to amphetamine HCl as listed in an early Pharmacopia.

 

[Dr. Trismegistus]

Anyone ever had the pleasure of "Selenium" Amphetamine ? One Introduces the Se #34 into the benzine ring. If you have any Selenium sittin around introduce the @mino to find the organic synthetic R1a1...hint: Mitsubishi early 2004 synthesized in America then flooded into Afghanistan. The drug even showed muscle over the ancient opium epidemic. [RARE KNOWN FACT]

 

[4DQSAR]

Ne hable drünkanese.

Do you perhaps refer to 2C-Se? Toxic and dimethylselinide is just awful to work with. The odour hangs around for weeks which is the least of the issues. First step 13% yield and it goes downhill from there.