Sciencemadness Discussion Board

2,5-DMPEA: hcl formation and preservation

opensrc - 4-11-2006 at 06:41

howdy ho neighbours !

keep having re-occuring yet skipping wet dreams that aint quite perfect, and hoping you can help me out with the missing link...

there's this oh so sexy triangle and its singing to me, but to translate what im trying to say so it can hear me sing it needs me to form the more stable hcl salt of 2,5-DMPEA (2,5-Dimethoxyphenethylamine) from the more sensitive freebase oil for long term storage to prevent oxidation and carbonisation occuring...

here is an example as taken from the doctors love manual:
Quote:

As the free base, it was suitable for most of the further synthetic steps that might be wanted, but in this form it picked up carbon dioxide rapidly when exposed to the air.

It was readily converted to the hydrochloride salt by dissolution in 6 volumes of IPA, neutralization with concentrated HCl, and addition of sufficient anhydrous Et2O to produce a permanent turbidity.

Crystals of 2,5-dimethoxyphenethylamine hydrochloride (2C-H) spontaneously formed and were removed by filtration, washed with Et2O, and air dried. The mp was 138-139 °C.



so my question for the out there in here is are there some other solvents that could be made anhydrous to substitute for the ethanol used above to as i assume crash out the hcl crystals from the solution... ???

:(

ps- if possible please state what your suggestions are based on, e.g. experience, reading, guestimation, references...

regards,

yet another linux fiend... ;)

[Edited on 5-11-2006 by opensrc]

[Edited on 5-11-2006 by opensrc]

[Edited on 5-11-2006 by opensrc]

Nicodem - 4-11-2006 at 06:52

No ethanol in any step is used in that citation you posted.

opensrc - 4-11-2006 at 07:44

boy do i feel like a silly duffer ;)

but at the same time much more relieved :)

perhaps then you or another member can suggest a possible substitute for diethyl ether ??
Quote:

> PiHKAL #109 mentions 'Et2O' in a number of places...however I have > no idea what Et2O is, and I can't find reference to it anywhere. I get > the feeling it's probably another name for something else that I > DO know what it is...would anyone care to enlighten me? Thanks!

Yes, Et2O is diethyl ether, two ethyls (Et) bonded to an oxygen (O), hence Et2O.

Rhodium


;) - thanks for the prompt reply...

Nicodem - 4-11-2006 at 08:17

Do you mind first explaining why do you need diethyl ether at all?
If you have a fairly pure amine you can just vacuum strip off the isopropanol and HCl(aq). You are not going to measure the melting point, right? So there is no need to induce crystallization!
Even if the amine is impure, you can still remove a lot of impurities by washing the residue a couple of times or alternatively, if you need it even more pure, you can just recrystallize it. But in no case is ether a strict requirement.

Dextrose - 4-11-2006 at 18:14

How about vacuum-destillation of the freebase, weight the freebase, then dissolve in 10x xylene (or maybe toluene).
Add 1.5x equimolar of HCl (aq) stir for 5 minutes, start MASSIVE stirring and steam-distill until dry (xylene and water forms an azeotrope).
Add 10x acetone, and suction-filter.

Wash with additional acetone if nessecary.

[Edited on 5-11-2006 by Dextrose]

opensrc - 4-11-2006 at 22:37

Nicodem:

-> to begin with there is a pure >98% freebase oil, not interested in purification or m.p. test, just want to form the more stable hcl salt powder/crystal for storage...
Quote:

But in no case is ether a strict requirement.


the ether is part of the "solvent system" added to percipitate out the hcl salt from the IPA solution...

so this is what im asking... is there another solvent i can substitute to "crash" out the salt from solution ??

Dextrose:
Quote:

Add 10x acetone, and suction-filter. Wash with additional acetone if nessecary.


this is the kinda info im looking for, are you suggesting 2ch-hcl could be insoluble in anhydrous acetone ??? or do you know from experience/reference ???

Nicodem - 4-11-2006 at 23:37

Quote:
Originally posted by opensrc
-> to begin with there is a pure >98% freebase oil, not interested in purification or m.p. test, just want to form the more stable hcl salt powder/crystal for storage...

Then, like I already said, there is no need to induce crystallization, just neutralize the amine in isopropanol with concentrated HCl (use 1.1 equivalents) and vacuum strip all the solvent while warming on a water bath. You can add a bit more isopropanol and strip it off again. If necessary you can repeat this a couple of times. This way you remove all the water and HCl residues, leaving the solid, crystalline hydrochloride in the flask. Triturate the residue in acetone and vacuum filter. This works on nearly every amine, except for a few very hygroscopic ones or the ones whose hydrochlorides are quite soluble in acetone (like 2C-B×HCl, for example).
Therefore, again like I already said, you don't need diethyl ether or any other solvent to crush out the crystals. Doing so would also never give you a quantitative recovery since there will always be some of the product remaining in solution (due to IPA and H2O). Using acetone instead ether in diluting the IPA/H2O solution of the hydrochloride does sometimes crush out certain hydrochlorides, but does not always work (and if does work the recovery is always lower compared to when using ether).
In my opinion you are just complicating a very simple issue. If your goal is to preserve the product you have, sealing it in a hermetic container as a free base and keeping it in the freezer will protect it from degradation for many years (unless the container leaks!). If you flush the container with argon before you close it, then you can be sure that it will not even darken. Besides the method for the hydrochloride crystallization that you posted is used for purification and inducing nice crystallization (serving also the purpose of identification by m.p. measurement). When these are not your goals you can simplify it to suit your goals.

the simple life

opensrc - 4-11-2006 at 23:56

thankyou, what you have explained is what i thought you were suggesting but after typing out a reply 3 times and loosing it different ways accidently i did the simple version... :)

the problem with 2ch freebase oil is it reacts with carbon dioxide readily to form carbonate, so just sealing it in a container and putting it in the freezer wont prevent this, though i guess it also depends on the amount of carbon-dioxide in the vessel... , this can and is prevented by nitrogen packing or keeping it in hcl-salt form...

i guess argon could work as well ??

can you get cheaper small canisters of these gases ??
Quote:

Triturate the residue in acetone and vacuum filter.



can you explain this step, what does it do, for what purpose ?? is this to "clean" the solid, crystalline hydrochloride ??


yes your right no need to have nice fluffy powder, big chunk fine just for storage purposes... and yes i was not keen on loosing product and excess waiting time for drying...

Nicodem - 5-11-2006 at 06:21

Argon or nitrogen, even methane or krypton if you prefer! It does not matter, any gas inert to the product you want to protect from atmospheric degradation will do. Argon is generally used in labs for this purpose since it is a heavier than air and thus remains in the container while long enough for the stopper to be screwed on. But anyway, again you are complicating things. Even if all the O2 in the container reacts with the amine, there will only be enough present to oxidize a couple of milligrams. And who cares about CO2? What's wrong if there forms some carbonate of your amine? I mean, you want to make its hydrochloride in order to protect it from forming the carbonate. Is this something to do with some kinky salt racism or what? :P
Anyway, for how many years do you want to store it?

Triturate means: "To rub, crush, grind, or pound into fine particles or a powder; pulverize." (source: TheFreeDictionary)
It is only to break apart larger chunks of crystalline mass with a spatula. Acetone helps removing it from the flask as well as to dissolve any potential non salt impurity that remained included among the crystalline mass. You can omit this if you want and try to scrap the salt out of the flask with any other method you prefer.

the saga continues

opensrc - 5-11-2006 at 07:01

i like the otc method suggestion of methane, any source suggestions ... ;)
Quote:
Even if all the O2 in the container reacts with the amine, there will only be enough present to oxidize a couple of milligrams.


true
Quote:
And who cares about CO2? What's wrong if there forms some carbonate of your amine? I mean, you want to make its hydrochloride in order to protect it from forming the carbonate.


yes, the formation of carbonate is apparently irreversible, and i was contagiously concerned about it's formation due to the ease that this is communicated to happen... but yes again, it would be such a small amount...
Quote:
Is this something to do with some kinky salt racism or what?


no (well not that im prepared to admit online), more an early chemhack stingy'ness that causes one to try to get another drop of oil out of the empty bottle, just to knock the collecting vessel over and loose a heap on your hands...
Quote:
Anyway, for how many years do you want to store it?


not sure, maybe 1-2 light years ... i was worried it might go bad/off or something, or be like some atomic chain reaction that would just carry on by itself feeding itself via one of many oh so common yet suppressed perpetual motion mechanism's

;)

as for your use of the term "Triturate", i was lazy to look it up and prefered to take the easier opinion that you had mispelled titrate even though knowing that if that were the case, the word titrate would have even less to do with what process i figured was being described... :D

plus it gave me something else to right back about and thus more reason to continue to feed my purposefull act of nothing-to-do-ness which is secretly infatuated in watching this forum for a reply from some other member of existence :(

nuff said ?

Nicodem - 5-11-2006 at 07:35

Quote:
Originally posted by opensrc
yes, the formation of carbonate is apparently irreversible, and i was contagiously concerned about it's formation due to the ease that this is communicated to happen...

What the hell are you talking about? This is an exemplary case of a reversible reaction! The amine carbonates are so instable that mere heating drives the CO2 and H2O off leaving the less volatile amine behind. Check the pKa's of carbonic acid and primary amines to see that that such salts are on the verge of stability. In aqueous solutions the amine carbonates are even so instable that the amine reacts like a free base would in most reactions involving amines (indicating that there is always a very large enough portion of the non-protonated amine in equilibrium with HCO3(-) and H2CO3).

opensrc - 5-11-2006 at 07:46

yeah i have no idea what-so-ever, and am just reposting old wives tales...



what you say sounds like music to my ears ... i might leave it at that then and go have some sleep with a complimentary serving of dreams

not_important - 6-11-2006 at 00:26

If you are using acetone, which is a bit better at dissolving some amine salts than ether is, you might consider making the amine sulfate or phosphate, which usually are less soluble in organics than the hydrochloride.

Dextrose - 8-11-2006 at 09:22

Quote:
Dextrose:

Quote:

Add 10x acetone, and suction-filter. Wash with additional acetone if nessecary.


this is the kinda info im looking for, are you suggesting 2ch-hcl could be insoluble in anhydrous acetone ??? or do you know from experience/reference ???


Yes.

This work-up is mine and others favorite of choice, after Zn/HCl or Al/Hg-reduction.