chemchemical
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Converting to the hydrochloric salt for storage?
Ok, so the last process in a synthesis is the conversion of the product to its HCl salt. They dissolve it in acetone and use HCL to crystallize it
out.
When I dissolve mine in acetone I got a precip. which dissolved upon mixing so I thought I should add more HCl, but it never came out.
I'm working with a tertiary amine (thats a nitrogen with 3 attachments, right?) so I'm assuming they're making the quarternary hcl salt?
The HCl I'm using is muriatic acid, 37%. The journal article did say wet HCl will produce wet crystals but thats it.
Never had to make a salt of my products before.
thanks
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panziandi
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OK well a few point...
1) Your amine is R3N at the moment then you add your HCl you will get (R3NH)+Cl- as the salt.. Ionic so should not be very soluble in the acetone.
That's the theory of your reaction...
2) Let me clear something up... Do you mean when your product was added to acetone it precipitated out or do you mean it didn't dissolve until you
stirred it? If your product is solid and you added it to the acetone it may not dissolve all until you stir the solution (this aids dissolution)
3) You are using concentrated hydrochloric acid.. WRONG.. You want to use anhydrous hydrogen chloride! Amine hydrochlorides are very soluble in water!
You want to drip your conc HCl into H2SO4 to generate the HCl gas (the fumes you see when you open the lid of the acid) you want to idelly pass that
gas through a wash bottle of H2SO4 to dry it then into you acetone. Your product should ppt out as a crystaline HCl salt, filter quickly and dry the
solid in a desiccator with paraffin wax and calcium chloride.
Hope that helps 
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Klute
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I agree with Panziandi, your amine must have dissolved in the water from the HCl. This can even happen if you use HCl gas that hasn't been properly
dried, or if your solution hasn't been dried enough (K2CO3 and KOH work well for such solutions in IPA? toluene etc, but not acetone and ethyl
acetate, were Na2SO4 can do if you leave it at least 20-30min).
Depending on how long you paln on storing your intermediate, keeping the freebase under argon in a fridge can be ok. Over a week, and you better be
off forming a salt.
To avoid HCl gas, whichis a pain in the ass to work with, you can form sulfates salt, by using conc. H2SO4 diluted in IPA, or oxalates, from anhydrous
oxalic acid in IPA or MeOH. The latter has been my favourite lately.
Commercial oxalic acid (dihydrate) can be dried using a Dean Stark with pet ether, or possibly in a oven (although there will be some sublimation).
Something that might work is to mix the dihydrate and excess IPA, remove the IPA/H2O azeotrope until anhydrous, but that might require large amouts of
IPA dependign on how well it removes the water.
Another option is commercial 6N HCl in IPA, I beleive ethereal HCL is also availble. Both solutions are very hygroscopic, but easy to work with,
measure out the maximum amount of HCl solution required if you had quantitative yields, and add dropwise to the cold amine solution with stirring,
until pH is slightly acidic. Then filter and wash your precipitate.
All these options are much more convinient than gaseous HCl IMHO, and actually often give a cleaner product (apart from the sulfates when excess acid
is used, but in most instance the sulfates cristaillize more easily and are less hygroscopic than the hydrochlorides).
\"You can battle with a demon, you can embrace a demon; what the hell can you do with a fucking spiritual computer?\"
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smuv
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If said oxalic acid amine salts were ingested do you think there would be a health(renal) hazard?
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Klute
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I think there is no problem on that side. I ahev seen oxalates been used in pharmacological evulations in animals and humans in various articles.
I don't think it's a hazard, any remaining impurities could be more dangerous than the oxalate anion IMHO.
\"You can battle with a demon, you can embrace a demon; what the hell can you do with a fucking spiritual computer?\"
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chemchemical
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sounds good, but it would still be possible to convert to the HCl salt with the acid, have it dissolve and then just remove the solvent?
Something I never really understood is why the salt is more stable compared to the freebase?
I may try a different salt since I'm not keen on the idea of working with HCl gas. What kind of glassware is used for HCl gas? I've seen special glass
gas generator equipment but it was more for forming hydrogen or CO2. Sulfates may be an idea, I was also considering phosphates too.
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ScienceSquirrel
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| Quote: | Originally posted by chemchemical
sounds good, but it would still be possible to convert to the HCl salt with the acid, have it dissolve and then just remove the solvent?
Something I never really understood is why the salt is more stable compared to the freebase?
I may try a different salt since I'm not keen on the idea of working with HCl gas. What kind of glassware is used for HCl gas? I've seen special glass
gas generator equipment but it was more for forming hydrogen or CO2. Sulfates may be an idea, I was also considering phosphates too.
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I think the free base is probably more susceptable to air oxidation of the amine functionality.
Hydrogen halides are favoured as they are strong monobasic acids and form straightforward salts.
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Klute
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Basicly, the nitrogen is under quaternary form, so no more double bond around. The nitrogen sin't nucleophilic anymore, so can't be oxidized or
attacked by any electrophile, polymerized, etc
Amine freebases are notorious for being unstable, often easily darkening when in presence of light and air.
EDIT: For HCl gassing, you need a generator, namely a flask containing conc. HCl, with an addition funnel charged with conc. HCl, a gas outlet on top
of the additon funnel, a in-line wash bottle or dryer (full of H2SO4, or Cacl2), and a glass tubing with a large opening to be immersed in the dried
solution of the freebase in some non-polar solvent (toluene for example). You need to work in dry conditions as traces of water will prevent cristn
and you will obtain a viscous liquid on the bottom of the beaker/erlenmeyer.
drying your amine solution over K2CO3 or KOH for 30-60min, drying your HCl gas by bubbling through H2SO4, and working in a dry, well ventilated place.
The HCl gas is generate dby dripping the conc. HCl on H2SO4. Other measn exist, such as adding H2SO4 to NaCl, etc but the former is my favourite.
It is a messy, unpractical procedure, and it's not uncommon that the hydrochloride dissolves from atmospheric humidity, in which case you ahev to
basify and start all over again...
Another possibility is too dissolve your amine freebase in dry IPA, add conc. HCl dropwise until neutralized, and remove the H2O/IPA azeotrope by
distn, preferably under vacuum. You can aslo do this with toluene, but the high temps involved cause excessive side reactions. Not recommended.
[Edited on 31-8-2008 by Klute]
\"You can battle with a demon, you can embrace a demon; what the hell can you do with a fucking spiritual computer?\"
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