Acid-base extraction

[Jenerate]

If you have a freebase drug dissolved in a non-polar solution, instead of bubbling HCL(g) through the solution, could you simply shake HCL(aq) with the freebase solution if you wanted to convert the freebase drug to a HCL salt? If you did do this, what PH would you make the aqueous portion?

 

[MattPsy]

Yes you cam but then you're going to have to separate them and evaporate (or boil off, if you can, by heat or vacuum) off the water.
The reason why the HCl(g) through non-polar solvent method is used is because the product precipitates right out of the solution and can then simply be filtered to recover the product.

 

[Jenerate]

If I were to sprinkle table salt over sulfuric acid in a beer bottle, would it work if I placed a plastic hose inside the beer bottle, sealed it with duct tape and then placed the other end inside the NP solvent with the freebase drug dissolved so that the HCL(g) bubbles through the solution?

 

[neuwelt]

No, the hydrochloric acid gas must be anhydrous i.e dried before you lead it into your solvent. In my opinion the easiest way to achieve this is do drop concentrated hydrochloric acid over calcium chloride. However, I must warn you that this gas is extremely corrosive and will corrode any metal in sight. It is really not fit for "kitchen chemistry". Extracting your product with aqeous HCl maybe doesn't work wonders, but it works and if you can evaporate your water/HCl in a safe enviroment for example outside, I would say that it is a much better alternative.

But depending on what drug we are talking about you may generate other salts, sulphates are nice if possible as sulphuric acid is a liquid at RT and can be had pure. Just slowly drip it in, and filter.

 

[Jenerate]

If I were to extract the freebase drug from the NP solvent with aqueous HCL what PH would I make the solution?

 

[neuwelt]

It is always a good idea to calculate how much HCl you will need, and then add a slight excess. Add enough HCl to reach a pH of 4-5. And don't use concentrated HCl, dilute with distilled water to something in the range of 2-4M.

 

[EarlGrey]

This is called TITRATION, it is an accepted method in itself. A seperatory funnel is an absolute must for this. A good method of determining if you need to add more acid is buy shaking the two NP and Polar layers, while still basic they will seperate immediately almost repelling each other; however, as the pH comes down they will not seperate so quickly if you overshoot and the pH goes down to pH1 it can take hours for seperation to occur.

If the pH is missed and you overshoot, don't worry, slowly evaporate and when the 'goods' are dry scrape up and try to get it as powdered as possible mix with acetone and pour through a filter - You will notice the acetone will be slightly yellow coloured, this is from the excess HCl and any other impurities. Keep washing with acetone until it is clear and a nice sparkly white product remains.

(if real dirty, you are better to mix with acetone in a beaker and pour off just the acetone rather than pouring the powder into the filter as well as it can start to channnel the acetone rather than getting to every particle. When it starts to get clean then pour all into the filter)

 

[retired_chemist]

This is called TITRATION, it is an accepted method in itself. A seperatory funnel is an absolute must for this. A good method of determining if you need to add more acid is buy shaking the two NP and Polar layers, while still basic they will seperate immediately almost repelling each other; however, as the pH comes down they will not seperate so quickly if you overshoot and the pH goes down to pH1 it can take hours for seperation to occur.

I don't think you can say categorically that this is true. The ease with which a two phase extraction mixture depends a lot on what is in solution, how much electroylyte is present, the solvent being used. If anything, from my experience basic solutions tend to be a *lot* more prone to forming emulsions than acidic ones.

A roll of pH paper is not difficult to come by.

As far as generating anhydrous HCl, definitely don't recommend it outside of a well ventilated lab, but ... typical lab setups for making anhydrous HCl involve dropping concentrated Sulfuric Acid onto a slurry of NaCl/Concentrated HCl, passing the HCl liberated through a bubbler filled with concentrated Sulfuric acid to give it a final drying. Look in a grad school level organic chem lab text to see how to set all this up.

 

[EarlGrey]

I don't think you can say categorically that this is true. The ease with which a two phase extraction mixture depends a lot on what is in solution, how much electroylyte is present, the solvent being used. If anything, from my experience basic solutions tend to be a *lot* more prone to forming emulsions than acidic ones.

A roll of pH paper is not difficult to come by.

As far as generating anhydrous HCl, definitely don't recommend it outside of a well ventilated lab, but ... typical lab setups for making anhydrous HCl involve dropping concentrated Sulfuric Acid onto a slurry of NaCl/Concentrated HCl, passing the HCl liberated through a bubbler filled with concentrated Sulfuric acid to give it a final drying. Look in a grad school level organic chem lab text to see how to set all this up.

Yes, you entirely correct and I should have made this a bit clearer - there can be other factors involved which may effect whether this is true or not. For instance - the choice of NP may well produce results that differ to those outlined - The product involved may also cause differences as might the acid used in titration. Also, one key and annoying little mo fo that might get in the way are nasty inactives or gakks in general.

Personally, I can only say this is true with a generic Zippo lighter fluid as the NP, with HCl as the acid and with Ephedrine/PSE/MA as the freebases under conversion - In such cases, it has proved to be a consistant and totally reliable indicator as to pH.

NOTE: This is NOT used as a total reliable pH detector but ONLY to give an indication as to where one is, when that point is reached Universal INdicator Papers take over, naturally.

This is extremely handy for anyone who has had the experience of adding endless amounts of HCl and got fed up of repeated testing by indicator papers only to find that nothing has changed after the 14th test! (Of course this could be worked out molar wise if one knew for certain what returns to expect and of course, how to work that out!)

Check it on a small sample of ones own particular combination to see if it proves to be so, if you use the same solvents with regularity it may be apparent to you already if it seperates with ease at the alkali stage and with difficulty at the acid stage. With experience, you will be able to note the instant the change has begun and start Indicator Paper testing at about pH 9.


The production of HCl gas that you outlined is the perfect method out of all methods. This is the best by far for producing a reliable dry gas with ease. The addition of an aquarium pump to 'push' the gas makes this even better and prevents any suckback. Plumes of HCl gas is produced at the flick of a switch and stops when switched off. (Using two coke bottles each with one input and one output at the top of the bottle apart from the 2nd bottle which has it's input tube going all the way to the bottom of the bottle to bubble the HCl gas through the H2SO4 to dry it)

Bottle 1 input comes from an aquarium pump, output goes into the input of bottle 2 and bubbles through the H2SO4 that it contains (only a little H2SO4 is needed). The output of bottle 2 leaves the bottle and is used as a 'gassing wand' (some put an aerator on the end of this tube to get a bigger surface area of the HCl gas)

 

[Acyl]

Just add the acid till the pH becomes slightly acidic, check with a pH paper. Calculations arent really necessary.

If youve got conc. HCl or conc H2SO4, dont dry it. Theres no need, just use it as it is.


Im going to vouch for the gassing method also.

 

[Acyl]

No, the hydrochloric acid gas must be anhydrous i.e dried before you lead it into your solvent. In my opinion the easiest way to achieve this is do drop concentrated hydrochloric acid over calcium chloride.

The easiest way to do this is to just heat a solution of HCl in a test tube connected to rubber tubing that transports the gas into an organic solution of your freebase.

Adding sodium chloride salt (CaCl is not as easy to get, id assume) to the solution would optimize gas production, but its not completely necessary.

 

[MattPsy]

^ That method will NOT produce anhydrous HCl.
Some of your product will dissolve in the water that ends up in your non-polar solution.

 

[EarlGrey]

^ Yep, that's true - thus drying the gas on its way is a good move.

Some methods of HCl gas production produce wetter gasses than others and have heard of NPolars going cloudy from the water content in the gas - alittle bit of water can consume, in some cases, a lot of product.