Questions about different Salts of Drugs

Soulfake

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I have a hard time understanding the chemistry behind the different salts of drugs/substances (especially amino acids) and how exactly they are bound to the molecules and why/how they bahave in several ways. For example: If I want to make an free base e.g. from phenibut HCl I can add sodium bicarbonate or other bases (which ones could be used that are relatively safe, easy available and don't produce sodium chloride? For daily consumption table salt isn't the nicest impurity in drugs) but what about making a salt from e.g. caffeine or phenibut? As far as I read caffeine citrate is just made by mixing citric acid with caffeine in water (one recipe said that sodium citrate is added, too. It's an acid buffer but I also don't really understand how they work, I know they keep solutions at a certain PH range but I don't now how they behave in such salt-base reactions, when they should be added etc.), wouldn't then the caffeine from energy drinks, cola or coffee be bound to the acids that are in those drinks? Like caffeine phosphate from the phosphoric acid in cola or caffeine bound to the caffeic acid in coffee (caffeine caffeate?). Would this work for phenibut "free base" / free amino acid, too? So if I make a solution of the phenibut, neutralize it with baking soda and then add citric acid, will it produce phenibut citrate?

Would this also work with vinegar essence (25% acetic acid)? If you make a caffeine solution and let it dry it will give caffeine monohydrate which is like a cob web of fluffy long needles, I added some of the vinegar essence to some water-free caffeine and it seemed to have produced some kind of salt/caffeine acetate as it is now a white powder instead of that fluffly needle stuff. What I don't really get is why e.g. morphine that is treated with vinegar essence is at least partially converted to the acetyl-ester while other substances like caffeine just give the acetate salt. Would the reaction of phenibut FAA with vinegar essence give the acetate and how different is this reaction from making an hypothetical phenibut-acetyl ester?

edit: sry I should have posted this to the Neuroscience and Pharmacology Discussion board. Wasn't there one about chemistry?
 
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Soulfake

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Doesn't anyone know about chemistry and could give me a short answer? It would be really nice as I can't find those infos on the web and I don't have the time to study all the details in chemistry to understand how I can calculate these things myself.

So my main question is if I make phenibut free amino acid by mixing the hcl with baking soda in a hot water solution (or with another base than baking soda, I'm still looking for one that doesn't produce sodium chloride or something similar longterm-unhealthy and hardly seperateable from the phenibut.) and then add citric acid to the solution or 25% vinegar essence to the dried powder it will create an citric- or acetate salt of phenibut (even if it's only partially converted to a salt or something like that)? And would that also apply to other amino acids like taurine? If it doesn't work, is there a method to make a simple salt without fancy chemicals and laboratory stuff? I know that esters and amides can be more difficult but salts are a quite simple thing as it's just an acid that is more or less losely bound to the molecule's base as far as I understand.
edit: added a picture. Would it also be possible to make a simple salt of butanediol and other glycols?
 
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S.J.P.

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For example: If I want to make an free base e.g. from phenibut HCl I can add sodium bicarbonate or other bases (which ones could be used that are relatively safe, easy available and don't produce sodium chloride? For daily consumption table salt isn't the nicest impurity in drugs)...
Any base that contains sodium will produce sodium chloride when reacted with the hydrochloride salt of an amine. However, the amount of salt you would produce in this manner is harmless.

...but what about making a salt from e.g. caffeine or phenibut? As far as I read caffeine citrate is just made by mixing citric acid with caffeine in water (one recipe said that sodium citrate is added, too. It's an acid buffer but I also don't really understand how they work, I know they keep solutions at a certain PH range but I don't now how they behave in such salt-base reactions, when they should be added etc.), wouldn't then the caffeine from energy drinks, cola or coffee be bound to the acids that are in those drinks? Like caffeine phosphate from the phosphoric acid in cola or caffeine bound to the caffeic acid in coffee (caffeine caffeate?). Would this work for phenibut "free base" / free amino acid, too? So if I make a solution of the phenibut, neutralize it with baking soda and then add citric acid, will it produce phenibut citrate?

Would this also work with vinegar essence (25% acetic acid)? If you make a caffeine solution and let it dry it will give caffeine monohydrate which is like a cob web of fluffy long needles, I added some of the vinegar essence to some water-free caffeine and it seemed to have produced some kind of salt/caffeine acetate as it is now a white powder instead of that fluffly needle stuff. What I don't really get is why e.g. morphine that is treated with vinegar essence is at least partially converted to the acetyl-ester while other substances like caffeine just give the acetate salt. Would the reaction of phenibut FAA with vinegar essence give the acetate and how different is this reaction from making an hypothetical phenibut-acetyl ester?
Citric acid is not a strong enough acid to protonate caffeine, which is very weakly basic, to an appreciable extent. Mixing these two in water would just give you a solution of caffeine and citric acid, not a salt. The same would be the case with acetic acid.

Phenibut is already a salt, even without an acid added to it: the amine is protonated and has a positive charge, while the acid is deprotonated and has a negative charge.

You can't acetylate morphine with vinegar under normal conditions and with any kind of reasonable yield, or people wouldn't bother with acetic anhydride. If you cook up alcohols and carboxylic acids hot enough, you will maybe get some acetylation, but it's really harsh chemistry and way, way, way slower than acid-base reactions between carboxylic acids and basic amines like morphine's. In any case, these reactions are independent of each other: the acetylation is occuring at the hydroxy groups, while the acid-base reaction is occuring at nitrogen.

Doesn't anyone know about chemistry and could give me a short answer? It would be really nice as I can't find those infos on the web and I don't have the time to study all the details in chemistry to understand how I can calculate these things myself.

So my main question is if I make phenibut free amino acid by mixing the hcl with baking soda in a hot water solution (or with another base than baking soda, I'm still looking for one that doesn't produce sodium chloride or something similar longterm-unhealthy and hardly seperateable from the phenibut.) and then add citric acid to the solution or 25% vinegar essence to the dried powder it will create an citric- or acetate salt of phenibut (even if it's only partially converted to a salt or something like that)? And would that also apply to other amino acids like taurine? If it doesn't work, is there a method to make a simple salt without fancy chemicals and laboratory stuff? I know that esters and amides can be more difficult but salts are a quite simple thing as it's just an acid that is more or less losely bound to the molecule's base as far as I understand.
edit: added a picture. Would it also be possible to make a simple salt of butanediol and other glycols?
With enough vinegar, you will make the acetate salt (one acetate) of phenibut, with the carboxylic acid on the phenibut being mostly protonated.

You will not make the structure on the top-right with acetic acid and phenibut. Again, carboxylic acids are very bad acetylating agents. You can do it on alcohols under really harsh (destructive to your molecule) conditions, but it's never going to happen with an amine (which will be protonated) or a carboxylic acid,

You can't form isolable salts of alcohols like butanediol.
 

Hodor

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Doesn't anyone know about chemistry and could give me a short answer? It would be really nice as I can't find those infos on the web and I don't have the time to study all the details in chemistry to understand how I can calculate these things myself.

So my main question is if I make phenibut free amino acid by mixing the hcl with baking soda in a hot water solution (or with another base than baking soda, I'm still looking for one that doesn't produce sodium chloride or something similar longterm-unhealthy and hardly seperateable from the phenibut.) and then add citric acid to the solution or 25% vinegar essence to the dried powder it will create an citric- or acetate salt of phenibut (even if it's only partially converted to a salt or something like that)? And would that also apply to other amino acids like taurine? If it doesn't work, is there a method to make a simple salt without fancy chemicals and laboratory stuff? I know that esters and amides can be more difficult but salts are a quite simple thing as it's just an acid that is more or less losely bound to the molecule's base as far as I understand.
edit: added a picture.
Sodium chloride isn't unhealthy at the doses we're talking about here. If you were to neutralize phenibut HCl with NaHCO3, you'd be forming roughly 1 gram of NaCl for every 3 grams of phenibut freebase. The recommended maximum daily intake of NaCl for an adult male is ~5 grams per day; the average adult in the Western world consumes around 8 grams per day.
If your intake of phenibut is getting you worried about taking in too much salt, then it's probably the phenibut and not the salt you should be worried about.

Would it also be possible to make a simple salt of butanediol and other glycols?
If you've got an extremely strong base (i.e. far stronger than NaOH) you can remove protons from alcohols to form their salts, called alkoxides (ex.: ethanol turns into sodium ethoxide). However, alkoxides are *very* strong bases (again, stronger than NaOH), and thus not something you would want to ingest under any circumstance.
Despite the "acetate" in its name, the 1,4-butanediol diacetate in your picture is not a salt, but an ester. Salts are *more* water soluble than their corresponding alcohols, while esters are *less* water soluble.

Oh, and speaking of water: Since the formation of an ester results in the elimination of water (alcohol + acid <> ester + H2O), this means that in the presence of water (like the 75% water in your 25% vinegar essence), the reaction equilibrium is going to shift away from the product. Acetylation of morphine into 6-MAM requires you to reflux it with glacial (i.e. pure) acetic acid. Making heroin from morphine (i.e. also acetylating the harder-to-acetylate 3-position) requires a stronger acetylating agent like acetic anhydride or acetyl chloride... refluxing with glacial acetic acid in the presence of concentrated sulfuric acid should also work.

Now, making an ester from 1,4-butanediol should be easier than making one from morphine, but it is way more complicated than just mixing 1,4-BDO and vinegar.
 

Hodor

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You can't form isolable salts of alcohols like butanediol.
You (as in "chemists") definitely can form salts of aliphatic alcohols, it just requires extremely strong bases like sodium hydride (or pure sodium metal) for a complete conversion.

However, such superbases are extremely caustic, and will require an aprotic solvent... and the resulting ethoxides are very strong bases in their own right. Oh, and they're probably highly hygroscopic, absorbing moisture out of the air to re-form into the corresponding alcohol and sodium hydroxide, i.e. something one definitely wouldn't want to ingest.

@OP, the reason you can easily make a salt out of GHB is that GHB itself is a weak acid, and so neutralizing it creates a weakly basic salt. However, since alcohols like BDO have a pKa value (a measure of acid strength) close to that of water, the resulting salt would be strongly basic.
Look at it this way:
If water is H2O and EtOH is ethanol, and we were to mix them individually with our superbase, NaH (sodium hydride), they would react analogously as follows:
H2O + NaH <> NaOH + H2
EtOH + NaH <> NaOEt + H2
in other words: "sodium ethoxide" (NaOEt) is to "ethanol" what "sodium hydroxide" is to "water".
 
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S.J.P.

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You (as in "chemists") definitely can form salts of aliphatic alcohols, it just requires extremely strong bases like sodium hydride (or pure sodium metal) for a complete conversion.
Yes, sorry, I meant specifically acid salts of alcohols. Alkali metal salts are isolable albeit not terribly air-stable.
 
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