Sciencemadness Discussion Board

napsylate to HCl salt conversion

aaronbegin - 10-8-2006 at 23:15

Hello! Wondering about a method to convert a certain compound, dextropropoxyphene napsylate to dextropropoxyphene hydrochloride. My first year chemistry ignorance is showing, I suppose that this whole summer away from the lab and a safe place for experiments hasn't helped any.

With any luck my signature should have the structures of these two relevant molecules. Here are the urls for images if I didn't manage to do that. napsylate: http://img.photobucket.com/albums/v181/aaronbegin3680/ca9e21...
hydrochloride: http://img.photobucket.com/albums/v181/aaronbegin3680/9d6957...

Hopefully someone will give me a hand here?

aaron

not_important - 10-8-2006 at 23:27

Myself, I would try mixing it with a solvent for the free (not as salt) dextropropoxyphene, then washing with sodium hydrogen carbonate solution. The naphthsulphonic acid is a strong acid, should reach with the NaHCO3 and go into the aqueous layer; at the same time NaHCO3 isn't a very strong base and should leave the ester alone. After that add HCl to the non-aqueous solution, if dry HCl gas is used then the hydrochloride may precipitate out.

aaronbegin - 10-8-2006 at 23:34

Alright, I'll post results as soon as I can get my hands on the necessary components, which may be quite awhile. Thank you for the amazingly quick response.

aaron

not_important - 10-8-2006 at 23:49

Check solubilities, if you can find them. If the free bse isn't soluble in much, this doesn't work well.

The other thing to worry about is the stability of the ester functionality.

Which is to say - don't use all your raw material at once. Also lock the doors, draw the shades, and don't obtain supplies from just one place as I suspect there are legal issues at work.

Nicodem - 11-8-2006 at 00:06

Quote:
Originally posted by not_important
Also lock the doors, draw the shades, and don't obtain supplies from just one place as I suspect there are legal issues at work.


If his intent would be to use it as an opiate for recreational whatever uses why the hell would he want to convert the naphtylsulphonate to the hydrochloride? Actually I can't find any reasonable reason for doing that.
Aaronbegin, please satisfy my curiosity and explain why you want to change the anionic part.

As far as the formation of hydrochloride salt, I think it would be hardly possible to crystallize it from water. At best the ester would hydrolyze during stripping off the water. Perhaps if done under efficient vacuum, yet it is not easy to remove moisture from the remaining hydrochloride crystals.
It is way more efficient if gaseous HCl is introduced to the ether solution of dextropropoxyphene. The hydrochloride should precipitate as crystalline powder and there is no problem with ester hydrolysis. The ether solution should be first thoroughly dried over Na2SO4, MgSO4 or other appropriate drying agents.

unionised - 11-8-2006 at 03:47

IIRC most anion exchange resins have much higher affinity for big organic ions than for things like chloride. Passing a solution of the napsylate through a cation exchange column previously loaded with chloride might work but some of the product would porbably absorb on the resin. If I were trying to do this reactioon on a large scale I would certainly give this a try.

not_important - 11-8-2006 at 04:45

Quote:
Originally posted by Nicodem
The ether solution should be first thoroughly dried over Na2SO4, MgSO4 or other appropriate drying agents.


Ah, yes, thanks. I omitted mentioning that, it's such a habit. Also give the non-aqueous layer a final wash with plain water before drying.

I've worked with esters that hydrolysed noticeably in contact with an almost neutral water solution; that's why I cautioned - knowing nothing on this specific case, especially where the tertiary amine group can work as a base.

aaronbegin - 11-8-2006 at 11:50

Quote:
Originally posted by Nicodem
Quote:
Originally posted by not_important
Also lock the doors, draw the shades, and don't obtain supplies from just one place as I suspect there are legal issues at work.


If his intent would be to use it as an opiate for recreational whatever uses why the hell would he want to convert the naphtylsulphonate to the hydrochloride? Actually I can't find any reasonable reason for doing that.
Aaronbegin, please satisfy my curiosity and explain why you want to change the anionic part.

As far as the formation of hydrochloride salt, I think it would be hardly possible to crystallize it from water. At best the ester would hydrolyze during stripping off the water. Perhaps if done under efficient vacuum, yet it is not easy to remove moisture from the remaining hydrochloride crystals.
It is way more efficient if gaseous HCl is introduced to the ether solution of dextropropoxyphene. The hydrochloride should precipitate as crystalline powder and there is no problem with ester hydrolysis. The ether solution should be first thoroughly dried over Na2SO4, MgSO4 or other appropriate drying agents.


I don't have any intent to put the end product to recreational use. I'll leave it to your imagination to come up with some other possible motivation.

On another possibly (guess) related note, the solubility of the dextropropoxyphene affects it's absorption rate by the body, though both are eventually metabolized to norpropoxyphene in the end.

So you're suggesting forgoing reaction of the napthylsulfonate with bicarbonate, and just causing precipitation of the hydrochloride salt from dried ether solution?

not_important - 11-8-2006 at 12:44

No, unless the napthylsulfonate is rather soluble in ether; as a salt it might not be although the anion is a fairly large organic molecule. As it is a strong acid, you would have to use an excess of (dry)HCl to force the reaction, even with the hydrochloride salt falling out of the solvent.

What he was saying is that you don't want to try to make the hydrochloride in water, as that has both isolation problems and increases the risk of hydrolysis. Precipitating amine salts out of non-aqueous solution is common, it usually gives a nice crystalline form while evaportating a water solution gives massive interlock crystals (or worse) with a lot of trapped solvent and trash.

The intended use isn't the issue, rather how legal authorities will see the situation. There is that recent drug manufacturing bust of a docter for buying red phosphorus and iodine, although there is no evidence that he had or intened to make speed.

Nicodem - 11-8-2006 at 13:49

Quote:
Originally posted by aaronbegin
I don't have any intent to put the end product to recreational use. I'll leave it to your imagination to come up with some other possible motivation.

On another possibly (guess) related note, the solubility of the dextropropoxyphene affects it's absorption rate by the body, though both are eventually metabolized to norpropoxyphene in the end.

So you're suggesting forgoing reaction of the napthylsulfonate with bicarbonate, and just causing precipitation of the hydrochloride salt from dried ether solution?

I couldn't care less if you intent to use the drug without prescription. I don't even know if and how it is regulated in your country, though since being a mu agonist it probably isn't available without prescription.
What I do care for, is why do you want to change the anion part? It can't be due to any pharmacological reason since both salts are equally potent by mol per mol scale. Since they are water soluble salts, the anion form also has no influence on the rate of absorption.
Please, I'm curious!

PS1: Base hydrolysis is not problematic since it is an ester of a tertiary alcohol, so NaOH or Na2CO3 can also be used to "freebase" the salt. Being an ester of a tertiary and furthermore benzylic alcohol, does however make it very susceptible to acid induced elimination, so I would go easy with HCl. An excess of HCl would probably cause elimination of propanoic acid. Perhaps the best option would be to use an equivalent of HCl by adding it as a standardized solution of HCl in eter or isopropanol (while cooling in an ice bath). Anyway, I don’t even know why you are asking forum members this question. A search in the patent literature would give you the exact and working procedure for the hydrochloride formation with all the details.

PS2: Saying that "both [salts] are eventually metabolized to norpropoxyphene in the end" makes no sense. They are both salts of norpropoxyphene, thus the cationic part is the identical active compound in its protonated form. The body knows nothing about the anion part of the cation. Protonated amines like this cation are in equilibrium with the non protonated (free base) form according to the pH of the medium. This is not metabolism. It is a reaction equilibrium governed by the dissociation constant of water and the pKa of the protonated amine. Nothing of this has anything to do with the anionic part. How could your body know you introduced the norpropoxyphene as a hydrochloride or else when your stomach is full of chloride anions and so is your blood? (well, unless you are some weird alien)

Sandmeyer - 17-8-2006 at 15:28

If I'm not misstaken some hyperlab bees claimed that 2C-B (?) fosfate gives in some way a diffrent experience from the hydrochloride (or bromide) when orally taken, unbelivably the actual trip was different and not only the rate of the onset and such.

[Edited on 17-8-2006 by Sandmeyer]

aaronbegin - 17-8-2006 at 21:38

Quote:
Originally posted by Nicodem
Quote:
Originally posted by aaronbegin
I don't have any intent to put the end product to recreational use. I'll leave it to your imagination to come up with some other possible motivation.

On another possibly (guess) related note, the solubility of the dextropropoxyphene affects it's absorption rate by the body, though both are eventually metabolized to norpropoxyphene in the end.

So you're suggesting forgoing reaction of the napthylsulfonate with bicarbonate, and just causing precipitation of the hydrochloride salt from dried ether solution?

I couldn't care less if you intent to use the drug without prescription. I don't even know if and how it is regulated in your country, though since being a mu agonist it probably isn't available without prescription.
What I do care for, is why do you want to change the anion part? It can't be due to any pharmacological reason since both salts are equally potent by mol per mol scale. Since they are water soluble salts, the anion form also has no influence on the rate of absorption.
Please, I'm curious!

PS1: Base hydrolysis is not problematic since it is an ester of a tertiary alcohol, so NaOH or Na2CO3 can also be used to "freebase" the salt. Being an ester of a tertiary and furthermore benzylic alcohol, does however make it very susceptible to acid induced elimination, so I would go easy with HCl. An excess of HCl would probably cause elimination of propanoic acid. Perhaps the best option would be to use an equivalent of HCl by adding it as a standardized solution of HCl in eter or isopropanol (while cooling in an ice bath). Anyway, I don’t even know why you are asking forum members this question. A search in the patent literature would give you the exact and working procedure for the hydrochloride formation with all the details.

PS2: Saying that "both [salts] are eventually metabolized to norpropoxyphene in the end" makes no sense. They are both salts of norpropoxyphene, thus the cationic part is the identical active compound in its protonated form. The body knows nothing about the anion part of the cation. Protonated amines like this cation are in equilibrium with the non protonated (free base) form according to the pH of the medium. This is not metabolism. It is a reaction equilibrium governed by the dissociation constant of water and the pKa of the protonated amine. Nothing of this has anything to do with the anionic part. How could your body know you introduced the norpropoxyphene as a hydrochloride or else when your stomach is full of chloride anions and so is your blood? (well, unless you are some weird alien)


I know that the anion hasn't anything to do with absorption once the molecule's dissociated. The only thing it affects as far as I know is the solubility of the salt [to clarify: the ease with which it dissociates], and the difference is negligible in recreational doses. Now I may be mistaken, or have been mislead. see: http://img.photobucket.com/albums/v181/aaronbegin3680/314159...

I should just point to: http://www.drugs.com/pdr/PROPOXYPHENE_NAPSYLATE.html

Also, this is [dextro]propoxyphene, not norpropoxyphene. Norpropoxyphene is the metabolite of propoxyphene [metabolized in the liver after absorption into bloodstream], and it has no bearing on the discussion since we both agree that once dissociated, the propoxyphene is the same regardless of the anion.

In any case, it will be awhile before I'll have access to the supplies I need and a safe (enough) place to use them.

And as for why I'm not just sifting through patents, it's because of course that I did not know at first [though have since made a brief unsuccesful effort], please forgive the ignorance.

Nicodem - 17-8-2006 at 23:48

Interesting, but that graph about plasma concentration does not say if the difference is statistically significant. So it actually does not confirm anything unless this is said in the paper from which you took it out. However, given that the napsylate dissolves more slowly than the hydrochloride it could well be that its absorption lags behind with the napsylate (though the difference in that graph is not really very notable).

To Sandmeyer: Since 2C-B is a psychedelic, there is no way of having two identical trips regarding quality and intensity. This can easily result in such fast conclusions, that the salt form really matter. Unless someone measures its concentration in the blood stream I wouldn’t mind such hearsays. Unlike with the boring and predictable effects of the opiates one can not easily differentiate the effects of two similar doses of a psychedelic since it is going to be different each time by definition. One time you can find 18mg of 2C-B a nice and moderately intensive trip if the setting is right and the other time you can take the same small amount and find the experience way less interesting or fail to break trough. Such hypotheses can only be proved clinically.