Fentanyl and friends.

[Ford Prefect]

This thread is now about 4-piperidone.

4-piperidone seems to be THE key ingredient to fentanyl. With it one can fairly simply make NPP under PTC conditions, the product of which is reacted with aniline, reduced with NaBH4 then introduced to a propionic derivative.

To the best of my knowledge 4-piperidone is usually made from PEA using one of the following methods:

Dieckman Cyclization method: Uses our friend Methyl acrylate. Doable, but nasty.

And, although I really don't know the legitimacy of it, the Double Mannich, using acetone, formaldehyde and PEA. I've also heard talk of using MEK for the ketone.

For a method with such simple precursors there isn't a whole lot literature around. If anybody does has "The Preparation of Some Piperidine Derivatives by the Mannich Reaction" (JACS 70,3853,1948) on there compy (or can find a copy), let me know.


I've also heard of divinyl ketone + MeAm and possibly piperidine -> piperidone. Thoughts on those would be appreciated too.

Thanks for the input!


-F☺rd

[stateofhack]

bump.

[eesakiwi]

E 280?

I think its used in Agricultural stuff, weedkillers or something, hormones?
I can't find my reference, it is a agro chemical here in NZ.

Its also used in Breadmaking, not much help there..

[Ford Prefect]

E 280?

I think its used in Agricultural stuff, weedkillers or something, hormones?
I can't find my reference, it is a agro chemical here in NZ.

Its also used in Breadmaking, not much help there..

Cool, I'll do a bit of research.

Propionic acid seems easy enough to make though, basically just a Calcium Hypochlorite oxidation of MEK. Plus you get a nice bit of chloroform out of the reaction. :)

I'm still real curious about this Double Mannich, 4-piperidone out of acetone, formaldehyde and PEA seems way too good to be true!

Any thoughts anybody?

-F☺rd

[eesakiwi]

Propanoic acid, its in Twinax, propranolol is also on the scrap of paper I have here.

[fcknut]

I'm still real curious about this Double Mannich, 4-piperidone out of acetone, formaldehyde and PEA seems way too good to be true!

Any thoughts anybody?

-F☺rd


Hmmm... Interesting, though I can't seem to find any citations for this method, having had a quick look.

It seem reasonable I guess, but I'm not sure you'll be able to avoid obtaining product mixtures, even though the second Mannich step is intramolecular.

Another issue might arise when dealing with formaldehyde - this depends on the tolerance of the reaction water, which I'm guessing won't be all that high, seeing as how you would be generating iminium species, though it may be absolutely fine - I'm no expert... Assuming water is OK, then you should be able to use formalin.

If not however, then you back to either using paraformaldehyd directly, which may or may not work (I forget what the limits are for this really, though I know there are a number of reactions which won't go) or to cracking paraformaldehyde to obtain straight formaldehyde (I think you can do this in a reasonably straightforward manner, and collect the depolymerised material in THF or something).

Sorry I can't be more helpful, just a few thoughts off the top of my head.

[Ford Prefect]

Hmmm... Interesting, though I can't seem to find any citations for this method, having had a quick look.

It seem reasonable I guess, but I'm not sure you'll be able to avoid obtaining product mixtures, even though the second Mannich step is intramolecular.

Another issue might arise when dealing with formaldehyde - this depends on the tolerance of the reaction water, which I'm guessing won't be all that high, seeing as how you would be generating iminium species, though it may be absolutely fine - I'm no expert... Assuming water is OK, then you should be able to use formalin.

If not however, then you back to either using paraformaldehyd directly, which may or may not work (I forget what the limits are for this really, though I know there are a number of reactions which won't go) or to cracking paraformaldehyde to obtain straight formaldehyde (I think you can do this in a reasonably straightforward manner, and collect the depolymerised material in THF or something).

Sorry I can't be more helpful, just a few thoughts off the top of my head.

Thanks! The only reference I've heard of is the one mentioned in the OP, but unfortunately I haven't been able to find a copy of even that.

Yeah, I'm a bit worried about the potential for polymerization and the fact that the reaction might mainly produce 2,2-dimethyl- or 2,2,6,6-tetramethyl-4-piperidone, but it looks like the potential is there.

Hydroquinone as stabilizer?

*This thread is now (mostly) about 4-piperidone btw.*

Kiwi: I couldn't find much on Twinax other than the cabling? Am I on track?

-F☺rd

[eesakiwi]

*This thread is now (mostly) about 4-piperidone btw.*

Kiwi: I couldn't find much on Twinax other than the cabling? Am I on track?

-F☺rd

Nah, way off, its a horticultural thing.
The cabling thing is all I found untill I put in 'horticultral' as well.

Headland Intake wetting agent?