Diamorphine -> Morphine

[haribo1]

I note that diamorphine (heroin) breaks down into 6 monoacetyl morphine and from there to morphine. Does this signify that the phenolic ester is stronger? If so, am I right in thinking 6 monoacetyl morphine can be produced with acetic acid, but to acetylate the 3 position requires acetic anhydride? Similarly, how easily does the 14-OH of oxycodone esterify? Could I esterify while leacing the 3 position alone?
What I'm leading up to here is 14-cinnamyl 3-acetyl ester of oxymorphone (with that 5 position turned into a methylene group, of course)...

 

[LuxEtVeritas]

not exactly sure where you are getting at or the starting material you seem to intend hypothetically of course, but one can i believe pretty easily get the 14-cinnamyl on oxycodone and ain;t that the objective desired

unless i am missing that a 3-acetyl is far better than a 3-OMe

hell why not than try 3,14-dicinammyl-oxymorphone

 

[Ham-milton]

I'm pretty sure that the 3-acetyl 14-cinnamyl was the most potent?

 

[Acyl]

I note that diamorphine (heroin) breaks down into 6 monoacetyl morphine and from there to morphine. Does this signify that the phenolic ester is stronger? If so, am I right in thinking 6 monoacetyl morphine can be produced with acetic acid, but to acetylate the 3 position requires acetic anhydride?

The phenol would probably turn into the ester the fastest in both cases.

 

[implicitprodigy]

14-cinnamyl 3-acetyl ester is the most potent derivative of oxymorphone

 

[johanneschimpo]

^ probably why he's interested in it, eh?

 

[immaturepoop]

(with that 5 position turned into a methylene group, of course)...

Are you talking about the ketone? Could that be done using a Ylide? that being triphenylphosphine + alkyl halide ---> desired ylide, then using the Wittig reaction to form the methylene group? I've been told Phosphorus is 'oxophilic' ;-) Hope this isn't too synthetical of a post!

 

[butane]

Bring that to blacklight and we'll talk.

Anyway, my preferred method of converting diamorphine into morphine is with my body's metabolism.

 

[MurphyClox]

I note that diamorphine (heroin) breaks down into 6 monoacetyl morphine and from there to morphine. Does this signify that the phenolic ester is stronger? If so, am I right in thinking 6 monoacetyl morphine can be produced with acetic acid[1], but to acetylate the 3 position requires acetic anhydride[2]? Similarly, how easily does the 14-OH of oxycodone esterify? Could I esterify while leacing the 3 position alone?
What I'm leading up to here is 14-cinnamyl 3-acetyl ester of oxymorphone (with that 5 position turned into a methylene group, of course)...

[1]You'll hardly get your ester, as the reaction equilibrium is on the side of the free alcohol/acetic acid. Using strong acids as catalysts (like dry HCl, H2SO4) may be a bit too harsh...
[2]Activated derivatives of acetic acid are the answer for both cases, like the already mentioned anhydride or the chloride. Some catalysts or coupling agents might help as well (e.g. 4-DMAP, DCC).

In general, the 6-hydroxy is more nucleophilic as it is an aliphatic alcohol. The phenol is...a phenol (i.e. an aromatic alcohol), which got some potencies lower nucleophilicity (?!). Take a look at the resonance structures and you'll see. In principle, you were right by guessing that it takes much more activated compounds to acylate a phenol than an aliphatic alcohol.

Murphy