What is known of 3,6-diesters with carboxylic acids, ala heroin?

Extraction of oxycontin with H2O will pull out the oxycodone HCl easily enough. Reflux of the freebase in dry toluene using propionyl chloride should yield the dipropionyl ester should it not?

Followed by gassing with HCl, filter off the dipropionyl ester of oxycodone, take this up in distilled H2O, addition of acetone should crash it out of solution?

Toady could use some quick input here. He has about 1.5-1.6g of oxycodone. His oxy script is simply not enough, and doctors here are fucking pussies when it comes to pain relief, even for those in severe pain.

So...he wants to spin out his rx, and turn it into something more potent...and preferably more enjoyable when IV'ed

The dipropionyl ester should bee considerably more potent, should it not? Although Toady is unfamiliar with oxycodone esters, he has never heard of them being used clinically, or produced by clan chemhacks.

So...what are the thoughts of his fellow hymenopterans on this matter?

Esterification of ketones requires an acid catalyst, I believe. Furthermore you would need to cleave the ether at 3 using e.g. thiophenol before you could produce an ester.

If you want to amp up your oxycodone, my suggestion is to make oxymorphone by demethylating with a thiol and a strong base. Cysteine or acetylcysteine may work.

Waggledance: you've switched the 3 and 6 positions in your post. The 3 position is on the benzene ring, the 6 position is where the *codones have been oxidized.

Prepare cinnamyl alcohol from cinnamaldehyde (cassia oil is something like 80-90% cinnamaldehyde) by grinding it with NaOH and distilling...

Since when can you reduce aldehydes to alcohols by grinding with NaOH ? Can you give any reference? Normal procedure would be Meerwein–Ponndorf–Verley reduction  with aluminium isopropoxide in i-PrOH.

H. Meerwein, R. Schmidt, Ann. 444, 221 (1925); W. Ponndorf, Angew. Chem. 39, 138 (1926); A. Verley, Bull. Soc. Chim. Fr. 37, 537, 871 (1925).

http://www.organic-chemistry.org/namedreactions/meerwein-ponndorf-verley-reduction.shtm   

The reduction of cinnamaldehyde to cinnamyl alcohol is the Cannizzaro reaction. The downside is yields are capped at 50% as one mole is reduced for every mole that is oxidized to cinnamic acid. The classic example given in textbooks is benzaldehyde, yielding benzyl alcohol and a benzoate salt.

Regarding potency, it would be wise to leave that 3-MeO attached. One, to get the potency down to something more reasonable (5-10x less), two, to retain high oral bioavailability so that needles are less of a temptation, and three, so acid/base extractions are still an option (the morphone is zwitterionic), which are essential for those without a column, unless you want to turn into a "krokodil"-type zombie (desomorphine is zwitterionic, so they just bang the raw reaction mixture - it's too bad they haven't tried using Li/NH3 instead of RP/I, as Li/NH3 won't snip the 3-MeO like RP/I will, and may give a cleaner product and better yields - it's little known, but Li/NH3 reduces allylic alcohols).

The product is an ether, not an ester. There's actually some important differences - esters of oxycodone, according to anecdotal reports, do not experience the same jump in potency as do the ethers - curiously, the esters of codeinone, as opposed to dihydrocodeinone (oxycodone), are very potent. You're probably already aware of Buckett's 14-acylcodeinone papers. There's some sporatic accounts of oxycodone esters being screened in the literature, but they're all erroneous - in each case they either drew the structure wrong or screwed up the nomenclature. The synthesis of oxycodone esters has been reported in the literature, but unfortunately, not the pharmacology - frustrating. The 14-O-cinnamyloxycodone ether proposed here was similarly prepared, but not screened, according to Schmidhammer's publications. However, 14-O-phenylpropoxymetopon (PPOM) was in fact prepared and screened, and had antinociceptive potency ranging from 8500-24,000x morphine - more potent than etorphine. Another compound related to 14-O-cinnamyloxycodone is 14-O-phenylpropoxynaltrexone, which was reported by Schmidhammer as 600x morphine. Naltrexone is freely available - either at an online pharmacy, or from a brick and mortar pharmacy for alcoholism. The pills are big too, 60mg each.

Another distinguishing characteristic of the ethers vs. the esters is their qualitative pharmacological profile - 14-O-benzylmorphinone being the best example, displaying no respiratory depression or motor coordination inhibition whatsoever, and improved anxiolytic effects (determined from behavioral studies with rats, and probably the PI as well - you never know what's in the coffee when you work in a lab like that). This should be possible to prepare easily using Dudley's reagent (unwatched), and given the presence of a 3-MeO ether, and 14-O-benzylmorphinone being 500x morphine, 14-O-benzyloxycodone is likely near that of fentanyl.

There are many potential paths to making ethers. The problem is that oxycodone is a very sterically hindered tertiary alcohol, built on a large, complex structure, which is sensitive to many reagents and conditions, side reactions either adding steps or irreversibly rendering it inactive. One way to avoid issues with sterics is acylation with cinnamoyl chloride, followed by reduction of the ester to the 14-O-phenylpropoxy ether using Et3SiH and InBr3. Fortunately, it is virtually impossible to effect elimination on this alcohol, unless conditions are so severe that the structure is destroyed.

You could always attempt a microgram scale synthesis to avoid potential problems, like dropping dead in the lab. Measure out your reactants in solution, clean up with an acid/base, evaporate, and resolvate for consumption.

The reduction of cinnamaldehyde to cinnamyl alcohol is the Cannizzaro reaction. The downside is yields are capped at 50% as one mole is reduced for every mole that is oxidized to cinnamic acid. The classic example given in textbooks is benzaldehyde, yielding benzyl alcohol and a benzoate salt.

Afaik, The Cannizzaro reaction is restricted to aldehydes which have no alpha-hydrogen. Cinnamaldehyde has an alpha hydrogen. Of course you can reduce Benzaldehyde through the cannizzaro reaction because its alpha carbon atom has 4 bonds to other carbon atoms, but no bond to a hydrogen atom.

Assyl,

Thank you very much for your info about 14-O-esters of codones/morphones.  This is, of course, a major bummer for the synth I had next on my list which was 1. hydrocinnamic acid --> hydrocinnamic anhydride. 2. naltrexone --> N-isobutyl-nor-naltrexone, 3. esterification and removal of 3-O-ester with potassium carbonate, leaving the 14-O-ester.

I am surprised that removal of that 7,8-double bond has such an effect on the pharmacology of 14-O-esters, especially ones with long chains and aromatic esters.  When I was running a lot of the molecular modelling, it didn't have a major effect on the aromatic group orienting perpendicular and slightly lower than ring A, but I don't recall if it affected whether the carbonyl group was oriented toward or away from the 7,8-position.  If you have any enlightening thoughts on why there is an issue with 14-O-esters of opioids saturated at the 7,8-position then I'd love to hear them.  I will look at the modelling program again with this in mind.  Reduction of the carbonyl in an opioid 14-O-ester seems like a real bitch.