It would have been nice if someone told me PdCl2 has an undesirable oxidation state.  so it goes.

I did two trials this weekend, both semi hap-hazard, but I'm learning.  The first I added .3 grams pdcl2 to 500 mgs codeine, and thought I'd try the sulfuric acid for reflux... well, I didn't wash the binders thoroughly and got a nice polymerized black nugget which interfered with the reflux.  did manage to salvage the codeine but it wasn't pretty.

Second shot instead of using a cold jacket condenser, I just a reflux pot and just kept the outside cold with paper towels.  This time I repeated the procedure with HCL and I washed the codeine better to remove binders.  Refluxed for 3 hours.  basified, extracted.

Thats all I had patience for this weekend after realizing the PdCl2 isn't going to cut it.  I'm either going have to reduce the pdcl2 to palladium black.  Or I just bought some palladium micro bead industrial catalysts, so I'm hoping those will work nicely.

The micro scale set turned out to be a pain in the ass.  In the future for reflux I think I am just going to fit a test tube in the opening of a bottle as a cold finger.  Make it airtight with rubber then just add ice to the test tube as it melts.

I also think the alcohol reaction is looking more and more attractive.  Next trial will be in alcohol.  I think purification from alcohol will prove by far the easiest.

I was thinking about the oxy-derivatives today.  Looked at the typical synthetic routes; most utilize dichromate to make the codeinone or 14-hydroxycodeinone.  Dichromate is biologically nasty in Stones opinion and was thinking about sodium hypochlorite to make codeinone via a PTC.

typically: Preparation of oxycodone from codeine

Abstract
A process is provided for preparing oxycodone from codeine comprising either: (A) the steps of (1) oxidizing codeine so as to form codeinone; (2) converting codeinone to oxycodone in a two-step-one-pot reaction: first reacting codeinone with hydrogen peroxide in water in the presence of an acid at from about 15.degree. to about 70.degree. C. to form 14-hydroxycodeinone and then catalytically hydrogenating 14-hydroxycodeinone in its original reaction mixture to form oxycodone; or (B) the steps of (1) oxydizing codeine so as to form codeinone; (2) reacting codeinone with an acylating agent so as to form codeinone dienol acylate; (3) oxidizing codeinone dienol acylate with an oxidation agent in water or a solubilizing solvent mixture in the presence of an acid at from about 15.degree. to about 70.degree. C. to form 14-hydroxycodeinone; (4) hydrogenating 14-hydroxycodeinone in its original reaction mixture to form oxycodone.


pubs.acs.org/doi/abs/10.1021/ja051682z
"Codeinone (3) was efficiently and directly converted to 14-hydroxycodeinone (1) by catalytic air oxidation in aqueous solution. A number of simple manganese and copper salts were identified to be effective catalysts, including MnSO4, KMnO4, and CuSO4. An appropriate reducing agent, such as sodium thiosulfate, is required in the reaction mixture presumably for the reduction of a detrimental peroxide intermediate. This discovery allows the more abundant codeine to be employed as the starting material for the synthesis of 14-hydroxylated opiate drugs without recourse to a thebaine-like intermediate. These discoveries were inspired from our study of microbial transformation of codeine to 14-hydroxycodeine by Mycobacterium neoaurum, where we found the actual 14-hydroxylation step is a chemical reaction rather than an enzymatic reaction, as previously believed."

Copper Sulfate is interesting in this paper but again we need codeinone.


All of the write ups I've looked over use dichromate exclusively!

On wiki- Household bleach, with a phase-transfer catalyst, has been reported to oxidize alcohols to the corresponding carbonyl compound.[5]

I'm curious if codeinone could be prepped via sodium hypochlorite and one of the many quaternary ammonium salts typically sold as fungicides for aquarium maintenance.  PTC reactions usually have few side products, and once we can isolate codeinone it is a quick step to the 14-hydroxycodeinone (H2O2) or using the prior mentioned copper sulfate method.

The last bit would be a simple hydrogenation using either a catalyst(Pd likely) or a parr hydrogenator.  I prefer the pd catalytic approach.

Any thoughts on the PTC reaction of codeine with sodium hypochlorite?  This could potentially produce a product with less chromate contamination...safer.  and it is all OTC.  The question is... will it work.


I thought this link is interesting: http://docs.google.com/viewer?a=v&q=cache:dx9uVclvv9sJ:iweb.tntech.edu/chem312-dc/OXIDN2.pdf+oxidation+of+secondary+alcohols+with+sodium+chlorite&hl=en&gl=us&pid=bl&srcid=ADGEESiMU8wNu09nltmRO-QCC5HCNVVOMDykk_6xrw4_aRfBeqsVWW3AMvVt4g0_htuy2I7pfOb8ahlFw_RtjoNQ0xEXPAvC5vIQnQ2QMAHmefOzUcF9b8EARP8ozVlnMyny4Xgmvw-b&sig=AHIEtbTxe0iwOONMl9PM_B2x6wYiT9tn6w

It outlines the oxidation of a secondary alcohol using sodium hypochlorite, and gives a detailed procedure. 

And to get rid of the excess hypochlorite... "In reaction with hydrogen peroxide it gives off molecular oxygen:
NaOCl + H2O2 ? H2O + NaCl + O2?"   essentially just drive off oxygen with the hydrogen peroxide that will be used in the next step of the procedure.

Nice book!  definitely seeding some ideas for further research.

So, I was looking at desomorphine today.  If hydrogenation of codeine was done at a neutral pH to yield dihydrocodeine.  Dihydrocodeines alcohol at the 6 position was eliminated by heating with H3PO4 or perhaps a small bit of sulfuric acid, isolated.  rehydrogenated at neutral pH, we should get desocodeine.  Followed with the HBr/GAA reflux should yield desomorphine.

"It has sedative and analgesic effects, and is around 10 times more potent than morphine."

This could be another interesting experiment.

Nice book!  definitely seeding some ideas for further research

  yeah its fascinating and I'm more than happy to share 'good finds' with those who can appreciate and (esp!) utilise this data for "The Cause"

: http://pubs.acs.org/doi/abs/10.1021/ja051682z
"Codeinone (3) was efficiently and directly converted to 14-hydroxycodeinone (1) by catalytic air oxidation in aqueous solution. A number of simple manganese and copper salts were identified to be effective catalysts, including MnSO4, KMnO4, and CuSO4. An appropriate reducing agent, such as sodium thiosulfate, is required in the reaction mixture presumably for the reduction of a detrimental peroxide intermediate. This discovery allows the more abundant codeine to be employed as the starting material for the synthesis of 14-hydroxylated opiate drugs without recourse to a thebaine-like intermediate. These discoveries were inspired from our study of microbial transformation of codeine to 14-hydroxycodeine by Mycobacterium neoaurum, where we found the actual 14-hydroxylation step is a chemical reaction rather than an enzymatic reaction, as previously believed.

   Sounds very cool, but where to get the "Mycobacterium neoaurum," amigo?

   I have to tell you solidman, my overall level of understanding chemistry is pretty basic, high school MANY moons past (300+!!!)yet I maintained a 'laymans interest' so to speak with ALL the "basic sciences", and because there are still so many 'gaps' in my knowledge and memory re; Organic chemistry, I think/feel I am still at the "basic relearning stage, so sometimes,, (often! you might go a little over my head, so pardon my sometimes ignorant questions, Other than that, I look forward to hearing more from you and the exciting experiments swss might be doing ( in his head,,like we all do, for the ideas we discuss here of course! yeah?
    
BTW(this is the second chemistry forum I've "ever" joined! that was just over a year ago)   and i've learned a lot about the "current state of 'honeymaking wasps' and their methods---------aside from cruising aroung erowid a bit,,I'd hardly spent anytime on the net,,,and then one day cruising around at SM  looking for AA synths-OTC of course! (the 'first' forum I ever "joined" Btw)  or as 'close' as we can get )  and I found a link to here, ...... and I've been thoroughly enjoying trying to learn as much as possible about chemistry, while keeping the "primary essence" of my learning,, to the numerous fascinating topics and substances discussed on this site, as it also has that fabulous Reference section, and the erowid and hive mirrors.So now I'm here, "online" from my room, for the FIRST time in my life, and with my computer, and google I'm pedalling as fast as I can  And Loving it!

  Cheers matey Hyppy

Essentially they initially thought the enzymes in the bacteria were responsible for the reaction, but this study proves otherwise!  No bacteria, just a semi-simple auto-oxidation using very common chemicals in supposedly good yields

 Yes, this is fascinating solidman

If the sodium hypochlorite oxidation of codeine to codeinone works, and this copper sulfate oxidation works to yield 14-hydroxy codeinone... this may become a preferred route to oxycodone and oxymorphone.  No more dichromates (they are god awful for the body) and hopefully better yields.  Time will tell

Again very nifty and as you say, a most definately "preferred" route!

  

Pick up some organic texts learn the rules of the game and hit the ground running.

 matey, this has been my PRIMARY Modus Operandi re; mainly Organic Chemistry for the last year,....I'm reading constantly,  just to give you an idea, nothing you said in this thread has gone far if at all, 'over my head'..but in some of your other threads, I may not be able to say the same thing and soon my "friend" will be doing some (hopefully interesting) practical work, of whic I am sure they will be sharing they trials and tribulations of lab life...but hey thats what all this study and work will hopefully, reflux down to in the end...

  bedtime for me 3:30am cheers hyppy

 Thanx for the clarification amigo, my bad, I didn't read your post quite thoroughly, my apologies its waaaay past my bedtime and i've gotta get up in 4 hrs, but its been a pleasure "sharing the love" buzzing around here  

try a much more aqueous solution,I think you firstly have a "solvent problem" its said several times"aqueous solutions" (titrations (adjusted strenghts of your solvents) can have MAJOR implications!   
Read a bit more stoneman and maybe do a slighly 'simpler' synth---man if you can get pyridine--think OTHER synths...easier with great products,

Anyway good luck and go hard matey, you'll get there, after all,,really "the ONLY failure is the failure to try..." 

  Check out the "codiene demethylation thread" here in this forum--there's a wealth of nifty data here....and the others re; your product of choice;..and have a look at this search link....

."http://au.search.yahoo.com/search?fr=yhs-avg&type=yahoo_avg_hs2-tb-web_au&p=esters%20of%2014-hydroxycodeinone"

cheers hyppy

Can you do a write-up of the procedure ? How Codeine is extracted ? Reaction time , Temp, Yeild ? ...
Nice post

And what about :

Codeine + sodium hypochlorite (Javel's) ==> Codeinone
Codeinone + Hydrogen peroxide + Catalyst (sulfuric acid) ==> 14-hydroxycodeinone
14-hydroxycodeinone + Cinnamoyl chloride ==> 14-cinnamoyloxycodeinone.

Would that work ?

And what about :

Codeine + sodium hypochlorite (Javel's) ==> Codeinone
Codeinone + Hydrogen peroxide + Catalyst (sulfuric acid) ==> 14-hydroxycodeinone
14-hydroxycodeinone + Cinnamoyl chloride ==> 14-cinnamoyloxycodeinone.

Would that work ?

I think the 14-cinnamate ester can be had from this method. Good thing codeine flows in Canada

After stone plans to do a HBr/GAA reflux to demythelate  the ester to give hydromorphone.  Any advice for this step?

hate to bust your balls stone but i tried that twice and got shit yeilds hbr in gaa
turned black and a big ball of resinous crap formed opiate chemistry is'nt always staightforward
i did recover enough to get properly fucked but i would'nt waste good hydrocodone on that.
and also catalytic rearrangement does'nt always go as smoothly as the papers suggest the by-product is o-desmethyl thebainone and the reason it forms is because the catalyst can abstract a proton from the epoxy bearing carbon and cause this black impurity to form as easily as it can abstract a proton from the alcohol to saturate the adjacent double bond.
the solution to this problem is to look up knoll pharmacuetical's patents on hydromorphone they bubble in .2 ml/minute h2 gas to slightly poison the catalyst so it's more selective pretty clever ayee?
yeilds are around 50%
and separation is done by forming the bisulphate adduct
for good measure happy reading see attached
p.s. hydrogen chloride also slightly poisons the catalyst

also bet you did'nt know this: 14 methyl codeinone is 10,000 times the potency of morphine and 14 ethyl about 20,000 times as potent, now nobody in thier right mind would synthesize much less try to titrate that but it's interesting to know.