2bob
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Dihydroxydesoxymorphine/levorphanol synthesis from codeine (UN)
look at this:
DIHYDRODESOXYMORPHINE D, DESOMORPHINE OR PERMONID
This compound (IX) was discovered by Small[3] in the course of his research on those derivatives of morphine and codeine in which oxygen is no longer
attached to carbon atom 6. It is prepared from α-chlorocodide (X), which is itself obtained by the action of thionyl chloride on codeine (III).
By catalytic reduction, α-chlorocodide (X) gives dihydrodesoxycodeine D (XI), which yields dihydrodesoxymorphine D on demethylation.
This substance appears to be remarkably active, with an analgesic effect about ten times greater than that of morphine; its toxicity, although
likewise exceeding that of morphine, is apparently only three times as great. Its action is described as being very rapid but of short duration, and
not accompanied by vomiting. It has been given the commercial name of permonid in Switzerland, where it is used.
(The diagrams to which this passage refers are located here: UNDOC).
The Dihydrodesoxymorphine D, is derived from the demethylation of the dihydrodesoxycodeine D, which demethylation gives a product (the
dihydrodesoxymorphine) which is indistinguishable from levorphanol (see picture), derived from a different synthesis (except of course for the oxygen
bridge). As levorphanol is marginally stronger than dihydrodesoxymorphine (2mg:3mg), there should not be any serious problem involved in the
demethylation of this molecule, as unlike most demethylation reactions involving opiates, it is actually preferable to destroy the oxygen bridge.
In any event, breaching the previously all important oxygen bridge (which was thought to provide much of the effectiveness of opiates), is not as big
a catastrophy to be avoided as it once would have appeared. The only benefit in not doing so, would of course be the fact that the
dihydrodesoxymorphine is not anywhere near as addictive(a) as morphine, despite being some 10 times more effective (compare Heroin, which is 2-3 times
stronger than morphine, but 5 times more addictive).
Therefore, contrary to the usual problem associated with the demethylation of opiates (particularly codeine, et al) in this instance it is immaterial
whether the oxygen bridge is ruptured (as to do so would simply make the resultant product even stronger), thus it is possible to utilize stronger
agents with which to bring about the demethylation, either Hydroiodic acid or Hydrobromic acid, or even Hydochloric acid could be utilized to
demethylate (and reduce) the product, making the synthetic opiate, levorphanol, from the ‘naturally’ occurring codeine, in three steps:
1. Codeine + thionyl chloride = chlorocodide
2. Chlorocodide + Ra/Ni; Ush/Ni; Al/Hg (+H) = dihydrodesoxycodeine
3. Dihydrodesoxycodeine + HCl/HBr/HI/etc. = levorphanol
With regard to step 3. if pyridine hydrochloride is utilized (in anhydrous conditions) as the chosen demethylation reagent, the product would be
dihydrodesoxymorphine. In any case, if this proposed synthesis can be demonstrated to be effective, it will render the current ‘homebake’
procedures (providing minute quantities of crap heroin) obsolete, as this procedure is of a similar degree of difficulty, but provides a far better
product.
(As to the use of HBr to demethylate/reduce this type of compound, please see UNDOC, (@ fn 23-25)). The compound, levorphonal is also referred to as
3-hydroxy-N-methylmorphinane (XXVIII).
The main article is here:
http://www.unodc.org/unodc/bulletin/bulletin_1951-01-01_2_pa...
The wikipedia entry on levorphanol is here:
http://en.wikipedia.org/wiki/Levorphanol
A synthesis for Levorphanol is here:
http://www.erowid.org/archive/rhodium/chemistry/levorphanol....
whilst the old 'homebake' method is here:
http://www.erowid.org/archive/rhodium/chemistry/codeine.home...
http://www.erowid.org/archive/rhodium/chemistry/codeine2morp...
If you are interested in this synthesis, please scroll through the UN article, and read it very carefully.
2bob
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ergoamide
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One problem, it does not equal levorphanol. Levorphanol form codiene is impossible, it's to hard to get a phenol group off wihtout detroying the rest
fo the molecule. Not to mention dihydrodesoxymorphine is not levorphanol, levorphanol doesnt have the ether bridge. However you do descirbe the
synthesis of desomorphine which is 10x as potent as morphine (if i recall) which is still good but lacks levorphanol duration. Still good post though.
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2bob
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yeah,
but the biggest problem with the homebake method (according to the two doc's from Rhodium's page) is that strong demethylating agents cannot be
utilised as they would destroy the oxygen bridge. That being so, and the oxygen bridge being the only difference between levorphanol and
dihydrodesoxymorphine, why not use either HI/HBr to demethylate the dihydrodesoxycodeine? According to Rhodium (and the analytical chemists writing
the review on the homebake method) this has the capacity to both demethylate and deoxygenate the codeine, so why would it act differently upon the
dihydrodesoxycodeine variant?
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ergoamide
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it destroys the oxygen bridge yes, but the oxygen moves to the more stable side, the benzene ring and becuase of that it cannot be removed. If there
were some way that you could get it to move to the cyclohexene ring then it would be no troubles and and excellant way to levorphanol. Also HBr cna eb
used ot demthylate once the double bond is gone fomr the cyclohexene or there is a 14-hydroxy. HI still cant be as it will open the ether bridge.
dihydrodesoxymorphine is good enough though, will a urushibara hydrogenate that double bond though, failing that dithionite will anyway.
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2bob
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I don't yet have an answer on that, I haven't managed to read Small's article on the chemistry that was used, but I believe that Ra/Ni was utilised
for this reaction at some point, thus it should be able to be reproduced using the Urushibara Ni/Zn catalyst (I am unsure, but I would probably try it
with the NaOH first, if that doesn't work use the Acetic acid).
There is a page here on the interchangeability of Ur/Ni for Ra/Ni:
http://www.erowid.org/archive/rhodium/chemistry/urushibara.h...
And here is another for the use of Ur:Ni/Al for the reduction of phenyl-nitropropene to benzedrine:
http://www.erowid.org/archive/rhodium/chemistry/amph.urushib...
SWIM must now dust of his skills and make some thionyl chloride, in order to facilitate the dream that swim feels is iminent (SWIM will also need to
isolate & oxidise some piperidine, then gas it with chlorine).
SWIM thanks ergoamide for his/her assistance in sorting out that problem, at least the dihydrodesoxymorphine that may be dreamed of is an extremely
potent, though not overly addictive, analgesic.
I personally thank the United Nations for this synthetic route on behalf of all those people WIM.
Once the oxygen bridge is ruptured, wouldn't that leave a methoxide and a methyl group? Couldn't these be removed somehow? I am not arguing with your
suggestions, however, I feel that if somebody is doing chemistry at uni (not me, I am doing law*), that this would be an excellent post-graduate study
opportunity.
* Maybe this would explain my inability to understand some of my more basic errors?
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