It is possible to convert Naltrexone or Naloxone into Oxymorphone?

Answer 1

I am going to answer this with my own limited and highly speculative research. Because I would have liked this info to be easily available when I myself was looking for it. now I give my own research, which at least has theoretical merit. Give something back to the internet and enjoy it more!

Simple answerThe shortest and most accurate answer is an unconditional "yes". The following sections are theoretical reflections on the practicality of the synthesis regardless of route, something which is good to read and think about, if you are not willing to use unlimited resources (money/effort/time) to succeed. If you are most interested in my reflection on possible way to perform the actual chemical synthesis, look at the "Chemistry" section.

Less simple answer

A much more complete answer includes a question that was indirectly but very obviously asked in the original question: "how difficult is it compared to the results". or specific to this kitchen-chemistry subject: "can I practically do it with my abilities and equipment, and if so how much work will it require."

An experienced organic chemists can perform almost all imaginable reactions, that are theoretically physically and PRACTICALLY possible, which makes the synthesis of any chemically stable compound from ANY other stable compound theoretically and almost always physically possible. Most of the time, it is ALSO practically possible, however difficulty determines how practical is really is, but normally it is only a mater of time before even the most complex synthesis can be mastered, like the synthesis of morphine from non-biological sources, that is purely synthetic, which took a very long time to successfully perform, and is still considered a very impressive, extremely complicated acrobatic exercise in organic chemistry, even by the most experienced in the field; more on this synthesis later.

Correct question

As I said, I am absolutely sure, that the person who wrote the question did not mean "can it be done" but rather or at least ALSO wanted to know how difficult if would be; This can be illustrated by the fact, that one could in THEORY make fentanyl out of air and wood as those two together contain C, H, O, N and it IS possible to make a molecule from its constituent elements, but for complex molecules this is so difficult and expensive that no one chemical plant in the world performs all the steps from pure elements to complex, organic molecules. One plant make pure elements and/or the simplest molecules into larger building blocks, and then another plant buys these compounds and makes larger, more complex, organic molecules of say 4 - 15 carbon atoms, like amino acids and sugars, then another plant assembles these compounds into macromolecules such as proteins, nucleic acids (DNA / RNA), polysaccharides (sugar molecules bound together in long chains) such as starch and cellulose, this last step is as far as today's conventional chemical technology has come, but in the very near future it will most likely be possible to assembler the macromolecules into the next sted up in complexity: actually organic "machines", like the organelles of a cell, a virus and eventually functioning, living synthetic cells.

The problem about answering the more important question; "is it practical" and how does one measure whether something is "practical"? The former is often defined as how difficult/expensive the process is compared to the benefits of the product. In the "real" pharmaceutical industry, this would be a simple subtraction: Result = Value_of_product - Cost_Of_Production. If this is more than 0, the process is practical. I our case Value_of_product is less easy to measure as it describes some emotional component like the subjetive recreational value of one dosage times number of dosages obtained from the process subtracted by the emotional drain that the process takes on the chemist, and I can even see know, that it is better expressed non-mathematically: are the effects AND the amount of compound =number of dosages = time you can feel the effects with the amount synthesized worth the effort? Here again it differ, some people who are highly opioid-dependent are willing do perform tasks most non-dependent people would never dream of, like criminal acts such as theft, robbery other violence or acts most find pepople would find degrading, humilitating and emotionally devastating such as prostitution, pornography and begging. This is very unquantifiable and definately did not need that much text in this answer, but I felt pretty clever when I wrote it, and we are all compelled to repeat and prolong pleasant experiences, like drug use and masturbation. Now onto to the actual chemistry, which is a very absolute science, or is it?

Chemistry

The simple answer here is that with both nalaxone and naltrexone, we want to change the group attached to the N with with a simple methyl-group, which is most easily done by removing the group attached to N and then in another step attach the methyl group to the N and voila, oxymorphone;

Step 2:

The latter step is easy, can be done by reductive amination (RA) (at least in theory, as RA usually works better, when the amine is the smaller molecule, but I would guess that some of the N-methylated product would form, if enough is another matter), or maybe a more effective way would be electrophilic substitution with methyliodide or possible a different methyl-halide which are all electrophiles because of all halogens excluding At have higher electronegativity than carbon, thus the carbon atom will be electron deprived and will attack the electronrich N atom of the molecule; the N i any amine is nucleophilic because of the lonepair electrons and because of the partial negative charge on it, arising from the difference in electronegativity between carbon and nitrogen. If only considering partial charge in the possible methyl-halides, methyl-flouride seems to be the strongest electrophile, but the chemical litterature suggests that methyl-iodide is a better leaving group, so maybe also in this case it is prefered.

Step 1

The most obvious problem with this step is the fact, that the molecule i a tertiary amine, and the reaction will only be practical, if is takes signigicantly less energy to break the bond between the N and the open ended group than the two bonds between the N and the bulk of the molecule or viewed differently, the bonds in the piperidine ring; if this ring can be viewed seperately as a normal piperidine ring, then the reaction should be possible, as most rings has more stable bond to ring members than to substituents on the ring as in most substituted benzene-molecules it is easier to break off a substituent then breaking the ring itself. But this step remains tricky; if assuming that the openenden substituent on N in both naltrexone and naloxone can be expected to behave somewhat like methyl-piperidine, one can first oxidize it and then remove both the Me and O- by deoxygenative demethylation, which will produce a mixture of the desired product and byproducts, which can be hard to seperate.

Alternate step 1

Instead of breaking of the entire group on the N, one could look for a way to shorten it to a methyl group or something similar, that can be converted to a methyl group.

Conclusion

Both conversions are certainly practical, as the desired compund is almost identical to the two source compound, however it seems that to get a pure product and a good yield, one would have to invest in a lot of lab equipment and be a descent chemist. But if the first step can be simplified, it will become kitchen chemistry.

Answer 2

It is not possible to directly convert Naltrexone or Naloxone into Oxymorphone as they are structurally different molecules and have different pharmacological properties. Oxymorphone is a semi-synthetic opioid derived from thebaine, while Naltrexone and Naloxone are opioid antagonists. Converting one to the other would require extensive chemical modifications that are not practical.