Alright, boys and girls, it's gone on waaayy, too long. We need a big fat hairy synth of safrole that proceeds directly from eugenol, in one step. They're just so fucking close, why does no one besides me go nearly insane trying to figure out ways to get eugenol to safrole in one high-yeilding step?
Ok, the only synth I've seen with any real promise is terb's alkali fusion synth. terbium: "Eugenol demethylation via alkali fusion." (Methods Discourse) It doesn't look like it'll apply to vanillin for piperonal synths, because it oxidizes the aldehyde to a carboxylic acid. But might very well be used for eugenol--> safrole synths. Now, let's look at it. This is all in reference to the Organic Synthesis article, by the way.
Ok, heating the substrate with NaOH and KOH is pretty obvious, it forms two KO-R groups, and cleaves the methoxy group in the process. But is that high of a temp really necessary? Can the methoxy group be cleaved at a lower temp?
Now, after that. The mixture is cooled dow to 150–160°, and water is added, to dissolve the fused product. Then SO2 is passed into it for a little bit, so as to "prevent the formation of a very dark-colored product when the reaction mixture is acidified with a strong acid." Terbium made the suggestion that a bisulfite could be used instead of having to fuck with SO2 gas. Thuis would definately be preferrable, but how much would need to be used? Does anyone know, or is it just going to have to be trial and error?
Now, for the good part. They say just to acidify the mix with HCl(aq), and you've got it. Now, I see this as being HCl + KO-R --> KCl + HO-R. Am I wrong? If this is the correct reaction, what is stoppong someone from using this opportunity to go directly to methylation with DCM? The medium is already basic, strongly, in fact. The substrate has already been cleaved of its methoxy group, and is primed for the final step. There is sulfur in the mix, which I'm assuming acts to prevent polymerization of the phenolic groups.
So could this final solution just be dripped into a refluxing solution of DMSO and DCM, as in
https://www.thevespiary.org/rhodium/Rhodium/chemistry/methylenation.html#DCM
, giving safrole in one big fat hairy reaction?
Thoughts?
Who is that masked man?