Eugenol-->Safrole directly?

[Osmium]

If you have to use shitty reagents like pyridine hydrochloride to demethylate cheap stuff like eugenol then better forget about this whole scheme right now.
Using difficult to aquire reagents like this one in the first step of a multi-step synth is ridiculous. Consider it a scientific curiosity, but not a working and worthwhile procedure.

I say it again: use aq. H2SO4 to demethylate. Anything else is too expensive, smelly, suspicious, costly and complicated.
I'm not fat just horizontally disproportionate.

[Rhodium]

Os: I have said it so many times before - H2SO4 should polymerize the ass of eugenol, unless you have at least a 1800's journal article from Uzbekistan to back it up...

[Osmium]

I don't know what exactly will happen to eugenol, but even if it produce only a 30% yield this is the way to go, since eugenol can be had for less than €20/liter.

I don't have any refs right now, but I have seen several ones over the years. Strong aq. acids will demethylate phenolethers. Look what Mr. Shulgin says:

The amphetamine metabolite, 4-hydroxyamphetamine hydrochloride (4-HA), was prepared by heating 5.0 g 4-MA in 20 mL concentrated HCl at 15 lbs/in. After recrystal-lization from aqueous EtOH, the product weighed 3.8 g and had a mp of 171-172 °C.

http://www.erowid.org/library/books_online/pihkal/pihkal097.shtml

I've seen several other reactions where phenolethers were refluxed with H2SO4, and at least partial demethylation took place. para MeO will hydrolyse the fastest, ortho-MeO the slowest. But they all will eventually come off.

If eugenol won't work satisfactorily then use something else. Vanillyl-methyl-ketone for example.

I'm not fat just horizontally disproportionate.

[Aurelius]

Rhodium?  you've been to Uzbekistan?  how interesting

Osmium, have you tried the rxn?  if you supply details for how you would run the rxn, aurelius will do the work in the lab.  (has more time in lab now) 

And just so everybody knows, THIO COMPOUNDS SUCK!!!!!!!!

[Rhodium]

Great Aurelius! If you actually try the reaction we can settle it once and for all if the reaction is indeed workable.

I wonder if it would be best to isolate the reaction product as the diacetoxy ester, as the diphenol is so oxidation sensitive, or if the best way would be to try to isolate all non-polymeric phenols and either methylenate them directly, or actually isolate the dihydroxyallylbenzene?

We have the physical properties of all the compounds in the database and at my site.

Thio compounds does not suck, but they sure smell. No, I haven't been in Uzbekistan, but all the most revolutionary syntheses we find are always written in an unreadable language...

[Chromic]

Would isoeugenol be less prone to polymerization? (for steric and stability reasons?) Just a thought. The ketone idea is nice too. I think a reflux in 20% HCl (that's the azeotrope, right?) for a couple days might be an idea as well.

[Antoncho]

Rhodi: i am absolutely confident that all scientific journals ever published in Uzbekistan are in Russian      It's especially funny since i am currently waiting for a very interesting article from an Uzbekian journal    So this discussion kinda caught my eye...

As for eugenol - guys, H2SO4 will add across the double bond bee4 it demethylates anything, correct?

Now, to dedmethylate vanillin w/it is indeeed a possibility

/to bee continued later/

[Aurelius]

should reflux be open-air?  what about distillation?  the diacetoxy compound?  do you mean using Acetyl chloride to give the compound or are you talking about a different compound?

[Rhodium]

The reflux should most preferably be done under inert atmopsphere (as dihydroxyallylbenzene is sensitive to oxidation). A tightly packed CaCl2 moisture protection tube should keep most of the air out of the reaction flask though.

I was referring to protecting the dihydroxyallylbenzene as the diacetoxyallylbenzene (acetylation of it all with acetyl chloride or acetic anhydride) while isolating/purifying it, it might help against decomposition. Some data on the dihydroxyallylbenzene can be found in

https://www.thevespiary.org/rhodium/Rhodium/chemistry/allylpyrocatechol.html

For suggestions on how to perform the H2SO4 demethylation, I think Osmium is more qualified to write an outline on how it should be done.

What is the best distillation vacuum you have available in your lab?

[Antoncho]

Elder bees, please excuse my ramblings, you of course know all this - and this topic has been discused zillion times bee4 -i just want to somewhat summarize the known facts for the ones still unfamiliar. Comments, please!

There are basically three types of demethylating agents (all acidic, alkaline is also possible, but i'll leave that out):

- mineral acids (HBr, HCl, H2SO4)
- metal halides (AlBr3, FeCl3, etc)
- hydroclorides of organic bases (pyridinium*HCl, anilinium*HCl)

So.... 1st, eugenol unaturated side-chain is profoundly rich in electrons, thus, any Lewis or Broensted acid, xept the mildest ones like organic amine chlorhydrates, will do things to it.

I suggested use of aniline HCl earlier - which has been mentioned as a good demethylating agent for vanillin in one of old Russian textbooks. BTW, remember, those were the pre-microwave days!

OTOH, the side-chain of MVK (methyl vanillyl ketone) is very electron-poor (acidic) - so acids won't hurt it, but there's a major BUT: any Lewis-acidic metal chloride will serve as a Friedel-Crafts catalyst for it, providing an excellent "process for producing polymer" as they say it at USPatent database

That's actually the reason for low yields in FC-acetonylation (P2P via chloroacetone).

I don't know if mineral acids can serve in the same manner (Rh? Os?), but i do know ketones react with strong acids.

Vanillin. This one, once demethylated, will of course bee more of a problem to convert to the desired product. But the odds of successful demethylation are much higher, it seems to me.

1st, it can bee demethylated w/H2SO4. There is a patent.... uh, lemme see....



I am awfully sorry to end my post so abruptly, but i just found something that definitely deserves a thread of it's own  sorry.


Antoncho

[foxy2]

Here it is!!!
However the yeild is only 50% and it takes quite allot of LiCl.  Hmm I wonder if you could recover the LiCl?

Patent EP1136481

A solution of 354 ml (2.30 mmol) of eugenol and 292 g (6.89 mol) of lithium chloride in 3.7 1 of N,N-dimethylformamide was refluxed for a total of 44 hours (h), and, after 4 h, 18 h and then 7 h, a further 292 g (6.89 mol) of lithium chloride were added each time. After cooling, 2 1 of toluene were added and the resultant precipitate was filtered off with suction and extracted with toluene. The organic extracts were combined and concentrated on a rotary evaporator. After flash chromatography (ether/pentane, 1:1, Rf = 0.37) on silica gel, 173 g (50%) of 4-allylcatechol were obtained.

Those who give up essential liberties for temporary safety deserve neither liberty nor safety

[foxy2]

Lignosulfonates.  XXVI.  Demethylation of lignin during pulping.    
Hayashi, Akira; Namura, Yoshifumi.   
Nippon Mokuzai Gakkaishi  (1967),  13(1),  24-7. (In English)
Abstract
Guaiacol, ethylated guaiacol, vanillyl alc., eugenol, ethylated eugenol, vanillin, ethylated vanillin, vanillic acid, and anisole as model compds. were cooked with 5% NaOH, 5% NaHSO3, and 5% Na2SO3 + 1% NaHCO3, and H2O, and the MeOH formed in the reaction mixt. was detd. to study the demethylation during the cooking process.  All guaiacyl compds. examd. were demethylated during the sulfite and the alkali cooking process.  Even ethylated compds. having no free phenolic OH groups and anisole were also demethylated.  Thus, demethylation is not a special reaction of lignin, but a general hydrolytic reaction of phenolic ethers that proceeds very slowly.
Those who give up essential liberties for temporary safety deserve neither liberty nor safety

[Rhodium]

Foxy: The latter reference has already been retrieved, and it gives <5% yield when checked by GC, I don't want to think of the isolable yield...

[Antoncho]

I adore thee. This LiCl/DMF procedure is awesome! Just what we needed.

Antoncho

[foxy2]

Rhodium
Do you mean the LiCl ref or the lignin?

Those who give up essential liberties for temporary safety deserve neither liberty nor safety

[Rhodium]

The latter - demethylation by base on lignin-like compounds.

Regarding the LiCl thing - there MUST be another usable salt...

[moo]

For some lithium salts are available, but not DMF. Any suggestions for a replacement? Of course, plain formamide could be prepared.

[Rhodium]

DMSO may be a suitable substitute.

[Aurelius]

Sorry, the strength of the vacuum pump is not known off-hand.  aurelius will find out asap.  how strong does it really need to be? 

[slappy]

Can't you just use a slight excess of BBr₃ in DCM? I think that you can also use Lithium Triethylborohydride to demethylate anisoleic methoxy groups.

Can you use Triethylamine Hydrochloride? Pyridine is readily available and cheap (aniline too, though more expensive), just take it up in DCM, and gas with HCl, and the respective *HCl salt will fall out, then wash, dry, and you're good to go.