Eugenol-->Safrole directly?

[El_Zorro]

Alright.  I'd like to start a discussion about going from eugenol directly to safrole.  In the past, all routs to safrole from eugenol have involved demethylating the methoxy group, then methylating the two phenols.  Why?, I asked.  Eugenol already has everything safrole has, the only difference is, the 4 position phenol isn't connected to the 3 postion methoxy.  So why go through several steps to get to safrole, when you could just hitch up the methoxy and the phenol in one step?

In the methylation step from catechol-->benzodioxole, a base is used to deprotonate the phenols in order to react the with the methylene halide.

Now, can't the phenol AND the methyl part of the methoxy group be deprotonated at the same time, and with perhaps a sodium halide, or even an elemental halide to react and close the bridge?  I've been reading that in order to deprotonate a methyl group if you use a base with a higher pK_a than the C-H bond.  Now, what I don't know is, what is the pK_a of the C-H bods in the 3 position methoxy group of eugenol.(or vanillin)  Comments?  What bases could be used to deprotonate both the methyl group and the phenol simultaneously?  Comments?
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[terbium]

Your superbase would be more likely to split the ether than abstract a proton. So, you would still get the dihydroxypropenylbenzene.

[Aurelius]

So what's the problem with getting dihydroxypropenylbenzene?  just methylenate the stupid thing and there's isosafrole.

[PrimoPyro]

Do you know of any suppliers other than Aldrich for that compound?

Im not asking for any, my question is as simple as it is stated: Do you know of any suppliers for that compound other than Aldrich (or other huge manufacturers)?

I don't. I've looked because I too was very very very interested in that compound as a source.

                                                   PrimoPyro
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[Chromic]

Last I checked eugenol is an allylbenzene (ie a 2-propenylbenzene) like safrole, not a propenylbenzene (ie a 1-propenylbenzene) like isosafrole. Like terb said, O-demethylation will occur before a hydrogen will leave from the methyl group, strong lewis acids/bases will cleave the ether bond... bridging it usually done with base-catalyzed methylenation with dichloromethane...

Why try and reinvent the wheel when there's so many refs showing this works as is?

[PrimoPyro]

But that phrase halts progress. It is anti-scientific.
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[Chromic]

Although I haven't looked at it, the reaction mechanism of bridging dichloromethane to two phenoxides ortho to each other is likely S_N2-type chemistry.

You have the phenoxide attacking dichloromethane, and one of the chlorine groups leave (I bet this would work even better with dibromomethane or diiodomethane as they're better leaving groups)... then you have an intermolecular williamson ether-type synthesis going on where the other phenoxide attacks the chloromethyl group that was just formed. This works because chlorine can turn into chloride (Cl-) which makes an excellent leaving group. Hydrogen would have to turn into hydride (H-) to make a good leaving group. Hydrides don't form easily, from what I know, unless you have a very electropositive species (like alkali metals) hydrogen is always going to be floating around as a proton (H+). The problem with El_Zorro's approach is that it's not possible to turn the hydrogen on the methyl into a good leaving group.

Or should I say... I don't think that's possible. I always stand to be corrected.  

Btw, point taken about furthering discussion/research...

[Rhodium]

PP: Source for what compound? Eugenol is all around us for just a few dollars a liter as clove oil.

[PrimoPyro]

A source for the compound stated in the post right before mine.
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[terbium]

A source for the compound stated in the post right before mine.
The source for dihydroxypropenylbenzene is the O-demethylation of eugenol.

[PrimoPyro]

I know that terbium.  

Perhaps I am not being clear enough. By "source" I do not imply origin, I imply "retailors of" said compound, that is why I specified Aldrich as an example, and not eugenol as an example.

My post was in its entirety a reply to the one preceeding it, which obviously implied purchasing said chemical, not manufacturing it.  

                                                    PrimoPyro
Vivent Longtemps La Ruche!

[Rhodium]

It is very unstable to oxidation, and thus not available from many places, except the microsoft/AOL companies of chemsuppliers.

[terbium]

Last I checked eugenol is an allylbenzene (ie a 2-propenylbenzene) like safrole, not a propenylbenzene (ie a 1-propenylbenzene) like isosafrole.
Yes, I was using the term propenylbenzene in an attempt to be ambiguous about the position of the double bond.

I was attempting to be ambiguous about the position of the double bond so that I could ignore whether or not a certain O-demethylation process might also isomerize the double bond.

[El_Zorro]

I realize that there are well-documented synths that involve demethylating the eugenol then methylating it, but they use a two-step synth, and I was looking for a one step, in order to minimize time and chems.

Alright, if the superbase would cleave the ether group and form dihydroxyallylbenzene, and the methylation is catylized by a base, could not the entire synth be performed in one step?  Hmmmm..... perhaps not, because polymerization during the methylation step is minimized by dripping the dihydroxy into the DCM.  Damn.  Even if it did work I have no doubt that it would result in low yeilds.

Second question.  What is the pK_a of the methyl section of the methoxy group in eugenol?  Without knowing we are all just guessing as to what would happen.
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[terbium]

What is the pKa of the methyl section of the methoxy group in eugenol?
This question does not make sense.

Without knowing we are all just guessing as to what would happen.
You are guessing. Needlessly now, I might add, since you have been told what would happen and had pointed out to you at least two major conceptual errors in your proposed process.

[Chromic]

It's got to be two steps unless there's another way to look at it... but maybe it could be done in one pot since at the end you'll likely vac distill it to remove the impurities that would be carried through.

If you use pyridine.hcl in say DMSO to demethylate, then basify with excess NaOH to form pyridine freebase and the phenoxide, you should be able to do the methylenation in the same pot (well, not really, it would mean pouring the rxn mix into an addition funnel and dripping it into DMSO with DCM, but you know what I mean..). I don't think the pyridine would interfere with the rxn. I'm sure Rhodium will swear and curse at me for making this recommendation (purify dem intermediates... grumble, grumble...) but, hey if you want to save time and have succeeded with the two pot synthesis of safrole from eugenol, why not try it out? We need folks like you to do the research!  

[Rhodium]

My instinct would say the yields/purity would be higher using a two-step rxn. Demethylate with Pyr*HCl in the microwave, and then methylenate using the two-phase PTC reaction on my page.

[El_Zorro]

Yeah, maybe you're right.  This all started when I saw that picture in

Post 238753

(Rhodium: "MDMA from only aliphatic precursors", Serious Chemistry), which basically showed closing the methylenedioxy ring on a eugenol derivative with a 75% yeild.  I really haven't been able to get it out of my mind since.  Does that SynGen program give references to the reactions it uses?
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[foxy2]

I know I've seen many similar reations with a higher yeild than 75%
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[El_Zorro]

Look up
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