Antoncho: Dimethylation of Hydroquinone

[PrimoPyro]

Dear bees, especially Antoncho:

I did not want to further stray from the topic of your post by changing the topic there to this question, so I have made a seperate thread to keep it intact.

The news of methylation of hydroquinone with benzoquinone, methanol, and sulfuric acid, to produce para-methoxyphenol, is wonderful indeed. I can see why it is so important to optimize the yield of the monomethyl ether, for the Reimer-Tiemann reaction. But I wonder about a seperate possibility: Is it known to be possible to dimethylate hydroquinone with the same procedure, with different conditions? Perhaps a higher benzoquinone/H2SO4/MeOH to hydroquinone ratio, by using less hydro per reaction, would result in higher yield of 2,5-dimethyoxybenzene?

Antoncho, I see in the posted reference that one of the reactions produced a 3% yield of the dimethylated product. It is possible I see, to produce dimethylated product afterall, but hopefully there are ways to drastically increase the yield of this product.

Is there more in the reference, anything related to this? Perhaps any references to negatives for the monomethylation reaction, such as, "Over addition of......results in the majority of yield being dimethylated product." or something similar?

The reaction mechanism stated does not seem to be so picky as to limit methylation to only one hydroxy. I do sincerely wonder about utilizing half the hydroquinone used in this reaction, with twice the reaction time, hopefully producing a majority of 2,5-dimethoxybenzene.

When you look at the dimethylated product as a benzene, it is not interesing, but when viewed as a phenyl hydride, you start thinking of alternative possibilities. Replace that hydrogen with a methyl group: toluhydroquinone --> 2,5-DiMeO-Toluene. Very cool.

Antoncho and others, what do you think?

                                                    PrimoPyro
The Water Will Be Your Only Mirror

[PolytheneSam]

Did you see this thread?

Post 218257

(PolytheneSam: "ArOR, Alternatives to dimethyl sulfate", Novel Discourse)
http://www.geocities.com/dritte123/PSPF.html

[PrimoPyro]

Yes, I had followed it very closely when it was hot. I just read through it again as well. Alkyl halides, phosphates, and sulfates are undesired here.

Thank you for posting it up again. I did however notice something I hadn't before: The use of ZnCl2 to condense alcohols with phenols. That is interesting, but this scheme is still much more highly desired.

                                                   PrimoPyro
The Water Will Be Your Only Mirror

[Rhodium]

When you look at the dimethylated product as a benzene, it is not interesing, but when viewed as a phenyl hydride, you start thinking of alternative possibilities.

To make the molecule behave like a phenyl hydride, you need to either lithiate it (add 1 eqv of BuLi) or brominate the ring and make the grignard. After that it can be reacted with methyl iodide or other suitable alkylating agent to form 2,5-dimethoxytoluene.

[PrimoPyro]

Yes, I understand.  

I was actually speaking figuratively, not chemically. I mean as a matter of thinking, not of the chemistry.

If one thinks of the benzene as a phenyl hydride derivative always, then one more normally thinks of more reactions suited for derivatives of benzene.

hence when I saw hydroquinone methylation, I thought of toluhydroquinone methylation instead.

                                                   PrimoPyro
The Water Will Be Your Only Mirror

[Antoncho]

Well Primo I must confess my view of this possibility suggested by you is rather dubious, if not negative

You see (I apologize if I'm being too scrupulous), the mechanism of this rxn is through the formation of an intermediate hemiketal of the quinone. Like, see the posted picture in the original monomethylation thread. The point is, that monomethylated HQ is unable to form such hemiketal any longer, 'cause to turn -OH to =O, and dearomatize the ring - one needs to withdraw at least two electrons, and methoxy isn't susceptible to oxidation.

So... I think that some dimethylated byproduct in the article is formed when both oxogroups of quinone are in the ketal state, and are simultaneously reduced. This is pretty consistent w/the fact that such rxn occurs w/excess of quinone in the rxn.

Now, if there was a way to stabilize that hemiketal somehow... And then - then - reduce it w/ an eq. of plain HQ or smth else, possibly...

Or - if we could know that - the equilibrium of the ketal formation was shifted considerably to the right - then no stabilization would bee needed... SW Really Isn't Me should definitely try it - this is very easy - but not SWIM, at least in the immediate future.

Antoncho

[PrimoPyro]

Antoncho, I am highly confused. I have read the original posting several times now.

What you describe sounds like the benzoquinone being methylated, yet the document explicitly states that the benzoquinone hemiketal reacts with hydroquinone to generate the methoxyphenol and regenerate the benzoquinone, thus effectively maintaining catalysis.

Ar=O --> Ar(OH)OMe
Ar(OH)OMe + Ar¹OH --> Ar=O + Ar¹OMe + H2O

I do not understand how the hydroquinone is oxidized to lose aromaticity. To me it seems that the benzoquinone hemiketal is unstable and methylates the hydroquinone in exchange for a proton, forming the dihydroxy derivative of the benzoquinone, which immediately degrades into benzoquinone and water.

Would this not then work for a standard phenol as well, forming methoxybenzene? And if so, a methoxyphenol would only be one step further.

Am I mistaken?

                                                   PrimoPyro
The Water Will Be Your Only Mirror

[Antoncho]

Dear Primo!

It is quite funny, but it appears like we were looking at the rxn's mechanism from two completely different points, each unaware of the other's. Funny is that the patent states it in such a way that both possibilities can bee implied.

So, you think that hemiketal acts as a methylating agent? As i said, this possibility never occurred to me, but it seems rather possible. Maybee someone more educated than me will care enough to express his thoughts and answer the question?

As for now, i still think that the 1st route - with hemiketal's molecule being reduced by HQ, which in turn beecomes a quinone molecule - is the correct one.

The reasons are:

1) A 'usual' methylation is always performed on a deprotonated molecule of phenol, which thus acts as a nucleophil - which isn't the case in this rxn.

2) If a HQ hydroxyl could bee methylated by BQ hemiketal, then the same would apply to the formed p-MeOphenol. While the selctivity in this case is very, very high - as compared to the other procedures of HQ methylation, when 80% selectivity at best is reached - with the use of special gimmicks. OTOH, the hemiketal red'n mechanism explains it very well - as i've noted, p-MeO-phenol isn't capable of forming a quinone any longer, thus remaining inert.

A very simple way to test this would bee to try to methylate phenol w/it - if there was any anisole present, ketal red'n hypothesis would fall apart, if not - it'd bee correct. But SWIM isn't planning to do that, maybee SWIPP will  

Ton ami sincère,

Antoncho

[PrimoPyro]

Perhaps so, but I don't know. The paper is extremely unclear as to what species is methylated, the hydroquinone or the benzoquinone.

In your original post, you told me that the alkylated species is the hydroquinone. If this is true, then it should dialkylate as well. The hydroquinone, if it is the alkylated species, never loses aromaticity, so I see no reason that it couldn't be dialkylated this way.

If however, the benzoquinone is the alkylated species, then you are most certainly correct, but that will also mean that my original assumption would be correct: the alkylated quinone with beta-alanine will monomethylate at one hydroxy, at least theoretically.

Personally, I would find the latter possibility more attractive than the former.

                                                    PrimoPyro
The Water Will Be Your Only Mirror