Rhodium
(Chief Bee)
05-21-02 22:28
No 312072
      Vanillin demethylation improvement
(Rated as: excellent)
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This variation on an old theme uses much less pyridine than earlier methods, and may also give higher yields.


Synthetic Communications Volume 32, Issue 4, Pages 641-649 (2002)

A simple, economical, selective and high-yielding procedure for the rapid demethylation of nitro-catechol methyl ethers has been developed using reagents and solvents suitable for production of medicinal products. This procedure is superior to other demethylation methodologies especially for larger-scale operations. The method should prove generally useful for the rapid demethylation of ortho-hydroxy arylmethyl ethers.

1-(3,4-Dihydroxy-5-nitrophenyl)-2-phenyl-ethanone (1)

To a stirred yellow suspension of 1-(4-hydroxy-3-methoxy-5-nitrophenyl)-2-phenyl-ethanone ((6), 50.0 g, 174 mmol) in ethyl acetate (500 ml) at room temperature was added aluminium chloride (27.84 g, 209 mmol) in one portion. To the resulting orange/red suspension was added dropwise pyridine (55.1 g, 56.2 ml, 696 mmol) causing the internal temperature to rise to 45C. The orange solution was then heated at reflux (77C) for 2 h and then allowed to cool to 60C whereupon the reaction mixture was carefully added to a mixture of ice/concentrated hydrochloric acid (200 ml). After stirring at 50C for 1 h, the mixture was cooled in an ice/water bath for 1 h and then filtered. The filter cake was washed by water and the product then dried (70C, 0.02 mmHg, 5 h) to afford the title product as a yellow solid, 47.21 g, (99.4%) of m.p. 177.6178.8C.

3,4-Dihydroxy-5-nitrobenzaldehyde (Entry 5)

Yellow-orange crystals, m.p. 142143C (lit12 m.p. 145146C).
 
 
 
 
    foxy2
(Distinctive Doe)
05-22-02 03:30
No 312249
      but  Bookmark   

"The method should prove generally useful for the rapid demethylation of ortho-hydroxy arylmethyl ethers."

Should prove or has PROVEN?
Is it as effective without that nitro group?

I don't think it is because the strong electron withdrawing effect of the nitro group stabilizes the phenolate ion.

Those who give up essential liberties for temporary safety deserve neither liberty nor safety
 
 
 
 
    terbium
(Old P2P Cook)
05-25-02 19:41
No 314066
      Eugenol demethylation via alkali fusion.  Bookmark   

Here is a high yield demethylation of vanillin. It would be very nice if this could be adapted to eugenol. Since the eugenol does have a free phenol it would seem that it might also be miscible with the fused alkali. Note the use of sulfur dioxide (a bisulfite could also be used) to prevent formation of black crap during acidification. 
http://www.orgsyn.org/orgsyn/prep.asp?prep=cv3p0745

It was Post 313045 (paracelsus: "Protocatechuic Acid from Turmeric", Chemicals & Equipment) by paracelsus that led me on the search where i found the above.
 
 
 
 
    PrimoPyro
(Hive Prodigy)
05-26-02 00:56
No 314171
      Isomerization  Bookmark   

Wouldn't the alkalai also isomerize the allyl group to a propenyl group, like in the standard alkalai isomerization?

Upon methylenation, this yields isosafrole, not safrole. smile

But the propenyl group would be more sensitive to oxidative cleavage to benzoic acid would it not?

                                                    PrimoPyro
 
 
 
 
    terbium
(Old P2P Cook)
05-26-02 03:38
No 314246
      Yes.  Bookmark   

Wouldn't the alkalai also isomerize the allyl group to a propenyl group, like in the standard alkalai isomerization?
Most likely.

Upon methylenation, this yields isosafrole, not safrole.
Yep, you are really sharp today.

But the propenyl group would be more sensitive to oxidative cleavage to benzoic acid would it not?
Why would you want to produce the benzoic acid?

 
 
 
 
    PrimoPyro
(Hive Prodigy)
05-26-02 03:41
No 314248
      Re: Yep, you are really sharp today.  Bookmark   


Yep, you are really sharp today.




Hey now, do I sense a little sarcasm? tongue


Why would you want to produce the benzoic acid?




I don't. I'm saying that it might be an unwanted side reaction.

                                                    PrimoPyro

 
 
 
 
    kid_trippin
(Newbee)
05-27-02 03:29
No 314602
      easy vanillin demethylation  Bookmark   

Terbium:  Wow, that looks incredibly simple.  That link only synths protocatechuic acid .  How hard is it to get from protocatechuic acid -> isosafrole.  How's it done?  I can't find any posts frown  Or are you saying that could be tried on eugenol to get the allylpyrocatechol?

Resistance to government is so valuable on certain occasions that I wish it to be always kept alive.
 
 
 
 
    terbium
(Old P2P Cook)
05-27-02 08:25
No 314668
      3,4-dihydroxypropenylbenzene.  Bookmark   

Or are you saying that could be tried on eugenol to get the allylpyrocatechol?
Almost, the isosafrole equivalent.
 
 
 
 
    starlight
(Stranger)
05-27-02 12:48
No 314716
      workup  Bookmark   

do you think the workup would have to be changed?
 
 
 
 
    terbium
(Old P2P Cook)
05-27-02 19:17
No 314822
      Same workup.  Bookmark   

I would think that the workup would be pretty much the same. I have no information about the physical properties of the ally and propenyl 3,4-dihydroxybenzene but would guess that they are solids at room temp. I especially like the innovation of using sulfur dioxide to prevent oxidation of the phenolics in acidic conditions.

As for the reaction conditions, I would expect that they could also be very much the same and with the same molar ratios. The one change I would make is that I would try to maintain an inert atmosphere in the reaction vessel out of concern that at the 240-245C reaction temperature the alkene side chain would air oxidize. The experimenters seem quite specific as to the temperature required for the demethylation; anyone who does this should have a thermocouple (or RTD) probe to monitor the temperature.
 
 
 
 
    starlight
(Stranger)
05-27-02 22:03
No 314873
      The melting point of allyl 3,4-dihydroxybenzene ..  Bookmark   


The melting point of allyl 3,4-dihydroxybenzene is around 46-48.5C (solid at room temp).

I don't know what the m.p. of propenyl 3,4-dihydroxybenzene is. Is it likely to be a bit lower? (m.p. of isosafrole is 4-4.5C lower than that of safrole)

That would make them both solids at room temperature.

The solubility of the allylpyrocatechol in water is 25 g/l at 26C.

I don't know what the solubility of the propenylpyrocatechol is.

The workup described ends up with 3l of water in the reaction mixture.

3l of water would be enough to solvate 75g of allyl pyrocatechol (and an unknown amount of pyrocatechol) at 26C.

Of course they cool down the reaction mixture in order to crystallise their product, and in addition the reaction mixture is acidic.

Anyone got an idea of the solubility of the propenyl pyrocatechol in acidic solution at 0C? Or in ether?

./
 
 
 
 
    terbium
(Old P2P Cook)
05-27-02 23:11
No 314900
      Concentrate perhaps.  Bookmark   

Sounds like it would be advantageous to concentrate the solution some. The concentrated salt in the solution should also help drive out the dihydroxypropenylbenzene.