Methylated PEA benzaldehyde precursors

[moo]

When we have obtained the 4-methoxy-2,6-dimethylphenol my next suggestion would be to perform a Reimer-Tiemann formylation on it. As there is only the ortho- position that can be formylated, a Reimer-Tiemann on this phenol should give decent yields of 2-hydroxy-5-methoxy-4,6-dimethylbenzaldehyde

Here is a mistake, unfortunately. There are two methyls both ortho to the phenolic hydroxyl group, so that position cannot be formylated by these methods. 4-methoxy-3,5-dimethylphenol is needed for that. Some time ago it occurred to me that it would be cool if it was possible to prepare 4-methoxy-3-methylphenol from toluhydroquinone through methylation with H₂SO₄/MeOH as this compound would have been a nice precursor for a DOM synth via phenol ortho-formylation. After drawing a few resonance structures it was obvious that the product would more likely be 4-methoxy-2-methylphenol, ruining the plan. I guess that this 2,6-dimethylhydroquinone methylation ref proves it, in addition to finding no such preparations in literature. Too bad.

[Vitus_Verdegast]

Thanks moo!  

I did a quick literature search for 4-methoxy-3,5-dimethylphenol but didn't came up with anything..


This could be an alternative approach, although allyltributyl stannate is pretty expensive (20 euro/gram):

Reactants: 2,6-dimethyl-[1,4]benzoquinone and allyl-tributyl-stannane
Product: 2-allyl-3,5-dimethylhydroquinone
Yield: 82 percent
Reagent: BF3*OEt2
Solvent: CH2Cl2
Temperature: -78 C

Naruta, Yoshinori;  J.Amer.Chem.Soc.; EN; 102; 11 (1980) 3774-3783.
http://pubs.acs.org/cgi-bin/sample.cgi/jacsat/1980/102/i11/pdf/ja00531a019.pdf

Methylation will give 2,5-dimethoxy-4,6-dimethyl-allylbenzene.


Mmm, this is probably a better way:

2-allyl-3,5-dimethylphenol is prepared by Claisen rearrangement of allyl-(3,5-dimethylphenyl)-ether using either:

* allyl bromide: Wehrli,R. et al.; Helv.Chim.Acta 60 (1977) 2034-2061.

* allyl chloride: Le Noble,W.J. et al.; J.Org.Chem. 36 (1971) 193-196.

http://pubs.acs.org/cgi-bin/sample.cgi/joceah/1971/36/i01/pdf/jo00800a039.pdf

EDIT: The title of the article starts with "Chemical reactions under high pressure", so I guess we better scratch this one.


Next, 2-allyl-3,5-dimethyl-1,4-benzoquinone is prepared from 2-allyl-3,5-dimethylphenol by oxidation with O₂ and Co(II) salts according to:
Matsumoto, Masakatsu; Watanabe, Nobuko; Mori, Eiko; Aoyama, Misao; Kusunoki, Jun and Yamaura, Tetsuaki; Heterocycles 38; 12 (1994) 2589-2592.

This paper also describes the reduction of the benzoquinone to 2-allyl-3,5-dimethylhydroquinone using NaBH₄.