You can try methylation using diazomethane (2 equiv) since its best reagent for methylation.

I think the following articles will help you....

Synthesis and anti-platelet activity of obovatol derivativesFull TextBy Kwak, Jae-Hwan et al From Archives of Pharmacal Research, 34(7), 1107-1112; 2011

Total syntheses of the metabolites of schizandrinFull TextBy Tanaka, Masahide et al From Tetrahedron, 51(43), 11703-24; 1995

Multi-functionalization of gallic acid towards improved synthesis of α- and β-DDBFull TextBy Alam, Ashraful et al From Tetrahedron, 61(7), 1909-1918; 2005

Synthesis of perrottetin F and G, two linear bis(bibenzyl) ethers from Radula perrottetiiFull TextBy Mezey-Vandor, Gabriella et al From Liebigs Annalen der Chemie, (4), 401-3; 1989

Multi-functionalization of gallic acid towards improved synthesis of α- and β-DDBFull TextBy Alam, Ashraful et al From Tetrahedron, 61(7), 1909-1918; 2005

Synthesis and biological evaluation of phenstatin metabolitesFull TextBy Ghinet, Alina et al From Bioorganic & Medicinal Chemistry, 19(20), 6042-6054; 2011

Synthesis of obovatol derivatives and their preliminary evaluation as antitumor agentsFull TextBy Lee, Mi-Sung et al From Bulletin of the Korean Chemical Society, 28(9), 1601-1604; 2007

Intramolecular biaryl coupling reaction of benzyl benzoate and phenyl benzoate derivatives, and its application to the formal synthesis of (-)-steganoneFull TextBy Takeda, Shigemitsu et al From Tetrahedron, 63(2), 396-408; 2006

Total syntheses of the metabolites of schizandrinFull TextBy Tanaka, Masahide et al From Tetrahedron, 51(43), 11703-24; 1995

I remember making the 'tri-methylated' derivative of this with sodium hydride iodomethane. Getting only the 'disubstitued' derivative will be tedious but not impossible. When I ran the column I remember getting an appreciable amount of the 'dimethylated' derivative (which I kept and converted to my intended product later). Perhaps changing the equivalents of base here and adding the CH3I at different times afterwards might offer you another alternative with a better yield. Although it is a rather brutal 'heavy handed approach' keep in mind it's not the most elegant of reactions to begin with.

I also noticed your sci-finder reference says 'one step'?? Did I read that correctly?? You will have to add 2/2.5 eq. of the K2CO3 then add your CH3I in a second step. I don't see why this doesn't work to begin with. The prevalence of the 'mono-methylated' product makes me wonder how this was run.

I also know that you can buy it rather cheaply. If your yields continue to be under par and you are burning through materials due to yield or method this also maybe worth the $$$ here in the beginning.

I would try completely methylating and then trying to demethylate the least hindered methoxy with boron trichloride. This may also demethylate the the ester which could be remethylated with diazomethane.

You may not get selective methylation direct route,

you may first do acetylation and than use the same method for methylation, it can work good.

Good luck

i must recommend you following articles.

Synthesis, crystal structure, and growth inhibition

of human hepatoma cell (HepG2) of polyphenolic

compounds based on gallates.

Can. J. Chem. 85: 951–957 (2007)

Total synthesis of two natural phenanthrenes: confusarin

and a regioisomer.

Tetrahedron 63 (2007) 12379–12387

I' ve found two articles: 1) Li Zuo, Shanyan Yao, Wei Wang, Wenhu Duan, Tetrahedron Letters 49 (2008) 4054–4056; 2)Kai Bao, Aixue Fan, Yi Dai, Liang Zhang, Weige Zhang, Maosheng Chenga and Xinsheng Yao, Org. Biomol. Chem., 2009, 7, 5084–5090. Bye

Grazia

I am sorry to say but most of the procedures presented here are quite lengthy and will give so many side products;

Except for the hydrogens on the hydroxy groups the whole (3,4,5-trihydroxy-benzoate) is planar.

Heres my opinion;

1) Use dil NaOH at low temperature ( below 5 C) and add in 1,4-dibromo-butane.

2)Let this overnight. I would create a diether linkage between the sp3 hybridized oxygen on the carboxylate portion and the oxygen of the hydroxyl groups which lies on its plane.

3) use any "less harsh" methylation agenf like iodomethane.

4) this would methylate the 4,5-postions

5)remove the diether using any "less harsh" agent for example use --- MeMgBr, CuBr, PBu3 at O degrees celcius.

This would give u ( 3-hydroxy-4,5-dimethoxy-benzoic acid. I HOPE THATS WHAT U WANT!

ok then bye!

cya later

Sid

Hi............you just use exact 2 equiv dimethyl sulfate in excess k2co3 in dry acetone........and see what happens

See synthesis of drugs in www.drugsyn.org

Try protection of 1,2 diol which you will get in the book Greene's protective group in organic synthesis and it may protect any of the two adjacent hydroxy groups. then protect the third hydroxy group with any protecting group which require different deprotection conditions ten the protected diol and I hope you can get the desired molecule. See above mentioned book its really helpful