Trimethylgallic acid

To a cold solution of 80 g. (2 moles) of sodium hydroxide in 500 cc. of water in a i-l. flask is added 50 g. (0.266 mole) of gallic acid. The flask is immediately tightly stoppered (Note i), and the mixture shaken occasionally until all the acid has dissolved 89 g. (67 cc.) of methyl sulfate (0.71 mole) is then added (Note 2) and the flask is shaken for twenty minutes, being cooled by means of cold water in order that the temperature does not rise above 30-35°. Occasionally the stopper is raised to release any pressure. A second portion of 89 g. of methyl sulfate is then added and shaking continued for ten minutes longer. During this second addition the temperature may rise to 40-45°. 

The flask is then fitted with a reflux condenser and the contents boiled for two hours. In order to saponify the small amount of ester which is produced, a solution of 20 g. of sodium hydroxide in 30 cc. of water is then added and boiling continued 

The alkaline solution immediately darkens somewhat, owing to the presence of dissolved air further oxidation must be limited by preventing access of air to the mixture. This is particularly necessary during the early stages with increasing methylation the tendency to absorb oxygen falls off rapidly. 

The toxic nature of methyl sulfate vapor must always be borne in mind. 

A further quantity can be recovered by concentrating the mother liquor. The residue of decolorizing carbon is also likely to contain an appreciable proportion of trimethylgallic acid, which can be extracted by boiling it with the mother liquor. 

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Trimethylgallic acid is most conveniently prepared by methylating gallic acid with methyl sulfate. It has also been obtained... 

Both bodies yield trimethylgallic acid, CyH2(COOH) OCH3)g, melting at 169°. on oxidation. 

Most of this acid required for the experiment work was obtained from the trimethylgallic acid by the method of Bogert and Ehrlich. 

Alimchandani and Meldrum, as well as others, have suggested the use of concentrated sulfuric, in place of the fuming acid, for accomplishing this demethylation but, in our experience, unless the reaction was conducted as follows, the product contained some unchanged trimethylgallic acid. 

Heffter (104,105,106) determined the empirical formula of mescaline and found that upon oxidation the base yields trimethylgallic acid. Unfortunately, mescaline behaves in methylimino determinations as though it contained an i f-methyl group. Heffter (107) synthesized 3 4 5-trimethoxybenzylmethylamine and found that it was not identical but isomeric with mescaline. 

Trichocereine contains three methoxyl and two iV-methyl groups. Upon oxidation with permanganate trimethylgallic acid is obtained. Trichocereine methiodide is identical with the methiodide obtained by exhaustive methylation of mescaline and trichocereine is therefore iV-dimethylmescaline. 

A similar differential reactivity is observed at the 2-position of pyrogallol trimethyl ethers and it forms the basis of the preparation of syringic acid (32) from trimethylgallic acid (31) by controlled demethylation in sulphuric acid [47] and of the derivative (34) from podophyllotoxin (33) by the action of hydrogen bromide [48]. 

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