Pyrogallol 1-monomethyl ether

The apparatus consists of a l-l. three-necked flask fitted with a gas inlet tube extending about 3 cm. into the flask and connected to the flask through a bubbler, a thermometer extending to the bottom, a mechanical stirrer, and a reflux condenser connected at the upper end with an exit tube leading to the hood. The reaction is carried out in an atmosphere of illuminating gas (Note 1). 

In the flask are placed 60.8 g. (0.4 mole) of 2-hydroxy-3-methoxybenzaldehyde (Note 2) and 200 ml. of 2N sodium hydroxide (0.4 mole). The mixture is stirred until almost all the solid has dissolved. The stirrer is replaced by a dropping funnel which contains 284 ml. (0.5 mole) of 6% hydrogen peroxide (Note 3). With occasional shaking, the hydrogen peroxide is added in portions of 20-25 ml. About 1 hour is required for the addition the temperature is kept between 40 and 50°. After the addition of the first portion of hydrogen peroxide, the temperature rises to about 45° and a dark solution results. The temperature is allowed to fall to 40° before the next portion of the peroxide is added. 

After all the hydrogen peroxide is added, the reaction mixture is allowed to cool to room temperature and is then saturated with sodium chloride, after which it is extracted four times with 100-ml. portions of ether. The combined extracts are dried over sodium sulfate. The ether is removed by distillation on a steam bath, and the residue is then distilled under reduced pressure, Pyrogallol monomethyl ether is collected at 136-138°/22 mm. The yield is 38-44.5 g. (68-80%) of a colorless to light t11ow oil which solidifies on standing (Note 4). 

Nitrogen can he used in place of illuminating gas. The gas is introduced at the rate of about 3 bubbles per second, 

Practical 2-hydroxy-3-methoxyben2aldehyde (Eastman Kodak Company) was used in this preparation. Care should be taken when working with this material as its vapors are irritating and will cause sneezing. 

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A unique feature of this procedure is the selective monode-methylation of the dimethyl ether. The scope of this reaction is illustrated6 in part by the preparation in high yield of p-methoxyphenol, guaiacol, and phloroglucinol dimethyl ether from the respective fully O-methylated compounds. An exception is pyrogallol trimethyl ether which affords pyrogallol 1-monomethyl ether in high yield.6... 

A. a-Methoxyphenasine condensation). Two hundred grams (0.42 mole) of powdered lead dioxide (Note 1) is added to a solution of 10 g. (0.07 mole) of pyrogallol monomethyl ether (p. 90) in 3 1. of dry benzene in a 1-gal. narrow-necked acid bottle. The bottle and contents are placed in a shaking machine and shaken for 10-20 minutes (Note 2). The reddish brown solid is filtered through an 11-cm. Buchner funnel, and the filter cake is washed once with 400 ml. of benzene. To this filtrate there is added, immediately and with mechanical stirring, a solution of 6 g. (0.06 mole) of o-phenylenediamine (Note 3) in a mixture of 80 ml. of glacial acetic acid and 200 ml. of benzene. The solu-... 

Pyrogallol monomethyl ether has been prepared by the methylation of pyrogallol with dimethyl sulfate or methyl iodide by the decarboxylation of 2,3-dihj droxy-4-methoxy-benzoic acid and by the methylation of pyrogallol carbonate with diazomethane and subsequent hydrolysis. The method described is taken from the improved procedure of Baker and Savage for the preparation of pyrogallol monomethyl ether from o-vanillin by oxidation with hydrogen peroxide. 

The oxidation of a catechol derivative to an o-benzoquinone is the first step in a synthesis of pyocyanine (6) introduced hy Wrede and Strack and further developed by Surrey. Pyrogallol monomethyl ether (1) is oxidized by shaking a solution in... 

The PMR spectra of (55) reveal distinctly a strong spin-spin couphng (Jj = 3 cps, J56 = 10 cps) typical of hydroxybenzenium ions. Protonation of tri-, di- and monomethyl ethers of pyrogallol proceeds analogously but in the latter two casra mixtures of isomeric ions are formed. An example below illustrates the protonation of 2,3-dimethoxyphenol ... 

Using methyl ethers of di- and tri-hydric phenols, selective mono-demethylation occurs, e.g. resorcinol monomethyl ether is obtained from resorcinol dimethyl ether and sodium ethanethiolate in DMF. An exception is pyrogallol trimethyl ether which afforded pyrogaUol 1-monomethyl ether in high yield. Methylene ethers, such as methylenedioxybenzene, can be quantitatively converted to catechol, via the intermediate formation of ethyl o-hydroxyphenoxymethyl sulphide . 

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