Pyrogallol trimethyl ether

Many patents have been issued on the use of pyrogallol derivatives as pharmaceuticals. Pyrogallol has been used externally in the form of an ointment or a solution in the treatment of skin diseases, eg, psoriasis, ringworm, and lupus erythematosus. Gallamine triethiodide (16) is an important muscle relaxant in surgery it also is used in convulsive-shock therapy. Trimethoprim (2,4-diamino-5-(3,4,5-trimethoxybenzyl)pyrimidine) is an antimicrobial and is a component of Bactrin and Septra. Trimetazidine (l(2,3,4-trimethoxybenzyl)piperazine (Vastarel, Yosimilon) is used as a coronary vasodilator. l,2,3,4-Tetrahydro-6-methoxy-l-(3,4,5-trimethoxyphenyl)-9.H-pyrido[3,4- ]indole hydrochloride is useful as a tranquilizer (52) (see HYPNOTICS, SEDATIVES, anticonvulsants, and anxiolytics). Substituted indanones made from pyrogallol trimethyl ether depress the central nervous system (CNS) (53). Tyrosine-and glycine(2,3,4-trihydroxybenzyl)hydrazides are characterized by antidepressant and anti-Parkinson activity (54). 

Colchicine (23) is a toxic substance occurring in Colchicum autumnale, it contains the nucleus of pyrogallol trimethyl ether. Colchicine has been used in the treatment of acute gout, and in plant genetics research to effect doubling of chromosomes. 

Derivatives, Oxidation of pyrogallol trimethyl ether with nitric acid, followed by reduction in acetic anhydride and treatment of the product with aluminum chloride, affords 3,6-dihydroxy-2,4-dimethoxyacetophenone (228). 3,4,5-Trimethoxyphenol (antiarol) has been prepared by treatment of... 

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... 

It should be noted that NBS can cause nuclear bromination when that reaction occurs readily. In the absence of a catalyst it can brominate the nucleus of condensed aromatic compounds such as naphthalene, anthracene, and phenanthrene,399 veratrole, the dimethyl ethers of resorcinol and hydro-quinone,389 and pyrogallol trimethyl ether.390 Pyrocatechol and 2 moles of NBS afford 4,5-dibromopyrocatechol resorcinol and 3 moles of NBS afford 2,4,6-tribromoresorcinol 391,392 and anthranilic or o- or/ -hydroxybenzoic acid with 2 moles of NBS afford the 4,5- or 3,5-dibromo derivatives.391-393 However, nuclear bromination of benzene and toluene is effected by NBS only if equimolar amounts of A1C13, ZnCl2, FeCl3, or H2S04 are added. 

Pyrogallol trimethyl ether was selectively demethylated in dichloromethane... 

The acid had already been prepared by Spath, but a more convenient route was discovered. When pyrogallol trimethyl ether is condensed with succinic anhydride in nitrobenzene with aluminum chloride it can yield either /3-2-hydroxy-3,4-dimethoxybenzoylpropionic acid (XLVIII),... 

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 . 

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]. 

Preparation by Friedel-Crafts acylation of pyrogallol trimethyl ether with p-anisoyl chloride (AlClj/CS / 3 h at r.t.), followed by demethylation (AlCl3/toluene/ 1 h at 120°) (65%). 

Preparation by reaction of benzoyl chloride with pyrogallol trimethyl ether,... 

Obtained, in mixture with 2-hydroxy-2, 3,4-trimethoxy-benzophenone, by reaction of 2-methoxybenzoyl chloride with pyrogallol trimethyl ether in ethyl ether in the presence of aluminium chloride for 8 h at r.t. (total yield 56-59%) [1010,1011]. 

Obtained by Friedel-Crafts acylation of pyrogallol trimethyl ether with 3-methoxy-4-methylbenzoyl chloride in the presence of aluminium chloride in boiling carbon disulfide for 4 h (22%) [1169,1170]. 

Preparation by action of o-anisoyl chloride with pyrogallol trimethyl ether in the presence of aluminium chloride. 

Also obtained by Friedel-Crafts reaction between benzoyl chloride and pyrogallol trimethyl ether, followed by demethylation of the obtained product [1505]. 

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