Patent GB-1038185-A (GB)
Title: New diphenyl ethers and processes for their production, and pharmaceutical compositions containing them
IPC: C07C69/34
Filed: 1964-02-21
Abstract: The invention relates to compounds of the general formula <FORM:1038185/C2/1> wherein X and Y independently of each other are chlorine or bromine and Z is hydrogen chlorine or bromine.  Among many compounds claimed per se are 2-hydroxy-4,41-dichloro- and 2 - hydroxy - 4,21,41, trichlorodiphenyl ether; 2 - hydroxy - 4,41 - dibromo - and 2 - hydroxy-4,21,41 - tribromodiphenyl ether; 2 - hydroxy-4 - chloro - 41 - bromodiphenyl ether; 2 - hydroxy, 4-bromo, 21,41-dichlorodiphenyl ether. The compounds may be prepared by (a) diazotizing and forming the diazonium salt e.g. sulphate of a substituted o-amino diphenyl ether of the general formula <FORM:1038185/C2/2> e.g. by nitrosyl sulphuric acid or sodium nitrite in sulphuric acid and boiling in water, an aqueous acid or 50-80 DEG C. sulphuric acid or in a higher boiling inert organic solvent; or (b) dealkylating by known methods for the cleavage of aryl-alkyl ethers an o-alkoxy diphenyl ether of the general formula <FORM:1038185/C2/3> where R is a low alkyl radical e.g. by treatment with aluminium chloride in an inert solvent, or by heating with concentrated aqueous hydrobromic acid, with hydrogen bromide in glacial acetic acid or a mixture of hydrobromic acid and acetic acid; or (c) by forming a diazonium salt of the compound of the general formula <FORM:1038185/C2/4> and converting it to the corresponding compound containing hydrogen instead of the amino group e.g. by boiling in low alkanol or dilute hydrophosphoric acid or until the evolution of N ceases; (d) by producing from the compounds of the general formula <FORM:1038185/C2/5> in which one or two of the symbols X1, Y1 and Z1 represent the amino group and the remaining symbol(s) have the meaning(s) given for X, Y or Z above, a diazonium salt and converting the latter into the corresponding compound containing chlorine or bromine instead of the original amino groups X1, Y1 or Z1 e.g. by treating the diazonium salt, in particular the chloride or bromide, in aqueous medium with cuprous chloride or cuprous bromide, or with the corresponding halogen hydracids in the presence of copper powder.  In an example 2-amino-4,41-dichlorodiphenyl ether is added to nitrosyl sulphuric acid in concentrated sulphuric acid. After stirring, water is poured in while cooling with ice and o-dichlorobenzene added and the mixture boiled until no more diazo compounds can be traced when the upper organic phase is removed, caustic soda added and the o-dichlorobenzene distilled off with steam.  The aqueous residue of this steam distillation contains the 2-hydroxy - 4,41 - dichlorodiphenyl ether dissolved therein as the sodium salt from which the 2 - hydroxy - 4,41 - dichlorodiphenyl ether is obtained by treatment with hydrochloric acid. By using instead of 2-amino-,4,41-dichlorodiphenyl ether the following: 2-amino-4,21,41-trichlorodiphenyl ether, 2-amino-4-chloro-41-bromodiphenyl ether, 2 - amino - 4 - bromo - 41-chlorodiphenyl ether, 2 - amino - 4,41 - di-bromodiphenyl ether or 2 - amino - 4,21,41-tribromodiphenyl ether the following substituted diphenyl ethers are respectively obtained: 2-hydroxy-4,21,41-trichloro-, 2-hydroxy-4 - chloro - 41 - bromo - 2 - hydroxy - 4 - bromo - 41 - chloro - 2 - hydroxy - 4,41 - dibromo -, and 2 - hydroxy - 4,21,41 - tribromodiphenyl ether. Other examples are given.  Starting material 2-hydroxy - 21 - amino - 4,41 - dichloro diphenyl ether for the preparation of 2-hydroxy-4,41-dichlorodiphenyl ether therefrom by forming the diazo salt is prepared by reacting 2-methoxy - 4 - chlorophenol and 2,5 - dichloro - 1 -nitrobenzene to produce 2-methoxy-21-nitro-4,41-dichlorodiphenyl ether which is reduced to produce the 2-methoxy-21-amino-4,41-dichloro diphenyl ether from which the corresponding 2-hydroxy compound is produced by reaction with hydrobromic acid and NaOH.  Another starting material 2-methoxy-4,21,41-trichloro diphenyl ether used to obtain 2-hydroxy-4,21, 41-trichlor diphenyl ether is produced by reacting 4-chloro-2-methoxy phenol with 3,4-dichloro-1-nitrobenzen to produce 2-methoxy-4,21 - dichloro - 41 - nitrodiphenyl which is catalytically hydrogenated to produce 2-methoxy-4,21-dichloro-41-aminodiphenyl ether and which is then diazotized and treated with HCl to yield 2-methoxy-4,21,41-trichlorodiphenyl ether.ALSO:Compounds of the general formula <FORM:1038185/A5-A6/1> wherein X and Y independently of each other are chlorine or bromine and Z is hydrogen chlorine or bromine are used as active ingredients for disinfectants for the hands, cosmetics, ointments for wounds, eye ointments and other agents for external use, as well as active ingredients for internal use e.g. tablets for the disinfection of the mouth and throat and tablets and sugar coated tablets (dragees) for the disinfection of the intestinal system and urinal tract.