Patent GB-749923-A (GB)
Title: Bis-(ú­-aminophenoxy) alkanes
Inventor: CALDWELL ALBERT GORDON
Filed: 1953-01-14
Abstract: The invention comprises compounds of the formula <FORM:0749923/IV(a)/1> and acid addition salts thereof where n is an integer from 4 to 9, more preferably from 6 to 9.  They are made by the following methods.  (1) A compound of the formula <FORM:0749923/IV(a)/2> where Z is a group convertible to an amino group is so converted, e.g. a group -NHR where R is a protecting group is converted by removing the group R, e.g. an acyl group such as acetyl, alkoxycarbonyl, toluene-p-sulphonyl, is removed by hydrolysis; a phthalimido group is converted by hydrolysis; a halogen such as bromine is converted by amination; a nitroso, nitro or azo group is converted by reduction; an aldimino group is converted by hydrolysis or reduction; a carboxylic acid group is converted by Curtius reaction via the acid azide which by treatment with an alcohol followed by hydrolysis gives in turn an alkoxy carbonamido group and the desired amino group; a carboxylic amide group is converted by the Hofmann reaction or an isocyanate or urea group is converted by hydrolysis.  (2) A disubstituted phenoxy alkane of the formula X(CH2)nX is reacted with a compound of the formula <FORM:0749923/IV(a)/3> where X and Y are groups capable of reacting together to form an ether linkage, and the group Z is subsequently converted into an amino group, for example Y may be hydroxy and an X may be halogen such as bromine or may be an alkanesulphonyl or aranesulphonyl group such as a methyl sulphonyl or toluene-b -sulphonyl group. The products may be used in the treatment of schistosomiasis.  In examples (1) p-nitrophenol is treated with 1:6-dibromo hexane and the resulting 1:6-bis-(p-nitrophenoxy) hexane is reduced to 1:6-bis-(p-aminophenoxy) hexane; (2) 1:6-bis-(p-nitrophenoxy) hexane is reduced in glacial acetic acid to give 1:6-bis-(p-acetamidophenoxy) hexane which is hydrolysed to the product of (1); (3) p-hydroxybenzanilide is treated with 1:5-dibromopentane and the resulting 1:5-bis-(p-benzamidophenoxy) pentane is hydrolysed to 1:5-bis-(p-aminophenoxy) pentane; (4) p-ethoxycarbonamidophenol, obtained by the action of ethyl chloroformate on p-aminophenol, is treated with 1:6-dibromohexane and the product is hydrolysed to give the product of (1); (5) benzylideneaminophenol is treated with 1:4-dibromobutane and the resulting 1:4-bis - (p - benzylideneaminophenoxy) butane is hydrolysed or reduced to 1:4-bis-(p-aminophenoxy) butane; (6) p-benzeneazophenol is treated with 1:6-dibromohexane and the resulting 1:6-bis-(p-benzeneazophenoxy) hexane benzoate is treated with 1:5-dibromopentane to give 1:5-bis-(p-ethoxycarbonylphenoxy) pentane, reaction of this with hydrazone gives the corresponding bis-hydrazide which is converted to the corresponding acid azide by treatment with sodium nitrite, the azide is refluxed with alcohol to give 1:5-bis-(p-ethoxycarbonylaminophenoxy) pentane and hydrolysis of this gives the product of (2); (8) p-phthalimidophenol is treated with 1:6-dibromohexane and the resulting 1:6-bis-(p-phthalimidophenoxy) hexane is hydrolysed to give the product of (1); (9) 1:6-bis-(p-bromophenoxy) hexane is aminated by treating with a mixture of liquid ammonia and ethyl alcohol in the presence of copper bronze at an elevated temperature and pressure to give the product of (1) and (10) p-hydroxyacetanilide is treated with 1:5-dibromopentane and the product is hydrolysed to give the product of (2).  The method of 10 is also used to prepare the full range of a :o -bis-(p-aminophenoxy) alkanes from butane to nonane.