Patent GB-770412-A (GB)
Title: Improvements in and relating to aminophenoxyalkanes
Inventor: RAISON CLIFFORD GORDON
Filed: 1954-03-18
Abstract: The invention comprises compounds of the formula <FORM:0770412/IV(b)/1> in which R1 and R2 may be the same or different and may be hydrogen atoms or alkyl groups of 1 to 4 carbon atoms, or alkyl groups of 2 to 4 carbon atoms, which may carry at least one hydroxyl group on a carbon atom or carbon atoms other than that adjacent to the nitrogen atom.  The compounds are made by treating a 1 : 4-disubstituted pentane of the formula X.CH(CH3).CH2.CH2.CH2.X with a disubstituted benzene of the formula <FORM:0770412/IV(b)/2> wherein X and Y are groups capable of reacting together to form an ether linkage, e.g. Y may be a hydroxy group and X may be halogen such as bromine, or an alkane sulphonyl, arylsulphonyl or aralkane sulphonyl group, and Z may be the group -NR1R2 when the latter is a tertiary amino group, or may be a group convertible to a primary, secondary or tertiary amino group which is subsequently so converted.  When -NR1R2 is to be a primary amino group, Z may be a nitro, aldimine or azo group, convertible by reduction; a group NHW, where W is a protecting group such as an acyl, toluene-p-sulphonyl or an alkoxycarbonyl group, convertible by hydrolysis or a halogen atom which may be aminated.  If NR1R2 is to be a secondary amino group, Z may be a group -NR1W, where W is a protecting group as above or a nitroso group removable by reduction. Where -NR1R2 is to be a tertiary amino group, a corresponding primary amine may be alkylated or a corresponding quaternary amino compound may be subjected to pyrolysis or hydrolysis by means of an alkali metal hydroxide or alkoxide.  In examples: (1) p-acetamidophenol is heated with 1 : 4-dibromopentane and the resulting 1 : 4 - bis (p - acetamidophenoxy) pentane is hydrolysed to give 1 : 4-bis (p-aminophenoxy) pentane as the dihydrochloride; (2) N - nitroso - p - methylaminophenol is heated with 1 : 4-dibromopentane and the resulting N : N1-dinitroso-1 : 4-bis (p-methylaminophenoxy)-pentane is reduced by hydrogen and Raney nickel to give 1 : 4-bis (p-aminophenoxy)-pentane; (3) 1 : 4 - bis (p - aminophenoxy)-pentane, obtained by basification of the product of (1) is alkylated with dimethyl sulphate to give 1 : 4 - bis (p - dimethylaminophenoxy) - pentane; (4) p-di-(hydroxyethylamino) phenol is heated with 1 : 4-dibromopentane to give 1 : 4-bis [p-di(hydroxyethyl) aminophenoxy]-pentane; and (5) 1 : 4 - bis - (p - hydroxyethylaminophenoxy) pentane is made by the method of (2).  The Provisional Specification describes also 1 : 4-diphenoxy pentanes of the above general formula wherein R1 and R2 may be hydrogen or alkyl groups of one to six carbon atoms or hydroxyalkyl groups of two to six carbon atoms having one or more hydroxy groups on a carbon atom, or carbon atoms, other than that adjacent to the nitrogen atom, or NR1R2 may be a piperidino or pyrrolidino ring, and the benzene nuclei may be substituted in the 2- and/or 3-positions by halogen atoms or hydroxy, alkyl or alkoxy groups, the latter having from one to four carbon atoms.  Specifications 749,907, 749,923, 758,382, 765,957 and 770,410 are referred to.