Patent GB-758382-A (GB)
Title: Improvements in bis-(ú­-aminophenoxy) alkane derivatives
Inventor: WALLS LESLIE PERCY
Filed: 1953-01-14
Abstract: The invention comprises compounds of the formula (I) <FORM:0758382/IV(a)/1> and acid addition salts thereof, where R1 and R2 may be methyl, ethyl, propyl or allyl groups and n is 5, 7, 8 or 9 when R1 and R2 are both methyl, but is any integer from 5 to 9 in other cases.  The compounds may be made from compounds of the formula (II) <FORM:0758382/IV(a)/2> where Z is a group convertible to -NR1R2, by effecting the required conversion, e.g. Z may be a quaternary ammonium hydroxide group which is converted by pyrolysis; a quaternary ammonium salt group which is converted by pyrolysis or by heating with alcoholic alkali or an alkali metal alcoholate; a quaternary ammonium salt group containing a benzyl group which is subjected to catalytic debenzylation, a primary or secondary amine group which is alkylated either directly or indirectly by heating with an alcohol in the presence of iodine, heating the hydrochloride salt in the presence of an alcohol or reductive alkylation in the presence of an aldehyde; a nitro group which is converted by reduction in the presence of an aldehyde; an alkylacylamino group which is reduced, suitably by means of lithium aluminium hydride, or a (carboxyalkyl) alkyamino group which is decarboxylated.  The compounds of the formula (II) are made by reacting an a  : o -disubstituted alkane of the formula (III) X-(CH2)n-X with a compound of the formula (IV) <FORM:0758382/IV(a)/3> where X and Y are groups capable of reacting together to form an ether linkage.  In this reaction Z may be a tertiary amino group or a group convertible to a tertiary amino group; in the former case the desired product is obtained directly.  Conveniently, Y may be a hydroxy group and X a halogen atom or an alkyl or aryl sulphonyloxy group.  Preferred products include 1 : 7-bis-(p-dimethylaminophenoxy) heptane, 1 : 7-bis-(p-diethylaminophenoxy) heptane, 1 : 5 - bis - (p - methylethylaminophenoxy) pentane, 1 : 7 - bis - (p-methylethylaminophenoxy) heptane and 1 : 8-bis-(p-methylethylaminophenoxy) octane, and their acid addition salts.  Many other products of the general formula (I) are exemplified.  Starting materials.  a  : o -Bis-(p-diquaternaryammonium phenoxy) alkane salts such as 1 : 6-bis-(p-diethylaminophenoxy) hexane diethiodide, 1 : 6 - bis - (p - diethylaminophenoxy) hexane dimethiodide, 1 : 5-bis-(p-benzylmethyl-aminophenoxy) pentane dimethiodide, 1 : 8-bis - (p - diethylaminophenoxy) octane diethiodide, 1 : 7 - bis - (p - di - n - propylaminophenoxy heptane dimethiodide and 1 : 5-bis-(p - dimethylaminophenoxy) pentane dimethiodide are made by treating the appropriate bis-primary or secondary amine with an alkyl iodide.  1 : 5-Bis-(p-(carbethoxymethyl) methylaminophenoxy) pentane is made by the action of ethyl chloroacetate on 1 : 5-bis-(p-methylaminophenoxy) pentane in the presence of sodium acetate; hydrolsis of the ester gives the free acid.  1 : 7-Bis-(toluene-p-sulphonyloxy) heptane is made by treating 1 : 7-heptane diol with toluene-p-sulphonyl chloride in pyridine.  1 : 7 - Bis - (p - acet - methylamidophenoxy) heptane is made by the action of a mixture of acetic acid and acetic anhydride on 1 : 7 - bis - (p - methylaminophenoxy) heptane.  1 : 5 - Bis - (p - nitrophenoxy) pentane is made by the condensation of p-nitrophenol and 1 : 5-dibromopentane.  Specification 636,648 is referred to.