Patent GB-768144-A (GB)
Title: Improvements in or relating to amines and to processes for their preparation
Inventor: ASHLEY JULIUS NICHOLSON
Filed: 1954-04-30
Abstract: The invention comprises compounds of the general formula <FORM:0768144/IV(b)/1> and their acid addition salts where R1 and R2 are hydrogen atoms, alkyl groups of not more than 6 carbon atoms, or hydroxyalkyl (including polyhydroxyalkyl) groups; A is a saturated unbranched hydrocarbon chain of 4 to 9 carbon atoms, and R is a hydrogen atom or a nitro or primary, secondary or tertiary amino group, preferably in the para position.  The invention also comprises formaldehyde bisulphite derivatives of primary amines of the above general formula.  Preferred products are compounds wherein R1 and R2 are both hydrogen atoms or hydroxyethyl groups or one represents hydrogen and the other represents an ethyl group, A is a pentamethylene chain and R is a hydrogen atom or a p-amino group. The compounds are made by condensing a compound of the formula <FORM:0768144/IV(b)/2> with a compound of the formula <FORM:0768144/IV(b)/3> where X is a tertiary amino group or an atom or group convertible to a primary secondary or tertiary amino group, M is an atom of hydrogen or of an alkali metal, A1 represents the group A or a corresponding less-saturated hydrocarbon linkage, Y represents the group R or a group which can be converted into R and Q represents a radical of a reactive ester such as a methanesulphonate group or a halogen atom.  If necessary, X and Y are then converted into the groups NR1R2 and R respectively and the group A1 is reduced to the group A. Suitably the groups represented by X and Y may be the following: (a) as groups convertible to primary amino; acylamido, nitro, nitroso, carbonamido, anil, alkoxycarboxylamino and arylazo; (b) as groups convertible to secondary amino; acylalkylamido (by hydrolysis) and anil, alkoxycarboxylamino or acylamido (by reduction) and (c) as groups convertible to tertiary amino; quaternary amino groups (by pyrolysis) and acylalkylamido groups (by reduction).  In examples: (1) 5-phenylpentyl bromide is heated with potassium p-nitrophenoxide and the resulting 1-p-nitrophenoxy-5-phenylpentane is catalytically reduced to 1-p-aminophenoxy-5-phenylpentane, which is converted into its methanesulphonate; (2) 5-phenylpentyl bromide is nitrated and the product is heated with potassium p-nitrophenoxide to give 1-p-nitrophenoxy-5-p-nitrophenyl-pentane, which is catalytically reduced to 1 - p - aminophenoxy - 5 - p - aminophenylpentane, isolated as its dimethanesulphonate; (3) 1 - p - aminophenoxy - 5 - phenyl - pentane methanesulphonate is treated with ethylene chlorohydrin to give 1-p-di-(2-hydroxyethyl)-aminophenoxy - 5 - phenyl - pentane; (4) 1 - p - aminophenoxy - 5 - phenylpentane methanesulphonate is acetylated with acetic anhydride and the resulting 1-p-acetamidophenoxy-5-phenylpentane is reduced with lithium aluminium hydride to 1-p-ethylaminophenoxy-5-phenyl-pentane; and (5) 1-p-aminophenoxy - 5 - phenylpentane methane sulphonate is treated with sodium formaldehyde bisulphite and sodium hydroxide to give the sodium formaldehyde bisulphite derivative of the amine.ALSO:Therapeutic compositions for the treatment of bitharziasis comprise compounds of general formula <FORM:0768144/VI/1> where R1 and R2 are each a hydrogen atom, a primary, secondary or tertiary am6 carbon atoms or a hydroxyalkyl (which may be polyhydroxyalkyl) group, A is a saturated unbranched hydrocarbon chain of 4 to 9 carbon atoms and R is a hydrogen atom, a primary, secondary or tertiary amino group or a nitro group, preferably in the p-position, acid addition salts of the above compounds and formaldehyde-bisulphite addition products of the above compounds which contain a primary amino group, adwixed with a pharmaceutical diluent.  Preferred therapeutic compounds are those wherein R1 and R2 both represent hydrogen atoms or hydroxyethyl groups or one represents a hydrogen atom and the other an ethyl group, A is a pentamethyllene chain and R represents a hydrogen atoms or a p-amino group; specified compounds being 1 - p - aminophenoxy - 5 - phenylpentane, 1 - p - di (2-hydroxyethyl) aminophenoxy - 5 - phenylpentane, 1 - p - aminophenoxy - 5 - p - aminophenylpentane and 1 - p - ethylaminophenoxy - 5 - phenylpentane. The active compounds are suitably employed as elixirs, tablets, powders, capsules, or injectable solutions.  The compositions may contain the active component in a liquid diluent such as water or admixed with solid diluents such as starch, lactose, stearic acid, talc, magnesium stearate or gums.  Examples describe compositions suitable for tablet-formation comprising (a) 1 - p - aminophenoxy - 5 - phenylpentane, methanesulphonate, starch, dextrin, magnesium stearate, stearic acid, sodium carboxymethylcellulose and (b) 1 - p - aminophenoxy - 5 - p-aminophenylpentane dimethanesulphonate, starch, dextrin, magnesium stearate, stearic acid, alginic acid and sodium lauryl sulphate.