Patent GB-811857-A (GB)
Title: Improvements in or relating to amines and to processes for their preparation
Inventor: ASHLEY JULIUS NICHOLSON
Filed: 1956-01-18
Abstract: The invention comprises compounds of the formula <FORM:0811857/IV (b)/1> and acid addition salts thereof, wherein R1 and R2 are the same or different and are each hydrogen or an alkyl group of 1-6 carbon atoms or an hydroxyalkyl (which may be polyhydroxyalkyl) group, R1 is an alkyl or alkoxy group of 1-4 carbon atoms, A1 is a saturated or ethylenically unsaturated hydrocarbon chain of 4-9 carbon atoms, optionally bearing lower alkyl substituents and R3 is hydrogen or an alkyl or alkoxy group of 1-4 carbon atoms or a primary, secondary or tertiary amino group or a nitro group, preferably in the p-position; and sodium formaldehyde bisulphite derivatives of the primary amines of the above formula.  The compounds are made by condensing a compound of the formula <FORM:0811857/IV (b)/2> with a compound of the formula <FORM:0811857/IV (b)/3> wherein X is a tertiary amino group or a group convertible to a primary, secondary or tertiary amino group, M is hydrogen or an alkali metal, A1 is the group A1 or a corresponding less-saturated group, Y is the group R3 or an atom or group convertible to R3, Q is the radical of a reactive ester such as a methanesulphonate group or a halogen atom and R11 represents R1 or an hydroxy group and if necessary converting X, Y, A1, and R11 into NR1R2, R3, A1 and R1, respectively.  Suitably the groups represented by X and Y may be the following: (a) as groups convertible into primary amino; acylamido, nitro, nitroso, carbonamido, anil, alkoxycarbonylamino and arylazo; (b) as groups convertible into secondary amino; acylalkylamido, anil, alkoxycarbonylamido and acylamido; and (c) as groups convertible into tertiary amino; quaternary amino (by pyrolysis) and acylalkylamido (by reduction). Examples describe the preparation of the 1-(2-methoxy-4-aminophenoxy) -, 5 - phenyl -, 5 - p - tolyl -, 5-o - tolyl -, 5 - p - methoxyphenyl -; 5 - p-aminophenyl and 5-p-nitrophenyl-, pentanes; the 1 - (o - methoxy - p - b  - hydroxyethylamino - phenoxy) -, 1 - (o - methoxy - p - dimethylaminophenoxy) - and 1 - (o - methyl - p-aminophenoxy) -, 5 - phenyl - pentanes; 1 - (o-methoxy - p - dimethylaminophenoxy) - 5 - p-dimethylaminophenyl - pentane; 5 - (o - methoxy - p - aminophenoxy) 1 - phenyl - hexane; 1 - (o - methoxy - p - aminophenoxy) 5 - p-methoxyphenyl pentene and 1 - (o - methoxy-p - aminophenoxy) 5 - phenyl - pentene.  Nitrophenoxy compounds corresponding to some of the above amines, for example the 1-o-methoxy - p - nitro - phenoxy -, 5 - phenyl -, 5-o and p - tolyl -, 5 - p - methoxyphenyl - and 5 - p - nitrophenyl -, pentanes and 5 - phenyl- and 5 - p - methoxyphenyl -, pentenes and 1-o - methyl - p - nitrophenoxy - 5 - phenylpentane and 5 - o - methoxy - p - nitrophenoxy - 1-phenyl-hexane are made by reaction of the appropriate aralkyl or aralkenyl bromide or tosylate with the corresponding alkali metal phenoxide.  Aralkyl halides. 5-p-Tolylpentyl bromide and 5-o-tolylpentyl bromide are made by esterifying the corresponding 5-tolylpentanol with hydrobromic acid. 5 - p - Nitrophenylpentyl bromide is made by nitrating 5-phenylpentyl bromide.  5 - p - Tolylpentanol is made by treating 2:3 - dichlorotetrahydropyran with p - tolyl magnesium bromide, hydrolysing and heating with sodium in ether, decomposing to give trans-5 - p - tolylpent - 4 - en - 1 - ol and reducing by catalytic hydrogenation. Trans - 5 - phenylpent - 4 - en - 1 - yl toluene-p-sulphonate is made by esterifying trans-5-phenylpent - 4 - en - 1 - ol with toluene - p-sulphonyl chloride.  1 - [4 - (2 - Chloroethoxycarbonylamino) 2-methoxyphenoxy] - 5 - phenylpentane is made by condensing 1 - [4 - amino - 2 - methoxyphenoxy) - 5 - phenylpentane with 2 - chloroethyl chloroformate.  1 - (4 - Dimethylamino - 2 - methoxyphenoxy) 5-p - dimethylaminophenylpentane bis - methiodide is made by treating 1-(4-amine-2-methoxy-phenoxy - 5 - p - aminophenylpentane with methyl iodide.  1 - (4 - Acetamido - 2 - methoxyphenoxy) 5-p-nitrophenylpentane is made by condensing 5-p-nitrophenylpentyl bromide with 4-acetamido 2-methoxyphenol.ALSO:Pharmaceutical preparations for the treatment of bilharziasis comprise compounds of the formula <FORM:0811857/VI/1> and acid addition salts thereof (see Group IV (b)) wherein R1 and R2 are hydrogen, alkyl groups of 1 to 6 carbon atoms or hydroxy alkyl (including polyhydroxyalkyl) groups, R1 is alkyl or alkoxy of 1 to 4 carbon atoms, A1 is an unbranched, saturated or ethylenically unsaturated hydrocarbon chain of 4 to 9 carbon atoms optionally bearing lower alkyl substituents and R3 is hydrogen, alkyl or alkoxy of 1 to 4 carbon atoms, primary, secondary or tertiary amino or a nitro group, preferably in the para position, including also formaldehydebisulphite compounds of primary amines of the above formula, in association with a pharmaceutical diluent.  The preparations may suitably take the form of elixirs, tablets, powders or capsules for oral administration, suitable diluents being starch, lactose, stearic acid, magnesium stearate and gums. Sterile liquid diluents, such as water, may be used for the preparation of solutions for parenteral injection.  Many suitable active compounds are specified.