Patent ES-350523-A1 (ES)
Title: Aryloxyisoalkyl-Delta<2>-Imidazolines
IPC: C07D233/22
Filed: 1968-02-15
Abstract: Novel imidazoline derivatives of the general Formula (I) wherein Ar represents a phenyl, naphthyl or partially hydrogenated naphthyl radical in which the aromatic ring may be substituted by one or more linear or branched, saturated or unsaturated hydrocarbon radicals, aryl and/or aralkyl radicals, by one or more trifluoromethyl, nitro, amino, hydroxy and/or lower alkoxy groups having 1 to 4 carbon atoms, by one or more halogen atoms and/or (from two ortho substituents together) by a methylene dioxy group R 1 represents a linear or branched alkyl radical with 1 to 4 carbon atoms when R 3 represents hydrogen, and hydrogen when R 3 does not represent hydrogen R 2 , R 3 and/or R 4 , which may be the same or different, each represents hydrogen or a lower linear or branched alkyl group having 1 to 4 carbon atoms, whilst n represents 0 or 1, and acid addition salts thereof are prepared by: (a) reacting a carboxylic acid of the Formula (II) wherein Ar, R 1 , R 2 , R 3 and n have the meanings given above or a functional derivative thereof, and an ethylene diamine derivative of the Formula (III): H 2 N-CH 2 -CH 2 -NH-R 4 , wherein R 4 has the meaning given above, or with a reactive N-derivative of the compound, or with ammonia or an ammonia-donor and a compound that can be converted into a compound of Formula (III) by reaction with ammonia, or an amine of the formula R 4 NH 2 (b) reducing or decarboxylating a compound corresponding to the general Formula (VII) in which Ar and R 4 have the meanings given above, Y 5 represents the group in which R represents hydrogen or a hydrocarbon radical, Y 6 represents a radical that can be converted into a = CHR 3 group by reduction or decarboxylation, and R 3 is as defined above (c) eliminating the compound H-X 2 from a compound of the general Formula (VIII) in which Ar, R 1 , R 2 , R 3 , R 4 and n have the meanings given above whilst X 2 represents hydroxyl, alkoxy- or an acyloxy group, or a halogen atom or (d) displacing the double bond in a compound of the Formula (IX) or (X) in which Ar, R 1 , R 2 , R 3 , R 4 and n have the meanings given above and n1 represents 1, into the 2,3-position. R-propionitriles where R represents:- (i) [alpha]-phenoxy (ii) [alpha]-(o-methoxyphenoxy) (iii) [alpha]-(p-methoxyphenoxy) (iv) [alpha]-(2,3-dimethylphenoxy) are prepared by:- (i) adding dry methyl ethyl ketone, anhydrous potassium carbonate, and potassium iodide to phenol and adding a solution of [alpha]-bromopropionitrile (ii) treating guaiacol with [alpha]-bromopropionitrile in the presence of anhydrous potassium carbonate (iii) reacting hydroquinone monomethyl ether with [alpha]-bromo-propionitrile in the presence of anhydrous potassium carbonate (iv) reacting vic-o-xylenol and [alpha]-bromopropionitrile as in (i). R1-propionimido-acid ethyl ester hydrochlorides where R1 represents:- (a) [alpha]-(phenoxy) (b) [alpha]-(2,3-dimethylphenoxy) are prepared by treating (a) [alpha]-phenoxypropionitrile or (b) [alpha]-(2,6-dimethylphenoxy)-propionitrile in absolute ethanol and chloroform with dried hydrogen chloride. Pharmaceutical compositions having vasoconstrictive, spasmolytic and antihistaminic activity and containing the compounds defined above, of Formula (I), together with a pharmaceutically-acceptable carrier are administered orally as tablets, or as nose-drops.