Patent GB-1181356-A (GB)
Title: Aryloxyisoalkyl-Delta<2>-Imidazolines
Inventor: BAGANZ HORST
IPC: C07D233/22
Filed: 1968-02-23
Abstract: 1,181,356. Aryloxyisoalkyl-#<SP>2</SP>-imidazolines. NORDMARK-WERKE G.m.b.H. 23 Feb., 1968 [23 Feb., 1967], No. 8875/68. Heading C2C. 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 n<SP>1</SP> represents 1, into the 2,3-position. R-propionitriles where R represents:- (i) α-phenoxy; (ii) α-(o-methoxyphenoxy); (iii) α-(p-methoxyphenoxy); (iv) α-(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 α-bromopropionitrile; (ii) treating guaiacol with α-bromopropionitrile in the presence of anhydrous potassium carbonate; (iii) reacting hydroquinone monomethyl ether with α-bromo-propionitrile in the presence of anhydrous potassium carbonate; (iv) reacting vic-o-xylenol and α-bromopropionitrile as in (i). R<SP>1</SP>-propionimido-acid ethyl ester hydrochlorides where R<SP>1</SP> represents:- (a) α-(phenoxy); (b) α-(2,3-dimethylphenoxy) are prepared by treating (a) α-phenoxypropionitrile or (b) α-(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.