Patent GB-1006335-A (GB)
Title: Basic ethers and process for preparing same
IPC: C07D295/092
Filed: 1962-12-17
Abstract: The invention comprises compounds of the formula <FORM:1006335/C2/1> in which Ph represents a 1,2-phenylene radical Ar represents a phenyl group substituted by a tertiary amino-C2-7-alkyl-oxy group, in which the tertiary amino group is separated from the oxygen atom by at least two carbon atoms, R represents a hydrogen atom or a C1-7-alkyl group, n is 3 or 4 and x is 2 or 4, the radical-(CnH2n-x)- being an unbranched divalent hydrocarbon radical, and acid-addition salts, N-oxides, acid-addition salts of N-oxides and quaternary ammonium compounds thereof, and, the preparation thereof by reacting a compound of the formula <FORM:1006335/C2/2> in which X represents a phenyl group substituted by a hydroxyl group, or a metal compound thereof, with a tertiary amino-C2-7-alkyl chloride, and if desired, converting a resulting acid-addition salt into the free compound, or into another acid-addition salt, and/or, if desired, converting a resulting compound into a N-oxide or a quaternary ammonium compound, and/or, if desired, converting a resulting compound or an N-oxide into an acid-addition salt thereof, and/or, if desired, converting a quaternary ammonium compound into another quaternary ammonium compound, and/or, if desired, separating a mixture of isomers into the single isomers.  The 1,2-phenylene radical and the phenyl group Ar may be substituted by one or more than one of the same or different substituents attached to any of the positions available for substitution.  The 1,2-phenylene radical may be substituted by, for example, C1-7-alkyl, C1-7-alkoxy, C2-7-alkenyloxy, C1-7-alkylenedioxy, halogen, nitro or CF3, and the Ar group may be substituted by, for example, halogen, C1-7-alkyl, halogen-C1-7-alkyl or an additional tertiary amino-C2-7-alkyl-oxy group as defined above.  1 - (3 - Chloro 4 hydroxy - phenyl) - indane and 1 - (3,5 - dichloro - 4 - hydroxy - phenyl) - indane are prepared by reacting the sodium salt of 1 - (4 - hydroxy - phenyl) - indene with chlorine. 1 - (3,5 - Dichloro - 4 - hydroxy - phenyl)-1 - methyl - 1,2,3,4 - tetrahydro - naphthalene is prepared by reacting 1-(4-hydroxy-phenyl)-1-methyl-1,2,3,4-tetrahydro-naphthalene with sulphuryl chloride.  1 - (4 - Hydroxy - phenyl) - 1,2,3,4 - tetrahydro - naphthalene and 1 - (3 - chloro - 4 - hydroxy - phenyl) - 1, 2,3,4 - tetrahydro - naphthalene are prepared by reacting 1,2,3,4-tetra-hydro-naphthalen-1-ol with phenol or o-chlorophenol, respectively, in the presence of AlCl3.  The chloro compound is purified by way of its benzyl ether.  1 - (4 - Hydroxy - phenyl) - 1 - methyl -1,2,3,4-tetrahydro-naphthalene is prepared by reacting phenol with 1-methyl-1,2,3,4-tetrahydro-naphthalene in the presence of AlCl3.  3 - (4 - Hydroxy - phenyl) - indene is prepared by Grignard reaction of p-bromo-magnesium-anisole with indan-1-one, treatment of the reaction mixture with an ammonium chloride solution to form 3-(4-methoxy-phenyl)-indene and hydrolysis of this by pyridine hydrochloride.ALSO:Pharmaceutical compositions, having antifungal, antibacterial, anti-protozoal and activity against actinomycetes, for enteral, parenteral or tropical use comprise a compound of the formula:  <FORM:1006335/A5-A6/1> in which PL represents a 1; 2-phenylene radical, Ar represents a phenyl group substituted by a tertiary amino-C2-7 alkyl-oxy group, in which the tertiary amino group is separated from the oxygen atom by at least two carbon atoms, R represents a hydrogen atom or a C1-7 alkyl group, n is 3 or 4 and x is 2 or 4, the radical -(CnH2n-x)-being an unbranched divalent hydrocarbon radical, or an acid-addition salt, N-oxide, acid-addition salt of an N-oxide or quaternary amonium compound thereof, together with a pharmaceutical carrier.  The compositions may be formulated as capsules, tablets, dragees, solutions, suspensions or emulsions, e.g. creams and ointments, and may contain preserving, stabilizing, wetting, emulsifying, coloring, and flavoring agents, salts for varying the osmotic pressure, or buffers, and may also contain other active ingredients, e.g. phenyl mercuric acetate.