Patent GB-998286-A (GB)
Title: New diphenylalkanes and process for preparing same
IPC: C07C215/40
Filed: 1963-01-14
Abstract: The invention comprises compounds of the formula <FORM:0998286/C2/1> in which R1 and R2 each represents an alkyl group, Am represents a tertiary amino group, the alkylene group of the formula -(CnH2n)-separates the group Am from the oxygen atom by at least two carbon atoms, n being an integer from 2 to 7, R3 and R4 each represents a hydrogen or halogen atom or a C1-7 alkyl, C1-7 alkoxy or trifluoromethyl group or the group of the formula -O-(CnH2n)-Am as defined above, and R5 represents a hydrogen atom or C1-7 alkyl, C1-7 alkoxy or trifluoromethyl group or halogen atoms or an unsubstituted phenyl radical or such a radical substituted by C1-7 alkyl, C1-7 alkoxy or trifluoromethyl groups or halogen atoms, and wherein at least one of R3, R4 and R5 is other than hydrogen; and acid-addition salts, N-oxides, acid-addition salts of N-oxides and quaternary ammonium compounds thereof.  The compounds are prepared by converting in a compound of the formula <FORM:0998286/C2/2> in which each of the symbols R6 and R7 stands for hydrogen, C1-7 alkyl, C1-7 alkoxy, halogeno, trifluoromethyl or hydroxyl, or a salt thereof, any hydroxyl group attached to the phenyl moiety into the group of the formula -O-(CnH2n)-Am. The conversion may be carried out by forming a salt of the starting material, e.g. an alkali metal salt, and reacting the salt with a compound of the formula X-(CnH2n)-Am, in which X stands for a halogen atom, in the presence of a diluent.  The free bases are converted to acid-addition salts, N-oxides, acid-addition salts of N-oxides and quaternary ammonium compounds by conventional methods.  A mixture of isomeric compounds of the invention may be separated into individual isomers.  The starting materials of Formula II are prepared by reacting a compound of the formula <FORM:0998286/C2/3> with a compound of the formula <FORM:0998286/C2/4> in the presence of a Lewis acid, particularly a Friedel-Crafts reagent, e.g. AlCl3.  2 - (4 - Chlorophenyl) - 2 - propanal is prepared by reacting 4-chloro-acetophenone with methyl magnesium iodide and decomposing the product with an aqueous solution of ammonium chloride. 2 - (4 - Bromophenyl) - 2 - propanol and 2 - (4 - iodophenyl) -2-propanol are similarly prepared.  2 - (4 - Chlorophenyl) - 2 - (3 - chloro - 4 - hydroxyphenyl) -propane is prepared by treating 2 - (4 - chlorophenyl) - 2 - (4 - hydroxyphenyl) - propane with sulphuryl chloride. 2-(p-Biphenylyl) - 2 - (3 - chloro - 4 - hydroxyphenyl) - propane is similarly prepared.  2 - (4 - Bromophenyl) - 2 - [4 - (2 - chloroethoxy) - phenyl] - propane is prepared by reacting 2-(4-bromophenyl)-2-(4-hydroxyphenyl) propane with ethylene chlorhydrin and reacting the resulting 2-(4-bromophenyl)-2-[4-(2-hydroxyethoxy) -phenyl]-propane with thionyl chloride.  Pharmaceutical compositions for enteral or topical administration having antifungal, antibacterial, anti-protozoal and anti-actinomycetal activity comprise a compound of the invention together with a pharmaceutical carrier.  The compositions may be formulated as capsules, tablets, dragees, solutions or emulsions, e.g. as creams or salves.