Patent GB-730922-A (GB)
Title: Aromatic amino-ketones and acid addition salts thereof and a process for the manufacture of same
Filed: 1953-04-22
Abstract: The invention comprises aromatic aminoketones of the general formula <FORM:0730922/IV (b)/1> wherein R1 and R2 and R3 each represent a hydrogen atom or a halogen or the methoxy group, Y represents the -CH = CH- or the -CH2CH2-group and B represents the radical of a secondary amine attached by the nitrogen to the lower alkylene group (which means one containing 1 to 3 carbon atoms), and salts thereof. Such compounds are obtained by reacting a phenyl styryl ketone derivative of the formula <FORM:0730922/IV (b)/2> wherein M represents an alkali metal with a basically substituted alkyl halide of the formula X-(lower alkylene)-B, wherein X stands for a halogen atom, and where a compound in which Y is -CH2CH2- is desired, hydrogenating the compound so produced.  B may represent, e.g., dialkyl amino, or a heterocyclic secondary amino radical such as 1,2,3,4-tetrahydroquinolino, piperidino or morpholino.  Salts mentioned are those of hydrochloric, sulphuric, acetic, oxalic and citric acids.  In example (1), the sodium salt of p-hydroxy-phenyl styryl ketone (from sodium methoxide and the hydroxy compound) and b -diethylamino-ethyl chloride are reacted to give the crude base from which, by adding oxalic acid to its ethanolic solution 4 - (b  - diethylaminoethoxy) - phenyl styryl ketone oxalate is precipitated. This is portitioned between ether and aqueous sodium hydroxide solution to give the free base, which is then converted to the hydrobromide.  The oxalate or hydrobromide on hydrogenation with a palladium oxide catalyst in ethanol give the 4 - (b  - diethylamino - ethoxy) - phenyl phenethyl ketone salts from which the free base is liberated with alkali and converted to its citrate.  By similar methods there are produced from the appropriate starting materials the compounds (2) 4 - (b  - diethylamino - ethoxy) - phenyl - 4 - methoxy-styryl ketone and its hydrobromide; (3) and (4) 4-(b -diethylamino-ethoxy)-phenyl p  2,4-dichloro-styryl ketone and its oxalate and hydrobromide, and 4-(b -diethylamino-ethoxy)-phenyl 2,4-dichloro-phenethylketone and its oxalate; (5) 4-(b -diethylamino-ethoxy)-phenyl 2-chloro-styryl and its hydrobromide; (6) 4-(b -diethylamino - ethoxy) - phenyl 4 - chloro - styryl ketone hydrobromide; (7) 3-(b -diethylamino - ethoxy) - phenyl 2,4 - dichloro - styryl ketone oxalate and 3-(b -diethylamino-ethoxy)-phenyl 2,4-dichloro-phenethyl ketone oxalate; (8) 3 - (b  - diethyl - amino - ethoxy) - phenyl 2 - chloro - styryl ketone oxalate; (9) 2 - (b  - diethylamino-ethoxy)-phenyl styryl ketone oxalate; (10) 4-(g -morpholino-propoxy)-phenyl styryl ketone and its nitrate; (11) 4-(g -piperidino-propoxy)-phenyl styryl ketone ethanolate and its citrate; (12) 4-(g -diethylaminopropoxy)-phenyl styryl ketone citrate and 4-(g -diethylamino - propoxy) - phenyl phenethyl ketone; (13) 4 - (b  - dimethylamino - ethoxy) - phenyl styryl ketone citrate and 4-(b -dimethylamino-ethoxy)-phenyl phenethyl ketone.  4 - Hydroxy - phenyl 2,4 - dichloro - styryl ketone is prepared by reacting p-hydroxy-acetophenone and 2,4 - dichlorobenzaldehyde in aqueous alcoholic sodium hydroxide solution. Similarly prepared are 4-hydroxy-phenyl 2- and 4-chloro-styryl ketones, 3-hydroxy-phenyl 2,4-dichloro-styryl ketone and 3-hydroxy-phenyl 2-chloro-styryl ketone.