Patent GB-377464-A (GB)
Title: Manufacture of substituted aromatic ketones
IPC: C07C45/71
Filed: 1931-08-24
Abstract: Aminoalkoxy derivatives of aromatic ketones are prepared by introducing an aminoalkyl residue, the tertiary amino group of which is substituted by alkyl, aralkyl or cycloalkyl, into an hydroxyl group of an aromatic ketone containing nuclear hydroxyl. The products are useful therapeutically.  According to the examples, (1) p-diethylaminoethoxyacetophenone is obtained by treating p-oxyacetophenone with chlorethyldiethylamine or by interaction of p-bromethoxyacetophenone (obtained, together with a little di-p-acetophenylglycolether, by interaction of p-oxyacetophenone with ethylene bromide) with diethylamine; (2) 2-diethylaminoethoxy-4-methoxyacetophenone is prepared by heating 2-oxy-4-methoxyacetophenone with bromoethyldiethylamine hydrobromide in the presence of potash; (3) (2-di-ethylaminoethoxy-4-methoxyphenyl)-benzyl-ketone results from the interaction of (2-oxy-4-methoxyphenyl)-benzylketone with chlorethyldiethylamine; (4) treatment of p-oxybenzophenone with chlorethyldicyclohexylamine gives p-dicyclohexylaminoethoxybenzophenone; (5) 2-oxy-4-methoxyacetophenone is heated with ethylene bromide in the presence of sodium alcoholate and the resulting 2-bromethoxy-4-methoxyacetophenone boiled with methylbenzylamine hydrobromide in benzene solution to form 2-methylbenzylaminoethoxy-4-methoxyacetophenone; (6) 2-oxyethoxy-4-methoxyacetophenone is first prepared by treating p 2-oxy-4-methoxyacetophenone with excess of ethylene oxide, then heated with phosphorus pentachloride, and the 2-chlorethoxy-4-methoxyacetophenone so obtained heated with diethylamine to give the 2-diethylaminoethoxy compound; (7) 2-diethylaminoisobutyloxy-4-methoxyacetophenone is obtained by heating 2-oxy-4-methoxyacetophenone with 1-diethyl-amino-3-chloro-n-butane in the presence of sodium alcoholate.  The following compounds are prepared in an analogous manner:--m-diethylaminoethoxyacetophenone, 2 - diethyl-aminoethoxy - 4 - methoxy - 5 - nitroacetophenone (which may be reduced to the 5-amino compound and this then acetylated) from 2-oxy-4-methoxy-5-nitroacetophenone, 2-diethylaminoethoxy-4-n-butyloxyacetophenone from 2-oxy-4-n-butyloxyacetophenone (obtainable by interaction of the monosodium salt of 1-acetyl-2 : 4-dioxybenzene with n-butyl bromide), 2-diethylaminoethoxy-4-benzyloxyacetophenone from 2-oxy-4-benzyloxyacetophenone (prepared by treatment of the monosodium salt of 1-acetyl-2 : 4-dioxybenzene with benzyl chloride), 1-di-ethylaminoethoxy-2-acetylnaphthalene, 2-di-ethylaminoethoxy - 4 - methoxybutyrophenone from 2-oxy-4-methoxybutyrophenone (obtained from the monosodium salt of 2 : 4-dioxybutyrophenone and dimethyl sulphate), p-diethylaminoethoxyphenylbenzylketone, (2-diethylaminoethoxy-4-benzyloxyphenyl)-benzylketone from (2-oxy-4-benzyloxyphenyl)-benzylketone (obtainable by interaction of the monosodium salt of 2 : 4-dioxyphenylbenzylketone with benzyl chloride), and 2-di-n-butylaminoethoxy-4-methoxyacetophenone.  The Specification as open to inspection under Sect. 91 (3) (a) describes also the aminoalkylation of aromatic aldehydes containing nuclear hydroxyl and includes an example of the preparation of o-diethylaminoethoxybenzaldehyde by interaction of salicylaldehyde with the p-toluenesulphonic ester of diethylaminoethanol.  This subject-matter does not appear in the Specification as accepted. 1-Diethylamino-3-chloro-n-butane is prepared by boiling b -diethylaminoethylmethylcarbinol (obtained by reduction of b -diethylaminoethylmethylketone) with thionyl chloride.