Patent GB-880400-A (GB)
Title: Improvements in or relating to penicillins
Inventor: DOYLE FRANK PETER
IPC: C07D499/74
Filed: 1959-07-15
Abstract: Relates to penicillins of the general formula <FORM:0880400/IV (b)/1> where R1, R2, R3, R4 and R5 ar each a hydrogen or halogen atom or an alkyl, aryl, acyl, aralkyl, cycloalkyl, heterocyclic, hydroxy, alkoxy, aryloxy, aralkoxy, alkenyl, alkenyloxy, alkenylthio, mercapto, alkylthio, arylthio, aralkylthio, acyloxy, acylthio, acylamino, alkoxycarbonyl, alkylsulphonyl, dialkylamino, sulphamyl or nitro group, the substituents being the same or different and not more than four being hydrogen atoms, or any two adjacent substituents together completing an unsaturated carbocyclic ring system which may itself be substituted, such as 3,5-dinitro-phenyl-2-chlorophenyl-, o-tolyl-, 3,4,5-trimethoxy-phenyl-, 2,4-dimethoxy-phenyl-, 6-ethoxy-2-methoxy-phenyl-, 2-methoxy-1-naphthyl-, 2-naphthyl- and 9-anthryl-penicillin, and non-toxic salts thereof. The Specification refers to many other penicillins of the above formula.  The penicillins may be prepared by reacting 6-amino-penicillanic acid or a liquor containing it with an acid chloride, bromide, anhydride or mixed anhydride derived from a carboxylic acid of the general formula <FORM:0880400/IV (b)/2> where R1, R2, R3, R4 and R5 ar as above.  2,6 diethoxybenzoic acid is prepared by alkaline hydrolysis of methyl 2,6-diethoxy benzoate, which is obtained by treating methyl 2,6 - dihydroxybenzoate with diethyl sulphate and potassium carbonate in acetone.  2,6-di-n-butoxy benzoic acid is prepared by alkaline hydrolysis of methyl 2,6-di-n-butoxybenzoate, which is obtained by treating methyl 2,6-dihydroxybenzoate with n-butyl bromide and potassium carbonate in acetone.  2,6-dibenzyloxybenzoic acid is obtained by alkaline hydrolysis of methyl 2,6-dibenzyloxybenzoate, which is obtained by treating methyl 2,6-dihydroxybenzoate with benzyl chloride and potassium carbonate in acetone. 2,6-di-n-propoxybenzoic acid is prepared by alkaline hydrolysis of methyl 2,6-di-n-propoxybenzoate, which is obtained by treating methyl 2,6-dihydroxybenzoate with n-propyl bromide and potassium carbonate in acetone.  2-ethoxy-6-methoxybenzoic acid is prepared by oxidizing 2-ethoxy-6-methoxy-toluene with potassium permanganate in pyridine, the 2-ethoxy-6-methoxy-toluene being prepared by the action of diethyl sulphate on 2-hydroxy-6-methoxy toluene. 4,6-diethyl-2-methoxybenzoyl chloride is prepared by the action of thionyl chloride on 4,6-diethyl-2-methoxybenzoic acid, which is obtained by the action of carbon dioxide on a lithium derivative prepared from 3,5-diethylanisole and butyl lithium.ALSO:Pharmaceutical compositions comprise a pharmaceutical carrier and a penicillin of the general formula <FORM:0880400/VI/1> or a non-toxic salt thereof, where R1, R2, R3, R4 and R5 are each a hydrogen or halogen atom or an alkyl, aryl, acyl, aralkyl, cycloalkyl, heterocyclic, hydroxy, alkoxy, aryloxy, aralkoxy, alkenyl, alkenyloxy, alkenylthio, mercapto, alkylthio, arylthio, aralkylthio, acyloxy, acylthio, acylamino, alkoxycarbonyl, alkylsulphonyl, dialkylamino, sulphamyl or nitro group, the substituents being the same or different and not more than four being hydrogen atoms, or any two adjacent substituents together completing an unsaturated carbocyclic ring system which may itself be substituted (see Group IV (b)).