Patent GB-855556-A (GB)
Title: New acetanilide derivatives
Inventor: OXLEY PETER
IPC: C07D307/73
Filed: 1958-05-06
Abstract: The invention comprises compounds of the general formula: <FORM:0855556/IV(b)/1> [wherein R1 is an aryl (except unsubstituted phenyl), aralkyl, aralkenyl, alkoxyalkyl, cycloaliphatic, aryloxyalkyl, aryloxyalkenyl, aryloxyaryl, heterocyclic, heterocyclicalkyl or heterocyclicalkenyl group or -R2COOR3 wherein R2 is an alkylene, arylene, arylenedioxyalkyl or divalent heterocyclic group and R3 is the 4-(dichloroacet-N-methylamido)phenyl group], together with their simple substituted derivatives containing one or more halogen atoms, alkyl, alkoxy, aryl, methanesulphonyl, nitro or amino groups in the groups other than -R2COOR3 represented by R1, and the preparation thereof by :(1) esterifying dichloroacet-4-hydroxy-N-methylanilide or a salt thereof; (2) protecting the amino group of p-aminophenol to get a compound of the general formula:  <FORM:0855556/IV(b)/2> (wherein -N=Y is -NHR7 wherein R7 is a formyl, acetyl or dichloroacetyl group; or -N=CHR8 wherein R8 is a phenyl group optionally having a substituent that cannot be esterified or methylated), esterifying this to form a compound of the general formula:  <FORM:0855556/IV(b)/3> methylating this and, save where R7 is a dichloroacetyl group, selectively hydrolysing the product to get a compound of the general formula: <FORM:0855556/IV(b)/4> (wherein R9 is a hydrogen atom or dichloroacetyl group), and where R9 is a hydrogen atom, dichloroacetylating; (3) reacting 4-(dichloroacet-N-methylamido) phenyl sulphite with an acid of the general formula:  R6COOH [wherein R6 is an aryl (except unsubstituted phenyl), aralkyl, aralkenyl, alkoxyalkyl, cycloaliphatic, aryloxyalkyl, aryloxyalkenyl, aryloxyaryl, heterocyclic, heterocyclicalkyl or heterocyclicalkenyl group or -R2COOH wherein R2 is an alkylene, arylene, arylenedioxyalkyl or divalent heterocyclic group] in the presence of an acid binding agent; and (4) reducing the corresponding nitro compound.  The mixed anhydride of b -phenoxypropionic acid and benzoic acid is made from sodium b -phenoxypropionate and benzoyl chloride.  4-(Dichloroacet-N-methylamido) phenyl sulphite is made from 4-(dichloroacet-N-methylamido) phenol and thionyl chloride. Specifications 767,148, 794,762 and 850,394 are referred to.ALSO:Therapeutic compositions comprise compounds of the general formula:  <FORM:0855556/VI/1> [Wherein R1 is an aryl (except unsubstituted phenyl), aralkyl aralkenyl, alkoxyalkyl, cycloaliphatic, aryloxyalkyl, aryloxyalkenyl, aryloxyaryl, heterocyclic, heterocyclicalkyl or heterocyclicalkenyl group or- R2COOR3 wherein R2 is an alkylene, arylene, arylenedioxyalkyl or divalent heterocyclic group and R3 is the 4-(dechloroacet-N-methylamido) phenyl group], together with their simple substituted derivatives containing one or more halogen atoms, alkyl, alkoxy, acyl, methanesulphonyl nitro or amino groups in the groups other than - R2COOR3 represented by R1, in association with a pharmaceutically acceptable carrier or diluent.  They may be administered externally or internally, preferably per as, and be in the form of capsules, liquids, lozenges or tablets, and the like; and have activity against chronic amoebiasis.  Specifications 767,148, 794,762 and 850,394 are referred to.