Patent GB-1244761-A (GB)
Title: Novel carboxylic acids, processes for their production and compositions containing same
IPC: C07D311/16
Filed: 1968-07-26
Abstract: 1,244,761. Heterocyclic carboxylic acids. J. R. GEIGY A.G. 26 July, 1968 [28 July, 1967; 29 Sept., 1967], No. 35698/68. Heading C2C. Novel heterocyclic carboxylic acids of the general Formula I wherein R represents H or (C 1 -C 4 ) alkyl group, X represents -O-, -S-, -NH-, or -N(CH 3 )-, Y represents H, F, Cl, Br atom or a CH 3  group, Z 1  and Z 2  represent independently H, a Cl, F, or Br atom or a (C 1 -C 4 ) alkyl or alkoxy group, and their salts with inorganic or organic bases are obtained (a) by decomposing a compound of the general Formula II wherein Am represents the radical of a secondary organic base, while splitting off an amine of the general Formula III (b) by reacting, according to Friedel-Crafts a compound of the general Formula IV with a carboxylic halide of the general Formula, V or with a carboxylic acid anhydride of the general Formula VI wherein Q represents halogen, (c) by splitting off simultaneously the ester group and the radical of the secondary organic base from a compound of the general Formula VII wherein R 1  represents a lower alkyl or the benzyl group, (d) by saponifying a compound of the general Formula VIII (e) by splitting off hydrogen halide from a compound of the general Formula IX wherein Q represents a halogen atom, (f) by treating a compound of the general Formula X wherein R 2  represents a lower alkyl with an alkylating group of the general Formula Xa wherein A represents the monovalent anion of a mineral acid, to give a ternary sulfonium compound of the general Formula Xb and boiling this compound in the presence of a weak base until the sulfonium group is split off, (g) by splitting off the alkylsulphonyl radical of a compound of the general Formula (XI) by boiling in the presence of a weak base in a solvent containing hydroxyl groups, and if desired converting the free acid obtained in any of these processes into a salt with an inorganic or organic base. Starting compounds of Formula II are obtained by condensing compounds of Formula IV under Friedel Craft conditions with compounds of the Formula IVa to obtain 5-alkanoyl derivatives which are then converted to the corresponding Mannich derivatives with the aid of formaldehyde or paraformaldehyde and a secondary organic base. Compounds of the Formula VII can be produced by esterifying a compound of the Formula II with an alkanol or benzylic alcohol. Compounds of the Formula VIII can be produced by heating a compound of the Formula VII in the presence of a weak base in a solvent containing hydroxyl groups. Compounds of the Formula IX can be produced by condensing a compound of the Formula IV according to Friedel-Crafts with a compound of the Formula IXa or by chlorinating or brominating a compound of the Formula IXb Compounds of the Formula X can be produced by boiling a compound of the Formula II with an excess of the sodium salt of a lower molecular alkyl sulphide of the general Formula Xc until the secondary organic base is replaced by the alkylsulphide group. Compounds of Formula XI can be produced by treating a compound of the Formula X in an organic solvent with a peracid or hydrogen peroxide. Pharmaceutical compositions containing the above compounds and having a diuretic and saluretic action are administered orally.