GB1268465A - Substituted salicylic acid compounds - Google Patents

Abstract

1,268,465. 5-Substituted salicydlic acids. MERCK & CO. Inc. 18 June, 1970 [25 June, 1969; 20 April, 1970], No. 29668/70. Heading C2C. The invention comprises compounds of formula wherein R is OH, NH 2 , alkoxy, alkylamino, dialkylamino, dialkylaminoalkylamino, dialkylaminoalkoxy, hydroxyalkoxy, polyhydroxyalkoxy, alkoxyalkoxy, phenylalkoxy, PhO (possibly substituted), (C 1-6 alkaroylamino)alkoxy, hydrazino, anilino, morpholino, piperidino, pyrrolidino, hydroxyalkylamino or an N-attached radical derived from an amino-acid; R 2 is H, acyl, alkyl or alkoxycarbonyl, R 3 is H, halogen, haloalkyl, alkyl, cycloalkyl or alkoxy; and each X is independently H, halogen, alkyl, OH, alkoxy, acyloxy, haloalkyl, NO 2 , NH 2 , alkylamino, dialkylamino, acylamino, SH, alkylthio, alkylsulphinyl, alkylsulphonyl, SO 2 NH 2 , SONH 2 , aminoalkyl, alkylaminoalkyl, dialkylaminoalkyl, hydroxyalkyl, alkoxyalkyl, mercaptoalkyl, alkylthioalkyl, CN, CO 2 H, alkoxycarbonyl, CONH 2 , aryl, aralkyl, salicyl, aryloxy or aralkoxy; and Y is CH 2 NH, NHCH 2 , CH : N, N : CH or CONH, all alkyl and alkoxy radicals (unless forming part of alkoxycarbonyl) containing up to 5 C atoms. These compounds may be prepared as follows: (1) (Y=CH : N or N : CH) condensation of the corresponding aldehyde and primary amine; (2) (Y=CH 2 NH) reduction of the compound where Y is CH : N; (3) (Y=NHCH 2 ) condensation of the corresponding aniline and halomethylsalicylic acid; (4) (Y=CONH) reduction of a 4-nitroanisole, reaction of the 4-aminoanisole with the appropriate benzoylhalide, demethylation of the 41- methoxybenzanilide and carboxylation of the product; (5) (Y=CONH) benzoylation of an aminosalicylic acid; (6) the standard procedures for interconversion of functional groups, e.g. hydrolysis of esters, esterifying, amidating or forming salts from acids, or alkylating OH groups. Intermediates.-Details are also given for the preparation of 4-amino- and 4-nitro-3-trifluoromethylanisoles; 4-(p-fluorobenzamido)-3-trifluoromethylphenol and its methyl ether; and compounds m-R<SP>1</SP>QC 6 H 4 COZ, where R<SP>1</SP> is Me or PhCH 2 , Q is O or S, and Z is OH or Cl. Therapeutic compositions for oral, parenteral, rectal or topical administration comprise compounds of the above formula, which have antiinflammatory, and in some cases antipyretic, analgesic, diuretic, antifibrinolytic and hypoglycaemic activity.