Patent GB-1272155-A (GB)
Title: Orthohydroxybiphenylenecarboxylic acids and their derivatives
Inventor: SHEN TSUNG-YING
IPC: C07C51/00
Filed: 1970-06-18
Abstract: 1,272,155. o-Hydroxybiphenylene carboxylic acids and derivatives. MERCK & CO. Inc. 18 June, 1970 [25 June, 1969; 20 April, 1970], No. 29540/70. Heading C2C. Novel compounds of Formula I in which R is a hydroxy, amino, alkoxy, alkylamino, dialkylamino, dialkylaminoalkyl, dialkylaminoalkoxy, hydroxyalkoxy, polyhydroxyalkoxy, alkoxyalkoxy, phenylalkoxy, phenoxy, alkoxyphenoxy, dialkylaminophenoxy, alkanoylaminophenoxy, carboxyphenoxy, alkoxycarbonylphenoxy, hydrazino, morpholino, piperidino, pyrrolidino, or hydroxyalkylamino radical; R 2  is a hydrogen atom or an acyl, alkyl or alkoxycarbonyl radical; R 3  is a hydrogen or halogen atom or a haloalkyl, alkyl, C 3-7  cycloalkyl, or alkoxy radical; and each of X 1 , X 2 , X 3  and X 4 , which may be the same as or different from the others, is a hydrogen or halogen atom or an alkyl, hydroxy, alkoxy, acyloxy, haloalkyl, nitro, amino, alkylamino, dialkylamino, acylamino, mercapto, alkylthio, alkylsulphinyl, alkylsulphonyl, sulphamoyl, aminoalkyl, alkylaminoalkyl, hydroxyalkyl, alkoxyalkyl, mercaptoalkyl, alkylthioalkyl, cyano, carboxy, alkoxycarbonyl, carbamoyl, aryl, alkaryl, aralkyl, aryloxy, aralkoxy or salicyl radical; and the OR 2  group is always ortho to the group and the alkyl and alkoxy groups and residues mentioned contain not more than five carbon atoms, are prepared by one of the following methods: (a) an appropriate hydroxybiphenylene compound is carboxylated by reaction with CO 2  preferably in the presence of an alkali metal carbonate, (b) by oxidation of the corresponding 2-formyl-3-hydroxybiphenylene compounds, (c) by ring closure of an appropriate biphenyl or (d) by a Fries rearrangement of an appropriate ester, Grignard or Lithio compound, optionally followed by esterification, amidification or salt formation. Numerous intermediates used as starting materials and in their preparation are prepared; they are the following phenylenes: 2-acetyloxy- 3-methoxy-, 2-hydroxy-3-methoxy-, 2-acetyloxy-3-carboxy-, 2-acetyloxy-3-trifluoromethyl-, 2-hydroxy-3-trifluoromethyl-, 2-acetyl-3,6-dimethoxy-, 2-acetyl-6-hydroxy-, 2-hydroxy-6- methoxy-, 2-ethyl-6-hydroxy-, 2-acetyl-6- nitro-, 2-hydroxy-6-nitro-, 2-benzoyl-6-chloro-, 2-hydroxy-6-chloro-, 2-carboxy-6-methoxy-, 2- carboxy-6-hydroxy-, 2-carboxy-6-acetyloxy-, 2- acetoxy-6-trifluoromethl-, -, 2-hydroxy-6-trifluoromethyl-, 2-acetyl-6-methoxy- and oxime thereof, 2-acetamido-6-methoxy-, 2-amino-6- methoxy, 2-methoxy-6-phenyl-, 2-hydroxy-6- phenyl-, 2-benzyl-6-methoxy-, 2-benzyl-6-hydroxy-, 6-acetyl-3-methyl-2-methoxycarbonyl-, 2-acetyl-7-methyl-, 2-acetyloxy-7-methyl-, 2- acetyloxy-7-bromomethyl-, 2-hydroxy-7-methoxymethyl-, 2-fluoro-6-hydroxy-, 2-hydroxy-7- mercaptomethyl-, 2 - hydroxy - 7 - hydroxymethyl-, 2-dimethylaminomethyl-7-hydroxy-, 2-aminomethyl-7-hydroxy-, 2-methoxy-6-phenoxy-, 2-hydroxy-6-phenoxy-, 2,3-dimethoxy-6- hydroxy-, 2-chloro-6-mercapto-, 2-chloro-6- methylthio-, 2-cyano-6-methylthio, and 2-carboxy-6-methylthio-, -phenylenes. Pharmaceutical compositions in conventional forms for oral, parenteral and topical administration and having anti-inflammatory, anti-pyretic, analgesic, diuretic, antifibrinolytic and hypoglycaemic activity, comprise an above novel compound and a carrier therefor.