Patent GB-1236041-A (GB)
Title: Aryl substituted-cyclohexenecarboxylic acids and derivatives thereof
IPC: A61K31/19
Filed: 1968-08-19
Abstract: 1,236,041. Aryl-substituted cyclohexene carboxylic acids and their derivatives. ORTHO PHARMACEUTICAL CORP. 19 Aug., 1968 [22 Aug., 1967(2); 24 July, 1968], No.39587/68. Addition to 1,192,943. Heading C2C. Novel compounds of the formula (wherein R is carboxy including alkali metal salts thereof, carbalkoxy of up to 9 carbon atoms, carbaryloxy, carbaralkoxy, hydroxymethyl or optionally N-alkylated carboxamido; each R<SP>1</SP> is independantly C 1-6  alkyl; the dotted lines represent a double bond in either the 3- or the 4-position; and Ar is 3,4-methylenedioxyphenyl, α- or #-naphthyl or 2-R 1 -3-R 2 -4-R 3 - phenyl in which R 1  is H, CH 3 , OH, C 1-4  alkoxy, acyloxy of up to 5 carbon atoms or tetrahydropyranyl - 2 - oxy (THP); R 2  is H, OH, C 1-4  alkyl, C 1-4  alkoxy, acyloxy of up to 5 carbon atoms, THP, Cl or CF 3  and R 3  is H, OH, C 1-4  alkyl, cyclopentoxy, acyloxy of up to 5 carbon atoms, diethylaminoethoxy, CF 3 , SCH 3 , N(CH 3 ) 2  or THP, and R 3  may be C 1-4  alkoxy when R is CH 2 OH, and wherein at least 1 but not more than 2 of R 1 , R 2  and R 3  is H, provided that when R 3  is OH or acyloxy and R 1  and R 2  are H then R is other than carboxy, salified carboxy or carbalkoxy) are prepared by dehydrating the the corresponding substituted 4-hydroxybenzoic acids or their esters with a strong acid in an organic solvent and, if desired, saponifying an ester product to the corresponding free acid; or by reacting a compound with acrylic acid; or by reacting a compound with a compound R<SP>1</SP>CH=CH.COOH; and, when the esters, amides or alkali metal salts of the acids are required, preparing these from the free acids by standard methods; and when the compounds wherein R is CH 2 OH are required, reducing the free acids. The dehydration of 4 - hydroxy - 4 - (o - acetoxyphenyl) - benzoic acids occurs spontaneously at room temperature. Predominant dehydration products are the #<SP>4</SP>-isomers which on prolonged heating are isomerized to the #<SP>3</SP>-compounds. Products containing free OH groups may be acylated and the acylates may be hydrolysed. 2 - Methyl - 3 - ethyl - 4 - hydroxy - 4 - (p-cyclopentoxyphenyl) - cyclohexanecarboxylic acid is prepared from p-cyclopentoxyphenyl magnesium bromide and the Li salt of 2-methyl-3-ethyl-4. ketocyclohexane - carboxylic acid (prepared from the free acid and lithium hydride) followed by hydrolysis. 2 - Methyl - 3 - ethyl - 4 - hydroxy-4- (o - tolyl) cyclohexanecarboxylic acid is prepared similarly but using o-tolyllithium or o-tolylmagnesium bromide. 2 - Methyl - 3 - ethyl - 4- (3,4 - methylenedioxyphenyl)- 3 - cyclohexenecarboxylic acid chloride is prepared from the free acid and thionyl chloride. 2-Methyl-3-ethyl-4- (p tolyl) - 3 - cyclohexenecarboxylic acid chloride, 2- methyl - 3 - ethyl - 4 - (o - tolyl) - 4 - cyclohexenecarbonyl chloride and 2 - methyl - 3 - ethyl- 4 - (p - cyclopentyloxyphenyl)- 3 - cyclohexenecarbonyl chloride are prepared analogously. Compounds of the above structural formula are stated to possess antilittering activity and may be made up with carriers into pharmaceutical compositions. The route of administration is not specified.