1,191,611. Aryloxyalkanoic acids. MERCK & CO. Inc. 18 March, 1968 [23 March, 1967], No. 13075/68. Heading C2C. Novel aryloxyalkanoic acids (I) (including esters and amides thereof) wherein R is alkyl, cycloalkyl, C 2-5 alkenyl, C 1-5 haloalkyl, carboxy C 1-5 alkyl, C 1-6 alkanoyl, aryl, carboxy substituted aryl, or aralkyl; RSP1/SP is hydrogen or alkyl; the X radicals are the same or different and signify hydrogen, halogen, alkyl and, taken together, two X radicals on adjacent carton atoms of the benzene ring may be joined to form a hydrocarbylene chain containing 3 or 4 carbons between their points of attachment; m is 1 to 4 and n is 1, 2 or 3, are prepared by the interaction of an appropriate mercaptan, RSH, and an intermediate ester of a 2-nitro-1-alkenylaryloxyalkanoic acid (the intermediate ester is prepared by reacting a primary amine with an ester of a formyl-aryloxyalkanoic acid and subsequently reacting the Schiff-base so formed with a nitroalkane) followed, optionally, by hydrolysis; esters and amides are prepared by standard methods. Alkyl formyl phenoxy-alkanoates (which may be substituted by X m ) are prepared by the interaction of the appropriate nuclear substituted hydroxy-arylaldehyde (obtained by reacting the corresponding phenol with chloroform in the presence of calcium hydroxide and sodium carbonate followed by acidification) and a haloalkanoic acid ester or an appropriately substituted propiolactone in the presence of a base; they may also be prepared by reacting the appropriate phenoxyalkanoic acid ester with formaldehyde and concentrated hydrochloric acid followed by treatment of the product so formed with hexamethylenetetramine. Ethyl-(2,3-dimethylphenoxy)acetate which is obtained by the interaction of 2,3-dimethylphenol and ethyl bromoacetate, is converted to ethyl - (2,3 - dimethyl - 4 - chloromethyl - phenoxy)- acetate by reaction with formaldehyde in the presence of concentrated hydrochloric acid. 3 - (2,3 - Dichloro - 4 -formylphenoxy) propionic acid is obtained from 2,3-dichloro-4-hydroxybenzaldehyde and #-propiolactone in the presence of acid; the corresponding ethyl ester is also described. [2,3 Dichloro - 4 - (1 - phenylthio - 2 - nitropropyl) phenoxy] acetyl chloride is obtained from the corresponding free acid utilizing thionyl chloride. Pharmaceutical preparations showing diuretic and saluretic activity contain as active ingredient compounds (I); administration is orally or by intravenous injection.
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