GB1026921A - 4-substituted-phenylacrylic acids and derivatives thereof - Google Patents

Abstract

The invention comprises compounds of formula <FORM:1026921/C2/1> wherein R represents a C2-C5 alkyl or C2-C4 alkenyl group, a C3-C7 cycloalkyl group optionally substituted by a methyl group in the 1-position, a C2-C3 alkoxy, an allyloxy or a phenoxy group, and X represents COOR1 wherein R1 is hydrogen or a C1- 4 alkyl group, COOH.B where B is a non-toxic organic base, COOM where M is a single equivalent of a non-toxic metallic cation or the ammonium ion, or CONH2. The free acids may be prepared by (1) reacting an a -keto-phenylacetic acid with a Grignard reagent to give an a -hydroxy-a -phenyl-propionic acid which is then dehydrated by fusion and distillation, (2) conversion of an a -bromo-styrene to a Grignard reagent and reaction of this compound with carbon dioxide, (3) reaction of an a -bromo-styrene with lithium butyl and carbon dioxide, (4) reaction of a phenyl-acetylene with nickel carbonyl in glacial acetic acid, (5) reacting a phenyl-malonic ester with methoxymethyl chloride and treating the a -phenyl-a -methoxy-methyl-malonic ester formed with 50% KOH, or (6) reacting a phenylmalonic acid with dimethylamine and formaldehyde, refluxing the a -dimethylaminomethyl-a -phenyl-malonic acid formed and treating it with hydrochloric acid. The salts may be prepared by neutralizing the acid with an organic or inorganic base. The amides may be prepared by reacting the appropriate acid halide with ammonia. The esters may be prepared by esterification of the free acid, conversion of the free acid to the acid chloride which is then reacted with an alcohol, or by reacting an a -keto-phenylacetic acid ester with a Grignard reagent and dehydrating the resulting a -hydroxy-a -phenylpropionic acid ester by fusion and distillation. Therapeutic compositions, which are useful for the relief of pain, fever and inflammation, and which may be administered orally as capsules, tablets, lozenges, effervescent granules, mixtures, elixirs, syrups or suspensions, topically as ointments, creams or lotions, or parenterally, contain as active ingredient compounds of Formula I above. a -Dimethylqminomethyl-a -4-cyclohexylphenyl-malonic acid is prepared by treating ethyl 4-cyclohexylphenylmalonate with sodium hydroxide, collecting the sodium salt which is then dissolved in water and the solution acidified to give 4-cyclohexylphenylmalonic acid which is reacted with an aqueous solution of dimethylamine and formaldehyde solution.