Synthesis of 5‐substituted 1‐aryl‐1<i>H</i>‐pyrazole‐4‐acetonitriles, 4‐methyl‐1‐phenyl‐1<i>H</i>‐pyrazole‐3‐carbonitriles and pharmacologically active 1‐aryl‐1<i>H</i>‐pyrazole‐4‐acetic acids

Abstract

Abstract Lithium aluminum hydride reduction of 5‐substituted or unsubstituted ethyl or methyl 1‐aryl‐1 H ‐pyrazole‐4‐carboxylates gave, generally in excellent yields, 5‐substituted or unsubstituted 1‐aryl‐1 H ‐pyrazole‐4‐methanols which afforded the corresponding 1‐aryl‐4‐(bromomethyl)‐1 H ‐pyrazoles with hydrobromic acid in acetic acid solution. These crude intermediates gave by reaction with potassium cyanide in dimethylsulfoxide solution 1‐aryl‐1 H ‐pyrazole‐4‐acetonitriles only in the case of 5‐unsubstituted compounds, otherwise mixtures of 5‐substituted 1‐aryl‐1 H ‐pyrazole‐4‐acetonitriles and 4‐methyl‐1‐phenyl‐1 H ‐pyrazole‐3‐carbonitriles were generally obtained. Acetonitriles IIIa,b,i,l gave in excellent yields the corresponding 1‐aryl‐1 H ‐pyrazole‐4‐acetic acids Va,b,i,l by alkaline hydrolysis. Compounds Vb,i,l showed in the writhing test appreciable analgesic properties, associated with low acute toxicity; moreover, compound VI exhibited a statistically significant antiinflammatory activity in the carrageenan‐induced edema assay.