SYNTHESIS OF 5-SUBSTITUTED 1-ARYL-1H-PYRAZOLE-4-ACETONITRILES, 4-METHYL-1-PHENYL-1H-PYRAZOLE-3-CARBONITRILES AND PHARMACOLOGICALLY ACTIVE 1-ARYL-1H-PYRAZOLE-4-ACETIC ACIDS

Lithium aluminum hydride reduction of 5-substituted or unsubstituted e thyl or methyl 1-aryl-1H-pyrazole-4-carboxylates gave, generally in ex cellent yields, 5-substituted or unsubstituted 1-aryl-1H-pyrazole-4-me thanols which afforded the corresponding 1-aryl-4-(bromomethyl)-1H-pyr azoles with hydrobromic acid in acetic acid solution. These crude inte rmediates gave by reaction with potassium cyanide in dimethylsulfoxide solution 1-aryl-1H-pyrazole-4-acetonitriles only in the case of 5-uns ubstituted compounds, otherwise mixtures of 5-substituted I-aryl-1H-py razole-4-acetonitriles and 4-methyl-1-phenyl-1H-pyrazole-3-carbonitril es were generally obtained. Acetonitriles IIIa,b,i,l gave in excellent yields the corresponding 1-aryl-1H-pyrazole-4-acetic acids Va,b,i,l b y alkaline hydrolysis. Compounds Vb,i,l showed in the writhing test ap preciable analgesic properties, associated with low acute toxicity; mo reover, compound Vl exhibited a statistically significant antiinflamma tory activity in the carrageenan-induced edema assay.