Regioselective Synthesis of 1,3,5-Trisubstituted Pyrazoles Containing an Anthranilic Acid Motif

An effective method was developed for the synthesis of 1,3,5-trisubstituted pyrazoles by using acetylenic ketones, obtained from ethyl 5-ethynylanthranilate, in reactions with substituted hydrazines and hydrazides. It was shown that the cyclization of ethyl 5-(3-aryl-3-oxopropinyl)- anthranilates with arylhydrazines proceeded regioselectively and led to the formation of 1,3,5-trisubstituted pyrazoles containing an anthranilate moiety at the position C-3. Significant deterioration of regioselectivity was observed in the reactions of ethyl 5-(3-aryl-3-oxopropinyl)anthranilates with N-methyl- and N-tert-butylhydrazines. The initial products formed in reactions of ethyl 5-[3-(4-fluorophenyl)-3-oxopropinyl]anthranilate with benzoyl and isonicotinoyl hydrazides were 5-hydroxypyrazolines, which underwent dehydration in the presence of pyridine and thionyl chloride in benzene, giving the respective 1,3,5-trisubstituted pyrazoles.