A REGIOSELECTIVE ROUTE TO 3-ALKYL-1-ARYL-1H-PYRAZOLE-5-CARBOXYLATES - SYNTHETIC STUDIES AND STRUCTURAL ASSIGNMENTS

Ethyl 2,4-dioxooctanoate (1) was selectively protected as the 2-(methoxyimino) derivative 2. When 2 was reacted with phenylhydrazine hydrochloride, ethyl 3-butyl-1-phenyl-1H-pyrazole-5-carboxylate (4) was favored over the corresponding 5-butyl-1-phenyl-1H-pyrazole-3-carboxylate product 5 by a ratio of at least 6:1, a complete reversal of the regioselectivity observed for 1. The structures of 4 and 5 were assigned definitively by NOE difference experiments. Regiochemical and configurational assignments of the mono- and bis(methoxyimino) derivatives of 1 were also achieved by ID and 2D H-1 and C-13 nmr methods.