SYNTHESIS AND CHARACTERIZATION OF 2-(SUBSTITUTED ARYL)-3, 3a-DIHYDRO-8H-PYRAZOLO [5,1'-a] ISOINDOL-8-.ONES VIA CHALCONE BASED N-FORMYL-PYRAZOLINES

Abstract

N-formyl-pyrazoline is the central intermediate in the biogenesis of naturally occurring pyrazoloisoindole derivatives and a useful material in the laboratory synthesis. These derivatives (N-formyl-pyrazoline and pyrazoloisoindoles) were displayed many interesting biological properties, such as hypoglycemic, antimicrobial, amoebicidal, antibacterial, antipyretic, and analgesic activities. An alternate synthetic approach of 2-(substituted aryl)-3,3a-dihydro-8H-pyrazolo [5,1-a] isoindol-8-ones via chalcone based N-formyl-pyrazolines is described. N-formyl-pyrazolines (lb-15b) were prepared in excellent yield (81-96%) by the reaction of chalcones (la-15a) with hydrazine hydrate in presence of formic acid, which undergoes intramolecular Friedal-Craft acylation in the presence of trifluoroacetic acid (TFA) as a catalyst to afford functionalized 2-(substituted phenyl)-3,3a-dihydro-8H-pyrazolo[5,1--a]isoindol-8-one (3c-15c) in good to excellent yield (74-94%) at refluxed in acetonitrile. Our synthetic route avoids expensive reagents and significantly improved the yield.