Synthesis of pyrazolo-enaminones, bipyrazoles and pyrazolopyrimidines and evaluation of antioxidant and antimicrobial properties

Abstract

• New pyrazolo-enaminones have been synthesized in three steps from DHA in good yields. • The pyrazolo-enaminone 3h shows antioxidant properties comparable to Vitamin C. • Pyrazolopyridines were prepared by double condensation of the aminopyrazoles with keto-esters. • The pyrazoles 3b , 3d , 3e and the pyrazolopyridine 4b showed activity against Gram+ and Gram− bacteria. A novel pyrazolo-enaminones, bipyrazoles and bipyrazolopyridines from 1-(5-hydroxy-3-methyl-1-phenyl-1 H -pyrazol-4-yl)butane-1,3-dione and 4-methyl-2-phenyl-2 H -pyrazolo[3,4- b ]pyridine-3,6(3 aH ,7 H )-dione have been synthesized by assisted heating with microwave radiation without any catalyst. The pyridine and pyrazole ring formation has been developed from easily accessible enamino keto esters by formylation followed by intramolecular cyclization. The general applicability for the synthesis of the important pyrazolo-enaminones, bipyrazoles and pyrazolo-pyridines heterocycles was attributed to simplicity of operation, synthesis without catalyst, energy efficiency (shorter reaction time under microwave irradiation), good yields, more environmentally friendly and more cost-effective procedure. The antioxidant activity of new heterocyclic compounds was evaluated by free radical scavenging by DPPH assay. Several of these compounds showed good activity against both Gram-positive ( S. aureus ) and Gram-negative ( E. coli ) bacteria.