Catalytic activity of HKUST-1 for the synthesis of fused N-heterocycles under microwave irradiation and studies of their in vitro anti-bacterial and anti-tubercular activities

Abstract

Strategies facilitating the synthesis of heterocycles using green methodologies have modernized their syntheses in synthetic and pharmaceutical chemistry. In the present study, a highly well-organized, eco-friendly and straightforward synthetic approach was developed for the microwave-assisted synthesis of fused pyrazolopyridines and spirooxindole-fused pyrazolopyridines using an economical metal–organic framework, HKUST-1, in ethanol. The prepared MOF was characterized through diverse techniques, including FT-IR, p-XRD, SEM, TEM, EDX, TGA and BET. This approach shows noteworthy advantages, such as good yields, simple and clean reaction conditions, shorter reaction time, use of a highly efficient and sustainable catalyst and no chromatographic separation as the entire products can be purified through recrystallization. Moreover, green chemistry metrics for compounds 4a, 6a, 8a and 9a were calculated and were found to be very close to ideal values. The TON and TOF of the catalyst reached 32.75 and 3.27 min⁻¹, respectively, for this transformation. In vitro anti-bacterial screening of these synthesized derivatives was performed against the Gram-negative bacteria Escherichia coli (E. coli) and Gram-positive bacteria Staphylococcus aureus (S. aureus). Compounds 4a and 6f showed activity against all the bacteria tested in the experiment. Further, the anti-tubercular study of the synthesized compounds revealed that compound 4b had the highest activity among all the synthesized derivatives.