Background: The development of novel synthetic methods for the synthesis of structurally
diverse drug-like molecules with environmentally friendly solvents and catalysts is significant in the
development of drug discovery research. The synthesis of fused heterocycles has attracted considerable
interest because the fusion of biologically active heterocyclic systems has proved to be an attractive and
useful approach for designing potential drugs with a wide spectrum of pharmacological activities. Multicomponent
reactions with their highly convergent characteristics offer an opportunity to provide druglike
small molecules with structural diversity and molecular complexity. The present synthetic protocol
involves the tandem reaction of hydrazine hydrate, 3-aminocrotononitrile, isatins and carbonyl compound
using GAAS as environmentally benign and sustainable catalytic solvent.
Method: spirooxindoles spiroannulated with indenopyrazolopyridine, chromenopyrazolopyridine, and
pyranopyrazolopyridine have been synthesized by multicomponent reaction of hydrazine hydrate, 3-
aminocrotononitrile, cyclic 1,3-diketones, and substituted isatines in the presence of gluconic acid
aqueous solution (GAAS, 50 wt%) as catalytic solvent.
Results: we have presented diversity oriented efficient and environmentally benign synthetic protocol
for the synthesis of structurally diverse spiroannulated pyrazolo[3,4-b]pyridines using gluconic acid
aqueous solution (GAAS, 50%, wt%) as an inexpensive and eco-friendly bio-based catalytic solvent.
Conclusion: The operational simplicity with mild reaction conditions, shorter reaction times, excellent
product yields and environmentally benign reaction conditions with reusability of catalytic solvent render
the present protocol both attractive and economically viable for the synthesis of medicinally privileged
spiroannulated heterocycles. We believe that the present work will contribute considerably not
only to the chemical research, but also to the medicinal research.