Abstract

Background: Spiro compounds are one of the most important organic molecules. Spiro rings such as spiroketals are present in numerous natural products; simple spiroketals are known insect pheromones. A small number of spiro containing drugs has been investigated during the last several decades. New attempts resulted in the incorporation of new synthetic building blocks for Spiro scaffold to facilitate more active drug molecules. Thus, we have redesigned the chemical process for the synthesis of active pharmacological Spiro derivatives in avoiding harmful organic solvent and toxic catalyst under ambient reaction conditions.

Methods: Spiro[furan-2,11'-indeno[1,2-b]quinoxaline]s were prepared through domino one-pot and multicomponent condensation reactions of 2,2-dihydroxy-1,3-indanedione, 1,2-diaminobenzenes, dialkyl acetylenedicarboxylates and alkyl isocyanides in the presence of 1-butyl-3-methylimidazolium tetrafluoroborate ([bmim] BF4) at ambient temperature. The whole of the products constructions were detected by elemental analyses and IR, 1H NMR, 13C NMR, mass spectra.

Results: A range of spiro[furan-2,11'-indeno[1,2-b]quinoxaline] derivatives were synthesized from a variety of substrates under the optimized reaction condition. Different types of dialkyl acetylenedicarboxylate and isocyanide derivatives were examined. All of them gave excellent yields of the desired products under the optimized reaction conditions. Also, we planned to perform the model reaction in the presence of neutral ionic liquids as reusable reaction medium. These results indicated that, in comparison with catalyst free conditions, ionic liquids resulted in a faster reaction with a higher yield. Also, hydrophilic [bmim] BF4 showed better results than hydrophobic [bmim] PF6.

Conclusion: It is noteworthy to mention that a very quick, efficient and eco-compatible process for the synthesis of spiro[furan-2,11'-indeno[1,2-b]quinoxaline]s is explained. These compounds were prepared through domino one-pot and multicomponent condensation reactions of 2,2-dihydroxy-1,3-indanedione, 1,2-diaminobenzene, dialkyl acetylenedicarboxylates and alkyl isocyanides in the presence of 1-butyl-3- methylimidazolium tetrafluoroborate ([bmim] BF4) at ambient temperature. Among the most important advantages of this method is simple work up procedure, excellent yields and high purity with short reaction times using ILs as green recoverable solvents.

Keywords: Alkyl isocyanide, [Bmim] BF4, four-component reaction, ionic liquid, one-pot synthesis, spiro compounds.

Graphical Abstract