Abstract

Aim: The study aimed to synthesize chromeno-pyrazolo[1,2-b]phthalazine-6,9,14(7H)-trione analogs with the help of silica-supported bismuth nitrate catalyst.

Background: Nitrogen-containing heterocyclic compounds are widespread, and their applications to pharmaceuticals, agrochemicals, and functional materials are becoming more and more important. Pyrazoles are an important class of compounds for new drug development, as they are the core structure of numerous biologically active compounds, including blockbuster drugs such as celecoxib, viagra, pyrazofurine, and many others. Similarly, heterocycles containing a phthalazine moiety are of current interest due to their pharmacological and biological activities; for example, pyrazolo[1,2-b]phthalazinedione is described as an anti-inflammatory, analgesic, antihypoxic, and antipyretic agent.

Objective: In continuation of our ongoing investigation for the synthesis of efficient and simple approaches for the preparation of heterogeneous catalysts, herein we wish to disclose a highly efficient, simple, and one-pot synthesis of chromeno-pyrazolo-phthalazine derivatives via a one-pot multi-component reaction between 4- hydroxycoumarin, aromatic/heterocyclic aldehydes and 2,3-dihydro-1,4-phthalazinedione using silica-supported bismuth nitrate as an inexpensive, environmentally friendly and reusable catalyst under solvent-free conditions.

Materials and Methods: Microanalytical data (C, H, and N) were collected on Carlo Erba analyzer model 1108. The microwave synthesis was performed in Anton Paar, Monowave 300 microwave synthesizer. Melting points were measured in open glass capillaries in the Kofler apparatus and are uncorrected. Spectroscopic data were obtained using the following instruments: Fourier transform infrared spectra (KBr discs, 4000-400 cm^-1) by Shimadzu IR-408 Perkin-Elmer 1800 instrument; ¹H NMR and ¹³C NMR spectra by Bruker Avance-II 400 MHz using DMSO-d₆ as a solvent containing TMS as the internal standard. Mass spectra were set down on a JEOL D-300 mass spectrometer.

Results: In continuation of our ongoing studies to synthesize heterocyclic and pharmaceutical compounds by mild, facile, and efficient protocols, herein we wish to report our experimental results of the synthesis of chromeno- pyrazolo-phthalazine derivatives under solvent-free condition derivatives, using various aromatic/heterocyclic aldehydes in the presence of silica-supported bismuth nitrate catalyst. The prepared catalyst was characterized by various physical and chemical techniques.

Conclusion: We have demonstrated an efficient reaction path for the synthesis of new aryl and heteroaryl chromeno-pyrazolo[1,2-b]phthalazine-6,9,14(7H)-trione by one-pot three-component condensation of aryl/ heteroaryl aldehydes, 2,3-dihydro-1,4-phthalazinedione and 4-hydroxy coumarin using silica-supported bismuth nitrate (SSBN) under microwave irradiation. The scheme not only offers the use of microwave at low temperatures and significant yield of products but also affords mild reaction conditions, without harmful solvent, shorter reaction times, high purity, operational simplicity, and easy workup.

Keywords: BiNO₃/SiO₂, Heterogeneous Lewis acid catalyst, Chromeno-pyrazolo[1 2-b] phthalazine-6 9 14(7H)-trione derivatives, Knoevenagel condensation, Michael reaction, bismuth nitrate.

Graphical Abstract