Green Synthesis of Fused Chromeno-pyrazolo-phthalazine Derivatives with Silicasupported Bismuth Nitrate under Solvent-free Conditions
Authors: Aslam Afroz , Parveen Mehtab , Singh Kushvendra , Azeem Mohammad 
Published: December 2020

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.

Material 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.