Catalyst‐Free Synthesis of Quinazolinone‐Fused Quinoxaline Derivatives under Mild Conditions: Characterization, In Silico Prediction and Biological Evaluation

Abstract Benzoyl indenoquinoxalines (BIQ) were synthesized by the cyclocondensation of 3,4‐diaminobenzophenone with 1,2‐diketone derivatives in the presence of ethanol at room temperature. The reaction protocol is very simple that avoids toxic solvents and catalysts, resulting in a more environmentally friendly synthetic method. Using this method, quinoxaline derivatives as biologically potent molecules are formed with excellent yields in shorter reaction times. Benzoyl indenoquinoxalines synthesized were characterized by using FT‐IR, NMR, and Mass spectral studies. The molecular structures of two selected benzoyl indenoquinoxalines were also confirmed by the single‐crystal X‐ray diffraction method. Moreover, molecular docking study of these compounds showed more effective binding with human epidermal growth factor receptor tyrosine kinase (4HJO). Theoretical calculations at the DFT (BP86/Def2‐TZVP) level supported the experimental findings. The reactivity of the quinoxaline compounds was examined using the global reactivity descriptors and the frontier molecules orbitals (FMOs). The antimicrobial activities of the synthesized quinoxaline compounds against bacterial species such as Streptococcus aureus, Escherichia coli , and Klebsiella pneumoniae in different concentrations reveal notable responses depending on the strain and the concentration of the compounds examined.