A Comprehensive Study of the Synthesis, Spectral Characteristics, Quantum-Chemical Molecular Electron Density Theory, and In Silico Future Perspective of Novel CBr-Functionalyzed Nitro-2-Isoxazolines Obtained via (3 + 2) Cycloaddition of ()-3,3,3-Tribromo-1-Nitroprop-1-ene.

The search for new heterocyclic compounds with biological potential is one of the current challenges in modern chemistry. Therefore, the comprehensive study of (3 + 2) cycloaddition (32CA) reactions between a series of aryl-substituted nitrile N-oxides (NOs) and ()-3,3,3-tribromo-1-nitroprop-1-ene (TBNP) is carried out. According to the experimental research, in all tested 32CAs, the proper (4,5)-3-aryl-4-nitro-5-tribromomethyl-2-isoxazolines are obtained as only one reaction product. In turn, the quantum-chemical MEDT study shows that the creation of heterocycles occur via the polar attack of zwitterionic moderate-nucleophilic NOs to strong electrophilic TBNP. The reactions are realized according to a two-stage, one-step asynchronous mechanism, in which the formation of the O-C(CBr) bond takes place once the C-C(NO) bond is already formed. What is more, the computational analysis confirmed the experimental results. At the end, the obtained 2-isoxazolines were docked to three proteins: gelatinase B, cyclooxygenase COX-1, and Caspase-7. We hope that the presented study will be helpful for searching for the future direction of application for this class of organic compounds.