Conclusions
In conclusion, this study takes advantage of our previous work on 1,3-dipolar cycloaddition where we synthesized 36 novel polyheterocyclic 1,2,4-oxadiazolindolone compounds by a one-step reaction.31 The 6-31G(d) basis set and B3LYP, M052X, M062X, and APFD functionals were used to optimize the geometries and determine the vibrational frequencies of 5 reactants, 5 intermediates, and 36 products. The results showed symmetry matching between the LUMO of substituted chloroxime compounds and HOMO of substituted isatin in the LUMO-controlled reaction. Furthermore, the presence of a phenyl group in chloroxime is more conducive to the reaction because an electron-withdrawing substituent on the phenyl group can reduce the LUMO energy level of the reactant and thus facilitate the reaction. When isatin is substituted with an electron-donating group, the HOMO energy level increases, which is also beneficial to the reaction. In this study, the applicability of the B3LYP functional to this system was determined, and the reaction mechanism was discussed at the B3LYP/6-31G(d) level. The three main elementary reactions and corresponding transition states, TS1, TS2, and TS3, in the liquid and gas phases were calculated and discussed. Using the IRC method, the accuracy of the transition states was confirmed, and the advantages and disadvantages of LQA, HPC, and GS2 in producing the IRC were compared. HPC produced an IRC curve with higher accuracy, and the two ends of the curve were closer to the structure of the product. The reaction process was calculated. Finally, by comparing the ΔE avalues for the gas- and liquid-phase reactions, it was proven that the solvent only has a minor effect on the reaction process. This study is expected to have a long-term significance by providing useful ideas for the design of more effective drugs of this kind in the future.
ASSOCIATED CONTENT
Supporting Information .
The following files are available free of charge.
The specific experimental steps, the energy difference between the lowest unoccupied molecular orbital (LUMOs) and the highest occupied molecular orbital (HOMOs) of the reactants at different levels, the ΔG of each reaction in the gas phase at different levels. And the Cartesian coordinates (Å) of the optimal structure of the fixed point in the liquid phase reaction can be seen in the attachment support information. (file type, i.e., PDF)
Notes
The authors declare no competing financial interest.