On Integral INICS Aromaticity of Pyridodiazepine Constitutional Isomers and Tautomers

The structure, energetics, and aromaticity of c.a. 100 constitutional isomers tautomers pyrido[m,n]diazepines (m = 1, 2; n 2, 3, 4, 5; m ≠ n) were studied at the B3LYP/cc-pVTZ level. pyrido[1,3]diazepines appear most, while pyrido[2,4]diazepines are least stable (ca. 26 kcal/mol). In pyrido[1,n]diazepine group (n 2–5), [1,5] higher in energy by ca. 4.5 kcal/mol [1,4] ones 7 kcal/mol, pyrido[1,2]diazepines 20 All most pyrido[1,n]diazepines have N-atoms near ring’s junction bond but on opposite sites. [2,n]-forms also those with pyridine ring N6-atom bond. Surprisingly, for [1,2]-, [1,3]-, [1,4]-isomer condensation types diazepine rings, same N9 > N7 N6 N8 stability pattern obeys. remains similar a water medium simulated Polarizable Continuum Model solvent is conserved when calculated using CAM-B3LYP or BHandHlyp functionals. pyridine[m,n]diazepines was established based integral INICS index resulting from NICSzz-scan curves’ integration. physically justified through its relation to ringcurrent as demonstrated Berger, R.J.F., et al. Phys. Chem. 2022, 24, 624. six-membered pyrido rings negative INICSZZ indices can be aromatic only if they not protonated N-atom. seven-membered exhibit meaningful positive values assigned antiaromatic. However, some non-protonated substantial A weak linear correlation (R2 0.72) between I(6) I(7) exists consequence communication π-electron systems two rings. juxtaposition descriptor six- diverse electron density parameters Ring Critical Points (RCP) revealed good correlations Electrostatic Potentials electrons nuclei (ESPe ESPn). relationships other RCP like Laplacian, total energy, Hamiltonian form kinetic split into parts: one nearly constant linearly correlating Thus, pyridodiazepines practically do change type labile proton position. contrast, display changes antiaromatic structural modifications.