Azine Steric Hindrances Switch Halogen Bonding to N-Arylation upon Interplay with σ-Hole Donating Haloarenenitriles

An interplay between 4-bromo- and 4-iodo-5-nitrophthalonitriles (XNPN, X=Br or I) and any one of the azines (pyridine 1, 4-dimethylaminopyridine 2, isoquinoline 3, 4-cyanopyridine 4, 2-methylpyridine 5, 2-aminopyridine 6, quinoline 7, 1-methylisoquinoline 8, and 2,2'-bipyridine 9) proceeds differently depending on steric and electronic effects of the heterocycles. Sterically unhindered azines 1-3 underwent N-arylation to give the corresponding azinium salts (characterized by H-1 and C-13{H} NMR and high-resolution ESI-MS). In contrast, azines 4-9 with sterically hindered N atoms or bearing an electron-withdrawing substituent, form stable co-crystals with XNPN, where two interacting molecules are bound by halogen bonding. In all obtained co-crystals, X....N structure-directed halogen bonds were recognized and theoretically evaluated including DFT calculations (PBE0-D3/def2-TZVP level of theory), QTAIM analysis, molecular electrostatic potential surfaces, and noncovalent interaction plot index. Estimated energies of halogen bonding vary from -7.6 kcal/mol (for 6 center dot INPN) to -11.4 kcal/mol (5 center dot INPN).

Automated summary

The reaction between XNPN and various azines proceeds differently based on the steric and electronic effects of the heterocycles. Sterically unhindered azines undergo N-arylation to form azinium salts, while sterically hindered or electron-deficient azines form stable co-crystals with XNPN through halogen bonding. The halogen bonds in the obtained co-crystals were analyzed and evaluated using various techniques, with estimated energies ranging from -7.6 kcal/mol to -11.4 kcal/mol.