Strong N−X···O−N Halogen Bonds: Comprehensive Study on N‐Halosaccharin Pyridine N‐oxide Complexes

A detailed study of the strong N−X⋯−O−N+ (X = I, Br) halogen bonding interactions in solution and in the solid‐state reports 2×27 donor×acceptor complexes of N‐halosaccharins and pyridine N‐oxides (PyNO). Density Functional Theory (DFT) calculations were used to investigate the X···O halogen bond (XB) interaction energies in 54 complexes. The XB interaction energies were found to vary from –47.5 to –120.3 kJ mol–1, with the strongest N−I⋯−O−N+ XBs approaching those of 3‐center‐4‐electron [N–I–N]+ halogen‐bonded systems (∼160 kJ mol–1). Using a subset of 32 complexes, stabilized only through N−X···−O−N+ XB interactions, a simplified, computationally fast, electrostatic model to predict the X···O bond energies, was developed. Energies predicted by this simple model and much higher‐level theory DFT calculations agree excellently, illustrating the usefulness of the simplified electrostatic model. In solution, the 1H NMR association constants (KXB) determined in CDCl3 and acetone‐d6 vary from 2.0 x100 to >108 M‐1 following accurately the calculated σ‐hole nature on the donor halogen. The donor×acceptor complexation enthalpies calculated in CHCl3 using polarized continuum model very between –38.4 and –77.5 kJ mol–1 and correlate well with the pKXB values determined by 1H NMR in CDCl3 indicating the formation of strong and robust 1:1 XB complexes in solution. In X‐ray crystal structures, the N‐iodosaccharin‐PyNO complexes manifest short normalized interaction ratios (RXB) between 0.65 – 0.67 for the N−I⋯−O−N+ halogen bond.