Discriminating halogen-bonding from other noncovalent interactions by a combined NOE NMR/DFT approach

Herein a combined NOE NMR/DFT methodology to discriminate between adducts held together by halogen bonding (XB) and other noncovalent interactions (non‐XB, such as lone pair/π), based on the determination of the XB donors′ and acceptors′ relative orientation, is proposed. In particular, ¹⁹F,¹H HOESY NMR spectroscopy experiments and DFT calculations on different XB donors, such as perfluorohexyl iodide (I1), iodopentafluorobenzene (I2) and bromopentafluorobenzene (Br), combined with different Lewis bases, such as 1,4‐diazabicyclo[2.2.2]octane (DABCO) and 2,4,6‐trimethylpyridine (Me₃Py), were performed. The results clearly show that in the case DABCO/I1 the XB adduct is practically the only one present in solution, whereas for the other pairs a certain amount of non‐XB adduct is present. Combining DFT and HOESY results, the amount of non‐XB adducts can be roughly quantified under our experimental conditions as 4 % for DABCO/I2, between 10 and 20 % for Me₃Py/I1 and Me3Py/I2, and 44 % for DABCO/Br.