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‐diazabicyclo2.2.2]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.