Evaluation of 6‐Halogenated 2‐Pyridone Moieties as Halogen Bond Donors

Abstract

In memory of Klaus Hafner.6-Halo-2-pyridones and their pyridol tautomers show different grades of polarization on their halogen substituents in DFT calculations. This and the fact that the tautomeric equilibrium is affected by the surrounding medium make them interesting candidates for a new platform of halogen bond donors. We therefore probed four simple halopyridones for their halogen bonding properties both in the solid state and in solution.Concurring with hydrogen bonding, halogen bonding indeed is found to be an interaction governing the packing motif in pyridone crystals, which is more pronounced in N-methylated congeners. Solution studies using a halide abstraction reaction, and NMR titrations against bromide salts, however, showed no clear evidence for halogen bonding in solution.[a] M.

Intrinsic bond strength index as a halogen bond interaction energy predictor

“…protein–ligand) and thus, we are still far from taking full advantage of XBs in the rational design of new systems, 19–21 even though various potential applications are constantly emerging. 22–25 There have been attempts to overcome this challenge and provide a solid basis for designing new halogen-bonded structures, 8,21,26–28 but accurate modelling of XBs is still not straightforward. This issue is paramount given the increased attention put on XBs and and their broad application in catalysis, 19,29–32 material design, 33–35 supramolecular 36–38 and medicinal 39–41 chemistry, among other areas.…”

Order versus Disorder in the Cocrystals of m-Halogenopyridines with m-Halogenobenzoic Acids: The Effects of the I···O Halogen Bond

“…However, a number of “traditional” hydrogen-bonded synthons have been demonstrated to be able to coexist with halogen bonds. For instance, 2-pyridone, 2-aminopyrazine, and pyridylamide homosynthons frequently serve as acceptors in combinations with perhalogenated benzenes as halogen bond donors, while introduction of the halogen atom in such molecules can result in one-component solids, whose crystal structures include both types of interactions. ,, …”

“…For instance, 2-pyridone, 18 2-aminopyrazine, 19 and pyridylamide 20 homosynthons frequently serve as acceptors in combinations with perhalogenated benzenes as halogen bond donors, while introduction of the halogen atom in such molecules can result in one-component solids, whose crystal structures include both types of interactions. 19,21,22 One of the classical hydrogen-bonded synthons, which could expectedly be particularly sensitive to competition between halogen and hydrogen bonds, is the carboxylic acid−pyridine synthon, since the pyridine nitrogen is also an excellent halogen bond acceptor, which reliably forms strong halogen bonds with "classical" strong halogen bond donors such as perfluorinated halogenocarbons, 23−29 iodoacetylides, 30−33 and haloimides. 34−37 This problem has been successfully overcome by asymmetric polytopic acceptors, which could bind selectively a carboxyl group via an HB and a halogen atom via an XB to different binding sites.…”