Halogen Bonding in N‐Alkyl‐Bromo‐/Lodo‐Pyridinium Salts and its Application in Chromatography

The alkylation of 3‐/4‐bromo‐ and ‐iodopyridine with methyl triflate smoothly affords the corresponding N‐methylpyridinium triflate salts. An anion exchange with NaI or [PPh4]Y (Y=Cl, Br, I) yields the corresponding halide salts. Most of them could be structurally characterized and their strong halogen bonds were investigated. While the halogen atom of 4‐halogenopyridinium is susceptible to nucleophilic substitution, 3‐halogenopyridinium ions are far more stable against nucleophilic attacks. Due to the comparable interaction strength of halogen bonds and hydrogen bonds, the latter of which is widely used in chromatography, the potential of 3‐halogenopyridinium moieties for an application in chromatography is obvious and was successfully employed in affinity chromatography of different proteins. Para‐ and meta‐halogenated pyridinium cations exhibit a high propensity for halogen bonding towards their anions, which we demonstrated by x‐ray crystallography and quantum‐chemical calculations. Due to the high stability of the meta‐halogenated derivatives against nucleophilic attack and even 0.1 M NaOH, the 3‐iodopyridinium moiety was grafted onto a polymer and successfully employed in affinity chromatography of different proteins.