Facile Synthesis and Characterization of a Bromine-Substituted (Chloromethyl)Pyridine Precursor towards the Immobilization of Biomimetic Metal Ion Chelates on Functionalized Carbons

Multidentate ligands involving tethered pyridyl groups coordinated to transition metal ions have been frequently used mimic the 3-histidine (3H), 2-histidine-1-carboxylate (2H1C) brace motifs or other combinations of histidine and carboxylate endogenous ligating residues found in bioinorganic metalloenzymes. It is interest immobilize these ligand chelates onto heterogeneous supports. This, however, requires use bromine-substituted (chloromethyl)pyridines, whose current synthetic routes involve extremely pyrophoric chemicals, such as n-butyllithium that require cryogenic reaction conditions, toxic thionyl chloride, are challenging handle extensive hazard controls. Herein, we report alternative methodologies towards syntheses 2-bromo-6-hydroxymethylpyridine 2-bromo-6-chloromethylpyridine from inexpensive commercially available 2,6-dibromopyridine using isopropylmagnesium chloride lithium complex (Turbo Grignard) cyanuric which easier milder conditions than conventional reagents. Gas chromatography-mass spectrometry (GC-MS) methods were developed simple 1H- 13C- nuclear magnetic resonance (NMR) Fourier-transform infrared (FT-IR) spectroscopies also monitor conversion both steps showed products could be obtained isolated through workups without presence unreacted starting material undesired overchlorinated 2-chloro-6-chloromethylpyridine side product.