2,2’-bipyridine ligands incorporated into ruthenium complexes have proven to be versatile in many areas. These complexes can assist in disrupting mitochondrial membranes associated with bladder cancer and their extensive conjugated system shows strong photovoltaic activity. However, these widely used ligands become increasingly expensive once the rings are substituted. Ring substitution with traditional EAS reactions is not feasible due to the poor nucleophilicity of these nitrogen-containing rings; however, it does support their participation in metal-mediated homo-coupling reactions.
The purpose of this study is to determine the most economical and efficient way to synthesize functionalized bipyridine adducts for future incorporation into ruthenium complexes. This goal will be achieved by comparing two distinct approaches. The first method focuses on using several disubstituted 2-bromopyridine substrates in homo-coupling reactions to create functionalized bipyridines, although these reactions require long reactions times. The second route relies on utilizing unsubstituted 2,2’-bipyridine, and then functionalizing it in a symmetrical pattern using a microwave synthesizer, to drastically shorten the reaction times.
The first mode utilizes deactivating groups on 2-bromopyridines, as prior studies done in our lab indicated they facilitate palladium catalyzed homo-coupling more efficiently. Thus, the efficiency of two catalysts, Pd[PPh₃]₄ and PdCl₂(PPh₃)₂, will be compared with each the following substrates: 2-bromo-6(1H-pyrazol-1-yl)-pyridine, methyl-6-bromopyridine carboxylate, 5-acetyl-2-bromopyridine, 2-bromopyridine-5-carboxaldehyde, and 6-bromo-2-pyridinecarbonitrile. Reactions are assembled and carried out under inert gas environment, using glovebox assembly and a Schlenk-line manifold for the duration. After 12-24h, product isolation is completed with a CombiFlash Rf 2000 Automated Flash Chromatography System.
The second mode requires the development of a novel microwave synthesis protocol to brominate unsubstituted 2,2’-bipyridines using an Anton Paar Microwave Reaction System. Based on the nitrogen’s directing effect, we expect bromination to occur at the 5,5’-positions, while considering a potential 3,3’-dibromination as well. Dibrominated bipyridines will then undergo a hetero-coupling process with pyrazole or thiophene rings to extend the conjugated framework of the ligand. Products will be characterized by ¹H-NMR in both modes.

Cameron Martinez

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