Synthesis of N-ferrocenyl isonicotinamide and Characterization of Its Adduct with Co(salen)
Authors:Bryan BBrautigam, William Farnsworth, Eric McDonald, Eric Patterson, Guang Wu
Mentor:Steven Contakes, Professor of Chemistry, Westmont College
We are currently investigating the preparation and oxygen reactivity of ferrocene (Fc)-modified CoIIsalen complexes in an attempt to prepare synthetic mimics of the liver detoxification enzyme cytochrome P450. In the present work we prepared and structurally characterized the axial ligand N-ferrocenyl Isonicotinamide and studied its ability to act as an axial ligand in Co(salen) complexes. The synthesis of N-ferrocenyl isonicotinamide was accomplished in 61% yield by coupling isonicotinic acid and aminoferrocene with HOBt/EDC and in 28% by refluxing isonicotinoyl chloride, aminoferrocene, and dry Et3N in CH2Cl2. UV-vis and ESI-MS studies indicate that N-ferrocenyl isonicotinamide reversibly forms a 1:1 adduct with [Co(salen)] under anaerobic conditions in dry CH2Cl2. ESI-MS studies and the dependence of [Co(salen)(pyCONHFc)]’s UV spectrum on concentration indicate that the resulting adduct, [Co(salen)(pyCONHFc)], forms the noncovalent dimer [Co(salen)(pyCONHFc)]2 in CH2Cl2 with a Kd ~ 77 mM. Studies of the concentration-dependence of [Co(salen)(pyCONHFc)]’s oxygen-reactivity indicate that the monomer is oxygen reactive while the dimer is not. Dilute solutions of [Co(salen)(pyCONHFc)] react rapidly with oxygen. In contrast, air-exposed solutions of 0.396 mM [Co(salen)(pyCONHFc)] in CH2Cl2,,which largely consists of the dimer, only react slowly with oxygen over a period of days. UV spectra indicate that the likely product is a k1 superoxide-containing [Co(salen)(O2)(pyCONHFc)] complex. However, bands consistent with both k1 superoxide and a m2-peroxide are present in the IR spectrum. After ~3 days the initial oxygenation product decomposes to give an insoluble brown precipitate we suspect to be [Co(salen)(pyCONHFc)]2(O2) in a zeroth order reaction with an apparent rate constant of 8.8 x 10-6 M/hr. The same or a similar species is formed when solvent is removed from solutions of [Co(salen)(O2)(pyCONHFc)] and the resulting residue is exposed to vacuum.