Spin Trapping of Carbon-Centered Ferrocenyl Radicals with Nitrosobenzene

In contrast to metal centered 17 valence electron radicals, such as [Mn(CO)(5)](center dot), ferrocenium ions [Fe(C5H5)(2)](+) (1(+)), [Fe(C5Me5)(2)](+) (2(+)), [Fe(C5H5)(C5H4Et)](+) (3(+)), [Fe (C5H5)(C5H4NHC(S)Me)](+) (4(+)), and [Fe(C5H5)(C5H4NHC(S)Me)](+) (5(+)) do not add to nitrosobenzene PhNO to give metal-coordinated stable nitroxyl radicals. In the presence of the strong and oxidatively stable phosphazene base tert-butylimino-tris (dimethylamino)-phosphorane, the quite acidic ferrocenium ions 1(+)-5(+) are deprotonated to give a pool of transient and persistent radicals with different deprotonation sites [1-HTx](center dot)-[5-H-x](center dot). One rather persistent iron-centered radical [4-H-N](center dot), deprotonated at the nitrogen atom, has been detected by rapid-freeze EPR spectroscopy at 77 K. This iron-centered radical [4-H-N](center dot) is also inert toward PhNO. The transient carbon-centered radicals [1-H-x](center dot) -[5-H-x](center dot) appear to rapidly abstract hydrogen atoms from the adjacent base or the solvent to regenerate the corresponding ferrocenes 1-5. These transient radicals are only present in trace amounts (<1%). However, some of the transient carbon-centered radicals in the radical pool can be trapped by 1-1.2 equiv of PhNO, even at room temperature. The corresponding resulting stable nitroxyl radicals [6](center dot)-[10](center dot) were studied by EPR spectroscopy at room temperature and at 77 K. The hyperfine coupling pattern to protons close to the spin center allows one to assign the site of PhNO attack in radicals [6](center dot)-[10](center dot), namely, at the C5115 ring in [6](center dot), [9(Cp)](center dot), and [10(Cp)](center dot), at a methyl group in [7](center dot), and at the methylene group in [8(1)](center dot). These studies give a deeper insight into the stability and reactivity of radicals derived from ferrocene derivatives which might also be relevant for the biological activity of high-potent antitumor and antimalaria ferrocene-based drugs and prodrugs such as ferrocifen or ferroquine.