Diverse and unexpected outcomes from oxidation of the platinum(II) anticancer agent [Pt{(p-BrC₆F₄)NCH₂CH₂NEt₂}Cl(py)]...

Oxidation of the anti-tumour agent [Pt{(p-BrC₆F₄)NCH₂CH₂NEt₂}Cl(py)], 1 (py = pyridine) with hydrogen peroxide under a variety of conditions yields a range of organoenamineamidoplatinum(II) compounds [Pt{(p-BrC₆F₄)NCH=C(X)NEt₂}Cl(py)] (X = H, Cl, Br) as well as species with shared occupancy involving H, Cl and Br. Thus, oxidation of the -CH₂-CH₂- backbone (dehydrogenation) occurs, often accompanied by substitution. Oxidation of 1 with H₂O₂ in acetone yielded 1:1 co-crystallized [Pt{(p-BrC₆F₄)NCH=CHNEt₂}Cl(py)], 1H and [Pt{(p-BrC₆F₄)NCH=C(Cl)NEt₂}Cl(py)], 1Cl. The former was obtained pure in low yield from the oxidation of 1 with (NH₄)₂[Ce(NO₃)₆] in acetone, and the latter was obtained from 1 and H₂O₂ in CH₂Cl₂ at near reflux. From the latter reaction under vigorous refluxing [Pt{(p-BrC₆F₄)NCH=C(Br)NEt₂}Cl(py)], 1Br was isolated. In refluxing acetonitrile, oxidation of 1 with H₂O₂ yielded [Pt{(p-BrC₆F₄)NCH=C(H₀.₂₅Br_0.75)NEt₂}Cl(py)], 1H_0.25Br_0.75, in which the alkene is mainly substituted by Br in a dual occupancy. Treatment of 1 with H₂O₂ and tetrabutylammonium hydroxide in acetone at room temperature formed [Pt{(p-HC₆F₄)NCH₂CH₂NEt₂}Cl(py)], 2. Oxidation of [Pt{(p-HC₆F₄)NCH₂CH₂NEt₂}Br(py)], 3 with H₂O₂ in boiling acetonitrile gave the ligand oxidation product [Pt{(p-HC₆F₄)NCH=C(Br)NEt₂}Br(py)], 3Br. All major products were identified by X-ray crystallography as well as by ¹H and ¹⁹F NMR spectra. In cases of mixed crystals or dual occupancy compounds, the ¹⁹F and ¹H NMR spectra showed dissociation into the components in the solution in the same proportions as in isolated crystalline material.