Diverse and unexpected outcomes from oxidation of the platinum(II) anticancer agent [Pt{(p-BrC 6 F 4 )NCH 2 CH 2 NEt 2 }Cl(py)] by hydrogen peroxide.

Oxidation of the anti-tumour agent [Pt{(p-BrC ₆ F ₄ )NCH ₂ CH ₂ NEt ₂ }Cl(py)], 1 (py = pyridine) with hydrogen peroxide under a variety of conditions yields a range of organoenamineamidoplatinum(II) compounds [Pt{(p-BrC ₆ F ₄ )NCH=C(X)NEt ₂ }Cl(py)] (X = H, Cl, Br) as well as species with shared occupancy involving H, Cl and Br. Thus, oxidation of the -CH ₂ -CH ₂ - backbone (dehydrogenation) occurs, often accompanied by substitution. Oxidation of 1 with H ₂ O ₂ in acetone yielded 1:1 co-crystallized [Pt{(p-BrC ₆ F ₄ )NCH=CHNEt ₂ }Cl(py)], 1H and [Pt{(p-BrC ₆ F ₄ )NCH=C(Cl)NEt ₂ }Cl(py)], 1Cl. The former was obtained pure in low yield from the oxidation of 1 with (NH ₄ ) ₂ [Ce(NO ₃ ) ₆ ] in acetone, and the latter was obtained from 1 and H ₂ O ₂ in CH ₂ Cl ₂ at near reflux. From the latter reaction under vigorous refluxing [Pt{(p-BrC ₆ F ₄ )NCH=C(Br)NEt ₂ }Cl(py)], 1Br was isolated. In refluxing acetonitrile, oxidation of 1 with H ₂ O ₂ yielded [Pt{(p-BrC ₆ F ₄ )NCH=C(H ₀ . ₂₅ Br _0.75 )NEt ₂ }Cl(py)], 1H _0.25 Br _0.75 , in which the alkene is mainly substituted by Br in a dual occupancy. Treatment of 1 with H ₂ O ₂ and tetrabutylammonium hydroxide in acetone at room temperature formed [Pt{(p-HC ₆ F ₄ )NCH ₂ CH ₂ NEt ₂ }Cl(py)], 2. Oxidation of [Pt{(p-HC ₆ F ₄ )NCH ₂ CH ₂ NEt ₂ }Br(py)], 3 with H ₂ O ₂ in boiling acetonitrile gave the ligand oxidation product [Pt{(p-HC ₆ F ₄ )NCH=C(Br)NEt ₂ }Br(py)], 3Br. All major products were identified by X-ray crystallography as well as by ¹ H and ¹⁹ F NMR spectra. In cases of mixed crystals or dual occupancy compounds, the ¹⁹ F and ¹ H NMR spectra showed dissociation into the components in the solution in the same proportions as in isolated crystalline material.
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