Syntheses and coordination chemistry of thiosemicarbazone-based titanium complexes†

Two routes leading to thiosemicarbazone-based complexes are reported with the view of developing ionic titanium complexes as cytotoxic metallodrugs. The reaction of bis(π-η⁵:σ-η¹-pentafulvene)titanium complexes with most thiosemicarbazones gives κ²N,S thiosemicarbazonido complexes via deprotonation of the acidic N–H bond by the pentafulvene ligand. The use of an o-cresyl TSCN revealed a κ²N,O coordination mode by deprotonation of the O–H bond. The protonolysis of the remaining pentafulvene unit in these complexes with Brønsted acids and further functionalization with multiple bond substrates were attempted. The reaction of titanocene(III) triflate with TSCN reveals an unprecedented reactivity and leads to Ti(III) thiosemicarbazone complexes. The Ti(IV) complexes were characterized using NMR experiments and the nitrogen cores were identified via¹H,¹⁵N HMBC experiments by coupling with the adjacent aldimine proton or the methyl group of the thiosemicarbazone. These are the first structural examples of thiosemicarbazone-based titanium complexes obtained from single-crystal X-ray diffraction.