Preparation and characterization of thiosemicarbazone ligands and study of their iron and palladium derivatives †

Transition metal complexes are useful in organic synthesis due to the capability of the metal to activate substrates [1-2]; in particular, cyclometallation reactions may lead to novel routes in organic synthesis. Thiosemicarbazones show a high coordinative capacity given that they possess several potential donor atoms through which they can bind to transition metals. In addition, thiosemicarbazones as well as their semicarbazones analogues have considerable biological and pharmacological interest [3] because of their antibacterial, antiviral and antitumor activity. Their derivatives with ferrocenyl phosphines such as 1,1′bis(diphenylphosphine)ferrocene (dppf) show a wide range of applications [4].


Synthesis of the ligands
Thiosemicarbazones are obtained by condensation reaction between the aldehyde or ketone carbonyl group and the amino group of a thiosemicarbazide.The synthesis of the thiosemicarbazone ligands was carried out in aqueous medium because the reaction product precipitates as a white solid.For this process acidification is necessary to activate the carbonyl group.Scheme 1. Synthesis of the thiosemicarbazone ligands.

Synthesis of the cyclometallated compounds
Cyclometallated compounds are those contain a σM-C bond and also a covalent coordinated bond with a donor atom.Palladium and platinum cyclometallated compounds with thiosemicarbazone ligands have been described, these compounds have a very characteristic tetranuclear structure (Figure 1), containing two types of Metal-S bonds: Metal-Schelate and Metal-Sbridging.The metal atom, is bonded to the carbon in the ortho position and coordinated to a nitrogen atom and two different sulfur atoms.Potassium tetrachloropalladate was used as metallating agent and a water-ethanol mixture as a solvent.The products precipitate within the solution and due to their tetrameric structure they are rather insoluble so they are usually characterized by proton NMR using DMSO-d6 as solvent.
Scheme 2. Synthesis of the cyclometallated compounds.

Synthesis of the compounds bearing phosphine
The synthesis of the cyclometallated compounds with phosphine ligands was carried out using acetone as solvent at room temperature.It is remarkable that although four equivalents of diphosphine were added, all the products obtained showed the diphosphine acts in a bridging mode.These products precipitate giving a pure product and leaving the diphosphine excess in solution.
Scheme 3. Synthesis of the compounds bearing phosphine.

Results and Discussion
Analysis of the 1 H-NMR data confirmed the formation of the ligand mainly due to the chemical shift of the signal of the hydrazinic proton (NNH).Cyclometallation was confirmed due to the differences of the signals in the aromatic zone with respect to those of the free ligand, namely the absence of the proton of the metallated carbon and also the signal for the hydrazinic proton disappears.In the IR spectra of the ligands, signals corresponding to ν (N-H) from the NNH and NHR 1 groups were observed, whereas in the cyclometallated compounds the number of signals decreases due to the disappearance of the hydrazinic hydrogen.The analysis of the 1 H-NMR data confirmed the coordination of the phosphorus atoms to the metal center.There was a large upfield displacement of the signal corresponding to the H 5 proton and coupling between H 5 and the phosphorus nucleus.On the other hand the 31 P-NMR showed the behavior of this phosphine as bidentate bridging because it showed a singlet signal (ca.+28 ppm) which indicates that both phosphorus nuclei are equivalent.

Figure 1 .
Figure 1.(a) Representation of a tetrameric structure.(b) X-Ray resolution of a tetrameric structure.

Figure 4 .
Figure 4. Two different views of the crystal structure of 2c.

Table 1 .
Infrared data in cm-1