Reactivity of functionalized thiosemicarbazone complexes towards phosphines †

Herein we report the design, synthesis and characterization of a series of phenylboronic cyclometallated derivatives bearing different phosphines. The compounds were prepared by reaction of cyclometallated species with different phosphine ligands and they were characterized by IR, 1H and 31P NMR spectroscopy.


Introduction
Thiosemicarbazones are versatile ligands which are able to coordinate to metals through C, N and S atoms.When bonding to the metal is through the sulfur, iminic nitrogen and a carbon atoms cyclometallated compounds are formed.These have aroused great interest due to their wide range of applications.Their biological activity depends on the parent aldehyde or ketone [1][2][3]; also, palladium (II) complexes have proved to be useful as catalysts in cross coupling reactions like the Heck and Suzuki-Miyaura cross-coupling reaction [4][5][6][7].
Previous studies have shown the tetranuclear structure of these compounds [8,9], which implies a low solubility in the common organic solvents, limiting their potential applications.For this reason we pursue tetranuclear compounds with better solution properties by using different organic precursors; in this particular case an organic precursor bearing the boronic acid functionality.The boronic acid could lead to further modification of the structure of the cyclometallated tetranuclear compound using the Suzuki cross-coupling reaction.Reactivity towards phosphine ligands provides different structures [10] that modulate the applicability to the coupling reaction.
Herein we report the synthesis of a series of cyclometallated compounds derived from a boronic thiosemicarbazone.

Methods
The ligands were prepared by the condensation of acetylphenylboronic acid with different thiosemicarbazides (Figure 1).Acetylphenylboronic acid and hydrochloric acid (35 %) were added to a suspension of the corresponding thiosemicarbazide in water (25 cm 3 ) to give a clear solution, which was stirred at room temperature for 4 h.The white solid that precipitated was filtered off, washed with cold water and dried in air.The palladium compounds were prepared by the addition of a solution of K2[PdCl4] in water to an ethanolic solution of the ligand, as appropriate (Figure 2).The reaction mixture was then kept at room temperature for 24 h.The precipitated yellow solids were filtered, redissolved in DCM and filtered.The solvent was removed to yield compounds in 78-88% yield.

Figure 2.
The synthesis of the phosphine derivatives was achieved by reaction of the palladacycles with the corresponding phosphine in the appropriate stoichiometric ratio.These reactions were carried out in oxygen-free acetone, under nitrogen at room temperature.After 5 hours, the solvent was removed under vacuum to give the target compounds (70-85% yield).The phosphines used in this work were triphenylphosphine, dppm and dppb (Figure 3).

Figure 3.
All the ligands and compounds were characterized by elemental analysis, IR spectroscopy, 1 H-NMR and, in the case of the phosphine bearing compounds, 31 P-{ 1 H}-NMR.

Results and discussion
Ligands were obtained by the condensation of acetylphenylboronic acid with different thiosemicarbazides.Elemental analysis data matched the expected results and the ligands were characterized by 1 H-NMR and IR.
The comparison of the 1 H-NMR of the ligand and their corresponding compounds made clear the metalation of the phenyl ring (figure 1).In the spectra of the ligands a singlet ca.10.2 ppm was assigned to the hydrazinic proton and an AA'BB' system ca.7.75 ppm to the phenyl protons (4H).The IR spectra of the ligands showed bands for the C=S group and hydrazinic ν(N-H) stretch, which are absent in the spectra of the compounds (Table 2), confirming deprotonation of the thiosemicarbazone and the coordination in the thiolic form.
The shift of the ν(C=N) band implies coordination is through the nitrogen lone pair and not through the C=N double bond.Table 1.IR data of the ligands and compounds.Then, the reactivity towards different phosphine ligands was studied.Due to their tetranuclear structure, the cyclometallated compounds present two types of Pd-S bonds, Metal-Schelate and Metal-Sbridging.The latter is weaker and the coordination of the phosphine ligands occurs at this position (Figure 5).

Figure 5. Reactivity of a palladacycle towards triphenylphosphine
The reaction of the cyclometallated compounds with triphenylphosphine gave the expected products.The 1 H-NMR spectra of these compounds showed multiplets in the aromatic region corresponding to the protons of the phenyl rings.The multiplicity of the aromatic protons of the compounds is preserved, but there are changes in the shift of these signals, due to the proximity of the phenyl groups of the phosphine (Figure 6).The 31 P-NMR spectra was a single singlet signal ca.36 ppm (Figure 7, Table 2).In the compounds with dppm the 1 H-NMR spectra was very similar to the previous case, with multiplets in the aromatic region and shift of the metallated ring resonances.A signal ca.3.5 ppm was assigned to the CH2 protons of the diphosphine.The 31 P-NMR spectra confirms that the dppm ligand is monodentate, showing two doublets for 31 P nuclei.(Figure8, Table 3).The compounds with dppb are dinuclear, with the phosphine ligand acting in the bridging mode between the two moieties.Their 1 H-NMR spectra, as in the previous cases, showed multiplet signals in the aromatic region.The signals of the diphosphine carbon chain appear as multiplets at 2.4 and 1.7 ppm (Figure 9).The 31 P-NMR spectra showed a singlet ca.29 ppm in agreement with equivalent 31 P nuclei.(Table 4).

Conclusions
The synthesis of a series of palladacycles was accomplished, and their reactivity towards different phosphine ligands gave mononuclear and dinuclear structures, as appropriate.

Figure 4 .
Figure 4. 1 H-NMR of ligand L2 (top) and its corresponding metallated compound C2 (bottom), showing the changes in the aromatic region and the absence of the hydrazinic proton in the palladacycles.