Synthesis and reactivity of a new type of crown ether thiosemicarbazone

: Palladacycle compounds containing a crown-ether moiety in their structure have been scarcely studied in the past years, although they offer the possibility of combining the crown-ether application as sensors with the catalytic behavior of palladacycles. Maybe the reason for this is because they present a strong interaction with silica making the purification of the new products a difficult task. Nevertheless, in this communication we present the synthesis and characterization of a new palladacycle bearing a 15-crown-5-ether.


Introduction
Palladacycles are very versatile compounds and they are known for a good number of ligands. Their main applications are as catalysts, [1,2] sensors [3] or as antitumor agents. [4] In the particular case of the thiosemicarbazone ligands, these react with palladium salts to give very robust cyclometallated compounds, [5] which present great air and thermal stability; the ligands themselves show a high biological activity. Moreover, when the corresponding thiosemicarbazone is functionalized with a crown-ether moiety, the resulting palladacycle behaves as a new type of sensor. [6] Once palladated the thiosemicarbazone ligand behaves as tridentate, thus occupying all but one of the coordination positions in the square planar environment of the palladium atom. [7] If the ligand is forced to react in the thione fashion with respect to the sulfur atom, the resulting palladacycle is a mononuclear species with the fourth coordination position readily accessible for further modifications. [8] In this communication we present the synthesis of [3,4-(C8H16O5) C6H3C(H)=NN(Me)C(=S)NH2] (1) and its reactivity towards a palladium salt to obtain the mononuclear cyclometallated compound [Pd{3,4-(C8H16O5)C6H3C(H)=NN(Me)C(=S)NH2}(Cl)] (1Pd). The characterization of the compounds was carried out using IR and 1 H NMR spectroscopies.

Discussion
The compounds described in this proceeding were characterized by elemental analysis (C, H, N, S), IR and 1 H NMR spectroscopies (see experimental section). The syntheses of all the compounds are depicted in Schemes 1 to 3 for the clarity of the reader. Ligand 1 was obtained by the reaction of precursor a, previously obtained by the Smith modification of the Duff reaction for the formylation of aromatic rings (Scheme 1), [9] and 2-methyl-3-thiosemicarbazide, in acidic solution (Scheme 2). The formation was monitored by the disappearance of the ν(C=O) stretching band in the IR spectra of compound 1 and the downfield shift of the signal corresponding to the HC=N proton due to the anisotropic deshielding of the iminic bond in the 1 H NMR spectra (see experimental section). The cyclometallation of 1 was carried out using a round bottom flask in a Radleys carrousel in inert atmosphere at 80⁰ C for 1h. The, NaOAc was added to the solution. Finally, the mixture is stirred at room temperature (Scheme 3). Compound 1Pd is a brown solid, highly insoluble in the common NMR solvents, thus its characterization was performed using IR spectroscopy. The value of the ν(Pd-Cl) band (384 cm -1 ) is in accordance with a chlorine acting as terminal ligand suggesting the formation of a mononuclear species. [8] In addition, the increase of the value of the ν(C=N) is 67 cm -1 indicative of a coordination by the non-binding electron pair on the nitrogen atom.

Experimental Section
All the solvents were purified using the standard methods, [10] chemicals were reagent grade.

Synthesis of [3,4-(C8H16O5)C6H3C(H)=NN(Me)C(=S)NH2] (1): To a solution of precursor a in
water, the necessary amount of thiosemicarbazide is added. The reaction is stirred for 8 h at room temperature and the white precipitate is filtered and dried, yield 65.7 %. Molecular formula:  [11] in methanol, the reaction is stirred under N2 atmosphere during 1 h, after that it is cooled until room temperature getting a brownish solution. The solvent is removed under reduced pressure obtaining a brown solid. Molecular formula: C17H24ClN3O5PdS (524.33 g/mol). IR

Conclusions
The first synthetic strategy to obtain mononuclear palladacycles derived from thiosemicarbazones containing a crown-ether in their structure has been described. It is worth noting that these new mononuclear species offer a switchable fourth coordination position at the palladium atom. This situation allows the system to be modified in order to improve the solubility and to be used as a sensor according to the size-selectivity of the entrapping application of 15-crown-5-ether functionality. More experiments in this line are undergoing.