Síntese de complexos organometálicos de paládio(II) derivados do Diazepam e reatividade frente a reações de inserção de alcalinos

Abstract

In this present work, we investigated the possibility of performing alkyne insertions in organometallic diazepam-palladium(II) complexes. Diazepam was chosen as a ligand in due to its well known bioactive potential and its ability to coordinate with metals. Palladium(II) chloride was used as metal source to synthesize the dimers: [(DZP)PdCl]2, bis[2-{(7-chloro-1-methyl-2-oxo-2,3dihydro-1H-benzodiazepin-5-yl)phenyl-κ2-C,N}-μ2-chloropalladium(II)] and [(DZP)PdI]2, bis[2-{(7-chloro-1-methyl-2-oxo-2,3-dihydro-1H-benzodiazepin-5-yl) phenyl-κ2-C,N}-μ2-iodopalladium(II)], this last one was synthesized by halogenic metathesis from [(DZP)PdCl]2. The corresponding monomers were synthesized from the addition of pyridine to the dimers, producing [(DZP)PdClPy] and [(DZP)PdIPy]. The reactivity of the dimers face to the insertion reactions was evaluated by using the alkynes methylphenylpropiolate (MPP) and dimethyl acetylenedicarboxylate (DMAD) in a 1:2 ratio of dimer:alkyne. MPP was also tested in di-insertion reaction in a 1:4 ratio of dimer:alkyne. The complexes were characterized by NMR, infrared spectrometry, mass spectroscopy and elemental analysis. The chlorine-iodine metastasis increased the reactivity of the dimer complexe, since the Pd-C bond became more polarized in the dimer bearing iodine. In addition, this process increases the formed complex solubility in the reaction medium. It has been possible to perform a double insertion of the alkyne molecule in each palladium centre. However, this study demands additional characterizations in order to elucidate the regioselectivity of the insertion when the dimer is treated with dissymmetric alkynes such as MPP. In the complexes obtained by monoinsertion, [(DZP)PdI(DMAD)]2 and [(DZP)PdI(MPP)]2, it was possible to identify significant changes in the NMR signals which reveals the insertion of the respective alkynes. For the compound synthesized by insertion, “DZP(MPP)2”, the decoordination of the metal was verified during the reaction and consequently the formation of an organic compound derived from diazepam. The MPP alkyne showed to be more reactive than DMAD, which was already predicted, since the DMAD is a symmetric alkyne, decreasing the polarity of the bond between the acetylenic carbons. Finally, from the obtained data, it is possible to note that the organometallic diazepam-palladium(II) complexes were obtained from CH activation reactions, as well as it was possible to perform insertions of alkynes in the Pd-C of the palladacycle, increasing the possibilities of planning and synthesizing new metallo-drugs by the inorganic medicinal chemistry.