Synthesis and characterization of novel ligands and application of their transition metal complexes as catalysts or anticancer agents

Abstract

In this Thesis work, we report an innovative approach for the synthesis of 2-bromoacrylic acid and its ester derivatives that are the key intermediates in the synthesis of chiral aryloxypropionic acid an important class of herbicides. The synthesis of the bromo substitued acrylics was carried out via carbonylation of (trimethylsilyl)acetylene using as catalytic system Pd(OCOCH3)2 in combination with CH3SO3H and 2-(6-methyl)(diphenylphosphine)pyridine. When the reaction is carried out in methanol, methyl 2-(trimethylsilyl)acrylate was obtained in good yields with a branched/linear ratio 95/5. On the other hand, hydroxycarbonylation reactions give 2-(trimethylsilyl)acrylic acid with lower conversions and selectivities (ca. 53%, and 93/7 respectively). The effects of phosphine/palladium, acid/palladium, reaction time, temperature, and CO pressure on the substrate conversion and selectivity towards branched isomer have been investigated. Methyl 2,3-dibromo-2-(trimethylsilyl)propanoate is easily prepared by reaction of methyl 2-(trimethylsilyl)acrylate with bromine in dry dichloromethane. Then bromodesylilation of 2-(trimethylsilyl)acrylate in the presence of an excess of base gives 2-bromoacrylic acid in good yield (ca. 90%). A series of triazole ligands were synthesized by the CuAAC reaction. They were employed as chelating ligands to prepare Ru(II), Pd(II), and Co(II) complexes. Ligands and metal complexes have been characterized by analytical data, ESI-MS and 1H and 13C NMR spectroscopy. The water soluble sodium 2-(1-((pyridin-2-yl)methyl)-1H-1,2,3-triazol-4-yl)ethyl sulfate ligand has been employed as ligand in biphasic water/organic solvent catalysis. A preformed ruthenium complex and an iridium system containing this water soluble pyridyl-triazolyl ligand were successfully employed in water/toluene biphasic catalytic hydrogenation of C=C and C=O double bonds. The hydrogenation of styrene, 2-cyclohexene-1-one, m-diisopropenylbenzene, and cinnamaldehyde has been investigated. The water soluble 2-(1-(2-(methylthio)ethyl)-1H-1,2,3-triazol-4-yl)ethanol ligand in combination with [RhCl(COD)]2 gives a system displaying good activity in olefin hydroformylation. The above water soluble [RuCl(η6-p-cymene)(sulphated ligand)] complex has been tested in vitro against several human cancer cell lines (A375, A431, BxPC3, A549 and HCT-15.) derived from solid tumors by the MTT test. Preliminary results indicate that the ruthenium complex is less cytotoxic than cisplatin but has a potential as antimetastatic agent.