Synthesis of fine chemicals, such as pharmaceuticals, agrochemicals, fragrances by using catalytic reactions under homogeneous, heterogeneous and biphasic reaction conditions

Abstract

The aim of this thesis work was the synthesis, characterization and application of new catalysts to be used in reactions as hydrogenation, Heck reaction, Friedel-Crafts acylations, etc., in homogeneous or heterogeneous and/or in biphase systems. These reactions were applied first on model substrates and then for the synthesis of target pharmaceuticals and for fine chemicals intermediate. In particular it was studied the hydrogenation of carbon-carbon double bonds catalyzed by: 1) new heterogeneous catalysts with a low content of precious metal (Pd 0.28%, Rh 0.18%) on alumina: these catalysts were very easily prepared in a new greener solvent and showed a very high activity and selectivity; 2) Rhodium and Palladium catalysts, with suitable ligands (in particular polysaccharides and lactic acid derivatives), able to operate in both aqueous biphasic or homogeneous system. Heck reactions were carried out in homogeneous system by using palladium based catalysts in the presence or absence of suitable phosphino ligands; Friedel-Crafts acylations of heterocyclic compounds were studied by using different metal catalysts, in particular new iron and gallium polymeric fluorosulphonate, easily prepared by a convenient protocol. Most of these reactions were applied for the synthesis of the two target pharmaceuticals, the calcimimetic Cinacalcet and the antimigrane Eletriptan. Finally, some reactions for the synthesis of Cinacalcet were carried out under microwaves conditions in order to reduce the catalyst amount, the reaction time and to increase the chemical yield. Moreover, these reactions were carried out in more environmentally friendly solvents as Me-THF, CPME and -valerolactone. When possible the activity of these new catalysts was compared to that of commercially available catalyst and in some cases they showed better performances with respect to largely applied industrial catalysts, appearing so suitable for a possible commercial development.