Sustainable catalytic systems based on imidazole derivatives

Abstract

This doctoral thesis describes the development of several catalytic systems containing imidazolium salts. It has been divided into four chapters: Chapter 1 describes a novel low transition temperature mixture (LTTM) based on 1-(methoxycarbonylmethyl)-3-methylimidazolium chloride and urea. The LTTM was characterized and then applied to the oxidation of boron compounds (i.e., boronic acids, boronic esters and trifluoroborates) to the corresponding alcohols, obtaining excellent results in short reaction times. The system, which acts as a co-solvent as well as source of oxidizer, achieved three synthetic cycles with a single imidazolium loading, greatly reducing the environmental impact of the protocol. Chapter 2 compiles our findings about the use of a LTTM based on iron(III) and 1-butyl-3-(methoxycarbonylmethyl)imidazolium chloride as a catalyst for the synthesis of quinazolines. The mixture, named IBIS, presents a bifunctional character as both Lewis acid and redox catalyst, affording the desired products in moderate to excellent yields using air as the terminal oxidant in the absence of solvent. In addition, a methodology for the direct synthesis of 2-arylquinazolines from 2-nitrobenzaldehydes is presented and discussed. Chapter 3 details the study of ionic organic solids (IOS) as metal-free heterogeneous catalysts. The IOS 1,3-bis(carboxymethyl)imidazolium chloride effectively catalyzed the C-3 allylation of indoles, providing a single regioisomer in up to quantitative yields and often, pure after simply filtering off the catalyst. The reaction could be performed in gram scale and the catalyst could be reused up to 5 consecutive times without loss of activity. The protocol was then extended to other π-excessive heterocycles, which experienced selective N-allylation. Overall, this methodology proved to be significantly superior in terms of sustainability than those reported in the literature. This chapter also presents the first synthesis of 1,3-bis(sulfomethyl)imidazole and a comparative study of its catalytic activity against carboxy-based IOS in the synthesis of quinolines as well as the allylation reaction discussed above. Chapter 4 describes the synthesis and characterization of a series of metal-organic frameworks based on 1,3-bis(carboxymethyl)imidazole and zirconium salts using a water-based methodology, as well as the preparation and study of a series of metal-organic gels based on the same components. The project is still ongoing, so only preliminary results are discussed. Sustainability metrics were calculated in all the above-mentioned projects, in order to unbiasedly assess the environmental impact of our synthetic protocols, as well as to compare with previously reported methodologies.