Construction of xanthines and pyrimido[4,5-d]pyrimidines via base metal-catalyzed direct oxidative coupling reactions
20 April 2018
Campus Middelheim, A.143 - Middelheimlaan 1 - 2020 Antwerpen (route: UAntwerpen, Campus Middelheim
Organization / co-organization:
Department of Chemistry
PhD defence Bénédicte Morel - Faculty of Science, Department of Chemistry
Purine derivatives, including xanthines and pyrimido-pyrimidines possess several interesting biological activities. The aim of this work is the development of new procedures for the construction of these nitrogen-containing heterocycles via a metal-catalyzed direct oxidative approach. A direct copper-catalyzed oxidative amidination was successfully developed for the synthesis of polysubstituted xanthines. Sustainable oxidants, t-Bu2O2 and O2, can be used in this oxidase type reaction. The health, safety and environmental impact of this new methodology was assessed and compared to the classical route towards xanthines.
A part of the assessment is based on quantitative green metrics such as Atom Economy (AE), Reaction Mass Efficiency (RME) and Process Mass Intensity (PMI). In addition, a qualitative analysis relies on toxicological data of the chemicals used (reactants, solvents, reagents and catalysts), and the energy requirements of the reaction. Finally, a new synthesis of 5-aminopyrimido[4,5-d]pyrimidine-2,4-ones was developed, via direct oxidative amidination with isocyanide insertion starting from N-uracil amidines.