Deep Eutectic Solvents as Sustainable Media for Pharmaceutical Purposes

This doctoral thesis explores the use of Deep Eutectic Solvents (DESs) as an environmentally friendly alternative to conventional solvents in common organic transformations and formulation processes within the pharmaceutical industry. For this purpose, the thesis has been divided into five distinct chapters: Chapter I details the development of a sustainable approach for the synthesis of amides, using Reactive Deep Eutectic Solvents (RDESs) that serve both as a reaction medium and as reagents. This innovative method aims to eliminate hazardous solvents, allowing efficient product recovery and avoiding the need for additional chromatographic purifications. The sustainability of the developed method was estimated through the assessment and comparison of sustainability metrics on a large scale compared to conventional industrial strategies. Chapter II delineates a pioneering use of a simple and commercially available ruthenium catalyst to carry out the photocatalytic amide synthesis in DES. Even in this case, the environmental impact of the new methodology has been assessed using green metrics. Chapter III presents an eco-sustainable method for the removal of the tert-butyl carbamate (Boc) group, widely used in organic chemistry for the protection of amine functionalities. The N-Boc deprotection procedure was carried out in the absence of organic solvent, using a DES based on choline chloride and p-toluenesulfonic acid, which acts both as a reaction medium and catalyst. This approach was tested for the deprotection of various N-Boc derivatives. Furthermore, the impact of the developed methodology was valuated using green metrics. Chapter IV aims to propose a green, "one-pot" synthesis in two stages of the Active Pharmaceutical Ingredient (API) Atenolol. Currently, Atenolol ranks among the top five best-selling drugs worldwide, belonging to a class of beta-blockers commonly used for treating angina, hypertension, and reducing the risk of mortality after a heart attack. The novel synthetic methodology for Atenolol involves a DES which acts both as reaction medium and catalyst, providing a sustainable and environmentally friendly alternative to conventional industrial synthetic routes. The environmental impact of this synthetic strategy has been assessed using sustainability metrics and compared with traditional procedures. Finally, Chapter V aims to delve into how DESs can be sustainably utilized as alternative solvents in the pharmaceutical sector due to their extraordinary ability to significantly enhance the solubilization and delivery of poorly water-soluble Active Pharmaceutical Ingredients (APIs) belonging to Biopharmaceutics Classification System (BCS) Classes II and IV. This exploration holds potential positive implications for the pharmaceutical, chemical, and other related industries.

Author

• Procopio, Debora

• Deep eutectic solvents
• Green solvents
• Green synthesis
• Sustainability

Identifier

hdl:10045/151230

OAI identifier oai:identifier

oai:rua.ua.es:10045/151230