The industrial organic synthesis still relies on tradition batch reactors and procedures, consuming energy and generating substantial waste. In the last two decades, researchers and industries have progressively paid more attention to a greener approach using a series of conceptual protocols, such as atom economy, the reduction of derivatization steps and the use of eco-friendly solvents, but this is not enough for a sustainable innovation. The continuous-flow methods and enabling technologies have emerged as can strongly promote process intensification. The flow chemistry, specifically, has become a powerful tool for organic synthesis progressively attracting the interest of the industry due to the potentially advantages over batch processes, among these it is worth mentioning heat and mass transfer maximized, more efficient and safer processes due to a better control over process parameters, significant acceleration and enchantments in yield/conversion contributing to energy savings and lower production costs and finally simplified process scale-up. The transition from batch to continuous-flow synthetic processes is one of the more relevant challenges for chemicals and pharmaceutical industries, but the flow technologies represent a great opportunity for creating a more sustainable future chemical production. The overall goal of this doctoral thesis is on the use of flow chemistry to improve the efficiency of pharmaceutical industrial reactions and processes. All the work disclosed is the results of a High-level Apprenticeship PhD realized thanks to the collaboration between Huvepharma Italia S.r.l. and the University of Turin - Department of Drug Science and Technology. Huvepharma Italia S.r.l. is a multinational pharmaceutical company located in Garessio (CN), north- western part of Italy, which develops, industrializes and produces APIs and intermediates for human and animal health. As PhD candidate and Chemical Engineer, I have given my contribution to optimize API/pharmaceutical intermediates synthetic processes having, in the meanwhile, a special focus on sustainable approaches using enabling technologies as an alternative to classical organic synthesis. A brief introduction to flow chemistry and some of the instrumentation used to perform it, as well as the integration of flow chemistry with other enabling technologies, is reported in chapter 1 to give background to the work contained herein. The chapter 2 contains a literature review about the application of flow synthetic methods for the API production. Chapter 3 investigates the benefits that continuous-flow chemistry could provide in the downstream process of a dietary supplement and in the decolorization process of a cosmetic ingredient both developed by Huvepharma Italia S.r.l. Finally, chapter 4 deals with the synthesis of ß-Adrenergic compound, currently produced by Huvepharma Italia S.r.l with batch mode, improved by microwaves (MW) and the possibility to produce it, at the industrial scale, under flow processing conditions assisted by MW. Given that two or even more enabling technologies can be combined to each other or sequentially hyphenated, the treatment of antibiotics in wastewater using new laboratory hybrid equipment that simultaneously combines HC and ED plasma is also investigate in the same chapter.
From Batch to Continuous Flow Production Process Optimization
colia, mariachiara
2023-01-01
Abstract
The industrial organic synthesis still relies on tradition batch reactors and procedures, consuming energy and generating substantial waste. In the last two decades, researchers and industries have progressively paid more attention to a greener approach using a series of conceptual protocols, such as atom economy, the reduction of derivatization steps and the use of eco-friendly solvents, but this is not enough for a sustainable innovation. The continuous-flow methods and enabling technologies have emerged as can strongly promote process intensification. The flow chemistry, specifically, has become a powerful tool for organic synthesis progressively attracting the interest of the industry due to the potentially advantages over batch processes, among these it is worth mentioning heat and mass transfer maximized, more efficient and safer processes due to a better control over process parameters, significant acceleration and enchantments in yield/conversion contributing to energy savings and lower production costs and finally simplified process scale-up. The transition from batch to continuous-flow synthetic processes is one of the more relevant challenges for chemicals and pharmaceutical industries, but the flow technologies represent a great opportunity for creating a more sustainable future chemical production. The overall goal of this doctoral thesis is on the use of flow chemistry to improve the efficiency of pharmaceutical industrial reactions and processes. All the work disclosed is the results of a High-level Apprenticeship PhD realized thanks to the collaboration between Huvepharma Italia S.r.l. and the University of Turin - Department of Drug Science and Technology. Huvepharma Italia S.r.l. is a multinational pharmaceutical company located in Garessio (CN), north- western part of Italy, which develops, industrializes and produces APIs and intermediates for human and animal health. As PhD candidate and Chemical Engineer, I have given my contribution to optimize API/pharmaceutical intermediates synthetic processes having, in the meanwhile, a special focus on sustainable approaches using enabling technologies as an alternative to classical organic synthesis. A brief introduction to flow chemistry and some of the instrumentation used to perform it, as well as the integration of flow chemistry with other enabling technologies, is reported in chapter 1 to give background to the work contained herein. The chapter 2 contains a literature review about the application of flow synthetic methods for the API production. Chapter 3 investigates the benefits that continuous-flow chemistry could provide in the downstream process of a dietary supplement and in the decolorization process of a cosmetic ingredient both developed by Huvepharma Italia S.r.l. Finally, chapter 4 deals with the synthesis of ß-Adrenergic compound, currently produced by Huvepharma Italia S.r.l with batch mode, improved by microwaves (MW) and the possibility to produce it, at the industrial scale, under flow processing conditions assisted by MW. Given that two or even more enabling technologies can be combined to each other or sequentially hyphenated, the treatment of antibiotics in wastewater using new laboratory hybrid equipment that simultaneously combines HC and ED plasma is also investigate in the same chapter.
I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
