Periodic Reporting for period 1 - MechanoExtrusion (A Continuous Process of the Direct Mechanocatalytic Suzuki Coupling)
Reporting period: 2023-06-01 to 2025-02-28
The chemical industry, one of Europe’s largest industrial sectors, is a major contributor to pollution, CO2 emissions, and waste production. A significant portion of this waste stems from solvents—particularly organic solvents, which are often toxic and environmentally harmful. As a result, solvent reduction is a key priority in the strategic agendas of chemical companies worldwide.
Our project takes this goal a step further by not only reducing solvent use in chemical reactions but eliminating solvents entirely from chemical processes. This is achieved through mechanochemistry, a technique that enables chemical transformations without solvents by employing mechanical energy, such as milling or kneading, in mechanochemical reactors like ball mills or extruders.
Specifically, our project focused on the well-known Suzuki coupling reaction, a palladium-catalyzed reaction that plays a crucial role in pharmaceutical and fine-chemical synthesis. The breakthrough of our work lies in the application of direct mechanocatalysis (DM)—a novel concept in which the catalyst is not added as a separate molecular or solid-phase component, as in traditional homogeneous or heterogeneous catalysis. Instead, the milling ball itself, made from a catalytic material, serves as the catalyst. This innovation allows for an unprecedentedly simple catalyst separation and reutilization: the milling ball can be directly removed from the reaction vessel and reused.
The ERC Proof-of-Concept (PoC) project MechanoExtrusion has successfully validated the DM principle for continuous production, demonstrating that the Suzuki reaction can be scaled up significantly. Our technical approach utilizes a twin-screw extruder as a mechanochemical reactor, where two rotating screws within a barrel apply shear forces to the reacting substances. This setup enables the continuous feeding of substrates and removal of products, marking a critical step toward industrial application.
Through this project, we aimed to further scale up the process and validate its feasibility for larger quantities in a continuous system. Our work represents a transition from a laboratory proof-of-concept to a viable innovation, offering a sustainable and greener alternative to conventional chemical manufacturing processes. By eliminating solvents, reducing waste, and enhancing catalyst efficiency, our project contributes to the broader goal of a more environmentally friendly and resource-efficient chemical industry.
Our project takes this goal a step further by not only reducing solvent use in chemical reactions but eliminating solvents entirely from chemical processes. This is achieved through mechanochemistry, a technique that enables chemical transformations without solvents by employing mechanical energy, such as milling or kneading, in mechanochemical reactors like ball mills or extruders.
Specifically, our project focused on the well-known Suzuki coupling reaction, a palladium-catalyzed reaction that plays a crucial role in pharmaceutical and fine-chemical synthesis. The breakthrough of our work lies in the application of direct mechanocatalysis (DM)—a novel concept in which the catalyst is not added as a separate molecular or solid-phase component, as in traditional homogeneous or heterogeneous catalysis. Instead, the milling ball itself, made from a catalytic material, serves as the catalyst. This innovation allows for an unprecedentedly simple catalyst separation and reutilization: the milling ball can be directly removed from the reaction vessel and reused.
The ERC Proof-of-Concept (PoC) project MechanoExtrusion has successfully validated the DM principle for continuous production, demonstrating that the Suzuki reaction can be scaled up significantly. Our technical approach utilizes a twin-screw extruder as a mechanochemical reactor, where two rotating screws within a barrel apply shear forces to the reacting substances. This setup enables the continuous feeding of substrates and removal of products, marking a critical step toward industrial application.
Through this project, we aimed to further scale up the process and validate its feasibility for larger quantities in a continuous system. Our work represents a transition from a laboratory proof-of-concept to a viable innovation, offering a sustainable and greener alternative to conventional chemical manufacturing processes. By eliminating solvents, reducing waste, and enhancing catalyst efficiency, our project contributes to the broader goal of a more environmentally friendly and resource-efficient chemical industry.
We successfully transferred the concept of Direct Mechanocatalysis (DM) into a continuous process using an extruder. A comprehensive study was conducted to define the optimal process parameters, ultimately leading to a robust and reproducible method.
One of the key achievements was the development of a durable coating sequence for the extruder barrel and screw. This sequence involved a base layer of low-chromium steel, followed by successive thin layers of copper, nickel, gold, and finally, the active palladium catalyst. By optimizing the process, we achieved stable operation for two hours while maintaining consistent catalytic activity.
The optimized process demonstrated:
• A space-time yield of 500 kg/day/m³
• A throughput of 0.4 kg/h
• Conversion rates of:
o 36% after one pass
o 51% after two cycles
o 75% after four cycles
Additionally, we adapted this process for another upscaled mechanochemical environment—an attritor mill—where we also achieved successful conversion rates (90% after 60 minutes of first cycle).
To evaluate the environmental impact, we conducted a life-cycle assessment (LCA) comparing the continuous DM approach in the extruder, the batch process in a ball mill, and the conventional solvent-based approach. The results confirmed that the extruder-based process has the lowest CO2 footprint and resource consumption among the three methods.
However, it is important to note that the extruder-based approach is currently limited to simple Suzuki reactions, as the energy input in an extruder is lower compared to ball mills.
One of the key achievements was the development of a durable coating sequence for the extruder barrel and screw. This sequence involved a base layer of low-chromium steel, followed by successive thin layers of copper, nickel, gold, and finally, the active palladium catalyst. By optimizing the process, we achieved stable operation for two hours while maintaining consistent catalytic activity.
The optimized process demonstrated:
• A space-time yield of 500 kg/day/m³
• A throughput of 0.4 kg/h
• Conversion rates of:
o 36% after one pass
o 51% after two cycles
o 75% after four cycles
Additionally, we adapted this process for another upscaled mechanochemical environment—an attritor mill—where we also achieved successful conversion rates (90% after 60 minutes of first cycle).
To evaluate the environmental impact, we conducted a life-cycle assessment (LCA) comparing the continuous DM approach in the extruder, the batch process in a ball mill, and the conventional solvent-based approach. The results confirmed that the extruder-based process has the lowest CO2 footprint and resource consumption among the three methods.
However, it is important to note that the extruder-based approach is currently limited to simple Suzuki reactions, as the energy input in an extruder is lower compared to ball mills.
Solvents are the primary contributors to chemical waste and represent a major source of risk in chemical processes. Completely eliminating their use would significantly enhance the safety, sustainability, and environmental footprint of chemical manufacturing. The Direct Mechanocatalysis (DM) process developed in this project offers a solvent-free alternative while also enabling catalyst reuse and easy separation.
A key advantage of our approach is the use of extruders, which allows for the continuous production of pharmaceuticals and fine chemicals via simple Suzuki reactions. From a technological perspective, the main challenges that need to be addressed for further industrial adoption include:
• Scaling up the extruder length to achieve complete conversion in a single pass.
• Ensuring durable coating stability to minimize material abrasion.
• Increasing energy input to enable more complex reactions beyond simple Suzuki couplings.
The findings of this project have been published in Chantrain et al., 2024, ChemSusChem. The life cycle assessment (LCA) presents an optimistic outlook regarding sustainability, especially when compared to conventional solvent-based processes. However, further studies are required to integrate multiple operational cycles and catalyst reuse into the assessment to provide a more comprehensive evaluation.
For commercialization, the next crucial step is to demonstrate the feasibility of Direct Mechanocatalysis for the synthesis of commercially relevant target molecules. This requires collaboration with industrial partners to validate the technology in real-world applications. Additionally, further research into process optimization, regulatory approval, and potential financial support mechanisms will be essential to bring this innovation to market.
A key advantage of our approach is the use of extruders, which allows for the continuous production of pharmaceuticals and fine chemicals via simple Suzuki reactions. From a technological perspective, the main challenges that need to be addressed for further industrial adoption include:
• Scaling up the extruder length to achieve complete conversion in a single pass.
• Ensuring durable coating stability to minimize material abrasion.
• Increasing energy input to enable more complex reactions beyond simple Suzuki couplings.
The findings of this project have been published in Chantrain et al., 2024, ChemSusChem. The life cycle assessment (LCA) presents an optimistic outlook regarding sustainability, especially when compared to conventional solvent-based processes. However, further studies are required to integrate multiple operational cycles and catalyst reuse into the assessment to provide a more comprehensive evaluation.
For commercialization, the next crucial step is to demonstrate the feasibility of Direct Mechanocatalysis for the synthesis of commercially relevant target molecules. This requires collaboration with industrial partners to validate the technology in real-world applications. Additionally, further research into process optimization, regulatory approval, and potential financial support mechanisms will be essential to bring this innovation to market.