During the first months of the project, the work has focused on adapting the reactions to function in a continuous process, known as flow chemistry. This has proven to be challenging, as the reactions behave differently compared to traditional batch production. For example, it has been necessary to use much more diluted solutions to avoid precipitation and clogging in tubes and hoses. Certain reaction conditions have caused reactants to precipitate or block the system, requiring adjustments in both chemistry and equipment.
At the same time, it has been observed that flow processes offer the opportunity to increase reaction rates, as it is possible to operate under higher temperatures and pressures than in batch. This is particularly interesting because higher dilution typically leads to slower reactions and can affect the byproduct profile. The fact that increased speed is still observed in flow presents an exciting potential for more efficient production and improved process control.
Through the work of adapting reactions to continuous production, the project has revealed both challenges and opportunities. The experiences from the first six months provide valuable insight into how chemical processes must be adjusted to function in flow and highlight the great potential for more efficient and scalable production of contrast agents. With continued research and optimization, this could help shape the production methods of the future – more precise, more sustainable, and better equipped to meet the needs of modern medical diagnostics.
The alkylation reactions are currently performed in batch mode. By carrying out the reactions in continuous mode, conditions (for example temperature, pH and the nature of base, addition regime of reagents, different solvents and rapid changes in temperature) that are not possible to apply in batch mode. Microwave can also be used when considered beneficial. How the different conditions influence selectivity and reaction rate will be studied. By-product profile at different conditions will be evaluated by HPLC, and if new and unknown by-products in significant amount appear, they will be isolated (for instance by preparative HPLC) and structure elucidated (MS, IR, and NMR). When the chemistry is is better understood, different continuous systems will be employed. In-line instruments such as Raman or similar will be used to monitor the reaction. A model for following the reaction will be built and developed if a suitable technique is identified.
