ESR1 studied chemistry involving highly reactive reagents and intermediates. Their work has explored the chemistry of organomagnesium and organolithium reagents in addition and C-H functionalization applications. The exothermic reactions and pyrophoric reagents present safety concerns and practical challenges upon scale-up in batch, and continuous flow protocols have been developed for both. Lastly the ESR explored Ritter synthesis of amides employing solid-supported Bronsted acid catalysts under. Here, placing the acid on a solid support significantly simplifies the work-up procedure, obviating the need to quench any acid. Manuscripts are in preparation for all three areas of study and we anticipate these will be published in the first half of 2024.ESR2 studied oxidation chemistry, examining the oxidation of alkenes to epoxides and alcohols to carbonyl compounds. These reactions used a homogeneous manganese catalyst and an organic peroxide (peracetic acid). The reactions are very fast and exothermic, therefore heat management is important in order to ensure safe operation and to avoid runaway reactions. Continuous flow is therefore the ideal way to develop a process which would be scalable for industrial exploitation. We designed and developed of a continuous flow process for carrying out these oxidation reactions, which used low loadings of an inexpensive catalyst. The peracetic acid was generated in situ and telescoped directly into the epoxidation reaction, which reduces the risks associated handling and storing this oxidant. The epoxidation study has been published (Org. Process Res. Dev. 2023, 27, 2, 262–268) and a manuscript on the oxidation of alcohols has been prepared and will be published in 2024.ESR3 developed flow processes associated with reduction chemistry, examining the catalytic reduction of nitrile compounds, an important class of model substrates. The project studied transfer hydrogenation methods and those also those that utilise hydrogen gas. The utilisation of pyrophoric materials (e.g. metal hydrides) and flammable gases pose significant challenges for scaling these in batch mode. The use of flow reactors enables smaller reactors to be used and the hazards can be more easily managed. ESR3 studied the catalytic transfer hydrogenation of benzonitrile to benzylamine using a palladium on carbon catalyst with triethylammonium formate as reducing agent. This system had previously only been studied under batch conditions. It was found that solvent choice was critical in overcoming rapid catalyst deactivation, which was important for developing a practical flow system. A 15-fold increase in catalyst productivity was observed in flow compared to batch. More details can be found in the published article (React. Chem. Eng., 2023,8, 1559-1564). This project also examined the use of H2 gas and therefore there was the need for pressurised flow systems. The reductive amination of nitriles was carried out with heterogeneous catalysts in fixed-bed reactor system. The flow system also used an in-line separator to improve the efficiency of product isolation. Finally, the system was shown to be applicable to the synthesis of API type compounds and a manuscript detailing these studies has been prepared and will be published in 2024.The ESRs disseminated their findings at a number of relevant international and regional conferences. The completion of the projects and writing of journal articles was slowed by the global pandemic, but all of the articles should be published in 2024, and these will be compiled on the ITN website.
