Flowid demonstrated that the SpinPro Reactor is well suited for performing hazardous and pyrophoric Lithium Halogen Exchange. An extensive engineering and safety effort resulted in successful experiments performed in Flowid’s own facilities in Eindhoven, The Netherlands.
Lithium Halogen Exchange is a type of carbon-carbon bond forming reaction frequently performed in lab scale organic synthesis. Although the reaction is performed at scale, producing pharmaceuticals, pesticides, polymers and others, the reaction requires cryogenic conditions in batch, as well as dilution of the substrates, even when performed in a plug flow reactor.
Butyl lithium is extremely reactive, and exposure to air can result in spontaneous ignition, creating a serious safety risks for handling. The need dilute the reaction as well as the need to cool batch processes to temperatures as low as -70 degrees Celsius, cause most development chemists to reconsider chemical routes involving this material. Moreover, due to poor solubility at low temperatures-many reactions using this reagent are difficult to scale due to poor scalability of the mixing process. As a result of the combination of these factors, processes using Butyl Lithium tend to be costly, due to added solvent removal, plant cooling, and the added safety engineering not to mention the difficulty in going up in scale.
Flowid’s SpinPro Reactor has high mass and heat transfer capabilities at industrial relevant throughputs. The chemistry can be intensified and controlled, which results in higher yield and less energy consumption, while operating safely.
In cooperation with the American process intensification company Proteaf Technologies, a model reaction, which has been demonstrated to work well in a laboratory scale spinning disk reactor(Tet. Lett., 2010, 51, p. 4793). This is a two step synthesis in which 1,4 bromochlorobenzene is firstly reacted with n-BuLi to create an intermediate. Rate enhancements of up to 100 fold have been observed for these reactions using spinning disk.
Proper engineering and an extensive safety study enabled Flowid to perform this reaction at its own facilities in Eindhoven. About a dozen of experimental runs were performed in which flow, flowrates, temperature and others were varied to check the performance of the reactor. The sensitive behaviour of the reaction could be altered clearly with the settings of the SpinPro Reactor. This shows a high degree of controllability of this reaction in this novel continuous reactor. Even at throughputs of almost 100 kg/hr and a reactor temperature of +15 degrees Celsius, the synthesis was performed without difficulty.