(521cv) Microreactors Enabling Safe Ozonolysis Processes with High Space-Time Yields

Ozonolysis reactions are generally high-yielding, highly selective, and sustainable processes, especially when performed in green solvents. However, the use of ozone (O₃) gas is underutilized in organic synthesis due to the associated process challenges. Earlier contributions by others have made significant advancements in the utilization of O₃ within microreactor and continuous flow platforms. However, the main limitation of many of these examples is that the achieved throughput is low.

We show that high-yielding and highly selective ozonolysis reactions have been developed within a dedicated microreactor system ensuring exquisite control over mass and heat transfer for these very fast gas-liquid transformations.¹ The system utilized a Modular MicroReaction System (MMRS) equipped with a FlowPlate Lab (LL mixing structure, 357 µL, nominal channel width 0.2 mm, Hastelloy C22). An ozone module from ThalesNano was utilized for the in-situ generation of O₃ from pure O₂, and for the controlled introduction of the gas feed into the reactor plate to generate an annular flow regime. The optimization of the reaction conditions for the ozonolysis of cyclohexene to hexanedial, and thioanisole to methyl phenyl sulfoxide is presented. Cyclohexene is transformed to hexanedial in 94% yield at 0 °C within 1.7 seconds. In a similar fashion, the ozonolysis of thioanisole was achieved in 99% yield at 0 °C within <1 second. A 3D printed heat flow calorimeter was used to measure the heat of reaction for the ozonolysis of thioanisole, giving a value of −165 ± 4 kJ/mol. A 3 hour long run achieved a throughput of 1.77 g/h for methyl phenyl sulfoxide, which corresponds to a space time yield of 1.84 kg L^-1 h^-1.

(1) D. Polterauer, D. M. Roberge, P. Hanselmann, P. Elsner, C. A. Hone, C. O. Kappe. Process intensification of ozonolysis reactions using dedicated microstructured reactors. React. Chem. Eng. 2021, 6, 2254-2258.