Taming explosive and highly energetic reactions: scaling up the liquid-phase aerobic oxidation of alcohols and aldehydes in flow
Résumé
In an era of growing environmental awareness, pharmaceutical companies, which undergo a significant number of non-optimized transformations during the early stages of synthesizing active pharmaceutical ingredients (APIs), need to evolve. This evolution can be achieved through new processes, protocols, and specific multiphasic continuous-flow reactors. Although this technology has been proven at the laboratory scale, its implementation at the pilot scale remains limited, especially for oxidation reactions using oxygen, a cost-effective and readily available green oxidizing agent. This limitation largely stems from the hazardous nature of these reactions and the challenges related to scaling up the gas-liquid process. Here, we present two examples of the successful, seamless scale-up of the aerobic oxidation of primary alcohols and aliphatic aldehydes in a compact heat exchanger reactor, while preserving the segmented flow characteristics and intensified conditions observed at the laboratory scale. The results crucially demonstrate the potential for implementing millistructured reactors in pharmaceutical process chemistry.
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