Sustainable Aldehyde Oxidations in Continuous Flow Using in Situ-Generated Performic Acid

The oxidation of aldehydes is one of the most prevalent methods for the synthesis of a diverse range of carboxylic acids. We herein present a performic acid generator and its application for aldehyde oxidations under continuous flow conditions. Low molecular weight performic acid, an environmentally benign and inexpensive oxidant, was readily formed in situ from formic acid and hydrogen peroxide. The safety hazards typically encountered when manipulating this potentially explosive reagent were eliminated, while at the same time a clean and efficient access to valuable carboxylic acids was ensured. By taking advantage of concentrated or even neat aldehyde streams, the amount of organic solvents utilized, and thus waste formation, was successfully minimized as demonstrated by E-factors in the range of 5-18. The process proved applicable for a wide range of aromatic as well as aliphatic aldehydes, while its synthetic utility and stability were corroborated by scale-out experiments leading to multigram-scale syntheses.