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

Abstract

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.

Mechanistic Insights into the Aerobic Oxidation of Aldehydes: Evidence of Multiple Reaction Pathways during the Liquid Phase Oxidation of 2-Ethylhexanal

“…From these results, one could conclude that this 190-year-old reaction , is well established and relevant as a green oxidation reaction. However, some issues are scattered throughout the general reaction pathway: In contrast to BV oxidation of ketones, , reports of BV oxidation of aldehydes are scarce, , and significant amounts of formates 6 are formed especially for electron-rich aromatic aldehydes (Dakin oxidation) . Conversely, the selectivity toward carboxylic acids is generally high (>95%) , for the aerobic oxidation of aromatic and aliphatic aldehydes (with the exception of β-aliphatic aldehydes, vide supra ). The presence of peracid 3 in the reaction mixture was seldom reported .…”

“…In contrast to BV oxidation of ketones, , reports of BV oxidation of aldehydes are scarce, , and significant amounts of formates 6 are formed especially for electron-rich aromatic aldehydes (Dakin oxidation) . Conversely, the selectivity toward carboxylic acids is generally high (>95%) , for the aerobic oxidation of aromatic and aliphatic aldehydes (with the exception of β-aliphatic aldehydes, vide supra ).…”

Photoinduced Protocol for Aerobic Oxidation of Aldehydes to Carboxylic Acids under Mild Conditions

“…Carboxylic acids have been found to have ubiquitous existence and extensive applications in nature products, pharmaceuticals, agrochemical chemicals, and organic synthesis (Figure ). − Therefore, the development of efficient and practical approaches for the synthesis of these compounds has attracted extensive attention. − Among the synthetic routes, the direct oxidation of aldehydes is one of the most highly attractive methodologies because aldehydes are inexpensive and readily available synthons in organic synthesis. − The traditional methods of oxidizing aldehydes to corresponding carboxylic acids usually employ a (super)­stoichiometric amount of hazardous oxidants, such as KMnO 4 , K 2 Cr 2 O 7 , CrO 3 , KIO 3, etc. (Scheme a, method 1), which not only increases safety risks but also is not conducive to post-treatment. − To overcome such problems, plenty of transition-metal-catalyzed reactions have been developed. − In 2015, Li and co-workers reported the first example of a homogeneous silver­(I)-catalyzed aerobic oxidation of aldehydes in water for the synthesis of carboxylic acids (Scheme a, method 2) .…”

Continuous-Flow Oxidation of Amines Based on Nitrogen-Rich Heterocycles: A Facile and Sustainable Approach for Promising Nitro Derivatives

“…Herein, we hypothesized that continuous-flow synthesis of nitro heteroarenes from amines can act as a facile and sustainable alternative instead of traditional oxidation batch processes. Hydrogen peroxide (H 2 O 2 ) was chosen as the oxidative reagent for the following considerations: (1) H 2 O 2 is much cheaper than oxone and effectively used to oxidize numerous functional groups, − for example, hydroxyl, aldehyde, phenol, carbonyl, and so on; (2) H 2 O 2 is environmentally friendly in nature; and (3) the employment of water as the solvent possesses several advantages, including low cost, nonflammable, and innocuity. These features make H 2 O 2 outstanding for large-scale applications utilizing continuous-flow technology.…”