Reinvestigation of the Organocatalyzed Aerobic Oxidation of Aldehydes to Acids

Abstract

The organocatalyzed aerobic oxidation of aldehydes to acids was reproduced from the original report. In- and ex-situ analysis of the reaction mixture as the function of time reveals that, unlike the claim in the publication, the aerobic oxidation of aromatic and aliphatic aldehydes leads predominantly to the formation of peracids. The latter are transformed into the corresponding carboxylic acids during the workup procedure. The buildup of peracids in solution poses safety problems that should not be overlooked. This finding has also an influence on the way new catalysts are investigated to improve this reaction as well as on aerobic aldehyde-mediated co-oxidation.

Aerobic Oxidative Cleavage of Vicinal Diol Fatty Esters by a Supported Ruthenium Hydroxide Catalyst

“…We have recently shown that 17 is easily transformed into the corresponding carboxylic acid 2a. 25 There has been speculation on the mechanism of formation products with one carbon less than expected but the only hypothesis (i.e. isomerization) was ruled out.…”

“…Proposed aerobic oxidation pathway of products with one carbon less than expected (i.e. compounds 13 from aldehyde 7) (adapted from25,[27][28] A mixture of aldehydes 7 and 8 (60/40) was synthesized according to the work of Lemaire et al29 and was oxidized under similar experimental conditions. At 150°C, the total conversion of a mixture of aldehydes 7 and 829 was obtained in less than 30 min(Figure 7).…”

N‐Hydroxyphthalimide Catalyzed Aerobic Oxidation of Aldehydes under Continuous Flow Conditions

“…As concerns the mechanism of the NHPI‐catalyzed aldehyde oxidation, it was originally hypothesized that as a result of a free radical chain reaction, a peracid ( I ) is formed as an intermediary product that would readily furnish the corresponding carboxylic acid with the involvement of a remaining aldehyde via a Criegee intermediate ( II ) [7b,11] . It was later highlighted that the formation of the Criegee intermediate from aldehydes is very slow, thereby resulting in considerable accumulation of peracid in the crude reaction mixture [7a,12] . In this manner, the formation of the carboxylic acid product ( III ) should rather be explained by the decomposition of the peracid, for example, during aqueous work‐up [12] .…”

“…It was later highlighted that the formation of the Criegee intermediate from aldehydes is very slow, thereby resulting in considerable accumulation of peracid in the crude reaction mixture [7a,12] . In this manner, the formation of the carboxylic acid product ( III ) should rather be explained by the decomposition of the peracid, for example, during aqueous work‐up [12] . It was recently demonstrated that carboxylic acid III may also be formed via dimerization of acylperoxy radical IV [13] .…”

Telescoped Continuous Flow Synthesis of Optically Active γ-Nitrobutyric Acids as Key Intermediates of Baclofen, Phenibut, and Fluorophenibut

“…Following unsuccessful trials on catalyst-free and platinum-catalyzed aerobic aldehyde oxidations (see the Supporting Information for details), 17 a novel flow method was attempted by using N -hydroxyphthalimide (NHPI) as a homogeneous oxidation catalyst in the presence of molecular O 2 as the oxidant. 18 The reaction was investigated in nitromethane so that it would be compatible with the organocatalytic conjugate addition upon telescoping. Following parameter optimization ( Tables S8 and S9 ), quantitative and selective oxidation of 2 was achieved by using the setup depicted in Figure 2 .…”