Microreactors in Organic Chemistry and Catalysis, Second Edition (2013)

5.7. Oxidation Reactions

Oxidation of primary and secondary alcohols to aldehydes and ketones with DMSO, oxalyl chloride, and a base is known as Swern-oxidation. When using oxalyl chloride as the dehydration agent, the reaction must be kept colder than −60 °C to avoid side reactions, such as Pummerer rearrangement. In contrast, when trifluoroacetic anhydride is used instead of oxalyl chloride, the reaction can be warmed to −30 °C without side reactions. Microflow systems offer a smart approach for controlling the reaction temperature and allow precise control of the residence time. Yoshida and coworkers reported a microflow Swern-oxidation that worked well even at room temperature [67]. By sequential mixing of DMSO, alcohols and reagents, with the aid of a serially connected network of micromixers (IMM) and microtube reactors, carbonyl products were obtained in good to excellent yields, and formation of undesired side-products was minimized as well (Scheme 5.49). The reaction was efficient even at 20 °C, provided that the residence time was very short (2–5 s). Such a short reaction time ensures immediate transfer of the highly unstable intermediates for the subsequent reaction before their decomposition. In addition, the process withstood extended run times (run time = 3 h), allowing for potential scale-up.

Scheme. 5.49

Nef oxidation was successfully carried out in a continuous flow system. Nitroalkanes were effectively transformed to aldehydes or carboxylic acids using KMnO₄ as an oxidant, where the ultrasound pulses were applied to the flow system to avoid blocking by generated MnO₂ [68]. The reaction of ethyl 4-nitrobutanoate (7.37 g) gave 5.05 g of the corresponding aldehyde in (87% yield) (Scheme 5.50).

Scheme. 5.50