Continuous, Fast, and Safe Aerobic Oxidation of 2‑Ethylhexanal: Pushing the Limits of the Simple Tube Reactor for a Gas/Liquid Reaction Laurent Vanoye, † Jiadi Wang, † Mertxe Pablos, † Re ́ gis Philippe, † Claude de Bellefon, † and Alain Favre-Re ́ guillon* ,†,‡ † Laboratoire de Ge ́ nie des Proce ́ de ́ s Catalytiques, UMR 5285, CPE Lyon, 43 bld du 11 nov. 1918, 69100 Villeurbanne, France ‡ Conservatoire National des Arts et Me ́ tiers, CASER-SITI, 292 rue Saint Martin, 75003 Paris, France * S Supporting Information ABSTRACT: A continuous-flow microreactor is applied for the selective aerobic neat oxidation of 2-ethylhexanal. Under 7.5 bar of O 2 and 10 ppm of Mn(II) as catalyst, a production of up to 130 g/h of 2-ethylhexanoic acid can be obtained with a PFA tubing of 7 m (Ø 1.65 mm, reactor volume ca. 15 mL). The synergistic use of alkali metal salts and Mn(II) as catalyst improve the selectivity up to 94% under those conditions. We show that the productivity of this simple tube microreactor is limited by the thermal management. ■ INTRODUCTION 2-Ethylhexanoic acid 1 is an important chemical intermediate used in the production of synthetic lubricants, film plasticizers for polyvinyl butyral, stabilizers for PVC as well as oil additives, and functional fluids like automotive coolants. 1,2 Moreover, metal salts of 2-ethylhexanoic acid are used in wood preservatives, as catalyst for polyurethane synthesis, as metal soaps in paint dryers, and in various other applications. 3 This product belongs to the C8 compounds family and is obtained through the aldol condensation of butyraldehyde 2. 4,5 An overview of the industrial synthetic pathway to 1 is shown in Scheme 1. According to the patent literature, the oxidation of 2- ethylhexanal 3 to 2-ethylhexanoic acid 1 is typically performed in a gas sparged stirred tank or gas lift bubble column reactors with air or enriched air as the gas phase using molecular oxygen as the terminal oxidant and with the optional presence of a catalyst. 6-9 However, this oxidation is strongly exothermic (Δ r H = -287 kJ/mol, adiabatic temperature rise of 1065 K for pure aldehyde) and proceeds via highly reactive free radical species; thus an efficient temperature control is claimed to be critical for the selectivity, the productivity, and the safety of the process. 6-9 This intrinsically fast reaction presents gas-liquid mass transfer limitation in most industrial reactors. 6-11 As a matter of fact, even at the lab scale, the productivities published in recent articles on aerobic oxidation are affected by the gas to liquid oxygen mass transfer rate. 12,13 In order to reach the chemical regime and improve the productivity, advanced microreactors can be used. They are known to provide better mass and heat transfers than classical vessels. 14-20 Thus, continuous flow micro- and millimetric reactors were demonstrated to be a valuable alternative for the safe and efficient chemical processing 21-24 and among them aerobic oxidation of aldehydes. 25,26 While this reaction could be performed without neither catalysts nor radical initiators, the reaction rate was greatly increased using metal ions as catalysts, such as Mn(II) and pure oxygen, inside segmented flow reactors. 27,28 Other advantages of continuous microreactors are the small inventory of potentially hazardous chemicals and intermediate species and their large surface to volume ratio which, besides its interest for mass and heat transfers, could contribute to inhibit gas-phase free-radical reactions by recombination on the reactor walls. 21 The selectivity of the oxidation process is known to be highly dependent on the aldehyde structure. 27-32 While high selectivity was observed with linear aliphatic aldehyde, 26 selectivity below 80% toward the corresponding carboxylic acid was obtained for the target reaction, i.e., the oxidation of 2- ethylhexanal 3. 12,25,27,30 The synergistic use of alkali metals salts (i.e., sodium 2-ethylhexanoate) or organic carboxylate salt (i.e., ionic liquid) and Mn(II) as catalyst can improve the selectivity up to 98% while maintaining good productivity of the process. 27,28 Under these conditions, total conversion of the aldehyde 3 was achieved using flow chemistry, and the selectivity was kept high. Herein, a study about further intensification of the aldehyde oxidation to the corresponding carboxylic acid using a simple tube continuous-flow reactor that used cheap, disposable PFA tubing and undergoing a G-L segmented flow (Taylor flow) is reported. Also, we sought to use this reactor for the visual monitoring of the flow. An increase of the internal diameter (i.d.) of PFA tubing (from 1 mm to 1.65 mm) was the only modification to our lab scale microreactor. 25,27 For higher i.d., regular Taylor flow could not be easily obtained within the range of the flow rates used. The productivity of this simple experimental setup was pushed to its limits using tools such as oxygen mass transfer, catalyst loading, and concentration in order to maximize the acid yield under safe conditions with a high purity of the product. Received: November 2, 2015 Communication pubs.acs.org/OPRD © XXXX American Chemical Society A DOI: 10.1021/acs.oprd.5b00359 Org. Process Res. Dev. XXXX, XXX, XXX-XXX