Subscribe to RSS
Please copy the URL and add it into your RSS Feed Reader.
https://www.thieme-connect.de/rss/thieme/en/10.1055-s-00043364.xml
Download PDF
CC BY 4.0 · Pharmaceutical Fronts 2025; 07(02): e65-e76
DOI: 10.1055/a-2550-9141
DOI: 10.1055/a-2550-9141
Review Article
Progress in Continuous-flow Oxidation of Aromatic Hydrocarbons
Funding None.
Abstract
Aromatic alcohols, aromatic aldehydes, and aromatic acids are usually synthesized by oxidation of the corresponding aromatic compounds and can be used as intermediates for the synthesis of pharmaceuticals, dyes, plasticizers, and fragrances. However, implementing these oxidations in conventional batch reactors, especially on larger scales, is often associated with severe safety risks and process challenges. The potential of explosion propagation within the reactor can be reduced using continuous-flow technology, which can eliminate or alleviate these safety hazards by reducing the size of the reactor and the size of the channel. In this paper, the research progress on aromatic hydrocarbon catalytic oxidation reactions using continuous-flow technology, as well as various catalytic systems and the corresponding selectivity, is reviewed. The translation of aerobic oxidation from batch oxidation to continuous-flow processes, including process intensification and equipment study, has also been discussed.
Publication History
Received: 10 October 2024
Accepted: 04 March 2025
Article published online:
22 April 2025
© 2025. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)
Georg Thieme Verlag KG
Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany
-
References
- 1 Zhou M, Li X, Bao L. et al. A new method for immobilization of NDHPI on SBA-15 carrier used as catalyst for selective oxidation of toluene. Catal Lett 2016; 146 (02) 383-390
- 2 Huang G, Wang PA, Liu YS. et al. An efficient oxidation of toluene over Co(II)TPP supported on chitosan using air. Catal Lett 2007; 114 (3–4): 174-177
- 3 Pieber B, Kappe CO. Aerobic oxidations in continuous flow. Top Organomet Chem 2015; 57: 1-40
- 4 Mahmoudi B, Rostami A, Kazemnejadi M, Hamah-Ameen BA. Catalytic oxidation of alcohols and alkyl benzenes to carbonyls using Fe3O4@SiO2@(TEMPO)-co-(Chlorophyll-Co-III) as a bi-functional, self-co-oxidant nanocatalyst. Green Chem 2020; 22 (19) 6600-6613
- 5 Yang F, Sun J, Zheng R, Qiu W, Tang J, He M. Oxidation of toluenes to benzoic acids by oxygen in non-acidic solvents. Tetrahedron 2003; 60 (05) 1225-1228
- 6 Plutschack MB, Pieber B, Gilmore K, Seeberger PH. The hitchhiker's guide to flow chemistry. Chem Rev 2017; 117 (18) 11796-11893
- 7 Yoshida J, Kim H, Nagaki A. Green and sustainable chemical synthesis using flow microreactors. ChemSusChem 2011; 4 (03) 331-340
- 8 Hu M, Wu W, Jiang H. Palladium-catalyzed oxidation reactions of alkenes with green oxidants. ChemSusChem 2019; 12 (13) 2911-2935
- 9 Lu B, Cai N, Sun J. et al. Solvent-free oxidation of toluene in an ionic liquid with H2O2 as oxidant. Chem Eng J 2013; 225 (01) 266-270
- 10 Yang WY, Tang XJ, Li WJ. et al. Fast and continuous synthesis of 2,5-furandicarboxylic acid in a micropacked-bed reactor. Chem Eng J 2022; 442: 136110
- 11 Zhang RZ, Wang LZ, Yin RH, Luo YH. Alteration in formation behaviors of chloroaromatic precursors of PCDD/Fs: an experimental study on the effect of extrinsic and intrinsic oxygen on chlorination. Chemosphere 2020; 243: 125319
- 12 Horvat M, Kodrič G, Jereb M, Iskra J. One pot synthesis of trifluoromethyl aryl sulfoxides by trifluoromethylthiolation of arenes and subsequent oxidation with hydrogen peroxide. RSC Adv 2020; 10 (57) 34534-34540
- 13 Ahmad S, Yasin K, Shah AT. Catalytic oxidation of toluene using Co-MCM-48 and CoMn-MCM-48 mesoporous material. J Chem Soc Pak 2018; 40 (01) 95-100
- 14 Liu S, Pasha M, Shang MJ. et al. Kinetic study on the reaction routes in the oxidation of K/A oil by nitric acid with microreactors. Chem Eng Sci 2023; 266: 118273
- 15 Liu DJ, Xu HC. Electrochemical rearrangement of indoles to spirooxindoles in continuous flow. Eur J Org Chem 2022; 26 (01) e202200987
- 16 Solís RR, Rivas FJ, Martínez-Piernas A, Agüera A. Ozonation, photocatalysis and photocatalytic ozonation of diuron. Intermediates identification. Chem Eng J 2016; 292: 72-81
- 17 Fujishima A, Honda K. Electrochemical photolysis of water at a semiconductor electrode. Nature 1972; 238 (5358) 37-38
- 18 Tang DY, Lu GL, Shen ZW. et al. A review on photo-, electro- and photoelectro- catalytic strategies for selective oxidation of alcohols. J Energy Chem 2023; 77: 80-118
- 19 Yang ZS, Zhang QQ, Song H. et al. Partial oxidation of methane by photocatalysis. Chin Chem Lett 2024; 35 (01) 108418
- 20 Long H, Chen TS, Song J, Zhu S, Xu HC. Electrochemical aromatic C-H hydroxylation in continuous flow. Nat Commun 2022; 13 (01) 3945
- 21 Chen TS, Long H, Gao Y, Xu HC. Continuous flow electrochemistry enables practical and site-selective C-H oxidation. Angew Chem Int Ed Engl 2023; 62 (40) e202310138
- 22 Zhu HF, Zhao JN, Li JN, Ma CF, Yu ZY, Meng QW. Visible-light-driven g-C3N4-doped Co catalyzed oxidation of benzylic hydroxylation of alkyl aromatic hydrocarbons. Chem Eng Sci 2023; 267: 118365
- 23 Lesieur M, Genicot C, Pasau P. Development of a flow photochemical aerobic oxidation of benzylic C-H bonds. Org Lett 2018; 20 (07) 1987-1990
- 24 Tomaszewski B, Lloyd RC, Warr AJ, Buehler K. Regioselective biocatalytic aromatic hydroxylation in a gas-liquid multiphase tube-in-tube reactor. ChemCatChem 2014; 6 (09) 2567-2576
- 25 Zhang C, Luo J, Xie B, Liu W, Zhang J. Green and continuous aerobic oxidation of ethylbenzene over homogeneous and heterogeneous NHPI in a micro-packed bed reactor. Chem Eng J 2023; 468: 143674
- 26 Chapman MR, Cosgrove SC, Turner NJ, Kapur N, Blacker AJ. Highly productive oxidative biocatalysis in continuous flow by enhancing the aqueous equilibrium solubility of oxygen. Angew Chem Int Ed Engl 2018; 57 (33) 10535-10539
- 27 Gutmann B, Elsner P, Roberge D, Kappe CO. Homogeneous liquid-phase oxidation of ethylbenzene to acetophenone in continuous flow mode. ACS Catal 2013; 3 (12) 2669-2676
- 28 Yang L, Liu P, Zhang HY, Zhang Y, Zhao J. Catalytic oxidation of o-chlorotoluene with oxygen to o-chlorobenzaldehyde in a microchannel reactor. Org Process Res Dev 2020; 24 (10) 2034-2042
- 29 Yun L, Zhao J, Tang X, Ma C, Yu Z, Meng QW. Selective oxidation of benzylic sp3 C-H bonds using molecular oxygen in a continuous-flow microreactor. Org Process Res Dev 2021; 25 (07) 1612-1618
- 30 Bannon R, Morrison G, Smyth M. et al. Continuous flow approach for benzylic photo-oxidations using compressed air. Org Process Res Dev 2024; 28 (08) 3307-3312
- 31 Gary M, Ruairí B, Scott W. et al. Continuous flow photooxidation of alkyl benzenes using fine bubbles for mass transfer enhancement. Tetrahedron Lett 2021; 90: 90153613
- 32 Greene JF, Hoover JM, Mannel DS, Root TW, Stahl SS. Continuous-flow aerobic oxidation of primary alcohols with a Copper(I)/TEMPO catalyst. Org Process Res Dev 2013; 17 (10) 1247-1251
- 33 Naik P, García-Lacuna J, O'Neill P, Baumann M. Continuous flow oxidation of alcohols using TEMPO/NaOCl for the selective and scalable synthesis of aldehydes. Org Process Res Dev 2023; 28 (05) 1587-1596
- 34 Blanchard V, Asbai Z, Cottet K, Boissonnat G, Port M, Amara Z. Continuous flow photo-oxidations using supported photocatalysts on silica . Org Process Res Dev 2020; 24 (05) 822-826
- 35 Liu JM, Xu QL, Ma FQ, Yang ZJ, Liu FF, Su WK. Metal-free catalyzed aerobic oxidation of 2-nitro-4-methylsulfone toluene to 2-nitro-4-methylsulfonylbenzoic acid using a continuous-flow reactor. J Flow Chem 2022; 12 (04) 409-417
- 36 Liu JM, Liu LC, Zhang W. et al. Continuous catalytic aerobic oxidation of o-chlorotoluene to o-chlorobenzoic acid under slug flow conditions. J Flow Chem 2023; 13 (03) 325-335
- 37 Prieschl M, Ötvös SB, Kappe CO. Sustainable aldehyde oxidations in continuous flow using in situ-generated performic acid. ACS Sustain Chem& Eng 2021; 9 (16) 5519-5525
- 38 Guo SZ, Yu ZQ, Yu CM. Kilogram-scale synthesis of 2,4-dichloro-5-fluorobenzoic acid by air oxidation under the continuous-flow process. Org Process Res Dev 2018; 22 (02) 252-256
- 39 Vanoye L, Aloui A, Pablos M. et al. A safe and efficient flow oxidation of aldehydes with O2 . Org Lett 2013; 15 (23) 5978-5981
- 40 Nagasawa Y, Tanba K, Tada N, Yamaguchi E, Itoh A. A study of aerobic photooxidation with a continuous-flow microreactor. Synlett 2015; 26 (03) 412-415
- 41 Kabeshov M, Musio B, Ley S. Continuous direct anodic flow oxidation of aromatic hydrocarbons to benzyl amides. React Chem Eng 2017; 2 (06) 822-825
- 42 Colella M, Degennaro L, Luisi R. Continuous flow synthesis of heterocycles: a recent update on the flow synthesis of indoles. Molecules 2020; 25 (14) 3242
- 43 Dai ZY, Zhang SQ, Hong X, Wang PS, Gong LZ. A practical FeCl3/HCl photocatalyst for versatile aliphatic C-H functionalization. Chem Catal 2022; 2 (05) 1211-1222