Progress in Continuous-flow Oxidation of Aromatic Hydrocarbons

Kaikai Zhang; Weike Su

doi:10.1055/a-2550-9141

Pharmaceutical Fronts, Table of Contents

CC BY 4.0 · Pharmaceutical Fronts 2025; 07(02): e65-e76
DOI: 10.1055/a-2550-9141

Review Article

Progress in Continuous-flow Oxidation of Aromatic Hydrocarbons

Kaikai Zhang

¹Key Laboratory for Green Pharmaceutical Technologies and Related Equipment of Ministry of Education and Key Laboratory of Pharmaceutical Engineering of Zhejiang Province, Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, Zhejiang University of Technology, Hangzhou, People's Republic of China

,

Weike Su

¹Key Laboratory for Green Pharmaceutical Technologies and Related Equipment of Ministry of Education and Key Laboratory of Pharmaceutical Engineering of Zhejiang Province, Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, Zhejiang University of Technology, Hangzhou, People's Republic of China

²Zhejiang Governor Triangle Biomedical Industrial Technology Research Park, Huzhou, People's Republic of China

› Author Affiliations

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.

Keywords

aromatic hydrocarbon - oxidization - continuous-flow

Full Text

References

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