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Continuous catalytic aerobic oxidation of o‑chlorotoluene to o-chlorobenzoic acid under slug flow conditions

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Abstract

A continuous-flow process was developed for the aerobic oxidation of o-chlorotoluene (OCT) to o-chlorobenzoic acid (OCBA) with pure oxygen. Acetic acid as cosolvent and CoBr2/MnBr2 as catalyst, with a small amount of acetaldehyde as the radical initiator to make the reaction rapidly stimulates. Through the regulation of gas–liquid mixing, slug flow obtains similar mass transfer coefficient of annular flow and the reactor volume was further reduced. The reaction parameters were easily controlled by take the advantages of continuous-flow reactor. Under the optimal reaction conditions, the isolated yield of OCBA reached up to 94%. Compared with the traditional batch process, shorter residence time, higher product yield and operation safety are achieved by adapting simple continuous-flow system.

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Acknowledgements

We are grateful for the Zhejiang Provincial Key R&D Project (No.2020C03006 & 2019-ZJ-JS-03 & 2018C03074) and Research and Application Service Platform Project of API Manufacturing Environmental Protection and Safety Technology in China (2020-0107-3-1)

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Authors and Affiliations

  1. National Engineering Research Center for Process Development of Active Pharmaceutical Ingredients, Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, Zhejiang University of Technology, Hangzhou, 310014, People’s Republic of China

    Jiming Liu, Peng Li, Xin Li, Zhiqun Yu & Weike Su

  2. Zhengjiang Tize Pharmaceuticals Co., Ltd, Zhengjiang, People’s Republic of China

    Linchang Liu

  3. Shanghai Changheng Biomedical Technology Co., Ltd, Shanghai, People’s Republic of China

    Wei Zhang & Weike Su

  4. Key Laboratory for Green Pharmaceutical Technologies and Related Equipment of Ministry of Education, College of Pharmaceutical Sciences, Zhejiang University of Technology, Hangzhou, 310014, People’s Republic of China

    Weike Su

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  1. Jiming Liu
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Liu, J., Liu, L., Zhang, W. et al. Continuous catalytic aerobic oxidation of o‑chlorotoluene to o-chlorobenzoic acid under slug flow conditions. J Flow Chem 13, 325–335 (2023). https://doi.org/10.1007/s41981-023-00272-2

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