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Synthesis of arenediazonium salts and Suzuki- Miyaura cross-coupling reaction in microreactors

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Abstract

The process characteristics of two main steps in the preparation of 4-nitrobiphenyl (4-NBP) from 4-nitroaniline (PNA) were clearly revealed by applying two continuous-flow microreactors. The first step was the synthesis of 4-nitrobenzene diazonium tetrafluoroborate (4-NBDT) through the diazotization reaction. The reaction temperature, the residence time, and the molar ratio of different reactants were investigated to achieve optimal reaction conditions with the highest yield of 4-NBDT. Notably, the yield of 4-NBDT reached 97% at 25 °C only in 2.3 s with the optimal molar ratio of HBF4, NaNO2 and PNA (i.e., 2.72:1.05:1). The second step was the Suzuki-Miyaura cross-coupling reaction, in which HNO3 was used to transform the reaction system into a homogeneous state. The effects of mixing performance, the molar percentage of Pd(OAc)2 to 4-NBDT, the reaction temperature and the residence time on the Suzuki-Miyaura cross-coupling reaction were investigated systematically. With the molar percentage of Pd(OAc)2 to 4-NBDT of 1 mol%, the yield of 4-nitrobiphenyl (4-NBP) was optimized to 99% in just 13 min at 25 °C. This study demonstrated the excellent potential of utilizing the continuous-flow microreactor for the diazotization and the following Suzuki-Miyaura cross-coupling reaction.

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Acknowledgments

We want to acknowledge financial support from the National Natural Science Foundation of China (No: 92034303), and the Shanghai Jiao Tong University Scientific and Technological Innovation Funds (No: 2019QYB06).

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Authors and Affiliations

  1. College of Environmental Chemistry and Engineering, Shanghai University of Electric Power, Shanghai, 200090, People’s Republic of China

    Xinxiang Jiang & Yuanhai Su

  2. School of Chemistry and Chemical Engineering, Shanghai Jiao Tong University, Shanghai, 200240, People’s Republic of China

    Guangxiao Li, Saier Liu & Yuanhai Su

  3. School of Chemical Engineering, Sichuan University, Sichuan, 610065, Chengdu, People’s Republic of China

    Yang Song

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Jiang, X., Li, G., Liu, S. et al. Synthesis of arenediazonium salts and Suzuki- Miyaura cross-coupling reaction in microreactors. J Flow Chem 11, 843–853 (2021). https://doi.org/10.1007/s41981-021-00160-7

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