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Development of large-scale oxidative Bromination with HBr-DMSO by using a continuous-flow microwave system for the subsequent synthesis of 4-Methoxy-2-methyldiphenylamine

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Abstract

An efficient procedure of continuous-flow microwave reactor, for oxidative bromination with HBr (hydrogen bromide) -DMSO (dimethyl sulphoxide) in large scale is described herein. The reaction is carried out in a metal-free manner, with the use of water as solvent under microwave irradiation conditions. The productivity of this continuous step attains 60 g/min under the optimal conditions, implying a theoretical productivity of 8.6 kg/day. The reaction mixture is screened by thermal insulation accelerometer to ensure the safe process of this reaction in these conditions. 4-Bromo-3-methylanisole is further reacted with formanilide in the presence of cuprous iodide (CuI) and potassium carbonate (K2CO3) to give 4-methoxy-2-methyldiphenylamine, a common intermediate in fine chemical industry such as dye and paper chemistry, in an isolated yield of 65.2%. with more than 200 g scale.

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Acknowledgments

We are grateful to Zhejiang Provincial National Science (LQ18B020003), Zhejiang Qianjiang Talent Program and Basic Public Welfare Research Project of Zhejiang (LGG18B020003) for financial support.

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Authors and Affiliations

  1. College of Chemical and Material Engineering, Quzhou University, Quzhou, 324000, People’s Republic of China

    Yi Jin, Xiaoliang Feng, Jie Li, Jianguo Xu, Xiaobin Chen, Yanwen Lv & Jiangang Yu

  2. Wenling Food and Drug Inspection Center, Wenzhou, 317500, People’s Republic of China

    Junhui Yang

  3. Juhua Group Technology Center, Quzhou fluorosilicone Technology Research Institute, Quzhou, 324004, People’s Republic of China

    Shuhua Wang

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  1. Yi Jin
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  2. Junhui Yang
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  3. Xiaoliang Feng
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  4. Jie Li
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  9. Jiangang Yu
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Correspondence to Yanwen Lv or Jiangang Yu.

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ESM 1.

NMR spectra of 4-methoxy-2-methyldiphenylamine and 4-methoxy-2-methyldiphenylamine, bromination reaction thermal insulation accelerometer test of increasing rate of temperature/temperature relationship and the data of batch synthesis of 4-bromo-3-methylanisole are included in the Supporting Information. (DOCX 147 kb)

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Jin, Y., Yang, J., Feng, X. et al. Development of large-scale oxidative Bromination with HBr-DMSO by using a continuous-flow microwave system for the subsequent synthesis of 4-Methoxy-2-methyldiphenylamine. J Flow Chem 10, 369–376 (2020). https://doi.org/10.1007/s41981-020-00094-6

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