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New insights into bromination process: effective preparation of Ambroxol

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Abstract

Ambroxol used as an expectorant in treating respiratory diseases was effectively prepared with a total yield of 62%, with o-toluidine as the feedstock via successive procedures of electrophilic bromination, acetylation, radical benzylic bromination, N-alkylation and hydrolysis processes. The addition of aqueous hydrogen peroxide could enhance the utilisation of liquid bromine in the electrophilic bromination of o-toluidine, avoiding the hazardous HBr generated as a by-product. In addition, liquid bromine promoted by MnO2 was used efficiently for the radical benzylic bromination of N-acetyl-N-(2,4-dibromo-6-methylphenyl)acetamide under mild conditions.

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Authors and Affiliations

  1. School of Chemical Engineering, Nanjing University of Science and Technology, Nanjing, 210094, China

    Jun-Hui Xu, Yan-Qiong Ma, Jian-Ping Wei, Fang-Mei Li & Xin-Hua Peng

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  1. Jun-Hui Xu
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  2. Yan-Qiong Ma
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  3. Jian-Ping Wei
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  4. Fang-Mei Li
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Correspondence to Xin-Hua Peng.

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Xu, JH., Ma, YQ., Wei, JP. et al. New insights into bromination process: effective preparation of Ambroxol. Chem. Pap. 69, 722–728 (2015). https://doi.org/10.1515/chempap-2015-0077

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