ISSN print edition: 0366-6352
ISSN electronic edition: 1336-9075
Registr. No.: MK SR 9/7
New insights into bromination process: effective preparation of Ambroxol
Jun-Hui Xu, Yan-Qiong Ma, Jian-Ping Wei, Fang-Mei Li, and Xin-Hua Peng
School of Chemical Engineering, Nanjing University of Science and Technology, Nanjing 210094, China
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.
Keywords: Ambroxol – electrophilic bromination – radical benzylic bromination – total synthesis
Full paper is available at www.springerlink.com.
Chemical Papers 69 (5) 722–728 (2015)