New insights into bromination process: effective preparation of Ambroxol

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 MnO 2 was used efficiently for the radical benzylic bromination of N -acetyl- N -(2,4-dibromo-6-methylphenyl)acetamide under mild conditions.