Novel Bromination Methods of 2-Acetamidopyridines

Abstract

Bromination of 2-acetamidopyridines [1], such as 2-acetamidopyridine [1 a], 2-acetamido3-methylpyridine [1 b], 2-acetamido-4-methylpyridine [1 c], 2-acetamido-5-methylpyridine [l d ], 2-acetamido-6-methylpyridine [1 e] and 2-acetamido-4, 6 -dimethylpyridine [1 f] was investigated.2-Acetamidopyridines HBr₃ [ 2 ] were prepared from the reaction of [1] with 48% HBr and Br₂. Compounds [ 2 ] were treated in water at 40 °Cto give 2-acetamido-5bromopyridines [ 3 ] in good yield via generation of Br₊OH_-. For example, 2-acetamido-5bromo-4-methylpyridine [3 c] was obtained from 2-acetamido-4-methylpyridine HBr3 [2 c]. Compounds [ 1 ] were reacted with Br₂ in basic buffer solutions such as Na₂HPO₄ or CH₃CO₂Na to give 2-acetamido-5-bromopyridines [ 3 ] in good yield. It is estimated that Br+NaHPO₄or Br+CH₃CO₂- is active species in these systems.