Synthesis of 2-Aminopyridines and 2-Amino-Quinolines from Their N-Oxides

Significance

An efficient one-pot transformation of pyridine N-oxides to 2-aminopyridines in good to excellent yields is reported. Although the 2-­amination of quinolines by reaction of quinoline N-oxides with NH₄OH-TsCl is known (R. A. Glennon et al. J. Med. Chem. 1986, 29, 2375), the attempts to apply this methodology to pyridines have been previously problematic due to side reactions such as dimerization, and poor C2 vs C4 selectivity. These problems are effectively solved by using t-BuNH₂ followed by tert-butyl group cleavage under acidic conditions. Both EWG- and EDG-containing pyridines participate in this reaction although only four non-4-substituted cases were tested. A few aminoquinolines and -isoquinolines were similarly prepared.