Oxidative Amino-Dehydrogenation of Azines

This chapter reviews the oxidative amino-dehydrogenation reactions. It focuses on reactions in which a substrate reacts with an aminating agent in the presence of an oxidant. This amination methodology is very useful to replace ring hydrogens in highly electron-deficient azaheterocycles by an amino, alkylamino, dialkylamino, or imino group. Aminations of azines are usually carried out by heating a π-deficient heterocycle with the metal salt of the conjugated base of an amine or amine in an inert, apolar solvent. Chichibabin amination is the first amino-dehydrogenation reaction. The treatment of pyridine with sodium amide in an inert aprotic solvent at elevated temperatures yields 2-aminopyridine in reasonable yield. The oxidative amination procedure is simple but varies depending on the structure of the substrate. The oxidative amino-dehydrogenation of monoazines, quinolines, naphthyridines, diazines, quinazolines, quinoxalines, triazines, tetrazines, and their bicyclic analogs is discussed in the chapter. Amination under homogeneous conditions is an important breakthrough in oxidative amination–dehydrogenation procedures. After addition of the amide ion to the azine, an anionic σ-adduct is formed, which is quite stable in the polar medium as shown by nuclear magnetic resonance (NMR) spectroscopy.