ChemInform Abstract: Advances in the Chichibabin Reaction

Abstract

Publisher Summary The Chichibabin reaction may be defined as the nucleophilic displacement by an amino group of a hydride ion attache3 to a ring carbon of an aromatic nitrogen heterocycle. The reaction was unexpectedly discovered by Chichibabin and Zeide, when they observed the formation of 2-amino-6- methylpyridine (2) while attempting to metallate 2-picoline (1) with sodium amide. After this discovery, Chichibabin and his students explored the amination of many heterocycles. The reaction has been influential in the development of heterocyclic chemistry. It has become of great industrial importance as many aminopyridines are valuable intermediates, especially in the pharmaceutical field. The Chichibabin reaction is usually done under heterogeneous conditions with sodium amide in inert aprotic solvents at elevated temperatures. Gas evolution and intense red color changes are typical indications of the progress of the reaction. The mechanism is still not clearly understood, largely due to the difficulties involved with handling the highly reactive alkali amides and investigating reaction kinetics at high temperatures under heterogeneous conditions. Chichibabin reaction proceeds under homogeneous and heterogeneous conditions; this chapter discusses each method separately. This chapter also attempts to cover the literature since 1967.