Chapter 6.1: Six-membered ring systems: pyridine and benzo derivatives

Abstract

This chapter provides an overview of six-membered ring systems, including pyridine and benzo derivatives. Pyridine derivatives are important heterocyclic systems whose preparation, reactivity, and properties are of continuing interest. The biological activity associated with naturally occurring and synthetic pyridines has led to the development of pyridine-containing medicinal scaffolds and investigations into their pharmacological properties. This chapter presents a summary of the methods developed for the syntheses and reactions of pyridines, quinolines, isoquinolines, and piperidines. Cyclocondensations and related polar cyclizations are the most widely used methods for preparing pyridines, dihydropyridines, and dihydropyridinones. Efforts have been directed towards utilizing multicomponent cyclocondensation reactions as one-pot procedures to conveniently synthesize a variety of pyridine derivatives in an efficient manner. In addition, much attention has been focused on improving efficiency with the incorporation of microwave technology and developing more environmentally friendly protocols. The Hantzsch synthesis of pyridine is a cyclocondensation method of considerable importance. This route classically involves the condensation of four components, including two molecules of β-carbonyl compounds, an aldehyde, and ammonia (or an equivalent) to form 1,4-dihydropyridines, which can be aromatized into pyridines.