2 - Ring Synthesis by Formation of One Bond

Abstract

This chapter focuses on the ring syntheses by formation of one bond. Synthetic procedures used for the formation of the 1,2 (or 2,3) bond apply to imidazoles and benzimidazoles. Closely related to the Wallach synthesis is the ring closure of an acylated glycine by heating with phosphorus pentachloride. Most recently, the method has been adapted to the preparation of imidazopyridines, by closing a 2-benzylamido side chain on to a pyridine nitrogen. Thus the Wallach reaction considers involving nitrile ylide species, with the limiting parameter being the electron-demanding nature of the heterocyclic ring which influences the facility of ionization of the halogen atom. The synthesis of 1-benzyl-5-chloroimidazole is reviewed. One of the more common methods of benzimidazole synthesis is that which cyclizes o-arylenediamines in which one of the amino groups has been acylated or thioacylated. The starting material must be functionalized in such a way that an aromatic product can be formed when cyclization takes place. It is more common with analogous aliphatic diamine derivatives for reduced imidazoles to be formed, but there are a number of synthetically useful processes which cyclize monoacylated alkylenediamines.