3 - Ring Syntheses Involving Formation of Two Bonds: [4+1] Fragments

Abstract

This chapter discusses the ring syntheses involving the formation of two bonds. The formation of 1,2 and 2,3 bonds are discussed in relation to imidazoles and benzimidazoles. The most common approaches to benzimidazoles involve cyclizations of o-arylenediamines with suitable carbonyl species. This general strategy can be applied to uncondensed imidazoles by similar cyclization of 1,2-alkylenediamines. Such syntheses have been best adapted to the preparation of 2-alkyl- and 2-arylimidazoles. A specific synthesis of 1,4- and 1,5-disubstituted imidazoles has been accomplished in about 70% yields by cyclization of 2-amino-3-methylaminopropanoic acid and 3-amino-2-methylaminopropanoic acid, respectively, with triethyl orthoformate. The most important synthetic methods for preparation of a wide range of benzimidazoles condense o-diaminobenzenes with carboxylic acids or derivatives. Benzimidazole itself can be made in greater than 80% yield merely by standing a mixture of o-phenylenediamine and formic acid at room temperature for 5 days. The most widely used conditions involve heating the reagents together in the presence of hydrochloric acid, usually around 4 M concentration.