ChemInform Abstract: Three‐Component Synthesis of Pyrrole‐Related Nitrogen Heterocycles by a Hantzsch‐Type Process: Comparison Between Conventional and High‐Speed Vibration Milling Conditions.

Abstract

The use of solvent-free, high-speed vibration milling conditions has allowed the development of a one-pot telescoped process for the synthesis of pyrroles starting from ketones, primary amines, and β-dicarbonyl compounds and comprising an initial α-iodination followed by an in situ three-component Hantzsch-type reaction. This method was compared with a solution-based protocol from α-iodoketones, primary amines, and β-dicarbonyl compounds. Although both protocols were far more general than previous Hantzsch-type pyrrole syntheses, the mechanochemical method was superior in that it afforded considerably higher yields in spite of comprising an additional step. The stereochemical integrity of the pyrroles obtained from chiral α-aminoesters was maintained. This solvent-free method was also used for the efficient preparation of ter- and quater-aryl/heteroaryl frameworks containing two pyrrole units and a variety of fused pyrrole systems, including benzo[g]indoles, indeno[1,2-b]pyrroles, indoles, and homoindoles.