Paal-Knorr synthesis of pyrroles: from conventional to green synthesis

The pyrrole molecular framework is found in a large number of natural and synthetic compounds of great importance. Since functionalized pyrroles are essential for the progress of many branches of science, its synthesis by simple, efficient and eco-friendly routes are particularly attractive in modern organic and bio-organic chemistry. To this end, a number of synthetic methods have been developed, in which the Paal-Knorr pyrrole synthesis stands out to be the easiest route to synthesize pyrroles. In spite of the efficiency, Paal-Knorr synthesis of pyrroles is considered limited by harsh reaction conditions, such as prolonged heating in acid, which may degrade sensitive functionalities in many potential precursors. Through this route almost all dicarbonyls can be converted to their corresponding heterocycles and therefore it is a synthetically valued process. To address the adverse issues this reaction route has undergone numerous modifications recently and today it can be said that this reaction route is a prominent green route for the synthesis of pyrroles. This review is a tour from the evolution and application of this harsh synthetic route to the eco-friendly greener route developed for the synthesis of pyrroles.