Green Synthesis of Pyrrole Derivatives

Abstract

Background: Pyrroles are organic cyclic compounds with an extensive and fascinating chemistry. These compounds have a wide structural variety and they are an important basis in technological development as they can be used as drugs, dyes, catalysts, pesticides, etc. Therefore, the production of these heterocyclic compounds by efficient clean methodologies is a great achievement in contemporary chemistry. In this paper, we show recent green procedures in the synthesis of pyrrole derivatives such as Hantzsch, Knorr and Paal- Knorr syntheses, as well as new eco-friendly synthetic procedures with high efficiency and low environmental impact. Objective: This work focusses on the recent advances in the pyrrole synthesis using clean techniques like ultrasound (US), microwaves (MW), high speed vibration milling (HSVM), catalysts use, solvent replace and other methodologies applied to common reactions to obtain the pyrrole core which follow the green chemistry principles. Conclusion: The main challenge of Green Chemistry is to gradually eliminate the generation of hazardous or harmful materials or replace them with less toxic and safer ones. However, this process must be driven by scientific developments. Its application in the synthesis of heterocyclic compounds such as pyrrole derivatives involves multiple economic and social benefits due to the biological importance of these compounds and their direct impact on the pharmaceutical industry. Although many processes are still under investigation using novel methodologies of green activation such as microwaves, ultrasound and HSVM, as well as synthetic processes in continuous flow and processes at room temperature, promising results such as cost and waste reduction and greater efficiency are achieved.

Two-Step, One-Pot Pyrrole Synthesis by Iron-Catalyzed ­Carboamination/Copper-Mediated Cyclization

“…Pyrroles are important N -heterocyclic motifs that play crucial roles in medicinal and materials chemistry. 1 2 Accordingly, significant research effort has been devoted to the discovery and development of methods for the synthesis of pyrroles, 3–6 notably those enabled by condensation chemistry including Paal–Knorr, 7 Hantzsch, 8 and Knorr 9 approaches. Multicomponent strategies for pyrrole synthesis are especially attractive given the potentially greater simplicity and accessibility of the starting materials.…”

Recent approaches in the organocatalytic synthesis of pyrroles

“…1 ). These tremendous biological activities, pharmaceutical applications, use as a synthetic intermediate in many natural products synthesis and material science application have stimulated interest in the synthesis of pyrroles starting from a traditional one, such as the Hantzsch pyrrole synthesis, 7 van Leusen, 8 Knorr, 9 Paal–Knorr pyrrole synthesis 10 to non-classical one, 11 and vast arrays of the synthetic pathway have been developed.…”

Solvent Free Three-Component Synthesis of 2,4,5-trisubstituted-1H-pyrrol-3-ol-type Compounds from L-tryptophan: DFT-B3LYP Calculations for the Reaction Mechanism and 3H-pyrrol-3-one↔1H-pyrrol-3-ol Tautomeric Equilibrium

“…All the described synthetic methods are diverse in terms of the employed reactants as well as the variation in the reaction conditions, comprising several representatives, such as Knorr, Hantzsch and Feist methodologies [ 16 , 17 , 18 ]. Some advantages have been achieved, primarily establishing more efficient and greener synthetic protocols [ 19 , 20 , 21 ]. Thus, the preparation of 3-substituted-4-(3-chloro-4-fluorophenyl)-1 H -pyrrole derivatives based on the Van Leusen pyrrole synthesis was performed through a metal-free synthetic method, involving a C-N bond cleavage under mild reaction conditions [ 22 ].…”