Hexafluoroisopropanol as solvent and promotor in the Paal-Knorr synthesis of N-substituted diaryl pyrroles

An additive-free synthesis of challenging N-substituted aryl pyrroles from the often poorly soluble corresponding 1,4-diketones by means of the Paal-Knorr pyrrole synthesis is reported, which makes use of the unique properties of 1,1,1,3,3,3-hexafluoroisopropanol (HFIP) as a solvent and reaction promotor. Our procedure offers simple execution and purification as well as easy scale-up and can be applied in the Paal-Knorr synthesis of a large number of structurally diverse pyrroles including the synthetically challenging tetra- and penta-substituted pyrroles in moderate to excellent yields. HFIP can also be used as solvent in the Paal-Knorr synthesis of furans and thiophenes; however, the solvent effect is more pronounced in synthesis of pyrroles. (C) 2021 Elsevier Ltd. All rights reserved.

Automated summary

An additive-free synthesis of challenging N-substituted aryl pyrroles from poorly soluble 1,4-diketones using HFIP as a solvent and reaction promotor is reported. The procedure offers simple execution and purification, and can be applied to a variety of structurally diverse pyrroles. HFIP can also be used as a solvent in the Paal-Knorr synthesis of furans and thiophenes, with a more pronounced solvent effect observed in pyrrole synthesis.