Hexafluoroisopropanol as solvent and promotor in the Paal-Knorr synthesis of N-substituted diaryl pyrroles. (12th March 2021)

• Record Type: Journal Article
• Authors: Schirmacher, Robert H.E.; Rösch, Daniel; Thomas, Franziska
• Is Part Of: Tetrahedron. Volume 83(2021)
• Publication Date: 2021-03-12
• Subjects: Fluorinated solvents -- Heterocycles -- Pyrroles -- Paal-knorr synthesis; Chemistry, Organic -- Periodicals; 547.005
• DOI: 10.1016/j.tet.2021.131985
• Languages: English
• ISSNs: 0040-4020

Abstract

Abstract: 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. Graphical abstract: Image 1 Highlights: 1, 1, 1, 3, 3, 3-Hexafluoroisopropanol (HFIP) promotes Paal-Knorr pyrrole synthesis. HFIP improves the solubility of 1, 4-diketone precursors with electron deficient aromatic substituents. Paal-Knorr pyrrole synthesis in is applicable with a broad range of 1, 4-diketones. 1HFIP can be used in catalytic amounts.