1,2,4-Triphenylpyrroles: Synthesis, Structure and Luminescence Properties

Abstract

Pyrroles are widely found in natural products and play an important role in biological processes. Certain pyrrole derivatives are fluorescent and may be used as molecular probes or biomarkers in the diagnosis of diseases, such as Alzheimer’s or Parkinson’s. Herein is reported the synthesis of five new pyrrole derivatives bearing phenyl rings on positions 1, 2, and 4, with electron-donating groups at the periphery. The introduction of more or stronger electron-donating groups red-shifts and increases the efficiency of the fluorescence emission.

Key words

triphenylpyrroles - Nef reaction - Paal–Knorr reaction - fluorescence - crystal structure

• References and Notes

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• 26 1,2,4-Triphenylpyrroles 4a–e; General Procedure The appropriate nitro ketone 2a–c (1 equiv) was dissolved in a mixture of MeOH (8 mL) and THF (12 mL) then KOH (1 equiv) was added. The mixture was stirred for 2 h. The solution, cooled in ice, was added dropwise to an ice-cold solution of concd H₂SO₄ (4 mL ) in MeOH (10 mL), and the mixture was stirred for ~1 h at rt. Half of the solvent was removed under reduced pressure and the mixture was poured in ice–water. The product was extracted with CH₂Cl₂ and the organic layer was dried (Na₂SO₄) and concentrated to dryness to give compound 3a–c, which was used in the following step without purification. The appropriate amine (1 equiv) was added to a solution of the acetal 3a–c (1 equiv) in MeOH (5 mL), and the resulting solution was stirred for 24 h at rt. During this time a precipitate formed. H₂O was then added, and the product was extracted with CH₂Cl₂. The organic phase was dried (Na₂SO₄) and concentrated under reduced pressure. The crude product was purified by flash column chromatography (silica gel).
• 27 1,2,4-Tris(4-methoxyphenyl)-1H-pyrrole (4c)Yellow–brown oil; yield: 23 mg (0.06 mmol, 11%). ¹H NMR (300 MHz, CDCl₃): δ = 7.50 (d, J = 8.8 Hz, 2 H), 7.15–7.08 (m, 4 H), 7.07 (d, J = 2.0 Hz, 1 H), 6.91 (d, J = 8.8 Hz, 2 H), 6.85 (d, J = 9.0 Hz, 2 H), 6.77 (d, J = 8.9 Hz, 2 H), 6.58 (d, J = 2.0 Hz, 1 H), 3.82 (s, 3 H), 3.81 (s, 3 H), 3.77 (s, 3 H). ¹³C NMR (75 MHz, CDCl₃): δ = 158.4, 158.3, 158.0, 134.7, 133.8, 129.7, 128.3, 127.1, 126.3, 125.6, 124.9, 119.8, 114.3, 114.3, 113.7, 107.3, 55.6, 55.4, 55.3. ESI(+)–HRMS: m/z [M + H]⁺ calcd for C₂₅H₂₄NO₃: 386.1751; found: 386.1743 (–1.99 ppm).
• 28 CCDC 1879235 contains the supplementary crystallographic data for compound 4b. The data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/getstructures.
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