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Synlett 2025; 36(15): 2328-2332
DOI: 10.1055/a-2577-0577
DOI: 10.1055/a-2577-0577
letter
Emerging Trends in Organic Chemistry: A Focus on India
Zinc Triflate Catalyzed Tandem One-Pot Regioselective Synthesis of Highly Functionalized Pyrrole Derivatives
Abstract
An efficient, zinc triflate catalyzed, tandem cyclization for the synthesis of highly functionalized pyrrole derivatives of potential medicinal significance has been developed. The four components—an arylamine, an aldehyde, acetylacetone, and nitromethane—were effectively cyclized in a single step with four different bonds (C–C and C–N). The readily available materials, broad substrate scope, excellent functional-group tolerance, mild conditions, scalability, and excellent yields of high-purity products are attractive features of this newly developed protocol.
Key words
zinc triflate - one-pot reaction - tandem reaction - cyclization - pyrroles - medicinal chemistrySupporting Information
- Supporting information for this article is available online at https://doi.org/10.1055/a-
2577-0577.
- Supporting Information
Publikationsverlauf
Eingereicht: 26. Februar 2025
Angenommen nach Revision: 07. April 2025
Accepted Manuscript online:
07. April 2025
Artikel online veröffentlicht:
02. Juni 2025
© 2025. Thieme. All rights reserved
Georg Thieme Verlag KG
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- 19 1-[1-(3-Chlorophenyl)-2-methyl-5-phenyl-1H-pyrrol-3-yl]ethanone (5): Typical Procedure Zn(OTf)2 (10 mol%) was added to a stirred solution of 3-chloroaniline (1a; 1 mmol), acetylacetone (3; 1 mmol), benzaldehyde (2a; 1 mmol), and nitromethane (4; 2 mmol) in EtOH (3 mL) and the mixture was heated at 70 °C for 2 h. When the reaction was complete (TLC), the mixture was cooled to r.t. and the excess solvent was evaporated under a vacuum. The crude residue was purified by column chromatography (silica gel, Ethyl acetate: Petroleum ether (05:95)) to give light-yellow crystals; yield: 87%; mp 112–114 °C. IR (KBr): 3111, 3080, 2922, 1647, 1496, 1410, 1228, 840, 767, 704 cm–1; 1H NMR (500 MHz, CDCl3): δ = 2.06 (s, 3 H, pyrrole CH3), 2.39 (s, 3 H, aliphatic CH3), 6.63 (s, 1 H), 7.25 (d, J = 8.5 Hz, 2 H), 7.27–7.47 (m, 5 H), 7.28 (d, J = 8.5 Hz, 2 H). 13C NMR (125 MHz, CDCl3): δ = 197.7. 139.9, 135.8, 135.2, 135.1, 130.4, 129.4, 128.4, 127.1, 126.8, 126.6, 124.5, 123.0, 120.4, 31.2, 13.0. HRMS (ESI): m/z [M + H]+ calcd for C19H17ClNO: 309.0912; found: 309.0918. Anal. Calcd for C19H16ClNO: C, 73.66; H, 5.21; N, 4.52. Found: C, 73.36; H, 5.56; N, 4.28. H.