Brønsted Acidic Ionic Liquid: An Efficient Organocatalyst for the Synthesis of Pyrrolo[1,2-a]indoles under Neat Conditions

Abstract

A new synthetic approach has emerged for constructing 9H-pyrrolo[1,2-a]indole scaffolds by the reactions between indoles and chalcones under metal- and solvent-free conditions at 80 °C. The reaction occurs smoothly in the presence of a Brønsted acidic ionic liquid, 1-methyl-3-(4-sulfobutyl)-1H-imidazol-3-ium tosylate, as a catalyst, permitting the synthesis of the desired products with satisfactory yields. The developed protocol is applicable to the construction of biologically important pyrrolo[1,2-a]indole derivatives from easily accessible chalcones having various substituents. The process commences with Michael addition to chalcones, followed by annulations induced by the elimination of a water molecule, yielding the 9H-pyrrolo[1,2-a]indole scaffolds. Several control experiments were carried out to achieve a better understanding of the reaction pathway. The feasibility of recycling the catalyst was also demonstrated. This method produces water as the sole byproduct and represents a green synthetic protocol. The clean reaction, easily accessible reactants, and the metal- and solvent-free and environmentally friendly reaction conditions are the notable advantages of this procedure.

Key words

ionic liquids - pyrrolo[1,2-a]indoles - solvent-free reaction - metal-free reaction - green chemistry

Publication History

Received: 13 July 2024

Accepted after revision: 10 September 2024

Accepted Manuscript online:
10 September 2024

Article published online:
01 October 2024

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• 35 Pyrrolo[1,2-a]indoles 3a–s; General Procedure An oven-dried tube equipped with a magnetic stirrer bar was charged with the appropriate 3-substituted indole 1 (0.6 mmol), chalcone 2 (0.5 mmol), and BAIL-1 (10 mol%), and the mixture was stirred at 80 °C under open-air conditions for two hours until the substrates were completely consumed (TLC). H₂O was added, and the mixture was extracted with EtOAc (×3). The extracts were dried (Na₂SO₄) and concentrated under vacuum, and the crude product was purified by column chromatography (silica gel). 1-(2,6-Dichlorophenyl)-9-methyl-3-phenyl-9H-pyrrolo[1,2-a]indole (3b) Red gummy material; yield: 158 mg (81%); R_f = 0.40 (PE–EtOAc, 98:4). ¹H NMR (400 MHz, CDCl₃): δ = 7.64 (d, J = 7.2 Hz, 2 H), 7.48–7.34 (m, 6 H), 7.19 (t, J = 8 Hz, 2 H), 7.15–7.06 (m, 2 H), 6.37 (s, 1 H), 4.20–4.14 (m, 1 H), 1.26 (d, J = 7.2 Hz, 3 H). ¹³C{¹H} NMR (100 MHz, CDCl₃): δ = 141.3, 141.2, 141.0, 136.3, 135.7, 133.9, 132.9, 129.1, 128.4 (2 C), 128.2, 128.0, 127.7, 127.4, 127.2, 124.6, 123.3, 115.7, 112.9, 112.0, 36.4, 17.2. HRMS (ESI-TOF): m/z [M + Na]⁺ calcd for C₂₄H₁₇Cl₂NNa: 412.0630; found: 412.0639.