Brønsted Acidic Ionic Liquid Catalyzed Three-Component Friedel–Crafts Reaction for the Synthesis of Unsymmetrical Triarylmethanes

Abstract

A convenient and practical method for the synthesis of unsymmetrical triarylmethanes was demonstrated through a one-pot three-component double Friedel–Crafts reaction of various aliphatic, aromatic, or heteroaromatic aldehydes with N,N-dialkylanilines and indoles by using a Brønsted acidic ionic liquid as the catalyst. This method was successfully applied under metal- and solvent-free conditions at 80 °C, affording the corresponding unsymmetrical triarylmethane products in moderate to high yields from a broad range of substrates. In addition, the mechanism of this reaction was studied by quantitative NMR analysis.

Key words

triarylmethanes - diarylmethylindoles - Friedel–Crafts reaction - Brønsted acid - ionic liquid - metal-free conditions

Publication History

Received: 14 February 2022

Accepted after revision: 28 March 2022

Accepted Manuscript online:
28 March 2022

Article published online:
15 June 2022

• References and Notes

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• 10 {4-[1H-Indol-3-yl(4-nitrophenyl)methyl]phenyl}dimethylamine (4a), 3,3′-[(4-nitrophenyl)methylene]bis-1H-indole (5a), and 4,4′-[(4-Nitrophenyl)methylene]bis(N,N-dimethylaniline) (6a): Typical Procedure A mixture of [bsmim][NTf₂] (10 mol%), 4-nitrobenzaldehyde (1a; 1.0 mmol), N,N-dimethylaniline (2a; 2.0 mmol), and indole (3a; 1.0 mmol) was stirred at 80 °C for 6.0 h.When the reaction was complete, the mixture was cooled to r.t. and the reaction was quenched with sat. aq NaHCO₃. The mixture was extracted with EtOAc (3×10 mL) and the combined organic layer was dried (Na₂SO₄) and concentrated in a rotary evaporator. The crude product was purified by column chromatography (silica gel, 20% EtOAc–hexane) to give 4a, 5a, and 6a. 4a Yellow oil; yield: 299 mg (81%); R_f = 0.25 (20% EtOAc–hexane). ¹H NMR (400 MHz, CDCl₃): δ = 8.13 (d, J = 8.8 Hz, 2 H), 8.07 (br s, 1 H), 7.40 (d, J = 8.8 Hz, 2 H), 7.37 (d, J = 8.0 Hz, 1 H), 7.23–7.17 (m, 2 H), 7.08 (d, J = 8.8 Hz, 2 H), 7.02 (td, J = 7.2, 0.8 Hz, 1 H), 6.71 (d, J = 8.8 Hz, 2 H), 6.59 (d, J = 1.6 Hz, 1 H), 5.68 (s, 1 H), 2.95 (s, 6 H). ¹³C NMR (100 MHz, CDCl₃): δ = 152.56, 149.36, 146.29, 136.71, 130.23, 129.64, 129.45, 126.61, 124.01, 123.47, 122.26, 119.59, 119.53, 118.98, 112.60, 111.18, 47.76, 40.55. 5a Yellow solid; yield: 30 mg (8%); mp 230–232 °C; R_f = 0.11 (20% EtOAc–hexane). ¹H NMR (400 MHz, CDCl₃): δ = 8.14 (d, J = 8.8 Hz, 2 H), 8.03 (br s, 2 H), 7.51 (d, J = 8.8 Hz, 2 H), 7.39 (d, J = 8.0 Hz, 2 H), 7.34 (d, J = 8.0 Hz, 2 H), 7.20 (td, J = 7.4, 1.2 Hz, 2 H), 7.03 (td, J = 7.6, 1.2 Hz, 2 H), 6.69 (dd, J = 2.4, 1.6 Hz, 2 H), 5.99 (s, 1 H). ¹³C NMR (100 MHz, CDCl₃): δ = 152.06, 146.39, 136.71, 129.46, 126.58, 123.74, 123.47, 122.01, 119.38, 119.28, 117.78, 111.27, 40.16. 6a Yellow solid; yield: 38 mg (10%); mp 172–174 °C; R_f = 0.47 (20% EtOAc–hexane). ¹H NMR (400 MHz, CDCl₃): δ = 8.11 (d, J = 8.8 Hz, 2 H), 7.29 (d, J = 8.4 Hz, 2 H), 6.95 (d, J = 8.4 Hz, 4 H), 6.67 (d, J = 8.8 Hz, 4 H), 5.45 (s, 1 H), 2.93 (s, 12 H). ¹³C NMR (100 MHz, CDCl₃): δ = 153.46, 149.23, 146.15, 130.91, 130.05, 129.81, 123.33, 112.52, 54.89, 40.55.
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