Indium(III) Trifluoromethanesulfonate: An Efficient Reusable Catalyst for the Alkynylation-Cyclization of 2-Aminoaryl Ketones and Synthesis of 2,4-Disubstituted Quinolines

 

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Abstract

An environmentally friendly and highly efficient procedure for the preparation of 2,4-disubstituted quinoline derivatives has been developed by a simple alkynylation-cyclization reaction of 2-aminoaryl ketones with phenylacetylenes in the presence of indium(III) trifluoromethanesulfonate In(OTf)₃ under microwave irradiation and solvent-free conditions. This catalyst can be recovered after the reaction and reused efficiently in subsequent runs.

References and Notes

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General Procedure for the Synthesis of 2,4-Disubstituted Quinoline Derivatives under Microwave IrradiationsA mixture of 5-chloro-2-aminobenzophenone (1a, 1.65 g, 5 mmol), phenylacetylene (0.52 g, 5 mmol), and In(OTf)₃ (0.03 g) was placed in a quartz reaction vessel of a Prolabo Synthwave Microwave Reactor 402 and allowed to react under microwave irradiation at 110 °C for 4.5 min. After completion (monitored by TLC), the reaction mixture was cooled to r.t. and cold MeOH (15 mL) added. The residue was filtered and the filtrate was evaporated to obtain the crude product which was then recrystallized from hot MeOH to afford quinoline 3a in 93% yield, mp 98 °C. The residue obtained after filtration contains In(OTf)₃ which was used as such in another experiment and the corresponding 6-chloro-2,4-diphenylquinoline was isolated in 90% yield.6-Chloro-2,4-diphenylquinoline (3a): mp 98 °C. IR (KBr): 1610, 1375, 1270, 1160, 1125 cm^-1. ¹H NMR (CDCl₃): δ = 7.10-7.23 (m, 8 H), 7.65 (m, 1 H), 7.95 (m, 1 H), 8.10-8.25 (m, 4 H). Anal. Calcd for C₂₁H₁₄ClN: C, 80.00; H, 4.44; N, 4.44. Found: C, 80.11; H, 4.52; N, 4.36. MS: m/z = 315 [M⁺].2,4-Diphenyl-quinoline (3b): mp 107 °C. IR (KBr): 1610, 1375, 1270, 1160, 1125 cm^-1. ¹H NMR (CDCl₃): δ = 7.10-7.23 (m, 9 H), 7.65 (m, 1 H), 7.95 (m, 1 H), 8.10-8.25 (m, 4 H). Anal. Calcd for C₂₁H₁₅N: C, 89.69; H, 5.34; N, 4.98. Found: C, 89.75; H, 5.42; N, 4.88. MS: m/z = 281 [M⁺].2-Phenyl-4-(2′-chlorophenyl)-6-chloroquinoline (3c): mp 112 °C. IR (KBr): 1610, 1375, 1270, 1160, 1125 cm^-1. ¹H NMR (CDCl₃): δ = 7.27 (s, 1 H), 7.39-7.84 (m, 7 H), 8.18 (s, 1 H), 8.19-8.21 (m, 4 H). Anal. Calcd for C₂₁H₁₃Cl₂N: C, 72.21; H, 3.72, N, 4.01. Found: C, 72.13; H, 3.82; N, 4.12. MS: m/z = 349 [M⁺].2,4-Diphenyl-6-nitroquinoline (3d): mp 264 °C. IR (KBr): 1625, 1370, 1240, 1150, 1035 cm^-1. ¹H NMR (CDCl₃): δ = 7.30-7.65 (m, 8 H), 7.80 (m, 1 H), 8.10-8.15 (m, 5 H). Anal. Calcd for C₂₁H₁₄N₂O₂: C, 77.30; H, 4.29; N, 8.59. Found: C, 77.39; H, 4.19; N, 8.66. MS: m/z = 326 [M⁺].2,4-Diphenyl-8-nitroquinoline (3e): mp 264 °C. IR (KBr): 1630, 1375, 1235, 1150, 1030 cm^-1. ¹H NMR (CDCl₃): δ = 7.25-7.60 (m, 8 H), 7.75 (m, 1 H), 8.12-8.20 (m, 5 H). Anal. Calcd for C₂₁H₁₄N₂O₂: C, 77.30; H, 4.29; N, 8.59. Found: C, 77.42; H, 4.35; N, 8.48. MS: m/z = 326 [M⁺].2-Phenyl-4-(2′-fluorophenyl)-6-chloroquinoline (3f): mp 124 °C. IR (KBr): 1610, 1375, 1270, 1160, 1125 cm^-1. ¹H NMR (CDCl₃): δ = 7.10-7.23 (m, 7 H), 7.65 (m, 1 H), 7.95 (m, 1 H), 8.10-8.25 (m, 4 H). Anal. Calcd for C₂₁H₁₃ClFN: C, 75.68; H, 3.90; N, 4.20. Found: C, 75.75; H, 3.98; N, 4.13. MS: m/z = 333 [M⁺].2-Phenyl-4-(2′-fluorophenyl)quinoline (3g): mp 90 °C. IR (KBr): 1610, 1375, 1270, 1160, 1125 cm^-1. ¹H NMR (CDCl₃): δ = 7.10-7.23 (m, 7 H), 7.65 (m, 1 H), 7.95 (m, 1 H), 8.10-8.25 (m, 4 H). Anal. Calcd for C₂₁H₁₄FN: C, 84.28; H, 4.68; N, 4.68. Found: C, 84.36; H, 4.59; N, 4.78. MS: m/z = 299 [M⁺].