Microwave-Promoted Efficient Synthesis of Benzo[h]quinolines by Solvent-Free Three-Component Imino-Diels–Alder Reaction under One-Pot Condi­tions

Abstract

An one-pot, solvent-free imino Diels–Alder reaction has been developed under microwave conditions using 1-naphthylamine, aldehydes, and electron-deficient terminal alkynes in the presence of a catalytic amount of In(OTf)₃ for construction of benzo[h]quinoline derivatives in short reaction times. The method is clean and operationally simple.

Key words

imino-Diels–Alder reaction - metal-catalyzed multicomponent reaction - microwave-assisted organic synthesis - benzo[h]quinolines

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• 17 General Procedure 1-Naphthylamine (1, 1.0 mmol), 4-fluorobenzaldehyde (2a, 1.0 mmol), and methyl propiolate (3a, 1.2 mmol) were irradiated in a closed vessel with In(OTf)₃ (10 mol%) without solvent in a Synthos 3000 microwave reactor at 720 W, 120 °C, and 10 bar for 8 min. The crude product mixture was dissolved in CHCl₃ and directly purified by column chromatography eluting with EtOAc–hexane (1:9) to obtain pure methyl-2-(4-fluorophenyl)benzo[h]quinoline-4-carboxylate (4a). Compound 4a: off-white solid; mp 116–117 °C. ¹H NMR (300 MHz, CDCl₃): δ = 9.32–9.37 (m, 1 H, arom), 8.64 (s, 1 H, COOCH₃C=CH), 7.05–7.95 (m, 9 H, arom), 3.81 (s, 3 H, CH₃). ¹³C NMR (75 MHz, CDCl₃): δ = 168.6, 155.5, 147.1, 138.6, 136.8, 136.7, 134.5, 131.07, 131.0, 130.9, 129.1, 128.6, 127.9, 127.3, 125.2, 124.8, 124.7, 123.9, 115.3, 115.0, 52.5. IR (CHCl₃): 1726.7, 1603.3, 1589.0, 1561.0, 1512.7 cm^–1. GC–MS: m/z = 331 [M]⁺. Anal. Calcd for C₂₁H₁₄FNO₂: C, 76.12; H, 4.26; F, 5.73; N, 4.23; O, 9.66. Found: C, 76.10; H, 4.20; F, 5.69; N, 4.21; O, 9.61.
• 18 Zani L, Bolm C. Chem. Commun. 2006; 4263 ; and references cited therein
• 19 1-Naphthylamine (1, 1.0 mmol), 4-fluorobenzaldehyde (2a, 1.0 mmol), and methyl propiolate (3a, 1.2 mmol) were refluxed with In(OTf)₃ (10 mol%) in toluene (10 mL) under air until completion (TLC), the solvent was distilled off under reduced pressure, and the product was purified by column chromatography eluting with EtOAc–hexane (1:9) to obtain pure methyl-2-(4-fluorophenyl)benzo[h]quinoline-4-carboxylate (4a).