An Expeditious Approach to Quinolines via Friedländer Synthesis Catalyzed by FeCl₃ or Mg(ClO₄)₂

 

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Abstract

A mild and efficient route for the synthesis of quinolines and polycyclic quinolines utilizing FeCl₃ or Mg(ClO₄)₂ as a novel catalyst via Friedländer annulation was described.

References

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General Procedure.
A mixture of the 2-aminoaryl ketone (0.5 mmol), α-methylene ketone (1.5 equiv) and FeCl₃ or Mg(ClO₄)₂ (10 mol%) in EtOH (5 mL) was stirred at r.t. After completion of the reaction as indicated by TLC, the reaction mixture was quenched with H₂O (15 mL) and extracted with EtOAc (2 × 10 mL). Evaporation of the solvent followed by purification on silica gel afforded pure quinoline (all the products are known compounds; the characterizations of these compounds are identical with the literature reports).
Ethyl 2-Methyl-4-phenylquinoline-3-carboxylate ( 3a) [9i]

¹H NMR (500 MHz, CDCl₃): δ = 0.94 (t, J = 7.1 Hz, 3 H), 2.79 (s, 3 H), 4.04-4.09 (m, 2 H), 7.36-7.72 (m, 8 H), 8.07 (d, J = 8.4 Hz, 1 H) ppm.
1-(2-Methyl-4-phenylquinolin-3-yl)ethanone ( 3b) [9i]

¹H NMR (400 MHz, CDCl₃): δ = 2.00 (s, 3 H), 2.71 (s, 3 H), 7.36-8.11 (m, 9 H) ppm.
9-Phenyl-2,3-dihydro-1 H -cyclopenta[ b ]quinoline ( 3c) [9i]

¹H NMR (400 MHz, CDCl₃): δ = 2.16-2.19 (m, 2 H), 2.91 (t, J = 7.3 Hz, 2 H), 3.25 (t, J = 7.6 Hz, 2 H), 7.36-8.10 (m, 9 H) ppm.
9-Phenyl-3,4-dihydroacridin-1 (2 H )-one ( 3d) [9e]

¹H NMR (400 MHz, CDCl₃): δ = 2.24-2.27 (m, 2 H), 2.69 (t, J = 6.6 Hz, 2 H), 3.36 (t, J = 6.4 Hz, 2 H), 7.17-7.19 (m, 2 H), 7.40-7.46 (m, 6 H), 8.05 (d, J = 8.7 Hz, 1 H) ppm.
Ethyl 2,4-Dimethylquinoline-3-carboxylate ( 3e) [9i]

¹H NMR (500 MHz, CDCl₃): δ = 1.41 (t, J = 7.1 Hz, 3 H), 2.61 (s, 3 H), 2.71 (s, 3 H), 4.45-4.49 (m, 2 H), 7.46 (t, J = 7.6 Hz, 1 H), 7.66 (t, J = 7.6 Hz, 1 H), 7.91 (d, J = 8.4 Hz, 1 H), 7.99 (d, J = 8.4 Hz, 1 H) ppm.
1-(2,4-Dimethylquinolin-3-yl)ethanone ( 3f) [9j]

¹H NMR (500 MHz, CDCl₃): δ = 2.54 (d, J = 12.3 Hz, 6 H), 2.62 (s, 3 H), 7.49 (t, J = 7.6 Hz, 1 H), 7.66 (t, J = 7.6 Hz, 1 H), 7.91 (d, J = 8.3 Hz, 1 H), 7.99 (d, J = 8.4 Hz, 1 H) ppm.
Ethyl 6-Chloro-2-methyl-4-phenylquinoline-3-carboxylate ( 3g) [9j]

¹H NMR (500 MHz, CDCl₃): δ = 0.94 (t, J = 7.1 Hz, 3 H), 2.77 (s, 3 H), 4.04-4.09 (m, 2 H), 7.34-7.66 (m, 7 H), 8.00 (d, J = 9.0 Hz, 1 H) ppm.
1-(6-Chloro-2-methyl-4-phenylquinolin-3-yl)ethanone ( 3h) [9i]

¹H NMR (500 MHz, CDCl₃): δ = 2.00 (s, 3 H), 2.68 (s, 3 H), 7.33-7.35 (m, 2 H), 7.53-7.66 (m, 5 H), 8.00 (d, J = 8.9 Hz, 1 H) ppm.
1-[6-Chloro-4-(2-chlorophenyl)-2-methylquinolin-3-yl]ethanone ( 3i) [9f]

¹H NMR (400 MHz, CDCl₃): δ = 2.15 (s, 3 H), 2.71 (s, 3 H), 7.23-7.28 (m, 2 H), 7.40-7.67 (m, 4 H), 8.01 (d, J = 9.2 Hz, 1 H) ppm.
7-Chloro-9-phenyl-2,3-dihydro-1 H -cyclo-penta[ b ]quinoline ( 3j) [9i]

¹H NMR (400 MHz, CDCl₃): δ = 2.14-2.18 (m, 2 H), 2.89 (t, J = 7.3 Hz, 2 H), 3.21 (t, J = 7.8 Hz, 2 H), 7.32-7.34 (m, 2 H), 7.52-7.53 (m, 5 H), 7.98 (d, J = 9.2 Hz, 1 H) ppm.