A New Green Approach to the Friedländer Synthesis of Quinolines

Abstract

A new approach to the Friedländer synthesis of quinolines is described. Polysubstituted quinolines are readily prepared under milder conditions than in other existing methods through a gold(III)-catalysed sequential condensation/annulation reaction of o-amino aromatic carbonyls and ketones containing active methylene groups.

Key words

quinolines - gold catalysis - annulations - o-amino aromatic carbonyls - domino reactions

References

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8

Arcadi, A.; Bianchi, G.; Di Giuseppe, S.; Marinelli, F. Green Chemistry, in press.

12

A typical procedure for quinoline 3 is as follows: to a solution of 2-amino-5-chlorobenzophenone 2c (0.2 g, 0.86 mmol) and 2,4-pentanedione 1b (0.13 g, 1.29 mmol) in EtOH (3 mL) NaAuCl₄·2H₂O was added at r.t. under nitrogen atmosphere. The reaction mixture was stirred for 48 h. The solvent was then evaporated under reduced pressure. The residue, purified by flash chromatography (silica gel, 95/5 v/v n-hexane/ethyl acetate), afforded 1-(6-chloro-2-methyl-4-phenyl-quinolin-3-yl)-ethanone 3f (0.23 g, 89% yield); mp 153-155 °C. IR (KBr): 1715 cm^-1. ¹H NMR (CDCl₃): δ = 2.00 (s, 3 H), 2.68 (s, 3 H), 7.33-7.96 (m, 8 H). ¹³C NMR (CDCl₃): δ = 23.8, 31.7, 124.8, 125.7, 128.9, 129.2, 129.8, 130.5, 130.8, 132.3, 134.4, 135.4, 142.9, 145.8, 153.8, 205.1. EI-MS: m/z (relative intensity) = 295 (39) [M⁺], 281 (100), 252 (22).

13

Selected data for 3g, 3i, 3j, 3g: Mp 80-81 °C. IR (KBr): 1750 cm^-1. ¹H NMR (CDCl₃): δ = 2.71 (s, 3 H), 7.34-7.67 (m, 9 H). ¹³C NMR (CDCl₃): δ = 23.8, 115,4 (q, J = 308 Hz), 126.3, 127.1, 127.6, 128.2, 129.1, 129.4, 130.3, 131.3, 131.6, 147.5, 148.3, 153.3, 189.4 (q, J = 38 Hz). EI-MS: m/z (relative intensity) = 315(68) [M⁺], 247 (100), 218 (27). 3i: Mp 118-120 °C. ¹H NMR (CDCl₃): δ = 1.33-1.47 (m, 6 H), 1.90-1.95 (m, 2 H), 2.73 (t, J = 5.6 Hz, 2 H), 3.21 (t, J = 6.1 Hz, 2 H), 7.18-7.26 (m, 4 H), 7.42-7.47 (m, 3 H), 7.52-7.60 (m, 1 H), 8.05-8.09 (m, 1 H). ¹³C NMR (CDCl₃): δ = 25.6, 26.5, 27.9, 31.0, 31.1, 36.2, 125.2, 125.9, 127.0, 127.4, 128.0, 128.1, 128.4, 129.1, 131.6, 137.4, 146.2, 146.3, 163.2. EI-MS: m/z (relative intensity) = 287 (100) [M⁺], 258 (27). 3j: Mp 194-196 °C. ¹H NMR (CDCl₃): δ = 2.02-2.06 (m, 2 H), 2.38 (t, J = 6.7 Hz, 2 H), 2.57 (t, J = 6.9 Hz, 2 H), 7.07-8.22 (m, 12 H). ¹³C NMR (CDCl₃): δ = 25.1, 29.6, 31.9, 115.8 (d, J = 22.2 Hz), 126.2, 126.3, 127.2, 127.9, 128.4, 128.6, 129.4, 129.5, 129.7, 130.4, 161.9 (d, J = 244.2 Hz). EI-MS: m/z (relative intensity) = 339 (100) [M⁺].

19

Selected data for 4: IR(neat): 3460, 3350, 1720, 1665 cm^-1. ¹H NMR (CDCl₃): δ = 2.05 (s, 3 H), 5.43 (s, 1 H), 7.27-7.66 (m, 9 H). ¹³C NMR (CDCl₃): δ = 20.3, 91.5, 114.4 (q, J = 218 Hz), 126.9, 127.3, 128.5, 129.4, 129.9, 130.7, 131.7, 133.5, 134.4, 137.6, 176.6 (q, J = 33 Hz), 195.3. EI-MS:
m/z (relative intensity) = 324 (100) [M + 1⁺], 265 (21), 220 (94), 105 (67).