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

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.

Key words

Friedländer synthesis - quinoline - catalyst - FeCl₃ - Mg(ClO₄)₂

References

• 1a Hall DG. Manku S. Wang F. J. Comb. Chem.  2001,  3:  125 
• 1b Nicolaou KC. Vourloumis D. Li T. Pastor J. Winssinger N. He Y. Ninkovis S. Sarabia F. Vallberg H. Roschanger F. King NP. Finlay RV. Giannakakou P. Verdier-Pinard P. Hamel E. Angew. Chem., Int. Ed. Engl.  1997,  36:  2097 
• 1c Nicolaou KC. Winssinger N. Vourloumis D. Ohshima T. Kim S. Pfefferkorn J. Su J.-Y. Li T. J. Am. Chem. Soc.  1998,  120:  10814 
• 1d Lee KJ. Angulo A. Ghazal P. Janda KD. Org. Lett.  1999,  1:  1859 
• 1e Xu R. Greiveldinger G. Marenus LE. Cooper A. Ellman JA. J. Am. Chem. Soc.  1999,  121:  4898 
• 1f Wipf P. Reeves JT. Balachandran R. Giuliano KA. Hamel E. Day BW. J. Am. Chem. Soc.  2000,  122:  9391 
• 1g Boger DL. Fink BE. Hedrick MP. J. Am. Chem. Soc.  2000,  122:  6382 
• 1h Nicolaou KC. Pfefferkorn JA. Barluenga S. Mitchell HJ. Roecker AJ. Cao G.-Q. J. Am. Chem. Soc.  2000,  122:  9968 ; and references cited therein
• 1i Roesch KR. Zhang H. Larock RC. J. Org. Chem.  2001,  66:  8042 
• 1j Roesch KR. Larock RC. J. Org. Chem.  2002,  67:  86 ; and references cited therein
• 1k Roesch KR. Larock RC. J. Org. Chem.  2001,  66:  412 
• 2a Larsen RD. Corley EG. King AO. Carrol JD. Davis P. Verhoeven TR. Reider PJ. Labelle M. Gauthier JY. Xiang YB. Zamboni R. J. Org. Chem.  1996,  61:  3398 
• 2b Chen YL. Fang KC. Sheu JY. Hsu SL. Tzeng CC. J. Med. Chem.  2001,  44:  2374 
• 2c Roma G. Braccio MD. Grossi G. Chia M. Eur. J. Med. Chem.  2000,  35:  1021 
• 2d Doube D. Bloun M. Brideau C. Chan C. Desmarais S. Eithier D. Falgueyeret JP. Friesen RW. Girad M. Girad Y. Guay J. Tagari P. Yong RN. Bioorg. Med. Chem. Lett.  1998,  8:  1255 
• 2e Maguire MP. Sheets KR. Mcvety K. Spada AP. Zilberstein A. J. Med. Chem.  1994,  37:  2129 
• 2f Bilker O. Lindo V. Panico M. Etiene AE. Paxton T. Dell A. Rogers M. Sinden RE. Morris HR. Nature (London)  1998,  289 
• 3a Aggarwal AK. Jenekhe SA. Macromolecules  1991,  24:  6806 
• 3b Zhang X. Shetty AS. Jenekhe SA. Macromolecules  1999,  32:  7422 
• 3c Jenekhe SA. Lu L. Alam MM. Macromolecules  2001,  34:  7315 
• 4 Hoemann MZ. Kumaravel G. Xie RL. Rossi RF. Meyer S. Sidhu A. Cuny GD. Hauske JR. Bioorg. Med. Chem. Lett.  2000,  10:  2675 
• A subset of recent work in this area includes:
• 5a Du W. Curran DP. Org. Lett.  2003,  5:  1765 
• 5b Lindsay DM. Dohle W. Jensen AE. Kopp F. Knochel P. Org. Lett.  2002,  4:  1819 
• 5c Matsugi M. Tabusa F. Minamikawa J. Tetrahedron Lett.  2000,  41:  8523 
• 5d Dormer PG. Eng KK. Farr RN. Humphrey GR. McWilliams JC. Reider PJ. Sager JW. Volante RP. J. Org. Chem.  2003,  68:  467 
• 6a Wu J. Zhang L. Sun X. Chem. Lett.  2005,  34:  796 
• 6b Wu J. Sun X. Zhang L. Chem. Lett.  2005,  34:  550 
• 7a Cho CS. Oh BH. Kim JS. Kim T.-J. Shim SC. Chem. Commun.  2000,  1885 
• 7b Jiang B. Si YC. J. Org. Chem.  2002,  67:  9449 
• 7c Skraup H. Chem. Ber.  1880,  13:  2086 
• 7d Friedländer P. Chem. Ber.  1882,  15:  2572 
• 7e Mansake RH. Kulka M. Org. React.  1953,  7:  59 
• 7f Linderman RJ. Kirollos SK. Tetrahedron Lett.  1990,  31:  2689 
• 7g Theclitou ME. Robinson LA. Tetrahedron Lett.  2002,  43:  3907 
• 8 Fehnel EA. J. Heterocycl. Chem.  1966,  31:  2899 
• 9a Strekowski L. Czamy A. J. Fluoresc. Chem.  2000,  104:  281 
• 9b Hu YZ. Zang G. Thummel RP. Org. Lett.  2003,  5:  2251 
• 9c Arcadi A. Chiarini M. Di Giuseppe S. Marinelli F. Synlett  2003,  203 
• 9d McNaughton BR. Miller BL. Org. Lett.  2003,  5:  4257 
• 9e Yadav JS. Reddy BV. Premlatha K. Synlett  2004,  963 
• 9f Yadav JS. Reddy BV. Sreedhar P. Rao RS. Nagaiah K. Synthesis  2004,  2381 
• 9g Mogilaih K. Reddy CS. Synth. Commun.  2003,  3131 
• 9h Walser A. Flyll T. Fryer RI. J. Heterocycl. Chem.  1975,  12:  737 
• 9i De S K. Gibbs RA. Tetrahedron Lett.  2005,  46:  1647 
• 9j Arumugam P. Karthikeyan G. Atchudan R. Muralidharan D. Perumal PT. Chem. Lett.  2005,  34:  314 
• 10 Bolm C. Legros J. Paih JL. Zani L. Chem. Rev.  2004,  104:  6217 

11

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.