Rapid One-Pot Synthesis of Antiparasitic Quinolines Based upon the Microwave-Assisted Coupling-Isomerization Reaction (MACIR)

 

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Abstract

2-Substituted quinolines and related derivatives can be rapidly prepared from (hetero)aryl halides and propargyl alcohols in the sense of a one-pot microwave-assisted coupling-isomerization reaction (MACIR). First biological tests against trypanosomes and protozoans have revealed antiparasitic activity in the lower micromolar range.

References and Notes

• 2 Wiesner J. Ortmann R. Jomaa H. Schlitzer M. Angew. Chem. Int. Ed.  2003,  43:  5274 
  Google Scholar
• 3 Gilles MH. Management of Severe Malaria: A Practical Handbook   2nd ed.:  World Health Organization; Geneva: 2000. 
  Google Scholar
• 4a O’Neill PM. Mukhtar A. Stocks PA. Randle LE. Hindley S. Ward SA. Storr RC. Bickley JF. O’Neil IA. Maggs JL. Hughes RH. Winstanley PA. Bray PG. Park BK. J. Med. Chem.  2003,  46:  4933 
  CrossrefGoogle Scholar
• 4b Ridley RG. Hofheinz W. Matile H. Jaquet C. Dorn A. Masciadri R. Jolidon S. Richter WF. Guenzi A. Girometta MA. Urwyler H. Huber W. Thaithong S. Peters W. Antimicrob. Agents Chemother.  1996,  40:  1846 
  CrossrefGoogle Scholar
• 4c Stocks PA. Raynes KJ. Bray PG. Park BK. O’Neill PM. Ward SA. J. Med. Chem.  2002,  45:  4975 
  CrossrefGoogle Scholar
• 4d Vlahov R. Pavrushev S. Vlahov J. Pure Appl. Chem.  1990,  62:  1303 
  CrossrefGoogle Scholar
• 4e Madrid PB. Sherrill J. Liou AP. Weisman JL. DeRisi JL. Kipling Guy R. Bioorg. Med. Chem. Lett.  2005,  15:  1015 
  CrossrefGoogle Scholar
• 5a Fournet A. Vagneur B. Richomme P. Bruneton J. Can. J. Chem.  1989,  67:  2116 
  CrossrefPubMedGoogle Scholar
• 5b Fournet A. Hocquemiller R. Roblot F. Cavé A. Richomme P. Bruneton J. J. Nat. Prod.  1993,  56:  1547 
  CrossrefPubMedGoogle Scholar
• 5c Fournet A. Barrios AA. Muñoz V. Hocquemiller R. Cavé A. Richomme P. Bruneton J. Antimicrob. Agents Chemother.  1993,  37:  859 
  CrossrefPubMedGoogle Scholar
• 6 Fakhfakh MA. Fournet A. Prina E. Mouscadet J.-F. Franck X. Hocquemiller R. Figadere B. Bioorg. Med. Chem.  2003,  11:  5013 
  CrossrefPubMedGoogle Scholar
• 7a Steel PJ. Coord. Chem. Rev.  1990,  106:  227 
  Google Scholar
• 7b Ernst S. Kaim W. J. Am. Chem. Soc.  1986,  108:  3578 
  Google Scholar
• 7c Mamo A. Nicolleti S. Cam Tat N. Molecules  2002,  7:  618 
  Google Scholar
• 7d Qaseer H. Croat. Chim. Acta  2005,  78:  79 
  Google Scholar
• 8 Balasubramanian M. Keay JG. In Comprehensive Hetrocyclic Chemistry II   Vol. 5:  Katrizky AR. Rees CW. Scriven EFV. Pergamon Press; Oxford: 1996.  Chap. 5.06. p.245 
  Google Scholar
• 9 Manske RHF. Kukla M. Org. React.  1953,  7:  59 
  Google Scholar
• 10 For a review on recent progress in the synthesis of quinolines, see: Kouznetsov VV. Mendez LY. Mendelez Gomez CM. Curr. Org. Chem.  2005,  9:  141 
  CrossrefGoogle Scholar
• For recent quinoline syntheses, see e.g.:
• 11a Cho CK. Oh BH. Shim SC. J. Heterocycl. Chem.  1999,  36:  1175 
  CrossrefGoogle Scholar
• 11b Cho CK. Oh BH. Shim SC. Tetrahedron Lett.  1999,  40:  1499 
  CrossrefGoogle Scholar
• 11c Cho CK. Oh BH. Shim SC. Oh DH. J. Heterocycl. Chem.  2000,  37:  1315 
  CrossrefGoogle Scholar
• 11d Cho CK. Oh BH. Kim JS. Kim T.-J. Shim SC. Chem. Commun.  2000,  1885 
  CrossrefGoogle Scholar
• 11e Sangu K. Fuchibe K. Akiyama T. Org. Lett.  2004,  6:  353 
  CrossrefGoogle Scholar
• 11f Jacob J. Jones WD. J. Org. Chem.  2003,  68:  3563 
  CrossrefGoogle Scholar
• 11g Akiyama T. Nakashima S. Yokota K. Fuchibe K. Chem. Lett.  2004,  33:  922 
  CrossrefGoogle Scholar
• 12a Cho CS. Lee NY. Kim T.-J. Shim SC. J. Heterocycl. Chem.  2004,  41:  409 
  CrossrefGoogle Scholar
• 12b Cho CS. J. Organomet. Chem.  2005,  690:  4094 
  CrossrefGoogle Scholar
• 13a Braun RU. Ansorge M. Müller TJJ. Chem. Eur. J.  2006,  12:  9081 
  CrossrefGoogle Scholar
• 13b Müller TJJ. Ansorge M. Aktah D. Angew. Chem. Int. Ed.  2000,  39:  1253 
  CrossrefGoogle Scholar
• 14a Liao W.-W. Müller TJJ. Synlett  2006,  3469 
  Article in Thieme ConnectGoogle Scholar
• 14b Schramm née Dediu OG. Müller TJJ. Adv. Synth. Catal.  2006,  348:  2565 
  Article in Thieme ConnectGoogle Scholar
• 14c Schramm née Dediu OG. Müller TJJ. Synlett  2006,  1841 
  Article in Thieme ConnectGoogle Scholar
• 15a Müller TJJ. Targets in Heterocyclic Systems  2006,  10:  54 
  CrossrefPubMedGoogle Scholar
• 15b Müller TJJ. Chim. Oggi/Chemistry Today  2007,  25(1):  70 
  CrossrefPubMedGoogle Scholar
• 15c D’Souza DM. Müller TJJ. Chem. Soc. Rev.  2007,  36:  1095 
  CrossrefPubMedGoogle Scholar

New address: Lehrstuhl für Organische Chemie, Institut für Organische Chemie und Makromolekulare Chemie der Heinrich-Heine-Universität Düsseldorf, Universitätsstraße 1, 40225 Düsseldorf, Germany.

Typical Procedure (3g, Table 1, Entry 7)
A magnetically stirred solution of 1d (234 mg, 1.00 mmol), 2a (139 mg, 1.05 mmol), (PPh₃)₂PdCl_{2 (}20 mg, 0.02 mmol), and CuI (2 mg, 0.01 mmol) in degassed DBU (2 mmol) and THF (1.5 mL) was stirred under nitrogen in a heavy-walled SmithCreator process vial in the microwave cavity at 150 °C for 30 min. After cooling to r.t. EtOAc (40 mL) and H₂O (40 mL) were added and the aqueous layer was extracted with EtOAc. The combined organic phases were dried with MgSO₄ and the solvents were removed in vacuo. The residue was chromatographed on silica gel (hexane-EtOAc, 5:1) and recrystallized from EtOH or pentane-CHCl₃ (1:1) to give 174 mg (79%) of 3g as light yellow crystals, mp 142 °C. ¹H NMR (300 MHz, CDCl₃): δ = 2.54 (s, 3 H), 7.44-7.54 (m, 3 H), 7.91 (d, J = 1.5 Hz, 1 H), 7.94 (d, J = 8.3 Hz, 1 H), 8.13 (d, J = 8.3 Hz, 1 H), 8.28 (dd, J = 8.3, 1.5 Hz, 2 H), 8.96 (d, J = 2.1 Hz, 1 H). ¹³C NMR (100 MHz, CDCl₃): δ = 18.6 (CH₃), 119.6 (CH), 121.3 (C_q), 127.8 (CH), 128.8 (CH), 129.9 (CH), 131.5 (C_q), 135.2 (CH), 137.1 (CH), 138.7 (C_q), 154.8 (C_q), 155.8 (CH), 159.3 (C_q). MS: (EI, 70 eV): m/z (%) = 220.1 (100) [M⁺], 205.1 (10) [M⁺ - CH₃], 77 (12) [C₆H₅ ⁺]. IR (KBr): ν = 3027, 1604, 1581, 1546, 1503, 1481, 1458, 1434, 1321, 1278, 1140, 1025, 898, 814, 766, 739, 703, 678, 568 cm^-1. Anal. Calcd for C₁₅H₁₂N₂ (220.3): C, 81.79; H, 5.49; N, 12.72. Found: C, 81.71; H, 5.38; N, 12.79.

All compounds have been fully characterized by ¹H, ¹³C and DEPT, COSY, NOESY, HETCOR and HMBC NMR experiments, IR, mass spectrometry, HRMS, and/or combustion analyses.

CCDC-669319 (3c) contains the supplementary crystallographic data for this paper. These data can be obtained free of charge via http://www.ccdc.cam.ac.uk/conts/retrieving.html [or from the Cambridge Crystallographic Data Center, 12 Union Road, Cambridge CB2 1EZ, UK; fax: +44 (1223)336033; or deposit@ccdc.cam.ac.uk].