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Synlett 2008(3): 410-412  
DOI: 10.1055/s-2007-1000875
LETTER
© Georg Thieme Verlag Stuttgart · New York

A Novel One-Pot Synthesis of N-Acylindoles from Primary Aromatic Amides

Mohammed Abid , Omar De Paolis, Béla Török*
Department of Chemistry, University of Massachusetts Boston, 100 Morrissey Blvd, Boston, MA 02125, USA
Fax: +1(617)2876030; e-Mail: bela.torok@umb.edu;
Further Information

Publication History

Received 10 September 2007
Publication Date:
21 December 2007 (online)

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Abstract

A novel one-pot synthesis of N-acylindoles via tandem cycloalkylation-annelation is described. This approach is based on the use of a strong solid-acid catalyst, montmorillonite K-10, and microwave irradiation under solvent-free conditions. The tandem cycloalkylation of amides and annelation of intermediate pyrroles were completed in minutes and provided good yields with high selectivities for the indoles. The safe, easy to handle catalyst, and the convenience of the product isolation make this process an attractive, environmentally benign alternative for the synthesis of N-acylindoles.

Keywords

amides - solid-acid catalysis - microwave heating - N-acylindole

    References and Notes

  • 1a Gribble GW. J. Chem. Soc., Perkin Trans. 1  2000,  1045 ; and references cited therein
    CrossrefPubMedGoogle Scholar
  • 1b Fürstner A. Szillat H. Gabor B. Mynott R. J. Am. Chem. Soc.  1998,  120:  8305 
    CrossrefPubMedGoogle Scholar
  • 1c Török M. Abid M. Mhadgut SC. Török B. Biochemistry  2006,  45:  5377 
    CrossrefPubMedGoogle Scholar
  • 1d Zhang Y. Wada T. Sasabe H. Chem. Commun.  1996,  621 
    CrossrefPubMedGoogle Scholar
  • 1e Sundberg RJ. Indoles   Academic Press; London: 1996. 
    CrossrefPubMedGoogle Scholar
  • 1f Robinson B. The Fischer Indole Synthesis   John Wiley and Sons; Chichester: 1982. 
    CrossrefPubMedGoogle Scholar
  • 1g Török B. Abid M. London G. Esquibel J. Török M. Mhadgut SC. Yan P. Prakash GKS. Angew. Chem. Int. Ed.  2005,  44:  3086 
    CrossrefPubMedGoogle Scholar
  • 2a Kohling P. Schmidt AM. Eilbracht P. Org. Lett.  2003,  5:  3213 
    Google Scholar
  • 2b Katritzky AR. Fali CN. Li J. J. Org. Chem.  1997,  62:  4148 
    Google Scholar
  • 2c Fayol A. Fang Y.-Q. Lautens M. Org. Lett.  2006,  8:  4203 
    Google Scholar
  • 2d Wagaw S. Yang BH. Buchwald SL. J. Am. Chem. Soc.  1998,  120:  6621 
    Google Scholar
  • 2e Bremner JB. Samosorn S. Ambrus JI. Synthesis  2004,  2653 
    Google Scholar
  • 2f Myznikov YE. Koldobskii GI. Vasil’eva IN. Ostrovskii VA. Zh. Org. Khim.  1988,  24:  1550 
    Google Scholar
  • 2g Hayakawa K. Yasukouchi T. Kanematsu K. Tetrahedron Lett.  1986,  27:  1837 
    Google Scholar
  • 2h Martin P. Helv. Chim. Acta  1984,  67:  1647 
    Google Scholar
  • 2i Terashima M. Fujioka M. Heterocycles  1982,  19:  91 
    Google Scholar
  • 2j Ikeda M. Ohno K. Uno T. Tamura Y. Tetrahedron Lett.  1980,  21:  3 
    Google Scholar
  • 2k Itahara T. Synthesis  1979,  151 
    Google Scholar
  • 2l Itahara T. Heterocycles  1986,  24:  2557 
    Google Scholar
  • 2m Aggarwal R. Benedetti F. Berti F. Buchini S. Colombatti A. Chem. Eur. J.  2003,  9:  3132 
    Google Scholar
  • 2n Bourgeois P. Mesdouze J. Philogene E. J. Heterocycl. Chem.  1983,  20:  1043 
    Google Scholar
  • 3a Fischer E. Ber. Dtsch. Chem. Ges.  1886,  19:  1563 
    CrossrefGoogle Scholar
  • 3b Hughes DL. Org. Prep. Proced. Int.  1993,  25:  607 
    CrossrefGoogle Scholar
  • 3c Reissert A. Ber. Dtsch. Chem. Ges.  1896,  29:  655 
    CrossrefGoogle Scholar
  • 3d Blasko G. Kerekes P. Makleit S. Alkaloids  1987,  31:  1 
    CrossrefGoogle Scholar
  • 3e Madelung W. Ber. Dtsch. Chem. Ges.  1912,  45:  3521 
    CrossrefGoogle Scholar
  • 3f Brown RK. In Indoles   Part 1:  Houlihan WJ. Wiley; New York: 1972.  p.385 
    CrossrefGoogle Scholar
  • 3g Zeni G. Larock RC. Chem. Rev.  2004,  104:  2285 
    CrossrefGoogle Scholar
  • 3h Kondo Y. Sakamoto T. Yamanaka H. Heterocycles  1989,  29:  1013 
    CrossrefGoogle Scholar
  • 3i Arcadi A. Cacchi S. Marinelli F. Tetrahedron Lett.  1989,  30:  2581 
    CrossrefGoogle Scholar
  • 3j Cacchi S. Fabrizi G. Marinelli F. Moro L. Pace P. Synlett  1997,  1363 
    CrossrefGoogle Scholar
  • 3k Cacchi S. Fabrizi G. Parisi LM. Synthesis  2004,  1889 
    CrossrefGoogle Scholar
  • 3l Kabalka GW. Wang L. Pagni RM. Tetrahedron  2001,  57:  8017 
    CrossrefGoogle Scholar
  • 4a Itahara T. Synthesis  1979,  151 
    Article in Thieme ConnectGoogle Scholar
  • 4b Bremner JB. Samosorn S. Ambrus JI. Synthesis  2004,  2653 
    Article in Thieme ConnectGoogle Scholar
  • 5a Corma A. Chem. Rev.  1995,  95:  559 
    CrossrefGoogle Scholar
  • 5b Gates BC. Catalysis by Solid Acids, In Encyclopedia of Catalysis   Vol. 2:  Horváth I. Wiley; New York: 2003.  p.104 
    CrossrefGoogle Scholar
  • 6a Balogh M. Laszlo P. Organic Chemistry Using Clays   Springer; Berlin, Heidelberg: 1993. 
    CrossrefGoogle Scholar
  • 6b Szöllösi G. Török B. Baranyi L. Bartók M. J. Catal.  1998,  179:  619 
    CrossrefGoogle Scholar
  • 6c Török B. London G. Bartók M. Synlett  2000,  631 
    CrossrefGoogle Scholar
  • 6d Abid M. Török B. Adv. Synth. Catal.  2005,  347:  1797 
    CrossrefGoogle Scholar
  • 6e Landge SM. Schmidt A. Outerbridge V. Török B. Synlett  2007,  1600 
    CrossrefGoogle Scholar
  • 6f Dasgupta S. Török B. Org. Prep. Proced. Int  2008,  40:  1 
    CrossrefGoogle Scholar
  • 7a Varma RS. Dahiya R. Kumar S. Tetrahedron Lett.  1997,  38:  2039 
    CrossrefGoogle Scholar
  • 7b Walla P. Kappe CO. Chem. Commun.  2004,  594 
    CrossrefGoogle Scholar
  • 7c Loupy A. Microwaves in Organic Synthesis   Wiley-VCH; Weinheim: 2005. 
    CrossrefGoogle Scholar
  • 7d Kappe CO. Stadler A. Microwaves in Organic and Medicinal Chemistry   Wiley-VCH; Weinheim: 2005. 
    CrossrefGoogle Scholar
  • 7e Landge SM. Atanassova V. Thimmaiah M. Török B. Tetrahedron Lett.  2007,  48:  5161 
    CrossrefGoogle Scholar
  • 8a Banik BK. Samajdar S. Banik I. J. Org. Chem.  2004,  69:  213 
    CrossrefPubMedGoogle Scholar
  • 9a De’Silva C. Walker DA. J. Org. Chem.  1998,  63:  6715 
    CrossrefGoogle Scholar
  • 9b McIntosh JM. J. Org. Chem.  1988,  53:  447 
    CrossrefGoogle Scholar
  • 9c Abid M. Landge S. Török B. Org. Prep. Proced. Int.  2006,  38:  495 
    CrossrefGoogle Scholar
  • 9d Abid M. Spaeth A. Török B. Adv. Synth. Catal.  2006,  348:  2191 
    CrossrefGoogle Scholar
  • 9e Abid M. Teixeira L. Török B. Tetrahedron Lett.  2007,  48:  4047 
    CrossrefGoogle Scholar
  • 10 All reactants including the catalyst, montmorillonite K-10, were purchased from Aldrich and used without further purification. The 1H NMR and 13C NMR spectra were obtained on a 300 MHz Varian NMR spectrometer in CDCl3. Tetramethylsilane or the residual solvent signal was used as reference. The mass spectrometric identification of the products was carried out on an Agilent 6850 GC and 5973 MS system (70 eV electron impact ionization) using a 30 m long DB-5 type column (J&W Scientific). The melting points were uncorrected and were recorded on a MEL-TEMP apparatus. General Procedure for the Synthesis of N -Acylindoles: An amide (1.0 mmol) and 2,5-dimethoxytetrahydrofuran (2.0 mmol) were dissolved in 3 mL of CH2Cl2 in a round-bottomed flask, then K-10 (500 mg) was added. After 5 min stirring, the solvent was removed to obtain the mixture of reactants adsorbed on the catalyst surface. The dry mixture was transferred into a glass reaction vial and irradiated in the microwave reactor (CEM Discover Benchmate, 80 °C). During optimization, the progress of the reaction was monitored by TLC and GC-MS to determine the necessary reaction times. After satisfactory conversion, CH2Cl2 was added to the cold mixture, and the product was separated from the catalyst by filtration. The products were isolated as crystals or oils and purified by flash chromatography. All products showed satisfactory spectral data (MS, 1H and 13C NMR). Here, the full spectral characterization is given for only the previously unknown products. Such data for the known compounds synthesized in this study are available from the authors. 1-(4-Fluorobenzoyl) indole (Table 1, Entry 5): mp 82.9-84.3 °C (MeOH); 1H NMR (300.12 MHz, CDCl3): δ = 8.36 (d, J = 7.8 Hz, 1 H), 7.79-7.74 (m, 2 H), 7.61 (d, J = 7.8 Hz, 1 H), 7.41-7.29 (m, 2 H), 7.27-7.18 (m, 3 H), 6.61 (d, J = 3.9 Hz, 1 H) ppm; 13C NMR (75.474 MHz, CDCl3): d = 166.6, 132.0, 131.8, 127.4, 126.9, 125.1, 124.2, 123.6, 121.1, 120.1, 116.4, 115.8, 108.9 ppm; MS for C15H10FNO(239): m/z (%) = 239 (40) [M+], 123 (100), 116 (5), 95 (30), 75 (15). Biphenyl-4-yl(1 H -indole-1-yl)methanone (Table 1, Entry 8): mp 98.2-100.1 °C (MeOH); 1H NMR (300.12 MHz, CDCl3): δ = 8.43 (d, J = 8.1 Hz, 1 H), 7.84-7.80 (m, 2 H), 7.76-7.67 (m, 2 H), 7.66-7.60 (m, 3 H), 7.52 (m, 3 H), 7.37-7.32 (m, 3 H), 6.65 (d, J = 3.6 Hz, 1 H) ppm; 13C NMR (75.474 MHz, CDCl3): δ = 166.0, 144.9, 130.0, 129.1, 128.4, 128.4, 127.7, 127.6, 127.4, 126.9, 121.0, 116.5, 108.7 ppm; MS for C21H15NO(297): m/z (%) = 297 (30) [M+], 181 (100), 152 (60), 116 (15), 77 (5)