Download PDF
Synthesis 2011(6): 873-880  
DOI: 10.1055/s-0030-1258445
PAPER
© Georg Thieme Verlag Stuttgart ˙ New York

A Practical Synthesis of 2-Aroylindoles from N-(2-Formylphenyl)trifluoro­acetamides in PEG-400

Yu Zhaoa, Deyao Lia, Liwen Zhaoa, Jiancun Zhang*a,b
a Guangzhou Institute of Biomedicine and Health, CAS, 190 Kai Yuan Avenue, Science Park, Guangzhou 510530, P. R. of China
Fax: +86(20)32015323; e-Mail: zhang_jiancun@gibh.ac.cn;
b State Key Laboratory of Respiratory Diseases, Guangzhou Medical College, Guangzhou 510120, P. R. of China
Further Information

Publication History

Received 18 November 2010
Publication Date:
18 February 2011 (online)

    Permissions and Reprints All articles of this category

Abstract

A one-pot and environmentally benign approach to the synthesis of highly functionalized 3-unsubstituted 2-aroylindoles is described. Moderate to good yields were obtained through the reaction of easily accessible N-(2-formylphenyl)trifluoroacetamides and α-bromoacetophenones in the presence of K2CO3. PEG-400 was found to be an efficient and reusable solvent in the process.

Key words

2-aroylindoles - PEG-400 - N-(2-formylphenyl)trifluoro­acetamides - heterocycles - cyclization

    References

  • 1 Humphrey GR. Kuethe JT. Chem. Rev.  2006,  106:  2875 
    CrossrefPubMedSearch in Google Scholar
  • 2a Romagnoli R. Baraldi PG. Sarkar T. Carrion MD. Cara CL. Cruz-Lopez O. Preti D. Tabrizi MA. Tolomeo M. Grimaudo S. Di Cristina A. Zonta N. Balzarini J. Brancale A. Hsieh H.-P. Hamel E. J. Med. Chem.  2008,  51:  1464 
    Search in Google Scholar
  • 2b Mahboobi S. Pongratz H. Hufsky H. Hockemeyer J. Frieser M. Lyssenko A. Paper DH. Bürgermeister J. Böhmer F.-D. Fiebig H.-H. Burger AM. Baasner S. Beckers T. J. Med. Chem.  2001,  44:  4535 
    Search in Google Scholar
  • 2c Beckers T. Reissmann T. Schmidt M. Burger AM. Fribig HH. Vanhoefer U. Pongratz H. hufsky H. Hockemeyer J. Frieser M. mahboobi S. Cancer Res.  2002,  62:  3113 
    Search in Google Scholar
  • 2d Brancale A. Silvestri R. Med. Res. Rev.  2007,  27:  209 
    Search in Google Scholar
  • 3 Mahboobi S. Sellmer A. Höcher H. Garhammer C. Pongratz H. Maier T. Ciossek T. Beckers T. J. Med. Chem.  2007,  50:  4405 
    CrossrefPubMedSearch in Google Scholar
  • 4 Mahboobi S. Teller S. Pongratz H. Hufsky H. Sellmer A. Botzki A. Uecker A. Beckers T. Baasner S. Schächtele C. Uberall F. Kassack MU. Dove S. Böhmer F.-D. J. Med. Chem.  2002,  45:  1002 
    CrossrefSearch in Google Scholar
  • 5 Willson TM. Brown PJ. Sternbach DD. Henke BR. J. Med. Chem.  2000,  43:  527 
    CrossrefPubMedSearch in Google Scholar
  • 6 Cruz-López O. Díaz-Mochón JJ. Campos JM. Entrena A. Núñez MT. Labeaga L. Orjales A. Gallo MA. Espinosa A. ChemMedChem  2007,  2:  88 
    CrossrefSearch in Google Scholar
  • 7a Saulnier MG. Gribble GW. J. Org. Chem.  1982,  47:  757 
    Search in Google Scholar
  • 7b Katritzky AR. Akutagawa K. Tetrahedron Lett.  1985,  26:  5935 
    Search in Google Scholar
  • 7c Takeda Y. Kikuchi A. Terashima M. Heterocycles  1993,  35:  573 
    Search in Google Scholar
  • 7d Kazunari N, William SR, Kiyoshi K, Chikara U, Hiroki K, and Stephane C. inventors; PCT Int. Appl. WO  9935130. 
  • 7e Thomas B, Siavosh M, Herwig P, Markus F, Harald H, Jörg H, and Udo V. inventors; PCT Int. Appl. WO  2003037861. 
  • 8a Arthuis M. Pontikis R. Florent J.-C. Org. Lett.  2009,  11:  4608 
    Search in Google Scholar
  • 8b Abbiati G. Casoni A. Canevari V. Nava D. Rossi E. Org. Lett.  2006,  8:  4839 
    Search in Google Scholar
  • 8c Labadie SS. Teng E. J. Org. Chem.  1994,  59:  4250 
    Search in Google Scholar
  • 8d Cenini S. Bettettini E. Fedele M. Tollari S. J. Mol. Catal. A: Chem.  1996,  111:  37 
    Search in Google Scholar
  • 9a Black DSt. C. Wong LCH. Chem. Commun.  1980,  4:  200 
    Search in Google Scholar
  • 9b Jones AW. Purwono B. Bowyer PK. Mitchell PSR. Kumar N. Nugent SJ. Jolliffe KA. Black DSt. C. Tetrahedron  2004,  60:  10779 
    Search in Google Scholar
  • 10a Jones CD. Suarez T. J. Org. Chem.  1972,  37:  3622 
    Search in Google Scholar
  • 10b Shiang J, Litz K, Celia JA, Chichak KS, and Ye Q. inventors; PCT Int. Appl. WO  2008014037. 
  • 12 Clark MP, Brugel TA, Sabat M, Golebiowski A, Bookland RG, and De B.. inventors; PCT Int. Appl. US 2008  0139588. 
  • For representative papers, see:
  • 13a Chandrasekhar S. Reddy NR. Sultana SS. Narsihmulu C. Reddy KV. Tetrahedron  2006,  62:  338 
    Search in Google Scholar
  • 13b Namboodiri VV. Varma RS. Green Chem.  2001,  3:  146 
    Search in Google Scholar
  • 15 Han R. Chen S. Lee SJ. Qi F. Wu X. Kim BH. Heterocycles  2006,  68:  1675 
    CrossrefSearch in Google Scholar
  • 16 Murakami Y. Heterocycles  1984,  22:  1211 
    CrossrefSearch in Google Scholar
11

The only reaction condition reported by Jones’ group was that DMF was used as the solvent. We examined different solvents including acetone, acetonitrile, toluene, DMF and PEG-400, and different bases including NaHCO3, Na2CO3, K2CO3 and Et3N. Only a trace amount of 2-aroylindole was obtained.

14

No attempt was made to free the PEG-400 of salts because the salts did not hamper the rate of the reaction