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Synthesis 2009(24): 4226-4234  
DOI: 10.1055/s-0029-1217060
PAPER
© Georg Thieme Verlag Stuttgart ˙ New York

Synthesis of Fluorescent 9-Aryl-Substituted Benzo[b]quinolizinium Derivatives

Maoqun Tian, Heiko Ihmels*
Organische Chemie II, Universität Siegen, Adolf-Reichwein-Strasse 2, 57068 Siegen, Germany
Fax: +49(271)7404052; e-Mail: ihmels@chemie.uni-siegen.de;
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Publication History

Received 12 June 2009
Publication Date:
19 October 2009 (online)

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Abstract

The arylation of readily available benzo[b]quinolizinium-9-boronic acid with carbocyclic or heterocyclic bromoarenes in the presence of a palladium catalyst [Pd(dppf)Cl2˙CH2Cl2 or Pd(PPh3)2Cl2] gives the corresponding cationic biaryl products in yields of 15-81%. All aryl-substituted benzo[b]quinolizinium (acridizinium) derivatives exhibit a long-wavelength absorption maximum between 409 and 422 nm in water, which change marginally in different solvents (Δλ <10 nm). As the only exception, the 9-(N,N-dimethylaminophenyl)benzo[b]quinolizinium exhibits pronounced solvatochromic behavior (H2O: λabs = 422 nm; MeCN: λabs = 474 nm; CH2Cl2: λabs = 507 nm) due to the strong donor-acceptor­ interplay in the cationic chromophore. Depending on the donor strength of the aryl substituent, the benzo[b]quinolizinium derivatives exhibit fluorescence bands in water with long-wavelength maxima between λfl = 452 nm (R = phenyl) and 529 nm (R = 4-methoxyphenyl). The non-fluorescent 9-(N,N-dimethylaminophenyl)benzo[b]quinolizinium may be employed as a pH-sensitive light-up probe (pH 2.8-4.8), since its emission intensity increases by a factor of 130 upon protonation.

Key words

arylations - biaryls - cationic hetarenes - heterocycles - fluorescent probes

    References

  • 1a Functional Dyes   Kim S.-H. Elsevier; Amsterdam: 2006. 
  • 1b Zollinger H. Color Chemistry   3rd ed.:  VCH; Weinheim: 2003. 
    Search in Google Scholar
  • 1c Lakowicz R. Principles of Fluorescence Spectroscopy   3rd ed.:  Plenum Publishing; New York: 2006. 
    Search in Google Scholar
  • 2a Martinez V. Burgos C. Alvarez-Builla J. Fernandez G. Domingo A. Garcia-Nieto R. Gago F. Manzanares I. Cuevas C. Vaquero JJ. J. Med. Chem.  2004,  47:  1136 
    Search in Google Scholar
  • 2b Molina A. Vaquero JJ. García-Navío JL. Alvarez-Builla J. Pascual-Teresa B. Gago F. Rodrigo MM. J. Org. Chem.  1999,  64:  3907 
    Search in Google Scholar
  • 2c Fontana A. Benito EJ. Martín JM. Sánchez N. Alajarin R. Vaquero JJ. Alvarez-Builla J. Lambel-Giraudet SL. Pierre A. Caignard D. Bioorg. Med. Chem. Lett.  2002,  12:  2611 
    Search in Google Scholar
  • 2d Ihmels H. Faulhaber K. Vedaldi D. Dall’Acqua F. Viola G. Photochem. Photobiol.  2005,  81:  1107 
    Search in Google Scholar
  • 2e Granzhan A. Ihmels H. Viola G. J. Am. Chem. Soc.  2007,  129:  1254 
    Search in Google Scholar
  • 3a Vaquero JJ. Alvarez-Builla J. Advances in Nitrogen Heterocycles   Vol. 4:  Moody CJ. JAI Press; Stamford CT: 2000. 
    Search in Google Scholar
  • 3b Bradsher CK. In Comprehensive Heterocyclic Chemistry   Vol. 2:  Boultier AJ. McKillop A. Pergamon Press; Oxford: 1985.  p.525 
    Search in Google Scholar
  • 4a Granzhan A. Ihmels H. ARKIVOC  2007,  (viii):  136 
    Search in Google Scholar
  • 4b van den Berg O. Jager WF. Picken SJ. J. Org. Chem.  2006,  71:  2666 
    Search in Google Scholar
  • 4c Naruto S. Mizuta H. Nishimura H. Tetrahedron Lett.  1976,  17:  1597 
    Search in Google Scholar
  • 5a Deiseroth HJ. Granzhan A. Ihmels H. Schlosser M. Tian M. Org. Lett.  2008,  10:  757 
    Search in Google Scholar
  • 5b Krapcho AP. Cadamuro SA. Macnee L. ARKIVOC  2007,  (ix):  28 
    Search in Google Scholar
  • 5c Mörler D. Kröhnke F. Liebigs Ann. Chem.  1971,  744:  65 
    Search in Google Scholar
  • 5d Arai S. Hida M. Advances in Heterocyclic Chemistry   Katritzky AR. Academic Press; Orlando: 1992. 
  • 5e Miyadera T. Tachikawa R. Tetrahedron  1969,  25:  837 
    Search in Google Scholar
  • 6a Barchín BM. Valenciano J. Cuadro AM. Alvarez-Builla J. Vaquero JJ. Org. Lett.  1999,  1:  545 
    Search in Google Scholar
  • 6b García-Cuadrado D. Cuadro AM. Barchín BM. Nuñez A. Cañeque T. Alvarez-Builla J. Vaquero JJ. J. Org. Chem.  2006,  71:  7989 
    Search in Google Scholar
  • 6c García D. Cuadro AM. Alvarez-Builla J. Vaquero JJ. Org. Lett.  2004,  6:  4175 
    Search in Google Scholar
  • 7 García-Cuadrado D. Cuadro AM. Alvarez-Builla J. Vaquero JJ. Synlett  2002,  1904 
    Thieme Connect
  • 8 Caneque T. Cuadro AM. Alvarez-Builla J. Vaquero JJ. Tetrahedron Lett.  2009,  50:  1419 
    CrossrefSearch in Google Scholar
  • 9a Miyaura N. Suzuki A. Chem. Rev.  1995,  95:  2457 
    Search in Google Scholar
  • 9b Miyaura N. Top. Curr. Chem.  2002,  219:  11 
    Search in Google Scholar
  • 9c Suzuki A. Chem. Commun.  2005,  4759 
  • 9d Miyaura N. In Metal-Catalyzed Cross-Coupling Reactions   Diederich F. de Meijere A. Wiley-VCH; New York: 2004.  Chap. 2.
  • 9e Martin R. Buchwald SL. Acc. Chem. Res.  2008,  41:  1461 
    Search in Google Scholar
  • 10a Nicolas M. Fabre B. Marchand G. Simonet J. Eur. J. Org. Chem.  2000,  1703 
  • 10b Zhang C. Zheng G. Fang L. Li Y. Synlett  2006,  475 
  • 11 Wright SW. Hageman DL. McClure LD. J. Org. Chem.  1994,  59:  6095 
    CrossrefSearch in Google Scholar
  • 12 Kudo N. Perseghini M. Fu GC. Angew. Chem. Int. Ed.  2006,  45:  1282 
    CrossrefSearch in Google Scholar
  • 13 Molander GA. Petrillo DE. Org. Lett.  2008,  10:  1795 
    CrossrefSearch in Google Scholar
  • 14 Molander GA. Canturk B. Kennedy LE. J. Org. Chem.  2009,  74:  973 
    Search in Google Scholar
  • 15 Saraf SUD. Heterocycles  1981,  16:  987 
    CrossrefSearch in Google Scholar
  • A similar effect has been observed in other chromophores, see:
  • 16a Choi SH. Kim K. Lee J. Do Y. Churchill DG. J. Chem. Crystallogr.  2007,  37:  315 
    Search in Google Scholar
  • 16b Baraldi I. Ginocchietti G. Mazzucato U. Spalletti A. Chem. Phys.  2007,  337:  168 
    Search in Google Scholar
  • 17 A similar effect was observed for 9-[(4-dimethyl­-amino)phenyl]-10-methylacridinium perchlorate, see: Ariese F. Verhoeven JW. Recl. Trav. Chim. Pays-Bas  1989,  108:  109 
    Search in Google Scholar
  • 18 Laage D. Thompson WH. Blanchard-Desce M. Hynes JT. J. Phys. Chem. A  2003,  107:  6032 
    CrossrefSearch in Google Scholar
  • 19a de Silva AP. Gunaratne HQN. Gunnalaugsson T. Huxley AJM. McCoy CP. Rademacher JT. Rice TE. Chem. Rev.  1997,  97:  1515 
    Search in Google Scholar
  • 19b Valeur B. Molecular Fluorescence: Principles and Applications   Wiley-VCH; Weinheim: 2002. 
  • 20 Polster J. Lachmann H. Spectrometric Titrations: Analysis of Chemical Equilibria   VCH; Weinheim: 1989. 
  • 21 Jonker SA. Vandijk SI. G oubitz K. Reiss CA. Schuddeboom W. Verhoeven JW. Mol. Cryst. Liq. Cryst.  1990,  183:  273 
    CrossrefSearch in Google Scholar
  • For other water-soluble pH probes, see for example:
  • 22a Evangelio E. Hernando J. Imaz I. Bardaj GG. Alibos R. Busquo F. Ruiz-Molina D. Chem. Eur. J.  2008,  14:  9754 
    Search in Google Scholar
  • 22b Bergen A. Granzhan A. Ihmels H. Photochem. Photobiol. Sci.  2008,  7:  405 
    Search in Google Scholar
  • 22c de Silva AP. de Silva SSK. Goonesekera NCW. Gunaratne HQN. Lynch PLM. Nesbitt KR. Patuwathavithana ST. Ramyalal NLDS. J. Am. Chem. Soc.  2007,  129:  3050 
    Search in Google Scholar
  • 22d Ikeda S. Okamoto A. Photochem. Photobiol. Sci.  2007,  6:  1197 
    Search in Google Scholar
  • 22e Yuasa H. Fujii N. Yamazaki S. Org. Biomol. Chem.  2007,  5:  2920 
    Search in Google Scholar
  • 22f Sun KM. McLaughlin CK. Lantero DR. Manderville RA. J. Am. Chem. Soc.  2007,  129:  1894 
    Search in Google Scholar
  • 22g Tang B. Liu X. Xu K. Huang H. Yang G. An L. Chem. Commun.  2007,  3726 
  • 22h Hilderbrand SA. Weissleder R. Chem. Commun.  2007,  2747 
  • 23 Bradsher CK. Sherer JP. Parham JH. J. Chem. Eng. Data  1965,  10:  180 
    CrossrefSearch in Google Scholar
  • 24 Harris RK. Becker ED. Cabral de Menezes S. Goodfellow R. Granger P. Pure Appl. Chem.  2001,  73:  1795 
    CrossrefSearch in Google Scholar
  • 25 Britton HTS. Robinson RA. J. Chem. Soc.  1931,  458 
    Crossref