Download PDF
Synthesis 2011(2): 251-256  
DOI: 10.1055/s-0030-1258371
PAPER
© Georg Thieme Verlag Stuttgart ˙ New York

Synthesis of 6-Amino-2-bromo-4-hydroxynicotinaldehyde Derivatives

Alexander V. Denisenkoa, Anton V. Tverdokhlebov*b, Andrey A. Tolmacheva,b, Yulian M. Volovenkoa, Svitlana V. Shishkinac, Oleg V. Shishkinc
a Kiev National Taras Shevchenko University, Volodimirska str., 62, 01033 Kiev, Ukraine
b Enamine Ltd., Alexandra Matrosova str., 23, 01103 Kiev, Ukraine
Fax: +380445373253; e-Mail: atver@univ.kiev.ua;
c STC Institute for Single Crystals, NAS of Ukraine, 60 Lenina ave., 61001 Kharkiv, Ukraine
Further Information

Publication History

Received 26 October 2010
Publication Date:
20 December 2010 (online)

   Permissions and Reprints All articles of this category
Preview

Abstract

Acylation of (1,3-dimethylbenzimidazol-2-ylidene)-, (3-methylbenzothiazol-2-ylidene)-, and (3,4-dimethylthiazol-2-ylidene)-acetonitriles with 1-(cyanoacetyl)-3,5-dimethylpyrazole was found to proceed at the exocyclic carbon atom, yielding the appropriate 2-heterylidene-3-oxopentanedinitriles. Treatment of the prepared dinitriles with hydrobromic acid in refluxing acetic acid afforded 2-(6-amino-2-bromo-4-hydroxypyridin-3-yl)-substituted quaternary salts of benzimidazolium, benzothiazolium, and thiazolium. Their structures were confirmed unambiguously by X-ray crystallographic studies. Reduction of these quaternary salts with excess sodium borohydride yielded the corresponding dihydro (in the case of benzoazoles) or tetrahydro (in the case of thiazole) derivatives, which were shown to be synthetic equivalents of the title nicotinaldehyde.

Key words

aldehydes - heterocycles - hydrazones - nitriles - pyridines

    References

  • 1a Tran JA. Jiang W. Tucci FC. Fleck BA. Wen J. Sai Y. Madan A. Chen TK. Markison S. Foster AC. Hoare SR. Marks D. Harman J. Chen CW. Arellano M. Marinkovic D. Bozigian H. Sanders J. Chen C. J. Med. Chem.  2007,  50:  6356 
    Search in Google Scholar
  • 1b Wang X. Snieckus V. Tetrahedron Lett.  1991,  32:  4883 
    Search in Google Scholar
  • 1c Harrowven DC. Tetrahedron Lett.  1993,  34:  5653 
    Search in Google Scholar
  • 1d Staab HA. Diehm M. Krieger C. Tetrahedron Lett.  1994,  35:  8357 
    Search in Google Scholar
  • 2a Chelucci G. Baldino S. Pinna GA. Sechi B. Tetrahedron Lett.  2008,  46:  2839 
    Search in Google Scholar
  • 2b Robert N. Hoarau C. Celanire S. Ribereau P. Godard A. Queguiner G. Marsais F. Tetrahedron  2005,  61:  4569 
    Search in Google Scholar
  • 2c Lyaskovskyy V. Fröhlich R. Würthwein E.-U. Synthesis  2007,  2135 
  • 2d Song ZJ. Zhao M. Desmond R. Devine P. Tschaen DM. Frey L. Heid R. Xu F. Foster B. Li J. Reamer R. Volante R. Grabowski EJJ. Dolling UH. Reider PJ. Okada S. Kato Y. Mano E. J. Org. Chem.  1999,  64:  9658 
    Search in Google Scholar
  • 2e Numata A. Kondo Y. Sakamoto T. Synthesis  1999,  306 
  • 3a de la Fuente MC. Dominguez D. Tetrahedron  2009,  65:  3653 
    Search in Google Scholar
  • 3b Srinivasan JM. Bruks HE. Smith CR. Viswanatan R. Johnston JN. Synthesis  2005,  330 
  • 3c Chelucci G. Addis D. Baldino S. Tetrahedron Lett.  2007,  48:  3359 
    Search in Google Scholar
  • 3d Kato Y. Niiyama K. Nemoto T. Jona H. Akao A. Okada S. Song ZJ. Zhao M. Tsuchiya Y. Tomimoto K. Mase T. Tetrahedron  2002,  58:  3409 
    Search in Google Scholar
  • 3e Song ZJ. Zhao M. Frey L. Li J. Tan L. Chen CY. Tschaen DM. Tillyer M. Grabowski EJJ. Volante R. Reider PJ. Org. Lett.  2001,  3:  3357 
    Search in Google Scholar
  • 4a Ilyashenko G. Choudhury R. Motevalli M. Watkinson M. Synlett  2006,  1759 
  • 4b Mase T. Houpis IN. Akao A. Dorriotis I. Emerson Kh. Hoang T. Iida T. Itoh T. Kamei K. Kato S. Kato Y. Kawasaki M. Lang F. Lee J. Lynch J. Maligres P. Molina A. Nemoto T. Okada S. Reamer R. Song JZ. Tschaen D. Wada T. Zewge D. Volante RP. Reider PJ. Tomimoto K. J. Org. Chem.  2001,  66:  6775 
    Search in Google Scholar
  • 4c Bracher F. J. Heterocycl. Chem.  1993,  30:  157 
    Search in Google Scholar
  • 4d Melnyk P. Gasche J. Thal C. Synth. Commun.  1993,  23:  2727 
    Search in Google Scholar
  • 5a Mandal AB. Augustine JK. Quattropani A. Bombrun A. Tetrahedron Lett.  2005,  46:  6033 
    Search in Google Scholar
  • 5b Horn U. Mutterer F. Weis CD. Helv. Chim. Acta  1976,  59:  211 
    Search in Google Scholar
  • 5c Mutterer F. Weis CD. Helv. Chim. Acta  1976,  59:  229 
    Search in Google Scholar
  • 6a Craig JC. Ekwuribe NN. Fu CC. Walker KAM. Synthesis  1981,  303 
  • 6b Ramos JM. Tarazi M. Wuest JD. J. Org. Chem.  1987,  52:  5437 
    Search in Google Scholar
  • 6c Katritzky AR. Aslan DC. Oniciu DC. Tetrahedron: Asymmetry  1998,  2245 
  • 6d Lee I.-SH. Jeoung EH. Kreevoy MM. J. Am. Chem. Soc.  1997,  119:  2722 
    Search in Google Scholar
  • 6e Lee I.-SH. Jeoung EH. J. Org. Chem.  1998,  63:  7275 
    Search in Google Scholar
  • 7a Chikashita H. Ikegami S. Okumura T. Itoh K. Synthesis  1986,  375 
  • 7b Chikashita H. Ishibaba M. Ori K. Itoh K. Bull. Chem. Soc. Jpn.  1988,  61:  3637 
    Search in Google Scholar
  • 7c Corey EJ. Boger DL. Tetrahedron Lett.  1978,  5 
  • 7d Corey EJ. Boger DL. Tetrahedron Lett.  1978,  9 
  • 7e Corey EJ. Boger DL. Tetrahedron Lett.  1978,  13 
  • 7f Chikashita H. Itoh K. Heterocycles  1985,  23:  295 
    Search in Google Scholar
  • 8a Tverdokhlebov AV. Denisenko AV. Tolmachev AA. Volovenko YuM. Synthesis  2007,  1811 
  • 8b Denisenko AV. Tverdokhlebov AV. Tolmachev AA. Volovenko YuM. Shishkina SV. Shishkin OV. Synthesis  2010,  1009 
  • 8c Tverdokhlebov AV. Denisenko AV. Tolmachev AA. Volovenko YuM. Shishkina SV. Shishkin OV. Synthesis  2009,  1265 
  • 9a Rudnev MI. Kurbatov VP. Chub NK. Osipov OA. J. Gen. Chem. USSR (Engl. Transl.)  1988,  58:  2077 ; Zh. Obshch. Khim. 1988, 58, 2334
    Search in Google Scholar
  • 9b Van Dormael A. Nys J. Bull. Soc. Chim. Belg.  1950,  59:  588 
    Search in Google Scholar
  • 9c Doyle FP, and Kendall JD. inventors; US Patent  2542401.  ; Chem. Abstr. 1951, 45, 10109
  • 10a Büttelmann B. Peters J.-U. Ceccarelli S. Kolczewski S. Vieira E. Prinssen EP. Spooren W. Schuler F. Huwyler J. Porter RHP. Jaeschke G. Bioorg. Med. Chem. Lett.  2006,  16:  1892 
    Search in Google Scholar
  • 10b Mascal M. Hext NM. Warmuth R. Arnall-Culliford JR. Moore MH. Turkenburg JP. J. Org. Chem.  1999,  64:  8479 
    Search in Google Scholar
  • 10c Carboni RA. Coffman DD. Howard EG. J. Am. Chem. Soc.  1958,  80:  2838 
    Search in Google Scholar
  • 11a Neumeyer JL. Weinhardt KK. J. Med. Chem.  1973,  16:  808 
    Search in Google Scholar
  • 11b Neumeyer JL. Weinhardt KK. J. Med. Chem.  1970,  13:  613 
    Search in Google Scholar
  • 11c Sommer MB. Begtrup M. Bøgesø KP. J. Org. Chem.  1990,  55:  4822 
    Search in Google Scholar
  • 11d Deady LW. Ganakas A.-M. Ong BH. Aust. J. Chem.  1989,  42:  1029 
    Search in Google Scholar
  • 11e Johnson F. Nasutavicus WA. J. Org. Chem.  1962,  27:  3953 
    Search in Google Scholar
  • 11f Wan Y. Niu W. Behof WJ. Wang Y. Boyle P. Gorman CB. Tetrahedron  2009,  65:  4293 
    Search in Google Scholar
  • 11g Frohn M. Bürli RW. Riahi B. Hungate RW. Tetrahedron Lett.  2007,  48:  487 
    Search in Google Scholar
  • 12a Koitz G. Thierrichter B. Junek H. Heterocycles  1983,  20:  2405 
    Search in Google Scholar
  • 12b Victory PJ. Teixido J. Borrell JI. Busquets N. Heterocycles  1993,  36:  1 
    Search in Google Scholar
  • 12c Victory PJ. Teixido J. Borrell JI. Heterocycles  1992,  34:  1905 
    Search in Google Scholar
  • 12d Hersperger R. Bray-French K. Mazzoni L. Müller T. J. Med. Chem.  2000,  43:  675 
    Search in Google Scholar
  • 12e Teixido J. Borrell JI. Serra B. Matallana JL. Colominas C. Carrion F. Pascual R. Falco JL. Batllori X. Heterocycles  1999,  50:  739 
    Search in Google Scholar
  • 12f Victory P. Busquets N. Borrell JI. Teixido J. Serra B. Matallana JL. Junek H. Sterk H. Heterocycles  1995,  41:  1013 
    Search in Google Scholar
  • 13 Ried W. Meyer A. Chem. Ber.  1957,  90:  2841 
    CrossrefSearch in Google Scholar
  • 14a Ried W. Schleimer B. Angew. Chem.  1958,  70:  164 
    Search in Google Scholar
  • 14b Gorobets NYu. Yousefi BH. Belaj F. Kappe CO. Tetrahedron  2004,  60:  8633 
    Search in Google Scholar
  • 14c Stetinova J. Kada R. Lesko J. Zalibera L. Ilavsky D. Bartovic A. Collect. Czech. Chem. Commun.  1995,  60:  999 
    Search in Google Scholar
  • 14d Stetinova J. Kada R. Lesko J. Dandarova M. Krublova M. Collect. Czech. Chem. Commun.  1996,  61:  921 
    Search in Google Scholar
  • 14e Ried W. Schleimer B. Justus Liebigs Ann. Chem.  1959,  626:  98 
    Search in Google Scholar
  • 14f Ried W. Köcher EU. Justus Liebigs Ann. Chem.  1961,  647:  116 
    Search in Google Scholar
  • 14g Ried W. Schubert HJ. Justus Liebigs Ann. Chem.  1962,  653:  181 
    Search in Google Scholar
  • 14h Ried W. Schleimer B. Justus Liebigs Ann. Chem.  1959,  626:  106 
    Search in Google Scholar
  • 14i Jahine H. Zaher HA. Sayed A. Seada M. Indian J. Chem., Sect. B: Org. Chem. Incl. Med. Chem.  1977,  15:  352 
    Search in Google Scholar
  • 14j Stetinova J. Kada R. Lesko J. Molecules  1996,  1:  251 
    Search in Google Scholar
  • 14k Stetinova J. Kada R. Dandarova M. Krublova M. Lesko J. Chem. Heterocycl. Compd. (Engl. Transl.)  1995,  31:  1231 
    Search in Google Scholar
  • 15a Zakhs ER. Ponyaev AI. Subbotina MA. El’tsov AV. Russ. J. Gen. Chem. (Engl. Transl.)  2001,  71:  1076 ; Zh. Obshch. Khim. 2001, 71, 1142
    Search in Google Scholar
  • 15b Yagupolski LM. Kulchitsky MM. Ilchenko AYa. J. Org. Chem. USSR (Engl. Transl.)  1974,  10:  1326 ; Zh. Org. Khim. 1974, 10, 1321
    Search in Google Scholar
  • 15c Zakhs ER. Subbotina MA. El’tsov AV. J. Org. Chem. USSR (Engl. Transl.)  1979,  15:  178 ; Zh. Org. Khim. 1979, 15, 200
    Search in Google Scholar
  • 16a Zhang MQ. Haemers A. van den Berghe D. Pattyn SR. Bollaert W. Levshin I. J. Heterocycl. Chem.  1991,  28:  685 
    Search in Google Scholar
  • 16b Clarke GM. Sykes P. J. Chem. Soc. C  1967,  1269 
  • 17 Menta E, Da Re G, and Grugni M. inventors; WO  2003105842. 
  • 18 Scheldrick GM. Acta Crystallogr., Sect. A: Found. Crystallogr.  2008,  64:  112 
    CrossrefSearch in Google Scholar