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Synthesis 2010(23): 4021-4032  
DOI: 10.1055/s-0030-1258292
PAPER
© Georg Thieme Verlag Stuttgart ˙ New York

A Green Approach to the Synthesis of Fused Uracils: Pyrano[2,3-d]pyrimidines. ‘On-Water’ One-Pot Synthesis by Domino Knoevenagel/Diels-Alder Reactions

Aleksandra Pałasz*
Department of Organic Chemistry, Jagiellonian University, ul. Ingardena 3, 30-060 Kraków, Poland
Fax: +48(12)6340515; e-Mail: palasz@chemia.uj.edu.pl;
Further Information

Publication History

Received 29 May 2010
Publication Date:
12 October 2010 (online)

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Abstract

‘On-water’ Knoevenagel condensations of 2-thiobarbituric acid and N,N-dimethylbarbituric acid with aromatic and heteroaromatic aldehydes were carried out without a catalyst and at room temperature. Condensations in aqueous suspensions occurred rapidly, giving excellent yields. Solvent-free hetero-Diels-Alder reactions of 5-arylidene derivatives of barbituric acids with ethyl vinyl ether were investigated at room temperature and pyrano[2,3-d]pyrimidines of potential pharmacological activity were obtained in excellent yields. Three-component one-pot syntheses of annulated uracils were performed in aqueous suspensions. Reactions of barbituric acids, aldehydes, and ethyl vinyl ether were carried out at ambient temperature, whereas the one-pot synthesis with barbituric acids, aldehydes, and styrene or N-vinyl-2-oxazolidinone required the heating of aqueous suspensions at 60 ˚C. ‘On-water’ cycloadditions were characterized by high diastereoselectivity in contrast to reactions carried out in homogeneous organic media (dichloromethane, toluene). They allowed the cis adducts to be obtained preferentially or exclusively. The presented green methods avoid the use of catalysts, the heating of reaction mixtures for long times at high temperatures, and the use of organic solvents, and make the synthesis of a variety of pyrano[2,3-d]pyrimidines chemically efficient. The results reveal water as the medium of choice for the examined cycloadditions.

Key words

Diels-Alder reactions - drugs - green chemistry - pyrano[2,3-d]pyrimidines - solvent effects

    References

  • 1a Rideout DS. Breslow R. J. Am. Chem. Soc.  1980,  102:  7816 
    Google Scholar
  • 1b Narayan S. Muldoon JM. Finn GV. Fokin V. Kolb HC. Sharpless KB. Angew. Chem. Int. Ed.  2005,  44:  3275 
    Google Scholar
  • 2 Jovanovic MV. Biel ER. J. Org. Chem.  1987,  24:  191 
    Google Scholar
  • 3 Haldar MK. Scott MD. Sule N. Srivastava DK. Mallik S. Bioorg. Med. Chem. Lett.  2008,  18:  2373 
    CrossrefGoogle Scholar
  • 4 Kitamura N, and Onishi A. inventors; EP  163599.  ; Chem. Abstr. 1984, 104, 186439
  • 5 Furuja S, and Ohtaki T. inventors; EP Application  608565.  ; Chem. Abstr. 1994, 121, 205395
  • 6 Heber D. Heers C. Ravens U. Pharmazie  1993,  48:  537 
    Google Scholar
  • 7 Coates W. inventors; EP  351058.  ; Chem. Abstr. 1990, 113, 40711
  • 8 Sakuma Y, Hasegawa M, Kataoka K, Hoshina K, Yamazaki N, Kadota T, and Yamaguchi H. inventors; WO Application  9105785.  ; Chem. Abstr. 1989, 115, 71646
  • 9 Anderson GL. Shim JL. Broom AD. J. Org. Chem.  1976,  41:  1095 
    CrossrefGoogle Scholar
  • 10a Ahluvalia VK. Sharma HR. Tyagi R. Tetrahedron  1986,  42:  4045 
    Google Scholar
  • 10b Wamhoff H. Muhr J. Synthesis  1988,  919 
    Google Scholar
  • 10c Ahluwalia VK. Kumar R. Khurana K. Batla R. Tetrahedron  1990,  46:  3953 
    Google Scholar
  • 10d Hirota K. Kuki H. Maki Y. Heterocycles  1994,  37:  563 
    Google Scholar
  • 10e Srivastava P. Saxena AS. Ram VJ. Synthesis  2000,  541 
    Google Scholar
  • 11 Devi I. Kumar BSD. Bhuyan PJ. Tetrahedron Lett.  2003,  44:  8307 
    CrossrefGoogle Scholar
  • 12 Devi I. Bhuyan PJ. Tetrahedron Lett.  2004,  45:  7727 
    CrossrefGoogle Scholar
  • 13 Devi I. Borah HN. Bhuyan PJ. Tetrahedron Lett.  2004,  45:  2405 
    CrossrefGoogle Scholar
  • 14 Naya S. Miyagawa M. Nitta M. Tetrahedron  2005,  61:  4919 
    CrossrefGoogle Scholar
  • 15a Brufola G. Fringuelli F. Piermatti O. Pizzo F. Heterocycles  1997,  45:  1715 
    Google Scholar
  • 15b Binev IG. Binev YG. Stamboliyska BA. Juchnovski IN. J. Mol. Struct.  1997,  435:  235 
    Google Scholar
  • 15c Ayoubi SA. Texier-Boullet F. Hamelin J. Synthesis  1994,  258 
    Google Scholar
  • 16 Jursic BS. Stevens ED. Tetrahedron Lett.  2003,  44:  2203 
    CrossrefGoogle Scholar
  • 17 Deb ML. Bhuyan PJ. Tetrahedron Lett.  2005,  46:  6453 
    CrossrefGoogle Scholar
  • 18 Paasz A. Monatsh. Chem.  2008,  139:  1397 
    CrossrefGoogle Scholar
  • 19 Bushweller CH. O’Neil JW. Tetrahedron Lett.  1969,  4713 
    CrossrefGoogle Scholar
  • 20 Sankararaman S. Pericyclic Reactions - A Textbook   Wiley-VCH; Weinheim: 2005. 
    Google Scholar
  • 21a Tietze LF. Meier H. Nutt H. Chem. Ber.  1989,  122:  643 
    Google Scholar
  • 21b Tietze LF. Stegelmeier H. Harms K. Brumby T. Angew. Chem., Int. Ed. Engl.  1982,  21:  863 
    Google Scholar
  • 21c Tietze LF. Brumby T. Brand S. Bratz M. Chem. Ber.  1988,  121:  499 
    Google Scholar
  • 21d Tietze LF. Bachmann J. Wichmann J. Burkhardt O. Synthesis  1994,  1185 
    Google Scholar
  • 21e Tietze LF. Brand S. Pfeiffer T. Antel JJ. Harms K. Sheldrick GM. J. Am. Chem. Soc.  1987,  109:  921 
    Google Scholar
  • 21f Tietze LF. Chem. Rev.  1996,  96:  115 
    Google Scholar
  • 21g Tietze LF. Brasche G. Gericke KM. Domino Reactions in Organic Synthesis   Wiley-VCH; Weinheim: 2006. 
    Google Scholar
  • 21h Tietze LF. Kettschau G. Top. Curr. Chem.  1997,  189:  1 
    Google Scholar
  • 22 Bogdanowicz-Szwed K. Paasz A. Z. Naturforsch., B  2001,  56:  416 
    Google Scholar
  • 23 Paasz A. Org. Biomol. Chem.  2005,  3:  3207 
    CrossrefGoogle Scholar
  • 24a Hu Y. Chen ZC. Le ZG. Zheng QG. Synth. Commun.  2004,  34:  4521 
    Google Scholar
  • 24b Wang C. Ma J. Zhou X. Zang X. Wang Z. Gao Y. Cui P. Synth. Commun.  2005,  35:  2759 
    Google Scholar
  • 24c Medien HAA. Zahran AA. Phosphorus, Sulfur Silicon Relat. Elem.  2003,  178:  1069 
    Google Scholar
  • 24d Shi DQ. Chen J. Zhuang QY. Wang XS. Hu HW. Chin. Chem. Lett.  2003,  14:  1242 
    Google Scholar
  • 24e Moskvin AV. Polkovnikova II. Ivin BA. Russ. J. Gen. Chem.  1998,  68:  801 
    Google Scholar