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Synlett 2011(2): 195-198  
DOI: 10.1055/s-0030-1259301
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Facile Route for Novel Quinazolinone-Fused Azauracils through Cyclodesulfurization of Thioquinazolinones

Raju R. Kale, Virendra Prasad, Vinod K. Tiwari*
Department of Chemistry, Centre of Advanced Study, Faculty of Science, Banaras Hindu University, Varanasi 221005, India
Fax: +91(542)2368174; e-Mail: vtiwari@ucdavis.edu, tiwari_chem@yahoo.co.in;
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Publication History

Received 15 October 2010
Publication Date:
05 January 2011 (online)

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Abstract

An efficient, novel, short, and high-yielding one-pot protocol for the synthesis of diverse quinazolinone-fused azauracil heterocycles through cyclodesulfurization and intramolecular cyclization of thioquinazolinone using silver cyanate is described.

Key words

thioquinazolinone - cyclodesulfurization - benzotriazole - cyclization - fused heterocycles

    References and Notes

  • 1a Evans BE. Rittle KE. Bock MG. DiPardo RM. Freidinger RM. Whitter WL. Lundell GF. Veber DF. Anderson PS. Chang RSL. Lotti VJ. Cerino DJ. Chen TB. Kling PJ. Kunkel KA. Springer JP. Hirshfield J. J. Med. Chem.  1988,  31:  2235 
    Google Scholar
  • 1b Horton DA. Bourne GT. Smythe ML. Chem. Rev.  2003,  103:  893 
    Google Scholar
  • 1c Kumar A. Maurya RA. Ahmad P. J. Comb. Chem.  2009,  11:  198 
    Google Scholar
  • 2 Kale RR. Prasad V. Mohapatra P. Tiwari VK. Monatsh. Chemie  2010,  141:  1159 
    Google Scholar
  • 3 Lawrence RN. Drug Discovery Today  2000,  5:  172 
    CrossrefGoogle Scholar
  • 4 Molnar A. Boros S. Simon K. Hermecz I. Gonczi C. ARKIVOC  2010,  (x):  199 
    Google Scholar
  • 5a Kim TH. Lee N. Lee G. Kim JN. Tetrahedron  2001,  57:  7137 
    Google Scholar
  • 5b Gama Y. Shibuya I. Shimizu M. Chem. Pharm. Bull.  2002,  50:  1517 
    Google Scholar
  • 5c Gama Y. Shibuya I. Shimizu M. Goto M. J. Carbohydr. Chem.  2001,  20:  459 
    Google Scholar
  • 5d Alhede B. Clamen FP. Christensen J. McCluskey KK. Preikschat HF. J. Org. Chem.  1991,  56:  2139 
    Google Scholar
  • 5e Chern J. Groziak MP. Townsend LB.
    J. Heterocycl. Chem.  1986,  23:  153 
    Google Scholar
  • 6 Mhaske SB. Argade NP. Tetrahedron  2006,  62:  9787 
    CrossrefGoogle Scholar
  • 7a Tiwari VK. Singh DD. Hussain HA. Mishra BB. Singh A. Monatsh. Chemie  2008,  139:  43 
    Google Scholar
  • 7b Tiwari VK. Hussain HA. Mishra BB. Singh DD. Tripathi V. Med. Chem. Res.  2007,  15:  325 
    Google Scholar
  • 7c Tiwari VK. Kale RR. Mishra BB. Singh A. ARKIVOC  2008,  (xiv):  27 
    Google Scholar
  • 8a Kale RR. Prasad V. Tiwari VK. Tetrahedron Lett.  2010,  51:  5740 
    Google Scholar
  • 8b Kale RR. Prasad V. Tiwari VK. Lett. Org. Chem.  2010,  7:  136 
    Google Scholar
  • 8c Tiwari VK. Singh A. Hussain HA. Mishra BB. Tripathi V. Monatsh. Chem.  2007,  138:  1297 
    Google Scholar
  • 8d Singh A. Kale RR. Tiwari VK. Trends Carbohydr. Res.  2009,  1:  80 
    Google Scholar
  • 9a Pandey J. Sharma A. Tiwari VK. Dube D. Ramachandran R. Chaturvedi V. Sinha S. Mishra NN. Shulka PK. Tripathi RP. J. Comb. Chem.  2009,  11:  422 
    Google Scholar
  • 9b Yu H. Cheng J. Ding L. Khedri Z. Chen Y. Lau K. Tiwari VK. Chen Xi. J. Am. Chem. Soc.  2009,  131:  18467 
    Google Scholar
  • 9c Tewari N. Katiyar D. Tiwari VK. Tripathi RP. Tetrahedron Lett.  2002,  44:  6639 
    Google Scholar
  • 9d Tewari N. Mishra RC. Tiwari VK. Tripathi RP. Synlett  2002,  1779 
    Google Scholar
  • 9e Tewari N. Tiwari VK. Mishra RC. Tripathi RP. Srivastava AK. Ahmad R. Srivastava R. Srivastava BS. Bioorg. Med. Chem.  2003,  11:  2911 
    Google Scholar
  • 9f Saxena N. Verma SS. Tiwari VK. Chaturvedi V. Manju YK. Srivastva AK. Gaikwad A. Sinha S. Tripathi RP. Bioorg. Med. Chem. Lett.  2006,  14:  8186 
    Google Scholar
10

Typical Experimental Procedure for the Synthesis of Quinazolinone-Fused Azauracil Compounds 3a-h
Diverse 2-thioxo-2,3-dihydroquinazolin-4 (1H)-ones 2a-h were obtained in good yield by the one-pot reaction of anthranilic acid/esters, primary amines, and bis(benzo-triazol-1-yl)methanethione in presence of the amidine base as per ref. 7. Thioquinazolinone (2a, 0.5 g 1.96 mmol) was added in anhyd MeCN (8 mL) and stirred for 10 min then AgCNO (0.59 g, 3.93 mmol) was added in above solution. Solid precipitated out within 5 min and reaction mixture was further stirred for 30 min, where reaction mass turns into greenish color. Progress of reaction was monitored by TLC (25% EtOAc in n-hexane). After completion of reaction, product was filtered, dried, and subjected to column chromatography (25% EtOAc in n-hexane) to obtain pure white solid (90-95% yield).
Compound 3a: yield 91%; mp 160-162 ˚C. IR (KBr): νmax = 3429 (NH), 1676, 1591, 1568, 1508 cm-¹. ¹H NMR (300 MHz, CDCl3): δ = 8.04 (d, J = 7.5 Hz, 1 H), 7.83 (t, J = 7.2 Hz, 1 H), 7.71 (d, J = 8.4 Hz, 1 H), 7.43 (m, 4 H), 6.77 (m, 2 H). ¹³C NMR (75 MHz, CDCl3): δ = 166.10, 161.03, 145.95, 139.88, 134.52, 129.39, 129.16, 128.14, 128.04, 126.49, 124.01, 119.64 ppm. Anal. Calcd for C16H10N4O3: C, 62.74; H, 3.29; N, 18.29. Found: C, 62.51; H, 3.75; N, 18.88.
Compound 3b: yield 91%; mp 178-180 ˚C. IR (KBr): νmax = 3431 (NH), 1669, 1596, 1569, 1511 cm-¹. ¹H NMR (300 MHz, CDCl3): δ = 11.02 (br s, 1 H, NH), 7.96 (d, J = 7.8 Hz, 2 H), 7.67 (t, J = 8.4 Hz, 2 H), 7.48 (d, J = 8.4 Hz, 1 H), 7.34 (t, J = 8.4 Hz, 1 H), 7.04 (t, J = 8.7 Hz, 2 H), 6.69 (s, 1 H). ¹³C NMR (75 MHz, CDCl3): δ = 167.84, 162.0, 140.91, 134.79, 134.79, 133.17, 133.06, 130.66, 129.96, 126.84, 123.90, 123.41, 118.27 ppm. Anal. Calcd for C19H11N5O3S: C, 58.61; H, 2.85; N, 17.99. Found: C, 58.22; H, 3.01; N, 18.45.
Compound 3c: yield 91%; mp 187-188 ˚C. IR (KBr): νmax = 3430, 1677, 1593, 1577, 1507 cm-¹. ¹H NMR (300 MHz, CDCl3): δ = 9.82 (br s, NH, 1 H), 8.42 (d, J = 9.0 Hz, 2 H), 8.23 (m, 2 H), 7.77 (t, J = 7.8 Hz, 1 H), 7.48 (d, J = 8.7 Hz, 1 H), 7.38 (m, 1 H), 7.15 (d, J = 8.7 Hz, 1 H). ¹³C NMR (75 MHz, CDCl3): δ = 165.5, 159.90, 145.33, 143.27, 137.98, 133.80, 129.00, 125.60, 124.35, 122.55, 122.42, 114.37, 114.17, 110.53 ppm.
Compound 3d: yield 91%; mp 171-173 ˚C. IR (KBr): νmax = 3433 (NH), 1677 (O=CN), 1622, 1529 cm-¹. ¹H NMR (300 MHz, CDCl3): δ = 8.35 (d, J = 8.7 Hz, 2 H), 7.99-7.89 (m, merged with J = 7.2 Hz, 2 H), 7.75 (d, J = 8.4 Hz, 1 H), 7.49 (d, J = 8.1 Hz, 2 H), 7.33 (t, J = 7.5 Hz, 1 H). ¹³C NMR (75 MHz, CDCl3): δ = 165.10, 159.07, 145.90, 139.54, 135.41, 130.72, 130.27, 130.17, 127.27, 126.27, 126.10, 124.39, 124.34 ppm. Anal. Calcd for C16H9FN4O3: C, 59.26; H, 2.80; N, 17.28. Found: C, 59.93; H, 2.74; N, 17.97.