Download PDF
Synlett 2010(6): 921-923  
DOI: 10.1055/s-0029-1219562
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

An Efficient Three-Component Synthesis of 3-(1-Hydroxyalkyl)[1,2,4]-triazolo[4,3-c]quinazolines

Mehdi Adib*a, Samira Ansaria, Shahzad Feizia, Hamid Reza Bijanzadehb
a School of Chemistry, University College of Science, University of Tehran, PO Box 14155-6455, Tehran, Iran
Fax: +98(21)66495291; e-Mail: madib@khayam.ut.ac.ir;
b Department of Chemistry, Tarbiat Modarres University, PO Box 14115-175, Tehran, Iran
Further Information

Publication History

Received 10 November 2009
Publication Date:
02 March 2010 (online)

    Permissions and Reprints All articles of this category

Abstract

An efficient three-component synthesis of 3-(1-hydroxyalkyl)[1,2,4]triazolo[4,3-c]quinazolines is described. A mixture of N-isocyaniminotriphenylphosphorane, an aldehyde, and a 4(3H)-quinazolinone undergo a 1:1:1 addition reaction in refluxing THF to afford the title compounds in good to excellent yields.

Key words

N-isocyaniminotriphenylphosphorane - 4(3H)-quin­azolinones - aldehydes - 3-(1-hydroxyalkyl)[1,2,4]triazolo[4,3-c]quin­azolines - multicomponent reactions - cyclizations - heterocycles

    References and Notes

  • 1a Multicomponent Reactions   Zhu J. Bienaymé H. Wiley; Weinheim: 2005. 
    Google Scholar
  • 1b Basso A. Banfi L. Riva R. Guanti G. J. Org. Chem.  2005,  70:  575 
    Google Scholar
  • 1c Ramón DJ. Yus M. Angew. Chem. Int. Ed.  2005,  44:  1602 
    Google Scholar
  • 1d Dömling A. Chem. Rev.  2006,  106:  17 
    Google Scholar
  • 1e Dömling A. Ugi I. Angew. Chem. Int. Ed.  2000,  39:  3168 
    Google Scholar
  • 2 Shaban MAE. Nasr AZ. Synthesis of Condensed 1,2,4-Triazolo[3,4-x]heterocycles, In Advances in Heterocyclic Chemistry   Vol. 49:  Katritzky AR. Academic Press; New York: 1990.  p.335-337  
    Google Scholar
  • 3 Hajós G. Riedl Z. In Comprehensive Heterocyclic Chemistry III   Vol. 11:  Katritzky AR. Ramsden CA. Scriven EFV. Taylor RJK. Elsevier Science; Oxford: 2008.  Chap. 16. p.671-762  ; and references therein
    Google Scholar
  • 4a Cipak L. Letasiova S. Repicky A. Jantova S. Neoplasma  2007,  54:  16 
    Google Scholar
  • 4b Jantová S. Letasiová S. Repický A. Ovádeková R. Lakatos B. Cell. Biochem. Funct.  2006,  24:  519 
    Google Scholar
  • 5a Mohamed MS. Ibrahim MK. Alafify AM. Abdel-Hamide SG. Mostafa AM. Int. J. Pharmacol.  2005,  1:  261 
    Google Scholar
  • 5b Gineinah MM. Nasr MN. Abdelal AM. El-Emam AA. Said SA. Med. Chem. Res.  2000,  10:  243 
    Google Scholar
  • 6 Hardtmann GE, and Kathawala FG. inventors; US  4,053,600.  ; Chem. Abstr. 1978, 88, 22970k
  • 7a Jantová S. Špirková K. Stankovský Š. Duchonová P. Folia Microbiol. (Praha)  1999,  44:  187 
    Google Scholar
  • 7b Jantová S. Stankovský Š. Špirková K. Biol. Brat.  2004,  59:  741 
    Google Scholar
  • 8 Hardtmann GE, and Kathawala FG. inventors; DE 2,261,095  (A1).  ; Chem. Abstr. 1973, 79, 66385s (A)
  • Chen P, and Hutchison A. inventors; US 5,677,309  (A).  ; Chem. Abstr. 1997, 127, 346408p
  • 9 Hergenrother PM. J. Heterocycl. Chem.  1972,  9:  131 
    CrossrefGoogle Scholar
  • 10a Sidhu GS. Thyarajan G. Rao N. Naturwissenschaften  1963,  50:  732 
    Google Scholar
  • 10b Spirkova K. Stankovsky S. Dandarova M. Collect. Czech. Chem. Commun.  1994,  59:  222 
    Google Scholar
  • 10c Spirkova K. Stankovsky S. Hornacek J. Collect. Czech. Chem. Commun.  1994,  59:  243 
    Google Scholar
  • 11 Breuer H. Tetrahedron Lett.  1976,  17:  1935 
    CrossrefGoogle Scholar
  • 12 Huisgen R. Sturm HJ. Seidel M. Chem. Ber.  1961,  94:  1555 
    CrossrefGoogle Scholar
  • 13 Stolzenberg H. Weinberger B. Fehlhammer WP. Pühlhofer FG. Weiss R. Eur. J. Inorg. Chem.  2005,  21:  4263 
    Google Scholar
  • 14 Chiu TW. Liu YH. Chi KM. Wen YS. Lu KL. Inorg. Chem.  2005,  44:  6425 
    CrossrefGoogle Scholar
  • 15 Souldozi A. Ramazani A. Bouslimani N. Welter R. Tetrahedron Lett.  2007,  48:  2617 
    CrossrefGoogle Scholar
  • 16 Souldozi A. Ramazani A. Tetrahedron Lett.  2007,  48:  1549 
    CrossrefGoogle Scholar
  • 17 Adib M. Riazati Kesheh M. Ansari S. Bijanzadeh HR. Synlett  2009,  1575 
    Article in Thieme ConnectGoogle Scholar
  • 18a Adib M. Sheibani E. Bijanzadeh HR. Zhu LG. Tetrahedron  2008,  64:  10681 
    Google Scholar
  • 18b Adib M. Sayahi MH. Ziyadi H. Zhu LG. Bijanzadeh HR. Synthesis  2008,  3289 
    Google Scholar
  • 18c Adib M. Mohammadi B. Bijanzadeh HR. Synlett  2008,  3180 
    Google Scholar
  • 18d Adib M. Mohammadi B. Bijanzadeh HR. Synlett  2008,  177 
    Google Scholar
  • 18e Adib M. Sayahi MH. Ziyadi H. Bijanzadeh HR. Zhu LG. Tetrahedron  2007,  63:  11135 
    Google Scholar
  • 18f Adib M. Aali Koloogani S. Abbasi A. Bijanzadeh HR. Synthesis  2007,  3056 
    Google Scholar
  • 18g Adib M. Sheibani E. Abbasi A. Bijanzadeh HR. Tetrahedron Lett.  2007,  48:  1179 
    Google Scholar
  • 18h Adib M. Sheibani E. Mostofi M. G hanbary K. Bijanzadeh HR. Tetrahedron  2006,  62:  3435 
    Google Scholar
  • 18i Adib M. Mahdavi M. Mahmoodi N. Pirelahi H. Bijanzadeh HR. Synlett  2006,  1765 
    Google Scholar
  • 20 Ugi I. Isonitrile Chemistry   Academic Press; London: 1971. 
    Google Scholar
  • 21 Ugi I. Angew. Chem., Int. Ed. Engl.  1982,  21:  810 
    CrossrefGoogle Scholar
  • 22 Walborsky HM. Periasamy MP. In The Chemistry of Functional Groups   Suppl. C:  Patai S. Rappaport Z. Wiley; New York: 1983.  Chap. 20. p.835-837  
    Google Scholar
19

General Procedure for the Preparation of Compounds 4a-l
A mixture of N-isocyaniminotriphenylphosphorane (1 mmol) and the appropriate aldehyde (1 mmol) was dissolved in hot THF (5 mL). Then the appropriate 4 (3H)-quinazo-linone (1 mmol) was added to the reaction mixture which was refluxed for 3 h. Then, the solvent was removed under the reduced pressure, and the residue was purified by TLC using CHCl3-EtOAc (3:1) as eluent. The solvent was removed, and the product was obtained as colorless crystals.
3-[1-Hydroxy-1-(4-fluorophenyl)methyl]-5-phenyl-[1,2,4]triazolo[4,3- c ]quinazoline (4c)
Yield 0.34 g (93%); colorless crystals; mp 192-193 ˚C. IR (KBr): 3266 (OH), 1609, 1515, 1374, 1332, 1264, 1211, 1187, 1156, 1106, 1056, 1019, 947, 863, 794, 769, 680 cm-¹. ¹H NMR (500.1 MHz, DMSO-d 6): δ = 5.35 (br s, 1 H, CH), 6.02 (d, J = 4.6 Hz, 1 H, OH), 7.08 (dd, J = 8.8, 8.9 Hz, 2 H, 2 × CH), 7.11-7.19 (m, 2 H, 2 × CH), 7.56-7.66 (m, 4 H, 4 × CH), 7.78 (dd, J = 6.8, 7.4 Hz, 2 H, 2 × CH), 7.86 (dd, J = 7.3, 8.1 Hz, 1 H, CH), 7.96 (d, J = 8.1 Hz, 1 H, CH), 8.54 (d, J = 7.9 Hz, 1 H, CH). ¹³C NMR (125.8 MHz, DMSO-d 6): δ = 65.94 (CH), 114.46 (d, ² J FC = 21.4 Hz, CH), 115.94 (C), 122.56, 127.89, 128.28 and 128.73 (4 × CH), 128.87 (d, ³ J FC = 8.1 Hz, CH), 129.25, 130.63 and 131.83 (3 × CH), 133.48 (C), 137.16 (d, 4 J FC = 2.7 Hz, C), 140.33, 145.65, 148.88 and 150.75 (4 × C), 161.45 (d, ¹ J CF = 243.2 Hz, CF). MS (EI): m/z (%) = 370 (6) [M+], 279 (20), 247 (12), 205 (9), 167 (23), 149 (100), 113 (10), 104 (9), 83 (9), 71 (18), 57 (29). Anal. Calcd for C22H15FN4O (370.38): C, 71.34; H, 4.08; N, 15.13. Found: C, 71.3; H, 4.2; N, 15.1.
3-[1-Hydroxy-1-(4-nitrophenyl)methyl]-5-(4-methyl-phenyl)[1,2,4]triazolo[4,3- c ]quinazoline (4f)
Yield 0.40 g (97%); colorless crystals; mp 228 ˚C. IR (KBr): 3344 (OH), 1614, 1511, 1466, 1335, 1181, 1105, 1069, 1039, 986, 948, 818, 769, 696 cm-¹. ¹H NMR (500.1 MHz, DMSO-d 6): δ = 2.42 (s, 3 H, CH3), 5.52 (d, J = 5.8 Hz, 1 H, CH), 6.25 (d, J = 5.8 Hz, 1 H, OH), 7.37 (d, J = 7.2 Hz, 2 H, 2 × CH), 7.49 (d, J = 8.7 Hz, 2 H, 2 × CH), 7.73 (d, J = 7.8 Hz, 2 H, 2 × CH), 7.79 (dd, J = 7.4, 7.7 Hz, 1 H, CH), 7.88 (t, J = 7.1, 7.2 Hz, 1 H, CH), 7.98 (d, J = 8.1 Hz, 1 H, CH), 8.16 (d, J = 8.7 Hz, 2 H, 2 × CH), 8.53 (d, J = 7.4 Hz, 1 H, CH). ¹³C NMR (125.8 MHz, DMSO-d 6): δ = 21.12 (CH3), 65.77 (CH), 115.83 (C), 122.61, 122.92, 127.93, 127.96, 128.75, 128.85, 129.26 (7 × CH), 130.59 (C), 131.98 (CH), 140.48, 140.52, 145.81, 146.79, 148.70, 149.08 and 150.11 (7 × C). MS (EI): m/z (%) = 411 (2) [M+], 386 (5), 370 (14), 277 (100), 247 (31), 205 (24), 183 (19), 152 (16), 123 (12), 97 (18), 77 (28). Anal. Calcd for C23H17N5O3 (411.41): C, 67.15; H, 4.16; N, 17.02. Found: C, 67.2; H, 4.2; N, 16.9.