Download PDF
Synlett 2014; 25(11): 1596-1600
DOI: 10.1055/s-0033-1341202
letter
© Georg Thieme Verlag Stuttgart · New York

An Efficient Approach to the Synthesis of Coumarin-Bearing 2,3-Dihydro-4(1H)-Quinazolinone Derivatives Using a Piperidine and Molecular Iodine Dual-Catalyst System

Abdolali Alizadeh*
a   Department of Chemistry, Tarbiat Modares University, P.O. Box 14115-175, Tehran, Iran   Fax: +98(21)88006544   Email: abdol_alizad@yahoo.com   Email: aalizadeh@modares.ac.ir
,
Rashid Ghanbaripour
a   Department of Chemistry, Tarbiat Modares University, P.O. Box 14115-175, Tehran, Iran   Fax: +98(21)88006544   Email: abdol_alizad@yahoo.com   Email: aalizadeh@modares.ac.ir
,
Long-Guan Zhu
b   Department of Chemistry, Zhejiang University, Hangzhou 310027, P. R. of China
› Author Affiliations
Further Information

Publication History

Received: 01 March 2014

Accepted: 22 March 2014

Publication Date:
10 April 2014 (online)

    Permissions and Reprints All articles of this category


Abstract

An efficient dual-catalyst system of piperidine and molecular iodine has been developed for the synthesis of 2-alkyl-2-(2-oxo-2H-chromen-3-yl)-2,3-dihydro-4(1H)quinazolinone derivatives by a four-component reaction of salicylaldehydes, β-keto esters, ammonium acetate, and isatoic anhydride. Good yields, mild reaction conditions, and easy purification are attractive features of the present method.

Key words

salicylaldehyde - β-keto ester - isatoic anhydride - ammonium acetate - 2-alkyl-2-(2-oxo-2H-chromen-3-yl)-2,3-dihydro-4(1H)quinazolinone - dual-catalyst system

Supporting Information

    for this article is available online at http://www.thieme-connect.com/ejournals/toc/synlett.
  • Supporting Information
 

  • References and Notes

  • 1 Murray RD. H In Progress in the Chemistry of Organic Natural Products . Vol. 83. Herz W, Falk H, Kirby GW, Moore RE. Springer Verlag; Wien: 2002: 1-529
    Search in Google Scholar
  • 2 Murray RD. H, Mendez J, Brown SA. The Natural Coumarins: Occurrence, Chemistry and Biochemistry . John Wiley and Sons; New York: 1982: 21
    Search in Google Scholar
  • 3 Kontogiorgis C, Hadjipavlou-Litina D. J. Enzyme Inhib. Med. Chem. 2003; 18: 63
    CrossrefSearch in Google Scholar
  • 5 Kirkiacharian S, Thuy DT, Sicsic S, Bakhchinian R, Kurkjian R, Tonnaire T. Farmaco 2002; 57: 703
    CrossrefSearch in Google Scholar
  • 8 Kennedy RO, Zhorenes RD. Coumarins: Biology, Applications and Mode of Action . John Wiley and Sons; Chichester: 1997
    Search in Google Scholar
  • 9 Zabradnik M. The Production and Application of Fluorescent Brightening Agents. John Wiley and Sons; New York: 1992
    Search in Google Scholar
  • 11 Piazzi L, Rampa A, Bisi A, Gobbi S, Belluti F, Cavalli A, Bartolini M, Andrisano V, Valenti P, Recanatini M. J. Med. Chem. 2003; 46: 2279
    CrossrefSearch in Google Scholar
  • 12 Opherk D, Schuler G, Waas W, Dietz R, Kubler W. Eur. Heart J. 1990; 11: 342
    Search in Google Scholar
  • 13 Cao YG, Liu XQ, Chen YC, Hao K, Wang GJ. Eur. J. Pharm. Sci. 2007; 30: 175
    CrossrefSearch in Google Scholar
  • 16 Noolvi MN, Patel HM, Bhardwaj V, Chauhan A. Eur. J. Med. Chem. 2011; 46: 2327
    CrossrefPubMedSearch in Google Scholar
  • 17 El-Helby AG. A, Wahab MH. A. Acta Pharm. 2003; 53: 127
    Search in Google Scholar
  • 18 Kabri Y, Azas N, Dumètre A, Hutter S, Laget M, Verhaghe P, Gellis A, Vanlee P. Eur. J. Med. Chem. 2010; 45: 616
    CrossrefSearch in Google Scholar
    • 20a Alanine A, Gobbi LC, Kolczewski S, Luebbers T, Peters JU, Steward L. US 2006293350 A1, 2006 ; Chem. Abstr. 2006, 146, 100721
    • 20b Chaturvedula PV, Chen L, Civiello R, Degnan AP, Dubowchik GM, Han X, Jiang XJ, Macor JE, Poindexter GS, Tora GO, Luo G. US 2007149503 A1, 2007 ; Chem. Abstr. 2007, 147, 118256
    • 20c Letourneau J, Riviello C, Ho KK, Chan JH, Ohlmeyer M, Jokiel P, Neagu I, Morphy JR, Napier SE. WO 2006095014 A1, 2006 ; Chem. Abstr. 2006, 145, 315012
  • 25 To a solution of isatoic anhdyride (1 mmol) in DMF (2 mL) was added NH4OAc (1 mmol), and the solution was stirred for 15 min at 60 °C. Then, salicylaldehyde 1 (1 mmol), β-keto ester 2 (1 mmol), and piperidine (0.1 mmol) were added, and the solution was stirred. After 10 min molecular iodine (0.15 mmol) was added to the reaction mixture, and the reaction was stirred about 5 h. Upon completion (monitored by TLC) the solvent was evaporated under reduced pressure, and the residue was recrystallized from EtOH to afford the pure product 3a–h. 2-Methyl-2-(2-oxo-2H-chromen-3-yl)-2,3-dihydro-4(1H)quinazolinone (3a) White powder; 0.257 g, 84% yield; mp 298 °C (decomp.). IR (KBr): 3441 and 3169 (2 NH), 1717 (C=O), 1664 (CONH), 1609, 1570 and 1525 (Ar), 1199 (CO) cm–1. 1H NMR (400 MHz, DMSO-d 6): δ = 1.81 (s, 3 H, CH3), 6.65 (t, 3 J HH = 7.6 Hz, 1 H, CH of Ar), 6.86 (d, 3 J HH = 8.0 Hz, 1 H, CH of Ar), 7.18 (s, 1 H, NH), 7.24 (td, 3 J HH = 7.6 Hz, 4 J HH = 1.6 Hz, 1 H, CH of Ar), 7.33 (t, 3 J HH = 7.6 Hz, 1 H, CH of Ar), 7.39 (d, 3 J HH = 8.4 Hz, 1 H, CH of Ar), 7.56 (d, 3 J HH = 8.0 Hz, 1 H, CH of Ar), 7.60 (td, 3 J HH = 7.6 Hz, 4 J HH = 1.6 Hz, 1 H, CH of Ar), 7.73 (dd, 3 J HH = 7.6 Hz, 4 J HH = 1.2 Hz, 1 H, CH of Ar), 7.84 (1 H, s, CH4 of coumarin), 8.46 (s, 1 H, NH). 13C NMR (100 MHz, DMSO-d 6): δ = 26.5 (CH3), 69.2 (C2 of quinazoline), 114.1 (C3 of coumarin), 114.6 (CH of Ar), 115.9 (CH of Ar), 117.5 (CH of Ar), 118.0 (C4a of coumarin), 124.8 (CH of Ar), 127.2 (CH of Ar), 128.7 (CH of Ar), 131.0 (C4a of quinazoline), 132.1 (CH of Ar), 133.5 (CH of Ar), 138.6 (CH4 of coumarin), 146.2 (C8a of quinazoline), 152.7 (C8a of coumarin), 159.0 (CO2), 163.2 (CONH). MS: m/z = 264, 173, 145, 132, 118, 101, 89, 63. Anal. Calcd for C18H14N2O3: C, 70.58; H, 4.61; N, 9.15. Found: C, 70.81; H, 4.69; N, 8.99. 2-(8-Methoxy-2-oxo-2H-chromen-3-yl)-2-methyl-2,3-dihydro-4(1H)-quinazolinone (3b) Beige powder; 0.259 g, 77% yield; mp 247–249 °C. IR (KBr): 3345 and 3188 (2 NH), 1706 (C=O), 1650 (CONH), 1612 and 1478 (Ar), 1276 and 1184 (CO) cm–1. 1H NMR (400 MHz, DMSO-d 6): δ = 1.81 (s, 3 H, CH3), 3.88 (s, 3 H, OCH3), 6.65 (t, 3 J HH = 7.4 Hz, 1 H, CH of Ar), 6.85 (d, 3 J HH = 8.0 Hz, 1 H, CH of Ar), 7.17 (s, 1 H, NH), 7.24–7.29 (m, 4 H, CH of Ar), 7.56 (dd, 3 J HH = 7.8 Hz, 4 J HH = 1.4 Hz, 1 H, CH of Ar), 7.81 (s, 1 H, CH4 of coumarin), 8.44 (s, 1 H, NH). 13C NMR (100 MHz, DMSO-d 6): δ = 26.4 (CH3), 56.1 (OCH3), 69.2 (C2 of quinazoline), 114.1 (C3 of coumarin), 114.3 (CH of Ar), 114.6 (CH of Ar), 117.5 (CH of Ar), 118.6 (C4a of coumarin), 119.8 (CH of Ar), 124.8 (CH of Ar), 127.2 (CH of Ar), 131.2 (C4a of quinazoline), 133.5 (CH of Ar), 138.8 (CH4 of coumarin), 142.1 (C8a of coumarin), 146.1 (C8a of quinazoline), 146.2 (C ipso -OCH3), 158.7 (CO2), 163.2 (CONH). MS: m/z (%) = 336 (5) [M+], 321 (67), 161 (100), 120 (76), 92 (81), 76 (26), 65 (43). Anal. Calcd for C19H16N2O4: C, 67.85; H, 4.79; N, 8.33. Found: C, 77.69; H, 4.88; N, 8.21.
  • 26 Frolova LV, Malik I, Uglinskii PY, Rogelj S, Kornienko A, Magedov IV. Tetrahedron Lett. 2011; 52: 6643
    CrossrefSearch in Google Scholar