Download PDF
Synlett 2009(11): 1847-1851  
DOI: 10.1055/s-0029-1217383
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Regioselective Synthesis of Quinolin-4-ones by Pyrolysis of Anilinomethylene Derivatives of Meldrum’s Acid

Lawrence Hilla, S. Haider Imama, Hamish McNab*b, William J. O’Neillb
a Durham Organics Ltd., Units 12-14, Langley Moor Industrial Estate, Langley Moor, Durham, DH7 8JE, UK
b School of Chemistry, The University of Edinburgh, West Mains Road, Edinburgh, EH9 3JJ, UK
Fax: +44(131)6504743; e-Mail: H.McNab@ed.ac.uk;
Further Information

Publication History

Received 30 January 2009
Publication Date:
16 June 2009 (online)

    Permissions and Reprints All articles of this category

Abstract

Electron-rich and electron-deficient anilinomethylene derivatives of Meldrum’s acid cyclize equally efficiently to quinolin-4-ones via imidoylketene intermediates under flash vacuum pyrolysis (FVP) conditions.

Key words

quinolin-4-ones - Meldrum’s acid - flash vacuum pyrolysis

    References and Notes

  • 1a Sterling Drug Inc. Brit.; 1,147,760 Chem. Abstr.  1969,  71:  49967a 
    Google Scholar
  • 1b Cassis R. Tapia R. Valderrama JA. Synth. Commun.  1985,  15:  125 
    Google Scholar
  • 1c Rotzoll S. Reinke H. Fischer C. Langer P. Synthesis  2009,  69 
    Google Scholar
  • 2 Gordon HJ. Martin JC. McNab H. J. Chem. Soc., Chem. Commun.  1983,  957 
    CrossrefGoogle Scholar
  • 3 Briehl H. Lukosch A. Wentrup C. J. Org. Chem.  1984,  49:  2772 
    CrossrefGoogle Scholar
  • 4 Review: Gaber AM. McNab H. Synthesis  2001,  2059 
    Article in Thieme ConnectGoogle Scholar
  • 5 Al-Awadi NA. Abdelhamid IA. Al-Etaibi AM. Elnagdi MH. Synlett  2007,  2205 
    Article in Thieme ConnectGoogle Scholar
  • 6 Ramana Rao VV. Wentrup C. J. Chem. Soc., Perkin Trans. 1  1998,  2583 
    CrossrefGoogle Scholar
  • 7 McNab H. Aldrichimica Acta  2004,  37:  19 
    Google Scholar
  • 8 George L. Netsch K.-P. Penn G. Kollenz G. Wentrup C. Org. Biomol. Chem.  2006,  4:  558 
    Google Scholar
  • 9 McNab H. Monahan LC. J. Chem. Soc., Perkin Trans. 1  1988,  863 
    CrossrefGoogle Scholar
  • 11 Hirano J. Hamase K. Zaitsu K. Tetrahedron  2006,  62:  10065 
    CrossrefGoogle Scholar
  • 13 Lauer WM. Arnold RT. Tiffany B. Tinker J. J. Am. Chem. Soc.  1946,  68:  1268 
    CrossrefGoogle Scholar
  • 14 For example, see: Harrison AG. Honnen LR. Dauben HJ. Lossing FP. J. Am. Chem. Soc.  1960,  82:  5593 
    CrossrefGoogle Scholar
  • 16 Reported by: Margolis BJ. Long KA. Laird DLT. Ruble JC. Pulley SR. J. Org. Chem.  2007,  72:  2232 
    CrossrefGoogle Scholar
  • 17 Reported by: Price CC. Snyder HR. Bullitt OH. Kovacic P. J. Am. Chem. Soc.  1947,  69:  374 
    CrossrefGoogle Scholar
  • 18 Sashida H. Kaname M. Tsuchiya T. Chem. Pharm. Bull.  1990,  38:  2919 
    Google Scholar
  • 19 For example, see: Fields EK. Meyerson S. Acc. Chem. Res.  1969,  2:  273 
    CrossrefGoogle Scholar
  • 21 Heindel ND. Kennewell PD. Fish VB. J. Heterocycl. Chem.  1969,  6:  77 
    Google Scholar
  • 22 Frisch MJ. Trucks GW. Schlegel HB. Scuseria GE. Robb MA. Cheeseman JR. Montgomery JA. Vreven T. Kudin KN. Burant JC. Millam JM. Iyengar SS. Tomasi J. Barone V. Mennucci B. Cossi M. Scalmani G. Rega N. Petersson GA. Nakatsuji H. Hada M. Ehara M. Toyota K. Fukuda R. Hasegawa J. Ishida M. Nakajima T. Honda Y. Kitao O. Nakai H. Klene M. Li X. Knox JE. Hratchian HP. Cross JB. Bakken V. Adamo C. Jaramillo J. Gomperts R. Stratmann RE. Yazyev O. Austin AJ. Cammi R. Pomelli C. Ochterski JW. Ayala PY. Morokuma K. Voth GA. Salvador P. Dannenberg JJ. Zakrzewski VG. Dapprich S. Daniels AD. Strain MC. Farkas O. Malick DK. Rabuck AD. Raghavachari K. Foresman JB. Ortiz JV. Cui Q. Baboul AG. Clifford S. Cioslowski J. Stefanov BB. Liu G. Liashenko A. Piskorz P. Komaromi I. Martin RL. Fox DJ. Keith T. Al-Laham MA. Peng CY. Nanayakkara A. Challacombe M. Gill PMW. Johnson B. Chen W. Wong MW. Gonzalez C. Pople JA. Gaussian 03   Gaussian, Inc.; Wallingford CT: 2004. 
    Google Scholar
  • 24 Dunwell DW. Evans D. J. Chem. Soc., Perkin Trans. 1  1973,  1588 
    CrossrefGoogle Scholar
10

Prior isolation of 1 provides much cleaner products 2 (³ 95% yield) than the one-pot method reported in ref. 5.

12

FVP of 2b (0.600 g, T f = 600 ˚C, T i = 170 ˚C, t = 50 min, P = 2.3˙10-5 bar) gave a yellow solid (0.403 g, quant.), recrystallization from MeOH gave 6-methoxy-1H-quinolin-4-one (3b, 0.234 g, 61%); mp 243-246 ˚C (from MeOH; lit.¹¹ 251-252 ˚C). ¹H NMR (360 MHz, DMSO-d 6): δ = 11.78 (1 H, br s), 7.87 (1 H, d, ³ J = 7.2 Hz), 7.53-7.52 (2 H, m), 7.30 (1 H, dd, ³ J = 9.1 Hz, 4 J = 2.1 Hz), 6.03 (1 H, d, ³ J = 7.2 Hz), 3.85 (3 H, s), see Figure  [¹] .
FVP of 2c (0.704 g, T f = 600 ˚C, T i = 160 ˚C, t = 1 h, P = 1.9˙10-5 bar) gave a yellow solid (0.414 g, 93%), in which the ratio 3ca/3cb was 7:93 by ¹H NMR spectroscopy, and which provided pure 7-methoxy-1H-quinolin-4-one (3cb, 0.277 g, 62%), after recrystallization from MeOH, mp 210-212 ˚C (from MeOH; lit.¹¹ 219-220 ˚C). ¹H NMR (360 MHz, DMSO-d 6): δ = 11.62 (1 H, br s), 8.00 (1 H, dd, ³ J = 7.6 Hz, 4 J = 2.5 Hz), 7.84 (1 H, d, ³ J = 7.6 Hz), 6.94-6.90 (2 H, m), 5.97 (1 H, d, ³ J = 7.6 Hz), 3.86 (3 H, s), see Figure  [²] .
FVP of 2d (0.850 g, T f = 500 ˚C, T i = 160 ˚C, t = 25 min, P = 3.6˙10-5 bar) gave 8-methoxy-1H-quinolin-4-one (3da, 0.535 g, 99%); mp 124-126 ˚C [from EtOH; lit.¹³ 134-135 ˚C(hydrate)]. ¹H NMR (360 MHz, DMSO-d 6): δ = 7.82 (1 H, d, ³ J = 7.2 Hz), 7.70 (1 H, dd, ³ J = 6.5 Hz, 4 J = 2.9 Hz), 7.30-7.28 (2 H, m), 6.12 (1 H, d, ³ J = 7.6 Hz), 4.30 (3 H, s), see Figure  [³] .

15

FVP of 2e (0.610 g, T f = 600 ˚C, T i = 200 ˚C, t = 1.25 h, P = 3.1˙10-5 bar) gave 6-cyano-1H-quinolin-4-one¹6 (3e) as an orange solid (0.358 g, 94%); mp 186 ˚C (from MeOH). ¹H NMR (250 MHz, DMSO-d 6): δ = 8.47 (1 H, dd, 4 J = 1.9 Hz, 5 J = 0.5 Hz), 8.06 (1 H, d, ³ J = 7.6 Hz), 8.02 (1 H, dd, ³ J = 8.7 Hz, 4 J = 1.9 Hz), 7.72 (1 H, dd, ³ J = 8.7 Hz, 5 J = 0.5 Hz), 6.20 (1 H, d, ³ J = 7.6 Hz).
FVP of 2f (0.306 g, T f = 650 ˚C, T i = 210 ˚C, t = 25 min, P = 4.0˙10-5 bar) gave a ca. 25:75 mixture of 5- and 7-cyano-1H-quinolin-4-ones¹7 (3fa and 3fb; 0.176 g, 94%). ¹H NMR (250 MHz, DMSO-d 6): δ (7-isomer, 250 MHz) = 8.28 (1 H, dd, ³ J = 8.3 Hz, 4 J = 0.4 Hz), 8.06 (1 H, m), 7.81 (1 H, m), 7.71 (1 H, dd, ³ J = 8.3 Hz, 4 J = 1.5 Hz), 6.21 (1 H, d, ³ J = 7.5 Hz).
FVP of 2g (0.604 g, T f = 600 ˚C, T i = 180 ˚C, t = 20 min, P = 3.7˙10-5 bar) gave 8-cyano-1H-quinolin-4-one (3g, 0.242 g, 64%); mp 234-236 ˚C (from MeOH; lit.¹8 260-262 ˚C). ¹H NMR (250 MHz, DMSO-d 6): δ = 8.43 (1 H, dd, ³ J = 8.0 Hz, 4 J = 1.7 Hz), 8.25 (1 H, dd, ³ J = 7.4 Hz, 4 J = 1.7 Hz), 8.00 (1 H, d, ³ J = 7.2 Hz), 7.51 (1 H, dd, ³ J = 8.0, 7.4 Hz), 6.32 (1 H, d, ³ J = 7.2 Hz).

20

FVP of 2h (0.664 g, T f = 600 ˚C, T i = 200 ˚C, t = 1 h, P = 3.2˙10-5 bar) gave 6-nitro-1H-quinolin-4-one (3h, 0.283 g, 66%); mp >320 ˚C (from MeOH; lit.²¹ 337-342 ˚C). ¹H NMR (250 MHz, DMSO-d 6): δ = 8.88 (1 H, d, ³ J = 2.8 Hz), 8.46 (1 H, dd, ³ J = 9.2 Hz, 4 J = 2.8 Hz), 8.09 (1 H, d, ³ J = 7.9 Hz), 7.76 (1 H, dd, ³ J = 9.2 Hz, 5 J = 0.5 Hz), 6.24 (1 H, d, ³ J = 7.9 Hz).

23

FVP of 7 (0.323 g, T f = 600 ˚C, T i = 200 ˚C, t = 1 h, P = 3.3˙10-5 bar) gave a yellow solid (0.182 g) and recrystalli-zation from MeOH provided 1H-benzo[4,5]imidazo[1,2-a]pyrimidin-4-one (8, 0.129 g, 62%); mp 285-287 ˚C (from MeOH; lit.²4 290 ˚C). ¹H NMR (250 MHz, DMSO-d 6): δ = 8.45 (1 H, d, ³ J = 8.0 Hz), 8.00 (1 H, d, ³ J = 6.9 Hz), 7.58 (1 H, d, ³ J = 7.6 Hz), 7.50 (1 H, td, ³ J = 7.6 Hz, 4 J = 1.3 Hz), 7.34 (1 H, td, ³ J = 8.0 Hz, 4 J = 1.3 Hz), 5.99 (1 H, d, ³ J = 6.9 Hz).