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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)

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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 
  • 1b Cassis R. Tapia R. Valderrama JA. Synth. Commun.  1985,  15:  125 
    Search in Google Scholar
  • 1c Rotzoll S. Reinke H. Fischer C. Langer P. Synthesis  2009,  69 
  • 2 Gordon HJ. Martin JC. McNab H. J. Chem. Soc., Chem. Commun.  1983,  957 
    Crossref
  • 3 Briehl H. Lukosch A. Wentrup C. J. Org. Chem.  1984,  49:  2772 
    CrossrefSearch in Google Scholar
  • 4 Review: Gaber AM. McNab H. Synthesis  2001,  2059 
    Thieme Connect
  • 5 Al-Awadi NA. Abdelhamid IA. Al-Etaibi AM. Elnagdi MH. Synlett  2007,  2205 
    Thieme Connect
  • 6 Ramana Rao VV. Wentrup C. J. Chem. Soc., Perkin Trans. 1  1998,  2583 
    Crossref
  • 7 McNab H. Aldrichimica Acta  2004,  37:  19 
    Search in Google Scholar
  • 8 George L. Netsch K.-P. Penn G. Kollenz G. Wentrup C. Org. Biomol. Chem.  2006,  4:  558 
    Search in Google Scholar
  • 9 McNab H. Monahan LC. J. Chem. Soc., Perkin Trans. 1  1988,  863 
    Crossref
  • 11 Hirano J. Hamase K. Zaitsu K. Tetrahedron  2006,  62:  10065 
    CrossrefSearch in Google Scholar
  • 13 Lauer WM. Arnold RT. Tiffany B. Tinker J. J. Am. Chem. Soc.  1946,  68:  1268 
    CrossrefSearch in Google Scholar
  • 14 For example, see: Harrison AG. Honnen LR. Dauben HJ. Lossing FP. J. Am. Chem. Soc.  1960,  82:  5593 
    CrossrefSearch in Google Scholar
  • 16 Reported by: Margolis BJ. Long KA. Laird DLT. Ruble JC. Pulley SR. J. Org. Chem.  2007,  72:  2232 
    CrossrefSearch in Google Scholar
  • 17 Reported by: Price CC. Snyder HR. Bullitt OH. Kovacic P. J. Am. Chem. Soc.  1947,  69:  374 
    CrossrefSearch in Google Scholar
  • 18 Sashida H. Kaname M. Tsuchiya T. Chem. Pharm. Bull.  1990,  38:  2919 
    Search in Google Scholar
  • 19 For example, see: Fields EK. Meyerson S. Acc. Chem. Res.  1969,  2:  273 
    CrossrefSearch in Google Scholar
  • 21 Heindel ND. Kennewell PD. Fish VB. J. Heterocycl. Chem.  1969,  6:  77 
    Search in 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. 
  • 24 Dunwell DW. Evans D. J. Chem. Soc., Perkin Trans. 1  1973,  1588 
    Crossref
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).