LETTER
Quinolin-4-ones
1851
1H-quinolin-4-ones17 (3fa and 3fb; 0.176 g, 94%). 1H NMR
(250 MHz, DMSO-d6): d (7-isomer, 250 MHz) = 8.28 (1 H,
dd, 3J = 8.3 Hz, 4J = 0.4 Hz), 8.06 (1 H, m), 7.81 (1 H, m),
7.71 (1 H, dd, 3J = 8.3 Hz, 4J = 1.5 Hz), 6.21 (1 H, d, 3J = 7.5
Hz).
FVP of 2g (0.604 g, Tf = 600 °C, Ti = 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-d6): d = 8.43 (1 H, dd,
3J = 8.0 Hz, 4J = 1.7 Hz), 8.25 (1 H, dd, 3J = 7.4 Hz, 4J = 1.7
Hz), 8.00 (1 H, d, 3J = 7.2 Hz), 7.51 (1 H, dd, 3J = 8.0, 7.4
Hz), 6.32 (1 H, d, 3J = 7.2 Hz).
References and Notes
(1) (a) Sterling Drug Inc. Brit.; 1,147,760 Chem. Abstr. 1969,
71, 49967a. (b) Cassis, R.; Tapia, R.; Valderrama, J. A.
Synth. Commun. 1985, 15, 125. (c) Rotzoll, S.; Reinke, H.;
Fischer, C.; Langer, P. Synthesis 2009, 69.
(2) Gordon, H. J.; Martin, J. C.; McNab, H. J. Chem. Soc.,
Chem. Commun. 1983, 957.
(3) Briehl, H.; Lukosch, A.; Wentrup, C. J. Org. Chem. 1984,
49, 2772.
(4) Review: Gaber, A. M.; McNab, H. Synthesis 2001, 2059.
(5) Al-Awadi, N. A.; Abdelhamid, I. A.; Al-Etaibi, A. M.;
Elnagdi, M. H. Synlett 2007, 2205.
(6) Ramana Rao, V. V.; Wentrup, C. J. Chem. Soc., Perkin
Trans. 1 1998, 2583.
(7) McNab, H. Aldrichimica Acta 2004, 37, 19.
(8) George, L.; Netsch, K.-P.; Penn, G.; Kollenz, G.; Wentrup,
C. Org. Biomol. Chem. 2006, 4, 558.
(9) McNab, H.; Monahan, L. C. J. Chem. Soc., Perkin Trans. 1
1988, 863.
(10) Prior isolation of 1 provides much cleaner products 2 (≥ 95%
yield) than the one-pot method reported in ref. 5.
(11) Hirano, J.; Hamase, K.; Zaitsu, K. Tetrahedron 2006, 62,
10065.
(16) Reported by: Margolis, B. J.; Long, K. A.; Laird, D. L. T.;
Ruble, J. C.; Pulley, S. R. J. Org. Chem. 2007, 72, 2232.
(17) Reported by: Price, C. C.; Snyder, H. R.; Bullitt, O. H. Jr.;
Kovacic, P. J. Am. Chem. Soc. 1947, 69, 374.
(18) Sashida, H.; Kaname, M.; Tsuchiya, T. Chem. Pharm. Bull.
1990, 38, 2919.
(19) For example, see: Fields, E. K.; Meyerson, S. Acc. Chem.
Res. 1969, 2, 273.
(20) FVP of 2h (0.664 g, Tf = 600 °C, Ti = 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-d6): d = 8.88 (1 H, d, 3J = 2.8 Hz),
8.46 (1 H, dd, 3J = 9.2 Hz, 4J = 2.8 Hz), 8.09 (1 H, d, 3J = 7.9
Hz), 7.76 (1 H, dd, 3J = 9.2 Hz, 5J = 0.5 Hz), 6.24 (1 H, d,
3J = 7.9 Hz).
(12) FVP of 2b (0.600 g, Tf = 600 °C, Ti = 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-d6):
d = 11.78 (1 H, br s), 7.87 (1 H, d, 3J = 7.2 Hz), 7.53–7.52 (2
H, m), 7.30 (1 H, dd, 3J = 9.1 Hz, 4J = 2.1 Hz), 6.03 (1 H, d,
3J = 7.2 Hz), 3.85 (3 H, s), see Figure 1.
(21) Heindel, N. D.; Kennewell, P. D.; Fish, V. B. J. Heterocycl.
Chem. 1969, 6, 77.
(22) Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.;
Robb, M. A.; Cheeseman, J. R.; Montgomery, J. A. Jr.;
Vreven, T.; Kudin, K. N.; Burant, J. C.; Millam, J. M.;
Iyengar, S. S.; Tomasi, J.; Barone, V.; Mennucci, B.; Cossi,
M.; Scalmani, G.; Rega, N.; Petersson, G. A.; 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, J. E.; Hratchian, H. P.; Cross, J. B.;
Bakken, V.; Adamo, C.; Jaramillo, J.; Gomperts, R.;
Stratmann, R. E.; Yazyev, O.; Austin, A. J.; Cammi, R.;
Pomelli, C.; Ochterski, J. W.; Ayala, P. Y.; Morokuma, K.;
Voth, G. A.; Salvador, P.; Dannenberg, J. J.; Zakrzewski,
V. G.; Dapprich, S.; Daniels, A. D.; Strain, M. C.; Farkas,
O.; Malick, D. K.; Rabuck, A. D.; Raghavachari, K.;
Foresman, J. B.; Ortiz, J. V.; Cui, Q.; Baboul, A. G.;
Clifford, S.; Cioslowski, J.; Stefanov, B. B.; Liu, G.;
Liashenko, A.; Piskorz, P.; Komaromi, I.; Martin, R. L.; Fox,
D. J.; Keith, T.; Al-Laham, M. A.; Peng, C. Y.;
Nanayakkara, A.; Challacombe, M.; Gill, P. M. W.; Johnson,
B.; Chen, W.; Wong, M. W.; Gonzalez, C.; Pople, J. A.
Gaussian 03; Gaussian, Inc.: Wallingford CT, 2004.
(23) FVP of 7 (0.323 g, Tf = 600 °C, Ti = 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-d6):
d = 8.45 (1 H, d, 3J = 8.0 Hz), 8.00 (1 H, d, 3J = 6.9 Hz), 7.58
(1 H, d, 3J = 7.6 Hz), 7.50 (1 H, td, 3J = 7.6 Hz, 4J = 1.3 Hz),
7.34 (1 H, td, 3J = 8.0 Hz, 4J = 1.3 Hz), 5.99 (1 H, d, 3J = 6.9
Hz).
FVP of 2c (0.704 g, Tf = 600 °C, Ti = 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-d6): d = 11.62 (1 H, br s), 8.00 (1 H, dd,
3J = 7.6 Hz, 4J = 2.5 Hz), 7.84 (1 H, d, 3J = 7.6 Hz), 6.94–
6.90 (2 H, m), 5.97 (1 H, d, 3J = 7.6 Hz), 3.86 (3 H, s), see
Figure 2.
FVP of 2d (0.850 g, Tf = 500 °C, Ti = 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-d6): d = 7.82
(1 H, d, 3J = 7.2 Hz), 7.70 (1 H, dd, 3J = 6.5 Hz, 4J = 2.9 Hz),
7.30–7.28 (2 H, m), 6.12 (1 H, d, 3J = 7.6 Hz), 4.30 (3 H, s),
see Figure 3.
(13) Lauer, W. M.; Arnold, R. T.; Tiffany, B.; Tinker, J. J. Am.
Chem. Soc. 1946, 68, 1268.
(14) For example, see: Harrison, A. G.; Honnen, L. R.; Dauben,
H. J. Jr.; Lossing, F. P. J. Am. Chem. Soc. 1960, 82, 5593.
(15) FVP of 2e (0.610 g, Tf = 600 °C, Ti = 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-d6): d = 8.47 (1 H, dd, 4J = 1.9 Hz,
5J = 0.5 Hz), 8.06 (1 H, d, 3J = 7.6 Hz), 8.02 (1 H, dd,
3J = 8.7 Hz, 4J = 1.9 Hz), 7.72 (1 H, dd, 3J = 8.7 Hz, 5J = 0.5
Hz), 6.20 (1 H, d, 3J = 7.6 Hz).
(24) Dunwell, D. W.; Evans, D. J. Chem. Soc., Perkin Trans. 1
1973, 1588.
FVP of 2f (0.306 g, Tf = 650 °C, Ti = 210 °C, t = 25 min,
P = 4.0·10–5 bar) gave a ca. 25:75 mixture of 5- and 7-cyano-
Synlett 2009, No. 11, 1847–1851 © Thieme Stuttgart · New York