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DOI: 10.1055/s-0029-1217383
Regioselective Synthesis of Quinolin-4-ones by Pyrolysis of Anilinomethylene Derivatives of Meldrum’s Acid
Publikationsverlauf
Publikationsdatum:
16. Juni 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
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References and Notes
Prior isolation of 1 provides much cleaner products 2 (³ 95% yield) than the one-pot method reported in ref. 5.
12FVP 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]
.
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).
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).
23FVP 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).