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P. Sanna et al. / Il Farmaco 54 (1999) 161–168
3.2.2. 6-Nitro- (4) and 7-nitro-3-ethoxycarbonyl-
methyl-2(1H)-quinoxalinone (5) in a mixture with 6-
nitro- (9) and 7-nitro-3-ethoxycarbonylmethylene-
1,2,3,4-tetrahydro-quinoxalin-2-one (10)
(1.4–1.7 g; 6.9–8.4 mmol) was added dropwise and the
mixture heated under reflux for 2 h. After removal of the
solvent in vacuo, the crude residue formed as a mixture
of the two isomers was purified by column chromatogra-
phy on silica gel, eluting with a mixture of diethyl
ether/light petroleum in a 70:30 ratio to give compounds
12–16 and 21 or diethyl ether/acetone in a 90:10 ratio
to give 17–20. In general, we observed that the 6-isomers
precede the 7-ones in the eluate.
The crude precipitate resulted in an isomeric mixture
(2 g; 56%) of quinoxalinones 4 and 5 with their
methylenic tautomers 9 and 10, respectively. After frac-
tional crystallizations from DMSO this gave 0.2 g (5.6%
yield) of a mixture of the two tautomers 5 and 10 in a
1:1 ratio, with no further separation possible: m.p.
280–290°C; IR: w 3250–3150, 1700, 1670, 1640, 1620
3.3.1. 6-Trifluoromethyl-3-(1-ethoxycarbonylethyl)-
2(1H)-quinoxalinone (12)
1
cm−1; UV: u 397, 383, 316, 263, 217 nm; H NMR
(DMSO-d6): l 11.93 (2H, br s, NH-1 of 5 and 10), 11.12
(1H, s, NH-4 of 10), 7.90–7.40 (6H, m, aromatic H of
5 and 10), 5.63 (1H, s, CHCO of 10), 4.18 (4H, q, J=6.8
Hz, CH2CH3 of 5 and 10), 2.54 (2H, s, CH2CO of 5), 1.25
(6H, t, J=6.8 Hz, CH3CH2 of 5 and 10); and also a
mixture of 0.1 g (2.8% yield) of 4 and 9 in a 1:1 ratio:
m.p. 270–280°C; IR: w 3250–3080, 1700, 1640, 1610
cm−1; UV: u 400, 385, 346, 332, 320 sh, 267, 216 nm;
1H NMR (DMSO-d6): l 12.20 (2H, br s, NH-1 of 4 and
9), 11.14 (1H, s, NH-4 of 9), 8.53 (2H, s, H-5 of 4 and
9), 7.56 (2H, d, J=8.4 Hz, H-7 of 4 and 9), 7.16 (2H,
d, J=8.4 Hz, H-8 of 4 and 9), 5.57 (1H, s, CHCO of
9), 4.17 (4H, q, J=6.8 Hz, CH2CH3 of 4 and 9), 2.51
(2H, s, CH2CO of 4), 1.26 (6H, t, J=6.8 Hz, CH3CH2
of 4 and 9).
0.75 g (42% yield); m.p. 153–155°C; IR: w 3160, 1740,
1
1675, 1630 cm−1; UV: u 317, 258, 218 nm; H NMR
(CDCl3): l 12.66 (1H, s, NH), 8.17 (1H, s, H-5), 7.63
(1H, dd, J=8.4 and 1.8 Hz, H-7), 7.44 (1H, d, J=8.4
Hz, H-8), 4.30 (1H, q, J=7.0 Hz, CHCH3), 4.22 (2H,
q, J=7.2 Hz, CH2CH3), 1.66 (3H, d, J=7.0 Hz,
CH3CH), 1.25 (3H, t, J=7.2 Hz, CH3CH2).
3.3.2. 7-Trifluoromethyl-3-(1-ethoxycarbonylethyl)-
2(1H)-quinoxalinone (13)
0.80 g (45% yield); m.p. 160–162°C; IR: w 3220, 1760,
1680, 1640 cm−1; UV: u 323, 316 infl, 258, 240, 212 nm;
1H NMR (CDCl3): l 12.36 (1H, s, NH), 7.99 (1H, d,
J=8.6 Hz, H-6), 7.58 (1H, d, J=8.6 Hz, H-5), 7.56 (1H,
s, H-8), 4.32 (1H, q, J=7.2 Hz, CHCH3), 4.23 (2H, q,
J=7.0 Hz, CH2CH3), 1.66 (3H, d, J=7.2 Hz, CH3CH),
1.27 (3H, t, J=7.0 Hz, CH3CH2).
The hydroalcoholic mother liquors, after evaporation
in vacuo, gave 0.74 g (37%) of unreacted 1b.
3.2.3. 6,7-Difluoro-3-ethoxycarbonylmethyl-2(1H)-
quinoxalinone (6) and 6,7-difluoro-3-ethoxycarbonyl-
methylene-1,2,3,4-tetrahydroquinoxalin-2-one (11)
The crude precipitate formed of the tautomeric pair
6/11, after fractional crystallization from ethanol, ini-
tially afforded 0.71 g (19% yield) of 11: m.p. 218–220°C;
IR: w 3200, 3180, 1690, 1650, 1630 cm−1; UV: u 388 sh,
3.3.3. 6-Nitro-3-(1-ethoxycarbonylethyl)-
2(1H)-quinoxalinone (14)
0.83 g (44% yield); m.p. 158–160°C; IR: w 3150, 1700,
1640 cm−1; UV: u 338, 267, 204 nm; 1H NMR (CDCl3+
DMSO-d6): l 12.92 (1H, br s, NH), 8.60 (1H, d, J=2.4
Hz, H-5), 8.29 (1H, dd, J=9.0 and 2.4 Hz, H-7), 7.48
(1H, d, J=9.0 Hz, H-8), 4.20–4.10 (3H, m, CHCH3+
CH2CH3), 1.56 (3H, d, J=7.2 Hz, CH3CH), 1.22 (3H,
t, J=7.2 Hz, CH3CH2).
1
374, 358, 280 sh, 253, 216 nm; H NMR (CDCl3+
DMSO-d6): l 11.70 (1H, s, NH-1), 11.04 (1H, s, NH-4),
7.56 (1H, dd, J=11.7 and 7.6 Hz, H-5), 6.97 (1H, dd,
J=10.6 and 7.8 Hz, H-8), 5.56 (1H, s, CHCO), 4.17 (2H,
q, J=6.8 Hz, CH2CH3), 1.28 (3H, t, J=6.8 Hz,
CH3CH2); and then 2.07 g (55.7% yield) of 6: m.p.
3.3.4. 7-Nitro-3-(1-ethoxycarbonylethyl)-2(1H)-
quinoxalinone (15)
0.80 g (42% yield); m.p. 165–167°C; IR: w 3200,
214–216°C; IR: w 3180, 1730, 1660, 1630, 1610 cm−1
;
1690, 1650 cm−1; UV: u 361, 281, 222 nm; H NMR
1
1
UV: u 388 sh, 352 sh, 342, 274, 226, 204 nm; H NMR
(CDCl3): l 12.85 (1H, br s, NH-1), 7.66 (1H, dd, J=10.0
and 7.8 Hz, H-5), 7.17 (1H, dd, J=10.0 and 7.2 Hz,
H-8), 4.26 (2H, q, J=7.0 Hz, CH2CH3), 3.98 (2H, s,
CH2CO), 1.32 (3H, t, J=7.0 Hz, CH3CH2).
(CDCl3+DMSO-d6): l 12.81 (1H, br s, NH), 8.18 (1H,
d, J=2.4 Hz, H-8), 8.07 (1H, dd, J=8.8 and 2.4 Hz,
H-6), 7.94 (1H, d, J=8.8 Hz, H-5), 4.20–4.05 (3H, m,
CHCH3+CH2CH3), 1.53 (3H, d, J=7.2 Hz, CH3CH),
1.20 (3H, t, J=7.2 Hz, CH3CH2).
3.3. General procedure for preparation of 6- and 7-
substituted 3-(1-ethoxycarbonylethyl)-2(1H)-quinoxalin-
2-ones (12–20) with 7-nitro-3-(1-ethoxycarbonyl-
ethylidene)-1,2,3,4-tetrahydroquinoxalin-2-one (21)
3.3.5. 7-Nitro-3-(1-ethoxycarbonylethylidene)-1,2,3,4-
tetrahydroquinoxalin-2-one (21)
0.18 g (10% yield); m.p. 220–222°C; IR: w 3170,
3070, 1670, 1620 cm−1; UV: u 421, 404, 318, 265, 221,
212 sh nm; 1H NMR (CDCl3+DMSO-d6): l 12.47
(1H, s, NH-1), 11.53 (1H, s, NH-4), 7.88 (1H, d, J=8.8
To a solution of the appropriate diamine 1a–e (1.0 g;
5.7–7.0 mmol) in ethanol (20 ml), diethyl oxalpropionate