[
L. Moradi et al. / Chinese Chemical Letters 24 (2013) 740–742
741
H
N
CO2R
O
NH2
NH2
NO2
SA
+
+
N
R'
CH3CN, reflux
CO2R
CO2R
1
2
R'
3
R= Me, Et
R'=C H5, p-CH3-C6H4, p-Cl-C6H4, p-NO -C6H4
6
2
Scheme 1. Synthesis of pyrrolo[1,2-a]pyrazines.
of Ar), 133.4 (N–CH55C) 161.0 (C55O), 170.9 (C55O). Anal. calcd. for
15H14N2O3 (270.29); C, 66.66; H, 5.22; N, 10.36%; Found: C, 66.58;
H, 5.19; N, 10.48.
1402, 1460. 1H NMR (250 MHz, CDCl3):
d
1.41 (t, 3H, 3JHH = 7.2 Hz,
C
CH3), 3.42 (t, 2H, 3JHH = 3.5 Hz, CH2), 3.50 (t, 2H, 3JHH = 3.5 Hz, CH2),
4.28 (q, 2H, 3JHH = 7.2 Hz, CH2), 6.56–7.24 (m, 6H, 6H), 8.26 (s, 1H,
Ethyl 1-oxo-7-p-tolyl-1,2,3,4-tetrahydropyrrolo[1,2-a]pyrazine-
8-carboxylate (3b): Gray crystals, yield 0.27 g (90%), mp 186–
190 8C (decomp). IR (KBr, cmꢀ1): nmax 3305 (NH broad), 1714
NH). 13C NMR (62.9 MHz, CDCl3):
d 13.2 (CH3), 40.2 (CH2), 44.4
(CH2), 62.3 (OCH2), 118.4 (N–CH55C), 120.8 (C), 123.1 (C), 125.4 (CH
of Ar), 126.7 (C of Ar), 127.2 (2CH of Ar), 128.7 (2CH of Ar), 133.3
(N–CH55C) 161.1 (C55O), 170.8 (C55O). Anal. calcd. For C16H16N2O3
(284.32) C, 67.59; H, 5.67; N, 9.85%; Found: C, 67.58; H, 5.79; N,
9.74.
(C55O), 1653 (C55O), 1604, 1552, 1495. 1H NMR (250 MHz, CDCl3):
d
3
1.44 (t, 3H, JHH = 7.2 Hz, CH3), 2.34 (s, 3H, CH3),3.48 (t, 2H,
3
3JHH = 3.5 Hz, CH2), 3.46 (t, 2H, JHH = 3.5 Hz, CH2), 4.29 (q, 2H,
3JHH = 7.2 Hz, CH2), 6.59–7.26 (m, 5H, 5H), 8.26 (s, 1H, NH). 13C
Ethyl
a]pyrazine-8-carboxylate (3g): Gray crystals; 0.26 g (80%). mp
188–190 8C (decomp). IR (KBr, cmꢀ1):
max 3210 (NH broad), 1716
7-(4-nitrophenyl)-1-oxo-1,2,3,4-tetrahydropyrrolo[1,2-
NMR (62.9 MHz, CDCl3):
d 13.1 (CH3), 22.3 (CH3), 40.2 (CH2), 45.3
(CH2), 62.4 (OCH2), 117.7 (N–CH55C), 121.8 (C), 122.8 (C of Ar),
125.1 (C of Ar), 128.6 (2CH of Ph), 129.8 (2CH of Ph), 131.2 (C),
131.8 (N–CH55C), 158.7 (C55O), 165.3 (C55O). MS: m/z (%) 298 (M+,
98), 269 (10), 253(100), 239(12), 226(30). Anal. calcd. for
n
(C55O), 1651 (C55O), 1563, 1520, 1417. 1H NMR (250 MHz, CDCl3):
d
1.23 (t, 3H, 3JHH = 7.1 Hz, CH3), 3.70 (t, 2H, 3JHH = 4.0 Hz, CH2), 4.11
(t, 2H, 3JHH = 4.0 Hz, CH2), 4.20 (q, 2H, 3JHH = 7.1 Hz, CH2), 7.72–7.85
C17H18N2O3 (298.34) C, 68.44; H, 6.08; N, 9.39%; Found: C,
(m, 5H, 5H), 8.74 (s, 1H, NH). 13C NMR (62.9 MHz, CDCl3):
d 14.3
68.36; H, 5.87; N, 10.12.
(CH3), 41.0 (CH2), 45.2 (CH2), 62.3 (OCH2), 118.8 (N–CH55C), 120.5
(C), 123.2 (C of Ar), 123.3 (C of Ar), 127.4 (2CH of Ph), 128.9 (2CH of
Ph), 130.9 (C), 132.6 (N–CH55C), 158.3 (C55O), 166.1 (C55O). Anal.
calcd. for C16H15N3O5 (329.32) C, 58.36; H, 4.59; N, 12.76%; Found:
C, 58.40; H, 4.40; N, 12.52.
Methyl 1-oxo-7-p-tolyl-1,2,3,4-tetrahydropyrrolo[1,2-a]pyrazine-
8-carboxylate (3c): Gray crystals, yield 0.27 g (95%), mp 190–192 8C
(decomp.). IR (KBr, cmꢀ1):
nmax 3304 (NH broad), 1713 (C55O), 1651
(C55O), 1600, 1553, 1499. 1H NMR (250 MHz, CDCl3):
d 2.30 (s, 3H,
CH3), 3.48 (t, 2H, 3JHH = 3.5 Hz, CH2), 3.46 (t, 2H, 3JHH = 3.5 Hz, CH2),
Methyl 7-(4-nitrophenyl)-1-oxo-1,2,3,4-tetrahydropyrrolo[1,2-
a]pyrazine-8-carboxylate (3h): Gray crystals; 0.25 g (82%). mp
3.80 (s, 3H, OCH3), 6.59–7.26 (m, 5H, 5H), 8.26 (s, 1H, NH). 13C NMR
(62.9 MHz, CDCl3):
d
22.3 (CH3), 40.2 (CH2), 45.3 (CH2), 52.4
192–194 8C (decomp). IR (KBr, cmꢀ1):
nmax 3213 (NH broad), 1714
(OCH3), 117.7 (N–CH55C), 121.8 (C), 122.8 (C of Ar), 125.1 (C of Ar),
128.6 (2CH of Ph), 129.8 (2CH of Ph), 131.2 (C), 131.8 (N–CH55C),
158.7 (C55O), 165.3 (C55O). Anal. calcd. for C16H16N2O3 (284.32) C,
67.59; H, 5.67; N, 9.85%; Found: C, 67.50; H, 5.87; N, 9.92.
Ethyl 7-(4-cholorophenyl)-1-oxo-1,2,3,4-tetrahydropyrrolo[1,2-
a]pyrazine-8-carboxylate (3d): Gray crystals; 0.28 g (88%), mp
(C55O), 1650 (C55O), 1561, 1522, 1414. 1H NMR (250 MHz, CDCl3):
3.66 (s, 3H, OCH3), 3.73 (t, 2H, JHH = 4.0 Hz, CH2), 4.14 (t, 2H,
3JHH = 4.0 Hz, CH2), 7.75–7.87 (m, 5H, 5H), 8.73 (s, 1H, NH). 13C
d
3
NMR (62.9 MHz, CDCl3):
d 41.2 (CH2), 45.1 (CH2), 52.5 (OCH3),
118.4 (N–CH55C), 122.5 (C), 123.3 (C of Ar), 124.3 (C of Ar), 127.2
(2CH of Ph), 128.8 (2CH of Ph), 130.6 (C), 132.2 (N–CH55C), 157.3
(C55O), 166.2 (C55O). Anal. calcd. for C15H13N3O5 (315.29) C, 57.14;
H, 4.16; N, 13.33%; Found: C, 57.32; H, 4.10; N, 13.22.
183–185 8C (decomp). IR (KBr, cmꢀ1):
nmax 3212 (NH broad), 1718
(C55O), 1650 (C55O), 1560, 1526, 1419. 1H NMR (250 MHz, CDCl3):
d
1.20 (t, 3H, 3JHH = 7.1 Hz, CH3), 3.72 (t, 2H, 3JHH = 4.0 Hz, CH2), 4.14
(t, 2H, 3JHH = 4.0 Hz, CH2), 4.21 (q, 2H, 3JHH = 7.1 Hz, CH2), 7.20–7.32
(m, 5H, 5H), 8.70 (s, 1H, NH). 13C NMR (62.9 MHz, CDCl3):
d 14.1
3. Results and discussion
(CH3), 41.1 (CH2), 45.2 (CH2), 62.4 (OCH2), 118.7 (N–CH55C), 120.7
(C), 123.2 (C of Ar), 123.3 (C of Ar), 127.6 (2CH of Ph), 128.9 (2CH of
Ph), 130.9 (C), 132.6 (N–CH55C), 158.4 (C55O), 166.1 (C55O). Anal.
calcd. for C16H15ClN2O3 (318.76) C, 60.25; H, 4.74; N, 8.79%; Found:
C, 60.40; H, 4.23; N, 8.52.
The reaction of ethylenediamine and acetylenic esters 1 with
nitrostyrene derivatives 2 in the presence of 20 mol% of SA
proceeded in CH3CN at reflux condition, and was finished after
24 h. Any product other than 3 could not be detected by NMR
spectroscopy. Satisfactorily, the reactions displayed high function-
al group tolerance and afforded the corresponding pyrazines with
great efficiency (Table 1). The structure of 3a–3h was determined
Methyl 7-(4-cholorophenyl)-1-oxo-1,2,3,4-tetrahydropyrrolo[1,2-
a]pyrazine-8-carboxylate (3e): Gray crystals; 0.27 g (89%), mp 193–
195 8C (decomp). IR (KBr, cmꢀ1): nmax 3210 (NH broad), 1720
(C55O), 1654 (C55O), 1568, 1529, 1429. 1H NMR (250 MHz, CDCl3):
d
3
3.70 (t, 2H, JHH = 4.0 Hz, CH2), 3.84 (s, 3H, OCH3), 4.11 (t, 2H,
3JHH = 4.0 Hz, CH2), 6.69 (s, 1H, CH), 6.83 (s, 1H, NH), 7.22–7.31 (m,
4H, 4H of Ph). 13C NMR (62.9 MHz, CDCl3):
d 40.1 (CH2), 44.3 (CH2),
Table 1
Substituted pyrrolo[1,2-a]pyrazines.
Compounds
R
R0
Yield (%)
52.4 (OCH3), 118.7 (N–CH55C), 120.8 (C), 123.3 (C of Ar), 124.3 (C of
Ar), 128.7 (2CH of Ph), 128.8 (2CH of Ph), 131.9 (C), 132.8 (N–
CH55C), 159.4 (C55O), 166.4 (C55O). Anal. calcd. for C15H13ClN2O3
(304.74) C, 59.12; H, 4.30; N, 9.19%; Found: C, 59.10; H, 4.23; N,
9.22.
3a
3b
3c
3d
3e
3f
CH3
C6H5
88
90
95
92
90
87
82
80
CH3CH2
CH3
p-CH3–C6H4
p-CH3–C6H4
p-Cl–C6H4
p-Cl–C6H4
C6H5
CH3CH2
CH3
CH3CH2
CH3
Ethyl 1-oxo-7-phenyl-1,2,3,4-tetrahydropyrrolo[1,2-a]pyrazine-
8-carboxylate (3f): Gray crystals; 0.24 g, 87%, mp 180–182 8C. IR
3g
3h
p-NO2–C6H4
p-NO2–C6H4
CH3CH2
(KBr, cmꢀ1):
nmax 3215 (NH broad), 1711 (C55O), 1653 (C55O), 1555,