Ligustrazine Derivatives As Potential Cardiovascular Agents
d, =CH-, J = 15.6 Hz), 7.20 (1H, t, Ar-H, J = 7.8 Hz), 7.13 (1H, d, Ar-
(E)-2-(3-methoxyl-2-hydroxylstyryl)-3,5,6-
trimethylpyrazine (A6)
H, J = 7.7 Hz), 7.10 (1H, s, Ar-H), 6.72 (1H, d, Ar-H, J = 7.3 Hz),
2.56 (3H, s, -CH3), 2.50 (3H, s, -CH3), 2.44 (3H, s, -CH3); 13C-NMR
(DMSO, dppm): 149.41, 178.67, 146.25, 137.63 (pyrazine-C), 157.54,
137.63, 133.02, 129.62, 122.77, 118.26, 115.51, 113.41 (-CH=CH-Ar-
C), 21.31 (-CH3), 21.25 (-CH3), 20.40 (-CH3); ESI-MS: m ⁄ z 241.4
(M + 1). C15H16N2O (Exact Mass: 240.13).
3-Methoxyl-2-hydroxyl benzaldehyde was used as the material of
Horner–Wadsworth–Emmons reaction. The crude product was sepa-
rated by flash column chromatography with eluent of ethyl ace-
tate ⁄ cyclohexane = 1:3 and purified by recrystallization from
methanol to give yellow crystal, mp 187–188 ꢀC.Yield: 35%. IR
(KBr, cm)1): 3052 (m=CH), 1625 (mCH=CH), 1602, 1581, 1477 (mCH=CH,
1
Ar), 1441, 1399 (mC=N), 717(c=CH); H-NMR (DMSO, dppm): 9.02 (1H,
(E)-2-(3-chlorostyryl)-3,5,6-trimethylpyrazine
(A3)
s, -OH), 8.02 (1H, d, =CH-, J = 15.8 Hz), 7.35 (1H, d, =CH-,
J = 15.8 Hz), 7.32 (1H, d, Ar-H, J = 7.7 Hz), 6.92 (1H, d, Ar-H,
J = 7.8 Hz), 6.80 (1H, t, Ar-H, J = 7.8 Hz), 3.83 (3H, s, -OCH3), 2.54
(3H, s, -CH3), 2.50 (3H, s, -CH3), 2.49 (3H, s, -CH3); 13C-NMR (DMSO,
dppm): 148.89, 148.03, 146.80, 145.14 (pyrazine-C), 149.21, 144.88,
128.37, 123.73, 122.36, 119.12, 118.81, 111.54 (-CH=CH-Ar-C), 56.02
(-OCH3), 21.59 (-CH3), 21.49 (-CH3), 20.71 (-CH3); ESI-MS: m ⁄ z 271.4
(M + 1). C16H18N2O2 (Exact Mass: 270.14).
3-Chlorobenzaldehyde was used as the material of Horner–Wads-
worth–Emmons reaction. The crude product was separated by flash
column chromatography with eluent of ethyl acetate ⁄ cyclohex-
ane = 1:5 and purified by recrystallization from methanol to give
yellow crystals, mp 92–94 ꢀC. Yield: 27%. IR (KBr, cm)1): 3054
(m=CH), 1631 (mCH=CH), 1589, 1559, 1473 (mCH=CH, Ar), 1424, 1405
(mC=N), 872, 799, 685 (c=CH); 1H-NMR (CDCl3,dppm): 7.73 (1H, d,
=CH-, J = 15.6 Hz), 7.29 (1H, d, =CH-, J = 15.7 Hz), 7.60 (1H, s, Ar-
H), 7.47 (1H, d, Ar-H, J = 7.6 Hz), 7.32 (1H, t, Ar-H, J = 7.9 Hz),
7.29 (1H, d, Ar-H, J = 7.4Hz), 2.64 (3H, s, -CH3), 2.56 (3H, s, -CH3),
2.54 (3H, s, -CH3); 13C-NMR (CDCl3,dppm): 150.62, 149.27, 147.29,
144.85 (pyrazine-C), 138.91, 134.72, 132.52, 129.93, 128.19, 126.84,
125.50, 124.39 (-CH=CH-Ar-C); 21.78, 20.96 (3-CH3); ESI-MS: m ⁄ z
259.2 (M + 1). C15H15ClN2 (Exact Mass: 258.09).
(E)-2-(2-hydroxylstyryl)-3,5,6-trimethylpyrazine
(A7)
2-Hydroxyl benzaldehyde was used as the material of Horner–
Wadsworth–Emmons reaction. The crude product was separated by
flash column chromatography with eluent of ethyl acetate ⁄ cyclohex-
ane = 1:3 and purified by recrystallization from methanol to give
yellow crystal, mp 221–222 ꢀC.Yield: 35%. IR (KBr,cm)1): 3068
(m=CH), 1620 (mCH=CH), 1601, 1539, 1498, 1458 (mCH=CH, Ar), 1408
1
(E)-2-(4-fluorostyryl)-3,5,6-trimethylpyrazine
(A4)
(mC=N), 742 (c=CH); H-NMR (DMSO, dppm): 9.90 (1H, s, -OH), 7.97
(1H, d, =CH-, J = 15.8Hz), 7.39 (1H, d, =CH-, J = 15.8 Hz), 7.69 (1H,
d, Ar-H, J = 7.8 Hz), 7.13 (1H, t, Ar-H, J = 8.3 Hz), 6.89 (1H, d, Ar-
H, J = 8.1 Hz), 6.83 (1H, t, Ar-H, J = 7.6 Hz), 2.54 (3H, s, -CH3),
2.47 (3H, s, -CH3), 2.43 (3H, s, -CH3); 13C-NMR (DMSO, dppm):
149.10, 148.73, 146.79, 145.40 (pyrazine-C), 153.67, 129.05, 128.77,
127.82, 124.11, 120.66, 120.20, 115.93 (-CH=CH-Ar-C), 21.28 (-CH3),
21.25 (-CH3), 20.55 (-CH3); ESI-MS: m ⁄ z 241.2 (M + 1). C15H16N2O
(Exact Mass: 240.13).
3-Fluorobenzaldehyde was used as the material of Horner–Wads-
worth–Emmons reaction. The crude product was separated by flash
column chromatography with eluent of ethyl acetate ⁄ cyclohex-
ane = 1:5 and purified by recrystallization from methanol to give
yellow crystal, mp 88–90 ꢀC. Yield: 43%. IR (KBr,cm)1): 3058 (m=CH),
1635 (mCH=CH), 1599, 1508 (mCH=CH, Ar), 1447, 1416 (mC=N), 824 (c=CH);
1H-NMR (CDCl3, dppm): 7.77 (1H, d, =CH-, J = 15.5 Hz), 7.20 (1H, d,
=CH-, J = 15.4 Hz), 7.58 (2H, t, Ar-H, J = 8.3 Hz), 7.08 (2H, t, Ar-H,
J = 8.4 Hz), 2.66 (3H, s, -CH3), 2.57 (3H, s, -CH3), 2.56 (3H, s, -CH3);
13C-NMR (CDCl3, dppm): 149.31, 148.83, 146.70, 144.90 (pyrazine-C),
132.49, 130.23, 128.46, 122.46, 115.46, 115.31 (-CH2=CH2-Ar-C),
21.44 (-CH3), 21.41 (-CH3), 20.79 (-CH3); ESI-MS: m ⁄ z 243.4 (M + 1).
C15H15FN2 (Exact Mass: 242.12).
(E)-2-(2,3-dimethoxylstyryl)-3,5,6-
trimethylpyrazine (A8)
2,3-Dimethoxyl benzaldehyde was used as the material of Horner–
Wadsworth–Emmons reaction. The crude product was separated by
flash column chromatography with eluent of ethyl acetate ⁄ cyclohex-
ane = 1:5 and purified by recrystallization from methanol to give yel-
low crystal, mp 87–88 ꢀC.Yield: 25%. IR (KBr,cm)1): 3069 (m=CH), 1634
(mCH=CH), 1576, 1559, 1477 (mCH=CH, Ar), 1455, 1429 (mC=N), 787 (c=CH);
1H-NMR (DMSO, dppm): 7.92 (1H, d, =CH-, J = 15.9 Hz), 7.43 (1H, d,
=CH-, J = 15.8 Hz), 7.44 (1H, d, Ar-H, J = 7.9 Hz), 7.11 (1H, t, Ar-H,
J = 7.8 Hz), 7.03 (1H, d, Ar-H, J = 8.2 Hz), 3.83 (3H, s, -OCH3), 3.76
(3H, s, -OCH3), 2.56 (3H, s, -CH3), 2.48 (3H, s, -CH3), 2.44 (3H, s, -CH3);
ESI-MS: m ⁄ z 285.4 (M + 1). C17H20N2O2 (Exact Mass: 284.15).
(E)-2-(2,5-dimethoxylstyryl)-3,5,6-
trimethylpyrazine (A5)
2,5-Dimethoxyl benzaldehyde was used as the material of Horner–
Wadsworth–Emmons reaction. The crude product was separated
by flash column chromatography with eluent of ethyl ace-
tate ⁄ cyclohexane = 1:3 and purified by recrystallization from meth-
anol to give yellow crystal, mp 124–126 ꢀC. Yield: 40%. IR
(KBr,cm)1): 3036 (m=CH), 1619 (mCH=CH), 1604, 1495, 1462 (mCH=CH,
1
Ar), 1443,1417 (mC=N), 839, 810, 708 (c=CH); H-NMR (CDCl3, dppm):
8.03 (1H, d, =CH-, J = 15.8 Hz), 7.34 (1H, d, =CH-, J = 15.8 Hz),
7.18 (1H, sd Ar-H, J = 2.8 Hz), 6.87 (2H, m, Ar-H), 3.88 (3H, s, -
OCH3), 3.84 (3H, s, -OCH3), 2.62 (3H, s, -CH3), 2.56 (3H, s, -CH3),
2.52 (3H, s, -CH3); ESI-MS: m ⁄ z 285.3 (M + 1). C17H20N2O2 (Exact
Mass: 284.15).
(E)-2-(4-nitrostyryl)-3,5,6-trimethylpyrazine (A9)
4-Nitrobenzaldehyde was used as the material of Horner–Wads-
worth–Emmons reaction. The crude product was separated by flash
column chromatography with eluent of ethyl acetate ⁄ cyclohex-
ane = 1:5 and purified by recrystallization from methanol to give
Chem Biol Drug Des 2012; 79: 731–739
733