Arch. Pharm. Chem. Life Sci. 2007, 340, 456–465
1-Cinnamyl-4-arylpiperazines: D2 and 5-HT1A Study
463
(d, 1H, J = 16 Hz), 6.84–7.05 (m, 4H) 7.49 (d, 2H, J = 8.6 Hz), 8.15
(d, 2H, J = 9 Hz); 13C-NMR (CDCl3) 50.38; 53.29; 55.08; 60.58;
110.90; 117.94; 120.77; 122.81; 123.77; 126.60; 130.67; 131.88;
140.94; 143.16; 146.59; 152.01; IR (cm– 1) 2930, 2812, 1595, 1510,
1343, 1240, 751; MS: m/e [M+H]+ 354.1843; mp. 1178C; Yield 92%.
General procedure for the synthesis of 1-[(1E)-3-
bromoprop-1-enyl]-methoxybenzenes 2e–2g
Hydrobromic acid (HBr) in acetic acid (33% solution, 2.24 g),
1.5 g (9.15 mmol) (2E)-3-(methoxyphenyl)prop-2-en-1-ol (1e or 1f
or 1g) in 20 mL dry diethyl ether, was stirred for 120 min at
room temperature under argon, and was then poured into a
water/diethyl ether mixture (20 / 20 mL). The organic layer was
separated, washed with saturated NaHCO3 solution, then water,
dried over anhydrous Na2SO4, and concentrated in vacuo. The
product was used immediately without further purification.
(2E)-4-(2-Methoxyphenyl)-1-[3-(2-methoxyphenyl)prop-
2-enyl]-piperazine 3e
1H-NMR (CDCl3) 2.72 (m, 4H), 3.13 (m, 4H), 3.25 (d, 2H, J = 6.8 Hz),
3.83 (s, 3H from OCH3), 3.84 (s, 3H from OCH3) 6.34 (dt, 1H, J = 16
Hz and J = 6.8 Hz), 6.83–7.04 (m, 7H), 7.24 (t, 1H, J = 7.6 Hz), 7.46
(d, 1H, J = 7.4 Hz); 13C-NMR (CDCl3) 50.51; 53.28; 55.17; 55.26;
61.52; 110.68; 110.97; 118.09; 120.21; 120.86; 122.77; 125.77;
General procedure for the synthesis of (2E)-1-(3-arylprop-
2-enyl)-4-(2-methoxyphenyl)piperazines 3a–j
126.69; 126.98; 127.76; 128.40; 141.20; 152.12; 156.44; IR (cm– 1
)
Cinnamyl halides 2a–j (10.0 mmol), 1-(2-methoxyphenyl)pipera-
zine (10.0 mmol) and 2.02 g (20.0 mmol) of triethylamine in
20 mL acetonitrile were stirred at room temperature for 24 h.
The reaction mixture was poured into water and extracted with
dichloromethane. After drying over Na2SO4 and concentration
in vacuum, the products were purified by dry-flash chromatog-
raphy using a gradient of methanol (0–5%) in dichloromethane
as a solvent.
2939, 2813, 1595, 1497, 1457, 1243, 1180, 1029, 750; MS: m/e
[M+H]+ 339.2067; mp 788C; Yield 57%.
(2E)-4-(2-Methoxyphenyl)-1-[3-(3-methoxyphenyl)prop-
2-enyl]-piperazine 3f
1H-NMR (CDCl3) 2.72 (m, 4H), 3.13 (m, 4H), 3.79 (s, 3H from OCH3),
3.84 (s, 3H from OCH3), 4.29 (d, 2H, J = 5.4 Hz) 6.32 (dt, 1H, J =
15.6 Hz and J = 5.4 Hz), 6.53 (d, 1H, J = 16 Hz), 6.76–7.04 (m, 7H),
7.22 (t, 1H, J = 8 Hz); 13C-NMR (CDCl3) 50.49; 53.29; 55.04; 55.19;
60.96; 110.96; 112.48; 113.23; 118.11; 118.95; 120.86; 122.86;
(2E)-4-(2-Methoxyphenyl)-1-(3-phenylprop-2-
enyl)piperazine 3a
1H-NMR (DMSO) 2.56 (m, 4H) 2.97 (m, 4H), 3.13–3.17 (m, 2H), 3.76
(s, 3H from OCH3), 6.33 (dt, 1H, J = 16 Hz and J = 6.0 Hz), 6.57 (d,
1H, J = 16 Hz), 6.87–6.95 (m, 4H), 7.2–7.36 (m, 3H), 7.45 (d, 2H, J =
6.8 Hz); 13C-NMR (CDCl3) 50.28; 53.812; 55.50; 60.49; 112.13;
118.16; 121.05; 122.60; 126.48; 127.26, 127.66; 128.85; 132.43;
136.91; 141.50; 152.25; IR (cm– 1) 2830, 2812, 1499, 1454, 1241,
746; MS: m/e [M+H]+ 308.4170; mp. 78–808C; Yield 87%.
126.72; 129.45; 133.01; 138.23; 141.13; 152.12; 159.68; IR (cm– 1
)
2939, 2831, 1590, 1498, 1454, 1242, 1036, 752; MS: m/e [M+H]+
339.2073; mp. 788C; Yield 45%.
(2E)-4-(2-Methoxyphenyl)-1-[3-(4-methoxyphenyl)prop-
2-enyl]-piperazine 3g
1H-NMR (CDCl3) 2.71 (m, 4H), 3.12 (m, 4H), 3.21 (d, 2H, J = 6.8 Hz),
3.78 (s, 3H from OCH3), 3.84 (s, 3H from OCH3), 6.17 (dt, 1H, J =
16 Hz and J = 6.8 Hz), 6.49 (d, 1H, J = 16 Hz), 6.82–7.04 (m, 6H),
7.32 (d, 2H, J = 8.8 Hz); 13C-NMR (CDCl3) 50.49; 53.26; 55.11; 55.15;
61.12; 110.96; 113.83; 118.08; 120.84, 122.79; 124.07; 127.36;
129.60; 132.55; 152.12; 159.01; IR (cm– 1) 2940, 2806, 1604, 1508,
1457, 1241, 1172, 1029, 752; MS: m/e [M+H]+ 339.2093; mp. 758C;
Yield 95%.
(2E)-1-[4-(2-Methoxyphenyl)-3-(2-nitrophenyl)prop-2-
enyl]-piperazine 3b
1H-NMR (CDCl3) 2.75 (m, 4H) 3.14 (m, 4H), 3.29 (d, 2H, J = 6.6 Hz),
3.86 (s, 3H from OCH3), 6.30 (dt, 1H, J = 15.8 Hz and J = 6.6 Hz),
6.84–6.98 (m, 4H), 7.04 (d, 1H, J = 16.2 Hz), 7.37 (t, 1H, J = 8.2 Hz),
7.55 (t, 1H, J = 7.6 Hz), 7.62 (d, 1H, J = 8.0 Hz), 7.90 (d, 1H, J =
7.8 Hz); 13C-NMR (CDCl3) 50.51; 53.35; 55.22; 60.67; 111.07;
118.11; 120.88; 122.86; 124.39; 127.93; 128.18; 128.60; 132.13;
132.97; 141.16; 147.66; 152.18; IR (cm– 1) 2938, 2814, 1523, 1501,
1347, 1241, 744; MS: m/e [M+H]+ 354.1854; oil; Yield 56%.
(2E)-1-[3-(2-Chlorophenyl)prop-2-enyl]-4-(2-
methoxyphenyl)piperazine 3h
1H-NMR (CDCl3) 2.74 (m, 4H), 2.76 (m, 4H), 3.28 (d, 2H, J = 6.8 Hz),
3.86 (s, 3H from OCH3), 6.31 (dt, 1H, J = 15.6 Hz and J = 6.8 Hz),
6.84–7.05 (m, 4H), 6.95 (d, 1H, J = 16 Hz), 7.15–7.26 (m, 1H) 7.18
(t, 1H, J = 5.2 Hz), 7.34 (d, 1H, J = 7 Hz), 7.55 (d, 1H, J = 7.4 Hz); 13C-
NMR (CDCl3) 50.58; 53.37; 55.26; 61.04; 111.067; 118.17; 120.94;
122.91; 126.81; 128.45; 129.18; 129.47; 129.62; 132.82; 134.97;
141.22; 152.22; IR (cm– 1) 2940, 2815, 1591, 1500, 1452, 1240,
1137, 1030, 748; MS: m/e [M+H]+ 342.1569; oil; Yield 71%.
(2E)-4-(2-Methoxyphenyl)-1-[3-(3-nitrophenyl)prop-2-
enyl]-piperazine 3c
1H-NMR (CDCl3) 2.74–2.76 (m, 4H), 3.14 (m, 4H), 3.28 (d, 2H, J =
6.0 Hz), 3.86 (s, 3H from OCH3), 6.55 (dt, 1H, J = 17 Hz and J =
6.2 Hz), 6.63 (d, 1H, J = 16 Hz), 6.85–7.05 (m, 4 H,), 7.47 (t, 1H, J =
8 Hz), 7.68 (d, 1H, J = 7.8 Hz), 8.07 (d, 1H, J = 8.2 Hz), 8.23 (s, 1H);
13C-NMR (CDCl3) 40.51; 53.37; 55.21; 60.59; 110.99; 118.09;
120.88; 121.94; 122.92; 129.36; 130.11; 130.60; 131.93; 138.61;
141.07; 148.46; 152.14; IR (cm– 1) 2972, 2810, 1529, 1499, 1456,
1351, 1238, 1132, 1018, 751; MS: m/e [M+H]+ 354.1816; mp. 818C;
Yield 66%.
(2E)-1-[3-(3-Chlorophenyl)prop-2-enyl]-4-(2-
methoxyphenyl)piperazine 3i
1H-NMR (CDCl3) 2.71 (m, 4H), 3.12 (m, 4H), 3.23 (d, 2H, J = 6.4 Hz),
3.85 (s, 3H from OCH3), 6.32 (dt, 1H, J = 15.8 Hz and J = 6.4 Hz),
6.50 (d, 1H, J = 15.8 Hz), 6.83–7.04 (m, 4H), 7.15–7.25 (m, 3H),
7.36 (s, 1H); 13C-NMR (CDCl3) 50.53; 53.33; 55.21; 60.80; 111.05;
118.11; 120.90; 122.86; 124.36; 126.25; 127.30; 128.20; 129.69;
131.62; 134.41; 138.74; 141.16; 152.16; IR (cm– 1) 2939, 2815,
(2E)-4-(2-Methoxyphenyl)-1-[3-(4-nitrophenyl)prop-2-
enyl]-piperazine 3d
1H-NMR (CDCl3) 2.74 (m, 4H), 3.14 (m, 4H), 3.28 (d, 2H, J = 6.0 Hz),
3.85 (s, 3H from OCH3), 6.50 (dt, 1H, J = 16 Hz and J = 6.0 Hz), 6.64
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