M. Tarleton et al. / European Journal of Medicinal Chemistry 57 (2012) 65e73
71
131.9, 130.9, 129.8, 127.8, 127.2, 126.1, 125.0, 122.8, 120.7, 119.2, 118.9,
112.2, 110.7, 99.6; IR (KBr) nmax/cmꢃ1: 3311 (NH), 2212 (CN), 1628
(C]C), 1574 (Ar), 732 (AreCl); m/z (APCI M ꢃ H) 311; HRMS (ESI
M ꢃ H): Calculated for C17H10Cl2N2; Exact Mass: 312.0221, found:
311.0160. Anal. C17H10Cl2N2 (C, H, N).
(DMSO-d6):
d
8.15 (d, J ¼ 8.8 Hz, 2H, H-30 and H-50), 7.90 (d,
J ¼ 8.8 Hz, 2H, H-20 and H-60), 7.83 (m, 1H, H-5), 7.61 (m, 2H, H-2
and H-6), 6.73 (s, 1H, CH]C); 13C NMR (DMSO-d6):
d 170.5, 145.6,
145.2, 143.9, 139.1, 131.0, 130.4, 130.0, 128.9 (2ꢄ Ar), 128.0, 126.4,
123.2 (2ꢄ Ar), 119.1; IR (KBr) nmax/cmꢃ1: 3347 (OH), 1594 (C]O),
1337 (NeO); m/z (APCI M ꢃ H) 336; HRMS (ESI M ꢃ H): Calculated
for C15H9Cl2NO4; Exact Mass: 335.9836, found: 335.9919. Anal.
C15H9Cl2NO4 (C, H, N).
6.2.5. (Z)-2-(3,4-Dichlorophenyl)-3-(furan-2-yl)acrylonitrile (4)
Synthesized using the general procedure as for (1), from furan-
2-carbaldehyde to afford (4) as a light orange solid (75%), m.p. 126e
128 ꢁC; 1H NMR (CDCl3):
d
7.72 (s, 1H, H-50), 7.63 (s, 1H, CH]C), 7.48
6.2.10. (Z)-2-(3,4-Dichlorophenyl)-3-(4-methoxyphenyl)acrylic
acid (9)
(m, 2H, H-5 and H-2), 7.36 (s, 1H, H-6), 7.23 (d, J ¼ 3.4 Hz, 1H, H-30),
6.61 (dd, J ¼ 3.2, 1.4 Hz, 1H, H-40); 13C NMR (CDCl3):
d
149.6, 145.6,
Synthesized using the general procedure as for (8), from 4-
methoxybenzaldehyde to afford (9) as a yellow solid (15%), m.p.
133.7, 133.1, 130.9, 129.2, 128.9, 127.2, 124.7, 117.0, 116.4, 113.0, 105.1;
IR (KBr) nmax/cmꢃ1: 2215 (CN), 1617 (C]C), 1466 (Ar); m/z (APCI
M ꢃ H) 363; HRMS (ESI M ꢃ H): Calculated for C13H7Cl2NO; Exact
Mass: 262.9905, found: 263.0243. Anal. C13H7Cl2NO (C, H, N).
221e223 ꢁC; 1H NMR (DMSO-d6):
d 7.75 (s, 1H, CH]C), 7.63 (d,
J ¼ 8.2 Hz, 1H, H-5), 7.46 (d, J ¼ 2.0 Hz, 1H, H-2), 7.15 (dd, J ¼ 2.0,
8.2 Hz, 1H, H-6), 7.04 (d, J ¼ 8.9 Hz, 2H, H-20 and H-60), 6.82 (d,
J ¼ 8.9 Hz, 2H, H-30 and H-50), 3.71 (s, 3H, OCH3); 13C NMR (DMSO-
6.2.6. (Z)-3-(Biphenyl-4-yl)-2-(3,4-dichlorophenyl)acrylonitrile (5)
Synthesized using the general procedure as for (1), from
biphenyl-4-carbaldehyde to afford (5) as a white solid (61%), m.p.
d6):
d
167.7,160.1,139.9,137.5,132.1 (2ꢄ Ar),132.0,131.6,131.1,130.7,
130.1, 128.1, 126.1, 114.0 (2ꢄ Ar), 55.1; IR (KBr) nmax/cmꢃ1: 3448
(OH), 1663 (C]O), 1172 (CeO); m/z (APCI M ꢃ H) 321; HRMS (ESI
M ꢃ H): Calculated for C16H12Cl2O3; Exact Mass: 321.0091, found:
321.0184. Anal. C16H12Cl2O3 (C, H, N).
230e232 ꢁC; 1H NMR (DMSO-d6):
d 8.23 (s, 1H, CH]C), 8.08e8.05
(m, 3H, H-2, H-30 and H-50), 7.89 (d, J ¼ 8.2 Hz, 2H, H-20 and H-60),
7.81e7.73 (m, 4H, H-200, H-300, H-500 and H-600), 7.53e7.49 (m, 2H, H-
5, H-400), 7.45e7.42 (m, 1H, H-6); 13C NMR (DMSO-d6):
d
144.6,
6.2.11. (Z)-2-(3,4-Dichlorophenyl)-3-(5-phenylfuran-2-yl)
acrylonitrile (10)
143.0, 139.3, 135.0, 132.8, 132.6, 132.2, 131.8, 130.5, 129.6, 128.7,
127.8, 127.6, 127.3, 126.6, 118.0, 107.9; IR (KBr) nmax/cmꢃ1: 2216 (CN),
1593 (Ar), 1474 (Ar), 1448 (Ar); m/z (APCI M ꢃ H) 349; HRMS (ESI
M ꢃ H): Calculated for C21H13Cl2N; Exact Mass: 349.0425, found:
349.0397. Anal. C21H13Cl2N (C, H, N).
Synthesized using the general procedure as for (1), from 5-
phenyl-2-furaldehyde and 3,4-dichlorophenylacetonitrile to
1
afford (10) as a yellow solid (94%), m.p. 141e143 ꢁC; H NMR
(DMSO-d6):
d
8.00 (s, 1H, CH]C), 7.95e7.94 (m, 1H, H-200), 7.90e
7.87 (m, 2H, H-600 and H-300), 7.72e7.62 (m, 2H, H-500 and H-5),
6.2.7. (Z)-2-(3,4-Dichlorophenyl)-3-(4-fluorophenyl)
acrylonitrile (6)
7.51e7.36 (m, 3H, H-400, H-2, and H-6), 7.27e7.25 (m, 1H, H-40),
7.18e7.17 (m, 1H, H-30); 13C NMR (DMSO-d6):
d 156.3, 148.6, 134.2,
Synthesized using the general procedure as for (1), from 4-
fluorobenzaldehyde and 4-chlorophenyl acetonitrile to afford (6)
as a white solid (94%), m.p. 156e157 ꢁC (Lit. [4] 155 ꢁC); 1H NMR
132.0, 131.1, 131.1, 131.0, 129.0, 128.9, 128.8, 126.6, 125.5, 124.4, 121.6,
117.5, 109.2, 102.2; IR (KBr) nmax/cmꢃ1: 2214 (CN), 1630 (C]C), 1578
(Ar),1507 (Ar),1448 (Ar), 798 (AreCl); m/z (APCI M ꢃ H) 339; HRMS
(APCI M ꢃ H): Calculated for C19H11Cl2NO; Exact Mass: 339.0218,
found: 339.0219. Anal. C19H11Cl2NO (C, H, N).
(CDCl3):
7.51e7.48 (m, 3H, H-30, H-50 and CH]C), 7.20e7.15 (m, 2H, H-2 and
H-6); 13C NMR (CDCl3):
d
7.93e7.88 (m, 2H, H-20 and H-60), 7.75e7.74 (m, 1H, H-5),
d
141.5, 133.7, 133.0 (2ꢄ Ar), 132.9, 131.1,
131.0, 130.5, 128.9, 127.1, 124.6 (2ꢄ Ar), 116.6, 115.9, 115.7; IR (KBr)
nmax/cmꢃ1: 2213 (CN), 1636 (C]C), 1596 (Ar), 809 (AreCl); m/z
(APCI M ꢃ H) 291; HRMS (APCI M ꢃ H): Calculated for C15H8Cl2FN;
Exact Mass: 291.0018, found: 291.0029. Anal. C15H8Cl2FN (C, H, N).
6.2.12. (Z)-2-(3,4-Dichlorophenyl)-3-(5-(hydroxymethyl)furan-2-
yl)acrylonitrile (11)
Synthesized using the general procedure as for (1), from 5-
(hydroxymethyl)-2-furaldehyde and 3,4-dichlorophenylacetonitrile
to afford (11) as a yellow solid (78%), m.p. 145e147 ꢁC; 1H NMR
6.2.8. (Z)-2-(3,4-Dichlorophenyl)-3-(4-methoxyphenyl)
acrylonitrile (7)
(CDCl3): d 7.70e7.69 (m,1H, H-2), 7.51e7.42 (m, 2H, H-5 and H-6), 7.32
(s,1H, CH]C), 7.14 (d, J ¼ 3.5 Hz,1H, H-40), 6.50(d, J ¼ 3.5 Hz,1H, H-30),
Synthesized using the general procedure as for (1), from 4-
methoxybenzaldehyde and 3,4-dichlorophenylacetonitrile to
afford (7) as a yellow solid (79%), m.p. 166e167 ꢁC (Lit. [4] 142 ꢁC);
1H NMR (DMSO-d6): 8.10 (s, 1H, CH]C), 8.00e7.96 (m, 3H, H-5, H-
20 and H-60), 7.77e7.75 (m, 1H, H-2), 7.70e7.67 (m, 1H, H-6), 7.13 (d,
J ¼ 8.9 Hz, 2H, H-30 and H-50), 3.85 (s, 3H, OCH3); 13C NMR (DMSO-
4.71 (s, 2H, CH2), 2.49 (br, OH); 13C NMR (CDCl3):
d 157.1, 148.8, 133.1,
133.0,132.5,130.5,128.2,126.6,124.1,117.1,116.6,110.2,104.3, 56.9; IR
(KBr) nmax/cmꢃ1: 3425 (OH), 2213 (CN), 1625 (C]C), 1513 (Ar),
796 (AreCl); m/z (APCI M ꢃ H) 293; HRMS (ESI M ꢃ H): Calculated for
C14H9Cl2NO2; Exact Mass: 293.0010, found: 293.0013. Anal.
C14H9Cl2NO2 (C, H, N).
d6):
d
162.1, 144.8, 135.4, 132.5, 132.0 (2ꢄ Ar), 131.7, 131.6, 127.4,
126.3, 126.2, 118.3, 115.1 (2ꢄ Ar), 104.9, 55.6; IR (KBr) nmax/cmꢃ1
:
6.2.13. (Z)-3-(Benzofuran-2-yl)-2-(3,4-dichlorophenyl)
acrylonitrile (12)
2212 (CN), 1638 (C]C), 1609 (Ar), 1593 (Ar), 1513 (Ar); m/z (APCI
M ꢃ H) 303; HRMS (APCI M ꢃ H): Calculated for C16H11Cl2NO; Exact
Mass: 303.0296, found: 303.0299. Anal. C16H11Cl2NO (C, H, N).
Synthesized using the general procedure as for (1), from 1-
benzofuran-2-carbaldehyde and 3,4-dichlorophenylacetonitrile to
afford (12) as a yellow solid (60%), m.p. 203e205 ꢁC; 1H NMR
6.2.9. (Z)-2-(3,4-Dichlorophenyl)-3-(4-nitrophenyl)acrylic acid (8)
Triethylamine (1.51 g, 15 mmol) was added to a solution of 4-
nitrobenzaldehyde (1.51 g, 10 mmol) and 2-(3,4-dichlorophenyl)
acetic acid (2.29 g, 11 mmol) in Ac2O (5 mL). The solution was
heated at 140 ꢁC under a nitrogen atmosphere for 1 h. After this
period, the solvent was removed in vacuo to yield a yellow oil which
was purified by flash silica chromatography (1:9 EtOAc:Hexanes) to
afford (8) as a yellow solid (1.76 g, 52%), m.p. 151e153 ꢁC; 1H NMR
(DMSO-d6):
4H, H-70, H-40, H-2, H-6), 7.55 (s, 1H, H-5), 7.50e7.45 (m, 1H, H-60),
7.36e7.31 (m, 1H, H-50); 13C NMR (DMSO-d6):
155.0, 150.7, 133.9,
d
8.21 (s, 1H, H-30), 8.06 (s, 1H, CH]C), 7.81e7.64 (m,
d
132.1, 131.9, 131.3, 130.2, 127.7, 127.5, 127.2, 126.0, 124.0, 122.7, 116.7,
114.4, 111.5, 106.5; IR (KBr) nmax/cmꢃ1: 2220 (CN), 1632 (C]C), 1578
(Ar), 1509 (Ar), 790 (AreCl); m/z (APCI M ꢃ H) 313; HRMS (APCI
M ꢃ H): Calculated for C17H9Cl2NO; Exact Mass: 313.0061, found:
313.0064. Anal. C17H9Cl2NO (C, H, N).