2900
S. Mishra et al. / Bioorg. Med. Chem. 16 (2008) 2894–2902
1H, C4-H), 6.91 (d, 2H, J = 15.8 Hz, C2-H and, C6-H),
7.04 (d, 2H, J = 15.8 Hz, C1-H and C7-H), 7.15–25 (m,
hyde)
(5 mmol),
curcumin
(6.5 mmol),
and
triphenylphosphine (20 mol%]) was stirred at 75–80 ꢁC
for 3.5 h. The progress of the reaction was monitored
by TLC. After complete conversion, as indicated by
TLC, the reaction mixture was diluted with water and
extracted with ethyl acetate (3 · 10 mL). The combined
organic extracts were concentrated in vacuo and the
resulting product was directly charged onto a small silica
gel column and eluted with a mixture of ethyl acetate/
hexane to afford pure product. All the products (9–11)
were prepared using the same procedure.
6H,
Ar-H),
7.48–7.54(m,
5H,
Ar-H).
13C
NMR(300 MHz, CDCl3): 155.6, 151.9, 151.4, 147.5,
146.5, 142.1, 138.4, 133.4, 131.5, 129.6, 129.1, 127.6,
125.4, 125.1, 121.0, 120.6, 120.1, 114.5, 113.7, 108.2,
107.1, 100.1, 55.6, 55.4. ESI–MS m/z [M+H]+441.2.
5.2.3. N-(4-Fluorophenylpyrazole) curcumin (5). The silica gel
eluent was hexane/ethyl acetate, 70:30. Rf = 0.75 (DCM/
1
MeOH 9:1), yield: 62%. mp 65 ꢁC. H NMR (300 MHz,
CDCl3): d 3.89 (s, 6H, 2 · OCH3), 6.79 (s, 1H, C4-H),
6.98 (d, 2H, J = 15.6 Hz, C2-H and, C6-H), 7.06 (d, 2H,
J = 15.6 Hz, C1-H and C7-H), 7.10–7.22 (m, 6H, Ar-H),
7.45–7.69 (m, 4H, Ar-H). 13C NMR (300 MHz, CDCl3):
157.8, 154.1, 148.7, 148.2, 145.8, 145.2, 139.5, 135.8, 132.3,
129.8, 129.2, 124.7, 122.1, 117.9, 117.7, 113.5, 110.2, 110.6,
107.6, 56.8. ESI–MS m/z [M+H]+459.10.
5.3.1. 4-Benzylidene curcumin (9). The silica gel eluent
was ethyl acetate/ hexane, 15:85. Rf = 0.62 (DCM/
MeOH 9:1), yield: 58%, mp 120 ꢁC. 1H NMR
(300 MHz, CDCl3): d 3.89 (s, 6H, 2 · OCH3), 6.68–
7.15 (m, 6H, Ar-H), 7.18 (d, 2H, J = 15.0 Hz, C2-H
and, C6-H), 7.85(d, 2H, J = 15.0 Hz, C1-H and C7-H),
7.35–7.48 (m, 5H, Ar-H), 8.16 (s, 1H, =CH–Ar). 13C
NMR(300 MHz, CDCl3): 184.7, 165.9, 149.8, 147.5,
145.8, 142.1, 131.2, 129.0, 128.4, 128.1, 127.2, 124.4
123.1, 117.2, 111.9, 56.5. ESI–MS: m/z [M+H]+457.23.
5.2.4. N-(3-Nitrophenylpyrazole) curcumin (6). The silica
gel eluent was hexane/ethyl acetate, 70:30. Rf = 0.65
(DCM/MeOH 9:1), yield: 46%, mp 93 ꢁC. 1H NMR
(300 MHz, CDCl3): d 3.90 (s, 6H, OCH3), 6.80 (s, 1H,
C4-H), 7.02 (d, 2H, J = 14.8 Hz, C2-H and, C6-H),
7.10 (d, 2H, J = 14.8 Hz, C1-H and C7-H), 7.15–7.32
(m, 6H, Ar-H), 7.65–7.71 (m, 1H, Ar-H), 7.98–8.12 (m,
1H, Ar-H), 8.22–8.26 (m, 1 H, Ar-H), 8.43 (d, 1H,
J = 8.2 Hz, Ar-H). 13C NMR(300 MHz, CDCl3): 157.3,
153.2, 152.1, 150.8, 147.4, 146.7, 142.5, 139.0, 134.2,
132.8, 130.4, 130.1, 126.1, 124.8, 124.5, 122.0, 121.3,
120.7, 116.9, 116.5, 115.4, 113.1, 112.7, 105.2, 56.8,
56.6. ESI–MS m/z [MÀH]+(484.1), [M+H]+486.1.
5.3.2. 4-(4-Hydroxybenzylidene) curcumin (10). The silica
gel eluent was ethyl acetate/hexane, 20:80. Rf = 0.55
(DCM/MeOH 9:1), yield: 60%, mp 93 ꢁC. 1H NMR
(300 MHz, CDCl3): d 3.89 (s, 6H, 2 · OCH3), 6.77–
7.15 (m, 8H, Ar-H), 7.22 (d, 2H, J = 15.2 Hz, C2-H
and, C6-H), 7.68 (d, 2H, J = 8.6 Hz), 7.84(d, 2H,
J = 15.2 Hz, C1-H and C7-H), 8.06 (s, 1H, =CH-Ar).
13C NMR (300 MHz, CDCl3): 184.3, 165.7, 156.8,
149.4, 1467.9, 146.8, 142.1, 130.5, 127.9, 126.5, 125.6,
123.1, 117.2, 115.9, 111.9, 56.1. ESI–MS m/z
[MÀH]+471.2.
5.2.5. N-(2,4-Dichlorophenylpyrazole) curcumin (7). The
silica gel eluent was hexane/ethyl acetate, 70:30.
Rf = 0.70 (DCM/MeOH 9:1), yield: 54%, mp 142 ꢁC.
5.3.3. 4-(4-Hydroxy-3-methoxybenzylidene) curcumin
(11). The silica gel eluent was ethyl acetate/hexane,
20:80. Rf = 0.60 (DCM/MeOH 9:1), yield: 65%, mp
96 ꢁC. 1H NMR (300 MHz, CDCl3): d 3.87 (s, 3H,
OCH3), 3.89 (s, 6H, 2 · OCH3), 6.77–7.13 (m, 9H, Ar-
H), 7.21 (d, 2H, J = 15.0 Hz, C2-H and, C6-H), 7.83(d,
2H, J = 15.0 Hz, C1-H and C7-H), 8.01 (s, 1H, =CH–
Ar). 13C NMR (300 MHz, CDCl3): 184.3, 165.7, 149.8,
149.3, 1467.9, 147.6, 146.8, 146.5, 142.1, 130.5, 128.6,
128.1, 126.4, 125.6, 123.1, 117.1, 116.1, 111.6, 56.1,
55.9. ESI–MS m/z [M+H]+503.2.
1H NMR (300 MHz, CDCl3):
d
3.89 (s, 6H,
2 · OCH3), 6.81 (s, 1H, C4-H), 7.01 (d, 2HJ = 15.6 Hz,
C2-H and, C6-H), 7.08 (d, 2H, J = 15.6 Hz, C1-H and
C7-H), 7.18–7.31 ( m, 6H, Ar-H), 7.45 (m, 1H, Ar-H),
7.58 (m, 1H, Ar-H), 7.78 (m, 1H, Ar-H). 13C NMR
(300 MHz, CDCl3): 156.6, 154.1, 147.7, 147.0, 144.2,
142.8, 135.8, 132.3, 129.8, 129.2, 124.7, 122.1, 117.9,
117.7, 113.5, 110.2, 110.6, 107.6, 56.8, 56.4. ESI–MS
m/z [M]+509.38.
5.2.6. N-(4-Methoxyphenylpyrazole) curcumin (8). The sil-
ica gel eluent was hexane/ethyl acetate, 80:20. Rf = 0.65
(DCM/MeOH 9:1), yield: 35%, mp 106 ꢁC. 1H NMR
(400 MHz, CDCl3): d 3.89 (s, 6H, 2 · OCH3), 3.90(s,
3H, OCH3), 6.79 (s, 1H, C4-H), 6.98 (d, 2H,
J = 16.2 Hz, C2-H and, C6-H), 7.04 (d, 2H, J = 16.2 Hz,
C1-H and C7-H), 7.09–7.20(m, 6H, Ar-H), 7.28–7.48 (m,
4H, Ar-H). 13C NMR(400 MHz, CDCl3): 158.6, 154.3,
148.5, 148.0, 146.2, 146.4, 137.8, 132.3, 130.5, 129.8,
129.2, 124.7, 122.1, 117.9, 117.7, 113.5, 110.2, 110.6,
107.6, 56.8, 55.4. ESI–MS m/z [M+H]+471.10.
5.4. Di-O-acetylcurcumin (12)
A solution of curcumin 0.736 g (2 mmol) in anhydrous
pyridine was treated with anhydrous Ac2O (0.28 mL;
3 mmol) and stirred overnight. It was then poured in
crushed ice, extracted with carbon tetrachloride, and
the organic layer was concentrated in vacuo. Organic
layer was washed with 1% NaHCO3until effervescence
ceased. The organic layer was dried over Na2SO4 and
crystallized from absolute ethanol. Compound 12 was
1
identified on the basis of H NMR data comparison
5.3. General procedure for preparation of various curcu-
min Knoevenagel condensates (9–11)
with literature values, yield 85% (0.768 g), Rf = 0.90
(DCM/MeOH 9:1), mp 170 ꢁC (lit. 170–172 ꢁC). 1H
NMR (400 MHz, CDCl3): d 2.3 (s, 6H, acetyl), 3.89 (s,
6H, 2 · OCH3), 4.71 (s, 2H, C4-H), 6.9 (d, 2H,
J = 6.2 Hz, C2-H and C6-H), 7.15–7.34 (m, 6H, Ar-H),
A mixture of aromatic aldehyde (benzaldehyde, 4-hy-
droxy-benzaldehyde, 4-hydroxy-3-methoxy-benzalde-