Vol. 30, No. 2 (2018) Synthesis andAntiinflammatoryActivity of Chalcone Derivatives Linked withApocynin and 5-Nitrofuran Moiety 313
reaction, checked by TLC, the reaction mixture was cooled to
room temperature and extracted with ethyl acetate (2 × 100 mL)
and the organic layer was washed with water, brine solution
and dried over anhydrous sodium sulphate, filtered and concen-
trated under reduced pressure to obtain 5-nitrofurfural 3.Yield:
5.10 g, 88 %. m.p.: 35-36 °C.
hydroxide (0.3 mmol) was thoroughly ground with a pestle in
an open mortar [17,18] at room temperature for 5-10 min.
After completion of the reaction, checked by TLC, the preci-
pitated solid was washed with water (4 mL) and further recrys-
tallized from ethanol (2 mL) to give the corresponding
chalcone derivatives (9A-K).Yields of the compounds varied
between 86-96 %.
(5-Nitrofuran-2-yl)methanol (4): To a stirred solution
of 5-nitrofurfural (3) (5 g, 35.44 mmol) in methanol (100 mL),
cooled to 0 °C, was added sodium borohydride (1.47 g, 38.98
mmol) portion-wise and continued to stirred for additional 30
min. After completion of the reaction, checked by TLC, the
solvent was concentrated under reduced pressure and the
residue was quenched with water (2 mL) and extracted with
cyclopentyl methylether (4 × 25 mL). The organic layer was
washed with water (2 × 30 mL), dried over Na2SO4 and evapo-
rated to obtain (5-nitrofuran-2-yl)methanol 4. Pale yellow oil;
Yield: 2.33 g, 46 %; 1H NMR (400 MHz, CDCl3) δ 2.50 (br s,
1H, OH), 4.73 (s, 2H, -CH2), 6.57 (d, 1H, J = 4 Hz, H3-furan),
7.30 (d, 1H, J = 4.0 Hz, H4-furan).
3-(4-Bromo-phenyl)-1-[3-methoxy-4-(5-nitro-furan-2-
ylmethoxy)phenyl]propenone (9A): Pale yellow solid;
Yield: 94 %; m.p.: 97-98 °C; IR (KBr, νmax, cm–1): 3110 (-C-H
stretch, aromatic), 2942 (-C-H stretch, aliphatic), 1655 (-C=O,
conjugated with -C=C and benzene ring), 1603, 1575(-C=C
of enone moiety), 1513 and 1340 (-NO2 stretch), 1069 (C-O
stretch); 1H NMR (400 MHz, CDCl3): δ 3.98 (s, 3H), 5.20 (s,
2H), 6.58 (s, 1H), 6.80 (s, 1H), 7.08 (d, J = 8.5 Hz, 1H), 7.58-
7.50 (m, 5H), 7.68 (d, J = 5.8 Hz, 2H), 7.80 (d, J = 12.4 Hz,
1H); ESI-MS: m/z, 458.1 (M+1).
3-(4-Chloro-phenyl)-1-[3-methoxy-4-(5-nitro-furan-2-
ylmethoxy)phenyl]propenone (9B): Yellow solid; Yield:
89 %; m.p.: 107-108 °C; IR (KBr, νmax, cm–1): 3112 (-C-H
stretch, aromatic), 2938 (-C-H stretch, aliphatic), 1654 (-C=O,
conjugated with -C=C and benzene ring), 1602, 1567 (-C=C
of enone moiety), 1513 and 1349 (-NO2 stretch), 1072 (C-O
stretch); 1H NMR (400 MHz, DMSO-d6): δ 3.85 (s, 3H), 5.29
(s, 2 H), 6.87 (s, 1H), 7.28 (d, J = 9.5 Hz, 2H), 7.46 (d, J = 7.6
Hz, 2H), 7.68 (d, J = 15.0 Hz, 1H), 7.65 (d, J = 18.0 Hz, 1H),
7.83 (d, J = 6.0 Hz, 1H), 7.95 (d, J = 8.5 Hz, 1H), 8.02 (s,
1H), 8.06 (d, J = 8.0 Hz, 1H); ESI-MS: m/z, 414.2 (M+1).
3-(4-Fluoro-phenyl)-1-[3-methoxy-4-(5-nitro-furan-2-
ylmethoxy)phenyl]propenone (9C): Off white solid; Yield:
88 %; m.p.: 123-124 °C; IR (KBr, νmax, cm–1): 2943 (-C-H stretch,
aromatic), 1655 (-C=O, conjugated with -C=C and benzene
ring), 1574 (-C=C of enone moiety), 1508 and 1350 (-NO2
stretch), 1024 (C-O stretch); 1H NMR (400 MHz, DMSO-d6):
δ 3.96 (s, 3H), 5.20 (s, 2H), 6.54 (d, J = 2.5 Hz, 1H), 6.78 (s,
1H), 7.04 (d, J = 8.0 Hz, 1H), 7.10 (s, 1H), 7.13 (d, J = 8.0
Hz, 1H), 7.48 (d, J = 15.5 Hz, 1H), 7.65 (d, J = 2.0 Hz, 2H),
7.64 (d, J = 3.0 Hz, 2H), 7.78 (d, J = 15.5 Hz, 1H); ESI-MS:
m/z, 398.3 (M+1).
2-(Bromomethyl)-5-nitrofuran (5): To a stirred solution
of triphenyl phosphine (39.40 g, 150.24 mmol, 4.3 eq) in
dichloromethane (200 mL) was added tribromoisocyanuric
acid (14.05 g, 38.34 mmol, 1.5 eq). After 30 min, the alcohol
(4) (5 g, 34.94 mmol, 1 eq) was added and the suspension was
stirred at room temperature for 4 h. After completion of the
reaction, the precipitated cyanuric acid was filtered off and
the organic layer was washed with water (4 × 100 mL) followed
by brine solution. The organic layer was dried over Na2SO4,
filtered and evaporated under reduced pressure. The obtained
residue was treated with n-hexane and filtered through a short
column packed with silica gel (100-200 mesh). Evaporation
of n-hexane gave the desired product 5. Yellow oily liquid;
Yield: 6.33 g, 84 %. IR (KBr, νmax, cm–1): 1526 and 1345 (NO2);
1H NMR (400 MHz, CDCl3) δ 4.49 (s, 2H), 6.64 (d, J = 4.0
Hz, 1H, H3-furan), 7.28 (d, J = 4.0 Hz, 1H, H4-furan).
1-(4-((5-Nitrofuran-2-yl)methoxy)-3-methoxyphenyl)-
ethanone (7): To a solution of apocynin (6) (1.5 g, 9.02 mmol,
1.0 eq) in 2-methyl tetrahydrofuran (25 mL) was added pota-
ssium carbonate (1.5 g, 10.82 mmol, 1.2 eq) at room tempe-
rature and stirred for 15 min. To the above reaction contents,
compound 5 (1.88 g, 9.11 mmol, 1.01 eq) was added slowly
over a period of 15 min and heated to reflux for 1 h. After the
completion of the reaction (checked by TLC), the reaction
mixture was diluted with water (15 mL) and stirred for 15 min.
The organic layer was washed with water (2 × 10 mL) followed
by brine solution, separated, dried over Na2SO4 (5 g), filtered
and evaporated under reduced pressure to obtain crude com-
pound. The crude compound was titrated with n-hexane to
obtain pure compound 7. Pale yellow solid;Yield: 3.65 g, 94 %;
m.p.: 72-73 °C; IR (KBr, νmax, cm–1): 3072 (-C-H stretch, aromatic),
1681 (-C=O stretch), 1587 (-C=C-stretch), 1512 and 1338 (-NO2
1-[3-Methoxy-4-(5-nitro-furan-2-ylmethoxy)phenyl]-
3-(4-trifluoromethoxyphenyl)propenone (9D): Pale yellow
solid;Yield: 90 %; m.p.: 76-77 °C; IR (KBr, νmax, cm–1): 3111
(-C-H stretch, aromatic), 1656 (-C=O, conjugated with -C=C
and benzene ring), 1603, 1574 (C=C of enone moiety), 1507
1
and 1351 (-NO2 stretch), 1106 (C-O stretch); H NMR (400
MHz, DMSO-d6): δ 3.97 (s, 3H), 5.20 (s, 2H), 6.54 (d, J = 3.5
Hz, 1H), 6.78 (d, J = 2.0 Hz, 1H), 7.04 (d, J = 8.5 Hz, 1H),
7.27 (d, J = 7.5 Hz, 2H), 7.51 (d, J = 15.5 Hz, 1H), 7.67 (d, J
= 16.5 Hz, 1H), 7.68 (d, J = 8.0 Hz, 3H), 7.78 (d, J = 15.5 Hz,
1H), ESI-MS: m/z, 464.1 (M+1).
1-[3-Methoxy-4-(5-nitro-furan-2-ylmethoxy)phenyl]-
3-(4-nitrophenyl)propenone (9E): Yellow solid; m.p.: 68-
69 °C; Yield: 94 %; IR (KBr, νmax, cm–1): 3120 (-C-H stretch,
aromatic), 2944 (-C-H stretch, aliphatic), 1655 (-C=O, conju-
gated with -C=C and benzene ring), 1574 (C=C of enone
moiety), 1517 and 1341 (NO2), 1169 (C-O stretch); 1H NMR
(400 MHz, DMSO-d6): δ 3.90 (s, 3H), 5.30 (s, 2H), 6.88 (s,
1H), 7.28 (s, 1H), 7.30 (d, J = 15.2 Hz, 1H), 7.65 (s, 1H), 7.76
1
stretch), 1084 (-C-O stretch); H NMR (400 MHz, DMSO-
d6): δ 2.58 (s, 3H), 3.98 (s, 3H), 5.20 (s, 2 H), 6.56 (s, 1H),
6.80 (s, 1H), 7.0 (d, J = 7.2 Hz, 1 H), 7.58 (s, 2 H); ESI-MS:
m/z, 292.1 (M+1).
General experimental preparation of chalcones deri-
vatives (9A-9K): A mixture of compound 7 (100 mg, 0.343
mmol), aromatic aldehydes (8A-K) (0.346 mmol) and sodium