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R.G. Soengas et al. / Tetrahedron 72 (2016) 3198e3203
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(1 mL). The reaction mixture was stirred at room temperature
over a period of 4 h. Then, diethyl ether was added (20 mL) and
the resulting mixture was taken to a separating funnel and
washed with a 1M aqueous solution of HCl (10 mL), water
(10 mL), an aqueous saturated solution of NaHCO3 (10 mL) and
brine (10 mL), dried over Na2SO4 and concentrated under vac-
uum to afford 3-(1-hydroxy-2-nitroethyl)-4H-chromones 2aee,
which were used in the next step without any further purifica-
tion. To a solution of the obtained nitrochromones 2aee in
chloroform (7 mL), acetic anhydride (0.5 mL) and pyridine
(0.25 mL) were added and the mixture was stirred at rt for 6 h.
The reaction mixture was then diluted with chloroform (10 mL)
and washed with H2O (10 mL), NaHCO3 (10 mL) and brine
(10 mL), dried over Na2SO4, filtered and evaporated under re-
duced pressure. The residue was purified by flash column chro-
matography eluting with mixtures of ethyl acetate and hexane to
yield (E)-3-(2-nitrovinyl)-4H-chromones 3aee (75% for 3a, 70%
for 3b, 81% for 3c, 72% for 3d, 79% for 3e).
([MþH]þ, 6%), 229 (100%), 197 (49%); HRMS (ESIþ) [MþH]þ calcd
for C18H14NO5, 324.0866; found, 324.0841.
4.2. General procedure for the preparation of 3-(3-aryl-1-
methyl-1H-pyrazol-5-yl)-4H-chromen-4-ones 6aeh
The appropriate aldehyde 4aee (0.28 mmol) was dissolved in
MeOH (2 mL) and then methylhydrazine (0.28 mmol, 14.7
added. After the mixture had been stirred at room temperature for
2 h, TFA (0.046 mmol, 3.5 L) and the appropriate (E)-3-(2-
mL) was
m
nitrovinyl)-4H-chromone 3aee (0.23 mmol) were added sequen-
tially, and the reaction solution was stirred open to air at room
temperature for 24 h. The solvent was evaporated, and the residue
was purified by column chromatography with EtOAc/hexane as
eluent to give compounds 6aeh in good yields (6a, 49.4 mg, 67%;
6b, 45.9 mg, 60%; 6c, 51.7 mg, 62%; 6d, 54.2 mg, 65%; 6e, 45.8 mg,
55%; 6f, 51.4 mg, 57%; 6g, 63.5 mg, 63%; 6h, 70.3 mg, 69%).
4.2.1. 3-[3-(4-Fluorophenyl)-1-methyl-1H-pyrazol-5-yl]-4H-chro-
men-4-one (6a). Yellow solid, mp 122e124 ꢀC (diethyl ether/hex-
ane); TLC (Hexane:EtOAc, 1:1 v/v): Rf¼0.57. 1H NMR (300.13 MHz,
4.1.1. (E)-3-(2-Nitrovinyl)-4H-chromen-4-one (3a). Yellow solid,
mp: 99e100 ꢀC (diethyl ether/hexane); TLC (Hexane:EtOAc, 2:1 v/
v): Rf¼0.31. 1H NMR (300.13 MHz, CDCl3):
d
8.81 (s, 1 H), 8.26e8.23
CDCl3): d 8.32e8.30 (m, 1 H), 8.13e8.10 (m, 1 H), 8.09 (s, 1 H),
(m, 1 H), 7.77e7.66 (m, 1 H), 7.50e7.42 (m, 2 H), 7.25 (dd, J 8.2,
7.79e7.74 (m, 2 H), 7.56e7.50 (m, 2 H), 7.17e7.05 (m, 2 H), 6.54 (s,
2.4 Hz, 1 H), 6.57 (d, J 8.2 Hz, 1 H); 13C NMR (75.47 MHz, CDCl3):
1 H), 3.88 (s, 3 H); 13C NMR (75.47 MHz, CDCl3):
d
175.3, 171.8 (d, J
d
175.9, 156.0, 154.9, 133.9, 126.2, 125.5, 123.8, 123.0, 119.8, 118.2,
244 Hz), 156.3, 155.2, 149.7, 135.7, 134.4, 132.9, 127.3 (d, J 8.5 Hz, 2C)
126.4, 126.0, 124.1, 118.3, 116.5, 115.8 (d, J 21 Hz, 2C), 104.9, 37.9; MS
(ESIþ-TOF, m/z, %): 343 ([MþNa]þ, 45), 321 ([MþH]þ, 100); HRMS
(ESIþ) [MþNa]þ calcd for C19H13FN2NaO2, 343.0853; found,
343.0861.
108.5; MS (ESIþ-TOF, m/z, %): 240 ([MþNa]þ, 28), 218 ([MþH]þ,
22%), 175 (100); HRMS (ESIþ) [MþH]þ calcd for C11H8NO4,
218.0448; found, 218.0443.
4.1.2. (E)-5-Methoxy-3-(2-nitrovinyl)-4H-chromen-4-one
(3b). Yellow solid, mp 114e115 ꢀC (diethyl ether/hexane); TLC
(Hexane:EtOAc, 2:1 v/v): Rf¼0.28. 1H NMR (300.13 MHz, DMSO-d6):
4.2.2. 3-[3-(4-Methoxyphenyl)-1-methyl-1H-pyrazol-5-yl]-4H-chro-
men-4-one (6b). Yellow amorphous solid; TLC (Hexane:EtOAc, 1:1
d
8.89 (s, 1 H), 8.48 (d, 1 H, J 13.1 Hz), 7.88 (d, 1 H, J 13.1 Hz),
v/v): Rf¼0.38. 1H NMR (300.13 MHz, CDCl3):
d 8.30 (dd, J 4.8,
1.0 Hz, 1 H), 8.07 (s, 1 H), 7.74e7.71 (m, 3 H), 7.54e7.47 (m, 2 H),
7.76e7.72 (m, 1 H), 7.22e7.07 (m, 2 H), 3.89 (s, 3 H); 13C NMR
(75.47 MHz, CDCl3): d 174.0, 161.4, 159.6, 156.8, 138.2, 135.23, 135.16,
6.93 (d, J 8.1 Hz, 2 H), 6.50 (s, 1 H), 3.86 (s, 3 H), 3.83 (s, 3 H); 13C
132.1,116.3,109.9,108.5, 56.3; MS (ESIþ-TOF, m/z, %): 270 ([MþNa]þ,
19%), 248 ([MþH]þ, 8%), 139 (47%), 106 (100%); HRMS (ESIþ)
[MþH]þ calcd for C12H10NO5, 248.0553; found, 248.0551.
NMR (75.47 MHz, CDCl3): d 175.3, 159.3, 156.3, 155.1, 150.5, 135.4,
134.3, 126.8, 126.4, 126.2, 125.9, 124.2, 118.3, 116.7, 114.0, 104.5,
55.3, 37.9; MS (ESIþ-TOF, m/z, %): 333 ([MþH]þ, 100); HRMS
(ESIþ) [MþH]þ calcd for C20H17N2O3, 333.1234; found, 333.1248.
4.1.3. (E)-5-Benzyloxy-3-(2-nitrovinyl)-4H-chromen-4-one
(3c). Yellow solid, mp 130e131 ꢀC (diethyl ether/hexane); TLC
(Hexane:EtOAc, 2:1 v/v): Rf¼0.30. 1H NMR (300.13 MHz, DMSO-d6):
4.2.3. 3-[3-(3,4-Dimethoxyphenyl)-1-methyl-1H-pyrazol-5-yl]-4H-
chromen-4-one (6c). Yellow amorphous solid; TLC (Hexane:EtOAc,
d
9.01 (s, 1 H), 8.55 (d, 1 H, J 13.1 Hz), 7.93 (d, 1 H, J 13.1 Hz),
1:1 v/v): Rf¼0.25. 1H NMR (300.13 MHz, CDCl3):
d 8.30 (dd,1 H, J 5.2,
7.50e7.34 (m, 7 H), 7.24e7.20 (m, 1 H), 5.28 (s, 2 H); 13C NMR
0.9 Hz), 8.09 (s, 1 H), 7.78e7.72 (m, 1 H), 7.55e7.46 (m, 2 H), 7.41 (d,
1 H, J 2.0 Hz), 7.30 (dd, 1 H, J 8.3, 2.0 Hz), 6.90 (d, J 8.4 Hz, 1 H), 6.53
(s, 1 H), 3.96 (s, 3 H), 3.91 (s, 3 H), 3.87 (s, 3 H); 13C NMR (75.47 MHz,
(75.47 MHz, DMSO-d6):
d
174.6,163.9,163.6,157.8,136.3,129.0 (ꢃ2),
128.7, 128.5 (ꢃ2), 127.3, 120.3, 118.7, 116.5, 103.0, 70.7; MS (ESIþ-
TOF, m/z, %): 324 ([MþH]þ, 5%), 175 (100%), 91 (80%); HRMS (ESIþ)
[MþH]þ calcd for C18H14NO5, 324.0866; found 324.0833.
CDCl3):
d 175.3, 156.3, 155.1, 150.5, 149.1, 148.7, 135.5, 134.3, 126.4,
126.3, 125.9, 124.1, 118.3, 118.1, 116.6, 111.2, 108.7, 104.7, 55.93, 55.91,
37.9; MS (ESIþ-TOF, m/z, %): 396 ([MþNa]þ, 21), 363 ([MþH]þ, 6),
191 (100); HRMS (ESIþ) calcd for C21H19N2O4 [MþH]þ 363.1339,
found 363.1342.
4.1.4. (E)-7-Methoxy-3-(2-nitrovinyl)-4H-chromen-4-one
(3d). Yellow oil; TLC (Hexane:EtOAc, 2:1 v/v): Rf¼0.28. 1H NMR
(300.13 MHz, CDCl3): d 8.68 (d, 1 H, J 13.1 Hz), 8.19 (d, 1 H, J 8.1 Hz),
8.16 (s,1 H), 7.62 (d,1 H, J 13.1 Hz), 7.06 (dd,1 H, J 8.1, 2.1 Hz), 6.92 (d,
4.2.4. 5-Methoxy-3-[3-(4-methoxyphenyl)-1-methyl-1H-pyrazol-5-
yl]-4H-chromen-4-one (6d). Yellow amorphous solid; TLC (Hex-
ane:EtOAc, 2:1 v/v): Rf¼0.28. 1H NMR (300.13 MHz, CDCl3): 7.95 (s,
1 H), 7.74 (d, J 8.8 Hz, 2 H), 7.62 (t, J 8.4 Hz,1 H), 7.08 (dd, J 8.4, 0.8 Hz,
1 H), 6.93 (d, J 8.8 Hz, 2 H), 6.88 (d, J 7.8 Hz,1 H), 6.50 (s, 1 H), 3.98 (s,
1 H, J 2.1 Hz), 3.93 (s, 3 H); 13C NMR (75.47 MHz, CDCl3):
d
177.0,
167.1, 165.4, 159.6, 130.2, 130.1, 127.8, 118.9, 117.6, 115.6, 100.5, 56.0;
MS (ESIþ-TOF, m/z, %): 248 ([MþH]þ, 10%), 227 (71%), 206 (100%);
HRMS (ESIþ) [MþH]þ calcd for C12H10NO5, 248.0553; found
248.0558.
3 H), 3.91 (s, 3 H), 3.82 (s, 3 H); 13C NMR (75.47 MHz, CDCl3):
d 174.8,
161.9, 159.4, 157.7, 154.5, 150.2, 135.5, 135.0, 127.9 (2 C), 125.7, 116.7,
115.2,114.0 (2 C),106.6,105.0, 56.2, 55.1, 37.8; MS (ESIþ-TOF, m/z, %):
363 ([MþH]þ, 100); HRMS (ESIþ) [MþH]þ calcd for C21H19N2O4,
363.1339; found, 363.1350.
4.1.5. (E)-7-Benzyloxy-3-(2-nitrovinyl)-4H-chromen-4-one
(3e). Yellow oil; TLC (Hexane:EtOAc, 2:1 v/v): Rf¼0.32. 1H NMR
(300.13 MHz, CDCl3):
d 8.68 (d, 1 H, J 13.1 Hz), 8.20e8.16 (m, 2 H),
7.62 (d, J 13.1 Hz, 1 H), 7.28e7.23 (m, 5 H), 7.13 (dd, J 8.9, 2.3 Hz, 1 H),
6.97 (d, J 2.3 Hz, 1 H), 5.19 (s, 2 H); 13C NMR (75.47 MHz, CDCl3):
4.2.5. 7-Methoxy-3-[3-(4-methoxyphenyl)-1-methyl-1H-pyrazol-5-
d
174.5, 163.8, 159.5, 157.2, 140.6, 135.3, 129.4 (ꢃ2), 128.6, 127.9,
yl]-4H-chromen-4-one (6e). Yellow amorphous solid; TLC (Hex-
127.5 (ꢃ2), 117.8, 116.2, 101.6, 70.8; MS (ESIþ-TOF, m/z, %): 324
ane:EtOAc, 2:1 v/v): Rf¼0.27. 1H NMR (300.13 MHz, CDCl3):
d 8.20