Synthesis and structure elucidation of three series of nitro-2- styrylchromones using 1D and 2D NMR spectroscopy

Article abstract of DOI:10.1002/mrc.2472

2-Styrylchromones, although scarce in nature, constitute a group of oxygen heterocyclic compounds which have shown significant biological activities. New nitro-2-styrylchromones have been synthesised by the Baker-Venkataraman method, and the structure elu

Full text of DOI:10.1002/mrc.2472

Spectral Assignments and Reference Data
Received: 28 March 2009
Revised: 30 May 2009
Accepted: 1 June 2009
Published online in Wiley Interscience: 2 July 2009
(www.interscience.com) DOI 10.1002/mrc.2472
Synthesis and structure elucidation of three
series of nitro-2-styrylchromones using 1D
and 2D NMR spectroscopy
Ana I. R. N. A. Barrosa∗ and Artur M. S. Silvab
2-Styrylchromones, although scarce in nature, constitute a group of oxygen heterocyclic compounds which have shown
significant biological activities. New nitro-2-styrylchromones have been synthesised by the Baker–Venkataraman method, and
the structure elucidation was accomplished using extensive 1D (1H, 13C) and 2D NMR spectroscopic studies (COSY, HSQC and
c
HMBC experiments). Copyright ꢀ 2009 John Wiley & Sons, Ltd.
Keywords: 1H NMR; 13C NMR; HMBC; nitro-2-styrylchromones
Introduction
were made with the aid of 2D gHSQC and gHMBC (delays for
one-bond and long-range J(C,H) couplings were optimised for 147
and 7 Hz, respectively) experiments. Electron impact (EI, 70 eV) MS
were recorded on VG Autospec Q and M spectrometers. Elemental
analyses (CHN) were obtained with a Carlo Erba 1108 CHNS
analyser and were in good agreement (0.4%) with the calculated
values. Preparative thin-layer chromatography was performed
with Merck silica gel 60 DGF254. Column chromatography was
performed with Merck silica gel 60, 70–230 mesh. All other
chemicals and solvents used were obtained from commercial
sources and used as received or dried using standard procedures.
Chromones are one of the most abundant groups of natu-
rally occurring heterocyclic compounds. Many pharmacological
properties have been ascribed to various members of this fam-
ily, including anti-inflammatory, anti-allergic and anti-tumour
activities.[1] Almost all the natural occurring chromones are 2-
and 3-phenyl derivatives, also called flavones and isoflavones, re-
spectively. However, other types of chromones have been found
in the plant kingdom, such as 3-methyl-, 2-hydroxymethyl- and
2-styrylchromones.[2]
Although only two 2-styrylchromones are known as
natural compounds (hormothamnione and 6-desmethoxy-
hormothamnione in the marine blue-green algae Chrysophaem
taylori),[3,4] numerous synthetic analogues have been prepared in
the last decades.[5]
Both natural and synthetic derivatives have shown a remarkable
variety of biological activities, such as important cytotoxicity
against human leukaemia cells,[3,4] as well as significant levels
of anti-allergic[6] and anti-cancer[7] activities. Some of the
derivatives obtained by synthesis exhibited xanthine oxidase
inhibitor properties.[8] Taking into account the potential biological
applications of chromones and especially those having 2-
substituents,wedecidedtodevotesomeattentiontothesynthesis
of new 2-styrylchromones.
Materials
The nitro-2-styrylchromones 5 were prepared in good overall
yields according to the three-step sequence, shown in Scheme 1.
For this purpose, the 2ꢁ-(nitrocinnamoyloxy)acetophenones 3a–j
were obtained from the reaction of the 2ꢁ-hydroxyacetophenone
derivatives 1a–d with the appropriate cinnamic acid 2a–c.
The rearrangement of the nitro-2ꢁ-cinnamoyloxy-acetophenones
3a–j into 3-hydroxy-1-(2-hydroxyphenyl)-5-(nitrophenyl)-2,4-
pentadien-1-ones 4a–j was performed upon treatment with
sodium hydride in dry tetrahydrofuran at reflux or with potassium
hydroxide in dimethyl sulfoxide at room temperature. Cyclization
ofcompounds4a–jintothedesirednitro-2-styrylchromones5a–j
was achieved by heating with p-toluenesulfonic acid in dimethyl
sulfoxide at 80–90 ◦C or with iodine in dimethyl sulfoxide at
80–90 ◦C.
Experimental
The nitro-2-styrylchromones bearing 7-methoxy substituents
(5d–f) were obtained only in moderate yields (27–61%), while the
others were obtained in better yields (67–79%); see Table 1.
The 1H and 13C NMR spectra were recorded at 25 ◦C with ca
5-mg samples dissolved in 0.5 ml of CDCl3 or DMSO-d6 in 5-mm
1
NMR tubes using a Bruker DRX 300 spectrometer (300.13 for H
and 75.47 for 13C). Chemical shifts (δ) are reported in ppm and
coupling constants (J) in Hz. The internal standard was TMS. The
Fourier-transform NMR measurement conditions were as follows:
for 1H NMR, pulse width 3.4 µs, pulse angle 30◦, acquisition time
2.7 s and number of scans 80; for 13C NMR, pulse width 1.7 ms,
pulse angle 30◦, acquisition time 0.8 s, number of scans 6144
and number of data points 16 384. Unequivocal 13C assignments
∗
Correspondence to: Ana I. R. N. A. Barros, Chemistry Department, University of
´
Tras-os-Montes e Alto Douro, 5001-911 Vila Real, Portugal.
E-mail: abarros@utad.pt
´
a
Chemistry Department, University of Tras-os-Montes e Alto Douro, 5001-911
Vila Real, Portugal
b
Chemistry Department, University of Aveiro, 3810-193 Aveiro, Portugal
c
Magn. Reson. Chem. 2009, 47, 885–896
Copyright ꢀ 2009 John Wiley & Sons, Ltd.

Ana I. R. N. A. Barros and Artur M. S. Silva
4ꢁ-Methoxy-2ꢁ-(4-nitrocy◦nnamoyloxy)acetophenone
(3f). Yield
64%; mp 142.6–143.9 C. MS: (EI, 70 eV): m/z (%) = 341 (M+•, 6),
299 (15), 176 (100), 166 (3), 151 (13), 130 (22), 118 (5), 102 (25), 90
(10), 76 (8); IR (KBr): ν = 1733, 1668, 1635, 1606, 1515, 1344, 1257,
Table 1. Compounds obtained and yields
Yield
(%)
Compound
R1
R2
R3
R4
R5
1143, 979, 842 cm−1
.
a
b
c
d
e
f
H
H
H
H
NO2
H
H
NO2
H
H
H
74
73
69
27
61
31
67
79
77
74
H
H
H
NO2
H
6ꢁ-Methoxy-2ꢁ-(2-nitrocynnamoyloxy)acetophenone (3g). Yield
OCH3
OCH3
OCH3
H
H
NO2
H
H
54%; mp 116.6–117.9 ◦C. MS: (EI, 70 eV): m/z (%) = 341 (M+•
,
H
NO2
H
H
100), 324 (22), 297 (14), 280 (67), 262 (54), 252 (26), 236 (15), 226
H
H
NO2
H
(22), 206 (54); IR (KBr): ν = 1735, 1708, 1641, 1606, 1521, 1469,
g
h
i
OCH3
OCH3
OCH3
OCH3
NO2
H
H
1440, 1351, 1141, 1081, 979 cm−1
.
H
NO2
H
H
H
H
NO2
H
j
OCH3
H
NO2
6ꢁ-Methoxy-2ꢁ-(3-nitrocynnamoyloxy)acetophenone (3h). Yield
78%; mp 121.6–122.4 ◦C. MS: (EI, 70 eV): m/z (%) = 341 (M+•
,
17), 297 (18), 176 (100), 166 (16), 151 (24), 129 (23), 118 (11), 102
(45), 76 (14), 63 (7); IR (KBr): ν = 1725, 1689, 1643, 1604, 1531,
General
method
for
the
synthesis
of
2ꢀ-
1469, 1353, 1276, 1228, 1151, 1076, 809, 744 cm−1
.
(nitrocinnamoyloxy)acetophenones 3a–j
Phosphorous oxychloride (15.6 mmol) was added to a solution
of the appropriate 2ꢁ-hydroxyacethophenone 1a–d (12 mmol)
and the appropriate nitrocinnamic acid 2a–c (15.6 mmol) in
dry pyridine. The solution was stirred at 60–70 ◦C for 3 h, then
poured into ice and water, and the reaction mixture acidified with
hydrochloric acid (pH ca 3). The obtained solid was removed by
filtration, taken in 100 ml CHCl3 and purified by silica gel column
chromatography using a 7 : 3 mixture of chloroform: n-hexane as
the eluent. The solvent was evaporated to dryness and the residue
recrystallised from ethanol, giving the expected compounds.
6ꢁ-Methoxy-2ꢁ-(4-nitrocy◦nnamoyloxy)acetophenone
(3i). Yield
70%; mp 193.4–195.0 C. MS: (EI, 70 eV): m/z (%) = 341 (M+•, 7),
297 (10), 176 (100), 151 (12), 130 (22), 118 (6), 102 (24), 90 (9), 76
(8), 63 (4); IR (KBr): ν = 1739, 1698, 1641, 1509, 1463, 1346, 1268,
1153, 1078, 983, 844 cm−1
.
4ꢁ,6ꢁ-Dimethoxy-2ꢁ-(3-nitrocynnamoyloxy)acetophenone
(3j).
Yield 75%; mp 132.0–133.6 ◦C. MS: (EI, 70 eV): m/z (%) = 371 (M+•
,
10), 356 (3), 312 (54), 196 (22), 176 (100), 167 (7), 129 (22), 102 (46),
76 (14); IR (KBr): ν = 1733, 1675, 1641, 1608, 1533, 1349, 1253,
2ꢁ-(2-Nitrocynnamoyloxy)acetophenone (3a). Yield 55%; mp
118.7–119.9 ◦C. MS: (EI, 70 eV): m/z (%) = 311 (M+•, 41), 296
(42), 279 (30), 265 (100), 250 (33), 238 (16), 220 (23), 190 (15); IR
(KBr): ν = 1731, 1668, 1612, 1571, 1525, 1349, 1278, 1199, 1132,
1226, 1151, 1095, 1074, 975, 813 cm−1
.
General method for the synthesis of 3-hydroxy-1-(2-
hydroxyphenyl)-5-(nitrophenyl)-2,4-pentadien-1-ones 4a–j
1068, 970, 750 cm−1
.
Potassium hydroxide powder (0.05 mmol, 2.8 g) was added to a
solution of 2ꢁ-(nitrocinnamoyloxy)acetophenones 3a–j (10 mmol)
in dimethyl sulfoxide (15 ml). The solution was stirred at room
temperature until complete disappearance of the starting material
which was monitored by tlc (ca 2 h). After that period, the solution
was poured into ice, water and hydrochloric acid (pH adjusted
to 5). The obtained solid was removed by filtration, dissolved in
chloroform (150 ml) and purified by silica gel chromatography
using chloroform: n-hexane (7 : 3) as eluent. The solvent was
evaporated to dryness and the residue was recrystallised from
ethanol, giving in each case, the expected compound.
2ꢁ-(3-Nitrocynnamoyloxy)acetophenone (3b). Yield 68%; mp
124.0–125.6 ◦C. MS: (EI, 70 eV): m/z (%) = 311 (M+•, 3), 176 (100),
145 (5), 129 (11), 121 (6), 102 (26), 76 (7), 63 (3); IR (KBr): ν = 1713,
1683, 1637, 1600, 1527, 1471, 1436, 1349, 1303, 1261, 1199, 1072,
810, 750 cm−1
.
2ꢁ-(4-Nitrocynnamoyloxy)acetophenone (3c). Yield 60%; mp
130.6–132.0 ◦C. MS: (EI, 70 eV): m/z (%) = 311 (M+•, 2), 176
(100), 130 (16), 118 (3), 102 (18), 90 (6), 76 (5); IR (KBr): ν = 1731,
1695, 1635, 1602, 1523, 1346, 1305, 1147, 960, 844, 755 cm−1
.
4ꢁ-Methoxy-2ꢁ-(2-nitrocynnamoyloxy)acetophenone (3d). Yield
52%; mp 95.7–96.9 ◦C. MS: (EI, 70 eV): m/z (%) = 341 (M+•, 7),
176 (100), 163 (11), 151 (26), 130 (98), 118 (4), 102 (29), 89 (6), 77
(16); IR (KBr): ν = 1732, 1665, 1609, 1569, 1524, 1349, 1277, 1229,
3-Hydroxy-1-(2-hydroxyphenyl)-5-(2-nitrophenyl)-2,4-pentadien-1-
one(4a). Yield 60%; mp 186.6–187.1◦C. MS: (EI, 70 eV): m/z (%) =
311 (M+•, 39), 294 (20), 264 (11), 176 (48), 163 (33), 145 (5), 130
(7), 121 (100), 102 (17), 93 (21), 77 (20), 65 (31); IR (KBr): ν = 1635,
1575, 1513, 1486, 1430, 1295, 1178, 955, 813, 750 cm−1
.
1198, 1065, 967 cm−1
.
4ꢁ-Methoxy-2ꢁ-(3-nitrocynnamoyloxy)acetophenone (3e). Yield
3-Hydroxy-1-(2-hydroxyphenyl)-5-(3-nitrophenyl)-2,4-pentadien-1-
one(4b). Yield 75%; mp 194.4–187.1◦C. MS: (EI, 70 eV): m/z (%) =
311 (M+•, 53), 294 (7), 189 (10), 176 (100), 160 (15), 129 (16), 121
(81), 115 (13), 102 (29), 93 (14), 77 (9), 65 (18); IR (KBr): ν = 1639,
70%; mp 125.6–126.4 ◦C. MS: (EI, 70 eV): m/z (%) = 341 (M+•
,
15), 282 (21), 176 (100), 166 (11), 151 (19), 129 (17), 118 (9), 102
(32), 76 (12); IR (KBr): ν = 1737, 1677, 1639, 1608, 1525, 1349, 1259,
1141, 1068, 811, 740 cm−1
.
1575, 1490, 1434, 1353, 1295, 1243, 750 cm−1
.
c
www.interscience.wiley.com/journal/mrc
Copyright ꢀ 2009 John Wiley & Sons, Ltd.
Magn. Reson. Chem. 2009, 47, 885–896

Spectral Assignments and Reference Data
3-Hydroxy-1-(2-hydroxyphenyl)-5-(4-nitrophenyl)-2,4-pentadien-1-
one(4c). Yield 84%; mp 198.2–199.7◦C. MS: (EI, 70 eV): m/z (%) =
311 (M+•, 54), 294 (12), 189 (13), 176 (100), 163 (9), 144 (8), 130
(28), 121 (95), 115 (10), 102 (23), 93 (14), 65 (15); IR (KBr): ν = 1600,
Method B
A catalytic amount of iodine (1.3 mmol, 0.33 g) was added to
a solution of the appropriate 3-hydroxy-1-(2-hydroxyphenyl)-5-
(nitrophenyl)-2,4-pentadien-1-ones 4d–f (6.5 mmol) in dimethyl
sulfoxide (20 ml). The solution was heated at 80–90 ◦C for 3 h
and poured into ice and water. The solid obtained was removed
by filtration, dissolved in chloroform (100 ml) and washed with
water. The organic layer was dried with anhydrous sodium sulfate.
The solvent was evaporated in each case to dryness and the
residue dissolved in chloroform (150 ml) and purified by silica gel
chromatography, using chloroform : n-hexane (7 : 3) as eluent.
The obtained solid was removed by filtration, dissolved in
chloroform (150 ml) and purified by silica gel chromatography,
using chloroform : n-hexane (6 : 4) as eluent. The solvent was
evaporated to dryness, and the residue was recrystallised from
ethanol.
1571, 1515, 1486, 13380, 1295, 1168, 954, 836, 759 cm−1
.
3-Hydroxy-1-(2-hydroxy-4-methoxyphenyl)-5-(2-nitrophenyl)-2,4-
pentadien-1-one (4d). Yield 16%; mp 190.2–191.8 ◦C. MS: (EI,
70 eV): m/z (%) = 341 (M+•, 100), 324 (26), 306 (17), 294 (14), 278
(18), 206 (64), 193 (73), 176 (42), 163 (51), 130 (28), 102 (9), 65 (8);
IR (KBr): ν = 1627, 1585, 1565, 1523, 1506, 1440, 1347, 1241, 1182,
1133, 962, 825 cm−1
.
3-Hydroxy-1-(2-hydroxy-4-methoxyphenyl)-5-(3-nitrophenyl)-2,4-
pentadien-1-one (4e). Yield 42%; mp 204.2–205.0 ◦C. MS: (EI,
70 eV): m/z (%) = 341 (M+•, 49), 324 (9), 271 (5), 176 (51), 151
(100), 137 (13), 124 (31), 102 (24), 69 (8); IR (KBr): ν = 1729, 1643,
1606, 1581, 1515, 1463, 1347, 1263, 1155, 1106, 1025, 954, 840,
2ꢁ-Nitro-2-styrylchromone (5a). Yield 74%; mp 210.6–211.4 ◦C.
MS: (EI, 70 eV): m/z (%) = 293 (M+•, 67), 292 (43), 273 (74), 264
(11), 247 (100), 236 (4), 218 (15), 189 (23), 165 (8), 145 (6), 132 (13),
119 (40), 104 (19), 92 (90), 76 (18), 64 (27); IR (KBr): ν = 1641, 1604,
1527, 1467, 1378, 1135, 777 cm−1. Anal. calcd for C17H11NO4: C,
69.62; H, 3.75; N, 4.78. Found: C, 69.55; H, 3.63; N, 4.78.
784 cm−1
.
3-Hydroxy-1-(2-hydroxy-4-methoxyphenyl)-5-(4-nitrophenyl)-2,4-
pentadien-1-one (4f). Yield 24%; mp 200.9–201.6 ◦C. MS: (EI,
70 eV): m/z (%) = 341 (M+•, 37), 326 (6), 311 (8), 279 (22), 252 (12),
167 (39), 149 (100), 124 (14), 105 (48), 91 (23), 71 (39); IR (KBr):
ν = 1731, 1645, 1581, 1523, 1463, 1347, 1266, 1159, 1110, 1025,
3ꢁ-Nitro-2-styrylchromone (5b). Yield 73%; mp 221.2–222.7 ◦C.
MS: (EI, 70 eV): m/z (%) = 293 (M+•, 100), 292 (34), 276 (18), 245
(77), 230 (6), 218 (21), 189 (20), 165 (5), 126 (13), 120 (33), 92 (61),
77 (13), 64 (18); IR (KBr): ν = 1652, 1621, 1517, 1463, 1394, 1351,
1126, 975, 769 cm−1. Anal. calcd for C17H11NO4: C, 69.62; H, 3.75;
N, 4.78. Found: C, 69.79; H, 3.81; N, 4.89.
956, 840, 784 cm−1
.
3-Hydroxy-1-(2-hydroxy-6-methoxyphenyl)-5-(2-nitrophenyl)-2,4-
pentadien-1-one (4g). Yield 54%; mp 199.9–200.6 ◦C. MS: (EI,
70 eV): m/z (%) = 341 (M+•, 78), 324 (35), 310 (65), 292 (8), 271
(16), 176 (74), 151 (100), 124 (38), 115 (15), 102 (42), 95 (10), 65
(17); IR (KBr): ν = 1738, 1640, 1567, 1525, 1460, 1344, 1264, 1159,
1106, 1014, 936, 870, 745 cm−1
.
4ꢁ-Nitro-2-styrylchromone (5c). Yield 69%; mp 282.6–283.0 ◦C.
MS: (EI, 70 eV): m/z (%) = 293 (M+•, 100), 292 (64), 276 (43), 263
(4), 246 (32), 230 (10), 218 (17), 200 (9), 189 (16), 165 (4), 121 (32),
92 (51), 77 (11), 64 (15); IR (KBr): ν = 1648, 1511, 1463, 1396, 1338,
1220, 973, 771 cm−1. Anal. calcd for C17H11NO4: C, 69.62; H, 3.75;
N, 4.78. Found: C, 69.58; H, 3.79; N, 4.73.
3-Hydroxy-1-(2-hydroxy-6-methoxyphenyl)-5-(3-nitrophenyl)-2,4-
pentadien-1-one (4h). Yield 60%; mp 201.4–202.6 ◦C. MS: (EI,
70 eV): m/z (%) = 341 (M+•, 78), 324 (35), 310 (65), 292 (8), 271
(16), 176 (74), 151 (100), 124 (38), 115 (15), 102 (42), 95 (10), 65
(17); IR (KBr): ν = 1736, 1643, 1564, 1520, 1456, 1340, 1262, 1149,
1110, 1023, 954, 864, 730 cm−1
.
7-Methoxy-2ꢁ-nitro-2-styrylchromone (5d). Yield 27%; mp
268.6–269.4 ◦C. MS: (EI, 70 eV): m/z (%) = 323 (M+•, 100), 322
(28), 306 (7), 151 (80), 122 (5), 79 (8); IR (KBr): ν = 1654, 1623,
1567, 1513, 1438, 1386, 1347, 1253, 1087 cm−1. Anal. calcd for
C18H13NO5: C, 63.15; H, 4.02; N, 4.33. Found: C, 63.53; H, 4.24; N,
4.48.
3-Hydroxy-1-(2-hydroxy-6-methoxyphenyl)-5-(4-nitrophenyl)-2,4-
pentadien-1-one (4i). Yield 72%; mp 193.6–194.3 ◦C. MS: (EI,
70 eV): m/z (%) = 341 (M+•, 100), 324 (38), 310 (98), 306 (8), 292
(30), 271 (22), 264 (6), 193 (13), 102 (35), 65 (16); IR (KBr): ν = 1708,
1627, 1592, 1569, 1511, 1428, 1336, 1238, 1083, 838, 690 cm−1
.
7-Methoxy-3ꢁ-nitro-2-styrylchromone (5e). Yield 61%; mp
149.9–150.4 ◦C. MS: (EI, 70 eV): m/z (%) = 323 (M+•, 100), 322
(38), 306 (12), 276 (51), 151 (40), 122 (14), 107 (13), 79 (8); IR (KBr):
General method for the synthesis of nitro-2-styrylchromones
Method A
ν = 1654, 1619, 1587, 1513, 1438, 1388, 1347, 1253, 973 cm−1
;
p-Toluenesulfonic acid (3.42 mmol) was added to a solution of
the appropriate 3-hydroxy-1-(2-hydroxyphenyl)-5-(nitrophenyl)-
2,4-pentadien-1-ones 4a–c and 4g–j (6.5 mmol) in dimethyl
sulfoxide (20 ml). The reaction mixture was heated at 90 ◦C for 2 h,
thenpouredintoiceandwaterandstirredfor10 min.Theobtained
solid was removed by filtration, dissolved in chloroform (100 ml)
and washed with a 20% aqueous solution of sodium thiosulfate.
Thesolventwasevaporatedtodrynessandtheresiduewaspurified
by silica gel chromatography, using chloroform : n-hexane (7 : 3)
as eluent.
Anal. calcd for C18H13NO5: C, 63.15; H, 4.02; N, 4.33. Found: C, 63.49;
H, 4.22; N, 4.40.
7-Methoxy-4ꢁ-nitro-2-styrylchromone (5f). Yield 31%; mp
249.6–250.4 ◦C. MS: (EI, 70 eV): m/z (%) = 323 (M+•, 100), 322
(35), 306 (11), 276 (49), 234 (9), 151 (40), 121 (15), 107 (14), 79 (8);
IR (KBr): ν = 1652, 1623, 1580, 1510, 1380, 1347, 1253, 953 cm−1
.
Anal. calcd for C18H13NO5: C, 63.15; H, 4.02; N, 4.33. Found: C, 63.26;
H, 4.09; N, 4.36.
c
Magn. Reson. Chem. 2009, 47, 885–896
Copyright ꢀ 2009 John Wiley & Sons, Ltd.
www.interscience.wiley.com/journal/mrc

Ana I. R. N. A. Barros and Artur M. S. Silva
5-Methoxy-2ꢁ-nitro-2-styrylchromone (5g). Yield 67%; mp
212.4–213.6 ◦C. MS (EI, 70 eV): m/z (%) = 323 (M+•, 100), 322
(28), 306 (39), 294 (23), 276 (32), 247 (19), 202 (12), 149 (7), 121
(11), 107 (26), 92 (28), 77 (14), 63 (13); IR (KBr): ν = 1653, 1604,
1519, 1473, 1398, 1359, 1268, 1087, 829, 754 cm−1. Anal. calcd for
C18H13NO5: C, 63.15; H, 4.02; N, 4.33. Found: C, 63.33; H, 4.14; N,
4.50.
different frequencies depending on the substitution pattern:
for the ortho-nitrated derivatives (a, d and g), C-1ꢁꢁ appears at
δ = 128.9–130.1 ppm, for the meta-nitrated derivatives (b, e,
h and j) its appears at δ = 135.7–136.7 ppm and for the para-
nitratedderivatives(c, f, andi), itappearsatδ = 140.0–140.2 ppm.
In addition, HMBC spectra allowed finding the correlations
between the H-β signal at δ = 7.86–8.28 ppm and the signals
of C-2ꢁꢁ/C-6ꢁꢁ and the signal of the carbonyl group of the ester
(δ = 163.9–164.8 ppm).
5-Methoxy-3ꢁ-nitro-2-styrylchromone (5h). Yield 79%; mp
212.4–213.6 ◦C. MS: (EI, 70 eV): m/z (%) = 323 (M+•, 100), 322
(19), 306 (52), 294 (18), 276 (88), 260 (7), 247 (24), 231 (12), 176
(7), 120 (17), 107 (41), 92 (34), 77 (20), 63 (17); IR (KBr): ν = 1644,
1604, 1525, 1471, 1390, 1347, 1263, 1083, 796 cm−1. Anal. calcd
for C18H13NO5: C, 63.15; H, 4.02; N, 4.33. Found: C, 63.48; H, 4.16; N,
4.28.
In the 1H NMR spectra of each 3-hydroxy-1-(2-hydroxyphenyl)-
5-(nitrophenyl)-2,4-pentadien-1-one, 4a–j, the presence of two
signals can be observed at δ = 10.73–12.63 ppm and δ
14.63–15.31 ppm, which are due to the protons involved in
hydrogen bonds. The former signals correspond to resonances
of the phenolic protons, whereas the latter are due to the
3-OH protons. From the 1H NMR spectra, one can be also
identify a singlet at δ = 6.38–6.96 ppm corresponding to the
resonance of H-2 and the presence of two signals at δ = δ
6.99–7.55 ppm and δ = 7.61–7.85 which were attributed to
H-4 and H-5. From the values of the coupling constants 3J(H-
4, H-5), it was possible to establish the trans configuration
of these two protons. On the basis of 13C NMR the following
assignments were made: (i) the C-2 signal at δ = 99.8–105.6 ppm,
(ii) the C-4 and C-5 signals at δ = 126.2–128.3 ppm and at
δ = 133.0–137.2 ppm, respectively, and (iii) the carbonyl (C-1)
signal at δ = 186.1–194.7 ppm.
5-Methoxy-4ꢁ-nitro-2-styrylchromone (5i). Yield 77%; mp
229.9–231.0 ◦C. MS: (EI, 70 eV): m/z (%) = 323 (M+•, 100), 322
(29), 306 (50), 294 (25), 276 (86), 247 (16), 231 (19), 218 (13), 167
(31), 149 (70), 121 (15), 107 (28), 92 (21), 77 (11), 57 (21); IR (KBr):
ν = 1727, 1641, 1508, 1471, 1436, 1388, 1334, 1261, 1083, 971,
848, 744 cm−1. Anal. calcd for C18H13NO5: C, 63.15; H, 4.02; N, 4.33.
Found: C, 63.43; H, 4.36; N, 4.31.
5,7-Dimethox◦y-3ꢁ-nitro-2-styrylchromone (5j). Yield 642%; mp
229.9–231.0 C. MS: (EI, 70 eV): m/z (%) = 353 (M+•, 100), 352
(25), 336 (29), 324 (20), 306 (25), 276 (19), 234 (6), 151 (17), 176
(7), 121 (9), 95 (7), 81 (12), 69 (22); IR (KBr): ν = 1617, 1590, 1525,
1486, 1455, 1394, 1347, 1205, 1159, 1093, 827 cm−1. Anal. calcd
for C18H13NO5: C, 63.59; H, 4.25; N, 3.97. Found: C, 64.36; H, 4.16; N,
3.88.
The NMR spectra of nitro-2-styrylchromones 5a–j show some
further typical proton and carbon resonances, namely those of
H-3 (singlet at δ = 6.22–6.56 ppm), C-3 (δ = 160.9–167.0 ppm)
and C-4 (δ = 176.5–178.2 ppm). The C-4 assignment is based
on their high frequency value since it is the most deshielded
carbon atom of 2-styrylchromones 5a–j while that of C-3 is
based on the correlation with H-3 in the HSQC of 5a–j. The
assignments of all carbon resonances of 2-styrylchromones 5a–j
are based on the analysis of the HSQC and HMBC spectra. Figure 1
shows some of the typical connectivities found in their HMBC
spectra.
Results and Discussion
The full characterisation of compounds 3, 4 and 5 is presented
1
Taking 5,7-dimethoxy-3ꢁ-nitro-2-styrylchromone (5j, Fig. 2a)
as an example, one can identify three singlets at δ = 3.93, 3.96
in the Tables 2–6. The H NMR spectra of the compounds were
well resolved, and unambiguous chemical shift assignments were
based on the multiplicity pattern of 1H resonances and also on the
use of homonuclear 1H–1H COSY spectra.
1
and 6.22 ppm in the H NMR spectra corresponding to the two
OCH3 and to H-3, respectively (Fig. 2b). In addition, one can
assign a pair of doublets corresponding to the resonances of H-α
and H-β protons at δ = 6.81 and δ 7.51 ppm, respectively; the
Some typical proton and carbon resonances can be found in
the NMR spectra of the 2ꢁ-(nitrocinnamoyloxy)acetophenones
3a–j: namely, it is possible in the 1H NMR spectra of all
2ꢁ-(nitrocinnamoyloxy)acetophenones 3a–j to identify the res-
onances of the vinylic protons H-α and H-β at δ = 6.51–7.12 ppm
and 7.86–8.28 ppm, respectively. These two signals appear in all
spectra as a pair of doublets, and the determination of its coupling
constants, J(H-α,H-β) = 15.8–16.2 Hz, allowed identification of
the trans configuration of this double bond. From the analysis of
the 13C NMR spectra of the 2ꢁ-(nitrocinnamoyloxy)acetophenones
3a–j and applying two-dimensional heteronuclear correlation
experiments (HSQC, 1H,13C), the resonances of C-α at δ =
119.9–122.1 ppm and of C-β at δ = 141.7–144.9 ppm were iden-
tified.Asexpected,C-β isdeshieldedrelativetoC-α duetoconjuga-
tion of the vinylic system with the carbonyl group. All other signals
of protonated carbons have also been identified by this technique.
The signals corresponding to quaternary carbons have been
assigned by applying HMBC spectroscopy. Thus, for example,
one can find a correlation between the signal of H-α at
δ = 6.51–7.12 ppm and the signal corresponding to the
resonance of C-1ꢁꢁ. The signal of this carbon appears at very
H
R5
H
H
R4
R1
O
O
R3
H
H
R2
Figure 1. Typical connectivities found in the 2-styrylchromones HMBC
spectra.
c
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Copyright ꢀ 2009 John Wiley & Sons, Ltd.
Magn. Reson. Chem. 2009, 47, 885–896

Spectral Assignments and Reference Data
CO2H
R3
2''
O
R4
R5
1''
3'
R1
O
3''
4''
5'
1
R3
R1
R2
2'
i
4'
5'
6
5
6''
2
6'
4'
3'
+
1'
5''
6'
R2
R4
3
1'
4
2'
OH
O
R5
O
3 a-j
1 a-d
2 a-c
ii
5'
R5
6'
1'
4'
5''
5'
R1
R2
R5
6'
1'
R4
3'
6''
2'
R3
4''
3''
4'
3'
4
8
R1
2
O
9
3
1
iii
R4
1''
7
6
2
2'
OH
2''
R3
5
3
O
10
HO
5
4
4 a-j
R2
O
5 a-j
1
2
a)
3
4
5
R =NO2, R =R =H
1
2
a)
b)
c)
d)
R =R =H
4
3
5
1
2
b)
c)
R =NO2, R =R =H
R =OMe, R =H
1
2
3
4
5
R =H, R =OMe
R =R =H, R =NO2
1
2
R =R =OMe
py, POCl3, 60-70 °C.
i)
ii)
ii) THF, NaH, 80-90 °C, or DMSO/KOH, room temperature
iii) DMSO/I2, 80-90 °C or DMSO/p-Toluenesulfonic acid, 80-90 °C
For compounds 3, 4 and 5
a
b
c
d
e
f
g
h
i
j
R1
R2
R3
R4
H
H
H
H
H
H
H
H
OMe
H
OMe OMe
H
H
H
OMe
H
H
H
H
H
OMe OMe OMe OMe
NO2
H
H
NO2
H
NO2
H
H
H
H
H
NO2
NO2
NO2
NO2
R5
H
H
NO2
H
H
NO2
H
H
NO2
H
Scheme 1. Structures of compounds 1 to 5.
corresponding coupling constants J(H-α, H-β) = 16.1 Hz indicate
a trans configuration of this double bond (Fig. 3) and a triplet
signal at a high frequency value of δ = 8.37 ppm and a small
coupling constant (J = 2.1 Hz). The latter signal corresponds to
H-2ꢁ (adjacent to the nitro group) and its multiplicity results from
the 4J couplings with the H-4ꢁ and H-6ꢁ protons.
H-8 with a small 4J coupling constant. Indeed, two doublets at
δ = 6.37 ppm and δ = 6.54 ppm can be identified with a coupling
of 2.3 Hz. The unambiguous assignment of these signals to H-6
and H-8 was verified by analysis of the HMBC spectrum. Further
assignments are (i) the signals corresponding to methoxy carbons
at δ = 55.8 and 56.4 ppm; (ii) the C-3 signal at δ = 113.5 ppm; (iii)
the C-α and C-β at δ = 123.7 and 132.8 ppm, respectively; (iv) the
C-2ꢁ signal at δ = 122.2 ppm.
Given the structure of the compound, the spectrum must also
display two doublets corresponding to the resonances of H-6 and
c
Magn. Reson. Chem. 2009, 47, 885–896
Copyright ꢀ 2009 John Wiley & Sons, Ltd.
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Ana I. R. N. A. Barros and Artur M. S. Silva
(a)
J4
H
J3
J3
5'
H
H
J4
J4
O
4'
3'
6'
1'
β
J4
NO2
2'
8
MeO
9
α
H
7
6
2
3
10
5
4
OMe O
(b)
Figure 2. 1H NMR spectra of 5,7-dimethoxy-3ꢁ-nitro-2-styrylchromone (5j) in CDCl3.
Figure 3. Expansion of the 1H NMR spectra of 5,7-dimethoxy-3ꢁ-nitro-2-styrylchromone (5j) in CDCl3.
In order to confirm the assignments based on HSQC and COSY
spectra and to deduce more information about the structure of
2-styrylchromone 5j, a 2D HMBC spectrum was recorded, resulting
in (i) H-3 signal at δ (H-3) = 6.36 ppm, which is correlated with the
carbon resonances of C-10, C-α and C-2, at δ = 114.6, 123.7 and
157.7 ppm, respectively; (ii) the H-α signal at δ (H-α) = 6.81 ppm,
which shows a long-range correlation with the carbon resonances
for C-3, C-β, C-1ꢁ and C-2, at δ = 114.6, 123.7 and 157.7 ppm,
respectively; (iii) the doublet signal at δ = 7.85 ppm, which is cor-
related with the carbon resonances for C-2ꢁ at δ = 122.2 ppm and
C-β at δ = 132.8 ppm. The signals of H-4ꢁ and H-5ꢁ were identified
bytheirmultiplicitiesandthoseoftheirattachedcarbonsbyHSQC.
Finally, a clear allocation of H-6 and H-8 is still missing. For the
analysisoftheHMBCspectrum, bothdoubletsignalsarecorrelated
c
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Spectral Assignments and Reference Data
c
Magn. Reson. Chem. 2009, 47, 885–896
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Ana I. R. N. A. Barros and Artur M. S. Silva
c
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Copyright ꢀ 2009 John Wiley & Sons, Ltd.
Magn. Reson. Chem. 2009, 47, 885–896

Spectral Assignments and Reference Data
c
Magn. Reson. Chem. 2009, 47, 885–896
Copyright ꢀ 2009 John Wiley & Sons, Ltd.
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Ana I. R. N. A. Barros and Artur M. S. Silva
c
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Copyright ꢀ 2009 John Wiley & Sons, Ltd.
Magn. Reson. Chem. 2009, 47, 885–896

Spectral Assignments and Reference Data
c
Magn. Reson. Chem. 2009, 47, 885–896
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Ana I. R. N. A. Barros and Artur M. S. Silva
with the carbon resonance for C-10 at δ = 114.6 ppm and with the
carbon resonance for C-7 at δ = 164.4 ppm, but only one of them
shows a long-range correlation with C-5. Thus, it was possible to
assign unambiguously the signals of H-6 (δ = 6.37 ppm) and H-8
(δ = 6.54 ppm).
[2] G. P. Ellis, Chromenes, Chromanones and Chromones, John Wiley &
Sons, New York, 1977, pp. 455–480.
[3] W. H. Gerwick, A. Lopez, G. D. Van Duyne, J. Clardy, W. Ortiz, A. Baez,
Tetrahedron Lett. 1986, 27, 1979.
[4] W. H. Gerwick, J. Nat. Prod. 1989, 22, 252.
[5] W. A. Price, A. M. S. Silva, J. A. S. Cavaleiro, Heterocycles 1993, 36,
2601.
[6] G. Doria, C. Romeo, A. Forgione, P. Sberze, N. Tibolla, Eur. J. Med.
Chem: Chim. Ther. 1979, 27, 347.
Acknowledgements
[7] (a) D. Brion, G. Le Baut, F. Zammatio, A. Pierre, G. Atassi, L. Belachm,
Eur Patent Application EP 454 : 587, 1991; (b) D. Brion, G. Le Baut,
F. Zammatio, A. Pierre, G. Atassi, L. Belachm, Chem. Abstr. 1992, 116,
106092k.
The authors acknowledge the financial support of FEDER, FCT-
Portugal, ResearchUnitofChemistryinVilaReal(POCTI-SFA-3-616)
and Research Unit 62/94 ‘Química Orgaˆnica, Produtos Naturais e
Agro-Alimentares’ of University of Aveiro.
[8] E. R. Fernandes,
F. Carvalho,
A. M. S. Silve,
C. M. M. Santos,
D. C. G. A. Pinto, J. A. S. Cavaleiro, M. L. Bastos, J. Enzyme Inhib.
Med. Chem. 2002, 17, 45.
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Magn. Reson. Chem. 2009, 47, 885–896