Syntheses of (E)- and (Z)-3-styrylchromones

Article abstract of DOI:10.1007/s00706-008-0926-0

Several (E)- and (Z)-3-styrylchromones were prepared by two different methodologies, the Wittig reaction of chromone-3-carboxaldehyde with benzylic ylides and the Knoevenagel condensation of chromone-3-carboxaldehyde with phenylacetic acids in the presence of potassium tert-butoxide under microwave irradiation. The Knoevenagel reaction followed by a decarboxylation offered an efficient and diastereoselective method for preparing (E)-3-styrylchromones in a shorter reaction time. It was also demonstrated that phenylacetic acid can also be substituted with success by phenylmalonic acid. The stereochemistry of all products was assigned by NMR experiments.

Full text of DOI:10.1007/s00706-008-0926-0

Monatsh Chem 139, 1307–1315 (2008)
DOI 10.1007/s00706-008-0926-0
Printed in The Netherlands
Syntheses of (E)- and (Z)-3-styrylchromones
1
1
1
1
´
Vera L. M. Silva , Artur M. S. Silva , Diana C. G. A. Pinto , Jose A. S. Cavaleiro ,
2
2
´
Attila Vasas , Tamas Patonay
1
Chemistry Department and QOPNA, University of Aveiro, Aveiro, Portugal
Department of Organic Chemistry, University of Debrecen, Debrecen, Hungary
2
Received 1 March 2008; Accepted 9 March 2008; Published online 2 June 2008
# Springer-Verlag 2008
Abstract Several (E)- and (Z)-3-styrylchromones were
prepared by two different methodologies, the Wittig
reaction of chromone-3-carboxaldehyde with benzyl-
ic ylides and the Knoevenagel condensation of chro-
mone-3-carboxaldehyde with phenylacetic acids in
the presence of potassium tert-butoxide under micro-
wave irradiation. The Knoevenagel reaction followed
by a decarboxylation offered an efficient and dia-
stereoselective method for preparing (E)-3-styryl-
chromones in a shorter reaction time. It was also
demonstrated that phenylacetic acid can also be
substituted with success by phenylmalonic acid. The
stereochemistry of all products was assigned by NMR
experiments.
exhibit potent cytotoxic, anti-allergic, antiviral, and
anticancer activity [3]. More recently, we have
shown that certain polyhydroxy-2-styrylchromones
are potent inhibitors of xanthine oxidase, potent hep-
atoprotectors against tert-butylhydroperoxide, and
potent inhibitors of the Cu(II)-induced peroxidation
of LDLs [4]. Despite the relationship of 3-styryl-
chromones with the well-studied 2-styrylchromones
very little is known about their biological activities;
only antifungal (A. niger and A. teniussiama) and
antibacterial (E. coli and S. albus) activities have
been reported [5].
The synthesis of 2-styrylchromones has been
extensively studied [6] while studies on synthesis
routes for 3-styrylchromones are not abundant [5,
7–14]. The first two methods involve the Heck reac-
tion of 3-bromochromone with styrene [7] and the
Wittig reaction of an appropriate phosphonium salt
with a benzaldehyde derivative [8]; each one of them
was used for the synthesis of only one derivative.
The third method consists in the oxidative rearrange-
ment of (E,E)-ꢀ-alkyl-20-hydroxycinnamylideneace-
tophenones with thallium(III) nitrate followed by
cyclisation into the corresponding (E)-3-(ꢁ-alkyl-
styryl)chromones by treatment with hydrochloric ac-
id [9]. This method is selective for (E)-isomers and
is the only known strategy which does not use a
chromone as starting material. Its drawback is the
use of the very toxic reagent like thallium(III)
nitrate, and only 3-styrylchromones bearing ꢁ-alkyl
Keywords Chromone-3-carboxaldehyde; 3-Styrylchromones;
Wittig reaction; Knoevenagel condensation; Microwave
irradiation.
Introduction
Styrylchromones constitute a significant subgroup
of oxygen heterocyclic compounds presenting im-
portant biological activities [1–4]. The only two
known naturally occurring 2-styrylchromones are
exceptionally cytotoxic in vitro to human leukemia
cell lines [2]. Synthetic 2-styrylchromone derivatives
Correspondence: Artur M. S. Silva, Chemistry Department,
University of Aveiro, 3810-193 Aveiro, Portugal. E-mail:
artur.silva@ua.pt

1308
Vera L. M. Silva et al.
substituents could be obtained. In the last decade,
the reactivity of the electrophilic 3-formyl group
of chromone-3-carboxaldehydes was successfully
exploited in the synthesis of 3-styrylchromones.
Some 3-styrylchromones have been obtained in mod-
erate yields, from the condensation of chromone-3-
carboxaldehyde with 6,8-dimethylcoumarin-4-acetic
acid [10], involving a Knoevenagel condensation
and a decarboxylation reaction. The condensation of
chromone-3-carboxaldehydes with 2,4-dinitrotoluene
or 4-nitrophenylacetic acid in pyridine afforded
several nitrated (E)-3-styrylchromones in moderate
yields [5, 11]. A modification of this method devel-
oped by our group involves the condensation of
chromone-3-carboxaldehydes with phenylacetic acids
followed by a decarboxylation reaction, under con-
ventional heating or microwave (MW) irradiation
and allowing a diastereoselective synthesis of new
(E)-3-stryrylchromones [12]. We studied the alter-
native Wittig approach, namely the reaction of chro-
mone-3-carboxaldehydes with benzylic ylides and
this new variant gave a diastereomeric mixture of
(E)- and (Z)-3-styrylchromones, the (Z) isomer be-
ing the more abundant one [13]. More recently, we
have disclosed a new solvent-free MW protocol
using chromone-3-carboxaldehydes and phenylma-
lonic acid on sodium acetate support affording (E)-
3-styrylchromones in moderate-to-good yields, with
complete diastereoselectivity [14]. Taking into con-
sideration all of our recent work on the synthesis of
3-styrylchromones, we decided to carry out a sys-
tematic study on the three referred methods in order
to evaluate their generality and to compare their
yields.
Results and discussion
Synthesis
In the Wittig reaction, a THF suspension of the ap-
propriate benzyl triphenylphosphonium halides 2a–
2e was treated with a molar equivalent of sodium
hydride; the solutions with the exception of 4-ethox-
yphenylphosphonium bromide (2d) became orange
after 3 h due to the formation of semi-stabilised
ylides 3a–3e (Table 1). After the addition of a molar
equivalent of chromone-3-carboxaldehyde 1a and 1b
and refluxing the mixture for a period given in
Table 1 it became yellow in colour. Wittig reactions
resulted in diastereomeric mixtures of (Z)- and (E)-
3-styrylchromones 4a–4k and 5a–5k that were sep-
arable by thin layer chromatography (Scheme 1). In
accordance with our previous observations [13] the
(Z)-isomers 4a–4k were the preferred diastereomers
independently of having electron-withdrawing or
electron-donating substituents on the phenyl ring
(Table 1). This stereochemical outcome could be
expected for the reaction of semi-stabilised ylides
with steric crowded carbonyl compounds [15].
Comparison of the yields of (Z)-3-styrylchromones
4a–4h, 4j, and 4k with those of previously synthe-
sized analogs without 5- or 7-methoxy or 30- or 40-
nitro substituents revealed that the incorporation of
the electron-withdrawing nitro group did not alter
the efficiency of the coupling. The effect of methoxy
substituent is ambiguous, the yields decreased in
10–20% in four cases (4a, 4b, 4e, 4h), but remained
essentially the same for derivatives 4c, 4d, 4f, and
4g. In summary, we can conclude that this synthetic
Table 1 Wittig reaction of chromone-3-carboxaldehydes 1a and 1b with benzylic ylides 3a–3e to yield 4a–4k and 5a–5k
Substituent
Ylide
synthesis=h
Reaction with
the chromone=h
Yield of
(Z)-isomer 4=%
Yield of
(E)-isomer 5=%
a R1 ¼ R3 ¼ R4 ¼ H; R2 ¼ OCH3
3.00
3.00
3.00
3.00
0.08
0.08
3.00
3.00
3.00
3.00
3.00
48
48
48
48
48
24
24
48
24
48
48
39
30
57
56
47
57
67
50
58
46
50
5
5
5
6
6
6
7
5
5
6
5
b R1 ¼ R2 ¼ OCH3; R3 ¼ R4 ¼ H
c R1 ¼ R3 ¼ H; R2 ¼ OCH3; R4 ¼ Cl
d R1 ¼ R2 ¼ OCH3; R3 ¼ H; R4 ¼ Cl
e R1 ¼ R3 ¼ H; R2 ¼ OCH3; R4 ¼ OC2H5
f R1 ¼ R2 ¼ OCH3; R3 ¼ H; R4 ¼ OC2H5
g R1 ¼ R3 ¼ H; R2 ¼ OCH3; R4 ¼ NO2
h R1 ¼ R2 ¼ OCH3; R3 ¼ H; R4 ¼ NO2
i R1 ¼ R2 ¼ R4 ¼ H; R3 ¼ NO2
j R1 ¼ OCH3; R2 ¼ R4 ¼ H; R3 ¼ NO2
k R1 ¼ R4 ¼ H; R2 ¼ OCH3; R3 ¼ NO2

Syntheses of (E)- and (Z)-3-styrylchromones
1309
Scheme 1
strategy is general and efficient for the preparation of
(Z)-3-styrylchromones 4a–4k.
(37–56%) (Scheme 2). These lower yields are proba-
bly due to decomposition of the starting chromone-
3-carboxaldehydes 1a and 1c or of the obtained
(E)-3-styrylchromones 5a and 5l, since the TLC
from the reaction mixture allowed the identification
of some phenylacetic acid derivative and a strongly
brownish colour at the base line. These data seem
to indicate that the incorporation of the electron-
donating groups in the A ring of chromone-3-car-
boxaldehydes led to a decrease in the yield of the
corresponding (E)-3-styrylchromone products.
We also extended our study to the condensation
of chromone-3-carboxaldehydes 1d–1f with phenyl-
malonic acid 8 (2.5 molar equivalents) under micro-
wave irradiation using the conditions described above.
(E)-3-Styrylchromones 5m–5o were obtained in
The low yield obtained in the synthesis of (E)-3-
styrylchromones by the Wittig reaction of chromone-
3-carboxaldehydes with benzylic ylides led us to
develop an alternative and diastereoselective meth-
odology to obtain this isomer [12]. Knoevenagel
condensation of chromone-3-carboxaldehyde with
phenylacetic acids in refluxing pyridine and in the
presence of potassium tert-butoxide gave (E)-3-styr-
ylchromones in an efficient way (48–99%). These
condensations under microwave irradiation gave the
expected 3-styrylchromones in comparable yields
(56–94%) but in a shorter reaction time [12]. In
the present work 3-styrylchromones 5a and 5l were
obtained by the latter method, but in lower yields
Scheme 2

1310
Vera L. M. Silva et al.
Scheme 3
Fig. 1 Important cross peaks observed in the 2D NOESY spectra of 3-styrylchromones 4a–4k and 5a–5o
very good yields (73–92%) and in a diastereoselec-
tive way, after one hour of irradiation at 180ꢀC
(Scheme 3). In that case two decarboxylations took
place after a Knoevenagel condensation. This syn-
thesis route is an improvement of our recent reported
green protocol [14], since the (E)-3-styrylchromones
were obtained in much better yields (73–92% when
compared with the previous values 48–61%) inde-
pendently of the electronic nature of the substituents
in ring A and retaining the complete (E)-diastereo-
selectivity.
These results confirm the cis configuration of the
C-ꢁ ¼ C-ꢂ double bond and also the conformation
of the styryl moiety relative to the chromone nucleus
3
(Fig. 1). The coupling constant values JH-ꢁ-H-ꢂ
ꢁ
16–17 Hz in the case of compounds 5a–5o establish
a trans configuration for their vinylic moiety. The
intense NOE cross peaks between the signals of
H-2 and those of H-ꢁ and H-ꢂ, observed in the 2D
NOESY experiment, suggests a free rotation around
the C-3-C-ꢁ bond (Fig. 1). It is also important to
1
report from the H NMR spectra of compounds
4a–4k and 5a–5o the singlet of H-2 at ꢃH ¼ 7.41–
7.71 and 7.63–8.16 ppm. In some cases this proton
resonance appears as a doublet due to the long-range
coupling with H-ꢁ (4J ꢁ 0.6–1.4 Hz).
NMR spectroscopy
The most important features of the 1H NMR spectra
of 3-styrylchromones 4a–4k and 5a–5o are the
resonances of their vinylic protons. The resonances
assigned to H-ꢂ (ꢃH ¼ 6.67–6.84 and 7.51–7.91ppm)
and C-ꢂ (ꢃC ¼ 129.1–132.4 and 129.1–132.1 ppm)
appeared at higher frequency values than those of
H-ꢁ (ꢃH ¼ 6.39–6.70 and 6.80–7.08 ppm) and C-ꢁ
(ꢃC ¼ 118.6–124.8 and 116.7–124.1 ppm). The cou-
Conclusion
We studied the Wittig reactions of chromone-3-car-
boxaldehydes 1a and 1b with benzylic ylides 3a–3e
giving both (Z)- and (E)-3-styrylchromones 4a–4k
and 5a–5k, but the (E)-isomers were minor products
in all cases. No significant substituent effect was
found. Studies on the Knoevenagel condensation of
chromone-3-carboxaldehydes 1a and 1c–1f and phe-
nylacetic acid 6 or phenylmalonic acid 8, followed
by decarboxylation under classical heating or mi-
crowave irradiation, proved the generality of this
approach although the incorporation of electron-do-
nating methoxy groups in the ring A resulted in
3
pling constant values of JH-ꢁ-H-ꢂ ꢁ12 Hz in the
case of 4a–4k indicate a cis configuration for their
vinylic system. The stereochemistry of these com-
pounds was also confirmed by 2D NOESY experi-
ment. Strong NOE cross peaks were observed
between the signals of H-ꢁ and H-ꢂ and also be-
tween that of H-ꢂ and H-20,60, while a weak cross
peak between that of H-2 and H-20,60 was also found.

Syntheses of (E)- and (Z)-3-styrylchromones
1311
5a, 14.5 mg, 5%; 4b, 77.4 mg, 30%; 5b, 12.9 mg, 5%; 4c,
185.4 mg, 57%; 5c, 16.3 mg, 5%; 4d, 199.7 mg, 56%; 5d,
21.4 mg, 6%; 4e, 157.6 mg, 47%; 5e, 20.1 mg, 6%; 4f,
208.9 mg, 57%; 5f, 22.0 mg, 6%; 4g, 225.2 mg, 67%; 5g,
23.6 mg, 7%; 4h, 183.7 mg, 50%; 5h, 18.3 mg, 5%; 4i,
176.9 mg, 58%; 5i, 15.3 mg, 5%; 4j, 154.7 mg, 46%; 5j,
20.2 mg, 6%; 4k, 168.1 mg, 50%; 5k, 16.8 mg, 5%).
lower product yields. The beneficial effect of micro-
wave irradiation was the shortening of the reaction
time compared to the reactions under conventional
heating conditions.
Experimental
General experimental procedure for the synthesis of (E)-3-
styrylchromones 5a, 5l by using Knoevenagel condensation
under microwave irradiation
Melting points were determined on a Reichert Thermovar
apparatus fitted with a microscope. NMR spectra were rec-
orded on Bruker Avance 300 (300.13 MHz for 1H and
75.47 MHz for 13C) and Bruker Avance 500 (500.13 MHz
A
mixture of chromone-3-carboxaldehydes 1a, 1c
1
for H and 125.76 MHz for 13C) spectrometers, with CDCl3
(0.574 mmol), 390 mg phenylacetic acid 6 (2.87 mmol) and
0.10g tert-BuOK (0.86 mmol) in 15cm3 dry pyridine was
irradiated in a 100 cm3 PFA sealed vessel of a high-pressure
rotor segment in an Ethos SYNTH microwave (Milestone
Inc), at a maximum temperature of 180ꢀC for 1 h (maximum
power of 800W). After that period the reaction mixture was
cooled to room temperature and poured into 25 cm3 H2O and
20g ice and the pH adjusted to 2 with a solution of HCl
(10%). The pale yellow precipitate was separated by filtration,
washed with H2O, and purified by thin layer chromatography
with a 7:3 mixture of CH2Cl2-light petroleum as eluent. The
obtained residue was crystallised from ethanol giving (E)-3-
styrylchromones 5a, 5l in moderate yields (5a, 89.4 mg, 56%;
5l, 59.1mg, 37%).
as solvent. Chemical shifts (ꢃ) are reported in ppm values and
coupling constants (J) in Hz. The internal standard was TMS.
1H assignments were made using 2D gCOSY and NOESY
(mixing time of 800 ms) experiments, while 13C assignments
were made using 2D gHSQC and gHMBC (long-range C=H
coupling constants were optimised to 7 Hz) experiments.
Electron impact (EI, 70 eV) and FABþ mass spectra were mea-
sured on a VG Autospec Q and M mass spectrometer [HRMS
were in good agreement (ꢂ0.5 ppm) with the calculated val-
ues], while electrospray mass spectra (positive mode, ESþ)
were measured on a Micromass Q-TOF-2TH spectrometer.
Elemental analyses were obtained with a LECO 932 CHN
analyser (University of Aveiro) and the results were in good
agreement (ꢂ0.4%) with the calculated values. Preparative
thin layer chromatography was carried out with Riedel silica
gel 60 DGF254, and column chromatography using Merk silica
gel 60, 70–230 mesh. Chromone-3-carboxaldehyde and ben-
zyltriphenylphosphonium salts are commercial reagents and
were obtained from Sigma-Aldrich. 3-(Nitrobenzyl)triphenyl-
phosphonium bromide was synthesised following the proce-
dure reported by Russell et al. [16]. All other chemicals and
solvents used were obtained from commercial sources and used
as received or dried using standard procedures.
General experimental procedure for the synthesis of (E)-3-
styrylchromones 5m–5o by using Knoevenagel condensation
under microwave irradiation
A
mixture of chromone-3-carboxaldehydes 1d–1f
(0.574mmol), 0.26g phenylmalonic acid 8 (1.44 mmol), and
0.10g tert-BuOK (0.86 mmol) in 15cm3 dry pyridine was
irradiated in a 100 cm3 PFA sealed vessel of a high-pressure
rotor segment in an Ethos SYNTH microwave (Milestone
Inc), at a maximum temperature of 180ꢀC for 1 h (maximum
power of 800W). After that period the reaction mixture was
cooled to room temperature and poured into 25 cm3 H2O and
20g ice and the pH adjusted to 2 with a solution of HCl
(10%). The pale yellow precipitate was separated by filtration,
washed with H2O, and purified by thin layer chromatography
with a 7:3 mixture of CH2Cl2-light petroleum as eluent. The
obtained residue was crystallised from ethanol giving (E)-3-
styrylchromones 5m–5o in good yields (5m, 111.1 mg, 78%;
5n, 118.5mg, 73%; 5o, 138.6 mg, 92%).
General experimental procedure for the synthesis of 3-styr-
ylchromones 4a–4k and 5a–5k by using Wittig reactions
Sodium hydride (25 mg, 1.04mmol) was added to a sus-
pension of the appropriate phosphonium halide (1.04 mmol)
in 25cm3 dry THF under nitrogen, and the reaction mixture
was refluxed with stirring for the adequate time (see Table 1).
The appearance of an orange colour and the disappearance of
the suspension of phosphonium salts indicated the ylide for-
mation. After that period, the appropriate chromone-3-carbox-
aldehyde 1a, 1b (1.04 mmol) was added and the reaction
mixture refluxed for the time given in Table 1. Then the
mixture was poured into 50 cm3 H2O and 30 g ice and acidi-
fied at pH 3 using HCl (20%). The organic layer was extracted
with 3ꢃ30cm3 CHCl3 and the solvent was evaporated to
dryness. The residue was taken in 20cm3 CH2Cl2 and purified
by thin layer chromatography using CH2Cl2 as eluent, lead-
ing to the isolation of two main spots, in each case. The
component of higher Rf value was identified in each case as
(E)-3-styrylchromones 5a–5k whereas the other was the (Z)-
3-styrylchromones 4a–4k (the main compounds). These com-
pounds were recrystallised from ethanol (4a, 112.9 mg, 39%;
(Z)-7-Methoxy-3-styrylchromone (4a, C18H14O3)
Mp 106–107ꢀC; 1H NMR (300.13 MHz): ꢃ ¼ 3.88 (s, 7-
OCH3), 6.53 (dd, J ¼ 12.0, 0.9 Hz, H-ꢁ), 6.76 (d, J ¼ 2.4 Hz,
H-8), 6.76 (d, J ¼ 12.0Hz, H-ꢂ), 6.98 (dd, J ¼ 8.9, 2.4 Hz, H-
6), 7.20–7.32 (m, H-20,30,40,50,60), 7.65 (d, J ¼ 0.9 Hz, H-2),
8.18 (d, J ¼ 8.9 Hz, H-5) ppm; 13C NMR (75.47 MHz):
ꢃ ¼ 55.8 (7-OCH3), 100.1 (C-8), 114.6 (C-6), 117.9 (C-10),
120.3 (C-ꢁ), 120.9 (C-3,40), 127.2 and 127.4 (C-20,60,30,50),
132.4 (C-ꢂ), 136.7 (C-10), 153.5 (C-2), 157.8 (C-9), 163.9
(C-7), 176.5 (C-4) ppm; MS (EI, 70eV): m=z (%) ¼ 279
þ
þ
þ
[(M þ H) , 24], 278 (M ꢄ, 100), 277 [(M ꢅ H) , 91], 261
(13), 249 [(M–HCO)þ, 10], 234 (4), 218 (2), 201 [(M–

1312
Vera L. M. Silva et al.
C6H5)þ, 30], 189 (3), 178 (6), 158 (3), 151 (27), 139 (7), 128
(39), 122 (16), 115 (8), 107 (15), 102 (10), 92 (4), 85 (6), 77
(11), 63 (9), 57 (6).
H-ꢂ), 6.77 (d, J ¼ 2.4 Hz, H-8), 6.98 (dd, J ¼ 8.9, 2.4 Hz, H-6),
7.23 (AB, J ¼ 8.0 Hz, H-20,30,50,60), 7.63 (d, J ¼ 1.2 Hz, H-2),
8.16 (d, J ¼ 8.9 Hz, H-5) ppm; 13C NMR (75.47 MHz):
ꢃ ¼ 55.7 (7-OCH3), 100.1 (C-8), 114.7 (C-6), 117.8 (C-10),
120.7 (C-3), 121.1 (C-ꢁ), 127.3 (C-5), 128.7 (C-30,50), 129.9
(C-20,60), 131.2 (C-ꢂ), 132.9 (C-40), 135.0 (C-10), 153.4 (C-2),
(E)-7-Methoxy-3-styrylchromone (5a, C18H14O3)
Mp 123–125ꢀC; 1H NMR (300.13 MHz): ꢃ ¼ 3.91 (s, 7-
OCH3), 6.85 (d, J ¼ 2.4 Hz, H-8), 6.98 (dd, J ¼ 16.6, 0.7 Hz,
H-ꢁ), 7.00 (dd, J ¼ 8.9, 2.4 Hz, H-6), 7.26–7.29 (m, H-40),
7.36 (t, J ¼ 7.4 Hz, H-30,50), 7.52 (d, J ¼ 7.4 Hz, H-20,60),
7.61 (d, J ¼ 16.6Hz, H-ꢂ), 8.05 (s, H-2), 8.20 (d, J ¼
8.9 Hz, H-5) ppm; 13C NMR (75.47 MHz): ꢃ ¼ 55.8 (7-
OCH3), 100.1 (C-8), 114.7 (C-6), 118.0 (C-10), 119.1 (C-ꢁ),
121.7 (C-3), 126.6 (C-20,60), 127.6 (C-5), 127.8 (C-40), 128.7
(C-30,50), 131.4 (C-ꢂ), 137.4 (C-10), 152.5 (C-2), 157.6 (C-9),
163.9 (C-7), 176.1 (C-4) ppm; MS (EI, 70 eV): m=z (%) ¼ 279
157.8 (C-9), 164.0 (C-7), 176.3 (C-4) ppm; MS (EI, 70 eV):
37
þ
þ
m=z (%) ¼ 314 [(M ꢄ, Cl), 44], 313 [(M þ H) , 46], 312
35
þ
þ
þ
[(M ꢄ, Cl), 100], 311 [(M ꢅ H) , 65], 295 [(M–OH) , 15],
283 [(M–HCO)þ, 9], 277 [(M–Cl)þ, 14], 268 (5), 201 [(M–
C6H4Cl)þ, 41], 189 (8), 176 [(M–C8H5Cl)þ, 5], 162 (23),
151 (44), 138 (9), 127 (24), 122 (20), 115 (4), 107 (15), 79
(11), 63 (12).
(E)-40-Chloro-7-methoxy-3-styrylchromone (5c, C18H13ClO3)
Mp 165–166ꢀC; 1H NMR (300.13 MHz): ꢃ ¼ 3.91 (s, 7-OCH3),
6.84 (d, J ¼ 2.4 Hz, H-8), 6.91 (dd, J ¼ 16.3, 1.4 Hz, H-ꢁ),
6.99 (dd, J ¼ 8.9, 2.4Hz, H-6), 7.31 (d, J ¼ 8.5 Hz, H-30,50),
7.43 (d, J ¼ 8.5Hz, H-20,60), 7.60 (d, J ¼ 16.3Hz, H-ꢂ), 7.63
(d, J ¼ 1.4 Hz, H-2), 8.16 (d, J ¼ 8.9Hz, H-5) ppm; 13C NMR
(75.47MHz): ꢃ ¼ 55.8 (7-OCH3), 100.1 (C-8), 114.7 (C-6),
117.9 (C-10), 119.8 (C-ꢁ), 121.3 (C-3), 127.6 (C-5), 127.7
(C-20,60), 128.8 (C-30,50), 130.2 (C-ꢂ), 133.3 (C-40), 135.9
(C-10), 152.9 (C-2), 157.5 (C-9), 164.0 (C-7), 176.0 (C-
þ
þ
þ
[(M þ H) , 26], 278 (M ꢄ, 100), 277 [(M ꢅ H) , 88], 261 [(M–
OH)þ, 16], 249 [(M–HCO)þ, 11], 234 (5), 218 (2), 207 (2),
201 (37), 189 (3), 178 (4), 161 (3), 151 (34), 139 (12), 128 (39),
122 (14), 107 (15), 94 (3), 89 (8), 83 (5), 77 (19), 63 (13).
(Z)-5,7-Dimethoxy-3-styrylchromone (4b, C19H16O4)
Mp 135–137ꢀC; 1H NMR (300.13MHz): ꢃ ¼ 3.83 (s, 7-
OCH3), 3.93 (s, 5-OCH3), 6.32 (d, J ¼ 2.3Hz, H-8), 6.34 (d,
J ¼ 2.3 Hz, H-6), 6.50 (dd, J ¼ 12.1, 0.9 Hz, H-ꢁ), 6.73 (d,
J ¼ 12.1Hz, H-ꢂ), 7.18–7.31 (m, H-20,30,40,50,60), 7.46 (d,
J ¼ 0.9 Hz, H-2) ppm; 13C NMR (75.47 MHz): ꢃ ¼ 55.6 (7-
OCH3), 56.2 (5-OCH3), 92.4 (C-8), 96.0 (C-6), 109.3 (C-10),
120.7 (C-ꢁ), 121.9 (C-3), 127.0 (C-40), 128.4 (C-20,60), 128.5
(C-30,50), 131.8 (C-ꢂ), 136.7 (C-10), 151.4 (C-2), 159.6 (C-
9), 161.0 (C-5), 163.7 (C-7), 175.9 (C-4) ppm; MS (EI,
37
þ
4) ppm; MS (EI, 70 eV): m=z (%) ¼ 314 [(M ꢄ, Cl), 47],
35
þ
þ
þ
313 [(M þ H) , 49], 312 [(M ꢄ, Cl), 100], 311 [(M ꢅ H) ,
64], 295 [(M–OH)þ, 15], 283 [(M–HCO)þ, 9], 277
[(M–35Cl)þ, 14], 268 (5), 201 [(M–C6H4Cl)þ, 44], 189
(8), 176 [(M–C8H5Cl)þ, 5], 162 (26), 156 (7), 151 (52), 150
(29), 138 (9), 127 (27), 122 (24), 115 (5), 107 (17), 79 (12),
63 (15).
þ
þ
70eV): m=z (%) ¼ 309 [(M þ H) , 308 (M ꢄ, 100), 28], 307
[(M ꢅ H)þ, 30], 291 [(M–OH)þ, 6], 280 [(M–CO)þ, 11], 279
(36), 277 [(M–OCH3)þ, 21], 261 (9), 249 (5), 231 [(M–
C6H5)þ, 23], 217 (3), 203 (11), 201 (12), 190 (13), 189
(78), 181 (11), 180 (17), 176 (11), 165 (7), 151 (32), 152
(21), 154 (12), 138 (5), 137 (31), 128 (30), 127 (15), 115
(16), 109 (9), 102 (11), 91 (15), 77 (16), 69 (12), 63 (16).
(Z)-40-Chloro-5,7-dimethoxy-3-styrylchromone
(4d, C19H15ClO4)
Mp 150–151ꢀC; 1H NMR (300.13 MHz): ꢃ ¼ 3.87 (s, 7-
OCH3), 3.96 (s, 5-OCH3), 6.36 (s, H-6,8), 6.51 (dd, J ¼
12.1, 0.9 Hz, H-ꢁ), 6.68 (d, J ¼ 12.1Hz, H-ꢂ), 7.23 (AB,
J ¼ 8.2Hz, H-20,30,50,60), 7.45 (d, J ¼ 0.9Hz, H-2) ppm; 13C
NMR (75.47MHz): ꢃ ¼ 55.7 (7-OCH3), 56.3 (5-OCH3), 92.6
(C-8), 96.2 (C-6), 109.4 (C-10), 121.7 (C-ꢁ), 121.9 (C-3),
128.7 (C-30,50), 130.0 (C-20,60), 130.8 (C-ꢂ), 132.8 (C-40),
135.3 (C-10), 151.4 (C-2), 159.7 (C-9), 161.1 (C-5), 164.0
(E)-5,7-Dimethoxy-3-styrylchromone (5b, C19H16O4)
Mp 152–155ꢀC; 1H NMR (300.13MHz): ꢃ ¼ 3.91 (s, 7-
OCH3), 3.99 (s, 5-OCH3), 6.40 (d, J ¼ 2.3 Hz, H-8), 6.46
(d, J ¼ 2.3 Hz, H-6), 6.96 (d, J ¼ 16.4Hz, H-ꢁ), 7.24–7.28
(m, H-40), 7.33–7.38 (m, H-30,50), 7.52 (d, J ¼ 8.6 Hz, H-
20,60), 7.64 (d, J ¼ 16.4Hz, H-ꢂ), 7.92 (s, H-2) ppm; 13C
NMR (75.47MHz): ꢃ ¼ 55.7 (7-OCH3), 56.3 (5-OCH3), 92.5
(C-8), 96.2 (C-6), 109.3 (C-10), 119.2 (C-ꢁ), 122.6 (C-3),
126.5 (C-20,60), 127.6 (C-40), 128.6 (C-30,50), 131.0 (C-ꢂ),
137.6 (C-10), 150.6 (C-2), 159.4 (C-9), 161.4 (C-5), 163.8
(C-7), 175.6 (C-4) ppm; MS (EI, 70eV): m=z (%) ¼ 308
(C-7), 175.9 (C-4) ppm; MS (EI, 70eV): m=z (%) ¼ 344
37
35Cl), 100],
þ
þ
þ
[(M ꢄ, Cl), 37] 343 [(M þ H) , 35], 342 [(M ꢄ,
341 [(M ꢅ H)þ, 41], 329 (2), 325 [(M–OH)þ, 7], 313 [(M–
HCO)þ, 23], 297 (6), 283 (3), 249 (2), 235 (10), 217 (4), 208
(2), 201 (11), 189 (100), 181 (30), 162 (14), 151 (25), 137
(33), 127 (25), 109 (10), 95 (7), 77 (9), 69 (12).
þ
þ
þ
(E)-40-Chloro-5,7-dimethoxy-3-styrylchromone
(M ꢄ, 100), 307 [(M ꢅ H) , 34], 291 [(M–OH) , 6], 279
[(M–HCO)þ, 32], 277 [(M–OCH3)þ, 16], 261 (7), 249 (4),
231 [(M–C6H5)þ, 19], 217 (3), 201 (9), 189 (69), 181 (13),
165 (6), 151 (27), 137 (26), 128 (23), 115 (12), 102 (7), 91
(12), 78 (6), 69 (9).
(5d, C19H15ClO4)
Mp 182–183ꢀC; 1H NMR (300.13 MHz): ꢃ ¼ 3.89 (s, 7-
OCH3), 3.97 (s, 5-OCH3), 6.38 (d, J ¼ 2.3 Hz, H-8), 6.45 (d,
J ¼ 2.3Hz, H-6), 6.88 (d, J ¼ 16.6Hz, H-ꢁ), 7.30 (d, J ¼
8.6 Hz, H-30,50), 7.41 (d, J ¼ 8.6Hz, H-20,60), 7.64 (d, J ¼
16.6Hz, H-ꢂ), 7.89 (s, H-2) ppm; 13C NMR (75.47 MHz):
ꢃ ¼ 55.7 (5-OCH3), 56.3 (5-OCH3), 92.6 (C-8), 96.2 (C-6),
109.4 (C-10), 121.7 (C-ꢁ), 121.9 (C-3), 128.7 (C-30,50),
(Z)-40-Chloro-7-methoxy-3-styrylchromone (4c, C18H13ClO3)
Mp 156–158ꢀC; 1H NMR (300.13MHz): ꢃ ¼ 3.88 (s, 7-
OCH3), 6.53 (dd, J ¼ 12.1, 1.2 Hz, H-ꢁ), 6.72 (d, J ¼ 12.1Hz,

Syntheses of (E)- and (Z)-3-styrylchromones
1313
þ
þ
þ
130.0 (C-20,60), 130.8 (C-ꢂ), 132.8 (C-40), 135.3 (C-10), 151.4
(C-2), 159.7 (C-9), 161.1 (C-5), 164.0 (C-7), 175.9 (C-4) ppm;
(%) ¼ 353 [(M þ H) , 34], 352 (M ꢄ, 100), 351 [(M ꢅ H) ,
29], 335 [(M–OH)þ, 7], 323 [(M–HCO)þ, 27] or 323 [(M–
C2H5)þ, 27], 309 (17), 293 (12), 277 (5), 265 (4), 250 (2),
237 (2), 231 [(M–C8H9O)þ, 9], 221 (1), 209 (1), 201 (3),
189 (3), 181 (15), 172 (11), 162 (16), 152 (11), 144 (18),
135 (52), 122 (6), 116 (8), 107 (33), 89 (7), 81 (3), 75 (5),
69 (8), 63 (11).
37Cl), 28], 343
þ
MS (EI, 70eV): m=z (%) ¼ 344 [(M ꢄ,
35Cl), 77], 341 [(M-H)þ, 12],
þ
þ
[(M þ H) , 20], 342 [(M ꢄ,
325 [(M–OH)þ, 2], 313 [(M–HCO)þ, 17], 311 [(M–
OCH3)þ, 8], 297 (4), 231 [(M–C6H4Cl)þ, 10], 217 (2), 201
(7), 189 (100), 180 (9), 162 (7), 151 (17), 137 (20), 125 (24),
109 (5), 91 (4), 77 (5), 63 (6).
(E)-40-Ethoxy-5,7-dimethoxy-3-styrylchromone (5f, C21H20O5)
1H NMR (300.13 MHz): ꢃ ¼ 1.41 (t, J ¼ 7.0 Hz, 40-OCH2-
CH3), 3.87 (s, 7-OCH3), 3.95 (s, 5-OCH3), 4.02 (q, J ¼
7.0 Hz, 40-OCH2CH3), 6.36 (d, J ¼ 2.2 Hz, H-8), 6.42 (d,
J ¼ 2.2 Hz, H-6), 6.80 (d, J ¼ 16.2Hz, H-ꢁ), 6.86 (d, J ¼
8.7 Hz, H-30,50), 7.41 (d, J ¼ 8.7Hz, H-20,60), 7.53 (d, J ¼
16.2Hz, H-ꢂ), 7.86 (s, H-2) ppm; 13C NMR (75.47 MHz):
ꢃ ¼ 14.8 (40-OCH2CH3), 55.7 (7-OCH3), 56.3 (5-OCH3),
63.4 (40-OCH2CH3), 92.5 (C-8), 96.1 (C-6), 109.4 (C-10),
114.5 (C-30,50), 116.8 (C-ꢁ), 122.8 (C-3), 127.7 (C-20,60),
130.2 (C-10), 130.5 (C-ꢂ), 150.0 (C-2), 158.6 (C-40), 159.4
(C-9), 161.3 (C-5), 163.7 (C-7),þ175.6 (C-4) pþpm; MS (EI,
70eV): m=z (%) ¼ 353 [(M þ H) , 23], 352 (M ꢄ, 100), 351
(Z)-40-Ethoxy-7-methoxy-3-styrylchromone (4e, C20H18O4)
Mp 90–92ꢀC; 1H NMR (300.13 MHz): ꢃ ¼ 1.39 (t, J ¼ 7.0 Hz,
40-OCH2CH3), 3.88 (s, 7-OCH3), 4.00 (q, J ¼ 7.0 Hz, 40-
OCH2CH3), 6.40 (dd, J ¼ 12.0, 1.2 Hz, H-ꢁ), 6.70 (d, J ¼
12.0Hz, H-ꢂ), 6.76 (d, J ¼ 2.4Hz, H-8), 6.78 (d, J ¼ 8.8 Hz,
H-30,50), 6.96 (dd, J ¼ 8.9, 2.4 Hz, H-6), 7.71 (d, J ¼ 1.2 Hz,
H-2), 7.23 (d, J ¼ 8.8Hz, H-20,60), 8.17 (d, J ¼ 8.9 Hz, H-5)
13
ppm; C NMR (75.47 MHz): ꢃ ¼ 14.7 (40-OCH2CH3), 55.7
(7-OCH3), 63.3 (40-OCH2CH3), 100.1 (C-8), 114.4 (C-
30,50), 114.5 (C-6), 117.9 (C-10), 118.6 (C-ꢁ), 121.2 (C-
3), 127.3 (C-5), 128.8 (C-10), 129.8 (C-20,60), 132.1 (C-ꢂ),
153.4 (C-2), 157.8 (C-9), 158.0 (C-40), 163.9 (C-7), 176.5
[(M ꢅ H)þ, 16], 335 [(M–OH)þ, 3], 323 [(M–HCO)þ, 14] or
323 [(M–C2H5)þ, 14], 309 (8), 293 (5), 277 (3), 265 (1), 231
[(M–C8H9O)þ, 5], 219 (2), 201 (1), 190 (7), 181 (9), 172 (4),
162 (11), 151 (5), 144 (12), 135 (35), 122 (2), 115 (14), 107
(19), 89 (3), 83 (9), 77 (5), 69 (15), 63 (4).
þ
(C-4) ppm; MS (EI, 70 eV): m=z (%) ¼ 322 (M ꢄ, 100),
305 [(M–OH)þ, 6], 293 [(M–HCO)þ, 60], 277 [(M–
OCH2CH3)þ, 9], 265 (7), 250 (8), 237 (2), 222 (3), 201
(8), 194 (2), 176 (24), 171 (2), 165 (5), 158 (2), 151 (25),
144 (15), 134 (7), 122 (11), 115 (36), 107 (14), 95 (3), 94
(3), 89 (8), 79 (11), 69 (3), 63 (26).
(Z)-7-Methoxy-40-nitro-3-styrylchromone (4g, C18H13NO5)
Mp 171–174ꢀC; 1H NMR (300.13 MHz): ꢃ ¼ 3.90 (s, 7-
OCH3), 6.70 (dd, J ¼ 12.2, 1.2 Hz, H-ꢁ), 6.80 (d, J ¼ 2.4 Hz,
H-8), 6.82 (d, J ¼ 12.2Hz, H-ꢂ), 7.01 (dd, J ¼ 8.9, 2.4 Hz, H-
6), 7.46 (d, J ¼ 8.7 Hz, H-20,60), 7.60 (d, J ¼ 1.2 Hz, H-2), 8.14
(d, J ¼ 8.7 Hz, H-30,50), 8.17 (d, J ¼ 8.9 Hz, H-5) ppm; 13C
NMR (75.47 MHz): ꢃ ¼ 55.9 (7-OCH3), 100.3 (C-8), 115.0
(C-6), 117.8 (C-10), 120.5 (C-3), 123.9 (C-20,60), 124.1 (C-
ꢁ), 127.4 (C-5), 129.4 (C-30,50), 130.6 (C-ꢂ), 143.6 (C-10),
146.6 (C-40), 153.6 (C-2), 157.9 (C-9), 164.3 þ(C-7), 176.0
(C-4) ppm; MS (EI, 70eV): m=z (%) ¼ 323 (M ꢄ, 100), 306
(E)-40-Ethoxy-7-methoxy-3-styrylchromone (5e, C20H18O4)
Mp 147–148ꢀC; 1H NMR (500.13 MHz): ꢃ ¼ 1.43 (t, J ¼
7.0 Hz, 40-OCH2CH3), 3.91 (s, 7-OCH3), 4.06 (q, J ¼ 7.0 Hz,
40-OCH2CH3), 6.84 (d, J ¼ 2.4Hz, H-8), 6.85 (d, J ¼ 16.4 Hz,
H-ꢁ), 6.88 (d, J ¼ 8.7 Hz, H-30,50), 6.99 (dd, J ¼ 8.9, 2.4 Hz,
H-6), 7.45 (d, J ¼ 8.7 Hz, H-20,60), 7.51 (d, J ¼ 16.4Hz, H-ꢂ),
8.03 (s, H-2), 8.20 (d, J ¼ 8.9Hz, H-5) ppm; 13C NMR
(125.76 MHz): ꢃ ¼ 14.8 (40-OCH2CH3), 55.8 (7-OCH3), 63.4
(40-OCH2CH3), 100.0 (C-8), 114.6 (C-6 and C-30,50), 116.7
(C-ꢁ), 117.6 (C-10), 121.9 (C-3), 127.8 (C-5 and C-20,60),
130.0 (C-10), 131.0 (C-ꢂ), 152.0 (C-2), 157.2 (C-40), 158.8
(C-9), 163.9 (C-7), 176.1 (C-4) ppm; MS (EI, 70 eV): m=z
(%) ¼ 322 (M ꢄ, 100), 305 [(M–OH) , 7], 293 [(M–HCO) ,
62] or [(M–C2H5)þ, 62], 277 [(M–C2H5O)þ, 11], 265 (8), 250
(8), 237 (2), 222 (3), 201 [(M–C8H9O)þ, 10], 176 (7), 165 (4),
158 (1), 151 (29), 144 (14), 135 (4), 122 (6), 115 (29), 107 (9),
94 (2), 89 (6), 77 (6), 63 (11).
[(M–OH)þ, 8], 293 [(M–NO)þ, 9], 276 (21), 260 (3), 248 (6),
234 (4), 201 [(M–C6H4NO2)þ, 61], 189 (3), 176 (5), 158 (3),
151 (40), 135 (3), 122 (23), 115 (9), 107 (17), 92 (4), 79 (12),
63 (17).
þ
þ
þ
(E)-7-Methoxy-40-nitro-3-styrylchromone (5g, C18H13NO5)
Mp 173–174ꢀC; 1H NMR (300.13 MHz): ꢃ ¼ 3.95 (s, 7-
OCH3), 6.89 (d, J ¼ 2.4 Hz, H-8), 7.05 (dd, J ¼ 8.8, 2.4Hz,
H-6), 7.08 (d, J ¼ 16.2Hz, H-ꢁ), 7.66 (d, J ¼ 8.8 Hz, H-20,60),
7.87 (d, J ¼ 16.2Hz, H-ꢂ), 8.10 (s, H-2), 8.23 (d, J ¼ 8.8 Hz,
H-5), 8.24 (d, J ¼ 8.8Hz, H-30,50) ppm; 13C NMR (75.47 MHz):
ꢃ ¼ 55.9 (7-OCH3), 100.2 (C-8), 115.0 (C-6), 118.0 (C-10),
120.7 (C-3), 124.0 (C-ꢁ and C-20,60), 126.9 (C-30,50), 127.6
(C-5), 129.4 (C-ꢂ), 144.1 (C-10), 146.8 (C-40), 154.2 (C-
2), 157.5 (C-9), 164.2 (C-7), 175.8 (C-4) ppm;þMS (EI,
(Z)-40-Ethoxy-5,7-dimethoxy-3-styrylchromone (4f, C21H20O5)
Mp 147–149ꢀC; 1H NMR (300.13 MHz): ꢃ ¼ 1.40 (t, J ¼
7.0 Hz, 40-OCH2CH3), 3.86 (s, 7-OCH3), 3.95 (s, 5-OCH3),
4.01 (q, J ¼ 7.0 Hz, 40-OCH2CH3), 6.36 (s, 2H, H-6,8), 6.39
(dd, J ¼ 12.1, 1.2 Hz, H-ꢁ), 6.67 (d, J ¼ 12.1Hz, H-ꢂ), 6.79
(d, J ¼ 8.7Hz, H-30,50), 7.22 (d, J ¼ 8.7 Hz, H-20,60), 7.54
(d, J ¼ 1.2 Hz, H-2) ppm; 13C NMR (75.47MHz): ꢃ ¼ 14.8
(40-OCH2CH3), 55.7 (7-OCH3), 56.3 (5-OCH3), 63.3 (40-
OCH2CH3), 92.6 (C-8), 96.1 (C-6), 109.5 (C-10), 114.4 (C-
30,50), 119.4 (C-ꢁ), 122.4 (C-3), 129.1 (C-ꢂ), 129.9 (C-20,60),
131.6 (C-10), 151.5 (C-2), 158.0 (C-40), 159.7 (C-9), 161.2 (C-
5), 163.8 (C-7), 176.1 (C-4) ppm; MS (EI, 70eV): m=z
þ
70 eV): m=z (%) ¼ 323 (M ꢄ, 100), 306 [(M–OH) , 6], 293
[(M–NO)þ, 11], 276 (16), 260 (2), 248 (4), 234 (3), 201
[(M–C6H4NO2)þ, 53], 189 (2), 176 (4), 158 (2), 151 (32),
143 (3), 122 (17), 115 (7), 107 (12), 92 (3), 79 (8), 63 (12),
57 (4).

1314
Vera L. M. Silva et al.
(ESþ): m=z (%) ¼ 294 [(M þ H)þ, 60], 316 [(M þ Na)þ, 84],
609 [(2 M þ Na)þ, 100], 902 [(3 M þ Na)þ, 12].
(Z)-5,7-Dimethoxy-40-nitro-3-styrylchromone(4h, C19H15NO6)
Mp 122–124ꢀC; 1H NMR (300.13MHz): ꢃ ¼ 3.87 (s, 7-
OCH3), 3.96 (s, 5-OCH3), 6.37 (d, J ¼ 2.2Hz, H-8), 6.39 (d,
J ¼ 2.2 Hz, H-6), 6.69 (dd, J ¼ 12.1, 1.0Hz, H-ꢁ), 6.77 (d, J ¼
12.1Hz, H-ꢂ), 7.41 (d, J ¼ 1.0Hz, H-2), 7.45 (d, J ¼ 8.7 Hz,
H-20,60), 8.13 (d, J ¼ 8.7 Hz, H-30,50) ppm; 13C NMR
(75.47 MHz): ꢃ ¼ 55.8 (7-OCH3), 56.4 (5-OCH3), 92.6 (C-
8), 96.4 (C-6), 109.3 (C-10), 121.7 (C-3), 124.1 (C-30,50),
124.8 (C-ꢁ), 129.5 (C-20,60), 130.0 (C-ꢂ), 143.8 (C-10),
146.6 (C-40), 151.5 (C-2), 159.8 (C-9), 161.2 (C-5), 164.2
(C-7), 175.7 (C-4) ppm; MS (EI, 70eV): m=z (%) ¼ 353
(Z)-5-Methoxy-30-nitro-3-styrylchromone (4j, C18H13NO5)
Mp 80–82ꢀC; 1H NMR (300.13 MHz): ꢃ ¼ 4.00 (s, 5-OCH3),
6.67 (dd, J ¼ 12.1, 1.1Hz, H-ꢁ), 6.78 (d, J ¼ 12.1Hz, H-ꢂ),
6.84 (d, J ¼ 8.2 Hz, H-8), 6.95 (dd, J ¼ 8.2, 0.9 Hz, H-6), 7.44
(t, J ¼ 8.2 Hz, H-7), 7.51 (d, J ¼ 1.1 Hz, H-2), 7.56 (t, J ¼
8.3 Hz, H-50), 7.60–7.64 (m, H-60), 8.07 (ddd, J ¼ 8.3, 2.0,
1.0 Hz, H-40), 8.16 (t, J ¼ 2.0 Hz, H-20) ppm; 13C NMR
(75.47MHz): ꢃ ¼ 56.5 (5-OCH3), 106.6 (C-8), 110.1 (C-6),
114.6 (C-10), 121.7 (C-3), 122.1 (C-40), 123.5 (C-20), 123.7
(C-ꢁ), 129.5 (C-7), 129.8 (C-ꢂ), 134.0 (C-50), 134.6 (C-60),
138.5 (C-10), 148.5 (C-30), 151.9 (C-2), 158.1 (C-9), 160.0 (C-
5), 176.5 (C-4) ppm; MS (ESþ): m=z (%) ¼ 324 [(M þ H)þ,
8], 346 [(M þ Na)þ, 100], 669 [(2Mþ Na)þ, 56].
þ
þ
þ
(M ꢄ, 100), 352 [(M ꢅ H) , 18], 336 [(M–OH) , 98], 323
[(M–NO)þ, 19], 306 [(M–HNO2)þ, 57], 292 (6), 277 (19),
261 (5), 249 (6), 231 (29), 201 (31), 189 (36), 181 (14), 165
(10), 152 (34), 143 (4), 137 (69), 126 (24), 115 (26), 109 (21),
95 (10), 77 (23), 69 (19), 63 (21).
(E)-5,7-Dimethoxy-40-nitro-3-styrylchromone(5h,C19H15NO6)
Mp 210–212ꢀC; 1H NMR (300.13MHz): ꢃ ¼ 3.90 (s, 7-
OCH3), 3.98 (s, 5-OCH3), 6.40 (d, J ¼ 2.3Hz, H-8), 6.46 (d,
J ¼ 2.3 Hz, H-6), 7.00 (d, J ¼ 16.6Hz, H-ꢁ), 7.59 (d, J ¼
8.8 Hz, H-20,60), 7.88 (d, J ¼ 16.6 Hz, H-ꢂ), 7.93 (s, H-2),
8.19 (d, J ¼ 8.8 Hz, H-30,50) ppm; 13C NMR (75.47MHz):
ꢃ ¼ 55.8 (7-OCH3), 56.4 (5-OCH3), 92.6 (C-6), 96.5 (C-8),
109.4 (C-10), 121.6 (C-3), 124.07 (C-30,50), 124.1 (C-ꢁ),
126.8 (C-20,60), 129.1 (C-ꢂ), 144.4 (C-10), 146.7 (C-40),
152.5 (C-2), 159.3 (C-9), 161.4 (C-5), 164.1 þ(C-7), 175.4
(C-4) ppm; MS (EI, 70eV): m=z (%) ¼ 353 (M ꢄ, 100), 336
(E)-5-Methoxy-30-nitro-3-styrylchromone (5j, C18H13NO5)
Mp 176–177ꢀC; 1H NMR (300.13 MHz): ꢃ ¼ 4.03 (s, 5-
OCH3), 6.86 (d, J ¼ 8.2Hz, H-6), 6.99 (d, J ¼ 16.4 Hz, H-
ꢁ), 7.05 (dd, J ¼ 8.2, 0.8 Hz, H-8), 7.51 (t, J ¼ 8.2 Hz, H-7),
7.58 (t, J ¼ 8.3 Hz, H-50), 7.75–7.79 (m, H-60), 7.91 (d, J ¼
16.4Hz, H-ꢂ), 8.00 (s, H-2), 8.10 (ddd, J ¼ 8.3, 2.1, 1.0 Hz, H-
40), 8.36 (t, J ¼ 2.1 Hz, H-20) ppm; 13C NMR (75.47 MHz):
ꢃ ¼ 56.5 (5-OCH3), 106.7 (C-8), 110.0 (C-6), 114.5 (C-10),
120.5 (C-20), 121.7 (C-3), 122.1 (C-40), 122.4 (C-ꢁ), 129.2
(C-ꢂ), 129.6 (C-7), 132.7 (C-60), 133.9 (C-50), 139.6 (C-
10), 145.4 (C-30), 152.7 (C-2), 157.7 (C-9), 160.3 (C-5),
176.4 (C-4) ppm; MS (ESþ) (with TFA): m=z (%) ¼ 324
[(M þ H)þ, 37], 346 [(M þ Na)þ, 54], 669 [(2M þ Na)þ,
100], 992 [(3M þ Na)þ, 22].
[(M–OH)þ, 91], 323 [(M–NO)þ, 16], 306 [(M–HNO2)þ, 45],
292 (4), 277 (12), 249 (3), 231 [(M–C6H4NO2)þ, 21], 201
(19), 189 (26), 180 (10), 165 (4), 151 (19), 137 (31), 127 (8),
115 (10), 109 (10), 89 (5), 77 (11), 63 (14).
(Z)-7-Methoxy-30-nitro-3-styrylchromone (4k, C18H13NO5)
Mp 92–93ꢀC; 1H NMR (300.13 MHz): ꢃ ¼ 3.90 (s, 7-OCH3),
6.67 (dd, J ¼ 12.3, 1.2 Hz, H-ꢁ), 6.79 (d, J ¼ 2.4Hz, H-8),
6.81 (d, J ¼ 12.3Hz, H-ꢂ), 7.00 (dd, J ¼ 9.0, 2.4Hz, H-6),
7.44 (t, J ¼ 8.0 Hz, H-50), 7.60–7.64 (m, H-60), 7.63 (d,
J ¼ 1.2 Hz, H-2), 8.07 (ddd, J ¼ 8.0, 2.1, 1.0 Hz, H-40),
8.17 (d, J ¼ 9.0 Hz, H-5), 8.17 (t, J ¼ 2.1 Hz, H-20) ppm;
13C NMR (75.47 MHz): ꢃ ¼ 55.9 (7-OCH3), 100.3 (C-8),
114.9 (C-6), 117.8 (C-10), 120.5 (C-3), 122.2 (C-40),
123.3 (C-ꢁ), 123.5 (C-20), 127.5 (C-5), 129.5 (C-50), 130.3
(C-ꢂ), 134.6 (C-60), 138.5 (C-10), 148.5 (C-30), 153.5 (C-2),
157.9 (C-9), 164.2 (C-7), 176.1 (C-4) ppm; MS (ESþ): m=z
(%) ¼ 324 [(M þ H)þ, 24], 346 [(M þ Na)þ, 100], 669
[(2M þ Na)þ, 56].
(Z)-30-Nitro-3-styrylchromone (4i, C17H11NO4)
Mp 94–96ꢀC; 1H NMR (300.13 MHz): ꢃ ¼ 6.69 (dd, J ¼ 12.1,
1.2 Hz, H-ꢁ), 6.84 (d, J ¼ 12.1Hz, H-ꢂ), 7.42 (d, J ¼ 8.6 Hz,
H-8), 7.45 (t, J ¼ 7.9 Hz, H-50), 7.40–7.47 (m, H-6), 7.60–7.65
(m, H-60), 7.69 (ddd, J ¼ 7.6, 8.6, 1.7Hz, H-7), 7.71 (d,
J ¼ 1.2 Hz, H-2), 8.08 (ddd, J ¼ 7.9, 2.1, 0.8 Hz, H-40), 8.17
(t, J ¼ 2.1 Hz, H-20), 8.27 (dd, J ¼ 8.1, 1.7 Hz, H-5) ppm; 13C
NMR (75.47MHz): ꢃ ¼ 118.2 (C-8), 120.6 (C-3), 122.2 (C-
40), 123.1 (C-ꢁ), 123.5 (C-20), 123.9 (C-10), 125.5 (C-6),
126.1 (C-5), 129.6 (C-50), 130.4 (C-ꢂ), 133.9 (C-7), 134.5
(C-60), 138.4 (C-10), 148.5 (C-30), 154.0 (C-2), 156.1 (C-9),
176.7 (C-4) ppm; MS (ESþ): m=z (%) ¼ 294 [(M þ H)þ, 28],
316 [(M þ Na)þ, 100], 609 [(2 M þ Na)þ, 15].
(E)-30-Nitro-3-styrylchromone (5i, C17H11NO4)
(E)-7-Methoxy-30-nitro-3-styrylchromone (5k, C18H13NO5)
Mp 198–200ꢀC; 1H NMR (300.13 MHz): ꢃ ¼ 3.93 (s, 7-
OCH3), 6.87 (d, J ¼ 2.4 Hz, H-8), 7.02 (dd, J ¼ 8.9, 2.4Hz,
H-6), 7.03 (d, J ¼ 16.3Hz, H-ꢁ), 7.52 (t, J ¼ 8.0Hz, H-50),
7.78–7.82 (m, H-60), 7.85 (d, J ¼ 16.3Hz, H-ꢂ), 8.08 (s, H-2),
8.11 (ddd, J ¼ 8.2, 1.8, 0.9 Hz, H-40), 8.21 (d, J ¼ 8.9 Hz, H-
5), 8.38 (t, J ¼ 1.8 Hz, H-20) ppm; 13C NMR (75.47MHz):
ꢃ ¼ 55.9 (7-OCH3), 100.2 (C-8), 114.9 (C-6), 120.6 (C-20),
122.2 (C-40), 122.5 (C-ꢁ), 127.6 (C-5), 129.4 (C-ꢂ), 129.6
(C-50), 132.6 (C-60), 139.4 (C-10), 146.2 (C-30), 153.9 (C-
2), 157.5 (C-9), 166.3 (C-7), 175.1 (C-4) ppm; MS (ESþ):
Mp 178–180ꢀC; 1H NMR (300.13 MHz): ꢃ ¼ 7.05 (d, J ¼
16.3Hz, H-ꢁ), 7.47 (ddd, J ¼ 7.6, 8.0, 1.1Hz, H-6), 7.51 (d,
J ¼ 8.1 Hz, H-8), 7.53 (t, J ¼ 8.0 Hz, H-50), 7.71 (ddd, J ¼ 7.6,
8.1, 1.6 Hz, H-7), 7.79–7.83 (m, H-60), 7.88 (d, J ¼ 16.3 Hz,
H-ꢂ), 8.11 (ddd, J ¼ 8.0, 2.1, 0.8Hz, H-40), 8.16 (s, H-2), 8.32
(dd, J ¼ 8.0, 1.6 Hz, H-5), 8.39 (t, J ¼ 2.1 Hz, H-20) ppm; 13C
NMR (75.47MHz): ꢃ ¼ 118.1 (C-8), 120.7 (C-20), 120.8 (C-
3), 122.2 (C-40), 122.4 (C-ꢁ), 124.1 (C-10), 125.6 (C-6), 126.3
(C-5), 129.6 (C-ꢂ,50), 132.7 (C-60), 133.8 (C-7),139.3 (C-10),
148.3 (C-30), 154.4 (C-2), 155.5 (C-9), 176.5 (C-4) ppm; MS

Syntheses of (E)- and (Z)-3-styrylchromones
1315
m=z (%) ¼ 324 [(M þ H)þ, 73], 669 [(2M þ Na)þ, 100], 992
[(3Mþ Na)þ, 35].
4. a) Fernandes E, Carvalho F, Silva AMS, Santos CMM,
Pinto DCGA, Cavaleiro JAS, Bastos ML (2002) J Enz
Inhib Med Chem 17:45; b) Fernandes E, Carvalho
M, Carvalho F, Silva AMS, Santos CMM, Pinto
DCGA, Cavaleiro JAS, Bastos ML (2003) Arch Tox-
The following products have been reported in literature and
in this work they were identified on the basis of their mps: (Z)-
5-Methoxy-3-styrylchromone (5l, C18H14O3), Mp 147–148ꢀC
(Ref. [13] 147–148ꢀC); (E)-3-Styrylchromone (5m), mp 163–
165ꢀC (Ref. [13] 168–169ꢀC); (E)-6-Chloro-3-styrylchromone
(5n), mp 200–201ꢀC (Ref. [14] 198–201ꢀC); (E)-6-Methyl-3-
styrylchromone (5o), mp 149–151ꢀC (Ref. [13] 151–152ꢀC).
`
icol 77:500; c) Filipe P, Silva AMS, Morliere P, Brito
CM, Patterson LK, Hug GL, Silva NJ, Cavaleiro JAS,
`
Maziere JC, Freitas JP, Santus R (2004) Biochem
Pharmacol 67:2207
5. Sonawane SA, Chavan VP, Shingare MS, Karale BK
(2002) Indian J Heterocycl Chem 12:65
6. a) Price WA, Silva AMS, Cavaleiro JAS (1993) Hetero-
cycles 36:2601; b) Silva AMS, Pinto DCGA, Cavaleiro
Acknowledgements
Thanks are due to the University of Aveiro, FCT, and FEDER
for funding the Organic Chemistry Research Unit. One of us
(VLMS) is also grateful to FCT and FSE for a PhD grant
(SFRH=BD=6647=2001).
´
JAS, Levai A, Patonay T (2004) Arkivoc vii:106
7. Davies SG, Mobbs BE, Goodwin CJ (1987) J Chem Soc
Perkin Trans 1:2597
8. Alonso R, Brossi A (1988) Tetrahedron Lett 29:735
9. Silva AMS, Cavaleiro JAS, Elguero J (1997) Liebigs Ann
Chem=Recueil:2065
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