Regioselective 3-nitration of flavones: A new synthesis of 3-nitro- and 3-aminoflavones

Article abstract of DOI:10.1055/s-0029-1219838

A new, general, and regioselective method for the 3-nitration of flavones have been developed. The nitration reaction is solvent dependent, proceeds via a nitro radical pathway, and the corresponding 3-nitroflavones have been obtained in moderate to very

Full text of DOI:10.1055/s-0029-1219838

LETTER
1381
Regioselective 3-Nitration of Flavones: A New Synthesis of 3-Nitro- and
3-Aminoflavones
New
Synthesis of
i
a
-
and Ami
nno)flavones a T. Patoilo, Artur M. S. Silva,* José A. S. Cavaleiro
Department of Chemistry & QOPNA, University of Aveiro, 3810-193 Aveiro, Portugal
Fax +351(234)370084; E-mail: artur.silva@ua.pt
Received 1 March 2010
nitrobenzoyl halides, by nitration at the more activated
positions of the flavone with nitric acid,3,8,9 or by cyclode-
hydrogenation of the corresponding nitro-2¢-hydroxychal-
cones.16 Routes for the synthesis of 3-nitro derivatives are
Abstract: A new, general, and regioselective method for the 3-ni-
tration of flavones have been developed. The nitration reaction is
solvent dependent, proceeds via a nitro radical pathway, and the
corresponding 3-nitroflavones have been obtained in moderate to
very good yields (up to 81%). The reduction of 3-nitroflavones al- scarce, only three methods are known. The first centers on
lowed the preparation of the corresponding 3-aminoflavones in very
good yields (up to 96%).
the synthesis of 3-nitroflavone (3a) in poor yield (42%),
by a multistep procedure starting from flavanone.17 The
Key words: flavones, nitration, regioselectivity, reduction, radical
reaction
second follows a three-step procedure via 3-nitrofla-
vanones, starting from 2¢-hydroxy-2-nitroacetophenones
and aryl aldehydes and producing 3-nitroflavones in mod-
erate yields.18 The third and the most utilized procedure
Flavones are a group of oxygen heterocyclic compounds was established by Dauzonne and co-workers wherein
found in a wide variety of plants where they participate in salicylaldehydes and (Z)-b-chloro-b-nitrostyrenes are
a variety of biological funtions.1 Their chemistry as well used as starting materials.6,10–12,19,20 The condensation of
as their biological and pharmacological properties have these reagents in the presence of triethylamine affords 2-
been widely studied and reviewed in the last decades.1,2 aryl-3-chloro-3,4-dihydro-4-hydroxy-3-nitro-2H-1-benzo-
Among the various pharmacological activities, those re- pyrans, which are then oxidized to 2-aryl-3-chloro-2,3-di-
lated with inflammation, cancer, and heart diseases have hydro-3-nitro-4H-1-benzopyran-4-ones by pyridinium
aroused substantial interest.2
chlorochromate under sonochemical conditions. These in-
termediates are easily converted into 3-nitroflavones by a
DBU-assisted elimination of hydrogen chloride.
More recently, it has also been demonstrated that nitro-
and aminoflavones possess important biological applica-
tions. 3¢-Nitroflavones are specific high-affinity ligands Aminoflavones and their 3-amino derivatives are normal-
for central benzodiazepine receptors, having an anxiolitic ly synthesized by reduction of the corresponding nitrofla-
action in mice and blocking the muscle-relaxant effect of vones with hydrogen/palladium on charcoal or tin/HCl
a full benzodiazepine receptor agonist.3,4 3¢-Methoxy-4¢- systems.6,8,9,12,20,21 However, there are other methods for
nitroflavone is an aryl hydrocarbon receptor antagonist5 the synthesis of specific derivatives, such as a palladium-
and 2¢,3¢-dinitroflavone-8-acetic acid proved to be noncy- catalyzed 7-amination of 7-triflyloxyflavones,22 direct
totoxic with the human U937 cell line, exhibiting an ex- amination of 3-tosyloxy- or 3-mesyloxyflavones with am-
clusive inhibitory aminopeptidase N/CD13 activity, by monia or primary amines,23 and a Claisen condensation of
reversible binding to the catalytic site of the enzyme.6 the appropriate aminoacetophenones and ethyl aminoben-
5,4¢-Diaminoflavones exhibit potent antitumor activity zoates followed by a cyclization of the obtained 1,3-dike-
against certain types of human cell lines both in vitro and tones in acid medium.7
in vivo,7 and 6-aminoflavones are inhibitors of protein-
The potential applications of 3-nitro- and 3-aminofla-
vones and the paucity of routes for their synthesis led us
tyrosine kinases8 and a-glucosidase.9 Certain 3-nitro- and
3-aminoflavones were found to be highly mutagenic
to initiate a program to study their synthesis. Several
through two different mechanisms and might be used as
methods are known for nitrating aromatic compounds but
cancer chemopreventive agents.10 Furthermore, some of
they usually require harsh reaction conditions and possess
these flavones inhibit the formation of colon aberrant
low selectivity, with mixtures of nitrated and dinitrated
crypt foci of rats11 and they have also shown antiprolifer-
compounds being obtained depending on substitution of
ative properties.12
the substrate.24 Mixtures of inorganic nitrate salts and
Flavones bearing nitro groups in the A and B rings can be strong organic acids or anhydrides have been shown to be
synthesized by the Baker–Venkataraman procedure,6,8,13– a selective and mild system for nitration of aromatic com-
15 starting from the appropriate nitroacetophenones and/or pounds and ipso-nitration of arylboronic acids.25 This
method was firstly introduced by Crivello,26 using ammo-
nium nitrate and trifluoroacetic anhydride (TFAA), at
25 °C, to nitrate benzene and other aromatic substrates
producing the corresponding nitro derivatives in good
SYNLETT 2010, No. 9, pp 1381–1385
Advanced online publication: 16.04.2010
DOI: 10.1055/s-0029-1219838; Art ID: D05810ST
x
x.
x
x.
2
0
1
0
© Georg Thieme Verlag Stuttgart · New York

1382
D. T. Patoilo et al.
LETTER
yields. Latter Njoroge and co-workers2,7 showed that aro- Since the result obtained in the nitration of 1d was unsat-
matic nitration with tetrabutylammonium nitrate–TFAA isfactory and the reduction of dinitro derivative 2d to the
proceed by a free-radical method. These results led us to corresponding 3-amino derivative was unselective, we de-
apply this method to the nitration of flavones 1a–e cided to perform the reduction of 4¢-nitroflavone (1d) and
(Scheme 1).
to study the nitration of the 4¢-aminoflavone (1e) so ob-
tained. The nitration reaction of 4¢-aminoflavone 1e af-
forded the 3-nitro derivative trifluoroacetylated in the 4¢-
amino group in good yield29 (73%, Table 1, entry 14), al-
though the acetyl group was easily removed in quantita-
tive yield by treatment with KOH in an H2O–EtOH (1:1)
mixture. The trifluoroacetylated 4¢-aminoflavone deriva-
tive 7e30 was obtained as byproduct (entries 12–14). Since
the 3-nitro-4¢-aminoflavone was not found in the reaction
mixture, the trifluoroacetylation probably occurs prior to
the nitration.
In a first attempt 4¢-chloroflavone (1b) was treated with an
excess of ammonium nitrate (3 equiv) and TFAA (10
equiv), in a CHCl3–MeCN (1:1) mixture, at 40 °C for 24
hours (Table 1, entry 1), with 4¢-chloro-3-nitroflavone
(2b) being obtained in 53% yield. We then studied the
reaction conditions in terms of solvent, amount of TFAA,
and reaction time with the best yield of 2b (72%) being
obtained with ammonium nitrate (3 equiv), TFAA (7
equiv), in a CH2Cl2–MeCN (1:1) mixture at 40 °C for 1 h
(Table 1, entry 3). 4¢-Chloro-6-nitroflavone (3b) was ob-
tained as a byproduct, resulting from aromatic nitration at From Table 1, one can also conclude that the solvent plays
one of the most activated positions of the flavone A ring.
an important role in the reaction rate and selectivity, as
mentioned by Crivello,26 the rate of the reaction seems to
be dependent on the solubility of the inorganic salt in
reaction medium. In substrates bearing electron-with-
drawing groups (deactivated substrates) the reactive spe-
cies formation should be faster in order to be readily
available to react with the substrate; thus a more polar sol-
vent is preferred. On the other hand, in substrates bearing
electron-donating substituents (activating substrates) a
slow formation of the reactive species is better in order to
have a more selective reaction and this is favored by a less
polar solvent.
We extended our study to the nitration of flavones 1a,c,d28
with the corresponding 3-nitro derivatives 2a,c,d being
obtained in moderate to good yields (Scheme 1, Table 1).
From the range of reaction conditions (amounts of reac-
tants and mixture of solvents) attempted, only those giv-
ing better yields in the formation of 2a–d are presented in
Table 1. These results show a regioselective 3-nitration of
flavones even in the presence of an activated aromatic B
ring (e.g., 1c).
R
R
B
R
OMe
NO2
O
C
O
NH4NO3
TFAA
A
O
O
O
NO2
O
O
O2N
1a R = H
1b R = Cl
2a R = H
2b R = Cl
O
1c R = OMe
1d R = NO2
1e R = NH2
2c R = OMe
3a R = H
3b R = Cl
3d R = NO2
4c
NO2
2d R = NO2
2e R = NHCOCF3
O
Scheme 1 Regioselective 3-nitration of flavones 1a–e
OMe
NO2
O2N
NO2
O
The formation of 2a–e is dependent on the B-ring substit-
uents of the starting materials 1a–e. Compound 1c, bear-
ing an electron-donating substituent (OMe), is very
reactive, requiring only one molar equivalent of ammoni-
um nitrate to obtain the 3-nitro derivative 2c in good yield
(50%), together with byproducts 4¢-methoxy-3¢-nitro-
flavone (4c) and 4¢-methoxy-3,3¢-dinitroflavone (5c,
Figure 1), resulting from the nitration at their activated ar-
omatic positions (Table 1, entry 6). Using a slight excess
of nitrating agent and other solvent mixtures than CHCl3–
MeCN the results did not give better results (Table 1, en-
tries 7, 8). Flavone 2d, having an electron-withdrawing
substituent (4¢-NO2), is less reactive, requiring a great ex-
cess (several batches) of nitrating agent for a short reac-
tion time (1 h) to obtain 3,4¢-dinitroflavone 1d in
moderate yield (33%, Table 1, entry 11). A small amount
of nitrating agent and longer reaction times results in a
smaller yield of 2d and higher yields of byproducts 3d and
6d (Table 1, entries 9, 10).
O
6d
NHCOCF3
NO2
O
O
O
5c
7e
Figure 1 Byproducts obtained in the nitration of flavones 1a–e
To determine whether the nitration reaction proceeds
through a nitronium ion (NO2 ) or a free-radical mecha-
+
nism, the nitration of 4¢-methoxyflavone (1c) was per-
formed in the presence of a free-radical scavenger
(TEMPO).27,32 Analysis after 24 hours showed that no ap-
preciable amount of 4¢-methoxy-3-nitroflavone (4c, 4%)
had been obtained and no side products were formed.
These results imply that the reaction occurs through a free
radical pathway. The proposed mechanism is similar to
Synlett 2010, No. 9, 1381–1385 © Thieme Stuttgart · New York

LETTER
New Synthesis of 3-(Nitro- and Amino)flavones
1383
Table 1 Regioselective 3-Nitration of Flavones 1a–e with Ammonium Nitrate and TFAA
Entry
1
Substratea
Reagents (equiv)
Solventsb
Temp (°C) Time (h) Yield of 2a–e (%) Yield of byproduct
(%)
4¢-ClFl
1b
NH4NO2 (3)
TFAA (10)
CHCl3
MeCN
40
40
40
40
40
r.t.
r.t.
r.t.
40
40
40
40
40
40
24
5
2b19b (53)c
2b19b (60)c
2b19b (72)c
2a19b (57)c
2a19b (81)
2c19b (50)
2c19b (53)
2c (29)
3b19b (2)
2
4¢-ClFl
1b
NH4NO2 (3)
TFAA (7)
CCl4
MeCN
3b19b (3)
3
4¢-ClFl
1b
NH4NO2 (3)
TFAA (7)
CH2Cl2
MeCN
1
3b19b (2)
4
Fl
1a
NH4NO2 (3)
TFAA (7)
CH2Cl2
MeCN
3
3a12 (2)
5
Fl
1a
NH4NO2 (3)
TFAA (7)
CCl4
MeCN
7
3a12 (4)
6
4¢-OMeFl
1c
NH4NO2 (1.1)
TFAA (2.5)
CH2Cl2
MeCN
7
4c31 (31), 5c12 (7)
4c31 (27), 5c12 (4)
4c31 (31), 5c12 (3)
6d12 (25)
7
4¢-OMeFl
1c
NH4NO2 (1.1+0.5)
TFAA (2.5)
CCl4
MeCN
5
8
4¢-OMeFl
1c
NH4NO2 (1.1 + 0.5)
TFAA (2.5)
TCB
MeCN
5
9
4¢-NO2Fl
1d
NH4NO2 (4)
TFAA (10)
CH2Cl2
MeCN
4
2d19b (16)
2d19b (16)
2d19b (33)
2e (41)
10
11
12
13
14
4¢-NO2Fl
1d
NH4NO2 (4)
TFAA (10)
CCl4
MeCN
22
1
3d15 (14), 6d12 (29)
6d12 (19)
4¢-NO2Fl
1d
NH4NO2 (7)
TFAA (14)
MeCN
4¢-NH2Fl
1e
NH4NO2 (2.2)
TFAA (5)
CCl4
MeCN
1
7e (56)
4¢-NH2Fl
1e
NH4NO2 (2.2)
TFAA (5)
CH2Cl2
MeCN
1
2e (27)
7e (23)
4¢-NH2Fl
1e
NH4NO2 (2.2)
TFAA (5)
TCB
MeCN
1
2e (73)
7e (6)
a Fl = flavone
b TCB = 1,2,4-trichlorobenzene.
c Some starting material was recovered.
that proposed by other authors,27,32 involving the reaction In the second part of this work, we studied the reduction
of ammonium nitrate with TFAA to form nitronium tri- of 3-nitroflavones 2a–e to the corresponding 3-amino de-
fluoroacetate which decomposes to trifluoroacetyl and ni- rivatives 8a–e with ammonium formate in the presence of
tro free radicals; the latter reacts with the substrate to give Pd/C (10%), in refluxing acetone (method A)33 and/or by
the nitro derivatives obtained (Scheme 2).
using tin (powder) with HCl (37%), in chloroform at room
temperature (method B,34 Table 2).
CF3
CF3
We started the reduction study with method A using meth-
anol as solvent. We found that there was no reaction for a
period of 5 minutes, and only after the addition of more
catalyst did the reaction proceed. Although it has been
stated that the catalytic cycle of this reaction is solvent de-
pendent and occurs very quickly when using methanol as
solvent;35 in our case the methanol proved not to be a good
solvent. However, when we changed to acetone, reaction
occurred with no need of additional catalyst and 3-ami-
noflavones 8a–c were obtained in good yields (87–96%,
•
+
(CF3CO)2O NH4NO3
+
NO2
•
O
O
ONO2
O
O
R
R
B
O
CF3
•
A
C
+
+ NO2
•
O
O
NO2
O
O
Scheme 2 Proposed mechanism for the regioselective 3-nitration of
flavones 1a–e
Synlett 2010, No. 9, 1381–1385 © Thieme Stuttgart · New York

1384
D. T. Patoilo et al.
LETTER
Table 2). Method A did not work for substrates 2d and 2e,
where only degradation products have been obtained.
Acknowledgment
Thanks are due to the University of Aveiro, FCT and FEDER for
funding the Organic Chemistry Research Unit and the grant to
Diana T. Patoilo.
The reduction of the 3-nitroflavones 2a–e using method B
afforded the expected 3-aminoflavones 8a–e36 in good
yields (60–88%), reaction being favored by the presence
of an electron-donating group on ring B (Scheme 3,
Table 2).
References and Notes
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R
R
O
O
A: HCO2NH4, Pd/C
(2) (a) Flavonoids in Health and Disease; Rice-Evans, C.;
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(b) Middleton, E. Jr.; Kandaswami, C.; Theoharides, T. C.
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(e) Manthey, J. A.; Guthrie, N.; Grohmann, K. Curr. Med.
Chem. 2001, 8, 135.
B: Sn (powder), HCl (aq)
NH2
NO2
O
O
2a R = H
2b R = Cl
8a R = H
8b R = Cl
2c R = OMe
8c R = OMe
2d R = NO2
8d R = NO2
2e R = NHCOCF3
8e R = NHCOCF3
Scheme 3 Synthesis of 3-aminoflavones 8a–e
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Table 2 Synthesis of 3-Aminoflavones 8a–e by Reduction of
3-Nitroflavones 2a–e
Entry Substrate
Methoda Time Yield of 8
(h)
(%)
1
2
3-nitroflavone
2a
A
B
A
B
A
B
A
B
A
B
3
8a12 (88)
(5) Davis, J. W. II.; Burdick, A. D.; Lauer, F. T.; Burchiel, S. W.
3-nitroflavone
2a
1
8a12 (80)
8b12 (96)
8b12 (71)
8c12 (87)
8c12 (88)
–
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3
4¢-Cl-3-nitroflavone
2b
3
4
4¢-Cl-3-nitroflavone
2b
1.5
1
5
4¢-OMe-3-nitroflavone
2c
6
4¢-OMe-3-nitroflavone
2c
1
7
3,4¢-dinitroflavone
2d
3.5
1
8
3,4¢-dinitroflavone
2d
8d12 (60)
–
9
4¢-(NHCOCF3)-3-nitroflavone
2e
5
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10
4¢-(NHCOCF3)-3-nitroflavone
2e
1
8e (83)
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In summary we have developed a new, general, and regio-
selective method for the radical 3-nitration of flavones
that allows the synthesis of 3-nitroflavones in moderate to
very good yields (up to 81%). The reduction of these 3-
nitroflavones permits the synthesis of the corresponding
3-aminoflavones in very good yields (up to 96%).
236.
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Synlett 2010, No. 9, 1381–1385 © Thieme Stuttgart · New York

LETTER
New Synthesis of 3-(Nitro- and Amino)flavones
1385
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DMSO-d6): d = 106.6 (C-3), 115.7 (Cq, J = 288.7 Hz, 4¢-
NHCOCF3), 118.6 (C-8), 121.1 (C-3¢,5¢), 123.4 (C-10),
124.9 (C-6), 125.6 (C-5), 127.4 (C-2¢,6¢), 127.9 (C-1¢), 134.4
(C-7), 139.6 (C-4¢), 154.8 (Cq, J = 37.3 Hz, 4¢-NHCOCF3),
155.7 (C-9), 162.0 (C-2), 177.2 (C-4) ppm. 19F NMR
(282.40 MHz, DMSO-d6): d = –97.39 (4¢-NHCOCF3) ppm.
ESI-MS (+): m/z (%) = 356 (21) [M + Na]+, 334 (100) [M +
1]+. Anal. Calcd for C17H10F3NO3: C, 61.27; H, 3.02; N,
4.20. Found: C, 61.06; H, 2.67; N, 4.43.
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(33) General Procedure for the Reduction of 3-Nitroflavones
2a–c (Method A): Synthesis of 3-Aminoflavones 8a–c
Ammonium formate (215 mg; 3.30 mmol) and Pd/C (33 mg)
were added to a solution of the 3-nitroflavone 2a–c (0.33
mmol) in acetone (5 mL), and the reaction mixture was
heated at 80 °C for 1 h. After cooling to r.t., the reaction
mixture was filtered through Celite, and the organic layer
was evaporated to dryness. The residue was purified by
column chromatography on silica gel and eluted with
CH2Cl2 to give the 3-aminoflavones 8a–c (for yield, see
Table 2).
To a solution of the appropriate flavone 1a–e (0.38 mmol) in
the requisite solvent (20 mL in total), cooled in an ice bath,
NH4NO3 and TFAA were added, and the reaction mixture
was stirred under conditions indicated in Table 1. After the
appropriate reaction time, the reaction mixture was poured
into H2O (20 mL), and extracted with CHCl3 (3 × 20 mL).
The combined organic extracts were dried over Na2SO4,
filtered, and evaporated to dryness. The mixture was purified
by silica gel column chromatography eluting with mixtures
of CH2Cl2–light PE of increasing polarity to afford the
3-nitroflavones and byproducts (Table 1).
(34) General Procedure for the Reduction of 3-Nitroflavones
2a–e (Method B): Synthesis of 3-Aminoflavones 8a–e
To a solution of the 3-nitroflavone 2a–e (0.33 mmol) in
CHCl3 (40 mL), tin(powder) (3.3 g), and HCl (37%, w/v;
11 mL) were added, and the reaction mixture was stirred
vigorously for 1 h at r.t. After this period, the reaction
mixture was neutralized with NaHCO3, filtered through
Celite, and the solid residue washed with H2O and CHCl3.
The filtrate was extracted with CHCl3, the organic layer was
dried over Na2SO4, filtered, and evaporated to dryness. The
mixture was purified by silica gel column chromatography,
eluting with CH2Cl2, giving 3-aminoflavones (for yield, see
Table 2).
(29) Physical Data for 3-Nitro-4¢-trifluoroacetamidoflavone
(1e)
Mp 228–230 °C. 1H NMR (300 MHz, DMSO-d6): d = 7.65
(ddd, 1 H, J = 8.1, 7.0, 1.0 Hz, H-6), 7.84 (d, 2 H, J = 8.8 Hz,
H-3¢,5¢), 7.86 (d, 1 H, J = 8.4 Hz, H-8), 7.95 (d, 2 H, J = 8.8
Hz, H-2¢,6¢), 7.98 (ddd, 2 H, J = 8.4, 7.0, 1.6 Hz, H-7), 8.19
(dd, 1 H, J = 8.1, 1.6 Hz, H-5), 11.69 (s, 1 H, 4¢-NHCOCF3)
ppm. 13C NMR (75.47 MHz, DMSO-d6): d = 115.6 (Cq,
J = 288.6 Hz, 4¢-NHCOCF3), 119.2 (C-8), 121.3 (C-3¢,5¢),
122.8 (C-10), 124.9 (C-5), 125.5 (C-6), 126.9 (C-1¢), 129.2
(C-2¢,6¢), 136.0 (C-7), 137.5 (C-3), 140.5 (C-4¢), 155.0 (Cq,
J = 37.0 Hz, 4¢-NHCOCF3), 155.2 (C-9), 159.4 (C-2), 168.5
(C-4) ppm. 19F NMR (282.40 MHz, DMSO-d6): d = –97.46
(4¢-NHCOCF3) ppm. ESI-MS (+): m/z (%) = 417 (22) [M +
K]+, 401 (100) [M + Na]+, 379 (88) [M + H]+. Anal. Calcd
for C17H9F3N2O5: C, 53.96; H, 2.40; N, 7.41. Found: C,
54.02; H, 2.26; N, 7.25.
(35) (a) Ram, S.; Ehrenkaufer, R. E. Synthesis 1986, 133.
(b) Haldar, P.; Mahajani, V. V. Chem. Eng. J. 2004, 104, 27.
(c) Byun, E.; Hong, B.; De Castro, K. A.; Kim, M.; Rhee, H.
J. Org. Chem. 2007, 72, 9815.
(36) Physical Data for 3-Amino-4¢-trifluoroacetamido-
flavone (8e)
Mp 195–196 °C. 1H NMR (300 MHz, DMSO-d6): d = 4.80
(s, 2 H, 3-NH2), 7.43 (ddd, 1 H, J = 8.1, 6.9, 1.2 Hz, H-6),
7.67 (ddd, 1 H, J = 8.6, 1.2, 0.5 Hz, H-8), 7.76 (ddd, 1 H,
J = 8.6, 6.9, 1.7 Hz, H-7), 8.04 (d, 2 H, J = 9.0 Hz, H-3¢,5¢),
7.89 (d, 2 H, J = 9.1 Hz, H-2¢,6¢), 8.10 (ddd, 1 H, J = 8.1, 1.7,
0.5 Hz, H-5), 11.51 (s, 1 H, 4¢-NHCOCF3) ppm. 13C NMR
(125.67 MHz, DMSO-d6): d = 115.8 (quart, J = 288.6 Hz, 4¢-
NHCOCF3), 118.3 (C-8), 120.1 (C-10), 121.0 (C-2¢,6¢),
124.3 (C-6), 125.0 (C-5), 128.2 (C-3¢,5¢), 128.6 (C-3), 129.6
(C-1¢), 133.3 (C-7), 137.2 (C-4¢), 142.3 (C-2), 154.7 (quart,
J = 37.1 Hz, 4¢NHCOCF3), 154.7 (C-9), 172.7 (C-4) ppm.
19F NMR (282.40 MHz, DMSO-d6): d = –97.36 (s, 4¢-
NHCOCF3) ppm. ESI-MS (+): m/z (%) = 371 (21) [M +
Na]+, 349 (100) [M + 1]+. Anal. Calcd for C17H11F3N2O3: C,
58.63; H, 3.18; N, 8.04. Found: C, 58.42; H, 3.49; N, 7.85.
(30) Physical Data for 4¢-Trifluoroacetamidoflavone (7e)
Mp 280–282 °C. 1H NMR (300 MHz, DMSO-d6): d = 7.05
(s, 1 H, H-3), 7.51 (ddd, 1 H, J = 8.1, 6.9, 1.4 Hz, H-6), 7.79
(dd, 1 H, J = 8.4, 1.0 Hz, H-8), 7.85 (ddd, 1 H, J = 8.4, 6.8,
1.6 Hz, H-7), 7.90 (d, 2 H, J = 8.9 Hz, H-3¢,5¢), 8.06 (dd, 1
H, J = 7.9, 1.4 Hz, H-5), 8.18 (d, 2 H, J = 8.9 Hz, H-2¢,6¢),
11.60 (s, 1 H, 4¢-NHCOCF3) ppm. 13C NMR (75.47 MHz,
Synlett 2010, No. 9, 1381–1385 © Thieme Stuttgart · New York

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