Efficient synthesis of nitroflavones by cyclodehydrogenation of 2prime;-hydroxychalcones and by the Baker-Venkataraman method

Article abstract of DOI:10.1007/s00706-006-0550-9

Several nitroflavone derivatives were synthesized by cyclodehydrogenation of 2′-hydroxychalcones and by the Baker-Venkataraman approach, starting from 2′-hydroxyacetophenones and benzoic acid derivatives. Nitroflavones synthesised by the first synthetic a

Full text of DOI:10.1007/s00706-006-0550-9

Monatshefte f€ur Chemie 137, 1505–1528 (2006)
DOI 10.1007/s00706-006-0550-9
Efficient Synthesis of Nitroflavones by
Cyclodehydrogenation of 20-Hydroxychalcones
and by the Baker-Venkataraman Method
Ana I. R. N. A. Barros1 and Artur M. S. Silva2;ꢀ
1
´
Chemistry Department, University of Tras-os-Montes e Alto Douro, Vila Real, Portugal
2
Chemistry Department, University of Aveiro, Aveiro, Portugal
Received May 13, 2006; accepted May 19, 2006
Published online October 16, 2006 # Springer-Verlag 2006
Summary. Several nitroflavone derivatives were synthesized by cyclodehydrogenation of 20-hydroxy-
chalcones and by the Baker-Venkataraman approach, starting from 20-hydroxyacetophenones and
benzoic acid derivatives. Nitroflavones synthesised by the first synthetic approach were obtained in
better global yields than those obtained by the later method. The structures of all new compounds were
elucidated by microanalyses, 1D and 2D NMR, IR, and mass spectroscopic measurements.
Keywords. Nitroflavones; Cyclodehydrogenation; 20-Hydroxychalcones; Baker-Venkataraman
method; NMR spectroscopy.
Introduction
Flavones (2-phenylchromones) are an important group of heterocyclic polypheno-
lic compounds widely distributed in the plant kingdom, where they participate in
several biological functions [1]. The synthesis of flavone derivatives has attracted
considerable attention due to their significant pharmaceutical [2], biocidal [3], and
antioxidant [4] activities. For instance, it has been found that several synthetic
nitroflavones are selective and competitive ligands for central benzodiazepine
receptors (BDZ-R) and possess anxiolytic activity in vivo, with minor sedative or
myorelaxant effects [5]. This led to postulate that these flavonoids represent a new
family of BDZ-R ligands possessing pharmacological properties distinct from clas-
sical BDZs, which bind in every region of the brain with similar affinities [5].
Recently it has also been found that several nitro derivatives are potent antipro-
liferative agents against human and murine tumor cell lines [6], and others act
as chemoprotective agents against colon aberrant crypt foci [7]. A specific nitro-
flavone derivative, 30-methoxy-40-nitroflavone, may act as an aryl hydrocarbon
ꢀ
Corresponding author. E-mail: arturs@dq.ua.pt

1506
A. I. R. N. A. Barros and A. M. S. Silva
receptor agonist or antagonist of tumor cells depending on its concentration as well
as the promoter context of a particular gene [8]. Although it has yet to be estab-
lished whether any of these nitroflavone derivatives may originate a useful thera-
peutic drug, it is deemed important to synthesize a wider series of analogous
compounds.
The synthesis of flavone derivatives has been extensively studied [9], whereas
to our knowledge only a few synthesis methods are available for the preparation
of their nitro derivatives, and only a few derivatives are described in literature
[5, 10]. Taking into account the potential biological applications of flavones, and
especially those having nitro-substituents and the scarce number of those nitro-
flavone derivatives described in literature, we decided to devote some attention to
the synthesis of a number of new nitroflavones. These compounds were obtained
by cyclodehydrogenation of 20-hydroxychalcones or by the Baker-Venkataraman
approach, starting from appropriate 20-hydroxyacetophenones and benzoic acid
derivatives [9].
Results and Discussion
Synthesis
Nitroflavones 4 were obtained by cyclodehydrogenation of 20-hydroxychalcones
obtained from an aldol condensation of 20-hydroxyacetophenones and adequate
benzaldehydes [11], and by the Baker-Venkataraman approach starting from 20-
hydroxyacetophenones and benzoic acid derivatives (Scheme 1). According to the
availability of benzaldehydes and benzoic acids with the same substitution pattern
and some difficulties in the synthesis of chalcones [11], nitroflavones 4a–4f, 4h,
and 4k were synthesized by both referred methods, trying to conclude which one is
more adequate to synthesise these compounds in terms of yields and practical
execution.
The oxidative cyclisation of 20-hydroxynitrochalcones 3a–3f, 3h, 3k, and
3x–3w into the corresponding nitroflavones 4a–4f, 4h, 4k, and 4x–4w was carried
out with a catalytic amount of iodine in DMSO at reflux, for 0.5 h [12]. These
nitroflavones were obtained in good yields (60–86%) with exception of the 20-nitro
derivatives 4a and 4d which were obtained in moderate yields (32–36%). The
presence of a 2-nitro-substituent on the starting 20-hydroxynitrochalcones 3a and
3d mode their cyclodehydrogenation difficult and led also to great decomposition
in the reaction mixture.
In the other synthesis approach, 20-(nitrobenzoyloxy)acetophenones 6a–6v and
6z were obtained from the reaction of the 20-hydroxyacetophenone derivatives
1a–1e with the appropriate benzoyl chlorides, prepared in situ from benzoic acids
5a–5f and phosphorous oxychloride. The Baker-Venkataraman rearrangement of
20-(nitrobenzoyloxy)acetophenones 6a–6v and 6z into the corresponding 1,3-di-
ketones, 1-(2-hydroxyphenyl)-3-(nitrophenyl)propan-1,3-diones 8a–8v and 8z, was
performed upon treatment with sodium hydride in dry THF at reflux (Scheme 1 and
Fig. 1). In CDCl3 solution these compounds were identified as a mixture of iso-
mers, 1,3-diketones 8a–8v and 8z and 3-hydroxy-1-(2-hydroxyphenyl)-3-(nitro-
phenyl)-2-propen-1-ones 7a–7v and 7z and=or 2-hydroxynitroflavanones 9a–9v

Efficient Synthesis of Nitroflavones
1507
Scheme 1
Fig. 1. Equilibrium between isomers 7a–7v, 7z, 8a–8v, 8z, and 9a–9v, 9z

1508
A. I. R. N. A. Barros and A. M. S. Silva
and 9z (Fig. 1) (vide Experimental). In Scheme 1 the structures of the enolic forms
7a–7v and 7z are shown because they are main isomeric structures of the major
part of synthesised compounds.
The treatment of 7a–7v and 7z (or the correspondent isomers 8a–8v and 8z or
9a–9v and 9z) with mixtures of DMSO=p-toluenesulfonic acid (method A) or
DMSO=iodine (method B) or acetic=sulfuric acid (1% v=v) (method C) led to their
cyclodehydration yielding the expected nitroflavones 4a–4v and 4z in moderate to
good yields (32–81%). The cyclodehydration of 7a, 7d, 7g, 7j, 7m, and 7r bearing
200-nitro and 60-methoxy substituents into the expected flavones 4a, 4d, 4g, 4j, 4m,
and 4r did not occur by using methods A and B, even for longer reaction times
(more than 60 h). After this long reaction time we could only isolated the corre-
sponding isomers 2-hydroxy-200-nitroflavanones 9a, 9d, 9g, 9j, 9m, and 9r. The
cyclodehydration of these flavone intermediates 7a, 7d, 7g, 7j, 7m, and 7r was
obtained upon treating them by method C (mixture of acetic and sulfuric acid). The
cyclodehydration of 1,3-diketones 8g and 8j bearing 200-nitro and 60-methoxy
substituents yielded the corresponding flavones 4g and 4j only in moderate yields
(32–38%), while the others were obtained in better yields (52–81%).
Comparing the two synthesis pathways (cyclodehydrogenation of 20-hydroxy-
chalcones and Baker-Venkataraman approach) to obtain nitroflavones 4a–4f, 4h,
and 4k, one can conclude that; i) in both methods the ortho-nitro derivatives were
obtained in lower yields than the other derivatives; ii) the approach involving
the cyclodehydrogenation of 20-hydroxychalcones is generally more favourable,
in terms of yields (ꢁ4% better) and practical execution; and iii) the meta- and
para-nitro derivatives were obtained in better global yields by the cyclodehydro-
genation of 20-hydroxychalcones approach (ꢁ50%) than those obtained by the
Baker-Venkataraman approach (ꢁ40%).
NMR Spectroscopy
The main features of the NMR spectra of 20-hydroxychalcones 3x–3w are: i) the
proton resonances of the vinylic system appearing as doublets at ꢀHꢁ ¼ 7.89–
7.91 ppm and ꢀHꢂ ¼ 8.14–8.16 ppm for 3y and 3w and ꢀHꢂ ¼ 7.92 ppm and
ꢀHꢁ ¼ 8.03 ppm for 3x. The inversion in these chemical shift values of 3x compared
to those of 3y and 3w is due to the close proximity of H-ꢁ to the 2-NO2 group in
3
the case of 3x [11]. The coupling constant of this vinylic system JHꢂꢂHꢁ ¼ 15.5–
15.6 Hz indicates their trans configuration; ii) the carbon resonances of the olefinic
system appearing at ꢀCꢂ ¼ 125.1–127.1 ppm and ꢀCꢁ ¼ 139.1–142.5 ppm. The res-
onances of C-ꢁ atoms appear at higher frequency values than those of C-ꢂ due to
deshielding mesomeric effect of the carbonyl group; iii) the proton resonance of the
hydroxyl group (ꢀOH ¼ 11.93–12.18 ppm). This high resonance frequency is due
the intramolecular hydrogen bond formed with the carbonyl group; iv) the carbon
resonance of the carbonyl group appearing at ꢀC¼O ¼ 191.6–192.2 ppm.
1
13
From the H and C NMR spectra of 20-(nitrobenzoyloxy)acetophenones
6a–6v and 6z it is important to note the proton and carbon resonances of the
2-CH3 group appearing at ꢀH ¼ 2.39–2.59 ppm and ꢀC ¼ 28.7–32.1 ppm, and also the
carbon resonances of the carbonyl groups appearing at ꢀC¼O ¼ 161.3–165.2 ppm
and ꢀC-1 ¼ 195.5–200.2 ppm.

Efficient Synthesis of Nitroflavones
1509
The Baker-Venkataraman rearrangement of 20-(nitrobenzoyloxy)acetophenones
6a–6v and 6z gave 1,3-diketones 8a–8v and 8z which are in equilibrium with their
isomeric structures 3-hydroxy-1-(2-hydroxyphenyl)-3-(nitrophenyl)-2-propen-1-
ones 7a–7v and 7z and 2-hydroxynitroflavanones 9a–9v and 9z in CDCl3 solutions
(Fig. 1). The proportion of these structures in equilibrium was determined from the
integral of H-2 in the case of diketones 8 and enolic forms 7 and of H-3 in the case
of flavanones 9. The main NMR features of diketones 8b–8d, 8g–8l, 8n, 8p, 8r,
and 8t–8v are the proton resonances of H-2 (singlet at ꢀ ¼ 4.22–4.92 ppm) and
2-hydroxyl group (singlet at ꢀ ¼ 11.20–13.65 ppm), while in the case of their eno-
lic forms 7a, 7b, 7c–7n, and 7p–7v one can observe the typical proton resonances
of H-2 (singlet at ꢀ ¼ 6.31–7.92 ppm), 20-OH (singlet at ꢀ ¼ 10.36–13.35 ppm), and
3-OH (singlet at ꢀ ¼ 13.80–16.38 ppm). From the 13C NMR spectra of the latter it
is possible to assign the resonances of C-2 (ꢀ ¼ 93.0–105.3 ppm), C-3 (ꢀ ¼ 168.9–
182.7 ppm), and C-1 (ꢀ ¼ 189.0–195.9 ppm). The presence of flavanones 7a–7c, 7i,
7n–7p, and 7z was concluded from their characteristic resonances of H-3 protons,
which appear as doublets (2J ꢁ 16 Hz) at ꢀ ¼ 2.77–3.03 and 3.24–3.60 ppm, and
C-2, C-3, and C-4 carbons, appearing at ꢀ ¼ 96.0–101.6, 47.6–50.4, and 188.5–
191.6 ppm. The assignments of all possible carbon resonances of the tautomeric
structures 7, 8, and 9 were based on the analysis of the HSQC and HMBC spectra.
Figure 2A shows some of the main connectivities found in the HMBC spectra of
7a–7c, 7i, 7n–7p, and 7z.
From the NMR spectra of flavones 4a–4z one can find some typical proton
and carbon resonances, namely those of H-3 (singlet at ꢀ ¼ 6.43–7.69 ppm), C-3
(ꢀ ¼ 107.5–114.1 ppm), and C-4 (ꢀ ¼ 174.8–177.8 ppm). C-4 assignment was based
on high frequency value, since it is the most deshielded carbon atom of the flavones
4a–4z, while that of C-3 was based on the correlation with H-3 in the HSQC of
4a–4z. The assignments of all carbon resonances of flavones 4a–4z were based on
the analysis of the HSQC and HMBC spectra. Figure 2B shows some of the typical
connectivities found in their HMBC spectra.
Experimental
Melting points were measured in a Buchi 535 apparatus. NMR spectra were recorded on a Bruker
Avance 300 spectrometer (300.13 MHz for 1H and 75.47 MHz for 13C). Chemical shifts (ꢀ) are
reported in ppm and coupling constants (J) in Hz. The internal standard was TMS. Unequivocal 13C
assignments were made by means of 2D gHSQC and gHMBC (delays for one bond and long-range
Fig. 2. Main connectivities found in the HMBC spectra of compounds 7a–7c, 7i, 7n–7p, 7z and
4a–4z

1510
A. I. R. N. A. Barros and A. M. S. Silva
C=H couplings were optimised for J ¼ 145 and 7 Hz, respectively) experiments. Electron impact (EI,
70eV) MS were recorded on VG Autospec Q and M spectrometers. Elemental analyses (CHN) were
obtained with a Carlo Erba 1108 CHNS analyzer and were in good agreement (ꢃ0.4%) 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. 20-Hydroxychalcones 3a–3f, 3h, and 3k have been prepared according to
Ref. [11].
General Method for the Synthesis of 20-Hydroxychalcones 3x–3w
NaH (0.88 g, 36.5 mmol) was slowly added to a solution of 1e (16.6 mmol) in 10 cm3 THF and
the reaction mixture was stirred at room temperature for 20 min. After this period the appropriate
2a–2c (18.3 mmol) dissolved 10 cm3 THF was added. The solution was stirred, under N2, at room
temperature until the starting materials disappeared. The solution was poured into 50 g ice and
100 cm3 H2O, and the pH was adjusted to 3 with HCl. The obtained solid was removed by
filtration, taken in 30 cm3 CHCl3, and washed with H2O (2ꢄ20 cm3). The organic layer was dried
(Na2SO4) and evaporated to dryness, and the residue obtained was purified by column chromato-
graphy using mixtures of chloroform: n-hexane as the eluent. The residue was recrystallised from
ethanol, giving 3x–3w.
50-Bromo-20-hydroxy-2-nitrochalcone (3x, C15H11NO4Br)
Yield 64%; mp 124–125ꢅC; 1H NMR (300 MHz, DMSO-d6): ꢀ ¼ 7.00 (d, J ¼ 8.8 Hz, H-30), 7.67–
7.74 (m, H-4 and H-40), 7.84 (t, J ¼ 7.8 Hz, H-5), 7.92 (d, J ¼ 15.5 Hz, H-ꢂ), 8.03 (d, J ¼ 15.5 Hz,
H-ꢁ), 8.10 (d, J ¼ 7.8 Hz, H-3), 8.17 (d, J ¼ 7.8 Hz, H-6), 8.24 (d, J ¼ 2.0 Hz, H-60), 11.93 (s,
13
20-OH) ppm; C NMR (75 MHz, DMSO-d6): ꢀ ¼ 110.5 (C-50), 120.1 (C-30), 123.6 (C-10), 124.8
(C-3), 127.1 (C-ꢂ), 129.5 (C-1), 129.6 (C-6), 131.4 (C-4), 132.7 (C-60), 133.8 (C-5), 138.3
(C-40), 139.1 (C-ꢁ), 148.8 (C-2), 159.8 (C-20), 191.6 (C¼O) ppm; IR (KBr): ꢃꢀ¼ 1641, 1585,
81Br, 18), 347
þ
1569, 1517, 1469, 1344, 1284, 1193 cmꢂ1
; MS (EI, 70 eV): m=z (%) ¼ 349 (M ꢆ,
79Br, 18), 330 (100), 300 (57), 225 (6), 201 (95), 171 (17), 149 (18), 120 (15), 102 (23),
þ
(M ꢆ,
77 (20), 65 (38).
50-Bromo-20-hydroxy-3-nitrochalcone (3y, C15H11NO4Br)
Yield 85%; mp 217–218ꢅC; 1H NMR (300MHz, DMSO-d6): ꢀ ¼ 7.00 (d, J ¼ 8.8Hz, H-30), 7.70 (dd,
J ¼ 2.3, 8.8Hz, H-40), 7.76 (t, J ¼ 8.1 Hz, H-5), 7.91 (d, J ¼ 15.6 Hz, H-ꢁ), 8.16 (d, J ¼ 15.6Hz, H-ꢂ),
8.29 (dd, J ¼ 2.0, 8.1 Hz, H-4), 8.35 (d, J ¼ 2.3Hz, H-60), 8.36 (d, J ¼ 8.1 Hz, H-6), 8.76 (d, J ¼ 2.0 Hz,
13
H-2), 12.18 (s, 20-OH) ppm; C NMR (75 MHz, DMSO-d6): ꢀ ¼ 110.5 (C-50), 120.2 (C-30), 123.2
(C-10), 123.4 (C-2), 125.1 (C-ꢂ and C-4), 130.5 (C-5), 132.7 (C-60), 135.6 (C-6), 136.3 (C-1), 138.5
(C-40), 142.5 (C-ꢁ), 148.4 (C-3), 160.2 (C-20), 192.2 (C¼O) ppm; IR (KBr): ꢃꢀ¼ 1644, 1587, 1571,
81
79Br,
þ
þ
1519, 1475, 1359, 1286, 1195 cmꢂ1
; MS (EI, 70 eV): m=z (%) ¼ 349 (M ꢆ, Br, 79), 347 (M ꢆ,
80), 330 (12), 300 (11), 225 (100), 200 (77), 176 (28), 165 (38), 142 (24), 129 (19), 100 (75), 77
(35), 64 (60).
50-Bromo-20-hydroxy-4-nitrochalcone (3w, C15H11NO4Br)
Yield 64%; mp 209–211ꢅC; 1H NMR (300MHz, DMSO-d6): ꢀ ¼ 7.02 (d, J ¼ 8.8Hz, H-30), 7.72 (dd,
J ¼ 2.3, 8.8 Hz, H-40), 7.89 (d, J ¼ 15.6Hz, H-ꢁ), 8.14 (d, J ¼ 15.6Hz, H-ꢂ), 8.19 (d, J ¼ 8.6 Hz,
H-2,6), 8.31 (d, J ¼ 8.6 Hz, H-3,5), 8,33 (d, J ¼ 2.3 Hz, H-60), 12.11 (s, 20-OH) ppm; 13C NMR
(75 MHz, DMSO-d6): ꢀ ¼ 110.5 (C-50), 120.1 (C-30), 123.5 (C-10), 124.0 (C-3,5), 126.6 (C-ꢂ), 130.2
(C-2,6), 132.7 (C-60), 138.5 (C-40), 140.9 (C-1), 141.9 (C-ꢁ), 148.3 (C-4), 160.0 (C-20), 192.0 (C¼O)
þ
ppm; IR (KBr): ꢃꢀ¼ 1639, 1585, 1511, 1463, 1336, 1184cmꢂ1
; MS (EI, 70 eV): m=z (%) ¼ 349 (M ꢆ,
79Br, 100), 330 (9), 302 (10), 225 (85), 200 (66), 176 (20), 165 (27), 142 (16),
81
þ
Br, 100), 347 (M ꢆ,
129 (13), 100 (51), 75 (21), 65 (35).

Efficient Synthesis of Nitroflavones
1511
General Method for the Synthesis of 20-(Nitrobenzoyloxy)acetophenones 6a–6v and 6z
The appropriate 5a–5f (14.5 mmol) and 1.40 cm3 POCl3 (14.5 mmol) were added to a solution of the
appropriate 1a–1e (12 mmoles) in 15cm3 dry pyridine. The solution was stirred at 60–70ꢅC for 3 h;
then poured into 80 g ice, 100 cm3 H2O, and HCl (pH adjusted to 5). The obtained solid was removed
by filtration, taken in 100 cm3 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
recrystallized from ethanol, giving the expected compound.
20-(2-Nitrobenzoyloxy)acetophenone (6a, C15H11NO5)
1
Yield 43%; mp 93–94ꢅC; H NMR (300MHz, CDCl3): ꢀ ¼ 2.54 (s, H-2), 7.34 (dd, J ¼ 1.1, 8.0Hz,
H-30), 7.51 (dt, J ¼ 1.1, 8.0 Hz, H-50), 7.74 (dt, J ¼ 1.5, 8.0 Hz, H-40), 7.88–7.98 (m, H-400,500,600), 8.04
(dd, J ¼ 1.5, 8.0 Hz, H-60), 8.17 (dd, J ¼ 1.1, 8.0 Hz, H-300) ppm; 13C NMR (75 MHz, CDCl3): ꢀ ¼ 29.2
(C-2), 123.3 (C-30), 124.1 (C-300), 125.4 (C-100), 127.1 (C-50), 130.2 (C-10), 130.3 (C-600), 131.1 (C-60),
133.5 (C-400), 134.0 (C-500), 134.1 (C-40), 147.9 (C-20), 147.7 (C-200), 163.1 (C¼O), 197.5 (C-1) ppm;
IR (KBr): ꢃꢀ¼ 1755, 1679, 1604, 1529, 1444, 1346, 1278, 1253, 1187, 1058, 761 cmꢂ1; MS (EI,
þ
70eV): m=z (%) ¼ 285 (M ꢆ, 21), 150 (100), 134 (5), 121 (4), 104 (37), 92 (13), 76 (34), 64 (6).
20-(3-Nitrobenzoyloxy)acetophenone (6b, C15H11NO5)
Yield 64%; mp 124–125ꢅC; 1H NMR (300MHz, CDCl3): ꢀ ¼ 2.54 (s, H-2), 7.43 (dd, J ¼ 1.2, 8.1Hz,
H-30), 7.51 (dt, J ¼ 1.2, 7.7Hz, H-50), 7.72 (ddd, J ¼ 1.7, 7.7, 8.1Hz, H-40), 7.92 (t, J ¼ 7.9Hz, H-500),
8.05 (dd, J ¼ 1.7, 7.7Hz, H-60), 8.52 (ddd, J ¼ 1.3, 2.2, 7.9Hz, H-600), 8.58 (ddd, J ¼ 1.3, 2.2, 7.9 Hz,
H-400), 8.77 (t, J ¼ 2.2Hz, H-200) ppm; 13C NMR (75 MHz, CDCl3): ꢀ ¼ 29.3 (C-2), 124.1 (C-30), 124.2
(C-200), 126.9 (C-50), 128.4 (C-400), 130.6 (C-10, C-100), 131.0 (C-60, C-500), 134.0 (C-40), 136.0 (C-600),
148.0 (C-300), 148.3 (C-20), 163.1 (C¼O), 197.5 (C-1) ppm; IR (KBr): ꢃꢀ¼ 1739, 1685, 1600, 1525,
þ
1442, 1347, 1265, 1245, 1191, 1124, 1076, 840, 765 cmꢂ1
; MS (EI, 70 eV): m=z (%) ¼ 285 (M ꢆ, 45),
270 (11), 223 (10), 197 (26), 168 (23), 150 (100), 104 (13), 92 (11), 76 (27).
20-(4-Nitrobenzoyloxy)acetophenone (6c, C15H11NO5)
1
Yield 62%; mp 93–95ꢅC; H NMR (300MHz, CDCl3): ꢀ ¼ 2.56 (s, H-2), 7.26 (dd, J ¼ 1.3, 8.1Hz,
H-30), 7.42 (dt, J ¼ 1.3, 7.6 Hz, H-50), 7.63 (ddd, J ¼ 1.8, 7.6, 8.1 Hz, H-40), 7.91 (dd, J ¼ 1.8, 7.6 Hz,
H-60), 8.34 (d, J ¼ 9.3 Hz, H-200,600), 8.38 (d, J ¼ 9.3 Hz, H-300,500) ppm; 13C NMR (75MHz, CDCl3):
ꢀ ¼ 29.6 (C-2), 123.6 (C-300,500), 123.7 (C-30), 126.5 (C-50), 130.0 (C-10, C-60), 131.3 (C-200,600), 133.7
(C-40), 134.8 (C-100), 148.7 (C-20), 150.7 (C-400), 163.4 (C¼O), 197.1 (C-1) ppm; IR (KBr): ꢃꢀ¼ 1743,
þ
1687, 1600, 1446, 1349, 1267, 1193, 1079, 767, 709 cmꢂ1
; MS (EI, 70 eV): m=z (%) ¼ 285 (M ꢆ, 31),
150 (100), 134 (4), 120 (12), 104 (33), 92 (24), 76 (23), 64 (7).
40-Methoxy-20-(2-nitrobenzoyloxy)acetophenone (6d, C16H13NO6)
1
Yield 44%; mp 138–139ꢅC; H NMR (300 MHz, CDCl3): ꢀ ¼ 2.50 (s, H-2), 3.89 (s, OCH3), 6.85
(d, J ¼ 2.5 Hz, H-30), 7.06 (dd, J ¼ 2.5, 8.8 Hz, H-50), 7.89–8.00 (m, H-400 and H-500), 8.05 (d,
J ¼ 8.8 Hz, H-60), 8.16 (dd, J ¼ 1.2, 7.7 Hz, H-300), 8.20 (dd, J ¼ 1.6, 7.7 Hz, H-600) ppm; 13C NMR
(75 MHz, CDCl3): ꢀ ¼ 28.9 (C-2), 56.1 (OCH3), 109.0 (C-30), 112.1 (C-50), 122.4 (C-10), 124.3
(C-300), 125.1 (C-100), 133.4 (C-60 and C-600), 133.6 (C-400), 136.8 (C-500), 148.1 (C-200), 150.0
(C-20), 162.7 (C¼O), 163.5 (C-40), 195.7 (C-1) ppm; IR (KBr): ꢃꢀ¼ 1760, 1675, 1610, 1565,
þ
1527, 1498, 1347, 1288, 1253, 1128, 1062, 800 cmꢂ1
; MS (EI, 70 eV): m=z (%) ¼ 315 (M ꢆ, 5),
150 (45), 104 (3), 83 (100), 76 (6).
40-Methoxy-20-(3-nitrobenzoyloxy)acetophenone (6e, C16H13NO6)
1
Yield 58%; mp 96–98ꢅC; H NMR (300MHz, CDCl3): ꢀ ¼ 2.51 (s, H-2), 3.89 (s, OCH3), 6.76 (d,
J ¼ 2.5 Hz, H-30), 6.91 (dd, J ¼ 2.5, 8.8 Hz, H-50), 7.74 (t, J ¼ 8.0Hz, H-500), 7.92 (d, J ¼ 8.8Hz, H-60),
8.48–8.55 (m, H-400 and H-600), 9.03 (t, J ¼ 1.7Hz, H-200) ppm; 13C NMR (75 MHz, CDCl3): ꢀ ¼ 29.6
(C-2), 55.8 (OCH3), 109.5 (C-30), 111.9 (C-50), 122.2 (C-10), 125.2 (C-200), 127.8 (C-400), 129.8 (C-500),

1512
A. I. R. N. A. Barros and A. M. S. Silva
131.3 (C-100), 132.9 (C-60), 133.9 (C-600), 148.2 (C-300), 151.0 (C-20), 163.2 (C¼O), 163.9 (C-40), 195.5
(C-1) ppm; IR (KBr): ꢃꢀ¼ 1731, 1675, 1608, 1548, 1494, 1434, 1351, 1284, 1261, 1143, 1066, 878,
þ
815, 711 cmꢂ1
; MS (EI, 70 eV): m=z (%) ¼ 315 (M ꢆ, 29), 300 (15), 150 (100), 104 (30), 76 (24).
40-Methoxy-20-(4-nitrobenzoyloxy)acetophenone (6f, C16H13NO6)
1
Yield 63%; mp 95–97ꢅC; H NMR (300MHz, CDCl3): ꢀ ¼ 2.50 (s, H-2), 3.86 (s, OCH3), 7.02 (d,
J ¼ 2.5 Hz, H-30), 7.03 (dd, J ¼ 2.5, 7.5 Hz, H-50), 8.04 (d, J ¼ 7.5Hz, H-60), 8.33 (d, J ¼ 8.8 Hz,
H-200,600), 8.42 (d, J ¼ 8.8Hz, H-300,500) ppm; 13C NMR (75 MHz, CDCl3): ꢀ ¼ 28, 9 (C-2), 56.1
(OCH3), 109.6 (C-30), 112.2 (C-50), 122.1 (C-10), 124.0 (C-300,500), 131.4 (C-200,600), 132.2 (C-60),
134.6 (C-100), 150.5 (C-20), 150.7 (C-400), 163.1 (C¼O), 163.5 (C-40), 195.5 (C-1) ppm; IR (KBr):
ꢃꢀ¼ 1743, 1671, 1608, 1565, 1527, 1347, 1267, 1240, 1137, 1074, 1014, 709 cmꢂ1; MS (EI, 70 eV):
þ
m=z (%) ¼ 315 (M ꢆ, 15), 150 (100), 104 (9), 76 (17).
60-Methoxy-20-(2-nitrobenzoyloxy)acetophenone (6g, C16H13NO6)
Yield 36%; mp 108–109ꢅC; 1H NMR (300 MHz, CDCl3): ꢀ ¼ 2.46 (s, H-2), 3.91 (s, OCH3), 6.95 (d,
J ¼ 8.3 Hz, H-30), 7.06 (d, J ¼ 8.3Hz, H-50), 7.58 (t, J ¼ 8.3 Hz, H-40), 7.91–7.98 (m, H-400,500,600), 8.19
(dd, J ¼ 1.0, 7.5Hz, H-300) ppm; 13C NMR (75 MHz, CDCl3): ꢀ ¼ 31.6 (C-2), 56.4 (OCH3), 110.3
(C-50), 114.4 (C-30), 123.6 (C-10), 124.5 (C-300), 125.1 (C-100), 130.0 (C-600), 131.8 (C-40), 133.6 (C-400),
134.1 (C-500), 146.3 (C-60), 147.6 (C-200), 157.3 (C-20), 163.0 (C¼O), 199.5 (C-1) ppm; IR (KBr):
ꢃꢀ¼ 1639, 1581, 1525, 1427, 1342, 1222, 1160, 1112, 971, 804, 732 cmꢂ1; MS (EI, 70eV):
þ
m=z (%) ¼ 315 (M ꢆ, 92), 300 (100), 298 (40), 284 (23), 277 (77), 104 (33), 76 (21).
60-Methoxy-20-(3-nitrobenzoyloxy)acetophenone (6h, C16H13NO6)
1
Yield 59%; mp 151–153ꢅC; H NMR (300 MHz, CDCl3): ꢀ ¼ 2.46 (s, H-2), 3.91 (s, OCH3), 7.03
(d, J ¼ 8.3 Hz, H-30), 7.16 (d, J ¼ 8.3 Hz, H-50), 7.56 (dt, J ¼ 8.3, 8.3 Hz, H-40), 7.92 (t, J ¼ 8.0 Hz,
H-500), 8.47 (dd, J ¼ 0.9, 8.0 Hz, H-600), 8.59 (dt, J ¼ 0.9, 8.0 Hz, H-400), 8.70 (br s, H-200) ppm; 13C
NMR (75 MHz, CDCl3): ꢀ ¼ 31.7 (C-2), 56.4 (OCH3), 110.1 (C-50), 115.2 (C-30), 123.5 (C-10),
124.1 (C-200), 128.6 (C-400), 130.1 (C-100), 131.0 (C-500), 131.7 (C-40), 135.8 (C-600), 146.9 (C-20),
148.0 (C-300), 157.3 (C-60), 162.7 (C¼O), 199.7 (C-1) ppm; IR (KBr): ꢃꢀ¼ 1741, 1685, 1604, 1525,
þ
1469, 1347, 1267, 1222, 1097, 846, 715 cmꢂ1
; MS (EI, 70 eV): m=z (%) ¼ 315 (M ꢆ, 26), 300
(20), 165 (4), 150 (100), 104 (34), 83 (23), 76 (28); 1741, 1685, 1604, 1525, 1469, 1347, 1267,
1222, 1097, 846, 715 cmꢂ1
.
60-Methoxy-20-(4-nitrobenzoyloxy)acetophenone (6i, C16H13NO6)
Yield 68%; mp 150–151ꢅC; 1H NMR (300 MHz, CDCl3): ꢀ ¼ 2.44 (s, H-2), 3.90 (s, OCH3), 7.01 (dd,
J ¼ 0.6, 8.2 Hz, H-30), 7.14 (d, J ¼ 8.2Hz, H-50), 7.54 (t, J ¼ 8.2 Hz, H-40), 8.27 (d, J ¼ 9.0 Hz,
H-200,600), 8.40 (d, J ¼ 9.0Hz, H-300,500) ppm; 13C NMR (75 MHz, CDCl3): ꢀ ¼ 31.7 (H-2), 56.4
(OCH3), 110.1 (C-50), 115.2 (C-30), 123.4 (C-10), 124.1 (C-300,500), 131.3 (C-200,600), 131.6 (C-40),
133.9 (C-100), 146.9 (C-400), 150.7 (C-60), 157.2 (C-20), 162.9 (C¼O), 199.6 (C-1) ppm; IR (KBr):
ꢃꢀ¼ 1741, 1685, 1602, 1525, 1467, 1440, 1347, 1265, 1218, 1095, 844, 782, 713 cmꢂ1; MS (EI, 70 eV):
þ
m=z (%) ¼ 315 (M ꢆ, 38), 300 (25), 284 (4), 150 (100), 104 (34), 83 (23), 76 (28).
40,60-Dimethoxy-20-(2-nitrobenzoyloxy)acetophenone (6j, C17H15NO7)
1
Yield 33%; mp 114–115ꢅC; H NMR (300MHz, CDCl3): ꢀ ¼ 2.52 (s, H-2), 3.88 (s, 2ꢄOCH3), 6.43
(d, J ¼ 2.2 Hz, H-30), 6.48 (d, J ¼ 2.2Hz, H-50), 7.68 (dt, J ¼ 1.4, 7.7 Hz, H-400), 7.79 (dt, J ¼ 1.0,
7.7 Hz, H-500), 8.00 (dd, J ¼ 1.4, 7.7 Hz, H-600), 8.08 (dd, J ¼ 1.0, 7.7Hz, H-300) ppm; 13C NMR
(75 MHz, CDCl3): ꢀ ¼ 32.1 (H-2), 55.8 (OCH3), 55.9 (OCH3), 97.3 (C-50), 99.5 (C-30), 116.5
(C-10), 124.0 (C-300), 127.9 (C-100), 130.0 (C-600), 131.6 (C-400), 133.8 (C-500), 146.9 (C-200), 157.3
(C-20), 159.7 (C-60), 162.7 (C-40), 164.1 (C¼O), 199.0 (C-1) ppm; IR (KBr): ꢃꢀ¼ 1749, 1671, 1614,
1575, 1531, 1342, 1282, 1259, 1226, 1151, 1122, 1078, 827, 792, 736 cmꢂ1; MS (EI, 70 eV):
þ
m=z (%) ¼ 345 (M ꢆ, 23), 330 (12), 181 (8), 167 (6), 150 (100), 104 (9), 76 (19), 69 (4).

Efficient Synthesis of Nitroflavones
1513
40,60-Dimethoxy-20-(3-nitrobenzoyloxy)acetophenone (6k, C17H15NO7)
Yield 56%; mp 143–145ꢅC; 1H NMR (300MHz, CDCl3): ꢀ ¼ 2.50 (s, H-2), 3.85 (s, OCH3), 3.90 (s,
OCH3), 6.37 (d, J ¼ 2.2Hz, H-30), 6.45 (d, J ¼ 2.2 Hz, H-50), 7.71 (t, J ¼ 8.0 Hz, H-500), 8.46–8.50 (m,
H-400 and H-600), 8.96 (t, J ¼ 2.0Hz, H-200) ppm; 13C NMR (75 MHz, CDCl3): ꢀ ¼ 32.1 (C-2), 55.7
(OCH3), 56.0 (OCH3), 96.9 (C-50), 100.2 (C-30), 116.5 (C-10), 125.2 (C-200), 127.9 (C-400), 129.8
(C-500), 131.1 (C-100), 135.9 (C-600), 148.3 (C-300), 149.8 (C-20), 159.8 (C-60), 162.6 (C-40), 163.2
(C¼O), 198.8 (C-1) ppm; IR (KBr): ꢃꢀ¼ 1745, 1660, 1610, 1569, 1344, 1251, 1116, 1066, 825,
þ
748, 707 cmꢂ1
; MS (EI, 70 eV): m=z (%) ¼ 345 (M ꢆ, 39), 330 (80), 195 (2), 178 (10), 150 (100),
137 (6), 104 (41), 76 (32).
40,60-Dimethoxy-20-(4-nitrobenzoyloxy)acetophenone (6l, C17H15NO7)
Yield 62%; mp 155–156ꢅC; 1H NMR (300MHz, CDCl3): ꢀ ¼ 2.39 (s, H-2), 3.83 (s, OCH3), 3.90 (s,
OCH3), 6.64 (d, J ¼ 2.2 Hz, H-30), 6.67 (d, J ¼ 2.2Hz, H-50), 8.26 (d, J ¼ 9.0 Hz, H-200,600), 8.41 (d,
J ¼ 9.0 Hz, H-300,500) ppm; 13C NMR (75 MHz, CDCl3): ꢀ ¼ 31.9 (C-2), 56.0 (OCH3), 56.4 (OCH3),
97.1 (C-50), 101.0 (C-30), 115.9 (C-10), 124.1 (C-300,500), 131.3 (C-200,600), 134.2 (C-100), 149.1 (C-20),
150.6 (C-400), 159.3 (C-60), 162.3 (C-40), 162.9 (C¼O), 198.1 (C-1) ppm; IR (KBr): ꢃꢀ¼ 1731, 1691,
þ
1616, 1527, 1347, 1218, 1159, 1130, 852, 823, 711 cmꢂ1
; MS (EI, 70eV): m=z (%) ¼ 345 (M ꢆ, 57),
330 (71), 178 (13), 150 (100), 120 (10), 104 (40), 92 (14), 76 (19).
20-(2-Methyl-3-nitrobenzoyloxy)acetophenone (6m, C16H13NO5)
Yield 59%; mp 103–104ꢅC; 1H NMR (300 MHz, CDCl3): ꢀ ¼ 2.58 (s, H-2), 2.65 (s, 200-CH3), 7.40 (dd,
J ¼ 1.1, 7.9Hz, H-30), 7.49 (dt, J ¼ 1.1, 7.9 Hz, H-50), 7.65 (t, J ¼ 8.0 Hz, H-500), 7.68–7.73 (m, H-40),
8.04–8.08 (m, H-400 and H-60), 8.40 (dd, J ¼ 1.1, 8.0 Hz, H-600) ppm; 13C NMR (75 MHz, CDCl3):
ꢀ ¼ 15.9 (200-CH3), 29.0 (C-2), 124.8 (C-30), 127.4 (C-50), 128.0 (C-400 and C-500), 129.0 (C-200), 131.5
(C-10), 131.6 (C-60), 133.4 (C-100), 135.0 (C-40 and C-600), 149.5 (C-20), 153.0 (C-300), 165.2 (C¼O),
198.0 (C-1) ppm; IR (KBr): ꢃꢀ¼ 1743, 1677, 1602, 1573, 1529, 1444, 1357, 1255, 1193, 1085, 1018,
þ
954, 730 cmꢂ1
; MS (EI, 70eV): m=z (%) ¼ 299 (M ꢆ, 4), 164 (100), 147 (6), 118 (23), 105 (3), 90 (22).
20-(4-Methyl-3-nitrobenzoyloxy)acetophenone (6n, C16H13NO5)
1
Yield 77%; mp 91–92ꢅC; H NMR (300MHz, CDCl3): ꢀ ¼ 2.51 (s, H-2), 2.64 (s, 400-CH3), 7.21 (d,
J ¼ 7.6 Hz, H-30), 7.36 (t, J ¼ 7.6 Hz, H-50), 7.48 (d, J ¼ 7.9Hz, H-500), 7.56 (dt, J ¼ 1.0, 7.6 Hz, H-40),
7.85 (dd, J ¼ 1.0, 7.6 Hz, H-60), 8.26 (dd, J ¼ 0.9, 7.9 Hz, H-600), 8.72 (d, J ¼ 0.9 Hz, H-200) ppm; 13C
NMR (75 MHz, CDCl3): ꢀ ¼ 20.5 (400-CH3), 28.9 (C-2), 123.6 (C-30), 126.2 (C-200), 126.3 (C-50), 128.5
(C-10), 130.0 (C-100), 130.5 (C-60), 130.7 (C-500), 133.5 (C-40), 133.8 (C-600), 139.1 (C-400), 148.6 (C-300),
148.9 (C-20) 163.1 (C¼O), 197.0 (C-1) ppm; IR (KBr): ꢃꢀ¼ 1745, 1687, 1600, 1527, 1446, 1355, 1294,
þ
1249, 1213, 1106, 848, 765, 738 cmꢂ1
; MS (EI, 70eV): m=z (%) ¼ 299 (M ꢆ, 20), 279 (5), 164 (100),
149 (16), 118 (28), 106 (3), 90 (22), 77 (4), 63 (9).
20-(3,5-Dinitrobenzoyloxy)acetophenone (6o, C15H10N2O7)
Yield 75%; mp 130–131ꢅC; 1H NMR (300MHz, CDCl3): ꢀ ¼ 2.59 (s, H-2), 7.29 (dd, J ¼ 1.1, 7.8Hz,
H-30), 7.49 (dt, J ¼ 1.1, 7.8Hz, H-50), 7.69 (dt, J ¼ 1.6, 7.8 Hz, H-40), 7.98 (dd, J ¼ 1.6, 7.8 Hz, H-60),
13
9.29–9.33 (m, H-200,600 and H-400) ppm; C NMR (75 MHz, CDCl3): ꢀ ¼ 28.7 (C-2), 122.8 (C-400),
123.9 (C-30), 127.1 (C-50), 129.0 (C-10), 130.1 (C-200,600), 131.2 (C-60), 133.4 (C-100), 134.3 (C-40),
148.5 (C-20), 148.7 (C-300,500), 161.6 (C¼O), 197.1 (C-1) ppm; IR (KBr): ꢃꢀ¼ 1745, 1689, 1631, 1604,
þ
1548, 1448, 1346, 1270, 1193, 1147, 1076, 717 cmꢂ1
; MS (EI, 70 eV): m=z (%) ¼ 330 (M ꢆ, 40), 315
(42), 195 (100), 179 (6), 163 (4), 149 (41), 121 (12), 103 (16), 92 (7), 75 (37), 63 (7).
40-Methoxy-20-(4-methyl-3-nitrobenzoyloxy)acetophenone (6p, C17H15NO6)
Yield 82%; mp 131–132ꢅC; 1H NMR (300MHz, CDCl3): ꢀ ¼ 2.46 (s, H-2), 2.64 (s, 400-CH3), 3.86 (s,
OCH3), 7.02 (d, J ¼ 2.4 Hz, H-30), 7.03 (dd, J ¼ 2.4, 7.2 Hz, H-50), 7.75 (d, J ¼ 8.1Hz, H-500), 8.03 (dd,
J ¼ 2.4, 7.2 Hz, H-60), 8.29 (dd, J ¼ 1.8, 8.1 Hz, H-600), 8.58 (d, J ¼ 1.8 Hz, H-200) ppm; 13C NMR

1514
A. I. R. N. A. Barros and A. M. S. Silva
(75 MHz, CDCl3): ꢀ ¼ 19.9 (400-CH3), 29.0 (C-2), 56.1 (OCH3), 109.6 (C-30), 112.2 (C-50), 122.3
(C-10), 125.5 (C-200), 128.4 (C-100), 133.1 (C-60), 133.8 (C-500), 133.9 (C-600), 138.9 (C-400), 149.0
(C-300), 150.7 (C-20), 162.8 (C¼O), 163.5 (C-40), 195.5 (C-1) ppm; IR (KBr): ꢃꢀ¼ 1733, 1675, 1614,
þ
1567, 1535, 1353, 1282, 1241, 1143, 1066, 875, 815 cmꢂ1
; MS (EI, 70 eV): m=z (%) ¼ 329 (M ꢆ, 33),
314 (7), 164 (100), 147 (13), 118 (33), 106 (5), 90 (25), 63 (8).
40-Methoxy-20-(3,5-dinitrobenzoyloxy)acetophenone (6q, C16H12N2O8)
Yield 76%; mp 103–104ꢅC; 1H NMR (300 MHz, CDCl3): ꢀ ¼ 2.51 (s, H-2), 3.89 (s, OCH3), 7.06 (d,
J ¼ 2.5 Hz, H-30), 7.07 (dd, J ¼ 2.5, 9.4 Hz, H-50), 8.09 (d, J ¼ 9.4Hz, H-60), 9.06 (d, J ¼ 2.1 Hz,
H-200,600), 9.13 (t, J ¼ 2.1 Hz, H-400) ppm; 13C NMR (75 MHz, CDCl3): ꢀ ¼ 28.8 (C-2), 56.1 (OCH3),
109.6 (C-30), 112.3 (C-50), 121.7 (C-10), 123.1 (C-400), 129.3 (C-200,600), 132.2 (C-100), 133.5 (C-60),
148.5 (C-300,500), 150.3 (C-20), 161.5 (C¼O), 163.6 (C-40), 195.7 (C-1) ppm; IR (KBr): ꢃꢀ¼ 1756, 1671,
þ
1610, 1548, 1461, 1347, 1272, 1159, 1070, 711 cmꢂ1
; MS (EI, 70 eV): m=z (%) ¼ 360 (M ꢆ, 53), 345
(100), 195 (87), 149 (45), 103 (12), 75 (47).
60-Methoxy-20-(2-methyl-3-nitrobenzoyloxy)acetophenone (6r, C17H15NO6)
Yield 78%; mp 137–138ꢅC; 1H NMR (300MHz, CDCl3): ꢀ ¼ 2.45 (s, H-2), 2.52 (s, 400-CH3), 3.90 (s,
OCH3), 7.02 (d, J ¼ 8.3 Hz, H-30), 7.14 (d, J ¼ 8.3 Hz, H-50), 7.54 (t, J ¼ 8.3 Hz, H-40), 7.65 (t,
J ¼ 7.9 Hz, H-500), 8.12–8.15 (m, H-400 and H-600) ppm; 13C NMR (75 MHz, CDCl3): ꢀ ¼ 15.5
(400-CH3), 31.7 (C-2), 56.4 (OCH3), 110.1 (C-50), 115.3 (C-30), 123.5 (C-10), 127.6 (C-500), 130.0
(C-400), 131.6 (C-100), 131.8 (C-40), 132.1 (C-200), 133.6 (C-600), 146.8 (C-20), 151.7 (C-300), 157.4
(C-60), 164.1 (C¼O), 200.0 (C-1) ppm; IR (KBr): ꢃꢀ¼ 1749, 1687, 1602, 1573, 1525, 1469, 1438,
þ
1344, 1276, 1213, 1101, 1022, 734 cmꢂ1
; MS (EI, 70 eV): m=z (%) ¼ 329 (M ꢆ, 12), 164 (100), 147
(6), 118 (24), 107 (8), 90 (27), 63 (11).
60-Methoxy-20-(4-methyl-3-nitrobenzoyloxy)acetophenone (6s, C17H15NO6)
Yield 87%; mp 117–118ꢅC; 1H NMR (300MHz, CDCl3): ꢀ ¼ 2.52 (s, H-2), 270 (s, 400-CH3), 3.90 (s,
OCH3), 6.85 (dd, J ¼ 0.6, 8.3 Hz, H-30), 6.91 (dd, J ¼ 0.6, 8.3 Hz, H-50), 7.43 (t, J ¼ 8.3 Hz, H-40), 7.50
(d, J ¼ 8.0 Hz, H-500), 8.23 (dd, J ¼ 1.8, 8.0Hz, H-600), 8.70 (d, J ¼ 1.8 Hz, H-200) ppm; 13C NMR
(75 MHz, CDCl3): ꢀ ¼ 20.7 (400-CH3), 31.7 (C-2), 56.0 (OCH3), 109.2 (C-50), 115.0 (C-30), 123.9
(C-10), 126.4 (C-200), 128.4 (C-100), 131.3 (C-40), 133.3 (C-500), 133.9 (C-600), 139.3 (C-400), 147.6
(C-300), 149.2 (C-20), 157.7 (C-60), 163.0 (C¼O), 200.2 (C-1) ppm; IR (KBr): ꢃꢀ¼ 1745, 1698, 1604,
þ
1521, 1473, 1346, 1292, 1234, 1124, 1068, 730 cmꢂ1
; MS (EI, 70 eV): m=z (%) ¼ 329 (M ꢆ, 32), 314
(14), 298 (5), 164 (100), 148 (21), 118 (36), 107 (13), 90 (29), 63 (11).
60-Methoxy-20-(3,5-dinitrobenzoyloxy)acetophenone (6t, C16H12N2O8)
Yield 54%; mp 180–182ꢅC; 1H NMR (300 MHz, CDCl3): ꢀ ¼ 2.56 (s, H-2), 3.94 (s, OCH3), 6.87 (dd,
J ¼ 0.6, 8.3 Hz, H-30), 6.97 (dd, J ¼ 0.6, 8.3 Hz, H-50), 7.49 (t, J ¼ 8.3Hz, H-40), 9.25 (d, J ¼ 2.1 Hz,
H-200,600), 9.28 (t, J ¼ 2.1 Hz, H-400) ppm; 13C NMR (75 MHz, CDCl3): ꢀ ¼ 32.0 (C-2), 56.1 (OCH3),
109.9 (C-50), 114.9 (C-30), 122.9 (C-400), 123.0 (C-10), 130.0 (C-200,600), 132.0 (C-40), 133.0 (C-100),
147.6 (C-20), 148.7 (C-300,500), 158.4 (C-60), 161.3 (C¼O), 199.9 (C-1) ppm; IR (KBr): ꢃꢀ¼ 1754, 1691,
1600, 1550, 1469, 1344, 1272, 1226, 1155, 1068, 921, 800 cmꢂ1; MS (EI, 70eV): m=z (%) ¼ 360
þ
(M ꢆ, 51), 345 (100), 195 (91), 179 (7), 149 (56), 103 (20), 91 (9), 75 (52).
40,60-Dimethoxy-20-(4-methyl-3-nitrobenzoyloxy)acetophenone (6u, C18H17NO7)
Yield 87%; mp 135–136ꢅC; 1H NMR (300MHz, CDCl3): ꢀ ¼ 2.48 (s, H-2), 2.69 (s, 400-CH3), 3.84 (s,
OCH3), 3.88 (s, OCH3), 6.36 (d, J ¼ 2.2 Hz, H-30), 6.43 (d, J ¼ 2.2 Hz, H-50), 7.49 (d, J ¼ 8.0 Hz,
H-500), 8.24 (dd, J ¼ 1.8, 8.0 Hz, H-600), 8.70 (d, J ¼ 1.8 Hz, H-200) ppm; 13C NMR (75 MHz, CDCl3):
ꢀ ¼ 20.7 (400-CH3), 32.0 (C-2), 55.4 (OCH3), 56.6 (OCH3), 96.8 (C-50), 100.1 (C-30), 116.5 (C-10),
126.4 (C-200), 128.6 (C-100), 133.2 (C-500), 134.0 (C-600), 139.1 (C-400), 149.2 (C-300), 149.7 (C-20), 159.7
(C-60), 162.5 (C-40), 163.1 (C¼O), 198.8 (C-1) ppm; IR (KBr): ꢃꢀ¼ 1743, 1670, 1612, 1577, 1533,

Efficient Synthesis of Nitroflavones
1515
1353, 1335, 1284, 1249, 1228, 1149, 1118, 1068, 836, 738 cmꢂ1; MS (EI, 70eV): m=z (%) ¼ 359
þ
(M ꢆ, 48), 344 (53), 181 (14), 164 (100), 147 (13), 137 (6), 118 (36), 90 (25), 63 (7).
40,60-Dimethoxy-20-(3,5-dinitrobenzoyloxy)acetophenone (6v, C17H14N2O9)
Yield 45%; mp 201–202ꢅC; 1H NMR (300MHz, CDCl3): ꢀ ¼ 2.42 (s, H-2), 3.85 (s, OCH3), 3.92 (s,
OCH3), 6.68 (d, J ¼ 2.0 Hz, H-30), 6.70 (d, J ¼ 2.0 Hz, H-50), 8.98 (t, J ¼ 2.1 Hz, H-200,600), 9.10 (t,
J ¼ 2.1 Hz, H-400) ppm; 13C NMR (75 MHz, CDCl3): ꢀ ¼ 32.0 (C-2), 56.0 (OCH3), 56.5 (OCH3), 97.3
(C-50), 101.0 (C-30), 115.5 (C-10), 123.2 (C-400), 129.2 (C-200,600), 131.8 (C-100), 148.5 (C-300,500), 149.0
(C-20), 159.6 (C-60), 161.3 (C-40), 164.2 (C¼O), 198.0 (C-1) ppm; IR (KBr): ꢃꢀ¼ 1762, 1683, 1608,
þ
1546, 1455, 1344, 1280, 1157, 1068, 919, 831, 715 cmꢂ1
; MS (EI, 70eV): m=z (%) ¼ 390 (M ꢆ, 41),
375 (100), 195 (56), 181 (14), 149 (39), 137 (7), 103 (13), 75 (27).
50-Bromo-20-(3,5-dinitrobenzoyloxy)acetophenone (6z, C15H9N2O7Br)
Yield 89%; mp 131–132ꢅC; 1H NMR (300 MHz, CDCl3): ꢀ ¼ 2.59 (s, H-2), 7.49 (d, J ¼ 8.6 Hz, H-30),
7.97 (dd, J ¼ 2.4, 8.6 Hz, H-40), 8.25 (d, J ¼ 2.4 Hz, H-60), 9,07 (d, J ¼ 2.0 Hz, H-200,600), 9.13 (t,
13
J ¼ 2.0 Hz, H-400) ppm; C NMR (75 MHz, CDCl3): ꢀ ¼ 29.3 (C-2), 97.3 (C-50), 101.0 (C-30), 119.4
(C-50), 123.3 (C-400), 126.3 (C-30), 129.4 (C-200,600), 131.5 and 131.8 (C-10 and C-100), 133.5 (C-60),
136.7 (C-40), 147.1 (C-20), 148.6 (C-300,500), 161.4 (C¼O), 196.7 (C-1) ppm; IR (KBr): ꢃꢀ¼ 1739, 1687,
1627, 1548, 1457, 1343, 1274, 1236, 1191, 1147, 1070, 713 cmꢂ1; MS (EI, 70 eV): m=z (%) ¼ 410
81
79Br, 26), 393 (4), 195 (100), 187 (3), 179 (6), 149 (36), 103 (14), 75 (39),
þ
þ
(M ꢆ, Br, 26), 408 (M ꢆ,
63 (19).
General Method for the Baker-Venkataraman Rearrangement of 20-(Nitrobenzoyloxy)
acetophenones 6a–6v and 6z
NaH (0.270g, 11.2mmol) was added to a solution of the appropriate 6a–6v and 6z (7mmol) in 15cm3
dry THF. The mixture was refluxed until complete disappearance of the starting material, which was
monitored by tlc (2h for ortho-nitro derivatives 6a, 6d, 6g, 6j; 3 h for meta- and para-nitro derivatives
6b, 6c, 6e, 6f, 6h, 6i, 6k, 6l; 3.5 h for dinitro derivatives 6o, 6q, 6t, 6v, 6z; 2.5 h for 40-methyl-30-nitro
derivatives 6n, 6p, 6s, 6u; 5 h for 20-methyl-30-nitro derivatives 6m, 6r). After that period, the solution
was poured into 50 g ice and 50 cm3 water, and pH was adjusted to 3 with HCl. The obtained solid was
removed by filtration, taken in 40cm3 CHCl3, and purified by silica gel column chromatography, using
CDCl3 as the eluent. The solvent was evaporated in each case to dryness and the residue was crystal-
lized from ethanol to give the expected products. From the NMR data one can find these compounds as
a mixture of two or three isomeric structures – 3-hydroxy-1-(2-hydroxyphenyl)-3-(nitrophenyl)-2-
propen-1-ones 7a–7v and 7z, or 1-(2-hydroxyphenyl)-3-(nitrophenyl)propan-1,3-diones 8a–8v, 8z, or
2-hydroxyflavanones 9a–9v and 9z. The reaction yields were calculated thinking to have the presence
of 3-hydroxy-1-(2-hydroxyphenyl)-3-(nitrophenyl)-2-propen-1-ones 7a–7v, 7z: 7a, 53%; 7b, 64%; 7c,
75%; 7d, 45%; 7e, 65%; 7f, 62%; 7g, 52%; 7h, 72%; 7i, 70%; 7j, 21%; 7k, 61%; 7l, 58%; 7m, 73%;
7n, 80%; 7o, 65%; 7p, 68%; 7q, 48%; 7r, 77%; 7s, 80%; 7t, 60%; 7u, 63%; 7v, 47%; 7z, 64%. We will
present data of the main isomeric structure present in the NMR spectra, together with the main NMR
features of the minor one(s).
Isomers 7a:9a in the Proportion of 8:92
3-Hydroxy-1-(2-hydroxyphenyl)-3-(2-nitrophenyl)-2-propen-1-one (7a, C15H11NO5)
1H NMR (300MHz, CDCl3): ꢀ ¼ 7.92 (s, H-2), 11.18 (s, 20-OH), 14.96 (s, 3-OH) ppm.
2-Hydroxy-20-nitroflavanone (9a, C15H11NO5)
1H NMR (300 MHz, CDCl3): ꢀ ¼ 2.92 (d, J ¼ 16.3 Hz, H-3), 3.43 (d, J ¼ 16.3Hz, H-3), 7.12–7.18 (m,
H-6 and H-8), 7.65 (t, J ¼ 7.7 Hz, H-7), 7.89 (d, J ¼ 8.1 Hz, H-5), 8.17 (d, J ¼ 8.2 Hz, H-50), 8.28 (d,
J ¼ 8.2 Hz, H-40), 8.36 (d, J ¼ 8.2 Hz, H-60), 8.46 (d, J ¼ 8.2 Hz, H-30) ppm; 13C NMR (75 MHz,

1516
A. I. R. N. A. Barros and A. M. S. Silva
CDCl3): ꢀ ¼ 49.6 (C-3), 96.7 (C-2), 118.5 (C-8), 120.5 (C-10), 122.0 (C-6), 123.6 (C-30), 125.6 (C-5),
126.6 (C-10), 131.6 (C-60), 133.9 (C-40), 135.0 (C-50), 135.9 (C-7), 148.0 (C-20), 157.5 (C-9), 190.6
(C-4) ppm.
IR (KBr): ꢃꢀ¼ 1635, 1575, 1513, 1486, 1430, 1295, 1178, 956, 813, 748 cmꢂ1; MS (EI, 70 eV):
þ
m=z (%) ¼ 285 (M ꢆ, 75), 268 (25), 163 (22), 150 (100), 134 (10), 121 (85), 104 (24), 92 (18), 76 (19),
65 (20).
Isomers 7b:8b:9b in the Proportion of 5:30:65
3-Hydroxy-1-(2-hydroxyphenyl)-3-(3-nitrophenyl)-2-propen-1-one (7b, C15H11NO5)
1H NMR (300MHz, CDCl3): ꢀ ¼ 7.57 (s, H-2), 11.19 (s, 20-OH), 16.38 (s, 3-OH) ppm.
1-(2-Hydroxyphenyl)-3-(3-nitrophenyl)propan-1,3-dione (8b, C15H11NO5)
1H NMR (300MHz, CDCl3): ꢀ ¼ 4.92 (s, H-2), 11.19 (s, 20-OH) ppm.
2-Hydroxy-30-nitroflavanone (9b, C15H11NO5)
1H NMR (300 MHz, CDCl3): ꢀ ¼ 2.92 (d, J ¼ 16.2Hz, H-3), 3.43 (d, J ¼ 16.2 Hz, H-3), 7.12–7.19
(m, H-6 and H-8), 7.65 (t, J ¼ 7.7 Hz, H-7), 7.80 (d, J ¼ 7.0Hz, H-5), 8.14 (d, J ¼ 7.9 Hz, H-50), 8.30
(d, J ¼ 7.9 Hz, H-40), 8.46 (d, J ¼ 7.9Hz, H-60), 8.51 (br s, H-20) ppm; 13C NMR (75 MHz, CDCl3):
ꢀ ¼ 48.9 (C-3), 96.7 (C-2), 118.6 (C-8), 120.5 (C-20), 121.4 (C-10), 121.7 (C-6), 123.6 (C-40), 125.7
(C-5), 127.0 (C-10), 130.1 (C-60), 132.6 (C-50), 136.3 (C-7), 147.6 (C-30), 157.8 (C-9), 190.6 (C-4) ppm.
IR(KBr):ꢃꢀ¼ 1600, 1577, 1529, 1486, 1432, 1346, 1295, 1201, 750 cmꢂ1; MS (EI, 70eV):m=z (%) ¼
þ
285 (M ꢆ, 73), 268 (24), 163 (18), 150 (100), 134 (9), 121 (83), 104 (22), 92 (16), 76 (19), 65 (18).
Isomers 8c:9c in the Proportion of 13:87
1-(2-Hydroxyphenyl)-3-(4-nitrophenyl)propan-1,3-dione (8c, C15H11NO5)
1H NMR (300MHz, CDCl3): ꢀ ¼ 4.87 (s, H-2), 11.16 (s, 20-OH) ppm.
2-Hydroxy-40-nitroflavanone (9c, C15H11NO5)
1H NMR (300MHz, CDCl3): ꢀ ¼ 2.89 (d, J ¼ 16.3Hz, H-3), 3.35 (d, J ¼ 16.3Hz, H-3), 7.14 (d,
J ¼ 7.8 Hz, H-6 and H-8), 7.64 (ddd, J ¼ 1.5, 7.2, 7.8Hz, H-7), 7.79 (dd, J ¼ 1.5, 7.2Hz, H-5), 7.95
(d, J ¼ 8.9Hz, H-20,60), 8.31 (d, J ¼ 8.9 Hz, H-30,50), 11.27 (br s, 2-OH) ppm; 13C NMR (75 MHz,
CDCl3): ꢀ ¼ 49.8 (C-3), 101.6 (C-2), 117.7 (C-10), 118.5 (C-8), 121.7 (C-6), 123.5 (C-30,50), 125.7 (C-5),
127.2 (C-20,60), 136.3 (C-7), 139.8 (C-10), 147.6 (C-9), 149.2 (C-40), 157.8 (C-9), 190.5 (C-4) ppm.
IR (KBr): ꢃꢀ¼ 1614, 1575, 1517, 1484, 1434, 1338, 1295, 1197, 1160, 1029, 757cmꢂ1; MS (EI,
þ
70eV): m=z (%) ¼ 285 (M ꢆ, 79), 268 (24), 163 (13), 150 (100), 134 (3), 121 (62), 104 (23), 92 (21),
76 (14), 65 (19).
Isomers 7d:8d in the Proportion of 75:25
3-Hydroxy-1-(2-hydroxy-4-methoxyphenyl)-3-(2-nitrophenyl)-2-propen-1-one (7d, C16H13NO6)
1H NMR (300MHz, CDCl3): ꢀ ¼ 3.86 (s, OCH3), 6.41 (s, H-2), 6.46 (d, J ¼ 2.3 Hz, H-30), 6.49 (dd,
J ¼ 2.3, 8.8 Hz, H-50), 7.56–7.65 (m, H-400 and H-500), 7.68 (d, J ¼ 8.8Hz, H-60), 7.70 (d, J ¼ 8.0 Hz,
H-300), 7.93 (d, J ¼ 7.6 Hz, H-600), 12.38 (s, 20-OH), 14.94 (s, 3-OH) ppm; 13C NMR (75 MHz, CDCl3):
ꢀ ¼ 55.8 (OCH3), 96.0 (C-2), 100.8 (C-30), 108.4 (C-50), 112.6 (C-10), 124.3 (C-600), 130.2 (C-300),
130.9 (C-60), 132.6 (C-500), 132.8 (C-400), 134.7 (C-100), 148.4 (C-200), 165.2 (C-20), 166.4 (C-40), 174.2
(C-3), 194.7 (C-1) ppm.
1-(2-Hydroxy-4-methoxyphenyl)-3-(2-nitrophenyl)propan-1,3-dione (8d, C16H13NO6)
1H NMR (300MHz, CDCl3): ꢀ ¼ 4.49 (s, H-2), 12.26 (s, 20-OH) ppm.
IR (KBr): ꢃꢀ¼ 1621, 1569, 1527, 1471, 1347, 1253, 1155, 1018, 788cmꢂ1; MS (EI, 70eV):
þ
m=z (%) ¼ 315 (M ꢆ, 59), 298 (22), 193 (16), 151 (100), 134 (5), 124 (15), 95 (5), 76 (10).

Efficient Synthesis of Nitroflavones
1517
3-Hydroxy-1-(2-hydroxy-4-methoxyphenyl)-3-(3-nitrophenyl)-2-propen-1-one (7e, C16H13NO6)
1H NMR (300MHz, CDCl3): ꢀ ¼ 3.86 (s, OCH3), 6.46 (d, J ¼ 2.4Hz, H-30), 6.51 (dd, J ¼ 2.4, 8.9Hz,
H-50), 6.77 (s, H-2), 7.66–7.71 (m, H-500), 7.72 (d, J ¼ 8.9 Hz, H-60), 8.24 (d, J ¼ 7.8 Hz, H-600), 8.37
(dd, J ¼ 1.2, 8.1 Hz, H-400), 8.72 (br s, H-200), 12.41 (s, 20-OH), 15.31 (s, 3-OH) ppm; 13C NMR
(75 MHz, CDCl3): ꢀ ¼ 55.6 (OCH3), 93.0 (C-2), 101.3 (C-30), 108.3 (C-50), 112.3 (C-10), 121.4
(C-200), 126.1 (C-400), 129.9 (C-500), 130.3 (C-60), 132.2 (C-600), 135.6 (C-100), 148.4 (C-300), 165.6
(C-20), 166.4 (C-40), 172.2 (C-3), 194.7 (C-1) ppm; IR (KBr): ꢃꢀ¼ 1616, 1585, 1519, 1444, 1342,
þ
1257, 1199, 1016, 786 cmꢂ1
; MS (EI, 70 eV): m=z (%) ¼ 315 (M ꢆ, 53), 298 (23), 193 (18), 151 (100),
124 (17), 104 (20), 76 (20).
3-Hydroxy-1-(2-hydroxy-4-methoxyphenyl)-3-(4-nitrophenyl)-2-propen-1-one (7f, C16H13NO6)
1H NMR (300MHz, CDCl3): ꢀ ¼ 3.87 (s, OCH3), 6.49 (d, J ¼ 2.5Hz, H-30), 6.51 (dd, J ¼ 2.5, 8.8Hz,
H-50), 6.76 (s, H-2), 7.68 (d, J ¼ 8.8 Hz, H-60), 8.06 (d, J ¼ 8.8 Hz, H-200,600), 8.31 (d, J ¼ 8.8 Hz,
H-300,500), 12.28 (s, 20-OH), 15.15 (s, 3-OH) ppm; 13C NMR (75 MHz, CDCl3): ꢀ ¼ 55.6 (OCH3),
94.1 (C-2), 101.7 (C-30), 108.4 (C-50), 112.7 (C-10), 123.9 (C-300,500), 127.5 (C-200,600), 130.3 (C-100),
133.6 (C-60), 149.9 (C-400), 165.9 (C-20), 166.7 (C-40), 172.4 (C-3), 194.9 (C-1) ppm; IR (KBr):
ꢃꢀ¼ 1616, 1585, 1519, 1342, 1275, 1199, 1133, 1016, 786 cmꢂ1; MS (EI, 70 eV): m=z (%) ¼ 315
þ
(M ꢆ, 58), 298 (20), 193 (12), 151 (100), 124 (18), 104 (22), 91 (24), 76 (21), 65 (19).
Isomers 7g:8g in the Proportion of 50:50
3-Hydroxy-1-(2-hydroxy-6-methoxyphenyl)-3-(2-nitrophenyl)-2-propen-1-one (7g, C16H13NO6)
1H NMR (300 MHz, CDCl3): ꢀ ¼ 3.79 (s, OCH3), 6.48–6.59 (m, H-30 and H-50), 6.42 (s, H-2), 7.39 (t,
J ¼ 8.3 Hz, H-40), 7.74–7.91 (m, H-400,500,600), 8.03 (dd, J ¼ 2.0, 8.7 Hz, H-300), 10.36 (s, 20-OH), 14.81
(s, 3-OH) ppm; 13C NMR (75 MHz, CDCl3): ꢀ ¼ 55.9 (OCH3), 102.4 (C-50), 105.1 (C-2), 109.7 (C-30),
112.9 (C-10), 124.5 (C-600), 129.8 (C-300), 131.9 (C-500), 133.3 (C-400), 134.2 (C-100), 135.5 (C-40), 148.2
(C-200), 158.4 (C-60), 160.7 (C-20), 173.6 (C-3), 191.7 (C-1) ppm.
1-(2-Hydroxy-6-methoxyphenyl)-3-(2-nitrophenyl)propan-1,3-dione (8g, C16H13NO6)
1H NMR (300 MHz, CDCl3): ꢀ ¼ 3.79 (s, OCH3), 4.63 (s, H-2), 6.48–6.59 (m, H-30 and H-50), 7.28 (t,
J ¼ 8.3 Hz, H-40), 7.74–7.91 (m, H-400,500,600), 8.03 (dd, J ¼ 2.0, 8.7 Hz, H-300), 10.36 (s, 20-OH) ppm;
13C NMR (75 MHz, CDCl3): ꢀ ¼ 50.0 (C-2), 57.0 (OCH3), 102.3 (C-50), 109.2 (C-30), 112.5 (C-10),
124.2 (C-300), 129.5 (C-600), 130.6 (C-100), 132.7 (C-400), 132.8 (C-40), 133.6 (C-500), 148.2 (C-200), 158.3
(C-60), 160.7 (C-20), 192.4 (C-3), 198.9 (C-1) ppm.
IR (KBr): ꢃꢀ¼ 1758, 1688, 1608, 1543, 1470, 1352, 1282, 1227, 1111, 1083, 783, 730cmꢂ1; MS
þ
(EI, 70 eV): m=z (%) ¼ 315 (M ꢆ, 11), 284 (4), 181 (15), 164 (19), 151 (100), 136 (14), 125 (19), 107
(23), 92 (11), 76 (24), 65 (19).
Isomers 7h:8h in the Proportion of 84:16
3-Hydroxy-1-(2-hydroxy-6-methoxyphenyl)-3-(3-nitrophenyl)-2-propen-1-one (7h, C16H13NO6)
1H NMR (300 MHz, CDCl3): ꢀ ¼ 4.00 (s, OCH3), 6.47 (d, J ¼ 8.3, H-30), 6.63 (dd, J ¼ 0.8, 8.3 Hz,
H-50), 7.38 (t, J ¼ 8.3 Hz, H-40), 7.47 (s, H-2), 7.69 (t, J ¼ 8.0 Hz, H-500), 8.23 (dd, J ¼ 1.1, 8.0 Hz,
H-600), 8.37 (ddd, J ¼ 1.1, 2.0, 8,0Hz, H-400), 8.74 (t, J ¼ 2.0 Hz, H-200), 12.43 (s, 20-OH), 15.50 (s,
13
3-OH) ppm; C NMR (75 MHz, CDCl3): ꢀ ¼ 56.1 (OCH3), 99.8 (C-2), 101.9 (C-30), 110.4 (C-50),
111.3 (C-10), 121.7 (C-200), 127.7 (C-400), 129.9 (C-500), 132.3 (C-600), 136.0 (C-40), 137.1 (C-100), 148.5
(C-300), 160.5 (C-60), 164.1 (C-20), 173.2 (C-3), 195.5 (C-1) ppm.
1-(2-Hydroxy-6-methoxyphenyl)-3-(3-nitrophenyl)propan-1,3-dione (8h, C16H13NO6)
1H NMR (300MHz, CDCl3): ꢀ ¼ 4.68 (s, H-2), 12.89 (s, 20-OH) ppm.
IR (KBr): ꢃꢀ¼ 1631, 1579, 1527, 1355, 1241, 1089, 821 cmꢂ1; MS (EI, 70 eV): m=z (%) ¼ 315
þ
(M ꢆ, 55), 298 (33), 284 (64), 193 (18), 150 (100), 136 (15), 122 (25), 104 (29), 92 (8), 76 (22), 65 (11).

1518
A. I. R. N. A. Barros and A. M. S. Silva
Isomers 7i:8i:9i in the Proportion of 46:15:39
3-Hydroxy-1-(2-hydroxy-6-methoxyphenyl)-3-(4-nitrophenyl)-2-propen-1-one (7i, C16H13NO6)
1H NMR (300MHz, CDCl3): ꢀ ¼ 3.82 (s, OCH3), 6.58 (d, J ¼ 8.3 Hz, H-30), 6.59 (d, J ¼ 8.3 Hz, H-50),
6.89 (s, H-2), 7.52 (t, J ¼ 8.3 Hz, H-40), 8.18 (d, J ¼ 8.7 Hz, H-200,600), 8.40 (d, J ¼ 8.7 Hz, H-300,500),
10.38 (s, 200-OH), 15.93 (s, 3-OH) ppm; 13C NMR (75 MHz, CDCl3): ꢀ ¼ 56.7 (OCH3), 101.3 (C-2),
102.2 (C-3 ), 109.5 (C-50), 110.4 (C-10), 124.4 (C-300,500), 128.6 (C-200,600), 130.0 (C-100), 136.4 (C-40),
149.7 (C-400), 158.5 (C-60), 160.1 (C-20), 176.6 (C-3), 192.8 (C-1) ppm.
1-(2-Hydroxy-6-methoxyphenyl)-3-(4-nitrophenyl)propan-1,3-dione (8i, C16H13NO6)
1H NMR (300MHz, CDCl3): ꢀ ¼ 4.74 (s, H-2), 12.24 (s, 20-OH) ppm.
2-Hydroxy-5-methoxy-40-nitroflavanone (9i, C16H13NO6)
1H NMR (300MHz, CDCl3): ꢀ ¼ 2.77 (d, J ¼ 15.6 Hz, H-3), 3.24 (d, J ¼ 15.6Hz, H-3), 3.88 (s,
OCH3), 6.70 (d, J ¼ 8.4 Hz, H-6), 6.73 (d, J ¼ 8.4 Hz, H-6), 7.29 (t, J ¼ 8.4 Hz, H-7), 7.93 (d,
J ¼ 8.7 Hz, H-20,60), 8.30 (d, J ¼ 8.7Hz, H-30,50) ppm; 13C NMR (75MHz, CDCl3): ꢀ ¼ 50.4 (C-3),
56.3 (OCH3), 96.0 (C-2), 105.3 (C-8), 110.6 (C-6), 120.6 (C-10), 123.9 (C-30,50), 127.5 (C-20,60), 130.4
(C-10), 133.0 (C-7), 147.9 (C-40), 157.5 (C-9), 159.7 (C-5), 188.5 (C-4) ppm.
IR (KBr): ꢃꢀ¼ 1725, 1621, 1594, 1457, 1344, 1236, 1182, 1093, 788, 727 cmꢂ1; MS (EI, 70 eV):
þ
m=z (%) ¼ 315 (M ꢆ, 37), 298 (41), 284 (65), 193 (11), 149 (100), 136 (10), 122 (18), 102 (27), 90
(11), 75 (18), 65 (10).
Isomers 7j:8j in the Proportion of 35:65
3-Hydroxy-1-(2-hydroxy-4,6-dimethoxyphenyl)-3-(2-nitrophenyl)-2-propen-1-one (7j, C17H15NO7)
1H NMR (300MHz, CDCl3): ꢀ ¼ 6.79 (s, H-2), 12.03 (s, 20-OH), 13.80 (s, 3-OH) ppm.
1-(2-Hydroxy-4,6-methoxyphenyl)-3-(2-nitrophenyl)propan-1,3-dione (8j, C17H15NO7)
1H NMR (300 MHz, CDCl3): ꢀ ¼ 3.82 (s, OCH3), 3.83 (s, OCH3), 4.65 (s, H-2), 6.10 (d, J ¼ 2.4 Hz,
H-50), 6.13 (d, J ¼ 2.4Hz, H-30), 7.81–7.84 (m, H-400), 7.89 (dt, J ¼ 1.5, 7.5 Hz, H-500), 7.98 (dd,
J ¼ 1.5, 7.5 Hz, H-600), 8.04 (dd, J ¼ 1.5, 8.5 Hz, H-300), 13.41 (s, 20-OH) ppm; 13C NMR (75 MHz,
CDCl3): ꢀ ¼ 55.8 (OCH3), 55.9 (OCH3), 56.3 (C-2), 91.0 (C-50), 93.9 (C-30), 105.4 (C-10), 124.1
(C-300), 129.6 (C-600), 130.0 (C-100), 132.3 (C-400), 133.4 (C-500), 147.3 (C-200), 161.4 (C-60), 166.4
(C-40), 166.7 (C-20), 194.8 (C-3), 197.8 (C-1) ppm.
IR (KBr): ꢃꢀ¼ 1617, 1594, 1565, 1525, 1434, 1353, 1255, 1214, 1157, 1108, 821cmꢂ1; MS (EI,
þ
70eV): m=z (%) ¼ 345 (M ꢆ, 10), 211 (11), 194 (8), 181 (100), 150 (11), 137 (14), 109 (12), 95 (18),
76 (25), 69 (22), 63 (13).
Isomers 7k:8k in the Proportion of 66:34
3-Hydroxy-1-(2-hydroxy-4,6-dimethoxyphenyl)-3-(3-nitrophenyl)-2-propen-1-one (7k, C17H15NO7)
1H NMR (300 MHz, CDCl3): ꢀ ¼ 3.89 (s, OCH3), 3.96 (s, OCH3), 6.01 (d, J ¼ 2.4 Hz, H-50), 6.06 (d,
J ¼ 2.4 Hz, H-30), 7.43 (s, H-2), 7.67 (t, J ¼ 8.1Hz, H-500), 8.20 (dt, J ¼ 2.0, 8.1 Hz, H-600), 8.35 (dt,
J ¼ 2.0, 8.1 Hz, H-400), 8.71 (t, J ¼ 2.0Hz, H-200), 13.33 (s, 20-OH), 15.35 (s, 3-OH) ppm; 13C NMR
(75 MHz, CDCl3): ꢀ ¼ 55.8 (OCH3), 56.0 (OCH3), 91.6 (C-50), 93.9 (C-30), 99.1 (C-2), 104.5 (C-10),
121.5 (C-200), 125.8 (C-400), 129.9 (C-500), 132.1 (C-600), 136.2 (C-100), 148.4 (C-300), 162.0 (C-60), 166.0
(C-40), 167.4 (C-20), 171.8 (C-3), 194.1 (C-1) ppm.
1-(2-Hydroxy-4,6-dimethoxyphenyl)-3-(3-nitrophenyl)propan-1,3-dione (8k, C17H15NO7)
1H NMR (300MHz, CDCl3): ꢀ ¼ 4.61 (s, H-2), 13.56 (s, 20-OH) ppm.
IR (KBr): ꢃꢀ¼ 1612, 1569, 1531, 1351, 1292, 1261, 1220, 1164, 1116, 811 cmꢂ1; MS (EI,
þ
70eV): m=z (%) ¼ 345 (M ꢆ, 36), 328 (23) 314 (24), 223 (8), 181 (100), 154 (22), 137 (6), 104
(9), 76 (10).

Efficient Synthesis of Nitroflavones
1519
Isomers 7l:8l in the Proportion of 42:58
3-Hydroxy-1-(2-hydroxy-4,6-dimethoxyphenyl)-3-(4-nitrophenyl)-2-propen-1-one (7l, C17H15NO7)
1H NMR (300 MHz, CDCl3): ꢀ ¼ 3.86 (s, OCH3), 3.91 (s, OCH3), 6.15 (d, J ¼ 2.4 Hz, H-50), 6.19 (d,
J ¼ 2.4 Hz, H-30), 7.25 (s, H-2), 7.90 (d, J ¼ 8.9 Hz, H-300,500), 8.14 (d, J ¼ 8.9Hz, H-200,600), 12.14 (s,
20-OH), 15.30 (s, 3-OH) ppm; 13C NMR (75 MHz, CDCl3): ꢀ ¼ 55.7 (OCH3), 55.9 (OCH3), 91.2
(C-50), 100.7 (C-30), 103.9 (C-10), 105.0 (C-2), 126.9 (C-300,500), 128.0 (C-200,600), 130.4 (C-100),
149.2 (C-400), 166.3 (C-60), 166.4 (C-40), 167.0 (C-20), 171.6 (C-3), 191.6 (C-1) ppm.
1-(2-Hydroxy-4,6-dimethoxyphenyl)-3-(4-nitrophenyl)propan-1,3-dione (8l, C17H15NO7)
1H NMR (300 MHz, CDCl3): ꢀ ¼ 3.88 (s, OCH3), 3.94 (s, OCH3), 4.70 (s, H-2), 6.05 (d, J ¼ 2.1 Hz,
H-50), 6.15 (d, J ¼ 2.1 Hz, H-30), 8.21 (d, J ¼ 8.7 Hz, H-300,500), 8.38 (d, J ¼ 8.7 Hz, H-200,600), 13.43 (s,
13
20-OH) ppm; C NMR (75 MHz, CDCl3): ꢀ ¼ 50.1 (C-2), 55.6 (OCH3), 56.0 (OCH3), 90.9 (C-50),
100.3 (C-30), 107.0 (C-10), 123.9 (C-300,500), 130.1 (C-200,600), 136.6 (C-100), 149.1 (C-400), 162.2 (C-60),
166.2 (C-40), 166.7 (C-20), 194.0 (C-3), 198.4 (C-1) ppm.
IR (KBr): ꢃꢀ¼ 1617, 1567, 1535, 1347, 1251, 1164, 1027, 790, 728 cmꢂ1; MS (EI, 70 eV):
þ
m=z (%) ¼ 345 (M ꢆ, 50), 328 (35), 314 (34), 223 (9), 181 (100), 154 (34), 137 (7), 104 (13), 76 (6).
3-Hydroxy-1-(2-hydroxyphenyl)-3-(2-methyl-3-nitrophenyl)-2-propen-1-one (7m, C16H13NO5)
1H NMR (300MHz, CDCl3): ꢀ ¼ 2.60 (s, CH3), 6.40–6.44 (m, H-30 and H-50), 6.90 (s, H-2), 7.48 (d,
J ¼ 9.2 Hz, H-40), 7.52 (t, J ¼ 8.0 Hz, H-500), 7.70 (dd, J ¼ 1.0, 8.0 Hz, H-600), 7.84 (dd, J ¼ 1.0, 8.0Hz,
H-400), 8.06 (d, J ¼ 7.8 Hz, H-60), 12.43 (s, 20-OH), 15.40 (s, 3-OH) ppm; 13C NMR (75 MHz, CDCl3):
ꢀ ¼ 16.5 (CH3), 99.6 (C-2), 119.4 (C-10), 117.4 (C-30), 119.4 (C-10), 119.6 (C-50), 127.4 (C-60), 127.6
(C-400), 127.9 (C-500), 131.4 (C-400), 135.6 (C-40), 137.6 (C-100), 141.9 (C-300), 150.9 (C-200), 178.6 (C-3),
190.0 (C-1) ppm; IR (KBr): ꢃꢀ¼ 1624, 1586, 1520, 1464, 1359, 1239, 1089, 717 cmꢂ1; MS (EI 70eV):
þ
m=z (%) ¼ 299 (M ꢆ, 60), 298 (50), 282 (47), 164 (100), 144 (70), 120 (27), 77 (12), 65 (28).
Isomers 7n:8n:9n in the Proportion of 43:7:50
3-Hydroxy-1-(2-hydroxyphenyl)-3-(4-methyl-3-nitrophenyl)-2-propen-1-one (7n, C16H13NO5)
1H NMR (300MHz, CDCl3): ꢀ ¼ 2.59 (s, CH3), 6.93–7.03 (m, H-30 and H-50), 7.49 (s, H-2), 7.50 (d,
J ¼ 9.6 Hz, H-40), 7.70 (d, J ¼ 8.0Hz, H-500), 7.91 (dd, J ¼ 1.6, 8.0 Hz, H-600), 8.06 (d, J ¼ 6.8 Hz,
H-60), 8.55 (d, J ¼ 1.2 Hz, H-200), 11.32 (s, 20-OH), 14.97 (s, 3-OH) ppm; 13C NMR (75 MHz, CDCl3):
ꢀ ¼ 19.7 (CH3), 96.1 (C-2), 117.6 (C-30), 119.4 (C-50), 119.8 (C-10), 122.7 (C-200), 129.8 (C-60), 130.6
(C-600), 133.5 (C-100), 133.6 (C-500), 135.3 (C-40), 137.3 (C-400), 149.3 (C-300), 159.5 (C-20), 179.2 (C-3),
189.0 (C-1) ppm.
1-(2-Hydroxyphenyl)-3-(4-methyl-3-nitrophenyl)propan-1,3-dione (8n, C16H13NO5)
1H NMR (300MHz, CDCl3): ꢀ ¼ 4.86 (s, H-2), 11.20 (s, 20-OH) ppm.
2-Hydroxy-40-methyl-30-nitroflavanone (9n, C16H13NO5)
1H NMR (300MHz, CDCl3): ꢀ ¼ 2.56 (s, CH3), 2.89 (d, J ¼ 16.1Hz, H-3), 3.39 (d, J ¼ 16.1Hz, H-3),
7.12 (d, J ¼ 7.7 Hz, H-6), 7.14 (d, J ¼ 7.7 Hz, H-8), 7.60 (t, J ¼ 7.7 Hz, H-7), 7.62 (d, J ¼ 7.6Hz, H-50),
7.79 (dd, J ¼ 1.1, 7.7 Hz, H-5), 8.22 (d, J ¼ 7.6Hz, H-60), 8.24 (d, J ¼ 1.6 Hz, H-20) ppm; 13C NMR
(75 MHz, CDCl3): ꢀ ¼ 19.6 (CH3), 49.6 (C-3), 101.3 (C-2), 118.6 (C-8), 120.6 (C-10), 121.6 (C-6),
125.6 (C-5), 131.1 (C-60), 133.2 (C-50), 133.4 (C-10), 136.2 (C-7), 142.1 (C-40), 148.6 (C-30), 157.5
(C-9), 190.7 (C-4) ppm.
IR (KBr): ꢃꢀ¼ 1614, 1577, 1529, 1488, 1432, 1340, 1305, 1207, 1047, 771 cmꢂ1; MS (EI, 70 eV):
þ
m=z (%) ¼ 299 (M ꢆ, 64), 282 (15), 164 (100), 148 (9), 121 (68), 90 (12), 77 (7), 65 (14).
2-Hydroxy-30,50-dinitroflavanone (9o, C15H10N2O7)
1H NMR (300 MHz, CDCl3): ꢀ ¼ 2.99 (d, J ¼ 16.3Hz, H-3), 3.56 (d, J ¼ 16.3 Hz, H-3), 7.01–7.21 (m,
H-6 and H-8), 7.67 (t, J ¼ 7.4 Hz, H-7), 7.83 (d, J ¼ 7.4 Hz, H-5), 8.87–8.90 (m, H-20,40,60) ppm; 13C

1520
A. I. R. N. A. Barros and A. M. S. Silva
NMR (75 MHz, CDCl3): ꢀ ¼ 50.1 (C-3), 100.9 (C-2), 118.6 (C-8), 119.0 (C-40), 120.6 (C-10), 122.0 (C-
6), 125.7 (C-5), 126.5 (C-20,60), 126.8 (C-10), 136.4 (C-7), 148.1 (C-30,50), 157.5 (C-9), 190.1 (C-4) ppm;
IR (KBr): ꢃꢀ¼ 1613, 1570, 1542, 1486, 1345, 1297, 1194, 1160, 917, 730 cmꢂ1; MS (EI, 70 eV): m=z
þ
(%) ¼ 330 (M ꢆ, 68), 313 (31), 195 (29), 183 (46), 163(31), 157 (8), 149(19), 121 (100), 92(23), 65 (17).
Isomers 7p:8p:9p in the Proportion of 40:13:47
3-Hydroxy-1-(2-hydroxy-4-methoxyphenyl)-3-(4-methyl-3-nitrophenyl)-2-propen-1-one (7p, C17H15NO6)
1H NMR (300 MHz, CDCl3): ꢀ ¼ 2.59 (s, CH3), 3.83 (s, OCH3), 6.52 (d, J ¼ 2.4 Hz, H-30), 6.57 (dd,
J ¼ 2.4, 9.0 Hz, H-50), 7.38 (s, H-2), 7.60 (d, J ¼ 8.2 Hz, H-600), 7.84 (d, J ¼ 8.2 Hz, H-500), 8.14 (d,
J ¼ 9.0 Hz, H-60), 8.25 (d, J ¼ 1.7 Hz, H-200), 11.95 (s, 20-OH), 15.93 (s, 3-OH) ppm; 13C NMR
(75 MHz, CDCl3): ꢀ ¼ 19.6 (CH3), 55.7 (OCH3), 94.5 (C-2), 100.9 (C-30), 107.5 (C-50), 112.7 (C-10),
121.5 (C-200), 130.3 (C-100), 130.6 (C-500), 131.9 (C-60), 133.1 (C-600), 136.5 (C-400), 149.4 (C-300), 164.7
(C-20), 165.8 (C-40), 175.0 (C-3), 191.1 (C-1) ppm.
1-(2-Hydroxy-4-methoxyphenyl)-3-(4-methyl-3-nitrophenyl)propan-1,3-dione (8p, C17H15NO6)
1H NMR (300MHz, CDCl3): ꢀ ¼ 4.86 (s, H-2), 11.90 (s, 20-OH) ppm.
2-Hydroxy-40-methyl-7-methoxy-30-nitroflavanone (9p, C17H15NO6)
1H NMR (300MHz, CDCl3): ꢀ ¼ 2.60 (s, CH3), 2.90 (d, J ¼ 16.0Hz, H-3), 3.56 (d, J ¼ 16.0Hz, H-3),
3.88 (s, OCH3), 6.70 (dd, J ¼ 2.4, 8.5 Hz, H-6), 6.71 (d, J ¼ 2.4Hz, H-8), 7.68 (d, J ¼ 8.0 Hz, H-50),
7.73 (d, J ¼ 8.5 Hz, H-5), 8.27 (d, J ¼ 8.0 Hz, H-60), 8.56 (d, J ¼ 1.6Hz, H-20) ppm; 13C NMR
(75 MHz, CDCl3): ꢀ ¼ 19.6 (CH3), 47.6 (C-3), 55.7 (OCH3), 100.7 (C-10), 101.5 (C-2), 101.9 (C-6),
109.6 (C-8), 114.3 (C-10), 122.4 (C-20), 124.6 (C-60), 126.5 (C-5), 133.5 (C-50), 136.9 (C-40), 148.6
(C-30), 157.8 (C-9), 162.6 (C-7), 191.6 (C-4) ppm.
IR (KBr): ꢃꢀ¼ 1600, 1527, 1498, 1349, 1255, 1135, 1018, 806 cmꢂ1; MS (EI, 70 eV): m=z (%) ¼
þ
329 (M ꢆ, 70), 312 (27), 193 (15), 164 (54), 151 (100), 124 (20), 108 (12), 90 (15), 77 (10).
3-Hydroxy-1-(2-hydroxy-4-methoxyphenyl)-3-(3,5-dinitrophenyl)-2-propen-1-one (7q, C16H12N2O8)
1H NMR (300MHz, CDCl3): ꢀ ¼ 3.89 (s, OCH3), 6.49 (d, J ¼ 2.5Hz, H-30), 6.57 (dd, J ¼ 2.5, 8.9Hz,
H-50), 6.87 (s, H-2), 7.76 (d, J ¼ 8.9 Hz, H-60), 9.05 (d, J ¼ 2.0 Hz, H-200,600), 9.17 (t, J ¼ 2.0 Hz, H-400),
12.30 (s, 20-OH), 15.34 (s, 3-OH) ppm; 13C NMR (75 MHz, CDCl3): ꢀ ¼ 55.8 (OCH3), 94.1 (C-2),
101.4 (C-30), 108.8 (C-50), 112.2 (C-10), 120.8 (C-400), 126.6 (C-200,600), 130.6 (C-60), 137.8 (C-100),
148.9 (C-300,500), 166.0 (C-20), 167.0 (C-40), 168.9 (C-3), 194.7 (C-1) ppm; IR (KBr): ꢃꢀ¼ 1612, 1585,
þ
1515, 1340, 1261, 1216, 1159, 1112, 750 cmꢂ1
; MS (EI, 70 eV): m=z (%) ¼ 360 (M ꢆ, 42), 343 (14),
193 (13), 151 (100), 137 (3), 124 (8), 95 (5), 75 (10), 69 (7).
Isomers 7r:8r in the Proportion of 86:14
3-Hydroxy-1-(2-hydroxy-6-methoxyphenyl)-3-(2-methyl-3-nitrophenyl)-2-propen-1-one (7r, C17H15NO6)
1H NMR (300MHz, CDCl3): ꢀ ¼ 2.62 (s, CH3), 3.88 (s, OCH3), 6.42 (dd, J ¼ 0.8, 8.4Hz, H-30), 6.62
(dd, J ¼ 0.8, 8.4 Hz, H-50), 6.92 (s, H-2), 7.36 (t, J ¼ 8.4Hz, H-40), 7.43 (t, J ¼ 8.0Hz, H-500), 7.72 (dd,
J ¼ 1.2, 8.0 Hz, H-600), 7.89 (dd, J ¼ 1.2, 8.0 Hz, H-400), 12.39 (s, 20-OH), 15.37 (s, 3-OH) ppm; 13C
NMR (75 MHz, CDCl3): ꢀ ¼ 16.7 (CH3), 56.0 (OCH3), 101.8 (C-30), 104.5 (C-2), 110.2 (C-10), 111.2
(C-50), 125.6 (C-400), 126.7 (C-500), 131.1 (C-200), 132.5 (C-600), 135.9 (C-40), 138.4 (C-100), 151.4
(C-300), 160.4 (C-60), 164.1 (C-20), 177.3 (C-3), 195.4 (C-1) ppm.
1-(2-Hydroxy-6-methoxyphenyl)-3-(2-methyl-3-nitrophenyl)propan-1,3-dione (8r, C17H15NO6)
1H NMR (300MHz, CDCl3): ꢀ ¼ 4.60 (s, H-2), 12.88 (s, 20-OH) ppm.
IR (KBr): ꢃꢀ¼ 1619, 1583, 1523, 1454, 1359, 1238, 1089, 717 cmꢂ1; MS (EI, 70 eV): m=z (%) ¼
þ
329 (M ꢆ, 60), 312 (25), 298 (53), 280 (8), 193 (14), 164 (85), 151 (100), 136 (20), 124 (17), 118 (26),
108 (23), 90 (27), 77 (16), 65 (18).

Efficient Synthesis of Nitroflavones
1521
3-Hydroxy-1-(2-hydroxy-6-methoxyphenyl)-3-(4-methyl-3-nitrophenyl)-2-propen-1-one
(7s, C17H15NO6)
1H NMR (300 MHz, CDCl3): ꢀ ¼ 2.37 (s, CH3), 3.78 (s, OCH3), 6.31 (s, H-2), 6.52–6.58 (m, H-30 and
H-50), 7.28 (t, J ¼ 8.3 Hz, H-40), 7.58 (d, J ¼ 7.6 Hz, H-500), 7.81 (d, J ¼ 7.6 Hz, H-600), 8.03 (d,
J ¼ 1.9 Hz, H-200), 10.39 (s, 20-OH), 15.38 (s, 3-OH) ppm; 13C NMR (75 MHz, CDCl3): ꢀ ¼ 15.30
(CH3), 55.9 (OCH3), 101.5 (C-30), 105.3 (C-2), 109.2 (C-50), 110.1 (C-10), 125.9 (C-200), 127.6 (C-500),
132.4 (C-600), 135.5 (C-40), 136.0 (C-100), 138.5 (C-400), 151.2 (C-300), 158.3 (C-60), 160.0 (C-20), 182.7
(C-3), 189.2 (C-1) ppm; IR (KBr): ꢃꢀ¼ 1619, 1583, 1525, 1455, 1361, 1240, 1091, 719 cmꢂ1; MS (EI
þ
70eV): m=z (%) ¼ 329 (M ꢆ, 69), 312 (41), 298 (83), 193 (17), 164 (56), 151 (100), 136 (19), 118
(32), 107 (29), 90 (27), 77 (16), 65 (18).
Isomers 7t:8t in the Proportion of 88:12
3-Hydroxy-1-(2-hydroxy-6-methoxyphenyl)-3-(3,5-dinitrophenyl)-2-propen-1-one (7t, C16H12N2O8)
1H NMR (300MHz, CDCl3): ꢀ ¼ 4.02 (s, OCH3), 6.49 (d, J ¼ 8.2 Hz, H-30), 6.62 (d, J ¼ 8.2 Hz, H-50),
7.41 (t, J ¼ 8.2 Hz, H-40), 7.57 (s, H-2), 9.03 (d, J ¼ 2.1 Hz, H-200,600), 9.16 (t, J ¼ 2.1Hz, H-400), 12.34
13
(s, 20-OH), 15.33 (s, 3-OH) ppm; C NMR (75 MHz, CDCl3): ꢀ ¼ 56.2 (OCH3), 100.8 (C-30), 101.9
(C-2), 110.2 (C-50), 111.5 (C-10), 120.7 (C-400), 126.3 (C-200,600), 136.6 (C-40), 138.1 (C-100), 148.9
(C-300,500), 160.6 (C-60), 164.5 (C-20), 169.5 (C-3), 195.9 (C-1) ppm.
1-(2-Hydroxy-6-methoxyphenyl)-3-(3,5-dinitrophenyl)propan-1,3-dione (8t, C16H12N2O8)
1H NMR (300MHz, CDCl3): ꢀ ¼ 4.74 (s, H-2), 12.66 (s, 20-OH) ppm.
IR (KBr): ꢃꢀ¼ 1610, 1573, 1542, 1448, 1342, 1220, 1180, 1083, 819, 730 cmꢂ1; MS (EI, 70 eV):
þ
m=z (%) ¼ 360 (M ꢆ, 56), 343 (35), 329 (68), 193 (21), 151 (100), 136 (15), 122 (21), 93 (6), 75 (24),
65 (10).
Isomers 7u:8u in the Proportion of 87:13
3-Hydroxy-1-(2-hydroxy-4,6-dimethoxyphenyl)-3-(4-methyl-3-nitrophenyl)-2-propen-1-one (7u, C18H17NO7)
1H NMR (300 MHz, CDCl3): ꢀ ¼ 2.67 (s, CH3), 3.86 (s, OCH3), 3.94 (s, OCH3), 5.99 (d, J ¼ 2.3 Hz,
H-50), 6.10 (d, J ¼ 2.3 Hz, H-30), 7.36 (s, H-2), 7.40–7.49 (m, H-500), 7.98 (dd, J ¼ 1.4, 8.1 Hz, H-600),
8.46 (d, J ¼ 1.4 Hz, H-200), 13.35 (s, 20OH), 15.37 (s, 3-OH) ppm; 13C NMR (75 MHz, CDCl3):
ꢀ ¼ 20.7 (CH3), 55.8 (OCH3), 56.0 (OCH3), 91.6 (C-50), 94.1 (C-30), 98.5 (C-2), 104.4 (C-10), 124.3
(C-200), 130.7 (C-500), 133.3 (C-600), 136.8 (C-100), 149.3 (C-400), 150.7 (C-300), 161.9 (C-60), 166.0
(C-40), 167.3 (C-20), 172.1 (C-3), 193.9 (C-1) ppm.
1-(2-Hydroxy-4,6-dimethoxyphenyl)-3-(4-methyl-3-nitrophenyl)propan-1,3-dione (8u, C18H17NO7)
1H NMR (300MHz, CDCl3): ꢀ ¼ 4.56 (s, H-2), 13.59 (s, 20-OH) ppm.
IR (KBr): ꢃꢀ¼ 1731, 1612, 1558, 1529, 1442, 1347, 1261, 1220, 1110, 821 cmꢂ1; MS (EI, 70 eV):
þ
m=z (%) ¼ 359 (M ꢆ, 47), 342 (27), 328 (29), 223 (8), 181 (100), 164 (18), 154 (38), 118 (13), 90 (10),
69 (5).
Isomers 7v:8v in the Proportion of 86:14
3-Hydroxy-1-(2-hydroxy-4,6-dimethoxyphenyl)-3-(3,5-dinitrophenyl)-2-propen-1-one (7v, C17H14N2O9)
1H NMR (300 MHz, CDCl3): ꢀ ¼ 3.85 (s, OCH3), 3.88 (s, OCH3), 6.28 (d, J ¼ 2.2 Hz, H-50), 6.30 (d,
J ¼ 2.2 Hz, H-30), 7.06 (s, H-2), 8.79 (d, J ¼ 2.0 Hz, H-200,600), 9.00 (t, J ¼ 2.0 Hz, H-400), 13.23 (s, 20-
OH), 15.25 (s, 3-OH) ppm; 13C NMR (75 MHz, CDCl3): ꢀ ¼ 55.4 (OCH3), 55.6 (OCH3), 93.2 (C-50),
94.7 (C-30), 99.9 (C-2), 106.6 (C-10), 122.1 (C-400), 126.0 (C-200,600), 136.8 (C-100), 148.0 (C-300,500),
161.3 (C-60), 162.7 (C-40), 166.0 (C-20), 170.8 (C-3), 195.9 (C-1) ppm.
1-(2-Hydroxy-4,6-dimethoxyphenyl)-3-(3,5-dinitrophenyl)propan-1,3-dione (8v, C17H14N2O9)
1H NMR (300MHz, CDCl3): ꢀ ¼ 4.22 (s, H-2), 13.65 (s, 20-OH) ppm.

1522
A. I. R. N. A. Barros and A. M. S. Silva
IR (KBr): ꢃꢀ¼ 1616, 1571, 1535, 1346, 1286, 1218, 1159, 1110, 833 cmꢂ1; MS (EI 70eV):
þ
m=z (%) ¼ 390 (M ꢆ, 40), 374 (6), 359 (28), 223 (16), 181 (100), 166 (8), 154 (22), 137 (10), 95
(9), 75 (16).
6-Bromo-2-hydroxy-30,500-dinitroflavanone (9z, C15H9N2O7Br)
1H NMR (300MHz, CDCl3): ꢀ ¼ 3.03 (d, J ¼ 16.2Hz, H-3), 3.60 (d, J ¼ 16.2Hz, H-3), 7.21 (d,
J ¼ 8.7 Hz, H-8), 7.83 (dd, J ¼ 2.4, 8.7 Hz, H-7), 7.89 (d, J ¼ 2.4Hz, H-5), 8.86 (d, J ¼ 1.8 Hz,
H-20,60), 8.91 (t, J ¼ 1.8 Hz, H-40) ppm; 13C NMR (75 MHz, CDCl3): ꢀ ¼ 48.3 (C-3), 100.4 (C-2),
48.3 (C-2), 101.3 (C-10), 113.7 (C-6), 119.2 (C-30,50), 121.3 (C-8), 122.1 (C-10), 126.5 (C-20,60
and C-40), 127.8 (C-5), 138.7 (C-7), 156.7 (C-9), 189.1 (C-4) ppm; IR (KBr): ꢃꢀ¼ 1621, 1567,
81Br,
þ
1542, 1529,þ1471, 1344, 1272, 1197, 829, 730 cmꢂ1
; MS (EI, 70 eV): m=z (%) ¼ 410 (M ꢆ
79Br, 75), 393 (14), 241 (19), 200 (100), 179 (15), 172 (27), 149 (46), 120 (11), 89 (16),
75), 408 (M ꢆ
75 (79), 63 (52).
General Method for the Preparation of Flavones 4a–4f, 4h, 4k, and 4x–4w from
20-Hydroxychalcones 3a–3f, 3h, 3k, and 3x–3w
Iodine (0.39 mmol) was added to a solution of 3a–3f, 3h, 3k, and 3x–3w (10 mmol) in 15cm3 DMSO.
The mixture was heated at reflux for 30 min, and then was poured into 150 g ice and 150 cm3 water
with a few crystals of sodium thiosulfate. The obtained solid was removed by filtration, taken in
150 cm3 CHCl3, and washed with a 20% aqueous solution of sodium thiosulfate (2ꢄ150 cm3). The
organic layer was dried (Na2SO4) and the solvent evaporated to dryness. The residue was purified by
column chromatography, using CHCl3 as the eluent. Finally the compound, in each case, was recrys-
tallized from ethanol. The obtained yields were as follows: 4a, 32%; 4b, 86%; 4c, 79%; 4d, 36%; 4e,
69%; 4f, 74%; 4h, 74%; 4k, 62%; 4x, 60%; 4y, 81%; 4w, 64%.
General Method for the Preparation of Flavones 4a–4v and 4z from 3-Hydroxy-1-
(2-hydroxyphenyl)-3-(nitrophenyl)-2-propen-1-ones 7a–7v and 7z
Method A
p-Toluenesulfonic acid (0.85 g, 4.4mmol) was added to a solution of the appropriate 7b, 7e, 7h, 7k,
7o, 7q, 7t, 7v, and 7z (8.8mmol) in 20 cm3 DMSO. The solution was heated at 80–90ꢅC until the
disappearance of the starting material (tlc). The solution was poured into 50 g ice and 50cm3 H2O and
the obtained solid was removed by filtration, taken in 20cm3 CHCl3, and purified by silica gel column
chromatography, using CHCl3 as the eluent. The solvent was evaporated to dryness and the residue was
recrystallized from ethanol:acetone to give the expected products: 4b, 68%, 4e, 58%; 4h, 65%; 4k,
53%; 4o, 59%; 4q, 57%; 4t, 82%; 4v, 63%; 4z, 63%.
Method B
Iodine (1.76 mmol) was added to a solution of the appropriate 7b, 7c, 7e, 7f, 7h, 7i, 7k, 7l, 7n, 7p, 7s,
and 7u (8.8mmol). The solution was heated, under N2, at 80–90ꢅC for 3 h. After that period it was
poured into 50g ice and 50 cm3 H2O with a few crystals of sodium thiosulfate. The solid obtained was
removed by filtration, taken in 50cm3 CHCl3, and purified by silica gel column chromatography, using
CHCl3 as the eluent. The solvent was evaporated to dryness and the residue was recrystallized from
ethanol or ethyl acetate to give the expected products: 4b, 72%; 4c, 71%; 4e, 64%; 4f, 80%; 4h, 71%;
4i, 78%; 4k, 65%; 4l, 52%; 4n, 70%; 4p, 81%; 4s, 72%; 4u, 54%.
Method C
A 1% (v=v) mixture of acetic acid=sulfuric acid (10 cm3) was added to a solution of the appropriate 7a,
7d, 7g, 7j, 7m, and 7r (8.8mmol). The reaction mixture was heated at 80–90ꢅC, under N2, for 6 h.
After that period it was poured into 50 g ice and 50cm3 H2O; the obtained solid was removed by
filtration, taken in 30 cm3 chloroform, and purified by silica gel column chromatography, using a 2:3

Efficient Synthesis of Nitroflavones
1523
mixture of n-hexane:CHCl3 as the eluent. The solvent was evaporated to dryness and the residue was
recrystallized from ethyl acetate to give the expected products: 4a, 64%; 4d, 47%; 4g, 32%; 4j, 38%;
4m, 63%; 4r, 60%.
20-Nitroflavone (4a, C15H9NO4)
1
Mp 181–183ꢅC; H NMR (300 MHz, CDCl3): ꢀ ¼ 6.77 (s, H-3), 7.52 (t, J ¼ 7.8 Hz, H-6), 7.57 (d,
J ¼ 7.8 Hz, H-8), 7.78–7.96 (m, H-40,50,60, H-7), 8.07 (dd, J ¼ 1.3, 7.8 Hz, H-5), 8.18 (dd, J ¼ 1.1,
7.9 Hz, H-30) ppm; 13C NMR (75 MHz, CDCl3): ꢀ ¼ 111.1 (C-3), 118.4 (C-8), 123.3 (C-10), 125.2
(C-30, C-5), 126.2 (C-6), 126.6 (C-10), 131.8 (C-60), 132.9 (C-40), 134.3 (C-50), 135.1 (C-7), 147.7
(C-20), 155.9 (C-9), 162.1 (C-2), 177.1 (C-4) ppm; IR (KBr): ꢃꢀ¼ 1646, 1610, 1533, 1477, 1380, 1347,
þ
781 cmꢂ1
; MS (EI, 70 eV): m=z (%) ¼ 267 (M ꢆ, 12), 246 (4), 239 (20), 211 (18), 195 (11), 181 (12),
165 (25), 152 (14), 139 (13), 120 (100), 104 (26), 92 (80), 83 (5), 76 (29), 63 (31).
30-Nitroflavone (4b)
Mp 196–197ꢅC (Ref. [10c] 197ꢅC, [10e] 200–201ꢅC, [10d] 194–195ꢅC).
40-Nitroflavone (4c)
Mp 242–244ꢅC (Ref. [10c] 242ꢅC, [10e] 246–247ꢅC, [10d] 244–245ꢅC).
7-Methoxy-20-nitroflavone (4d, C16H11NO5)
Mp 181–182ꢅC; 1H NMR (300 MHz, CDCl3): ꢀ ¼ 3.90 (s, OCH3), 6.64 (s, H-3), 7.00 (d,
J ¼ 1.8 Hz, H-8), 7.11 (dd, J ¼ 1.8, 8.4 Hz, H-6), 7.84–7.94 (m, H-40, H-50, H-60), 8.00 (d,
J ¼ 8.4 Hz, H-5), 8.20 (d, J ¼ 7.7 Hz, H-30) ppm; 13C NMR (75 MHz, CDCl3): ꢀ ¼ 56.0 (OCH3),
100.5 (C-8), 110.7 (C-3), 114.9 (C-6), 116.9 (C-10), 124.7 (C-30), 126.3 (C-5), 126.1 (C-10), 131.4
(C-60), 132.3 (C-40), 133.9 (C-50), 147.3 (C-20), 157.5 (C-9), 161.2 (C-2), 164.1 (C-7), 175.8 (C-4)
ppm; IR (KBr): ꢃꢀ¼ 1643, 1612, 1519, 1442, 1376, 1347, 1247, 858 cmꢂ1; MS (EI, 70 eV): m=z
þ
(%) ¼ 297 (M ꢆ, 24), 276 (3), 254 (4), 240 (5), 227 (8), 196 (3), 180 (4), 168 (5), 150 (100), 134
(6), 122 (57), 107 (30), 92 (13), 79 (18), 63 (16).
7-Methoxy-30-nitroflavone (4e, C16H11NO5)
Mp 213–214ꢅC; 1H NMR (300MHz, CDCl3): ꢀ ¼ 3.95 (s, OCH3), 7.09 (dd, J ¼ 2.4, 8.8 Hz, H-6), 7.12
(s, H-3), 7.37 (d, J ¼ 2.4Hz, H-8), 7.86 (t, J ¼ 8.0 Hz, H-50), 7.96 (d, J ¼ 8.8 Hz, H-5), 8.50 (ddd,
J ¼ 1.0, 2.0, 8.0 Hz, H-40), 8.51 (t, J ¼ 1.0, 2.0, 8.0 Hz, H-60), 8.80 (t, J ¼ 2.0 Hz, H-20) ppm; 13C NMR
(75 MHz, CDCl3): ꢀ ¼ 56.0 (OCH3), 101.0 (C-8), 108.2 (C-3), 114.9 (C-6), 117.0 (C-10), 120.5 (C-20),
125.7 (C-40), 126.1 (C-5), 130.6 (C-50), 132.6 (C-60), 132.9 (C-10), 148.3 (C-30), 157.4 (C-9), 159.6 (C-2),
164.0 (C-7), 175.8 (C-4) ppm; IR (KBr): ꢃꢀ¼ 1641, 1531, 1440, 1382, 1346, 1280, 1166, 862 cmꢂ1
;
þ
MS (EI, 70 eV): m=z (%) ¼ 297 (M ꢆ, 100), 269 (43), 254 (23), 223 (11), 208 (9), 196 (3), 180 (3), 150
(18), 122 (14), 107 (9), 79 (7).
7-Methoxy-40-nitroflavone (4f, C16H11NO5)
Mp 213–214ꢅC (Ref. [10a] 216–217ꢅC); 1H NMR (300MHz, CDCl3): ꢀ ¼ 3.95 (s, OCH3), 7.10 (dd,
J ¼ 2.2, 8.9 Hz, H-6), 7.13 (s, H-3), 7.34 (d, J ¼ 2.2 Hz, H-8), 7.98 (d, J ¼ 8.9Hz, H-5), 8.38 (br s, H-
20,60 and H-30,50) ppm; 13C NMR (75 MHz, CDCl3): ꢀ ¼ 56.0 (OCH3), 100.9 (C-8), 109.0 (C-3), 114.8
(C-6), 117.0 (C-10), 123.8 (C-30,50), 126.2 (C-5), 127.4 (C-20,60), 137.1 (C-10), 148.9 (C-40), 157.4 (C-
9), 159.7 (C-2), 164.1 (C-7), 176.1 (C-4) ppm; IR (KBr): ꢃꢀ¼ 1650, 1612, 1517, 1442, 1347, 1089,
þ
852 cmꢂ1
; MS (EI, 70eV): m=z (%) ¼ 297 (M ꢆ, 100), 269 (43), 254 (20), 239 (9), 223 (14), 208 (10),
196 (4), 180 (3), 150 (24), 122 (23), 107 (19), 85 (8), 79 (13), 63 (14).
5-Methoxy-20-nitroflavone (4g, C16H11NO5)
1
Mp 144–145ꢅC; H NMR (300 MHz, CDCl3): ꢀ ¼ 4.01 (s, OCH3), 6.51 (s, H-3), 6.85 (dd, J ¼ 0.8,
8.4 Hz, H-6), 6.93 (dd, J ¼ 0.8, 8.4Hz, H-8), 7.56 (t, J ¼ 8.4Hz, H-7), 7.67–7.79 (m, H-40, H-50 and

1524
A. I. R. N. A. Barros and A. M. S. Silva
H-60), 8.05 (dd, J ¼ 1.4, 8.1 Hz, H-30) ppm; 13C NMR (75 MHz, CDCl3): ꢀ ¼ 56.5 (OCH3), 106.8 (C-6),
109.9 (C-8), 112.7 (C-3), 114.4 (C-10), 124.9 (C-30), 127.3 (C-10), 131.0 (C-40), 131.7 (C-60), 133.3
(C-50), 134.2 (C-7), 148.1 (C-20), 158.3 (C-9), 159.7 (C-2), 159.9 (C-5), 177.7 (C-4) ppm; IR (KBr):
ꢃꢀ¼ 1644, 1606, 1529, 1475, 1440, 1384, 1353, 1259, 1110, 1078, 860, 754 cmꢂ1; MS (EI, 70 eV): m=z
þ
(%) ¼ 297 (M ꢆ, 100), 296 (17), 279 (13), 268 (18), 250 (9), 239 (16), 221 (11), 165 (19), 149 (50),
132 (20), 120 (30), 107 (32), 92 (33), 76 (26), 63 (17).
5-Methoxy-30-nitroflavone (4h, C16H11NO5)
1
Mp 162–166ꢅC; H NMR (300MHz, CDCl3): ꢀ ¼ 4.02 (s, OCH3), 6.82 (s, H-3), 6.88 (d, J ¼ 8.4 Hz,
H-6), 7.20 (d, J ¼ 8.4 Hz, H-8), 7.63 (t, J ¼ 8.4 Hz, H-7), 7.73 (t, J ¼ 8.0 Hz, H-50), 8.19 (d, J ¼ 8.0 Hz,
H-60), 8.38 (d, J ¼ 8.0 Hz, H-40), 8.77 (s, H-20) ppm; 13C NMR (75 MHz, CDCl3): ꢀ ¼ 56.5 (OCH3),
106.8 (C-6), 110.1 (C-8), 110.2 (C-3), 114.4 (C-10), 121.0 (C-20), 125.7 (C-40), 130.2 (C-50), 131.5
(C-60), 133.3 (C-10), 134.3 (C-7), 148.7 (C-30), 158.0 (C-2), 158.2 (C-9), 159.8 (C-5), 177.8 (C-4) ppm;
IR (KBr): ꢃꢀ¼ 1648, 1602, 1527, 1475, 1344, 1267, 1108, 1035, 836 cmꢂ1; MS (EI, 70 eV): m=z
þ
(%) ¼ 297 (M ꢆ, 100), 296 (41), 279 (13), 268 (38), 251 (50), 239 (16), 222 (23), 205 (28), 193
(12), 176 (6), 165 (22), 152 (10), 120 (31), 107 (24), 101 (7), 92 (27), 75 (19), 63 (15).
5-Methoxy-40-nitroflavone (4i, C16H11NO5)
1
Mp 264–265ꢅC; H NMR (300MHz, CDCl3): ꢀ ¼ 4.02 (s, OCH3), 6.83 (s, H-3), 6.88 (d, J ¼ 8.5 Hz,
H-6), 7.17 (dd, J ¼ 0.9, 8.5Hz, H-8), 7.63 (t, J ¼ 8.5 Hz, H-7), 8.08 (d, J ¼ 9.0 Hz, H-20,60), 8.37 (d,
J ¼ 9.0 Hz, H-30,50) ppm; 13C NMR (75 MHz, CDCl3): ꢀ ¼ 56.6 (OCH3), 106.9 (C-6), 110.0 (C-8),
111.1 (C-3), 114.5 (C-10), 124.2 (C-30,50), 127.0 (C-20,60), 134.4 (C-7), 137.4 (C-10), 149.2 (C-40),
158.1 (C-2), 158.4 (C-9), 159.8 (C-5), 177.8 (C-4) ppm; IR (KBr): ꢃꢀ¼ 1639, 1606, 1515, 1475, 1342,
þ
1267, 1097, 1029, 848, 752 cmꢂ1
; MS (EI, 70eV): m=z (%) ¼ 297 (M ꢆ, 100), 296 (43), 279 (10),
268 (36), 251 (51), 239 (15), 222 (26), 205 (34), 181 (6), 165 (21), 149 (23), 120 (41), 105 (27), 90
(30), 64 (13).
5,7-Dimethoxy-20-nitroflavone (4j, C17H13NO6)
Mp 215–216ꢅC; 1H NMR (300 MHz, CDCl3): ꢀ ¼ 3.86 (s, OCH3), 3.96 (s, OCH3), 6.35 (d, J ¼ 2.2 Hz,
H-6), 6.39 (d, J ¼ 2.2 Hz, H-8), 6.46 (s, H-3), 7.66–7.76 (m, H-40, H-50, and H-60), 8.05 (dd, J ¼ 1.5,
7.4 Hz, H-30) ppm; 13C NMR (75 MHz, CDCl3): ꢀ ¼ 55.7 (OCH3), 56.4 (OCH3), 92.5 (C-6), 96.5
(C-8), 109.1 (C-10), 112.8 (C-3), 124.8 (C-30), 127.4 (C-10), 131.0 (C-40), 131.6 (C-60), 133.3 (C-50),
148.0 (C-20), 159.3 (C-2), 160.0 (C-9), 160.9 (C-5), 164.3 (C-7), 176.9 (C-4) ppm; IR (KBr): ꢃꢀ¼ 1654,
þ
1616, 1571, 1527, 1457, 1349, 1164, 1120, 1083, 829cmꢂ1
; MS (EI, 70eV): m=z (%) ¼ 327 (M ꢆ,
100), 326 (27), 313 (9), 298 (21), 281 (8), 179 (42), 150 (26), 137 (13), 122 (22), 76 (8), 63 (10).
5,7-Dimethoxy-30-nitroflavone (4k, C17H13NO6)
Mp 206–207ꢅC; 1H NMR (300 MHz, CDCl3): ꢀ ¼ 3.84 (s, OCH3), 3.92 (s, OCH3), 6.52 (d, J ¼ 2.1 Hz,
H-6), 6.95 (d, J ¼ 2.1Hz, H-8), 7.00 (s, H-3), 7.83 (t, J ¼ 8,0 Hz, H-50), 8.39 (dd, J ¼ 1.5, 8.0Hz, H-40),
8.49 (d, J ¼ 8.0 Hz, H-60), 8.76 (br s, H-20) ppm; 13C NMR (75 MHz, CDCl3): ꢀ ¼ 56.0 (OCH3), 56.1
(OCH3), 91.9 (C-6), 96.9 (C-8), 108.4 (C-10), 109.8 (C-3), 120.4 (C-20), 125.8 (C-40), 130.7 (C-50),
132.3 (C-60), 132.7 (C-10), 148.4 (C-30), 157.2 (C-2), 159.1 (C-5), 164.0 (C-7), 160.3 (C-9), 164.0
(C-2), 175.5 (C-4) ppm; IR (KBr): ꢃꢀ¼ 1660, 1610, 1527, 1463, 1342, 1272, 1124, 1056, 747 cmꢂ1
;
þ
MS (EI, 70 eV): m=z (%) ¼ 327 (M ꢆ, 100), 326 (37), 310 (4), 298 (28), 281 (30), 269 (10), 254 (15),
235 (9), 223 (11), 208 (7), 150 (20), 137 (8), 122 (7), 107 (6), 75 (11), 63 (7).
5,7-Dimethoxy-40-nitroflavone (4l, C17H13NO6)
Mp 235–236ꢅC (Ref. [10a] 235ꢅC); 1H NMR (300MHz, CDCl3): ꢀ ¼ 3.96 (s, OCH3), 4.00 (s, OCH3),
6.44 (d, J ¼ 2.2 Hz, H-6), 6.62 (d, J ¼ 2.2 Hz, H-8), 7.69 (s, H-3), 8.07 (d, J ¼ 8.8Hz, H-20,60), 8.38 (d,
J ¼ 8.8 Hz, H-30,50) ppm; 13C NMR (75 MHz, CDCl3): ꢀ ¼ 55.9 (OCH3), 56.3 (OCH3), 92.8 (C-6),
96.5 (C-8), 109.3 (C-10), 111.2 (C-3), 124.2 (C-30,50), 126.8 (C-20,60), 137.5 (C-10), 149.1 (C-40), 157.9

Efficient Synthesis of Nitroflavones
1525
(C-2), 159.8 (C-9), 161.1 (C-5), 164.5 (C-7), 177.0 (C-4) ppm; IR (KBr): ꢃꢀ¼ 1650, 1610, 1511, 1467,
þ
1342, 1220, 1159, 1025, 850 cmꢂ1
; MS (EI, 70eV): m=z (%) ¼ 327 (M ꢆ, 100), 326 (35), 298 (27),
281 (33), 269 (19), 252 (15), 235 (11), 180 (3), 150 (12), 137 (7), 107 (6), 75 (11), 69 (8).
20-Methyl-30-nitroflavone (4m, C16H11NO4)
1
Mp 183–184ꢅC; H NMR (300 MHz, CDCl3): ꢀ ¼ 2.49 (s, CH3), 6.61 (s, H-3), 7.53 (dt, J ¼ 0.8,
7.7 Hz, H-6), 7.63 (t, J ¼ 8.0Hz, H-50), 7.70 (d, J ¼ 8.2 Hz, H-8), 7.84 (ddd, J ¼ 1.7, 7.7, 8.2Hz, H-7),
7.94 (dd, J ¼ 1.0, 8.0Hz, H-60), 8.08 (dd, J ¼ 1.0, 8.0 Hz H-40), 8.12 (dd, J ¼ 1.7, 7.7Hz, H-5) ppm;
13C NMR (75 MHz, CDCl3): ꢀ ¼ 15.7 (CH3), 112.5 (C-3), 118.3 (C-8), 123.1 (C-10), 124.7 (C-5),
125.4 (C-50), 125.6 (C-40), 125.7 (C-6), 130.1 (C-20), 133.5 (C-60), 134.3 (C-7), 135.0 (C-10), 150.9
(C-30), 155.8 (C-9), 163.0 (C-2), 176.6 (C-4) ppm; IR (KBr): ꢃꢀ¼ 1639, 1606, 1523, 1467, 1374, 1340,
þ
827, 779 cmꢂ1
; MS (EI, 70 eV): m=z (%) ¼ 281 (M ꢆ, 100), 264 (25), 234 (49), 221 (5), 205 (10), 178
(16), 152 (6), 146 (44), 121 (74), 115 (11), 92 (56), 76 (11), 63 (21).
40-Methyl-30-nitroflavone (4n, C16H11NO4)
1
Mp 198–199ꢅC; H NMR (300 MHz, CDCl3): ꢀ ¼ 2.50 (s, CH3), 7.10 (s, H-3), 7.50 (t, J ¼ 7.3 Hz,
H-6), 7.68 (d, J ¼ 7.9Hz, H-50), 7.77–7.86 (m, H-7 and H-8), 8.05 (d, J ¼ 7.3 Hz, H-5), 8.29 (d,
J ¼ 7.9 Hz, H-60), 8.58 (br s, H-20) ppm; 13C NMR (75 MHz, CDCl3): ꢀ ¼ 18.9 (CH3), 107.6 (C-3),
118.3 (C-8), 121.5 (C-20), 123.1 (C-10), 124.5 (C-5), 125.4 (C-6), 130.1 (C-60), 130.3 (C-10), 133.3
(C-50), 134.1 (C-7), 135.6 (C-40), 149.5 (C-30), 155.4 (C-9), 160.1 (C-2), 176.7 (C-4) ppþm; IR (KBr):
ꢃꢀ¼ 1643, 1533, 1461, 1376, 1338, 1139, 728 cmꢂ1
; MS (EI, 70eV): m=z (%) ¼ 281 (M ꢆ, 100), 264
(50), 236 (27), 208 (18), 178 (14), 120 (34), 115 (9), 92 (37), 63 (13).
30,50-Dinitroflavone (4o, C15H8N2O6)
Mp 272–273ꢅC; 1H NMR (300MHz, CDCl3): ꢀ ¼ 7.53 (s, H-3), 7.57 (dd, J ¼ 1.2, 7.7Hz, H-6), 7.89–
7.92 (m, H-7), 7.96 (d, J ¼ 7.7Hz, H-8), 8.08 (dd, J ¼ 1.2, 7.7 Hz, H-5), 8.99 (t, J ¼ 2.0 Hz, H-40), 9.23
(d, J ¼ 2.0 Hz, H-20,60) ppm; 13C NMR (75 MHz, CDCl3): ꢀ ¼ 109.8 (C-3), 119.0 (C-8), 120.9 (C-40),
123.3 (C-6), 124.9 (C-5), 126.1 (C-10), 126.6 (C-20,60), 134.6 (C-10), 134.9 (C-7), 148.8 (C-30,50),
155.7 (C-9), 158.4 (C-2), 177.2 (C-4) ppm; IR (KBr): ꢃꢀ¼ 1639, 1604, 1521, 1465, 1374, 1338, 1132,
þ
777 cmꢂ1
; MS (EI, 70 eV): m=z (%) ¼ 312 (M ꢆ, 100), 284 (23), 219 (10), 192 (8), 163 (11), 145 (8),
120 (33), 92 (29); HRMS (EI): Calcd for C15H8N2O6 312.0382, found: 312.0388.
40-Methyl-7-methoxy-30-nitroflavone (4p, C17H13NO5)
1
Mp 233–234ꢅC; H NMR (300MHz, CDCl3): ꢀ ¼ 2.57 (s, CH3), 3.93 (s, OCH3), 6.99 (s, H-3), 7.04
(dd, J ¼ 2.3, 8.8Hz, H-6), 7.28 (d, J ¼ 2.3 Hz, H-8), 7.65 (d, J ¼ 8.0Hz, H-50), 7.92 (d, J ¼ 8.8 Hz,
H-5), 8.24 (dd, J ¼ 1.6, 8.0 Hz, H-60), 8.54 (d, J ¼ 1.6 Hz, H-20) ppm; 13C NMR (75 MHz, CDCl3):
ꢀ ¼ 18.8 (CH3), 55.9 (OCH3), 100.8 (C-8), 107.5 (C-3), 114.5 (C-6), 117.0 (C-10), 121.2 (C-20), 125.9
(C-5), 129.9 (C-60), 130.3 (C-10), 133.3 (C-50), 135.3 (C-40), 149.4 (C-30), 157.2 (C-9), 159.5 (C-2),
163.0 (C-7), 175.9 (C-4) ppm; IR (KBr): ꢃꢀ¼ 1631, 1600, 1525, 1438, 1247, 1085cmꢂ1; MS (EI,
þ
70eV): m=z (%) ¼ 311 (M ꢆ, 100), 294 (20), 283 (14), 266 (9), 238 (29), 222 (18), 165 (17), 150 (21),
122 (25), 107 (20), 89 (9), 63 (19).
7-Methoxy-30,50-dinitroflavone (4q, C16H10N2O7)
Mp 300–302ꢅC; 1H NMR (300MHz, CDCl3): ꢀ ¼ 3.97 (s, OCH3), 7.10–7.14 (m, H-6), 7.35 (s, H-3),
7.45 (d, J ¼ 1.4Hz, H-8), 7.99 (d, J ¼ 9.0 Hz, H-5), 8.98 (br s, H-40), 9.18 (br s, H-20,60) ppm; 13C
NMR (75 MHz, CDCl3): ꢀ ¼ 56.1 (OCH3), 101.1 (C-8), 109.6 (C-3), 115.1 (C-6), 117.0 (C-10), 120.3
(C-40), 126.1 (C-20,60 and C-5), 134.5 (C-10), 148.7 (C-30,50), 157.4 (C-9), 157.8 (C-2), 164.2 (C-7),
176.0 (C-4) ppm; IR (KBr): ꢃꢀ¼ 1643, 1606, 1536, 1440, 1382, 1340, 1282, 1093, 865 cmꢂ1; MS (EI,
þ
70eV): m=z (%) ¼ 342 (M ꢆ, 46), 314 (12), 299 (5), 242 (23), 222 (6), 150 (8), 107 (7), 91 (100), 79
(6), 65 (14); HRMS (EI): Calcd for C16H10N2O7 342.0488, found 342.0480.

1526
A. I. R. N. A. Barros and A. M. S. Silva
2-Methyl-5-methoxy-30-nitroflavone (4r, C17H13NO5)
Mp 189–190ꢅC; 1H NMR (300 MHz, CDCl3): ꢀ ¼ 2.43 (s, CH3), 3.88 (s, OCH3), 6.43 (s, H-3), 7.02 (d,
J ¼ 8.3 Hz, H-6), 7.18 (d, J ¼ 8.3 Hz, H-8), 7.61 (t, J ¼ 7.9 Hz, H-50), 7.70 (t, J ¼ 8.3 Hz, H-7), 7.91 (d,
J ¼ 7.9 Hz, H-60), 8.07 (d, J ¼ 7.9 Hz, H-40) ppm; 13C NMR (75 MHz, CDCl3): ꢀ ¼ 16.2 (CH3), 56.3
(OCH3), 107.5 (C-6), 110.0 (C-8), 113.7 (C-10), 114.1 (C-3), 126.0 (C-40), 127.6 (C-50), 130.4 (C-20),
133.8 (C-60), 134.7 (C-7), 134.8 (C-10), 151.0 (C-30), 157.9 (C-9), 159.2 (C-5), 160.7 (C-2), 176.2
(C-4) ppm; IR (KBr): ꢃꢀ¼ 1641, 1602, 1475, 1374, 1320, 1267, 1081, 800 cmꢂ1; MS (EI, 70eV): m=z
þ
(%) ¼ 311 (M ꢆ, 100), 310 (32), 293 (9), 282 (27), 265 (34), 247 (11), 219 (12), 178 (7), 151 (6), 121
(17), 107 (25), 92 (16), 63 (16).
40-Methyl-5-methoxy-30-nitroflavone (4s, C17H13NO5)
1
Mp 201–203ꢅC; H NMR (300 MHz, CDCl3): ꢀ ¼ 2.59 (s, CH3), 3.88 (s, OCH3), 6.91 (s, H-3),
7.02 (d, J ¼ 8.3 Hz, H-6), 7.30 (d, J ¼ 8.3 Hz, H-8), 7.67–7.74 (m, H-50 and H-7), 8.24 (dd,
J ¼ 1.8, 8.1 Hz, H-60), 8.53 (d, J ¼ 1.8 Hz, H-20) ppm; 13C NMR (75 MHz, CDCl3): ꢀ ¼ 18.7
(CH3), 56.0 (OCH3), 107.5 (C-6), 109.0 (C-3), 109.8 (C-8), 113.8 (C-10), 121.1 (C-20), 129.7
(C-60), 130.0 (C-10), 133.2 (C-50), 134.0 (C-7), 135.1 (C-40), 149.5 (C-30), 157.2 (C-9), 157.6
(C-2), 159.0 (C-5), 175.8 (C-4) ppm; IR (KBr): ꢃꢀ¼ 1652, 1602, 1525, 1469, 1376, 1261, 1103,
þ
1031, 840, 754 cmꢂ1
; MS (EI, 70 eV): m=z (%) ¼ 311 (M ꢆ, 100), 310 (23), 293 (7), 282 (22),
265 (44), 236 (28), 219 (25), 208 (14), 178 (21), 165 (23), 152 (11), 115 (29), 107 (58), 92 (56),
76 (20), 63 (29).
5-Methoxy-30,50-dinitroflavone (4t, C16H10N2O7)
1
Mp 286–287ꢅC; H NMR (300MHz, CDCl3): ꢀ ¼ 3,90 (s, OCH3), 7.04 (d, J ¼ 8.4 Hz, H-6), 7.21 (s,
H-3), 7.37 (d, J ¼ 8.4 Hz, H-8), 7.73 (t, J ¼ 8.4 Hz, H-7), 8.95 (s, H-40), 9.11 (s, H-20,60) ppm; 13C
NMR (75 MHz, CDCl3): ꢀ ¼ 56.1 (OCH3), 107.7 (C-6), 109.9 (C-8), 111.0 (C-3), 113.7 (C-10), 120.1
(C-40), 125.8 (C-20,60), 134.2 (C-10), 134.4 (C-7), 148.6 (C-30,50), 155.7 (C-2), 157.2 (C-9), 159.0 (C-5),
175.8 (C-4) ppm; IR (KBr): ꢃꢀ¼ 1644, 1602, 1536, 1473, 1363, 1342, 1041, 952, 730 cmꢂ1; MS (EI,
þ
70eV): m=z (%) ¼ 342 (M ꢆ, 100), 341 (23), 324 (8), 313 (24), 296 (26), 284 (8), 250 (17), 232 (10),
221 (15), 192 (10), 163 (17), 150 (10), 120 (24), 107 (25), 69 (25); HRMS (EI): Calcd for C16H10N2O7
342.0488, found 342.0480.
40-Methyl-5,7-dimethoxy-30-nitroflavone (4u, C18H15NO6)
1
Mp 246–247ꢅC; H NMR (300 MHz, CDCl3): ꢀ ¼ 2.69 (s, CH3), 3.94 (s, OCH3), 3.97 (s, OCH3),
6.41 (d, J ¼ 2.3 Hz, H-6), 6.62 (d, J ¼ 2.3 Hz, H-8), 6.71 (s, H-3), 7.50 (d, J ¼ 8.1 Hz, H-50), 7.94
(dd, J ¼ 1.8, 8.1 Hz, H-60), 8.52 (d, J ¼ 1.8 Hz, H-20) ppm; 13C NMR (75 MHz, CDCl3): ꢀ ¼ 20.6
(CH3), 55.9 (OCH3), 56.5 (OCH3), 92.8 (C-6), 96.5 (C-8), 109.2 (C-10), 109.7 (C-3), 122.0
(C-20), 129.6 (C-60), 130.8 (C-10), 133.6 (C-50), 136.5 (C-40), 149.6 (C-30), 157.9 (C-2), 159.7
(C-5), 160.9 (C-7), 164.3 (C-9), 177.1 (C-4) ppm; IR (KBr): ꢃꢀ¼ 1654, 1612, 1571, 1527, 1347,
þ
1276, 1122, 825 cmꢂ1
; MS (EI, 70 eV): m=z (%) ¼ 341 (M ꢆ, 100), 340 (33), 330 (5), 312 (19),
295 (26), 266 (11), 249 (7), 222 (6), 181 (4), 150 (15), 122 (8), 69 (6).
5,7-Dimethoxy-30,50-dinitroflavone (4v, C17H12N2O8)
Mp 244–245ꢅC; 1H NMR (300 MHz, CDCl3): ꢀ ¼ 3.85 (s, OCH3), 3.93 (s, OCH3), 6.51 (d, J ¼ 1.7 Hz,
H-6), 6.91 (d, J ¼ 1.7 Hz, H-8), 7.11 (s, H-3), 8.92 (s, H-40), 9.07 (s, H-20,60) ppm; 13C NMR (75 MHz,
CDCl3): ꢀ ¼ 55.9 (OCH3), 56.0 (OCH3), 93.5 (C-6), 96.6 (C-8), 110.9 (C-3 and C-10), 119.9 (C-40),
125.6 (C-20,60), 134.3 (C-10), 148.5 (C-30,50), 155.1 (C-2), 158.8 (C-5), 160.2 (C-9), 164.0 (C-7), 174.8
(C-4) ppm; IR (KBr): ꢃꢀ¼ 1643, 1600, 1536, 1471, 1340, 1263, 1041, 728 cmꢂ1; MS (EI, 70eV): m=z
þ
(%) ¼ 372 (M ꢆ, 100), 371 (39), 354 (8), 343 (31), 326 (35), 314 (14), 299 (7), 279 (22), 251 (18), 234
(13), 207 (14), 172 (10), 150 (13), 137 (10), 107 (7), 79 (4); HRMS (EI): Calcd for C17H12N2O8
372.0594, found 372.0581.

Efficient Synthesis of Nitroflavones
1527
6-Bromo-20-nitroflavone (4x, C15H8NO4Br)
Mp 208–210ꢅC; 1H NMR (300 MHz, CDCl3): ꢀ ¼ 6.86 (s, H-3), 7.55 (d, J ¼ 8.9 Hz, H-8), 7.88 (ddd,
J ¼ 1.8, 7.2, 8.0 Hz, H-40), 7.92–7.96 (m, H-50 and H-60), 7.98 (dd, J ¼ 2.3, 8.9 Hz, H-7), 8.14 (d,
J ¼ 2.3 Hz, H-5), 8.21 (d, J ¼ 8.0 Hz, H-30) ppm; 13C NMR (75 MHz, CDCl3): ꢀ ¼ 111.0 (C-3), 118.4
(C-6), 120.9 (C-8), 124.6 (C-10), 125.1 (C-30), 126.3 (C-10), 127.1 (C-5), 131.7 (C-60), 132.8 (C-40),
134.2 (C-50), 137.4 (C-7), 147.4 (C-20), 154.7 (C-9), 162.2 (C-2), 175.6 (C-4) ppm; IR (KBr):
ꢃꢀ¼ 1658, 1604, 1523, 1469, 1361, 1282, 1133, 813, 709 cmꢂ1; MS (EI, 70eV): m=z (%) ¼ 347
81
79Br, 100), 300 (3), 289 (13), 238 (20), 220 (10), 210 (25), 198 (75),
þ
þ
(M ꢆ Br, 98), 345 (M ꢆ
163 (47), 146 (15), 119 (100), 104 (43), 90 (35), 75 (46), 63 (70).
6-Bromo-30-nitroflavone (4y, C15H8NO4Br)
1
Mp 243–244ꢅC; H NMR (300 MHz, CDCl3): ꢀ ¼ 7.26 (s, H-3), 7.85–7.90 (m, H-8 and H-50), 8.01
(dd, J ¼ 2.4, 8.9 Hz, H-7), 8.13 (d, J ¼ 2.4Hz, H-5), 8.43 (ddd, J ¼ 0.8, 1.5, 8.0 Hz, H-40), 8.53 (dd,
J ¼ 0.8, 8.0 Hz, H-60), 8.82 (t, J ¼ 1.5 Hz, H-20) ppm; 13C NMR (75 MHz, CDCl3): ꢀ ¼ 108.3 (C-3),
118.0 (C-6), 120.8 (C-20), 121.2 (C-8), 124.7 (C-10), 126.0 (C-40), 126.7 (C-5), 130.6 (C-50), 132.5
(C-60), 132.5 (C-10), 136.9 (C-7), 148.3 (C-30), 154.5 (C-9), 160.4 (C-2), 175.6 (C-4) ppm; IR (KBr):
ꢃꢀ¼ 1641, 1598, 1527, 1436, 1344, 1137, 937, 777 cmꢂ1
81Br,
þ
; MS (EI, 70eV): m=z (%) ¼ 347 (M ꢆ,
79Br, 100), 317 (16), 271 (5), 220 (12), 198 (55), 163 (24), 81 (15), 74 (23), 64 (38).
þ
100), 345 (M ꢆ,
6-Bromo-40-nitroflavone (4w, C15H8NO4Br)
1
Mp 237–238ꢅC; H NMR (300MHz, CDCl3): ꢀ ¼ 7.24 (s, H-3), 7.82 (d, J ¼ 8.9 Hz, H-8), 8.02 (dd,
J ¼ 2.5, 8.9Hz, H-7), 8.16 (d, J ¼ 2.5 Hz, H-5), 8.38 (br s, H-20,60 and H-30,50) ppm; 13C NMR
(75 MHz, CDCl3): ꢀ ¼ 109.0 (C-3), 117.9 (C-6), 121.1 (C-8), 123.7 (C-30,50), 124.6 (C-10), 126.7
(C-5), 127.7 (C-20,60), 136.6 (C-10), 137.0 (C-7), 149.1 (C-40), 154.5 (C-9), 160.4 (C-2), 175.5 (C-4)
ppm; IR (KBr): ꢃꢀ¼ 1641, 1598, 1527, 1436, 1344, 1237, 937, 777cmꢂ1; MS (EI, 70 eV): m=z (%) ¼
81
79Br, 100), 317 (13), 299 (7), 220 (10), 198 (60), 170 (27), 163 (20),
þ
þ
347 (M ꢆ, Br, 100), 345 (M ꢆ,
117 (9), 74 (20), 64 (35).
6-Bromo-30,50-dinitroflavone (4z, C15H7N2O6Br)
1
Mp 300–302ꢅC; H NMR (300MHz, CDCl3): ꢀ ¼ 7.46 (s, H-3), 7.92 (d, J ¼ 8.9 Hz, H-8), 8.04 (dd,
J ¼ 2.4, 8.9Hz, H-7), 8.17 (d, J ¼ 2.4 Hz, H-5), 9.00 (t, J ¼ 2.0 Hz, H-40), 9.20 (d, J ¼ 2.0 Hz, H-20,60)
ppm; 13C NMR (75 MHz, CDCl3): ꢀ ¼ 109.6 (C-3), 118.0 (C-6), 120.5 (C-40), 121.2 (C-8), 124.6 (C-
10), 126.3 (C-20,60), 126.7 (C-5), 134.2 (C-10), 137.0 (C-7), 148.6 (C-30,50), 154.4 (C-9), 158.5 (C-2),
175.5 (C-4) ppm; IR (KBr): ꢃꢀ¼ 1658, 1531, 1459, 1436, 1342, 1274, 948, 7819cmꢂ1; MS (EI, 70 eV):
81
79Br, 100), 362 (7), 299 (8), 270 (2), 198 (37), 170 (20),
þ
þ
m=z (%) ¼ 392 (M ꢆ, Br, 100), 390 (M ꢆ,
163 (14), 100 (4), 74 (12), 63 (24); HRMS (EI): Calcd for C15H7N2O6Br 391.9467, found 391.9486.
References
[1] The Flavonoids – Advances in Research Since 1986 (1994) Harborne JB (ed) Chapman and Hall,
London
[2] a) Flavonoids in Health and Disease (1998) Rice-Evans CA, Packer L (eds) Marcel Dekker,
New York; b) Middleton E Jr, Kandaswami C, Theoharides TC (2000) Pharmacol Rev 52: 673;
c) Harborne JB, Williams CA (2000) Phytochemistry 55: 481; d) Nijveldt RJ, van Nood E,
van Hoorn DEC, Boelens PG, van Norren K, van Leeuwen PAM (2001) Am J Clin Nutr 74: 418;
e) Ren W, Qiao Z, Wang H, Zhu L, Zhang L (2003) Med Res Rev 23: 519
[3] a) Borges ML, Matos OC, Pais I, Melo JS, Ricardo CP, Mac°anita AL, Becker RS (2002) Pestic
Sci 44: 155; b) Parmar VS, Bisht KS, Jain R, Singh S, Charma SK, Gupta S, Malhotra S,
Tyagi OD, Vardhan A, Pati HN, Vanden Bergh D, Vlietinck AJ (1996) Indian J Chem 35B: 220;
€
c) Silva AMS, Weidenborner M, Cavaleiro JASC (1998) Mycol Res 102: 638; d) Borges M,

1528
A. I. R. N. A. Barros and A. M. S. Silva: Efficient Synthesis of Nitroflavones
~
Romao A, Matos O, Marzano C, Caffieri S, Becker RS, Mac
Photobiol 75: 97
°anita AL (2002) Photochem
ꢁ
[4] a) Cotelle N, Bernier JL, Henichart JP, Catteau JP, Gaydou E, Wallet JC (1992) Free Rad Biol
Med 13: 211; b) Rice-Evans CA, Miller NJ, Paganga G (1996) Free Rad Biol Med 20: 933;
c) Bors W, Heller W, Michel C, Stettmaier in Handbook of Antioxidants (1996) Cadenas E,
Packer L (eds) Marcel Dekker, New York, p 409; d) Pietta PG (2000) J Nat Prod 63: 1035;
d) Rice-Evans CA (2001) Curr Med Chem 8: 797
[5] a) Marder M, Viola H, Wasowski C, Wolfman C, Waterman PG, Medina JH, Paladini AC (1995)
Bioorg Med Chem Lett 5: 2717; b) Wolfman C, Viola H, Marder M, Wasowski C, Ardenghi P,
Izquierdo I, Paladini AC, Medina JH (1996) Eur J Pharmacol 318: 23; c) Viola H, Marder M,
Wolfman C, Wasowski C, Medina JH, Paladini AC (1997) Bioorg Med Chem Lett 7: 373; d)
Marder M, Viola H, Bacigaluppo JA, Colombo MI, Wasowski C, Wolfman C, Medina JH,
ꢁ
Ruveda EA, Paladini AC (1998) Biochem Biophys Res Commun 249: 481
´
[6] a) Blank VC, Poli C, Marder M, Roguin LP (2004) Bioorg Med Chem Lett 14: 133; b) Cardenas
M, Marder M, Blank VC, Roguin LP (2006) Bioorg Med Chem 14: 2966
[7] Steele VE, Boone CW, Dauzonne D, Rao CV, Bensasson RV (2002) Cancer Res 62: 6506
[8] a) Lu Y-F, Santostefano M, Cunningham BD, Threadgill MD, Safe S (1995) Arch Biochem
Biophys 316: 470; b) Henry EC, Kende AS, Rucci G, Totleben MJ, Willey JJ, Dertinger SD,
Pollenz RS, Jones JP, Gasiewicz TA (1999) Mol Pharmacol 55: 716; c) Zhou J, Gasiewsicz T
(2003) Arch Biochem Biophys 416: 68; d) Davis II JW, Burdick AD, Lauer FT, Burchiel SW
(2003) Toxicol Appl Pharmacol 188: 42
[9] Wagner H, Farkas L in The Flavonoids – Advances in Research Since 1986 (1994) Harborne JB
(ed) Chapman and Hall, London, Chapter 4, pp 127
[10] a) Anand N, Venkataraman FA (1947) Proc Ind Acad Sci A 26: 279; b) Dauzonne D, Grandjean C
(1992) Synthesis, p 677; c) Cunningham BDM, Threadgill MD, Groundwater PW, Dale IL,
Hickman JA (1992) Anticancer Drug Design 7: 365; d) Khanna MS, Singh OV, Garg CP,
Kapoor RP (1992) J Chem Soc, Perkin Trans 1: 2565; e) Cushman M, Zhu H, Geahlen RL,
Kraker AJ (1994) J Med Chem 37: 3353; f) Dauzonne D, Martinez L (1995) Tetrahedron Lett 36:
1845; g) Tang L, Zhang S, Yang J, Gao W, Cui J, Zhuang T (2004) Molecules 9: 842; h) Tang L,
Zhang S, Yang J, Gao W, Cui J, Zhuang T (2005) Synth Commun 35: 315 and references therein
[11] Barros AIRNA, Silva AMS, Alkorta I, Elguero J (2004) Tetrahedron 60: 6513
[12] a) Cavaleiro JAS, Elguero J, Jimeno ML, Silva AMS (1991) Chem Lett, p 445; b) Makrandi JK,
Seema Indian J Chem 30B: 788; c) Pinto DCGA, Silva AMS, Cavaleiro JAS (1996) J Heterocycl
Chem 33: 1887