A new synthesis of benzo[b]acridones

Article abstract of DOI:10.1055/s-0028-1087372

A novel and efficient route for the synthesis of new benzo[6]acridones has been described. It involves the Diels-Alder reaction of N-substituted-4- quinolone-3-carbaldehyde with ortho-benzoquinodimethanes giving benzo[b]-1,6,6a,12a-tetrahydroacridones, which are the result of a cycloaddition reaction followed by an in situ deformylation. The oxidation of these tetrahydroacridones in dimethyl sulfoxide using a catalytic amount of iodine gives the new benzo[b]acridone derivatives. It was demonstrated that the cycloaddition reaction is only efficient if an electron-withdrawing N-protecting group is present. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-0028-1087372

LETTER
3193
A New Synthesis of Benzo[b]acridones
S
ynthesisof Be
n
a
b
]acrido
q
nes uel S. G. R. Seixas, Artur M. S. Silva,* Diana C. G. A. Pinto, 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 4 September 2008
sides these classical syntheses, other methods involve the
intermolecular nucleophilic coupling of arynes with 2-
aminobenzoates and subsequent intramolecular nucleo-
philic cyclization,16 and the anionic N-Fries rearrange-
Abstract: A novel and efficient route for the synthesis of new ben-
zo[b]acridones has been described. It involves the Diels–Alder re-
action of N-substituted-4-quinolone-3-carbaldehyde with ortho-
benzoquinodimethanes giving benzo[b]-1,6,6a,12a-tetrahydroacri-
dones, which are the result of a cycloaddition reaction followed by ment of N-carbamoyl diarylamines to anthranilamides
followed by smoothly cyclization with tryflic anhydride.17
an in situ deformylation. The oxidation of these tetrahydroacridones
in dimethyl sulfoxide using a catalytic amount of iodine gives the
Benzo[b]acridones have also been obtained by the
new benzo[b]acridone derivatives. It was demonstrated that the
Friedel–Crafts reaction of 3,5-dimethoxyacetanilide with
cycloaddition reaction is only efficient if an electron-withdrawing
2-methoxy-1-naphthoyl chloride followed by base-
N-protecting group is present.
catalyzed cyclization.11
Key words: 4-quinolone-3-carbaldehydes, benzo[b]acridones, Diels–
The variety of important potential applications of acri-
dones and their benzo[b]acridone derivatives highlight
these compounds as targets for the preparation of new de-
rivatives or/and to develop new strategies for their synthe-
sis. In the present communication we describe a new
method for the synthesis of novel benzo[b]acridones by
Diels–Alder reaction of N-substituted-4-quinolone-3-
carbaldehyde, acting as a dienophile, with the highly reac-
tive dienes ortho-benzoquinodimethanes, followed by ox-
idation of the obtained intermediates.
Alder reactions, oxidation, N-protecting groups.
Acridones are a group of naturally occurring nitrogen
heterocyclic compounds found exclusively in plants be-
longing to the Rutaceae family.1 Both natural and synthet-
ic acridone derivatives exhibit a variety of important
biological activities. They are known to present important
antiparasitic activity, against leishmania and malaria, and
antifungal activities.2,3 Certain derivatives are important
anticancer,4,5 and antiviral compounds,6–8 some of them
being selective inhibitors of human immunodeficiency
virus type-1 (HIV-1) replication in chronically HIV-1 in-
fected cells. Another important potential applications of
acridones is their possible use as fluorescent agents,9 such
as labels for fluorescence detection of target biological
materials and as fluorescent anion receptors and sensors.
Initial experiments considered the Diels–Alder reaction of
1-methyl-4-quinolone-3-carbaldehyde (1)18 with ortho-
benzoquinodimethane (3a), formed in situ by thermal ex-
trusion of sulfur dioxide from 1,3-dihydroben-
zo[c]thiophene 2,2-dioxide (2a).19 This reaction afforded
a diastereomeric mixture of benzo[b]-1,6,6a,12a-tetrahy-
droacridone derivatives 4 and 5 and benzo[b]acridone 6
(Scheme 1, Table 1).20 Tetrahydroacridones 421 and 522
are the result of the predicted cycloaddition reaction fol-
lowed by deformylation of the expected cycloadduct, a
b-ketoaldehyde 7, under the experimental conditions.23
Benzo[b]acridone 624 is presumably obtained by the in
situ oxidation of tetrahydroacridones 4 and 5.25 However,
even after several attempts using different experimental
conditions (varying amounts of diene, catalysts, reaction
time, and heating conditions) low overall yields were ob-
tained in the formation of compounds 4, 5, and 6.20
There are only a few examples of benzo[b]acridones de-
scribed in the literature where an additional aromatic ring
is linearly fused to the acridone moiety.10 The most com-
mon derivatives of this type of compounds are the ben-
zo[b]acronycines which present potent antitumour
activity,10–13 being found to be more active than acrony-
cine,10 a natural pyranoacridone alkaloid that exhibits
promising activity against a broad spectrum of tumors.14
cis-1,2-Diacetoxy-1,2-dihydrobenzo[b]acronycine has also
shown an impressive broad spectra of antitumor activities,
and it is currently in phase II clinical trials.12
The stereochemistry of diastereomers 4 and 5 was as-
signed as cis and trans, respectively, based on the NOESY
studies. In the NOESY spectrum of isomer 4 there is a
NOE cross peak between signals of H-12a (multiplet,
dH = 3.31–3.36) and H-6a (double triplet, dH = 3.95), due
to their spatial proximity, while in the spectrum of isomer
5 the NOE cross peak was not present (H-12a, multiplet,
dH = 2.80–2.90; H-6a, multiplet, dH = 3.57–3.63). The
Acridones and their benzo[b]derivatives are usually pre-
pared by the Ullmann condensation of anilines with ortho-
halogen-substituted benzoic or naphthoic acids followed
by the acid induced ring closure of the N-phenyl anthra-
nilic acids,3,5,7,13,15 or by the condensation of 3-amino-2-
naphthalenecarboxylic acid with phloroglucinol.8,10 Be-
1
main H NMR features to support the structure of acri-
SYNLETT 2008, No. 20, pp 3193–3197
1
6
.1
2
.2
0
0
8
done 6 is the absence of aliphatic signals and the three sin-
glets at dH = 3.95 (N-Me), 7.77 (H-6), and 9.13 (H-1). The
Advanced online publication: 26.11.2008
DOI: 10.1055/s-0028-1087372; Art ID: D32208ST
© Georg Thieme Verlag Stuttgart · New York

3194
R. S. G. R. Seixas et al.
LETTER
SO2
∆
2a
Me
N
Me
N
Me
N
H
H
H
i
+
CHO
H
O
O
O
1
3a
4
5
Me
Me
N
H
N
CHO
O
O
7
6
Scheme 1 Reagents and conditions: (i) 1,2,4-trichlorobenzene, reflux.
Table 1 Reaction Conditions for the Syntheses of Compounds 4–6
Entry
Time (h)
Sulfone 2a (equiv) Conditions
Catalyst
Yield (%)
4 + 5a
6
1b
59
51
40
27
21
0
1
2
3
4
5
6
7
7
16
16
24
24
20
26
2
2
TCB, reflux N2
–
7
9
<5
6
TCB, reflux N2
TCB, reflux N2
TCB, reflux N2
TCB, reflux
–
5
–
14
14
13
0
8
10
10
10
10
–
11
15
5
–
TCB, reflux N2
TCB, reflux N2
AlCl3
La(OTf)3
4
3
6
a Although we present the combined yield, these compounds were isolated as pure compounds (in a 4:1 proportion of 4/5) by preparative TLC.
b Recovered starting material.
high frequency of the latter signal is due to the anisotropic group. It was found that the 1-ethoxycarbonyl-4-quinolone-
and mesomeric deshielding effects of the carbonyl group. 3-carbaldehyde (9) was not stable on silica gel since a par-
tial hydrolysis of the carbamate occurred during purifica-
Since the yields obtained were not satisfactory we decided
tion by column chromatography. However, after several
to reduce the electronic density of the C2=C3 double
attempts with different reaction conditions; changing the
bound of 4-quinolone-3-carbaldehyde (8) by introducing
an electron-withdrawing ethoxycarbonyl N-protecting
base (Et3N, PS-TBD, NaH), the solvent (THF, CHCl3),
CO2Et
R1
CO2Et
N
H
N
H
N
R2
R2
i
CHO
CHO
H
O
R1
O
O
10a–c
ii
9
+
8
R1
R1
CO2Et
R2
R2
R2
R2
H
N
∆
SO2
H
O
11
R1
R1
3a–c
2a–c
a R1 = R2 = H; b R1 = OMe, R2 = H; c R1 = OMe, R2 = Br
Scheme 2 Reagents and conditions: (i) K2CO3, ClCO2Et, acetone, r.t.; (ii) 1,2,4-trichlorobenzene, reflux.
Synlett 2008, No. 20, 3193–3197 © Thieme Stuttgart · New York

LETTER
Synthesis of Benzo[b]acridones
3195
and the reaction temperature (r.t. to 60 °C), we found the sition. However, oxidation of benzo[b]-1,6,6a,12a-
optimal method (1.5 equiv of ethyl chloroformate, K2CO3 tetrahydroacridone 10a with dimethyl sulfoxide using a
as base, acetone as solvent, and r.t.) to isolation of 1- catalytic amount of iodine,27,28 did give the expected acri-
ethoxycarbonyl-4-quinolone-3-carbaldehyde (9) in good done derivatives (Scheme 3). When the reaction was per-
yield (96%) without need for purification (Scheme 2).
formed at 170–180 °C mixtures of the expected 7-
ethoxycarbonylbenzo[b]acridone derivatives 12a–c29 and
the unprotected benzo[b]acridone derivatives 13a–c30
were isolated in good overall yields (62–86%), the latter
being slightly more abundant. When the temperature was
increased to 190–200 °C the reaction was more selective,
and we obtained mainly the unprotected benzo[b]acridone
derivatives 13a–c, in good yields (59–82%), and a very
small amount of the 7-ethoxycarbonylbenzo[b]acridone
derivatives 12a–c (2–4%).
After several attempts, we found that the Diels–Alder re-
action of 1-ethoxycarbonyl-4-quinolone-3-carbaldehyde
(9) with ortho-benzoquinodimethane (3a) in refluxing
1,2,4-trichlorobenzene afforded the cis-benzo[b]tetra-
hydroacridone 10a (Table 2, entries 1–4). A better yield
(71%) was obtained when using two molar equivalents of
sulfone 2a and 9 hours reaction time. Traces of the trans-
diastereomer 11 were found when the reaction proceeded
for 16 hours (Table 2, entry 2). Applying these optimized
conditions to the cycloaddition might give rise to the ex-
pected adduct 13, a b-ketoaldehyde which was prone to
deformylation under the reactions conditions, yielding the
mixture of diastereomers 8 and 9, which could be separat-
ed by thin-layer chromatography (TLC). This type of de-
formylation was already reported by Wallace conditions
to the cycloaddition reactions of 9 with substituted ortho-
benzoquinodimethanes 3b,c,26 the corresponding ben-
zo[b]-1,6,6a,12a-tetrahydroacridones 10b,c were ob-
tained in good yields (84% and 81%, Table 2, entries 5
and 6).
CO2Et
N
R1
CO2Et
N
R1
R2
R2
R2
R2
i
O
R1
O
R1
10a–c
12a–c
R1
5
H
N
8
6
7a
6a
5a
1a
R2
R2
4
3
a R1 = H; R2 = H
9
b R1 = OMe, R2 = H
c R1 = OMe, R2 = Br
12
10
11a
12a
2
1
11
O
R1
13a–c
Table 2 Reaction Conditions and Yields in the Diels–Alder Reac-
tion of 1-Ethoxycarbonyl-4-quinolone-3-carbaldehyde 9 with ortho-
Benzoquinodimethanes 3a–c
Scheme 3 Reagents and conditions: (i) I2, DMSO.
The main features in the 1H NMR of 12a–c and 13a–c that
allow us to differentiate them are: i) the signals of the
ethyl group of 12a–c at dH = 1.42–1.44 (CH3) and dH =
4.47–4.50 (CH2); and ii) the signals of the NH proton of
13a–c at dH = 11.75–12.05. Both compounds present two
singlets at high frequency due to the resonances of H-1
(dH = 8.85–9.22 for 12a–c; dH = 8.94–9.11 for 13a–c) and
H-6 (dH = 8.37–8.63 for 12a–c; dH = 7.96–8.21 for 13a–c).
Entry Time Sulfone 2a–c R1
R2
Yield (%)
(h)
(equiv)
10a–c
11
1
2
3
4
5
6
4
16
9
2a 5
2a 5
2a 5
2a 2
2b 2
2c 2
H
H
H
H
H
H
Br
49
–
H
57
64
71
84
81
1
–
–
–
–
H
9
H
In conclusion, a new methodology for the synthesis of
benzo[b]acridones has been developed. This synthetic
route comprises three steps, the synthesis of 4-quinolone-
3-carbaldehyde, followed by their reaction with ortho-
benzoquinodimethanes, and then oxidation of the ob-
tained products. The cycloaddition reaction is only effi-
cient if an electron-withdrawing N-protecting group is
present.
9
OMe
OMe
9
The stereochemistry of compounds 10a–c was established
as cis based on the presence of a NOE cross peak between
the signals of H-12a (multiplet, dH = 3.33–3.42) and H-6a
(multiplets, dH = 5.25–5.34) in their NOESY spectrum.
The last step of our procedure considered the oxidation of
benzo[b]-1,6,6a,12a-tetrahydroacridones 10a–c in order
to obtain the corresponding benzo[b]acridones 12a–c.
Firstly, we studied oxidation of benzo[b]-1,6,6a,12a-tetra-
hydroacridone 10a with a large excess of chloranil in re-
fluxing dry 1,4-dioxane; however, after 26 hours there
was no reaction. In a second attempt, we used a large ex-
cess of 2,3-dichloro-5,6-dicyano-p-benzoquinone in re-
fluxing dry 1,4-dioxane with the result that a small
quantity of the desired 7-ethoxycarbonylbenzo[b]acri-
done 12a was obtained accompanied by much decompo-
Acknowledgment
Thanks are due to University of Aveiro, FEDER, and FCT for fun-
ding the Organic Chemistry Research Unit and project POCI/QUI/
58835/2004. Raquel Seixas also thanks FEDER and FCT for a PhD
grant (SFRH/BD/30734/2006).
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LETTER
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A mixture of 1-methyl-4-quinolone-3-carbaldehyde (1,
121.7 mg, 0.65 mmol) and 1,3-dihydrobenzo[c]thiophene
2,2-dioxide (2a) in 1,2,4-trichlorobenzene (TCB, 6 mL) was
refluxed under a variety of reaction conditions (see Table 1).
After cooling to r.t., the reaction mixture was purified by
silica gel column chromatography; the TCB solvent was
removed using light PE as eluent, and then the cycloadducts
were eluted with a mixture of light PE–EtOAc (4:1). The
solvent was evaporated to dryness and the mixture of
diastereomers was separated by preparative thin-layer
chromatography using a mixture of light PE–EtOAc (9:1).
The 7-methylbenzo[b]-1,6,6a,12a-tetrahydroacridones 4
and 5 and the benzo[b]acridone(6) were obtained as yellow
compounds.
(21) Physical Data for cis-7-Methylbenzo[b]-1,6,6a,12a-
tetrahydroacridone (4)
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1H NMR (300.1 MHz, CDCl3): d = 2.80–3.02 (m, 3 H,
1 × H-1, 2 × H-6), 3.11 (s, 3 H, NCH3), 3.31–3.36 (m, 1 H,
H-12a), 3.81 (dd, 1 H, J = 1.6, 17.3 Hz, H-1), 3.95 (dt, 1 H,
J = 5.5, 11.0 Hz, H-6a), 6.69 (d, 1 H, J = 8.6 Hz, H-8), 6.71
(ddd, 1 H, J = 0.9, 7.3, 7.6 Hz, H-10), 6.96 (d, 1 H, J = 7.4
Hz, H-5), 7.06 (dt, 1 H, J = 1.5, 7.4 Hz, H-4), 7.13 (dt, 1 H,
J = 1.3, 7.4 Hz, H-3), 7.20 (d, 1 H, J = 7.4 Hz, H-2), 7.41
(ddd, 1 H, J = 1.7, 7.3, 8.6 Hz, H-9), 7.86 (dd, 1 H, J = 1.7,
7.6 Hz, H-11). 13C NMR (75.47 MHz, CDCl3): d = 26.1 and
26.6 (C-1 and C-6), 37.6 (NCH3), 45.1 (C-12a), 60.4 (C-6a),
113.1 (C-8), 116.6 (C-10), 118.8 (C-11a), 125.8 (C-4), 126.4
(C-3), 127.9 (C-11), 129.1 and 129.2 (C-2 and C-5), 133.0
(C-5a), 133.8 (C-1a), 135.6 (C-9), 150.0 (C-7a), 194.1 (C-
12). ESI+-MS: m/z (%) = 264 (100) [M + H]+, 286 (93) [M +
Na]+, 302 (8) [M + K]+, 549 (47) [2 M + Na]+. HRMS (EI,
70 eV): m/z calcd for C18H17NO: 263.1310; found:
263.1309.
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(22) Physical Data for trans-7-Methylbenzo[b]-1,6,6a,12a-
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J. Med. Chem. 2006, 49, 3383.
1H NMR (300.1 MHz, CDCl3): d = 2.80–2.90 (m, 1 H,
H-12a), 2.91–3.01 (m, 1 H, H-1), 3.07 (s, 3 H, NCH3), 3.11–
3.16 (m, 1 H, H-6), 3.49–3.56 (m, 2 H, H-1, H-6), 3.57–3.63
(m, 1 H, H-6a), 6.81 (ddd, 1 H, J = 0.9, 7.3, 7.6 Hz, H-10),
6.90 (d, 1 H, J = 8.7 Hz, H-8), 7.18–7.25 (m, 4 H, H-2 to
(12) Koch, M. Bull. Acad. Nat. Med. 2007, 191, 83.
Synlett 2008, No. 20, 3193–3197 © Thieme Stuttgart · New York

LETTER
H-5), 7.46 (ddd, 1 H, J = 1.8, 7.3, 8.7 Hz, H-9), 7.96 (dd,
Synthesis of Benzo[b]acridones
3197
to r.t., the reaction mixture was poured onto ice (10 g) and
H2O (10 mL), a small amount of Na2S2O3 was added to
eliminate the remaining traces of iodine, and the reaction
mixture was stirred for some minutes. The yellow solid
obtained was filtered off, washed with H2O (2 × 20 mL),
dissolved in EtOAc (20 mL), and washed with H2O (2 × 20
mL). The solvent was evaporated to dryness and the residue
was purified by silica gel column with a mixture of light PE–
EtOAc (4:1 to 2:1). The 7-ethoxycarbonylbenzo[b]acridones
12a–c were obtained as yellow solids and the
1 H, J = 1.8, 7.6 Hz, H-11).
13C NMR (75.47 MHz, CDCl3): d = 29.1 (C-1), 34.1
(NCH3), 36.6 (C-6), 46.8 (C-12a), 59.0 (C-6a), 113.9 (C-8),
117.5 (C-10), 119.6 (C-11a), 126.2 and 126.6 (C-3 and C-4),
127.9 (C-1), 128.9 and 129.0 (C-2 and C-5), 132.9 (C-5a),
134.4 (C-1a), 135.7 (C-9), 152.7 (C-7a), 194.6 (C-12). ESI+-
MS: m/z (%) = 264 (100) [M + H]+, 286 (25) [M + Na]+, 549
(19) [2 M + Na]+. HRMS (EI, 70 eV): m/z calcd for
C18H17NO: 263.1310; found: 263.1312.
(23) This type of deformylation reaction has been previously
reported for similar compounds, see: (a) Cremins, P. J.;
Saengchantara, S. T.; Wallace, T. W. Tetrahedron 1987, 43,
3075. (b) Sandulache, A.; Silva, A. M. S.; Cavaleiro, J. A. S.
Tetrahedron 2002, 58, 105.
benzo[b]acridones 13a–c were obtained as orange solids.
When the reactions were carried out 170–180 °C; the results
were as follows: 12a, 37%; 13a, 49%; 12b, 25%; 13b, 37%;
12c, 25%; 13c, 45%. When the reactions were carried in
refluxing DMSO, the yields were: 12a, 2%; 13a, 59%; 12b,
2%; 13b, 59%; 12c, 4%; 13c, 82%.
(24) Physical Data for 7-Methylbenzo[b]acridone (6)
1H NMR (300.1 MHz, CDCl3): d = 3.95 (s, 1 H, NCH3), 7.26
(ddd, 1 H, J = 0.8, 6.8, 7.9 Hz, H-10), 7.43 (ddd, 1 H, J = 1.2,
6.7, 8.1 Hz, H-3), 7.50 (d, 1 H, J = 8.6 Hz, H-8), 7.57 (ddd,
1 H, J = 1.3, 6.7, 8.2 Hz, H-4), 7.74 (ddd, 1 H, J = 1.7, 6.8,
8.6 Hz, H-9), 7.81 (s, 1 H, H-6), 7.90 (d, 1 H, J = 8.2 Hz,
H-5), 8.05 (d, 1 H, J = 8.1 Hz, H-2), 8.57 (dd, 1 H, J = 1.7,
7.9 Hz, H-11), 9.13 (s, 1 H, H-1). 13C NMR (75.47 MHz,
CDCl3): d = 33.8 (NCH3), 110.5 (C-6), 114.4 (C-8), 120.5
(C-10), 121.3 (C11a), 122.6 (C-12a), 124.5 (C-3), 126.9
(C-5), 127.9 (C-1a), 128.0 (C-11), 128.7 (C-4), 129.0 (C-1),
129.5 (C-2), 134.4 (C-9), 136.4 (C-5a), 139.7 (C-6a), 143.6
(C-7a), 179.4 (C-12). ESI+-MS: m/z (%) = 260 (100) [M +
H]+, 282 (33) [M + Na]+, 541 (54) [2 M + Na]+. HRMS (EI,
70 eV): m/z calcd for C18H13NO: 259.0997; found:
259.0999.
(25) Although the cycloaddition reactions were carried out under
nitrogen to avoid moisture, the reaction medium was not
deoxygenated, the residual oxygen presumably being the
oxidant.
(26) 4,7-Dimethoxy-1,3-dihydrobenzo[c]thiophene 2,2-dioxides
2b,c were prepared according to the following literature
procedure: Sandulache, A.; Silva, A. M. S.; Cavaleiro,
J. A. S. Monatsh. Chem. 2003, 134, 551.
(29) Physical Data for 7-Ethoxycarbonylbenzo[b]-acridone
(12a)
Mp 118–120 °C. 1H NMR (300.1 MHz, CDCl3): d = 1.42 (t,
3 H, J = 7.1 Hz, NCO2CH2CH3), 4.47 (q, 2 H, J = 7.1 Hz,
NCO2CH2CH3), 7.39 (ddd, 1 H, J = 1.1, 7.4, 7.7 Hz, H-10),
7.52 (ddd, 1 H, J = 1.2, 6.8, 8.1 Hz, H-3), 7.62 (ddd, 1 H,
J = 1.3, 6.8, 8.2 Hz, H-4), 7.66 (ddd, 1 H, J = 1.7, 7.4, 8.4
Hz, H-9), 7.86 (d, 1 H, J = 8.4 Hz, H-8), 7.92 (d, 1 H, J = 8.2
Hz, H-5), 8.04 (d, 1 H, J = 8.1 Hz, H-2), 8.31 (dd, 1 H,
J = 1.7, 7.7 Hz, H-11), 8.37 (s, 1 H, H-6), 8.85 (s, 1 H, H-1).
13C NMR (75.47 MHz, CDCl3): d = 14.1 (NCO2CH2CH3),
64.2 (NCO2CH2CH3), 119.8 (C-6), 122.6 (C-8), 124.6
(C-10), 125.4 (C-12a), 125.8 (C-11a), 126.1 (C-3), 126.8
(C-11), 127.7 (C-5), 128.0 (C-1), 128.9 (C-4), 129.5 (C-2),
129.9 (C-1a), 133.0 (C-9), 135.2 (C-5a), 135.9 (C-6a), 140.8
(C-7a), 153.8 (NCO2CH2CH3), 181.0 (C-12). ESI+-MS: m/z
(%) = 318 (75) [M + H]+, 340 (31) [M + Na]+, 356 (11)
[M + K]+, 657 (100) [2 M + Na]+, 974 (30) [3 M + Na]+.
HRMS (EI, 70 eV): m/z calcd for C20H15NO3: 317.1052;
found: 317.1053.
(30) Physical Data for Benzo[b]acridone (13a)
Mp >300 °C. 1H NMR (300.1 MHz, CDCl3): d = 7.22 (ddd,
1 H, J = 0.8, 6.9, 8.0 Hz, H-10), 7.44 (ddd, 1 H, J = 0.9, 7.1,
7.9 Hz, H-3), 7.55 (d, 1 H, J = 8.4 Hz, H-8), 7.60 (ddd, 1 H,
J = 1.1, 7.1, 8.2 Hz, H-4), 7.76 (ddd, 1 H, J = 1.5, 6.9, 8.4
Hz, H-9), 7.96 (s, 1 H, H-6), 8.01 (d, 1 H, J = 8.2 Hz, H-5),
8.17 (d, 1 H, J = 7.9 Hz, H-2), 8.26 (dd, 1 H, J = 1.5, 8.0 Hz,
H-11), 8.94 (s, 1 H, H-1), 11.75 (s, 1 H, NH). 13C NMR
(75.47 MHz, CDCl3): d = 112.0 (C-6), 117.0 (C-8), 118.9
(C-11a), 120.2 (C-10), 121.2 (C-12a), 124.1 (C-3), 126.4
(C-11), 126.5 (C-5), 127.3 (C-1), 127.7 (C-1a), 128.5 (C-4),
129.7 (C-2), 134.3 (C-9), 135.9 (C-5a), 137.9 (C-6a), 142.1
(C-7a), 178.2 (C-12). ESI+-MS: m/z (%) = 246 (100) [M +
H]+. HRMS (EI, 70 eV): m/z calcd for C17H11NO: 245.0841;
found: 245.0842.
(27) A reagent system used by our group in the cyclodehydro-
genation of 2¢-hydroxychalcones and dehydrogenation of
tetrahydroxanthones, see: (a) Silva, A. M. S.; Pinto, D.;
Tavares, H. R.; Cavaleiro, J. A. S.; Jimeno, M. L.; Elguero,
J. Eur. J. Org. Chem. 1998, 2031. (b) Barros, A.; Silva,
A. M. S. Magn. Reson. Chem. 2006, 44, 1122. (c) Barros,
A.; Silva, A. M. S. Monatsh. Chem. 2006, 137, 1505.
(28) Optimized Experimental Procedure
Iodine (4%) was added to a solution of the appropriate
7-ethoxycarbonylbenzo[b]-1,6,6a,12a-tetrahydroacridones
10a–c (0.16 mmol) in DMSO (3 mL). The solution was
heated at 170–180 °C or at reflux, for 50 min. After cooling
Synlett 2008, No. 20, 3193–3197 © Thieme Stuttgart · New York

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