Studies on the chemistry of 2-[3-(2-nitrophenyl)-2-oxopropyl]benzaldehydes: Novel syntheses of 5h-benzo[b]carbazole-6,11-diones and indolo[1,2-b] isoquinoline-6,11-diones

Article abstract of DOI:10.1055/s-0029-1216919

Syntheses of 5H-benzo[b]carbazole-6,11-diones and indolo[1,2-b] isoquinoline-6,11-diones are described. Both compounds are synthesized from 2-[3-(2-nitrophenyl)-2-oxopropyl]benzaldehydes, which were obtained from commercially available indan-1-ones in six

Full text of DOI:10.1055/s-0029-1216919

PAPER
3051
Studies on the Chemistry of 2-[3-(2-Nitrophenyl)-2-oxopropyl]benzaldehydes:
Novel Syntheses of 5H-Benzo[b]carbazole-6,11-diones and Indolo[1,2-b]isoqui-
noline-6,11-diones
S
tudies on the Chemist
a
ry of 2-[3-(
r
2-Nitrop
c
henyl)-2-ox
o
opropyl]ben
s
zaldehydes Fernández
Hospital Materno-Infantil, Xubias de Arriba s/n, 15006 A Coruña, Spain
Fax +34(981)178144; E-mail: Marcos.Fernandez.Villar@sergas.es
Received 10 February 2009; revised 6 May 2009
interesting, due to the structural similarities between
them, to perform the same assays utilizing indolo[1,2-
b]isoquinoline-6,11-diones 16 to check whether or not
they represent an alternative.
Abstract: Syntheses of 5H-benzo[b]carbazole-6,11-diones and in-
dolo[1,2-b]isoquinoline-6,11-diones are described. Both com-
pounds
are
synthesized
from
2-[3-(2-nitrophenyl)-2-
oxopropyl]benzaldehydes, which were obtained from commercially
available indan-1-ones in six steps.
There are few syntheses of indolo[1,2-b]isoquinoline-
6,11-diones 16 in the literature.12 These compounds are
structurally related to indolo[1,2-b]isoquinolinones, some
of which have been synthesized.14
Key words: ozonolysis, ketoaldehyde, aldol condensation, hydro-
genation, indole
In this paper, 5H-benzo[b]carbazole-6,11-diones 11 and
indolo[1,2-b]isoquinoline-6,11-diones 16 have been ob-
tained from the same intermediates, 2-[3-(nitrophenyl)-2-
oxopropyl]benzaldehydes 7a,b.
5H-Benzo[b]carbazole-6,11-diones 11 are synthetic com-
pounds that have been known for quite some time,1 whose
nitrogen atom has been related to biological activity,2
such as anticarcinogenic properties.3 Moreover, com-
pounds 11 contain a planar 2-phenyl-1,4-naphthoquinone
subunit4 which is thought to facilitate interaction with nu-
cleic acids and, therefore, prevent them from carrying out
their role in the replication and recombination of these
acids. In fact, benzo[b]carbazole-6,11-diones 11 have
shown promising antileukemic activity.5 In addition to
this, they are similar to ellipticine quinones,6 which
present cytotoxic activity against HeLa cell lines.
This new route was firstly applied to the synthesis of the
unsubstituted benzo[b]carbazole-6,11-dione 11a. The
starting
2-[3-(nitrophenyl)-2-oxopropyl]benzaldehyde
(7a) was obtained as depicted in Scheme 1.
The condensation of ethyl indanecarboxylate 2a15 with 2-
nitrobenzyl bromide under basic conditions gave ethyl 2-
(2-nitrobenzyl)indane-2-carboxylate 3a (84% yield),15
which when subjected to decarboxylation under acidic
conditions provided 2-(2-nitrobenzyl)indanone 4a (74%
yield). Subsequent reduction of this indanone with sodium
borohydride led to a mixture of indanols 5,16 which was
directly converted into 2-(2-nitrobenzyl)indene 6a by re-
fluxing with 10% hydrochloric acid in dioxane for 30
minutes. Finally, indene 6a was transformed into the de-
sired ketoaldehyde 7a by oxidative cleavage with osmium
tetroxide followed by sodium periodate (56% yield),17 as
the route by ozonolysis afforded a lower yield (35%) be-
cause of the formation of keto acid 7c (31% yield).18 The
1H NMR of ketoaldehyde 7a shows a singlet at d = 10.01
due to the aldehyde proton. Several representative signals
in the 13C NMR include the corresponding to the aldehyde
and the ketone at d = 193.6 and 202.4, respectively.
Most methods developed for the synthesis of 5H-ben-
zo[b]carbazole-6,11-diones 11 involve the sequential
construction of the central rings B and C in that order. The
last step of these methods normally includes the intramo-
lecular cyclization of 2-(phenylamino)-1,4-naphtho-
quinones.5,7 A new route was reported8 in which the usual
order of the construction of the B and C rings is reversed.
Moreover, some methods have been developed in which
2-(2-nitrophenyl)-1,4-naphthoquinones, such as in this
paper, are used as intermediates for benzo[b]carbazole-
6,11-diones 11, but they are obtained in a different way.
For instance, they are formed from {[(nitrophe-
nyl)acetyl]phenyl}acetic acids,9 by coupling (2-
acetylphenyl)acetic acids with 1-fluoro-2-nitrobenzenes10
or by rearrangement of 3-(2-nitrobenzylidene)isochro-
mane-1,4-diones resulting from the condensation of 2-ni-
trobenzaldehydes with isochromane-1,4-diones.11
Intramolecular aldol condensation of ketoaldehyde 7a us-
ing previous conditions19 was not successful, whilst 3-(2-
nitrophenyl)naphthol 8a was obtained in a quantitative
yield employing acetic acid and piperidine.20 Treatment of
this compound with benzeneseleninic anhydride yielded
o-quinone 9a in 94% yield accompanied by a small por-
tion of naphthol 8aa (6% yield).21 o-Quinone 9a was
transformed into p-quinone 10a under acidic conditions
(H2SO4, MeOH, reflux).22 Finally, when this compound
reacted with sodium borohydride in propan-2-ol, the tar-
get benzo[b]carbazole-6,11-dione 11a was obtained in
Indolo[1,2-b]isoquinoline-6,11-diones 16 are synthetic12
compounds structurally related to 9,10-dimethylindo-
lo[1,2-a]quinoline-8,11-dione, a compound whose bioas-
says have been negative.13 Nevertheless, it would be
SYNTHESIS 2009, No. 18, pp 3051–3060
x
x.
x
x
.
2
0
0
9
Advanced online publication: 23.07.2009
DOI: 10.1055/s-0029-1216919; Art ID: T02909SS
© Georg Thieme Verlag Stuttgart · New York

3052
M. Fernández
PAPER
Br
O2N
NO2
R
R
R
i
CO2Et
CO2Et
ii
O
O
O
2a, 76%
2b, 85%
3a, 84%
3b, 80%
1
iii
R
R
iv
v
R
NO2
NO2
NO2
O
OH
6a, 82%
6b, 76%
5a, 99%
5b, 77%
4a, 74%
4b, 78%
vi
O2N
NO2
R
vii
O
Y
R
OH
7a R = H, Y = CHO 56% (a) 35% (c)
7b R = OMe, Y = CHO 39% (b)
7c R= H, Y = CO2H 31% (c) (formed in the ozonolysis)
7d R = OMe, Y = CO2H 19% (b)
viii
8a, 100%
8b, 95%
O2N
O2N
O
x
+
NO2
R
O
R
OH
R
OH
O
SePh
O
10a, 77%
10b, 70%
9a, 94%
9b, 74%
8aa, 6%
8bb, 19%
ix
xi
R = H, 93%
R = OMe, 96%
O
B
D
C
A
N
R
H
O
11a, 24%
11b, 22%
Scheme 1 Substituents: a R = H; b R = OMe. Reaction conditions: (i) CO(OEt)2, NaH, benzene, reflux, 5 h; (ii) NaH, DMF, 60 °C, 42–62 h;
(iii) 48% HBr, AcOH, 120 °C, 0.5–2 h; (iv) NaBH4, MeOH, 0–5 °C, 1–1.25 h; (v) 10% HCl, dioxane, reflux, 0.5 h; (vi) (a) 1. OsO4, dioxane–
H2O, r.t., 5 min; 2. NaIO4, 66 h (for 7a); (b) 1. O3, CH2Cl2, –40 °C, 0.5 h; 2. Me2S, –40 °C, 45 min then –40 °C to r.t., 40 min (for 7a,c); (c) 1.
O3, CH2Cl2, –78 °C, 3.5 min; 2. Me2S, –78 °C to r.t., 2.5 h (for 7b,d); (vii) glacial AcOH, piperidine, benzene, reflux, 2.25–3 h; (viii)
[PhSe(O)]2O, THF, r.t., 2.75–7 h; (ix) [PhSe(O)]2O, THF, 50 °C, 0.5–1.75 h; (x) 20% H2SO4, MeOH, reflux, 33–80 h; (xi) NaBH4, i-PrOH,
r.t., 3.75–4.25 h.
24% yield.9b Its 1H NMR shows a broad singlet for NH at nyl)naphthol 8b, o-quinone 9b, and p-quinone 10b. Again
d = 12.94. In its 13C NMR, two peaks (corresponding to in this case, ozonolysis of 2-(2-nitrobenzyl)indene 6b
the two carbonyls of quinone) appear at d = 179.2.
gave a mixture of ketoaldehyde 7b (39% yield) and keto
acid 7d (19% yield).
This methodology permitted the preparation of ben-
zo[b]carbazole-6,11-dione 11a without substituents, not The key intermediates, ketoaldehydes 7a,b, were also uti-
accessible using previously developed methodology.9b
lized to synthesize the target indolo[1,2-b]isoquinoline-
6,11-diones 16a,b (Scheme 2).
Similarly, 5-methoxyindanecarboxylate 2b was trans-
formed into 8-methoxybenzo[b]carbazole-6,11-dione 11b Jones oxidation of ketoaldehyde 7a led to keto acid 7c
via indanecarboxylate 3b, benzylindanone 4b, 2-(2-ni- (72% yield).23 Its 1H NMR shows the typical broad singlet
trobenzyl)indene 6b, ketoaldehyde 7b, 3-(2-nitrophe- of carboxylic acid protons at d =12.92. Fischer esterifica-
Synthesis 2009, No. 18, 3051–3060 © Thieme Stuttgart · New York

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Studies on the Chemistry of 2-[3-(2-Nitrophenyl)-2-oxopropyl]benzaldehydes
3053
NO2
NO2
NO2
R
R
i
R
O
CO2H
O
O
CHO
CO2Me
ii
7c, 72%
7d, 56%
12a, 100%
12b, 94%
7a,b
+
O
O
R
NO2
13
iii
O
O
R
R
v
iv
N
O
HN
N
30%
CO2Me
15a, 81%
15b, 20%
14a, 50%
14b, 62%
16a
vi
29%
O
MeO
N
O
16b
Scheme 2 Substituents: a R = H; b R = OMe. Reaction conditions: (i) Jones’ reagent, acetone, r.t., 1–1.25 h; (ii) H2SO4, MeOH, reflux, 4–5
h; (iii) H2, 10% Pd/C, MeOH, 1013 mb, r.t., 1 h; (iv) (a) NaOMe, MeOH, r.t., 11.5 h; (b) 20% NaOH, EtOH, reflux, 25 min; (v) CrO3, glacial
AcOH, H2O, reflux, 5 min; (vi) NaOMe, MeOH, r.t., 20 h.
tion of keto acid 7c afforded a mixture of keto ester 12a confirmed by mass spectrometry. Its 1H NMR contains a
and lactone 13a (as shown by a singlet at d =6.26 corre- multiplet between d = 7.24 and 7.35, corresponding to the
sponding to the alkene proton). This mixture was directly alkene proton, and signals between d = 7.51 and 8.61 due
employed in the next reaction for two reasons. The first is to the eight aromatic protons. Two characteristic peaks in
that the two compounds are very difficult to separate, be- its 13C NMR were observed at d = 158.7 and 182.8 due to
cause they have very similar retention times and the sec- the lactam and the ketone carbonyl, respectively.
ond is that both compounds are in equilibrium in solution.
The methoxylated analogous series was obtained in a sim-
In this way, the mixture of 12a/13a was subjected to con- ilar way to the one just described, even though it is impor-
trolled catalytic hydrogenation providing indole 14a in tant to emphasize that the cyclization of indole 14b was
50% yield,24 as a result of the reduction of the nitro group performed in two different ways. Treatment of this com-
followed by intramolecular attack of the resulting amine pound with sodium hydroxide in ethanol at reflux led to 9-
group to the ketone. Several representative signals of this methoxyindolo[1,2-b]isoquinolin-6-one 15b in only 20%
compound are: the NH band at 3340 cm–1 in the infrared yield, nevertheless, when indole 14b reacted with sodium
spectrum and a broad singlet at d = 9.95 (corresponding to methoxide in methanol at room temperature, the target
the indolic proton) in its 1H NMR. Heteroannulation of in- 16b was directly obtained in 29% yield. This reaction was
dole 14a under basic conditions (NaOMe/MeOH) gave carried out under a dry atmosphere, but not under argon
indolo[1,2-b]isoquinolin-6-one 15a (81% yield) as shown because it needs oxygen. 9-Methoxyindolo[1,2-b]iso-
by the disappearance of the indolic proton in its 1H NMR quinoline-6,11-diones 16b shows in its 13C NMR two
and the appearance of a peak at d = 161.1 (corresponding peaks at d = 163.2 and 181.3, due to the lactam and the ke-
to the lactam carbonyl) in its 13C NMR. Finally, the com- tone carbonyl, respectively.
pound 15a was oxidized with chromium(VI) oxide in ace-
In conclusion, a divergent synthesis of benzo[b]carba-
tic acid25 to furnish the target 16a in 30% yield. The
zole-6,11-diones 11 and indolo[1,2-b]isoquinoline-6,11-
molecular formula of this compound (C16H9NO2) was
diones 16 from 2-[3-(2-nitrophenyl)-2-oxopropyl]benzal-
Synthesis 2009, No. 18, 3051–3060 © Thieme Stuttgart · New York

3054
M. Fernández
PAPER
give 4a (687 mg, 74%) as a solid that decomposed on silica gel and
in soln; mp 93–95 °C (MeOH).
previously described one.9b In this way, this new route has IR (KBr): 1705 (C=O), 1523, 1350 cm–1 (NO2).
dehydes 7a,b has been reported. The route via these ke-
toaldehydes constitutes a more generalized version of a
1H NMR: d = 2.83–2.90 (m, 1 H, CH2), 3.03–3.13 (m, 2 H, CH2),
provided the first total synthesis of benzo[b]carbazole-
6,11-diones 11 through 2-[3-(2-nitrophenyl)-2-oxopro-
pyl]benzaldehydes 7a,b. Moreover, indolo[1,2-b]isoquin-
oline-6,11-diones 16 have been synthesized for the first
time through 2-[3-(2-nitrophenyl)-2-oxopropyl]benzoic
acids 7c,d; 9-methoxyindolo[1,2-b]isoquinoline-6,11-di-
one 16b has been synthesized for the first time.
3.22–3.31 (m, 1 H, CH2), 3.56–3.63 (m, 1 H, CH), 7.34–7.47 (m, 4
Harom), 7.53–7.61 (m, 2 Harom), 7.76 (m, 1 Harom), 7.94 (m, 1 Harom).
13C NMR (75.47 MHz): d = 32.4 (CH2), 33.4 (CH2), 47.7 (CH),
123.9 (CH), 124.8 (CH), 126.5 (CH), 127.5 (CH), 127.5 (CH),
132.3 (CH), 132.9 (CH), 134.7 (C), 134.9 (CH), 136.2 (C), 149.6
(C), 153.0 (C–NO2), 206.7 (C=O).
MS (CI): m/z (%) = 268 (M+ + 1, 100), 250 (31), 221 [M+ – 46
(NO2), 32], 220 (65).
Melting points were determined on the following apparatuses: a
Kofler Thermogerate, a Gallenkamp and a Büchi. IR spectra were
recorded on Bruker IFS66V and Midac GRAMS/386 spectropho-
tometers. NMR spectra were recorded, unless otherwise specified,
on a Bruker DPX-250 apparatus, using CDCl3 solns containing
TMS as internal standard. Mass spectra were obtained on the fol-
lowing mass spectrometers: HP 5988A (EI), Thermo Finnigan
MAT95XP (HRMS-EI), TRACEMS Thermo (CI) and Autospec
Micromass (FAB). Elemental analyses were performed on EA 1108
CHNS-O Fisons and EA 1108 CHNS-O Carlo Erba spectrometers.
TLC was carried out using Merck GF254 type 60 silica gel and
CH2Cl2–MeOH mixtures as eluents; the TLC spots were visualized
with UV light or I2 vapor. Column chromatography was performed
using Merck 230–400 mesh (flash 0.04–0.063 mm) type 60 silica
gel. Solvents were purified as given in the literature.26 Solns of ex-
tracts in organic solvents were dried with anhyd Na2SO4. Com-
pounds 2 have been previously prepared.19
2-(2-Nitrobenzyl)-2,3-dihydro-1H-inden-1-ol (5a); Typical Pro-
cedure
A portion of NaBH4 (788 mg, 20.83 mmol, 2.8 equiv) was added to
a soln of 4a (1.855 g, 7.38 mmol) in anhyd MeOH (100 mL) cooled
to 0–5 °C using an ice-water bath. The mixture was stirred at r.t. for
1.25 h and poured into H2O (250 mL). The MeOH was evaporated
in vacuo and the subsequent suspension was extracted with CH2Cl2
(3 × 150 mL). The combined organic extracts were washed with
H2O (3 × 100 mL), dried, and concentrated to dryness in vacuo.
2-(2-Nitrobenzyl)-1H-indene (6a); Typical Procedure
10% HCl (56 mL) was added to a soln of the remaining solid of 5a
(1.842 g, 6.84 mmol) in dioxane (56 mL). The mixture was refluxed
for 30 min. H2O was added and the suspension was extracted with
cyclohexane (3 × 125 mL). The combined organic extracts were
dried and concentrated to dryness in vacuo. The ensuing residue
was submitted to flash column chromatography (CH2Cl2–hexane,
3:7) to give 6a (1.403 g, 82%) as a yellow solid; mp 79–81 °C
(MeOH).
Ethyl 2-(2-Nitrobenzyl)-1-oxo-2,3-dihydro-1H-indene-2-car-
boxylate (3a); Typical Procedure
A mixture of 2a (2.56 g, 12.5 mmol), 80% NaH (414 mg, 13.8
mmol, 1.1 equiv), and DMF (5 mL) was heated at 60 °C for 1 h. A
soln of 2-nitrobenzyl bromide (2.931 g, 13.7 mmol, 1.1 equiv) in
DMF (8 mL) was added and the mixture was heated at 60 °C for 42
h. H2O (few drops) was added and the suspension was extracted
with Et2O (3 × 20 mL). The combined organic extracts were washed
with sat. aq NaCl, dried, and concentrated to dryness in vacuo.
Crystallization of the solid residue (MeOH) yielded 3a (3.558 g,
84%) as yellow crystals; mp 99–101 °C (MeOH).
IR (KBr): 1526, 1336 cm–1 (NO2).
1H NMR: d = 3.32 (s, 2 H, CH2), 4.13 (s, 2 H, CH2), 6.42 (s, 1 H,
CH), 7.07–7.22 (m, 3 Harom), 7.33–7.41 (m, 3 Harom), 7.51–7.57 (m,
1 Harom), 7.93–7.97 (m, 1 Harom).
13C NMR (75.47 MHz): d = 34.5 (CH2), 41.1 (CH2), 120.4 (CH),
123.4 (CH), 124.2 (CH), 124.9 (CH), 126.3 (CH), 127.5 (CH),
128.6 (CH), 132.4 (CH), 133.0 (CH), 134.8 (C), 143.1 (C), 144.8
(C), 146.7 (C), 149.2 (C–NO2).
IR (KBr): 1741 (C=O, ketone), 1705 (C=O, ester), 1522, 1341
cm–1 (NO2).
1H NMR: d = 1.16 (t, J = 7.1 Hz, 3 H, CH3), 3.04 (d, J = 17.5 Hz, 1
H, CHH), 3.59–3.75 (m, 2 H, CH2), 3.93 (d, J = 14.7 Hz, 1 H,
CHH), 4.15 (c, J = 7.1 Hz, 2 H, CH2O), 7.28–7.41 (m, 5 Harom),
7.53–7.60 (m, 1 Harom), 7.74–7.85 (m, 2 Harom).
13C NMR: d = 13.8 (CH3), 34.5 (CH2), 36.2 (CH2), 61.3 (C*), 61.9
(CH2O), 124.6 (CH), 126.1 (CH), 127.6 (CH), 127.8 (CH), 131.5
(C), 132.1 (CH), 132.5 (CH), 134.7 (C), 135.4 (CH), 150.3 (C),
153.1 (C), 170.3 (CO2Et), 201.7 (C=O).
MS (CI): m/z (%) = 252 [(M+ + 1), 48], 234 (100), 218 (33), 206
[(M+ + 1) – 46 (NO2), 39].
Anal. Calcd for C16H13NO2: C, 76.48; H, 5.22; N, 5.58. Found: C,
76.09; H, 5.14; N, 5.53.
2-[3-(2-Nitrophenyl)-2-oxopropyl]benzaldehyde (7a); Typical
Procedure
A 4% aq OsO4 (225 mg, 0.035 mmol, 0.02 equiv) was added to a
suspension of 6a (500 mg, 1.99 mmol) in dioxane (11 mL) and H2O
(3.5 mL). The mixture was stirred at r.t. for 5 min and small portions
of NaIO4 (793 mg, 3.71 mmol, 1.86 equiv) were added for 30 min.
The resulting suspension was stirred at r.t. for 66 h. H2O (15 mL)
was added, and the mixture was extracted with Et2O (3 × 20 mL).
The combined organic extracts were washed with H2O, dried, and
concentrated to dryness in vacuo. The solid residue was submitted
to flash column chromatography (CH2Cl2) to give 7a (313 mg,
56%) as a white solid; mp 112–114 °C (MeOH).
MS (CI): m/z (%) = 340 (M+ + 1, 92), 294 [(M+ + 1) – 46 (NO2),
100], 292 (96), 264 (23).
Anal. Calcd for C19H17NO5: C, 67.25; H, 5.05; N, 4.13. Found: C,
67.05; H, 4.98; N, 4.12.
2-(2-Nitrobenzyl)-2,3-dihydro-1H-inden-1-one (4a); Typical
Procedure
IR (NaCl): 1717 (CHO), 1693 (C=O), 1523, 1352 cm–1 (NO2).
A suspension of 3a (1172 mg, 3.45 mmol), 48% HBr (2.3 mL), and
96% AcOH (2 mL) was stirred at 120 °C for 2 h. The mixture was
cooled and diluted with H2O (10 mL). The organic material was ex-
tracted with Et2O (3 × 15 mL) and the combined organic extracts
were dried and concentrated in vacuo. The solid residue was sub-
mitted to flash column chromatography (CH2Cl2–hexane, 7:3) to
1H NMR: d = 4.30 (s, 2 H, CH2), 4.36 (s, 2 H, CH2), 7.30–7.62 (m,
6 Harom), 7.78–7.82 (m, 1 Harom), 8.10 (m, 1 Harom), 10.01 (s, 1 H,
CHO).
13C NMR (75.47 MHz): d = 47.5 (CH2), 47.8 (CH2), 125.1 (CH),
127.8 (CH), 128.3 (CH), 130.5 (C), 133.1 (CH), 133.5 (CH), 133.8
Synthesis 2009, No. 18, 3051–3060 © Thieme Stuttgart · New York

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Studies on the Chemistry of 2-[3-(2-Nitrophenyl)-2-oxopropyl]benzaldehydes
3055
(CH), 133.9 (CH), 134.0 (C), 135.4 (CH), 135.5 (C), 148.0 (C),
193.6 (CHO), 202.4 (C=O).
MS (CI): m/z (%) = 284 [(M+ + 1), 52], 266 (100), 248 (27).
equiv) in anhyd THF (4 mL). The mixture was stirred at 50 °C for
30 min and cooled. The solvent was removed and the subsequent
residue was submitted to flash column chromatography (CH2Cl2–
hexane, 9:1) to give 9a (120 mg, 93%).
Anal. Calcd for C16H13NO4: C, 67.84; H, 4.63; N, 4.95. Found: C,
67.48; H, 4.38; N, 4.83.
2-Hydroxy-3-(2-nitrophenyl)naphthalene-1,4-dione (10a); Typ-
ical Procedure
3-(2-Nitrophenyl)naphthalen-2-ol (8a); Typical Procedure
Glacial AcOH (0.1 mL) and piperidine (0.1 mL) were added to a
soln of 7a (110 mg, 0.39 mmol) in benzene (3 mL). The mixture was
refluxed for 2.25 h. 10% Aq HCl (5 mL) was added and the suspen-
sion was extracted with CH2Cl2 (3 × 5 mL). The combined organic
extracts were dried and concentrated to dryness in vacuo. The re-
sulting solid was submitted to flash column chromatography
(CH2Cl2–hexane, 9:1) to give 8a (103 mg, quant.) as a yellow solid;
mp 247–49 °C (abs EtOH–CH2Cl2).
IR (NaCl): 3391 (OH), 1522, 1353 cm–1 (NO2).
1H NMR (300.14 MHz, DMSO): d = 7.15–8.05 (m, 10 Harom), 10.16
(s, 1 H, OH).
13C NMR (75.47 MHz, DMSO): d = 108.2 (CH), 122.9 (CH), 123.7
(CH), 125.4 (CH), 126.4 (CH), 127.6 (CH), 127.8 (C), 128.1 (C),
128.5 (CH), 128.7 (CH), 132.5 (C), 132.6 (CH), 133.3 (CH), 134.1
(C), 149.0 (C–NO2), 151.9 (C–OH).
MS (EI, 70 eV): m/z (%) = 265 (M+, 100), 220 (32), 219 [M+–46
(NO2), 16], 189 (93), 165 (52).
20% Aq H2SO4 (6 mL) was added to a suspension of 9a (74 mg,
0.27 mmol) in MeOH (6 mL), and the mixture was refluxed for 80
h. The MeOH was removed in vacuo and the resulting suspension
was poured into 20% aq HCl, and extracted with CH2Cl2 (3 × 20
mL). The combined organic extracts were dried and concentrated to
dryness in vacuo. The solid residue was submitted to flash column
chromatography (adsorbed on silica gel, CH2Cl2–MeOH, 9.8:0.2) to
give 10a (60 mg, 77%) as yellow crystals; mp 264–265 °C (MeOH–
acetone).
IR (NaCl): 2918 (OH), 1674 (C=O), 1631 (C=O), 1515, 1348 cm–1
(NO2).
1H NMR (300.14 MHz, CDCl3–CD3OD–DMSO): d = 7.51–7.58
(m, 2 Harom), 7.66–7.82 (m, 3 Harom), 8.10–8.16 (m, 3 Harom).
13C NMR (75.47 MHz, CDCl3–CD3OD–DMSO): d = 120.2 (C),
123.8 (CH), 125.7 (CH), 126.3 (CH), 126.4 (C), 128.6 (CH), 129.7
(C), 132.0 (C), 132.4 (CH), 132.5 (CH), 132.7 (CH), 134.3 (CH),
148.6 (C–NO2), 154.3 (C–OH), 181.2 (C=O), 182.4 (C=O).
MS (CI): m/z (%) = 296 (M+ + 1, 100), 264 (38), 249 [M+ – 46
(NO2), 19].
3-(2-Nitrophenyl)naphthalene-1,2-dione (9a) and 3-(2-Nitro-
phenyl)-1-(phenylselanyl)naphthalen-2-ol (8aa); Typical Proce-
dure
Anal. Calcd for C16H9NO5: C, 65.09; H, 3.07; N, 4.74. Found: C,
65.06; H, 2.99; N, 4.69.
Benzeneseleninic acid anhydride (558 mg, 1.55 mmol, 1.06 equiv)
was added to a soln of 8a (388 mg, 1.46 mmol) in anhyd THF (7.5
mL). The mixture was stirred at r.t. for 7 h. The solvent was re-
moved in vacuo, and the resultant solid residue (consisting of o-
quinone 9a, naphthol 8aa and diphenyl diselenide) was submitted to
flash column chromatography (gradient, CH2Cl2–hexane, 4:6 to
separate naphthol 8aa and CH2Cl2–hexane, 9:1 to separate o-quino-
ne 9a) to give 9a (385 mg, 94%) and 8aa (24 mg, 6%).
5H-Benzo[b]carbazole-6,11-dione (11a);10 Typical Procedure
Small portions of NaBH4 (1086 mg, 28.7 mmol, 84.4 equiv) were
added for 2 h to a soln (prepared by heating) of p-quinone 10a (100
mg, 0.34 mmol) in i-PrOH (19 mL). The mixture was stirred at r.t.
for 3.75 h, and the resulting suspension was poured into H2O (50
mL) and acidified drop-by-drop with 20% aq HCl until it turned red.
Next, the suspension was extracted with CHCl3. The combined or-
ganic extracts were dried and concentrated to dryness in vacuo to
give a solid residue that was crystallized (MeOH), yielding 11a (20
mg, 24%) as red crystals; mp>380 °C (MeOH).
3-(2-Nitrophenyl)naphthalene-1,2-dione (9a)
Mp 235–236 °C (acetone).
IR (KBr): 1675 (2 C=O), 1519, 1342 cm–1 (NO2).
1H NMR (300.14 MHz, DMSO): d = 7.58–7.73 (m, 5 Harom), 7.74–
7.89 (m, 2 Harom), 7.99 (d, J = 7.4 Hz, 1 H, C=CH), 8.12 (dd, J = 8.1,
1.1 Hz, 1 Harom).
13C NMR (75.47 MHz, DMSO): d = 124.3 (CH), 129.1 (CH), 129.3
(C), 130.1 (CH), 130.7 (CH), 130.8 (CH), 131.0 (C), 131.8 (CH),
134.1 (CH), 134.7 (C), 135.9 (CH), 136.8 (C), 141.8 (CH), 148.3
(C–NO2), 177.6 (C=O), 177.9 (C=O).
IR (KBr): 3440 (NH), 1623 (C=O), 1599 cm–1 (C=O).
1H NMR (300.14 MHz, DMSO): d = 7.25–7.35 (m, 2 Harom), 7.55–
7.57 (m, 2 Harom), 7.78–7.84 (m, 1 Harom), 7.95–8.07 (m, 3 Harom),
12.94 (br s, 1 H, NH).
13C NMR (75.47 MHz, TFA): d = 113.3 (CH), 121.0 (C), 123.5 (C),
125.1 (CH), 128.1 (C), 128.9 (CH), 130.2 (CH), 130.3 (CH), 130.4
(CH), 134.5 (CH), 136.3 (CH), 140.6 (C), 148.4 (C–NH), 154.3
(O=C–C–NH), 179.2 (2 C=O).
MS (EI, 70 eV): m/z (%) = 247 (M+, 44), 219 (100), 190 (47).
MS (EI, 70 eV): m/z (%) = 279 (M+, 3), 167 (14), 149 (71), 58 (100).
Anal. Calcd for C16H9NO4: C, 68.82; H, 3.25; N, 5.02. Found: C,
68.58; H, 3.12; N, 5.06.
Ethyl 5-Methoxy-2-(2-nitrobenzyl)-1-oxo-2,3-dihydro-1H-in-
dene-2-carboxylate (3b)
Following the typical procedure for 3a using 2b (3.278 g, 14 mmol)
and 2-nitrobenzyl bromide for 62 h furnished a residue that was sub-
mitted to flash column chromatography (CH2Cl2–hexane, 8.5:1.5)
to give 3b (4.087 g, 80%) as a light brown oil.
3-(2-Nitrophenyl)-1-(phenylselanyl)naphthalen-2-ol (8aa)
1H NMR (300.14 MHz): d = 7.13–7.26 (m, 6 Harom), 7.38–7.43 (m,
1 Harom), 7.50–7.59 (m, 3 Harom), 7.69–7.75 (m, 1 Harom), 7.85 (d,
J = 7.8 Hz, 1 Harom), 7.92 (s, 1 Harom), 8.09–8.12 (m, 1 Harom), 8.29
(d, J = 8.3 Hz, 1 Harom).
MS (EI, 70 eV): m/z (%) = 421 (M+, 35), 341 (23), 219 (34), 189
(91), 51 (100).
IR (NaCl): 1737 (C=O, ketone), 1706 (C=O, ester), 1527, 1347
(NO2), 1264 cm–1 (C–OMe).
1H NMR (300.14 MHz): d = 0.94 (t, J = 7.1 Hz, 3 H, CH3), 2.84 (d,
J = 17.6 Hz, 1 H, CHH), 3.37–3.54 (m, 2 H, CH2), 3.61 (s, 3 H,
OMe), 3.75 (d, J = 14.8 Hz, 1 H, CHH), 3.93 (c, J = 7.1 Hz, 2 H,
CH2O), 6.65–6.69 (m, 2 Harom), 7.09–7.20 (m, 1 Harom), 7.22–7.25
(m, 2 Harom), 7.45 (d, J = 8.5 Hz, 1 Harom), 7.59–7.62 (m, 1 Harom).
3-(2-Nitrophenyl)naphthalene-1,2-dione (9a) by Oxidation 8aa;
Typical Procedure
A soln of 8aa (194 mg, 0.46 mmol) in anhyd THF (4 mL) was added
to a soln of benzeneseleninic anhydride (172 mg, 0.48 mmol, 1.04
Synthesis 2009, No. 18, 3051–3060 © Thieme Stuttgart · New York

3056
M. Fernández
PAPER
13C NMR (75.47 MHz): d = 13.3 (CH3), 34.0 (CH2), 35.7 (CH2),
55.1 (OMe), 60.9 (C*), 61.3 (CH2O), 108.8 (CH), 115.5 (CH),
124.1 (CH), 125.6 (CH), 127.3 (C), 127.4 (CH), 131.1 (C), 131.5
(CH), 132.1 (CH), 149.9 (C), 155.9 (C–NO2), 165.4 (C–OMe),
170.0 (CO2Et), 199.0 (C=O).
6-Methoxy-2-(2-nitrobenzyl)-1H-indene (6b)
Following the typical procedure for 6a using 5b (540 mg, 1.80
mmol) gave 6b (384 mg, 76%) as yellow solid; mp 73–75 °C
(MeOH).
IR (KBr): 1524, 1338 cm–1 (NO2).
1H NMR (300.14 MHz): d = 3.30 (s, 2 H, CH2), 3.80 (s, 3 H, OMe),
4.11 (s, 2 H, CH2), 6.37 (s, 1 H, C=CH), 6.76–6.80 (m, 1 Harom), 6.97
(d, J = 1.8 Hz, 1 Harom), 7.14 (d, J = 8.0 Hz, 1 Harom), 7.36–7.42 (m,
2 Harom), 7.52–7.57 (m, 1 Harom), 7.96 (d, J = 1.7 Hz, 1 Harom).
MS (CI): m/z (%) = 370 (M+ + 1, 100), 324 (53).
Anal. Calcd for C20H19NO6: C, 65.03; H, 5.19; N, 3.79. Found: C,
65.36; H, 5.28; N, 3.64.
5-Methoxy-2-(2-nitrobenzyl)-2,3-dihydro-1H-inden-1-one (4b)
Following the typical procedure for 4a using 3b (435 mg, 1.18
mmol) with HBr and AcOH for 0.5 h provided a residue that was
submitted to flash column chromatography (CH2Cl2–hexane,
8.5:1.5) to give 4b (272 mg, 78%), which decomposed on silica gel
and in soln; mp 94–96 °C (MeOH).
13C NMR (75.47 MHz): d = 34.4 (CH2), 41.2 (CH2), 55.5 (OMe),
110.3 (CH), 111.8 (CH), 114.1 (C), 120.6 (CH), 124.8 (CH), 127.5
(CH), 128.0 (CH), 132.3 (CH), 133.0 (CH), 135.0 (C), 138.0 (C),
144.3 (C), 145.0 (C–NO2), 157.5 (C–OMe).
MS (CI): m/z (%) = 282 (M+ + 1, 94), 264 (100), 248 (56), 236 (30),
189 (21), 177 (27).
IR (KBr): 1701 (C=O), 1524, 1342 (NO2), 1257 cm–1 (C–OMe).
Anal. Calcd for C17H15NO3: C, 72.58; H, 5.38; N, 4.98. Found: C,
72.32; H, 5.29; N, 4.87.
1H NMR (300.14 MHz): d = 2.75–2.81 (m, 1 H, CHH), 3.01–3.21
(m, 3 H, CH2, CHH), 3.54–3.60 (m, 1 H, CH), 3.83 (s, 3 H, OMe),
6.81–6.88 (m, 2 Harom), 7.33–7.50 (m, 2 Harom), 7.51–7.55 (m, 1
Harom), 7.64–7.67 (m, 1 Harom), 7.89 (dd, J = 8.1, 1.1 Hz, 1 Harom).
13C NMR (75.47 MHz): d = 32.4 (CH2), 33.5 (CH2), 47.9 (CH),
55.6 (OMe), 109.6 (CH), 115.5 (CH), 124.7 (CH), 125.7 (CH),
127.5 (CH), 129.4 (C), 132.3 (CH), 132.9 (CH), 134.8 (C), 150.0
(C), 156.1 (C–NO2), 165.4 (C–OMe), 204.9 (C=O).
4-Methoxy-2-[3-(2-nitrophenyl)-2-oxopropyl]benzaldehyde
(7b) and 4-Methoxy-2-[3-(2-nitrophenyl)-2-oxopropyl]benzoic
Acid (7d)
N2 and O2 were bubbled consecutively for 10 min each through a
soln of 6b (581 mg, 2.07 mmol) in HPLC-grade CH2Cl2 (90 mL) at
–78 °C connected to an ozonizer. O3 was then bubbled through the
soln for 3.5 min until a blue color appeared due to the presence of
ozonide. O2 was then bubbled through for 10 min to destroy the ex-
cess O3 and finally N2 was bubbled through for 5 min. Me2S (3.0
mL, 40.8 mmol, 23.2 equiv) was added and the mixture was stirred
under argon for 2.5 h, while the temperature rose from –78 °C to r.t.
The solvent was removed in vacuo, and the solid residue was sub-
mitted to flash column chromatography (gradient, CH2Cl2–hexane,
7:3, CH2Cl2, CH2Cl2–MeOH, 9.75:0.25) to give 7b (255 mg, 39%)
and 7d (128 mg, 19%) as white solids.
MS (CI): m/z (%) = 298 (M+ + 1, 100), 251 (59).
Anal. Calcd for C17H15NO4: C, 68.68; H, 5.09; N, 4.71. Found: C,
68.92; H, 4.83; N, 4.61.
5-Methoxy-2-(2-nitrobenzyl)-2,3-dihydro-1H-inden-1-ol (5b)
Following the typical procedure for 5a using 4b (315 mg, 1.05
mmol), MeOH (15.5 mL), and NaBH4 (125 mg, 3.30 mmol, 3.14
equiv) for 1 h gave a residue that was submitted to flash column
chromatography (CH2Cl2–1% MeOH) to give the least polar inde-
nol (11 mg, 3.5%) (formed by a couple of enantiomers), the most
polar indenol (24 mg, 7.5%) (formed by a couple of enantiomers),
and a four diastereomer mixture (209 mg, 66%).
4-Methoxy-2-[3-(2-nitrophenyl)-2-oxopropyl]benzaldehyde
(7b)
Mp 90–92 °C (MeOH).
IR (KBr): 1723 (CHO), 1678 (C=O), 1522, 1257 cm–1 (NO2).
Least Polar Indenol
IR (KBr): 3141 (OH), 1523, 1345 (NO2), 1248 cm–1 (C–OMe).
1H NMR: d = 3.84 (s, 3 H, OMe), 4.25 (s, 2 H, CH2), 4.36 (s, 2 H,
CH2), 6.78 (s, 1 Harom), 6.92 (d, J = 8.0 Hz, 1 Harom), 7.40 (t, J = 7.6
Hz, 2 Harom), 7.53–7.59 (m, 1 Harom), 7.69 (d, J = 8.4 Hz, 1 Harom),
8.07 (d, J = 8.0 Hz, 1 Harom), 9.83 (s, 1 H, CHO).
13C NMR (75.47 MHz): d = 47.7 (CH2), 47.7 (CH2), 55.5 (OMe),
112.5 (CH), 118.9 (CH), 125.0 (CH), 127.5 (C), 128.2 (CH), 130.5
(C), 133.5 (CH), 133.9 (CH), 138.1 (C), 138.1 (CH), 148.5 (C–
NO2), 163.6 (C–OMe), 192.0 (CHO), 202.3 (C=O).
1H NMR (300.14 MHz): d = 2.71 (s, 1 H, CHH), 2.85 (d, J = 8.1 Hz,
2 H, CH2), 3.07–3.14 (m, 1 H, CHH), 3.37–3.44 (m, 1 H, CH), 3.79
(s, 3 H, OMe), 4.87 (s, 1 H, CHOH), 6.77 (s, 2 Harom), 7.34 (d,
J = 26.1 Hz, 2 Harom), 7.57 (s, 2 Harom), 7.92 (d, J = 7.7 Hz, 1 Harom).
13C NMR (75.47 MHz): d = 32.0 (CH2), 36.1 (CH2), 46.6 (CH),
55.4 (OMe), 75.3 (CHOH), 110.1 (CH), 112.9 (CH), 124.8 (CH),
125.6 (CH), 127.1 (CH), 132.7 (CH), 136.3 (C), 137.0 (C), 145.1
(C–NO2), 160.5 (C–OMe).
MS (CI): m/z (%) = 314 [(M+ + 1), 100], 296 (47), 286 (82), 266
(29), 248 (49).
MS (EI, 70 eV): m/z (%) = 299 (M+, 36), 264 (100), 251 (38), 162
(60), 149 (91).
Anal. Calcd for C17H15NO5: C, 65.17; H, 4.83; N, 4.47. Found: C,
64.91; H, 4.83; N, 4.50.
Most Polar Indenol
IR (KBr): 2936 (OH), 1492, 1347 (NO2), 1253 cm–1 (C–OMe).
4-Methoxy-2-[3-(2-nitrophenyl)-2-oxopropyl]benzoic Acid (7d)
Mp 176–178 °C (benzene).
IR (KBr): 3447 (OH), 1686 (2 C=O), 1522, 1253 cm–1 (NO2).
1H NMR (500.14 MHz, DMSO): d = 3.80 (s, 3 H, OMe), 4.20 (s, 2
H, CH2), 4.31 (s, 2 H, CH2), 6.85 (d, J = 2.4 Hz, 1 Harom), 6.90 (dd,
J = 8.7, 2.4 Hz, 1 Harom), 7.42 (d, J = 7.6 Hz, 1 Harom), 7.53 (t, J = 7.8
Hz, 1 Harom), 7.68 (t, J = 7.5 Hz, 1 Harom), 7.90 (d, J = 8.7 Hz, 1
Harom), 8.03 (d, J = 8.1 Hz, 1 Harom), 12.58 (s, 1 H, CO2H).
1H NMR (300.14 MHz): d = 2.51–2.62 (m, 2 H, CH2), 2.96–3.12
(m, 2 H, CH2), 3.33–3.39 (m, 1 H, CH), 3.78 (s, 3 H, OMe), 4.89 (d,
J = 6.0 Hz, 1 H, CHOH), 6.70 (d, J = 2.2 Hz, 1 Harom), 6.78 (dd,
J = 8.3, 2.4 Hz, 1 Harom), 7.27 (d, J = 8.4 Hz, 1 Harom), 7.36–7.45 (m,
2 Harom), 7.55 (dd, J = 7.5, 1.3 Hz, 1 Harom), 7.93 (dd, J = 8.1, 1.3 Hz,
1 Harom).
MS (EI, 70 eV): m/z (%) = 299 (M+, 6), 264 (100), 251 (43), 162
(58), 149 (59).
13C NMR (125.77 MHz, DMSO): d = 46.9 (CH2), 48.4 (CH2), 55.6
(OMe), 112.3 (CH), 118.4 (CH), 121.9 (C), 124.7 (CH), 128.6
Synthesis 2009, No. 18, 3051–3060 © Thieme Stuttgart · New York

PAPER
Studies on the Chemistry of 2-[3-(2-Nitrophenyl)-2-oxopropyl]benzaldehydes
3057
(CH), 130.3 (C), 133.1 (CH), 133.8 (CH), 133.8 (CH), 139.4 (C),
2-Hydroxy-7-methoxy-3-(2-nitrophenyl)naphthalene-1,4-di-
149.1 (C–NO2), 162.1 (C–OMe), 167.8 (CO2H), 202.8 (C=O).
one (10b)
Following the typical procedure for 10a using 9b (50 mg, 0.162
mmol) with 20% aq H2SO4 for 33 h gave a residue that was ad-
sorbed on silica gel and submitted to flash column chromatography
(CH2Cl2–MeOH, 9.7:0.3) to give 10b (37 mg, 70%) as a dark or-
ange solid; mp 235–36 °C (MeOH).
MS (CI): m/z (%) = 330 [(M+ + 1), 53], 312 (100), 282 (27), 193
(60).
Anal. Calcd for C17H15NO6: C, 62.00; H, 4.59; N, 4.25. Found: C,
62.37; H, 4.59; N, 3.98.
IR (KBr): 3331 (OH), 1675 (C=O), 1637 cm–1 (C=O).
7-Methoxy-3-(2-nitrophenyl)naphthalen-2-ol (8b)
Following the typical procedure for 8a using 7b (435 mg, 1.39
mmol), AcOH, and piperidine for 3 h gave a residue that crystal-
lized (abs EtOH–CH2Cl2) to give 8b (390 mg, 95%) as yellow crys-
tals; mp 228–230 °C (abs EtOH–CH2Cl2).
IR (KBr): 3420 (OH), 1516, 1354 cm–1 (NO2).
1H NMR (300.14 MHz, DMSO): d = 3.84 (s, 3 H, OMe), 6.95 (dd,
J = 9.3, 2.4 Hz, 1 Harom), 7.11–7.13 (m, 2 Harom), 7.55–7.61 (m, 2
1H NMR (CDCl3–CD3OD): d = 3.97 (s, 3 H, OMe), 7.24–7.28 (m,
1 Harom), 7.50–7.61 (m, 3 Harom), 7.67–7.74 (m, 2 Harom), 8.09 (d,
J = 9.0 Hz, 1 Harom), 8.17 (dd, J = 8.1, 1.1 Hz, 1 Harom).
MS (CI): m/z (%) = 326 (M+ + 1, 100), 294 (45), 278 (27), 179 (17).
8-Methoxy-5H-benzo[b]carbazole-6,11-dione (11b)6d
Following the typical procedure for 11a using 10b (95 mg, 0.29
mmol) for 4.25 h gave 11b (18 mg, 22%) as purple crystals;
mp>386 °C (MeOH).
Harom), 7.72–7.78 (m, 3 Harom), 7.99 (d, J = 7.9 Hz, 1 Harom), 10.13
(s, 1 H, OH).
IR (KBr): 3436 (NH), 1614 (2 C=O), 1243 cm–1 (C–OMe).
13C NMR (75.47 MHz, DMSO): d = 55.1 (OMe), 104.1 (CH), 107.8
(CH), 115.5 (CH), 123.2 (C), 123.7 (CH), 125.4 (C), 128.3 (CH),
128.6 (CH), 129.2 (CH), 132.6 (CH), 132.7 (C), 133.2 (CH), 135.7
(C), 149.1 (C–NO2), 152.5 (C–OMe), 157.8 (C–OH).
MS (EI, 70 eV): m/z (%) = 295 (M+, 100), 250 (11), 205 (24), 178
(18).
1H NMR (300.14 MHz, DMSO): d = 3.87 (s, 3 H, OMe), 7.23–7.38
(m, 3 Harom), 7.43–7.54 (m, 1 Harom), 7.68 (d, J = 7.6 Hz, 1 Harom),
7.93–7.99 (m, 1 Harom), 8.53 (d, J = 8.6 Hz, 1 Harom), 12.80 (br s, 1
H, NH).
13C NMR (75.47 MHz, TFA): d = 54.8 (OMe), 112.7 (CH), 115.0
(C), 117.5 (CH), 119.6 (CH), 120.5 (C), 125.3 (CH), 129.9 (CH),
130.4 (CH), 130.6 (C), 132.2 (CH), 140.5 (C), 150.0 (C), 153.8 (C),
165.5 (O=C–C–NH), 179.3 (2 C=O).
Anal. Calcd for C17H13NO4: C, 69.14; H, 4.44; N, 4.74. Found: C,
68.98; H, 4.41; N, 4.84.
7-Methoxy-3-(2-nitrophenyl)naphthalene-1,2-dione (9b) and 7-
Methoxy-3-(2-nitrophenyl)-1-(phenylselanyl)naphthalen-2-ol
(8bb)
Following the typical procedure for 9a using 8b (374 mg, 1.27
mmol) for 2.75 h gave a solid residue that was submitted to flash
column chromatography (gradient, CH2Cl2–hexane, 1:1 and
CH2Cl2) to give 9b (290 mg, 74%) as a purple solid and a solid iden-
tified as 8bb (102 mg, 19%).
MS (EI, 70 eV): m/z (%) = 277 (M+, 42), 249 (53), 234 (73), 207
(28), 29 (100).
2-[3-(2-Nitrophenyl)-2-oxopropyl]benzoic Acid (7c) and 2-[3-
(2-Nitrophenyl)-2-oxopropyl]benzaldehyde (7a); Typical Pro-
cedure
N2 and O2 were bubbled consecutively for 10 min each through a
soln of 6a (3567 mg, 14.2 mmol) in HPLC-grade CH2Cl2 (350 mL)
at –40 °C connected to an ozonizer. O3 was then bubbled through
the soln for 30 min until a blue color appeared due to the presence
of ozonide. O2 was then bubbled through for 10 min to destroy the
excess O3, and finally, N2 was bubbled through for 10 min. Me2S
(20.9 mL, 284.6 mmol, 20.0 equiv) was added and the mixture was
stirred at –40 °C under argon for 45 min and rising from –40 °C to
r.t. for 40 min. The solvent was removed in vacuo and the solid res-
idue was submitted to flash column chromatography (gradient,
CH2Cl2–hexane, 6:4, CH2Cl2, and CH2Cl2–MeOH, 9.7:0.3), to give
7a [1.40 g, 35%; 112–114 °C (MeOH)] and 7c (1.30 g, 31%) as
white solids.
7-Methoxy-3-(2-nitrophenyl)naphthalene-1,2-dione (9b)
Mp 210–12 °C (acetone–CH2Cl2).
IR (KBr): 1665 (2 C=O), 1516, 1338 (NO2), 1282 cm–1 (C–OMe).
1H NMR (DMSO): d = 3.89 (s, 3 H, OMe), 7.33–7.71 (m, 5 Harom),
7.85 (t, J = 7.5 Hz, 2 Harom), 8.09 (d, J = 8.0 Hz, 1 H, C=CH).
13C NMR (75.47 MHz, DMSO): d = 56.2 (OMe), 114.4 (CH), 121.5
(CH), 124.6 (CH), 128.0 (C), 129.7 (C), 130.2 (CH), 132.1 (CH),
132.8 (C), 133.1 (CH), 134.1 (C), 134.4 (CH), 142.6 (CH), 148.7
(C–NO2), 161.6 (C–OMe), 177.9 (C=O), 178.2 (C=O).
MS (CI): m/z (%) = 310 (M+ + 1, 1), 292 (2), 278 (5), 17 (100).
2-[3-(2-Nitrophenyl)-2-oxopropyl]benzoic Acid (7c)
Anal. Calcd for C17H11NO6: C, 66.02; H, 3.59; N, 4.53. Found: C,
65.92; H, 3.37; N, 4.48.
Mp 167–169 °C (benzene).
IR (KBr): 3433 (OH), 1728 (C=O, acid), 1699 (C=O, ketone), 1521,
1344 cm–1 (NO2).
1H NMR (300.14 MHz, DMSO): d = 4.25 (s, 2 H, CH2), 4.32 (s, 2
H, CH2), 7.28–7.56 (m, 5 Harom), 7.66–7.72 (m, 1 Harom), 7.91 (d,
J = 7.6 Hz, 1 Harom), 8.04 (d, J = 8.1 Hz, 1 Harom), 12.92 (s, 1 H,
CO2H).
13C NMR (75.47 MHz, DMSO): d = 46.7 (CH2), 47.9 (CH2), 124.6
(CH), 127.1 (CH), 128.4 (CH), 130.1 (C), 130.5 (CH), 132.0 (CH),
132.7 (CH), 133.6 (CH), 136.4 (C), 148.9 (C–NO2), 168.2 (CO2H),
202.8 (C=O).
7-Methoxy-3-(2-nitrophenyl)-1-(phenylselanyl)naphthalen-2-ol
(8bb)
MS (EI, 70 eV): m/z (%) = 451 (M+, 100), 371 (51).
HRMS (EI): m/z (M+) calcd for C23H17O4N80Se: 451.0317; found:
451.0313.
7-Methoxy-3-(2-nitrophenyl)naphthalene-1,2-dione (9b) by
Oxidation of 8bb
Following the procedure used for the preparation of 9a from 8aa
using 8bb (102 mg, 0.230 mmol) to give 9b (67 mg, 96%).
MS (CI): m/z (%) = 300 (M+ + 1, 15), 282 [M+ – 17 (OH), 100], 252
(50).
Anal. Calcd for C16H13NO5: C, 64.21; H, 4.38; N, 4.68. Found: C,
64.22; H, 4.37; N, 4.66.
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3058
M. Fernández
PAPER
2-[3-(2-Nitrophenyl)-2-oxopropyl]benzoic Acid (7c) by Jones
Oxidation of 7a; Typical Procedure
11H-Indolo[1,2-b]isoquinolin-6-one (15a)
To a suspension of 14a (292 mg, 1.04 mmol) in anhyd MeOH (29
mL) was added 95% NaOMe (194 mg, 3.59 mmol, 3.45 equiv). The
resulting mixture was stirred at r.t. for 11.5 h. After that, H2O and
10% aq HCl (drops) were added. The solvent was removed in vac-
uo, and the resultant suspension was extracted with EtOAc (3 × 30
mL). The combined organic extracts were dried and concentrated to
dryness in vacuo. The ensuing residue was submitted to flash col-
umn chromatography (CH2Cl2–hexane, 8:2) to give 15a (195 mg,
81%) as a white solid; mp 199–201 °C (MeOH).
Jones’ reagent [4 mL, from CrO3 (1.5 g), H2O (3 mL), H2SO4 (1.5
mL)] were added to a soln of 7a (1.44 g, 5.10 mmol) in acetone (64
mL). The mixture was stirred at r.t. for 1.25 h, i-PrOH (16 mL) was
added and acetone was evaporated in vacuo. The resulting suspen-
sion was extracted with EtOAc (4 × 40 mL) and the combined or-
ganic layers were dried and concentrated to dryness in vacuo. The
resulting solid residue was purified by washing with benzene to
give 7c (1.1 g, 72%).
IR (KBr): 1668 (C=O), 1637 cm–1 (C=N).
Methyl 2-[3-(2-Nitrophenyl)-2-oxopropyl]benzoate (12a); Typi-
cal Procedure
1H NMR (300.14 MHz): d = 4.18 (s, 2 H, CH2), 6.65 (s, 1 H, CH),
7.36–7.64 (m, 6 Harom), 8.49 (d, J = 8.3 Hz, 1 Harom), 8.73 (d, J = 8.1
Hz, 1 Harom).
13C NMR (75.47 MHz): d = 34.0 (CH2), 102.5 (C=CH), 117.6 (CH),
124.2 (CH), 124.3 (C), 125.4 (CH), 125.5 (CH), 126.0 (CH), 127.6
(CH), 127.9 (CH), 128.6 (C), 132.2 (CH), 136.4 (C–C=O), 141.6
(CN), 142.6 (CN), 161.1 (C=O).
A soln of 7c (2.435 g, 8.14 mmol) and concd H2SO4 (13 mL) in
MeOH (260 mL) was refluxed in a dry atmosphere for 5 h. MeOH
was evaporated in vacuo, and H2O (125 mL) was added to the re-
sulting residue. The suspension was extracted with CH2Cl2 (3 × 100
mL). The combined organic layers were dried and concentrated to
dryness in vacuo. The solid residue was submitted to flash column
chromatography (gradient, CH2Cl2–hexane, 9:1 and CH2Cl2) to
give a mixture (2.16 g, 85%) of 12a (351 mg, 14%) and 13a (12 mg,
0.5%).
MS (EI, 70 eV): m/z (%) = 233 (M+, 100), 204 (20).
Indolo[1,2-b]isoquinoline-6,11-dione (16a)12a
A soln of CrO3 (193 mg, 4.44 mmol, 12.3 equiv) in glacial AcOH
(15 mL) and H2O (2.5 mL) was added to a soln of 15a (84 mg, 0.36
mmol) in glacial AcOH (15 mL). The resulting mixture was re-
fluxed for 5 min. After cooling to r.t. AcOH was evaporated in vac-
uo, and H2O (15 mL) was added to the ensuing suspension. The
subsequent mixture was extracted with EtOAc (3 × 20 mL), and the
combined organic extracts were dried and concentrated to dryness
to give 16a (27 mg, 30%) as a yellow solid; mp 236–38 °C (MeOH).
IR (KBr): 1702 (C=O), 1666 (O=CN), 1642 cm–1 (C=N).
1H NMR (300.14 MHz): d = 7.24–7.35 (m, 1 H, CH), 7.51–7.77 (m,
6 Harom), 8.40 (d, J = 7.8 Hz, 1 Harom), 8.61 (d, J = 7.7 Hz, 1 Harom).
Methyl 2-[3-(2-Nitrophenyl)-2-oxopropyl]benzoate (12a)
White solid; mp 97–99 °C (MeOH).
IR (KBr): 1716 (2 C=O), 1527, 1346 cm–1 (NO2).
1H NMR (300.14 MHz): d = 3.85 (s, 3 H, OMe), 4.26 (d, J = 7.4 Hz,
4 H, 2 CH2), 7.25–7.56 (m, 6 Harom), 7.99–8.06 (m, 2 Harom).
13C NMR (75.47 MHz): d = 47.4 (CH2), 48.8 (CH2), 51.9 (OMe),
124.8 (CH), 127.1 (CH), 128.0 (CH), 128.8 (C), 130.4 (C), 130.7
(CH), 132.3 (CH), 132.6 (CH), 133.2 (CH), 133.6 (CH), 136.2 (C),
148.3 (C–NO2), 167.1 (CO2Me), 202.6 (C=O).
MS (FAB): m/z (%) = 314 [(M+ + 1), 28], 154 (100).
13C NMR (75.47 MHz): d = 109.9 (CH), 117.8 (CH), 124.1 (C),
124.4 (CH), 125.9 (CH), 128.4 (CH), 129.7 (CH), 129.8 (C), 130.2
(CH), 133.1 (CH), 133.2 (C), 134.3 (C), 136.7 (CH), 147.3
(O=CCN), 158.7 (O=CN), 182.8 (C=O).
Lactone 13a
1H NMR (300.14 MHz): d = 4.23–4.31 (m, 2 H, CH2), 6.26 (s, 1 H,
CH), 7.25–7.69 (m, 6 Harom), 8.04 (d, J = 8.2 Hz, 1 Harom), 8.21–8.24
(m, 1 Harom).
MS (EI, 70 eV): m/z (%) = 247 (M+, 100), 219 (14), 190 (20).
Anal. Calcd for C16H9NO2: C, 77.72; H, 3.67; N, 5.67. Found: C,
77.32; H, 3.51; N, 5.73.
Methyl 2-(1H-Indol-2-ylmethyl)benzoate (14a)
10% Pd-C (274 mg, 27.4 mg of Pd, 0.257 mmol, 0.035 equiv) was
added to a deoxygenated soln of a mixture of 12a and 13a (2.238 g,
7.37 mmol) plus 12a (256 mg, 0.817 mmol) in MeOH (750 mL).
The resulting suspension was stirred under an H2 atmosphere (1013
mb) at r.t. for 1 h. After removal of the excess of H2 in vacuo, the
mixture was filtered through Celite, which was eluted with CH2Cl2.
The filtrate was concentrated to dryness in vacuo and the resulting
residue was submitted to flash column chromatography (CH2Cl2–
hexane, 4:6) to give 14a (1063 mg, 50%) as a white solid; mp 118–
20 °C (MeOH).
Oxidation of 4-Methoxy-2-[3-(2-nitrophenyl)-2-oxopropyl]ben-
zaldehyde (7b)
Following the typical procedure for 7c (from Jones’ oxidation of
7a) using 7b (851 mg, 2.72 mmol) for 1 h gave 7d (500 mg, 56%).
Methyl 4-Methoxy-2-[3-(2-nitrophenyl)-2-oxopropyl]benzoate
(12b)
Following the typical procedure for 12a, using 7d (670 mg, 2.04
mmol) for 4 h gave a residue that was submitted to flash column
chromatography (gradient, CH2Cl2 and CH2Cl2–MeOH, 9.9:0.1), to
give a mixture of 12b and 13b (643 mg, 94%); all possible 12b was
separated (35% yield); mp 85–86 °C (MeOH).
IR (KBr): 3340 (NH), 1711 (C=O), 1271 cm–1 (C–OMe).
1H NMR (300.14 MHz): d = 4.90 (s, 3 H, OMe), 5.30 (s, 2 H, CH2),
7.26 (s, 1 H, CH), 7.95–8.02 (m, 2 Harom), 8.17 (d, J = 6.9 Hz, 2
Harom), 8.26–8.32 (m, 2 Harom), 8.45 (d, J = 8.2 Hz, 1 Harom), 8.78 (d,
J = 7.7 Hz, 1 Harom), 9.95 (br s, 1 H, NH).
13C NMR (75.47 MHz): d = 32.9 (CH2), 52.5 (OMe), 99.7 (CH),
110.6 (CH), 119.2 (CH), 119.7 (CH), 120.9 (CH), 126.4 (CH),
128.3 (C), 128.9 (C), 130.3 (CH), 131.5 (CH), 132.4 (CH), 135.9
(C), 138.5 (C–NH), 140.8 (C–NH), 168.7 (CO2Me).
IR (KBr): 1719 (C=O, ester), 1697 (C=O, ketone), 1523, 1262
cm–1 (NO2).
1H NMR (300.14 MHz): d = 3.83 (s, 3 H, OMe), 3.84 (s, 3 H, OMe),
4.23 (s, 2 H, CH2), 4.29 (s, 2 H, CH2), 6.77–6.85 (m, 2 Harom), 7.35–
7.44 (m, 2 Harom), 7.56 (t, J = 7.4 Hz, 1 Harom), 8.00 (d, J = 8.7 Hz,
1 Harom), 8.08 (d, J = 8.2 Hz, 1 Harom).
13C NMR (75.47 MHz): d = 47.4 (CH2), 49.2 (CH2), 51.7 (OMe),
55.4 (OMe), 112.7 (CH), 118.1 (CH), 121.1 (C), 125.0 (CH), 128.1
(CH), 130.7 (C), 133.1 (CH), 133.4 (CH), 133.9 (CH), 139.1 (C),
148.7 (C–NO2), 162.6 (C–OMe), 167.0 (CO2Me), 202.8 (C=O).
MS (FAB): m/z (%) = 266 [(M+ + 1), 84], 265 (100).
Anal. Calcd for C17H15NO2: C, 76.96; H, 5.70; N, 5.28. Found: C,
76.67; H, 5.71; N, 5.35.
Synthesis 2009, No. 18, 3051–3060 © Thieme Stuttgart · New York

PAPER
Studies on the Chemistry of 2-[3-(2-Nitrophenyl)-2-oxopropyl]benzaldehydes
3059
MS (FAB): m/z (%) = 344 [(M+ + 1), 5], 154 (100).
(CH), 134.0 (C), 134.4 (C), 136.6 (C), 136.9 (CH), 147.7 (CN),
152.1 (C–OMe), 163.2 (N–C=O), 181.3 (C=O).
MS (EI, 70 eV): m/z (%) = 277 (M+, 100), 206 (19).
Methyl 2-(1H-Indol-2-ylmethyl)-4-methoxybenzoate (14b)
Following the typical procedure for 12a using a mixture of 12b and
13b (643 mg, 1.98 mmol) gave a residue that was submitted to flash
column chromatography (gradient, CH2Cl2–hexane, 4:6 and 1:1) to
give 14b (365 mg, 62%) as a white solid; mp 128–30 °C (MeOH).
Anal. Calcd for C17H11NO3: C, 73.64; H, 4.00; N, 5.05. Found: C,
73.27; H, 3.90; N, 4.98.
IR (KBr): 3340 (NH), 1705 (C=O), 1255 cm–1 (C–OMe).
1H NMR (500.14 MHz): d = 3.79 (s, 3 H, OMe), 3.92 (s, 3 H,
CO2Me), 4.35 (s, 2 H, CH2), 6.34 (s, 1 H, CH), 6.74–6.76 (m, 1
References
(1) Taylor, D. A.; Mehdi Baradarani, M.; Martínez, S. J.; Joule,
J. A. J. Chem. Res., Synop. 1979, 387; J. Chem. Res.,
Miniprint 1979, 4801.
(2) Biochemistry of Quinones; Morton, R. A., Ed.; Academic
Press: New York, 1965.
(3) Bernardo, P. H.; Chai, C. L. L.; Le Guen, M.; Smith, G. D.;
Waring, P. Bioorg. Med. Chem. Lett. 2007, 17, 82.
(4) (a) Cheng, C. C. Progress in Medicinal Chemistry, Vol. 25;
Ellis, G. P.; West, G. B., Eds.; Elsevier: Amsterdam, 1988.
(b) Asche, C.; Frank, W.; Albert, A.; Kucklaender, U.
Bioorg. Med. Chem. 2005, 13, 819.
(5) (a) Luo Y.-L., Chou T.-C., Cheng C. C.; J. Heterocycl.
Chem.; 1996, 33: 113. (b) Mocellin S.; Microarray
Technology and Cancer Gene Profiling; Springer:
Heidelberg, 2007; Chap. 8, 98.
Harom), 6.87 (d, J = 2.2 Hz, 1 Harom), 7.00–7.09 (m, 2 Harom), 7.25 (d,
J = 6.4 Hz, 1 Harom), 7.51 (d, J = 7.6 Hz, 1 Harom), 7.89 (d, J = 8.8
Hz, 1 Harom), 9.08 (s, 1 H, NH).
13C NMR (125.77 MHz): d = 33.2 (CH2), 55.1 (OMe), 55.3 (OMe),
99.8 (CH), 110.7 (CH), 112.0 (CH), 116.9 (CH), 119.3 (CH), 119.8
(CH), 121.0 (CH), 121.2 (C), 128.5 (C), 132.9 (CH), 136.1 (C),
138.7 (CN), 143.9 (CN), 162.7 (C–OMe), 168.5 (CO2Me).
MS (CI): m/z (%) = 296 [(M+ + 1), 100], 264 (14).
Anal. Calcd for C18H17NO3: C, 73.20; H, 5.80; N, 4.74. Found: C,
73.06; H, 5.76; N, 4.75.
9-Methoxy-11H-indolo[1,2-b]isoquinolin-6-one (15b)
20% Aq NaOH (3 mL) was added to a soln of 14b (98 mg, 0.33
mmol) in 96% EtOH (3 mL). The resulting mixture was refluxed for
25 min, changing the color from white to yellow and finally dark
brown. The solvent was evaporated and concd HCl (1 mL) and H2O
(10 mL) were added. The ensuing suspension was extracted with
CH2Cl2 (3 × 10 mL). The combined organic extracts were dried and
concentrated to dryness in vacuo. The subsequent residue was sub-
mitted to flash column chromatography (gradient, CH2Cl2 and
CH2Cl2–MeOH, 9.9:0.1) to give 15b (17 mg, 20%) as a white solid.
(6) (a) Bennasar, M.-L. l.; Roca, T.; Ferrando, F. J. Org. Chem.
2005, 70, 9077. (b) Bernardo, P. H.; Chai, C. L. L.; Heath,
G. A.; Mahon, P. J.; Smith, G. D.; Waring, P.; Wilkes, B. A.
J. Med. Chem. 2004, 47, 4958. (c) Mal, D.; Senapati, B. K.;
Pahari, P. Tetrahedron 2007, 63, 3768. (d) Ashcroft, W. R.;
Dalton, L.; Beal, M. G.; Humphrey, G. L.; Joule, J. A.
J. Chem. Soc., Perkin Trans. 1 1983, 2409.
(7) (a) Hagelin, H.; Oslob, J. D.; Akermark, B. Chem. Eur. J.
1999, 5, 2413. (b) Knoelker, H.-J.; O’Sullivan, N.
Tetrahedron 1994, 50, 10893. (c) O’Sullivan, P. J.; Moreno,
R.; Murphy, W. S. Tetrahedron Lett. 1992, 33, 535.
(d) Bittner, S.; Krief, P.; Massil, T. Synthesis 1991, 215.
(8) Fernández, M.; Barcia, C.; Estévez, J. C.; Estévez, R. J.;
Castedo, L. Synlett 2004, 267.
IR (KBr): 1668 (C=O), 1638 cm–1 (C=N).
1H NMR (300.14 MHz): d = 3.92 (s, 3 H, OMe), 4.19 (s, 2 H, CH2),
6.61 (t, J = 1.8 Hz, 1 H, CH), 6.86 (d, J = 2.5 Hz, 1 Harom), 7.05 (dd,
J = 8.9, 2.4 Hz, 1 Harom), 7.21–7.24 (m, 1 Harom), 7.36–7.43 (m, 2
Harom), 8.43 (d, J = 8.9 Hz, 1 Harom), 8.72–8.75 (m, 1 Harom).
13C NMR (75.47 MHz): d = 34.0 (CH2), 55.5 (OMe), 102.3 (CH),
106.7 (CH), 115.5 (CH), 117.6 (CH), 119.4 (C), 124.3 (CH), 125.3
(CH), 128.1 (CH), 128.5 (C), 129.8 (CH), 138.7 (C), 142.6 (CN),
143.0 (CN), 161.0 (C–OMe), 162.9 (C=O).
(9) (a) Cruces, J.; Martínez, E.; Treus, M.; Martínez, L. A.;
Estévez, J. C.; Estévez, R. J.; Castedo, L. Tetrahedron 2002,
58, 3015. (b) Estévez, J. C.; Estévez, R. J.; Castedo, L.
Tetrahedron Lett. 1993, 34, 6479.
(10) Cruces, J.; Estévez, J. C.; Castedo, L.; Estévez, R. J.
MS (CI): m/z (%) = 264 [(M+ + 1), 100], 263 (39).
Tetrahedron Lett. 2001, 42, 4825.
(11) Barcia, J. C.; Cruces, J.; Estévez, J. C.; Estévez, R. J.;
Castedo, L. Tetrahedron Lett. 2002, 43, 5141.
(12) (a) Gribble, G. W.; Saulnier, M. G.; Obaza-Nutaitis, J. A.;
Ketcha, D. M. J. Org. Chem. 1992, 57, 5891. (b) Merour, J.
Y.; Piroelle, S.; Cossais, F. Heterocycles 1993, 36, 1287.
(c) Fraser, H. L.; Gribble, G. W. Can. J. Chem. 2001, 79,
1515.
9-Methoxyindolo[1,2-b]isoquinoline-6,11-dione (16b)
To a suspension of 14b (100 mg, 0.34 mmol) in anhyd MeOH (10
mL) was added 95% NaOMe (60 mg, 1.11 mmol, 3.36 equiv). The
resulting mixture was stirred under a dry atmosphere at r.t. for 20 h.
After that, H2O and 10% aq HCl (some drops) were added. The sol-
vent was removed in vacuo, and the resultant suspension was ex-
tracted with EtOAc (3 × 15 mL). The combined organic extracts
were dried and concentrated to dryness in vacuo. The ensuing resi-
due was submitted to flash column chromatography (gradient,
CH2Cl2–hexane, 6:4, CH2Cl2, CH2Cl2–MeOH, 9.9:0.1, CH2Cl2–
MeOH, 9.7:0.3 and CH2Cl2–MeOH, 9.5:0.5) to give 16b (27 mg,
29%) as a yellow solid and the starting indole 14b (30 mg, 30%);
mp 269–71 °C (MeOH).
IR (KBr): 1709 (C=O), 1661 (N–C=O), 1646 (N=C), 1605 cm–1
(HC=CN).
1H NMR (300.14 MHz): d = 3.95 (s, 3 H, OMe), 7.09–7.35 (m, 4
Harom), 7.70 (t, J = 7.0 Hz, 1 H, CH), 7,84 (d, J = 7.5 Hz, 1 Harom),
8.41 (d, J = 8.3 Hz, 1 Harom), 8.68 (d, J = 8.0 Hz, 1 Harom).
(13) http://www.ncbi.nlm.nih.gov/sites/entrez, search PubChem
Compound for CID362142.
(14) (a) Hooper, M.; Pitkethly, W. N. J. Chem. Soc., Perkin
Trans. 1 1972, 1607. (b) Rajeswaran, W. G.; Srinivasan, P.
C. Synthesis 1994, 270. (c) Bennasar, M.-L.; Roca, T.;
Ferrando, F. Tetrahedron Lett. 2004, 45, 5605.
(15) Nieman, J. A.; Keay, B. A. Tetrahedron: Asymmetry 1995,
6, 1575.
(16) Campbell, N.; Davison, P. S.; Heller, H. G. J. Chem. Soc.
1963, 993.
(17) Kometani, T.; Yoshii, E. J. Chem. Soc., Perkin Trans. 1
1981, 1191.
(18) Ko, K.-Y.; Eliel, E. L. J. Org. Chem. 1986, 51, 5353.
(19) Martínez, A.; Fernández, M.; Estévez, J. C.; Estévez, R. J.;
Castedo, L. Tetrahedron 2005, 61, 1353.
13C NMR (75.47 MHz): d = 55.8 (OMe), 109.9 (CH), 111.7 (CH),
117.9 (CH), 118.6 (CH), 124.2 (C), 124.5 (CH), 125.8 (CH), 130.6
Synthesis 2009, No. 18, 3051–3060 © Thieme Stuttgart · New York

3060
M. Fernández
PAPER
(20) Wolinsky, J.; Slabaugh, M. R.; Gibson, T. J. Org. Chem.
1964, 29, 3740.
(21) Barton, D. H. R.; Brewster, A. G.; Ley, S. V.; Read, C. M.;
Rosenfeld, M. N. J. Chem. Soc., Perkin Trans. 1 1981, 1473.
(22) Mackenzie, N. E.; Surendrakumar, S.; Thomson, R. H.;
Cowe, H. J.; Cox, P. J. J. Chem. Soc., Perkin Trans. 1 1986,
2233.
(23) Martínez, A.; Fernández, M.; Estévez, J. C.; Estévez, R. J.;
Castedo, L. Tetrahedron 2005, 61, 485.
(24) Cruces, J.; Estévez, J. C.; Estévez, R. J.; Castedo, L.
Heterocycles 2000, 53, 1041.
(25) Robineon, R. K.; Moeettig, E. J. Am. Chem. Soc. 1939, 61,
1148.
(26) Perrin, D. D.; Armarego, W. L. F. Purification of Laboratory
Chemicals; Pergamon: Oxford, 1988.
Synthesis 2009, No. 18, 3051–3060 © Thieme Stuttgart · New York