An easy access to carbazolones and 2,3-disubstituted indoles

Article abstract of DOI:10.1002/ejoc.201001357

Synthesis of carbazol-4-ones, 3,4-dihydrocyclopental-indol-1-one, and indole derivatives by a Fe/AcOH-mediated intramolecular reductive N-heteroannulation of 3-hydroxy-2-(2-nitrophenyl)enones is demonstrated. The same protocol has been extended to access indolocarbazolone and indoloquinolone derivatives. Synthesis ofderivatives by a Fe/AcOH-mediated intramolecular reductive N-heteroannulation strategy is demonstrated. The starting materials were easily accessed from C-arylation of 1,3-diketones by o-nitroiodobenzenes. Copyright

Full text of DOI:10.1002/ejoc.201001357

FULL PAPER
DOI: 10.1002/ejoc.201001357
An Easy Access to Carbazolones and 2,3-Disubstituted Indoles
Donala Janreddy,[a] Veerababurao Kavala,[a] J. W. John Bosco,[a] Chun-Wei Kuo,[a] and
Ching-Fa Yao*[a]
Keywords: Nitrogen heterocycles / Cyclization / Iron
Synthesis of carbazol-4-ones, 3,4-dihydrocyclopental-indol-
1-one, and indole derivatives by a Fe/AcOH-mediated intra-
molecular reductive N-heteroannulation of 3-hydroxy-2-(2-
nitrophenyl)enones is demonstrated. The same protocol has
been extended to access indolocarbazolone and indoloquin-
olone derivatives.
Although many methods are available in the literature
that describe the synthesis of carbazolones,[9] Fischer indole
synthesis[10] is one of the most common and conventional
methods employed in this area. However, this method re-
quires highly acidic conditions and poor regioselectivity
is usually observed when unsymmetrical substrates are
used.
Introduction
Carbazolone derivatives have drawn a great deal of inter-
est from the scientific community because of their utiliza-
tion as building blocks in the total synthesis of many natu-
ral products. Such products include alkaloids such as py-
rayaquinone A and B,[1] murrayaquinone A,[2] koenigine-
quinone A,[2] and murrayafoline A.[3] In addition, many
compounds displaying potent biological activity are also re-
ported to be accessed from the carbazolone derivatives,
which are known to be active as potassium-channel block-
ers,[4] HIV-integrase inhibitors,[5] as ligands for the α1-ad-
renergic receptor subtypes,[6] and antipsychotics.[7] Further-
more, the synthetic drug ondansetron[8] can also be classed
as a carbazolone. Ondansetron is a 5HT3 receptor agonist
administered against nausea for cancer patients who un-
dergo chemotherapy and radiation treatment. A few exam-
ples of the diverse application of carbazolones in synthetic
organic and medicinal chemistry is depicted in Figure 1.
As an alternative, palladium-catalyzed oxidative cycliza-
tion of arylenaminones,[11] and palladium[12] and copper[13]
catalyzed intramolecular cyclization of halo aryl enami-
nones have been reported. Sorensen and Pombo-Villar[14]
showed that palladium-catalyzed intramolecular cyclization
of haloaryl enaminones is quite exciting in this category. As
far as the protocols associated with the reductive cyclization
is concerned, Scott and Söderberg[15] have reported palla-
dium-catalyzed reductive N-hetero-annulation of variety of
substituted 2-(2-nitrophenyl)-2-cycloalkenones. These au-
thors also extended the same catalytic system to 3-hydroxy-
2-(2-nitrophenyl)cyclohex-2-enone. However, this reaction
requires extended reaction times (90–96 h). Moreover, cost
effectiveness and use of carbon monoxide are serious con-
cerns associated with this approach. Subsequently, Scott et
al. attempted same reaction with Pd/C,[16] however, a mix-
ture of carbazolone (43%) and 1,2,3,4-tetrahydrocarbazole
(22%) was obtained. More recently, Bunce and Nammal-
war reported the synthesis of carbazolone derivatives from
1H-indole-2-butanoic acid.[17] Available methods that are
described in the literature for the synthesis of the carbaz-
olone moiety is summarized in Figure 2.
On the other hand, iron-mediated reductive transforma-
tions has been well-documented in the literature,[18] and the
combination of iron/acetic acid is one of the most popular
systems among the iron-promoted reductive transforma-
tions.[19] Recently, our group has investigated applications
of the conventional Fe/AcOH system for versatile heterocy-
clic synthesis.[20] Encouraged by our previous results, we
were prompted to use the Fe/AcOH system for the reductive
cyclization of 3-hydroxy-2-(2-nitrophenyl)cycloalkenones.
Figure 1. Natural products and biologically active compounds de-
rived from carbazolones.
[a] Department of Chemistry, National Taiwan Normal University,
88, Sec. 4, Tingchow Road, 116 Taipei, Taiwan
E-mail: cheyaocf@ntnu.edu.tw
cheyaocf@yahoo.com.tw
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Carbazolones and 2,3-Disubstituted Indoles
Table 1. Synthesis of carbazolones by Fe/AcOH-mediated reductive
cyclization of 3-hydroxy-2-(2-nitrophenyl)cyclohexenones.
Figure 2. Common synthetic strategies available to access carbaz-
olones.
Results and Discussion
To pursue our goal, we first synthesized the starting ma-
terials by arylation of 1,3-cyclic diketones with 2-nitro-
iodoarenes through a straightforward literature method
(Scheme 1).[21]
Scheme 1. Outline of the synthetic route to carbazolone derivatives.
Initially, we tested our assumption with 3-hydroxy-2-(2-
nitrophenyl)cyclohexenone as a model substrate. When this
compound was treated with Fe/AcOH under reflux condi-
tions, the expected carbazolone was obtained as the sole
product in 86% yield after 2.5 h. Encouraged by this intri-
guing result, we applied the same reaction conditions to a
[a] Reactions carried out on 1 mmol scale [Fe (6 mmol), AcOH
(5 mL)]. [b] Isolated yield.
range of substituted 3-hydroxy-2-(2-nitrophenyl)cyclohex- substitution in the cyclohexenone counterpart of the sub-
enones. The results are summarized in Table 1.
strate did not effect the product yields (Table 1, entries 7–
The experimental results revealed that the nature of the 9).
substituent on the benzene ring of the substrate did not
In a continuation, the synthesis of 2,3-dihydrocyclo-
significantly effect the product yields. However, dimethoxy- penta[b]-indol-1(4H)-ones by Fe/AcOH-mediated reductive
substituted 3-hydroxy-2-(2-nitrophenyl)cyclohex-2-enone cyclization of 3-hydroxy-2-(2-nitrophenyl)cyclopentenones
(Table 1, entry 5) gave slightly lower yield than other sub- was also attempted (Table 2). Substitution on C4 slightly
strates. Moreover, the reaction of 3-hydroxy-2,4-dinitro-2- reduced the yield compared with the unsubstituted precur-
(2-nitrophenyl)cyclohex-2-enone (Table 1, entry 4) showed sor, despite the shorter reaction time (Table 2, entries 1 and
a remarkable selectivity towards reduction of the o-nitro 2). On the other hand, the present methodology was also
group. In this case, the desired 7-nitrocarbazolone was ob- amenable to the synthesis of indeno-indole derivatives from
tained in good yield with a trace amount of 7-amino carb- the corresponding 3-hydroxy-2-(2-nitrophenyl)-1H-inden-1-
azole formed as a side product. Similarly, geminal dimethyl one derivatives (Table 2, entries 3 and 4). It is noteworthy
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C.-F. Yao et al.
FULL PAPER
that indeno-indole derivatives are known to act as ligands hibit a considerable effect on the cyclization. Precursors
at the melatonin binding site MT3.[22] The crystal structure containing an electron-releasing group produced lower
of indeno-indole 12a is shown in Figure 3.
yields of the desired product than with the unsubstituted
substrate and the substrate containing an electron-with-
drawing group. Unsubstituted 4-hydroxy-3-(2-nitrophenyl)-
pent-3-en-2-ones gave the 2-methyl-3-acetyl indole in a
shorter reaction time and in good yield (Table 3, entry1).
The methyl-substituted precursor (Table 3, entry 2) afforded
the corresponding 3-acetyl-2-methylindole derivative in
72% yield. Substitution with Br at C4 also produced a good
yield, however, the required time was longer than for the
unsubstituted and methoxy-substituted precursor (Table 3,
entry 3). Disubstitution with electron-donating methoxy
groups dramatically suppressed the yield despite shorter re-
action time (Table 3, entry 4). In the same way, aromatic
substitution at C4 in 3-hydroxy-2-(2-nitrophenyl)-1,3-di-
phenylprop-2-en-1-one also gave a lower yield than the un-
substituted substrate (Table 3, entries 5 and 6).
Table 2. Fe/AcOH-mediated reductive cyclization of 3-hydroxy-2-
(2-nitrophenyl)cyclopentenones and 3-hydroxy-2-(2-nitrophenyl)-
1H-inden-1-ones.
Table 3. Synthesis of indoles by Fe/AcOH-mediated reductive cycli-
zation of 4-hydroxy-3-(2-nitrophenyl)eneones.
[a] Reactions carried out on 1 mmol scale [Fe (6 mmol), AcOH
(5 mL)]. [b] Isolated yield.
Figure 3. ORTEP diagram of the single-crystal X-ray structure of
12a.[25]
After the successful reductive cyclization of a range of C-
arylated products obtained from the arylation of 1,3-cyclic
diketones with 2-nitroiodoarenes, we next explored the re-
ductive cyclization of C-arylated products derived from the
acyclic 1,3-diketones and 2-nitroiodoarenes under similar
reaction conditions. The C-arylated acyclic 1,3-diketone
[a] Reactions carried out on 1 mmol scale [Fe (6 mmol), AcOH
(5 mL)]. [b] Isolated yield.
On the other hand, the reaction of C-arylated precursors
precursors obtained from symmetrical 1,3-diketones, gave derived from unsymmetrical dicarbonyl compounds and 2-
exclusively 2,3-disubstituted indoles (Table 3). Substituents nitroiodoarenes gave a mixture of regioisomers 21a and
on the precursors obtained from the pentane-2,4-dione ex- 21b, together with substantial amounts of the N-hydroxy-
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Carbazolones and 2,3-Disubstituted Indoles
indole derivatives 21c and 22b formed as side products
(Scheme 2). The N-hydroxy compounds were identified by
single-crystal X-ray diffraction analysis (Figure 4).
Conclusions
A simple and efficient synthetic protocol that involves
Fe/AcOH-mediated N-heteroannulation to achieve a library
of carbazol-4-ones, 3,4-dihydrocyclopental-indol-1-one, and
indole derivatives, has been developed. Moreover, this ap-
proach enables easy access to indolocarbazolone and indol-
oquinolinone derivatives. Once the reaction is complete, the
product can be obtained simply by filtering the resulting
precipitate and, significantly, no work up involving a base
is required to remove the acetic acid. The starting materials
were also readily attained by arylation of commercially
available 1,3-diketones. Furthermore, the conventional Fe/
AcOH system is much more cost effective than existing
methods involving transition metals. Hence, short reaction
time, high yield, economical viability, and the ready avail-
Scheme 2. Reductive cyclization of C-arylated precursors derived
from unsymmetrical dicarbonyl compounds and 2-nitroiodoarenes. ability and accessibility of starting materials are salient fea-
tures of this method. Furthermore, this method is also ap-
plicable to the synthesis of indazolocarbazolone derivatives
and the natural product precursor of cryptosanguinolen-
tine.
Experimental Section
General Information: All reactions were performed under reflux
conditions. Analytical thin-layer chromatography (TLC) was per-
formed with E. Merck silica gel 60F glass plates, and flash
Figure 4. ORTEP diagram of the single-crystal X-ray structure of
chromatography by the use of E. Merck silica gel 60 (230–
400 mesh). MS and HRMS were measured with JEOL JMS-D300
or JEOL JMS-HX110 spectrometers. 1H and 13C NMR spectra
were recorded with a Bruker Avance EX 400 spectrometer.
21c.[25]
To further explore the scope of our protocol, we applied
the method to the double reductive cyclization of 2,2Ј-(4,6-
dinitro-1,3-phenylene)bis(3-hydroxy-5,5-dimethylcyclo-
hex-2-enone) to obtain the indolocarbazolone derivative
23a (Scheme 3). It is worth noting that the indolocarbazole
derivatives are an important class of natural products that
possess diverse biological activities.[23]
General Experimental Procedure for the Reductive Cyclization: Sub-
strate (1 mmol) was taken in acetic acid (5 mL) and heated until
the solution became homogeneous. Fe powder (0.335 g, 6 mmol)
was added and the mixture was heated to reflux temperature; the
reaction was monitored by TLC. Upon completion, the reaction
mixture was cooled to room temperature and acetic acid was re-
moved in vacuo. The reaction mixture was diluted with EtOAc
(10 mL), stirred for 10 min, and filtered through a pad of Celite to
remove any iron impurities. The filtrate was dried with anhydrous
Na2SO4, concentrated under reduced pressure, and the resulting
crude product was purified by column chromatography to afford
the desired product.
Note: Because of problems with solubility, for compounds 4a and
23a, the mixture were diluted with methanol instead of EtOAc then
filtered through a pad of Celite.
Scheme 3. Double reductive cyclization of 23.
Finally, we successfully extended this method to the syn-
thesis of indoloquinolinone derivative 24a, which is a pre-
cursor compound for indoloquinoline alkaloids such as
cryptosanguinolentine, which has shown antiplasmodial
properties (Scheme 4).[24]
7-Methyl-2,3-dihydro-1H-carbazol-4(9H)-one (2a): Yield 159 mg
(80%); white solid; m.p. 294–296 °C. FTIR (KBr): ν = 3150,
˜
1645 cm–1. 1H NMR (400 MHz, [D6]DMSO): δ = 11.69 (br. s, 1
H), 7.85 (d, J = 8.0 Hz, 1 H), 7.19 (s, 1 H), 6.95 (d, J = 7.9 Hz, 1
H), 3.77, 2.92 (t, J = 5.9 Hz, 2 H), 2.41–2.38 (m, 5 H), 2.09 (t, J =
6.1 Hz, 2 H) ppm. 13C NMR (100 MHz, [D6]DMSO): δ = 192.7,
151.8, 136.3, 131.5, 122.9, 122.3, 119.8, 111.7, 111.4, 37.7, 23.4,
22.7, 21.2 ppm. MS (EI): m/z (%) = 199 (100) [M]+, 171 (19).
HRMS: calcd. for C13H13O2N [M]+ 199.2441; found 199.2450.
7-Nitro-2,3-dihydro-1H-carbazol-4(9H)-one(4a): Because of prob-
lems with solubility, the mixture was diluted with methanol instead
of EtOAc then filtered through a pad of Celite. Yield 191 mg
Scheme 4. Synthesis of cryptosanguinolentine precursor 24a.
(83%); yellow solid; m.p. 330–332 °C. FTIR (KBr): ν = 3234,
˜
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C.-F. Yao et al.
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1638 cm–1. 1H NMR (400 MHz, [D6]DMSO): δ = 12.51 (br. s, 1
135.0, 132.5, 129.2, 122.2, 119.8, 118.5, 116.5, 114.2, 112.3, 97.3,
H), 8.29 (d, J = 1.9 Hz, 1 H), 8.10–8.04 (m, 2 H), 3.06 (t, J =
55.3 ppm. MS (EI): m/z (%) = 249 (100) [M]+, 234 (38). HRMS:
6.2 Hz, 2 H), 2.51–2.49 (m, 2 H), 2.18–2.14 (m, 2 H) ppm. 13C calcd. for C16H11O2N [M]+ 249.0784; found 249.0795.
NMR (100 MHz, [D6]DMSO): δ = 193.1, 157.3, 142.6, 134.7,
7-Bromoindeno[1,2-b]indol-10(5H)-one (14a): Yield 199 mg (67%);
129.4, 119.9, 116.9, 112.1, 107.9, 37.7, 23.0, 22.9 ppm. MS (EI):
red crystalline solid; m.p. 236–238 °C. FTIR (KBr): ν = 3243,
˜
m/z (%) = 230 (100) [M]+, 202 (38). HRMS: calcd. for C12H10O3N2
1643 cm–1. 1H NMR (400 MHz, [D6]DMSO): δ = 12.66 (br. s, 1
H), 7.66 (d, J = 1.2 Hz, 1 H), 7.48 (d, J = 8.4 Hz, 1 H), 7.41–7.37
(m, 1 H), 7.35 (t, J = 5.96 Hz, 2 H), 7.28–7.25 (m, 2 H) ppm. 13C
NMR (100 MHz, [D6]DMSO): δ = 184.3, 159.3, 142.4, 140.0,
134.2, 132.7, 129.9, 125.8, 122.5, 121.3, 120.7, 119.3, 116.2, 115.0,
113.9 ppm. MS (EI): m/z (%) = 299 (100) [M + 2], 297 (99) [M]+.
HRMS: calcd. for C15H8ON79Br [M]+ 296.9789; found 296.9792.
[M]+ 230.0686; found 230.0694.
6,7-Dimethoxy-2,3-dihydro-1H-carbazol 4(9H)-one (5a): Yield
184 mg (75%); pale-brown solid; m.p. 215–217 °C. FTIR (KBr): ν
˜
= 3186, 1638 cm–1. 1H NMR (400 MHz, [D6]DMSO): δ = 11.56
(br. s, 1 H), 7.43 (s, 1 H), 6.93 (s, 1 H), 3.77 (s, 3 H), 3.76 (s, 3 H),
2.90 (t, J = 6.0 Hz, 2 H), 2.38 (t, J = 6.2 Hz, 2 H), 2.10–2.07 (m,
2 H) ppm. 13C NMR (100 MHz, [D6]DMSO): δ = 192.7, 150.4,
146.6, 145.9, 129.9, 117.2, 111.8, 102.7, 95.6, 55.7, 37.7, 23.6,
22.7 ppm. MS (EI): m/z (%) = 245 (100) [M]+, 230 (23). MS: calcd.
for C14H15O3N [M]+ 245.1046; found 245.1053.
1-(2,6-Dimethyl-1H-indol-3-yl)ethanone (16a): Yield 159 mg (85%);
white solid; m.p. 225–227 °C. FTIR (KBr): ν = 3175, 1640 cm–1.
˜
1H NMR (400 MHz, [D6]DMSO): δ = 11.65 (br. s, 1 H), 7.86 (d,
J = 8.1 Hz 1 H), 7.14 (s, 1 H), 6.95 (d, J = 8.1 Hz 1 H), 2.67 (s, 3
H), 2.50 (s, 3 H), 2.41 (s, 3 H) ppm. 13C NMR (100 MHz, [D6]-
DMSO): δ = 192.8, 143.5, 135.0, 130.8, 124.7, 122.8, 120.3, 113.4,
111.0, 30.8, 21.1, 14.9 ppm. MS (EI): m/z (%) = 187 (100) [M]+, 172
(39). HRMS: calcd. for C11H11ON [M]+ 187.2350; found 187.2343.
5,7-Dimethyl-2,3-dihydro-1H-carbazol-4(9H)-one
(6a):
Yield
179 mg (84%); pale-yellow solid; m.p. 220–222 °C. FTIR (KBr): ν
˜
= 3174, 1617 cm–1. 1H NMR (400 MHz, [D6]DMSO): δ = 11.70
(br. s, 1 H), 6.95 (s, 1 H), 6.70 (s, 1 H), 2.91 (t, J = 6.2 Hz, 2 H),
2.76 (s, 3 H), 2.41 (t, J = 6.3 Hz, 2 H), 2.32 (s, 3 H), 2.08–1.99 (m,
2 H) ppm. 13C NMR (100 MHz, [D6]DMSO): δ = 191.4, 151.9,
136.9, 131.8, 130.7, 124.8, 121.9, 112.9, 108.8, 38.9, 23.3, 22.9, 22.5,
20.9 ppm. MS (EI): m/z (%) = 213 (100) [M]+, 185 (28). HRMS:
calcd. for C14H15ON [M]+ 213.1148; found 213.1157.
1-(5,6-Dimethoxy-2-methyl-1H-indol-3-yl)ethanone (18a): Yield
179 mg (77%); colorless solid; m.p. 180–182 °C. FTIR (KBr): ν =
˜
1
3182, 1623 cm–1. H NMR (400 MHz, [D6]DMSO): δ = 11.50 (br.
s, 1 H), 7.58 (s, 1 H), 6.89 (s, 1 H), 3.78 (s, 6 H), 2.63 (s, 3 H), 2.50
(s, 3 H) ppm. 13C NMR (100 MHz [D6]DMSO): δ = 192.7,146.3,
145.7, 141.9, 128.8, 119.9, 113.7, 103.8, 94.9, 55.9, 55.7, 30.6,
15.0 ppm. MS (EI): m/z (%) = 233 (100) [M]+, 218 (35). HRMS:
calcd. for C13H15O3N [M]+ 233.1046; found 233.1054.
7-Methoxy-2,2-dimethyl-2,3-dihydro-1H-carbazol-4(9H)-one (8a):
Yield 209 mg (86%); colorless solid; m.p. 245–247 °C. FTIR (KBr):
1
ν = 3432, 1615 cm–1. H NMR (400 MHz, [D ]DMSO): δ = 11.62
˜
6
(br. s, 1 H), 7.76 (d, J = 8.5 Hz 1 H), 6.89 (d, J = 2.1 Hz, 1 H),
6.77 (dd, J = 8.6, 2.2 Hz, 1 H), 3.76 (s, 3 H), 2.81 (s, 2 H), 2.29 (s,
2 H), 1.07 (s, 6 H) ppm. 13C NMR (100 MHz, [D6]DMSO): δ =
191.9, 156.0, 150.2, 137.1, 120.6, 118.3, 110.5, 95.5, 55.2, 51.8, 36.4,
35.3, 28.2 ppm. MS (EI): m/z (%) = 243 (100) [M]+, 187 (35).
HRMS: calcd. for C15H17O2N [M]+ 243.1254; found 243.1264.
(1-Hydroxy-2-methyl-1H-indol-3-yl)(phenyl)methanone (21c): Yield
60 mg (24%); colorless solid; m.p. 182–184 °C. FTIR (KBr): ν =
˜
1
3361, 1632 cm–1. H NMR (400 MHz, [D6]DMSO): δ = 11.70 (br.
s, 1 H), 7.62–7.59 (m, 3 H), 7.54–7.48 (m, 3 H), 7.37 (d, J = 8.0 Hz,
1 H), 7.21 (t, J = 7.4 Hz, 1 H), 7.07 (t, J = 7.4 Hz, 1 H), 2.40 (s, 3
H) ppm. 13C NMR (100 MHz, [D6]DMSO): δ = 191.0, 141.6,
141.5, 133.0, 131.1, 128.4, 128.0, 122.6, 122.1, 121.6, 120.0, 108.7,
107.6, 11.2 ppm. MS (EI): m/z (%) = 251 (100) [M]+, 234 (17), 216
(13). HRMS: calcd. for C16H13O2N [M]+ 251.0835; found
251.0843.
7-Bromo-2,2-dimethyl-2,3-dihydro-1H-carbazol-4(9H)-one
(9a):
Yield 251 mg (86%); brown solid; m.p. 270–272 °C. FTIR (KBr):
1
ν = 3132, 1627 cm–1. H NMR (400 MHz, [D ]DMSO): δ = 11.95
˜
6
(br. s, 1 H), 7.84 (d, J = 8.3 Hz 1 H), 7.59 (s, 1 H), 7.27 (dd, J =
8.3, 1.4 Hz, 1 H), 2.84 (s, 2 H), 1.90 (s, 2 H), 1.07 (s, 6 H) ppm.
13C NMR (100 MHz, [D6]DMSO): δ = 192.2, 151.9, 137.1, 124.3,
123.3, 121.6, 114.7, 114.3, 110.4, 51.7, 36.2, 35.2, 28.1 ppm. MS
(EI): m/z (%) = 291 (100) [M]+, 235 (25), 234 (22). HRMS: calcd.
for C14H14ON79Br [M]+ 291.0253; found 291.0256; calcd. for
C14H14ON81Br [M+ + 2] 293.0233; found 293.0227.
5,5,11,11-Tetramethyl-4,5,6,10,11,12-hexahydroindolo[2,3-b]-
carbazole-7,9(1H,3H)-dione (23a): Because of problems with solu-
bility, the mixture was diluted with methanol instead of EtOAc
then filtered through a pad of Celite. Yield 278 mg (80%); yellow
solid; m.p. 282–284 °C. FTIR (KBr): ν = 3430, 1636 cm–1. 1H
˜
NMR (400 MHz, [D6]DMSO): δ = 12.31 (br. s, 1 H), 10.7 (br. s, 1
H), 8.03 (s, 1 H), 7.73 (s, 1 H), 2.50–2.31 (m, 8 H), 1.12 (s, 6 H),
1.10 (s, 6 H) ppm. 13C NMR (100 MHz, [D6]DMSO): δ = 192.4,
155.4, 144.8, 133.8, 127.3, 124.0, 122.7, 113.5, 110.5, 108.2, 51.7,
46.4, 36.4, 35.2, 31.6, 28.6, 27.9, 27.4 ppm. MS (EI): m/z (%) = 350
(100) [M + 2]+, 219 (12), 250 (10), 88 (100). HRMS: calcd. for
C22H24O2N2 [M]+ 348.1832; found 348.1836.
6-Methoxy-2,3-dihydrocyclopenta[b]indol 1(4H)-one (11a): Yield
175 mg (87%); brown solid; m.p. 215–217 °C. FTIR (KBr): ν =
˜
1
3188, 1644 cm–1. H NMR (400 MHz, [D6]DMSO): δ = 11.83 (br.
s, 1 H), 7.54 (d, J = 8.5 Hz, 1 H), 6.96 (d, J = 1.8 Hz, 1 H), 6.79
(dd, J = 8.5, 2.0 Hz, 1 H), 3.79 (s, 3 H), 3.04–3.02 (m, 2 H), 2.80–
2.77 (m, 2 H) ppm. 13C NMR (100 MHz, [D6]DMSO): δ = 194.3,
167.2, 156.3, 143.3, 119.9, 119.0, 114.9, 110.3, 96.5, 55.2, 40.6,
21.1 ppm. MS (EI): m/z (%) = 201 (100) [M]+, 186 (30), 172 (18),
158 (15). HRMS: calcd. for C12H11O2N [M]+ 201.0784; found
201.0791.
Acknowledgments
Financial support for this work by the National Science Council
of the Republic of China and National Taiwan Normal University
(grant number 99T3030-2 and 99D) is gratefully acknowledged.
7-Methoxyindeno[1,2-b]indol-10(5H)-one (13a): Yield 189 mg
(76%); dark-red crystalline solid; m.p. 285–287 °C. FTIR (KBr): ν
˜
= 3233, 1650 cm–1. 1H NMR (400 MHz, [D6]DMSO): δ = 12.34
(br. s, 1 H), 7.44 (d, J = 8.6 Hz, 1 H), 7.35–7.31 (m, 1 H), 7.27 (d,
J = 6.9 Hz, 1 H), 7.23–7.17 (m, 2 H), 6.96 (d, J = 1.8 Hz, 1 H),
6.80 (dd, J = 8.6, 2.1 Hz, 1 H), 3.80 (s, 3 H) ppm. 13C NMR
(100 MHz, [D6]DMSO): δ = 184.4, 158.0, 156.4, 142.7, 140.1,
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Received: September 30, 2010
Published Online: March 3, 2011
Eur. J. Org. Chem. 2011, 2360–2365
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
2365