Substituted benzo[a]carbazoles and indoleacetic acids from arylglyoxals and enamines through domino condensation, thermal cyclization, and aromatization

Article abstract of DOI:10.1002/ejoc.201402085

A two-step method has been developed in which cyclohexanone-fused 2-(3-pyrrolyl)-2-cyanoacetamides, the condensation products of enamines, arylglyoxals, and malononitrile, are converted into highly substituted benzo[a]carbazoles through a one-step thermal cyclization and palladium-catalyzed aromatization. The biologically important indoleacetic acid derivatives are also obtained in good yields from the hydrolysis and aromatization of the same cyanoacetamides. Copyright

Full text of DOI:10.1002/ejoc.201402085

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FULL PAPER
DOI: 10.1002/ejoc.201402085
Substituted Benzo[a]carbazoles and Indoleacetic Acids from Arylglyoxals and
Enamines through Domino Condensation, Thermal Cyclization, and
Aromatization
Subhendu Maity,[a] Sudipta Pathak,[a] and Animesh Pramanik*[a]
Keywords: Synthetic methods / Domino reactions / Cyclization / Nitrogen heterocycles / Aromatization
A two-step method has been developed in which cyclohex-
anone-fused 2-(3-pyrrolyl)-2-cyanoacetamides, the conden-
sation products of enamines, arylglyoxals, and malononitrile,
are converted into highly substituted benzo[a]carbazoles
through a one-step thermal cyclization and palladium-cata-
lyzed aromatization. The biologically important indoleacetic
acid derivatives are also obtained in good yields from the
hydrolysis and aromatization of the same cyanoacetamides.
functionalized indoleacetic acids, such as (4-hydroxy-1,2-di-
phenyl-1H-3-indolyl)acetic acids. Therefore, we wish to re-
port, herein, an efficient synthesis for both highly substi-
tuted benzo[a]carbazoles and indoleacetic acid derivatives
from a common intermediate that follows reaction proto-
cols with a minimum number of steps.
Introduction
The carbazole core is present in a number of naturally
occurring molecules that exhibit remarkable biological ac-
tivity in living cells.[1] Carbazole ring compounds also have
wide applicability in materials science as organic light-emit-
ting materials as a result of their wide band gap, high lumi-
nescent activity, and flexibility with regard to the chemical
manipulation of the parent carbazole framework.[2] Among
various carbazole derivatives, the aryl- and heteroaryl-
annulated[a]carbazoles have drawn significant biological
and pharmacological interest that has ensued from their af-
finity toward nucleic acids.[3] Particularly, the benzo[a]carb-
azole frameworks may exhibit antitumor activity,[4a] anties-
trogenic properties[4b] or kinase inhibitory activities.[4c]
Hence, these are appealing targets for organic chemists. A
number of useful synthetic methods for the preparation of
carbazole derivatives are available that utilize metal-medi-
ated C–C and C–N bond formation[5] as well as thermal
and photochemical cyclization reactions of different substi-
tuted indoles or arylamines.[6] Although these methods are
useful to synthesize carbazole derivatives, there are some
significant limitations, such as most of them require
multistep reaction protocols and demonstrate poor atom
economy. Therefore, a simple, efficient, regiocontrolled, and
diversified synthesis for carbazole derivatives that contain
specific substitution patterns is still highly attractive. On the
other hand, the indoleacetic acid derivatives, the analogues
of plant growth regulatory hormones,[7a,7b] are also impor-
tant target molecules to synthetic chemists.[7c–7f] However,
until now there has been no report of the synthesis of highly
Results and Discussion
Recently, some reports have shown that the domino con-
densation of arylglyoxals and enamines can produce
densely substituted pyrrole derivatives.[8] Similarly, when a
mixture of the enamine 3-(phenylamino)cyclohex-2-enone
(1, R1 = phenyl), phenylglyoxal monohydrate (2, R2 = H),
and malononitrile (3) was heated at reflux in ethanol, the
new compound 2-cyano-2-(4-oxo-1,2-diphenyl-4,5,6,7-
tetrahydro-1H-3-indolyl)acetamide (4a) was formed in high
yield through a domino condensation (see Scheme 1). Inter-
[a] Department of Chemistry, University of Calcutta,
92, A. P. C. Road, Kolkata 700009, India
E-mail: animesh_in2001@yahoo.co.in
http://www.caluniv.ac.in/academic/chemistry.htm
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201402085.
Scheme 1. Synthesis of pyrrole-substituted 2-cyanoacetamide deriv-
atives 4.
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estingly, under the reaction conditions, one of the two into an amide group. By using this approach, a series of 2-
cyano groups of malononitrile was selectively hydrolyzed (1,2-diaryl-4-oxo-4,5,6,7-tetrahydro-1H-3-indolyl)-2-cyano-
Table 1. Synthesis of pyrrole-substituted 2-cyanoacetamide derivatives 4.[a]
[a] Isolated yield.
2
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Benzo[a]carbazoles and Indole Acetic Acids
acetamides 4a–4w were synthesized by varying the starting
enamine as well as the arylglyoxal monohydrate (see
Scheme 1 and Table 1). All of the compounds 4a–4w were
1
fully characterized by H and 13C NMR spectroscopy, and
the X-ray crystal structure analysis of 2-[1,2-bis(4-
chlorophenyl)-4-oxo-4,5,6,7-tetrahydro-1H-3-indolyl]-2-
cyanoacetamide (4u) further confirmed the structural as-
signments (see Figure 1).[9] The synthesis of 4a by using the
same starting materials, as described above, but with other
solvents such as acetonitrile, dioxone, and N,N-dimethyl-
formamide (DMF) also afforded a good yield of product
(69–77%) within 0.5 h when the reaction mixture was
heated at reflux (see Supporting Information, Table S1).
Some cyclohexanone-fused pyrrole derivatives have also
been synthesized by using a different approach.[10]
A proposed mechanism for the formation of compound
4a is shown in Scheme 2.[8e,11] Initially, arylglyoxal monohy-
drate 2 undergoes a Knoevenagel condensation with ma- Figure 1. ORTEP diagram of X-ray crystal structure of 4u.
lononitrile to produce α,β-unsaturated nitrile intermediate
5. Then, a Michael-type 1,4-addition of enamine 1 with in-
termediate 5 produces imminium intermediate 6, which phenyl-4,5,6,7-tetrahydro-1H-3-indolyl)acetamide (4a) was
subsequently tautomerizes to give 7. Intermediate 7 the un- heated at reflux in diphenyl ether in the presence of palla-
dergoes a tandem cyclization to form fused furano-pyrrole dium on carbon (Pd/C) for 1 h. Surprisingly, the highly sub-
intermediate 8. Finally, the rearrangement of intermediate stituted carbazole derivative 5,7-dihydroxy-11-phenyl-11H-
8 leads to pyrrole-substituted cyanoacetamides 4, which re- benzo[a]carbazole-6-carbonitrile (9a) was formed instead of
sults in the selective hydrolysis of one of the two nitrile
a
hydroxy indole derivative. The reaction proceeded
groups.
through an intramolecular thermal cyclization between the
After the successful synthesis of compounds 4a–4w, we amide carbonyl and the adjacent aromatic ring carbon of
thought that the fused cyclohexanone ring of 4a–4w could 4a followed by an aromatization step to produce carbazole
be aromatized to produce biologically important 4-hydroxy- derivative 9a. The reaction is very significant from an atom
indole derivatives. Therefore, 2-cyano-2-(4-oxo-1,2-di- economy point of view, as it liberates only one molecule of
Scheme 2. Plausible mechanism for the formation of cyanoacetamide derivatives 4.
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S. Maity, S. Pathak, A. Pramanik
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ammonia during the course of reaction. By using this (see Figure 2).[9] When compound 4k was heated at reflux
method, different substituted 11-aryl-5,7-dihydroxy-11H- in diphenyl ether for 1 h without the Pd/C catalyst, the cy-
benzo[a]carbazole-6-carbonitriles 9a–9l were synthesized in clized product 10k was formed in good yield (see
moderate yields (see Scheme 3 and Table 2). The results Scheme 4), which confirms that the cyclization is a thermal
demonstrate that the reaction can tolerate various electron- process.
donating and electron-withdrawing groups on the 2-aryl
moiety as well as on the N-aryl and -alkyl substituents of
compounds 4. All of the compounds 9a–9l were fully char-
1
acterized by H and 13C NMR spectroscopic analyses. The
X-ray crystal structure determination of 11-(4-fluoro-
phenyl)-5,7-dihydroxy-11H-benzo[a]carbazole-6-carbo-
nitrile (9c) further confirmed the formation of the product
Scheme 3. Synthesis of benzo[a]carbazole derivatives 9.
Table 2. Synthesis of benzo[a]carbazole derivatives 9.[a]
Figure 2. ORTEP diagram of X-ray crystal structure of 9c.
[a] Isolated yield.
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Benzo[a]carbazoles and Indole Acetic Acids
reaction, however, produced only 3-methyl-1,2-diphenyl-1H-
indol-4-ol (12a) through decarboxylation (see Scheme 5).
To overcome the difficulties, the carboxyl group of 11a
was protected as a methyl ester through a reaction with
thionyl chloride and dry methanol to produce methyl (4-
oxo-1,2-diphenyl-4,5,6,7-tetrahydro-1H-indol-3-yl)acetate
(13a). Then, ester 13a was heated at reflux with Pd/C in
diphenyl ether for 0.5 h to produce the desired methyl (4-
hydroxy-1,2-diphenylindol-3-yl)acetate (14a) in good yield
(see Scheme 6 and Table 3). It is interesting to note that no
benzo[a]carbazole derivative was formed through a thermal
cyclization between the ester carbonyl and the adjacent aro-
matic ring, as previously observed in the case of 4a. By
using this method, several methyl (1,2-diaryl-4-hydroxy-
indol-3-yl)acetates 14 were synthesized (see Scheme 6 and
Table 3). All of the compounds were fully characterized by
1H and 13C NMR spectroscopic analysis. The X-ray crystal
structure of methyl (1-benzyl-2-phenyl-4-hydroxyindol-3-
yl)acetate (14e) is shown in Figure 3.[9]
Scheme 4. Synthesis of compound 10k.
After the syntheses of benzo[a]carbazoles 9a–9l, we fo-
cused our attention on the preparation of the analogues of
biologically important plant growth regulatory hormones,[7]
the indoleacetic acid derivatives, from cyanoacetamides 4.
Thus, acetamide 4a was initially heated to reflux in a mix-
ture of concentrated HCl and acetic acid (1:1) for 0.5 h to
afford (4-oxo-1,2-diphenyl-4,5,6,7-tetrahydro-1H-3-indolyl)-
acetic acid (11a) through hydrolysis and decarboxylation
(see Scheme 5). Subsequently, acetic acid derivative 11a was
heated at reflux in diphenyl ether with Pd/C in anticipation
that it would produce the indoleacetic acid derivative. The
Figure 3. ORTEP diagram of X-ray crystal structure of 14e.
Conclusions
In summary, we have successfully developed a simple and
concise two-step method for the synthesis of highly substi-
tuted benzo[a]carbazole derivatives that proceeds with high
atom economy from easily available precursors. Further-
more, the syntheses of biologically important indoleacetic
acid derivatives and other indole derivatives from the same
intermediate demonstrate the diversity of the approach.
Scheme 5. Synthesis of 3-methyl-1,2-diphenyl-1H-indol-4-ol (12a).
Experimental Section
General Methods: All reagents for the reactions were purchased
from commercial sources and used without further purification.
Solvents were used after distillation. Enamines 1 and arylglyoxals
2 were prepared according to the literature procedure.[8a] Reactions
1
with Pd/C were performed under dry N2. The H NMR spectro-
scopic data were recorded at 300 MHz, and and chemical shifts are
reported in ppm. The 13C NMR spectroscopic data were recorded
at 75 MHz with a Bruker AVANCE 300 spectrometer, and the sam-
ples were dissolved in CDCl3 or deuterated dimethyl sulfoxide
{[D6]DMSO}. Elemental analyses were performed with a Perkin–
Elmer instrument. X-ray crystallography was performed with a
Bruker APEX-II instrument.
Scheme 6. Synthesis of indoleacetic acid derivatives 14.
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Table 3. Synthesis of indoleacetic acid derivatives 14.[a]
[a] Isolated yield.
Synthesis of 2-(1,2-Diaryl-4-oxo-4,5,6,7-tetrahydro-1H-3-indolyl)-2-
cyanoacetamides 4: A mixture of enamine 1 (2.0 mmol), arylglyoxal
monohydrate 2 (2.0 mmol), and malononitrile (2.2 mmol) in eth-
anol (15 mL) was heated at reflux for 0.5 h. Upon completion of
the reaction, the crude mass was poured into a saturated brine
solution. A white precipitate formed, and this was isolated by fil-
tration and then dried. Recrystallization (ethanol/chloroform) af-
forded 4 as colorless crystals.
crude residue was purified by chromatography on a silica gel col-
umn (EtOAc/hexane, 1:3) to give pure 9 as a yellow solid.
Synthesis of 5-Hydroxy-3-methoxy-7-oxo-11-p-tolyl-8,9,10,11-tetra-
hydro-7H-benzo[a]carbazole-6-carbonitrile (10k): 2-Cyano-2-[2-(4-
methoxyphenyl)-4-oxo-1-p-tolyl-4,5,6,7-tetrahydro-1H-3-indolyl]-
acetamide (4k, 1 mmol) in diphenyl ether (10 mL) was heated at
reflux for 1 h under N2. Upon completion of the reaction, the crude
mass was purified by chromatography on a silica gel column
(EtOAc/hexane, 1:1) to give pure 10k as a yellow solid.
Synthesis of 11-Aryl-5,7-dihydroxy-11H-benzo[a]carbazole-6-carb-
onitriles 9: A mixture of 2-(1,2-diaryl-4-oxo-4,5,6,7-tetrahydro-1H-
3-indolyl)-2-cyanoacetamide 4 (1 mmol) and Pd/C (20 mol-%) in
diphenyl ether (10 mL) was heated at reflux for 1 h under N2. Upon
completion of reaction, the crude mass was filtered through a bed
of Celite (ethyl acetate), and the filtrate was concentrated. The
Synthesis of 2-(4-Oxo-1,2-diphenyl-4,5,6,7-tetrahydro-1H-3-indolyl)-
acetic Acid (11a): 2-Cyano-2-(4-oxo-1,2-diphenyl-4,5,6,7-tetra-
hydro-1H-3-indolyl)acetamide (4a, 1 mmol) in concentrated HCl/
AcOH (1:1, 10 mL) was heated at reflux for 1 h. Upon completion
6
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Benzo[a]carbazoles and Indole Acetic Acids
of the reaction, the mixture was poured into water. A white solid
precipitate formed, and this was isolated by filtration and then
dried to produce 11a as a white powdery product.
C23H18FN3O2 (387.40): calcd. C 71.31, H 4.68, N 10.85; found C
71.20, H 4.59, N 10.77.
2-Cyano-2-[1-(4-methoxyphenyl)-4-oxo-2-phenyl-4,5,6,7-tetrahydro-
Synthesis of 3-Methyl-1,2-diphenyl-1H-3-indol-4-ol (12a): 2-(4-Oxo-
1,2-diphenyl-4,5,6,7-tetrahydro-1H-3-indolyl)acetic acid (11a,
0.5 mmol) and Pd/C (20 mol-%) in diphenyl ether (7 mL) was
heated at reflux for 0.5 h under N2. Upon completion of reaction,
the crude mass was filtered through a bed of Celite (ethyl acetate),
and the filtrate was concentrated. The crude residue was purified
by chromatography on a silica gel column (EtOAc/hexane, 1:4) to
produce 12a as a white solid.
1H-3-indolyl]acetamide (4d): White solid (606 mg, 76% yield); m.p.
140–142 °C. H NMR (300 MHz, [D6]DMSO): δ = 7.52 (s, 1 H),
1
7.32–7.26 (m, 4 H), 7.21–7.17 (m, 4 H), 6.92 (d, J = 8.7 Hz, 2 H),
5.01 (s, 1 H), 3.72 (s, 3 H), 2.62–2.57 (m, 2 H), 2.45–2.44 (m, 2 H),
2.07–2.03 (m, 2 H) ppm. 13C NMR (75 MHz, [D6]DMSO): δ =
193.8, 165.8, 158.8, 145.7, 135.2, 130.7, 129.2, 129.1, 128.3, 128.2,
116.9, 116.7, 114.2, 108.9, 55.3, 37.8, 35.7, 23.0, 22.3 ppm. IR
(KBr): ν = 2246, 1707, 1667 cm–1. C H N O (399.44): calcd. C
˜
24 21
3
3
72.16, H 5.30, N 10.52; found C 72.08, H 5.23, N 10.41.
Synthesis of Methyl (1,2-Diaryl-4-oxo-4,5,6,7-tetrahydro-1H-indol-
3-yl)acetates 13: 2-(1,2-Diaryl-4-oxo-4,5,6,7-tetrahydro-1H-3-
indolyl)-2-cyanoacetamide 4 (1 mmol) in concentrated HCl/AcOH
(1:1, 10 mL) was heated at reflux for 1 h. Upon completion of reac-
tion, the mixture was poured into water. A white solid precipitate
formed, and this was isolated by filtration and then dried to pro-
duce 11 as a white powdery product. The white crude product 11
was dissolved in dry methanol (10 mL), and thionyl chloride
(1.5 mmol) was added under ice-cold conditions. The reaction mix-
ture was then kept at room temperature for 1 h. Upon completion
of the reaction, the methanol was removed, and the reaction mix-
ture was neutralized by the addition of aqueous NaHCO3. The
resulting mixture was extracted with ethyl acetate, and the organic
phase was dried and concentrated to produce 13 as a white solid.
2-(1-Benzyl-4-oxo-2-phenyl-4,5,6,7-tetrahydro-1H-3-indolyl)-2-
cyanoacetamide (4e): White solid (572 mg, 72% yield); m.p. 200–
202 °C. 1H NMR (300 MHz, [D6]DMSO): δ = 7.42–7.41 (m, 4 H),
7.29–7.23 (m, 6 H), 6.91 (d, J = 6.9 Hz, 2 H), 5.05 (s, 3 H), 2.69–
2.67 (m, 2 H), 2.40–2.39 (m, 2 H), 2.06–2.02 (m, 2 H) ppm. 13C
NMR (75 MHz, [D6]DMSO): δ = 194.3, 166.1, 145.3, 137.3, 135.2,
131.2, 129.5, 129.3, 129.1, 129.0, 127.8, 126.4, 117.4, 117.1, 109.4,
47.7, 38.1, 35.8, 23.4, 22.1 ppm. IR (KBr): ν = 2249, 1711,
˜
1669 cm–1. C24H21N3O2 (383.44): calcd. C 75.18, H 5.52, N 10.96;
found C 75.10, H 5.46, N 10.87.
2-Cyano-2-(1-methyl-4-oxo-2-phenyl-4,5,6,7-tetrahydro-1H-3-
indolyl)acetamide (4f): White solid (448 mg, 73% yield); m.p. 196–
198 °C. 1H NMR (300 MHz, [D6]DMSO): δ = 7.50–7.48 (m, 3 H),
7.41–7.39 (m, 3 H), 7.25 (s, 1 H), 4.99 (s, 1 H), 3.35 (s, 3 H), 2.85–
2.82 (m, 2 H), 2.40–2.38 (m, 2 H), 2.11–2.10 (m, 2 H) ppm. 13C
Synthesis of Methyl (1,2-Diaryl-4-hydroxyindol-3-yl)acetates 14: A
mixture of compound methyl (1,2-diaryl-4-oxo-4,5,6,7-tetrahydro-
1H-3-indolyl)acetate 13 (0.5 mmol) and Pd/C (20 mol-%) in di- NMR (75 MHz, [D6]DMSO): δ = 194.0, 166.3, 145.4, 134.9, 131.1,
phenyl ether (7 mL) was heated at reflux for 0.5 h under N2. Upon
completion of the reaction, the crude mass was filtered through a
bed of Celite (ethyl acetate), and the filtrate was concentrated. The
crude residue was purified by chromatography on silica gel column
(EtOAc/hexane, 1:4) to produce 14 as a yellow solid.
129.5, 129.2, 129.0, 117.3, 116.6, 108.8, 38.8, 35.9, 32.1, 23.2,
21.8 ppm. IR (KBr): ν = 2247, 1701, 1660 cm–1. C18H17N3O2
˜
(307.34): calcd. C 70.34, H 5.58, N 13.67; found C 70.25, H 5.50,
N 13.59.
2-Cyano-2-(4-oxo-1,2-di-p-tolyl-4,5,6,7-tetrahydro-1H-3-indolyl)acet-
2-Cyano-2-(4-oxo-1,2-diphenyl-4,5,6,7-tetrahydro-1H-3-indolyl)acet- amide (4g): White solid (587 mg, 74% yield); m.p. 76–78 °C. 1H
1
amide (4a): White solid (582 mg, 79% yield); m.p. 216–218 °C. H
NMR (300 MHz, [D6]DMSO): δ = 7.53 (s, 1 H), 7.40–7.34 (m, 4
H), 7.27–7.25 (m, 5 H), 7.18–7.16 (m, 2 H), 5.03 (s, 1 H), 2.69–2.59
(m, 2 H), 2.49–2.45 (m, 2 H), 2.08–2.04 (m, 2 H) ppm. 13C NMR
(75 MHz, [D6]DMSO): δ = 193.9, 165.8, 145.4, 136.5, 135.0, 130.7,
129.1, 128.5, 128.3, 128.2, 127.9, 116.9, 109.2, 37.8, 35.7, 23.1,
NMR (300 MHz, [D6]DMSO): δ = 7.48 (s, 1 H), 7.28 (s, 1 H),
7.18–7.13 (m, 4 H), 7.10–7.01 (m, 4 H), 4.96 (s, 1 H), 2.58–2.52 (m,
2 H), 2.42–2.32 (m, 2 H), 2.26 (s, 3 H), 2.22 (s, 3 H), 2.10–2.01 (m, 2
H) ppm. 13C NMR (75 MHz, [D6]DMSO): δ = 194.1, 166.1, 145.7,
138.2, 138.0, 135.4, 134.3, 130.8, 129.9, 129.5, 128.0, 126.5, 117.3,
117.1, 109.2, 38.2, 36.0, 23.4, 22.6, 21.1, 20.9 ppm. IR (KBr): ν =
˜
22.3 ppm. IR (KBr): ν = 2244, 1709, 1676 cm–1. C23H19N3O2
2250, 1705, 1669 cm–1. C25H23N3O2 (397.46): calcd. C 75.54, H
5.83, N 10.57; found C 75.45, H 5.73, N 10.48.
˜
(369.41): calcd. C 74.78, H 5.18, N 11.37; found C 74.70, H 5.12,
N 11.29.
2-Cyano-2-[1-(4-fluorophenyl)-4-oxo-2-p-tolyl-4,5,6,7-tetrahydro-
2-Cyano-2-(4-oxo-2-phenyl-1-p-tolyl-4,5,6,7-tetrahydro-1H-3-
1H-3-indolyl]acetamide (4h): White solid (585 mg, 73% yield); m.p.
1
indolyl)acetamide (4b): White solid (566 mg, 74% yield); m.p. 138– 108–110 °C. H NMR (300 MHz, [D6]DMSO): δ = 7.47 (s, 1 H),
1
140 °C. H NMR (300 MHz, [D6]DMSO): δ = 7.41 (s, 1 H), 7.22– 7.29–7.23 (m, 2 H), 7.22–7.19 (m, 3 H), 7.04–7.00 (m, 4 H), 4.92
7.17 (m, 4 H), 7.10–7.03 (m, 6 H), 4.92 (s, 1 H), 2.54–2.49 (m, 2
(s, 1 H), 2.54–2.45 (m, 2 H), 2.42–2.39 (m, 2 H), 2.19 (s, 3 H), 2.01–
H), 2.41–2.35 (m, 2 H), 2.1 (s, 3 H), 1.98–1.89 (m, 2 H) ppm. 13C 1.94 (m, 2 H) ppm. 13C NMR (75 MHz, [D6]DMSO): δ = 194.2,
NMR (75 MHz, [D6]DMSO): δ = 193.9, 165.7, 145.5, 137.9, 135.0,
133.9, 130.6, 129.6, 129.1, 128.3, 128.2, 127.6, 116.9, 116.8, 109.0,
166.2, 163.2, 145.9, 138.2, 135.6, 133.3, 130.9, 130.5, 129.3, 126.4,
117.4, 116.6, 116.3, 109.4, 38.2, 36.1, 23.4, 22.6, 21.2 ppm. IR
37.8, 35.6, 23.0, 22.3, 20.6 ppm. IR (KBr): ν = 2251, 1708,
(KBr): ν = 2254, 1703, 1654 cm–1. C H FN O (401.43): calcd. C
˜
24 20 3 2
˜
1661 cm–1. C24H21N3O2 (383.44): calcd. C 75.18, H 5.52, N 10.96;
found C 75.09, H 5.45, N 10.87.
71.81, H 5.02, N 10.47; found C 71.70, H 4.92, N 10.36.
2-Cyano-2-[1-(4-methoxyphenyl)-4-oxo-2-p-tolyl-4,5,6,7-tetrahydro-
2-Cyano-2-[1-(4-fluorophenyl)-4-oxo-2-phenyl-4,5,6,7-tetrahydro- 1H-3-indolyl]acetamide (4i): White solid (628 mg, 76% yield); m.p.
1H-3-indolyl]acetamide (4c): White solid (596 mg, 77% yield); m.p.
90–92 °C. 1H NMR (300 MHz, [D6]DMSO): δ = 7.46 (s, 1 H), 7.25
88–90 °C. 1H NMR (300 MHz, [D6]DMSO): δ = 7.50 (s, 1 H), (s, 1 H), 7.15 (d, J = 4.8 Hz, 2 H), 7.11–7.01 (m, 4 H), 6.88 (d, J
7.42–7.17 (m, 8 H), 7.15–7.12 (m, 2 H), 4.97 (s, 1 H), 2.65–2.57 (m,
2 H), 2.42–2.36 (m, 2 H), 2.11–2.03 (m, 2 H) ppm. 13C NMR
(75 MHz, [D6]DMSO): δ = 193.8, 165.7, 162.8, 159.7, 145.5, 135.5,
132.8, 130.7, 130.2, 128.9, 128.4, 128.2, 116.8, 116.1, 115.8, 109.1,
= 8.1 Hz, 2 H), 4.92 (s, 1 H), 3.68 (s, 3 H), 2.54–2.52 (m, 2 H),
2.45–2.38 (m, 2 H), 2.19 (s, 3 H), 2.02–1.94 (m, 2 H) ppm. 13C
NMR (75 MHz, [D6]DMSO): δ = 194.2, 166.3, 159.2, 145.9, 138.2,
135.6, 133.3, 130.9, 129.5, 129.2, 126.6, 117.4, 117.0, 114.6, 109.1,
37.8, 35.6, 23.0, 22.2 ppm. IR (KBr): ν = 2255, 1705, 1664 cm–1. 55.7, 38.2, 36.1, 23.4, 22.7, 21.2 ppm. IR (KBr): ν = 2248, 1701,
˜
˜
Eur. J. Org. Chem. 0000, 0–0
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
7

Job/Unit: O42085
/KAP1
Date: 10-06-14 12:32:24
Pages: 13
S. Maity, S. Pathak, A. Pramanik
FULL PAPER
1669 cm–1. C25H23N3O3 (413.46): calcd. C 72.62, H 5.61, N 10.16;
found C 72.54, H 5.52, N 10.03.
3.72 (s, 3 H), 3.69 (s, 3 H), 2.57–2.56 (m, 2 H), 2.43–2.42 (m, 2 H),
2.05–2.01 (m, 2 H) ppm. 13C NMR (75 MHz, [D6]DMSO): δ =
193.8, 165.9, 159.1, 158.8, 145.4, 135.2, 132.0, 129.2, 129.1, 121.2,
117.0, 116.5, 114.2, 113.6, 108.6, 55.3, 55.0, 37.8, 35.7, 23.0,
2-Cyano-2-[2-(4-methoxyphenyl)-4-oxo-1-phenyl-4,5,6,7-tetrahydro-
1H-3-indolyl]acetamide (4j): White solid (598 mg, 75% yield); m.p.
22.2 ppm. IR (KBr): ν = 2254, 1710, 1670 cm–1. C25H23N3O4
˜
1
198–200 °C. H NMR (300 MHz, [D6]DMSO): δ = 7.41 (s, 1 H),
(429.46): calcd. C 69.92, H 5.40, N 9.78; found C 69.82, H 5.32, N
9.71.
7.33–7.28 (m, 3 H), 7.22 (s, 1 H), 7.17 (d, J = 6.6 Hz, 2 H), 6.99
(d, J = 8.7 Hz, 2 H), 6.74 (d, J = 8.7 Hz, 2 H), 4.92 (s, 1 H), 3.61
(s, 3 H), 2.52–2.49 (m, 2 H), 2.36–2.35 (m, 2 H), 1.98–1.94 (m, 2 2-[1-Benzyl-2-(4-methoxyphenyl)-4-oxo-4,5,6,7-tetrahydro-1H-3-
H) ppm. 13C NMR (75 MHz, [D6]DMSO): δ = 194.3, 166.2, 159.5, indolyl]-2-cyanoacetamide (4p): White solid (586 mg, 71 % yield);
1
145.5, 137.0, 135.4, 132.5, 129.5, 128.8, 128.4, 121.5, 117.4, 117.2,
114.1, 109.3, 55.4, 38.2, 36.1, 23.5, 22.7 ppm. IR (KBr): ν = 2244,
m.p. 150–152 °C. H NMR (300 MHz, [D6]DMSO): δ = 7.17 (s, 1
H), 7.08–6.96 (m, 6 H), 6.74–6.67 (m, 4 H), 4.81 (s, 1 H), 4.79 (s,
˜
1710, 1670 cm–1. C24H21N3O3 (399.44): calcd. C 72.16, H 5.30, N 2 H), 3.52 (s, 3 H), 2.43–2.42 (m, 2 H), 2.15–2.14 (m, 2 H), 1.81–
10.52; found C 72.07, H 5.22, N 10.43.
1.79 (m, 2 H) ppm. 13C NMR (75 MHz, [D6]DMSO): δ = 193.8,
165.8, 159.7, 144.6, 137.0, 134.7, 132.2, 128.7, 127.3, 125.9, 120.8,
117.0, 116.6, 114.0, 108.9, 55.1, 47.2, 37.7, 35.5, 22.9, 21.7 ppm. IR
2-Cyano-2-[2-(4-methoxyphenyl)-4-oxo-1-p-tolyl-4,5,6,7-tetrahydro-
1H-3-indolyl]acetamide (4k): White solid (594 mg, 72% yield); m.p.
(KBr): ν = 2247, 1709, 1664 cm–1. C H N O (413.46): calcd. C
˜
25 23
3
3
1
178–180 °C. H NMR (300 MHz, [D6]DMSO): δ = 7.48 (s, 1 H),
72.62, H 5.61, N 10.16; found C 72.52, H 5.53, N 10.07.
7.29 (s, 1 H), 7.19–7.07 (m, 6 H), 6.82 (d, J = 8.7 Hz, 2 H), 4.98
(s, 1 H), 3.68 (s, 3 H), 2.58–2.57 (m, 2 H), 2.43–2.42 (m, 2 H), 2.26 2-Cyano-2-[2-(4-methoxyphenyl)-1-methyl-4-oxo-4,5,6,7-tetrahydro-
(s, 3 H), 2.05–2.01 (m, 2 H) ppm. 13C NMR (75 MHz, [D6]DMSO): 1H-3-indolyl]acetamide (4q): White solid (484 mg, 73% yield); m.p.
1
δ = 193.8, 165.8, 159.1, 145.2, 137.8, 135.0, 134.0, 132.0, 129.6,
180–182 °C. H NMR (300 MHz, [D6]DMSO): δ = 7.40 (s, 1 H),
7.33 (d, J = 8.7 Hz, 2 H), 7.25 (s, 1 H), 7.06 (d, J = 8.7 Hz, 2 H),
5.00 (s, 1 H), 3.81 (s, 3 H), 3.33 (s, 3 H), 2.86–2.82 (m, 2 H), 2.41–
2.37 (m, 2 H), 2.11–2.07 (m, 2 H) ppm. 13C NMR (75 MHz, [D6]-
DMSO): δ = 194.0, 166.4, 160.0, 145.2, 134.8, 132.5, 121.5, 117.4,
116.5, 114.5, 108.6, 55.6, 38.1, 35.9, 32.0, 23.2, 21.8 ppm. IR (KBr):
127.6, 121.2, 116.9, 116.7, 113.6, 108.8, 55.0, 37.8, 35.7, 23.0, 22.3,
20.6 ppm. IR (KBr): ν = 2247, 1708, 1669 cm–1. C25H23N3O3
˜
(413.46): calcd. C 72.62, H 5.61, N 10.16; found C 72.52, H 5.53,
N 10.07.
2-Cyano-2-[2-(4-fluorophenyl)-4-oxo-1-phenyl-4,5,6,7-tetrahydro-
1H-3-indolyl]acetamide (4l): White solid (557 mg, 72% yield); m.p.
80–82 °C. 1H NMR (300 MHz, [D6]DMSO): δ = 7.51 (s, 1 H),
ν = 2250, 1709, 1669 cm–1. C H N O (337.37): calcd. C 67.64,
˜
19 19
3
3
H 5.68, N 12.46; found C 67.55, H 5.61, N 12.38.
7.39–7.31 (m, 4 H), 7.24 (d, J = 8.1 Hz, 2 H), 7.19 (d, J = 8.4 Hz, 2-[1-(4-Chlorophenyl)-4-oxo-2-phenyl-4,5,6,7-tetrahydro-1H-3-
2 H), 7.13–7.05 (m, 2 H), 5.11 (s, 1 H), 2.61–2.54 (m, 2 H), 2.47–
2.40 (m, 2 H), 2.04–2.01 (m, 2 H) ppm. 13C NMR (75 MHz, [D6]-
DMSO): δ = 194.4, 166.1, 164.0, 160.7, 145.7, 136.7, 134.3, 133.5,
133.4, 129.6, 128.9, 128.4, 126.0, 117.3, 115.7, 115.4, 109.8, 38.2,
indolyl]-2-cyanoacetamide (4r): White solid (622 mg, 77 % yield);
m.p. 232–234 °C. H NMR (300 MHz, [D6]DMSO): δ = 7.52 (s, 1
1
H), 7.47 (d, J = 8.7 Hz, 2 H), 7.39–7.29 (m, 6 H), 7.16 (t, J =
3.6 Hz, 2 H), 5.0 (s, 1 H), 2.67–2.60 (m, 2 H), 2.50–2.44 (m, 2 H),
2.08–2.06 (m, 2 H) ppm. 13C NMR (75 MHz, [D6]DMSO): δ =
193.8, 165.7, 145.4, 135.4, 135.0, 133.1, 130.7, 129.8, 129.2, 128.9,
128.5, 128.3, 117.0, 116.9, 109.4, 37.8, 35.6, 23.0, 22.2 ppm. IR
36.0, 23.5, 22.7 ppm. IR (KBr): ν = 2255, 1705, 1664 cm–1
.
˜
C23H18FN3O2 (387.40): calcd. C 71.31, H 4.68, N 10.85; found C
71.23, H 4.58, N 10.75.
(KBr): ν = 2255, 1710, 1664 cm–1. C H ClN O (403.86): calcd.
˜
23 18
3
2
2-[1-Benzyl-2-(4-fluorophenyl)-4-oxo-4,5,6,7-tetrahydro-1H-3-
indolyl]-2-cyanoacetamide (4m): White solid (569 mg, 71% yield);
m.p. 74–76 °C. 1H NMR (300 MHz, [D6]DMSO): δ = 7.46 (s, 1 H),
C 68.40, H 4.49, N 10.40; found C 68.31, H 4.43, N 10.32.
2-[1-(4-Bromophenyl)-4-oxo-2-phenyl-4,5,6,7-tetrahydro-1H-3-
7.31–7.21 (m, 8 H), 6.90 (d, J = 6.9 Hz, 2 H), 5.14 (s, 1 H), 5.03 indolyl]-2-cyanoacetamide (4s): White solid (636 mg, 71 % yield);
1
(s, 2 H), 2.71–2.69 (m, 2 H), 2.41–2.38 (m, 2 H), 2.05–2.04 (m, 2 m.p. 196–198 °C. H NMR (300 MHz, [D6]DMSO): δ = 7.59–7.50
H) ppm. 13C NMR (75 MHz, [D6]DMSO): δ = 194.4, 166.1, 161.3, (m, 3 H), 7.27–7.22 (m, 6 H), 7.16–7.13 (m, 2 H), 4.99 (s, 1 H),
145.2, 137.2, 133.9, 133.6, 129.1, 127.8, 126.4, 117.0, 116.0, 115.7,
2.65–2.58 (m, 2 H), 2.44–2.43 (m, 2 H), 2.08–2.03 (m, 2 H) ppm.
13C NMR (75 MHz, [D6]DMSO): δ = 194.0, 165.9, 145.7, 136.1,
135.2, 132.4, 130.9, 130.3, 129.1, 128.7, 128.6, 121.8, 117.3, 117.1,
109.7, 47.7, 38.1, 35.7, 23.3, 22.1 ppm. IR (KBr): ν = 2249, 1711,
˜
1669 cm–1. C24H20FN3O2 (401.43): calcd. C 71.81, H 5.02, N 10.47;
found C 71.70, H 4.91, N 10.33.
109.6, 38.1, 35.9, 23.3, 22.5 ppm. IR (KBr): ν = 2252, 1704,
˜
1659 cm–1. C23H18BrN3O2 (448.31): calcd. C 61.62, H 4.05, N 9.37;
found C 61.53, H 3.97, N 9.30.
2-[1-(4-Chlorophenyl)-2-(4-methoxyphenyl)-4-oxo-4,5,6,7-tetra-
hydro-1H-3-indolyl]-2-cyanoacetamide (4n): White solid (668 mg,
1
77% yield); m.p. 186–188 °C. H NMR (300 MHz, [D6]DMSO): δ 2-[2-(4-Chlorophenyl)-4-oxo-1-phenyl-4,5,6,7-tetrahydro-1H-3-
= 7.41–7.37 (m, 3 H), 7.23–7.20 (m, 3 H), 7.01 (d, J = 8.4 Hz, 2 indolyl]-2-cyanoacetamide (4t): White solid (628 mg, 78 % yield);
1
H), 6.77 (d, J = 7.8 Hz, 2 H), 4.91 (s, 1 H), 3.62 (s, 3 H), 2.54–2.52 m.p. 236–238 °C. H NMR (300 MHz, [D6]DMSO): δ = 7.53 (s, 1
(m, 2 H), 2.41–2.35 (m, 2 H), 1.98–1.97 (m, 2 H) ppm. 13C NMR
(75 MHz, [D6]DMSO): δ = 193.8, 165.8, 159.2, 145.2, 135.5, 134.9,
133.0, 132.1, 129.8, 129.2, 120.8, 116.9, 113.8, 109.1, 55.0, 37.8,
H), 7.43–7.32 (m, 6 H), 7.27 (d, J = 7.2 Hz, 2 H), 7.19–7.16 (dd,
J1 = 7.2 Hz, J2 = 1.8 Hz, 2 H), 5.17 (s, 1 H), 2.62–2.60 (m, 2 H),
2.45–2.43 (m, 2 H), 2.07–2.04 (m, 2 H) ppm. 13C NMR (75 MHz,
[D6]DMSO): δ = 194.0, 165.7, 145.5, 136.2, 133.6, 133.3, 132.5,
35.7, 23.0, 22.2 ppm. IR (KBr): ν = 2251, 1708, 1671 cm–1
.
˜
C24H20ClN3O3 (433.88): calcd. C 66.44, H 4.65, N 9.68; found C 129.3, 128.6, 128.2, 128.1, 127.9, 116.9, 109.6, 37.8, 35.4, 23.0,
66.34, H 4.57, N 9.60.
22.3 ppm. IR (KBr): ν = 2243, 1708, 1664 cm–1. C H ClN O
˜
23 18 3 2
(403.86): calcd. C 68.40, H 4.49, N 10.40; found C 68.29, H 4.40,
N 10.33.
2-Cyano-2-[1,2-bis(4-methoxyphenyl)-4-oxo-4,5,6,7-tetrahydro-1H-
3-indolyl]acetamide (4o): White solid (626 mg, 73 % yield); m.p.
1
140–142 °C. H NMR (300 MHz, [D6]DMSO): δ = 7.48 (s, 1 H), 2-[1,2-Bis(4-chlorophenyl)-4-oxo-4,5,6,7-tetrahydro-1H-3-indolyl]-2-
7.29 (s, 1 H), 7.18 (d, J = 8.7 Hz, 2 H), 7.09 (d, J = 8.7 Hz, 2 H),
6.91 (d, J = 9.0 Hz, 2 H), 6.83 (d, J = 8.7 Hz, 2 H), 4.98 (s, 1 H),
cyanoacetamide (4u): White solid (640 mg, 73% yield); m.p. 199–
201 °C. 1H NMR (300 MHz, [D6]DMSO): δ = 7.53–7.47 (m, 3 H),
8
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© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 0000, 0–0

Job/Unit: O42085
/KAP1
Date: 10-06-14 12:32:24
Pages: 13
Benzo[a]carbazoles and Indole Acetic Acids
7.39–7.31 (m, 5 H), 7.19 (d, J = 8.1 Hz, 2 H), 5.15 (s, 1 H), 2.68–
2.63 (m, 2 H), 2.51–2.45 (m, 2 H), 2.08–2.06 (m, 2 H) ppm. 13C
NMR (75 MHz, [D6]DMSO): δ = 193.9, 165.6, 145.6, 135.2, 133.6,
133.4, 133.2, 132.5, 129.8, 129.3, 128.4, 127.9, 117.1, 116.8, 109.8,
1H NMR (300 MHz, [D6]DMSO): δ = 10.57 (br. s, 1 H), 10.44 (s,
1 H), 8.41 (d, J = 8.1 Hz, 1 H), 7.53–7.51 (m, 1 H), 7.45–7.33 (m,
1
2
4 H), 7.25–7.13 (m, 3 H), 6.66–6.62 (dd, J = 7.8 Hz, J = 2.1 Hz,
1 H), 6.45–6.41 (dd, J1 = 8.1 Hz, J2 = 2.4 Hz, 1 H), 3.90 (s, 3
37.8, 35.4, 23.0, 22.2 ppm. IR (KBr): ν = 2252, 1709, 1668 cm–1. H) ppm. 13C NMR (75 MHz, [D6]DMSO): δ = 160.0, 155.1, 153.8,
˜
C23H17Cl2N3O2 (438.30): calcd. C 63.03, H 3.91, N 9.59; found C
62.96, H 3.82, N 9.51.
144.8, 132.3, 130.3, 129.6, 128.6, 127.2, 125.4, 124.6, 124.5, 123.9,
122.1, 117.9, 116.0, 115.5, 110.7, 105.8, 101.5, 91.4, 56.0 ppm. IR
(KBr): ν = 3358, 2217 cm–1. C H N O (380.39): calcd. C 75.78,
˜
24 16
2
3
2-[2-(4-Chlorophenyl)-1-(4-methoxyphenyl)-4-oxo-4,5,6,7-tetra-
H 4.24, N 7.36; found C 75.70, H 4.16, N 7.25.
hydro-1H-3-indolyl]-2-cyanoacetamide (4v): White solid (676 mg,
1
78% yield); m.p. 115–117 °C. H NMR (300 MHz, [D6]DMSO): δ
11-Benzyl-5,7-dihydroxy-11H-benzo[a]carbazole-6-carbonitrile (9e):
White solid (184 mg, 51 % yield); m.p. 226–228 °C. 1H NMR
(300 MHz, [D6]DMSO): δ = 10.50 (s, 1 H), 10.43 (s, 1 H), 8.40 (t,
J = 5.4 Hz, 1 H), 8.33 (t, J = 5.4 Hz, 1 H), 7.58–7.55 (m, 2 H),
7.29–7.20 (m, 5 H), 7.06 (d, J = 8.1 Hz, 2 H), 6.64 (d, J = 7.8 Hz,
1 H), 6.04 (s, 2 H) ppm. 13C NMR (75 MHz, [D6]DMSO): δ =
154.8, 153.8, 143.7, 138.1, 130.7, 129.3, 129.1, 127.6, 127.4, 126.3,
126.2, 125.4, 124.6, 123.9, 122.7, 117.9, 115.4, 110.5, 105.6, 101.0,
= 7.52 (s, 1 H), 7.35 (d, J = 8.4 Hz, 3 H), 7.22–7.17 (m, 4 H), 6.95–
6.92 (m, 2 H), 5.15 (s, 1 H), 3.74 (s, 3 H), 2.61–2.57 (m, 2 H), 2.46–
2.42 (m, 2 H), 2.07–2.03 (m, 2 H) ppm. 13C NMR (75 MHz, [D6]-
DMSO): δ = 194.0, 165.7, 158.9, 145.8, 133.8, 133.2, 132.5, 129.1,
128.8, 128.2, 116.9, 116.7, 114.3, 109.3, 55.4, 37.8, 35.5, 23.0,
22.7 ppm. IR (KBr): ν = 2249, 1706, 1675 cm–1. C H ClN O
˜
24 20
3
3
(433.88): calcd. C 66.44, H 4.65, N 9.68; found C 66.36, H 4.58, N
9.61.
91.6, 49.6 ppm. IR (KBr): ν = 3358, 2217 cm–1. C24H16N2O2
˜
(364.39): calcd. C 79.11, H 4.43, N 7.69; found C 79.02, H 4.36, N
7.60.
2-[1-Benzyl-2-(4-chlorophenyl)-4-oxo-4,5,6,7-tetrahydro-1H-3-
indolyl]-2-cyanoacetamide (4w): White solid (610 mg, 73% yield);
m.p. 157–159 °C. H NMR (300 MHz, [D6]DMSO): δ = 7.39–7.36
(m, 3 H), 7.22–7.14 (m, 6 H), 6.81 (d, J = 6.9 Hz, 2 H), 5.11 (s, 1
H), 4.95 (s, 2 H), 2.61–2.59 (m, 2 H), 2.32–2.30 (m, 2 H), 1.97–1.93
(m, 2 H) ppm. 13C NMR (75 MHz, [D6]DMSO): δ = 194.4, 166.0,
145.4, 137.2, 134.4, 133.7, 133.1, 129.1, 129.0, 128.3, 127.8, 126.3,
1
5,7-Dihydroxy-11-methyl-11H-benzo[a]carbazole-6-carbonitrile (9f):
Yellow solid (144 mg, 50 % yield); m.p. 272–274 °C. 1H NMR
(300 MHz, [D6]DMSO): δ = 10.45 (s, 1 H), 10.34 (s, 1 H), 8.82 (d,
J = 8.4 Hz, 1 H), 8.45 (d, J = 8.4 Hz, 1 H), 7.79 (t, J = 7.2 Hz, 1
H), 7.66 (t, J = 7.5 Hz, 1 H), 7.27 (t, J = 7.8 Hz, 1 H), 7.17 (d, J
= 8.1 Hz, 1 H), 6.61 (d, J = 7.5 Hz, 1 H), 4.31 (s, 3 H) ppm. 13C
NMR (75 MHz, [D6]DMSO): δ = 154.4, 153.7, 143.4, 129.7, 128.9,
126.9, 125.4, 124.5, 124.4, 123.1, 118.0, 114.7, 110.3, 105.0, 101.0,
117.3, 117.1, 109.9, 47.7, 38.1, 35.6, 23.3, 22.1 ppm. IR (KBr): ν =
˜
2254, 1709, 1671 cm–1. C24H20ClN3O2 (417.88): calcd. C 68.98, H
4.82, N 10.06; found C 68.88, H 4.73, N 9.97.
91.5, 35.0 ppm. IR (KBr): ν = 3353, 2210 cm–1. C18H12N2O2
5,7-Dihydroxy-11-phenyl-11H-benzo[a]carbazole-6-carbonitrile (9a):
White solid (185 mg, 53 % yield); m.p. 238–240 °C. 1H NMR
(300 MHz, [D6]DMSO): δ = 10.57 (s, 1 H), 10.43 (s, 1 H), 8.38 (d,
J = 8.1 Hz, 1 H), 7.65–7.60 (m, 3 H), 7.51–7.47 (m, 3 H), 7.33 (t,
J = 6.9 Hz, 1 H), 7.21 (d, J = 8.4 Hz, 1 H), 7.13 (t, J = 8.1 Hz, 1
H), 6.61 (d, J = 7.5 Hz, 1 H), 6.41 (d, J = 8.1 Hz, 1 H) ppm. 13C
NMR (75 MHz, [D6]DMSO): δ = 154.9, 153.4, 144.0, 139.5, 130.5,
129.3, 129.0, 128.8, 128.2, 127.0, 125.1, 124.2, 124.0, 123.4, 121.7,
˜
(288.30): calcd. C 74.99, H 4.20, N 9.72; found C 74.90, H 4.12, N
9.63.
5,7-Dihydroxy-3-methyl-11-p-tolyl-11H-benzo[a]carbazole-6-carbo-
1
nitrile (9g): Yellow solid (197 mg, 52% yield); m.p. 228–230 °C. H
NMR (300 MHz, [D6]DMSO): δ = 10.43 (s, 1 H), 10.38 (s, 1 H),
8.18 (s, 1 H), 7.48 (d, J = 7.5 Hz, 2 H), 7.36 (d, J = 7.8 Hz, 2 H),
7.21–7.09 (m, 3 H), 6.61 (d, J = 7.5 Hz, 1 H), 6.42 (d, J = 8.1 Hz,
1 H), 2.48 (s, 3 H), 2.43 (s, 3 H) ppm. 13C NMR (75 MHz, [D6]-
DMSO): δ = 154.8, 153.6, 144.4, 139.1, 137.3, 134.9, 131.4, 130.4,
130.1, 129.6, 128.8, 127.9, 127.0, 124.6, 123.6, 122.1, 122.0, 117.9,
117.4, 115.4, 110.4, 105.5, 101.0, 91.0 ppm. IR (KBr): ν = 3358,
˜
2215 cm–1. C23H14N2O2 (350.36): calcd. C 78.84, H 4.03, N 8.00;
found C 78.76, H 3.96, N 7.92.
5,7-Dihydroxy-11-p-tolyl-11H-benzo[a]carbazole-6-carbonitrile (9b):
White solid (186 mg, 51 % yield); m.p. 220–222 °C. 1H NMR
(300 MHz, [D6]DMSO): δ = 10.61 (s, 1 H), 10.47 (s, 1 H), 8.43 (d,
J = 8.4 Hz, 1 H), 7.55–7.48 (m, 3 H), 7.38–7.29 (m, 3 H), 7.20–
7.04 (m, 2 H), 6.65 (d, J = 7.8 Hz, 1 H), 6.44 (d, J = 8.1 Hz, 1 H),
2.48 (s, 3 H) ppm. 13C NMR (75 MHz, [D6]DMSO): δ = 155.2,
153.8, 144.6, 139.2, 137.3, 131.4, 130.5, 129.8, 128.8, 128.4, 127.3,
125.4, 124.6, 123.9, 122.1, 117.9, 115.7, 110.8, 105.8, 101.5, 91.4,
105.8, 101.4, 91.5, 21.6, 21.3 ppm. IR (KBr): ν = 3357, 2213 cm–1.
˜
C25H18N2O2 (378.42): calcd. C 79.35, H 4.79, N 7.40; found C
79.25, H 4.70, N 7.32.
11-(4-Fluorophenyl)-5,7-dihydroxy-3-methyl-11H-benzo[a]carbazole-
6-carbonitrile (9h): White solid (195 mg, 51 % yield); m.p. 251–
1
253 °C. H NMR (300 MHz, [D6]DMSO): δ = 10.43 (br. s, 2 H),
8.20 (s, 1 H), 7.57–7.53 (m, 4 H), 7.28 (d, J = 6.0 Hz, 1 H), 7.16
(t, J = 8.1 Hz, 2 H), 6.65 (d, J = 7.5 Hz, 1 H), 6.45 (d, J = 8.1 Hz,
1 H), 2.45 (s, 3 H) ppm. 13C NMR (75 MHz, [D6]DMSO): δ =
154.9, 153.7, 144.4, 135.0, 131.4, 131.3, 130.6, 129.6, 127.2, 124.7,
123.7, 122.0, 118.0, 117.7, 115.2, 110.9, 106.0, 101.3, 91.4,
21.1 ppm. IR (KBr): ν = 3357, 2213 cm–1. C H N O (364.39):
˜
24 16
2
2
calcd. C 79.11, H 4.43, N 7.69; found C 79.02, H 4.34, N 7.61.
11-(4-Fluorophenyl)-5,7-dihydroxy-11H-benzo[a]carbazole-6-
carbonitrile (9c): White solid (202 mg, 55% yield); m.p. 262–264 °C.
1H NMR (300 MHz, [D6]DMSO): δ = 10.49 (br. s, 2 H), 8.42 (d,
J = 8.4 Hz, 1 H), 7.63–7.52 (m, 5 H), 7.44 (t, J = 7.2 Hz, 1 H),
7.27 (d, J = 8.4 Hz, 1 H), 7.18 (t, J = 8.1 Hz, 1 H), 6.66 (d, J =
7.8 Hz, 1 H), 6.45 (d, J = 8.1 Hz, 1 H) ppm. 13C NMR (75 MHz,
[D6]DMSO): δ = 164.1, 160.8, 155.4, 153.8, 144.6, 136.3, 131.5,
129.4, 128.8, 127.5, 125.5, 124.7, 124.5, 123.8, 122.0, 118.0, 117.7,
21.6 ppm. IR (KBr): ν = 3360, 2221 cm–1. C H FN O (382.38):
˜
24 15
2
2
calcd. C 75.38, H 3.95, N 7.33; found C 75.30, H 3.88, N 7.24.
5,7-Dihydroxy-11-(4-methoxyphenyl)-3-methyl-11H-benzo[a]carb-
azole-6-carbonitrile (9i): Yellow solid (209 mg, 53 % yield); m.p.
1
240–242 °C. H NMR (300 MHz, [D6]DMSO): δ = 10.44 (br. s, 1
H), 10.38 (s, 1 H), 8.19 (s, 1 H), 7.42 (d, J = 7.8 Hz, 2 H), 7.24–
7.21 (m, 4 H), 7.14 (t, J = 7.8 Hz, 1 H), 6.62 (d, J = 7.8 Hz, 1 H),
6.43 (d, J = 8.4 Hz, 1 H), 3.91 (s, 3 H), 2.45 (s, 3 H) ppm. 13C
NMR (75 MHz, [D6]DMSO): δ = 159.9, 154.7, 153.6, 144.6, 134.9,
132.3, 130.5, 130.3, 129.8, 127.0, 124.7, 123.6, 122.0, 118.0, 116.0,
115.9, 110.9, 106.0, 101.4, 91.3 ppm. IR (KBr): ν = 3356,
˜
2214 cm–1. C23H13FN2O2 (368.35): calcd. C 74.99, H 3.56, N 7.60;
found C 74.90, H 3.47, N 7.51.
5,7-Dihydroxy-11-(4-methoxyphenyl)-11H-benzo[a]carbazole-6-
carbonitrile (9d): White solid (213 mg, 56% yield); m.p. 280–282 °C.
114.8, 110.7, 105.7, 101.4, 91.7, 56.0, 21.6 ppm. IR (KBr): ν = 3361,
˜
Eur. J. Org. Chem. 0000, 0–0
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
9

Job/Unit: O42085
/KAP1
Date: 10-06-14 12:32:24
Pages: 13
S. Maity, S. Pathak, A. Pramanik
FULL PAPER
2227 cm–1. C25H18N2O3 (394.42): calcd. C 76.13, H 4.60, N 7.10;
found C 76.05, H 4.51, N 7.01.
NMR (300 MHz, CDCl3): δ = 7.31–7.26 (m, 3 H), 7.20–7.18 (m, 3
H), 7.09–7.05 (m, 4 H), 3.75 (s, 2 H), 3.72 (s, 3 H), 2.69–2.65 (m,
2 H), 2.53–2.49 (m, 2 H), 2.15–2.10 (m, 2 H) ppm. 13C NMR
(75 MHz, CDCl3): δ = 194.9, 172.9, 144.3, 137.3, 134.2, 130.5,
129.0, 128.1, 128.0, 127.9, 127.7, 127.4, 119.1, 113.5, 51.7, 38.3,
5,7-Dihydroxy-3-methoxy-11-phenyl-11H-benzo[a]carbazole-6-
carbonitrile (9j): Yellow solid (198 mg, 52 % yield); m.p. 230–
232 °C. 1H NMR (300 MHz, [D6]DMSO): δ = 10.47 (s, 1 H), 10.39
(s, 1 H), 7.79 (s, 1 H), 7.75–7.66 (m, 3 H), 7.51 (d, J = 7.8 Hz, 2
H), 7.23–7.01 (m, 3 H), 6.64 (d, J = 7.8 Hz, 1 H), 6.43 (d, J =
8.4 Hz, 1 H), 3.88 (s, 3 H) ppm. 13C NMR (75 MHz, [D6]DMSO):
δ = 157.1, 154.2, 153.5, 144.2, 140.0, 131.0, 129.9, 129.7, 129.2,
128.2, 126.9, 125.9, 119.8, 118.7, 117.9, 114.1, 110.9, 106.0, 104.4,
31.2, 23.4, 23.1 ppm. IR (KBr): ν = 1739, 1642 cm–1. C H NO
˜
23 21
3
(359.41): calcd. C 76.86, H 5.89, N 3.90; found C 76.78, H 5.81, N
3.82.
Methyl [1-(4-Methoxyphenyl)-4-oxo-2-phenyl-4,5,6,7-tetrahydro-
1H-indol-3-yl]acetate (13d): White solid (334 mg, 86% yield); m.p.
62–64 °C. 1H NMR (300 MHz, CDCl3): δ = 7.21–7.19 (m, 3 H),
7.08–7.05 (m, 2 H), 7.01 (d, J = 9.0 Hz, 2 H), 6.81 (d, J = 9.0 Hz,
2 H), 3.78 (s, 3 H), 3.74 (s, 2 H), 3.71 (s, 3 H), 2.66–2.62 (m, 2 H),
2.52–2.48 (m, 2 H), 2.14–2.10 (m, 2 H) ppm. 13C NMR (75 MHz,
CDCl3): δ = 194.9, 172.9, 158.9, 144.6, 134.4, 130.5, 130.4, 130.1,
128.7, 128.0, 127.4, 118.9, 114.1, 113.2, 55.4, 51.7, 38.3, 31.2, 23.6,
101.3, 91.8, 55.8 ppm. IR (KBr): ν = 3360, 2228 cm–1. C H N O
˜
24 16
2
3
(380.39): calcd. C 75.78, H 4.24, N 7.36; found C 75.69, H 4.17, N
7.28.
5,7-Dihydroxy-3-methoxy-11-p-tolyl-11H-benzo[a]carbazole-6-
carbonitrile (9k): Yellow solid (197 mg, 50 % yield); m.p. 170–
172 °C. 1H NMR (300 MHz, [D6]DMSO): δ = 10.45 (s, 1 H), 10.38
(s, 1 H), 7.49 (d, J = 8.1 Hz, 2 H), 7.36 (d, J = 8.1 Hz, 2 H), 7.26–
7.01 (m, 3 H), 6.86 (d, J = 8.7 Hz, 1 H), 6.63 (d, J = 7.5 Hz, 1 H),
6.41 (d, J = 8.1 Hz, 1 H), 3.84 (s, 3 H), 2.49 (s, 3 H) ppm. 13C
NMR (75 MHz, [D6]DMSO): δ = 157.1, 154.1, 153.5, 144.3, 139.2,
137.3, 131.9, 130.1, 128.9, 127.9, 126.8, 125.9, 123.9, 119.7, 118.8,
117.9, 114.4, 110.8, 105.9, 104.3, 101.4, 55.8, 21.3 ppm. IR (KBr):
23.0 ppm. IR (KBr): ν = 1737, 1644 cm–1. C H NO (389.44):
˜
24 23
4
calcd. C 74.02, H 5.95, N 3.60; found C 73.93, H 5.87, N 3.52.
Methyl (1-Benzyl-4-oxo-2-phenyl-4,5,6,7-tetrahydro-1H-indol-3-
yl)acetate (13e): White solid (302 mg, 81% yield); m.p. 98–100 °C.
1H NMR (300 MHz, CDCl3): δ = 7.33–7.27 (m, 5 H), 7.24–7.20
(m, 3 H), 6.89 (d, J = 6.6 Hz, 2 H), 4.98 (s, 2 H), 3.68 (s, 3 H),
3.67 (s, 2 H), 2.64–2.60 (m, 2 H), 2.48–2.44 (m, 2 H), 2.15–2.09 (m,
2 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 194.6, 172.9, 143.6,
137.2, 134.4, 130.7, 130.3, 128.8, 128.5, 128.3, 127.4, 125.7, 118.9,
ν = 3354, 2231 cm–1. C H N O (394.42): calcd. C 76.13, H 4.60,
˜
25 18
2
3
N 7.10; found C 76.05, H 4.51, N 7.02.
3-Fluoro-5,7-dihydroxy-11-phenyl-11H-benzo[a]carbazole-6-carbo-
1
nitrile (9l): Yellow solid (199 mg, 54% yield); m.p. 248–250 °C. H
113.2, 51.6, 47.9, 38.1, 31.0, 23.5, 22.3 ppm. IR (KBr): ν = 1735,
˜
1640 cm–1. C24H23NO3 (373.44): calcd. C 77.19, H 6.21, N 3.75;
found C 77.10, H 6.13, N 3.66.
NMR (300 MHz, [D6]DMSO): δ = 10.70 (s, 1 H), 10.50 (s, 1 H),
8.11 (d, J = 2.4 Hz, 1 H), 7.82–7.70 (m, 3 H), 7.52 (d, J = 7.5 Hz,
2 H), 7.37–7.14 (m, 3 H), 6.66 (d, J = 7.8 Hz, 1 H), 6.44 (d, J =
8.1 Hz, 1 H) ppm. 13C NMR (75 MHz, [D6]DMSO): δ = 161.4,
154.3, 153.8, 144.4, 139.7, 131.1, 129.9, 129.1, 127.7, 125.7, 124.9,
120.9, 118.2, 117.9, 117.5, 115.5, 110.7, 108.6, 106.1, 101.4,
Methyl (1-Methyl-4-oxo-2-phenyl-4,5,6,7-tetrahydro-1H-indol-3-yl)-
acetate (13f): White solid (238 mg, 81% yield); m.p. 100–102 °C.
1H NMR (300 MHz, CDCl3): δ = 7.46–7.35 (m, 3 H), 7.31–7.26
(m, 2 H), 3.67 (s, 3 H), 3.63 (s, 2 H), 3.38 (s, 3 H), 2.82–2.78 (m, 2
H), 2.49–2.44 (m, 2 H), 2.21–2.15 (m, 2 H) ppm. 13C NMR
(75 MHz, CDCl3): δ = 194.3, 172.9, 143.5, 134.0, 130.6, 130.5,
128.5, 128.2, 118.3, 112.7, 51.7, 38.0, 31.6, 31.0, 23.3, 22.1 ppm. IR
92.7 ppm. IR (KBr): ν = 3354, 2205 cm–1. C H FN O (368.35):
˜
23 13
2
2
calcd. C 74.99, H 3.56, N 7.60; found C 74.91, H 3.47, N 7.52.
5-Hydroxy-3-methoxy-7-oxo-11-p-tolyl-8,9,10,11-tetrahydro-7H-
benzo[a]carbazole-6-carbonitrile (10k): Yellow solid (225 mg, 57%
(KBr): ν = 1733, 1641 cm–1. C H NO (297.34): calcd. C 72.71,
˜
18 19
3
1
yield); m.p Ͼ300 °C. H NMR (300 MHz, [D6]DMSO): δ = 10.63
H 6.44, N 4.71; found C 72.62, H 6.36, N 4.63.
(s, 1 H), 7.70 (s, 1 H), 7.48–7.41 (m, 4 H), 7.03–6.94 (m, 2 H), 3.82
(s, 3 H), 2.60–2.57 (m, 2 H), 2.47 (s, 3 H), 2.05–1.97 (m, 2 H), 1.31–
Methyl [2-(4-Methoxyphenyl)-4-oxo-1-phenyl-4,5,6,7-tetrahydro-
1H-indol-3-yl]acetate (13j): White solid (338 mg, 87% yield); m.p.
136–138 °C. 1H NMR (300 MHz, CDCl3): δ = 7.35–7.28 (m, 3 H),
7.09–7.07 (m, 2 H), 6.99 (d, J = 8.7 Hz, 2 H), 6.73 (d, J = 8.7 Hz,
2 H), 3.74 (s, 3 H), 3.73 (s, 2 H), 3.72 (s, 3 H), 2.67–2.63 (m, 2 H),
2.52–2.48 (m, 2 H), 2.16–2.09 (m, 2 H) ppm. 13C NMR (75 MHz,
CDCl3): δ = 194.9, 173.0, 158.9, 144.0, 137.4, 134.1, 131.6, 128.9,
127.8, 127.6, 122.7, 119.0, 113.5, 113.1, 55.1, 51.7, 38.3, 31.2, 23.6,
1.21 (m, 2 H) ppm. IR (KBr): ν = 3342, 2201 cm–1. C H N O
˜
25 20
2
3
(396.43): calcd. C 75.74, H 5.08, N 7.07; found C 75.64, H 5.01, N
6.96.
2-(4-Oxo-1,2-diphenyl-4,5,6,7-tetrahydro-1H-3-indolyl)acetic Acid
(11a): White solid (310 mg, 90% yield); m.p. 198–200 °C. 1H NMR
(300 MHz, CDCl3): δ = 7.35–7.30 (m, 3 H), 7.27–7.17 (m, 5 H),
7.08–7.06 (m, 2 H), 3.61 (s, 2 H), 2.74–2.64 (m, 4 H), 2.07–2.16 (m,
2 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 199.1, 172.3, 147.0,
136.9, 135.7, 130.7, 129.3, 129.0, 128.5, 128.2, 127.9, 127.5, 118.8,
23.1 ppm. IR (KBr): ν = 1735, 1646 cm–1. C H NO (389.44):
˜
24 23
4
calcd. C 74.02, H 5.95, N 3.60; found C 73.92, H 5.86, N 3.53.
112.5, 37.6, 33.9, 23.6, 23.0 ppm. IR (KBr): ν = 2943, 1706 cm–1.
˜
Methyl [2-(4-Methoxyphenyl)-4-oxo-1-p-tolyl-4,5,6,7-tetrahydro-
1H-indol-3-yl]acetate (13k): White solid (338 mg, 84% yield); m.p.
140–142 °C. 1H NMR (300 MHz, CDCl3): δ = 7.10 (d, J = 7.8 Hz,
2 H), 7.00–6.94 (m, 4 H), 6.74 (d, J = 8.7 Hz, 2 H), 3.75 (s, 2 H),
3.72 (s, 6 H), 2.66–2.62 (m, 2 H), 2.51–2.47 (m, 2 H), 2.33 (s, 3 H),
2.15–2.07 (m, 2 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 194.9,
173.0, 158.9, 144.1, 137.7, 134.8, 134.1, 131.7, 129.5, 127.4, 122.8,
118.9, 113.6, 112.9, 55.1, 51.7, 38.3, 31.2, 23.6, 23.1, 21.0 ppm. IR
C
22H19NO3 (345.39): calcd. C 76.50, H 5.54, N 4.06; found C
76.41, H 5.47, N 3.97.
3-Methyl-1,2-diphenyl-1H-3-indol-4-ol (12a): White solid (209 mg,
70% yield); m.p. 136–138 °C. 1H NMR (300 MHz, CDCl3): δ =
7.31–7.19 (m, 6 H), 7.18–7.13 (m, 4 H), 6.96 (d, J = 7.8 Hz, 1 H),
6.86 (d, J = 8.4 Hz, 1 H), 6.48–6.45 (dd, J1 = 7.5 Hz, J2 = 1.0 Hz,
1 H), 2.60 (s, 3 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 150.7,
139.8, 138.7, 136.1, 131.9, 130.7, 128.9, 127.9, 127.8, 127.1, 126.7,
(KBr): ν = 1738, 1644 cm–1. C H NO (403.47): calcd. C 74.42,
˜
25 25
4
H 6.25, N 3.47; found C 74.34, H 6.17, N 3.36.
123.0, 117.6, 109.8, 105.1, 103.6, 11.6 ppm. IR (KBr): ν =
˜
3450 cm–1. C21H17NO (299.36): calcd. C 84.25, H 5.72, N 4.68;
found C 84.17, H 5.65, N 4.60.
Methyl [1-Benzyl-2-(4-fluorophenyl)-4-oxo-4,5,6,7-tetrahydro-1H-
indol-3-yl]acetate (13m): White solid (317 mg, 81% yield); m.p. 79–
Methyl (4-Oxo-1,2-diphenyl-4,5,6,7-tetrahydro-1H-indol-3-yl)acet- 81 °C. 1H NMR (300 MHz, CDCl3): δ = 7.32–7.25 (m, 3 H), 7.19–
ate (13a): White solid (294 mg, 82% yield); m.p. 180–182 °C. 1H
10
7.17 (m, 2 H), 7.01 (t, J = 8.7 Hz, 2 H), 6.87 (d, J = 7.2 Hz, 2 H),
www.eurjoc.org
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 0000, 0–0

Job/Unit: O42085
/KAP1
Date: 10-06-14 12:32:24
Pages: 13
Benzo[a]carbazoles and Indole Acetic Acids
4.95 (s, 2 H), 3.68 (s, 3 H), 3.63 (s, 2 H), 2.65–2.61 (m, 2 H), 2.49–
H), 3.77 (s, 3 H), 3.75 (s, 2 H), 3.55 (s, 3 H) ppm. 13C NMR
2.45 (m, 2 H), 2.16–2.08 (m, 2 H) ppm. 13C NMR (75 MHz, (75 MHz, CDCl3): δ = 176.1, 150.4, 139.3, 138.3, 130.9, 128.5,
CDCl3): δ = 194.5, 172.7, 143.5, 137.0, 133.1, 132.5, 132.4, 128.8,
123.4, 117.5, 107.3, 103.3, 102.4, 52.8, 32.0, 31.2 ppm. IR (KBr): ν
˜
127.4, 126.2, 125.5, 118.7, 115.6, 115.3, 113.4, 51.6, 47.6, 38.0, 30.8,
= 3489, 1752 cm–1. C18H17NO3 (295.33): calcd. C 73.20, H 5.80, N
4.74; found C 73.11, H 5.72, N 4.65.
23.4, 22.1 ppm. IR (KBr): ν = 1733, 1645 cm–1. C24H22FNO3
˜
(391.43): calcd. C 73.64, H 5.66, N 3.58; found C 73.57, H 5.58, N
3.50.
Methyl [4-Hydroxy-2-(4-methoxyphenyl)-1-phenylindol-3-yl]acetate
(14j): White solid (118 mg, 61% yield); m.p. 160–162 °C. H NMR
1
(300 MHz, CDCl3): δ = 8.40 (s, 1 H), 7.34–7.23 (m, 3 H), 7.16–
7.12 (m, 4 H), 7.04 (t, J = 8.1 Hz, 1 H), 6.85–6.79 (m, 3 H), 6.73
(d, J = 7.2 Hz, 1 H), 3.86 (s, 2 H), 3.84 (s, 3 H), 3.79 (s, 3 H) ppm.
13C NMR (75 MHz, CDCl3): δ = 176.1, 159.2, 150.3, 139.6, 138.3,
137.8, 132.1, 129.0, 128.1, 127.0, 123.7, 123.0, 117.9, 113.6, 108.0,
Methyl [1,2-Bis(4-methoxyphenyl)-4-oxo-4,5,6,7-tetrahydro-1H-
indol-3-yl]acetate (13o): White solid (343 mg, 82% yield); m.p. 148–
150 °C. 1H NMR (300 MHz, CDCl3): δ = 7.01–6.98 (m, 4 H), 6.82
(d, J = 8.7 Hz, 2 H), 6.74 (d, J = 8.7 Hz, 2 H), 3.78 (s, 3 H), 3.75
(s, 3 H), 3.72 (s, 5 H), 2.64–2.60 (m, 2 H), 2.51–2.47 (m, 2 H), 2.13–
2.09 (m, 2 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 194.9, 173.0,
158.9, 144.3, 134.2, 131.7, 130.2, 128.8, 122.8, 118.8, 114.1, 113.6,
113.5, 112.8, 55.4, 55.1, 51.7, 38.3, 31.2, 23.6, 23.0 ppm. IR (KBr):
104.8, 103.5, 55.1, 52.9, 32.1 ppm. IR (KBr): ν = 3486, 1754 cm–1.
˜
C24H21NO4 (387.42): calcd. C 74.40, H 5.46, N 3.62; found C
74.31, H 5.35, N 3.55.
ν = 1740, 1642 cm–1. C H NO (419.46): calcd. C 71.58, H 6.01, Methyl [4-Hydroxy-2-(4-methoxyphenyl)-1-p-tolylindol-3-yl]acetate
˜
25 25
5
N 3.34; found C 71.47, H 5.94, N 3.25.
(14k): White solid (120 mg, 60% yield); m.p. 148–150 °C. 1H NMR
(300 MHz, CDCl3): δ = 8.38 (s, 1 H), 7.15–7.10 (m, 4 H), 7.03 (t,
J = 8.1 Hz, 3 H), 6.82 (d, J = 8.4 Hz, 3 H), 6.71 (d, J = 7.5 Hz, 1
Methyl [1-Benzyl-2-(4-methoxyphenyl)-4-oxo-4,5,6,7-tetrahydro-
1H-indol-3-yl]acetate (13p): White solid (322 mg, 80% yield); m.p.
110–112 °C. 1H NMR (300 MHz, CDCl3): δ = 7.32–7.24 (m, 3 H),
7.13 (d, J = 8.7 Hz, 2 H), 6.90–6.83 (m, 4 H), 4.96 (s, 2 H), 3.78
(s, 3 H), 3.70 (s, 3 H), 3.64 (s, 2 H), 2.63–2.59 (m, 2 H), 2.47–2.43
(m, 2 H), 2.14–2.10 (m, 2 H) ppm. 13C NMR (75 MHz, CDCl3): δ
= 194.6, 173.0, 159.7, 143.4, 137.3, 134.2, 132.0, 128.8, 127.4, 125.7,
122.4, 118.4, 114.0, 113.0, 55.2, 51.6, 47.8, 38.1, 31.1, 23.5,
H), 3.85 (s, 2 H), 3.81 (s, 3 H), 3.78 (s, 3 H), 2.33 (s, 3 H) ppm. 13
C
NMR (75 MHz, CDCl3): δ = 176.1, 159.2, 150.2, 139.8, 137.9,
136.8, 135.7, 132.1, 129.6, 127.8, 123.5, 123.2, 117.8, 113.5, 107.9,
104.5, 103.6, 55.1, 52.8, 32.1, 21.0 ppm. IR (KBr): ν = 3483,
˜
1755 cm–1. C25H23NO4 (401.45): calcd. C 74.79, H 5.77, N 3.49;
found C 74.70, H 5.69, N 3.38.
22.2 ppm. IR (KBr): ν = 1738, 1643 cm–1. C H NO (403.47):
Methyl [1-Benzyl-2-(4-fluorophenyl)-4-hydroxyindol-3-yl]acetate
(14m): White solid (119 mg, 61% yield); m.p. 116–118 °C. 1H NMR
(300 MHz, CDCl3): δ = 8.27 (s, 1 H), 7.29–7.20 (m, 5 H), 7.12–
7.02 (m, 3 H), 6.90 (d, J = 7.2 Hz, 2 H), 6.78 (d, J = 8.1 Hz, 1 H),
6.68 (d, J = 7.8 Hz, 1 H), 5.12 (s, 2 H), 3.76 (s, 2 H), 3.74 (s, 3
H) ppm. 13C NMR (75 MHz, CDCl3): δ = 175.8, 164.6, 161.3,
150.4, 138.9, 137.8, 137.3, 132.8, 128.6, 127.2, 126.7, 126.0, 123.7,
117.7, 115.7, 115.4, 107.6, 104.4, 103.3, 52.8, 47.9, 32.0 ppm. IR
˜
25 25
4
calcd. C 74.42, H 6.25, N 3.47; found C 74.33, H 6.17, N 3.38.
Methyl (4-Hydroxy-1,2-diphenylindol-3-yl)acetate (14a): White so-
lid (110 mg, 62% yield); m.p. 186–188 °C. 1H NMR (300 MHz,
CDCl3): δ = 8.31 (s, 1 H), 7.34–7.20 (m, 8 H), 7.16–7.14 (m, 2 H),
7.07 (d, J = 8.4 Hz, 1 H), 6.86 (d, J = 8.4 Hz, 1 H), 6.74 (d, J =
7.2 Hz, 1 H), 3.82 (s, 2 H), 3.83 (s, 3 H) ppm. 13C NMR (75 MHz,
CDCl3): δ = 176.1, 150.3, 139.8, 138.2, 137.9, 130.9, 130.8, 129.0,
128.1, 128.0, 127.9, 127.8, 127.1, 123.9, 108.2, 105.2, 103.5, 52.9,
(KBr): ν = 3490, 1756 cm–1. C H FNO (389.41): calcd. C 74.02,
˜
24 20
3
H 5.18, N 3.60; found C 73.93, H 5.10, N 3.51.
32.0 ppm. IR (KBr): ν = 3480, 1745 cm–1. C H NO (357.40):
˜
23 19
3
Methyl [4-Hydroxy-1,2-bis(4-methoxyphenyl)indol-3-yl]acetate
(14o): White solid (131 mg, 63% yield); m.p. 120–122 °C. 1H NMR
(300 MHz, CDCl3): δ = 8.39 (s, 1 H), 7.14 (d, J = 8.7 Hz, 2 H),
7.09–7.02 (m, 3 H), 6.88–6.77 (m, 5 H), 6.71 (d, J = 7.5 Hz, 1 H),
3.85 (s, 2 H), 3.82 (s, 3 H), 3.79 (s, 3 H), 3.78 (s, 3 H) ppm. 13C
NMR (75 MHz, CDCl3): δ = 176.2, 159.2, 158.4, 150.2, 132.2,
131.1, 129.2, 123.5, 123.1, 117.7, 114.2, 113.5, 107.9, 104.2, 103.5,
calcd. C 77.29, H 5.36, N 3.92; found C 77.20, H 5.28, N 3.82.
Methyl [4-Hydroxy-1-(4-methoxyphenyl)-2-phenylindol-3-yl]acetate
(14d): White solid (122 mg, 63% yield); m.p. 188–190 °C. 1H NMR
(300 MHz, CDCl3): δ = 8.36 (s, 1 H), 7.29–7.20 (m, 5 H), 7.07 (d,
J = 6.6 Hz, 3 H), 6.83 (d, J = 6.9 Hz, 3 H), 6.71 (d, J = 7.5 Hz, 1
H), 3.87 (s, 2 H), 3.82 (s, 3 H), 3.78 (s, 3 H) ppm. 13C NMR
(75 MHz, CDCl3): δ = 176.0, 158.4, 150.3, 140.1, 138.1, 131.0,
130.9, 129.1, 128.0, 127.8, 123.7, 117.7, 114.2, 107.9, 104.7, 103.6,
55.3, 55.1, 52.8, 32.1 ppm. IR (KBr): ν = 3479, 1746 cm–1
.
˜
C
25H23NO5 (417.45): calcd. C 71.93, H 5.55, N 3.36; found C
55.3, 52.8, 32.1 ppm. IR (KBr): ν = 3482, 1748 cm–1. C H NO
˜
71.85, H 5.47, N 3.27.
24 21
4
(387.42): calcd. C 74.40, H 5.46, N 3.62; found C 74.32, H 5.36, N
3.54.
Methyl [1-Benzyl-4-hydroxy-2-(4-methoxyphenyl)indol-3-yl]acetate
(14p): White solid (128 mg, 64% yield); m.p. 116–118 °C. 1H NMR
(300 MHz, CDCl3): δ = 8.38 (s, 1 H), 7.24–7.17 (m, 5 H), 7.02 (t,
J = 7.8 Hz, 1 H), 6.94–6.91 (m, 4 H), 6.75 (d, J = 7.5 Hz, 1 H),
6.67 (d, J = 7.5 Hz, 1 H), 5.13 (s, 2 H), 3.82 (s, 2 H), 3.76 (s, 3 H),
3.75 (s, 3 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 176.2, 159.9,
150.3, 138.8, 138.4, 138.0, 132.1, 128.6, 127.1, 126.1, 123.4, 122.8,
117.8, 113.9, 107.5, 103.8, 103.3, 55.3, 52.8, 47.9, 32.1 ppm. IR
Methyl (1-Benzyl-4-hydroxy-2-phenylindol-3-yl)acetate (14e): White
1
solid (122 mg, 66% yield); m.p. 189–191 °C. H NMR (300 MHz,
CDCl3): δ = 8.34 (s, 1 H), 7.40 (t, J = 7.8 Hz, 3 H), 7.32–7.29 (dd,
J1 = 6.6 Hz, J2 = 2.7 Hz, 2 H), 7.22–7.17 (m, 3 H), 7.03 (t, J =
3.0 Hz, 1 H), 6.93–6.90 (m, 2 H), 6.77 (d, J = 8.4 Hz, 1 H), 6.68
(d, J = 7.8 Hz, 1 H), 5.14 (s, 2 H), 3.77 (s, 2 H), 3.76 (s, 3 H) ppm.
13C NMR (75 MHz, CDCl3): δ = 176.0, 150.4, 139.0, 138.5, 137.9,
130.9, 130.7, 128.7, 128.6, 128.4, 127.1, 126.1, 123.6, 117.8, 107.5,
(KBr): ν = 3487, 1750 cm–1. C H NO (401.45): calcd. C 74.79,
˜
25 23
4
H 5.77, N 3.49; found C 74.70, H 5.69, N 3.41.
104.1, 103.4, 52.8, 47.9, 32.1 ppm. IR (KBr): ν = 3488, 1751 cm–1.
˜
Supporting Information (see footnote on the first page of this arti-
1
cle): H and 13C NMR spectra of all synthesized compounds.
C24H21NO3 (371.42): calcd. C 77.61, H 5.70, N 3.77; found C
77.50, H 5.62, N 3.69.
Methyl (4-Hydroxy-1-methyl-2-phenylindol-3-yl)acetate (14f):
Acknowledgments
White solid (88 mg, 60 % yield); m.p. 116–118 °C. 1H NMR
(300 MHz, CDCl3): δ = 8.37 (s, 1 H), 7.53–7.38 (m, 5 H), 7.13 (t, S. M. and S. P. thank the Council of Scientific and Industrial Re-
J = 8.1 Hz, 1 H), 6.91 (d, J = 7.8 Hz, 1 H), 6.69 (d, J = 7.5 Hz, 1 search (CSIR), New Delhi for offering them SRF. The financial
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Job/Unit: O42085
/KAP1
Date: 10-06-14 12:32:24
Pages: 13
S. Maity, S. Pathak, A. Pramanik
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CCDC-960635 (for 4u), -983375 (for 9c), and -983376 (for 14e)
contain the supplementary crystallographic data for this paper.
These data can be obtained free of charge from The Cambridge
Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_
request/cif.
assistance of the Council of Scientific and Industrial Research
(CSIR), New Delhi is gratefully acknowledged [Major Research
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Received: February 15, 2014
Published Online: ᭿
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Date: 10-06-14 12:32:24
Pages: 13
Benzo[a]carbazoles and Indole Acetic Acids
Carbazole Synthesis
S. Maity, S. Pathak,
A. Pramanik* .................................. 1–13
Substituted Benzo[a]carbazoles and Ind-
oleacetic Acids from Arylglyoxals and En-
amines through Domino Condensation,
Thermal Cyclization, and Aromatization
Keywords: Synthetic methods / Domino re-
actions / Cyclization / Nitrogen hetero-
cycles / Aromatization
The domino condensation of enamines, ar-
ylglyoxals, and malononitrile produced
cyclohexanone-fused 2-(3-pyrrolyl)-2-
cyanoacetamides, which were transformed
into highly substituted benzo[a]carbazoles
through a one-step thermal cyclization and
aromatization. The cyanoacetamides also
underwent hydrolysis and aromatization re-
actions to give the biologically important
indoleacetic acid derivatives.
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13