Palladium-catalyzed synthesis of quino[2,3- a ]carbazoles and indolo[2,3- a ]carbazoles via intramolecular ortho -arylation

Article abstract of DOI:10.1055/s-0033-1340678

An efficient palladium-catalyzed synthesis of quino[2,3-a]carbazoles and indolo[2,3-a]carbazoles from indole-3-acetonitrile via Knoevenagel condensation followed by intramolecular ortho-arylation has been demonstrated. Georg Thieme Verlag Stuttgart · New York.

Full text of DOI:10.1055/s-0033-1340678

PAPER
▌955
paper
Palladium-Catalyzed Synthesis of Quino[2,3-a]carbazoles and Indolo[2,3-a]car-
bazoles via Intramolecular ortho-Arylation
Quino[2,3-a]carbazoles and Indolo[2,3-a]carbazoles
Mayavan Viji, Suman Kr Ghosh, Rajagopal Nagarajan*
School of Chemistry, University of Hyderabad, Hyderabad 500 046, India
Fax +91(40)66794831; E-mail: rnsc@uohyd.ernet.in
Received: 18.12.2013; Accepted after revision: 08.01.2014
O
N
Abstract: An efficient palladium-catalyzed synthesis of quino[2,3-
a]carbazoles and indolo[2,3-a]carbazoles from indole-3-acetoni-
trile via Knoevenagel condensation followed by intramolecular
ortho-arylation has been demonstrated.
N
N
N
Br
H
O
H
Key words: heterocycles, condensation, palladium, arylation
calothrixin B
Br
dibromoquino[4,3-a]carbazole
H
N
alkaloid
Heteroannulated carbazoles play an essential role in vari-
ous areas of synthetic and medicinal chemistry that have
been comprehensively reviewed;1 they are versatile com-
pounds due to their biological and pharmacological rele-
vance. As a result, the preparation of heteroannulated
carbazoles has received much attention and substantial ef-
forts have been made by several research groups in the
area of carbazole chemistry, especially Knölker1a–d who
extensively reviewed carbazole alkaloids.
O
N
N
N
N
O
H
OH
O
H
MeO
HN
OH
OH
Me
tjipanazole G1
(+) staurosporinone
Quinocarbazoles have received considerable attention in
terms of their biological activity, such as potent antitumor,
antibacterial, anti-inflammatory, and antihistamine prop-
erties.2 Hence, several synthetic methodologies have been
reported for the preparation of quinocarbazole deriva-
tives.3 In 2012 a new alkaloid dibromoquinocarbazole de-
rivative (Figure 1) with a indolo[3,2-k]phenanthridine
skeleton was isolated from the marine sponge Penares
sp.3f Indolocarbazole is a significant heterocyclic template
broadly found in many natural products, and many of
these compounds have a wide range of medicinal applica-
tions.4 In view of their importance, several research
groups have reported the isolation and synthesis of indolo-
carbazole alkaloids and their derivatives.5
Figure 1 Quino- and indolocarbazole alkaloids
At the outset of our investigation, we chose 1a and 2a as
model substrate for the intramolecular ortho-arylation re-
action. The first objective was to prepare the required 1-
methyl-1H-indole-3-acetonitrile (1a) and 2-chloroquino-
line-3-carbaldehyde (2a); they were prepared by previ-
ously reported procedures.7,8 The original impetus for this
research came from an earlier observation that quinocar-
bazole 3a could be obtained in 26% yield when 1a reacted
with 2a in N,N-dimethylacetamide (DMA) at 130 °C in
the presence of 10 mol% of palladium(II) acetate (Table
1, entry 1). To achieve suitable conditions for the synthe-
sis of 3a, we tested the reaction under various conditions
by changing catalysts, bases, solvents, ligands and the re-
sults are shown in Table 1. The palladium catalyst (10
mol%) is active in several solvents including N,N-dimeth-
ylacetamide (25%, entry 2), N,N-dimethylformamide
(72%, entry 15), and N-methylpyrrolidin-2-one (20%, en-
try 18) but less active or inactive in toluene, dimethyl sulf-
oxide, and dioxane (entry 3). When the reaction was
carried out at lower temperatures, such as room tempera-
ture or 70 °C, the reaction did not occur. When palladi-
um(II) acetate was used without a ligand, only a moderate
yield of the anticipated product 3a was observed (entries
12 and 17). The efficiency of this catalyst was superior to
the other palladium catalysts such as palladium(II) chlo-
ride, dichlorobis(triphenylphosphine)palladium(II), and
palladium(II) trifluoroacetate, which requires at least 20
mol% catalyst and longer reaction times to obtain the
For the past decade, transition-metal-catalyzed ortho-ary-
lation reactions have had a major impact on the synthesis
cyclic compounds, and this is now a well-known method.6
Recently, much effort has gone into the development of
palladium-catalyzed ortho-arylation reaction, which is a
dominant method in organic synthesis for construction of
carbon–carbon and carbon–heteroatom bonds. Herein, we
wish to report a palladium-catalyzed ortho-arylation reac-
tion for the synthesis of heteroannulated carbazoles from
indole-3-acetonitrile. Various chloroquinoline- and chlo-
roindolecarbaldehydes were converted into the corre-
sponding quino- and indolocarbazoles in the presence of
palladium(II) acetate in good yields.
SYNTHESIS 2014, 46, 0955–0961
Advanced online publication: 10.02.2014
0
0
3
9
-
7
8
8
1
1
4
3
7
-
2
1
0
X
DOI: 10.1055/s-0033-1340678; Art ID: SS-2013-T0589-OP
© Georg Thieme Verlag Stuttgart · New York

956
M. Viji et al.
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product (entries 9, 7 and 18, respectively). We have also were observed, potassium acetate and cesium carbonate
examined other metal catalysts such as ruthenium(III) (entries 1 and 5) gave 3a in moderate yields, whereas so-
chloride and chlorotris(triphenylphosphine)rhodium (en- dium acetate did not give the desired product (entry 4).
tries 10 and 11), but neither gave the desired product. In- Further, we found that Lewis acids were unsuccessful in
terestingly, the reaction proceeded reasonably even with a promoting the reaction. After examining various reaction
lower concentration of the catalyst, such as 5 mol% of pal- conditions, we were pleased to find that the reaction pro-
ladium(II) acetate, to give 3a in 48% yield, although a lon- ceeded smoothly and provided the quinocarbazole 3a in
ger reaction time was necessary for the conversion (entry 72% yield at 120 °C in the presence of 10 mol% of palla-
14).
dium(II) acetate with 30 mol% of triphenylphosphine and
2.5 equiv of potassium carbonate.
No reaction occurred in the absence of a palladium cata-
lyst; 30 mol% of triphenylphosphine ligand is sufficient With the optimized conditions in hand, various substrates
for the reaction, but in its absence or in presence of other were examined to explore the scope of the reaction
ligands, the product was obtained in low yields or did not (Scheme 1). We proceeded with the preparation of differ-
form (entries 4, 5, and 16). Differences among the bases ent starting materials 1a–e and 2a–c and reacted them in
Table 1 Optimization Conditions for the Synthesis of the Quinocarbazole 3aa
CN
CN
OHC
Cl
catalyst, ligand
solvent, temp
+
N
N
N
N
Me
2a
Me
1a
3a
Entry
Catalyst
Ligand
Base
Solvent
Temp (°C)
Time (h)
Yieldb (%)
1
2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(PPh3)4
Ph3P
Ph3P
Ph3P
i-Pr2NH
Cy3P
Ph3P
Ph3P
Cy3P
Ph3P
Ph3P
Ph3P
–
KOAc
K2CO3
K2CO3
NaOAc
Cs2CO3
K2CO3
K2CO3
NaOAc
K2CO3
K2CO3
K2CO3
Cs2CO3
K2CO3
K2CO3
K2CO3
K2CO3
KOAc
K2CO3
DMA
DMA
solventc
DMA
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
NMP
130
130
130
120
140
120
120
130
120
120
120
120
130
120
120
130
140
120
24
20
36
24
24
12
36
36
24
36
36
18
24
24
18
18
12
24
26
25
d
3
–
d
4
–
5
31
26
16
6
7
PdCl2(PPh3)2
Pd(OAc)2
PdCl2
d
8
–
9
15
d
10
11
12
13
14e
15
16
17f
18
RuCl3
–
d
RhCl(PPh3)3
Pd(OAc)2
–
–
51
d
Ph3P
Ph3P
Ph3P
dppe
–
–
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OCOCF3)2
48
72
37
32
20
Ph3P
a Unless otherwise mentioned, all the reactions were conducted in a Schlenk tube using 1-methyl-1H-indole-3-acetonitrile (1a, 1.0 equiv), 2-
chloro-6-methylquinoline-3-carbaldehyde (2a, 1.0 equiv), base (2.5 equiv), catalyst (10 mol%), ligand (30 mol%), solvent (3 mL).
b Isolated yields.
c Toluene, DMSO, or dioxane.
d No result.
e 5 mol% of catalyst was used.
f 15 mol% of catalyst used.
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Quino[2,3-a]carbazoles and Indolo[2,3-a]carbazoles
957
R2
R2
K2CO3 (2.5 equiv)
Pd(OAc)2 (10 mol%)
Ph3P (30 mol%)
OHC
Cl
R3
+
N
DMF, 120 °C, 18–24 h
N
R1
N
R1
1a–e
N
R3
2a–c
3b–i
R1 = Me, Et, Bn
R2 = CN, CO2Et
R
3 = H, Me, OMe
CN
CN
CO2Me
N
N
N
N
N
N
Et
Me
Me
3d, 18 h, 75%
3c, 20 h, 70%
3b, 18 h, 68%
CN
CN
CO2Et
N
N
N
N
Bn
N
N
Bn
Et
3g, 18 h, 71%
3f, 20 h, 76%
3e, 20 h, 76%
CN
CO2Et
N
N
N
N
OMe
Me
Et
3h, 22 h, 70%
3i, 20h, 62%
Scheme 1 Synthesis of quino[2,3-a]carbazole derivatives; all reactions were conducted in a Schlenk tube using 1a–e (1.0 equiv), 2-chloro-
quinoline-3-carbaldehyde 2a–c (1.0 equiv), Pd(OAc)2 (10 mol%), Ph3P (30 mol%), K2CO3 (2.5 equiv), DMF (3 mL) at 120 °C. Yields are iso-
lated yields.
the presence of palladium(II) acetate and triphenylphos- is described in Scheme 3. Base-induced Knoevenagel
phine, potassium carbonate in N,N-dimethylformamide to condensation reaction between 1 and 2 gives an interme-
afford quino[2,3-a]carbazoles 3b–i in 62–76% yields. diate 4. Thus, the oxidative addition of the C–Cl bond to
The observed result clearly demonstrates that this method the Pd(0) species provides an intermediate (aryl)Pd com-
is useful for synthesis of 3b–i under the optimized reac- plex 5. Then, intramolecular ortho-arylation to the adja-
tion conditions. Though this reaction worked well with cent aryl C–H bond gives the seven-membered
electron-donating substituents like Me and OMe on the 2- palladacycle intermediate 6, followed by reductive elimi-
chloroquinoline-3-carbaldehyde moiety, when electron- nation, thus yielding the desired product 3 and regenerat-
withdrawing substituents, such as Cl, Br, or CO2Me, were ing the Pd(0) catalyst.
present, the reaction gave an inseparable mixture of the
Further, we studied the mechanistic pathway of the reac-
corresponding products in low yields. Next, using an in-
tion, where we isolated the intermediate to verify whether
dole-3-acetonitrile with the indole nitrogen free or pro-
the first step was formation of the Knoevenagel condensa-
tected with Boc did not give the desire products. Further,
tion intermediate or not. We isolated the intermediate in
74% yield, with some starting material remaining, by
we extended this ortho-arylation strategy to 2-chloro-1-
ethyl-1H-indole-3-carbaldehyde (2d) with a view to syn-
treating 2-chloroquinoline-3-carbaldehyde (2a) and 1a in
thesizing indolo[2,3-a]carbazole frameworks 3j,k
the presence of potassium carbonate in dry N,N-dimethyl-
(Scheme 2). Thus, we obtained the substituted indolo[2,3-
formamide at 120 °C after six hours (Scheme 4). Next, we
a]carbazoles 3j,k in good yields from 2-chloroindole-3-
treated the intermediate with palladium(II) acetate (10
mol%), triphenylphosphine (30 mol%), and potassium
carbaldehyde 2d under the optimized reaction conditions.
On the basis of the previous reports9 a plausible mechanistic carbonate (2.5 equiv) in dry N,N-dimethylformamide at
scenario for the formation of the product via Knoevenagel 120 °C for 20 hours, but the reaction did not go to comple-
condensation followed by intramolecular ortho-arylation tion and we obtained 3a in only 52% yield.
© Georg Thieme Verlag Stuttgart · New York
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958
M. Viji et al.
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R1
R1
K2CO3 (2.5 equiv)
Pd(OAc)2 (10 mol%)
Ph3P (30 mol%)
OHC
Cl
+
N
DMF, 120 °C, 18–24 h
N
N
N
Et
1b,c
R1 = CN, CO2Et
Et
Et
Et
2d
3j,k
CN
CO2Et
N
N
N
N
Et
Et
Et
Et
3j, 20 h, 74%
3k, 18 h, 68%
Scheme 2 Synthesis of indolo[2,3-a]carbazole derivatives; all reactions were conducted in a Schlenk tube using 1b,c (1.0 equiv), 2-chloro-1-
ethyl-1H-indole-3-carbaldehyde (2d, 1.0 equiv), Pd(OAc)2 (10 mol%), Ph3P (30 mol%), K2CO3 (2.5 equiv), DMF (3 mL) at 120 °C. Yields are
isolated yields.
Z
O
H
N
Cl
N
R
1
2
Pd(OAc)2
Pd0Ln
Z
N
N
Cl
Z
N
N
R
R
4
3
Z
N
Ln
Pd
Cl
Z
N
R
N
II
Pd
5
N
R
6
Scheme 3 Plausible mechanism
NC
NC
NC
O
K2CO3, DMF
120 °C, 6 h
Pd(OAc)2, Ph3P
N
+
Cl
K2CO3, DMF
120 °C
N
N
Cl
N
N
N
Me
Me
Me
Knoevenagel condensed
intermediate (3aa, 74%)
3a, 52%
Scheme 4 Mechanistic proof
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Quino[2,3-a]carbazoles and Indolo[2,3-a]carbazoles
959
13C NMR (100 MHz, CDCl3): δ = 168.3, 148.0, 142.1, 141.0, 137.1,
134.3, 130.3, 129.6, 128.2, 125.7, 125.5, 125.3, 124.7, 124.0, 123.8,
121.7, 120.1, 116.6, 109.5, 52.4, 33.6.
In summary, we have developed a novel palladium(II)
acetate catalyzed intramolecular ortho-arylation reaction
of indole-3-acetonitrile with 2-chloroquinoline-3-carbal-
dehyde, which afforded quino[2,3-a]carbazole deriva-
tives in good yields. This methodology also extended to
the synthesis of indolo[2,3-a]carbazoles in good yields,
starting from 2-chloroindole-3-carbaldehyde.
HRMS: m/z [M + H] calcd for C22H17N2O2: 341.1291; found:
341.1293.
13-Methyl-13H-indolo[3,2-c]acridine-5-carbonitrile (3c)
Orange-colored solid; yield: 0.029 g (70%); mp 240 °C; Rf = 0.62
(hexanes–EtOAc, 7:3).
IR (KBr): 3398, 2928, 2818, 1707, 1450, 1375, 1331, 1128, 1111,
1047, 1020, 889, 702 cm–1.
1H NMR (400 MHz, CDCl3): δ = 8.84 (s, 1 H), 8.71 (d, J = 8.0 Hz,
1 H), 8.31 (d, J = 8.4 Hz, 1 H), 8.09 (s, 1 H), 8.05 (d, J = 8.4 Hz, 1
H), 7.88 (t, J = 8.0 Hz, 1 H), 7.68–7.60 (m, 2 H), 7.44 (t, J = 7.6 Hz,
2 H), 4.90 (s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 147.6, 140.7, 136.5, 130.4, 128.7,
127.7, 126.7, 125.6, 125.3, 125.0, 124.5, 123.8, 121.2, 120.1, 119.4,
118.4, 117.9, 116.1, 115.4, 109.3, 33.1.
All 1H and 13C NMR spectra were recorded on a AV-400 spectrom-
eter operating at 400 and 100 MHz respectively relative to TMS
(δ = 0.00) or CDCl3 (δC = 77.0).Chemical shifts of common trace 1H
NMR impurities (CDCl3): δ = 1.56 (H2O); 1.26, 2.05, 4.12 (EtOAc);
5.30 (CH2Cl2); 7.26 ppm (CDCl3). IR spectra were recorded on
FT/IR-5300 spectrophotometer. Mass spectra were recorded on ei-
ther using EI technique or LCMS-2010A mass spectrometer. Ele-
mental analyses (C, H, and N) were recorded on EA 1112 analyzer
in the School of Chemistry, University of Hyderabad. Routine mon-
itoring of the reactions was performed by TLC silica gel plates 60
F254 were used. Compounds were visualized with a UV light at 254
nm. Further visualization was achieved by staining with I2. Column
chromatography was carried out employing silica gel 100 mesh.
Commercially available reagents and solvents were used without
further purification and were purchased. Melting points were mea-
sured in open capillary tubes and are uncorrected. LCMS system,
whereas MS (EI) were recorded with a Jeol JMS600H mass spec-
trometer. HRMS (ESI) were recorded using a Bruker Maxis mass
spectrometer.
LC-MS (–): m/z = 306 (M – H)–.
Anal. Calcd for C21H13N3: C, 82.06; H, 4.26; N, 13.67. Found: C,
82.16; H, 4.21; N, 13.58.
13-Ethyl-9-methyl-13H-indolo[3,2-c]acridine-5-carbonitrile
(3d)
Yellow-colored solid; yield: 0.032 g (75%); mp 98 °C; Rf = 0.45
(hexanes–EtOAc, 7:3).
IR (KBr): 3238, 2968, 2918, 2538, 1707, 1450, 1365, 1341, 1258,
1151, 1087, 1020, 989, 785 cm–1.
1H NMR (400 MHz, CDCl3): δ = 8.86 (d, J = 8.2 Hz, 1 H), 8.77 (s,
1 H), 8.72 (d, J = 7.8 Hz, 1 H), 8.20 (d, J = 8.6 Hz, 1 H), 8.11 (s, 1
H), 7.81 (s, 1 H), 7.71 (d, J = 8.2 Hz, 2 H), 7.55–7.52 (m, 1 H), 4.89
(q, J = 7.2 Hz, 2 H), 2.63 (s, 3 H), 1.65 (t, J = 7.0 Hz, 3 H).
13C NMR (100 MHz, CDCl3): δ = 142.0, 136.3, 135.9, 133.8, 129.3,
128.5, 127.2, 127.1, 126.4, 125.97, 125.92, 124.9, 124.3, 122.2,
121.5, 120.8, 120.7, 120.5, 109.7, 108.9, 38.7, 21.8, 14.9.
9,13-Dimethyl-13H-indolo[3,2-c]acridine-5-carbonitrile (3a);
Typical Procedure
1-Methyl-1H-indole-3-acetonitrile (1a, 1.0 equiv), 2-chloro-6-
methylquinoline-3-carbaldehyde (2a, 1.0 equiv), K2CO3 (2.5
equiv), Pd(OAc)2 (10 mol%), and Ph3P (30 mol%) were transferred
to an oven-dried 25-mL Schlenk tube. The tube was evacuated and
refilled with N2 (3 ×). After addition of DMF (3 mL) under a posi-
tive pressure of N2 via syringe, the Schlenk tube was placed in a 120
°C oil bath and stirred for 18 h. Upon completion of the reaction
(TLC monitoring), the mixture was poured into H2O (25 mL) and
the contents were extracted with EtOAc (2 × 20 mL). Then the com-
bined organic extracts were dried (anhyd Na2SO4) and concentrated
under reduced pressure to obtain crude 3a. The crude product was
purified by column chromatography (silica gel, hexanes–EtOAc,
95:5) to afford 3a as a yellow-colored solid; yield: 0.030 g (72%);
mp 68 °C; Rf = 0.36 (hexanes–EtOAc, 7:3).
LC-MS (+): m/z = 336 [M + H]+.
Anal. Calcd for C23H17N3: C, 82.36; H, 5.11; N, 12.53. Found: C,
82.12; H, 5.16; N, 12.56.
Ethyl 13-Ethyl-13H-indolo[3,2-c]acridine-5-carboxylate (3e)
Orange-colored solid; yield: 0.033 g (76%); mp 136 °C; Rf = 0.52
(hexanes–EtOAc, 7:3).
IR (KBr): 3412, 3151, 2458, 1717, 1532, 1477, 1370, 1321, 1228,
1140, 1101, 1087, 889, 781, 728 cm–1.
IR (KBr): 3408, 2912, 1701, 1587, 1477, 1338, 1331, 1252, 1180,
1087, 1020, 992, 781 cm–1.
1H NMR (400 MHz, CDCl3): δ = 8.91 (s, 1 H), 8.70 (d, J = 8.0 Hz,
1 H), 8.32–8.30 (m, 2 H), 8.06 (d, J = 8.4 Hz, 1 H), 7.86–7.82 (m, 1
H), 7.72–7.70 (m, 1 H), 7.62–7.55 (m, 2 H), 7.36 (t, J = 7.2 Hz, 1
H), 5.60 (q, J = 7.0 Hz, 2 H), 4.64 (q, J = 7.2 Hz, 2 H), 1.66 (t,
J = 7.0 Hz, 3 H), 1.56 (t, J = 7.2 Hz, 3 H).
13C NMR (100 MHz, CDCl3): δ = 168.0, 148.3, 141.7, 139.9, 139.3,
136.9, 130.2, 129.7, 128.1, 126.1, 125.7, 125.2, 124.8, 124.1, 123.5,
121.9, 120.0, 116.7, 114.0, 109.4, 61.4, 40.8, 15.3, 14.4.
1H NMR (400 MHz, CDCl3): δ = 8.62 (d, J = 8.0 Hz, 1 H), 8.56 (s,
1 H), 8.09 (d, J = 8.8 Hz, 1 H), 7.90 (s, 1 H), 7.66 (s, 1 H), 7.63–7.61
(m, 1 H), 7.59–7.57 (m, 2 H), 7.42–7.38 (m, 1 H), 4.78 (s, 3 H), 2.58
(s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 147.0, 140.6, 140.4, 136.2, 135.7,
133.8, 133.5, 129.0, 127.1, 126.3, 125.8, 125.6, 124.6, 121.1, 120.7,
120.5, 118.8, 116.0, 109.7, 104.0, 33.3, 21.8.
HRMS: m/z [M + H] calcd for C22H16N3: 322.1345; found:
322.1345.
HRMS: m/z [M + Na] calcd for C24H20N2NaO2: 391.1423; found:
391.1423.
Methyl 13-Methyl-13H-indolo[3,2-c]acridine-5-carboxylate
13-Benzyl-9-methyl-13H-indolo[3,2-c]acridine-5-carbonitrile
(3b)
(3f)
Yellow-colored solid; yield: 0.029 g (68%); mp 78 °C; Rf = 0.56
Yellow-colored solid; yield: 0.033 g (76%); mp 212 °C; Rf = 0.48
(hexanes–EtOAc, 7:3).
(hexanes–EtOAc, 7:3).
IR (KBr): 3477, 2959, 2928, 2851, 1727, 1635, 1587, 1477, 1450,
1228, 1180, 1151, 1087, 1008, 915 cm–1.
1H NMR (400 MHz, CDCl3): δ = 8.85 (s, 1 H), 8.69 (d, J = 8.2 Hz,
1 H), 8.31 (d, J = 8.6 Hz, 1 H), 8.28 (s, 1 H), 8.04 (d, J = 8.4 Hz, 1
H), 7.84 (t, J = 7.6 Hz, 1 H), 7.66–7.64 (m, 1 H), 7.58 (q, J = 7 Hz,
2 H), 7.37 (t, J = 8.0 Hz, 1 H), 4.94 (s, 3 H), 4.15 (s, 3 H).
IR (KBr): 3451, 1637, 1262, 1221, 1019, 1008, 920, 889, 781, 729
cm–1.
1H NMR (400 MHz, CDCl3): δ = 8.70 (d, J = 8.0 Hz, 1 H), 8.60 (s,
1 H), 8.05 (d, J = 8.8 Hz, 1 H), 8.00 (s, 1 H), 7.67 (s, 1 H), 7.63–7.61
© Georg Thieme Verlag Stuttgart · New York
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M. Viji et al.
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(m, 2 H), 7.56–7.52 (m, 1 H), 7.45–7.41 (m, 1 H), 7.29–7.28 (m, 1
H), 7.24–7.16 (m, 4 H), 6.77 (s, 2 H), 2.56 (s, 3 H).
IR (KBr): 3477, 3051, 2960, 2928, 2868, 1607, 1477, 1450, 1375,
1351, 1228, 1151, 1087, 1008, 920 cm–1.
13C NMR (100 MHz, CDCl3): δ = 147.2, 140.4, 140.2, 138.7, 136.3,
135.9, 133.9, 133.2, 129.1, 128.5, 127.7, 127.1, 126.9, 126.3, 126.1,
125.8, 124.7, 121.5, 121.1, 120.7, 118.7, 116.5, 110.5, 104.1, 49.2,
21.8.
1H NMR (400 MHz, CDCl3): δ = 8.82 (d, J = 8.0 Hz, 1 H), 8.22 (s,
1 H), 8.19 (d, J = 7.6 Hz, 1 H), 7.59–7.54 (m, 2 H), 7.47–7.44 (m, 2
H), 7.34–7.30 (m, 2 H), 4.80 (q, J = 7.2 Hz, 2 H), 4.48 (q, J = 7.2
Hz, 2 H), 1.58 (t, J = 7.2 Hz, 3 H), 1.49 (t, J = 7.2 Hz, 3 H).
LC-MS (+): m/z = 398 [M + H]+.
13C NMR (100 MHz, CDCl3): δ = 141.5, 141.2, 135.8, 134.2, 127.1,
126.8, 123.6, 123.0, 122.1, 122.0, 121.0, 120.1, 119.5, 119.0, 118.5,
108.9, 108.4, 104.5, 82.8, 38.5, 37.7, 14.8, 13.9.
Anal. Calcd for C28H19N3: C, 84.61; H, 4.82; N, 10.57. Found: C,
84.52; H, 4.76; N, 10.45.
LC-MS (+): m/z = 338 [M + H]+.
13-Benzyl-13H-indolo[3,2-c]acridine-5-carbonitrile (3g)
Yellow-colored solid; yield: 0.031 g (71%); mp 180 °C; Rf = 0.52
(hexanes–EtOAc, 7:3).
Anal. Calcd for C23H19N3: C, 81.87; H, 5.68; N, 12.45. Found: C,
81.76; H, 5.61; N, 12.36.
IR (KBr): 3412, 3001, 2868, 2858, 1707, 1687, 1450, 1365, 1331,
1228, 1180, 1151, 1087, 1020, 889, 721 cm–1.
Ethyl 11,12-Diethyl-11,12-dihydroindolo[2,3-a]carbazole-5-
carboxylate (3k)
Orange-colored solid; yield: 0.031 g (68%); mp 186 °C; Rf = 0.58
(hexanes–EtOAc, 7:3).
1H NMR (400 MHz, CDCl3): δ = 8.76 (s, 1 H), 8.71 (d, J = 8.0 Hz,
1 H), 8.17 (d, J = 8.6 Hz, 1 H), 8.05 (s, 1 H), 7.98 (d, J = 8.4 Hz, 1
H), 7.83–7.79 (m, 1 H), 7.63–7.61 (m, 1 H), 7.59–7.53 (m, 2 H),
7.45–7.42 (m, 1 H), 7.31–7.29 (m, 2 H), 7.23–7.15 (m, 3 H), 6.77
(s, 2 H).
13C NMR (500 MHz, CDCl3): δ = 148.4, 141.0, 140.4, 138.6, 137.0,
133.1, 131.0, 129.5, 128.55, 128.50, 128.2, 127.7, 127.0, 126.8,
126.3, 125.7, 124.7, 121.5, 121.2, 120.8, 118.6, 116.9, 110.5, 104.5,
49.3.
IR (KBr): 3462, 3041, 2963, 2912, 2858, 1587, 1467, 1375, 1311,
1248, 1180, 1151, 1087, 1020, 891 cm–1.
1H NMR (400 MHz, CDCl3): δ = 8.81–8.79 (m, 2 H), 8.50 (s, 1 H),
8.30–8.28 (m, 2 H), 7.60–7.58 (m, 1 H), 7.53–7.49 (m, 1 H), 7.40–
7.33 (m, 2 H), 4.94 (q, J = 7.2 Hz, 2 H), 4.61 (q, J = 7.2 Hz, 2 H),
4.47 (q, J = 7.2 Hz, 2 H), 1.80 (t, J = 7.2 Hz, 3 H), 1.58–1.53 (m, 6
H).
13C NMR (100 MHz, CDCl3): δ = 168.5, 142.5, 141.1, 140.5, 135.4,
126.5, 125.8, 125.0, 124.6, 124.2, 124.1, 122.6, 121.7, 121.5, 119.6,
117.4, 108.5, 107.7, 98.1, 61.0, 40.8, 37.7, 15.3, 14.5, 13.4.
HRMS: m/z [M + H] calcd for C27H18N3: 384.1501; found:
384.1500.
Ethyl 13-Ethyl-9-methyl-13H-indolo[3,2-c]acridine-5-carbox-
ylate (3h)
LC-MS (+): m/z = 385 [M + H]+.
Yellow-colored solid; yield: 0.029 g (70%); mp 184 °C; Rf = 0.45
(hexanes–EtOAc, 7:3).
Anal. Calcd for C25H24N2O2: C, 78.10; H, 6.29; N, 7.29. Found: C,
78.21; H, 6.21; N, 7.36.
IR (KBr): 3352, 3011, 2928, 2818, 1707, 1525, 1477, 1355, 1331,
1228, 1110, 1087, 1020, 880, 781 cm–1.
(E)-3-(2-Chloroquinolin-3-yl)-2-(1-methyl-1H-indol-3-yl)acry-
lonitrile (3aa)
Yellow-colored solid; yield: 0.065 g (74%); mp 142 °C; Rf = 0.45
(hexanes–EtOAc, 7:3).
1H NMR (400 MHz, CDCl3): δ = 8.80 (s, 1 H), 8.70 (d, J = 8.0 Hz,
1 H), 8.29 (s, 1 H), 8.22 (d, J = 8.8 Hz, 1 H), 7.81 (s, 1 H), 7.69 (t,
J = 8.2 Hz, 2 H), 7.57–7.54 (m, 1 H), 7.37–7.33 (m, 1 H), 5.60 (q,
J = 7.2 Hz, 2 H), 4.63 (q, J = 7.2 Hz, 2 H), 2.63 (s, 3 H), 1.68–1.64
(m, 6 H).
13C NMR (100 MHz, CDCl3): δ = 166.2, 148.1, 144.5, 141.7, 139.1,
138.3, 137.0, 135.2, 133.1, 132.6, 131.1, 127.3, 126.2, 125.4, 124.2,
122.8, 120.2, 118.1, 114.4, 109.4, 59.8, 38.6, 21.3, 14.7, 14.2.
IR (KBr): 2953, 2920, 1687, 1627, 1539, 1473, 1320, 1221, 1024,
821, 734 cm–1.
1H NMR (400 MHz, CDCl3): δ = 8.89 (s, 1 H), 8.07 (d, J = 8.0 Hz,
1 H), 8.04 (d, J = 8.4 Hz, 1 H), 7.96 (s, 2 H), 7.78 (t, J = 7.2 Hz, 1
H), 7.62 (d, J = 7.6 Hz, 1 H), 7.58 (s, 1 H), 7.43–7.34 (m, 3 H), 3.87
(s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 150.0, 147.1, 138.1, 136.9, 131.3,
130.1, 128.3, 128.2, 127.6, 127.5, 127.0, 124.5, 123.4, 121.7, 120.0,
117.7, 111.2, 110.4, 110.3, 33.3.
LC-MS (+): m/z = 383 [M + H]+.
Anal. Calcd for C25H22N2O2: C, 78.51; H, 5.80; N, 7.32. Found: C,
78.36; H, 5.72; N, 7.23.
HRMS: m/z [M + H] calcd for C21H15Cl35N3: 344.0955; found:
344.0954; m/z [M + H] calcd for C21H15Cl37N3: 346.0925; found:
346.0923.
9-Methoxy-13-methyl-13H-indolo[3,2-c]acridine-5-carboni-
trile(3i)
Yellow-colored solid; yield: 0.047 g (62%); mp 184 °C; Rf = 0.6
(hexanes–EtOAc, 7:3).
IR (KBr): 3117, 2926, 2224, 1687, 1632, 1479, 1221, 909, 739 cm–1.
Acknowledgement
1H NMR (400 MHz, CDCl3): δ = 8.71 (s, 2 H), 8.20 (d, J = 9.2 Hz,
1 H), 8.07 (s, 1 H), 7.68 (d, J = 8.0 Hz, 1 H), 7.62 (t, J = 8.0 Hz, 1
H), 7.55 (dd, J = 9.2, 2.8 Hz 1 H), 7.46–7.43 (m, 1 H), 7.22 (d,
J = 2.4 Hz, 1 H), 4.90 (s, 3 H), 4.02 (s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 157.6, 145.4, 140.6, 139.7, 134.7,
134.0, 131.1, 126.8, 126.7, 126.0, 125.8, 125.1, 121.3, 120.8, 120.6,
118.9, 115.9, 109.8, 104.4, 103.4, 55.7, 33.4.
We gratefully acknowledge DST (Project number: SR/S1/OC-
70/2008) for financial support and for the single-crystal X-ray dif-
fractometer facility in our school. M.V. and S.K.G thanks CSIR &
UGC for senior research fellowship and junior research fellowship.
Supporting Information for this article is available online at
http://www.thieme-connect.com/ejournals/toc/synthesis. Included
are NMR, HRMS, LC-MS and elemental analysis data. SunogIopiftrmanSrtnuIpgrfoi
HRMS: m/z [M + H] calcd for C22H16N3O: 338.1293; found:
338.1290.
m
p
nirtat
11,12-Diethyl-11,12-dihydroindolo[2,3-a]carbazole-5-carboni-
trile (3j)
Orange-colored solid; yield: 0.034 g (74%); mp 204 °C; Rf = 0.36
(hexanes–EtOAc, 7:3).
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Synthesis 2014, 46, 955–961