RuCl3/SnCl2 mediated synthesis of pyrrolo[2,3-c]carbazoles and consequent preparation of indolo[2,3-c]carbazoles

Article abstract of DOI:10.1016/j.tet.2012.01.070

A simple method for the synthesis of pyrrolo[2,3-c]carbazoles from N-alkylated-3-aminocarbazole derivatives and ethylene glycol has been developed via heteroannulation reaction using RuCl₃/SnCl₂ system. Moreover indolo[2,3-c]carbazol

Full text of DOI:10.1016/j.tet.2012.01.070

Tetrahedron 68 (2012) 2453e2458
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Tetrahedron
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RuCl3/SnCl2 mediated synthesis of pyrrolo[2,3-c]carbazoles and consequent
preparation of indolo[2,3-c]carbazoles
*
Mayavan Viji, Rajagopal Nagarajan
School of Chemistry, University of Hyderabad, Hyderabad 500 046, India
a r t i c l e i n f o
a b s t r a c t
Article history:
A simple method for the synthesis of pyrrolo[2,3-c]carbazoles from N-alkylated-3-aminocarbazole de-
rivatives and ethylene glycol has been developed via heteroannulation reaction using RuCl3/SnCl2 sys-
tem. Moreover indolo[2,3-c]carbazoles were prepared from various pyrrolo[2,3-c]carbazoles in good
yields.
Received 26 December 2011
Received in revised form 19 January 2012
Accepted 24 January 2012
Available online 31 January 2012
Ó 2012 Elsevier Ltd. All rights reserved.
Keywords:
Heteroannulation
3-Aminocarbazoles
RuCl3
Pyrrolo[2,3-c]carbazoles
Indolo[2,3-c]carbazoles
1. Introduction
isolated from dictyodendrilla verongiformis, the first marine natural
products with telomerase inhibitory properties showing 100% in-
Aryl- and heteroaryl-annulated carbazoles, such as pyr-
idocarbazoles, indolocarbazoles, and pyrrolocarbazoles have
attracted growing attention since they are distributed in numerous
natural products with diverse useful bioactivities.1 Among them,
many efforts have been devoted to the design and synthesis of
pyrrolocarbazoles,2 which seem to be the most intriguing, and thus
have proven to be very important in medicinal chemistry. For ex-
ample, the pyrrolo[2,3-a] and [3,4-c]carbazoles have great impor-
tance due to their inhibiting properties toward pim kinase
inhibitors3 and Chk1 inhibitors,4 respectively. Having a common
core of pyrrolo[2,3-c]carbazole, dictyodendrins AeE (Fig. 1) were
hibition at 50 m
g/mL.5
Indolocarbazole, the benzene analog of pyrrolocarbazole, rep-
resents one of the most important classes of heterocycles. The syn-
theses of indolocarbazoles6 have received great attention because of
their existence in many natural products with potent biological ac-
tivities.1 Over the past few decades, transition metal-catalyzed re-
actions have been recognized as a useful synthetic tool for the
construction of wide range of compounds in organic synthesis.7 In
recent years ruthenium has been emerged as one of the most useful
transition metal catalyst in organic synthesis.8 As a result, various
useful ruthenium catalyzed reactions have been explored.
In this paper, we describe a regioselective and good yielding
procedure for the preparation of pyrrolo[2,3-c]carbazoles from
heteroannulation of N-alkylated-3-aminocarbazoles with ethylene
glycol, mediated by RuCl3/SnCl2 system in the presence of 1,2-
bis(diphenylphosphino)ethane (dppe) as a ligand. This method
provides a route for the construction of a variety of substituted
pyrrolo[2,3-c]carbazole derivatives as shown in Scheme 1. More-
over, we wish to report an annulation of this pyrrolo[2,3-c]carba-
zoles extend into indolo[2,3-c]carbazoles by reacting with
acetonylacetone using p-TSA as catalyst.
Fig. 1. Pyrrolo[2,3-c]carbazole and indolo[2,3-a]carbazole alkaloids.
2. Results and discussion
3-Aminocarbazole derivatives can be easily prepared based
on literature procedure.9 An initial experiment 9-ethyl-3-
* Corresponding author. Tel.: þ91 40 23012460; fax: þ91 4023134831; e-mail
addresses: rnsc@uohyd.ernet.in, naga_indole@yahoo.co.in (R. Nagarajan).
0040-4020/$ e see front matter Ó 2012 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2012.01.070

2454
M. Viji, R. Nagarajan / Tetrahedron 68 (2012) 2453e2458
Table 2
Ligand effect on heteroannulation of 1aa
Scheme 1. The schematic representation of present work.
aminocarbazole 1a was reacted with ethylene glycol 2 in the
presence of RuCl3, SnCl2$2H2O, and dppe in acetonitrile. The de-
sired heteroannulated product 3a was isolated in low yield. En-
couraged by this result 1a and 2 were taken as model substrates,
and the representative results are summarized in Tables 1 and 2.
With the preliminary result in hand, we investigated various re-
action parameters. On the basis of the aforementioned line of
reasoning, an array of solvents was undertaken, such as toluene,
CHCl3, THF, acetonitrile, DMA, acetone, and dioxane. Interestingly,
CHCl3, DMA, dioxane/H2O, and acetonitrile gave the desired prod-
uct in lower yields, whereas no product was detected when using
THF and acetone as shown in Table 1. The best yields were obtained
when the reactions were carried out in toluene.
Entry
Ligand
Temp/ꢀC, time (h)
Yieldb
1
2
3
4
5
6
7
8
9
dppe
dppe
d
120, 4
120, 8
42
73
14
36
35
21
42
21
28
140, 24
140, 12
140, 12
140, 12
140, 12
140, 24
140, 24
P(OEt)3
PCy3
BINAP
PPh3
dppp
dppf
a
All the reactions were carried out in a pressure tube using 5.0 mL toluene,
18 mol % RuCl3, 15 mol % ligand, 1.0 equiv 9-ethyl-3-aminocarbazole, 2.0 equiv
ethylene glycol, 3.0 equiv SnCl2$2H2O.
b
Isolated yields.
Table 1
Optimization condition for the conversion of 1a to 3aa
RuCl3 was found to be an efficient catalyst in this reaction
compared with other catalysts, such as PdCl2(PPh3)2 and
RhCl(PPh3)3. The best result was achieved by using 18 mol % RuCl3,
15 mol % dppe, and 3.0 equiv of SnCl2 in 5 mL of toluene at 120 ꢀC
for 8 h. Further increase in temperature did not show any signifi-
cant improvement in yield (Table 1, entry14). Attempts to reduce
the catalyst loading were only partly successful as lesser amount of
pyrrolo[2,3-c]carbazole 3a was formed, when 6 mol % catalyst was
employed. On the other hand, using 18 mol % catalyst loading gave
good conversion, and identical yields were obtained with 24 mol %
catalyst loading, although the reaction time was slightly prolonged
as shown in Table 1.
Subsequently, the effect of ligands were further investigated
under the above optimized solvent, catalyst, and co-catalyst, it in-
dicated that ligands played an important role in this hetero-
annulation reaction. All the results are listed in Table 2. When
heteroannulation of 1a was carried out in the absence of ligand, the
corresponding product 3a was obtained in 16% yield (Table 2, entry
3). While in the presence of ligand the product 3a was obtained
with improved yield, which confirms the key role of ligand in this
heteroannulation reaction. We were delighted to find that dppe
was the most effective ligand for this reaction. In the presence of
dppe the cyclization of 1a afforded 3a in 73% yield under the op-
timized condition (Table 2, entry 2).
S.No Catalyst
Co-catalyst
PdCl2(PPh3)2 SnCl2$2H2O
RuCl3 SnCl2$2H2O
RhCl(PPh3)3 SnCl2$2H2O
Solvent
Temp/ꢀC, time/h Yielde
1b
2b
3b
4
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
120, 12
120, 12
120, 12
120, 12
120, 12
120, 12
120, 12
120, 12
120, 12
120, 12
d
30
16
d
12
30
25
28
d
d
35
42
73
73
d
18
15
d
26
d
RuCl3
RuCl3
RuCl3
RuCl3
RuCl3
RuCl3
RuCl3
RuCl3
RuCl3
RuCl3
RuCl3
RuCl3
RuCl3
RuCl3
RuCl3
RuCl3
RuCl3
InCl3
SbCl3
CeCl3$7H2O
AlCl3
ZnCl2
5
6
7
8
9
Bi(NO2)3$5H2O Toluene
10
11c
12
13
14d
15
16
17
18
19
20
FeCl3$6H2O
SnCl2$2H2O
SnCl2$2H2O
SnCl2$2H2O
SnCl2$2H2O
SnCl2$2H2O
SnCl2$2H2O
SnCl2$2H2O
SnCl2$2H2O
SnCl2$2H2O
d
Toluene
Dioxane/H2O 120, 12
Toluene
Toluene
Toluene
THF
CHCl3
DMA
Acetone
Acetonitrile
Toluene
120, 4
120, 12
140, 12
120, 12
120, 12
140, 12
120, 12
120, 12
140, 12
With optimized conditions in our hand, we explored the scope
of this method with respect to an array of N-alkylated-3-
aminocarbazoles 1aek as summarized in Table 3. Various de-
rivatives of 1aek smoothly underwent heteroannulation reaction to
afford the desired pyrrolo[3,2-c]carbazole 3aek in good yields
(Scheme 2). When R4 was substituted with methyl group pyrrolo[3,2-
b]carbazole 3l was obtained in good yield. The structure of product 3c
was also confirmed by single-crystal X-ray analysis10 (Fig. 2).
Carbazole is obtained by the reaction of acetonylacetone with
indole in the presence of Lewis acid.9e We wish to apply this
methodology for pyrrolo[2,3-c]carbazole into indolo[2,3-c]carba-
zoles (Scheme 3). The desired indolo[2,3-c]carbazoles were suc-
cessfully synthesized in good yields by reacting acetonylacetone
(1.0 equiv) with various pyrrolo[2,3-c]carbazoles (1.0 equiv) and
using p-toluenesulfonic acid (p-TSA, 0.5 equiv) as a catalyst. The
yield of the product was slightly lower when toluene was used as
solvent instead of ethanol. Reaction of pyrrolocarbazoles (3j, 3k,
and 3l) with acetonylacetone works well however the products are
not identifiable from the spectroscopic data (Table 4).
The bold letter indicates the optimized condition of this reaction.
a
Unless otherwise stated, all the reactions were carried out in a pressure tube
using 5.0 mL solvent, 18 mol % catalyst, 15 mol % of dppe, 1.0 equiv 9-ethyl-3-
aminocarbazole, 2.0 equiv ethylene glycol, 3.0 equiv co-catalyst.
b
Catalyst (6 mol %), 5 mol % dppe, and 3.0 equiv co-catalyst were used.
Dioxane/H2O in the ratio 9:1.
Catalyst (24 mol %) and 20 mol % dppe were used.
Isolated yields.
c
d
e
When 1a and 2 were treated with RuCl3 (6 mol %) and dppe
(5 mol %) in the presence of SnCl2 (3.0 equiv) for 12 h at 120 ꢀC,
compound 3a was obtained in 30% yield (Table 1, entry 2). It is
intriguing to note that without the addition of SnCl2 hetero-
annulation reaction could not be promoted (Table 1, entry 20),
while in the presence of SnCl2 (3.0 equiv), compound 3a was ob-
tained in 73% yield. We screened other co-catalysts, such as SbCl3,
CeCl3$7H2O, AlCl3, ZnCl2, which took longer reaction times (12 h)
and gave lower yields of 3a (Table 1, entries 5e8). No product was
formed by using InCl3, Bi(NO2)3$5H2O, FeCl3$6H2O (Table 1, entries
4, 9, and 10).

M. Viji, R. Nagarajan / Tetrahedron 68 (2012) 2453e2458
2455
Table 3
Table 4
RuCl3/SnCl2 catalyzed heteroannulation of various N-alkylated-3-aminocarbazolesa
Preparation of indolo[2,3-c]carbazoles form pyrrolo[2,3-c]carbazolesa
a
All the reactions were carried out in a pressure tube using 5.0 mL
ethanol, 1.0 equiv pyrrolocarbazole, 1.0 equiv acetonylacetone,
0.5 equiv p-TSA stirred at 80 ꢀC for 1 h.
Path a:
a
All the reactions were carried out in a pressure tube using 5.0 mL toluene,
1.0 equiv 3-aminocarbazoles, 2.0 equiv ethylene glycol, 3.0 equiv SnCl2$2H2O,
18 mol % RuCl3, 15 mol % dppe, 120 ꢀC.
Path b:
Scheme 2. Synthesis of various pyrrolo[2,3-c]carbazole derivatives.
Scheme 4. Possible mechanism for synthesis of 3a.
3. Conclusions
Fig. 2. ORTEP diagram of 3c.
In summary, we have developed a unique and direct approach
for constructing pyrrolo[2,3-c]carbazole and pyrrolo[3,2-b]carba-
zole in good yields using RuCl3/SnCl2 mediated system. The syn-
thesized pyrrolo[2,3-c]carbazoles easily converted into indolo
[2,3-c]carbazoles on reaction with acetonylacetone in good yields.
4. Experimental section
4.1. General information
Scheme 3. Synthesis of indolo[2,3-c]carbazoles.
Based on the mechanism proposed for the synthesis of indole
from aniline,11 the possible reaction pathways for the synthesis
of pyrrolocarbazole are shown in Scheme 4 with path a and path
b. In the first step RuCl3 oxidized the ethylene glycol (2) forming
the imine intermediate, and then SnCl2 reduces this imine into
IA, this IA is again oxidized by RuCl3 and gives rise to IIA.
Then in path a, after formation of IIA followed by the proton
exchange producing the IIIA. Elimination of water molecule gives
rise to the final product 3a.
All 1H, 13C NMR spectra were recorded on AV-400 spectrometer
operating at 400 and 100 MHz, respectively. Chemical shifts for 1H
NMR are expressed in parts per million (ppm) relative to tetra-
methylsilane (
expressed in parts per million relative to CDCl3
d
0.00 ppm). Chemical shifts for 13C NMR are
(d 77.0 ppm).
Multiplicities were indicated as follows s¼singlet, d¼doublet,
t¼triplet, q¼quartet, m¼multiplet, and coupling constants (Hz).
Chemical shifts of common trace 1H NMR impurities (CDCl3, ppm):
H2O, 1.56; EtOAc, 1.26, 2.05, 4.12; CH2Cl2, 5.30; CDCl3, 7.26. IR
spectra were recorded on FT/IR-5300 spectrometer; absorptions
are reported in cmꢁ1. Mass spectra were recorded on either using EI
technique or LCMS-2010A mass spectrometer. Elemental analyses
In path b, after the formation of IIA, one more 3-aminocarbazole
molecule (1a) reacts with IIA and gives rise to the IIIA, in the final
step removal of 1a produced the desired product 3a.

2456
M. Viji, R. Nagarajan / Tetrahedron 68 (2012) 2453e2458
(C, H, and N) were recorded on EA 1112 analyzer in School of
Chemistry, University of Hyderabad. Routine monitoring 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 iodine. Column chro-
matography was carried out employing neutral alumina. Com-
mercially available reagents and solvents were used without
further purification and were purchased. Melting points were
measured in open capillary tubes and are uncorrected.
formula C15H11N2Cl; C, 70.73; H, 4.35; N, 11.00%; found: C, 70.81; H,
4.26; N, 10.85%.
4.3.3. 7,9-Dichloro-6-methyl-3,6-dihydropyrrolo[2,3-c]carbazole
(3c). White colored solid; yield: 76%, mp: 142 ꢀC; IR (KBr): 3441,
3406, 2922, 1657, 1550, 1456, 1367, 1284, 1107, 844, 775, 731,
706 cmꢁ1; EtOAc/hexanes (3:7); Rf¼0.54; 1H NMR (400 MHz, TMS,
CDCl3):
d 8.40 (s, 1H), 8.066e8.061 (m, 1H), 7.54e7.52 (m, 1H),
7.37e7.36 (m, 1H), 7.33e7.32 (m, 1H), 7.24e7.22 (m, 1H), 7.00e6.99
(m, 1H), 4.21 (s, 3H); 13C NMR (100 MHz, TMS, CDCl3):
d
137.7, 133.8,
130.8, 126.5, 125.2, 124.7, 123.5, 120.8, 119.3, 116.1, 112.6, 111.4, 104.5,
100.8, 32.3; LCeMS: m/z¼287 (MꢁH)ꢁ, 289 (Mþ2) negative mode;
Anal. Calcd for molecular formula C15H10N2Cl2; C, 62.03; H, 3.49; N,
9.69%; found; C, 64.76; H, 5.38; N, 8.54%.
4.2. General procedure for the preparation of pyrrolo[2,3-c]
carbazole (3ael)
An oven dried 25 mL Ace pressure tube was charged with RuCl3
(18 mol %), dppe (15 mol %), and toluene (5 mL) along with N-alky-
lated-3-aminocarbazole 1ael (1.0 equiv), SnCl2 (3.0 equiv), and
ethylene glycol2 (2.0 equiv), andthen capped witha Teflonscrewcap
and the mixture was heated to 120 ꢀC and stirred for 8 h. After
completion of the reaction, followed by thin layer chromatography
(TLC), the mixture was cooled to room temperature, the solvent was
evaporated, and dissolved in EtOAc. The resulting solution was di-
rectly filtered through a pad of Celite and washed with EtOAc. The
combined organic layers were washed with water, dried over anhy-
drous Na2SO4, and then concentrated under reduced pressure to give
a crude product. The crude product was purified by column chro-
matography on neutral alumina using EtOAc/hexane as the eluent.
The solvent was evaporated to dryness to get the pure product 3ael.
4.3.4. 9-Bromo-6-ethyl-3,6-dihydropyrrolo[2,3-c]carbazole
(3d).
Brown colored viscous liquid; yield: 72%, IR (KBr): 3414, 2959,
2926, 2856, 2058, 1996, 1712, 1616, 1462, 1367, 1302, 1091, 794,
742 cmꢁ1; EtOAc/hexanes (3:7); Rf¼0.60; 1H NMR (400 MHz, TMS,
CDCl3): d 8.45 (s, 1H), 8.375e8.370 (m, 1H), 7.57e7.48 (m, 2H), 7.40
(s, 1H), 7.37e7.28 (m, 2H), 7.07 (s, 1H), 4.43 (q, 2H, J¼7.28 Hz), 1.43
(t, 3H, J¼7.24 Hz); 13C NMR (100 MHz, TMS, CDCl3):
d 137.6, 135.4,
130.6, 126.4, 124.7, 124.4, 123.7, 121.3, 112.8, 111.1, 110.6, 109.7, 104.3,
100.9, 37.9, 14.0; LCeMS: m/z¼315 (MþH)þ, 317 (Mþ2), positive
mode; Anal. Calcd for molecular formula C16H13N2Br; C, 61.36; H,
4.18; N, 8.94%; found: C, 61.28; H, 4.21; N, 8.86%.
4.3.5. 9-Chloro-6-ethyl-3,6-dihydropyrrolo[2,3-c]carbazole
(3e).
Brown colored viscous liquid; yield: 74%, IR (KBr): 3393, 2924, 2858,
4.3. General procedure for the preparation of indolo[2,3-c]
carbazole (5aec)
1736, 1622, 1462, 1302, 1259, 1099, 794 cmꢁ1; EtOAc/hexanes (3:7);
Rf¼0.51; 1H NMR (400 MHz, TMS, CDCl3):
d 8.40 (s, 1H), 8.23 (s, 1H),
7.57e7.55 (m, 1H), 7.40e7.38 (m, 3H), 7.31e7.29 (m, 1H), 7.08 (s, 1H),
An oven dried 25 mL Ace pressure tube was charged with pyrro-
locarbazole 3aec (1.0 equiv), acetonylacetone 4 (1.0 equiv), and p-
toluenesulfonic acid (p-TSA) (0.5 equiv) along with 5 mL of ethanol
then capped with a Teflon screw cap and the mixture was stirred at
80 ꢀC for 1 h. After completion of the reaction, followed by thin layer
chromatography (TLC), the mixture was cooled to room temperature,
the solvent was evaporated and dissolved in EtOAc. The resulting
organic layer was washed with water, dried over anhydrous Na2SO4,
and then concentrated under reduced pressure to give a crude
product. The crude product was purified by column chromatography
on neutral alumina using EtOAc/hexane as the eluent. The solvent
was evaporated to dryness to get the pure product 5aec.
4.43 (q, 2H, J¼7.2 Hz), 1.44 (t, 3H, J¼7.2 Hz); 13C NMR (100 MHz, TMS,
CDCl3): d137.3,135.5,131.8,131.1,130.5,128.8,124.4,123.8,121.3,120.7,
110.6, 109.2, 104.3, 100.8, 37.9, 14.0; LCeMS: m/z¼269 (MþH)þ, 270
(Mþ1) positive mode; Anal. Calcd for molecular formula C16H13N2Cl;
C, 71.51; H, 4.88; N, 10.42%; found: C, 71.65; H, 4.79; N, 10.36%.
4.3.6. 6-Butyl-3,6-dihydropyrrolo[2,3-c]carbazole (3f). Brown col-
ored viscous liquid; yield: 73%, IR (KBr): 3402, 3051, 2959, 2928,
2872, 1689, 1583, 1481, 1456, 1367, 1329, 1151, 1084, 1020, 881, 781,
748 cmꢁ1. EtOAc/hexanes (3:7); Rf¼0.68; 1H NMR (400 MHz, TMS,
CDCl3):
d
8.35 (s, 1H), 8.31 (d, 1H, J¼7.64 Hz), 7.54e7.43 (m, 3H),
7.39e7.37 (m, 1H), 7.34e7.29 (m, 2H), 7.13 (s, 1H), 4.40 (t, 2H,
J¼7.08 Hz), 1.93e1.88 (m, 2H), 1.47e1.39 (m, 2H), 0.95 (t, 3H,
4.3.1. 6-Ethyl-3,6-dihydropyrrolo[2,3-c]carbazole (3a). Brown col-
ored viscous liquid; yield: 73%; IR (KBr): 3408, 3051, 2968, 2928,
2858, 1707, 1587, 1477, 1450, 1375, 1331, 1228, 1180, 1151, 1087, 1020,
889, 781, 748 cmꢁ1; EtOAc/hexanes (3:7); Rf¼0.57; 1H NMR
J¼7.28 Hz); 13C NMR (100 MHz, TMS, CDCl3):
d 139.5, 135.4, 130.5,
124.1, 123.8, 123.7, 122.9, 121.4, 121.2, 118.2, 109.7, 108.5, 104.6, 101.0,
43.1, 31.4, 20.6, 13.9; LCeMS: m/z¼263 (MþH)þ, positive mode;
Anal. Calcd for molecular formula C18H18N2; C, 82.41; H, 6.92; N,
10.68%; found: C, 82.55; H, 6.81; N, 10.56%.
(400 MHz, TMS, CDCl3):
d 8.35e8.33 (m, 2H), 7.52e7.50 (m, 3H),
7.34e7.32 (m, 3H), 7.13 (s, 1H), 4.46 (q, 2H, J¼5.76 Hz), 1.46 (t, 3H,
J¼6.64 Hz); 13C NMR (100 MHz, TMS, CDCl3):
d
139.0, 134.9, 130.5,
4.3.7. 9-Bromo-6-butyl-3,6-dihydropyrrolo[2,3-c]carbazole
(3g).
124.2, 123.8, 123.1, 121.4, 121.3, 118.3, 113.6, 109.9, 108.3, 104.2,
100.8, 37.7, 14.3; LCeMS: m/z¼235 (MþH)þ, positive mode; Anal.
Calcd for molecular formula C16H14N2; C, 82.02; H, 6.02; N, 11.98%;
found: C, 82.15; H, 6.38; N, 11.86%.
Greenish colored viscous liquid; yield: 74%, IR (KBr): 3400, 2957,
2926, 2856, 1720, 1606, 1454, 1375, 1329, 1099, 1016, 794 cmꢁ1
.
EtOAc/hexanes (3:7); Rf¼0.63; 1H NMR (400 MHz, TMS, CDCl3):
d
8.74 (s, 1H), 8.22e8.18 (m, 2H), 7.52e7.49 (m, 3H), 7.45e7.43 (m,
1H), 7.31e7.27 (m, 1H), 4.36 (t, 2H, J¼7.12 Hz), 1.98e1.89 (m, 2H),
4.3.2. 9-Chloro-6-methyl-3,6-dihydropyrrolo[2,3-c]carbazole (3b).
White colored solid; yield: 71%, mp: 116 ꢀC; IR (KBr): 3427, 2924,
2854, 1714, 1456, 1361, 1290, 1062, 1014, 868, 788 cmꢁ1; EtOAc/
1.47e1.41 (m, 2H), 0.97 (t, 3H, J¼7.32 Hz); 13C NMR (100 MHz, TMS,
CDCl3):
d 138.1, 135.8, 130.5, 126.4, 124.5, 124.4, 123.6, 121.2, 112.6,
110.9, 110.5, 109.9, 104.5, 100.8, 43.2, 31.3, 20.5, 13.8; LCeMS: m/
z¼341 (MþH)þ, 343 (Mþ2), positive mode; Anal. Calcd for molec-
ular formula C18H17N2Br; C, 63.35; H, 5.02; N, 8.21%; found: C,
63.48; H, 4.91; N, 8.15%.
hexanes (3:7); Rf¼0.42; 1H NMR (400 MHz, TMS, CDCl3):
d 8.32 (s,
1H), 8.21e8.20 (m, 1H), 7.53e7.51 (m, 1H), 7.39e7.31 (m, 3H),
7.26e7.24 (m, 1H), 7.05 (s, 1H), 3.86 (s, 3H); 13C NMR (100 MHz,
TMS, CDCl3): d 138.4, 136.7, 130.6, 124.5, 123.95, 123.91, 123.8, 121.2,
120.6, 112.7, 110.6, 109.2, 104.3, 100.8, 29.5; LCeMS: m/z¼256
4.3.8. 6-Butyl-7,9-dichloro-3,6-dihydropyrrolo[2,3-c]carbazole
(3h). White colored solid; yield: 75%, mp: 138 ꢀC; IR (KBr): 3389,
(MþH)þ, 257 (Mþ1) positive mode; Anal. Calcd for molecular

M. Viji, R. Nagarajan / Tetrahedron 68 (2012) 2453e2458
2457
2961, 2926, 2856, 1620, 1554, 1469, 1371, 1296, 1109, 777, 734 cmꢁ1
;
(s, 3H), 2.61 (s, 3H), 1.51 (t, 3H, J¼7.2 Hz); 13C NMR (100 MHz, TMS,
EtOAc/hexanes (3:7); Rf¼0.66; 1H NMR (400 MHz, TMS, CDCl3):
CDCl3): d 139.6, 139.5, 135.9, 135.0, 131.0, 125.7, 125.0, 124.4, 123.4,
d
8.45 (s, 1H), 8.129e8.125 (m, 1H), 7.56 (d, 1H, J¼8.84 Hz),
123.2, 121.5, 117.1, 116.5, 116.1, 116.0, 109.3, 108.0, 107.3, 37.8, 23.4,
16.6,13.9; LCeMS: m/z¼313 (MþH)þ, positive mode; Anal. Calcd for
molecular formula C22H20N2; C, 84.58; H, 6.45; N, 8.97%; found: C,
84.46; H, 6.41; N, 9.07%.
7.39e7.38 (m, 2H), 7.30e7.26 (m, 1H), 7.04 (s, 1H), 4.73 (t, 2H,
J¼7.52 Hz), 1.91e1.83 (m, 2H), 1.47e1.40 (m, 2H), 0.96 (t, 3H,
J¼7.32 Hz); 13C NMR (100 MHz, TMS, CDCl3):
d 137.1, 133.1, 130.7,
126.8,125.3,124.7,123.5,120.9,119.3,115.9,112.7,111.4,104.8,100.8,
44.6, 33.0, 20.1, 13.9; LCeMS: m/z¼331 (MþH)þ, 333 (Mþ2), posi-
tive mode; Anal. Calcd for molecular formula C18H16N2Cl2; C, 65.27;
H, 4.87; N, 8.46%; found: C, 62.43; H, 3.55; N, 9.61%.
4.3.14. 11-Chloro-1,4,8-trimethyl-5,8-dihydroindolo[2,3-c]carbazole
(5b). Yellow colored solid; yield 78%, mp: 98 ꢀC; IR Neat: 3402,
2926, 2852, 1728, 1668, 1454, 1317, 1257, 1149, 1089, 1022,
794 cmꢁ1; EtOAc/hexanes (3:7); Rf¼0.64; 1H NMR (400 MHz, TMS,
4.3.9. 6-Methyl-3,6-dihydropyrrolo[2,3-c]carbazole (3i). Pale black
colored viscous liquid; yield: 74%, IR (KBr): 3393, 2920, 2851, 1699,
1647, 1539, 1450, 1242, 1018, 966 cmꢁ1; EtOAc/hexanes (3:7);
CDCl3):
d
8.38 (d, 1H, J¼1.72 Hz), 8.16 (s, 1H), 7.63e7.61 (m, 1H),
7.51e7.49 (m, 1H), 7.42e7.36 (m, 2H), 7.23 (d, 1H, J¼7.28 Hz),
7.11e7.09 (m, 1H), 3.93 (s, 3H), 2.98 (s, 3H), 2.60 (s, 3H); 13C NMR
Rf¼0.65; 1H NMR (400 MHz, TMS, CDCl3):
d
8.32 (s, 1H), 8.28 (d, 1H,
(100 MHz, DMSO-d6): d 139.9, 138.9, 137.4, 135.9, 129.2, 126.0, 124.3,
J¼7.72 Hz), 7.50e7.48 (m, 1H), 7.45e7.44 (m, 2H), 7.34 (s, 1H),
123.7, 123.0, 122.1, 121.9, 121.3, 117.3, 114.6, 113.9, 111.8, 110.8, 108.7,
29.9, 23.4, 17.1; LCeMS: m/z¼333 (MþH)þ, 335 (Mþ2) positive
mode; Anal. Calcd for molecular formula C21H17N2Cl; C, 75.78; H,
5.15; N, 8.42%; found: C, 75.86; H, 5.09; N, 8.37%.
7.29e7.27 (m, 2H), 7.09 (s, 1H), 3.90 (s, 3H); 13C NMR (100 MHz, TMS,
CDCl3):
d 140.1, 136.0, 130.6, 124.2, 123.9, 122.9, 121.4, 121.2, 118.4,
113.5, 109.8, 108.3, 104.3, 100.9, 29.4; LCeMS: m/z¼221 (MþH)þ,
positive mode; Anal. Calcd for molecular formula C15H12N2; C, 81.79;
H, 5.49; N, 12.72%; found: C, 81.68; H, 5.56; N, 12.65%.
4.3.15. 9,11-Dichloro-1,4,8-trimethyl-5,8-dihydroindolo[2,3-c]carba-
zole (5c). Yellow colored solid; yield 80%, mp: 132 ꢀC; IR Neat:
3433, 2924, 2854, 1722, 1651, 1456, 1315, 1261, 1105, 1074,
1028 cmꢁ1; EtOAc/hexanes (3:7); Rf¼0.70; 1H NMR (400 MHz, TMS,
4.3.10. 6-Benzyl-3,6-dihydropyrrolo[2,3-c]carbazole (3j). Black col-
ored viscous liquid; yield: 73%, IR (KBr): 3354, 3061, 2916, 2858,
1959, 1907, 1819, 1685, 1614, 1579, 1494, 1448, 1359, 1263, 1205,
1165, 1120, 1076, 1018, 908, 823, 752, 700 cmꢁ1; EtOAc/hexanes
CDCl3): d 8.24 (s, 1H), 8.20 (s, 1H), 7.67e7.65 (m, 1H), 7.54e7.52 (m,
1H), 7.38 (s, 1H), 7.23 (s, 1H), 7.10 (d, 1H, J¼7.4 Hz), 4.34 (s, 3H), 2.88
(3:7); Rf¼0.60; 1H NMR (400 MHz, TMS, CDCl3):
d
8.37 (s, 1H), 8.34
(s, 3H), 2.60 (s, 3H); 13C NMR (100 MHz, TMS, CDCl3):
d
139.6, 138.5,
(d, 1H, J¼7.72 Hz), 7.48e7.46 (m, 1H), 7.44e7.43 (m, 2H), 7.40e7.39
(m, 1H), 7.26 (s, 1H), 7.24e7.22 (m, 3H), 7.15e7.12 (m, 4H), 5.62 (s,
135.3, 134.4, 130.5, 126.8, 126.2, 125.8, 122.8, 122.7, 122.3, 122.0,
116.3, 115.8, 115.7, 115.0, 110.9, 107.7, 32.5, 23.4, 16.6; LCeMS: m/
z¼365 (MꢁH)ꢁ, 367 (Mþ2) negative mode; Anal. Calcd for mo-
lecular formula C21H16N2Cl2; C, 68.68; H, 4.39; N, 7.63%; found: C,
68.56; H, 4.45; N, 7.58%.
2H); 13C NMR (100 MHz, TMS, CDCl3):
d 139.8, 137.7, 135.6, 130.7,
128.79, 128.70, 127.2, 126.3, 124.3, 124.2, 123.2, 121.4, 121.3, 118.8,
110.0, 108.7, 104.7, 101.0, 46.7; LCeMS: m/z¼297 (MþH)þ, positive
mode; Anal. Calcd for molecular formula C21H16N2; C, 85.11; H,
5.44; N, 9.45%; found; C, 85.06; H, 5.48; N, 9.56%.
Acknowledgements
4.3.11. 6-Ethyl-9-methyl-3,6-dihydropyrrolo[2,3-c]carbazole
(3k). Pale white colored solid; yield: 71%, mp: 48 ꢀC; IR (KBr): 3443,
2924, 2856, 1651, 1456, 1371, 1294, 1244, 1143, 1018 cmꢁ1. EtOAc/
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. thanks CSIR for a senior
research fellowship. M.V. also thanks Nagarjuna Reddy, Anand,
Bharat, Naba for helping in crystal studies.
hexanes (3:7); Rf¼0.60; 1H NMR (400 MHz, TMS, CDCl3):
d 8.24 (s,
1H), 8.06 (s, 1H), 7.45e7.42 (m, 1H), 7.35e7.33 (m, 1H), 7.30e7.24
(m, 3H), 7.09e7.08 (m, 1H), 4.39 (q, 2H, J¼7.2 Hz), 2.59 (s, 3H), 1.39
(t, 3H, J¼7.2 Hz); 13C NMR (100 MHz, TMS, CDCl3):
d 137.4, 135.1,
Supplementary data
130.4, 127.5, 125.3, 124.0, 123.3, 121.5, 121.3, 113.4, 109.6, 108.0,
104.3, 100.9, 37.8, 21.5, 14.1; LCeMS: m/z¼247 (MꢁH)ꢁ, negative
mode; Anal. Calcd for molecular formula C17H16N2; C, 82.22; H,
6.49; N, 11.28%; found: C, 82.13; H, 6.51; N, 11.36%.
Spectroscopic data, LCeMS, and elemental analysis for all new
compounds. Supplementary data related to this article can be found
online at doi:10.1016/j.tet.2012.01.070.
4.3.12. 5-Ethyl-4,10-dimethyl-1,5-dihydropyrrolo[3,2-b]carbazole
(3l). Pale black colored viscous liquid; yield: 72%, IR (KBr): 3400,
2922, 2852, 2368, 1712,1647,1458,1093,1016 cmꢁ1; EtOAc/hexanes
References and notes
(3:7); Rf¼0.70; 1H NMR (400 MHz, TMS, CDCl3):
d 8.24 (d, 1H,
€
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1H, J¼2.64 Hz), 7.21e7.17 (m, 1H), 6.719e6.715 (m, 1H), 4.63 (q, 2H,
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d 142.5, 134.9, 131.1, 128.6, 124.8, 124.58,
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2926, 2849, 1651, 1275, 1103, 1022, 750 cmꢁ1; EtOAc/hexanes (3:7);
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8.45 (d, 1H, J¼8.04 Hz),
d
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7.25e7.21 (m, 2H), 7.04 (d, 1H, J¼6.9 Hz), 4.51 (q, 2H, J¼6.4 Hz), 3.00

2458
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10. The CCDC deposition number for compound 3c is 841557; molecular formula:
C15H10Cl2N2. chemical formula weight is 289.15; monoclinic; unit cell param-
ꢁ
ꢁ
ꢁ
a
eters: a¼9.274(2) A, b¼5.6445(9) A, c¼24.572(4) A,
¼90ꢀ,
b
¼95.794(17)ꢀ,
g
¼90ꢀ. Space group P21/n.
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