A tandem route to the synthesis of carbazolo[1,2-b]carbazoles

Article abstract of DOI:10.1055/s-0030-1289514

A simple and facile synthesis of carbazolo[1,2-b]carbazole derivatives via Michael addition of 2-methylindole, condensation of methyl group with the carbonyl, dehydration followed by aromatization by heating in hydrothermal oven is reported. Georg Thieme

Full text of DOI:10.1055/s-0030-1289514

LETTER
2559
A Tandem Route to the Synthesis of Carbazolo[1,2-b]carbazoles
S
ynthesisof Ca
.
rbazolo[1,2-
K
b
]carbazoles rishna Chaitanya, Rajagopal Nagarajan*
School of Chemistry, University of Hyderabad, Hyderabad 500046, India
Fax +91(40)23012460; E-mail: rnsc@uohyd.ernet.in
Received 25 June 2011
lo[3,2-b]carbazoles in lower yields.10 In this context, de-
velopment of an efficient methodology for the synthesis
of these derivatives is highly desirable.
Abstract: A simple and facile synthesis of carbazolo[1,2-b]carba-
zole derivatives via Michael addition of 2-methylindole, condensa-
tion of methyl group with the carbonyl, dehydration followed by
aromatization by heating in hydrothermal oven is reported.
Synthesis of heterocycles employing tandem reactions is
Key words: carbazolocarbazoles, tandem cyclization, tetrahydro- one of the most economical and desirable synthetic strat-
egies.11 Tandem processes are well explored in the litera-
carbazole, carbazole, p-donor complexes
ture and development of new tandem processes is of
continuous synthetic interest. In continuation of our inter-
est in the development of efficient methodologies for new
heteroarylcarbazole derivatives,12 we wish to report here
a simple and efficient route for the synthesis of carbazo-
lo[1,2-b]carbazole derivatives.
Carbazole derivatives have been attracting increasing in-
terest of synthetic chemists for many years.1 A broad
range of carbazole alkaloids with interesting structural
motifs and useful biological applications such as pyri-
docarbazoles,2 pyranocarbazoles,3 furocarbazoles,4 in-
dolocarbazoles, benzocarbazoles, etc.,5 which have a
heteroarylcarbazole skeleton, have been isolated from di-
verse natural sources. This initiated the development of
many novel and efficient synthetic methods for these het-
eroarylcarbazole derivatives.
We envisioned that 2-alkylindoles on condensation with
the chalcones of 1-ketotetrahydrocarbazole followed by
aromatization can provide the desired products. We em-
ployed various solvent systems like water, DMF, DMSO;
but we found negligible conversion of starting materials.
When we conducted the reaction in acetic acid, we were
successful in obtaining the products in moderate yields
(Scheme 1). The role of the acid is explained in the mech-
anism. Aryl chalcones of 1-ketotetrahydrocarbazole13 on
reacting with 2-methylindole in the presence of palladium
charcoal in acetic acid upon heating at 180 °C in a hydro-
thermal oven for 48 hours provided the carbazolo[1,2-
b]carbazole derivatives in moderate yields.14 When we
carried out the reaction without Pd/C, product formation
was not observed.
H
N
HN
NH
N
H
carbazolo[3,4-c]carbazole
carbazolo[2,1-a]carbazole
Figure 1 Carbazolocarbazoles
Ar
Carbazolocarbazoles are a new class of heteroarylcarba-
zoles where a carbazole is fused with another carbazole at
various positions. These molecules are little explored, and
very few reports are available in the literature, though they
are reported to form stronger p-donor complexes.6 Carba-
zolo[3,4-c]carbazole and tetranitro fluorenone are report-
ed to form a strong electron-donor–acceptor complex
(EDA complex).7 The synthesis of carbazolocarbazoles is
less explored and very few reports are available for the
synthesis. Zander et al. have reported the synthesis of car-
bazolo[3,4-c]carbazoles and carbazolo[2,1-a]carbazoles
from dinaphthols, phenyl hydrazine, and sodium bisulfite
(Figure 1).8 A series of carbazolo[2,1-a]carbazoles were
prepared from Fischer indole synthesis of 4-oxo-1,2,3,4-
tetrahydrobenzocarbazole derivatives by Kirsch et al.9
Haider and coworkers reported the synthesis of carbazo-
Ar
2-methylindole
N
N
Pd/C, AcOH
3 Å MS
180 °C, 48 h
35–47%
H
HN
O
H
3a–g
1a–g
Scheme 1 Synthesis of carbazolo[1,2-b]carbazoles
The products are well characterized by NMR spectrosco-
py. In the 1H NMR spectra, the absence of peaks in the al-
iphatic region and two singlets around d = 12 and 11 ppm,
which correspond to the two NH protons clearly indicate
the formation of desired products. A sharp singlet at d =
8.5 ppm corresponds to the CH at 1-position, indicating
the complete aromatization of the product. Electron-with-
drawing substituents on the aryl ring of chalcones gave
better yields. When we carried out the reactions with 4-
cyano and 4-nitro aldehydes, we obtained a complex mix-
ture of products. Reaction with 2-benzylindole employing
SYNLETT 2011, No. 17, pp 2559–2561
x
x
.x
x
.2
0
1
1
Advanced online publication: 06.10.2011
DOI: 10.1055/s-0030-1289514; Art ID: B11911ST
© Georg Thieme Verlag Stuttgart · New York

2560
T. K. Chaitanya, R. Nagarajan
LETTER
Ar
HN
N
N
Ar
H
O
H
Ar
HO
O
N
H
HN
H
HN
Ar
Pd/C
3 Å MS
– H2O
N
HN
H
HN
HO
Ar
H
H
HN
Ar
HN
HN
Scheme 2 Proposed mechanism for carbazolocarbazoles
similar conditions did not yield the product and starting
materials were recovered.
The possible mechanism for this tandem process is ex-
plained in Scheme 2. 2-Methylindole acts as a nucleophile
to attack in Michael fashion on chalcone to give the addi-
tion product. In the presence of acid, the equilibrium of
iminium intermediates of indole followed by aldol con-
densation of one of the intermediate enamine occurs.
Elimination of a water molecule gives the tetrahydrocar-
bazole derivative, which undergoes aromatization in the
presence of Pd/C to furnish the desired carbazolo[1,2-
b]carbazole (Figure 2). The presence and position of sub-
stituent on aryl ring seems to have no effect on the reac-
tion. All the substituents provided products in similar
yields.
N
N
H
H
N
N
H
H
3a 43%
3b 40%
Cl
F
N
N
H
H
N
N
H
H
In conclusion, we report here a simple and facile synthesis
of carbazolo[1,2-b]carbazole derivatives via Michael ad-
dition of 2-methylindole, condensation of the methyl
group with the carbonyl, and elimination of a water mole-
cule followed by aromatization. This tandem process is
noteworthy as it involves easily accessible starting mate-
rials and provides carbazolocarbazoles in moderate
yields.
3c 47%
3d 40%
Br
OMe
N
N
H
H
N
N
H
H
3e 42%
3f 39%
Supporting Information for this article is available online at
http://www.thieme-connect.com/ejournals/toc/synlett.
N
Acknowledgment
N
We acknowledge DST for financial assistance (Project number:
SR/S1/OC-70/2008) and for providing single-crystal X-ray diffrac-
tometer facility in our school. TKC thanks CSIR for Senior Re-
search Fellowship.
H
N
H
3g 35%
Figure 2 Carbazolo[1,2-b]carbazoles
Synlett 2011, No. 17, 2559–2561 © Thieme Stuttgart · New York

LETTER
Synthesis of Carbazolo[1,2-b]carbazoles
2561
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9-Phenyl-2,14-dihydrocarbazolo[1,2-b]carbazole
Yield 43%; mp 176–178 °C. IR (KBr): nmax = 3412, 1602,
1466, 1317, 740, 694 cm–1. 1H NMR (400 MHz, DMSO-d6):
d = 11.66 (s, 1 H), 10.82 (s, 1 H), 8.50 (s, 1 H), 8.01 (d,
J = 8.0 Hz, 1 H), 7.81 (d, J = 8.0 Hz, 1 H), 7.56–7.64 (m, 4
H), 7.49 (d, J = 7.6 Hz, 2 H), 7.27–7.42 (m, 4 H), 7.17 (t,
J = 7.6 Hz, 1 H), 6.76–6.83 (m, 2 H). 13C NMR (100 MHz,
DMSO-d6): d = 142.8, 139.2, 139.1, 138.6, 135.6, 133.2,
133.0, 132.2, 129.7, 127.2, 125.2, 124.6, 123.9, 122.6,
122.2, 122.1, 121.2, 120.0, 119.5, 118.9, 117.5, 116.7,
116.4, 111.8, 111.1, 100.6. MS (pos. Mode): m/z = 382.
Anal. Calcd (%) for C28H18N2: C, 87.93; H, 4.74; N, 7.32.
Found: C, 87.85; H, 4.81; N, 7.26.
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