Facile synthesis of novel indolo[3,2-b]carbazole derivatives and a chromogenic-sensing 5,12-dihydroindolo[3,2-b]carbazole

Article abstract of DOI:10.1039/b807255h

Novel indolo[3,2-b]carbazole derivatives and a chromogenic-sensing 5,12-dihydroindolo[3,2-b]carbazole have been synthesized starting from tetra-tert-butylated 6,12-diaryl-5,11-dihydroindolo[3,2-b]carbazoles, which were prepared via an efficient tert-butylation of 6,12-diaryl-5,11-dihydroindolo[3, 2-b]carbazoles. The Royal Society of Chemistry 2008.

Full text of DOI:10.1039/b807255h

View Article Online / Journal Homepage / Table of Contents for this issue
COMMUNICATION
www.rsc.org/obc | Organic & Biomolecular Chemistry
Facile synthesis of novel indolo[3,2-b]carbazole derivatives and a
chromogenic-sensing 5,12-dihydroindolo[3,2-b]carbazole†
Rong Gu, Koen Robeyns, Luc Van Meervelt, Suzanne Toppet and Wim Dehaen*
Received 29th April 2008, Accepted 29th May 2008
First published as an Advance Article on the web 10th June 2008
DOI: 10.1039/b807255h
Novel indolo[3,2-b]carbazole derivatives and a chromogenic-
sensing 5,12-dihydroindolo[3,2-b]carbazole have been synthe-
sized starting from tetra-tert-butylated 6,12-diaryl-5,11-
dihydroindolo[3,2-b]carbazoles, which were prepared via an
efficient tert-butylation of 6,12-diaryl-5,11-dihydroindolo-
[3,2-b]carbazoles.
In this communication, we disclose a facile method to prepare
indolo[3,2-b]carbazole derivatives in good yields based on tert-
butylated ICZs which show an increased solubility in organic
solvents. Moreover, a novel 5,12-dihydroindolo[3,2-b]carbazole
was synthesized for the first time and this ICZ derivative can act
as a selective colorimetric sensor either for F− or Brønsted acids
in aprotic solvents.
In our previous work,8 we reported a three-stage one pot
approach to synthesize 6-monosubstituted ICZs which have better
solubility in organic solvents. Thus, we tried to prepare indolo[3,2-
b]carbazoles starting from 6-pentyl-5,11-dihydroindolo[3,2-b]-
carbazole 3a. In 2000, Yudina et al. showed that 5,11-dihydro-
indolo[3,2-b]carbazole can be oxidized to indolo[3,2-b]carbazole 2
with DDQ in a large volume of ethyl acetate (30 mg ICZ in 200 mL
ethyl acetate).7b Under the same conditions, we treated 6-pentyl-
5,11-dihydroindolo[3,2-b]carbazole 3a with 2 equivalents DDQ in
ethyl acetate under reflux. After 5 hours, much longer than the
described reaction time, we did not observe the corresponding
indolo[3,2-b]carbazole formed, and only the starting materials
were present in the reaction solution. As reported by Horner et al.
in 1982, the deprotonated 5,11-dihydro ICZs are a two-step redox
system, in which the three oxidation levels are separated by the
redox potentials E1 and E2 (Fig. 2).9 Apparently, SEM state is
the intermediate for the preparation of indolo[3,2-b]carbazoles,
which is the OX state in the redox process. Moreover, the
final OX state has partial biradical character, which may lead
to decomposition via coupling reactions. We have previously
observed such C–C and C–N coupling reactions on treating ICZ
derivatives with oxidants.10 It has been reported that a stable
radical compound was successfully prepared from 1,3,6,8-tetra-
tert-butyl-9H-carbazole.11 Thus, the tert-butyl group can stabilize
the indolo[3,2-b]carbazoles. Furthermore, tert-butyl groups can
improve the solubility of ICZs in organic solvents. We have applied
the same method to increase the yield of Ullmann coupling
reactions with 3,6-di-tert-butylcarbazole.12
5,11-Dihydroindolo[3,2-b]carbazole (ICZ) 1a (Fig. 1) is formed in
acidic medium as a condensation product of indole-3-carbinol,
which originates from cruciferous vegetables. It has been reported
that the ICZ is a natural agonist of the TCDD (2,3,7,8-tetra-
chlorodibenzo-p-dioxin) receptor (Ah receptor)1 and 6-formyl-
indolo[3,2-b]carbazole 1b has indeed an extremely strong affinity
to the Ah receptor, binding 5–8 times as strong to the receptor as
TCDD itself.2 Since the last decade, the electrical and optical prop-
erties of ICZs have been widely studied. 5,11-Dihydroindolo[3,2-
b]carbazoles and polyindolo[3,2-b]carbazoles can be used as active
materials for organic light-emitting diodes,3 organic field-effect
transistors,4 organic thin-film transistors5 and photovoltaic cells.6
Two-step redox processes of ICZ have been studied and the first
indolo[3,2-b]carbazole derivative 2 was prepared by the oxidation
of 5,11-dihydroindolo[3,2-b]carbazole 1a with PbO2 or DDQ.7
Until now, only one such indolo[3,2-b]carbazole derivative has
been reported, mainly because of poor solubility in organic
solvents and lack of chemical stability.
Fig. 1
First we studied the tert-butylation of 6-pentyl-5,11-
dihydroindolo[3,2-b]carbazole 3a. AlCl3 or ZnCl2 were used as a
Lewis acid and chloroform or nitromethane were used as solvents
for Friedel–Crafts tert-butylation. It turned out that ZnCl2 and
chloroform were the best combination for the tert-butylation.
The reaction of compound 3a with excess ZnCl2 and tert-butyl
Department of Chemistry, University of Leuven, Celestijnenlaan
200F, B-3001, Leuven, Belgium. E-mail: wim.dehaen@chem.kuleuven.be;
Fax: +32(16)327990;; Tel: +32(16)327439
† Electronic supplementary information (ESI) available: Details for the
synthesis and characterization of compounds and X-ray crystallography
of compound 4a and 5b. See DOI: 10.1039/b807255h
Fig. 2 Two-step redox process of deprotonated ICZs.
2484 | Org. Biomol. Chem., 2008, 6, 2484–2487 This journal is
The Royal Society of Chemistry 2008
©

View Article Online
chloride (5 equivalents) mainly afforded the tetra-tert-butylated
6-pentyl ICZ 4a in 77% yield (Scheme 1). Even when we treated
6-pentyl ICZ with large excesses (10 equivalents) of ZnCl2 and
tert-butyl chloride, we only obtained the tetra-substituted ICZ
with a trace amount of tri- and di-substituted ICZ and none of
the penta-substituted or more complex ICZs. From the X-ray
crystallography of compound 4a, we can confirm that the tert-
butyl groups were indeed at the 2,4,8,10-positions of the ICZ ring
(Fig. 3).‡
as the reaction with DDQ. Interestingly, we found the oxidation
reagent DDQ is not necessary for the preparation of indolo[3,2-
b]carbazoles. When we treated compound 4b only with 4 equiv-
alents of t-BuOK at −40 C, most of the 5,11-dihydro ICZ was
◦
oxidized to the indolo[3,2-b]carbazole after 4 hours (monitored
by TLC) and we isolated compound 5b in 50% yield. Keeping the
reaction going for a longer time did not help the conversion of
all of the starting material to the desired product. Later we found
that t-BuLi was a more efficient base for the preparation of the
oxidized ICZs 5b–c. We treated compound 4b with 4 equivalents
of t-BuLi in dry THF at 0 ◦C and then the reaction solution was
stirred at room temperature for 4 hours to afford 2,4,8,10-tetra-
tert-butyl-6,12-diphenyl-indolo[3,2-b]carbazole 5b in 73% yield
(Scheme 2). From the structure determination of compound 5b
(Fig. 4), the bond lengths confirmed the formation of the 1,4-
quinonediimine structure. There was no stable analogue of 5
formed when we treated compound 4a and 6,12-diphenyl-5,11-
dihydroindolo[3,2-b]carbazole 3b, which are insufficiently shielded
for coupling reactions, with the same method.
Scheme 1 tert-Butylation of ICZs.
Scheme 2 Synthesis of indolo[3,2-b]carbazole derivatives.
Fig. 3 ORTEP representation of 4a with thermal displacement ellipsoids
shown at the 50% probability level.‡
Recently, we have reported a two-step method to prepare
6,12-diaryl-5,11-dihydroindolo[3,2-b]carbazoles 3b–c in moderate
yields.13 These symmetrical molecules are slightly soluble in
chloroform. However, the tert-butylation leading to ICZs 4b–c was
successfully accomplished in good yields (47–66%). Compounds
4b–c were only slightly soluble in polar solvents, such as ethyl
acetate or methanol. This allowed an easy purification of the
compounds 4b–c, simply by dispersing the crude product in ethyl
acetate or methanol and then filtering the pure products. On
the other hand, these tert-butylated 6,12-diaryl ICZs have good
solubility in less polar organic solvents such as chloroform and
dichloromethane. Therefore, 2,4,8,10-tetra-tert-butyl-6,12-diaryl-
5,11-dihydroindolo[3,2-b]carbazoles are good candidates for our
preparation of indolo[3,2-b]carbazole derivatives.
When we treated compound 4b with 2 equivalents of DDQ
in dry THF at room temperature or 70 ◦C, we found that only
part of the starting material converted to the oxidized product 5b.
When compound 4b was deprotonated with 2 equivalents of t-
BuOK in dry THF at 0 ◦C and then oxidized with 2 equivalents of
DDQ at room temperature or 70 ◦C, the same result was observed
Fig. 4 ORTEP representation of 5b with thermal displacement ellipsoids
shown at the 50% probability level.‡
After we used n-BuLi as a base during the optimization of
the reaction condition of the synthesis of compound 5b, we
isolated an orange compound with MS (ESI) m/z 689 ([M +
H]+). The structure of this compound was assigned as a novel
5,12-dihydroindolo[3,2-b]carbazole based on 1D and 2D NMR
spectra. The reasonable mechanism was that the deprotonated
ICZ was oxidized by oxygen to indolo[3,2-b]carbazole, and
then the Michael addition of n-BuLi to the formed indolo[3,2-
b]carbazole occurred. To test our hypothesis, we treated compound
This journal is
The Royal Society of Chemistry 2008
Org. Biomol. Chem., 2008, 6, 2484–2487 | 2485
©

View Article Online
5b with 1 equivalent of n-BuLi in the dark. The 5,12-dihydro
ICZ was formed after 4 hours at room temperature. In our
optimized reaction conditions, we first treated compound 4b with
2 equivalents of n-BuLi at −76 ◦C in the dark for 20 minutes,
then 1 equivalent of n-BuLi was added at the same temperature.
After 20 minutes, the reaction was stopped by the addition of
H2O. Thus, we prepared 5,12-dihydroindolo[3,2-b]carbazole 6 in
64% yield (Scheme 3).
Fig. 6 UV–Vis spectra of compound 6 in MeCN (5.0 × 10−5M) after the
addition of 25 equivalents of various anions and Brønsted acids (none,
AcO−, HSO4−, F−, AcOH, CF3COOH).
Scheme 3 Synthesis of 5,12-dihydro ICZ.
It has been demonstrated that 3,3ꢀ-bis(indolyl)methene 7 (Fig. 5)
can act as a selective colorimetric sensor either for F− in aprotic
−
solvent or for HSO4 and weak acidic species in a water-
containing medium.14 The 5,12-dihydro ICZ 6, which contains
a 2,3-bis(indolyl)methene moiety with an acidic H-bond donor
–NH and a basic H-bond acceptor nitrogen, has some similarity
with compound 7.
Fig. 5 3,3ꢀ-Bis(indolyl)methene 7.
In the aprotic solvent, acetonitrile, we observed a significant
color change of compound 6 from yellow to blue after the addition
of 25 equivalents of F−. A similar, but more remarkable spectral
change was observed upon the addition of a Brønsted acid, such as
acetic acid and trifluoroacetic acid. There was no noticeable color
Fig. 7 UV–Vis spectra of compound 6 (5.0 × 10−5M) in MeCN after the
addition of 1, 2, 3, 4, 6, 8, 10 equivalents of CF3COOH.
change on addition of AcO− and HSO4 anions (Fig. 6). A dra-
−
first time, which can act as a selective chemosensor in aprotic
solvents, either for F− or Brønsted acids.
matic color change was caused by the deprotonation/protonation
of indolyl moieties. The band at 480 nm of the starting solution
was red-shifted to 554 nm in the presence of F− and to 595 nm on
addition of acetic acid or trifluoroacetic acid, while the intensity
of the red-shifted band remarkably increased in the presence of the
stronger Brønsted acid, CF3COOH. The titration of compound 6
with trifluoroacetic acid showed three isosbestic points at 297 nm,
343 nm and 517 nm and in the presence of 10 equivalents of
CF3COOH, the band at 595 nm almost reached the maximum
(Fig. 7).
Acknowledgements
The authors thank the Research Fund of the K. U. Leuven,
the FWO and the Ministerie voor Wetenschapsbeleid for their
continuing support.
Notes and references
In summary, the Friedel–Crafts tert-butylation of 6-pentyl
and 6,12-diaryl-5,11-dihydroindolo[3,2-b]carbazoles has been ac-
complished by using ZnCl2 as a Lewis acid and chloroform
as a solvent in moderate to good yields. Novel indolo[3,2-
b]carbazole derivatives 5b–c have been successfully synthesized
based on the tert-butylated 6,12-diaryl ICZs. Meanwhile, a 5,12-
dihydroindolo[3,2-b]carbazole derivative 6 was prepared for the
‡ CCDC reference numbers 686527 and 686528. For crystallographic data
in CIF or other electronic format see DOI: 10.1039/b807255h
1 (a) M. Gillner, J. Bergman, C. Cambillau, B. Fernstrom and J. A.
Gustafsson, Mol. Pharmacol., 1985, 28, 357; (b) U. Rannug, E. Agurell,
A. Rannug and H. Cederberg, Environ. Mol. Mutagen., 1992, 20,
289; (c) M. Gillner, J. Bergman, C. Cambillau, M. Alexandersson, B.
Fernstrom and J. A. Gustafsson, Mol. Pharmacol., 1993, 44, 336; (d) H.
2486 | Org. Biomol. Chem., 2008, 6, 2484–2487
This journal is
The Royal Society of Chemistry 2008
©

View Article Online
Liu, M. Wormke, S. H. Safe and L. F. Bjeldanes, J. Natl. Cancer Inst.,
1994, 86, 1758.
7 (a) S. Hu¨nig and H. C. Steinmetzer, Justus Liebigs Ann. Chem., 1976,
1090; (b) L. N. Yudina, M. N. Preobrazhenskaya and A. M. Korolev,
Chem. Heterocycl. Compd., 2000, 36, 1112.
8 (a) R. Gu, A. Hameurlaine and W. Dehaen, Synlett, 2006, 10, 1535;
(b) R. Gu, A. Hameurlaine and W. Dehaen, J. Org. Chem., 2007, 72,
7207.
9 M. Horner, S. Hu¨nig and H. Pu¨tter, Electrochim. Acta, 1982, 27, 205.
10 R. Gu, K. Van Hecke, L. Van Meervelt, S. Toppet and W. Dehaen, Org.
Biomol. Chem., 2006, 4, 3785.
2 J. Tholander and J. Bergman, Tetrahedron, 1999, 55, 6243.
3 (a) H. X. Hu, S. Xie, Z. Popovic, B. Ong and A. M. Hor, J. Am. Chem.
Soc., 1999, 121, 5097; (b) H. P. Zhao, X. T. Tao, P. Wang, Y. Ren, J. X.
Yang, Y. X. Yuan, C. X. Yuan, H. J. Liu and D. C. Zhou, Org. Electron.,
2007, 8, 673; (c) H. P. Zhao, X. T. Tao, F. Z. Wang, Y. Ren, X. Q. Sun,
J. X. Yang, Y. X. Yan, D. C. Zou, X. Zhao and M. H. Jiang, Chem.
Phys. Lett., 2007, 439, 132.
4 S. Wakim, J. Bouchard, M. Simard, N. Drolet, Y. Tao and M. Leclerc,
Chem. Mater., 2004, 16, 4386.
5 (a) Y. L. Wu, Y. N. Li, S. Gardner and B. S. Ong, J. Am. Chem. Soc.,
2005, 127, 614; (b) Y. N. Li, Y. L. Wu, S. Gardner and B. S. Ong,
Adv. Mater., 2005, 17, 849; (c) Y. N. Li, Y. L. Wu and B. S. Ong,
Macromolecules, 2006, 39, 6521.
6 (a) N. Blouin, A. Michaud, S. Wakim, P. L. T. Boudreault, M. Leclerc,
B. Vercelli, S. Zecchin and G. Zotti, Macromol. Chem. Phys., 2006, 207,
166; (b) N. Blouin, M. Leclerc, B. Vercelli, S. Zecchin and G. Zotti,
Macromol. Chem. Phys., 2006, 207, 175.
11 F. A. Neugebauer, H. Fischer, S. Bamberger and H. O. Smith, Chem.
Ber., 1972, 105, 2694.
12 (a) A. Hameurlaine and W. Dehaen, Tetrahedron Lett., 2003, 44, 957;
(b) N. D. McClenaghan, R. Passalacqua, F. Loiseau, S. Campagna,
B. Verheyde, A. Hameurlaine and W. Dehaen, J. Am. Chem. Soc.,
2003, 125, 5356; (c) F. Loiseau, S. Campagna, A. Hameurlaine and W.
Dehaen, J. Am. Chem. Soc., 2005, 127, 11352.
13 R. Gu, K. Ahmad and W. Dehaen, unpublished results.
14 X. M. He, S. Z. Hu, K. Liu, Y. Guo, J. Xu and S. J. Shao, Org. Lett.,
2006, 8, 333.
This journal is
The Royal Society of Chemistry 2008
Org. Biomol. Chem., 2008, 6, 2484–2487 | 2487
©