Synthesis of novel 2,8-disubstituted indolo[3,2-b]carbazoles

Article abstract of DOI:10.1039/c1ob06298k

A new synthetic pathway towards 2,8-difunctionalised indolo[3,2-b] carbazoles was investigated. The presented method offers a short and high yielding route towards 2,8-dibromo-5,11-dihexyl-6,12-diphenyl-indolo[3,2-b] carbazole. It is demonstrated that the latter compound is a versatile building block, enabling the synthesis of a number of previously unreported 5,11-dialkyl-6,12-diphenyl-indolo[3,2-b]carbazoles in moderate to good yields, using Suzuki and Sonogashira cross-coupling reaction. Furthermore it is shown that 2,8-dibromo-5,11-dihexyl-6,12-diphenyl-indolo[3,2-b]carbazole can be easily formylated, giving rise to the 2,8-diformyl-5,11-dihexyl-6,12-diphenyl-indolo- [3,2-b]carbazole. The latter compound was successfully subjected to condensation reactions.

Full text of DOI:10.1039/c1ob06298k

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Synthesis of novel 2,8-disubstituted indolo[3,2-b]carbazoles†
Sven Van Snick and Wim Dehaen*
Received 29th July 2011, Accepted 31st August 2011
DOI: 10.1039/c1ob06298k
A new synthetic pathway towards 2,8-difunctionalised indolo[3,2-b]carbazoles was investigated. The
presented method offers a short and high yielding route towards 2,8-dibromo-5,11-dihexyl-6,12-
diphenyl-indolo[3,2-b]carbazole. It is demonstrated that the latter compound is a versatile building
block, enabling the synthesis of a number of previously unreported 5,11-dialkyl-6,12-diphenyl-
indolo[3,2-b]carbazoles in moderate to good yields, using Suzuki and Sonogashira cross-coupling
reaction. Furthermore it is shown that 2,8-dibromo-5,11-dihexyl-6,12-diphenyl-indolo[3,2-b]carbazole
can be easily formylated, giving rise to the 2,8-diformyl-5,11-dihexyl-6,12-diphenyl-indolo-
[3,2-b]carbazole. The latter compound was successfully subjected to condensation reactions.
Even though many pathways towards indolo[3,2-b]carbazole
Introduction
exist, few allow for the synthesis of 2,8-difunctionalized ICZs.
Usually these ICZs are prepared in low to moderate yield by
double Fischer cyclisation of phenylhydrazones, obtained through
condensation between 1,4-cyclohexanedione and the appropriate
substituted hydrazine.11
Herein we report an alternative fast and robust method for
synthesizing various 2,8-difunctionalized ICZs in high yield and
with improved solubility, by the use of cheap commercially
available starting materials.
Indolocarbazoles represent an important class of N-heterocycles
characterized by an array of applications depending on the con-
sidered structural isomer. Among the five possible isomers, 5,11-
dihydroindolo[3,2-b]carbazoles (which we will subsequently call
indolo[3,2-b]carbazoles or ICZs for short) have attracted a large
interest because of their structural and electronic properties (high
charge carrier mobility), combined with good stability towards
atmospheric conditions, which makes them ideal components for
use in organic electronics. Hence, indolo[3,2-b]carbazoles have
been successfully implemented in OFETs,1 OLEDs,2 DSSCs3 and
even PSCs.4
Results and discussion
Although the field of applications is broad, the search for
new functional materials for ICZ-based electronics has reached
an impasse, which can mainly be attributed to the lack of high
yielding synthetic pathways towards various functionalised ICZs
and the sizeable presence of alternatives such as thiophene-based
oligomers and polymers, which benefit from the well established
knowledge concerning their reactivity.5,6
One of the first syntheses of indolo[3,2-b]carbazole, by cy-
clodehydrogenation of N,N¢-diphenyl-p-phenylenediamine, was
reported in 1961 by Grotta et al.7 Ever since, many other
syntheses have been reported in the literature, most of which
depend on multi-step sequences characterized by low overall
yields.8 In contrast, a notable result was obtained by Pindur
et al. who isolated the parent indolo[3,2-b]carbazole in 80%
yield by condensation of 3,3¢-bis(indolyl)methane with triethyl
orthoformate.9 For a detailed overview on both synthesis and
characterisation of indolo[3,2-b]carbazoles excellent reviews can
be found in the literature.10
The presented method is a continuation of our work previously
done on 6-monosubstituted indolo[3,2-b]carbazoles and 6,12-
diaryl-indolo[3,2-b]carbazoles.12,13 It was demonstrated that the
latter ICZs could be obtained in moderate to good yields using
a two-step method involving the condensation of an aromatic
aldehyde and indole under acid catalysis (HI) in CH3CN, yielding
a mixture of indolo[3,2-b]carbazole and 5,6,11,12-tetrahydro-
indolo[3,2-b◦]carbazole. The reaction proceeded overnight and
heating (80 C) was imperative to ensure higher amounts of the
oxidized derivative.
However, a second oxidation step with I2 in CH3CN was still
necessary to convert the remaining non-oxidized derivative into
indolo[3,2-b]carbazole. This method was further optimized to a
one-pot procedure and expanded to various aromatic aldehydes,
yielding the expected ICZs in good yields.13 (Fig. 1)
While this method produced the desired compounds, the low
solubility in organic solvents hampered further functionalisation
of the ICZ-backbone.
As a continuation of this work, we planned to address the
problem of low solubility by alkylating the two nitrogens present
in the ICZ backbone. It has previously been shown that this
is indeed a facile and flexible strategy to obtain highly soluble
Division of Molecular Design and Synthesis, Department of Chemistry, K.
U. Leuven, Celestijnenlaan 200F, B-3001, Leuven, Belgium
† Electronic supplementary information (ESI) available. See DOI:
10.1039/c1ob06298k
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Table 1 Alkylation of 2
Compound
RX
Reaction time
Yield (%)
5a
5b
6a
6b
CH3I
48 h
48 h
3 h
90
C3H7Br
C6H13Br
C12H25Br
86
67a
50a,b
3 h
a Non-oxidized ICZ. b Only trans-isomer.
From our previous research it was apparent that elevated
temperatures during the condensation favoured the oxidized ICZ
1. Therefore we envisioned to condense indole with benzaldehyde
under acid catalysis, but this time at room temperature in order to
obtain only non-oxidized ICZ 2.
Fig. 1 Synthesis of indolo[3,2-b]carbazole. (i) CH3CN, HI (57%), 80 ◦C,
14 h. (ii) CH3CN, I2, 80 ◦C, 14 h. R = Aryl.
A convincing result was obtained when MS-analysis and NMR
demonstrated the presence of only 5,6,11,12-tetrahydroindolo[3,2-
b]carbazole 2, as a mixture of both the cis- and trans-ICZ
(1 : 2), in the reaction mixture and no trace of the oxidized
analogue. This product was easily isolated by filtration (97%
yield) and subsequently alkylated to improve its solubility. We
found that upon alkylation of 2, the length of the chosen
alkyl chain was determinative for the reaction products formed.
When methyl iodide was used, ICZ 5a was formed in 90% yield
ICZs.1 Compound 1 was easily converted to the 5,11-dihexyl-
6,12-diphenyl-indolo[3,2-b]carbazole 3, by treating the former
with a 50% NaOH solution and subsequent addition of the
1-bromohexane alkylating reagent at room temperature. The
alkylated compound was obtained in 78% yield and indeed shows
greatly improved solubility in CH2Cl2 as compared to the non-
alkylated derivative. (Scheme 1)
1
after 48 h stirring at room temperature. H NMR analysis of
the isolated compound indicated that not only alkylation but
also oxidation proceeded, evidenced by the disappearance of
the characteristic singlets corresponding to the benzylic protons
of both the cis- and trans-5,11-dimethyl-6,12-diphenyl-5,6,11,12-
tetrahydroindolo[3,2-b]carbazole 2. The oxidation here apparently
is affected by DMSO and/or advantageous oxygen. A similar
resultwas obtainedwhenalkylating 2 with n-propyl bromide. After
48 h, 5b was obtained in 86% yield. Conversely, upon alkylating
2 with longer alkyl chains such as hexyl, we did not observe any
oxidation products being formed after 24 h. It was found that
the yield of alkylated ICZ 6a did not increase when the reaction
proceeded longer than three hours and thus ICZ 6a could be
isolated in 67% yield as a mixture of the cis- and trans-isomers
(1 : 3). Alkylation with dodecyl bromide was also performed using
these reaction conditions, with a comparable result, however in
this case crystallization resulted in the isolation of only the trans-
isomer in 50% yield. (Scheme 2, Table 1)
Scheme 1 (i) DMSO, 50% NaOH, C6H13Br. (ii) AcOH, NBS.
In order to create a functionalisable substrate we envisioned to
brominate 3. We have previously demonstrated that bromination
of the 6-unsubstituted ICZ derivatives using 3 eq. NBS yielded the
2,6,8-tribrominated ICZ in 20% yield.12 However, upon treating
3 under similar conditions we did not observe any trace of
the expected 2,8-dibromo-5,11-dihexyl-6,12-diphenyl-indolo[3,2-
b]carbazole 4. Starting compound 3 was recovered nearly com-
pletely.
We then considered to functionalise the 5,6,11,12-
tetrahydroindolo[3,2-b]carbazole 2 prior to oxidation. Because
the latter corresponds to two indole nuclei connected via a
methylene bridge, the reactivity of 2 should be similar to that
of 2,3-disubstituted indoles and bromination of indoles is well
described in literature.14,15 Hence, we explored a way to obtain
ICZ 2 as the major reaction product in the initial condensation
reaction.
Scheme 2 (i) DMSO, 50% NaOH, R1X. (ii) DMSO, 50% NaOH, R2Br.
80 | Org. Biomol. Chem., 2012, 10, 79–82
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With the alkylated, non-oxidized ICZ 6a available we set out
to brominate this compound using NBS in acetic acid. 1H NMR
analysis of the compound isolated from this reaction after aqueous
work-up confirmed the oxidation of 6a, but also the presence
of two doublets at 7.37 ppm and 7.10 ppm, indicating the 2,8-
dibromination of the ICZ-backbone. Further characterization of
6a by ESI-MS showed the expected mass corresponding to the
dibrominated ICZ 4. In view of the failed bromination of the
ICZ 3, we can safely assume that bromination takes place before
aromatisation.
Since aryl halides are very versatile substrates in vari-
ous transition metal catalyzed cross coupling reactions,16 we
envisioned to expand the conjugation of the ICZs by use
of Suzuki, Stille and Sonogashira coupling reactions us-
ing the newly obtained 5,11-dihexyl-2,8-dibromo-6,12-diphenyl-
indolo[3,2-b]carbazole 4. (Scheme 3)
with styrene also yielded no expected products and in all cases
only starting material 4 was recovered.
Compound 4 also allows to synthesize the diformylated deriva-
tive 8. By treatment of the former with BuLi at -78 ◦C in
THF, followed by the addition of DMF the diformylated ICZ
8 was obtained in 81% yield. The presence of two aldehyde
moieties allowed us to further expand the conjugation of ICZ
8 by conducting condensation reactions, yielding two previously
unreported 2,8-difunctionalized ICZs.
Firstly, the Horner–Wadsworth–Emmons modification to the
Wittig reaction was performed by condensing 8 with diethylbenzyl
phosphonate in the presence of KHMDS, resulting in the forma-
tion of 9 in 74% yield. (Scheme 4)
Scheme 4 (i) THF, -78 ◦C, n-BuLi, DMF. (ii) THF, KOtBu, 0 ◦C,
BnP( O)OEt2.
Scheme 3 (i) AcOH, 4 eq. NBS, 3 h.
Secondly, in order to overcome the difficulties encountered when
trying to introduce an acetylene functional group by Sonogashira
reaction and with the diformylated ICZ 8 available, we were
able to transform the latter to 11 according to the Corey–Fuchs
protocol.17 To accomplish this, 8 was firstly converted to the
bisdibromovinyl-ICZ 10, followed by treatment with n-BuLi at
-78 ◦C leading to 11 in 65% yield. (Scheme 5)
The obtained dialkyne 11 was then treated with bromobenzene
under standard Sonogashira reaction conditions, yielding 12
without problems in 57% yield.
The Suzuki coupling proved to be troublesome at first, but
during optimisation procedure it became quickly apparent that
the coupling was sensitive to the chosen base. Ultimately, upon
treatment of 4 with phenylboronic acid under optimized reaction
conditions we were able to isolate the expected compound in 92%
yield. (Table 2)
An attempt was also made to react 4 under Sonogashira reaction
conditions, using a 1 : 1 ratio of THF/iPr2NH, CuI and various
acetylene substrates, such as TMS-acetylene, phenylacetylene
and 2-methyl-3-butyn-2-ol. However, TLC analysis during these
reactions showed no reactivity of the ICZ. The Stille coupling with
2-(tributylstannyl)thiophene and the Mizoroki–Heck reaction
Conclusions
An efficient method has been developed for the synthesis of 2,8-
difunctionalised ICZs in good overall yields by use of cheap
starting materials and straightforward reactions. The other-
wise not easily accessible 2,8-dibromo-5,11-dihexyl-indolo[3,2-
b]carbazole can be obtained in high yield using a one pot
bromination/aromatisation of the dialkylated indolocarbazole
derivative. The versatility of this dibrominated building block has
been demonstrated by implementing several standard reaction
protocols. Amongst these, the double Suzuki coupling and the
introduction of two aldehyde functional groups and subsequent
conversion to styryl and phenylacetylene derivatives offer a solid
Table 2 Suzuki cross-coupling of 4
Entry Solvent (4/1) Pd(PPh3)4 (mol%) Base (5 eq.) Time Yield (%)
1
2
3
4
5
6
7
DMF/H2O 10
Cs2CO3
K2CO3
Cs2CO3
Cs2CO3
Cs2CO3
KOH
16 h
16 h
16 h
16 h
16 h
2 h
—
36
44
63
65
90
THF/H2O
THF/H2O
THF/H2O
THF/H2O
THF/H2O
THF/H2O
1
1
5
10
10
5
KOH
30 min 92
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reactions. Therefore, the 2,8-disubstituted ICZs also represent
viable building blocks for ICZ-containing polymers, which will
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Acknowledgements
The authors thank IMEC for a fellowship, and the F.W.O.-
Vlaanderen, The “Ministerie voor Wetenschapsbeleid” (Grant
IAP-IV-27), and the University of Leuven for continuing financial
support.
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82 | Org. Biomol. Chem., 2012, 10, 79–82
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