One-pot MCR-oxidation approach toward indole-fused heteroacenes

Article abstract of DOI:10.1021/acs.joc.7b02039

A straightforward synthetic route toward indole-fused heteroacenes was developed. The strategy is composed of a one-pot process starting with a multi-component reaction of cyclohexanone, primary amine and N-tosyl-3-nitroindole followed by an oxidation step. The one-pot approach was found to be general, affording both symmetric and nonsymmetric indolo[3,2-b]indoles in good yields. The strategy was also utilized for accessing 5-ring fused benzo[g]indolo[3,2-b]indole. We could extend the methodology for the synthesis of benzothieno[3,2-b]indoles starting from 3-nitrobenzothiophene. The importance of the developed method was exemplified by performing the reaction sequence on gram scale and also by the synthetic transformations of indolo[3,2-b]indoles. In addition, the change in photophysical properties with extension of conjugation of the synthesized heteroacenes was studied.

Full text of DOI:10.1021/acs.joc.7b02039

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Article
A One-Pot MCR-Oxidation Approach towards Indole-fused Heteroacenes
P. V. Santhini, Akhil Krishnan R, Sheba Ann Babu, Betna Shamlin
Simethy, Gourab Das, Vakayil K. Praveen, Sunil Varughese, and Jubi John
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.7b02039 • Publication Date (Web): 14 Sep 2017
Downloaded from http://pubs.acs.org on September 14, 2017
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A One-Pot MCR-Oxidation Approach towards Indole-fused Heteroacenes
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P. V. Santhini,a,b Akhil Krishnan R.,a Sheba Ann Babu,a Betna Shamlin Simethy,a Gourab Das,b,c
Vakayil K. Praveen,b,c Sunil Varughesea,b and Jubi John*a,b
a Organic Chemistry Section, Chemical Sciences and Technology Division, CSIR-National Institute for
Interdisciplinary Science and Technology (CSIR-NIIST), Thiruvananthapuram-695019, India
E-mail: jubijohn@niist.res.in
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b Academy of Scientific and Innovative Research (AcSIR), CSIR-NIIST Campus, Thiruvananthapuram-695019, India
c Photosciences and Photonics Section, Chemical Sciences and Technology Division, CSIR-National Institute for
Interdisciplinary Science and Technology (CSIR-NIIST), Thiruvananthapuram-695019, India
Abstract
A straightforward synthetic route towards indole-fused heteroacenes was developed. The
strategy comprises of a one-pot process starting with a multicomponent reaction of
cyclohexanone, primary amine and N-tosyl-3-nitroindole followed by an oxidation step. The
one-pot approach was found to be general affording both symmetric and non-symmetric
indolo[3,2-b]indoles in good yields. The strategy was also utilized for accessing 5-ring fused
benzo[g]indolo[3,2-b]indole. We could extend the methodology for the synthesis of
benzothieno[3,2-b]indoles starting from 3-nitro-benzothiophene. The importance of the
developed method was exemplified by performing the reaction sequence in gram scale and also
by the synthetic transformations of indolo[3,2-b]indoles. In addition, the change in
photophysical properties with extension of conjugation of the synthesized heteroacenes was
studied.
Introduction
The past decades have witnessed intensive research for the development of polycyclic aromatic
hydrocarbons/acenes due to its intriguing electronic and luminescent properties.1 These
features of polycondensed acenes have made them interesting candidates for applications in
organic semiconductors, light-emitting diodes, field-effect transistors and photovoltaics.1
Recently, N-heteroacenes have emerged as excellent additions to the family of polycyclic
aromatic compounds which exhibit analogues properties required for applications as functional
materials.2 These characteristics have fuelled the research for the development of facile
synthetic routes toward extended π-conjugated N-heteroacenes.3 In the present report, we
disclose a practical one-pot transition metal-free approach towards indolo-fused heteroacenes.
Indolo[3,2-b]indole moieties are known to be excellent electron donors with better charge
mobility.4 These indole fused heteroacenes were made use for developing high spin organic
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polymers,5a as core donor in heterojunction solar cell,5b in organic field-effect transistors5c and
organic photovoltaics.5d-f Despite of these interesting properties, the wide application of these
heteroacenes are limited due to the lack of short and efficient synthetic routes.6 The existing
methods for the synthesis of indolo[3,2-b]indole involve multiple steps and majority of them
require metal catalysed reduction as the final step (Scheme 1). One of the first reports for the
synthesis of this heteroacene involved the bromination of o,o’-dinitrotolan followed by
reduction of the intermediate dibromostyrene with Sn/HCl.6b A reductive ring closure route was
recently described which involves an intermolecular cyclization of o-aminobenzoic acid ester
followed by chlorination and finally reductive ring closure of the diimidoyl chloride.6e-f
Indolo[3,2-b]indole was also synthesized by metal catalyzed routes, the first one being a Pd-
catalysed double N-arylation of anilines with the dihalobiaryls.6g Soon after, a copper-catalysed
intramolecular oxidative diamination of bis(2-aminophenyl)acetylene was reported for
accessing these heteroacenes.6h
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Scheme 1. Synthetic routes towards indolo[3,2-b]indole.
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The chemistry of electrophilic indoles7 were thoroughly studied by different groups for
functionalization and annulation of indole moiety.8 Different N-heterocycles were synthesized
from enamines derived from enoloisable ketones and primary amines.9 Based on these
literature precedents, recently we have unraveled a general multicomponent reaction involving
an enolizable ketone, a 1o amine and N-tosyl-3-nitroindole for the syntheses of pyrrolo[3,2-
b]indole heterocycles.10 The multicomponent reaction proceeds via the formation of enamine
from the condensation of the enolizable ketone and primary amine. The enamine then adds to
3-nitroindole and subsequently pyrrole-annulation occurs by the elimination of hyponitrous
acid and water. We envisaged that indolo[3,2-b]indoles could be synthesized in ‘one-pot’ by
starting with cyclohexanone as the enolizable ketone in the multicomponent reaction followed
by an oxidation step (Scheme 1) and in our initial communication we showed that pyrrolo[3,2-
b]indole could be easily oxidized to indolo[3,2-b]indole. In this article we report our entire
efforts in developing a general one-pot strategy toward indolo[3,2-b]indoles and
benzothieno[3,2-b]indole.
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Results and Discussion
We initiated our studies with N-tosyl-3-nitroindole 1a, cyclohexanone 2a and n-hexylamine as
substrates. After completion of the MCR for the synthesis of the intermediate pyrrolo[3,2-
o
b]indole, DDQ was added and the reaction was left at 60 C for 12 h. As expected, indolo[3,2-
b]indole 4a was obtained in 25% yield (Scheme 2).
Scheme 2. One-pot approach towards indolo[3,2-b]indole 4a.
The optimal conditions for the ‘one-pot’ fused heteroacene synthesis were identified with
3-nitroindole 1a, cyclohexanone 2a and n-hexyl amine as substrates (Table 1). The initial
o
reaction at 60 C afforded the product in 25% yield (Table 1, Entry 1). By increasing the
temperature to 80 oC, the yield of 4a rose to 45% (Table 1, Entries 1-2). Changing the oxidant to
chloranil improved the yield to 63% at 80 oC (Table 1, Entries 3-4). Screening of various solvents
such as CH3CN, DCM, DCE showed that toluene was the most suitable medium for this reaction
o
(Table 1, Entry 4-7). The best yield of 72% was obtained for 4a from the reaction at 100 C
(Table 1, Entry 8). Further increase in the temperature diminished the yield of the indoloindole
4a (Table 1, Entry 9).
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Table 1. Optimization studiesa
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a Reaction conditions: 1) 1a (1.0 equiv., 0.16 mmol), 2a (2.0 equiv.), 3 (2.0 equiv.), 4Å MS (50 mg), solvent, 60 oC, 12
h. 2) Oxidant (3.0 equiv.), solvent, T oC, 12 h. Isolated yield
Table 2 depicts the results of the detailed studies on the scope of indolo[3,2-b]indole
synthesis. Straight chain amines, benzylamines and p-anisidine underwent the MCR-oxidation
sequence with N-tosyl-3-nitro-indole 1a and cyclohexanone 2a to furnish the expected products
4a to 4e in good yields. The structure of the fused indole was confirmed from X-ray crystal data
of 4c. Indoloindoles 4f to 4h were obtained in moderate to good yields with different amines
when the N-protection was changed to ‘Boc’ group. Again, 4i was obtained in 60% yield from 3-
nitroindole with carboethoxy group protecting the indole N-atom. Our next task was to study
the reactivity of different substituted cyclohexanones which would enable the synthesis of
unsymmetrical indolo[3,2-b]indoles (with respect to substituents on the aryl ring), the synthesis
of which was not possible/tedious with reported procedures.6 To our delight, 4-methyl-, 4-
phenyl- & 2-methyl cyclohexanones reacted well under the ‘one-pot’ reaction conditions
affording the corresponding unsymmetrical indoloindoles 4j to 4m in moderate to good yields
(Table 2). The one-pot process with 3-methylcyclohexanone afforded a 1:0.12 mixture of
regioisomers 4n and 4n’ in 50% yield. The investigations on the generality of the methodology
were concluded with the reactions of halogen (Br&Cl) substituted 3-nitroindoles from which the
expected products 4o to 4r were isolated in good yields. The value of the developed
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methodology escalates due to the possibility of synthesizing halogen substituted indolo[3,2-
b]indole moieties which can be further functionalized for material applications.
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Table 2. Generality of indolo[3,2-b]indole synthesisa
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aReaction conditions: (i) 1 (50 mg), 2 (2.0 equiv.), 3 (2.0 equiv.), 4 Å MS (50 mg), toluene (0.3 mL), 60 oC, 12 h. (ii)
Chloranil (3.0 equiv.), toluene (0.7 mL), 100 oC, 12 h.
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Having developed a general and efficient methodology for accessing indolo[3,2-b]indoles,
we were motivated to extent the strategy for the synthesis of a pentacyclic N-heteroacene. The
obvious choice towards this goal would be to start with α-tetralone as the enolizable ketone for
the MCR. But, we have already reported that α-tetralone failed to react due to electronic
reasons.10 Hence we chose to proceed with 1-decalone (mixture of cis and trans isomers) as the
ketone moiety in the sequential MCR-oxidation protocol (Scheme 3). To our joy and as
expected, the corresponding benzo[g]indolo[3,2-b]indole 4s was obtained in 52% yield.
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Scheme 3. One-pot approach towards benzo[g]indolo[3,2-b]indole 4s.
Our success in the heteroannulation of indole prompted us to investigate the reactivity of 3-
nitro-benzothiophene under the same one-pot heteroannulation protocol. The MCR-oxidation
reaction sequence with 3-nitrobenzothiophene 5, cyclohexanone and 4-methoxy benzylamine
afforded the expected benzothieno[3,2-b]indole 6a in 65% yield (Table 3). Analogues of
benzothieno[3,2-b]indole11 are used for material applications and also have shown promising
biological activity.12 Majority of the reported procedures for the synthesis of these
heteroacenes involves the use of transition metal catalysts.11 A metal-free route involving
multiple steps was reported for the synthesis of the estrogen receptor modulator starting from
benzenethiol (Figure shown in Table 3).12a Our one-pot process worked well with n-hexyl and
decyl amines affording the corresponding products 6c and 6d in good yields. Substituted
cyclohexanones also furnished the expected benzothienoindoles 6e and 6f in good yields. 4-
methoxyaniline was also compatible with the developed conditions affording the product 6g in
55% yield. Benzothienoindole 6h was obtained in good yield starting with 2-phenylethylamine
as the amine moiety. Next, we were interested in checking the reactivity of naturally available
amines towards the annulation reaction with the aim for synthesizing benzothienoindoles with
potential bioactivities. Both tyramine and tryptamine participated in the one-pot MCR-
oxidation reaction sequence affording products 6i and 6j respectively in good yields. Finally, the
methodology also worked perfectly with 5-bromo-3-nitrobenzo[b]thiophene yielding the
corresponding products 6k and 6l in good yields.
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Table 3. Generality of benzothieno[3,2-b]indole synthesisa
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aReaction conditions: (i) 5 (50 mg), 2 (2.0 equiv.), 3 (2.0 equiv.), 4 Å MS (50 mg), toluene (0.3 mL), 60 C, 12 h. (ii)
Chloranil (3.0 equiv.), toluene (0.7 mL), 100 oC, 12 h.
To further highlight the synthetic utility of the developed heteroannulation process, we
attempted the gram scale synthesis of indolo[3,2-b]indole. Starting from one gram of N-tosyl-3-
nitroindole 1a, we obtained the corresponding product 4a in 68% yield (Scheme 4). The tosyl-
group on the N-atom of the indolo[3,2-b]indole 4a could be directly removed by treatment with
NaOH.13 The deprotected compound 7 was easily N-alkylated by treating with bromohexane
under baisic conditions to afford 5,10-dihexyl-5,10-dihydroindolo[3,2-b]indole 8 in 85% yield. It
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is noteworthy to mention that indolo[3,2-b]indoles can be synthesized with different groups on
both N-atoms, depending on the application. 10-hexyl-pyrrolo[3,2-b]indole 9 was also N-
alkylated towards dihexyl-pyrrolo[3,2-b]indole 8-P following the above mentioned alkylation
procedure. These dihexyl pyrroloindole 8-P and indoloindole 8 were syntheized to study and
compare their basic photophysical properties. Finally, we did a Suzuki reaction of indoloindole
4o with phenyl boronic acid, hence proving that the compounds synthesized with our strategy
can be easily functionalized at multiple centers.
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Scheme 4. Scale-up and synthetic transformations of indoloindoles.
The initial stage of the mechanism for this one-pot reaction is the MCR to furnish the
intermediate pyrrolo[3,2-b]indole (Scheme 5). The mechanism of the MCR is the same as was
described in our communication.10 The reaction commences with the condensation of
cyclohexanone I and amine II to furnish the imine III. The enamine form IV which is in
equilibrium with the imine then participates in a Michael addition to the C-2 position of 3-nitro-
N-Tosyl indole to form the intermediate VI. The pyrroline intermediate VII is generated by the
attack of the enamine to the C-3 carbon of the nitronate in VI. The pyrroloindole VIII is then
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formed by the elimination of hyponitrous acid and water from the intermediate VII. Finally, the
oxidation of pyrroloindole with chloranil affords the corresponding indolo[3,2-b]indole IX.
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Scheme 5. Mechanism of indoloindole formation.
In order to understand the impact of oxidation induced aromatization of pyrrolo[3,2-
b]indole and benzothieno[3,2-b]pyrrole, we have compared the photophysical properties of
compounds 8-P, 8, 6c-P and 6c. Due to the solubility reason, we have selected acetonitrile as
the solvent for conducting the photophysical studies where the compounds were found to exist
as molecularly dissolved species (1 x 10-5 M). The results of the photophysical properties have
been summarized in Figure 1, 2 and Table 4. Pyrrolo[3,2-b]indole 8-P showed two well distinct
absorption maxima at 258 (
ε
= 2.35 x 104 L mol-1 cm-1) and 318 nm (
ε
= 1.05 x 104 L mol-1 cm-1)
and a broad emission profile with maximum at 389 nm (ΦF = 0.31,
τ
= 7.18 ns). The lowest
energy absorption centered at 318 nm can be assigned to S0 → S1 transition and the intense
absorption band at 258 nm is most likely originated from the higher energy electronic
transiton.6f,6g In the case of indolo[3,2-b]indole 8 the absorption maxima was found to be
slightly red shifted (λmax = 261 nm,
ε ε
= 6.74 x 104 L mol-1 cm-1; λmax = 323 nm, = 2.37 x 104 L
mol-1 cm-1) along with the formation of a new shoulder band at 353 nm (ε = 0.86 x 104 L mol-1
cm-1). The long-wavelength absorption band at 353 nm involve electronic transition from S0
ground state to relatively low-lying S1 excited state.6f,6g The absorption maximum at 323 nm
with a weak shoulder can be assigned to S0 → S2 transition and the higher energy absorption
band (S0 → S5) is centered at 261 nm. Interestingly, the emission spectrum of 8 was found to be
shifted towards longer wavelength region with maximum at 407 nm (ΦF = 0.46,
with a shoulder band at 388 nm. This observation implies that the indolo[3,2-b]indole 8 is
having improved photophysical features (molar extinction coefficient, and fluorescence
quantum yield, F) than that of the parent pyrrolo[3,2-b]indole 8-P (Figure 1).
τ = 6.12 ns)
ε
Φ
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b)
c)
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8-P
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8-P
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Wavelength (nm)
Wavelength (nm)
Figure 1. a) Molecular structure of pyrrolo[3,2-b]indole 8-P and indolo[3,2-b]indole 8. b) UV-Vis
absorption and c) fluorescence spectra of 8-P and 8 in acetonitrile (1 x 10-5 M), λex = 318 (8-P) and 323
nm (8).
We then extended similar kind of studies to compare the properties of benzothieno[3,2-
b]indole 6c with its parent benzothieno[3,2-b]pyrrole molecule 6c-P (Figure 2). In the case of
6c-P, a broad absorption spectrum was obtained with maxima at 259 (
1), 274 ( = 1.13 x 104 L mol-1 cm-1) and 297 nm ( = 1.26 x 104 L mol-1 cm-1). Furthermore, the
molecule 6c-P was found to be non-emissive. On contrary, 6c displayed a well-resolved
absorption spectrum with maxima at 252 nm (
= 2.31 x 104 L mol-1 cm-1), 308 ( =1.83 x 104 L
mol-1 cm-1) and 342 nm ( = 0.71 x 104 L mol-1 cm-1). This molecule also showed weak emission
feature with maximum centered at 375 nm ( F = 0.04, = 0.36 ns) along with a weak vibronic
ε
= 1.20 x 104 L mol-1 cm-
ε
ε
ε
ε
ε
Φ
τ
shoulder band at 360 nm. Similar to previous case, here also we have observed that oxidation
of the parent benzothieno[3,2-b]pyrrole 6c-P leads to improved photophysical properties.
b)
0.3
0.2
0.1
0.0
c)
6
4
2
0
6c
6c-P
6c
6c-P
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300
400
500
400
500
600
Wavelength (nm)
Wavelength (nm)
Figure 2. a) Molecular structure of benzothieno[3,2-b]pyrrole 6c-P and benzothieno[3,2-b]indole 6c. b)
UV-Vis absorption and c) fluorescence spectra of 6c-P and 6c in acetonitrile (1 x 10-5 M), λex = 297 (6c-P)
and 308 nm (6c).
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Table 4. Photophysical properties of compound 8-P, 8, 6c-P and 6c in acetonitrile (1 x 10-5 M)
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a
b
λabs
λem
τc
Compound
ΦF
ε
(104 L mol-1 cm-1)
(nm)
(nm)
(ns)
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8-P
8
258, 318
2.35, 1.05
389
0.31 7.18
261, 323, 353
259, 274, 297
252, 308, 342
6.74, 2.37, 0.86
1.2, 1.13, 1.26
2.31, 1.83, 0.71
388, 407 0.46 6.12
6c-P
6c
-
-
-
360, 375 0.04 0.36
a Excitation wavelength, λex = 318 (8-P), 323 (8), and 308 nm (6c). Fluorescence quantum yields were
b
determined using quinine sulphate as the standard (ΦF = 0.546 in 0.1 N H2SO4). cλex = 330 nm is used for
fluorescence lifetime (τ) measurements.
Conclusion
In conclusion, we have developed a simple, metal-free and one-pot method for the synthesis of
indolo[3,2-b]indole, the most general and applicable route reported to-date. We could
demonstrate the applicability of the sequential MCR-oxidation strategy for the generation of
symmetrical and unsymmetrical indolo[3,2-b]indoles; highly relevant for material applications
and which was not probable with existing methods. In addition, by selecting an appropriate
enolizable ketone, we were able to synthesize 5-ring fused benzo[g]indolo[3,2-b]indole. We
could also extend the strategy for accessing benzothieno[3,2-b]indole, another moiety of
medicinal and material interest. The importance of the one-pot heteroannulation process was
demonstrated by synthesizing indoloindole in gram-scale and also by synthetic modification of
fused-indole moieties. Finally, we have also evaluated and compared the basic photophysical
properties of the synthesized N-heteroacenes.
Experimental Section
General experimental methods: All chemicals were of the best grade commercially available
and are used without further purification. All solvents were purified according to standard
procedure; dry solvents were obtained according to the literature methods and stored over
molecular sieves. Analytical thin layer chromatography was performed on glass plates coated
with silica gel containing calcium sulfate binder. Gravity column chromatography was
performed using neutral alumina and mixtures of hexane-ethyl acetate were used for elution.
Melting points were determined on a Buchi melting point apparatus and are uncorrected.
Proton nuclear magnetic resonance spectra (1H NMR) were recorded on a Bruker AMX 500
1
spectrophotometer (CDCl3 and CD3CN as solvents). Chemical shifts for H NMR spectra are
reported as δ in units of parts per million (ppm) downfield from SiMe4 (δ 0.0) and relative to the
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signal of chloroform-d (δ 7.25ppm) CD3CN (1.94 ppm). Multiplicities were given as: s (singlet); d
(doublet); t (triplet); q (quadret); dd (double doublet); m (multiplet). Coupling constants are
reported as J value in Hz. Carbon nuclear magnetic resonance spectra (13C NMR) are reported as
δ in units of parts per million (ppm) downfield from SiMe4 (δ 0.0) and relative to the signal of
chloroform-d (δ 77.03 ppm) CD3CN (1.32 ppm),. In some of the cases, the 13C of compound
were recorded in a 7:3 mixture of CDCl3 and CCl4. In those 13C a spectrum, the peak seen at δ
96.0 ppm corresponds to the carbon of CCl4. Mass spectra were recorded under ESI/HRMS at
60,000 resolution using Thermo Scientific Exactive mass spectrometer with orbitrap analyzer. IR
spectra were recorded on Bruker FT-IR spectrometer. The 1-tosyl-3-nitroindoles were prepared
by following literature report.14 Pyrrolo[3,2-b]indole 8-P and benzothieno[3,2-b]pyrrole 6c-P
were synthesized following our initial communication.10 The electronic absorption spectra were
recorded on a Shimadzu spectrophotometer UV-2100. The fluorescence spectra were recorded
on a SPEX-Fluorolog-3 FL3-221 spectrofluorimeter. Optical studies in solution-state were carried
out in a 1 cm quartz cuvette. Relative quantum yield measurements were carried out using
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quinine sulphate in 0.1 N H2SO4 as the standard which has a reported quantum yield of ΦF
=
0.546.15,16 Fluorescence lifetime measurements were carried out using IBH (model 5000 DPS)
time-correlated single photon counting system. The lifetime values were obtained using DAS6
decay analysis software. The quality of the fit has been judged by the fitting parameters such as
χ2 (< 1.1) as well as the visual inspection of the residuals.
Synthetic procedure for the Multicomponent Reaction toward Indole-fused Heteroacenes
Genral procedure for the synthesis of indolo[3,2-b]indole (4a-4s): The enolizable ketone,
cyclohexanone (31 mg, 0.32 mmol) and primary amine, n-hexylamine (32 mg, 0.32 mmol) were
weighed into a dry reaction tube. Dry toluene (0.3 mL) along with 4 Å MS (50 mg) was added
o
and allowed to stir at 60 C for 1 hour, after which 3-nitro-N-tosyl indole (50 mg, 0.16 mmol)
was added into it and again kept it for stirring at the same temperature for 11 hours. After the
complete consumption of 3-nitro-N-tosyl indole, Chloranil (117 mg, 0.47 mmol) along with
o
toluene (0.7 mL) was added and kept at 100 C for 10 hours. The solvent was evaporated in
vacuo and the residue on activated neutral alumina column chromatography yielded
indolo[3,2-b]indole with hexanes and ethyl acetate as eluent.
Synthesis and characterization of indolo[3,2-b]indole (4a-4s)
5-Hexyl-10-tosyl-5,10-dihydroindolo[3,2-b]indole (4a): The reaction was performed according
to general procedure with 3-nitro-N-tosyl indole (50 mg, 0.16 mmol), n-hexylamine (32 mg, 0.32
mmol), cyclohexanone (31 mg, 0.32 mmol), and chloranil (117 mg, 0.47 mmol). The crude
product was purified by activated neutral alumina column chromatography (3% ethyl acetate in
hexane) to afford the desired product as a colourless viscous liquid (51 mg, 72%). Analytical
Data of 4a: TLC (SiO2): Rf; 0.43 (7% ethyl acetate in hexane). IR (neat) νmax: 2919, 2849, 1911,
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1879, 1796, 1675, 1603, 1507, 1383, 1353, 1246, 1167, 1029, 947 cm-1. H NMR (500 MHz,
CDCl3, TMS): δ 8.53 (d, J = 7.5 Hz, 1H), 8.35 (d, J = 8 Hz, 1H), 7.62-7.58 (m, 2H), 7.41-7.28 (m,
3H), 7.23-7.22 (m, 1H), 7.16-7.14 (m, 2H), 6.99 (d, J = 8Hz, 2H), 4.39 (t, J = 7Hz, 2H), 2.22 (s,
3H),1.88-1.84 (m, 2H), 1.29-1.21(m, 6H), 0.81 (t, J = 7Hz, 3H). 13C NMR (125 MHz, CDCl3): δ
144.0, 140.7, 140.5, 134.3, 130.2, 129.4, 126.8, 124.4, 123.9, 122.6, 120.7, 120.1, 117.5, 116.4,
109.6, 45.0, 31.5, 30.2, 26.6, 22.5, 21.4, 13.9. HRMS (ESI-Orbitrap) m/z: (M+Na)+ calcd for
C27H28N2O2SNa 467.1763; Found: 467.1763.
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5-Dodecyl-10-tosyl-5,10-dihydroindolo[3,2-b]indole (4b): The reaction was performed
according to general procedure with 3-nitro-N-tosyl indole (50 mg, 0.16 mmol), dodecylamine
(59 mg, 0.32 mmol) and cyclohexanone (31 mg, 0.32 mmol) and chloranil (117 mg, 0.47 mmol).
The crude product was purified by activated neutral alumina column chromatography (3% ethyl
acetate in hexane) to afford the desired product as a colourless viscous liquid (50 mg, 60%).
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Analytical Data of 4b: TLC (SiO2): Rf; 0.41 (7% ethyl acetate in hexane). H NMR (500 MHz,
CDCl3, TMS): δ 8.55 (d, J = 8 Hz, 1H), 8.36 (d, J = 8 Hz, 1H), 7.65-7.58 (m, 3H), 7.44-7.42 (m, 1H),
7.38-7.29 (m, 4H), 7.02-6.99 (m, 2H), 4.39 (t, J = 7 Hz, 2H), 2.21 (s, 3H), 1.87- 1.85 (m, 2H),
1.25-1.11 (m, 18H) 0.87 (t, J = 7Hz, 3H). 13C NMR (125 MHz, CDCl3): δ 144.3, 140.7, 140.5, 134.2,
130.3, 129.4, 126.8, 124.5, 123.9, 122.6, 120.7, 120.0, 117.7, 116.4, 109.7, 45.1, 31.9, 30.2,
29.6, 29.5, 29.3, 27.0, 22.7, 21.4, 14.1. HRMS (ESI-Orbitrap) m/z: (M+H)+ calcd for C33H41N2O2S
529.2883; Found: 529.2875.
5-(4-Methoxybenzyl)-10-tosyl-5,10-dihydroindolo[3,2-b]indole (4c): The reaction was
performed according to general procedure with 3-nitro-N-tosyl indole (50 mg, 0.16 mmol), 4-
methoxybenzylamine (44 mg, 0.32 mmol) and cyclohexanone (31 mg, 0.32 mmol) and chloranil
(117 mg, 0.47 mmol). The crude product was purified by activated neutral alumina column
chromatography (7% ethyl acetate in hexane) to afford the desired product as a white solid (46
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mg, 60%). Analytical Data of 4c: Mp; 195-197 C. H NMR (500 MHz, CDCl3, TMS): δ 8.56-8.54
(m, 1H), 8.33 (d, J = 8.5Hz, 1H), 7.60-7.58 (m, 2H), 7.46-7.45 (m, 1H), 7.38-7.28 (m, 4H), 7.22-
7.20 (m, 1H), 7.02-6.96 (m, 4H), 6.73-6.72 (m, 2H), 5.55 (s, 2H), 3.71 (s, 3H), 2.24 (s, 3H). 13C
NMR (125 MHz, CDCl3): δ 159.1, 144.0, 140.9, 140.7, 134.4, 130.5, 129.5, 129.4, 129.0, 127.4,
126.6, 124.5, 123.9, 123.0, 122.4, 120.8, 120.5, 120.2, 117.7, 116.7, 116.4, 114.3, 114.0, 109.9,
55.1, 47.9, 21.5. HRMS (ESI-Orbitrap) m/z: (M+Na)+ calcd for C29H24N2O3SNa 503.1399; Found:
503.1406.
5-(4-Chlorobenzyl)-10-tosyl-5,10-dihydroindolo[3,2-b]indole (4d): The reaction was performed
according to general procedure with 3-nitro-N-tosyl indole (50 mg, 0.16 mmol), 4-
chlorobenzylamine (45 mg, 0.32 mmol) and cyclohexanone (31 mg, 0.32 mmol) and chloranil
(117 mg, 0.47 mmol). The crude product was purified by activated neutral alumina column
chromatography (7% ethyl acetate in hexane) to afford the desired product as a white solid (53
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mg, 69%). Analytical Data of 4d: Mp; 195-197 C. H NMR (500 MHz, CDCl3, TMS): δ 8.58-8.56
(m, 1H), 8.34 (d, J = 8.5 Hz, 1H), 7.60-7.59 (m, 2H), 7.33-7.32 (m, 4H), 7.19-7.17 (m, 4H), 7.02-
6.94 (m, 2H), 6.95 (d, J = 8.5 Hz, 2H) 5.57 (s, 2H), 2.24 (s, 3H). 13C NMR (125 MHz, CDCl3): δ
144.3, 140.8, 140.7, 135.6, 134.2, 133.6, 129.6, 129.4, 129.1, 128.8, 127.5, 127.3, 127.1, 126.8,
124.7, 124.0, 123.2, 120.8, 120.7, 120.0, 117.5, 116.5, 109.8, 47.8, 21.5. HRMS (ESI-Orbitrap)
m/z: (M+H)+ calcd for C28H22 ClN2O2S 485.1085; Found: 485.1088.
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5-(4-Methoxyphenyl)-10-tosyl-5,10-dihydroindolo[3,2-b]indole (4e): The reaction was
performed according to general procedure with 3-nitro-N-tosyl indole (50 mg, 0.16 mmol), 4-
methoxyaniline (39 mg, 0.32 mmol) and cyclohexanone (31 mg, 0.32 mmol) and chloranil (117
mg, 0.47 mmol). The crude product was purified by activated neutral alumina column
chromatography (7% ethyl acetate in hexane) to afford the desired product as a white solid (47
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mg, 63%). Analytical Data of 4e: Mp; 195-200 C. H NMR (500 MHz, CDCl3, TMS): δ 8.59-8.58
(m, 1H), 8.34 (d, J = 8.5Hz, 1H), 7.68-7.65 (m, 2H), 7.46 -7.44 (m, 2H), 7.39 -7.37 (m, 1H), 7.34 -
7.29 (m, 3H), 7.18 -7.11 (m, 2H), 7.08-7.04 (m , 4H), 3.92 (s, 3H), 2.25 (s, 3H). 13C NMR (125
MHz, CDCl3): δ 159.3, 144.4, 141.8, 140.8, 134.8, 130.6, 129.7, 128.1, 127.1, 124.9, 123.8, 123.4,
121.2, 120.9, 120.1, 118.4, 116.3, 115.0, 110.9, 55.7, 21.7. HRMS (ESI-Orbitrap) m/z: (M+Na)+
calcd for C28H22N2O3SNa 489.1243; Found: 489.1239.
tert-Butyl 10-hexylindolo[3,2-b]indole-5(10H)-carboxylate (4f): The reaction was performed
according to general procedure with 3-nitro-N-Boc indole (50 mg, 0.19 mmol), n-hexylamine (38
mg, 0.38 mmol) and cyclohexanone (37 mg, 0.38 mmol) and chloranil (140 mg, 0.57 mmol). The
crude product was purified by activated neutral alumina column chromatography (2% ethyl
acetate in hexane) to afford the desired product as a viscous liquid (45 mg, 60%). Analytical
Data of 4f: TLC (SiO2): Rf; 0.65 (7% ethyl acetate in hexane). 1H NMR (500 MHz, CDCl3, TMS): 1H
NMR (500MHz,CDCl3,TMS): δ 8.49 (d, J = 8 Hz, 1H), 8.31 (brs, 1H), 7.76 (d, J = 7.5 Hz, 1H), 7.41
(d, J = 8 Hz, 1H), 7.35-7.27 (m, 3H), 7.19 (t, J = 8 Hz, 1H), 4.46 (t, J = 7 Hz, 2H), 1.95-1.90 (m, 2H),
1.80 (s, 9H), 1.40-1.24 (m, 6H), 0.84 (t, J = 7 Hz, 3H). 13C NMR (125 MHz, CDCl3): δ 150.7, 140.4,
123.9, 122.6, 122.2, 118.9, 117.4, 116.9, 116.3, 109.4, 83.8, 45.0, 31.6, 30.4, 28.6, 26.7, 22.5,
14.0. HRMS (ESI-Orbitrap) m/z: (M+Na)+ calcd for C25H30N2O2Na 413.2199; Found: 413.2205.
tert-Butyl 10-(4-methoxybenzyl)indolo[3,2-b]indole-5(10H)-carboxylate (4g): The reaction was
performed according to general procedure with 3-nitro-N-Boc indole (50 mg, 0.19 mmol), 4-
methoxy benzylamine (52 mg, 0.38 mmol) and cyclohexanone (37mg, 0.38 mmol) and chloranil
(140 mg, 0.57 mmol). The crude product was purified by activated neutral alumina column
chromatography (5% ethyl acetate in hexane) to afford the desired product as a white solid (45
mg, 55%). Analytical Data of 4g: Mp; 155-157 oC. 1H NMR (500 MHz, CDCl3, TMS): δ 8.52 (d, J =
7.5 Hz, 1H), 8.29 (brs, 1H), 7.60 (d, J = 7.5 Hz, 1H), 7.40 (d, J = 8 Hz, 1H), 7.32-7.27 (m, 2H), 7.23-
7.21 (m, 2H), 7.09 (d, J = 9 Hz, 2H), 6.78-6.76 (m, 2H), 5.63 (s, 2H), 3.72 (s, 3H), 1.81 (s, 9H). 13C
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NMR (125 MHz, CDCl3): δ 159.0, 150.8, 140.7, 129.5, 127.5, 124.0, 122.6, 119.4, 118.8, 117.5,
116.9, 116.6, 114.2, 109.6, 84.0, 55.2, 47.9, 28.6. HRMS (ESI-Orbitrap) m/z: (M+Na)+ calcd for
C27H26N2O3Na 449.1835; Found: 449.1852.
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tert-Butyl 10-(4-methoxyphenyl)indolo[3,2-b]indole-5(10H)-carboxylate (4h): The reaction
was performed according to general procedure with 3-nitro-N-Boc indole (50 mg, 0.19 mmol),
4-methoxy aniline (47 mg, 0.38 mmol) and cyclohexanone (37mg, 0.38 mmol) and chloranil
(140 mg, 0.57 mmol). The crude product was purified by activated neutral alumina column
chromatography (5% ethyl acetate in hexane) to afford the desired product as a white solid (40
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mg, 51%). Analytical Data of 4h: Mp; 160-162 C. H NMR (500 MHz, CDCl3, TMS): δ 8.54-8.53
(m, 1H), 8.30-8.28 (m, 1H), 7.54-7.52 (m, 2H), 7.41- 7.39 (m, 1H), 7.33-7.30 (m, 3H), 7.25-7.23
(m, 1H), 7.17-7.12 (m, 3H), 3.94 (s, 3H), 1.82 (s, 9H). 13C NMR (125 MHz, CDCl3): δ 158.9, 150.8,
141.4, 130.8, 128.0, 124.2, 122.8, 122.4, 121.7, 120.0, 117.9, 116.8, 114.8, 110.4, 84.1, 55.6,
28.6. HRMS (ESI-Orbitrap) m/z: (M+Na)+ calcd for C26H24N2O3Na 435.1679; Found: 435.1689.
Ethyl 10-(4-methoxyphenyl)indolo[3,2-b]indole-5(10H)-carboxylate (4i): The reaction was
performed according to general procedure with ethyl 3-nitro-1H-indole-1-carboxylate (50 mg,
0.21 mmol), 4-methoxy aniline (52 mg, 0.42 mmol) and cyclohexanone (41mg, 0.42 mmol) and
chloranil (155 mg, 0.63 mmol). The crude product was purified by activated neutral alumina
column chromatography (5% ethyl acetate in hexane) to afford the desired product as a white
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solid (49 mg, 60%). Analytical Data of 4i: Mp; 120-125 C. H NMR (500 MHz, CDCl3, TMS): δ
8.35-8.21 (m, 2H), 7.52-7.46 (m, 2H), 7.39-7.34 (m, 3H), 7.24-7.15 (m, 3H), 7.12-7.09 (m, 2H),
4.72-4.65 (m, 2H), 3.92(s, 3H), 1.65-1.60 (m, 3H). 13C NMR (125 MHz, CDCl3): δ 159.2, 141.6,
130.7, 130.1, 128.8, 127.9, 124.7, 122.9, 120.8, 120.2, 118.6, 117.9, 116.9, 115.0, 114.8, 110.5,
63.2, 55.5, 14.8. HRMS (ESI-Orbitrap) m/z: (M)+ calcd for C24H20N2O3 384.1468; Found:
384.1479.
10-(4-Chlorobenzyl)-3-methyl-5-tosyl-5,10-dihydroindolo[3,2-b]indole (4j): The reaction was
performed according to general procedure with 3-nitro-N-tosyl indole (50 mg, 0.16 mmol), 4-
chlorobenzylamine (45 mg, 0.32 mmol) and 4-methyl cyclohexanone (36 mg, 0.32 mmol) and
chloranil (117 mg, 0.47 mmol). The crude product was purified by activated neutral alumina
column chromatography (7% ethyl acetate in hexane) to afford the desired product as a white
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solid (43 mg, 56%). Analytical Data of 4j: Mp; 185-190 C. H NMR (500 MHz, CDCl3, TMS): δ
8.36-8.32 (m, 2H), 7.61-7.58 (m, 3H), 7.40-7.39 (m, 1H), 7.33-7.31 (m, 1H), 7.23-7.14 (m, 4H),
7.04- 7.01 (m, 2H), 6.95- 6.90 (m, 2H), 5.54 (s, 2H), 2.58 (s, 3H), 2.24 (s, 3H). 13C NMR (125
MHz, CDCl3): δ 144.4, 140.7, 139.4, 135.7, 134.1, 133.5, 131.4, 130.6, 130.2, 129.6, 129.4, 129.0,
128.8, 127.5, 127.2, 127.1, 126.8, 124.8, 124.6, 124.0, 120.4, 120.1, 117.5, 116.5, 109.5, 47.8,
21.7, 21.5. HRMS (ESI-Orbitrap) m/z: (M+Na)+ calcd for C29H23ClN2O2SNa 521.1061; Found:
521.1065.
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10-Hexyl-4-methyl-5-tosyl-5,10-dihydroindolo[3,2-b]indole (4k): The reaction was performed
according to general procedure with 3-nitro-N-tosyl indole (50 mg, 0.16 mmol), n-hexylamine
(32 mg, 0.32 mmol), 4-methyl cyclohexanone (36 mg, 0.32 mmol) and chloranil (117 mg, 0.47
mmol). The crude product was purified by activated neutral alumina column chromatography
(2% ethyl acetate in hexane) to afford the desired product as a colourless viscous liquid (44 mg,
61%). Analytical Data of 4k: TLC (SiO2): Rf; 0.43 (7% ethyl acetate in hexane). 1H NMR (500 MHz,
CDCl3, TMS): δ 8.33 -8.30 (m, 2H), 7.60 -7.56 (m, 3H), 7.35 -7.27 (m, 3H), 7.15 -7.14 (m, 1H),
6.98 (d, J = 8 Hz, 2H), 4.35 (t, J = 7 Hz, 2H), 2.58 (s, 3H), 2.21 (s, 3H), 1.85 -1.81 (m, 2H), 1.29 -
120 (s, 6H), 0.80 (t, J = 7 Hz, 3H). 13C NMR (125 MHz, CDCl3): δ 143.9, 140.7, 139.0, 134.3,
130.4, 129.3, 126.8, 124.3, 123.8, 121.6, 120.4, 120.3, 117.5, 116.6, 116.5, 109.6, 45.0, 31.5,
30.2, 26.6, 22.4, 21.8, 21.5, 13.9. HRMS (ESI-Orbitrap) m/z: (M+Na)+ calcd for C28H30N2O2SNa
481.1920; Found: 481.1924.
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10-Hexyl-3-phenyl-5-tosyl-5,10-dihydroindolo[3,2-b]indole (4l): The reaction was performed
according to general procedure with 3-nitro-N-tosyl indole (50 mg, 0.16 mmol), n-hexylamine
(32 mg, 0.32 mmol), 4-phenyl cyclohexanone (56 mg, 0.32 mmol) and chloranil (117 mg, 0.47
mmol). The crude product was purified by activated neutral alumina column chromatography
(2% ethyl acetate in hexane) to afford the desired product as a colourless viscous liquid (45 mg,
55%). Analytical Data of 4l: TLC (SiO2): Rf; 0.37 (7% ethyl acetate in hexane). 1H NMR (500 MHz,
CDCl3, TMS): δ 8.78 (s, 1H), 8.36 (d, J = 8 Hz, 1H), 7.79- 7.77 ( m, 2H), 7.63- 7.58 (m, 4H), 7.49-
7.44 (m, 2H), 7.38- 7.29 (m, 4H), 6.99 (d, J = 8 Hz, 2H), 4.40 (t, J = 7.5 Hz, 2H), 2.21 (s, 3H), 1.90-
1.87 (m, 2H), 1.34-1.18 (m, 6H), 0.82 (t, J = 7 Hz, 3H). 13C NMR (125 MHz, CDCl3): δ 144.0, 142.2,
140.8, 140.0, 133.5, 130.8, 129.4, 128.7, 128.6, 127.4, 126.8, 126.4, 124.6, 123.9, 122.3, 120.2,
119.0, 117.6, 116.5, 109.9, 45.2, 31.5, 30.3, 26.7, 22.5, 21.5, 14.0. HRMS (ESI-Orbitrap) m/z:
(M+Na)+ calcd for C33H32N2O2SNa 543.2076; Found: 543.2076.
10-Hexyl-1-methyl-5-tosyl-5,10-dihydroindolo[3,2-b]indole (4m): The reaction was performed
according to general procedure with 3-nitro-N-tosyl indole (50 mg, 0.16 mmol), n-hexylamine
(32 mg, 0.32 mmol), 2-methyl cyclohexanone (36 mg, 0.32 mmol) and chloranil (117 mg, 0.47
mmol). The crude product was purified by activated neutral alumina column chromatography
(2% ethyl acetate in hexane) to afford the desired product as a colourless viscous liquid (38 mg,
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52%). Analytical Data of 4m: TLC (SiO2): Rf; 0.41 (7% ethyl acetate in hexane). H NMR (500
MHz, CDCl3, TMS): δ 8.46 (d, J = 7 Hz, 1H), 8.38 (d, J = 7 Hz, 1H), 7.63-7.56 (m, 3H), 7.38-7.35
(m, 2H), 7.19-7.16 (m, 1H), 7.07-6.98 (m, 3H), 4.59 (t, J = 7.5 Hz, 2H), 2.79 (s, 3H), 2.21 (s, 3H),
1.80-1.77 (m, 2H), 1.28-1.19 (m, 6H), 0.83 (t, J = 7 Hz, 3H). 13C NMR (125 MHz, CDCl3): δ 144.2,
140.9, 134.1, 129.4, 126.8, 124.4, 123.9, 122.3, 121.2, 120.6, 120.3, 118.9, 117.7, 117.5, 116.6,
47.4, 32.0, 31.5, 26.3, 22.5, 21.5, 20.4, 13.9. HRMS (ESI-Orbitrap) m/z: (M+Na)+ calcd for
C28H30N2O2SNa 481.1920; Found: 481.1932.
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10-Hexyl-2-methyl-5-tosyl-5,10-dihydroindolo[3,2-b]indole (4n) & 10-hexyl-4-methyl-5-tosyl-
5,10-dihydroindolo[3,2-b]indole (4n’): The reaction was performed according to general
procedure with 3-nitro-N-tosyl indole (50 mg, 0.16 mmol), n-hexylamine (32 mg, 0.32 mmol), 3-
methyl cyclohexanone (36 mg, 0.32 mmol) and chloranil (117 mg, 0.47 mmol). The crude
product was purified by activated neutral alumina column chromatography (2% ethyl acetate in
hexane) to afford the desired product as a 1:0.12 mixture of regioisomers (from 1H NMR
analysis) and appeared as a colourless viscous liquid (36 mg, 50%). Analytical Data of 4n&4n’:
TLC (SiO2): Rf; 0.41 (7% ethyl acetate in hexane). 1H NMR (500 MHz, CDCl3, TMS): 8.40 (d, J = 8.5
Hz, 1H), 8.33 (d, J = 8 Hz, 1H), 8.23 (d, J = 8.5 Hz, .12H) 7.61-7.58 (m, 3H), 7.35-7.29 (m, 2.25H),
7.24-7.23 (m, .33 H), 7.20 (s, 1H), 7.12 (d, J = 8 Hz, 1H), 6.99 (d, J = 8 Hz, 2H), 6.96-6.94 (m,
.35H), 6.75 (d, J = 8 Hz, .3H), 4.35 (t, J = 7.5 Hz, 2H), 4.28 (t, J = 7.5 Hz, .25H), 2.98 (s, 0.32 H),
2.57 (s, 3H), 2.20 (s, 3H), 2.15 (s, 0.48H), 1.86-1.83 (m, 2H), 1.31-1.22 (m, 9H), 0.82-0.79 (m,
3.23H). 13C NMR (125 MHz, CDCl3): δ 144.2, 140.9, 140.4, 134.2, 132.7, 129.8, 129.4, 126.8,
124.1, 123.8, 121.8, 120.5, 120.3, 117.4, 116.3, 114.3, 109.8, 45.0, 31.5, 30.2, 26.6, 22.5, 22.1,
21.4, 13.9. HRMS (ESI-Orbitrap) m/z: (M+H)+ calcd for C28H31N2O2S 459.2100; Found: 459.2115.
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3-Bromo-5-hexyl-10-tosyl-5,10-dihydroindolo[3,2-b]indole (4o): The reaction was performed
according to general procedure with 5-bromo-3-nitro-N-tosyl indole (50 mg, 0.13 mmol), n-
hexylamine (26 mg, 0.26 mmol) and cyclohexanone (26mg, 0.26 mmol) and chloranil (96 mg,
0.39 mmol). The crude product was purified by activated neutral alumina column
chromatography (2% ethyl acetate in hexane) to afford the desired product as a pale yellow
viscous liquid (50 mg, 76%). Analytical Data of 4o: TLC (SiO2): Rf; 0.41 (7% ethyl acetate in
hexane). 1H NMR (500 MHz, CDCl3, TMS): δ 8.52 (d, J = 8 Hz, 1H), 8.22 (d, J = 9 Hz, 1H), 7.70 (s,
1H), 7.57-7.54 (m, 2H), 7.45-7.27 (m, 4H), 7.03-7.00 (m, 2H), 4.35 (t, J = 7 Hz, 2H), 2.23 (s, 3H),
1.88-1.82 (m, 2H), 1.28-1.19 (m, 6H), 0.82 (t, J = 7Hz, 3H). 13C NMR (125 MHz, CDCl3): δ 144.5,
140.8, 139.3, 134.0, 129.5, 127.1, 126.8, 123.3, 121.7, 120.9, 120.3, 117.7, 117.3, 116.1, 109.9,
45.0, 31.4, 30.2, 26.6, 22.4, 21.5, 13.9. HRMS (ESI-Orbitrap) m/z: (M+Na)+ calcd for
C27H27BrN2O2SNa 545.0868; Found: 545.0874.
3-Bromo-5-(4-methoxybenzyl)-10-tosyl-5,10-dihydroindolo[3,2-b]indole (4p): The reaction
was performed according to general procedure with 5-bromo-3-nitro-N-tosyl indole (50 mg,
0.13 mmol), 4-methoxy benzylamine (36 mg, 0.26 mmol) and cyclohexanone (26mg, 0.26
mmol) and chloranil (96 mg, 0.39 mmol). The crude product was purified by activated neutral
alumina column chromatography (5% ethyl acetate in hexane) to afford the desired product as
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a white solid (49 mg, 68%). Analytical Data of 4p: Mp; 175-180 C. H NMR (500 MHz, CDCl3,
TMS): δ 8.55-8.53 (m, 1H), 8.21-8.19 (m, 1H), 7.57 (d, J = 8 Hz, 2H), 7.41-7.36 (m, 2H), 7.32-7.30
(m, 2H), 7.26-7.24 (m, 1H), 7.02 (d, J = 8 Hz, 2H), 6.96 (d, J = 9 Hz, 2H), 6.75-6.74 (m, 2H), 5.49 (s,
2H), 3.73 (s, 3H), 2.24 (s, 3H). 13C NMR (125 MHz, CDCl3): δ 159.1, 144.6, 141.2, 139.2, 134.6,
133.9, 130.2, 129.6, 127.5, 126.9, 126.8, 123.6, 121.6, 120.9, 120.7, 120.5, 117.6, 117.4, 116.4,
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114.4, 110.2, 108.3, 55.2, 48.0, 21.5. HRMS (ESI-Orbitrap) m/z: (M+Na)+ calcd for
C29H23BrN2O3SNa 581.0505; Found: 581.0509.
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3-Chloro-5-hexyl-10-tosyl-5,10-dihydroindolo[3,2-b]indole (4q): The reaction was performed
according to general procedure with 5-chloro-3-nitro-N-tosyl indole (50 mg, 0.14 mmol), n-
hexylamine (28 mg, 0.28 mmol) and cyclohexanone (27mg, 0.28 mmol) and chloranil (103 mg,
0.39 mmol). The crude product was purified by activated neutral alumina column
chromatography (2% ethyl acetate in hexane) to afford the desired product as a white solid (54
mg, 79%). Analytical Data of 4q: Mp; 135-140 oC. 1H NMR (500 MHz, CDCl3, TMS): δ 8.54 (d, J =
8 Hz, 1H), 8.28 (d, J = 9 Hz, 1H), 7.58-7.56 (m, 3H), 7.44-7.30 (m, 4H), 7.02-7.01 (m, 2H), 4.36
(t, J = 7 Hz, 2H), 2.22 (s, 3H), 1.88-1.82 (m, 2H), 1.27-1.22 (m, 6H), 0.81 (t, J = 7 Hz, 3H). 13C NMR
(125 MHz, CDCl3): δ 144.6, 140.8, 138.9, 133.9, 129.7, 129.5, 126.8, 124.4, 123.3, 121.3, 120.8,
120.3, 117.3, 116.1, 109.9, 45.1, 31.4, 30.2, 26.6, 22.4, 21.5, 13.9. HRMS (ESI-Orbitrap) m/z:
(M+Na)+ calcd for C27H27ClN2O2SNa 501.1374; Found: 501.1385.
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tert-Butyl 8-bromo-10-hexylindolo[3,2-b]indole-5(10H)-carboxylate (4r): The reaction was
performed according to general procedure with 5-bromo-3-nitro-N-Boc indole (50 mg, 0.15
mmol), n-hexylamine (30 mg, 0.30 mmol) and cyclohexanone (29 mg, 0.30 mmol) and chloranil
(111 mg, 0.45 mmol). The crude product was purified by activated neutral alumina column
chromatography (2% ethyl acetate in hexane) to afford the desired product as a pale yellow
viscous liquid (48 mg, 70%). Analytical Data of 4r: TLC (SiO2):Rf; 0.71 (7% ethyl acetate in
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hexane). H NMR (500 MHz, CDCl3, TMS): δ 8.44-8.43 (m, 1H), 8.14-8.13 (m, 1H), 7.78 (s, 1H),
7.41-7.35 (m, 2H), 7.29-7.26 (m, 1H), 7.16 (t, J = 8 Hz, 1H), 4.38 (t, J = 8 Hz, 2H), 1.92-1.86 (m,
2H), 1.79 (s, 9H), 1.38-1.25 (m, 6H), 0.85 (t, J = 7 Hz, 3H). 13C NMR (125 MHz, CDCl3): δ 159.1,
144.6, 141.2, 139.2, 134.6, 133.9, 130.2, 129.6, 127.5, 126.9, 126.8, 123.6, 121.6, 120.9, 120.7,
120.5, 117.6, 117.4, 116.4, 114.4, 110.2, 108.3, 55.2, 48.0, 21.5. HRMS (ESI-Orbitrap) m/z:
(M+Na)+ calcd for C25H29BrN2O2Na 491.1304; Found: 491.1325.
12-hexyl-7-tosyl-7,12-dihydrobenzo[g]indolo[3,2-b]indole (4s): The reaction was performed
according to general procedure with 3-nitro-N-tosyl indole (50 mg, 0.16 mmol), n-hexylamine
(32 mg, 0.32 mmol) and 1-decalone (48 mg, 0.32 mmol) and chloranil (194 mg, 0.80 mmol). The
crude product was purified by activated neutral alumina column chromatography (2% ethyl
acetate in hexane) to afford the desired product as a pale yellow viscous liquid (41 mg, 52%).
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Analytical Data of 4s: TLC (SiO2): Rf; 0.61 (7% ethyl acetate in hexane). H NMR (500 MHz,
CDCl3, TMS): δ 8.71 (d, J = 8.5 Hz, 1H), 8.43-8.36 (m, 2H), 8.04 (s, 1H), 7.71-7.68 (m, 2H), 7.59-
7.50 (m, 4H), 7.38 – 7.35 (m, 2H), 6.96 (d, J = 8 Hz, 2H), 4.87-4.84(m, 2H), 2.19 (s, 3H), 2.08-2.07
(m, 2H), 1.42-1.30 (m, 6H), 0.85-0.82 (m, 3H). 13C NMR (125 MHz, CDCl3): δ 144.3, 141.1, 133.9,
133.7, 131.7, 130.5, 129.5, 129.4, 126.8, 125.6, 124.3, 124.1, 123.9, 123.2, 122.8, 121.9, 120.8,
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120.2, 117.2, 116.8, 113.7, 48.8, 31.4, 26.4, 22.5, 21.4, 13.9. HRMS (ESI-Orbitrap) m/z: (M+Na)+
calcd for C31H30N2O2SNa 517.1920; Found: 517.1932.
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General procedure for the synthesis of benzothieno[3,2-b]indoles (6a – 6l): The enolizable
ketone, cyclohexanone (55 mg, 0.56 mmol) and primary amine, n-hexylamine (56 mg, 0.56
mmol) were weighed into a dry reaction tube. Dry toluene (0.3 mL) along with 4 Å MS (50 mg)
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was added and allowed to stir at 60 C for 1 hour, after which 3-nitro-benzo[b]thiophene (50
mg, 0.28 mmol) was added into it and again kept it for stirring at the same temperature for 11
hours. After the complete consumption of 3-nitro-benzo[b]thiophene, Chloranil (206 mg, 0.84
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mmol) along with toluene (0.7 mL) was added and kept at 100 C for 12 h. The solvent was
evaporated in vacuo and the residue on activated neutral alumina column chromatography
yielded benzothieno[3,2-b]indoles with hexanes and ethyl acetate as eluent.
Synthesis and Characerisation of benzothieno[3,2-b]indoles (6a – 6l)
10-(4-methoxybenzyl)-10H-benzo[4,5]thieno[3,2-b]indole (6a): The reaction was performed
according to general procedure with 3-nitro-benzo[b]thiophene (50 mg, 0.28 mmol), 4-methoxy
benzylamine (77 mg, 0.56 mmol) and cyclohexanone (55 mg, 0.56 mmol) and chloranil (206 mg,
0.84 mmol). The crude product was purified by activated neutral alumina column
chromatography (3% ethyl acetate in hexane) to afford the desired product as white solid (62
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mg, 65%). Analytical Data of 6a: Mp; 135-148 C. H NMR (500 MHz, CDCl3, TMS): δ 7.91-7.89
(m, 1H), 7.85-7.81 (m, 2H), 7.45 (d, J = 8 Hz, 1H), 7.35-7.31 (m, 3H), 7.24-7.20 (m, 1H), 7.10 (d, J
= 8.5 Hz, 2H), 6.83-6.79 (m, 2H), 5.76 (s, 2H), 3.73 (s, 3H). 13C NMR (125 MHz, CDCl3): δ 159.0,
143.2, 141.8, 137.7, 129.4, 127.3, 127.2, 126.9, 124.5, 124.3, 123.9, 123.2, 121.9, 120.0, 119.8,
119.5, 115.8, 114.3, 110.2, 55.3, 47.9. HRMS (ESI-Orbitrap) m/z: (M+H)+ calcd for C22H18NOS
344.1103; Found: 344.1102.
10-(benzyl)-10H-benzo[4,5]thieno[3,2-b]indole (6b): The reaction was performed according to
general procedure with 3-nitro-benzo[b]thiophene (50 mg, 0.28 mmol), benzylamine (60 mg,
0.56 mmol) and cyclohexanone (55 mg, 0.56 mmol) and chloranil (206 mg, 0.84 mmol). The
crude product was purified by activated neutral alumina column chromatography (3% ethyl
acetate in hexane) to afford the desired product as white solid (51 mg, 58%). Analytical Data of
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6b: Mp; 132-135 C. H NMR (500 MHz, CDCl3, TMS): δ 7.91-7.90 (m, 1H), 7.83-7.81 (m, 2H),
7.45 (d, J = 8.5 Hz, 1H), 7.34-7.31 (m, 4H), 7.28-7.26 (m, 1H), 7.25-7.23 (m, 2H), 7.17 (d, J = 7.5
Hz, 2H), 5.83 (s, 2H). 13C NMR (125 MHz, CDCl3): δ 143.2, 141.9, 137.4, 129.0, 127.7, 126.1,
124.5, 124.3, 123.9, 123.2, 120.0, 119.9, 119.5, 110.1, 48.4. HRMS (ESI-Orbitrap) m/z: (M+H)+
calcd for C21H16NS 314.0998; Found: 314.0986.
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10-Hexyl-10H-benzo[4,5]thieno[3,2-b]indole (6c): The reaction was performed according to
general procedure with 3-nitro-benzo[b]thiophene (50 mg, 0.28 mmol), n-hexylamine (56 mg,
0.56 mmol) and cyclohexanone (55 mg, 0.56 mmol) and chloranil (206 mg, 0.84 mmol). The
crude product was purified by activated neutral alumina column chromatography (2% ethyl
acetate in hexane) to afford the desired product as a pale yellow viscous liquid (56 mg, 65%).
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Analytical Data of 6c: TLC (SiO2): Rf; 0.72 (5% ethyl acetate in hexane). H NMR (500 MHz,
CDCl3, TMS): δ 7.99 (d, J = 8 Hz, 1H), 7.92 (d, J = 8 Hz, 1H), 7.78 (d, J = 8 Hz, 1H), 7.49-7.44 (m,
2H), 7.37-7.33 (m, 2H), 7.23-7.20 (m, 1H), 4.57 (t, J = 7.5 Hz, 2H), 1.99-1.93 (m, 2H), 1.48 -1.45
(m, 2H), 1.34-1.25 (m, 4H), 0.87 (t, J = 7 Hz, 3H). 13C NMR (125 MHz, CDCl3): δ 143.3, 141.5,
127.0, 124.6, 124.2, 123.8, 122.8, 120.0, 119.4, 115.3, 109.9, 45.1, 31.6, 30.5, 26.7, 22.5, 14.0.
HRMS (ESI-HRMS) (m/z): Calcd for C20H21NS, (M)+: 307.13947; Found: 307.13926. HRMS (ESI-
Orbitrap) m/z: (M+H)+ calcd for C20H22NS 308.1467; Found: 308.1473.
10-dodecyl-10H-benzo[4,5]thieno[3,2-b]indole (6d): The reaction was performed according to
general procedure with 3-nitro-benzo[b]thiophene (50 mg, 0.28 mmol), n-dodecylamine (104
mg, 0.56 mmol) and cyclohexanone (55 mg, 0.56 mmol) and chloranil (206 mg, 0.84 mmol). The
crude product was purified by activated neutral alumina column chromatography (2% ethyl
acetate in hexane) to afford the desired product as a pale yellow viscous liquid (68 mg, 62%).
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Analytical Data of 6d: TLC (SiO2): Rf; 0.75 (5% ethyl acetate in hexane). H NMR (500 MHz,
CDCl3, TMS): δ 7.98 (d, J = 8 Hz, 1H), 7.91 (d, J = 8 Hz, 1H), 7.77 (d, J = 8 Hz, 1H), 7.48-7.43 (m,
2H), 7.36-7.32 (m, 2H), 7.22-7.19 (m, 1H), 4.56 (t, J = 7.5 Hz, 2H), 1.98-1.92 (m, 2H), 1.46 -1.43
(m, 2H), 1.33-1.23 (m, 16H), 0.87 (t, J = 7 Hz, 3H). 13C NMR (125 MHz, CDCl3): δ 143.3, 141.5,
137.4, 127.0, 124.6, 124.3, 123.8, 122.8, 121.6, 119.9, 119.4, 115.3, 109.9, 45.1, 31.9, 30.5,
29.6, 29.5, 29.4, 29.3, 27.1, 22.7, 14.1. HRMS (ESI-Orbitrap) m/z: (M)+ calcd for C26H33NS
391.2328; Found: 391.2336.
10-(4-Methoxybenzyl)-3-phenyl-10H-benzo[4,5]thieno[3,2-b]indole (6e): The reaction was
performed according to general procedure with 3-nitro-benzo[b]thiophene (50 mg, 0.28 mmol),
4-methoxy benzylamine (77 mg, 0.56 mmol) and 4-phenyl cyclohexanone (98 mg, 0.56 mmol)
and chloranil (206 mg, 0.84 mmol). The crude product was purified by activated neutral alumina
column chromatography (3% ethyl acetate in hexane) to afford the desired product as a White
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solid (65 mg, 56%). Analytical Data of 6e: Mp; 152-155 C. H NMR (500 MHz, CDCl3, TMS):
δ 7.90-7.88 (m, 1H), 7.83-7.81 (m, 1H), 7.68 (d, J = 7.5 Hz, 2H), 7.56-7.53 (m, 1H), 7.46-7.43 (m,
3H), 7.34-7.29 (m, 3H), 7.09 (d, J = 9 Hz, 2H), 6.78 (d, J = 9 Hz, 2H), 5.71 (s, 2H), 3.70 (s, 3H). 13C
NMR (125 MHz, CDCl3): δ 159.1, 143.3, 142.0, 141.3, 138.2, 133.4, 129.3, 128.8, 127.4, 127.3,
126.6, 124.6, 124.4, 124.0, 122.9, 122.3, 120.1, 117.9, 116.0, 114.4, 110.4, 55.3, 48.0. HRMS
(ESI-Orbitrap) m/z: (M+Na)+ calcd for C28H21NOSNa 442.1236; Found: 442.1234.
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10-(4-Methoxybenzyl)-1-methyl-10H-benzo[4,5]thieno[3,2-b]indole (6f): The reaction was
performed according to general procedure with 3-nitro-benzo[b]thiophene (50 mg, 0.28 mmol),
4-methoxy benzylamine (77 mg, 0.56 mmol) and 2-methyl cyclohexanone (63 mg, 0.56 mmol)
and chloranil (206 mg, 0.84 mmol). The crude product was purified by activated neutral alumina
column chromatography (3% ethyl acetate in hexane) to afford the desired product as a whit
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solid (64 mg, 64%). Analytical Data of 6f: Mp; 135-138 C. H NMR (500 MHz, CDCl3, TMS):
δ 7.89-7.87 (m, 1H), 7.73-7.21 (m, 1H), 7.65 (d, J = 7.5 Hz, 1H), 7.28-7.27 (m, 2H), 7.12 (t, J = 7.5
Hz, 1H), 7.05-7.02 (m, 3H), 6.82 (d, J = 8.5 Hz, 2H), 5.99 (s, 2H), 3.74 (s, 3H), 2.65 (s, 3H). 13C
NMR (125 MHz, CDCl3): δ 158.9, 143.2, 138.5, 130.9, 127.1, 126.6, 126.5, 124.5, 124.2, 123.7,
122.7, 121.9, 120.1, 117.6, 114.4, 55.2, 49.7, 19.8. HRMS (ESI-Orbitrap) m/z: (M+Na)+ calcd for
C23H19NOSNa 380.1079; Found: 380.1083.
10-(4-methoxyphenyl)-10H-benzo[4,5]thieno[3,2-b]indole (6g): The reaction was performed
according to general procedure with 3-nitro-benzo[b]thiophene (50 mg, 0.28 mmol), 4-methoxy
aniline (69 mg, 0.56 mmol) and cyclohexanone (55mg, 0.56 mmol) and chloranil (206 mg, 0.84
mmol). The crude product was purified by activated neutral alumina column chromatography
(3% ethyl acetate in hexane) to afford the desired product as white solid (51 mg, 55%).
Analytical Data of 6g: Mp; 125-128 oC. 1H NMR (500 MHz, CDCl3, TMS): δ 7.89 (d, J = 8 Hz, 1H),
7.83-7.81 (m, 1H), 7.50-7.49 (m, 2H), 7.33-7.27 (m, 4H), 7.25-7.24 (m, 1H), 7.23-7.19 (m, 1H),
7.15-7.13 (m, 2H), 3.96 (s, 3H). 13C NMR (125 MHz, CDCl3): δ 159.5, 154.5, 142.9, 129.0, 124.3,
124.0, 123.9, 123.3, 122.5, 120.4, 120.2, 119.3, 114.9, 111.0, 55.6. HRMS (ESI-Orbitrap) m/z:
(M+H)+ calcd for C21H16NOS 330.0947; Found: 330.0950.
10-phenethyl-10H-benzo[4,5]thieno[3,2-b]indole (6h): The reaction was performed according
to general procedure with 3-nitro-benzo[b]thiophene (50 mg, 0.28 mmol), 2-phenylethylamine
(67 mg, 0.56 mmol) and cyclohexanone (55mg, 0.56 mmol) and chloranil (206 mg, 0.84 mmol).
The crude product was purified by activated neutral alumina column chromatography (3% ethyl
acetate in hexane) to afford the desired product as an amorphous solid (62 mg, 68%).
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Analytical Data of 6h: Mp; 98-100 C. H NMR (500 MHz, CDCl3, TMS): δ 8.00 (d, J = 8 Hz, 1H),
7.93 (d, J = 8 Hz, 1H), 7.78 (d, J = 8 Hz, 1H), 7.47-7.44 (m, 1H), 7.38-7.35 (m, 1H), 7.32-7.27 (m,
4H), 7.23-7.19 (m, 4H), 4.79 (t, J = 8 Hz, 2H), 3.21 (t, J = 8 Hz, 2H). 13C NMR (125 MHz, CDCl3):
δ 143.3, 141.3, 138.1, 137.2, 128.8, 126.8, 124.6, 124.3, 123.8, 123.0, 121.7, 119.7, 119.6,
119.4, 109.8, 46.7, 36.8. HRMS (ESI-Orbitrap) m/z: (M+H)+ calcd for C22H18NS 328.1154; Found:
328.1161.
4-(2-(10H-benzo[4,5]thieno[3,2-b]indol-10-yl)ethyl)phenol (6i): The reaction was performed
according to general procedure with 3-nitro-benzo[b]thiophene (50 mg, 0.28 mmol), tyramine
(77 mg, 0.56 mmol) and cyclohexanone (55mg, 0.56 mmol) and chloranil (206 mg, 0.84 mmol).
The crude product was purified by activated neutral alumina column chromatography (3% ethyl
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acetate in hexane) to afford the desired product as an amorphous solid (62 mg, 61%).
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Analytical Data of 6i: TLC (SiO2): Rf; 0.51 (30% ethyl acetate in hexane). H NMR (500 MHz,
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CDCl3, TMS): δ 7.98 (d, J = 8 Hz, 1H), 7.93 (d, J = 8.5 Hz, 1H), 7.77 (d, J = 8 Hz, 1H), 7.47-7.43 (m,
1H) 7.37-7.34 (m, 2H), 7.31-7.28 (m, 1H), 7.22-7.19 (m, 1H ), 7.05 (d, J = 8 Hz, 2H), 6.74-6.72 (m,
2H), 4.75 (t, J = 8 Hz, 2H), 3.14 (t, J = 8 Hz, 2H). 13C NMR (125 MHz, CDCl3): δ 154.4, 141.3,
130.4, 130.0, 126.9, 124.6, 124.3, 123.8, 122.9, 121.7, 120.2, 119.7, 119.5, 119.4, 115.6, 109.9,
46.9, 35.9. HRMS (ESI-Orbitrap) m/z: (M+Na)+ calcd for C22H17NOSNa 366.0923; Found:
366.0917.
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10-(2-(1H-indol-3-yl)ethyl)-10H-benzo[4,5]thieno[3,2-b]indole (6j): The reaction was
performed according to general procedure with 3-nitro-benzo[b]thiophene (50 mg, 0.28 mmol),
tryptamine (89 mg, 0.56 mmol) and cyclohexanone (55mg, 0.56 mmol) and chloranil (206 mg,
0.45 mmol). The crude product was purified by activated neutral alumina column
chromatography (3% ethyl acetate in hexane) to afford the desired product as an amorphous
solid (110 mg, 54%). Analytical Data of 6j: TLC (SiO2): Rf; 0.54 (20% ethyl acetate in hexane). 1H
NMR (500 MHz, CDCl3, TMS): δ 7.93–7.90 (m, 2H), 7.78 (d, J = 8 Hz, 1H), 7.69 (d, J = 7.5 Hz, 1H),
7.37–7.33 (m, 4H), 7.29-7.27 (m, 1H), 7.24–7.18 (m, 3H), 6.86 (s, 1H), 4.87 (t, J = 8 Hz, 2H), 3.39
(t, J = 7.5 Hz, 2H).13C NMR (125 MHz, CDCl3): δ 143.2, 141.4, 136.3, 124.5, 123.8, 122.9, 122.3,
119.8, 119.7, 119.5, 119.4, 118.4, 111.3, 109.9, 45.7, 29.7. HRMS (ESI-Orbitrap) m/z: (M+H)+
calcd for C24H19N2S 367.1263; Found: 367.1267.
8-bromo-10-(4-methoxybenzyl)-10H-benzo[4,5]thieno[3,2-b]indole (6k): The reaction was
performed according to general procedure with 5-bromo 3-nitro-benzo[b]thiophene (50 mg,
0.19 mmol), 4-methoxybenzylamine (53 mg, 0.38 mmol) and cyclohexanone (37 mg, 0.38
mmol) and chloranil (140 mg, 0.57 mmol). The crude product was purified by activated neutral
alumina column chromatography (3% ethyl acetate in hexane) to afford the desired product as
o
1
white solid (53 mg, 66%). Analytical Data of 6k: Mp; 118-120 C. H NMR (500 MHz, CDCl3,
TMS): δ 7.95 (s, 1H), 7.81 (d, J = 8 Hz, 1H), 7.74 (d, J = 7.5 Hz, 1H), 7.45 (d, J = 8.5 Hz, 1H), 7.41-
7.39 (m, 1H), 7.34 (t, J = 8 Hz, 1H), 7.25-7.23 (m, 1H), 7.09 (d, J = 8.5 Hz, 2H), 6.82 (d, J = 8.5 Hz,
2H), 5.71 (s, 2H), 3.75 (s, 3H). 13C NMR (125 MHz, CDCl3): δ 159.2, 142.0, 141.7, 136.5, 129.0,
128.3, 127.3, 127.2, 126.7, 125.6, 123.8, 122.8, 121.6, 120.1, 119.6, 118.1, 114.5, 110.3, 55.3,
48.0. HRMS (ESI-Orbitrap) m/z: (M)+ calcd for C22H16BrNOS 421.0130; Found: 421.0130.
8-bromo-10-dodecyl-10H-benzo[4,5]thieno[3,2-b]indole (6l): The reaction was performed
according to general procedure with 5-bromo 3-nitro-benzo[b]thiophene (50 mg, 0.19 mmol),
1-dodecylamine (70 mg, 0.38 mmol) and cyclohexanone (37 mg, 0.38 mmol) and chloranil (140
mg, 0.57 mmol). The crude product was purified by activated neutral alumina column
chromatography (3% ethyl acetate in hexane) to afford the desired product as viscous liquid (62
mg, 69%). Analytical Data of 6l: TLC (SiO2): Rf; 0.75 (7% ethyl acetate in hexane). 1H NMR (500
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MHz, CDCl3, TMS): δ 8.09 (s, 1H), 7.78-7.76 (m, 2H), 7.49 (d, J = 8 Hz, 1H), 7.45 (d, J = 8.5 Hz,
1H), 7.38-7.36 (m, 1H), 7.24-7.21(m, 1H), 4.54 (t, J = 7.5 Hz, 2H), 1.96-1.93 (m, 2H), 1.47-1.43
(m, 2H), 1.37-1.34 (m, 2H), 1.29-1.24 (m, 14H), 0.87 (t, J = 7 Hz, 3H). 13C NMR (125 MHz, CDCl3):
δ 141.7, 136.2, 128.5, 126.5, 125.7, 123.4, 122.6, 121.3, 119.6, 118.1, 116.8, 110.1, 45.1, 30.4,
29.6, 29.5, 29.4, 29.3, 27.0, 22.7, 14.1. HRMS (ESI-Orbitrap) m/z: (M)+ calcd for C26H32BrNS
469.1433; Found: 469.1435.
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Procedure for Scale up Synthesis of 4a: The enolizable ketone, cyclohexanone (621 mg, 6.33
mmol) and primary amine, n-hexylamine (640 mg, 6.33 mmol) were weighed into a dry reaction
o
tube. Dry toluene (6 mL) along with 4 Å MS (1 g) was added and allowed to stir at 60 C for 1
hour, after which 3-nitro-N-tosyl indole (1g, 3.16 mmol) was added into it and again kept for
stirring for 11 hours at the same temperature. After the complete consumption of 3-nitro-N-
tosyl indole, Chloranil (2.3 g, 9.48 mmol) along with toluene (14 mL) was added and kept for
o
stirring for 10 hours at 100 C. The solvent was evaporated in vacuo and the residue on
activated neutral alumina column chromatography yielded indolo[3,2-b]indole with mixtures of
hexane and ethyl acetate as eluent (956 mg, 68%).
Synthesis and characterization of 5-hexyl-5,10-dihydroindolo[3,2-b]indole (7): A solution of
NaOH (2.0 M, 2.0 mL) in MeOH was added to a stirring solution of of indoloindole 4a (100 mg,
0.226 mmol) in dry THF (1.0 mL) and the resulting mixture was refluxed under nitrogen for
overnight. Upon completion, the reaction mixture was concentrated under reduced pressure
and water was added and extracted with EtOAc. The organic layer washed successively with
brine and the combined organic layer was dried over anhydrous Na2SO4 and concentrated
under reduced pressure and the residue on activated neutral alumina column chromatography
(5% ethyl acetate in hexane) yielded the deprotected compound 7 as white solid (54 mg, 82%).
o
Analytical Data of 7: Mp; 145-148 C. 1H NMR (500MHz, CD3CN,TMS): δ 9.41 (brs, 1H), 7.90-
7.79 (m, 2H), 7.57-7.54 (m, 2H), 7.30-7.24 (m, 2H), 7.19-7.13 (m, 2H), 4.55 (t, J = 7 Hz, 2H),
1.95-1.92 (m, 2H), 1.31-1.22 (m, 6H), 0.82 (t, J = 7 Hz, 3H). 13C NMR (125 MHz, CD3CN): 13C NMR
(125 MHz, CD3CN): δ 141.8, 141.6, 122.9, 122.7, 119.7, 118.3, 113.3, 110.9, 45.8, 32.3, 27.3,
23.2, 14.2. HRMS (ESI-Orbitrap) m/z: (M)+ calcd for C20H22N2 290.1777; Found: 290.1780.
Synthesis and characterization of 5,10-dihexyl-5,10-dihydroindolo[3,2-b]indole (8): To a
stirred solution of 7 (100 mg, 0.34 mmol) in a mixture of THF:DMF (4:1, 5 mL), NaH (12 mg, 0.51
o
mmol) was added portion wise under nitrogen atmosphere at 0 C. The reaction mixture was
then warmed to room temperature and stirred for 30 minutes. The reaction mixture was cooled
again to 0 oC and 1-bromohexane (67 mg, 0.41 mmol) was added dropwise and stirred at room
temperature for 8 hours. Upon completion, water was added and then extracted with EtOAc.
The organic layer washed successively with brine and the combined organic layer was dried
over anhydrous Na2SO4 and concentrated under reduced pressure and the residue on activated
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neutral alumina column chromatography (2% ethyl acetate in hexane) yielded the deprotected
compound 8 as a white solid (108 mg, 85%). Analytical Data of 8: Mp; 68 C. 1H NMR
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(500MHz, CDCl3,TMS): δ 7.84-7.83 (m, 2H), 7.47-7.46 (m, 2H), 7.29-7.25 (m, 2H), 7.18-7.12 (m,
2H), 4.48 (s, 4H), 1.97-1.96 (m, 4H), 4.48 (brs, 4H), 1.30-1.26 (m, 8H), 0.84 (m, 6H). 13C NMR
(125 MHz, CDCl3): 13C NMR (125 MHz, CD3CN): δ 140.6, 125.9, 121.5, 117.9, 117.7, 114.6, 109.7,
45.3, 31.6, 30.3, 26.8, 22.5, 14.0. HRMS (ESI-Orbitrap) m/z: (M)+ calcd for C26H34N2 374.2716;
Found: 374.2736.
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Synthesis and characterization of 10-hexyl-1,2,3,4,5,10-hexahydroindolo[3,2-b]indole (9)10: A
solution of NaOH (2.0 M, 2.0 mL) in MeOH was added to a stirring solution of 10-hexyl-5-tosyl-
1,2,3,4,5,10-hexahydroindolo[3,2-b]indole (100 mg, 0.22 mmol) in dry THF (1 mL) and the
resulting mixture was refluxed under nitrogen for overnight. Upon completion, the reaction
mixture was concentrated under reduced pressure and water was added and then extracted
with EtOAc. The organic layer washed successively with brine and the combined organic layer
was dried over anhydrous Na2SO4 and concentrated under reduced pressure and the residue on
activated neutral alumina column chromatography (5% ethyl acetate in hexane) yielded the
deprotected compound 9 as an amorphous pale yellow solid (56 mg, 85%). Analytical Data of 9:
1
TLC (SiO2): Rf; 0.33 (7% ethyl acetate in hexane). H NMR (500MHz, CD3CN,TMS):
δ
8.56 (brs,
1H), 7.56-7.54 (m, 1H), 7.32-7.31 (m, 1H), 6.99-6.98 (m, 2H), 4.08 (t, J = 7 Hz, 2H), 2.71 (t, J = 6
Hz, 2H), 2.63(t, J = 6 Hz, 2H), 1.93-1.87 (m, 2H), 1.84-1.73 (m, 4H) 1.31-1.25 (m, 6H), 0.84 (t, J =
7 Hz, 3H). 13C NMR (125 MHz, CD3CN): δ 140.6, 133.0, 131.5, 120.3, 119.7, 118.5, 116.0, 111.9,
100.5, 45.2, 31.9, 31.5, 26.8, 23.8, 23.7, 23.0, 22.9, 21.9, 13.8. HRMS (ESI-Orbitrap) m/z: (M-H)+
calcd for C20H25N2 293.2012; Found: 293.2017.
Synthesis and characterization of 5,10-dihexyl-1,2,3,4,5,10-hexahydroindolo[3,2-b]indole (8-
P): To a stirred solution of 9 (100 mg, 0.34 mmol) in a mixture of THF:DMF (4:1, 5 mL), NaH (12
o
mg, 0.51 mmol) was added portion wise under nitrogen atmosphere at 0 C. The reaction
mixture was then warmed to room temperature and stirred for 30 minutes. The reaction
o
mixture was cooled again to 0 C and 1-bromohexane (67 mg, 0.41 mmol) was added dropwise
and stirred at room temperature for 8 hours. Upon completion, the reaction mixture was
concentrated under reduced pressure and water was added, and then extracted with EtOAc.
The organic layer washed successively with brine and the combined organic layer was dried
over anhydrous Na2SO4 and concentrated under reduced pressure and the residue on activated
neutral alumina column chromatography (2% ethyl acetate in hexane) yielded the deprotected
o
compound 8-P as a white solid (99 mg, 77%). Analytical Data of 8-P: Mp; 58-60 C. 1H NMR
(500MHz, CDCl3,TMS): δ 7.56 (d, J = 7.5 Hz, 1H), 7.27 (d, J = 8 Hz, 1H), 7.09 (t, J = 8 Hz, 1H), 7.03
(t, J = 7.5 Hz, 1H), 4.18 (t, J = 7.5 Hz, 2H), 4.08 (t, J = 7.5 Hz, 2H), 2.84 (t, J = 6 Hz, 2H), 2.74 (t, J =
6 Hz, 2H), 1.92 – 1.79 (m, 8H), 1.42 – 1.25 (m, 12H), 0.89-0.85 (m, 6H). 13C NMR (125 MHz,
CDCl3): 13C NMR (125 MHz, CD3CN): δ 139.8, 132.2, 132.1, 119.2, 118.9, 117.2, 115.7, 115.7,
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108.8, 99.6, 45.2, 44.9, 31.7, 31.1, 30.8, 26.9, 26.7, 23.5, 23.2, 22.8, 22.6, 22.0, 14.0. HRMS (ESI-
Orbitrap) m/z: (M+H)+ calcd for C26H39N2 379.3107; Found: 379.3114.
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Synthesis and characterization of 5-hexyl-3-phenyl-10-tosyl-5,10-dihydroindolo[3,2-b]indole
(10): A mixture of indoloindole 4o (100 mg, 0.192 mmol), phenyl boronicacid (35 mg, 0.288
mmol), Pd(PPh3)4 (21 mg, 0.019 mmol), K2CO3 (130 mg, 0.960 mmol) were weighed into a
Schlenk tube and degassed for 10 minutes. Dry THF (1.5 mL) and water (0.5 mL) was added
then, the reaction mixture was purged with argon and allowed to stir at 65 oC for 24 hours. The
solvent was evaporated in vacuum and the residue on activated neutral alumina column
chromatography (3% ethyl acetate in hexane) yielded the product as a white amorphous solid
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(81 mg, 81%). Analytical Data of 10: TLC (SiO2): Rf; 0.37 (7% ethyl acetate in hexane). H NMR
(500 MHz, CDCl3, TMS): δ 8.56 (d, J = 8 Hz, 1H), 8.40 (d, J = 8.5 Hz, 1H), 7.80 (s, 1H), 7.65-7.45
(m, 4H), 7.60 ( s, 1H), 7.49-7.45 (m, 3H), 7.39-7.30 (m, 3H), 7.02 (d, J = 8 Hz, 2H), 4.44 (t, J = 7
Hz, 2H), 2.21 (s, 3H), 1.91-1.88 (m, 2H), 1.27-1.19 (m, 6H), 0.80 (t, J = 7 Hz, 3H). 13C NMR (125
MHz, CDCl3): δ 144.4, 141.1, 140.6, 140.0, 137.3, 134.2, 130.2, 129.5, 128.9, 127.3, 127.3, 126.8,
123.9, 122.8, 120.8, 120.6, 116.1, 45.1, 31.5, 30.2, 29.7, 26.6, 22.5, 21.5, 13.9. HRMS (ESI-
Orbitrap) m/z: (M+H)+ calcd for C33H33N2O2S 521.2257; Found: 521.2259.
Acknowledgements
The authors thank Dr. K. V. Radhakrishnan, Principal Scientist, CSIR-NIIST for the constructive
discussions. SPV and GD thanks UGC and CSIR for research fellowship. J.J. thanks Department of
Science and Technology (DST)-SERB, India, for a Young Scientist Start-Up Research Grant
(SB/FT/CS-107/2014). V.K.P. thanks DST-SERB, Government of India for a Young Scientist
Fellowship. The authors also thank Mrs. Saumini Mathew, Mrs. Viji S. and Ms. Aathira S. of
CSIR-NIIST for recording NMR and mass spectra respectively. We would also like to
acknowledge the editorial team and reviewers for the constructive comments and suggestions.
Supporting Information
The Supporting Information is available free of charge on the ACS Publications website.
Copies of 1H and 13C NMR spectra of all newly synthesized compounds (PDF) and
crystallographic data for 4c.
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