A mild and sequentially Pd/Cu-catalyzed domino synthesis of acidochromic Indolo[3,2-a]carbazoles – Free bases of apocyanine dyes

Article abstract of DOI:10.1016/j.dyepig.2019.107890

A sequentially Pd(II)/Cu(II)-catalyzed dimerization of indoles with subsequent oxidative cycloaromatization with alkynes give rise to the formation of strongly violet to blue solution and solid state emissive indolo[3,2-a]carbazoles in a domino fashion un

Full text of DOI:10.1016/j.dyepig.2019.107890

Journal Pre-proof
A mild and sequentially Pd/Cu-catalyzed domino synthesis of acidochromic
Indolo[3,2-a]carbazoles – Free bases of apocyanine dyes
Patrik Niesobski, Jennifer Nau, Lars May, Alae-Eddine Moubsit, Thomas J.J. Müller
PII:
S0143-7208(19)31393-2
DOI:
https://doi.org/10.1016/j.dyepig.2019.107890
DYPI 107890
Reference:
To appear in: Dyes and Pigments
Received Date: 14 June 2019
Revised Date: 7 August 2019
Accepted Date: 16 September 2019
Please cite this article as: Niesobski P, Nau J, May L, Moubsit A-E, Müller TJJ, A mild and sequentially
Pd/Cu-catalyzed domino synthesis of acidochromic Indolo[3,2-a]carbazoles – Free bases of apocyanine
dyes, Dyes and Pigments (2019), doi: https://doi.org/10.1016/j.dyepig.2019.107890.
This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition
of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of
record. This version will undergo additional copyediting, typesetting and review before it is published
in its final form, but we are providing this version to give early visibility of the article. Please note that,
during the production process, errors may be discovered which could affect the content, and all legal
disclaimers that apply to the journal pertain.
© 2019 Published by Elsevier Ltd.

A Mild and Sequentially Pd/Cu-catalyzed Domino Synthesis of Acidochromic Indolo[3,2-
a]carbazoles – Free Bases of Apocyanine Dyes
Patrik Niesobski,a Jennifer Nau,a Lars May,a Alae-Eddine Moubsit,a and Thomas J. J. Müller*,a
aInstitut für Organische Chemie und Makromolekulare Chemie, Heinrich-Heine-Universität
Düsseldorf, Universitätsstrasse 1, D-40225 Düsseldorf, Germany
Email: ThomasJJ.Mueller@hhu.de
Keywords: Acidochromism; Apocyanine Dyes; Domino Reaction; Fluorescence; Indolo[3,2-
a]carbazoles; Sequential Catalysis.
ABSTRACT
A sequentially Pd(II)/Cu(II)-catalyzed dimerization of indoles with subsequent oxidative
cycloaromatization with alkynes give rise to the formation of strongly violet to blue solution and solid
state emissive indolo[3,2-a]carbazoles in a domino fashion under mild conditions and in moderate to
good yields. Upon protonation the absorption bands are significantly red-shifted with concomitant
quenching of the fluorescence. The site of protonation was scrutinized by NMR studies of the
protonated species and confirmed by DFT calculations. The obtained chromophores of the
acidochromicity of the title compounds are rarely described apocyanine dyes. The relevant absorption
bands can be unambiguously assigned by TDDFT calculations.
1

1.
Introduction
The steadily growing quest for novel functional organic materials, such as chromophores, fluorophores
and electrophores [1], with heterocyclic core structures is an ongoing challenge for synthetic chemistry
and in recent years the concepts of multicomponent processes [2] and domino reactions [3] have
opened new opportunities for modular syntheses of these targets. These functional π-systems are
underlying molecular entities in molecule based electronics such as organic light-emitting diodes
(OLEDs) [4], dye-sensitized solar cells (DSSCs) [5], and organic photovoltaics (OPVs) [6], or bio and
environmental analytics [7]. Particularly interesting are sensitive dyes which undergo changes in their
absorption and/or emission properties by external stimuli such as light [8], heat [9], current [10],
mechanical pressure [11], solvent polarity [12] or pH changes [13]. The latter phenomenon is called
halo- or acidochromism founding the principle of pH indicators [14] and smart inks [15]. In addition,
fluorohalochromic dyes, which are both fluorescent and halochromic have as dual readout
chromophores advantages such as high sensitivity and fast read-outs using relatively simple and
inexpensive instruments, for instance by ratiometric intensity analysis at a certain wavelengths [16].
With respect to intensity, for instance fluorescent chemosensors, in particular fused nitrogen
heterocycles, are either quenched (turn OFF) or induced (turn ON) upon protonation.
First indolocarbazoles [17] were first mentioned in the late 1950s [18], but received attention only 30
years later, when biologically active natural products such as the alkaloids K-252a [19] or
staurosporine [20] were isolated. Ever since this scaffold has not only been used for the development
of potential novel drugs [21] but increasingly for conceptualizing functional materials [22]. Out of five
possible isomers, indolo[3,2-a]carbazoles have scarcely been studied, but in the last few years some
methods have been developed starting from hydrazines [23], 2,3-biindolyls [24], and indoles [25].
Very recently, Kumar's group has disclosed a Pd-catalyzed [2 + 2 + 2] annulation of indoles or
azaindoles with alkynes, starting with indoles dimerization to give 2,3-biindolyls, which subsequently
cyclizes with alkynes giving indolo[3,2-a]carbazoles (Scheme 1a), however, substrates with strongly
electron withdrawing groups were not converted [26]. About the same time, motivated by our interest
in sequentially bimetallically Pd/Cu-catalyzed processes [27] as a rapid entry to multicomponent
syntheses of heterocycles in a one-pot fashion [28], we probed the reaction of indoles and alkynes at
2

lower temperatures in the presence of Pd(II) and Cu(II) catalysts to give intensively luminescent
indolo[3,2-a]carbazoles (Scheme 1b).
Scheme 1. Approaches to the domino synthesis of indolo[3,2-a]carbazoles.
As part of our program to explore diversity oriented one-pot syntheses of functional chromophores by
multicomponent [1] and domino reactions [3], we have reported domino syntheses of protochromic
“ON–OFF–ON” luminescent 2-styryl quinolines [29] and “OFF–ON” cation-induced fluorescent 2,4-
diarylpyrano[2,3-b]indoles [30]. Herein, we report a modified pseudo-three-component synthesis of
electronically interesting indolo[3,2-a]carbazoles, a class of tetracyclic fused indoles and discuss their
hitherto unexplored photophysical properties and acidochromicity.
2.
Results and discussion
Synthesis
2.1.
The reaction of 1-methylindole (1a) (R1 = H) and tolane (2a) (R2 = R3 = Ph) in DMSO in the presence
of catalytic amounts of Pd(OAc)2 and Cu(OAc)2 · H2O as an oxidant under oxygen atmosphere was
selected as a model system and optimized (for the optimization, see Supp Inf Table S1). Unlike
Kumar's work, whose optimization was initiated at 80 °C by variation of the cooxidant, we started the
domino reaction at room temp with a stoichiometric amount of Cu(OAc)2 · H2O and then successively
increased the reaction temperature and reduced the amount of copper oxidant to find that at 50 ° C and
3

in the presence of catalytic amounts of Cu(II) salts, the best result was achieved, whereas without
cooxidant as well as at 80 °C significantly less yield was observed. Kumar, on the other hand, who had
also experimented with Cu(OAc)2, found out that omitting the cooxidant at 80 °C led to more product
but could not reproduce the yield at lower temperatures [26]. As such, we decided to synthesize and
discuss only electronically interesting indolo[3,2-a]carbazole with our conditions, a modified, milder
variant of Kumar's method, and therefore the preparative studies were performed with electron-rich
and electron-poor 1-methyl indoles 1 and alkynes 2 to give 5,12-dimethyl-indolo[3,2-a]carbazoles 3 in
moderate to good yields in the sense of a domino reaction representing a quadruple CH-
functionalization (Scheme 2). All title compounds 3 were isolated as colorless solids which fluoresce
violet to blue both in solution and in the solid state. The structural assignment was unambiguously
1
corroborated by extensive H and 13C NMR and IR spectroscopy, and mass spectrometry, and the
molecular composition was verified by combustion analyses.
Scheme 2. Pseudo-three-component domino synthesis of indolo[3,2-a]carbazoles 3 by oxidative
Pd/Cu-catalyzed quadruple CH-functionalization of indoles 1 with alkynes 2.
With this protocol electron-donating methoxy substituents can be introduced either via the indole or
the alkyne (Table 1, entries 2 and 3), as well as the strongly electron withdrawing cyano groups after a
prolonged reaction time of 24 h (Table 1, entries 5 and 6), in contrast to Kumar’s method [26]. While
the methoxy substituent can be simultaneously incorporated via both starting materials (Table 1, entry
4), this transformation does not work with the cyano group.
In addition to Kumar’s work, the triisopropyl-protected alkyne 2d was selectively transformed into the
simply phenylated indolocarbazole 3g (Table 1, entry 7). To the best of our knowledge, only one
method has been developed for 7-phenylindolo[3,2-a]carbazoles to date, starting from indoles and β-
nitrostyrenes that are reacted with tin and manganese salts for prolonged reaction times to give only
4

low yields [31]. Here, the selectivity is very likely affected by the steric hindrance of the TIPS
substituent which is cleaved off in the course of the reaction. Kumar [26] proposed a mechanistic
rationale that commences with an electrophilic palladation, followed by subsequent migration [32],
insertion of the second indole and reductive elimination [33] to form 2,3-biindolyls. The subsequent
palladium-catalyzed oxidative cycloaromatization of the intermediate with alkyne via dual CH-
activation leads to the title compounds 3 [24]. In our approach, the addition of catalytic amounts of
copper acetate allows to lower the reaction temperature, presumably due to a more efficient
reoxidation of the palladium catalyst, comparable to Wacker oxidations [34].
Table 1. Pseudo-three-component domino synthesis of indolo[3,2-a]carbazoles 3.
entry
indole 1
alkyne 2
indolo[3,2-a]carbazole 3 (yield)[b]
1[c]
R1 = H (1a)
R2 = R3 = Ph (2a)
3a (72%)
2[c]
R1 = OMe (1b)
2a
3b (73%)
3[c]
R2 = R3 = p-MeOC6H4 (2b)
1a
3c (68%)
4[c]
1b
2b
3d (60%)
5

5[d]
R1 = CN (1c)
2a
3e (58%)
6[d]
R2 = R3 = p-NCC6H4 (2c)
1a
1a
3f (51%)
3g (68%)
7[c][e]
R2 = Ph, R3 = SiiPr3 (2d)
[a] Reaction conditions: indole 1 (0.50 mmol), alkyne 2 (0.25 mmol), Pd(OAc)2 (0.05 mmol),
Cu(OAc)2 · H2O (0.125 mmol), DMSO (5 mL), 50 °C under O2.[b] Isolated yield. [c] Reaction time: 8
h. [d] Reaction time: 24 h. [e] 0.50 mmol of 2d.
2.2.
Photophysical properties
Already previous studies on substituted indolo[3,2-a]carbazoles indicated interesting photophysical
properties [24]. With a small library of 5,12-dimethyl-indolo[3,2-a]carbazoles in hand we decided to
assess the substitution effects on the optical properties. All derivatives were characterized by
quantitative absorption and emission spectroscopy as well as relative fluorescence quantum yields ΦF
were determined (Table 2).
Table 2. Selected photophysical properties of indolo[3,2-a]carbazoles 3 (recorded in CH2Cl2 at T =
293 K).
λ
max,em [nm] [b]
Stokes shift ∆ν̃
max,abs [nm] (ε
[L·mol-1·cm-1])[a]
entry compound
λ
[cm-1][d]
[c]
(
Φf )
250 (41100), 295 (53600), 354 (10100), 370
(16000)
253 (47400), 282 (44700), 311 (41200), 349
(11400), 365 (14900)
253 (46100), 296 (59100), 354 (11000), 370
(17600)
1
2
3
390 (0.50)
395 (0.45)
389 (0.52)
3a
3b
3c
1400
2100
1300
249 (44900), 303 (50700), 365 (10500), 383
(16900)
298 (80900), 358 (10300), 375 (17100)
244 (55500), 292 (44400), 355 (11400), 372
(15200)
4
5
6
7
403 (0.48)
391 (0.52)
436 (0.29)
407 (0.54)
3d
3e
3f
1300
2400
4000
2800
251 (39300), 295 (45200), 350 (9200), 366
3g
6

(11800)
[a] c(3) = 10-5
M
. [b] c(3) = 10-7
M
,
λexc = 280 nm. [c] Recorded at λexc = 280 nm, c(3) = 10-7
M,
-1
determined with 2,5-diphenyloxazole as a standard in cyclohexane, (
Φ
F=1.00 [35]). [d] ∆
ν
̃
=
λmax(abs)
-1
-
λmax(em)
.
Generally, the absorption characteristics of all compounds are quite similar, whereby the longest
wavelength absorption band appears at around 370 nm. The compounds 3a-g show a strong blue
luminescence in solution (dichloromethane) (Figure 1), with Stokes shifts in a range from 1300 to
4000 cm-1. The emission maximum of the derivatives 3a-c and 3e can all be found at around 390 nm
(Figure 2). The tetramethoxy substituted indolo[3,2-a]carbazole 3d is slightly bathochromic shifted
emission maximum at 403 nm, also the unsymmetrically substituted indolo[3,2-a]carbazole 3g
displays a slight red-shift to 407 nm in comparison to compound 3a. For the cyano-substituted
derivative 3f substantial bathochromic shift to 436 nm is determined.
Figure 1. Visual impression of indolocarbazoles 3 under daylight (top) and hand-held UV lamp
(bottom) in dichloromethane (c(3) = 10-5
M
, λexc = 365 nm).
7

Figure 2. Normalized UV/Vis absorption (recorded in CH2Cl2, T = 293 K, c(3) = 10-5, bold line) and
emission bands (recorded in CH2Cl2, T = 293 K, c(3) = 10-7,
dashed line) of indolocarbazoles 3a,c,f,g.
λexc(3a) = 294 nm, λexc(3c,f,g) = 280 nm,
Furthermore, relative fluorescence quantum yields [36] were measured with 2,5-diphenyloxazole as a
standard in cyclohexane (ΦF = 1.00 [35]). The compounds 3a-e and 3g show a similar distinctive
fluorescence in dichloromethane with quantum yields ranging from 45 to 54%. Interestingly, only the
p-cyanophenyl substitution in positions R2 and R3 (3f) leads to a significant decrease in fluorescence
(ΦF = 29%).
Most remarkably, the addition of trifluoroacetic acid clearly changes the absorption and emission
spectra of the indolocarbazoles 3, which is a consequence of a selective protonation of the carbazole
core (vide infra). This acidochromism was studied by absorption spectroscopy for all indolo[3,2-
a]carbazoles 3 (Table 3).
8

Table 3. Comparison of absorption maxima of non-protonated 3 and protonated indolo[3,2-
a]carbazoles 3-H+.
λ
max,abs [nm] (
3
ε
[L·mol-1·cm-1])[a]
3-H+[b]
entry compound
acidochromicity shift [cm-1][c]
6200
277 (31400), 297
(30100), 367 (6300),
479 (12200)
250 (41100), 295 (53600),
354 (10100), 370 (16000)
1
2
3
3a
3b
3c
253 (47400), 282 (44700),
311 (41200), 349 (11400),
365 (14900)
297 (40500), 363sh
(8000), 499 (8300)
7400
6300
278 (27800), 300
(23400), 399sh (5800),
482 (10200)
253 (46100), 296 (59100),
354 (11000), 370 (17600)
249 (44900), 303 (50700),
365 (10500), 383 (16900)
298 (80900), 358 (10300),
375 (17100)
244 (55500), 292 (44400),
355 (11400), 372 (15200)
287sh (25500), 301
(28500), 506 (9000)
301 (68700), 358
(10400), 375 (15600)
280 (38200), 289
(38500), 372 (11600)
277 (21400), 295
(22400), 368 (4300),
466 (9300)
4
5
6
6300
3d
3e
3f
0
0
251 (39300), 295 (45200),
350 (9200), 366 (11800)
7
5900
3g
[a] Recorded in CH2Cl2, T = 293 K, c = 10-5 M. [b] Transferred into the cell (3 mL), addition of 200
-1
-1
µL trifluoroacetic acid (TFA). [c] ∆ν̃ = λmax(abs[3]) - λmax(abs[3-H+]) .
All free bases give colorless solutions, whereby after addition of trifluoroacetic acid (TFA) the
methoxy and phenyl derivates 3a-d and 3g became yellow to red solutions (Figure 3). Interestingly, in
the protonation studies with cyano-substituted indolo[3,2-a]carbazoles 3e and 3f no significant change
in the absorption spectra was detected. Presumably by strongly electron withdrawing cyano groups
their basicity is too low.
9

Figure 3. Visual color impression of indolocarbazoles 3 under daylight (top) and hand-held UV lamp
(bottom) after the addition of TFA (recorded in CH2Cl2, c(3) = 10-4 M,
λ
exc = 365 nm).
In all other absorption spectra of the conjugated indolocarbazole salts of 3a-d and 3g, a new red-
shifted absorption maximum forms between 466 and 506 nm. Thereby the tetramethoxy substituted
indolo[3,2-a]carbazole 3d shows the largest bathochromic shift with an absorption maximum at
506 nm. Moreover, the acidochromic shifts of compounds 3a-d and 3g range from 5900 (3g) to 7400
cm-1 (3b). The protonation has also an interesting effect on the emission properties of the indolo[3,2-
a]carbazoles. The fluorescence of all compounds, including the cyano-substituted derivatives, is
noticeably quenched after addition of an excess amount of TFA. The process can be reversed by
adding triethylamine and all solutions are colorless again as prior to the treatment with TFA, and they
fluoresce violet to blue under the hand-held UV lamp.
In addition, we photometrically determined the pKa value of the conjugated base of 3a. Therefore,
trifluoroacetic acid was chosen as a suitable acid because it is completely dissociated in
dichloromethane. For the pKa determination by absorption spectroscopy, the pH-value was
10

successively lowered from 1.58 to 0.28 and the corresponding absorption spectra were recorded
(Figure 4). With successive addition of TFA, the maxima at 354 and 370 nm of 3a disappear and a
new red-shifted maximum at 480 nm was detected for the protonated species 3a-H+. From these
titrations a pKa value of 0.75 for 3a-H+ was determined (for experimental details, see Supp Inf).
Figure 4. Absorption spectra of 3a in the presence of increasing amounts of TFA (recorded in CH2Cl2,
c(3a) = 10-5 m, T = 293 K).
Furthermore, the fluorescence quenching of 3a after addition of trifluoroacetic acid was quantitatively
monitored (Figure 5).
11

Figure 5. Emission spectra of 3a in the presence of increasing aliquots of TFA (recorded in CH2Cl2,
c(3a) = 10-7 m, T = 293 K,
λ
exc = 294 nm).
The Stern-Volmer plot of F0/F against the concentration of TFA reveals a linear correlation (Figure 6)
and the Stern-Volmer constant Ksv was determined to 49.940 Lmol-1. The Stern-Volmer constant Ksv
correlates by definition of steady-state quenching to the pKa value of 3a. The pKa is calculated
therefrom to 1.97, which is in reasonably good agreement with pKa value determined by absorption
spectroscopy.
12

Figure 6. Stern-Volmer plot of 3a (c0(3a) = 10-7 m in CH2Cl2, T = 293 K, λmax(em) = 390 nm; F0/F =
0.52932 + 49.904[H+]; r2 = 0.97826).
2.3.
NMR protonation studies
Intrigued by the observed acidochromocity of the title compounds 3, NMR studies were performed to
localize the protonation site of indolo[3,2-a]carbazoles 3. The 1H NMR spectra of 3a and 3a-H+ reveal
that upon protonation only a single new species was formed, supported by the appearance of a single
set of signals, accompanied by an additional singlet at
δ 5.37 arising from the trifluoroacetic acid
proton (Figure 7). 2D NMR experiments, such as NOESY and HMBC, allowed the unambiguous
assignment of position 6 as the site of protonation (for details and spectra, see Supp Inf). In principle,
most of the signals of the protonated species 3a-H+ are shifted to lower field, where increased
deshielding indicates the formation of a resonance stabilized cation. For instance, the methyl protons
at position 5 are shifted from δ
3.26 (3a) to 3.73 (3a-H+). The protonation of 3a to 3a-H+ also causes a
significant change in the molecular geometry supported by the splitting the phenyl proton resonances.
The resonances of 6-Ph (blue circles, Figure 7) split into a doublet and two triplets, which is indicative
of the free rotation of the phenyl ring, whereas for 7-Ph (orange circles, Figure 7) split into five
13

broaden signals that appear between
δ 6.59 and 7.72. This phenyl ring obviously is considerably
restricted in its rotational freedom and therefore splits into five chemically inequivalent signals.
Figure 7. Partial 1H NMR spectra (600 MHz, 293 K, CD2Cl2) of 3a before (a) and after (b) the addition
of 75 equiv of CF3CO2H.
2.4.
Calculated electronic structure
Ground state geometries of all structures 3 and 3a-H+ were optimized using the Gaussian09 program
package [37], the PBE0 hybrid-functional by Perdew, Burke and Ernzerhof [38] and the 6-311G(d,p)
basis set [39]. The optimized geometries were confirmed as minima by analytical frequency analyses.
14

Excitation energies were calculated with TDDFT [40] methods implemented in the Gaussian09
program package [37], PBE0 [38], and the 6-311+G(d,p) basis set [39]. The polarizable continuum
model (PCM) with dichloromethane as a solvent was applied for the calculations each [41]. The
Mulliken population analysis was extracted from the Gaussian09 calculation outputs by the help of the
Multiwfn software [42].
The site of protonation in structure 3a-H+, experimentally assigned by NMR experiments, was further
corroborated by DFT calculations also to gain a deeper insight into the observed acidochromism. All
ground state geometries and excitation energies of the protonated species 3a-H+ and 3a were calculated
(for details, see Supp Inf). We hypothesized that in addition to the two indolyl nitrogen atoms, the
three β-positions of the indoles are potential sites of protonation, i.e. a total of five different
protonation sites have to be considered (Figure 8). The calculations on the different protonated species
3a-H+ reveal in agreement with the NMR spectroscopic study that protonation at position 6 forms the
thermodynamically most stable cation (Table 4). Moreover, the position bearing the largest HOMO
coefficient in the non-protonated compound 3a was protonated (Table 4).
Figure 8. Potential protonation sites of 3a.
Table 4. Relative free enthalpies (PBE0/6-311G(d,p) PCM CH2Cl2) of 3a-H+ protonated in all tested
positions and the corresponding HOMO-coefficients of non-protonated 3a.
position i
5
6
0
7a
12
12b
+13.30
0.26
+8.81
13.28
+9.11
13.64
+6.00
5.63
∆∆G(position i → position 6) [kcal/mol]
HOMO coefficients of 3a [%]
15.52
15

For the structure 3a-H+ with protonation at position 6 the UV/Vis spectrum was calculated on the
TDDFT level of theory. The first states S1, S2, and S3 nicely reproduce the experimentally observed
absorption bands (Table 5). While the longest wavelength absorption band (S1) can be described as a
HOMO→LUMO transition (99%), the following bands consist of HOMO-2→LUMO (S2, 94 %) and
HOMO→LUMO+1 transitions (S3, 84%) (for full details, see Supp Inf).
Table 5. Comparison of calculated UV/Vis-absorption of 3a-H+ (PBE0/6-311+G(d,p) PCM CH2Cl2),
protonated in position 6, and experimental UV/Vis-absorption of 3a-H+.
λmax, exp[a] [nm]
λmax, calc[b] [nm]
oscillator strength
0.245
FMO contribution
HOMO → LUMO (99 %)
479
458
HOMO-2 → LUMO (94 %)
HOMO→LUMO+1 (3 %)
HOMO-7 → LUMO (7 %)
HOMO-2 → LUMO (3 %)
HOMO → LUMO+1 (84 %)
HOMO-8 → LUMO (20 %)
HOMO-5 → LUMO+1 (2 %)
HOMO-1 → LUMO+1 (47 %)
HOMO-1 → LUMO+2 (9 %)
HOMO → LUMO+2 (8 %)
HOMO → LUMO+7 (3 %)
HOMO → LUMO+8 (3 %)
367
360
0.162
297
288
0.544
277
256
0.387
[a] Recorded in CH2Cl2, c(3a) = 10-5 M, pH = 0.25, T = 293 K. [b] PBE0/6-311+G(d,p) with PCM
(CH2Cl2).
Based upon the spectroscopic and computational studies supporting the protonation of structure 3a at
position 6 resonance structures of 3a-H+ can be assigned, suggesting that the formed chromophore is
an apocyanine (Figure 9). An apocyanine is a rare type of cyanine where the two terminal nitrogen
atoms are conjugatively linked without methine groups, i.e. only quaternary sp2-hybridized carbon
centers [43]. This special topology rationalizes the bathochromic shift upon protonation (Figure 10).
As seen from the NMR studies both phenyl groups are no longer parallel to each other and the
substituent at position 7 planarizes with the indolocarbazole and participates in the conjugation with
the apocyanine system.
16

H
H
N
N
N
N
Figure 9. Resonance structures of a closed apocyanine system (red) arising from protonation of
compound 3a.
Figure 10. Jablonski diagram before (left) and after (right) protonation of 3a and assignment of the
FMO-transitions in the longest wavelength absorption bands (PBE0/6-311+G(d,p) PCM CH2Cl2,
isosurface value at 0.04 a.u.).
17

3.
Conclusion
In summary starting from indoles and alkynes we have disclosed an efficient and mild sequentially
Pd(II)/Cu(II)-catalyzed pseudo-three-component domino reaction to give indolo[3,2-a]carbazoles even
with strongly electron withdrawing groups. In addition, with a TIPS-protected alkyne as a substrate, it
was possible to selectively obtain the mono-phenylated 7-phenylindolo[3,2-a]carbazole via in situ
desilylation. The study of the electronic properties of the indolocarbazoles revealed in addition to the
known fluorescence, to the best of our knowledge a hitherto unknown acidochromism of this class of
compounds, indicating that the title compounds are reversibly pH-sensitive. The protonation site was
unambiguously localized by NMR spectroscopy and confirmed by quantum chemical calculations.
Protonation generates a rarely described intensively orange to red apocyanine system. Syntheses and
applications of these novel electronically interesting apocyanine dyes are currently underway.
4.
Experimental
4.1.
General considerations
All reactions were carried out in flame-dried Schlenk tubes by using syringes under an oxygen
atmosphere. Oxygen was used from a bottle of Air Liquide (ALPHAGAZTM 1 O2, 99.998 %). Indoles
1b [44] and 1c [32], as well as alkynes 2b [45], 2c [45], and 2d [46] were synthesized according to
literature procedures as indicated. Commercial grade reagents were purchased from Sigma Aldrich,
Alfa Aesar, ABCR, Fluorochem and ACROS and used as supplied without further purification. Crude
mixtures were adsorbed on Celite® 545 (0.02-0.20 mm) from Carl Roth GmbH Co.KG. The
purification of products was performed on silica gel 60 M (0.04–0.063 mm) from Macherey–Nagel by
using the flash technique under a pressure of 2 bar. For TLC silica gel coated aluminium plates (60,
1
13
F254) from Merck were employed. The spots were detected with UV light at 254 or 365 nm. H, C,
and DEPT NMR spectra were recorded at 293 K on 300 MHz (Bruker AVIII) or 600 MHz
(BrukerAvance III-600) and the resonances of the residues of non-deuterated CD2Cl2 were locked as
1
internal standards (CD2Cl2: H
δ δ = 54.00 ppm). The multiplicities of signals are
= 5.32 ppm, 13C
abbreviated as follows: s = singlet, d = doublet, t = triplet, dd = doublet of doublets, ddd = doublet of
18

doublets of doublets and m = multiplet. The assignments of Cquat, CH, CH2 and CH3 nuclei are based
on DEPT spectra. IR spectra were recorded on a Shimadzu IR Affinity-1 with ATR technique. The
intensities of IR signals are abbreviated as s (strong), m (medium) and w (weak). EI mass spectra were
recorded on Triple-Quadrupole mass spectrometer TSQ 7000 (Finnigan MAT). Absorption spectra
were recorded in CH2Cl2 high performance liquid chromatography (HPLC) grade at 293 K on Perkin
Elmer UV/VIS/ NIR Lambda 19 spectrometer. Emission spectra were recorded in CH2Cl2 HPLC
grade at 293 K on a Perkin Elmer LS55 spectrometer. The melting points (uncorrected) were measured
on a Büchi Melting Point B-540. The elemental analyses were carried out on a Perkin Elmer Series II
Analyser 2400 at the Institute for Pharmaceutical and Medicinal Chemistry at Heinrich-Heine-
University Düsseldorf.
4.2.
General procedure (GP) for the domino synthesis of indolo[3,2-a]carbazoles 3
Palladium(II)acetate (11.2 mg, 50.0 µmol, 10 mol%), copper(II)acetate monohydrate (24.9 mg, 125
µmol, 25 mol%), indole 1 (500 µmol, 1.00 equiv) and/or alkyne 2 (250 µmol, 0.50 equivs), if solid,
were placed in a Schlenk tube, which was evacuated and flushed with oxygen three times. Then,
indole 1 (500 µmol, 1.00 eq.) and/or alkyne 2 (250 µmol, 0.50 equivs), if present as a liquid, and
DMSO (5 mL) were added. The reaction mixture was stirred until complete conversion (8 or 24 h,
monitored by TLC, eluent: n-hexane/ethyl acetate) at 50 °C under an oxygen atmosphere. After
cooling to room temp, the solvent was removed under reduced pressure, the product mixture adsorbed
on Celite® and purified by column chromatography on silica gel (eluent: n-hexane/dichloromethane).
Table 6. Experimental details of the domino synthesis of indolo[3,2-a]carbazoles 3.
indolo[3,2-a]carbazoles 3
entry
indole 1
alkyne 2
(yield)
65.6 mg (0.50 mmol) of 1-
methylindole (1a)
80.6 mg (0.50 mmol) of 5-
methoxy-1-methylindole (1b)
44.6 mg (0.25 mmol) of tolane (2a)
44.6 mg (0.25 mmol) of 2a
78.7 mg (72%) of 3a
1
2
90.8 mg (73%) of 3b
57.1 mg (0.25 mmol) of 1,2-bis(4-
methoxyphenyl)ethyne (2b)
57.1 mg (0.25 mmol) of 2b
65.6 mg (0.50 mmol) of 1a
85.0 mg (68%) of 3c
83.3 mg (60%) of 3d
3
4
80.6 mg (0.50 mmol) of 1b
78.1 mg (0.50 mmol) of 1-
methyl-indole-5-carbonitrile
(2c)
44.6 mg (0.25 mmol) of 2a
70.0 mg (58%) of 3e
62.5 mg (51%) of 3f
5
6
57.1 mg (0.25 mmol) of 4,4'-(ethyne-
65.6 mg (0.50 mmol) of 1a
1,2-diyl)dibenzonitrile (2c)
19

129 mg (0.50 mmol) of
triisopropyl(phenylethynyl)silane (2d)
65.6 mg (0.50 mmol) of 1a
61.5 mg (68%) of 3g
7
4.2.1. 5,12-Dimethyl-6,7-diphenyl-5,12-dihydroindolo[3,2-a]carbazole (3a)
According to the GP compound 3a (78.7 mg, 72%) was obtained as a colorless solid. Mp 141–142 °C
1
(lit. 140–142 °C [26]). H NMR (CD2Cl2, 600 MHz):
δ 3.14 (s, 3 H), 4.39 (s, 3 H), 6.32 (d, J = 7.9
Hz, 1 H), 6.76 (t, J = 7.5 Hz, 1 H), 7.10–7.15 (m, 5 H), 7.15–7.25 (m, 7 H), 7.32 (d, J = 8.1 Hz, 1 H),
7.37 (t, J = 7.6 Hz, 2 H), 8.54 (d, J = 8.1 Hz, 1 H). 13C NMR (CD2Cl2, 151 MHz):
δ
33.3 (CH3), 36.0
(CH3), 107.6 (Cquat), 109.5 (CH), 109.7 (CH), 115.5 (Cquat), 118.9 (Cquat), 119.7 (2xCH), 121.3 (Cquat),
121.5 (CH), 123.2 (CH), 124.3 (CH), 124.9 (CH), 124.9 (Cquat), 127.2 (CH), 127.2 (CH), 127.8 (CH),
128.4 (CH), 130.9 (CH), 133.0 (CH), 136.1 (Cquat), 137.4 (Cquat), 139.4 (Cquat), 139.8 (Cquat), 140.9
(Cquat), 142.4 (Cquat), 142.9 (Cquat). EI-MS (70 eV, m/z (%)): 436 ([M]+, 100), 421 ([M-CH3]+, 15), 406
([M-2x(CH3)]+, 9), 203 (16), 202 (17), 201 (11), 196 (11). IR (ATR): [cm-1] 3044 (w), 1580 (m),
ν̃
1570 (m), 1558 (m), 1441 (m), 1329 (m), 1315 (m), 1256 (m), 1024 (m), 968 (m), 918 (m), 768 (m),
752 (m), 729 (s), 718 (s). Anal. calcd. for C32H24N2 (436.6): C 88.04, H 5.54, N 6.42; Found: C 88.11,
H 5.55, N 6.20.
4.2.2. 2,9-Dimethoxy-5,12-dimethyl-6,7-diphenyl-5,12-dihydroindolo[3,2-a]carbazole (3b)
According to the GP compound 3b (90.8 mg, 73%) was obtained as a colorless solid. Mp 197–198 °C
(lit. 160–165 °C [26]). 1H NMR (CD2Cl2, 600 MHz):
δ 3.19 (s, 3 H), 3.88 (s, 3 H), 3.94 (s, 3 H), 4.41
(s, 3 H), 6.29 (d, J = 8.2 Hz, 1 H), 6.48 (dd, J = 8.6, 2.1 Hz, 1 H), 6.86 (s, 1 H), 6.91–6.94 (m, 1 H),
6.95 (d, J = 2.1 Hz, 1 H), 7.20–7.25 (m, 5 H), 7.26–7.33 (m, 5 H), 8.47 (d, J = 8.8 Hz, 1 H). 13C NMR
(CD2Cl2, 151 MHz):
δ 33.4 (CH3), 35.9 (CH3), 56.1 (CH3), 56.1 (CH3), 93.7 (CH), 94.2 (CH), 107.6
(CH), 107.9 (Cquat), 108.1 (CH), 115.1 (Cquat), 115.8 (Cquat), 118.8 (Cquat), 119.0 (Cquat), 122.1 (CH),
123.9 (CH), 125.4 (CH), 127.1 (CH), 127.7 (CH), 128.4 (CH), 131.1 (CH), 132.9 (CH), 134.1 (Cquat),
136.7 (Cquat), 139.2 (Cquat), 139.6 (Cquat), 141.0 (Cquat), 143.9 (Cquat), 144.2 (Cquat), 158.4 (Cquat), 158.6
(Cquat). EI-MS (70 eV, m/z (%)): 497 ([MH]+, 100), 482 ([M-CH3]+, 14), 453 (12), 438 (11), 395 (11),
248 (22), 196 (11), 189 (12), 97 (13), 85 (10), 83 (12), 71 (13), 69 (12), 57 (18), 55 (12). IR (ATR): ν̃
[cm-1] 3019 (w), 1585 (w), 1393 (m), 1219 (m), 1086 (s), 1032 (m), 982 (m), 802 (s), 706 (s). Anal.
calcd. for C34H28N2O2 (496.6): C 82.23, H 5.68, N 5.64; Found: C 81.97, H 5.53, N 5.62.
20

4.2.3. 6,7-Bis(4-methoxyphenyl)-5,12-dimethyl-5,12-dihydroindolo[3,2-a]carbazole (3c)
According to the GP compound 3c (85.0 mg, 68%) was obtained as a colorless solid. Mp 334–335 °C
1
(dec.). H NMR (CD2Cl2, 300 MHz):
δ 3.28 (s, 3 H), 3.80 (s, 3 H), 3.84 (s, 3 H), 4.51 (s, 3 H), 6.53
(d, J = 7.9 Hz, 1 H), 6.76–6.81 (m, 2 H), 6.84–6.92 (m, 2 H), 7.11–7.15 (m, 2 H), 7.16–7.20 (m, 2 H),
7.29–7.36 (m, 2 H), 7.42–7.51 (m, 3 H), 8.64 (d, J = 8.1 Hz, 1 H). 13C NMR (CD2Cl2, 75 MHz):
δ
33.4
(CH3), 36.1 (CH3), 55.8 (CH3), 55.8 (CH3), 107.7 (Cquat.), 109.5 (CH), 109.8 (CH), 113.4 (CH), 114.0
(CH), 116.1 (Cquat.), 119.2 (Cquat.), 119.7 (CH), 119.8 (CH), 121.5 (Cquat.), 121.7 (CH), 123.2 (CH),
124.3 (CH), 124.9 (CH), 125.3 (Cquat.), 131.8 (Cquat.), 132.0 (CH), 133.4 (Cquat.), 133.9 (CH), 136.4
(Cquat.), 137.5 (Cquat.), 140.4 (Cquat.), 142.6 (Cquat.), 143.1 (Cquat.), 159.1 (Cquat.), 159.1 (Cquat.). EI-MS (70
eV, m/z (%)): 496 ([M]+, 100), 196 (12), 189 (12). IR (ATR): [cm-1] 2951 (w), 2932 (w), 2900 (w),
ν̃
1518 (m), 1449 (m), 1315 (m), 1282 (m), 1240 (s), 1177 (m), 1030 (m), 826 (m), 781 (m), 739 (s).
Anal. calcd. for C34H28N2O2 (496.6): C 82.23, H 5.68, N 5.64; Found: C 82.29, H 5.55, N 5.59.
4.2.4. 2,9-Dimethoxy-6,7-bis(4-methoxyphenyl)-5,12-dimethyl-5,12-dihydroindolo[3,2-
a]carbazole (3d)
According to the GP compound 3d (83.3 mg, 60%) was obtained as a colorless solid. Mp 238–239 °C.
1H NMR (CD2Cl2, 300 MHz):
δ 3.23 (s, 3 H), 3.50 (s, 3 H), 3.78 (s, 3 H), 3.79 (s, 3 H), 3.97 (s, 3 H),
4.44 (s, 3 H), 5.92 (d, J = 2.6 Hz, 1 H), 6.77 (d, J = 8.6 Hz, 2 H), 6.86 (d, J = 8.6 Hz, 2 H), 6.92 (dd, J
= 8.8, 2.6 Hz, 1 H), 7.08–7.20 (m, 5 H), 7.34 (t, J = 8.7 Hz, 2 H), 8.11 (d, J = 2.4 Hz, 1 H). 13C NMR
(CD2Cl2, 75 MHz):
δ 33.4 (CH3), 36.2 (CH3), 55.7 (CH3), 55.9 (CH3), 55.9 (CH3), 56.8 (CH3), 104.9
(CH), 107.4 (CH), 107.7, 110.0 (CH), 110.2 (CH), 112.9 (CH), 113.3 (CH), 113.4 (CH), 114.0 (CH),
118.9 (Cquat), 121.8 (Cquat), 125.9 (Cquat), 131.7 (Cquat), 132.2 (CH), 133.4 (Cquat), 133.9 (CH), 136.4
(Cquat), 137.8 (Cquat), 138.1 (Cquat), 138.3 (Cquat), 141.0 (Cquat), 154.3 (Cquat), 154.4 (Cquat), 159.1 (Cquat),
159.2 (Cquat). EI-MS (70 eV, m/z (%)): 556 ([M]+, 100), 541 ([M-CH3]+, 21), 278 (15), 247 (9), 196
(8). IR (ATR): ν̃
[cm-1] 3063 (w), 2830 (w), 2359 (w), 2342 (w), 1518 (m), 1508 (m), 1487 (m), 1448
(m), 1375 (w), 1302 (m), 1244 (s), 1233 (s), 1213 (s), 1175 (s), 1150 (s), 1105 (m), 1030 (s), 978 (m),
935 (m), 874 (m), 849 (m), 831 (m), 808 (m), 781 (s), 756 (m), 729 (m), 687 (m). Anal. calcd. for
C36H32N2O4 (556.7): C 77.68, H 5.79, N 5.03. Found: C 77.39, H 5.87, N 4.96.
21

4.2.5. 5,12-Dimethyl-6,7-diphenyl-5,12-dihydroindolo[3,2-a]carbazole-2,9-dicarbonitrile (3e)
According to the GP compound 3e (70.0 mg, 58%) was obtained as a colorless solid. Mp 381–383 °C
(dec.). 1H NMR (CD2Cl2, 300 MHz):
δ 3.31 (s, 3 H), 4.55 (s, 3 H), 6.64–6.67 (m, 1 H), 7.19–7.23 (m,
2 H), 7.25–7.30 (m, 5 H), 7.34–7.41 (m, 3 H), 7.51 (d, J = 8.6 Hz, 1 H), 7.55–7.59 (m, 1 H), 7.61 (dd,
J = 8.5, 1.5 Hz, 1 H), 7.75 (dd, J = 8.6, 1.5 Hz, 1 H), 8.93 (d, J = 1.2 Hz, 1 H). 13C NMR (CD2Cl2,
75 MHz):
δ 33.9 (CH3), 36.2 (CH3), 103.1 (Cquat), 103.1 (Cquat), 107.4 (Cquat), 110.4 (CH), 110.8 (CH),
116.0 (Cquat), 120.7 (Cquat), 120.9 (Cquat), 121.1 (Cquat), 121.3 (Cquat), 124.9 (Cquat), 126.6 (CH), 127.9
(CH), 128.0 (CH), 128.1 (CH), 128.1 (CH), 128.2 (CH), 128.5 (CH), 129.0 (CH), 130.6 (CH), 132.8
(CH), 137.8 (Cquat), 138.0 (Cquat), 138.3 (Cquat), 139.7 (Cquat), 141.2 (Cquat), 144.2 (Cquat), 144.3 (Cquat).
EI-MS (70 eV, m/z (%)): 486 ([M]+, 100), 471 ([M-CH3]+, 11), 236 (15), 228 (11), 227 (12), 214 (10).
IR (ATR): ν̃
[cm-1] 3065 (w), 2916 (w), 2802 (w), 2214 (m), 1576 (m), 1489 (m), 1441 (m), 1300 (m),
1261 (m), 976 (w), 935 (w), 820 (s), 704 (s). Anal. calcd. for C34H22N4 (486.6): C 83.93, H 4.56, N
11.51; Found: C 83.85, 4.40, N 11.34.
4.2.6. 4,4'-(5,12-Dimethyl-5,12-dihydroindolo[3,2-a]carbazole-6,7-diyl)dibenzonitrile (3f)
According to the GP compound 3f (62.5 mg, 51%) was obtained as a colorless solid. Mp 323–324 °C.
1H NMR (CD2Cl2, 300 MHz):
δ 3.27 (s, 3 H), 4.52 (s, 3 H), 6.46 (d, J = 7.9 Hz, 1 H), 6.92 (ddd, J =
8.1, 7.1, 1.0 Hz, 1 H), 7.31–7.41 (m, 6 H), 7.45–7.56 (m, 5 H), 7.62 (d, J = 8.3 Hz, 2 H), 8.67 (d, J =
8.1 Hz, 1 H). 13C NMR (CD2Cl2, 75 MHz):
δ
34.0 (CH3), 36.1 (CH3), 108.6 (Cquat), 109.9 (CH), 110.1
(CH), 111.7 (Cquat), 111.9 (Cquat), 115.0 (Cquat), 116.8 (Cquat), 119.2 (Cquat), 119.4 (Cquat), 120.3 (CH),
120.3 (CH), 121.2 (CH), 123.5 (CH), 124.3 (Cquat), 125.0 (CH), 125.6 (CH), 131.9 (CH), 132.0 (CH),
132.7 (CH), 133.6 (CH), 133.9 (Cquat), 138.2, (Cquat) 139.4 (Cquat), 142.7 (Cquat), 143.1 (Cquat), 144.4
(Cquat), 145.5 (Cquat). EI-MS (70 eV, m/z (%)): 486 ([M]+, 100), 471 ([M-CH3]+, 14), 236 (15). IR
(ATR): ν̃
[cm-1] 2990 (w), 2899 (w), 2365 (w), 2361 (w), 2231 (w), 1589 (m), 1585 (m), 1474 (m),
1389 (m), 1319 (m), 1258 (m), 1179 (m), 1092 (m), 1016 (m), 995 (m), 974 (m), 864 (m), 781 (m),
746 (m), 731 (s), 689 (m). Anal. calcd. for C34H22N4 (486.6): C 83.93, H 4.56, N 11.51. Found: C
83.98, H 4.52, N 11.53.
22

4.2.7. 5,12-Dimethyl-7-phenyl-5,12-dihydroindolo[3,2-a]carbazol (3g)
According to the GP compound 3g (61.5 mg, 68%) was obtained as a colorless solid. Mp 192–194 °C.
1H NMR (CD2Cl2, 300 MHz):
δ 3.94 (s, 3H), 4.53 (s, 3 H), 6.98 (ddd, J = 8.0, 7.0, 1.1 Hz, 1 H), 7.19
(s, 1 H), 7.26 (d, J = 7.9 Hz, 1 H), 7.29–7.40 (m, 2 H), 7.48–7.61 (m, 6 H), 7.66–7.70 (m, 2 H), 8.63
(d, J = 8.2 Hz, 1 H). 13C NMR (CD2Cl2, 75 MHz):
δ
30.2 (CH3), 35.6, (CH3) 104.1 (Cquat), 104.1
(Cquat), 106.6 (Cquat), 109.4 (CH), 109.5 (CH), 119.6 (CH), 119.7 (CH), 121.6 (CH), 121.7 (Cquat),
123.4 (CH), 124.3 (CH), 124.6 (Cquat), 124.9 (CH), 125.6 (Cquat), 128.2 (CH), 129.0 (CH), 130.1 (CH),
138.7 (Cquat), 141.5 (Cquat), 142.0 (Cquat), 142.2 (Cquat), 142.8 (Cquat). EI-MS (70 eV, m/z (%)): 360
([M]+, 100), 345 ([M-CH3]+, 20), 330 ([M-2x(CH3)]+, 10), 180 (12), 172 (32), 165 (18). IR (ATR):
ν̃
[cm-1] 2984 (w), 2970 (w), 2901 (w), 1591 (w), 1558 (m), 1479 (m), 1448 (m), 1435 (m), 1408 (m),
1348 (m), 1317 (s), 1250 (m), 1231 (m), 1190 (m), 1119 (m),1057 (m), 1024 (m), 972 (m), 960 (m),
921 (w), 885 (m), 841 (m), 820 (m), 773 (m), 756 (m), 742 (s), 727 (s), 708 (s), 696 (s), 650 (m). Anal.
calcd. for C26H20N2 (360.5): C 86.64, H 5.59, N 7.77. Found: C 86.93, H 5.74, N 7.87.
5.
Acknowledgements
We cordially thank the Fonds der Chemischen Industrie and Deutsche Forschungsgemeinschaft (Mu
1088/9-1) for the financial support. And we are grateful to M. Sc. Tobias Wilcke for taking the
photographs. Computational support and infrastructure was provided by the “Centre for Information
and Media Technology” (ZIM) at the University of Düsseldorf (Germany).
6.
References
[1]
a) Levi L, Müller TJJ. Multicomponent Syntheses of Functional Chromophores. Chem Soc
Rev 2016;45:2825-46; b) Levi L, Müller TJJ. Multicomponent Syntheses of Fluorophores
Initiated by Metal Catalysis. Eur J Org Chem 2016;2016:2902-18; c) Müller TJJ, Bunz UHF,
eds., Functional Organic Materials. Weinheim: Wiley-VHC; 2007.
[2]
[3]
a) Zhu J, Wang Q, Wang M, Multicomponent Reactions in Organic Synthesis Weinheim:
Wiley-VHC; 2014; b) Müller T, Multicomponent Reactions 1. General Discussion and
Reactions Involving a Carbonyl Compound as Electrophilic Component. Stuttgart: Georg
Thieme; 2014; c) D'Souza DM, Müller TJJ. Multi-component Syntheses of Heterocycles by
Transition-Metal Catalysis. Chem Soc Rev 2007;36:1095-108; d) Dömling A, Ugi I.
Multicomponent Reactions with Isocyanides. Angew Chem Int Ed 2000;39:3168-210.
a) D'Souza DM, Kiel A, Herten D-P, Rominger F, Müller TJJ. Synthesis, Structure and
Emission Properties of Spirocyclic Benzofuranones and Dihydroindolones: A Domino
Insertion–Coupling–Isomerization– Diels–Alder Approach to Rigid Fluorophores. Chem Eur J
23

2008;14:529-47; b) D'Souza DM, Rominger F, Müller TJJ. A Domino Sequence Consisting of
Insertion, Coupling, Isomerization, and Diels–Alder Steps Yields Highly Fluorescent
Spirocycles. Angew Chem Int Ed 2005;44:153-8.
[4]
[5]
a) Park J-S, Chae H, Chung HK, Lee SI. Thin Film Encapsulation for Flexible AM-OLED: a
Review. Semicond Sci Technol 2011;26:034001; b) Thejo Kalyani N, Dhoble SJ. Organic
Light Emitting Diodes: Energy Saving Lighting Technology—A Review. Renew Sustain
Energy Rev 2012;16:2696-723.
a) Shalini S, Balasundaraprabhu R, Kumar TS, Prabavathy N, Senthilarasu S, Prasanna S.
Status and Outlook of Sensitizers/Dyes Used in Dye Sensitized Solar Cells (DSSC): A
Review. Int J Energy Res 2016;40:1303-20; b) Sugathan V, John E, Sudhakar K. Recent
Improvements in Dye Sensitized Solar Cells: A Review. Renew Sustain Energy Rev
2015;52:54-64; c) Richhariya G, Kumar A, Tekasakul P, Gupta B. Natural Dyes for Dye
Sensitized Solar Cell: A Review. Renew Sustain Energy Rev 2017;69:705-18.
a) Lizin S, Van Passel S, De Schepper E, Maes W, Lutsen L, Manca J, Vanderzande D. Life
Cycle Analyses of Organic Photovoltaics: A Review. Energy Environ Sci 2013;6:3136-49; b)
Yu J, Zheng Y, Huang J. Towards High Performance Organic Photovoltaic Cells: A Review
of Recent Development in Organic Photovoltaics. Polymers 2014;6; c) Su Y-W, Lan S-C, Wei
K-H. Organic Photovoltaics. Mater Today 2012;15:554-62.
a) Chen C-T, Wagner H, Still WC. Fluorescent, Sequence-Selective Peptide Detection by
Synthetic Small Molecules. Science 1998;279:851; b) Nilsson D, Kugler T, Svensson P-O,
Berggren M. An All-Organic Sensor–Transistor Based on a Novel Electrochemical
Transducer Concept Printed Electrochemical Sensors on Paper. Sens Actuator B Chem
2002;86:193-7; c) Grunwald C, Schulze K, Reichel A, Weiss VU, Blaas D, Piehler J,
Wiesmüller K-H, Tampé R. In Situ Assembly of Macromolecular Complexes Triggered by
Light. Proc Natl Acad Sci 2010;107:6146;d) McQuade DT, Pullen AE, Swager TM.
Conjugated Polymer-Based Chemical Sensors. Chem Rev 2000;100:2537-74.
[6]
[7]
[8]
a) Irie M, Fukaminato T, Matsuda K, Kobatake S. Photochromism of Diarylethene Molecules
and Crystals: Memories, Switches, and Actuators. Chem Rev 2014;114:12174-277; b) Klajn
R. Spiropyran-based Dynamic Materials. Chem Soc Rev 2014;43:148-84.
[9]
Seeboth A, Lötzsch D, Ruhmann R, Muehling O. Thermochromic Polymers—Function by
Design. Chem Rev 2014;114:3037-68.
[10]
[11]
Yang P, Sun P, Mai W. Electrochromic Energy Storage Devices. Mater Today 2016;19:394-
402.
a) Jaffe A, Lin Y, Mao WL, Karunadasa HI. Pressure-Induced Conductivity and Yellow-to-
Black Piezochromism in a Layered Cu–Cl Hybrid Perovskite. J Am Chem Soc
2015;137:1673-8; b) Sui Q, Ren X-T, Dai Y-X, Wang K, Li W-T, Gong T, Fang J-J, Zou B,
Gao E-Q, Wang L. Piezochromism and Hydrochromism through Electron Transfer: New
Stories for Viologen Materials. Chem Sci 2017;8:2758-68.
[12]
[13]
a) Machado VG, Stock RI, Reichardt C. Pyridinium N-Phenolate Betaine Dyes. Chem Rev
2014;114:10429-75; b) Reichardt C. Solvatochromic Dyes as Solvent Polarity Indicators.
Chem Rev 1994;94:2319-58.
a) Ghazvini Zadeh EH, Tang S, Woodward AW, Liu T, Bondar MV, Belfield KD.
Chromophoric Materials Derived from a Natural Azulene: Syntheses, Halochromism and One-
Photon and Two-Photon Microlithography. J Mater Chem C 2015;3:8495-503; b) Sachdeva T,
Milton MD. Logic Gate based Novel Phenothiazine-pyridylhydrazones: Halochromism in
Solid and Solution State. Dyes Pigment 2019;164:305-18; c) Stolar M, Baumgartner T.
Synthesis and Unexpected Halochromism of Carbazole-functionalized Dithienophospholes.
New J Chem 2012;36:1153-60; d) Singh P, Baheti A, Thomas KRJ. Synthesis and Optical
Properties of Acidochromic Amine-Substituted Benzo[a]phenazines.
J
Org Chem
2011;76:6134-45.
[14]
[15]
Speight JG, Lange's Handbook of Chemistry. New York: McGraw-Hill Education; 2005.
a) Garcia-Amorós J, Swaminathan S, Raymo FM. Saving Paper with Switchable Ink. Dyes
Pigment 2014;106:71-3; b) Sheng L, Li M, Zhu S, Li H, Xi G, Li Y-G, Wang Y, Li Q, Liang
S, Zhong K, Zhang SX-A. Hydrochromic Molecular Switches for Water-jet Rewritable Paper.
Nat Commun 2014;5:3044.
[16]
Lakowicz JR, Principles of Fluorescence Spectroscopy. 3 ed. New York, NY: Springer; 2006.
24

[17]
[18]
Janosik T, Rannug A, Rannug U, Wahlström N, Slätt J, Bergman J. Chemistry and Properties
of Indolocarbazoles. Chem Rev 2018;118:9058-128.
a) Mann FG, Willcox TJ. 305. The Synthesis of Indolo(2′ : 3′-1 : 2)- and Indolo(3′ : 2′-1 : 2)-
carbazole. J Chem Soc 1958:1525-9; b) Brunton RJ, Drayson FK, Plant SGP, Tomlinson ML.
933. Experiments on the Preparation of Indolocarbazoles. Part IX. The Preparation of 9-
Methylindolo(2′ : 3′-1 : 2)carbazole. J Chem Soc 1956:4783-5.
[19]
[20]
[21]
Kase H, Iwahashi K, Nakanishi S, Matsuda Y, Yamada K, Takahashi M, Murakata C, Sato A,
Kaneko M. K-252 Compounds, Novel and Potent Inhibitors of Protein Kinase C and Cyclic
Nucleotide-dependent Protein Kinases. Biochem Biophys Res Commun 1987;142:436-40.
Furusaki A, Hashiba N, Matsumoto T, Hirano A, Iwai Y, Mura S. The Crystal and Molecular
Structure of Staurosporine, a New Alkaloid from a Streptomyces Strain. Bull Chem Soc Jpn
1982;55:3681-5.
a) Civenni G, Longoni N, Costales P, Dallavalle C, García Inclán C, Albino D, Nuñez LE,
Morís F, Carbone GM, Catapano CV. EC-70124, a Novel Glycosylated Indolocarbazole
Multikinase Inhibitor, Reverts Tumorigenic and Stem Cell Properties in Prostate Cancer by
Inhibiting STAT3 and NF-κB. Mol Cancer Ther 2016;15:806; b) Bailly C, Riou J-F, Colson P,
Houssier C, Rodrigues-Pereira E, Prudhomme M. DNA Cleavage by Topoisomerase I in the
Presence of Indolocarbazole Derivatives of Rebeccamycin. Biochemistry 1997;36:3917-29; c)
Yoshinari T, Ohkubo M, Fukasawa K, Egashira S-i, Hara Y, Matsumoto M, Nakai K,
Arakawa H, Morishima H, Nishimura S. Mode of Action of a New Indolocarbazole
Anticancer Agent, J-107088, Targeting Topoisomerase I. Cancer Res 1999;59:4271; d) Salas
JA, Méndez C. Indolocarbazole Antitumor Compounds by Combinatorial Biosynthesis. Curr
Opin Chem Biol 2009;13:152-60; e) Bailly C, Qu X, Chaires JB, Colson P, Houssier C,
Ohkubo M, Nishimura S, Yoshinari T. Substitution at the F-Ring N-Imide of the
Indolocarbazole Antitumor Drug NB-506 Increases the Cytotoxicity, DNA Binding, and
Topoisomerase I Inhibition Activities. J Med Chem 1999;42:2927-35.
[22]
a) Brown A, Mullen KM, Ryu J, Chmielewski MJ, Santos SM, Felix V, Thompson AL,
Warren JE, Pascu SI, Beer PD. Interlocked Host Anion Recognition by an Indolocarbazole-
Containing [2]Rotaxane. J Am Chem Soc 2009;131:4937-52; b) Park JH, Lee HS, Park S, Min
S-W, Yi Y, Cho C-G, Han J, Kim TW, Im S. Photo-Stable Organic Thin-Film Transistor
Utilizing a New Indolocarbazole Derivative for Image Pixel and Logic Applications. Adv
Funct Mater 2014;24:1109-16; c) Mai R, Wu X, Jiang Y, Meng Y, Liu B, Hu X, Roncali J,
Zhou G, Liu J-M, Kempa K, Gao J. An Efficient Multi-functional Material based on
Polyether-substituted Indolocarbazole for Perovskite Solar Cells and Solution-processed non-
Doped OLEDs. J Mater Chem A 2019;7:1539-47; d) Lai C-C, Huang M-J, Chou H-H, Liao C-
Y, Rajamalli P, Cheng C-H. m-Indolocarbazole Derivative as a Universal Host Material for
RGB and White Phosphorescent OLEDs. Adv Funct Mater 2015;25:5548-56; e) Zhang D,
Song X, Cai M, Kaji H, Duan L. Versatile Indolocarbazole-Isomer Derivatives as Highly
Emissive Emitters and Ideal Hosts for Thermally Activated Delayed Fluorescent OLEDs with
Alleviated Efficiency Roll-Off. Adv Mater 2018;30:1705406; f) Jiang H, Hu P, Ye J,
Chaturvedi A, Zhang KK, Li Y, Long Y, Fichou D, Kloc C, Hu W. From Linear to Angular
Isomers: Achieving Tunable Charge Transport in Single‐Crystal Indolocarbazoles Through
Delicate Synergetic CH/NH⋅⋅⋅π Interactions. Angew Chem Int Ed 2018;57:8875-80; g) Chen
G, Sun S, Yang Y, Lan L, Ying L, Yang W, Zhang B, Cao Y. A Solution-processed and low
Threshold voltage Voltage p-type Small Molecule based on Indolocarbazole- and
Benzothiophene-fused Rings. Dyes Pigment 2017;144:32-40.
[23]
Kotha S, Saifuddin M, Aswar VR. A Diversity-oriented Approach to Indolocarbazoles via
Fischer indolization and Olefin Metathesis: Total Synthesis of Tjipanazole D and I. Org
Biomol Chem 2016;14:9868-73.
[24]
[25]
Shi Z, Ding S, Cui Y, Jiao N. A Palladium-Catalyzed Oxidative Cycloaromatization of Biaryls
with Alkynes Using Molecular Oxygen as the Oxidant. Angew Chem Int Ed 2009;48:7895-8.
a) An Y-L, Yang Z-H, Zhang H-H, Zhao S-Y. Palladium-Catalyzed Tandem Regioselective
Oxidative Coupling from Indoles and Maleimides: One-Pot Synthesis of
Indolopyrrolocarbazoles and Related Indolylmaleimides. Org Lett 2016;18:152-5; b) Nair V,
Nandialath V, Abhilash KG, Suresh E. An Efficient Synthesis of Indolo[3,2-a]carbazoles via
25

the Novel Acid Catalyzed Reaction of Indoles and Diaryl-1,2-diones. Org Biomol Chem
2008;6:1738-42.
[26]
[27]
Kumar KS, Meesa SR, Naikawadi PK. Palladium-Catalyzed [2 + 2 + 2] Annulation via
Transformations of Multiple C–H Bonds: One-Pot Synthesis of Diverse Indolo[3,2-
a]carbazoles. Org Lett 2018;20:6079-83.
a) Niesobski P, Klukas F, Berens H, Makhloufi G, Janiak C, Müller TJJ. De Novo Ring-
Forming Consecutive Four-Component Syntheses of 4-Pyrazolyl-1,2,3-triazoles from
(Triisopropylsilyl)butadiyne as a C4 Building Block. J Org Chem 2018;83:4851-8; b) Merkul
E, Klukas F, Dorsch D, Grädler U, Greiner HE, Müller TJJ. Rapid Preparation of Triazolyl
Substituted NH-Heterocyclic Kinase Inhibitors via One-pot Sonogashira Coupling–TMS-
Deprotection–CuAAC Sequence. Org Biomol Chem 2011;9:5129-36; c) Merkul E, Urselmann
D, Müller TJJ. Consecutive One-Pot Sonogashira–Glaser Coupling Sequence – Direct
Preparation of Symmetrical Diynes by Sequential Pd/Cu Catalysis. Eur J Org Chem
2011;2011:238-42; d) Niesobski P, Santana Martínez I, Kustosz S, Müller TJJ. Sequentially
Pd/Cu-catalyzed Alkynylation-Oxidation Synthesis of 1,2-Diketones and Consecutive One-Pot
Generation of Quinoxalines. Eur J Org Chem 2019;submitted for publication.
[28]
[29]
[30]
Lessing T, Müller TJJ. Sequentially Palladium-Catalyzed Processes in One-Pot Syntheses of
Heterocycles. Appl Sci 2015;5.
Cinar R, Nordmann J, Dirksen E, Müller TJJ. Domino Synthesis of Protochromic “ON–OFF–
ON” Luminescent 2-Styryl Quinolines. Org Biomol Chem 2013;11:2597-604.
a) Schönhaber J, Frank W, Müller TJJ. Insertion−Coupling−Cycloisomerization Domino
Synthesis and Cation-Induced Halochromic Fluorescence of 2,4-Diarylpyrano[2,3-b]indoles.
Org Lett 2010;12:4122-5; b) Wilcke T, Glißmann T, Lerch A, Karg M, Müller TJJ.
Acidochromic Turn-on 2,4-Diarylpyrano[2,ꢀ3-b]indole Luminophores with Solubilizing
Groups for A Broad Range of Polarity. ChemistrySelect 2018;3:10345-51.
[31]
Dupeyre G, Lemoine P, Ainseba N, Michel S, Cachet X. A One-pot Synthesis of 7-
Phenylindolo[3,2-a]carbazoles from Indoles and β-Nitrostyrenes, via an Unprecedented
Reaction Sequence. Org Biomol Chem 2011;9:7780-90.
[32]
[33]
Lane BS, Brown MA, Sames D. Direct Palladium-Catalyzed C-2 and C-3 Arylation of
Indoles:ꢀ A Mechanistic Rationale for Regioselectivity. J Am Chem Soc 2005;127:8050-7.
Guchhait SK, Chaudhary V, Rana VA, Priyadarshani G, Kandekar S, Kashyap M. Oxidative
Dearomatization of Indoles via Pd-Catalyzed C–H Oxygenation: An Entry to C2-Quaternary
Indolin-3-ones. Org Lett 2016;18:1534-7.
[34]
[35]
[36]
[37]
Keith JA, Nielsen RJ, Oxgaard J, Goddard WA. Unraveling the Wacker Oxidation
Mechanisms. J Am Chem Soc 2007;129:12342-3.
Taniguchi M, Lindsey JS. Database of Absorption and Fluorescence Spectra of >300 Common
Compounds for use in PhotochemCAD. Photochem Photobiol 2018;94:290-327.
Fery-Forgues S, Lavabre D. Are Fluorescence Quantum Yields So Tricky to Measure? A
Demonstration Using Familiar Stationery Products. J Chem Phys 1999;76:1260.
Frisch M, Trucks G, B Schlegel B, E Scuseria E, Robb M, Cheeseman J, Scalmani G, Barone
V, Mennucci B, A. H. Petersson G, Nakatsuji H, Caricato M, Li X, P Hratchian H, F Izmaylov
A, Bloino J, Zheng G, Sonnenberg J, Hada M, Fox D, Gaussian 09 (Revision A02); 2009.
a) Ernzerhof M, Scuseria GE. Assessment of the Perdew–Burke–Ernzerhof Exchange-
Correlation Functional. J Chem Phys 1999;110:5029-36; b) Adamo C, Scuseria GE, Barone V.
Accurate Excitation Energies from Time-Dependent Density Functional Theory: Assessing the
PBE0 model. J Chem Phys 1999;111:2889-99.
a) McLean AD, Chandler GS. Contracted Gaussian Basis Sets for Molecular Calculations. I.
Second Row Atoms, Z=11–18. J Chem Phys 1980;72:5639-48; b) Krishnan R, Binkley JS,
Seeger R, Pople JA. Self‐Consistent Molecular Orbital Methods. XX. A Basis Set for
Correlated Wave Functions. J Chem Phys 1980;72:650-4.
a) Bauernschmitt R, Ahlrichs R. Treatment of electronic excitations within the adiabatic
approximation of time dependent density functional theory. Chem Phys Lett 1996;256:454-64;
b) Casida ME, Jamorski C, Casida KC, Salahub DR. Molecular Excitation Energies to High-
[38]
[39]
[40]
lying
Bound
States
from
Time-DependentꢀDensity-FunctionalꢀResponseꢀTheory:
Characterizationꢀand
CorrectionꢀofꢀtheꢀTime-DependentꢀLocalꢀDensityꢀApproximation
Ionization Threshold. J Chem Phys 1998;108:4439-49; c) Stratmann RE, Scuseria GE, Frisch
26

MJ. An Efficient Implementation of Time-Dependent Density-Functional Theory for the
Calculation of Excitation Energies of Large Molecules. J Chem Phys 1998;109:8218-24.
Scalmani G, Frisch MJ. Continuous Surface Charge Polarizable Continuum Models of
Solvation. I. General formalism. J Chem Phys 2010;132:114110.
Lu T, Chen F. Multiwfn: A Multifunctional Wavefunction Analyzer. J Comput Chem
2012;33:580-92.
a) Wang Y, Yang Z, Zhan F, Lyu Z, Han C, Wang X, Chen W, Ding M, Wang R, Jiang Y.
Indolizine Quaternary Ammonium Salt Inhibitors part II: A Reinvestigation of an Old-
fashioned Strong Acid Corrosion Inhibitor Phenacyl Quinolinium Bromide and its Indolizine
Derivative. New J Chem 2018;42:12977-89; b) Yang Z, Zhan F, Pan Y, Lyu Z, Han C, Hu Y,
Ding P, Gao T, Zhou X, Jiang Y. Structure of a Novel Benzyl Quinolinium Chloride
Derivative and its Effective Corrosion Inhibition in 15wt.% Hydrochloric Acid. Corros Sci
2015;99:281-94; c) Afarinkia K, Ansari M-R, Bird CW, Gyambibi I. A Reinvestigation of the
Structure of the Erythro and Xanthoapocyanine Dyes: Some Unusual Aspects of Quinoline
Chemistry. Tetrahedron Lett 1996;37:4801-4.
[41]
[42]
[43]
[44]
[45]
Caramenti P, Nicolai S, Waser J. Indole- and Pyrrole-BX: Bench-Stable Hypervalent Iodine
Reagents for Heterocycle Umpolung. Chem Eur J 2017;23:14702-6.
Chuentragool P, Vongnam K, Rashatasakhon P, Sukwattanasinitt M, Wacharasindhu S.
Calcium Carbide as a Cost-effective Starting Material for Symmetrical Diarylethynes via Pd-
Catalyzed Coupling Reaction. Tetrahedron 2011;67:8177-82.
[46]
Hein SJ, Arslan H, Keresztes I, Dichtel WR. Rapid Synthesis of Crowded Aromatic
Architectures from Silyl Acetylenes. Org Lett 2014;16:4416-9.
Graphical abstract
27

Highlights
The urgency and relevance of our contribution for a broad readership of organic, dye and
materials chemists is justified by the following aspects:
1) Our general approach is the concept of modular one-pot syntheses of functional
dyes, predominantly fluorophores. Indolo[3,2-a]carbazoles are accessible by a
Pd/Cu-catalyzed oxidative four-fold CH-activation that proceeds in a pseudo-
threecomponent domino reaction.
2) During our methodological studies we not only noticed that the title compounds are
intensively violet to blue emissive in solution and in the solid state, but also
acidochromic, i.e. a significant red shift of the absorption bands with concomitant
fluorescence quenching.
3) By comprehensive NMR studies the site of protonation as assessed, showing that
the protonated species falls into the rarely occurring class of apocyanines. The site of
protonation was additionally corroborated by DFT calculations on various
conceivable isomers.
4) The isosbestic points in the protonated absorption spectra as well as the static
fluorescence quenching (Stern-Vollmer plot) furthermore allows determining the pKa
of conjugated acids of the title compounds, i.e. apocyanines.
5) The elucidation of the electronic structure by DFT and TD DFT calculations using
the PBEh1PBE functional reveals that the longest wavelength chromogenic
absorption band can be indeed assigned to dominant cyanine like HOMO-LUMO
transitions.