Iodine Catalysed Synthesis of Luminescent β-Carboline Tethered Thiazolo[4,5-c]carbazole and Naphtho[2,1-d]thiazole Derivatives and Estimation of their Light Emitting Properties

Article abstract of DOI:10.1002/ejoc.201901908

A Simple, convenient and highly efficient I₂-catalysed approach has been unfolded towards the synthesis of highly fluorescent β-carboline C-1(3)-tethered thiazolo[4,5-c]carbazoles, naphtho[2,1-d]thiazoles and benzothiazole derivatives using Kumujian C as a template. This domino strategy proceeds through assembly of 1-formyl-9H-β-carbolines, arylamines and elemental sulfur via formation of one C–N and two C–S bonds in a single operation. Importantly, the methodology was found applicable to β-carboline acetals also. A diversely substituted library of 37 β-carboline tethered arylthiazole hybrids was prepared in excellent yields. The strategy was found appropriate for gram scale synthesis also. The photophysical properties of these fluorophores were also estimated and showed excellent fluorescence properties with quantum yield (Φ_F) up to 92 %.

Full text of DOI:10.1002/ejoc.201901908

A Journal of
Accepted Article
Title: Iodine Catalysed Synthesis of Luminescent β-Carboline Tethered
Thiazolo[4,5-c]carbazole and Naphtho[2,1-d]thiazole Derivatives
and Estimation of their Light Emitting Properties
Authors: Manpreet Singh, Pamita Awasthi, and Virender Singh
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10.1002/ejoc.201901908
European Journal of Organic Chemistry
FULL PAPER
Iodine Catalysed Synthesis of Luminescent β-Carboline Tethered
Thiazolo[4,5-c]carbazole and Naphtho[2,1-d]thiazole Derivatives
and Estimation of their Light Emitting Properties
Manpreet Singh,[a] Pamita Awasthi,[b] and Virender Singh*[a]
(This manuscript is dedicated to Dr Sanjay Batra on his 55th Birthday)
Abstract: A simple, convenient and highly efficient I2-catalysed
approach has been unfolded towards the synthesis of highly
fluorescent β-carboline C-1(3)-tethered thiazolo[4,5-c]carbazoles,
naphtho[2,1-d]thiazoles and benzothiazole derivatives using
Kumujian C as a template. This domino strategy proceeds through
assembly of 1-formyl-9H-β-carbolines, aryl amines and elemental
sulfur via formation of one C-N and two C-S bonds in a single
operation. Importantly, the methodology was found applicable to β-
carboline acetals also. A diversely substituted library of 37 β-
carboline tethered arylthiazole hybrids was prepared in excellent
yields. The strategy was found appropriate for gram scale
synthesis also. The photophysical properties of these fluorophores
were also estimated and showed excellent fluorescence properties
with quantum yield (ΦF) up to 92%.
copper ions at PPB level.5 The interesting chemical and
physical properties of β–carbolines make them a subject of
intense research.6
Similarly, benzothiazole is another important privileged
scaffold7 which have delivered several drugs being utilized
over the years for treating Alzheimer’s disease, inflammation,
diabetes, tuberculosis and viral infections.8 In addition to this,
benzothiazole derivatives have received considerable attention
owing to their impending applications as industrial dyes and
organic luminescent materials.9 Benzothiazole derivatives have
also been used as fluorescent probe for imaging live cells.10
Attracted by the interesting chemical and physical
properties of these two privileged scaffolds, it was
envisaged to generate a molecular hybrid of these two
frameworks (β-carboline and benzothiazole). In this
context, our group used the classical approach toward
synthesis of designed prototype via condensation of 1-
formyl β-carbolines with 2-aminothiophenoles using ZnO
nanoparticles (Figure 2, Eq 4).11 Interestingly, these
benzothiazole derivatives exhibited quantum yield (ΦF) up
to 28%. However, the scope of previous strategy was
hampered by the lack of availability of diversely
substituted 2-aminothiophenoles derivatives.
Introduction
The pool of natural products have been an important source of
novel chemotypes and bioactive molecules for the
development of new drug candidates.1 Pyrido[3,4-b]indole
commonly regarded as β–carboline is an important structural
motif represented by large number of alkaloids and bioactive
compounds (Figure 1) known to exhibit broad spectrum of
pharmacological properties including anticancer, antiviral,
antibacterial, anti-HIV, antifungal, antimalarial etc.2 The β-
carboline derivatives are specifically known to intercalate into
DNA and inhibit the action of topoisomerase I-II, IkK kinase
complex, cyclin-dependent kinase and arrest the cell
proliferation at various stages which is responsible for their
anticancer properties.3 Abecarnil, Tadalfil and Cipargamin are
the few β-carboline based drugs which are used commercially.4
Recently, the fluorescence properties of β–carboline
derivatives have also been explored for the development of
novel chemosensors for quantitative detection of fluoride and
[a]
[b]
Mr. Manpreet Singh and Dr. Virender Singh*
Department of Chemistry,
Dr B R Ambedkar National Institute of Technology (NIT) Jalandhar,
144011, Punjab, India.
Fax: (+) 91 181-2690301; (+) 91-9780998060;
e-mail: singhv@nitj.ac.in:,
Homepage: http://www.nitj.ac.in/index.php/nitj_cinfo/Faculty/20
Dr. Pamita Awasthi
Figure 1. Selected examples of biologically active β-carboline and
benzothiazole derivatives
Department of Chemistry, National Institute of Technology
Hamirpur, Himachal Pradesh, India; e-mail: pamita@nith.ac.in
Supporting information for this article is given via a link at the end of
the document.
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Results and Discussion
The study initiated with the synthesis of β-carboline alkaloid,
Kumujian C (4) and its derivatives (5-9) which were realized via
modification in the previous procedure as depicted in Scheme
1.15 The Pictet-Spengler reaction was performed between L-
tryptophan (1) and 2,2-dimethoxyacetaldehyde (60% aq.
solution) in presence of TFA which afforded the tetrahydro-β-
carboline derivative (THβC, 2) in 94% yield within 1 h. The
decarboxylative oxidation of C-ring in THβC derivative 2 with
NCS furnished the β-carboline acetal derivative 3 (79%).
Further, versatility of I2 was utilized for the de-protection of
acetal 3 to furnish Kumujian C (4) in 78% yield.[1e] The N-alkyl
derivatives of Kumujian C, 5-9 were prepared in 85-88% yield
via N-alkylation of Kumujian C (4) with suitable alkyl halides in
presence of Cs2CO3 in dry DMF (Scheme 1).
Scheme 1. Synthesis of Kumujian C and N-alkyl derivatives
Similarly, other analogues of Kumujian C were prepared in the
form of methyl 1-formyl-9H-pyrido[3,4-b]indole-3-carboxylate
(11) and its N-alkyl derivatives (19-24) from L-tryptophan
methyl ester.HCl (generated in situ from L-tryptophan)
(Scheme 2). The Pictet-Spengler reaction was executed in
water at 80 oC which afforded tetrahydro-β-carboline ester
derivative (THβC, 10) in 88% yield within 30 min. The
versatility of iodine was again demonstrated for the
simultaneous oxidation of THβC 10 as well as in situ de-
protection of acetal to afford methyl 1-formyl-9H-pyrido[3,4-
b]indole-3-carboxylate (11) by using a combination of iodine
with H2O2 (30% aq.) in DMSO. To our delight, oxidation of C-
ring as well as de-protection of acetal was completed within 4 h
to yield the desired product 11 in 60% yields. The N-alkyl
derivatives of 11 were prepared indirectly via selective
oxidation of THβC 10 with KMnO4 followed by N-alkylation and
de-protection of acetal with aqueous AcOH (Scheme 2).
Gratifyingly, during the synthesis of N-alkyl 1-formyl pyrido[3,4-
b]indole-3-carboxylate derivatives (19-24), purification by
column chromatographic was not mandatory at any step and
the analytically pure products could be synthesized at gram
scale.
Figure 2. Previous findings related to the synthesis of a designed prototype
The high cost and un-availability of 2-aminothiophenoles
have inspired the researchers to develop alternate
approaches for the construction of C-S bond. Therefore,
various sulfuration agents, such as Belleau’s reagent,
inorganic
metal
sulfides,
Lawesson’s
reagent,
thioacetates, thiourea and thiocyanates have been
explored as the source of sulfur for the generation of C-S
bond.12 The growing environmental concerns have
resulted in rise of elemental sulfur as a surrogate option
for C-S bond formation. Several research groups13 have
developed many environmentally benign approaches for
the construction of C-S bond using elemental sulfur
(Figure 2, Eq. 1-3).14 As a part of our research project
towards development of novel β-carboline based
molecular hybrids with fluorescent properties using iodine
and metal catalysts, we have synthesized β-carboline N-
fused imidazoles, oxadiazoles, pyrazoles and lactones.15
The molecular iodine has attracted substantial attention
owing to its less expensive, low-toxicity, readily availability
and more versatile nature in contrast to transition-metal
catalysts.16 Therefore, focused efforts were directed
toward development of
-carboline C-1(3) tethered
thiazole derivatives with extended conjugation to prepare
new fluorophores with improved optical properties.11 With
successful synthesis of designed prototypes, the
fluorescence properties of these annulated benzothiazole
derivatives were also investigated and excellent results
were obtained with quantum yield (ΦF) up to 92%. The
results of this detailed study are presented herein.
Scheme 2. Synthesis of 1-formyl β-carboline derivatives
2
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To achieve the synthesis of targeted prototypes, β-carboline
entries 4-6). While the reaction was conducted in NMP, 85%
yield of desired product 5a was obtained (Table 1, entry 7).
Surprisingly, use of I2 in ACN resulted in formation of imine
only and the reaction failed to yield the desired product even
after 24 h (Table 1, entry 8). Therefore, it was considered to
explore KI as a catalyst instead of I2 and a clean reaction with
excellent yield (92%) was obtained within 5 h in DMSO at 130
oC (Table 1, entry 9). However, the reaction under similar
conditions in dry DMF yielded the desired product 5a in less
quantity (85%, Table 1, entry 10). To our pleasure, when the
reaction was executed in DMSO with 20 mol% iodine, the
reaction time was reduced to 3.5 h and yield improved to 98%
(Table 1, entry 11). At this stage, it was realized that nature of
solvent (DMSO) and temperature had a visible impact on the
yield of this three component annulation, as it significantly
reduced the reaction time and offered the desired product in
quantitative amount (98%).
linked arylthiazoles; we set up screening of conditions for the
reaction of N-methyl Kumujian C,
5
with 3-amino-9-
ethylcarbazole (a) and elemental sulfur. Initially, model
substrate; 5, 3-amino-9-ethylcarbazole (a) and sulfur powder
were reacted using I2 (20 mol%) as a catalyst in dry DMF at
o
130 C in presence of 4Ao molecular sieves. It was delighting
that a clean reaction was obtained and a less polar fluorescent
product was isolated in 89% yield (Table 1, entry 1). The
analysis of spectroscopic data confirmed the structure of
isolated product as β-carboline C-1 tethered thiazolo[4,5-
c]carbazole derivative 5a. However, when the same reaction
was examined at 100 oC, the yield was reduced to 60% (Table
1, entry 2). It was found that when the reaction was performed
in 1,4-dioxane, the desired product was obtained in 71% yield
after 12 h (Table 1 entry 3). We further investigated the
reaction in THF, DCE and toluene using I2 as a catalyst but no
improvement in yield of desired product was observed (Table 1,
Table 1. Optimisation of reaction conditionsa
Entry
Catalyst (20 mol%)
Solventb
Temp (oC)
Time (h)
Yieldsc (%)
1
2
I2
I2
I2
I2
I2
I2
I2
I2
KI
KI
I2
I2
I2
I2
I2
I2
I2
I2
I2
-
DMF
130
100
130
130
130
130
130
80
8.5 h
10 h
12 h
6 h
89%
DMF
60%
3
1,4-dioxane
THF
71%
4
77%
5
DCE
7.5 h
12 h
6 h
60%
6
toluene
NMP
3% (5a) + imine
85%
7
8
ACN
24 h
5 h
imine + 5
92%
9
DMSO
DMF
130
130
130
130
80
10
11
12d
13
14
15
16
17e
18f
19g
20h
21i
6 h
85%
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
3.5 h
6.5 h
11 h
9 h
98%
78%
48%
100
110
140
130
130
130
130
130
70%
6.5 h
3.5 h
5 h
85%
90%
90%
4 h
94%
4 h
95%
6 h
58%
I2
8 h
70%
[a] All reactions were performed with 0.95 mmol of 5, 1.05 mmol of a and 4.76 mmol of sulfur powder in presence of 20 mol% of I2 and 100 mg of 4Ao MS in 1.5
mL of anhydrous solvent. [b] Dry solvents were used. [c] Isolated yields of the purified product. [d] 10 mol% of I2 was used. [e] 2.0 equiv. of sulfur powder was
used. [f] 3.0 equiv. of sulfur powder was used. [g] 4.0 equiv. of sulfur powder was used. [h] No catalyst was used. [i] The reaction was performed without 4Ao
MS.
3
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To investigate the effect of catalyst loading, the reaction was
attempted with 10 mol% of iodine, but, a significant decline in
the yield (78%) was noted (Table 1, Entry 12). Further, we
probed the effect of temperature on the yield and the reaction
As all the reactions were performed in presence of molecular
sieves (MS), a reaction was examined in the absence of MS and
a negative effect on the yield of desired product was noted
(Table 1, entry 21) showing the significance of MS. Eventually,
the optimization study led to the inference that DMSO was the
best solvent and iodine or KI were the suitable catalysts for this
desired transformation and 5 equiv. of S8 with MS were vital for
excellent yield of product.
With standardized conditions in hand, the scope of this domino
reaction was investigated with Kumujian C (4) and its analogues
(5-9, 19-24) with 3-amino-9-ethylcarbazole (a) and sulfur powder
as depicted in Scheme 3. This strategy was found general in
nature and bright fluorescent thiazolo[4,5-c]carbazole derivatives
(4a-9a, 19a-23a) were delivered in 70-98% yields within 3-10 h.
It is noteworthy to mention that in all cases, a clean reaction was
obtained (except 24a) and only a small column chromatographic
purification was necessary just to remove the excess sulfur. 1-
Formyl β-carboline bearing N-propargyl moiety 24 afforded the
desired carbazole annulated thiazole derivative 24a in poor yield
(31%) even after repeated attempts as formation of impurities
was observed (Scheme 3).
o
o
o
o
o
was performed at 80 C, 100 C, 110 C, 130 C and 140 C
(Table 1, entries 13-16). A drastic decreased in yield of 5a was
observed (48%) when the reaction temperature was decreased
to 80 oC (Table 1, entry 13). As expected, a continuous increase
in yield of product (70-85%) was noted with rise in temperature
o
(Table 1, entries 14-15). The yield was optimal at 130 C (98%)
but a further rise in temperature to 140 oC decreased the yield to
90% (Table 1, entries 11, 16). It was also observed that reducing
the amount of S8 from 5 equiv. to 2-4 equiv. had negative impact
and yield of the desired product was decreased to 90-95%
(Table 1, Entries 17-19). As the reaction progressed with ease in
all cases with different catalysts and solvents (except toluene
and ACN) to afford the product in good to excellent yields, it was
considered worthwhile to investigate the reaction without
catalyst. Surprisingly, the reaction yielded the desired product
under catalyst-free condition also albeit in low yields (58%,
Table 1, entry 20).
Next, we sought to extend the scope and generality of this
methodology for the preparation of β-carboline C-1 tethered
naphtho[2,1-d]thiazole derivatives (Scheme 4). Accordingly, the
methodology was evaluated with 2-naphthylamine (b) for
reaction with 1-formyl-9H-β-carboline derivatives (5-9, 19-23).
Gratifyingly, under optimized conditions, diversely substituted 1-
formyl-9H-β-carboline derivatives (5-9, 19-23) reacted efficiently
with 2-naphthylamine (b) and elemental sulfur within 3.5-8 h to
easily furnish the corresponding 2-(9H-pyrido[3,4-b]indol-1-yl)
naphtho[2,1-d]thiazole derivatives (5b-9b, 19b-23b) in 70-95%
yield (Scheme 4).
Scheme 3. Iodine catalysed synthesis of β-carboline C-1 tethered thiazolo[4,5-
c]carbazole derivatives
Scheme 4. Synthesis of β-carboline C-1 substituted naphtho[2,1-d]thiazole
derivatives
4
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Motivated by the successful synthesis of diversely substituted β-
carboline C-1 substituted thiazolo[4,5-c]carbazoles and
naphtho[2,1-d]thiazole derivatives, the scope of study was
further extended towards construction of β-carboline linked
benzothiazoles using substituted anilines c-k as demonstrated in
Scheme 5. The anilines containing electron-donating
substituents c-h responded positively towards this iodine
assisted tandem process to furnish the corresponding β-
carboline C-1 substituted benzothiazoles (4d, 5g, 11d, 19c-19f,
19h, 23d) in 50-87% yield (Scheme 5). Surprisingly, aniline
derivatives i-k containing electron withdrawing groups such as
chloro, bromo and nitro failed to deliver the desired products 19i-
19k as the reaction could not proceed beyond imine formation.
The desired products 19i-19k were formed in trace amount only
under the optimized conditions and could not be isolated from
column chromatography even after repeated attempts.
pyrido[3,4-b]thiazolo[5,4-e]indol-2-yl)-9-methyl-9H-pyrido[3,4-
b]indole-1-carbaldehyde 27 instead of anticipated β-carboline
acetal derivatives 25a. It was inferred that in situ de-masking of
acetal group in 25a afforded the product 27. Moreover, the
reaction of 1-(4-bromophenyl)-9-ethyl-9H-pyrido[3,4-b]indole-3-
carbaldehyde (26) with 3-amino-9-ethylcarbazole (a) and sulfur
powder under optimized conditions afforded the expected
product 26a in 75% yield.
Scheme 6. Synthesis of β-carboline C-3 substituted thiazolo[4,5-c]carbazole
derivatives
In order to demonstrate the application of present methodology
for industrial applications, a gram scale reaction of 9-methyl-9H-
pyrido[3,4-b]indole-1-carbaldehyde
(5)
and
3-amino-9-
ethylcarbazole (a) with sulfur powder was also performed and to
our pleasure, the targeted thiazolo[4,5-c]carbazole derivative
(5a) was obtained in 94% within
5
h
after column
chromatographic purification (Scheme 7).
Scheme 5. Synthesis of β-carboline C-1 substituted benzothiazole derivatives
Scheme 7. Gram scale synthesis of β-carboline C-1 tethered thiazolo[4,5-
c]carbazole
Delighted by the successful synthesis of β-carboline C-1
tethered benzothiazole derivatives from 1-formyl β-carbolines,
we investigated the scope of this methodology for the
preparation of β-carboline C-3 tethered thiazolo[4,5-c]carbazole
derivatives from 3-formyl β-carbolines 25-26 (Scheme 6).17
Interestingly, reaction of 1-(dimethoxymethyl)-9-methyl-9H-
Delighted by these fruitful results, we next turned our attention to
broaden the substrate scope of reaction by using 2-
aminopyridine (m) as the amine component (Scheme 8).
Accordingly,
the
9-methyl-9H-
pyrido[3,4-b]indole-1-
carbaldehyde (5) was treated with 2-aminopyridine (m) and
elemental sulfur under optimized conditions. It was pleasing to
find that the anticipated product 5m was generated in 40% yield
under the catalysis of I2 in DMSO.
pyrido[3,4-b]indole-3-carbaldehyde
(25)
with
3-amino-9-
ethylcarbazole (a) and elemental sulfur in DMSO in presence of
20 mol% iodine generated a product in 58% yield which was
anticipated to be 25a. However, the spectroscopic analysis of
isolated product revealed its structure as 3-(6-ethyl-6H-
5
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tethered benzothiazole derivatives (4d, 11d, 5l, 5m) in 35-86%
yield as depicted in Scheme 10.
Scheme 8. Synthesis of β-carboline C-1 substituted 2-(9-methyl-9H-
pyrido[3,4-b]indol-1-yl)thiazolo[4,5-b]pyridine form 2-aminopyridine
Furthermore, the catalytic property of I2 in DMSO was
demonstrated for the conventional condensation of 2-
aminothiophenol (n) containing pre-installed thiol moiety with
methyl
9-ethyl-1-formyl-9H-pyrido[3,4-b]indole-3-carboxylate
(20) at room temperature (Scheme 9).11 Interestingly, the
desired product, β-carboline C-1 substituted benzothiazole
derivative 20n was achieved in 72% yields. The reaction under
o
heating condition at 130 C completed in less time (4.5 h) but
yielded the desired product in 52% yield as impurities were
generated under heating condition.
Scheme 9. Classical approach towards I2 catalysed synthesis of β-carboline
C-1 substituted benzothiazole derivative form 2-aminothiophenol
Scheme 10. Synthesis of β-carboline C-1 linked benzothiazoles form acetal
derivatives
During the synthesis of 25a (27) in Scheme 6, it was realized
that under optimum conditions, the de-protection of acetal
functionality occurred. Therefore, it was considered worthwhile
to take advantage of this observation and investigate the scope
of present strategy for the synthesis of benzothiazoles from
aromatic acetals instead of aldehydes. Accordingly, 1-
(dimethoxymethyl)-9H-pyrido[3,4-b]indole (3, 10 and 28)
containing acetal moiety at C-1 position were employed as
substrate for reaction with 3-amino-9-ethylcarbazole (a) and S8
instead of aldehyde as it may reduce one step in the synthesis
of proposed prototypes. Alternatively, it may open up avenues
for the synthesis of benzothiazole derivatives from acetals where
aldehydes are unstable. It was noticed that the reaction of acetal
3 under optimized condition in I2 gave the desired product
identical to 4a in 70% yield in 4 h. But, when the same reaction
was performed under the catalysis of KI (20 mol%) instead of I2,
then respective product 4a was isolated in much better yield
(85%) in less time (3.5 h). Similarly, 5a and 11a were obtained in
80-89% yields. Therefore, KI turned out be a better catalyst than
I2 for synthesis of desired prototypes from acetals. Further, we
investigated the scope of this alternate approach with anilines
and 2-aminopyridine (d, l and m). To our pleasure, electron
donating anilines as well as 2-aminopyridine reacted readily in
presence of KI in DMSO to generate the anticipated β-carboline
To probe the mechanistic route of this reaction, some control
experiments (A-F) were conducted as presented in Scheme 11.
The reaction of N-methyl Kumujian C (5) was carried out with 3-
amino-9-ethylcarbazole (a) and S8 in presence of I2 in DMSO at
o
130 C but the reaction was quenched after 30 min. A column
chromatographic purification of reaction mixture yielded the
imine intermediate 29 (80%, analyzed by spectroscopy) and β-
carboline C-1 tethered thiazolo[4,5-c]carbazole 5a (15%).
Similarly, a reaction of 28 with 3-amino-9-ethylcarbazole (a) and
S8 in presence of KI in DMSO in 1.5 h generated the imine
intermediate 29 (72%) and anticipated product 5a (14%)
(Scheme 11, A-B). This isolated imine intermediate 29 was
again reacted with elemental sulfur in presence of I2 as well as
KI in DMSO which smoothly yielded the desired product 5a in
99% and 91% yields respectively (Scheme 11, C). These results
clearly indicated that reaction proceeds through formation of
imine intermediate followed by sulfur insertion. Next, we
speculated that 3-amino-9-ethyl-9H-carbazole-4-thiol (30) may
be formed a key intermediate before cyclisation with 5, (thought
appeared from Scheme 9) therefore we performed another
controlled experiment (D) in the absence of 5 to understand the
reaction mechanism, but 3-amino-9-ethylcarbazole did not
6
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10.1002/ejoc.201901908
European Journal of Organic Chemistry
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convert into thiol derivative 30 (Scheme 11, D). In another
control experiment (E), the reaction was performed in presence
of radical scavenger (2.0 equiv. TEMPO), however, the reaction
proceeded smoothly to afford desired product 5a in 80% yield
(Scheme 11, E) which ruled out the possibility of a free radicals
mechanism. It was also found that the acetal de-protection can
be effected with both I2 as well as KI in DMSO under heating
conditions at 100 oC (Scheme 11, F). However, during the
synthesis of arylthiazole derivatives from acetals with KI
(Scheme 10), it was observed that free aldehyde was not
detected in reaction mixture at any interval of time and either
acetal or imine or final product was detected (Although acetal
could be de-protected with KI, F).
Based on results of controlled experiments and previous
findings13 a reasonable mechanism for the formation of β-
carboline C-1(3) tethered thiazolo[4,5-c]carbazoles, naphtho[2,1-
d]thiazoles and benzothiazole derivatives is depicted in Figure 3.
The reaction proceeds with the formation of imine intermediate
29 by condensation of 1-formyl β-carboline 5 or acetal 28 and 3-
amino-9-ethyl-9H-carbazole (a) in presence of I2 or KI in DMSO.
Further N-iodination of imine 29 may lead to the generation of
iodonium intermediate 30. Now the reaction may follow two
different possible pathways (Figure 3). The electrophilic attack
of sulfur at the electron rich ortho position of amine in aromatic
ring (carbazole) may proceed through the path 1, where
elimination of S7 may result in formation of sulfurated imine
intermediate 32. The desired product 5a may be formed through
intramolecular cyclization of 32 followed by oxidative
aromatization of 33 which may be assisted by the presence of
sulfur (Figure 3). Alternatively, the reaction may follow path 2
where the nucleophilic addition of sulfur at the imine carbon may
generate intermediate 34. The subsequent intramolecular
electrophilic addition of sulfur on the aromatic ring of amine may
lead to the formation of cyclic intermediate 35. The
deprotonation of 35 may lead to dihydrothiazolo[4,5-c]carbazole
derivative 36 which after oxidation may yield final product 5a. It
seems that reaction favors the path 1 and evidence appears
from Scheme 5, where it was observed that the reaction with
anilines bearing electron withdrawing substituents failed to
generate the desired benzothiazole derivatives.
Figure 3. Proposed mechanism for the formation of β-carboline C-1
tethered thiazolo[4,5-c]carbazole derivative
Photophysical Studies
The benzothiazole derivatives have emerged as excellent
fluorophores owing to their luminescent properties,9-10 therefore,
light emitting properties of β-carboline C-1(3) tethered
thiazolo[4,5-c]carbazole,
naphtho[2,1-d]thiazole
and
benzothiazole derivatives were analyzed. The fluorescence
quantum yield (ΦF) of these β-carboline tethered arylthiazole
derivatives was calculated relative to quinine sulphate (ΦR
=
0.546 in 0.1 M H2SO4 at 350 nm) as a standard fluorophore. The
brightness of these newly generated fluorophores was
measured by multiplication of quantum yield () with their molar
extinction coefficient (Ɛ). In order to measure the UV-Vis
absorption and fluorescence emission of samples, stock
solutions of 1.0 mM concentration were prepared and diluted to
Scheme 11. Control experiments
7
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10.1002/ejoc.201901908
European Journal of Organic Chemistry
FULL PAPER
5.0 μM concentration using DCM as the solvent. The quantum
yields were calculated as per the equation:
2
IS AR S
S  R 


2
IR AS
R
R  Reference ;S Sample
In order to achieve maximum emission, the optimization of
solvents was carried out by using β-carboline C-1 tethered
thiazolo[4,5-c]carbazole 21a as the model substrate (Figure 4). It
was observed that the synthesized products were readily soluble
in DCM, DMSO, THF and ACN but moderately soluble in MeOH.
The thiazolo[4,5-c]carbazole derivative 21a exhibited significant
fluorescence emission in DCM, THF, DMSO as well as ACN but
the maximum fluorescence emission was obtained in DCM
(Figure 5). Expectedly, the maximum quantum yield (Φ) was
produced in DCM (52%) as illustrated in Table 2. We also
calculated the Stokes shits, molar extinction coefficient as well
as brightness for compound 21a in different solvent (Table 2).
As the best results were obtained in DCM, therefore, the
photophysical properties of all other synthesised compounds
were analysed in DCM as a solvent.
Figure 5. Fluorescence spectra of compound 21a in THF, DCM, DMSO and
ACN at 5 µM concentration
It is worthwhile to mention that we have analysed the
fluorescence spectra of most of the β-carboline derivatives at
two or three excitation wavelengths as presented in Table 3-5
and also calculated the corresponding luminescence quantum
yields. Initially, the photophysical properties of β-carboline C-1
tethered thiazolo[4,5-c]carbazole derivatives (4a-9a, 11a, 19a-
23a and 26a) were evaluated in DCM. It was realized that the
carbon length of R2 substituents at N-9 position and H/ester
functionality at C-3 position had clear impact on the emission
maxima and quantum yield of these compounds (4a-9a, 11a,
19a-23a and 26a). The red shift was observed in emission
maxima of 4a-9a (except 8a) excited at 290-299 nm (Figure 6)
with increase in length of carbon chain at N-9 position. The
fluorophore, 4a-9a displayed strong fluorescence intensity
and quantum yield (ΦF up to 92%). Similarly, bathochromic
shift was observed in emission maxima of 19a-23a excited at
297-298 nm with lengthening of carbon chain at N-9 position as
depicted in Table 3. The β-carboline C-1 tethered thiazolo[4,5-
c]carbazole derivatives 4a-9a exhibited higher fluorescence
intensity (Figures 6-7) and quantum yield (Table 3) as compared
to similar analogues bearing ester moiety at C-3 position, though
a regular trend was not present. In this series, the propyl chain
Table 2. Optimisation of solvents for analysis of photophysical properties of β-
carboline C-1 tethered thiazolo[4,5-c]carbazolea
Solve
nts
UV-
Vis
Fluorescence
Molar
Extinct
ion
Coeff.
(Ɛ) (M-
1cm-1)
62000
Bright Stoke Quantum
ness
s shift Yieldb
(nm
)
ΦF
λEx
(nm) (nm)
λEm
Intensity
(a.u.)
21a
THF
296
299
296
299
465
467
478
469
692.63
762.13
452.13
652.25
18600
25584
18048
15428
169
168
183
170
0.30
DCM
DMSO
ACN
49600
56400
40600
0.52
0.32
0.38
[a] The Photophysical properties were measured at 5 µM concentration. [b]
The quantum yields (ΦF) were calculated relative to quinine sulfate as a
reference.
at N-9 position was optimum for excellent quantum yield
(7a, ΦF
92% and 21a ΦF 82%). In short, all the β-carboline C-1(3)
,
tethered thiazolo[4,5-c]carbazole derivatives showed excellent
photophysical properties with quantum yield (ΦF) ranging from
26 to 92 %. These β-carboline derivatives (4a-9a, 11a, 19a-23a
and 26a) exhibited maximum molar extinction coefficient of
132600 (M-1Cm-1) with highest brightness up to 37468 as
presented in Table 3.
Table 3. Photophysical properties of β-carboline C-1(3) tethered thiazolo[4,5-
c]carbazole derivativesa
Com
poun
d
UV-
Vis
Fluorescence
Molar
Extincti
on
Coeff.
(Ɛ)
(M-1cm-1)
Bright
ness
Stoke
s shift
(nm)
Quant
um
Yieldb
ΦF
No.
λEx
(nm
)
λEm
(nm
)
Intensi
ty
(a.u.)
Figure 4. UV-Visible spectra of compound 21a in THF, DCM, DMSO and
ACN at 5 µM concentration
8
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10.1002/ejoc.201901908
European Journal of Organic Chemistry
FULL PAPER
4a
297
397
414
458
469
456
200.97
163.52
190.65
21000
13000
14800
6930
5330
6068
161
65
42
0.33
0.41
0.41
5a
6a
7a
290
399
464
463
640.90
354.65
37600
16200
21432
11826
174
64
0.57
0.73
299
400
465
465
999.00
947.33
132600
55600
37128
31692
166
65
0.28
0.57
299
350
400
466
465
465
998.00
659.07
962.57
129200
26000
54000
37468
23920
31320
167
115
65
0.29
0.92
0.58
8a
299
400
463
466
996.04
919.20
124200
51800
37260
30044
164
66
0.30
0.58
9a
299
399
466
465
815.15
464.84
49200
22000
27552
16280
167
66
0.56
0.74
11a
19a
20a
21a
22a
23a
26a
297
418
472
465
86.84
27.21
8200
5000
3936
1150
175
47
0.48
0.23
Figure 7. Fluorescence spectra of β-carboline C-1(3) tethered thiazolo[4,5-
c]carbazole derivatives excited (λEx) at 372–418 nm
298
400
466
465
998.00
785.87
122000
45400
36600
26786
168
65
0.30
0.59
In the case of β-carboline C-1 substituted naphtho[2,1-d]thiazole
derivatives (5b-9b, 19b, 21b, 22b); the compounds 5b-8b
excited at 395-396 nm (Figure 9) surprisingly exhibited
hypsochromic shift (Blue-shift) in 460-443 nm emission
wavelength with lengthening of aliphatic chain at N-9 position of
β-carboline ring i.e. methyl < ethyl < n-propyl < n-butyl at the N-9
position as presented in Table 4 and Figure 9. However, the
compounds 19b, 21b and 22b showed bathochromic shift (red-
shift) in emission wavelength at 457-462 nm when excited at
286-288 nm (Figure 8) with increase in length of aliphatic chain
at N-9 position i.e. methyl < n-propyl < n-butyl. In this series also,
the propyl chain at N-9 position was optimum for excellent
quantum yield (7b, ΦF 26% and 21b, ΦF 31%) as shown in
Table 4. The β-carboline linked naphtho[2,1-d]thiazole
derivatives displayed good quantum yield ranging from 12 to
31% which was significantly less than corresponding
thiazolo[4,5-c]carbazole analogues (26-92 %).
299
399
467
468
755.89
393.61
53200
19800
26068
13266
168
69
0.49
0.67
299
399
467
468
762.13
391.60
49600
16200
25584
13284
168
69
0.52
0.82
299
400
468
468
695.77
347.03
41000
14800
23780
11544
169
68
0.58
0.78
299
399
471
459
806.81
440.35
54400
21800
27744
15042
172
60
0.51
0.69
297
372
429
430
304.73
332.65
39000
35400
10140
10620
132
58
0.26
0.30
[a] The photophysical properties were measured at 5 µM concentration. [b]
The quantum yields (ΦF) were calculated relative to quinine sulfate as a
standard.
Table 4. Photophysical properties of β-carboline C-1 tethered naphtho[2,1-
d]thiazole derivativesa.
Com
poun
d
UV-
Vis
Fluorescence
Molar
Extinct
ion
Bright Stokes Quantu
ness
shift mYieldb
(nm)
ΦF
No.
Coeff.
(Ɛ) (M-
1cm-1)
λEx
(nm) (nm)
λEm
Intensity
(a.u.)
5b
6b
7b
289
395
452
460
105.70
61.96
28800
16800
4032
2016
163
65
0.14
0.12
288
396
461
458
109.21
64.51
21800
9400
3924
2068
176
62
0.18
0.22
290
399
445
450
179.78
103.55
28000
13000
6160
3380
155
51
0.22
0.26
8b
9b
299
399
446
443
212.90
77.90
37000
17800
7030
2492
147
44
0.19
0.14
289
394
452
455
261.06
180.85
65000
32000
8450
5760
163
61
0.13
0.18
Figure 6. Fluorescence spectra of β-carboline C-1(3) tethered thiazolo[4,5-
c]carbazole derivatives excited (λEx) at 290–299 nm
19b
21b
286
395
287
399
457
458
460
451
258.91
163.96
65.60
98400
37600
8600
8856
5264
2666
960
171
63
0.09
0.14
0.31
0.30
173
52
27.21
3200
9
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10.1002/ejoc.201901908
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22b
288
399
462
461
236.59
116.93
43000
16000
8170
3840
174
62
0.19
0.24
tethered benzothiazole derivatives (11d, 19c, 5g, 19f and 23d)
was found to be 74000 mol-1cm-1 for 19f while highest stokes
shift was 182 nm (Table 5 and Figure 11). Interestingly, the
thiazolo[4,5-b]pyridine derivative 5m afforded from 2-
aminopyridine showed single absorption and excitation maxima
and exhibited 15% quantum yield (Table 5). In summary, the β-
carboline C-1(3) tethered thiazolo[4,5-c]carbazole, naphtho[2,1-
d]thiazole and benzothiazole derivatives showed a wide region
[a] The photophysical properties were measured at 5 µM concentration. [b]
The quantum yields (ΦF) were calculated relative to quinine sulfate (0.1 M aq.
H2SO4, excited at 350 nm) as a reference.
of fluorescence emissions (λEm, 428–470 nm) along with
excellent quantum yields (up to 92%). The thiazolo[4,5-
c]carbazole derivatives displayed maximum quantum yield (26-
92%) followed by benzothiazole
s (ΦF = 8-68%) and then
naphtho[2,1-d]thiazole derivatives (ΦF = 12-31%).
Table 5. Photophysical properties of β-carboline C-1 tethered benzothiazole
derivativesa
Com
poun
d No.
UV-
Vis
Fluorescence
Molar
Extinct
ion
Bright Stokes Quantum
ness
shift
Yieldb
(nm)
ΦF
Coeff.
(Ɛ) (M-
1cm-1)
9000
λEx
(nm) (nm)
λEm
Intensity
(a.u.)
5g
302
374
457
459
13.19
7.91
810
374
155
85
0.09
0.11
3400
11d
277
407
388
280
318
387
279
394
448
447
447
449
444
446
457
462
136.74
148.33
139.11
291.76
258.91
181.59
757.29
540.87
6000
52800
44600
34600
25400
16400
74000
37200
480
4752
4460
9688
8382
5904
25900
17856
171
40
59
0.08
0.09
0.10
0.28
0.33
0.36
0.35
0.48
Figure 8. Fluorescence spectra of β-carboline C-1 tethered naphtho[2,1-
d]thiazole derivatives excited (λEx) at 286–299 nm
19c
169
126
59
19f
178
68
23d
279
392
461
463
431.14
281.17
30200
14200
15100
9656
182
71
0.50
0.68
5m
301
459
36.28
12400
1860
158
0.15
20n
287
385
441
443
197.99
118.67
52600
19800
6312
3762
154
59
0.12
0.19
[a] The photophysical properties were measured at 5 µM concentration. [b]
The quantum yields (ΦF) were calculated relative to quinine sulfate (0.1 M aq.
H2SO4, excited at 350 nm) as a reference.
Figure 9. Fluorescence spectra of β-carboline C-1 tethered naphtho[2,1-
d]thiazole derivatives excited (λEx) at 394–399 nm
The emission maxima of β-carboline substituted benzothiazole
derivatives (afforded from anilines) 11d, 19c, 5g, 19f, 23d
showed bathochromic shift when excited at 277-302 nm (Figure
10) with variation in substituents (H, Me and benzyl) at N-9
position of β-carboline ring and obtained emission ranging from
448 to 461 nm. Considering the regioisomeric effects of specific
auxochromes such as methoxy and methyl groups in the
benzothiazole ring, the fluorophore 19c, 19f and 23d showed
excellent fluorescence quantum yields (36-68%) while 11d
devoid of substitution at N-9 position in β-carboline ring showed
low quantum yield (10%) in this series as shown in Table 5. The
maximum molar extinction coefficient for these β-carboline C-1
Figure 10. Fluorescence spectra of β-carboline C-1 substituted benzothiazole
derivatives excited (λEx) at 277–302 nm
10
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10.1002/ejoc.201901908
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QTOF B.05.01 (B5125). Room temperature varied between 25–40 oC.
The multiplicity in the 1H NMR spectra is as follows: s for singlet, d for
doublet, t for triplet, q for quartet, dd for doublet of doublet and m for
multiplet.
General procedure for preparation of Kumujian C (9H-pyrido[3,4-
b]indole-1-carbaldehyde,
4).To
a
stirred
solution
of
1-
(dimethoxymethyl)-9H-pyrido[3,4-b]indole (3; 2 g, 8.26 mmol) in dry
DMSO (15 mL); I2 (2.30 g, 9.08 mmol) was added and the reaction
mixture was stirred for 1 h at 100 oC. After completion of reaction, as
monitored by TLC, the content was cooled to room temperature and
quenched with 10% aqueous solution of sodium thiosulfate. Thereafter,
reaction content was poured into ice cold water (50 mL) under stirring
which resulted in formation of yellow precipitates. These precipitates
were filtered through Buckner funnel and dried in air under suction. the
product was further triturated and washed with diethyl ether to yield
analytically pure product as yellow solid, 4 (1.26 g, 78%; Rf = 0.49
(hexane/EtOAc, 70: 30, v/v).
General procedure for preparation of N-alkyl derivatives of
Kumujian C (4-9) as exemplified for 9-methyl-9H-pyrido[3,4-b]indole-
1-carbaldehyde (5). To a stirred solution of Kumujian C (4; 1.00 g, 5.1
mmol) in dry DMF (30 mL), CS2CO3 (2.9 g, 9.18 mmol) was added and
stirred the reaction mixture at room temperature for 10 min. Thereafter,
methyl iodide (0.38 mL, 6.12 mmol) was added drop-wise and the
reaction mixture was stirred for additional 1 h at room temperature. On
completion of the reaction, as monitored by TLC, the content was poured
into ice cold water (40 mL) under stirring which resulted in formation of
yellow precipitates. The precipitates were filtered through Buckner funnel
and dried in air under vacuum. The precipitates were triturated and
washed twice with cold ether to get yellow solid product, 5 (0.95 g, 88%;
Rf = 0.65 (hexane/EtOAc, 70:30, v/v).
Figure 11. Fluorescence spectra of β-carboline C-1 substituted benzothiazole
derivatives excited (λEx) at 374–407 nm
Conclusions
In conclusion, a simple and highly efficient I2-catalysed oxidative
annulation strategy has been developed for the first time for the
synthesis of β-carboline C-1(3) tethered benzothiazoles,
naphtho[2,1-d]thiazoles and thiazolo[4,5-c]carbazoles via three
component assembly of Kumujian C (1-formyl 9H β-carbolines),
3-aminocarbazole/anilines/2-aminopyridine/naphthylamine and
elemental sulfur. Importantly, the strategy was applicable to
acetal derivatives also and could be used where aldehydes are
not stable. This modular approach could produce the products in
excellent yields with ease which makes the methodology highly
efficient and practical for the preparation of this class of
compounds. Furthermore, this efficient and operationally simple
protocol features use of non-toxic and inexpensive catalyst
(I2/KI) and the strategy is amenable to gram scale synthesis.
Moreover, light emitting properties of the synthesized
compounds were also investigated and these molecular
hybrids emerged as excellent fluorophores with quantum
yield (ΦF) up to 92%. The thiazolo[4,5-c]carbazole derivatives
displayed maximum quantum yield (26-92%) followed by
General procedure for the preparation of methyl 1-formyl-9H-
pyrido[3,4-b]indole-3-carboxylate (11). To a stirred solution of methyl
1-(dimethoxymethyl)-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole-3-
carboxylate (10; 5g, 16.4 mmol) in DMSO at room temperature, H2O2 (2.4
mL, 98.6 mmol, 6 equiv., 30% aq.) and I2 (0.835 g, 3.39 mmol) were
added. The reaction temperature was then slowly raised to 100 oC and
stirred for 4 h. After completion of the reaction as revealed by TLC, the
reaction mixture was cooled to room temperature and quenched with
sodium thiosulfate (50 mL, 10% aqueous solution) under stirring which
resulted in formation of yellow precipitates. The reaction mass was
filtered through the Buckner funnel and dried in air which was further
purified by column chromatography on silica gel (EtOAc/-hexane 15:85,
v/v) to obtain the pure product as a yellow solid, 11 (2.5 g, 60% yield; Rf
= 0.47 (hexane/EtOAc, 70:30, v/v). It was noted that after mixing of 10
with H2O2 and I2; a solid reaction mass is formed at room temperature
under stirring which should be heated at 100 oC for 4 h but reaction
benzothiazoles (ΦF
= 8-68%) and then naphtho[2,1-d]thiazole
derivatives (ΦF = 12-31%
.
o
temperature should be raised slowly to 100 C as reaction was observed
to exothermic in nature.
Experimental Section
General procedure for the preparation of 3a-9a, 11a, 19a-24a, 26a,
27 5b-9b, 19b-23b 4d, 5g, 11d, 19c-19f, 19h-19k, 23d and 5m as
exemplified for 6-ethyl-2-(9-methyl-9H-pyrido[3,4-b]indol-1-yl)-6H-
thiazolo[4,5-c]carbazole (5a). To a stirred solution of 9-methyl-9H-
pyrido[3,4-b]indole-1-carbaldehyde (5; 0.20 g, 0.95 mmol) in anhydrous
DMSO (1.5 mL); 3-amino-9-ethylcarbazole (a; 0.220 g, 1.05 mmol), S8
(0.152 g, 4.76 mmol), I2 (20 mol %, 0.048 g) and 4Å molecular sieves
All Chemicals and reagents were purchased from Sigma Aldrich, Acros,
Spectrochem Ltd. and Avera Synthesis and used without further
purification. Commercially available anhydrous solvents (DMSO, THF,
MeOH, toluene, ACN, diethylether and DMF) were used as received
without further distillation. Thin layer chromatography (TLC) was
performed on precoated aluminum plates (E. Merck; silica gel 60 PF254,
0.25 mm). Column chromatography was performed on silica gel (SRL;
60–120 mesh). Melting points were determined in open-ended capillary
tubes on a Precision Digital melting-point apparatus (LABCO) that
contained silicon oil and are uncorrected. IR spectra were recorded on an
Agilent FTIR spectrophotometer. 1H and 13C NMR spectra were recorded
on an Avance III Bruker spectrometer at operating frequencies of 400
MHz, 500 MHz (1H) or 100 MHz, 125 MHz (13C), as shown in the
individual spectrum, by using tetramethylsilane (TMS) as an internal
standard. HRMS spectra were recorded on 6200 series TOF/6500 series
o
(100 mg) were added and reaction content was heated at 130 C for 3.5
h. On completion of the reaction, as confirmed by TLC, the reaction
content was cooled to room temperature and quenched with sodium
thiosulfate (10% aqueous solution). Thereafter, reaction mixture was
poured into ice cold water (30 mL) under stirring which resulted in
formation of yellow precipitates. The precipitates were filtered through
Buckner funnel under vacuum. The product was further purified by a
short silica-gel (60-120 mesh) column chromatography using
EtOAc/hexane (10:90, v/v) as an eluent to obtain the pure product as a
yellow solid, 5a (0.405 g, 98%; Rf = 0.78 (hexane/EtOAc, 70:30, v/v). It is
11
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10.1002/ejoc.201901908
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mentioned that in all cases, a clean reaction was obtained (except 24a)
and column chromatographic purification was required to remove excess
sulfur only. All the products had good solubility and were easily eluted
using EtOAc: Hexane (10:90, v/v).
stirred a solution of 1-(dimethoxymethyl)-9-methyl-9H-pyrido[3,4-b]indole
(28; 0.200 g, 0.78 mmol) in anhydrous DMSO (1.5 mL); 3-amino-
9ethylcarbazole (a; 0.180 g, 0.859 mmol), S8 (0.125 g, 3.91 mmol), KI
(0.026 g, 20 mol%) and 4Å MS (100 mg) were added and stirred the
reaction mixture at 130 oC for 1.5 h. The progress of reaction was
analysed by TLC and the reaction was quenched with ice cold water (20
mL) after 1.5 h in order to isolate the imine intermediate 29. The reaction
mixture was poured into ice cold water (30 mL) under stirring which
resulted in formation of yellow precipitates. The solid reaction mass was
filtered through Buchner funnel and further purified by column
chromatography on silica gel using EtOAc/hexane (25:75, v/v) as an
eluent which afforded the imine intermediate in pure form as a yellow
solid, 29 (0.225 g, 72%; Rf = 0.43 (hexane/EtOAc, 70 : 30, v/v) along with
5a as (0.048 g, 14%; Rf = 0.78 (hexane/EtOAc, 70 : 30, v/v).
Gram scale synthesis of 6-ethyl-2-(9-methyl-9H-pyrido[3,4-b]indol-1-
yl)-6H-thiazolo[4,5-c]carbazole (5a). A 50 mL round bottom flask was
charged with 9-methyl-9H-pyrido[3,4-b]indole-1-carbaldehyde (5; 1 g,
4.76 mmol), 3-amino-9-ethylcarbazole (a; 1.1 g, 5.24 mmol), S8 (0.761 g,
23.8 mmol), I2 (20 mol %, 0.241 g), 4Å MS (400 mg), DMSO (10 mL) and
were heated at 130 oC for 5 h. On completion of the reaction, as
monitored by TLC, reaction content was cooled to room temperature and
quenched with sodium thiosulfate (10% aqueous solution). Thereafter,
the reaction content was poured into crushed ice/ice cold water (70 mL)
under stirring which resulted in formation of precipitates. The solid mass
was filtered through Buckner funnel to get the product. Which was further
purified by column chromatography on silica gel using (EtOAc/hexane
10:90, v/v) as an eluent to obtain the pure product as a yellow solid, 5a
(1.93 g, 94% yield; Rf = 0.78 (hexane/EtOAc, 70:30, v/v).
Procedure for the synthesis of 6-ethyl-2-(9-methyl-9H-pyrido[3,4-
b]indol-1-yl)-6H-thiazolo[4,5-c]carbazole 5a from imine intermediate
29. To a stirred solution of (E)-9-ethyl-N-((9-methyl-9H-pyrido[3,4-b]indol-
1-yl)methylene)-9H-carbazol-3-amine (29; 0.200g, 0.50 mmol) in
anhyrous DMSO (1.5 mL); S8 (0.79 g, 2.49 mmol), I2 (0.25 g, 20 mol%)
and 4Å MS (100 mg) were added and stirred the reaction mixture for 2.5
h at 130 oC. After completion of the reaction (monitored by TLC), the
reaction mixture was quenched with sodium thiosulfate (10% aqueous
solution). Thereafter, the reaction content was poured into ice cold water
(30 mL) under stirring which resulted in formation of yellow precipitates.
The precipitates were filtered through Buckner funnel to get the solid
product which was further purified by column chromatography on silica
gel using EtOAc/hexane (10:90, v/v) as an eluent to obtain pure product
as yellow solid, 5a (0.212 g, 99% yield; Rf = 0.78 (hexane/EtOAc, 70:30,
v/v). Similarly, reaction with KI (0.016 g, 20 mol%) as catalyst yielded the
pure product as yellow solid 5a in 91% yield (0.196 g).
General procedure for the preparation of 4a, 5a, 11a, 4d, 11d, 5l
and 5m as exemplified for 6-ethyl-2-(9H-pyrido[3,4-b]indol-1-yl)-6H-
thiazolo[4,5-c]carbazole (4a). To
a stirred the solution of 1-
(dimethoxymethyl)-9H-pyrido[3,4-b]indole (3; 0.200 g, 0.83 mmol) in
DMSO (1.5 mL); 3-amino-9-ethylcarbazole (a; 0.190 g, 0.91 mmol), S8
(0.132 g, 4.13 mmol), KI (0.027 g, 20 mol%), and 4Å MS (100 mg) were
added and heated at 130 oC for 3.5 h. On completion of reaction, as
confirmed by TLC, the reaction content was poured into ice cold water
(40 mL) under stirring which resulted in generation of yellow precipitates.
The yellow precipitates were filtered through Buchner funnel under
suction and further purified by column chromatography on silica gel using
EtOAc/hexane (10:90, v/v) as an eluent to obtain the pure product as a
yellow solid, 4a (0.295 g , 85% yield ; Rf = 0.62 (hexane/EtOAc, 70:30,
v/v).
Procedure for the preparation of 6-ethyl-2-(9-methyl-9H-pyrido[3,4-
b]indol-1-yl)-6H-thiazolo[4,5-c]carbazole (5a) in presence of TEMPO.
To a stirred the solution 1-(dimethoxymethyl)-9-methyl-9H-pyrido[3,4-
b]indole (28; 0.20 g, 0.78 mmol) in anhyrous DMSO (1.5 mL); 3-amino-9-
ethylcarbazole (a 0.180 g, 0.859 mmol), S8 (0.125 g, 3.91 mmol), KI
(0.026 g, 20 mol%), TEMPO (0.243 g, 1.56 mmol) and 4Å MS (100 mg)
were added and stirred the reaction mixture at 130 oC for 5.5 h. On
completion of reaction, as monitored by TLC, the reaction mixture was
cooled to room temperature and the reaction content was poured into ice
cold water (30 mL) under stirring. The reaction mass was filtered through
Buckner funnel to get the solid product which was further purified by
column chromatography on silica gel using EtOAc/hexane (10:90, v/v) as
an eluent to obtain pure product as yellow solid, 5a (0.33 g, 80% yield; Rf
= 0.78 (hexane/EtOAc, 70:30, v/v).
Procedure for the preparation of methyl 1-(benzo[d]thiazol-2-yl)-9-
ethyl-9,9a-dihydro-4aH-pyrido[3,4-b]indole-3-carboxylate (20n). To a
stirred the solution of methyl 9-ethyl-1-formyl-9H-pyrido[3,4-b]indole-3-
carboxylate (20; 0.200 g, 0.71 mmol) in DMSO (1.5 mL); 2-
aminobenzenethiol (n; 0.097 g, 0.78 mmol), I2 (0.036 g, 20 mol%, 0.14
mmol) and 4Å MS (100 mg) were added at room temperature for 8 h.
The progress of reaction was monitored by TLC and after completion of
reaction; the content was quenched with sodium thiosulfate (10%
aqueous solution). Thereafter, reaction content was poured into ice cold
water (40 mL) under stirring. The solid reaction mass was filtered through
Buchner funnel to get the solid product which was further purified by
column chromatography on silica gel using EtOAc/hexane (15:85, v/v) as
an eluent to obtain the pure product as a yellow solid, 20n (0.20 g, 72%;
Rf = 0.68 (hexane/EtOAc, 70:30, v/v).
9-Ethyl-9,9 a-dihydro-4aH-pyrido[3,4-b]indole-1-carbaldehyde (6).
Yield: 84% (0.92 g from 1.0 g) as a light green solid; m.p. 98-100 oC; Rf =
1
0.71 (hexane/EtOAc, 90:10, v/v); IR (neat): νmax (cm-1) = 1689 (CHO); H
NMR (400 MHz, CDCl3) δ = 1.40 (t, J = 7.1 Hz, 3H, NCH2CH3), 4.89 (q, J
= 7.1 Hz, 2H, NCH2CH3), 7.35 (t, J = 7.4 Hz, 1H, ArH), 7.54 (d, J = 8.3
Hz, 1H, ArH), 7.63–7.68 (m, 1H, ArH), 8.13–8.16 (m, 2H, ArH), 8.62–8.63
(m, 1H, ArH), 10.33 (s, 1H, ArH) ppm; 13C NMR (100 MHz, CDCl3) δ =
15.0, 41.9, 110.5, 118.8, 120.8, 121.0, 121.5, 129.5, 132.7, 135.0, 137.7,
138.4, 142.2, 194.2 ppm; HRMS (ESI) m/z: calcd. for C14H12N2O [M +
H+]: 225.1028, found: 225.1011.
General procedure for the preparation of (E)-9-ethyl-N-((9-methyl-
9H-pyrido[3,4-b]indol-1-yl)methylene)-9H-carbazol-3-amine (29). To a
stirred solution of 9-methyl-9H-pyrido[3,4-b]indole-1-carbaldehyde (5;
0.200 g, 0.95 mmol) in DMSO (1.5 mL); 3-amino-9-ethylcarbazole (a;
0.220 g, 1.05 mmol), S8 (0.152 g, 4.76 mmol), I2 (20 mol %, 0.048 g) and
o
4Å MS (100 mg), were added and heated the reaction mixture at 130 C
for 30 min. The progress of reaction was monitored by TLC and the
reaction was quenched with sodium thiosulfate (10% aqueous solution)
after 1.5 h to isolate the imine intermediate 29 midway. Thereafter,
reaction content was poured into ice cold water (30 mL) under stirring
which resulted formation of yellow precipitates. The yellow precipitate
was filtered through Buckner funnel. Which was further purified by
column chromatography on silica gel using (EtOAc/hexane 25:75, v/v) as
an eluent to obtain the pure product as a yellow solid, 29 (0.305 g, 80%
yield; Rf = 0.43 (hexane/EtOAc, 70 : 30, v/v) along with 5a as (0.063 g,
15%; Rf = 0.78 (hexane/EtOAc, 70 : 30, v/v).
9-Propyl-9H-pyrido[3,4-b]indole-1-carbaldehyde (7). Yield: 83% (1.0 g
from 1.0 g) as a light yellow solid; m.p. 165-167 oC; Rf = 0.60
(hexane/EtOAc, 90:10, v/v); IR (neat): νmax (cm-1) = 1697 (CHO); 1H NMR
(400 MHz, CDCl3) δ = 0.92 (t, J = 7.4 Hz, 3H, NCH2CH2CH3), 1.74–1.84
(m, 2H, NCH2CH2CH3), 4.78–4.82 (m, 2H, NCH2CH2CH3), 7.31–7.35 (m,
1H, ArH), 7.52 (d, J = 8.4 Hz, 1H, ArH), 7.62–7.66 (m, 1H, ArH), 8.11–
8.15 (m, 2H, ArH), 8.62 (d, J = 4.8 Hz, 1H, ArH), 10.31 (s, 1H, CHO)
ppm; 13C NMR (100 MHz, CDCl3) δ = 11.2, 23.1, 48.3, 110.7, 118.7,
120.8, 121.4, 129.4, 132.5, 135.3, 137.7, 138.4, 142.6, 194.1 ppm;
HRMS (ESI) m/z: calcd. for C15H14N2O [M + H+]: 239.1184, found:
239.1154.
Procedure for the synthesis of (E)-9-ethyl-N-((9-methyl-9H-
pyrido[3,4-b]indol-1-yl)methylene)-9H-carbazol-3-amine
(29).
To
12
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10.1002/ejoc.201901908
European Journal of Organic Chemistry
FULL PAPER
9-Butyl-9H-pyrido[3,4-b]indole-1-carbaldehyde (8). Yield: 85% (1.1 g
from 1.0 g) as
215-217 oC; Rf = 0.82 (hexane/EtOAc, 70:30, v/v); IR (neat): νmax (cm-1)
C=N (1623), C-S (731); 1H NMR (400 MHz, CDCl3) δ = 0.76 (t, J = 7.4
Hz, 3H, NCH2CH2CH3), 1.53 (t, J = 7.3 Hz, 3H, NCH2CH3), 1.71–1.81 (m,
2H, NCH2CH2CH3), 4.52 (q, J = 7.2 Hz, 2H, NCH2CH3), 5.09 (t, J = 7.7
Hz, 2H, NCH2CH2CH3), 7.33–7.36 (m, 1H, ArH), 7.38–7.42 (m, 1H, ArH),
7.54–7.57 (m, 2H, ArH), 7.59–7.68 (m, 3H, ArH), 8.11 (d, J = 4.9 Hz, 1H,
ArH), 8.20 (d, J = 7.8 Hz, 1H, ArH), 8.23 (d, J = 8.6 Hz, 1H, ArH), 8.28 (d,
J = 7.5 Hz, 1H, ArH), 8.62 (d, J = 4.9 Hz, 1H, ArH) ppm; 13C NMR (100
MHz, CDCl3) δ = 11.3, 14.3, 23.1, 38.2, 47.8, 108.2, 109.0, 110.8, 115.7,
119.8, 120.2, 121.0, 121.2, 121.4, 121.6, 122.2, 125.6, 128.9, 129.4,
131.0, 132.4, 134.0, 136.3, 137.7, 138.1, 139.8, 143.1, 149.0, 166.1
ppm; HRMS (ESI) m/z: calcd. for C29H24N4S [M + H+]: 461.1800, found:
461.1790.
a = 0.60
light yellow solid; m.p. 62-65 oC; Rf
(hexane/EtOAc, 90:10, v/v); IR (neat): νmax (cm-1) = 1703 (CHO); 1H NMR
(400 MHz, CDCl3) δ = 0.92 (t, J = 7.4 Hz, 3H, NCH2CH2CH2CH3), 1.31–
1.40 (m, 2H, NCH2CH2CH2CH3), 1.71–1.75 (m, 2H, NCH2CH2CH2CH3),
4.85 (t, J = 7.62, 2H, NCH2CH2CH2CH3), 7.33–7,36 (m,1H), 7.63–7.67
(m, 1H, ArH), 8.13–8.16 (m, 2H, ArH), 8.63 (d, J = 4.9 Hz, 1H, ArH) 10.32
(s, 1H, CHO) ppm; 13C NMR (100 MHz, CDCl3) δ = 14.0, 20.1, 31.9,
46.7, 110.7, 118.8, 120.9, 121.5, 129.4, 132.6, 135.3, 137.8, 138.4,
142.6, 194.1 ppm; HRMS (ESI) m/z: calcd. for C16H16N2O [M + H+]:
253.1341, found: 253.1326.
9-Benzyl-9H-pyrido[3,4-b]indole-1-carbaldehyde (9). Yield: 87% (1.3 g
from 1.0 g) as a light yellow solid; m.p. 120-122 oC; Rf = 0.60
(hexane/EtOAc, 90:10, v/v); IR (neat): νmax (cm-1) = 1698 (CHO); 1H NMR
(500 MHz, CDCl3) δ = 6.19 (s, 2H, CH2Ar). 6.93–6.96 (m, 2H, ArH), 7.19
(d, J = 7.2 Hz, 3H, ArH), 7.38 (t, J = 7.5 Hz, 1H, ArH), 7.50 (d, J = 8.3 Hz,
1H, ArH), 7.60–7.63 (m, 1H, ArH), 8.21 (d, J = 7.7 Hz, 1H, ArH), 8.24 (d,
J = 4.8 Hz, 1H, ArH), 8.68 (d, J = 4.9 Hz, 1H, ArH), 10.22 (s, 1H, CHO);
13C NMR (125 MHz, CDCl3) δ = 50.2, 111.1, 118.9, 121.2, 121.5, 126.2,
127.1, 127.4, 127.6, 127.7, 128.7, 129.7, 130.2, 132.9, 135.8, 137.7,
138.1, 138.9, 143.0, 194.0 ppm; HRMS (ESI) m/z: calcd. for C19H14N2O
[M + H+]: 287.1184, found: 287.1152.
2-(9-Butyl-9H-pyrido[3,4-b]indol-1-yl)-6-ethyl-6H-thiazolo[4,5-
c]carbazole (8a). Yield: 85% (0.16 g from 0.10) g as a yellow solid; m.p.
178-180 oC; Rf = 0.85 (hexane/EtOAc, 70:30, v/v); IR (neat): vmax (cm-1)
1619 (C=N), 656 (C-S); 1H NMR (500 MHz, CDCl3) δ = 0.76 (t, J = 7.4
Hz, 3H, NCH2CH2CH2CH3), 1.15–1.22 (m, 2H, NCH2CH2CH2CH3), 1.51
(t, J = 7.2 Hz, 3H, NCH2CH3), 1.67–1.72 (m, 2H, NCH2CH2CH2CH3), 4.49
(q, J = 7.2 Hz, 2H, NCH2CH3), 5.12 (t, J = 7.7 2H, NCH2CH2CH2CH3),
7.34 (t, J = 7.3 Hz, 1H, ArH), 7.39–7.42 (m, 1H, ArH), 7.52–7.56 (m, 2H,
ArH), 7.58–7.61 (m, 2H, ArH), 7.65 (t, J = 7.5 Hz, 1H; ArH), 8.09 (d, J =
4.9 Hz, 1H, ArH), 8.20 (t, J = 9.1 Hz, 2H, ArH), 8.29 (d, J = 7.8 Hz, 1H,
ArH), 8.62 (d, J = 5.0 Hz, 1H, ArH) ppm; 13C NMR (125 MHz,CDCl3) δ =
14.0, 14.3, 20.2, 31.9, 38.2, 46.1, 108.2, 109.1, 110.8, 115.7, 119.9,
120.2, 121.0, 121.3, 121.5, 122.2, 125.6, 129.0, 129.4, 132.5, 134.0,
136.3, 137.7, 138.1, 139.8, 143.0, 149.0, 166.1 ppm; HRMS (ESI) m/z:
calcd. for C30H26N4S [M + H+]: 475.1956, found: 4751955.
6-Ethyl-2-(9H-pyrido[3,4-b]indol-1-yl)-6H-thiazolo[4,5-c]carbazole
(4a). Yield: 93% (0.19 g from 0.10 g) as a yellow solid; m.p. >250 oC; Rf =
0.62 (hexane/EtOAc, 70:30, v/v); IR (neat): νmax (cm-1) = 3406 (NH), 1624
(C=N), 745 (C-S); 1H NMR (400 MHz, CDCl3) δ = 1.52 (t, J = 7.3 Hz, 3H;
NCH2CH3), 4.51 (q, J = 7.2 Hz, 2H, NCH2CH3), 7.35 (t, J = 7.4 Hz, 1H,
ArH), 7.39–7.43 (m, 1H), 7.53–7.59 (m, 2H, ArH), 7.62–7.65 (m, 2H, ArH)
7.73 (d, J = 8.1 Hz, 1H, ArH), 8.05 (d, J = 5.1 Hz, 1H, ArH), 8.20 (d, J =
7.8 Hz, 1H, ArH), 8.26 (d, J = 7.7 Hz, 1H, ArH), 8.31 (d, J = 8.8 Hz, 1H,
ArH), 8.59 (d, J = 5.1 Hz, 1H, ArH), 10.79 (s, 1H, NH) ppm. The 13C NMR
spectrum could not be recorded due to solubility problem in CDCl3 as
well as DMSO-d6; HRMS (ESI) m/z: calcd. for C26H18N4 [M + H+]:
419.1330, found: 419.1321.
2-(9-Benzyl-9H-pyrido[3,4-b]indol-1-yl)-5-ethyl-5H-thiazolo[4,5-
b]carbazole (9a). Yield: 84% (0.22 g from 0.15) as a yellow solid; m.p.
188-190 oC; Rf = 0.79 (hexane/EtOAc, 70:30, v/v); IR (neat): νmax (cm-1)
1621 (C=N), 732 (C-S); 1H NMR (400 MHz, CDCl3) δ = 1.51 (t, J = 7.2
Hz, 3H, NCH2CH3). 4.49 (q, J = 7.2 Hz, 2H, NCH2CH3), 6.40 (s, 2H,
CH2Ar), 6.84–6.86 (m, 2H, ArH), 7.04–7.11 (m, 3H, ArH), 7.35–7.40 (m,
2H, ArH ), 7.51–7.57 (m, 4H, ArH), 7.59–7.63 (m, 1H, ArH), 7.90 (d, J =
8.9 Hz, 1H, ArH), 8.12 (d, J = 5.0 Hz, 1H, ArH), 8.22 (dd, J1 = 7.7 J2 = 3.8
Hz, 2H, ArH), 8.63 (d, J = 4.9 Hz, 1H, ArH) ppm; 13C NMR (100 MHz,
CDCl3) δ = 14.2, 38.1, 50.1, 108.1, 109.0, 111.4, 115.5, 115.7, 119.8,
120.7, 121.0, 121.5, 121.5, 122.2, 125.6, 126.3, 126.9, 127.0, 128.4,
128.9, 129.2, 129.4, 132.8, 134.6, 136.7, 137.7, 138.4, 138.6, 139.8,
143.7, 148.7, 165.7 ppm; HRMS (ESI) m/z: calcd. for C33H24N4S [M +
H+]: 509.1800, found: 509.1790.
Methyl
9-butyl-1-(5-ethyl-5H-thiazolo[4,5-b]carbazol-2-yl)-9H-
pyrido[3,4-b]indole-3-carboxylate (5a). Yield: 98% (0.40 g from 0.20 g)
as a yellow solid; m.p. 196-198 oC; Rf = 0.78 (hexane/EtOAc, 70:30, v/v);
IR (neat): νmax (cm-1) = 1621 (C=N), 718 (C-S); 1H NMR (400 MHz,
CDCl3) δ = 1.50 (t, J = 6.9 Hz, 3H, NCH2CH3), 4.28 (s, 3H, NCH3), 4.47
(q, J = 7.0 Hz, 2H, NCH2CH3), 7.34 (t, J = 7.3 Hz, 1H, ArH), 7.40 (t, J =
7.0 Hz, 1H, ArH), 7.54 (t, J = 8.1 Hz, 3H, ArH), 7.60 (d, J = 8.9 Hz, 1H,
ArH), 7.64 (t, J = 7.7 Hz, 1H, ArH), 8.06 (d, J = 4.6 Hz, 1H, ArH), 8.17 (d,
J = 7.7 Hz, 1H, ArH), 8.24 (t, J = 9.8 Hz, 2H, ArH), 8.61 (d, J = 4.7 Hz,
1H, ArH) ppm; 13C NMR (100 MHz, CDCl3) δ = 14.2, 34.8, 38.1, 108.2,
109.0, 110.5, 115.6, 119.8, 120.3, 121.0, 121.1, 121.4, 121.5, 122.2,
125.6, 129.1, 129.3 132.3, 135.1, 136.4, 137.7, 138.3, 139.8, 143.9,
148.8, 165.6 ppm; HRMS (ESI) m/z: calcd. for C27H20N4S [M + H+]:
433.1487, found: 433.1466.
Methyl
1-(6-ethyl-6H-thiazolo[4,5-c]carbazol-2-yl)-9H-pyrido[3,4-
b]indole-3-carboxylate (11a). Yield: 87% (0.16 g from 0.10 g) as a
yellow solid; m.p. >250 oC; Rf = 0.60 (hexane/EtOAc, 70:30, v/v); IR
(neat): νmax (cm-1) = 1717 (CO2CH3), 3375 (NH), 1610 (C=N), 736 (C-S);
δ = 1H NMR (400 MHz, CDCl3) δ = 1.51 (t, J = 7.2 Hz, 3H, NCH2CH3),
4.15 (s, 3H, CO2CH3), 4.47 (q, J = 7.2 Hz, 2H, NCH2CH3), 7.38–7.44 (m,
2H, ArH), 7.52–7.57 (m, 2H, ArH), 7.60 (d, J = 9.0 Hz, 1H, ArH), 7.66 (t, J
= 7.6 Hz, 1H, ArH), 7.74 (d, J = 8.2 Hz, 1H, ArH), 8.23 (d, J = 7.9 Hz, 1H,
ArH), 8.28 (t, J = 8.8 Hz, 2H, ArH), 8.92 (s, 1H, ArH), 11.01 (s, 1H, ArH)
ppm; 13C NMR spectra could not be recorded due to solubility problem in
CDCl3 & DMSO-d6; HRMS (ESI) m/z: calcd. for C28H20N4O2S [M + Na+]:
499.1205, found: 499.1202.
6-Ethyl-2-(9-ethyl-9H-pyrido[3,4-b]indol-1-yl)-6H-thiazolo[4,5-c]
carbazole (6a). Yield: 92% (0.18 g from 0.10 g) as a yellow solid; m.p.
220-222 oC; Rf = 0.80 (hexane/EtOAc, 70:30, v/v); IR (neat): νmax (cm-1)
C=N (1618), C-S (732); 1H NMR (400 MHz, CDCl3) δ = 1.33 (t, J = 7.1
Hz, 3H, NCH2CH3carbazole), 1.53 (t, J = 7.2 Hz, 3H, CH2CH3), 4.53 (q, J =
7.2 Hz, 2H, NCH2CH3carbazole), 5.15 (q, J = 7.1 Hz, 2H, NCH2CH3), 7.34–
7.37 (m, 1H, ArH), 7.38–7.42 (m, 1H, ArH), 7.55–7.57 (m, 2H, ArH),
7.61–7.64 (m, 2H, ArH), 7.65–7.68 (m, 1H, ArH), 8.10 (d, J = 4.9 Hz, 1H,
ArH), 8.19–8.24 (m, 2H, ArH), 8.28 (d, J = 7.6 Hz, 1H, ArH), 8.62 (d, J =
4.9 Hz, 1H, ArH) ppm; 13C NMR (100 MHz, CDCl3) δ = 14.3, 14.9, 38.2,
41.3, 108.2, 109.1, 110.7, 115.6, 115.7, 119.9, 120.3, 121.1, 121.5,
121.6, 122.2, 125.7, 129.1, 129.4, 132.7, 133.9, 136.3, 137.8, 138.1,
139.8, 142.8, 148.9, 165.8 ppm; HRMS (ESI) m/z: calcd. for C28H22N4S
[M + H+]: 447.1643, found: 447.1658.
Methyl
1-(5-ethyl-5H-thiazolo[4,5-b]carbazol-2-yl)-9-methyl-9H-
pyrido[3,4-b]indole-3-carboxylate (19a). Yield: 80% (0.22 g from 0.15
g) as a yellow solid; m.p. 199-200 oC; Rf = 0.64 (hexane/EtOAc, 70:30,
v/v); IR (neat): νmax (cm-1) = 1708 (CO2CH3), 1620 (C=N), 739 (C-S); 1H
NMR (400 MHz, CDCl3) δ = 1.50 (t, J = 7.2 Hz, 3H, NCH2CH3) 4.13 (s,
3H, CO2CH3), 4.27 (s, 3H, NCH3), 4.46 (q, J = 7.0 Hz, 2H, NCH2CH3),
7.40 (t, J = 7.1 Hz, 2H, ArH), 7.51–7.54 (m, 2H, ArH). 7.56–7.58 (m, 2H,
ArH), 7.67 (t, J = 7.5 Hz, 1H, ArH), 8.21 (d, J = 8.3 Hz, 2H, ArH), 8.26 (d,
J = 7.7 Hz, 1H, ArH), 8.90 (s, 1H, ArH) ppm; 13C NMR (100 MHz, CDCl3)
δ = 14.3, 34.9, 38.2, 53.0, 108.3, 109.1, 110.7, 118.1, 119.9, 121.1,
121.3, 121.3, 121.6, 122.1, 125.7, 128.9, 129.5, 129.7, 131.0, 132.3,
6-Ethyl-2-(9-propyl-9H-pyrido[3,4-b]indol-1-yl)-6H-thiazolo[4,5-c]
carbazole (7a). Yield: 93% (0.18 g from 0.10 g) as a yellow solid; m.p.
13
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10.1002/ejoc.201901908
European Journal of Organic Chemistry
FULL PAPER
136.0, 136.2, 136.7, 137.8, 139.8, 144.0, 148.7, 164.5, 166.3 ppm;
HRMS (ESI) m/z: calcd. for C29H22N4O2S [M + H+]: 491.1542, found:
491.15.
Methyl 1-(6-ethyl-6H-thiazolo[4,5-c]carbazol-2-yl)-9-(prop-2-yn-1-yl)-
9H-pyrido[3,4-b]indole-3-carboxylate (24a). Yield: 31% (0.11 g from
0.20) as a light Orange solid; m.p. 200-202 oC; Rf = 0.61 (hexane/EtOAc,
70:30, v/v) IR (neat): νmax (cm-1) = 1705 (CO2CH3), 1628 (C=N), 738 (C-
S); 1H NMR (500 MHz, CDCl3) δ = 1.54 (t, J = 7.2 Hz, 3H, NCH2CH3),
2.13 (t, J = 2.2 Hz, 1H, C≡CH), 4.15 (s, 3H, CO2CH3), 4.52 (q, J = 7.2 Hz,
2H, NCH2CH3), 6.17 (d, J = 2.1 Hz, 2H, NCH2), 7.52–7.54 (m, 1H, ArH),
7.56–7.57 (m, 2H, ArH), 7.63 (d, J = 8.8 Hz, 1H, ArH), 7.70–7.77 (m, 3H,
ArH), 8.25–8.27 (m, 2H, ArH), 8.31 (d, J = 7.5 Hz, 1H, ArH), 8.95 (s, 1H,
ArH) ppm; 13C NMR (100 MHz,CDCl3) δ = 14.3, 37.0, 38.2, 53.1, 72.9,
78.8, 108.4, 109.1, 110.5, 111.4, 115.6, 118.1, 119.9, 121.2, 121.7,
121.8, 122.0, 122.2, 125.7, 129.8, 133.4, 135.0, 136.3, 137.5, 137.9,
138.9, 139.8, 143.1, 148.8, 150.1, 165.5, 166.1, ppm; HRMS (ESI) m/z:
calcd. for C31H22N4O2S [M + H+]: 515.1542, found: 515.1511.
Methyl
9-ethyl-1-(5-ethyl-5H-thiazolo[4,5-b]carbazol-2-yl)-9H-
pyrido[3,4-b]indole-3-carboxylate (20a). Yield: 83% (0.29 g from 0.20
g) as a yellow solid; m.p. 195-196 oC; Rf = 0.68 (hexane/EtOAc, 70:30,
v/v); IR (neat): νmax (cm-1) = 1707 (CO2CH3), 1622 (C=N), 723 (C-S); 1H
NMR (400 MHz, CDCl3) δ = 1.35 (t, J = 7.1 Hz, 3H, NCH2CH3carbazole),
1.54 (t, J = 7.3 Hz, 3H, CH2CH3), 4.14 (s, 3H, CO2CH3), 4.53 (q, J = 7.2
Hz, 2H, NCH2CH3carbazole), 5.15 (q, J = 7.1 Hz, 2H, NCH2CH3), 7.40–7.44
(m, 2H, ArH), 7.56–7.58 (m, 2H, ArH), 7.62–7.66 (m, 2H, ArH), 7.68–7.72
(m, 1H, ArH), 8.22 (d, J = 8.8 Hz, 1H, ArH), 8.27 (d, J = 7.8 Hz, 1H, ArH),
8.30–8.32 (m, 1H, ArH), 8.98 (s, 1H, ArH) ppm; 13C NMR (100 MHz,
CDCl3) δ = 14.2, 15.0, 38.1, 41.5, 53.0, 108.2, 109.0, 110.9, 115.5,
118.1, 119.8, 121.0, 121.2, 121.7, 122.1, 125.6, 128.9, 129.4, 129.8
131.0, 132.6, 135.0, 135.9, 136.5, 137.7, 139.7, 142.8, 148.7, 164.8,
166.2 ppm; HRMS (ESI) m/z: calcd. for C30H24N4O2S [M + H+]: 505.1698
found: 505.1664.
2-(9-Methyl-9H-pyrido[3,4-b]indol-1-yl)naphtho[2,1-d]thiazole
(5b).
Yield: 77% (0.20 g from 0.15) as a yellow solid; m.p. 196-198 oC; Rf =
0.74 (hexane/EtOAc, 70:30, v/v); IR (neat): νmax (cm-1) = 1623 (C=N), 727
(C-S); 1H NMR (400 MHz, CDCl3) δ = 4.27 (s, 3H, CO2CH3). 7.34–7.38
(m, 1H, ArH), 7.55–7.58 (m, 1H, ArH), 7.59–7.61 (m, 1H, ArH), 7.63–7.65
(m, 1H, ArH), 7.66–7.69 (m, 1H, ArH), 7.93 (d, J = 8.8 Hz, 1H, ArH),
7.99–8.01 (m, 1H, ArH), 8.10 (d, J = 5.0 Hz, 1H, ArH), 8.15–8.16 (m, 1H,
ArH), 8.17–8.20 (m, 2H, ArH), 8.60 (d, J = 4.9 Hz, 1H, ArH) ppm; 13C
NMR (100 MHz, CDCl3) δ = 34.9, 110.5, 116.0, 120.5, 121.1, 121.5,
122.0, 125.7, 126.4, 127.3, 127.4, 128.4, 129.1, 129.2, 131.3, 132.5,
133.7, 135.2, 135.9, 138.4, 143.9, 152.1, 168.6 ppm; HRMS (ESI) m/z:
calcd. for C23H15N3S [M + H+]: 366.1065, found: 366.1071.
Methyl 1-(5-ethyl-5H-thiazolo[4,5-b]carbazol-2-yl)-9-propyl-9H-pyrido
[3,4-b]indole-3-carboxylate (21a). Yield: 75% (0.26 g from 0.20 g) as a
yellow solid; m.p. 194-196 oC; Rf = 0.72 (hexane/EtOAc, 70:30, v/v); IR
(neat): νmax (cm-1) = 1701 (CO2CH3), 1623 (C=N), 734 (C-S); 1H NMR
(400 MHz, CDCl3) δ = 0.75 (t, J = 7.4 Hz, 3H, NCH2CH2CH3), 1.52 (t, J =
7.2 Hz, 3H, NCH2CH3), 1.76 (m, 2H, NCH2CH2CH3), 4.15 (s, 3H,
CO2CH3), 4.48 (q, J = 7.2, 2H, NCH2CH3), 5.06 (t, J = 7.7, 2H,
NCH2CH2CH3), 7.39 (d, J = 7.4 Hz, 1H, ArH), 7.41–7.43 (m, 1H, ArH),
7.54 (t, J = 8.5 Hz, 2H, ArH), 7.58–7.61 (m, 2H, ArH), 7.67 (t, J = 7.6 Hz,
1H, ArH), 8.20 (d, J = 8.7 Hz, 1H, ArH), 8.24 (d, J = 7.8 Hz, 1H, ArH),
8.30 (d, J = 7.7 Hz, 1H, ArH), 8.96 (s, 1H, ArH) ppm; 13C NMR (100 MHz,
CDCl3) δ = 11.3, 14.3, 23.2, 38.1, 47.9, 53.0, 108.3, 109.1, 110.1, 115.6,
118.1, 119.9, 121.0, 121.2, 121.5, 121.7, 122.1, 125.7, 129.4, 129.9,
132.5, 135.2, 136.9, 136.5, 137.8, 139.8, 143.2, 148.8, 165.0, 166.3
ppm; HRMS (ESI) m/z: calcd. for C31H26N4O2S [M + H+]: 519.1855,
found: 519.1868.
2-(9-Ethyl-9H-pyrido[3,4-b]indol-1-yl)naphtho[2,1-d]thiazole (6b).
Yield: 88% (0.15 g from 0.10) as a brown solid; m.p. 138-142 oC; Rf =
0.73 (hexane/EtOAc, 70:30, v/v); IR (neat): νmax (cm-1) = 1664 (C=N), 739
(C-S); 1H NMR (400 MHz, CDCl3) δ = 1.33 (t, J = 7.0 Hz, 3H, NCH2CH3),
5.11 (q, J = 7.0 Hz, 2H, NCH2CH3), 7.33–7.37 (m, 1H, ArH), 7.57–7.62
(m, 2H, ArH), 7.63–7.69 (m, 2H, ArH), 7.92 (d, J = 8.8 Hz, 1H, ArH), 8.01
(d, J = 7.8 Hz, 1H, ArH), 8.10–8.15 (m, 2H, ArH), 8.19 (t, J = 8.1 Hz, 2H,
ArH), 8.59 (d, J = 5.1 Hz, 1H, ArH) ppm; 13C NMR (100 MHz, CDCl3) δ =
14.9, 41.3, 110.7, 116.0, 120.4, 121.4, 121.6, 122.0, 125.7, 126.4, 127.2,
127.3, 128.3, 129.1, 131.3, 132.8, 133.8, 133.9, 135.9, 138.2, 142.8,
152.2, 169.0 ppm; HRMS (ESI) m/z: calcd. for C24H17N3S [M + H+]
380.1221, found: 380.1206.
Methyl
9-butyl-1-(5-ethyl-5H-thiazolo
[4,5-b]carbazol-2-yl)-9H-
pyrido[3,4-b]indole-3-carboxylate (22a). Yield: 70% (0.24 g from 0.20
g) as a yellow solid; m.p. 174-176 oC; Rf = 0.76 (hexane/EtOAc, 70:30,
v/v); IR (neat): νmax (cm-1) = 1702 (CO2CH3), 1615 (C=N), 743 (C-S); 1H
NMR (400 MHz, CDCl3) δ = 0.73 (t, J = 7.1 Hz, 3H, NCH2CH2CH2CH3),
1.12–1.22 (m, 2H, NCH2CH2CH2CH3), 1.53 (t, J = 6.9 Hz, 3H, NCH2CH3),
1.60–1.70 (m, 2H, NCH2CH2CH2CH3), 4.14 (s, 3H, CO2CH3), 4.51 (q, J =
6.7 Hz, 2H, NCH2CH3), 5.12 (t, J = 7.2 Hz, 2H, NCH2CH2CH2CH3), 7.41–
7.57 (m, 4H, ArH), 7.62 (d, J = 8.5 Hz, 2H, ArH), 7.69 (t, J = 7.4 Hz, 1H,
ArH), 8.20 (d, J = 8.7 Hz, 1H, ArH), 8.26 (d, J = 7.6 Hz, 1H, ArH), 8.31 (d,
J = 7.6 Hz, 1H, ArH), 8.98 (s, 1H, ArH) ppm; 13C NMR (100 MHz, CDCl3)
δ = 13.9, 14.3, 20.2, 31.9, 38.1, 46.3, 53.0, 108.3, 109.0, 111.1, 115.6,
118.1, 119.9, 121.0, 121.2, 121.6, 121.7, 122.1, 122.7, 129.4, 129.8,
132.6, 135.2, 136.0, 136.5, 137.8, 139.8, 143.2, 148.7, 165.1, 166.3
ppm; HRMS (ESI) m/z: calcd. for C32H28N4O2S [M + Na+]: 555.1831,
found: 555.1811.
2-(9-Propyl-9H-pyrido[3,4-b]indol-1-yl)naphtho[2,1-d]thiazole
(7b).
Yield: 78% (0.129 g from 0.10 g) as a yellow solid; m.p. 181-183 oC; Rf =
0.78 (hexane/EtOAc, 70:30, v/v) IR (neat): νmax (cm-1) = 1620 (C=N), 739
(C-S); 1H NMR (400 MHz, CDCl3) δ = 0.76 (t, J = 7.4 Hz, 3H,
NCH2CH2CH3), 1.69–1.80 (m, 2H, NCH2CH2CH3), 5.05 (t, J = 7.7 2H,
NCH2CH2CH3), 7.35 (t, J = 7.4 Hz, 1H, ArH), 7.57–7.61 (m, 2H, ArH),
7.63–7.68 (m, 2H, ArH), 7.92 (d, J = 8.8 Hz, 1H; ArH), 8.01 (d, J = 8.0 Hz,
1H, ArH), 8.12–8.21 (m, 4H, ArH), 8.59 (d, J = 4.9 Hz, 1H, ArH) ppm; 13
C
NMR (100 MHz, CDCl3) δ = 11.3, 23.0, 47.8, 110.8, 116.0, 120.3, 121.1,
121.5, 121.9, 125.7, 126.4, 127.2, 127.4, 128.3, 129.1, 131.3, 132.6,
133.8, 134.0, 135.8, 138.1 143.1, 152.2, 169.1 ppm; HRMS (ESI) m/z:
calcd. for C25H19N3S [M + H+] 394.1378, found: 394.1384.
Methyl
9-benzyl-1-(6-ethyl-6H-thiazolo
[4,5-c]carbazol-2-yl)-9H-
2-(9-Butyl-9H-pyrido[3,4-b]indol-1-yl)naphtho[2,1-d]thiazole
(8b).
o
pyrido[3,4-b]indole-3-carboxylate (23a). Yield: 88% (0.145 g from
0.10) as a yellow solid; m.p. 180-182 oC; Rf = 0.78 (hexane/EtOAc, 70:30,
v/v); IR (neat): νmax (cm-1) = 1702 (CO2CH3), 1626 (C=N), 731 (C-S); 1H
NMR (400 MHz, CDCl3) δ = 1.52 (t, J = 7.2 Hz, 3H, NCH2CH3), 4.13 (s,
3H, CO2CH3), 4.50 (q, J = 7.2 Hz, 2H, NCH2CH3), 6.42 (s, 2H, CH2Ar),
6.76 (d, J = 7.1 Hz, 2H, ArH), 6.99–7.03 (m, 2H, ArH), 7.04–7.08 (m, 1H,
ArH), 7.38–7.42 (m, 1H, ArH), 7.45 (d, J = 7.6 Hz, 1H, ArH), 7.55–7.56
(m, 2H, ArH), 7.58–7.61 (m, 2H, ArH), 7.64–7.68 (m, 1H, ArH), 7.96 (d, J
= 8.9 Hz, 1H, ArH), 8.24 (d, J = 7.7 Hz, 1H, ArH), 8.30 (d, J = 7.8 Hz, 1H,
ArH), 9.00 (s, 1H, ArH) ppm; 13C NMR (100 MHz, CDCl3) δ = 14.3, 38.2,
50.1, 53.1, 108.3, 109.0, 111.6, 115.5, 118.1, 119.8, 121.0, 121.6, 121.8,
122.1, 125.6, 126.2, 127.2, 128.5, 129.7, 129.8, 133.0, 135.7, 136.5,
137.1, 137.7, 137.8, 139.8, 143.9, 148.6, 164.7, 166.2 ppm; HRMS (ESI)
m/z: calcd. for C35H26N4O2S [M + H+]: 567.185, found: 567.18.
Yield: 79% (0.191 g from 0.15) as a yellow solid; m.p. 158-160 C; Rf =
0.81 (hexane/EtOAc, 70:30, v/v) IR (neat): νmax (cm-1) 1580 (C=N), 672
(C-S); 1H NMR (500 MHz, CDCl3) δ = 0.76 (t, J = 7.4 Hz, 3H,
NCH2CH2CH2CH3), 1.13–1.22 (m, 2H, NCH2CH2CH2CH3), 1.64–1.71 (m,
2H, NCH2CH2CH2CH3), 5.08 (t, J = 7.7 Hz, 2H, NCH2CH2CH2CH3), 7.34
(t, J = 7.4 Hz, 1H, ArH), 7.57–7.60 (m, 2H, ArH), 7.63–7.67 (m, 2H, ArH),
7.91 (d, J = 8.8 Hz, 1H, ArH), 8.00 (d, J = 8.0 Hz, 1H, ArH), 8.10 (d, J =
4.9 Hz, 1H, ArH), 8.12 (d, J = 8.7 Hz, 1H, ArH), 8.18 (dd, J1 = 7.8, J2 =
2.6 Hz, 2H, ArH), 8.59 (d, J = 4.9 Hz, 1H, ArH) ppm; 13C NMR (125 MHz,
CDCl3) δ = 14.0, 20.1, 31.8, 46.1, 110.8, 116.0 120.3, 121.2, 121.5,
121.9, 125.7, 126.4, 127.2, 127.4, 128.3, 129.1, 131.3, 132.7, 133.8,
134.0, 135.8, 138.1, 143.0, 152.2, 169.1 ppm; HRMS (ESI) m/z: calcd.
for C26H21N3S [M + H+]: 408.1534, found: 408.1512.
14
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201901908
European Journal of Organic Chemistry
FULL PAPER
2-(9-Benzyl-9H-pyrido[3,4-b]indol-1-yl)naphtho[2,3-d]thiazole
(9b).
111.2, 118.5, 121.4, 121.6, 121.8, 121.9, 125.9, 126.6, 127.4, 127.6,
128.4, 129.2, 129.6, 131.5, 132.9, 134.4, 135.3, 135.5, 136.6, 143.3,
152.1, 166.2, 168.1 ppm; HRMS (ESI) m/z: calcd. for C28H23N3O2S [M +
H+]: 466.1589, found: 466.1541.
Yield: 88% (0.20 g from 0.15) as a yellow solid; m.p. 205-210 oC; Rf =
0.74 (hexane/EtOAc, 70:30, v/v) IR (neat): νmax (cm-1) 1620 (C=N), 729
(C-S); 1H NMR (500 MHz, CDCl3) δ = 6.34 (s, 2H, CH2Ar). 6.80 (d, J =
7.1 Hz, 2H, ArH), 7.03–7.11 (m, 3H, ArH), 7.37 (t, J = 7.3 Hz, 1H, ArH),
7.53–7.58 (m, 2H, ArH), 7.60–7.63 (m, 2H, ArH), 7.82–7.86 (m, 2H, ArH),
7.97 (d, J = 7.9 Hz, 1H, ArH), 8.09 (d, J = 7.9 Hz, 1H, ArH), 8.13 (d, J =
5.0 Hz, 1H, ArH), 8.22 (d, J = 7.8 Hz, 1H, ArH), 8.60 (d, J = 4.9 Hz, 1H,
ArH) ppm; 13C NMR (125 MHz, CDCl3) δ = 50.1, 111.3, 116.0, 120.8,
121.5, 121.6, 121.9, 125.7, 126.2, 126.3, 127.0, 127.2, 127.3, 128.3,
128.5, 129.1, 129.4, 131.3, 133.0, 133.8, 134.6, 136.3, 138.2, 138.7,
143.7, 152.0, 168.6 ppm; HRMS (ESI) m/z: calcd. for C29H19N3S [M +
H+]: 442.1378, found: 442.1377.
Methyl
9-benzyl-1-(naphtho[2,1-d]
thiazol-2-yl)-9H-pyrido[3,4-
b]indole-3-carboxylate (23b). Yield: 75% (0.11 g from 0.10) as a light
yellow solid; m.p. 190-192 oC; Rf = 0.79 (hexane/EtOAc, 70:30, v/v); IR
(neat): νmax (cm-1) = 1708 (CO2CH3), 1622 (C=N), 732 (C-S); 1H NMR
(400 MHz, CDCl3) δ = 4.11 (s, 3H, CO2CH3), 6.38 (s, 2H, CH2Ar), 6.72 (d,
J = 7.2 Hz, 2H, ArH), 6.98–7.02 (m, 2H, ArH), 7.05–7.09 (m,1H, ArH),
7.42–7.46 (m, 1H, ArH), 7.56–7.58 (m, 1H, ArH), 7.60–7.63 (m, 2H, ArH),
7.64–7.68 (m, 1H, ArH), 7.85–7.90 (m, 2H, ArH), 7.97–7.99 (m, 1H, ArH),
8.12 (d, J = 7.6 Hz, 1H, ArH), 8.30 (d, J = 7.8 Hz, 1H, ArH), 9.01 (s, 1H,
ArH) ppm; 13C NMR (100 MHz,CDCl3) δ = 50.0, 53.0, 111.5, 118.4, 121.7,
121.8, 125.7, 126.1, 126.5, 127.2, 127.5, 128.2, 128.5, 129.0, 129.8,
131.3, 133.2, 134.4, 135.7, 136.0, 137.1, 137.5, 143.9, 151.8, 166.1,
167.6 ppm; HRMS (ESI) m/z: calcd. for C31H21N3O2S [M + H+]: 500.1433,
found: 500.1385.
Methyl
9-methyl-1-(naphtho[2,3-d]thiazol-2-yl)-9H-pyrido[3,4-
b]indole-3-carboxylate (19b). Yield: 70% (0.17 g from 0.15 g) as a
brown solid; m.p. 210-212 oC; Rf = 0.64 (hexane/EtOAc, 70:30, v/v); IR
(neat): νmax (cm-1) = 1711 (CO2CH3) 1618 (C=N), 739 (C-S); 1H NMR
(400 MHz, CDCl3) δ = 4.11 (s, 3H, CO2CH3), 4.30 (s, 3H, NCH3), 7.43 (t,
J = 7.6 Hz, 1H, ArH), 7.58–7.63 (m, 2H, ArH), 7.64–7.68 (m, 1H, ArH),
7.69–7.73 (m, 1H, ArH), 7.93 (d, J = 8.8 Hz, 1H, ArH), 8.01 (d, J = 7.8 Hz,
1H, ArH), 8.15 (d, J = 8.9 Hz, 1H, ArH), 8.20 (d, J = 8.0 Hz, 1H, ArH),
8.26 (d, J = 7.9 Hz, 1H, ArH), 8.97 (s, 1H, ArH), ppm; 13C NMR (100 MHz,
CDCl3) δ = 35.0, 53.0, 110.8, 118.4, 121.4, 121.8, 122.0, 125.8, 126.6,
127.3, 127.6, 128.2, 129.1, 129.7, 131.4, 132.6, 134.2, 135.6, 136.3,
136.8, 144.0, 152.0, 166.2, 167.5 ppm; HRMS (ESI) m/z: calcd. for
C25H17N3O2S [M + H+]: 424.1120, found: 424.1090.
5,6-Dimethoxy-2-(9H-pyrido[3,4-b] indol-1-yl)benzo[d]thiazole (4d).
Yield: 86% (0.16 g from 0.10 g) as a brown solid; m.p. 205–208 oC; Rf =
0.53 (hexane/EtOAc, 70:30, v/v); IR (neat): νmax (cm-1) = 3372 (NH); 1H
NMR (500 MHz, CDCl3) δ = 4.01 (s, 3H, OCH3). 4.06 (s, 3H, OCH3),
7.33–7.37 (m, 1H, ArH), 7.38 (s, 1H, ArH), 7.62 (t, J = 7.5 Hz, 1H, ArH),
7.65 (s, 1H, ArH), 7.68 (d, J = 8.2 Hz, 1H, ArH), 8.02 (d, J = 5.1 Hz, 1H,
ArH), 8.18 (d, J = 7.8 Hz, 1H, ArH), 8.52 (d, J = 5.0 Hz, 1H, ArH), 10.68
(s, 1H, NH) ppm; 13C NMR (100 MHz, CDCl3) δ = 56.3, 56.5, 102.8,
104.7, 112.2, 116.1, 120.5, 121.4, 122.1, 127.5, 129.0, 130.5, 133.3,
138.9, 141.0, 148.8, 149.1, 149.6 ppm; HRMS (ESI) m/z: calcd. for
C20H15N3O2S [M + H+]: 362.0963, found: 362.0955.
Methyl 9-ethyl-1-(naphtho[2,3-d]thiazol-2-yl)-9H-pyrido[3,4-b]indole-
3-carboxylate (20b). Yield: 76% (0.12 g from 0.10 g) as a yellow solid;
m.p. 194-195 oC; Rf = 0.70 (hexane/EtOAc, 70:30, v/v); IR (neat): νmax
(cm-1) = 1719 (CO2CH3); 1613 (C=N), 737 (C-S); 1H NMR (400 MHz,
CDCl3) δ = 1.35 (t, J = 7.1 Hz, 3H, NCH2CH3), 4.12 (s, 3H, CO2CH3),
5.12 (q, J = 7.1 Hz, 2H, NCH2CH3), 7.40–7.44 (m, 1H, ArH), 7.58–7.64
(m, 2H, ArH), 7.65–7.66 (m, 1H, ArH), 7.67–7.72 (m, 1H, ArH), 7.92 (d, J
= 8.8 Hz, 1H, ArH), 8.01 (d, J = 7.7 Hz, 1H, ArH), 8.13 (d, J = 8.8 Hz, 1H,
ArH), 8.21 (d, J = 8.0 Hz, 1H, ArH), 8.26 (d, J = 7.8 Hz, 1H, ArH), 8.98 (s,
1H, ArH) ppm; 13C NMR (100 MHz, CDCl3) δ = 15.0, 41.5, 53.0, 111.1,
118.5, 121.4, 121.8, 121.9, 122.0, 125.9, 126.6, 127.4, 127.6, 128.4,
129.2, 129.7, 131.5, 133.0, 134.4, 135.2, 135.5, 136.7, 143.0, 152.1,
166.3, 168.0 ppm; HRMS (ESI) m/z: calcd. for C26H19N3O2S [M + H+]:
438.1276, found: 438.1287.
2-(9-Methyl-9H-pyrido[3,4-b]indol-1-yl)-6,7-dihydro-
[1,4]dioxino[2',3':4,5] benzo[1,2-d]thiazole. (5g) Yield: 57% (0.10 g
from 0.10 g) as a yellow solid; m.p. 215-220 oC; Rf = 0.67 (hexane/EtOAc,
1
70:30, v/v); IR (neat): νmax (cm-1) = 1624 (C=N), 741 (C-S); H NMR (400
MHz, CDCl3) δ = 4.15 (s, 3H, NCH3), 4.35 (s, 4H, (OCH2)2Ar), 7.33 (t, J =
7.4 Hz, 1H, ArH), 7.43 (s, 1H, ArH), 7.53 (d, J = 8.3 Hz, 1H, ArH), 7.62–
7.66 (m, 2H, ArH), 8.04 (d, J = 4.8 Hz, 1H, ArH), 8.15 (d, J = 7.7 Hz, 1H,
ArH), 8.53 (d, J = 4.9 Hz, 1H, ArH) ppm; 13C NMR (100 MHz, CDCl3) δ =
34.7, 64.4, 64.6, 108.7, 110.5, 110.7, 115.8, 120.4, 121.1, 121.5, 129.1,
129.4, 132.3, 135.2, 136.1, 138.3, 143.6, 144.0, 149.1, 168.1 ppm;
HRMS (ESI) m/z: calcd. for C21H15N3O2S [M + H+]: 374.0963, found:
374.0953.
Methyl
1-(naphtho[2,1-d]thiazol-2-yl)-9-propyl-9H-pyrido[3,4-
b]indole-3-carboxylate (21b). Yield: 95% (0.14 g from 0.10) as a yellow
o
solid; m.p. 198-200 C; Rf = 0.73 (hexane/EtOAc, 70:30, v/v); IR (neat):
Methyl
1-(5,6-dimethoxybenzo[d]
thiazol-2-yl)-9H-pyrido[3,4-
νmax (cm-1) = 1737 (CO2CH3), 1618 ( C=N), 735 (C-S); 1H NMR (400 MHz,
CDCl3) δ = 0.76 (t, J = 7.4 Hz, 3H,NCH2CH2CH3), 1.71–1.81 (m, 2H,
NCH2CH2CH3), 4.12 (s, 3H, CO2CH3), 5.07 (t,
b]indole-3-carboxylate (11d). Yield: 87% (0.14 g from 0.10 g) as a
yellow solid; m.p. 238-240 oC; Rf = 0.59 (hexane/EtOAc, 90:10, v/v); IR
(neat): νmax (cm-1) = 1710 (CO2CH3), 3399 (NH), 1626 (C=N), 742 (C-S);
δ = 1H NMR (400 MHz, CDCl3) δ = 4.00 (s, 3H, OCH3), 4.05 (s, 3H,
OCH3), 4.10 (s, 3H, CO2CH3), 7.34 (s, 1H, ArH), 7.37–7.41 (m, 1H, ArH),
7.62 (d, J = 4.5 Hz, 1H, ArH), 7.65–7.67 (m, 1H, ArH), 7.69–7.71 (m, 1H,
ArH), 8.21 (d, J = 7.8 Hz, 1H, ArH), 8.89 (s, 1H, ArH), 10.87 (s, 1H, NH)
ppm; 13C NMR (100 MHz, CDCl3) δ = 53.0, 56.3, 56.5, 102.6, 104.6,
112.5, 118.8, 121.4, 122.2, 127.8, 128.9, 129.5, 130.6, 131.0, 134.5,
137.5, 141.2, 148.5, 149.3, 149.7, 166.4, 167.1 ppm; HRMS (ESI) m/z:
calcd. for C22H17N3O4S [M + H+]: 420.1018, found: 420.1026.
J = 7.7 Hz 2H,
NCH2CH2CH3), 7.42 (t, J = 7.2 Hz, 1H, ArH), 7.59–7.66 (m, 1H, ArH),
7.68–7.72 (m, 3H, ArH), 7.93 (d, J = 8.8 Hz, 1H, ArH), 8.01 (d, J = 7.7 Hz,
1H, ArH), 8.14 (d, J = 8.7 Hz, 1H, ArH), 8.21 (d, J = 8.0 Hz, 1H, ArH),
8.27 (d, J = 7.8 Hz, 1H, ArH), 8.99 (s, 1H, ArH), 13C NMR (100 MHz,
CDCl3) δ = 11.2, 23.1, 48.0, 53.0, 110.1, 118.4, 121.3, 121.3, 121.5,
121.7, 121.9, 125.8, 126.5, 127.3, 128.3, 129.1, 129.5, 131.4, 132.8,
134.4, 135.2, 135.4, 136.5, 143.2, 152.1, 166.2, 168.1 ppm; HRMS (ESI)
m/z: calcd. for C27H21N3O2S [M + H+]: 452.1433, found: 452.1411.
Methyl 9-butyl-1-(naphtho[2,1-d] thiazol-2-yl)-9H-pyrido[3,4-b]indole-
3-carboxylate (22b). Yield: 89% (0.13 g from 0.10) as a yellow solid; m.p.
194-196 oC; Rf = 0.76 (hexane/EtOAc, 70:30, v/v); IR (neat): νmax (cm-1) =
Methyl
1-(6-methoxybenzo[d]thiazol-2-yl)-9-methyl-9H-pyrido[3,4-
b]indole-3-carboxylate. (19c). Yield: 65% (0.195 g from 0.20 g) as a
light yellow solid; m.p. 184-190 oC; Rf = 0.62 (hexane/EtOAc, 70:30, v/v);
1
IR (neat): νmax (cm)-1 = 1709 (CO2CH3), 1605 (C=N), 742 (C-S); H NMR
1
1709 (CO2CH3), 1621 (C=N), 739 (C-S); H NMR (400 MHz, CDCl3) δ =
0.74 (t,
J = 7.4 Hz, 3H, NCH2CH2CH2CH3), 1.11–1.20 (m, 2H,
(400 MHz, CDCl3) δ = 3.94 (s, 3H, OCH3Ar), 4.08 (s, 3H, CO2CH3), 4.25
(s, 3H, NCH3), 7.14 (dd, J1 = 9.0, J2 = 2.4 Hz, 1H, ArH), 7.39–7.46 (m, 2H,
ArH), 7.59 (d, J = 8.4 Hz, 1H, ArH), 7.70 (t, J = 7.6 Hz, 1H, ArH), 8.01 (d,
J = 9.0 Hz, 1H, ArH), 8.24 (d, J = 7.8 Hz, 1H, ArH), 8.95 (s,1H, ArH) ppm;
13C NMR (100 MHz, CDCl3) δ = 34.8, 53.0, 56.0, 104.0, 110.8 116.0,
118.3, 121.4, 121.7, 124.3, 129.6, 132.4, 135.7, 136.2, 136.7, 138.0,
NCH2CH2CH2CH3), 1.64–1.72 (m, 2H, NCH2CH2CH2CH3), 4.12 (s, 3H,
CO2CH3), 5.11 (t, J = 7.7 2H, NCH2CH2CH2CH3), 7.42 (t, J = 7.3 Hz, 1H,
ArH), 7.59–7.66 (m, 3H, ArH), 7.68–7.72 (m, 1H, ArH), 7.93 (d, J = 8.8
Hz, 1H, ArH), 8.01 (d, J = 7.9 Hz, 1H, ArH), 8.12 (d, J = 8.9 Hz, 1H, ArH),
8.22 (d, J = 8.0 Hz, 1H, ArH), 8.27 (d, J = 7.8 Hz, 1H, ArH), 8.99 (s, 1H,
ArH) ppm; 13C NMR (100 MHz, CDCl3) δ = 14.0, 20.2, 31.9, 46.4, 53.1,
15
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10.1002/ejoc.201901908
European Journal of Organic Chemistry
FULL PAPER
144.0, 148.5 158.4, 165.9, 166.2 ppm; HRMS (ESI) m/z: calcd. for
C22H17N3O3S [M + H+]: 404.1069, found: 404.1058.
3-(6-Ethyl-6H-thiazolo[4,5-c]carbazol-2-yl)-9-methyl-9H-pyrido[3,4-
b]indole-1-carbaldehyde (27). Yield: 58% (0.94 g from 0.10) as a
greenish solid; m.p. 200-204 oC; Rf = 0.63 (hexane/EtOAc, 75:30, v/v); IR
(neat): νmax (cm-1) = 1692 (CHO), 1621 (C=N), 731 (C-S); 1H NMR (500
MHz, CDCl3) δ = 1.53 (t, J = 7.2 Hz, 3H, NCH2CH3). 4.36 (s, 3H,
CO2CH3), 4.53 (q, J = 7.3 2H, NCH2CH3), 7.43–7.46 (m, 2H, ArH), 7.57 (t,
J = 7.4 Hz, 2H, ArH), 7.60–7.62 (m, 1H, ArH), 7.63–7.66 (m, 1H, ArH),
7.71–7.74 (m, 1H, ArH), 8.23–8.30 (m, 3H, ArH), 8.80 (s, 1H, ArH), 10.34
(s, 1H, CHO) ppm; 13C NMR (125 MHz,CDCl3) δ = 14.3, 38.2, 38.3,
108.5, 109.1, 109.2, 109.8, 110.7, 110.11, 119.9, 120.0, 120.7, 121.2,
121.6, 122.0, 122.6, 122.8, 130.0, 137.4, 137.5, 137.6, 137.7, 151.9,
173.9, 193.6 ppm; HRMS (ESI) m/z: calcd. for C28H20N4OS [M + Na+]:
483.1256, found: 483.1218.
Methyl
1-(5,6-dimethoxybenzo[d]thiazol-2-yl)-9-methyl-9H-
pyrido[3,4-b]indole-3-carboxylate (19d). Yield: 55% (0.18 g from 0.20
o
g) as a brown solid; m.p. 220-222 C; Rf = 0.62 (hexane/EtOAc, 70:30,
v/v); IR (neat): νmax (cm-1) = 1702 (CO2CH3), 1618 (C=N), 726 (C-S); 1H
NMR (400 MHz, CDCl3) δ = 4.01 (s, 6H, (OCH3)2Ar), 4.07 (s, 3H,
CO2CH3), 4.21 (s, 3H, NCH3), 7.38 (t, J = 7.32 Hz, 2H, ArH), 7.53–7.56
(m, 2H, ArH), 7.67 (t, J = 7.8 Hz, 1H, ArH), 8.20 (d, J = 7.8 Hz, 1H, ArH),
8.90 (s, 1H, ArH) ppm; 13C NMR (100 MHz, CDCl3) δ = 34.7, 53.0, 56.2,
56.5, 102.4, 105.0, 110.7, 118.2, 121.3, 121.7, 128.9, 129.5, 131.0,
132.3, 135.8, 136.1, 136.6, 143.9, 148.3, 149.2, 149.5, 166.1, 166.3
ppm; HRMS (ESI) m/z: calcd. for C23H19N3O4S [M + Na+]: 456.0994,
found: 456.0992.
2-(1-(4-Bromophenyl)-9-ethyl-9H-pyrido[3,4-b]indol-3-yl)-6-ethyl-6H-
thiazolo[4,5-c]carbazole. (26a) Yield: 75% (0.18 g from 0.15) as a
Brown solid; m.p. more than 250 oC; Rf = 0.74 (hexane/EtOAc, 70:30,
Methyl 1-(5,6-dimethylbenzo[d]thiazol-2-yl)-9-methyl-9H-pyrido[3,4-
b]indole-3-carboxylate (19e). Yield: 56% (0.17 g from 0.20 g) as a
yellow solid; m.p. 170-175 oC; Rf = 0.73 (hexane/EtOAc, 70:30, v/v); IR
(neat): νmax (cm-1) = 1702 (CO2CH3), 1620 (C=N), 736 (C-S); 1H NMR
(400 MHz, CDCl3), δ = 2.45 (s, 6H, (CH3)2Ar), 4.08 (s, 3H, CO2CH3), 4.20
(s, 3H, NCH3), 7.41 (t, J = 7.4 Hz, 1H, ArH), 7.58 (d, J = 8.3 Hz, 1H, ArH),
7.70 (t, J = 7.5 Hz, 1H, ArH), 7.77 (s, 1H, ArH), 7.91 (s, 1H, ArH), 8.25 (d,
J = 7.7 Hz, 1H, ArH), 8.96 (s, 1H, ArH) ppm; 13C NMR (100 MHz, CDCl3)
δ = 20.4, 20.5, 34.7, 53.0, 110.8, 118.4, 120.8, 121.4, 121.8, 123.9,
129.0, 129.6, 132.4, 133,7, 134.0, 135.7, 135.9, 136.3, 136.7, 144.0,
152.7, 166.2, 167.0 ppm; HRMS (ESI) m/z: calcd. for C23H19N3O2S [M +
Na+]: 424.1096, found: 424.1052.
1
v/v); IR (neat): νmax (cm-1) = 1619 (C=N ), 742 (C-S); H NMR (400 MHz,
CDCl3) δ = 1.03 (t, J = 7.1 Hz, 3H, NCH2CH3Carbazole), 1.51 (t, J = 7.2 Hz,
3H, NCH2CH3), 4.08 (q, J = 7.1 Hz, 2H, NCH2CH3Carbazole), 4.49 (q, J =
7.2 Hz, 2H, NCH2CH3), 7.33–7.36 (m, 1H, ArH), 7.37–7.39 (m, 1H, ArH),
7.48 (d, J = 8.3 Hz, 1H, ArH), 7.51–7.53 (m, 2H, ArH), 7.58–7.60 (m, 2H,
ArH), 7.61–7.62 (m, 1H, ArH), 7.63–7.66 (m, 1H, ArH), 7.78–7.80 (m, 2H,
ArH), 8.22–8.25 (m, 2H, ArH), 8.32 (d, J = 7.8 Hz, 1H, ArH), 9.11 (s, 1H,
ArH) ppm; 13C NMR (100 MHz, CDCl3) δ = 14.1, 14.2, 38.1, 38.6, 108.0,
109.0, 110.5, 110.9, 111.0, 115.9, 119.6, 120.6, 121.7, 122.2, 122.3,
125.5, 128.4, 128.8, 128.9, 129.5, 129.6, 131.6, 135.6, 137.5 139.8,
141.3, 142.6, 143.9, 149.3, 167.8 ppm; HRMS (ESI) m/z: calcd. for
C34H25BrN4S [M + H+]: 601.1062, found: 601.1035.
Methyl
9-methyl-1-(6-methylbenzo[d]thiazol-2-yl)-9H-pyrido[3,4-
2-(9-Methyl-9H-pyrido[3,4-b]indol-1-yl)thiazolo[4,5-b]pyridine (5m).
Yield: 40% (0.06 g from 0.10) as a light blue solid; m.p. 165-167 oC; Rf =
0.61 (hexane/EtOAc, 70:30, v/v); IR (neat): νmax (cm-1) = 1622 (C=N), 740
(C-S); 1H NMR (400 MHz, CDCl3) δ = 4.25 (s, 3H, NCH3). 7.07–7.10 (m,
1H, ArH), 7.33 (t, J = 7.4 Hz, 1H, ArH), 7.54 (d, J = 8.2 Hz, 1H, ArH),
7.66 (t, J = 7.6 Hz, 1H, ArH), 7.76–7.80 (m, 1H, ArH), 8.13–8.15 (m, 2H,
b]indole-3-carboxylate (19f). Yield: 50% (0.14 g from 0.20 g) as a
yellow solid; m.p. 198-200 oC; Rf = 0.71 (hexane/EtOAc, 70:30, v/v); IR
(neat): νmax (cm-1) = 1707 (CO2CH3), 1624 (C=N), 731 (C-S); 1H NMR
(400 MHz, CDCl3) δ = 2.55 (s, 3H, CH3Ar), 4.09 (s, 3H, CO2CH3), 4.22 (s,
3H, NCH3), 7.35 (dd, J1 = 8.3, J2 = 1.4 Hz, 1H, ArH), 7.39–7.45 (m, 1H,
ArH), 7.59 (d, J = 8.4 Hz, 1H, ArH), 7.68–7.72 (m, 1H, ArH), 7.81 (m, 1H,
ArH), 8.02 (d, J = 8.3 Hz, 1H, ArH), 8.23–8.25 (m, 1H, ArH), 8.96 (s, 1H,
ArH) ppm; 13C (125 MHz, CDCl3) δ = 21.8, 34.7, 53.0, 110.7, 118.4,
121.3, 121.4, 121.6, 121.7, 123.2, 128.0, 129.7, 132.4, 135.7, 136.2,
136.3, 136.7, 144.1, 152.1, 166.2, 167.3 ppm; HRMS (ESI) m/z: calcd.
for C22H17N3O2S [M + H+]: 388.1120, found: 388.1110.
ArH), 8.39–8.43 (m, 1H, ArH), 8.45 (d, J = 8.2 Hz, 1H; ArH) ppm; 13
C
NMR (100 MHz, CDCl3) δ = 35.0, 110.4, 110.5, 114.0, 117.8, 119.8,
120.5, 121.4, 121.5, 129.4, 133.1, 134.0, 136.7, 138.4, 144.0, 148.4,
151.8, 164.2 ppm; HRMS (ESI) m/z: calcd. for C18H12N4S [M + H+]:
317.086, found: 317.0832.
Methyl
1-(benzo[d]thiazol-2-yl)-9-ethyl-9H-pyrido[3,4-b]indole-3-
Methyl 1-(4,6-dimethylbenzo[d]thiazol-2-yl)-9-methyl-9H-pyrido[3,4-
b]indole-3-carboxylate (19h). Yield: 52% (0.16 g from 0.20 g) as a
yellow solid; m.p. 178-180 oC; Rf = 0.73 (hexane/EtOAc, 70:30, v/v); IR
(neat): νmax (cm-1) = 1702 (CO2CH3), 1610 (C=N), 733 (C-S), 1H NMR
(400 MHz, CDCl3) δ = 2.49 (s, 3H, CH3Ar), 2.78 (s, 3H, CH3Ar), 4.08 (s,
3H, CO2CH3), 4.28 (s, 3H, NCH3), 7.15 (s, 1H, ArH), 7.40 (t, J = 7.5 Hz,
1H, ArH), 7.57 (d, J = 8.4 Hz, 1H, ArH), 7.62 (s, 1H, ArH), 7.69 (t, J = 7.7
Hz, 1H, ArH), 8.22 (d, J =7.8 Hz, 1H, ArH), 8.93 (s, 1H, ArH) ppm; 13C
NMR (100 MHz, CDCl3) δ = 18.6, 21.8, 35.0, 52.9, 110.7, 118.3, 119.0,
121.3, 121.7, 128.5, 129.5, 131.0, 132.4, 133.0, 135.8, 136.0, 136.1,
136.5, 136.6, 143.9, 151.6. 166.2, 167.9 ppm; HRMS (ESI) m/z: calcd.
for C23H19N3O2S [M + H+]: 402.1276, found: 401.1255.
carboxylate (20n). Yield: 72% (0.20 g from 0.20 g) as a light yellow
solid; m.p. 200-202 oC; Rf = 0.68 (hexane/EtOAc, 70:30, v/v); IR (neat):
νmax (cm-1) = 1709 (CO2CH3), 1615 (C=N), 738 (C-S); 1H NMR (500 MHz,
CDCl3) δ = 1.34 (t, J = 7.1 Hz, 3H, NCH2CH3). 4.09 (s, 3H, CO2CH3),
5.06 (q, J = 7.1 Hz, 2H, NCH2CH3), 7.41–7.44 (m, 1H, ArH), 7.46–7.50
(m, 1H, ArH), 7.53–7.56 (m, 1H, ArH), 7.63 (d, J = 8.3 Hz, 1H, ArH),
7.70–7.72 (m, 1H, ArH), 8.03 (d, J = 7.7 Hz, 1H, ArH), 8.13 (d, J = 8.0
Hz, 1H,ArH), 8.26 (d, J = 7.8 Hz, 1H, ArH), 8.98 (s, 1H, ArH) ppm; 13C
NMR (125 MHz, CDCl3) δ = 15.0, 41.5, 53.0, 110.9, 118.6, 121.4, 121.7,
121.8, 121.9, 123.7, 125.9, 126.3, 129.6, 132.9, 135.1, 135.6, 142.9,
154.0, 166.1, 168.9 ppm; HRMS (ESI) m/z: calcd. for C22H17N3O2S [M +
H+]: 390.1276, found: 390.1245.
Methyl
9-benzyl-1-(5,6-dimethoxybenzo
[d]thiazol-2-yl)-9H-
6-(9-Methyl-9H-pyrido[3,4-b]indol-1-yl)-
pyrido[3,4-b]indole-3-carboxylate (23d). Yield: 76% (0.17 g from 0.15
g) as a yellow solid; m.p. 180-182 oC; Rf = 0.64 (hexane/EtOAc, 70:30,
v/v); IR (neat): νmax (cm-1) = 1709 (CO2CH3), 1620 (C=N), 732 (C-S); 1H
NMR (500 MHz, CDCl3) δ = 3.95 (s, 3H, OCH3Ar), 3.99 (s, 3H, OCH3Ar),
4.07 (s, 3H, CO2CH3), 6.23 (s, 2H, CH2Ar), 6.73 (d, J = 7.1 Hz, 2H, ArH),
7.04–7.08 (m, 2H, ArH), 7.09–7.12 (m, 1H, ArH), 7.21 (s, 1H, ArH), 7.31
(s, 1H, ArH), 7.40–7.43 (m, 1H, ArH), 7.55 (d, J = 8.3 Hz, 1H, ArH), 7.62–
7.65 (m, 1H, ArH), 8.27 (d, J = 7.8 Hz, 1H, ArH), 8.96 (s, 1H, ArH) ppm;
13C NMR (125 MHz, CDCl3) δ = 50.0, 53.0, 56.2, 56.4, 102.3, 104.8,
111.4, 118.1, 121.7, 121.8, 126.1, 127.1, 128.5, 129.1, 129.7, 133.0,
135.7, 136.3, 137.1, 137.7, 144.0, 148.1, 149.2, 149.4, 166.1 ppm;
HRMS (ESI) m/z: calcd. for C29H23N3O4S [M + H+]: 510.1088, found:
510.1067.
[1,3]dioxolo[4',5':4,5]benzo[1,2-d]thiazole (5l). Yield: 65% (0.22 g from
0.20 g) as a yellow solid; m.p. 208-210 oC; Rf = 0.66 (hexane/EtOAc,
1
70:30, v/v); IR (neat): νmax (cm-1) = 1630 (C=N), 743 (C-S); H NMR (500
MHz, CDCl3) δ = 4.18 (s, 3H, NCH3), 6.10 (s, 2H, (O)2CH2)Ar), 7.34 (t, J
= 7.42 Hz, 1H, ArH), 7.37 (s, 1H, ArH), 7.53 (s, 1H, ArH), 7.54 (d, J = 8.4
Hz, 1H, ArH), 7.66 (t, J = 7.6 Hz, 1H, ArH), 8.05 (d, J = 4.9 Hz, 1H, ArH),
8.17 (d, J = 7.8 Hz, 1H, ArH), 8.53 (d, J = 4.9 Hz, 1H, ArH) ppm; 13C
NMR (125 MHz, CDCl3) δ = 34.7, 100.5, 101.9, 103.0, 110.5, 115.7,
120.4, 121.1, 121.5, 129.1, 129.8, 132.3, 135.0, 136.1, 138.3, 143.9,
147.4, 148.0, 149.1, 167.6 ppm; HRMS (ESI) m/z: calcd. for
C20H13N3O2S [M + H+]: 360.081, found: 360.080.
16
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201901908
European Journal of Organic Chemistry
FULL PAPER
(E)-9-ethyl-N-((9-methyl-9H-pyrido[3,4-b]indol-1-yl)methylene)-9H-
carbazol-3-amine (29). Yield: 97% (0.37 g from 0.20 g) as a yellow solid;
m.p. 180-182 oC; Rf = 0.41 (hexane/EtOAc, 70:30, v/v); IR (neat): νmax
U. Dighe, S. Khan, I. Soni, P. Jain, S. Shukla, R. Yadav, P. Sen, S.
M. Meeran, S. Batra, J. Med. Chem. 2015, 58, 3485-3499.
L. A. Sorbera, L. Martin, P. A. Leeson, J. Castaner, Drugs Future,
2001, 26, 15-19.
4.
5.
1
(cm-1) = 1623 (C=N); H NMR (500 MHz, CDCl3) δ = 1.48 (t, J = 7.2 Hz,
3H, NCH2CH3). 4.31 (s, 3H, NCH3), 4.42 (q, J = 7.2 Hz, 2H, NCH2CH3),
7.28–7.36 (m, 2H, ArH), 7.44 (d, J = 8.2 Hz, 1H, ArH), 7.47–7.52 (m, 2H,
ArH), 7.57 (d, J = 8.3 Hz, 1H, ArH), 7.64–7.69 (m, 2H, ArH), 8.07 (d, J =
4.9 Hz, 1H, ArH), 8.14 (d, J = 7.7 Hz, 1H, ArH), 8.19 (d, J = 7.8 Hz, 1H,
ArH), 8.22 (d, J = 2.0 Hz, 1H, ArH), 8.62 (d, J = 4.9 Hz, 1H, ArH), 9.29 (s,
1H, CH) ppm; 13C NMR (125 MHz, CDCl3) δ = 14.0, 35.0, 37.8, 108.8,
109.0, 110.2, 113.1, 115.7, 119.2, 120.2, 120.3, 120.7, 121.2, 121.5,
123.2, 123.7, 126.1, 129.0, 131.8, 136.4, 138.7, 139.3, 139.8, 140.7,
143.1, 143.5, 157.2 ppm; HRMS (ESI) m/z: calcd. for C27H22N4 [M + H+]:
403.1923, found: 403.1911.
a) A. Das, S. U. Dighe, N. Das, S. Batra, P. Sen, Spectrochim.
Acta Part A. 2019, 220, 1-18; b) S. Swami, D. Behera, A. Agarwala,
V. P. Verma, R. Shrivastava, New J. Chem. 2018, 42, 10317-
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Acknowledgment
M. S. gratefully acknowledges Council of Scientific & Industrial
Research (CSIR), New Delhi, India for Senior Research
Fellowship. V. S. is also highly grateful to Council of Scientific &
Industrial Research New Delhi, India for research grants
[(02)0356/19/EMR-II) and (02)0202/14/EMR-II)] for supporting
this research work. The financial support from Department of
Science and Technology, Science and Engineering Research
Board, New Delhi (EMR/2017/000155, SB/FT/CS-188/2011 and
DST-FIST CSI-228/2011) is also acknowledges. The central
facility at IIT Ropar is also gratefully acknowledged. The
motivation by Dr. Sanjay Batra (CSIR-CDRI) and Prof Y. D.
Vankar (IIT Kanpur) is gratefully acknowledged.
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Keywords: β–Carboline • Benzothiazole • Iodine • Fluorescent •
Thiazolocarbazole • Photophysical Properties
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10.1002/ejoc.201901908
European Journal of Organic Chemistry
FULL PAPER
Layout 2:
FULL PAPER
Fluorescent Materials*
Manpreet Singh, Pamita Awasthi
Virender Singh*
Page No. – Page No.
Iodine
Catalysed
Expeditious
Text for Table of Contents (about 350 characters)
Synthesis of Highly Fluorescent -
Carboline
C-1(3)
Tethered
and
Thiazolo[4,5-c]carbazole,
Naphtho[2,1-d]thiazole
Benzothiazole
Derivatives
and
Estimation of their Light Emitting
This methodology provides an easy access to gram scale synthesis of highly fluorescent β-carboline tethered thiazolo[4,5-
c]carbazoles and benzothiazole derivatives in excellent yields. The synthesized analogues may find wide application in
medicinal chemistry with potential scope as anticancer agents or DNA staining agents and in material science as fluorescent
probes and chemosensors.
This article is protected by copyright. All rights reserved.
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