An organocatalytic highly efficient approach to the direct synthesis of substituted carbazoles in water

Article abstract of DOI:10.1039/c3ob42034e

A simple, mild, green, catalytic and general procedure for the direct synthesis of highly functionalized 1-methoxycarbonyl-2-aryl/alkyl-3-nitro-9H- carbazoles has been achieved in water medium via a one-pot domino Michael-Henry/aromatization reaction of methyl 2-(3-formyl-1H-indol-2-yl) acetates with aryl/alky-substituted β-nitroolefins under air using DABCO (30 mol%) as an organocatalyst. In addition, the bench scale synthesis can be performed without using toxic organic solvents and a biologically important new fused carbazole has been prepared.

Full text of DOI:10.1039/c3ob42034e

Organic &
Biomolecular Chemistry
View Article Online
View Journal | View Issue
PAPER
An organocatalytic highly efficient approach to the
direct synthesis of substituted carbazoles in water†
Cite this: Org. Biomol. Chem., 2013, 11,
8410
Pradeep Kumar Jaiswal, Soumen Biswas, Shivendra Singh and Sampak Samanta*
A simple, mild, green, catalytic and general procedure for the direct synthesis of highly functionalized
1-methoxycarbonyl-2-aryl/alkyl-3-nitro-9H-carbazoles has been achieved in water medium via a one-pot
domino Michael–Henry/aromatization reaction of methyl 2-(3-formyl-1H-indol-2-yl)acetates with aryl/
alky-substituted β-nitroolefins under air using DABCO (30 mol%) as an organocatalyst. In addition, the
bench scale synthesis can be performed without using toxic organic solvents and a biologically important
new fused carbazole has been prepared.
Received 11th October 2013,
Accepted 17th October 2013
DOI: 10.1039/c3ob42034e
www.rsc.org/obc
with cyclohexanone at 140 °C. However, these protocols,
although metal free, are not much appreciated from an
Introduction
The development of an efficient and sustainable protocol for environmental point of view. A primary reason is that they
the construction of a functionalized carbazole framework has often suffer from one or more disadvantages such as the use
been a key research area in recent years because this moiety is of volatile organic solvents, stoichiometric amounts of strong
found in a variety of active drug candidates and natural pro- oxidants, longer reaction periods, higher temperatures, un-
ducts.1,2 Its several synthetic analogues display remarkable satisfactory yields, etc. To overcome these limitations, the
biological activities as described profusely in the literature.2 development of a one-pot metal free based catalytic system
Apart from this, they have many useful applications in for the synthesis of substituted carbazoles in water under
materials science,3 e.g. in organic light emitting diodes aerobic conditions is still of great interest for synthetic organic
(OLED), photovoltaic cells, field effect transistors, etc. Owing chemists.
to their several applications in various fields, a large number
In recent years, the organocatalytic domino7 Michael–
of classical and modern techniques have been developed for Henry8 reaction has been one of the most straightforward
their synthesis.1–3 Among them, the most common routes routes for assembling a diverse range of multifaceted architec-
involve the palladium4 catalyst, namely, oxidative cyclodehy- tures in a highly practical manner. Such a process is likely to
drogenation of diarylamines, annulations of arynes with have notable advantages as compared to a conventional step-
2-haloacetamides, the domino N–H/C–H bond activation by-step operation because of potential structural alterations,
reaction of anilines with dihaloarenes, etc. Besides, other reduction in the number of synthetic steps, minimizing the by-
transition metal (Cu, Pt, Au, Rh, etc.)5 mediated syntheses of products, avoiding the tedious extraction and purification
carbazole derivatives have been also well documented. steps, etc. As part of our continuing interest in the develop-
However, because of potential environmental concerns about ment of environmentally friendly protocols in organic trans-
metal catalysts in general, organocatalysis has gained much formations as well as metal free mediated based catalytic
recognition in the context of green chemistry.
systems for the synthesis of N-heterocycles,9 we have reported
In this connection, a few metal free mediated one-pot on the one-pot domino Michael–Henry reaction for the syn-
syntheses of carbazoles have been successfully developed,6 thesis of highly functionalized tetrahydrocarbazoles in THF
which include the hypervalent iodine mediated intramolecular medium using DABCO as a catalyst.9d Against this background,
oxidative C–N bond formation of N-substituted amidobiphenyls, we envisaged that this domino route is expected to be useful
iodine mediated cascade cyclization of N,N-dimethyl-2-[2- for assembling the benzene ring of the carbazole moiety under
(2-ethynylphenyl)-ethynyl]anilines, and HCl salt of arylhydrazine mild conditions (Scheme 1). Herein, we report a mild, simple,
catalytic and robust procedure for the synthesis of highly func-
tionalized carbazoles through a one-pot domino Michael–
Indian Institute of Technology Indore, 452017 Indore, Madhya Pradesh, India.
Henry/aromatization reaction of aryl/alkyl-substituted trans-
E-mail: sampaks@iiti.ac.in; Fax: +91-731-2364182; Tel: +91-731-2438742
†Electronic supplementary information (ESI) available: Copies of 1H and
13C NMR spectra. See DOI: 10.1039/c3ob42034e
β-nitroolefins with methyl 2-(3-formyl-1H-indol-2-yl)acetates in
water under air using DABCO as an organocatalyst.
8410 | Org. Biomol. Chem., 2013, 11, 8410–8418
This journal is © The Royal Society of Chemistry 2013

View Article Online
Organic & Biomolecular Chemistry
Paper
sequence provided the desired carbazole 3aa in moderate 60%
yield along with the unexpected denitrated carbazole 4aa in
low 27% yield. The products were fully characterized by their
spectroscopic data (1H and 13C NMR, HRMS). In order to
improve the yield of the desired compound 3aa and suppress
the formation of 4aa, we tested common organic solvents such
as dioxane, MeOH and EtOH for this two-step process. All
these cases led to moderate yields of targeted product 3aa
(55–58%, entries 2–4) and an unavoidable side product 4aa
(25–33%, entries 2–4). Next, our efforts were focused on optimi-
zation of the second step by treatment of different organic
acids such as TFA and AcOH under various conditions (entries
5–8). In all these cases, the results were unsatisfactory. More-
over, there was no substantial beneficial effect observed when
a DDQ in acetic acid was used as an oxidant (entry 9). At this
juncture, we realized that denitrated product 4aa was formed
during aromatization (step 2) in the presence of an acid. As
such, we surmised that this problem might be resolved if the
aromatization step would be conducted in a basic medium
under air. With this understanding, the reaction was per-
formed at 50 °C in THF medium in the presence of DABCO
(10 mol%). Surprisingly, after 30 h, we found only the desired
carbazole 3aa in 57% yield (entry 10). From the green chem-
istry standpoint, the use of water in the reaction medium is
an inevitable choice for synthetic organic chemists.10 In this
regard, we performed the reaction in water instead of THF at
50 °C; pleasantly, after 24 h, very good results were observed
(63%, 3a, entry 11). For this catalyst, on further increasing the
reaction temperature from 50 °C to 70 °C as well as the catalyst
loading from 10 mol% to 30 mol%, the yield improved signifi-
cantly from 63% to 97% (entries 13) in a shorter time. Next, we
investigated the effects of bases on this reaction. The results
showed that DABCO was a superior catalyst as compared to
Et3N and DBU (entries 14 and 15) in terms of reactivity under
identical conditions. In particular, no significant positive
effect was observed when the reaction was carried out in the
presence of oxygen instead of air (entry 16).
Scheme 1 Retro-synthetic path.
Results and discussion
Initially, to obtain the 1-methoxycarbonyl-2-phenyl-3-nitro-9H-
carbazole (3aa), we carried out the reaction between methyl
2-(3-formyl-1H-indol-2-yl)acetate 1a and trans-β-nitrostyrene 2a
at room temperature in THF medium for 7 h using 10 mol%
loading of the catalyst DABCO, followed by aromatization
using aqueous 8 N HCl (entry 1, Table 1). This two-step
Table 1 Optimization of the reaction conditions
Yieldg (%)
Entry
Step
Conditions
3aa : 4aa
67 : 33
68 : 28
65 : 35
60 : 40
55 : 45
—
3aa
60
57
58
55
50
<7
33
28
60
4aa
27
25
28
33
39
1
2
3
4
5
6
7
8
9
Ia
THF, DABCO, RT, 7 h
8 N HCl, RT, 16 h
Dioxane, DABCO, RT, 7 h
8 N HCl, RT, 16 h
EtOH, DABCO, 7 h, RT
8 N HCl, RT, 16 h
MeOH, DABCO, RT, 7 h
8 N HCl, RT, 16 h
THF, DABCO, RT, 7 h
TFA, RT, 16 h
THF, DABCO, RT, 7 h
AcOH, RT, 20 h
THF, DABCO, RT, 7 h
AcOH, 50 °C, 20 h
DCM, DABCO, RT, 7 h
AcOH, 50 °C, 20 h
DCM, DABCO, RT, 7 h
AcOH, DDQ, 50 °C, 10 h
THF, DABCO, 50 °C, 30 h
H2O, DABCO, 50 °C, 24 h
H2O, DABCO, 70 °C, 14 h
H2O, DABCO, 70 °C, 10 h
H2O, Et3N, 70 °C, 10 h
H2O, DBU, 70 °C, 10 h
H2O, DABCO, 70 °C, 10 h
IIb
Ia
IIb
Ia
IIb
Ia
IIb
Ia
Due to the unexpected formation of denitrated carbazole
4aa, we were curious to study the general trends of this
phenomenon which may further help us in establishing the
reaction mechanism. In this line, a series of reactions were
carried out between aryl-substituted β-nitrostyrenes (2e, 2g and
2l) and 1a in MeOH medium under air at room temperature
using a catalytic amount of DABCO (10 mol%) for 7 h followed
by 8 N HCl as a two-step sequence. In all these cases, similar
kinds of denitrated carbazoles (4ae–4al) were obtained in poor
yields (33–40%) as shown in Scheme 2.
IIc
Ia
IIc
Ia
63 : 37
55 : 35
68 : 32
18
19
22
IIc
Ia
IIc
Ia
IId
Ia
10
11
12
13
14
15
16
100 : 0
100 : 0
100 : 0
100 : 0
100 : 0
100 : 0
100 : 0
57
63
80
97
41
88
96
—
—
—
—
—
—
—
Ia
Ie
If
If
If
Ih
a Unless otherwise mentioned, all the reactions were performed with
compound 1a (0.25 mmol), 2a (0.3 mmol) and catalyst (10 mol%) in
specified solvents (1.0 mL) and temperatures under air. b 8 N HCl
(4.0 mL) was used. c Acid (1.0 ml) was used. d Glacial AcOH (0.5 mL)
and DDQ (1.5 equiv.) were used. e 20 mol% DABCO was used. f 30 mol%
catalyst. g The products 3aa and 4aa were isolated after column
chromatography. h The reaction was carried out under an O2 atmosphere.
Scheme 2 Synthesis of 1-methoxycarbonyl-2-aryl-9H-carbazoles (4ae–4al).
Org. Biomol. Chem., 2013, 11, 8410–8418 | 8411
This journal is © The Royal Society of Chemistry 2013

View Article Online
Paper
Organic & Biomolecular Chemistry
Table 2 DABCO catalyzed one-pot synthesis of 1-methoxycarbonyl-2-aryl/
alkyl-3-nitro-9H-carbazoles (3aa–3bn)a
Entry
R1
X
T (h)
Product
Yieldb (%)
1
2
3
4
5
6
7
8
C6H5
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
I
10
12
12
20
20
20
20
10
10
10
10
10
13
16
16
16
16
12
12
12
15
3aa
3ab
3ac
3ad
3ae
3af
3ag
3ah
3ai
3aj
3ak
3al
3am
3an
3ao
3ap
3aq
3ba
3bi
97 (89)c
93 (81)c
90 (82)c
92 (85)c
89 (79)c
88 (83)c
93 (81)c
91
3-Me-C6H4
4-Me-C6H4
2-MeO-C6H4
4-MeO-C6H4
2,5-(OMe)2-C6H3
4-BnO-3-MeO-C6H3
2-Cl-C6H4
Scheme 3 Proposed mechanism for the formation of compounds 3aa
and 4aa.
On the basis of the above results, we propose the following
probable mechanism for the formation of carbazoles 3aa and
4aa. In the first step, the tetrahydrocarbazole 3 is formed via a
domino Michael–Henry reaction of 1a with 2a in the presence
of DABCO as reported earlier.9d Next, an intermediate 8 is gen-
erated by a protonation of the secondary hydroxyl group of 3
by an acid (HCl) followed by dehydration as depicted in path A
(Scheme 3). Finally, the desired carbazole 3aa is formed via an
aerial oxidation of compound 8. Alternatively, the nitrogen
lone pair pushes out the protonated hydroxyl group to form an
intermediate 9 as follows in path B. The latter undergoes
imine–enamine tautomerization to give 10 and subsequently
eliminates nitrous acid to form 4aa. On the other hand, the
intermediate 8 can be generated from an anionic intermediate
7 via elimination of water in path C which upon aerial oxi-
dation leads to 3aa.
9
4-Cl-C6H4
4-Br-C6H4
96
10
11
12
13
14
15
16
17
18
19
20
21
97 (87)c
96 (86)c
93 (88)c
96 (84)c
88
2-NO2-C6H4
4-NO2-C6H4
4-CN-C6H4
2-Furyl
2-Thiophenyl
PhCH2CH2
MeCH2CH2
C6H5
91
83
82
93 (82)c
95 (86)c
92
4-Cl-C6H4
4-BnO-3-MeO-C6H3
2-Furyl
I
I
I
3bg
3bn
93
a Unless otherwise specified, all the reactions were carried out with
1a–b (0.25 mmol), substituted trans-β-nitroolefins (2a–q, 0.3 mmol)
and DABCO (30 mol%) at 70 °C in water (1.0 mL). b Isolated yield after
column chromatography (method B). c In parentheses, isolated yield
after filtration (method A).
To understand the scope and limitations of this one-pot
domino Michael–Henry/aromatization reaction, we studied a entries 16 and 17). Similarly, a sterically challenging methyl
group of structurally varied trans-aryl/alkyl-substituted 2-(3-formyl-4-iodo-1H-indol-2yl)acetate (1b) underwent clean and
β-nitroolefins (2a–q) with methyl 2-(3-formyl-1H-indol-2-yl)- complete conversions of several aryl and hetero-aryl substi-
acetates 1a–b using 30 mol% loading of DABCO as a catalyst tuted trans-β-nitroolefins by this protocol to provide the corres-
under our standard conditions. The desired carbazoles were ponding anticipated products in excellent yields (92–95%,
isolated by either the column chromatography method or the method B, entries 18–21). It is noteworthy that even though
direct filtration technique (details in the Experimental direct filtration (method A) resulted in slightly (5–12%) lower
section). The results are compiled in Table 2. As is evident chemical yields of final products (81–89% vs. 88–97%, entries
from Table 2, both electron-donating (Me, OMe and OBn, 1–7, Table 2) as compared to the column chromatography
entries 2–7) and electron-withdrawing (Cl, Br, NO2 and CN, method, the former method offers superior eco-sustainability.
entries 8–13) substituents on the aromatic nucleus of aryl-sub- A wide range of sensitive functional groups, namely OMe,
stituted β-nitroolefins reacted smoothly with substrate 1a, OBn, Cl, Br, I, CN, NO2, furyl, and thiophenyl, are well toler-
leading to the formation of 1-methoxycarbonyl-2-aryl-3-nitro- able under these reaction conditions. Thus, a possibility of a
9H-carbazoles (entries 2–13) in good to excellent yields suitable therapeutic target may be achieved by synthetic modi-
(88–97%, 3ab–3am, method B). During our investigations, we fications of the above functional groups depending on the
had noticed that electron withdrawing groups on aromatic requirements.
rings reacted slightly faster than electron donating ones (10 h
Besides, the bench-scale preparation of 1-methoxycarbonyl-
vs. 20 h). Hetero-aryl substituted-β-nitroolefins (2n and 2o, 2-phenyl-3-nitro-9H-carbazole (3aa) was performed under our
entries 14 and 15) were also good Michael-acceptors for these best conditions. To a stirred heterogeneous reaction mixture of
reactions, resulting in excellent 88% and 91% yields of the starting material 1a (10.0 mmol) and trans-β-nitrostyrene (2a,
corresponding products 3an and 3ao respectively. The alkyl 11.0 mmol) in water (30.0 mL) was added DABCO (3.0 mmol)
substituted β-nitroolefins are well known to be poor Michael at 70 °C for 14 h (monitored by TLC). After that, the solid car-
acceptors. Gratifyingly, under our conditions, 2p and 2q ran bazole 3aa was precipitated out which was easily isolated in
smoothly with substrate 1a, providing the anticipated carb- 92% yield by simple filtration followed by washing with a
azoles (3ap and 3aq) in high yields (82–83%, method B, small amount of EtOH. This exciting result reveals that our
8412 | Org. Biomol. Chem., 2013, 11, 8410–8418
This journal is © The Royal Society of Chemistry 2013

View Article Online
Organic & Biomolecular Chemistry
Paper
Table 3 DABCO catalyzed one-pot synthesis of 3-aryl-4-methoxycarbonyl-2-
nitro-9H-carbazole derivatives (3ca–3dn)a
Scheme 4 Synthesis of pentacyclic coumarin fused carbazole derivative (3ar).
Entry
R1
R
T (h)
Product
Yieldb (%)
1
2
3
4
5
6
7
8
9
C6H5
C6H5
H
11
24
24
36
36
22
22
24
26
3ca
3da
3dc
3de
3dg
3dh
3dj
87 (81)c
92
90
87
89
91
90
87
86
Bn
Bn
Bn
Bn
Bn
Bn
Bn
Bn
4-Me-C6H4
4-MeO-C6H4
4-BnO-3-OMe-C6H3
2-Cl-C6H4
4-Br-C6H4
2-NO2C6H4
2-Furyl
Scheme 5 Synthesis of quinolinone fused carbazole derivative.
3dk
3dn
a Unless otherwise specified, all reactions were carried out with 1c–d
(0.25 mmol), substituted trans-β-nitroolefins (2a–n, 0.3 mmol) and
DABCO (30 mol%) at 70 °C in water (1.0 mL). b Yield of the pure
product after column chromatography (method B). c In parentheses,
isolated yield after filtration (method A).
Scheme 6 Synthesis of pyrimidocarbazole derivative 14.
present conditions can be applied to milligram to gram scale
synthesis. We believe that this method provides a practical
alternative to existing methods.
Finally, we used compound 3aa for the synthesis of biologi-
cally significant (topoisomerase II inhibitors12) pyrimidocarba-
zole derivative 14 which was obtained in excellent 88% yield
from 12 (two steps) as shown in Scheme 6.
Next we performed the reaction between methyl 2-(2-formyl-
1H-indol-3-yl)acetate 1c (reverse regioisomer of 1a) and 2a
under our optimal conditions. Gratifyingly, after 11 h, a high
yield (87%, method B) of the desired 3-phenyl-4-methoxycarbo-
nyl-2-nitro-9H-carbazole (3ca) was isolated (entry 1, Table 3).
Even though the substrate 1c was witnessed to be a good
Michael donor, its synthesis is rather difficult. Therefore, we
studied further N-benzyl protected methyl 2-(2-formyl-1H-
indol-3-yl)acetate 1d with various aryl/hetero-substituted
β-nitroolefins (2a–2n). In all these cases, the corresponding
anticipated carbazoles (3da–3dn) were obtained in high to
excellent yields (86–92%, entries 2–9, Table 3). It is noteworthy
that N-benzyl protected indole derivative 1d is less reactive
than its unprotected version 1c towards trans-β-nitrostyrene
under identical conditions (24 h vs. 11 h, entries 1 and 2).
Similarly, various sensitive functional groups such as OMe, Cl,
Br, furyl, NO2, Bn, etc. are compatible under the present
conditions.
Experimental
All reactions were carried out under air and monitored by TLC
using Merck 60 F254 precoated silica gel plates (0.25 mm
thickness) and the products were visualized by UV detec-
tion. Flash chromatography was carried out with silica gel
1
(200–300 mesh). H and 13C NMR spectra were recorded using
a Bruker Avance (III) 400 MHz spectrometer. High resolution
mass spectral analyses (HRMS) were carried out using ESI-
TOF-MS. All the starting materials and catalysts were either
synthesized by literature known procedures or purchased from
commercial sources.
Representative experimental procedure for the synthesis of
1-methoxycarbonyl-2-phenyl-3-nitro-9H-carbazole (3aa)
The development of a simple route for the synthesis of a
fused carbazole scaffold remains a challenging task for syn-
thetic organic chemists. In this context, the current proto- Method A: A heterogeneous mixture of methyl 2-(3-formyl-1H-
col can be applied to one-pot synthesis of 7-nitrochromeno- indol-2-yl)acetate (1a, 54.3 mg, 0.25 mmol), trans-β-nitrostyrene
[3,4-a]carbazol-1(13H)-one (3ar) in 88% yield via a Michael– (2a, 44.7 mg, 0.3 mmol) and DABCO (8.5 mg, 0.075 mmol)
Henry/aromatization reaction of 1a with 2r under our standard in water (1.0 mL) was heated at 70 °C under air for 10 h. The
reaction conditions (Scheme 4).
Next, we extended compound 3ak into a biologically impor- completion of the reaction, the solid product was isolated by
tant11 quinolinone fused carbazole derivative 11 via
filtration, washed with water, cold ethanol and dried under
progress of the reaction mixture was monitored by TLC. After
a
reduction of nitro to amine using Fe–NH4Cl in aqueous reduced pressure to provide the desired carbazole 3aa (89%).
ethanol under refluxing conditions for 10 h followed by intra- The product was characterized by its spectroscopic data
molecular cyclization as shown in Scheme 5.
(1H and 13C NMR, HRMS).
This journal is © The Royal Society of Chemistry 2013
Org. Biomol. Chem., 2013, 11, 8410–8418 | 8413

View Article Online
Paper
Method B: A heterogeneous mixture of methyl 2-(3-formyl-
Organic & Biomolecular Chemistry
1-Methoxycarbonyl-2-(3-methylphenyl)-3-nitro-9H-carbazole
1H-indol-2-yl)acetates (54.3 mg, 0.25 mmol), trans-β-nitro- (3ab). White powder; mp 196–198 °C; 1H NMR (400 MHz,
styrene (44.7 mg, 0.3 mmol) and DABCO (8.5 mg, 0.075 mmol) CDCl3) δ 9.96 (s, 1H, 8.71 (s, 1H), 8.13 (d, J = 8.0 Hz, 1H),
in water (1.0 mL) was heated at 70 °C under air for 10 h (moni- 7.56–7.57 (m, 2H), 7.35–7.39 (m, 1H), 7.27–7.31 (m, 1H),
tored by TLC). After completion of the reaction, the water was 7.19–7.21 (m, 1H), 7.08–7.10 (m, 2H), 3.57 (s, 3H), 2.39 (s, 3H);
removed by decantation. The crude product was purified by 13C NMR (100 MHz, CDCl3) δ 167.7, 143.8, 141.3, 140.6, 137.3,
column chromatography over silica gel to yield the desired 136.8, 135.5, 129.0, 128.6, 128.1, 127.6, 125.7, 123.1, 122.2,
carbazole 3aa (97%).
121.4, 121.0, 120.0, 112.8, 111.7, 52.1, 21.4; HRMS (ESI) m/z
All known and unknown compounds in Tables 2 and 3 calcd for C21H16N2O4[M + Na]+ 383.1008; Found 383.1002.
were fully characterized by their spectroscopic data (1H and
13C NMR, HMRS).
1-Methoxycarbonyl-2-(4-methylphenyl)-3-nitro-9H-carbazole
(3ac). White solid; mp 219–221 °C; 1H NMR (400 MHz, CDCl3)
1-Methoxycarbonyl-2-phenyl-3-nitro-9H-carbazole (3aa). Yellow- 9.95 (s, 1H), 8.68 (s, 1H), 8.13–8.11 (m, 1H), 7.57–7.54 (m, 2H),
ish solid; mp 214–216 °C; 1H NMR (400 MHz, CDCl3) δ 9.94 7.39–7.35 (m, 1H), 7.23–7.16 (m, 4H), 3.59 (s, 3H), 2.42 (s, 3H);
(s, 1H), 8.65 (s, 1H), 8.05 (d, J = 7.76 Hz, 1H), 7.50–7.48 13C NMR (100 MHz, CDCl3) δ 167.6, 144.0, 141.3, 140.6, 137.5,
(m, 2H), 7.35–7.28 (m, 4H), 7.22–7.19 (m, 2H), 3.48 (s, 3H); 135.4, 133.9, 128.6, 128.4, 128.1, 123.1, 122.2, 121.3, 121.0,
13C NMR (100 MHz, CDCl3) δ 167.6, 143.7, 141.4, 140.6, 119.9, 112.8, 111.7, 52.2, 21.4; HRMS (ESI) m/z calcd for
137.0, 135.4, 128.5, 128.2, 128.0, 127.8, 123.3, 122.2, 121.4, C21H16N2O4[M + Na]+ 383.1008; Found 383.1002.
121.0, 120.1, 112.7, 111.8, 52.2; HRMS (ESI) m/z calcd for
1-Methoxycarbonyl-2-(2-methoxyphenyl)-3-nitro-9H-carbazole
(3ad). Light yellowish solid; mp 203–205 °C; 1H NMR
C20H14N2O4[M + Na]+ 369.0851; Found 369.0846.
1-Methoxycarbonyl-2-phenyl-9H-carbazole (4aa). Yellowish (400 MHz, CDCl3) δ 9.96 (s, 1H), 8.78 (s, 1H), 8.12 (d, J =
solid; mp 96–98 °C; 1H NMR (400 MHz, CDCl3) δ 9.75 7.6 Hz, 1H), 7.52–7.55 (m, 2H), 7.33–7.40 (m, 2H), 7.08–7.11
(br s, 1H), 8.12 (dd, J = 0.8, 8.0 Hz, 1H), 8.01 (dd, J = 0.8, (m, 1H), 6.96–7.03 (m, 2H), 3.75 (s, 3H), 3.58 (s, 3H); 13C NMR
8.0 Hz, 1H), 7.44–7.27 (m, 7H), 7.21–7.16 (m, 1H), 7.11 (d, (100 MHz, CDCl3) δ 167.7, 156.6, 143.5, 141.7, 140.5, 132.3,
J = 8.0 Hz, 1H), 3.55 (s, 1H); 13C NMR (100 MHz, CDCl3) 129.5, 129.4, 128.0, 126.5, 123.2, 122.3, 121.3, 120.9, 120.6,
δ 167.9, 141.4, 141.0, 139.6, 138.9, 127.8, 126.6, 125.8, 125.5, 120.4, 113.2, 111.7, 110.4, 55.7, 52.1; HRMS (ESI) m/z calcd for
122.7, 122.6, 121.4, 119.3, 118.9, 110.1, 109.9, 50.5; HRMS C21H16N2O5[M + Na]+ 399.0957; Found 399.0951.
(ESI) m/z calcd for C20H15NO2[M + Na]+ 324.0095; Found
324.1026.
1-Methoxycarbonyl-2-(4-methoxyphenyl)-3-nitro-9H-carbazole
(3ae). Light yellowish solid; mp 198–200 °C; 1H NMR
1-Methoxycarbonyl-2-(4-methoxyphenyl)-9H-carbazole (4ae). (400 MHz, CDCl3) 9.97 (s, 1H), 8.67 (s, 1H), 8.12 (d, J = 8.04 Hz,
Yellow solid; mp 122 °C; 1H NMR (400 MHz, CDCl3) δ 9.79 1H), 7.59–7.56 (m, 2H), 7.39–7.35 (m, 1H), 7.20 (d, J = 8.52 Hz,
(s, 1H), 8.19 (d, J = 8.0 Hz, 1H), 8.09 (d, J = 8.0 Hz, 1H), 2H), 6.94 (d, J = 8.52 Hz, 2H), 3.87 (s, 3H), 3.61 (s, 3H);
7.45–7.54 (m, 2H), 7.28–7.32 (m, 3H), 7.18–7.19 (m, 1H), 13C NMR (100 MHz, CDCl3) δ 167.7, 159.3, 144.2, 141.3, 140.6,
6.95–6.97 (m, 2H), 3.88 (s, 3H), 3.68 9 s, 3H); 13C NMR 135.0, 129.7, 129.0, 128.1, 123.1, 122.2, 121.3, 120.1, 119.9,
(100 MHz, CDCl3) δ 169.0, 158.7, 149.7, 141.7, 140.6, 139.9, 113.4, 112.9, 111.7, 55.3, 52.3; HRMS (ESI) m/z calcd for
135.3, 129.9, 126.4, 125.4, 123.7, 123.3, 122.6, 122.5, 120.3, C21H16N2O5[M + Na]+ 399.0957; Found 399.0951.
119.9, 113.2, 111.0, 55.3, 51.6; HRMS (ESI) m/z calcd for
1-Methoxycarbonyl-2-(2,5-dimethoxyphenyl)-3-nitro-9H-carb-
azole (3af). Yellowish solid; mp 209–211 °C; IR; 1H NMR
C21H17NO3[M + Na]+ 354.1101; Found 354.1103.
1-Methoxycarbonyl-2-(4-benzyloxy-3-methoxyphenyl)-9H-carb- (400 MHz, DMSO-d6) δ 11.83 (s, 1H), 9.08 (s, 1H), 8.37 (d,
azole (4ag). Yellow solid; mp 128 °C; 1H NMR (400 MHz, J = 8.0 Hz, 1H), 7.70–7.72 (m, 1H), 7.54–7.58 (m, 1H), 7.31–7.35
CDCl3) δ 9.78 (s, 1H), 8.18 (d, J = 8.0 Hz, 1H), 8.09 (d, J = (m, 1H), 6.93–7.00 (m, 2H), 6.70–6.71 (m, 1H), 3.72 (s, 3H),
7.6 Hz, 1H), 7.45–7.52 (m, 3H), 7.37–7.41 (m, 2H), 7.28–7.33 3.67 (s, 3H), 3.60 (s, 3H); 13C NMR (100 MHz, DMSO-d6)
(m, 2H), 7.20 (d, J = 8.0 Hz, 1H), 6.93–6.94 (m, 2H), 6.74–6.87 δ 165.8, 153.0, 150.3, 142.2, 141.3, 139.1, 129.3, 127.7, 126.4,
(m, 1H), 5.23 (s, 2H), 3.92 (s, 3H), 3.64 (s, 3H); 13C NMR 122.4, 121.7, 121.3, 120.6, 119.6, 115.7, 115.4, 113.6,
(100 MHz, CDCl3) δ 169.1, 149.0, 147.3, 141.6, 140.6, 139.9, 112.3, 111.8, 55.8, 55.4, 52.3; HRMS (ESI) m/z calcd for
137.2, 136.3, 128.5, 127.9, 127.4, 126.5, 123.6, 123.5, 122.5, C22H18N2O6[M + Na]+ 429.1063; Found 429.1057.
122.4, 121.2, 120.3, 120.0, 113.6, 113.1, 111.1, 111.0, 71.2, 56.1,
51.6; HRMS (ESI) m/z calcd for C28H23NO4[M + Na]+ 460.1519; 9H-carbazole (3ag). Light yellowish solid; mp 199–201 °C;
Found 460.1514.
1H NMR (400 MHz, CDCl3) δ 9.94 (s, 1H), 8.66 (s, 1H), 8.11
1-Methoxycarbonyl-2-(4-benzyloxy-3-methoxyphenyl)-3-nitro-
1-Methoxycarbonyl-2-(4-nitrophenyl)-9H-carbazole (4al). Yellow (dd, J = 0.8, 8.0 Hz, 1H), 7.53–7.58 (m, 2H), 7.47–7.49 (m, 2H),
solid; 1H NMR (400 MHz, CDCl3) δ 9.94 (s, 1H), 8.25–8.29 7.29–7.40 (m, 4H), 6.92 (d, J = 8.4 Hz, 1H), 6.84–6.85 (m, 1H),
(m, 3H), 8.12 (d, J = 8.0 Hz, 1H), 7.50–7.56 (m, 4H), 7.30–7.33 6.74–6.76 (m, 1H), 5.20–5.22 (m, 2H), 3.87 (s, 3H), 3.54 (s, 3H);
(m, 1H), 7.12 (d, J = 7.6 Hz, 1H), 3.67 (s, 1H); 13C NMR 13C NMR (100 MHz, CDCl3) δ 167.8, 149.2, 147.9, 144.0, 141.3,
(100 MHz, CDCl3) δ 167.9, 150.2, 146.8, 140.7, 140.1, 139.5, 140.6, 137.1, 134.7, 129.9, 128.6, 128.1, 127.9, 127.4, 123.1,
129.7, 127.1, 124.8, 124.1, 122.9, 122.2, 121.8, 120.6, 120.4, 122.2, 121.4, 121.1, 121.0, 119.7, 113.5, 113.0, 112.7, 111.7,
111.2, 110.3, 51.8; HRMS (ESI) m/z calcd for C20H14N2O4- 71.1, 56.2, 52.2; HRMS (ESI) m/z calcd for C28H22N2O6[M + Na]+
[M + Na]+ 369.0846; Found 369.0875.
505.1376; Found 505.1370.
8414 | Org. Biomol. Chem., 2013, 11, 8410–8418
This journal is © The Royal Society of Chemistry 2013

View Article Online
Organic & Biomolecular Chemistry
Paper
1-Methoxycarbonyl-2-(2-chlorophenyl)-3-nitro-9H-carbazole (m, 3H); 13C NMR (100 MHz, CDCl3) δ 167.1, 146.9, 143.4,
(3ah). White solid; mp 217–219 °C; 1H NMR (400 MHz, CDCl3) 143.0, 141.1, 140.8, 128.6, 124.3, 123.8, 122.0, 121.5, 121.1,
δ 10.21 (s, 1H), 8.90 (d, J = 0.4 Hz, 1H), 8.15 (dd, J = 0.4, 8.0 Hz, 120.1, 113.4, 111.8, 111.4, 110.1, 52.9; HRMS (ESI) m/z calcd
1H), 7.56–7.61 (m, 2H), 7.47–7.50 (m, 1H), 7.29–7.41 (m, 3H), for C18H12N2O5[M + Na]+ 359.0644; Found 359.0638.
7.19–7.21 (m, 1H), 3.61 (s, 3H); 13C NMR (100 MHz, CDCl3)
1-Methoxycarbonyl-2-(2-thiophenyl)-3-nitro-9H-carbazole (3ao).
δ 167.0, 142.7, 141.9, 140.7, 136.6, 133.5, 132.9, 129.5, 129.1, Yellowish solid; mp 180–182 °C; 1H NMR (400 MHz, CDCl3)
128.8, 128.4, 126.4, 124.0, 122.1, 121.6, 121.1, 121.0, 112.3, δ 9.96 (s, 1H), 8.65 (s, 1H), 8.11 (d, J = 7.2 Hz, 1H), 7.62–7.52
111.8, 52.5; HRMS (ESI) m/z calcd for C20H13ClN2O4[M + Na]+ (m, 2H), 7.46 (dd, J = 0.16 Hz, 5.2 Hz, 1H), 7.39–7.35 (m, 1H),
403.0462; Found 403.0456.
7.09–7.07 (m, 1H), 7.02–7.01 (m, 1H), 3.69 (s, 3H); 13C NMR
1-Methoxycarbonyl-2-(4-chlorophenyl)-3-nitro-9H-carbazole (100 MHz, CDCl3) δ 167.3, 144.6, 141.0, 140.7, 136.4, 128.5,
(3ai). Light yellowish solid; mp 216–218 °C; 1H NMR 128.1, 127.1, 127.0, 126.7, 124.0, 122.1, 121.5, 121.1, 119.6,
(400 MHz, CDCl3) δ 10.07 (s, 1H), 8.75 (s, 1H), 8.14 (d, J = 114.1, 111.8, 52.6; HRMS (ESI) m/z calcd for C18H12N2O4S[M + Na]+
8.0 Hz, 1H), 7.56–7.61 (m, 2H), 7.37–7.41 (m, 3H), 7.21–7.24 (m, 375.0415; Found 375.0410.
2H), 3.61 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 167.3, 143.5,
1-Methoxycarbonyl-2-(2-ethylphenyl)-3-nitro-9H-carbazole (3ap).
141.5, 140.7, 135.6, 134.1, 133.9, 129.9, 128.4, 128.0, 123.6, Yellow solid; mp 137–139 °C; 1H NMR (400 MHz, CDCl3)
122.1, 121.5, 121.1, 120.3, 112.4, 111.8, 52.3; HRMS (ESI) m/z δ 10.03 (s, 1H), 8.70 (d, J = 0.48 Hz, 1H), 8.08 (dd, J = 0.80 Hz,
calcd for C20H13ClN2O4[M + Na]+ 403.0462; Found 403.0456.
7.6 Hz, 1H), 7.53–7.55 (m, 2H), 7.31–7.37 (m, 5H),
1-Methoxycarbonyl-2-(4-bromophenyl)-3-nitro-9H-carbazole 7.22–7.27 (m, 1H), 4.11 (s, 3H), 3.54–3.59 (m, 2H), 3.06–3.11
(3aj). Light yellowish solid; mp 235–237 °C; 1H NMR (m, 2H); 13C NMR (100 MHz, CDCl3) δ 167.5, 144.7, 142.3,
(400 MHz, CDCl3) δ 10.07 (s, 1H), 8.74 (d, J = 0.76 Hz, 1H), 8.13 141.7, 140.3, 136.1, 128.5 (2C), 127.9, 126.2, 122.5, 122.2,
(dd, J = 0.8, 7.76 Hz, 1H), 7.59–7.53 (m, 4H), 7.41–7.37 (m, 1H), 121.3, 121.2, 120.8, 112.2, 111.6, 52.7, 37.7, 32.7; HRMS
7.17–7.15 (m, 2H), 3.61 (s, 3H); 13C NMR (100 MHz, CDCl3) (ESI) m/z calcd for C22H18N2O4[M + Na]+ 397.1164; Found
δ 167.3, 143.4, 141.5, 140.7, 136.1, 134.1, 130.9, 130.2, 128.4, 397.1159.
123.6, 122.1, 122.0, 121.5, 121.0, 120.3, 112.3, 111.8, 52.3;
HRMS (ESI) m/z calcd for C20H13BrN2O4[M + Na]+ 446.9956; ish solid; mp 146–148 °C; 1H NMR (400 MHz, CDCl3) δ 9.96 (s,
Found 446.9951 and [M + Na + 2] 448.9931. 1H), 8.61 (s, 1H), 8.05 (d, J = 7.78 Hz, 1H), 7.48–7.53 (m, 2H),
1-Methoxycarbonyl-2-propyl-3-nitro-9H-carbazole (3aq). Yellow-
1-Methoxycarbonyl-2-(2-nitrophenyl)-3-nitro-9H-carbazole (3ak). 7.30–7.34 (m, 1H), 4.09 (s, 3H), 3.20–3.24 (m, 2H), 1.70–1.80
Brown solid; mp 218–220 °C; 1H NMR (400 MHz, CDCl3) (m, 2H), 1.05 (t, J = 7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3)
δ 10.19 (s, 1H), 8.93 (d, J = 0.8 Hz, 1H), 8.34–8.36 (m, 1H), δ 167.7, 144.8, 142.2, 140.2, 137.2, 127.8, 122.2 (2C), 121.2,
8.12–8.14 (m, 1H), 7.52–7.66 (m, 4H), 7.38–7.42 (m, 1H), 120.9, 120.7, 112.1, 111.5, 52.6, 32.2, 25.3, 14.5; HRMS
7.14–7.17 (m, 1H), 3.60 (s, 3H); 13C NMR (100 MHz, CDCl3) (ESI) m/z calcd for C17H16N2O4[M + Na]+ 335.1002; Found
δ 166.2, 148.4, 142.1, 141.2, 140.6, 134.3, 133.9, 133.3, 129.7, 335.1021.
128.7, 128.4, 124.4, 123.9, 122.1, 121.7, 121.6, 121.0, 111.9,
110.6, 52.6; HRMS (ESI) m/z calcd for C20H13N3O6[M + Na]+ Light yellowish solid; mp 198–200 °C; 1H NMR (400 MHz,
414.0702; Found 414.0697. CDCl3) δ 10.18 (s, 1H), 9.60 (s, 1H), 7.81 (d, J = 7.6 Hz, 1H),
1-Methoxycarbonyl-5-iodo-2-phenyl-3-nitro-9H-carbazole (3ba).
1-Methoxycarbonyl-2-(4-nitrophenyl)-3-nitro-9H-carbazole (3al). 7.57 (d, J = 8.0 Hz, 1H), 7.41–7.42 (m, 3H), 7.24–7.26 (m, 3H),
Brown solid; mp 223–225 °C; 1H NMR (400 MHz, CDCl3) 3.55 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 163.3, 139.1, 137.3,
δ 10.19 (s, 1H), 8.89 (d, J = 0.48 Hz, 1H), 8.32–8.28 (m, 2H), 136.9, 132.4, 131.6, 128.0, 124.5, 124.1, 123.6, 123.5, 119.5,
8.19–8.16 (m, 1H), 7.62–7.61 (m, 2H), 7.48–7.46 (m, 2H), 119.4, 116.3, 108.1, 107.2, 83.5, 47.9; HRMS (ESI) m/z calcd for
7.44–7.40 (m, 1H), 3.60 (s, 3H); 13CNMR (100 MHz, CDCl3) C20H13IN2O4[M + Na]+ 494.9818; Found 494.9812.
δ 166.7, 147.4, 144.7, 142.6, 141.7, 140.8, 133.3, 129.6, 128.8,
124.3, 123.0, 122.0, 121.8, 121.2, 120.9, 112.0, 111.8, 52.4; azole (3bi). White solid; mp 233–235 °C; H NMR (400 MHz,
HRMS (ESI) m/z calcd for C20H13N3O6[M + Na]+ 414.0702; CDCl3) δ 10.23 (s, 1H), 9.63 (s, 1H), 7.82 (dd, J = 0.8, 7.6 Hz,
1-Methoxycarbonyl-5-iodo-2-(4-chlorophenyl)-3-nitro-9H-carb-
1
Found 414.0697.
1H), 7.59 (dd, J = 0.8, 7.6 Hz, 1H), 7.38–7.42 (m, 2H), 7.29–7.21
1-Methoxycarbonyl-2-(4-cyanophenyl)-3-nitro-9H-carbazole (m, 3H), 3.60 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 167.3,
(3am). White solid; 1H NMR (400 MHz, CDCl3) δ 10.17 (s, 1H), 143.2, 141.7, 141.3, 135.3, 134.7, 134.0, 132.5, 129.8, 128.9,
8.86 (s, 1H), 8.17 (d, J = 8.0 Hz, 1H), 7.72 (d, J = 8.0 Hz, 2H), 128.1, 124.1, 123.8, 120.8, 112.2, 111.6, 87.9, 52.4; HRMS
7.59–7.63 (m, 2H), 7.39–7.43 (m, 3H), 3.59 (s, 3H); 13C NMR (ESI) m/z calcd for C20H12ClIN2O4[M + Na]+ 528.9428; Found
(100 MHz, DMSO-d6) δ 170.5, 147.6, 146.7, 146.5, 144.5, 528.9422.
137.0, 136.9, 134.9, 133.4, 128.4, 126.8, 126.7, 126.2, 125.7,
124.0, 119.7, 117.8, 115.6, 57.7; HRMS (ESI) m/z calcd for nitro-9H-carbazole (3bg). Brown solid; mp 180–182 °C;
C21H13N3O4[M + 1]+ 372.0906; Found 372.0979. 1H NMR (400 MHz, CDCl3) δ 10.09 (s, 1H), 9.51 (s, 1H), 7.67
1-Methoxycarbonyl-5-iodo-2-(4-benzyloxy-3-methoxyphenyl)-3-
1-Methoxycarbonyl-2-(2-furyl)-3-nitro-9H-carbazole (3an). (d, J = 7.6 Hz, 1H), 7.46–7.54 (m, 3H), 7.21–7.40 (m, 4H), 6.93
Brown solid; mp 175–177 °C; 1H NMR (400 MHz, CDCl3) δ 9.99 (d, J = 8.0 Hz, 1H), 6.64–6.85 (m, 1H), 6.74–6.77 (m, 1H),
(s, 1H), 8.70 (s, 1H), 8.09 (d, J = 8.0 Hz, 1H), 7.53–7.61 (m, 3H), 5.19–5.20 (m, 2H), 3.87 (s, 3H) 3.53 (s, 3H); 13C NMR
7.35–7.38 (m, 1H), 6.52–6.53 (m, 1H), 6.42–6.44 (m, 1H), 3.78 (100 MHz, CDCl3) δ 167.8, 149.2, 148.0, 143.6, 141.4, 141.2,
This journal is © The Royal Society of Chemistry 2013
Org. Biomol. Chem., 2013, 11, 8410–8418 | 8415

View Article Online
Paper
Organic & Biomolecular Chemistry
137.0, 135.3, 132.3, 129.6, 128.7, 128.6, 127.9, 127.5, 123.8, (s, 3H); 13C NMR (100 MHz, CDCl3) δ 168.4, 149.3, 148.0,
123.5, 121.1, 120.2, 113.5, 112.7, 112.6, 111.5, 87.6, 71.1, 56.2, 147.4, 142.9, 138.6, 137.0, 135.6, 129.1, 129.0, 128.6, 128.5,
52.2; HRMS (ESI) m/z calcd for C28H21IN2O6[M
+
Na]+ 128.4, 128.1, 127.9, 127.5, 126.3, 125.0, 122.5, 122.0, 121.6,
121.0, 120.2, 113.7, 113.0, 109.8, 106.1, 71.0, 56.1, 52.7, 46.9;
631.0342; Found 631.0337.
1-Methoxycarbonyl-5-iodo-2-(2-furyl)-3-nitro-9H-carbazole HRMS (ESI) m/z calcd for C35H28N2O6[M + Na]+ 595.1840;
1
(3bn). Pale yellow solid; mp 190–192 °C; H NMR (400 MHz, Found 595.1840.
CDCl3) δ 10.15 (s, 1H), 9.62 (s, 1H), 7.81 (dd, J = 0.8, 8.0 Hz,
9-Benzyl-4-methoxycarbonyl-3-(2-chlorophenyl)-2-nitro-9H-
1H), 7.55–7.61 (m, 2H), 7.24–7.28 (m, 1H), 6.53–6.54 (m, 1H), carbazole (3dh). Yellowish solid; mp 178–180 °C; 1H NMR
6.46–6.47 (m, 1H), 3.79 (s, 3H); 13C NMR (100 MHz, CDCl3) (400 MHz, CDCl3) δ 8.26 (s, 1H), 7.99–8.01 (m, 1H), 7.55–7.59
δ 167.2, 146.7, 143.2, 143.0, 141.4, 141.3, 132.5, 129.1, 124.7, (m, 2H), 7.46–7.49 (m, 2H), 7.29–7.37 (m, 6H), 7.16–7.18 (m,
124.4, 123.7, 120.6, 113.0, 111.6, 111.5, 110.4, 88.0, 53.0; 2H), 5.64 (s, 2H), 3.67 (s, 3H); 13C NMR (100 MHz, CDCl3)
HRMS (ESI) m/z calcd for C18H11IN2O5[M + Na]+ 484.9610; δ 167.8, 145.9, 143.2, 139.2, 135.5, 135.3, 134.3, 132.1, 130.9,
Found 484.9605.
129.4, 129.2, 129.1, 128.9, 128.1, 126.5, 126.3, 123.2, 122.9,
4-Methoxycarbonyl-3-phenyl-2-nitro-9H-carbazole (3ca). Yellow- 122.8, 121.1, 120.2, 109.9, 106.9, 52.5, 47.1; HRMS (ESI) m/z
ish solid; 1H NMR (400 MHz, CDCl3) δ 8.60 (s, 1H), 8.07 calcd for C27H19ClN2O4[M + Na]+ 493.0931; Found 493.0926.
(s, 1H), 7.94 (d, J = 8.0 Hz, 1H), 7.51–7.57 (m, 2H), 7.39–7.44
9-Benzyl-4-methoxycarbonyl-3-(4-bromophenyl)-2-nitro-9H-
1
(m, 3H), 7.32–7.35 (m, 2H), 7.27–7.31 (m, 1H), 3.67 (s, 3H); carbazole (3dj). Light orange solid; mp 230–232 °C; H NMR
13C NMR (100 MHz, CDCl3) δ 168.2, 141.7, 137.4, 135.6, (400 MHz, CDCl3) δ 8.04 (s, 1H), 7.96 (d, J = 8.0 Hz, 1H),
129.9, 129.7, 129.1, 128.8, 128.6, 128.2, 128.0, 122.6, 122.4, 7.53–7.59 (m, 3H), 7.47 (d, J = 8.4 Hz, 1H), 7.28–7.33 (m, 4H),
121.1, 120.4, 111.3, 108.0, 52.5; HRMS (ESI) m/z calcd for 7.20–7.23 (m, 2H), 7.13–7.15 (m, 2H), 5.61 (s, 2H), 3.73 (s, 3H);
C20H14N2O4[M + Na]+ 369.0851; Found 369.0846.
13C NMR (100 MHz, CDCl3) δ 168.0, 146.7, 143.1, 138.8, 135.5,
9-Benzyl-4-methoxycarbonyl-3-phenyl-2-nitro-9H-carbazole 134.7, 131.4, 130.8, 129.1, 128.8, 128.7, 128.2, 126.3, 124.2,
(3da). Light yellowish solid; mp 209–211 °C; 1H NMR 122.5, 122.4, 122.3, 121.1, 120.1, 109.8, 106.5, 52.6, 47.0;
(400 MHz, CDCl3) δ 8.01 (s, 1H), 7.97–8.00 (m, 1H), 7.54–7.58 HRMS (ESI) m/z calcd for C27H19BrN2O4[M + Na]+ 537.0426;
(m, 1H), 7.46–7.48 (m, 1H), 7.39–7.44 (m, 3H), 7.28–7.36 (m, Found 537.0395 and [M + Na + 2]+ 539.0540.
6H), 7.13–7.15 (m, 2H), 5.61 (s, 2H), 3.68 (s, 3H); 13C NMR
9-Benzyl-4-methoxycarbonyl-3-(2-nitrophenyl)-4-nitro-9H-car-
(100 MHz, CDCl3) δ 168.3, 147.1, 143.0, 138.7, 135.7, 135.6, bazole (3dk). Orange solid; mp 213–215 °C; 1H NMR
129.1, 129.0, 128.9, 128.6, 128.2, 128.1, 128.0, 126.3, 125.5, (400 MHz, CDCl3) δ 8.41 (s, 1H), 8.25–8.27 (m, 1H), 7.96 (d, J =
122.6, 122.2, 121.0, 120.2, 109.8, 106.3, 52.5, 47.0; HRMS (ESI) 8.0 Hz, 1H), 7.66–7.69 (m, 1H), 7.55–7.63 (m, 2H), 7.46–7.48
m/z calcd for C27H20N2O4[M + Na]+ 459.1321; Found 459.1315.
(m, 1H), 7.28–7.36 (m, 5H), 7.16–7.18 (m, 2H), 5.65 (s, 2H),
9-Benzyl-4-methoxycarbonyl-3-(4-methylphenyl)-2-nitro-9H- 3.61 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 167.5, 148.3, 144.9,
carbazole (3dc). Yellowish solid; mp 223–225 °C; 1H NMR 143.3, 139.9, 135.5, 133.1, 132.4, 131.6, 129.2, 129.1, 129.0,
(400 MHz, CDCl3) δ 7.97–7.99 (m, 2H), 7.54–7.58 (m, 1H), 7.45 128.2, 127.2, 126.4, 124.6, 123.2, 123.0, 122.9, 121.2,
(d, J = 8.0 Hz, 1H), 7.29–7.33 (m, 4H), 7.20–7.25 (m, 4H), 120.0, 109.9, 107.6, 52.5; 47.0; HRMS (ESI) m/z calcd for
7.12–7.14 (m, 2H), 5.60 (s, 2H), 3.73 (s, 3H), 2.41 (s, 3H); C27H19N3O6[M + Na]+ 504.1172; Found 504.1166.
13C NMR (100 MHz, CDCl3) δ 168.3, 147.3, 142.9, 138.6, 137.6,
9-Benzyl-4-methoxycarbonyl-3-(2-furyl)-2-nitro-9H-carbazole
135.6, 132.5, 129.1, 129.0, 128.9, 128.8, 128.5, 128.1, 126.3, (3dn). Light brownish solid; mp 173–175 °C; 1H NMR
125.4, 122.3, 122.0, 120.9, 120.2, 109.7, 106.2, 52.5, 46.9, 21.3; (400 MHz, CDCl3) δ 7.99–8.02 (m, 2H), 7.54–7.59 (m, 2H), 7.44
HRMS (ESI) m/z calcd for C28H22N2O4[M + Na]+ 473.1477; (d, J = 8.8 Hz, 1H), 7.26–7.35 (m, 4H), 7.08–7.10 (m, 2H),
Found 473.1472.
6.51–6.55 (m, 2H), 5.57 (s, 2H), 3.93 (s, 3H); 13C NMR
9-Benzyl-4-methoxycarbonyl-3-(4-methoxyphenyl)-2-nitro-9H- (100 MHz, CDCl3) δ 168.1, 147.1, 146.4, 143.5, 142.8, 139.1,
carbazole (3de). White solid; mp 206–208 °C; 1H NMR 135.4, 129.1, 128.8, 128.7, 128.1, 126.2, 122.5, 122.0, 121.2,
(400 MHz, CDCl3) δ 7.96–7.99 (m, 2H), 7.54–7.58 (m, 2H), 7.45 120.1, 114.6, 111.4, 110.1, 109.9, 106.8, 53.0, 46.8; HRMS (ESI)
(d, J = 8.0 Hz, 1H), 7.28–7.33 (m, 4H), 7.24–7.26 (m, 1H), m/z calcd for C25H18N2O5[M + Na]+ 449.1113; Found 449.1108.
7.12–7.15 (m, 2H), 6.93–6.97 (m, 2H), 5.60 (s, 2H), 3.86 (s, 3H),
7-Nitrochromeno[3,4-a]carbazol-1(13H)-one (3ar). Brown
3.74 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 168.4, 159.4, 147.4, solid, mp 260 °C (decompose); H NMR (400 MHz, DMSO-d6)
142.9, 138.5, 135.6, 130.5, 130.3, 129.1, 128.5, 128.1, 127.6, δ 12.43 (s, 1H), 9.26 (s, 1H), 8.36 (d, J = 8.0 Hz, 1H), 7.90 (d, J =
126.3, 125.0, 122.4, 121.9, 120.9, 120.1, 113.8, 109.8, 106.1, 8.0 Hz, 1H), 7.56–7.66 (m, 4H); 7.35–7.42 (m, 2H); 13C NMR
55.3, 52.6, 46.9; HRMS (ESI) m/z calcd for C28H22N2O5[M + Na]+ (100 MHz, DMSO-d6) δ 159.2, 150.6, 141.7, 139.2, 138.8, 131.5,
1
489.1426; Found 489.1421.
128.0, 125.0, 124.8, 124.2, 123.9, 122.3, 121.4, 121.3,
9-Benzyl-4-methoxycarbonyl-3-(4-benzyloxy-3-methoxy-phenyl)- 121.2, 118.0, 114.5, 113.4, 105.1; HRMS (ESI) m/z calcd for
2-nitro-9H-carbazole (3dg). Light yellowish; mp 179–181 °C; C19H10N2O4[M + Na]+ 353.0538; Found 353.0533.
1H NMR (400 MHz, CDCl3) δ 7.97 (d, J = 7.6 Hz, 1H), 7.94
7-Amino-2,13-dihydro-1H-idolo[2,3-i]phenanthridin-1-one
(s, 1H), 7.53–7.58 (s, 1H), 7.44–7.48 (m, 3H), 7.37–7.41 (m, 2H), (11). A mixture of compound 3ak (196.0 mg, 0.5 mmol), Fe
7.27–7.34 (m, 5H), 7.11–7.13 (m, 2H), 6.90–6.95 (m, 2H), powder (280 mg, 5.0 mmol) and NH4Cl (321 mg, 6.0 mmol) in
6.82–6.85 (m, 1H), 5.59 (s, 2H), 5.20 (s, 2H), 3.87 (s, 3H), 3.70 EtOH–H2O (20 mL, 4 : 1) was heated at 80 °C for 10 h.
8416 | Org. Biomol. Chem., 2013, 11, 8410–8418
This journal is © The Royal Society of Chemistry 2013

View Article Online
Organic & Biomolecular Chemistry
Paper
Afterwards the reaction mixture was concentrated under purified by column chromatography over silica-gel (eluent:
reduced pressure. The crude residue was extracted with ethyl DCM–MeOH = 19 : 1) to afford the pure product 14 in 88%
acetate. The combined organic solvent evaporated under yield.
reduced pressure followed by purification through a pad of
silica-gel (eluent: hexane–EtOAc = 3 : 1) afforded the pure δ 8.52–8.54 (m, 2H), 8.04–8.05 (m, 1H), 7.65–7.69 (m, 1H),
product 11 (136 mg, 91%). 7.48–7.56 (m, 4H), 7.34–7.35 (m, 2H), 4.22 (t, J = 6.4 Hz, 2H),
Yellowish solid; 196–198 °C; 1H NMR (400 MHz, CDCl3)
Brown solid; 1H NMR (400 MHz, DMSO-d6) δ 11.77 (br s, 2.66 (br s, 2H), 2.33 (br s, 6H); 13C NMR (100 MHz, CDCl3)
1H), 11.52 (br s, 1H), 9.27 (d, J = 8.0 Hz, 1H), 8.04–8.07 (m, δ 159.7, 148.2, 147.5, 138.8, 138.2, 136.1, 130.0, 128.7, 128.3,
2H), 7.78–7.80 (m, 1H), 7.41–7.46 (m, 3H), 7.17–7.26 (m, 2H), 128.1, 125.6, 123.9, 123.7, 121.5, 120.0, 116.3, 111.1, 55.5, 45.5,
5.19 (br s, 2H); 13C NMR (100 MHz, DMSO-d6) δ 162.3, 140.5, 39.2; HRMS (ESI) m/z calcd for C24H22N4O4[M + 1]+ 429.1563;
138.7, 135.9, 132.9, 127.6, 126.3, 125.7, 122.1, 121.5, 121.4, Found 429.1557.
120.6, 119.7, 119.5, 118.6, 115.7, 114.2, 112.2, 110.3; HRMS
(ESI) m/z calcd for C19H14N3O [M + H]+ 300.1137; Found
300.1160.
Conclusions
1-Carboxylic acid-2-phenyl-3-nitro-9H-carbazole (12). To a
stirred solution of compound 3aa (346 mg, 1.0 mmol) in a
mixture of MeCN–H2O (5 mL, 7 : 3) was added LiOH·H2O
(84 mg, 2.0 mmol) at room temperature. After that the reaction
mixture was heated at 40 °C for 24 h (monitored by TLC). Next,
the reaction mixture was extracted with ethyl acetate before
being acidified with HCl. The evaporation of the solvent left
the crude product which was purified by column chromato-
graphy over silica-gel (eluent: hexane–ethyl acetate = 3 : 7) to
furnish the pure product 12 (309.0 mg, 93%). The product was
characterized by spectroscopic data (1H and 13C NMR and
HRMS).
In the current paper, we have developed a clean, expedient,
mild and general method for the synthesis of functionalized
carbazole derivatives in water medium via a one-pot domino
Michael–Henry/aromatization reaction under aerobic con-
ditions. Our current method avoids the use of acids, metals,
toxic organic solvents, stoichiometric amounts of strong oxi-
dants, any need for an inert atmosphere, multiple steps, etc. In
addition, a marketable organocatalyst, operational simplicity,
excellent yields (≤97%), a broad substrate scope, suitability for
bench scale synthesis, and environmentally friendly reaction
conditions make this procedure more convenient as compared
to the existing ones. Furthermore, biologically attractive pyri-
mido, quinolinone and coumarin fused carbazole derivatives
have been prepared. Investigations into the application of
these molecules are in progress.
White solid; 1H NMR (400 MHz, DMSO-d6) δ 13.4 (br s, 1H),
11.8 (s, 1H), 9.03 (s, 1H), 8.36 (d, J = 7.6 Hz, 1H), 7.72 (d,
J = 8.0 Hz, 1H), 7.52–7.57 (m, 1H), 7.29–7.44 (m, 6H); 13C NMR
(100 MHz, DMSO-d6) δ 167.00, 142.4, 141.5, 138.9, 136.6,
132.0, 128.6, 127.8, 127.6, 127.5, 122.2, 121.7, 121.2, 120.5,
118.5, 117.1, 112.5; HRMS (ESI) m/z calcd for C19H12N2O4[M − 1]−
331.0719; Found 331.0713.
Acknowledgements
2-[2-(Dimethylamino)ethyl]-5-nitro-1H-pyrimido[5,6,1-jk]carb-
The authors acknowledge a CSIR research grant (project no.
02(0019)/11/EMR-II) for the generous financial support. P. K.
Jaiswal is also thankful to CSIR for his Research Associate
fellowship. S. B. and S. S. are grateful for their UGC and CSIR
fellowships. The authors are thankful to Mr K. Pandey for
recording the NMR spectra.
azole-1,3(2H)-dione (14). To
a mixture of compound 12
(166 mg, 0.5 mmol), EDC·HCl (135 mg, 0.7 mmol), HOBt
(95.0 mg, 0.7 mmol) and Et3N (0.42 mL, 3.0 mmol) in DMF
(5.0 mL) was added N,N-dimethylethylenediamine (66.0 mg,
0.75 mmol) at room temperature. The reaction mixture was
stirred for 8 h (monitored by TLC). After that the reaction
mixture was quenched with water before being removed DMF
under reduced pressure. Then the reaction mixture was
extracted with EtOAc (3 × 10 mL), washed with water, brine
and dried with Na2SO4. The combined organic solvent was
evaporated under reduced pressure to afford crude product 13
which was sufficiently pure and directly used for the next step.
To a stirred solution of the above compound 13 in dry DMF
(5.0 mL) under an argon atmosphere was added NaH (50–55%
dispersion in mineral oil; 72 mg) at 0 °C. After being stirred
for 1 h at the same temperature, EtO2Cl (1.0 mmol) was added
into the above reaction mixture and stirring was continued for
12 h at room temperature. Then the reaction mixture was
quenched with water, extracted with ethyl acetate (3 × 10 mL),
washed with water and brine, and dried with Na2SO4. The
combined organic solvent was concentrated in a vacuum
under reduced pressure to give the crude residue which was
Notes and references
1 For selected reviews on carbazole synthesis, see:
(a) H.-J. Knölker and K. Reddy, Chem. Rev., 2002, 102, 4303;
(b) A. W. Schmidt, K. R. Reddy and H.-J. Knölker, Chem.
Rev., 2012, 112, 3193; (c) H.-J. Knölker and K. R. Reddy,
Chemistry and Biology of Carbazole Alkaloids In The Alka-
loids, ed. G. A. Cordell, Academic Press, Amsterdam, 2008,
vol. 65, p. 1; (d) J. Roy, A. K. Jana and D. Mal, Tetrahedron,
2012, 68, 6099.
2 (a) J. A. Joule and K. Mills, Heterocyclic Chemistry, Blackwell
Science, Oxford, UK, 4th edn, 2000; (b) W. Lin, Y. Wang,
S. Lin, C. Li, C. Zhou, S. Wang, H. Huang, P. Liu, G. Ye and
X. Shen, Eur. J. Med. Chem., 2012, 47, 214; (c) W. Maneerat,
T. Ritthiwigrom, S. Cheenpracha, T. Promgool, K. Yossathera,
This journal is © The Royal Society of Chemistry 2013
Org. Biomol. Chem., 2013, 11, 8410–8418 | 8417

View Article Online
Paper
S. Deachathai, W. Phakhodee and S. Laphookhieo, J. Nat.
Organic & Biomolecular Chemistry
133, 5996; (d) C.-C. Chen, S.-C. Yang and M.-J. Wu, J. Org.
Chem., 2011, 76, 10269.
Prod., 2012, 75, 741; (d) Y. Qiu, D. Ma, C. Fu and S. Ma,
Org. Biomol. Chem., 2013, 11, 1666; (e) T. Thongthoom,
U. Songsiang, C. Phaosiri and C. Yenjai, Arch. Pharmacal
Res., 2010, 33, 675.
3 (a) Organic Light Emitting Devices: Synthesis Properties, and
Applications, ed. K. Müllen and U. Scherf, Wiley-VCH,
Weinheim, 2006; (b) Y. Tao, C. Yang and J. Qin, Chem. Soc.
Rev., 2011, 40, 2943; (c) J. Li and A. Grimsdale, Chem. Soc.
Rev., 2010, 39, 2399; (d) S. L. Lai, Q. X. Tong, M. Y. Chan,
T. W. Ng, M. F. Lo, C. C. Ko, S. T. Lee and C. S. Lee, Org.
Electron., 2011, 12, 541.
4 (a) L. Ackermann and A. Althammer, Angew. Chem., Int.
Ed., 2007, 46, 1627; (b) C. Lu, N. A. Markina and
R. C. Larock, J. Org. Chem., 2012, 77, 11153; (c) W. C. Tsang,
N. Zheng and S. L. Buchwald, J. Am. Chem. Soc., 2005, 127,
14560; (d) B. Liegault, D. Lee, M. P. Huestis, D. R. Stuart
and K. Fagnou, J. Org. Chem., 2008, 73, 5022; (e) T. Watanabe,
S. Ueda, S. Inuki, S. Oishi, N. Fujii and H. Ohno, Chem.
Commun., 2007, 4516; (f) V. Sridharan, M. J. Carlos
and M. M. Antonia, Eur. J. Org. Chem., 2009, 4614;
(g) C. S. Nervig, P. J. Waller and D. Kalyani, Org. Lett.,
2012, 14, 4838; (h) J. Jordan, C. Johansson, M. Gulias,
E. Beck and M. J. Gaunt, J. Am. Chem. Soc., 2008, 130,
16184.
7 For reviews on organocatalyzed domino, see: (a) A. Moyano
and R. Rios, Chem. Rev., 2011, 111, 4703; (b) D. Enders,
C. Grondal and M. R. M. Hüttl, Angew. Chem., Int. Ed.,
2007, 46, 1570; (c) X. Yu and W. Wang, Org. Biomol. Chem.,
2008, 6, 2037; (d) A.-N. Alba, X. Companyo, M. Viciano and
R. Rios, Curr. Org. Chem., 2009, 13, 1432; (e) C. Vaxelaire,
P. Winter and M. Christmann, Angew. Chem., Int. Ed., 2011,
50, 3605; (f) H. Pellissier, Adv. Synth. Catal., 2012, 354, 237.
8 (a) M. Tsakos, M. R. J. Elsegood and C. G. Kokotos, Chem.
Commun., 2013, 49, 2219; (b) Q. Dai, H. Arman and
J. C.-G. Zhao, Chem.–Eur. J., 2013, 19, 1666; (c) S. Varga,
G. Jakab, L. Drahos, T. Holczbauer, M. Czugler and T. Soós,
Org. Lett., 2011, 13, 5416; (d) B. Zhang, L. Cai, H. Song,
Z. Wang and Z. He, Adv. Synth. Catal., 2010, 352, 97;
(e) M. Rueping, A. Kuenkel and R. Fröhlich, Chem.–Eur. J.,
2010, 16, 4173; (f) B. Tan, Y. Lu, X. Zeng, P. J. Chua and
G. Zhong, Org. Lett., 2010, 12, 2682; (g) Y. Hayashi,
T. Okano, S. Aratake and D. Hazelard, Angew. Chem., Int.
Ed., 2007, 46, 4922.
9 (a) T. Bhattacharya, T. K. Sarma and S. Samanta, Catal.
Sci. Technol., 2012, 2, 2216; (b) S. Singh, A. Srivastava and
S. Samanta, Tetrahedron Lett., 2012, 53, 6087; (c) A. Srivastava,
S. Singh and S. Samanta, Tetrahedron Lett., 2013, 54, 1444;
(d) P. K. Jaiswal, S. Biswas, S. Singh, B. Pathak, S. M. Mobin
and S. Samanta, RSC Adv., 2013, 3, 10644; (e) S. Biswas,
P. K. Jaiswal, S. Singh, S. M. Mobin and S. Samanta, Org.
Biomol. Chem., 2013, 11, 7084.
5 For other than Pd metal mediated carbazole syntheses, see:
(a) T. Noji, H. Fujiwara, K. Okano and H. Tokuyama, Org.
Lett., 2013, 15, 1946; (b) K. Hirano, Y. Inaba, K. Takasu,
S. Oishi, Y. Takemoto, N. Fujii and H. Ohno, J. Org. Chem.,
2011, 76, 9068; (c) T. Tsuchimoto, H. Matsubayashi, 10 (a) V. K. Ahluwalia and R. S. Varma, Green Solvents for
M. Kaneko, Y. Nagase, T. Miyamura and E. Shirakaw, J. Am.
Chem. Soc., 2008, 130, 15825; (d) R. Xie, Y. Ling and H. Fu,
Chem. Commun., 2012, 48, 12210; (e) W. Kong, C. Fu and
S. Ma, Chem. Commun., 2009, 45, 4572; (f) H. K. Grover,
T. P. Lebold and M. A. Kerr, Org. Lett., 2011, 13, 220;
Organic Synthesis, Alpha Science International, Abingdon,
UK, 2009; (b) U. M. Lindström, Organic Reactions in Water:
Principles, Strategies and Applications, Blackwell, Oxford,
2007; (c) R. N. Butler and A. G. Coyne, Chem. Rev., 2010,
110, 6302.
(g) L. Wang, G. Li and Y. Liu, Org. Lett., 2011, 13, 3786; 11 M. Laronze-Cochard, F. Cochard, E. Daras, A. Lansiaux,
(h) B. J. Stokes, B. Jovanović, H. Dong, K. Richert, R. Riell
and T. Driver, J. Org. Chem., 2009, 74, 3225.
6 For one-pot transition metal free carbazole synthesis, see:
A. Brassart, E. Vanquelef, E. Prost, J.-M. Nuzillard,
B. Baldeyrou, J.-F. Goosens, O. Lozach, L. Meijer, J.-F. Riou,
E. Henon and J. Sapi, Org. Biomol. Chem., 2010, 8, 4625.
(a) F. Xiao, Y. Liao, M. Wu and G.-J. Deng, Green Chem., 12 J. Kamata, T. Okada, Y. Kotake, J. Niijima, K. Nakamura,
2012, 14, 3277; (b) A. P. Antonchick, R. Samanta, K. Kulikov
and J. Lategahn, Angew. Chem., Int. Ed., 2011, 50, 8605;
(c) S. H. Cho, J. Yoon and S. Chang, J. Am. Chem. Soc., 2011,
T. Uenaka, A. Yamaguchi, K. Tsukahara, T. Nagasu,
N. Koyanagi, K. Kitoh, K. Yoshimatsu, H. Yoshino and
H. Sugumi, Chem. Pharm. Bull., 2004, 52, 1071.
8418 | Org. Biomol. Chem., 2013, 11, 8410–8418
This journal is © The Royal Society of Chemistry 2013