Synthesis of Pyrrolo[3,2- B ]carbazole derivatives via palladium-catalyzed C-H activation

Article abstract of DOI:10.1055/s-0033-1338597

A simple method for the synthesis of different pyrrolo[3,2-b]carbazole derivatives by the reaction of 3-(acetylamino)carbazoles with various symmetrical diaryl-substituted alkynes via palladium-catalyzed C-H activation is reported. Georg Thieme Verlag Stuttgart.New York.

Full text of DOI:10.1055/s-0033-1338597

PAPER
▌1211
paper
Synthesis of Pyrrolo[3,2-b]carbazole Derivatives via Palladium-Catalyzed
C–H Activation
Synthesis of Pyrrolo[3,2-b]carbazoles
Rama Raju Jella, Rajagopal Nagarajan*
School of Chemistry, University of Hyderabad, Hyderabad 500046, India
Fax +91(40)23012460; E-mail: rnsc@uohyd.ernet.in
Received: 12.12.2013; Accepted after revision: 22.01.2014
the synthesis of different pyrrolo[3,2-b]carbazole deriva-
tives in a regioselective manner via palladium-catalyzed
C–H activation.
Abstract: A simple method for the synthesis of different pyrro-
lo[3,2-b]carbazole derivatives by the reaction of 3-(acetylami-
no)carbazoles with various symmetrical diaryl-substituted alkynes
via palladium-catalyzed C–H activation is reported.
We started with the reaction of 3-(acetylami-
Key words: 3-aminocarbazoles, palladium catalysis, pyrrolo[3,2- no)carbazole10 1a and diphenylacetylene (2a) (Table 1)
b]carbazoles, C–H activation, diarylacetylenes
with 10 mol% of Pd(OAc)2 using Cu(OAc)2 as oxidant,
and we obtained the product as a single regioisomer, but
in trace yield (Table 1, entry 2). When CuCl2 was used as
oxidant, the yield was significantly improved, but a com-
plex mixture of byproducts was observed (Table 1, entries
3 and 4). Meanwhile, when we used Cu(OTf)2 as oxidant,
the product 3a was obtained without any byproducts, but
in low yield. We continued optimization by using differ-
ent additives (Ag2CO3, AgOAc, Ag2O) and found that
Ag2O gave a moderate yield when used as additive (Table
1, entries 5–9). We also screened different palladium
sources [Pd(OAc)2, PdCl2, Pd(PPh3)2Cl2]; Pd(OAc)2 was
found to be the best catalyst (Table 1, entries 6, 10 and
11). N,N-Dimethylacetamide (DMA) proved to be the
best solvent, based on a better solubility of the starting
materials. Finally, the best optimized conditions were as
follows: 3-(acetylamino)carbazole (1.0 equiv), alkyne
(1.5 equiv), Pd(OAc)2 (10 mol%), Cu(OTf)2 (1 equiv) and
Ag2O (1 equiv) in DMA at 120 °C under N2 (Table 1, en-
try 6).
The synthesis of different heteroaryl-condensed carba-
zoles has emerged as a major research area due to the
promising biological properties of such compounds.1,2
Their derivatives also show promising electronic and op-
tical properties.3 The pyrrolocarbazole skeleton, with a
pyrrole ring fused to a carbazole, frequently occurs in ma-
rine alkaloids4 such as the dictyodendrins A–E (Figure 1).
These compounds have a broad spectrum of bioactivities
including anticancer, antidiabetic, neurotrophic and pro-
tein kinase C (PKC) inhibitory properties.5 Pyrrolo[3,2-
b]carbazoles exhibit high antitumour activity with low
toxicity against normal cell lines.6a In the literature, the
synthesis of pyrrolo[3,2-b]carbazoles has been less ex-
plored than other pyrrolocarbazole analogues.6b–e
In recent years, direct C–H bond activation by using dif-
ferent transition-metal catalysts has attracted significant
interest because these methods eliminate the multistep
preparation of preactivated starting materials.7,8 The pal-
ladium-catalyzed direct functionalization of C–H bonds
via the C–H activation pathway represents an important
and atom-economic strategy to prepare complex struc-
tures.9 The transition-metal-catalyzed direct C–H bond
activation of N-aryl amides coupled with alkynes has at-
tracted much attention due to its sustainable and environ-
mentally benign features.7 In this paper, we wish to report
With these optimized conditions, we examined the scope
of the reaction by taking different N9-substituted and 6-
substituted 3-aminocarbazoles 1 (Table 2). A variety of
internal alkynes 2 having electron-donating or electron-
withdrawing groups were also employed in this reaction.
The reaction went smoothly with the 6-methyl-substituted
3-aminocarbazole 1 (R1 = Et, R2 = Me), and gave the
product 3f in 70% yield, while the 6-bromo-substituted 3-
HO
MeO2C
HO
O
OH
OR
OH
N
N
OH
N
OH
N
H
O
NaO3SO
H
OH
NaO3SO
dictyodendrin C (R = H)
dictyodendrin D (R = SO3Na)
dictyodendrin A
Figure 1 Naturally occurring pyrrolocarbazole alkaloids
SYNTHESIS 2014, 46, 1211–1216
Advanced online publication: 05.03.2014
0
0
3
9
-
7
8
8
1
1
4
3
7
-
2
1
0
X
DOI: 10.1055/s-0033-1338597; Art ID: SS-2013-Z0808-OP
© Georg Thieme Verlag Stuttgart · New York

1212
R. R. Jella, R. Nagarajan
PAPER
Table 1 Optimization of the Reaction Conditions for the Synthesis
of Pyrrolo[3,2-b]carbazole 3aa
Table 2 Synthesis of Various Pyrrolo[3,2-b]carbazole Derivatives 3
Ac
R2
R2
R3
N
NHAc
Ac
Pd(OAc)2 (10 mol%)
Cu(OTf)2 (1 equiv)
R3
NHAc
Ph
N
Pd catalyst
oxidant
Ph
R3
Ag2O (1 equiv), DMA
120 °C, 12–16 h
N
R1
N
R1
R3
additive, DMA
120 °C, 12 h
Ph
N
N
Ph
Et
Et
1
2
3a–m
1a
2a
3a
3
R1
R2
R3
Time (h) Yield (%)
Entry Catalyst
(10 mol%)
Oxidant
(equiv)
Additive
(equiv)
Yieldb
(%) of 3a
3a
3b
3c
3d
3e
3f
Et
H
H
H
H
Br
Ph
12
12
12
12
16
12
12
12
14
12
12
14
12
64
62
64
58
54
70
68
68
52
66
72
58
68
Me
n-Bu
Bn
Et
Ph
1
2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
PdCl2
air
–
–
–
–
Ph
Cu(OAc)2 (2.0)
CuCl2 (2.0)
CuCl2 (2.0)
Cu(OTf)2 (2.0)
trace
30
Ph
3
Ph
4
Ag2CO3 (1.0) 24
Et
Me
H
Ph
5
–
35
64
3g
3h
3i
Et
4-MeC6H4
4-MeOC6H4
4-ClC6H4
3,5-Me2C6H3
4-MeOC6H4
4-MeOC6H4
4-MeOC6H4
6
Cu(OTf)2 (1.0) Ag2O (1.0)
Et
H
7
Cu(OTf)2 (1.0) Ag2CO3 (1.0) 20
Cu(OTf)2 (1.0) AgOAc (1.0) 12
Et
H
8
3j
Et
H
9
Cu(OTf)2 (0.5) Ag2O (1.0)
Cu(OTf)2 (1.0) Ag2O (1.0)
30
25
10
3k
3l
Et
Me
Cl
H
10
11
Et
Pd(PPh3)2Cl2 Cu(OTf)2 (1.0) Ag2O (1.0)
a Reaction conditions: 1a (0.4 mmol), 2a (0.6 mmol), Pd catalyst (10
mol%), DMA (3.0 mL), 120 °C, under N2.
b Isolated yield.
3m
n-Hex
ended up with inseparable mixtures of products in low
yields.
aminocarbazole 1 (R1 = Et, R2 = Br) gave the product 3e
in 54% yield. The diarylacetylenes bearing electron-
donating groups gave better yields than the alkynes with
electron-withdrawing groups. We also investigated the re-
action with unsymmetrically disubstituted alkynes, but
The structures of products 3a, 3e and 3i were further con-
firmed by single crystal X-ray analysis,11 as shown in Fig-
ure 2.
Based on the literature,9f the mechanism for the palladi-
um-catalyzed C–H activation reaction involves a six-
membered palladacycle generated by the acetylamino
group, that gives a vinylic palladium(II) intermediate by
the insertion of alkyne 2 (Scheme 1). Intramolecular am-
ide attack and subsequent deprotonation gives a palladium
amide intermediate, which on reductive elimination af-
fords the corresponding pyrrolocarbazole product 3.
Cu(OTf)2 and Ag2O are utilized for the reoxidation of the
palladium(0) complex to the palladium(II) species in the
reaction.
In summary, we have developed a simple method with
easily prepared starting materials for the synthesis of dif-
ferent pyrrolo[3,2-b]carbazoles in moderate to good
yields via palladium-catalyzed C–H activation. The reac-
tion occurs regioselectively giving exclusively one regio-
isomer. The reaction works well with various symmetrical
diaryl-substituted alkynes bearing electron-donating or
electron-withdrawing substituents.
Figure 2 X-ray crystal structures of 3a, 3e and 3i
Synthesis 2014, 46, 1211–1216
© Georg Thieme Verlag Stuttgart · New York

PAPER
Synthesis of Pyrrolo[3,2-b]carbazoles
1213
13C NMR (100 MHz, CDCl3): δ = 171.4, 141.1, 138.1, 135.9, 133.6,
133.3, 131.8, 130.8, 130.2, 129.0, 128.5, 128.3, 126.9, 125.7, 123.9,
123.6, 122.5, 120.6, 118.5, 108.1, 108.0, 97.1, 37.5, 28.1, 13.5.
H
O
N
N
R2
O
R2
R3
oxidation
MS (ESI, +): m/z = 429 [M + H]+.
Pd(OAc)2
N
R1
1
Anal. Calcd for C30H24N2O: C, 84.08; H, 5.65; N, 6.54. Found: C,
84.22; H, 5.58; N, 6.65.
R3
N
R1
C–H activation
3
Pd(0)
1-(5-Methyl-2,3-diphenyl-1,5-dihydropyrrolo[3,2-b]carbazol-1-
yl)ethanone (3b)
AcOH
H
N
O
N
Colorless solid; yield: 0.102 g (62%); mp 130–132 °C.
R2
R2
IR (KBr): 3379, 3055, 2928, 1682, 1599, 1422, 1365, 1298, 1091,
802, 744 cm–1.
1H NMR (400 MHz, CDCl3): δ = 9.30 (s, 1 H), 8.27 (d, J = 7.6 Hz,
O
Pd
Pd
2
R3
AcO
N
R1
N
R1
R3
1 H), 7.53–7.19 (m, 14 H), 3.84 (s, 3 H), 2.08 (s, 3 H).
R3
13C NMR (100 MHz, CDCl3): δ = 171.4, 142.2, 139.3, 135.8, 133.5,
133.3, 131.8, 130.8, 130.2, 129.1, 128.5, 128.3, 126.9, 125.7, 123.9,
123.4, 122.3, 120.5, 118.5, 108.1, 107.9, 97.2, 29.2, 28.1.
O
R2
OAc
alkyne
insertion
AcOH
NH
Pd
R3
intramolecular
N-attack
R3
MS (ESI, +): m/z = 415 [M + H]+.
2
N
R1
R3
Anal. Calcd for C29H22N2O: C, 84.03; H, 5.35; N, 6.76. Found: C,
84.12; H, 5.32; N, 6.81.
Scheme 1 Proposed mechanism for palladium-catalyzed C–H acti-
vation
1-(5-Butyl-2,3-diphenyl-1,5-dihydropyrrolo[3,2-b]carbazol-1-
yl)ethanone (3c)
Brown solid; yield: 0.117 g (64%); mp 194–196 °C.
Unless otherwise stated, all commercial reagents were used without
further purification. All solvents were dried and distilled according
to standard procedures. The 1H NMR and 13C NMR spectra were re-
corded at 400 MHz and 100 MHz, respectively, on a Bruker AV-
400 instrument. The chemical shifts are reported in ppm downfield
to TMS (δ = 0) for 1H NMR data and relative to the central CDCl3
resonance (δ = 77.0) for 13C NMR data. The coupling constants J
are given in Hz. IR spectra were recorded on a JASCO FT/IR-5300
spectrophotometer by using KBr pellets. Mass spectra were record-
ed on either a VG7070H mass spectrometer using EI techniques or
a Shimadzu LCMS-2010 A mass spectrometer. The X-ray diffrac-
tion measurements were carried out at 298 K on an automated En-
raf-Nonius MACH 3 diffractometer using graphite monochromated
Mo Kα (λ = 0.71073 Å) radiation with CAD4 software or the X-ray
intensity data were measured at 298 K on a Bruker SMART APEX
CCD area detector system equipped with a graphite monochromator
and a Mo Kα fine-focus sealed tube (λ = 0.71073 Å). For thin-layer
chromatography (TLC), silica gel plates (Merck 60 F254) were
used. Column chromatography was performed on silica gel (100–
200 mesh) in glass columns for compound purification. Melting
points were measured in open capillary tubes and are uncorrected.
IR (KBr): 3387, 3055, 2953, 2860, 1691, 1602, 1466, 1394, 1296,
1126, 879 cm–1.
1H NMR (400 MHz, CDCl3): δ = 9.29 (s, 1 H), 8.26 (d, J = 7.6 Hz,
1 H), 7.51–7.47 (m, 1 H), 7.40–7.33 (m, 12 H), 7.28–7.24 (m, 1 H),
4.30 (t, J = 6.8 Hz, 2 H), 2.06 (s, 3 H), 1.85 (t, J = 7.4 Hz, 2 H),
1.41–1.35 (m, 2 H), 0.93 (t, J = 7.2 Hz, 3 H).
13C NMR (100 MHz, CDCl3): δ = 171.4, 141.6, 138.7, 135.9, 133.6,
133.3, 131.7, 130.8, 130.2, 129.0, 128.5, 128.3, 126.9, 125.6, 123.8,
123.5, 122.4, 120.5, 118.4, 108.4, 107.9, 97.3, 42.8, 30.9, 28.0,
20.5, 13.9.
MS (ESI, +): m/z = 456 [M]+.
Anal. Calcd for C32H28N2O: C, 84.18; H, 6.18; N, 6.14. Found: C,
83.75; H, 6.51; N, 6.23.
1-(5-Benzyl-2,3-diphenyl-1,5-dihydropyrrolo[3,2-b]carbazol-1-
yl)ethanone (3d)
Colorless solid; yield: 0.114 g (58%); mp 210–212 °C.
IR (KBr): 3414, 2922, 1684, 1601, 1437, 1369, 1178, 1024, 958,
877 cm–1.
1H NMR (400 MHz, CDCl3): δ = 9.31 (s, 1 H), 8.28 (d, J = 7.2 Hz,
1 H), 7.43–7.38 (m, 6 H), 7.32–7.13 (m, 13 H), 5.51 (s, 2 H), 2.05
(s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 171.4, 141.7, 138.9, 137.2, 135.9,
133.3, 133.2, 132.0, 130.8, 130.1, 129.1, 128.7, 128.5, 128.3, 127.3,
126.9, 126.4, 125.9, 123.79, 123.73, 122.5, 120.6, 119.0, 108.7,
108.0, 97.7, 46.6, 28.0.
Palladium-Catalyzed Synthesis of Pyrrolo[3,2-b]carbazoles 3;
General Procedure
To a Schlenk tube, a 3-(acetylamino)carbazole 1 (0.4 mmol), a di-
arylacetylene 2 (0.6 mmol), Pd(OAc)2 (10 mol%), Ag2O (1.0
equiv), Cu(OTf)2 (1.0 equiv) and DMA (3.0 mL) were added suc-
cessively under N2. The mixture was stirred at r.t. for a few min.
Then, the tube was placed in a preheated (120 °C) oil bath, and
stirred. After completion of the reaction (TLC monitoring), the so-
lution was cooled to r.t., diluted with EtOAc (30 mL), washed with
H2O (10 mL), dried over anhydrous Na2SO4, filtered and concen-
trated under reduced pressure. The residue was purified by column
chromatography (hexanes–EtOAc, 8.5:1.5) to afford the product 3.
MS (ESI, –): m/z = 490 [M]–.
Anal. Calcd for C35H26N2O: C, 85.69; H, 5.34; N, 5.71. Found: C,
85.51; H, 5.41; N, 5.65.
1-(8-Bromo-5-ethyl-2,3-diphenyl-1,5-dihydropyrrolo[3,2-
b]carbazol-1-yl)ethanone (3e)
Yellow solid; yield: 0.109 g (54%); mp 202–204 °C.
1-(5-Ethyl-2,3-diphenyl-1,5-dihydropyrrolo[3,2-b]carbazol-1-
yl)ethanone (3a)
Brown solid; yield: 0.110 g (64%); mp 162–164 °C.
IR (KBr): 3057, 2974, 1685, 1458, 1392, 1302, 1186, 1109, 964,
860 cm–1.
1H NMR (400 MHz, CDCl3): δ = 9.24 (s, 1 H), 8.36 (d, J = 1.6 Hz,
1 H), 7.57–7.55 (m, 1 H), 7.39–7.37 (m, 8 H), 7.34–7.25 (m, 4 H),
4.33 (q, J = 7.2 Hz, 2 H), 2.06 (s, 3 H), 1.40 (t, J = 7.2 Hz, 3 H).
IR (KBr): 2964, 1689, 1601, 1473, 1439, 1394, 1300, 1261, 1099,
800, 744 cm–1.
1H NMR (400 MHz, CDCl3): δ = 9.29 (s, 1 H), 8.26 (d, J = 8.0 Hz,
1 H), 7.51–7.47 (m, 1 H), 7.41–7.32 (m, 12 H), 7.28–7.24 (m, 1 H),
4.35 (q, J = 7.2 Hz, 2 H), 2.06 (s, 3 H), 1.40 (t, J = 7.2 Hz, 3 H).
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2014, 46, 1211–1216

1214
R. R. Jella, R. Nagarajan
PAPER
13C NMR (100 MHz, CDCl3): δ = 171.3, 139.7, 138.3, 136.4, 133.4,
133.1, 131.9, 130.7, 130.2, 129.7, 128.6, 128.5, 128.4, 128.2, 127.0,
125.4, 123.7, 123.3, 121.3, 111.2, 109.5, 108.2, 97.3, 37.7, 28.0,
13.4.
7.24–7.22 (m, 3 H), 4.35 (q, J = 7.2 Hz, 2 H), 2.10 (s, 3 H), 1.40 (t,
J = 7.2 Hz, 3 H).
13C NMR (100 MHz, CDCl3): δ = 170.9, 141.2, 138.1, 134.8, 134.6,
133.1, 131.9, 131.4, 129.0, 128.8, 128.6, 125.9, 123.4, 123.2, 122.8,
120.7, 118.6, 108.2, 108.0, 96.8, 37.5, 28.2, 13.5.
MS (ESI, –): m/z = 506 [M]–.
Anal. Calcd for C30H23BrN2O: C, 71.01; H, 4.57; N, 5.52. Found: C,
71.12; H, 4.52; N, 5.61.
MS (ESI, +): m/z = 498 [M + 2 H]+.
Anal. Calcd for C30H22Cl2N2O: C, 72.44; H, 4.46; N, 5.63. Found:
C, 72.59; H, 4.42; N, 5.71.
1-(5-Ethyl-8-methyl-2,3-diphenyl-1,5-dihydropyrrolo[3,2-
b]carbazol-1-yl)ethanone (3f)
Brown solid; yield: 0.124 g (70%); mp 104–106 °C.
1-(2,3-Bis(3,5-dimethylphenyl)-5-ethyl-1,5-dihydropyrrolo[3,2-
b]carbazol-1-yl)ethanone (3j)
Brown solid; yield: 0.128 mg (66%); mp 106–108 °C.
IR (KBr): 3443, 3055, 2922, 2854, 1682, 1483, 1367, 752, 698
cm–1.
1H NMR (400 MHz, CDCl3): δ = 9.25 (s, 1 H), 8.07 (s, 1 H), 7.38–
7.28 (m, 13 H), 4.33 (q, J = 7.2 Hz, 2 H), 2.58 (s, 3 H), 2.06 (s, 3 H),
1.38 (t, J = 7.2 Hz, 3 H).
13C NMR (100 MHz, CDCl3): δ = 171.3, 139.4, 138.4, 135.8, 133.6,
133.3, 131.6, 130.8, 130.2, 128.9, 128.5, 128.3, 127.8, 126.9, 123.9,
123.7, 122.4, 120.7, 107.9, 107.8, 97.0, 37.5, 28.1, 21.4, 13.5.
IR (KBr): 3449, 2918, 1693, 1601, 1466, 1442, 1304, 1157, 1033,
848, 742 cm–1.
1H NMR (400 MHz, CDCl3): δ = 9.27 (s, 1 H), 8.25 (d, J = 7.6 Hz,
1 H), 7.50–7.46 (m, 1 H), 7.40–7.39 (m, 2 H), 7.27–7.23 (m, 1 H),
7.01–6.96 (m, 6 H), 4.36 (q, J = 7.2 Hz, 2 H), 2.31–2.30 (m, 12 H),
2.07 (s, 3 H), 1.40 (t, J = 7.2 Hz, 3 H).
13C NMR (100 MHz, CDCl3): δ = 171.7, 141.1, 138.1, 137.8, 137.5,
136.2, 133.4, 133.1, 131.7, 130.0, 129.3, 128.5, 128.0, 125.5, 123.7,
122.3, 120.6, 118.4, 108.1, 107.9, 97.2, 37.5, 28.0, 21.4, 21.2, 13.5.
MS (ESI, –): m/z = 441 [M – H].
Anal. Calcd for C31H26N2O: C, 84.13; H, 5.92; N, 6.33. Found: C,
84.31; H, 5.85; N, 6.29.
MS (ESI, +): m/z = 485 [M + H]+.
Anal. Calcd for C34H32N2O: C, 84.26; H, 6.66; N, 5.78. Found: C,
84.15; H, 6.62; N, 5.71.
1-(5-Ethyl-2,3-di-p-tolyl-1,5-dihydropyrrolo[3,2-b]carbazol-1-
yl)ethanone (3g)
Brown solid; yield: 0.124 g (68%); mp 220–222 °C.
1-(5-Ethyl-2,3-bis(4-methoxyphenyl)-8-methyl-1,5-dihydropyr-
rolo[3,2-b]carbazol-1-yl)ethanone (3k)
Brown solid; yield: 0.144 g (72%); mp 212–214 °C.
IR (KBr): 3412, 3028, 2974, 1687, 1602, 1469, 1394, 1302, 1184,
1018, 962, 881 cm–1.
1H NMR (400 MHz, CDCl3): δ = 9.28 (s, 1 H), 8.26 (d, J = 7.6 Hz,
1 H), 7.49 (t, J = 7.6 Hz, 1 H), 7.39 (d, J = 5.2 Hz, 2 H), 7.28–7.23
(m, 5 H), 7.19 (d, J = 8.0 Hz, 4 H), 4.35 (q, J = 7.2 Hz, 2 H), 2.40
(s, 6 H), 2.06 (s, 3 H), 1.40 (t, J = 7.2 Hz, 3 H).
13C NMR (100 MHz, CDCl3): δ = 171.5, 141.1, 138.4, 138.1, 136.4,
135.9, 131.7, 130.6, 130.4, 130.0, 129.2, 129.1, 125.5, 123.6, 123.5,
122.3, 120.6, 118.4, 108.1, 108.0, 97.1, 37.5, 28.0, 21.4, 21.3, 13.5.
IR (KBr): 3412, 2932, 1685, 1610, 1493, 1392, 1367, 1298, 1246,
1174, 1032, 962, 877 cm–1.
1H NMR (400 MHz, CDCl3): δ = 9.23 (s, 1 H), 8.05 (s, 1 H), 7.33–
7.24 (m, 7 H), 6.93–6.89 (m, 4 H), 4.32 (q, J = 7.2 Hz, 2 H), 3.84 (s,
6 H), 2.57 (s, 3 H), 2.06 (s, 3 H), 1.37 (t, J = 7.2 Hz, 3 H).
13C NMR (100 MHz, CDCl3): δ = 171.4, 159.6, 158.4, 139.3, 138.3,
135.5, 133.0, 132.0, 131.5, 131.2, 129.2, 127.7, 126.8, 125.9, 125.6,
123.8, 123.2, 122.1, 120.6, 114.0, 113.8, 108.0, 107.8, 96.9, 55.26,
55.20, 37.5, 28.0, 21.4, 13.5.
MS (ESI, +): m/z = 457 [M + H]+.
Anal. Calcd for C32H28N2O: C, 84.18; H, 6.18; N, 6.14. Found: C,
84.07; H, 6.09; N, 6.19.
MS (ESI, +): m/z = 503 [M + H]+.
Anal. Calcd for C33H30N2O3: C, 78.86; H, 6.02; N, 5.57. Found: C,
78.69; H, 6.12; N, 5.65.
1-(5-Ethyl-2,3-bis(4-methoxyphenyl)-1,5-dihydropyrrolo[3,2-
b]carbazol-1-yl)ethanone (3h)
Brown solid; yield: 0.133 g (68%); mp 232–234 °C.
1-(8-Chloro-5-ethyl-2,3-bis(4-methoxyphenyl)-1,5-dihydropyr-
rolo[3,2-b]carbazol-1-yl)ethanone (3l)
Brown solid; yield: 0.121 g (58%); mp 196–198 °C.
IR (KBr): 3449, 2976, 2841, 1682, 1602, 1396, 1365, 1244, 1126,
1024, 962, 875 cm–1.
1H NMR (400 MHz, CDCl3): δ = 9.28 (s, 1 H), 8.25 (d, J = 7.6 Hz,
1 H), 7.50–7.46 (m, 1 H), 7.40–7.36 (m, 2 H), 7.30–7.25 (m, 5 H),
6.93–6.90 (m, 4 H), 4.35 (q, J = 7.2 Hz, 2 H), 3.85 (s, 6 H), 2.07 (s,
3 H), 1.40 (t, J = 7.2 Hz, 3 H).
13C NMR (100 MHz, CDCl3): δ = 171.4, 159.6, 158.4, 141.0, 138.1,
135.6, 132.0, 131.6, 131.2, 129.3, 125.9, 125.5, 123.6, 123.2, 122.3,
120.6, 118.4, 114.0, 113.8, 108.1, 97.0, 55.2, 55.0, 37.5, 28.0, 13.5.
IR (KBr): 3414, 2932, 1685, 1610, 1458, 1392, 1298 cm–1.
1H NMR (400 MHz, CDCl3): δ = 9.21 (s, 1 H), 8.18 (s, 1 H), 7.42–
7.23 (m, 7 H), 6.92–6.90 (m, 4 H), 4.31 (q, J = 7.2 Hz, 2 H), 3.84 (s,
6 H), 2.06 (s, 3 H), 1.38 (t, J = 7.2 Hz, 3 H).
13C NMR (100 MHz, CDCl3): δ = 171.3, 159.7, 158.5, 139.3, 138.5,
136.1, 131.9, 131.2, 130.0, 128.1, 125.7, 125.4, 124.8, 123.9, 121.2,
120.2, 114.0, 113.9, 109.0, 108.2, 97.2, 55.27, 55.20, 37.7, 28.0,
13.5.
MS (ESI, +): m/z = 489 [M + H]+.
Anal. Calcd for C32H28N2O3: C, 78.67; H, 5.78; N, 5.73. Found: C,
78.56; H, 5.71; N, 5.66.
MS (ESI, +): m/z = 524 [M + 2 H]+.
Anal. Calcd for C32H27ClN2O3: C, 73.49; H, 5.20; N, 5.36. Found:
C, 73.32; H, 5.31; N, 5.15.
1-(2,3-Bis(4-chlorophenyl)-5-ethyl-1,5-dihydropyrrolo[3,2-
b]carbazol-1-yl)ethanone (3i)
Brown solid; yield: 0.104 g (52%); mp 202–204 °C.
1-(5-Hexyl-2,3-bis(4-methoxyphenyl)-1,5-dihydropyrrolo[3,2-
b]carbazol-1-yl)ethanone (3m)
Brown solid; yield: 0.148 g (68%); mp 204–206 °C.
IR (KBr): 3437, 3055, 1682, 1604, 1477, 1392, 1128, 1086, 1012,
875, 821 cm–1.
1H NMR (400 MHz, CDCl3): δ = 9.23 (s, 1 H), 8.24 (d, J = 7.6 Hz,
IR (KBr): 3441, 2928, 1691, 1604, 1583, 1439, 1363, 1244, 1174,
1026, 962, 829 cm–1.
1 H), 7.52–7.48 (m, 1 H), 7.44–7.36 (m, 5 H), 7.31–7.28 (m, 3 H),
1H NMR (400 MHz, CDCl3): δ = 9.28 (s, 1 H), 8.25 (d, J = 7.6 Hz,
1 H), 7.48 (t, J = 7.6 Hz, 1 H), 7.41–7.38 (m, 2 H), 7.32–7.26 (m, 5
Synthesis 2014, 46, 1211–1216
© Georg Thieme Verlag Stuttgart · New York

PAPER
Synthesis of Pyrrolo[3,2-b]carbazoles
1215
H), 6.94–6.92 (m, 4 H), 4.29 (t, J = 7.0 Hz, 2 H), 3.86 (s, 6 H), 2.08
(s, 3 H), 1.90–1.83 (m, 2 H), 1.38–1.30 (m, 6 H), 1.28 (t, J = 6.8 Hz,
3 H).
13C NMR (100 MHz, CDCl3): δ = 171.4, 159.6, 158.4, 141.5, 138.6,
135.6, 132.0, 131.6, 131.2, 129.3, 125.9, 125.5, 123.5, 123.2, 122.1,
120.5, 118.4, 114.0, 113.8, 108.3, 108.0, 97.2, 55.27, 55.20, 43.0,
31.5, 28.6, 28.0, 26.9, 22.5, 14.0.
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Filippakopoulos, P.; Bullock, A. N.; Bain, J.; Cohen, P.;
Prudhomme, M.; Anizon, F.; Moreau, P. J. Med. Chem.
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Angeles, T. S.; Gessner, G. W.; Mallamo, J. P. J. Med.
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Delfourne, E. Mar. Drugs 2009, 7, 754. (d) Palmer, B. D.;
Thompson, A. M.; Booth, R. J.; Dobrusin, E. M.; Kraker, A.
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MS (ESI, +): m/z = 543 [M – H]–.
Anal. Calcd for C36H36N2O3: C, 79.38; H, 6.66; N, 5.14. Found: C,
79.18; H, 6.61; N, 5.21.
Acknowledgment
We gratefully acknowledge DST for financial assistance (project
number: SR/S1/OC-70/2008) and for providing a single-crystal X-
ray diffractometer facility to our school. R.R.J. thanks CSIR for a
Senior Research Fellowship.
Supporting Information for this article is available online at
http://www.thieme-connect.com/ejournals/toc/synthesis.SnuIomprifgtooatrinSugpIoi
nnfomartit
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© Georg Thieme Verlag Stuttgart · New York
Synthesis 2014, 46, 1211–1216

1216
R. R. Jella, R. Nagarajan
PAPER
C30H24N2O; unit cell parameters: a = 10.2471(14) Å,
b = 11.6921(11) Å, c = 19.105(3) Å, β = 99.605(11)°, space
group P21/c. Compound 3e: C30H23BrN2O; unit cell
parameters: a = 6.6599(13) Å, b = 19.948(4) Å,
c = 17.974(3) Å, β = 98.107(18)°, space group P21/n.
Compound 3i: C30H22Cl2N2O; unit cell parameters:
a = 8.3466(18) Å, b = 33.171(5) Å, c = 10.746(3) Å,
β = 126.096(16)°, space group P21/c.
(11) The crystal data for compounds 3a, 3e and 3i have been
deposited with the Cambridge Crystallographic Data Centre
as supplementary publication nos. CCDC 892569 (3a),
892570 (3e) and 892571 (3i). Copies of the data can be
obtained free of charge on application to CCDC, 12 Union
Road, Cambridge CB2 1EZ, UK [Fax: +44(1223)336033;
E-mail: deposit@ccdc.cam.ac.uk] or via
www.ccdc.cam.ac.uk/data_request/cif. Compound 3a:
Synthesis 2014, 46, 1211–1216
© Georg Thieme Verlag Stuttgart · New York