Synthesis of functionalized ellipticinium and ellipticine derivatives via electrophilic cyclization

Article abstract of DOI:10.1039/c1ob05258f

An efficient methodology for the synthesis of highly functionalized ellipticinium and ellipticine derivatives starting from the corresponding 2-bromocarbazoles via an AgOTf or CuI catalyzed electrophilic cyclization of 2-alkynyl-3-carbazolylaldimines is reported.

Full text of DOI:10.1039/c1ob05258f

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PAPER
Synthesis of functionalized ellipticinium and ellipticine derivatives via
electrophilic cyclization†
T. Krishna Chaitanya and Rajagopal Nagarajan*
Received 17th February 2011, Accepted 22nd March 2011
DOI: 10.1039/c1ob05258f
An efficient methodology for the synthesis of highly functionalized ellipticinium and ellipticine
derivatives starting from the corresponding 2-bromocarbazoles via an AgOTf or CuI catalyzed
electrophilic cyclization of 2-alkynyl-3-carbazolylaldimines is reported.
reports available in the literature on the synthesis of these diverse
and functionalized ellipticinium and ellipticine derivatives. In this
context, the development of a useful methodology for the synthesis
of various functionalized ellipticinium and ellipticine derivatives is
Introduction
Ellipticine, 5,11-dimethyl-6H-pyrido[4,3-b]carbazole, was first
isolated in 1959 by Goodwin et al.1 The first total synthesis
was reported by Woodward and co-workers in the same year.2
important. In continuation of our research in the development of
efficient methodologies for the synthesis of heteroarylcarbazoles,8
we started working on the development of a simple and facile
methodology for the synthesis of ellipticine derivatives.
Ellipticine and its derivatives gained considerable attention from
1967 onwards due to their potential antitumour activity.3 The
antitumour properties of ellipticine derivatives are considered to
be mainly due to their binding with DNA and/or the inhibition of
enzyme topoisomerase II.4 The synthetic and biological profiles
of ellipticines have been extensively reviewed in the literature.5
Ellipticine and its derivatives have drawn tremendous attention
from synthetic chemists, and many syntheses of ellipticine and
its derivatives have been reported.6 Some of them, such as
elliptinium (ellipticinium acetate), datelliptium, retellipticine (BD-
84), pazellipticine, etc. (Fig. 1), were also tested for clinical
use.7 Elliptinium has been used in the treatment of advanced
myeloblastic leukemia.
Recently, there has been immense synthetic interest in the
application of 2-alkynyl arylaldehydes towards the synthesis
of isoquinolines, benzofurans, benzopyrans, benzimidazoles and
their derivatives by employing various catalysts, including metal
salts of Pd, Ag(I) and Cu(I), iodine, etc.9,10 2-Alkynyl arylaldehydes,
on reacting with amines in the presence of various Lewis acidic
metal salts, undergo a facile electrophilic cyclization to furnish
isoquinolines and their derivatives in excellent yields.9,10 We
envisaged that 2-alkynyl-3-formylcarbazoles would be excellent
precursors for the synthesis of ellipticine derivatives. These 2-
alkynyl-3-formylcarbazoles, on reacting with various amines, can
be successfully converted into their corresponding ellipticine
derivatives efficiently. Furthermore, this methodology can be of
broad scope in terms of functionalizing the basic ellipticine motif
at more positions and so is significant in the synthesis of further
derivatives of ellipticines and ellipticiniums.
Results and discussion
As outlined in Scheme 1, these precursor molecules can be
prepared from their corresponding 2-bromoformyl carbazoles,
which can be further obtained from their corresponding 2-
bromocarbazoles.
The syntheses of 2-bromo-9-ethylcarbazoles 8a and 8b are
depicted in Scheme 2. Arylboronic acids 4a and 4b, subjected
to Suzuki coupling with 4-bromo-2-nitroiodobenzene 5 in the
presence of palladium acetate and PPh3, provided 4-bromo-2-
nitrobiaryls 6a and 6b in excellent yields. 6a and 6b were subjected
to reductive cyclization using triethylphosphite under reflux to give
the corresponding bromocarbazoles 7a and 7b, which, upon N-
alkylation using ethyl bromide and potassium hydroxide as base
Fig. 1 Ellipticinium derivatives.
In most cases, these compounds were derivatized directly
from ellipticine, leaving limited scope to prepare more diverse
candidates for clinical trials. Furthermore, there are very few
School of Chemistry, University of Hyderabad, Hyderabad 500046, India.
E-mail: rnsc@uohyd.ernet.in; Fax: +91 40-23012460
† Electronic supplementary information (ESI) available: 1H, 13C, LC-MS
and elemental analysis spectra of all compounds. CCDC 804670. For ESI
and crystallographic data in CIF or other electronic format see DOI:
10.1039/c1ob05258f
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Scheme 1 Outline of the synthetic plan.
Scheme 4 Synthesis of precursor 1c.
2-bromo-6,8-dimethyl-3-formyl derivative 13 in 40% yield, along
with the 7-formyl derivative in 20% yield. As expected, when N-
methylformanilide was employed as the formylating agent instead
of DMF, exclusively 13 was obtained in 80% yield. Because of the
bulkiness of the Vilsmeier salt formed from N-methylformanilide,
the formation of the 7-formyl derivative was hindered. 13, on
coupling with phenylacetylene under Sonogashira conditions,
afforded precursor 1c in 87% yield.
The
synthesis
of
precursor
6-tert-butyl-3-formyl-2-
phenylethynylcarbazole (1d) starting from 4-bromo-2,5-
dimethyl-2¢-nitrobiphenyl 14 is outlined in Scheme 5. Biphenyl
14 was prepared by the Suzuki coupling of the 4-bromo-
2,5-dimethylphenylboronic acid with 2-iodonitrobenzene
using Pd(OAc)2 and PPh3. Reductive cyclization of 14 in
triethylphosphite under reflux followed by N-alkylation with ethyl
bromide using potassium hydroxide as the base afforded 2-bromo-
1,4-dimethyl-9-ethylcarbazole (16) in 65% overall yield. Upon
the Friedel–Crafts alkylation of 16 using tert-butyl chloride and
aluminium chloride, 2-bromo-6-tert-butyl-9-ethyl-1,4-dimethyl-
9H-carbazole was obtained regioselectively in 94% yield. The
formation of the other possible 3-tert-butyl regioisomer was not
observed, probably due to the bulkier 2-bromo substituent. The
2-bromo-1,4-dimethyl-3-formyl derivative, 18, was obtained in
75% yield by a Vilsmeier–Haack formylation of the 6-tert-butyl
derivative. A Sonogashira reaction of 18 with phenylacetylene
using Pd(PPh3)2Cl2 afforded precursor 1d in 85% yield.
Scheme 2 Synthesis of bromocarbazoles.
in acetone, provided 2-bromo-9-ethylcarbazoles 8a and 8b in 96%
and 95% yields, respectively.
As shown in Scheme 3, upon the Vilsmeier–Haack formylation
of 8a, the desired 3-formyl regioisomer, 10, was obtained in a
very low yield, whereas 6-formyl derivative 9 was formed as a
major isomer. When we attempted the formylation of 8a using
N-methylformanilide as the formylating agent, 9 was obtained
exclusively. These observations led us to conclude that it may
be due to the bulkiness and deactivating effect of the bromo
group that the 6-formyl product is formed as the major isomer.
A Wolff–Kishner reduction of 6-formyl derivative 9 provided
the 2-bromo-9-ethyl-6-methyl-9H-carbazole in excellent yield. A
Vilsmeier–Haack formylation of the 6-methyl derivative provided
the 2-bromo-3-formyl-6-methyl derivative, 12, in 70% yield. 12,
upon Sonogashira coupling with phenylacetylene employing
bis(triphenylphospine)palladium dichloride, copper(I) iodide and
triethylamine as a base, afforded precursor 1a in 85% yield. By
employing similar conditions, precursor 1b was obtained from 10
in 85% yield.
Scheme 5 Synthesis of precursor 1d.
Then we attempted the electrophilic cyclization of 1a with p-
toluidine by employing AgOTf (Table 1). When the reaction was
carried out in one-pot involving both Schiff base formation and
Scheme 3 Synthesis of precursors 1a and 1b.
˚
cyclization using 4 A molecular sieves in ethanol, the correspond-
The synthesis of precursor molecule 6,8-dimethyl-3-formyl-2-
phenylethynylcarbazole (1c) starting from 2-bromo-6,8-dimethyl-
9-ethylcarbazole (8b) is outlined in Scheme 4. A Vilsmeier–Haack
formylation of 8b using DMF and POCl3 at 70 ◦C for 5 h provided
ing ellipticinium triflate was obtained in 70% yield. But, to our
delight, when we carried out the cyclization of isolated aldimines
by employing AgOTf in dichloromethane, the ellipticinium triflate
was obtained in almost quantitative yield. Precursor molecules
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Table 1 Synthesis of ellipticinium derivatives
Fig. 2 ORTEP diagram of 19. Hydrogen atoms are omitted for clarity.
Scheme 6 Synthesis of ellipticine derivatives.
the tert-butyl group of the amine and the methyl group of the
carbazole.
Conclusion
In conclusion, we have developed a novel and efficient method-
ology for the synthesis of diverse and highly functionalized
ellipticinium and ellipticine derivatives in excellent yields. Many
carbazole intermediates of potential synthetic scope were synthe-
sized for the first time. The scope of this synthetic route is general
and all the products were obtained in excellent yields. The overall
modularity of this process is noteworthy. It is anticipated that this
methodology will be extremely valuable for the development of
selective anti-cancer agents with a pyrido[4,3-b]carbazole skeleton.
Studies towards this end will be the focus of future work in our
laboratory.
1a–1d were subjected to electrophilic cyclization with various
aliphatic and aromatic amines under the optimized conditions to
provide highly functionalized ellipticinium derivatives in excellent
yields. The results are summarized in Table 1. The structures of
compounds 19 and 23 were also determined unambiguously by
X-ray crystallography.11 The ORTEP diagram of 19 is shown
in Fig. 2. It is worth noting that various amines with diverse
functionalities were employed and that all the ellipticiniums were
obtained in excellent yields.
Then we turned our attention towards the synthesis of ellipticine
derivatives from the same precursor molecules. By employing
the optimized conditions, we successfully prepared ellipticine
derivatives in good yields. As described in Scheme 6, 1a, 1b and
1c, on reaction with tert-butyl amine followed by a CuI-induced
cyclization in DMF, provided the corresponding ellipticines 3a,
3b and 3c in 85–90% yields. Precursor 1d failed to form an imine
with tert-butyl amine, probably due to steric hindrance between
Experimental section
General information
1H and 13C NMR spectra were recorded at 400 and 100 MHz,
respectively. Chemical shifts are reported in ppm downfield from
1
TMS (d = 0) for H NMR, and relative to the central CDCl3
resonance (d = 77.0) and DMSO-d6 (d = 39.51) for 13C NMR. The
coupling constants, J, are given in Hz. IR spectra were recorded
on a FT/IR-5300 instrument. X-Ray diffraction measurements
were carried out at 298 K on an automated diffractometer using
˚
graphite-monochromated Mo-Ka (l = 0.71073 A) radiation with
CAD4 software or the X-ray intensity data were measured at
298 K equipped with a graphite monochromator and a Mo-
˚
Ka fine-focus sealed tube (l = 0.71073 A). Melting points were
measured in open capillary tubes and are uncorrected. All reaction
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solvents used are of GR grade and used without drying unless
mentioned. Triethylphosphite, N-methylformanilide, palladium
acetate, Pd(PPh3)2Cl2, silver triflate (AgOTf) and copper(I) io-
dide were used directly as purchased. Phenylacetylene, phospho-
ryl chloride, ethyl bromide, hydrazine hydrate and magnesium
sulfate were purchased from local manufacturers. 4-Bromo-2-
iodonitrobenzene, 3,5-dimethylphenylboronic acid and 4-bromo-
2,5-dimethylphenylboronic acid were prepared according to meth-
ods reported in the literature.12
MHz, CDCl3) d 191.6, 143.6, 141.4, 129.0, 127.5, 123.5, 122.6,
121.9, 121.9, 120.4, 112.3, 108.9, 38.1, 13.8; m/z = 303, positive
mode; anal. calc. for C15H12BrNO: C, 59.62; H, 4.00; N, 4.64%;
found: C, 59.72; H, 4.08; N, 4.55%
2-Bromo-9-ethyl-9H-carbazole-3-carbaldehyde
(10). White
solid; mp: 125–127 ◦C; nmax (KBr)/cm-1: 2974, 2852, 1680, 1589,
1
1469, 1425, 1346, 1317, 1236, 912, 838, 792, 742, 430; H NMR
(400 MHz, CDCl3) d 10.42 (s, 1H), 8.63 (s, 1H), 8.08 (d, J = 7.6
Hz, 1H), 7.52–7.57 (m, 2H), 7.40 (d, J = 8.2 Hz, 1H), 7.32 (t, J =
7.6 Hz, 1H), 4.28 (q, J = 7.6 Hz, 2H), 1.45 (t, J = 7.6 Hz, 3H);
13C NMR (100 MHz, CDCl3) d 191.7, 143.7, 140.8, 127.2, 124.8,
124.1, 122.8, 122.7, 122.5, 121.0, 120.8, 112.7, 109.3, 37.8, 13.8;
m/z = 303, positive mode; anal. calc. for C15H12BrNO: C, 59.62;
H, 4.00; N, 4.64%; found: C, 59.48; H, 4.12; N, 4.71%.
2-Bromo-9-ethyl-9H-carbazole (8a). An oven-dried 250 mL
round-bottomed flask equipped with a Teflon-coated magnetic
stirring bar is charged with 10 g (0.04 M) of 2-bromocarbazole
and 100 mL of acetone under stirring. 6.8 g (0.12 M) of potassium
hydroxide is added and refluxed for 30 min. 5.8 mL (0.08 M)
of ethyl bromide is added slowly and reflux continued for 1 h,
after which time TLC (90 : 10 hexanes : ethyl acetate) indicated
complete conversion. The reaction is allowed to cool to room
temperature and acetone is removed under reduced pressure.
Residue is dissolved in ethyl acetate, washed with 2% dilute
hydrochloric acid, water and brine. The organic layer is dried
over anhydrous sodium sulfate and the solvent is removed under
reduced pressure to give a white solid. The crude material is
used further without purification. Yield: 96% mp: 77–79 ◦C; nmax
(KBr)/cm-1: 3057, 2970, 1591, 1489, 1473, 1448, 1323, 1230, 1153,
2-Bromo-9-ethyl-6-methyl-9H-carbazole (11). An oven-dried
250 mL round-bottomed flask equipped with a Teflon-coated
magnetic stirring bar is charged with 5 g (0.016 M) of 7-bromo-
9-ethyl-9H-carbazole-3-carbaldehyde and 100 mL of ethylene
glycol under stirring. 1.85 g (0.033 M) of potassium hydroxide
and 1.65 mL (0.033 M) of hydrazine hydrate are added under
stirring. The reaction mixture is refluxed at 200 ◦C for 3 h,
after which time TLC (90 : 10 hexanes : ethyl acetate) indicated
complete conversion. The reaction is allowed to cool to room
temperature and quenched with ice. The reaction mass is poured
into crushed ice slowly, neutralized with 2% dilute hydrochloric
acid and extracted with ethyl acetate. The organic layer is washed
with water and brine, dried over anhydrous sodium sulfate and the
solvent is removed under reduced pressure to give the 2-bromo-
9-ethyl-6-methyl-9H-carbazole as a pure white solid in almost
quantitative yield. Yield: 95%. mp: 78–80 ◦C; nmax (KBr)/cm-1:
2974, 2922, 1682, 1628, 1593, 1483, 1442, 1228, 1084, 1060, 842,
798, 592, 416; 1H NMR (400 MHz, CDCl3) d 7.91 (d, J = 8.0 Hz,
1H), 7.87 (s, 1H), 7.54 (s, 1H), 7.31–7.33 (m, 3H), 4.29 (q, J = 8.0
Hz, 2H), 2.56 (s, 3H), 1.42 (t, J = 8.0 Hz, 3H); 13C NMR (100
MHz, CDCl3) d 141.0, 138.4, 128.7, 127.4, 122.6, 121.7, 121.6,
121.5, 120.4, 119.1, 111.5, 108.4, 37.7, 21.4, 13.7; m/z = 289,
positive mode; anal. calc. for C15H14BrN: C, 62.52; H, 4.90; N,
4.86%; found: C, 62.45; H, 4.95; N, 4.81%.
1
1122, 1053, 900, 830, 806, 746, 717, 428; H NMR (400 MHz,
CDCl3) d 8.10 (d, J = 7.6 Hz, 1H), 7.97 (d, J = 8.0 Hz, 1H), 7.59
(s, 1H), 7.53 (t, J = 6.8 Hz, 1H), 7.43 (d, J = 8.0 Hz, 1H), 7.37
(dd, J = 6.8, 1.6 Hz, 1H), 7.29 (t, J = 8.0 Hz, 1H), 4.28 (q, J =
8.0 Hz, 2H), 1.45 (t, J = 8.0 Hz); 13C NMR (100 MHz, CDCl3) d
140.8, 140.1, 126.1, 122.4, 121.9, 121.9, 121.5, 120.4, 119.4, 119.3,
115.6, 108.7, 37.7, 13.8; m/z = 275, positive mode; anal. calc. for
C14H12BrN: C, 61.33; H, 4.41; N, 5.11%; found: C, 61.23; H, 4.48;
N, 5.15%.
Formylation of 2-bromo-9-ethyl-9H-carbazole (9 and 10). An
oven-dried 250 mL round-bottomed flask equipped with a Teflon-
coated magnetic stirring bar is charged with 10 g (0.036 M)
of 2-bromo-9-ethylcarbazole and 80 mL of dimethylformamide
under stirring and cooled to 0 ◦C. 10 mL (0.11 M) of phosphoryl
chloride is added dropwise for 15 min. The rea◦ction is allowed
to warm to room temperature and heated at 70 C for 5 h, after
which time TLC (90 : 10 hexanes : ethyl acetate) indicated complete
conversion. The reaction is allowed to cool to room temperature
and quenched with ice. The reaction mass is poured into crushed
ice slowly, neutralized with 5% aq. sodium hydroxide and extracted
with ethyl acetate. The organic layer is washed with water and
brine, dried over anhydrous sodium sulfate and the solvent is
removed under reduced pressure. The crude material is purified by
column chromatography (eluent: 5–10% ethyl acetate in hexane).
The 3-formyl derivative is eluted in 5% eluent as the minor isomer
and 6-formyl derivative is eluted in 10% eluent as the major isomer.
Yield: 70%.
2-Bromo-9-ethyl-6-methyl-9H-carbazole-3-carbaldehyde (12).
The procedure for the preparation of 9 is followed to give 2-
bromo-9-ethyl-6-methyl-9H-carbazole-3-carbaldehyde as a white
solid after column chromatography. Yield: 70%. mp: 148–150 ◦C;
nmax (KBr)/cm-1: 2916, 2843, 1670, 1595, 1479, 1350, 1302, 1224,
1
1145, 856, 790, 761, 694, 464, 420; H NMR (400 MHz, CDCl3)
d 10.39 (s, 1H), 8.57 (s, 1H), 7.84 (s, 1H), 7.48 (s, 1H), 7.34 (d,
J = 8.0 Hz, 1H), 7.27 (d, J = 8.0 Hz, 1H), 4.24 (q, J = 7.6 Hz,
2H), 2.53 (s, 3H), 1.42 (t, J = 7.6 Hz, 3H); 13C NMR (100 MHz,
CDCl3) d 143.8, 139.6, 130.3, 128.5, 124.5, 123.9, 123.0, 122.5,
122.5, 121.0, 112.5, 108.9, 38.0, 21.4, 13.8; m/z = 317, positive
mode; anal. calc. for C16H14BrNO: C, 60.78; H, 4.46; N, 4.43%;
found: C, 60.58; H, 4.40; N, 4.51%.
7-Bromo-9-ethyl-9H-carbazole-3-carbaldehyde
(9). White
9-Ethyl-6-methyl-2-(phenylethynyl)-9H-carbazole-3-carbalde-
hyde (1a). An oven-dried 50 mL Schlenk tube equipped with a
Teflon-coated magnetic stirring bar is charged with 1 g (3 mmol)
of 12, 1 g of molecular sieves and 0.42 mL (3.8 mmol) of phenyl
acetylene. The tube is evacuated and filled with nitrogen. To it,
10 mL of dry THF and 5 mL of freshly distilled triethylamine are
solid; mp: 129–131 ◦C; nmax (KBr)/cm-1: 2974, 2814, 2723, 1582,
1
1622, 1585, 1485, 1431, 1234, 1170, 1143, 908, 804, 742, 549; H
NMR (400 MHz, CDCl3) d 10.12 (s, 1H), 8.52 (s, 1H), 8.02 (d,
J = 8.0 Hz, 1H), 7.94 (d, J = 8.0 Hz, 1H), 7.45 (s, 1H), 7.40–7.43
(m, 2H), 4.30 (q, 2H), 1.43 (t, J = 7.6 Hz, 3H); 13C NMR (100
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added under nitrogen, and the reaction is stirred for 10 min at
room temperature. 42 mg of Pd(PPh3)2Cl2 (2 mol%) and 6 mg of
CuI (1 mol%) are added under nitrogen and the Schlenk tube is
heated at 60 ◦C for 4 h, after which time TLC (85 : 15 hexanes : ethyl
acetate) indicated complete conversion. The reaction is allowed to
cool to room temperature and filtered. The filtrate is poured into
crushed ice slowly and extracted with ethyl acetate. The organic
layer is washed with water and brine, dried over anhydrous sodium
sulfate and the solvent is removed under reduced pressure. The
crude material is purified by column chromatography (eluent: 8–
15% ethyl acetate in hexane). The product is eluted in 12% eluent as
a pale yellow solid. Yield: 85%. mp: 137–139 ◦C; nmax (KBr)/cm-1:
2916, 2843, 1670, 1595, 1479, 1350, 1302, 1224, 1145, 856, 790,
761, 694, 464, 420; 1H NMR (400 MHz, CDCl3) d 10.72 (s, 1H),
8.68 (s 1H), 7.91 (s, 1H), 7.63–7.65 (m, 2H), 7.55 (s, 1H), 7.31–
7.43 (m, 5H), 4.33 (q, J = 8.0 Hz, 2H), 2.56 (s, 3H), 1.47 (t, J =
8.0 Hz, 3H); 13C NMR (100 MHz, CDCl3) d 191.4, 142.8, 139.6,
131.6, 130.1, 128.8, 128.6, 128.5, 127.7, 123.7, 123.3, 123.1, 122.8,
121.1, 120.6, 112.3, 108.8, 95.1, 86.7, 37.9, 21.4, 13.8; m/z = 338,
positive mode; anal. calc. for C24H19NO: C, 85.43; H, 5.68; N,
4.15%; found: C, 85.21; H, 5.72; N, 4.22%.
95% yield. mp: 123–125 ◦C; nmax (KBr)/cm-1: 3468, 2922, 2864,
1593, 1471, 1439, 1331, 1219, 1055, 889, 842, 804, 582; 1H NMR
(400 MHz, CDCl3) d 7.88 (d, J = 8.0 Hz, 1H), 7.73 (s, 1H), 7.53 (s,
1H), 7.32 (d, J = 8.0 Hz, 1H), 7.07 (s, 1H), 4.49 (q, J = 7.6 Hz, 2H),
2.78 (s, 3H), 2.52 (s, 3H), 1.41 (t, J = 7.6 Hz, 3H); 13C NMR (100
MHz, CDCl3) d 141.7, 137.1, 130.9, 128.9, 123.5, 122.1, 121.8,
121.2, 119.9, 119.1, 118.1, 111.6, 39.5, 21.1, 19.8, 15.5; m/z = 303,
positive mode; anal. calc. for C16H16BrN: C, 63.59; H, 5.34; N,
4.63%; found: C, 63.52; H, 5.41; N, 4.55%.
2-Bromo-9-ethyl-6,8-dimethyl-9H -carbazole-3-carbaldehyde
(13). An oven-dried 50 mL round-bottomed flask equipped
with a Teflon-coated magnetic stirring bar is charged with 2
g (6.6 mmol) of 8b, 10 mL of chloroform and 3 mL of N-
methylformanilide. The reaction mixture is cooled in an ice bath at
0–5 ◦C for 15 min. 2 mL of POCl3 is added to the reaction mixture
dropwise under stirring. The reaction mixture is allowed to warm
room temperature and refluxed for 6 h, after which time TLC
(90 : 10 hexanes : ethyl acetate) indicated complete conversion. The
reaction is allowed to cool to room temperature and quenched
with ice. The reaction mass is poured into crushed ice slowly,
neutralized with an ice cold solution of aq. 5% sodium bicarbonate
and extracted with ethyl acetate. The organic layer is washed with
water and brine, dried over anhydrous sodium sulfate and the
solvent is removed under reduced pressure. The crude material is
purified by column chromatography (eluent: 5–10% ethyl acetate
in hexane). The product is eluted in 10% eluent as a white solid.
Yield: 80%. mp: 139–141 ◦C; nmax (KBr)/cm-1: 3013, 2878, 2916,
2852, 1668, 1593, 1469, 1442, 1342, 1309, 1222, 1155, 1005, 848,
704, 569, 416; 1H NMR (400 MHz, CDCl3) d 10.42 (s, 1H), 8.59
(s, 1H), 7.74 (s, 1H), 7.51 (s, 1H), 7.09 (s, 1H), 4.48 (q, J = 7.6
Hz, 2H), 2.76 (s, 3H), 2.42 (s, 3H), 1.45 (t, J = 7.6 Hz, 3H);
13C NMR (100 MHz, CDCl3) d 191.7, 144.5, 137.7, 132.0, 130.4,
124.7, 123.9, 123.8, 122.8, 122.2, 120.4, 118.7, 112.7, 39.8, 21.0,
19.6, 15.5; m/z = 331, positive mode; anal. calc. for C17H16BrNO:
C, 61.83; H, 4.88; N, 4.24%; found: C, 61.75; H, 4.81; N, 4.36%.
9-Ethyl-2-(phenylethynyl)-9H-carbazole-3-carbaldehyde (1b).
By employing a similar procedure for the synthesis of 1a, 1b is
obtained as a yellow solid in 85% yield. mp: 110–112 ◦C; nmax
(KBr)/cm-1: 3057, 2970, 2843, 1672, 1620, 1589, 1494, 1469,
1452, 1359, 1329, 1232, 1159, 1126, 1103, 923, 898, 852, 760, 738,
719, 696, 665, 528, 468; 1H NMR (400 MHz, CDCl3) d 10.74 (s,
1H), 8.74 (s, 1H), 8.14 (d, J = 8.0 Hz, 1H), 7.52–7.65 (m, 4H),
7.41–7.46 (m, 4H), 7.34 (t, J = 7.6 Hz, 1H), 4.38 (q, J = 7.6 Hz,
2H), 1.49 (t, J = 7.6 Hz, 3H); 13C NMR (100 MHz, CDCl3) d
191.5, 142.7, 141.3, 131.6, 128.8, 128.5, 127.9, 127.3, 123.9, 123.3,
123.1, 122.7, 121.2, 120.7, 120.6, 112.4, 109.1, 95.2, 86.5, 38.0,
13.8; m/z = 324, positive mode; anal. calc. for C23H17NO: C,
85.42; H, 5.30; N, 4.33%; found: C, 85.31; H, 5.41; N, 4.41%.
4-Bromo-3¢,5¢-dimethyl-2-nitrobiphenyl (6b). By employing a
similar procedure for the synthesis of 6a, 6b is obtained as a yellow
liquid in 85% yield which solidified gradually. mp: 53–55 ◦C; nmax
(KBr)/cm-1: 3086, 2914, 1601, 1523, 1346, 1271, 1205, 1151, 1018,
883, 852, 831, 709, 688, 551, 432; 1H NMR (400 MHz, CDCl3) d
8.02 (s, 1H), 7.73 (d, J = 8.4 Hz, 1H), 7.07 (s, 1H), 6.92 (s, 2H),
2.37 (s, 6H); 13C NMR (100 MHz, CDCl3) d 149.6, 138.5, 136.2,
135.5, 135.2, 133.2, 130.3, 126.9, 125.5, 121.0, 21.3; m/z = 308,
positive mode; anal. calc. for C14H12BrNO2: C, 54.92; H, 3.95; N,
4.51%; found: C, 54.85; H, 3.92; N, 4.51%.
9-Ethyl-6,8-dimethyl-2-(phenylethynyl)-9H -carbazole-3-car-
baldehyde (1c). The general procedure for the synthesis of 1a and
1b is employed. 1c is obtained in 87% yield. mp: 157–159 ◦C; nmax
(KBr)/cm-1: 3009, 2964, 2916, 2843, 1670, 1595, 1496, 1466, 1309,
1217, 842, 763, 690, 578; 1H NMR (400 MHz, CDCl3) d 10.73 (s,
1H), 8.68 (s, 1H), 7.80 (s, 1H), 7.63–7.65 (m, 2H), 7.57 (s, 1H),
7.41–7.44 (m, 3H), 7.11 (s, 1H), 4.58 (q, J = 7.0 Hz, 2H), 2.86 (s,
3H), 2.79 (s, 3H), 1.45 (t, J = 7.0 Hz, 3H); 13C NMR (100 MHz,
CDCl3) d 191.4, 143.5, 138.3, 132.1, 131.6, 130.2, 128.7, 128.5,
128.0, 124.3, 123.6, 123.5, 122.8, 120.4, 120.3, 118.9, 112.5, 94.9,
86.7, 39.8, 21.0, 19.7, 15.6; m/z = 352, positive mode; anal. calc.
for C25H21NO: C, 85.44; H, 6.02; N, 3.99%; found: C, 85.32; H,
6.11; N, 3.89%.
7-Bromo-1,3-dimethyl-9H-carbazole (7b). By employing a
similar procedure for the synthesis of 7a, 7b is obtained in 70%
yield. mp: 123–125 ◦C; nmax (KBr)/cm-1: 3431, 3074, 2918, 2860,
1882, 1599, 1429, 1331, 1302, 1226, 1051, 1033, 850, 814, 584, 432,
1
414; H NMR (400 MHz, CDCl3) d 8.41 (bs, 1H), 7.87 (d, J =
4-Bromo-2,5-dimethyl-2¢-nitrobiphenyl (14). The procedure for
the synthesis of 6a and 6b is employed. Starting from 2-
iodonitrobenzene and 4-bromo-2,5-dimethylphenylboronic acid,
the biphenyl 14 is obtained in 85% yield. The crude product is
used further without purification. mp: 56–58 ◦C; nmax (KBr)/cm-1:
3088, 2924, 1600, 1527, 1346, 1270, 1204, 1153, 1018, 851, 831,
8.4 Hz, 1H), 7.69 (s, 1H), 7.59 (s, 1H), 7.30–7.33 (m, 1H), 7.10
(s, 1H), 4.15 (q, 2H), 2.52–2.55 (t, 6H), 1.38 (t, J = 7.6 Hz, 3H);
13C NMR (100 MHz, CDCl3) d 140.6, 137.3, 129.3, 128.3, 122.6,
122.4, 122.2, 121.4, 119.7, 118.7, 117.6, 113.8, 21.4, 16.2; m/z =
275, positive mode; anal. calc. for C14H12BrN: C, 61.33; H, 4.41;
N, 5.11%; found: C, 61.24; H, 4.52; N, 5.31%.
1
708; H NMR (400 MHz, CDCl3) d 8.04 (d, J = 8.0 Hz, 1H),
7-Bromo-9-ethyl-1,3-dimethyl-9H-carbazole (8b). By employ-
ing a similar procedure for the synthesis of 8a, 8b is obtained in
7.66 (t, J = 7.2 Hz, 1H), 7.55 (t, J = 8.1 Hz, 1H), 7.47 (s, 1H),
7.31 (d, J = 7.6 Hz, 1H), 6.98 (s, 1H), 2.38 (s, 3H), 2.06 (s, 3H);
4666 | Org. Biomol. Chem., 2011, 9, 4662–4670
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13C NMR (100 MHz, CDCl3) d 148.9, 136.7, 135.6, 135.1, 135.0,
133.5, 132.7, 132.1, 130.3, 128.5, 124.5, 124.2, 22.3, 19.1; m/z =
306; 279 for the demethylated fragment, positive mode; anal. calc.
for C14H12BrNO2: C, 54.92; H, 3.95; N, 4.57%; found: C, 54.85; H,
4.03; N, 4.51%.
white solid. Yield: 75%. mp: 126–128 ◦C; nmax (KBr)/cm-1: 2964,
2916, 2856, 1672, 1593, 1440, 1340, 1309, 1222, 1155, 898, 846,
1
704, 569; H NMR (400 MHz, CDCl3) d 10.66 (s, 1H), 8.31 (s,
1H), 7.65 (dd, J = 1.6 Hz, 8.4 Hz, 1H), 7.41 (d, J = 1.2 Hz, 1H),
4.56 (q, J = 7.6 Hz, 2H), 3.10 (s, 3H), 2.90 (s, 3H), 1.50 (s, 12H);
13C NMR (100 MHz, CDCl3) d 195.8, 143.5, 141.5, 139.9, 135.7,
128.4, 125.5, 124.2, 123.6, 122.7, 119.7, 118.0, 108.8, 40.3, 34.8,
32.0, 19.0, 17.1, 15.6; m/z = 386, positive mode, 330 and 332 for the
fragment without the t-butyl group; anal. calc. for C21H24BrNO:
C, 65.29; H, 6.26; N, 3.63%; found: C, 65.41; H, 6.23; N, 3.56%.
2-Bromo-1,4-dimethyl-9H-carbazole (15). The general proce-
dure for the synthesis of 7a is applied. Starting from 14, the
bromocarbazole is obtained in 70% yield. The crude product is
used further without purification. mp: 86–88 ◦C; nmax (KBr)/cm-1:
3412, 3040, 2916, 2856, 1593, 1579, 1454, 1377, 1319, 1288, 1014,
1
773, 750, 731, 441; H NMR (400 MHz, CDCl3) d 8.14 (d, J =
6-tert-Butyl-9-ethyl-1,4-dimethyl-2-(phenylethynyl)-9H-carba-
zole-3-carbaldehyde (1d). General Sonogashira reaction condi-
tions are employed as in the cases of 1a–1c. 1d is obtained as a
light yellow solid in 85% yield. mp: 130–132 ◦C; nmax (KBr)/cm-1:
8.0 Hz, 1H), 7.50 (bs, 1H), 7.46–7.48 (m, 2H), 7.28–7.33 (m, 1H),
7.24 (s, 1H), 2.81 (s, 3H), 2.57 (s, 3H); 13C NMR (100 MHz,
CDCl3) d 139.4, 139.1, 125.4, 124.7, 124.1, 122.5, 121.2, 120.6,
119.9, 116.8, 110.7, 20.1, 16.6; m/z = 275, positive mode; anal.
calc. for C14H12BrN: C, 61.33; H, 4.41; N, 5.11%; found: C, 61.23;
H, 4.46; N, 5.19%.
1
2957, 1674, 1556, 1487, 1342, 1307, 1228, 802, 754, 688, 526; H
NMR (400 MHz, CDCl3) d 11.06 (s, 1H), 8.37 (s, 1H), 7.62–7.65
(m, 3H), 7.42–7.43 (m, 4H), 4.60 (q, J = 7.6 Hz, 2H), 3.24 (s, 3H),
3.05 (s, 3H), 1.51 (s, 12H); 13C NMR (100 MHz, CDCl3) d 195.4,
143.4, 141.1, 140.2, 135.7, 131.4, 128.6, 128.5, 126.6, 125.9, 124.3,
123.9, 123.3, 123.2, 120.2, 119.9, 108.7, 101.0, 86.3, 39.9, 34.8,
32.0, 17.0, 16.99, 15.7; m/z = 408, positive mode; anal. calc. for
C29H29NO: C, 85.47; H, 7.17; N, 3.44%; found: C, 85.32; H, 7.21;
N, 3.51%.
2-Bromo-9-ethyl-1,4-dimethyl-9H-carbazole (16). The general
procedure for the synthesis of 8a is applied. Starting from 15,
the N-ethyl-2-bromocarbazole (16) is obtained in 95% yield. The
crude product is used further without purification. mp: 110–
112 ◦C; nmax (KBr)/cm-1: 2966, 2920, 1608, 1560, 1456, 1346, 1302,
1
1157, 1113, 1005, 868, 781, 744, 723, 545; H NMR (400 MHz,
CDCl3) d 8.19 (d, J = 8.0 Hz, 1H), 7.53 (t, J = 8.0 Hz, 1H), 7.46
(d, J = 8.0 Hz, 1H), 7.28–7.32 (m, 2H), 4.60 (q, J = 7.6 Hz, 2H),
2.93 (s, 3H), 2.83 (s, 3H), 1.48 (t, J = 8.0 Hz, 3H); 13C NMR (100
MHz, CDCl3) d 141.2, 139.5, 132.1, 125.3, 125.2, 123.7, 123.4,
122.5, 121.8, 119.5, 117.1, 108.8, 39.9, 20.5, 18.9, 15.5; m/z = 302,
positive mode; anal. calc. for C16H16BrN: C, 63.59; H, 5.34; N,
4.63%; found: C, 63.48; H, 5.43; N, 4.55%.
General procedure for the synthesis of ellipticinium triflates. An
oven-dried 10 mL round-bottomed flask equipped with a Teflon-
coated magnetic stirring bar is charged with 0.3 mmol of 3-
formyl-2-phenylethynylcarbazole, 0.3 mmol of amine, 0.5 g of
anhydrous magnesium sulfate and 5 mL of dichloromethane. The
reaction mixture is refluxed for 1–2 h under stirring. The yellow
solution is filtered and the filtrate is concentrated under vacuum.
The compound is freshly dissolved in 5 mL of dichloromethane
under stirring. To it, 0.3 mmol silver triflate is added and stirred
at room temperature for 1 h. The reaction mass is diluted
with dichloromethane, filtered and the solvent is removed under
reduced pressure. The crude product is recrystallized from ethanol
as a dark yellow crystalline solid.
2-Bromo-6-tert-butyl-9-ethyl-1,4-dimethyl-9H-carbazole (17).
An oven-dried 100 mL round-bottomed flask equipped with a
Teflon-coated magnetic stirring bar is charged with 2 g (6.6 mmol)
of 16, 40 mL of dichloromethane and 0.9 g (6.6 mmol) of
anhydrous aluminium chloride under stirring. To it, 2 mL of
tert-butyl chloride is added slowly and the reaction mixture is
stirred at room temperature for 6 h, after which time TLC
(98 : 02 hexanes : ethyl acetate) indicated complete conversion. The
reaction mass is poured into crushed ice slowly, neutralized with
a solution of aq. 5% sodium bicarbonate and extracted with ethyl
acetate. The organic layer is washed with water and brine, dried
over anhydrous sodium sulfate and the solvent is removed under
reduced pressure to give 17 as a white solid in 94% yield. mp: 82–
84 ◦C; nmax (KBr)/cm-1: 2962, 2862, 1566, 1462, 1375, 1309, 1236,
1172, 1120, 1020, 949, 879, 833, 802, 640, 561, 443; 1H NMR (400
MHz, CDCl3) d 8.18 (d, J = 1.6 Hz, 1H), 7.60 (dd, J = 8.8, 2 Hz,
2H), 7.40 (d, J = 8.8 Hz, 1H), 7.28 (s, 1H), 4.60 (q, J = 7.6 Hz,
2H), 2.92 (s, 3H), 2.84 (s, 3H), 1.50 (s, 12H); 13C NMR (100 MHz,
CDCl3) d 142.3, 139.8, 139.3, 131.8, 125.3, 123.6, 123.3, 123.1,
122.0, 118.6, 117.0, 108.3, 39.0, 34.6, 32.0, 20.6, 19.1, 15.6; m/z =
359, positive mode; anal. calc. for C20H24BrN: C, 67.04; H, 6.75;
N, 3.91%; found: C, 67.12; H, 6.63; N, 3.85%.
2-(4-Chlorophenyl)-6-ethyl-9-methyl-3-phenyl-6H-pyrido[4,3-
b]carbazol-2-ium triflate (19). mp: 189–191 ◦C; nmax (KBr)/cm-1:
3488, 2959, 1622, 1454, 1412, 1257, 1035, 837, 765, 632; 1H NMR
(400 MHz, CDCl3) d 10.23 (s, 1H), 9.33 (s, 1H), 8.54 (s, 1H), 8.41
(s, 1H), 8.32 (s, 1H), 7.78 (d, J = 8.4 Hz, 1H), 7.71–7.73 (d, 2H),
7.61–7.64 (m, 3H), 7.43 (s, 6H), 4.63 (d, J = 7.6 Hz, 2H), 2.57
(s, 3H), 2.50 (s, 3H), 1.44 (t, J = 7.6 Hz, 3H); 13C NMR (100
MHz, CDCl3) d 152.0, 146.4, 143.1, 141.4, 141.3, 136.1, 135.2,
133.5, 131.6, 131.4, 130.6, 130.1, 129.8, 129.6, 129.1, 128.9, 124.7,
123.9, 122.7, 121.7, 120.2, 112.2, 110.7, 38.5, 21.3, 13.6; m/z = 448,
positive mode; anal. calc. for C30H24ClN2: C, 80.43; H, 5.40; N,
6.25%; found: C, 80.25; H, 5.48; N, 6.17%.
6-Ethyl-9-methyl-3-phenyl-2-p-tolyl-6H-pyrido[4,3-b]carbazol-
2-ium triflate (20). mp: 212–214 ◦C; nmax (KBr)/cm-1: 3028, 2924,
1608, 1564, 1494, 1435, 1259, 1028, 763, 698, 638, 516; 1H NMR
(400 MHz, CDCl3) d 10.13 (s, 1H), 9.27 (s, 1H), 8.49 (s, 1H), 8.43
(s, 1H), 8.38 (s, 1H), 7.64 (d, J = 8.0 Hz, 2H), 7.40–7.57 (m, 5H),
7.34 (s, 1H), 7.03 (d, J = 8.0 Hz, 2H), 4.74 (q, J = 8.0 Hz, 2H), 3.77
(s, 1H), 2.82 (s, 3H), 1.15 (t, J = 8.0 Hz, 3H); 13C NMR (100 MHz,
CDCl3) d 160.3, 152.0, 147.0, 143.4, 139.7, 136.0, 135.5, 134.8,
133.8, 131.4, 130.5, 129.9, 129.2, 128.9, 128.8, 124.9, 123.2, 122.7,
2-Bromo-6-tert-butyl-9-ethyl-1,4-dimethyl-9H -carbazole-3-
carbaldehyde (18). The general procedure for Vilsmeir–Haack
formylation is used. Starting from 17, the formylated product is
obtained as a white solid after column purification (eluent: 5–10%
ethyl acetate in hexane). The product is eluted in 7% eluent as a
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121.6, 120.4, 120.3, 114.7, 103.3, 56.1, 40.4, 21.0, 19.4, 15.2; m/z =
428, positive mode; anal. calc. for C31H27N2: C, 87.06; H, 6.37; N,
6.55%; found: C, 87.15; H, 6.34; N, 6.68%.
1.7 Hz, 1H), 4.58 (q, J = 7.6 Hz, 2H), 2.57 (s, 3H), 1.40 (t, J =
7.6 Hz, 3H); 13C NMR (100 MHz, CDCl3) d 150.8, 146.1, 143.2,
141.4, 135.5, 133.07, 132.6, 131.4, 131.2, 130.8, 130.3, 129.3, 129.0,
125.5, 123.3, 122.7, 121.7, 120.6, 120.3, 110.5, 103.16, 59.6, 38.4,
21.4, 13.6; m/z = 432, positive mode; anal. calc. for C30H27N2O:
C, 83.50; H, 6.31; N, 6.49%; found: C, 83.39; H, 6.28; N, 6.53%.
6-Ethyl-9-methyl-2-pentyl-3-phenyl-6H-pyrido[4,3-b]carbazol-
2-ium triflate (21). mp: 193–195 ◦C; nmax (KBr)/cm-1: 3419, 2916,
2862, 2259, 2112, 1653, 1477, 1440, 1019, 1076, 826, 759; 1H NMR
(400 MHz, CDCl3) d 10.15 (s, 1H), 9.31 (s, 1H), 8.52 (s, 1H), 8.38
(s, 1H), 8.27 (s, 1H), 7.75 (d, J = 8.0 Hz, 1H), 7.53 (d, J = 8.0 Hz,
1H), 7.46–7.39 (m, 7H), 7.32 (d, J = 8.0 Hz, 2H), 4.60 (q, J = 8.0
Hz, 2H), 2.56 (s, 3H), 1.43 (t, J = 8.0 Hz, 3H); 13C NMR (100
MHz, CDCl3) d 151.8, 146.3, 143.2, 141.4, 140.3, 136.0, 133.7,
131.5, 131.4, 130.5, 130.2, 129.9, 129.0, 128.8, 127.3, 124.9, 123.8,
122.6, 121.7, 120.2, 110.6, 103.2, 38.0, 21.3, 21.1, 13.6; m/z =
408, positive mode; anal. calc. for C29H31N2: C, 85.46; H, 7.67; N,
6.87%; found: C, 85.23; H, 7.76; N, 6.75%.
2-(4-Chlorophenyl)-6-ethyl-7,9-dimethyl-3-phenyl-6H -pyri-
do[4,3-b]carbazol-2-ium triflate (26). mp: 197–199 ◦C; nmax
(KBr)/cm-1: 3485, 2957, 1626, 1458, 1410, 1257, 1032, 833, 763,
638; 1H NMR (400 MHz, CDCl3) d 10.09 (s, 1H), 8.59 (s, 1H), 8.45
(s, 1H), 7.83 (t, J = 6.8 Hz, 2H), 7.58 (d, J = 7.6 Hz, 2H), 7.10–7.46
(m, 5H), 7.02 (d, J = 8.0 Hz, 2H), 4.82 (s, 2H), 3.96 (s, 3H), 3.69
(s, 3H), 3.15 (s, 3H), 1.46 (s, 12H); 13C NMR (100 MHz, CDCl3) d
160.3, 149.1, 145.0, 144.8, 142.8, 142.4, 135.6, 135.2, 134.7, 134.0,
130.8, 129.7, 129.2, 128.7, 128.0, 127.4, 122.0, 121.8, 121.1, 120.2,
114.6, 111.2, 110.5, 56.1, 40.1, 35.1, 32.1, 15.9, 15.7, 14.4; m/z =
463, positive mode; anal. calc. for C31H26ClN2: C, 80.59, H, 5.67,
N, 6.06%; found: C, 80.45, H, 5.71, N, 6.12%.
2-Allyl-6-ethyl-9-methyl-3-phenyl-6H-pyrido[4,3-b]carbazol-2-
ium triflate (22). mp: 185–187 ◦C; nmax (KBr)/cm-1: 3418, 2872,
1
2254, 2127, 1651, 1487, 1439, 1028, 1006, 825, 763; H NMR
(400 MHz, CDCl3) d 10.08 (s, 1H), 9.10 (s, 1H), 8.21–8.28 (m,
2-Allyl-6-ethyl-7,9-dimethyl-3-phenyl-6H -pyrido[4,3-b]car-
bazol-2-ium triflate (27). mp: 157–159 ◦C; nmax (KBr)/cm-1: 3417,
2869, 2248, 2129, 1660, 1488, 1440, 1029, 1011, 825, 762; 1H NMR
(400 MHz, CDCl3) d 9.98 (s, 1H), 9.22 (s, 1H), 8.32 (s, 1H), 8.25
(s, 1H), 8.10 (s, 1H), 7.61–7.70 (m, 5H), 7.28 (s, 1H), 6.00 (m, 1H),
5.28 (d, J = 10.4 Hz, 1H), 5.17 (d, J = 4.4 Hz, 2H), 4.95 (d, J = 17.2
Hz, 1H), 4.67 (d, J = 8.0 Hz, 2H), 2.78 (s, 3H), 2.48 (s, 3H), 1.41
(t, J = 8.0 Hz, 3H); 13C NMR (100 MHz, CDCl3) d 150.6, 146.7,
143.0, 139.7, 135.5, 134.7, 133.1, 132.5, 131.2, 130.8, 130.3, 129.9,
129.3, 129.1, 125.5, 122.7, 122.6, 122.0, 121.4, 120.7, 120.4, 103.2,
59.6, 21.0, 19.4, 15.3; m/z = 392, positive mode; anal. calc. for
C28H27N2: C, 85.89, H, 6.95, N, 7.15%; found: C, 85.76, H, 6.91,
N, 7.07%.
3H), 7.72–7.73 (m, 6H), 7.50 (d, 1H), 4.52 (t, 4H), 2.53 (s, 3H),
1.70 (s, 2H), 1.37 (t, J = 7.2 Hz, 3H), 1.08 (s, 4H), 0.71 (s, 3H); 13
C
NMR (100 MHz, CDCl3) d 150.5, 145.9, 142.8, 141.3, 135.2, 133.2,
131.3, 131.0, 130.3, 121.4, 128.8, 125.5, 123.0, 122.6, 122.62, 120.5,
110.3, 103.0, 57.6, 38.3, 30.1, 28.0, 21.6, 21.3, 13.9, 13.6; m/z =
376, negative mode; anal. calc. for C27H25N2: C, 85.90; H, 6.68; N,
7.42%; found: C, 85.96; H, 6.61; N, 7.32%.
6-Ethyl-7,9-dimethyl-3-phenyl-2-p-tolyl-6H-pyrido[4,3-b]car-
bazol-2-ium triflate (23). mp: 211–213 ◦C; nmax (KBr)/cm-1: 3418,
2916, 2253, 2125, 166, 1651, 1271, 1224, 1159, 1024, 823, 760; 1H
NMR (400 MHz, CDCl3) d 10.17 (s, 1H), 8.45 (s, 1H), 7.85 (t,
J = 7.2 Hz, 2H), 7.83 (d, J = 8.0 Hz, 2H), 7.40–7.72 (m, 7H),
4.84 (q, J = 7.2 Hz, 2H), 3.40 (s, 3H), 3.16 (s, 3H), 1.39 (s, 12H);
13C NMR (100 MHz, CDCl3) d 149.0, 145.2, 144.9, 142.4, 141.3,
135.3, 135.1, 135.0, 133.7, 130.9, 129.9, 129.6, 128.8, 128.1, 127.5,
123.1, 122.2, 121.8, 121.2, 120.2, 119.2, 111.3, 110.5, 40.1, 35.1,
32.1, 15.9, 15.7, 13.9; m/z = 442, positive mode; anal. calc. for
C32H29N2: C, 87.04; H, 6.62; N, 6.34%; found: C, 87.12; H, 6.59;
N, 6.45%.
9-tert-Butyl-2-(4-chlorophenyl)-6-ethyl-5,11-dimethyl-3-phenyl-
6H-pyrido[4,3-b]carbazol-2-ium triflate (28). mp: 193–195 ◦C;
nmax (KBr)/cm-1: 3057, 2957, 1732, 1624, 1587, 1510, 1458, 1410,
1280, 1255, 1141, 1030, 763, 636, 515; 1H NMR (400 MHz,
CDCl3) d 10.10 (d, J = 5.6 Hz, 1H), 8.60 (d, J = 6.0 Hz, 1H),
8.45 (d, J = 6.0 Hz, 1H), 7.83 (d, 2H), 7.27–7.54 (m, 9H), 4.82
(s, 2H), 3.89 (s, 3H), 3.16 (s, 3H), 2.33 (s, 3H), 1.46 (s, 12H); 13C
NMR (100 MHz, CDCl3) d 148.9, 145.1, 144.8, 142.6, 142.4,
140.3, 140.1, 135.2, 134.8, 134.0, 130.8, 130.0, 129.8, 128.7, 127.6,
127.4, 122.7, 122.3, 121.9, 121.1, 120.2, 111.2, 110.5, 60.2, 35.1,
32.1, 21.2, 15.9, 14.5, 13.9; m/z = 518, positive mode; anal. calc.
for C35H34ClN2: C, 81.14; H, 6.61; N, 5.41%; found: C, 81.32; H,
6.57; N, 5.45%.
6-Ethyl-2-(4-methoxyphenyl)-7,9-dimethyl-3-phenyl-6H-pyri-
do[4,3-b]carbazol-2-ium triflate(24). mp: 204–206 ◦C; nmax
(KBr)/cm-1: 2916, 2856, 1606, 1493, 1439, 1265, 1145, 1028, 634,
1
516; H NMR (400 MHz, CDCl3) d 10.14 (s, 1H), 9.29 (s, 1H),
8.33 (s, 1H), 8.26 (s, 1H), 8.13 (s, 1H), 7.64–7.68 (m, 6H), 7.29 (s,
1H), 6.42 (q, J = 1.2 Hz, 1H), 6.14 (d, J = 3.6 Hz, 1H), 5.86 (s, 2H),
4.68 (d, 2H), 2.78 (s, 3H), 2.50 (s, 3H), 1.42 (t, J = 7.2 Hz, 3H);
13C NMR (100 MHz, CDCl3) d 150.2, 147.3, 146.8, 144.8, 142.7,
139.7, 135.6, 134.7, 132.9, 131.2, 130.8, 130.3, 129.4, 129.2, 125.7,
123.0, 122.7, 121.5, 120.6, 120.5, 111.5, 111.4, 103.3, 54.0, 21.0,
19.3, 15.2; m/z = 458, positive mode; anal. calc. for C32H29N2O:
C, 83.99; H, 6.39; N, 6.12%; found: C, 83.85; H, 6.41; N, 6.32%.
9-tert-Butyl-6-ethyl-5,11-dimethyl-3-phenyl-2-p-tolyl-6H-pyri-
0do[4,3-b]carbazol-2-ium triflate (29). mp: 183–185 ◦C; nmax
(KBr)/cm-1: 3057, 2916, 1626, 1601, 1521, 1452, 1275, 1221, 852,
1
763, 740; H NMR (400 MHz, CDCl3) d 10.17 (s, 1H), 9.28 (s,
1H), 8.51 (s, 1H), 8.39 (s, 1H), 8.13 (s, 1H), 7.69 (d, J = 8.4 Hz,
2H), 7.60 (d, J = 8.4 Hz, 2H), 7.41 (bs, 5H), 7.35 (s, 1H), 4.75 (q,
J = 7.2 Hz, 2H), 3.40 (s, 3H), 2.82 (s, 3H), 1.44 (t, J = 7.2 Hz,
3H); 13C NMR (100 MHz, CDCl3) d 151.8, 147.2, 142.9, 141.3,
139.8, 136.1, 135.2, 134.9, 133.4, 131.5, 130.6, 130.1, 129.8, 128.9,
124.9, 123.5, 122.7, 121.7, 120.4, 120.3, 103.4, 40.1, 21.0, 19.4,
15.2; m/z = 498, positive mode; anal. calc. for C36H37N2: C, 86.88;
H, 7.49; N, 5.63%; found: C, 86.73; H, 7.55; N, 5.71%.
6-Ethyl-2-(furan-2-ylmethyl)-7,9-dimethyl-3-phenyl-6H-pyri-
do[4,3-b]carbazol-2-ium triflate (25). mp: 219–221 ◦C; nmax
1
(KBr)/cm-1: 2947, 2872, 1647, 1518, 1269, 1161, 1028, 825; H
NMR (400 MHz, CDCl3) d 10.06 (s, 1H), 9.34 (s, 1H), 8.37 (s,
1H), 8.32 (d, 2H), 7.59–7.76 (m, 7H), 6.0 (m, J = 5.2 Hz, 1H),
5.28 (d, J = 10.2 Hz, 1H), 5.18 (d, J = 5.2 Hz, 1H), 4.95 (d, J =
4668 | Org. Biomol. Chem., 2011, 9, 4662–4670
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9-tert-Butyl-6-ethyl-2-(4-methoxyphenyl)-5,11-dimethyl-3-phen-
yl-6H-pyrido[4,3-b]carbazol-2-ium triflate (30). mp: 251–253 ◦C;
nmax (KBr)/cm-1: 3466, 2916, 2852, 1606, 1494, 1435, 1332, 1263,
1032, 763, 698, 516; 1H NMR (400 MHz, CDCl3) d 10.16 (s, 1H),
9.29 (s, 1H), 8.50 (s, 1H), 8.40 (s, 1H), 8.11 (s, 1H), 7.31–7.51
(m, 10H), 4.76 (s, 2H), 2.83 (s, 3H), 2.33 (s, 3H), 1.45 (s, 3H);
13C NMR (100 MHz, CDCl3) d 151.9, 147.0, 143.2, 140.2, 139.8,
136.0, 134.8, 133.8, 131.4, 130.5, 130.2, 129.9, 129.2, 128.8, 127.3,
125.0, 123.3, 122.7, 121.7, 120.4, 103.5, 21.2, 21, 19.4, 15.2; m/z =
514, positive mode; anal. calc. for C36H37N2O: C, 84.17; H, 7.26;
N, 5.45%; found: C, 84.07; H, 7.31; N, 5.56%.
for C25H22N2: C, 85.68; H, 6.33; N, 7.99%; found: C, 85.51; H,
6.39; N, 7.86%.
Acknowledgements
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. T. K. C. thanks CSIR
for a Senior Research Fellowship.
Notes and references
General procedure for the synthesis of ellipticines. An oven-
dried 10 mL round-bottomed flask equipped with a Teflon-coated
magnetic stirring bar is charged with 0.3 mmol of 3-formyl-2-
phenylethynylcarbazole and 1 mL of tert-butylamine. The reaction
mixture is stirred at room temperature for 12 h and excess tert-
butylamine is removed under vacuum. The residue is dissolved in
3 mL of DMF, CuI (0.03 mmol) is added and heated at 90 ◦C for 2
h. The reaction is allowed to cool to room temperature, poured into
ice and extracted with ethyl acetate. The organic layer is washed
with water and brine, dried over anhydrous sodium sulfate and
the solvent is removed under reduced pressure. The crude material
is purified by column chromatography (eluent: 10% ethyl acetate
in hexane). The product is eluted in 10% eluent as a light yellow
solid.
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(3a).
mp: 176–178 ◦C; nmax (KBr)/cm-1: 3433, 3057, 2976, 2868, 1876,
1697, 1612, 1412, 1300, 1221, 1016, 935, 696, 464; 1H NMR (400
MHz, CDCl3) d 9.47 (s, 1H), 8.60 (s, 1H), 8.20–8.22 (d, 2H),
8.16 (s, 1H), 8.03 (s, 1H), 7.54–7.58 (m, 3H), 7.40–7.47 (m, 2H),
7.31 (s, 1H), 4.35 (q, J = 7.6 Hz, 2H), 2.60 (s, 3H), 1.48 (t, J =
7.6 Hz, 3H); 13C NMR (100 MHz, CDCl3) d 153.0, 149.5, 142.7,
140.8, 140.2, 135.2, 129.0, 129.0, 128.7, 128.1, 127.0, 126.2, 122.8,
122.6, 121.4, 119.0, 115.8, 108.1, 101.4, 37.7, 21.4, 13.2; m/z =
337, positive mode; anal. calc. for C24H20N2: C, 85.68; H, 5.99; N,
8.33%; found: C, 85.51; H, 5.91; N, 8.45%.
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6-Ethyl-3-phenyl-6H-pyrido[4,3-b]carbazole (3b). mp: 170–
172 ◦C; nmax (KBr)/cm-1: 2966, 2924, 1630, 1601, 1466, 1261, 1097,
1018, 800, 690, 468; 1H NMR (400 MHz, CDCl3) d 9.48 (s, 1H),
8.63 (s, 1H), 8.17–8.23 (m, 4H), 7.52–7.67 (m, 4H), 7.39–7.45 (m,
2H), 7.31 (t, J = 7.6 Hz, 1H), 4.37 (q, J = 7.2 Hz, 2H), 1.49 (t,
J = 7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3) d 153.0, 149.6,
142.6, 140.1, 135.2, 128.2, 127.8, 127.0, 126.2, 122.7, 122.7, 121.3,
119.6, 115.9, 108.4, 101.5, 37.7, 29.7, 28.3, 13.3; m/z = 323, positive
mode; anal. calc. for C23H18N2: C, 85.68; H, 5.63; N, 8.69%; found:
C, 85.49; H, 5.71; N, 8.61%.
6-Ethyl-7,9-dimethyl-3-phenyl-6H-pyrido[4,3-b]carbazole (3c).
mp: 183–185 ◦C; nmax (KBr)/cm-1: 3435, 3052, 2971, 2866, 1873,
8 D. K. Sreenivas and R. Nagarajan, Tetrahedron, 2010, 66, 9650; S.
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1
1692, 1612, 1409, 1302, 1223, 1016, 690; H NMR (400 MHz,
CDCl3) d 9.45 (s, 1H), 8.58 (s, 1H), 8.18 (d, J = 1.6 Hz, 2H), 8.15
(s, 1H), 7.88 (s, 1H), 7.57 (s, 1H), 7.55 (t, J = 7.6 Hz, 2H), 7.44
(t, J = 7.2 Hz, 1H), 7.12 (s, 1H), 4.57 (q, J = 7.2 Hz, 2H), 2.78 (s,
3H), 2.53 (s, 3H), 1.45 (t, J = 7.2 Hz, 3H); 13C NMR (100 MHz,
CDCl3) d 152.9, 149.4, 143.6, 140.2, 139.4, 135.2, 132.6, 129.2,
128.7, 128.1, 127.0, 126.5, 123.7, 122.7, 119.7, 119.1, 118.6, 115.1,
101.7, 39.7, 29.0, 19.8, 15.0; m/z = 351, positive mode; anal. calc.
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Org. Biomol. Chem., 2011, 9, 4662–4670 | 4669
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11 The CCDC deposition number of 19 is 804670; molecular formula:
C31H24C11F3N2O3S1, unit cell parameters: a = 8.1010(16), b = 11.081(2),
˚
¯
c = 16.926(3) A; space group P1. The CCDC deposition number of 23 is
805312; molecular formula: C33H29F3N2O3S1, unit cell parameters: a =
8.1925(3), b = 16.7763(8), c = 21.6041(10); space group Pna2†.
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4670 | Org. Biomol. Chem., 2011, 9, 4662–4670
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©