Novel 13H-indolo[3,2-c]acridines and their methyl derivatives

Article abstract of DOI:10.3184/030823407X198410

7-Phenyl-13H-indolo[3,2-c]acridines (2a-e) have been prepared from 2,3,4,9-tetrahydro-1H-carbazol-1-ones (1a-e) via the intermediate 5,6-dihydro-derivatives (3a-e), and 13H-indolo[3,2-c]acridines (8a-e) from the 1-(N-phenylamino)carbazoles (7a-e). Methyla

Full text of DOI:10.3184/030823407X198410

164 RESEARCH PAPER
MARCH, 164–169
JOURNAL OF CHEMICAL RESEARCH 2007
Novel 13H-indolo[3,2-c]acridines and their methyl derivatives
Makuteswaran Sridharan and Karnam Jayarampillai Rajendra Prasad*
Department of Chemistry, Bharathiar University, Coimbatore 641046, Tamil Nadu, India
7-Phenyl-13H-indolo[3,2-c]acridines (2a–e) have been prepared from 2,3,4,9-tetrahydro-1H-carbazol-1-ones
(1a–e) via the intermediate 5,6-dihydro-derivatives (3a–e), and 13H-indolo[3,2-c]acridines (8a–e) from the 1-(N-
phenylamino)carbazoles (7a–e). Methylations of 2 and 8 have been carried out, and UV spectral studies on the title
compounds and the methylated products are presented, along with plausible mechanisms for the formation of the
final compounds.
Keywords: fused acridines, indoles, carbazoles, methylation, Vilsmeier reagent
Nitrogen containing heterocyclic compounds are the key
building blocks used to develop compounds of biological
and medicinal interest to chemists. Among the nitrogen
heterocycles, indole, its benzo-analog carbazole, and acridine
are important structural components in alkaloids and many
pharmaceutical agents,1-15 and also they exhibit a high degree
of biological activity including anti-fungal, anti-bacterial,
anti-tumour, anti-HIV and DNA interactions.16-23 Substituted
indoles have been referred to as “privileged structures” since
they are capable of binding to many receptors with high
affinity.24 Acridine derivatives are well known therapeutic
agents, whose mutagenic properties depend on their ability
to interact with nucleic acids.16,17 We expect therefore the
combination of indole and acridine structures may play a
vital role in biological as well as pharmaceutical systems. In
some cases, specific substitution patterns like indoloacridine
remain difficult to obtain by standard indole-forming or
acridine-forming reactions; thus new methodologies emerge.
The present investigation was aimed to devise a viable
synthetic route to the hitherto unknown title compounds,
the 13H-indolo[3,2-c]acridines, starting from 1-oxo-1,2,3,4-
tetrahydrocarbazoles†25,26 which may show properties of
pharmacological interest.
over silica gel yielded a yellow amorphous solid melting at
156–158°C. Its IR spectrum showed a strong νNH band at 3275
cm-1 and νC=N at 1680 cm-1. The UV absorption spectrum
in methanol showed an extensive pattern of intense bands
peaking between 241 and 339 nm (see Experimental section).
1
Its H NMR spectrum (CDCl3) showed as significant peaks
the carbazole NH proton as a broad singlet at d 10.18, the
aromatic protons as a cluster from d 8.02–6.94, a four proton
multiplet in the region d 2.90–2.54, and a three-proton singlet
at d 2.34 for the CH3 group. The mass spectrum showed
M+ at m/z 360. These spectral details and also the elemental
analysis were in good agreement with the molecular formula
C26H20N2, corresponding to the structure 5,6-dihydro-3-
methyl-7-phenyl-13H-indolo[3,2-c]acridine (3a) and not
the desired 3-methyl-7-phenyl-13H-indolo[3,2-c]acridine
(2a) (Scheme 1). We reported a similar type of reaction of 1
with o-aminoacetophenone that resulted in the formation of
the aromatised product27 in a single step, but in the present
case the aerial oxidation did not take place; instead it led to
the dihydro derivative 3a. Similar compounds (3b–e) were
obtained by repeating the experiment on 1b–e.
To produce the required product 2 we treated 5,6-dihydro-
3-methyl-7-phenyl-13H-indolo[3,2-c]acridine (3a) with 5%
palladised charcoal (Pd/C) in diphenyl ether for 5 h to yield
a dark brown product. This on purification using column
chromatography over silica gel afforded a yellow solid
melting at 162–164°C. Its IR spectrum showed a strong νNH
band at 3422 cm-1, and a νC=N band at 1667 cm-1. The UV
spectrum (see Experimental) was qualitatively similar to that
With the aim to construct indoloacridines we took 1-oxo-
1,2,3,4-tetrahydrocarbazoles (1) as potential precursors and
o-aminobenzophenone as reactant as shown in Scheme 1.
6-Methyl-1-oxo-1,2,3,4-tetrahydrocarbazole (1a) on treatment
with o-aminobenzophenone in glacial acetic acid yielded an
orange solid. This on purification by column chromatography
R1
R1
COC6H5
+
C6H5
R2
N
H
R2
N
H
NH2
R3
N
R3
O
3
1
Pd/C
a : R1=CH3, R2=R3=H
b : R1 =R2 =H, R3 = CH3
c : R1 =R3 =H, R2 = CH3
d : R1 =R2 =R3 = H
1, 2, 3
R1
R2
C6H5
N
H
e : R1 =Cl, R2= R3 =H
R3
N
2
Scheme 1
* Correspondent. E-mail: prasad_125@yahoo.com
† For simplicity, these compounds are named in the text as oxo- and
amino-carbazoles, rather than as carbazolones and carbazolamines.
PAPER: 06/4352

JOURNAL OF CHEMICAL RESEARCH 2007 165
R1
R2
R1
R2
NH2
+
N
H
N
H
R3
O
R3
N
4
1
(i) Ph-N =C=O
(ii) Pd/C
R1
R2
R1
NHPh
(i) EtOH/HCl
N
O
C
H
R3
N
R2
(ii) PPA
(iii) POCl3/C6H5NH2
N
H
NHPh
R3
HN
6
5
1,4,5,6, a-e : R1, R2, R3 as Scheme 1
Scheme 2
of 1a. The 1H NMR was also similar to that of 1a, but for the
4H high-field multiplet, which was lacking, and the methyl
signal, which was shifted to d 2.66. The molecular ion peak
appeared at m/z 358 in the MS. The spectral and analytical
details attest the compound as 3-methyl-7-phenyl-13H-indolo-
[3,2-c]acridine (2a). A series of similar compounds 2b–e was
obtained by dehydrogenating compounds 3b–e.
As part our program to devise new synthetic avenues
to the indoloacridine system, we attempted to prepare
the imine 4, from which the target system 6 can readily be
reached, as shown in Scheme 2. 6-Methyl-1-oxo-1,2,3,4-
tetrahydrocarbazole (1a) was therefore treated with aniline in
the presence of a catalytic amount of p-toluenesulfonic acid to
yield a product which melted at 192–194°C. Its IR spectrum
showed two strong bands at 3388 and 3343 cm-1 from two
N–H groups. Two νC=N bands appeared at 1586 and 1582
cm-1. In the 1H NMR spectrum, apart from the carbazole NH
proton, a broad singlet at d 7.71, and a second NH signal at
d 5.65, and the methyl protons at C6, a 3H singlet at d 2.45, the
remaining signals were all from aromatic protons. The absence
of absorption in the region d 3.25–2.45 clearly demonstrates
that the expected product 6-methyl-1-(N-phenylimino)-
1,2,3,4-tetrahydrocarbazole (4a) was not formed Further, the
appearance of the molecular ion peak at m/z 272 in its MS, and
elemental analysis, agreed well with the molecular formula
C19H16N2. From the spectral and analytical data, the structure
the product was 6-methyl-1-(N-phenylamino)carbazole† (7a)
as shown in Scheme 3 and not 4a as proposed in Scheme 2.
A similar series of compounds was obtained from 1b–e to
form the corresponding derivatives 7b–e. Evidently the 1-
(N-phenylimino)-1,2,3,4-tetrahydrocarbazole (4), formed
in situ from the 1-oxo-1,2,3,4-tetrahydrocarbazole (1) and
aniline, tautomerises to the anilinodihydrocarbazole (4'), and
this on aerial oxidation yields the aromatised product 7.
In order to prepare indoloacridines, 6-methyl-1-(N-
phenylamino)carbazole (7a) was treated with DMF/
POCl3 (Vilsmeier–Haack reagent) in the ratio 3:7 at room
temperature for about 3 h to yield a brown coloured product.
This on purification by column chromatography over silica
gel afforded a yellow solid which melted at 147–149°C. From
the spectral and analytical data, the structure of the product
was inferred to be the expected 3-methyl-13H-indolo[3,2-c]-
acridine (8a). Its IR spectrum showed strong bands at 3417 and
1665 cm-1 (νNH and νC=N respectively). The 1H NMR spectrum
exhibited a one proton singlet at d 8.80 assigned to C7–H. The
indole NH (N13-H) proton appeared as broad singlet at d 8.65,
and C4–H showed as a singlet at d 8.26. A three proton singlet
at d 2.50 was due to C3-CH3, and the remaining proton signals
R1
R2
R1
NH2
R1
+
R2
N
H
N
H
R2
N
R3
HN
R3
N
H
R3
O
4'
4
1
[O]
R1
R2
R1
R2
DMF/POCl3
N
N
H
H
R3
HN
R3
N
1, 4, 7, 8, R1, R2, R3 as Scheme 1
7
8
Scheme 3
PAPER: 06/4352

166 JOURNAL OF CHEMICAL RESEARCH 2007
were all doublets or multiplets. The M+ ion peak at m/z 282
in the MS, and the elemental analysis agreed well with the
molecular formula C20H14N2. The generality of this reaction
was tested with the other carbazoles. A plausible mechanism
for the formation of the products 8 is given in Scheme 4.
The initial step is the formation of ortho N-arylamino-
aldehyde intermediate I from the substrate 7 by electrophilic
ortho formylation reaction, which cyclises to intermediate II.
This on prototropic shift yields the intermediate III which
eliminates water to give compound 8.
respectively. The elemental analysis was in good agreement
with the molecular formula C21H16N2. Based on the above data
we conclude the compound to be 3,13-dimethyl-indolo[3,2-c]-
acridine (11a). The generality of the methylation was tested
with derivative 8b which yielded the corresponding derivative
1,13-dimethylindolo[3,2-c]acridine (11b). Again, from the
UV spectrum we infer that the methylation took place at the
pyrrole N rather than the pyridine N.
In conclusion, syntheses of indoloacridines and their
methylated derivatives were achieved using different synthetic
pathways. It remains to be seen whether the compounds
thus obtained possess applications in medicine as well as in
synthetic chemistry.
Further, our interest turned to methylation of title
compounds 2 in order to discover whether simple methylation
either at the pyrrole N occurs, to afford 9, or whether, after
deprotonation of the pyrrole N, methylation at pyridine N may
result in 10. So we subjected 2a to methylation using methyl
iodide/K2CO3. This yielded a single product which melted at
237–238°C. (Scheme 5). Its IR spectrum showed νC=N at 1651
cm-1 but no νNH band. The UV (see Experimental) was closely
similar to that of the starting material (2a). We concluded
therefore that the methylation had taken place at the pyrrole
N to give 9, rather than at the pyridine N (forming 10).
Furthermore, the 1H NMR spectrum showed a fourteen–proton
multiplet between d 8.10 and 7.17, a three-proton singlet
Experimental
Melting points were determined using a Mettler FP 51 apparatus
(Mettler Instruments, Switzerland). IR spectra were recorded
using KBr discs on a Shimadzu FTIR-8201PC spectrophotometer
(Shimadzu, Japan). UV spectra were recorded in UV spectral grade
methanol using a Perkin-Elmer UV-VIS spectrophotometer. NMR
spectra were recorded in CDCl3 on a Varian AMX 400 FT NMR
(Varian Australia) using TMS as internal standard. Mass spectra were
recorded on JEOL D-300 Mass spectrometer. Micro analyses were
performed on a Vario EL III model CHNS analyser (Vario, Germany)
at the Department of Chemistry, Bharathiar University. The purity
of the products was tested by TLC with plates coated with silica
gel-G with petroleum ether and ethyl acetate (85:15) as developing
solvents.
25
at d 4.20 for N13–CH3 and another at d 2.66 (C3–CH3),
all agreed with the proposed structure as 3,13-dimethyl-
7-phenylindolo[3,2-c]acridine (9a). A similar result was
obtained with the more sterically-hindered derivative 2b,
which yielded the corresponding product 1,13-dimethyl-7-
phenylindolo[3,2-c]acridine (9b).
5,6-Dihydro-7-phenyl-13H-indolo[3,2-c]acridines (3a–e), general
procedure
The appropriate 1-oxo-1,2,3,4–tetrahydrocarbazole (1, 5 mmol)
and o-aminobenzophenone (0.985 g, 5 mmol) was refluxed for 8 h
in glacial acetic acid (4 ml) containing one drop of sulfuric acid.
The reaction was monitored by TLC. After the completion of the
reaction, it was poured into crushed ice, extracted with chloroform,
and the organic layer dried (Na2SO4). The crude product obtained
on removal of the solvent was purified by column chromatography
over silica gel using pet. ether:ethyl acetate (98:5) to yield the 5,6-
dihydro-7-phenyl-13H-indolo[3,2-c]acridine (3).
We methylated 8a (Scheme 5) under the same reaction
conditions, to yield a single product 11a or 12a which melted
at 291–294°C. Its IR spectrum showed νC=N at 1653 cm-1 and
absence of νNH. The possible structure 12a was ruled out on
the basis of the UV spectrum, which showed no major change
from that of 8a. Its 1H NMR spectrum exhibited the following
peaks: a singlet at d 8.82 (C7-H), A nine-proton multiplet at d
8.40–7.30 for aromatic protons, and two three-proton singlets
at d 3.80 and 2.59 accounted for N13–CH3 and C3–CH3
5,6-Dihydro-3-methyl-7-phenyl-13H-indolo[3,2-c]acridine (3a):
Yellow amorphous solid (1.12 g, 62%), m.p.156–158°C. IR: νmax
R1
R1
R1
N
C
N
N
- Cl
R2
N
H
R2
R2
N
H
N
H
CH
CH
Cl
Cl
H
R3
R3
HN
H
R3
HN
H
HN
7
R1
R1
R1
H
H
H
R2
N
H
R2
N
H
R2
N
CHO
H
C
O
H
O
R3
R3
HN
R3
HN
HN
II
I
Prototropic shift
R1
R1
-H2O
H
7, 8a-e: R1- R3 as Scheme 1
H
OH
R2
N
R2
N
H
H
R3
N
R3
N
III
8
A plausible mechanism for the formation of 8a-e from 7a-e
Scheme 4
PAPER: 06/4352

JOURNAL OF CHEMICAL RESEARCH 2007 167
1
1
1
2
R
R
R
4
CH I
4
4
3
R
R
R
2
2
N
H
R
N
R
N
R
K CO /acetone
2
3
3
3
3
R
N
R
CH
N
R
N
3
H C
3
9,11
,
2,8
10 12
1
2
3
4
1
2
3
4
2, 9, 10 a: R = CH , R = R = H, R = C H
8, 11, 12 a: R = CH , R = R = R = H
3
6
5
3
1
2
3
4
1
3
4
2
b: R = R = H, R = CH , R = C H
b: R = R = R = H, R = CH
3
6 5
3
Scheme 5
3275, 2980, 2895, 1680, 1581, 1441, 801 cm-1. UV: λmax (log ε) 241
2H, C2–, C1–H), 2.97–2.85 (m, 4H, C6–2H, C5–2H). 13C NMR: d
159.8 (C12a), 153.4 (C7), 151.8 (C11a), 134.9 (C1'), 130.9 (C13a), 129.5
(C12b), 128.5 (C6'), 128.9 (C4'), 128.4 (C6a), 128.1 (C3'), 127.9 (C10),
127.7 (C5'), 127.4 (C11), 126.5 (C2'), 126.1 (C4a), 125.7 (C9), 125.6
(C3), 124.4 (C8), 121.5 (C4), 120.3 (C2), 120.0 (C7a), 119.5 (C1), 112.4
(C4b), 30.1 (C5), 30.0 (C6). MS: m/z (%) 382/380 (M+, 14/46), 303
(16), 269 (32), 244 (17), 219 (27), 194 (37), 181 (20), 168 (13), 91
(15). Anal. Calc. for C25H17ClN2: C, 78.84; H, 4.50; N, 7.35. Found:
C, 78.78; H, 4.56, N, 7.33%.
7-Phenyl-13H-indolo[3,2-c]acridines (2a–e), general procedure
The appropriate 5,6-dihydro-7-phenyl-13H-indolo[3,2-c]acridine (3,
1 mmol) and Pd/C (0.050 g) was refluxed in diphenyl ether (3 ml) for
about 5 h. The reaction was monitored by TLC. It was then filtered
through Whatman-41 filter paper to remove Pd/C. After removal of
solvent the mixture was poured into crushed ice, extracted with ethyl
acetate, and dried (Na2SO4). The crude product obtained by removal
of solvent was purified by column chromatography over silica gel
using pet. ether: ethyl acetate (98:2) to yield the corresponding
7-phenyl-13H-indolo[3,2-c]acridine (2).
(4.23), 248 (4.89), 282 (3.85), 294 (4.95), 310 (3.97), 326 (3.94), 339
1
nm (3.92). H NMR: d 10.18 (b s, 1H, N13–H), 8.02–7.15 (m, 10H,
C11–, C10–, C9–, C8–, C4–, C2'–, C3'–, C4'–, C5'–, C6'–H), 7.10–6.94
(m, 2H, C2–, C4–H), 2.90–2.54 (m, 4H, C6–2H, C5–2H), 2.34 (s, 3H,
C3–CH3). 13C NMR: d 158.3 (C12a), 151.4 (C7), 150.5 (C11a), 136.1
(C1'), 131.4 (C13a), 129.6 (C12b), 128.7 (C3'), 128.4 (C10), 128.1 (C6'),
128.0 (C4'), 127.9 (C5'), 127.7 (C11), 127.6 (C6a), 126.9 (C3), 126.6
(C2'), 125.9 (C9), 125.5 (C4a), 124.3 (C8), 120.6 (C4), 120.6 (C7a),
120.4 (C2), 112.2 (C4b), 109.5 (C1), 29.3 (C6), 28.4 (C3–CH3), 27.4
(C5). MS: m/z (%) 360 (M+, 67), 283 (44), 269 (20), 218 (14), 181
(27), 168 (24), 143 (11), 114 (19), 77 (16). Anal. Calc. for C26H20N2:
C, 86.64; H, 5.59; N, 7.77. Found: C, 86.60; H, 5.45; N, 7.62%.
5,6-Dihydro-1-methyl-7-phenyl-13H-indolo[3,2-c]acridine (3b):
Spongy yellow solid (1.15 g, 64%), m.p. 268–270°C. IR: νmax 3461,
2962, 2923, 1672, 1547, 801 cm–1. UV: λmax (log ε) 226 (4.61), 248
(4.68), 285 (3.93), 295 (4.16), 310 (3.97), 333 (3.71), 346 nm (3.67).
1H NMR: d 8.68 (b s, 1H, N13–H), 7.68–7.06 (m, 10H, C11–, C10–,
C9–, C8–, C3–, C2'–, C3'–, C4'–, C5'–, C6'–H), 7.00–6.94 (m, 2H, C4–,
C2–H), 2.90–2.54 (m, 4H, C6–2H, C5–2H), 2.41 (s, 3H, C1–CH3).
13C NMR: d 156.3 (C12a), 152.0 (C7), 149.3 (C11a), 136.2 (C1'), 131.4
(C13a), 129.1 (C12b), 128.7 (C3'), 128.5 (C6'), 128.4 (C10), 127.9 (C4'),
127.9 (C11), 127.6 (C5'), 127.4 (C6a), 126.1 (C2'), 125.9 (C9), 125.2
(C4a), 124.3 (C8), 122.4 (C3), 122.3 (C1), 121.3 (C2), 120.9 (C4),
120.5 (C7a), 112.2 (C4b), 29.3 (C6), 27.6 (C5), 24.3 (C1–CH3). MS:
m/z (%) M+ 360 (57), 283 (39), 269 (24), 218 (19), 181 (17), 168
(28), 143 (17), 114 (22), 77 (10). Anal. Calc. for C26H20N2: C, 86.64;
H, 5.59; N, 7.77. Found: C, 86.57; H, 5.58; N, 7.71%.
3-Methyl-7-phenyl-13H-indolo[3,2-c]acridine (2a): Pale yellow
solid (0.23 g, 64%), m.p. 162–164°C. IR: νmax 3422, 2965, 2783,
1667, 1589, 743 cm–1. UV: λmax (log ε) 255 (4.89), 263 (4.34), 270
1
(3.86), 290 (4.82), 304 (3.66), 320 (3.87), 334 nm (3.84). H NMR:
d 10.13 (b s, 1H, N13–H), 8.34–7.35 (m, 14H, C11–, C10–, C9–, C8–,
C6–, C5–, C4–, C2–, C1–, C2'–, C3'–, C4'–, C5'–, and C6'–H), 2.66
(s, 3H, C3–CH3). 13C NMR: d 150.5 (C12a), 147.4 (C11a), 139.5 (C1'),
138.2 (C7), 133.5 (C4'), 132.5 (C5'), 131.6 (C3'), 130.4 (C11), 130.3
(C2'), 130.1 (C4b), 129.7 (C6'), 129.6 (C10), 129.4 (C6), 128.8 (C9),
128.4 (C8), 127.6 (C12b), 127.1 (C5), 125.3 (C13a), 125.1 (C2), 124.6
(C3), 123.6 (C7a), 121.1 (C4), 118.1 (C6a), 113.4 (C1), 111.2 (C4a) and
25.0 (C3–CH3). MS: m/z (%) 358 (M+, 49), 281 (23), 267(31), 197
(27), 166 (17), 116 (28), 77 (17). Anal. Calc. for C26H18N2: C, 87.12;
H, 5.06; N, 7.82. Found: C, 87.09; H, 5.04; N, 7.80%.
5,6-Dihydro-2-methyl-7-phenyl-13H-indolo[3,2-c]acridine (3c):
Yellow amorphous solid (1.04 g, 58%), m.p. 138–141°C. IR: νmax
3431, 2962, 2360, 1679, 1579, 1443, 800 cm–1. UV: λmax (log ε) 238
(4.64), 250 (4.85), 282 (3.87), 296 (4.05), 307 (3.98), 328 (3.59), 339
1
nm (3.54). H NMR: d 10.07 (b s, 1H, N13–H), 8.03–6.92 (m, 10H,
C11–, C10–, C9–, C8–, C1–, C2'–, C3'–, C4'–, C5'–, C6'–H), 6.84–6.67
(m, 2H, C4–, C3–H), 2.83–2.52 (m, 4H, C6–2H, C5–2H), 2.32 (s, 3H,
C2–CH3). 13C NMR: d 155.8 (C12a), 150.4 (C7), 150.1 (C11a), 135.6
(C1'), 131.0 (C13a), 129.4 (C12b), 128.7 (C6'), 128.3 (C10), 128.2 (C3'),
128.1 (C4'), 127.9(C6a), 127.6 (C11), 127.1 (C5'), 125.9 (C2'), 125.4
(C9), 125.0 (C4a), 123.9 (C8), 121.4 (C3), 120.9 (C2), 120.6 (C4),
119.9 (C7a), 111.9 (C4b), 109.9 (C1), 29.4 (C6), 28.0 (C5), 26.2 (C2–
CH3). MS: m/z (%) 360 (M+, 61), 283 (34), 269 (27), 218 (11), 181
(26), 168 (20), 143 (19), 114 (11), 77 (16). Anal. Calc. for C26H20N2:
C, 86.64; H, 5.59; N, 7.77. Found: C, 86.39; H, 5.63; N, 7.81%.
5,6-Dihydro-7-phenyl-13H-indolo[3,2-c]acridine (3d): Yellow
amorphous solid (1.07 g, 62%), m.p. >300°C. IR: νmax 3413, 2922,
2360, 1689, 1548 cm–1. UV: λmax (log ε) 229 (4.44), 243 (4.62),
250 (4.46), 261 (4.34), 295 (4.21), 306 (3.96), 322 (3.94), 335 nm
(3.92). 1H NMR: d 12.30 (b s, 1H, N13–H), 8.57–6.96 (m, 13H, C11–,
C10–, C9–, C8–, C4–, C3–, C2–, C1–, C2'–, C3'–, C4'–, C5'–, C6'–H),
3.08–2.93 (m, 4H, C6–2H, C5–2H). 13C NMR: d 157.2 (C12a), 151.1
(C7), 150.4 (C11a), 136.9 (C1'), 131.5 (C13a), 129.9 (C12b), 128.9 (C10),
128.4 (C4'), 128.3 (C3'), 128.2 (C5'), 128.0 (C11), 127.9 (C6'), 127.6
(C6a), 126.5 (C2'), 125.3 (C4a), 124.9 (C9), 124.2 (C3), 124.1 (C8),
123.0 (C2), 120.9 (C4), 120.5 (C7a), 111.9 (C4a), 111.5 (C1), 29.4 (C6),
27.4 (C5). MS: m/z (%) 346 (M+, 44), 269 (57), 219 (16), 197(21),
181 (23), 143 (11), 114 (16), 77 (12). Anal. Calc. for C25H18N2: C,
86.68; H, 5.24; N, 8.08. Found: C, 86.51; H, 5.19; N, 8.03%.
1-Methyl-7-phenyl-13H-indolo[3,2-c]acridine
(2b):
Yellow
spongy mass (0.243 g, 68%), m.p. >300°C. IR: νmax 3276, 2922,
2358, 1672, 746 cm–1. UV, λmax (log ε) 265 (4.71), 254 (4.34), 239
(4.84), 244 (4.13), 264 (3.89), 288 (4.04), 302 (3.45) 341 (3.14), 352
(3.15), 347 (3.84). 1H NMR: d 10.14 (b s, 1H, N13–H), 8.72–7.03 (m,
14H, C11–, C10–, C9–, C8–, C6–, C5–, C4–, C3–, C2–, C2'–, C3'–, C4'–,
C5'–, and C6'–H), 2.47 (s, 3H, C1–CH3). 13C NMR: d 150.4 (C12a),
147.4(C11a), 138.5 (C1'), 137.9 (C7), 133.4 (C4'), 131.5 (C3'), 131.0
(C4b), 130.9 (C5'), 130.1 (C2'), 129.5 (C10), 129.1 (C11), 128.8 (C6),
128.4 (C6'), 128.3 (C8), 127.9 (C9), 127.6 (C5), 126.9 (C12b), 125.5
(C13a), 124.1 (C3), 123.4 (C7a), 120.1 (C2), 118.9 (C1), 118.5 (C4),
117.9 (C6a), 110.9 (C4a), 21.6 (C1–CH3). MS: m/z (%) 358 (M+, 51),
281 (20), 267(28), 197 (30), 166 (15), 116 (21), 77 (14). Anal. Calc.
for C26H18N2: C, 87.12; H, 5.06; N, 7.82. Found: C, 87.15; H, 5.00;
N, 7.77%.
2-Methyl-7-phenyl-13H-indolo[3,2-c]acridine
(2c):
Yellow
amorphous solid (0.215 g, 60%), m.p. 228–230°C. IR: νmax 3417,
2781, 2359, 1665, 743 cm–1. UV: λmax (log ε) 267 (4.74), 254 (4.36),
240 (4.27), 250 (4.13), 266 (3.84), 291 (4.46), 309 (3.56) 326 (3.84),
334 (3.14), 346 nm (3.88). 1H NMR: d 10.80 (b s, 1H, N13–H), 8.35–
6.98 (m, 14H, C11–, C10–, C9–, C8–, C6–, C5–, C4–, C3–, C1–, C2'–,
C3'–, C4'–, C5'–, and C6'–H), 2.46 (s, 3H, C2–CH3). 13C NMR: d 149.9
(C12a), 147.5 (C11a), 139.4 (C1'), 138.5 (C7), 133.6 (C4'), 131.9 (C5'),
131.5 (C3'), 130.5 (C11), 129.9 (C4b), 129.4 (C2'), 129.1 (C6'), 128.9
(C10), 128.7 (C6), 128.5 (C9), 128.1 (C8), 127.6 (C12b), 127.1 (C5),
126.2 (C2), 124.9 (C13a), 122.9 (C7a), 121.5 (C3), 120.6 (C4), 118.5
(C6a), 115.4 (C1), 111.5 (C4a), 27.7 (C2–CH3). MS: m/z (%) 358 (M+,
40), 281 (19), 267(33), 197 (29), 166 (14), 116 (24), 77 (10). Anal.
Calc. for C26H18N2: C, 87.12; H, 5.06, N, 7.82. Found: C, 86.95; H,
5.10; N, 7.76%.
3-Chloro-5,6-dihydro-7-phenyl-13H-indolo[3,2-c]acridine (3e):
Greenish yellow solid (1.20 g, 63%), m.p. >300°C. IR: νmax 3434,
2962, 2923, 2360, 1668, 1463, 801 cm–1. UV: λmax (log ε) 229 (4.65),
251 (4.69), 288 (3.96), 298 (4.18), 318 (3.99), 338 (3.74), 354 nm
(3.70). 1H NMR: d 10.58 (b s, 1H, N13–H), 8.01–7.20 (m, 10H, C11–,
C10–, C9–, C8–, C4–, C2'–, C3'–, C4'–, C5'–, C6'–H), 7.12–7.04 (m,
PAPER: 06/4352

168 JOURNAL OF CHEMICAL RESEARCH 2007
7-Phenyl-13H-indolo[3,2-c]acridine (2d): Yellow amorphous solid
(0.206 g, 60%), m.p. >300°C. IR: νmax 3415, 2783, 2359, 1668, 1592,
746 cm–1. UV, λmax (log ε) 265 (4.65), 250 (4.14), 242 (4.77), 254
(4.34), 260 (3.46), 291 (3.87), 330 (3.84), 340 nm (3.94).1H NMR:
d 11.30 (b s, 1H, N13–H), 8.28–7.23 (m, 15H, C11–, C10–, C9–, C8–,
1-(N-phenylamino)carbazole(7d):Dirtywhitesolid(0.541g, 42%);
m.p. 143–145°C. IR: νmax 3392, 3365, 3033, 2841, 1599, 1579, 1404,
755 cm–1. 1H NMR: d 8.12–8.08 (m, 2H, C2–, C4–H), 7.92 (b s, 1H,
N9–H), 7.31–7.18 (m, 7H, C5–, C6–, C7–, C8–, C3'–, C4'–, C5'–H),
6.90–6.74 (m, 3H, C3–, C2'–, C6'–H), 5.78 (br. s, 1H, C1–NH). 13C
NMR: d 138.5 (C1'), 134.7 (C9a), 130.2 (C4a), 129.2 (C3'), 128.1 (C5'),
125.6 (C6), 125.2 (C1), 121.9 (C8a), 120.9 (C3), 118.9 (C6'), 118.5
(C5), 117.3 (C2'), 116.9 (C4'), 114.9 (C7), 111.8 (C2), 111.5 (C8), 107.0
(C5a), 104.7 (C4). MS: m/z (%) 258 (M+, 100), 205 (11), 195 (18), 180
(17), 167 (11), 151 (10), 128 (24), 77 (9). Anal. Calc. for C18H14N2:
C, 83.69; H, 5.46; N, 10.84. Found: C, 83.68; H, 5.48; N, 10.88%.
6-Chloro-1-(N-phenylamino)carbazole (7e): Dirty white solid
(0.584 g, 40%); m.p. 152–154°C. IR: νmax 3408, 3361, 2923, 2854,
1601, 1589, 1499, 748 cm–1. 1H NMR: d 8.04 (b s, 1H, N9–H),
7.96–7.84 (m, 2H, C2–, C4–H), 7.38–7.20 (m, 6H, C5–, C7–, C8–,
C2'–, C4'–, C5'–H), 6.93–6.74 (m, 3H, C3–, C2'–, C6'–H), 5.60 (b s,
1H, C1–NH). 13C NMR: d 136.1 (C1'), 135.9 (C9a), 129.4 (C4a), 129.3
(C6), 128.1 (C3'), 126.8 (C5'), 125.8 (C1), 123.1 (C8a), 120.4 (C3),
119.0 (C5), 117.9 (C6'), 117.7 (C4'), 117.5 (C2'), 114.8 (C7), 112.3
(C2), 110.2 (C8), 107.2 (C4), 106.2 (C5a). MS: m/z (%) 294/292 (M+,
17/57), 205 (15), 195 (21), 181 (17), 169 (13), 152 (19), 128 (16), 77
(8). Anal. Calc. for C18H13ClN2: C, 73.85; H, 4.48; N, 9.56. Found:
C, 73.81; H, 4.51; N, 9.50%.
C6–, C5–, C4–, C3–, C2–, C1–, C2'–, C3'–, C4'–, C5'–, and C6'–H). 13
C
NMR: d, CDCl3 150.9 (C12a), 148.0 (C11a), 139.4 (C1'), 138.2 (C7),
133.5 (C4'), 131.4 (C5'), 130.9 (C3'), 130.5 (C4b), 130.2 (C2'), 129.9
(C2), 129.8 (C6), 129.6 (C6'), 129.3 (C10), 128.2 (C9), 127.9 (C8),
127.3 (C5), 127.1 (C12b), 125.6 (C13a), 124.3 (C3), 123.6 (C7a), 121.3
(C2), 119.4 (C4), 118.3 (C6a), 112.4 (C1), 111.3 (C4a). MS: m/z (%)
344 (M+, 42), 343 (16), 267 (31), 197 (27), 166 (17), 116 (28), 77
(17). Anal. Calc. for C25H16N2: C, 87.18; H, 4.68; N, 8.13. Found: C,
87.15; H, 4.68; N, 8.12%.
3-Chloro-7-phenyl-13H-indolo[3,2-c]acridine (2e): Pale yellow
powder (0.234 g, 62%), m.p. 178–180°C. IR: νmax 3415, 2783, 2359,
1668, 1590, 1492, 746 cm–1. UV, λmax (log ε) 265 (4.65), 251 (4.34),
244 (4.84), 257 (4.18), 267 (3.76), 284 (4.04), 331 (3.80), 341 nm
(3.24). 1H NMR: d 10.40 (b s, 1H, N13–H), 6.98–8.25 (m, 14H, C11–,
C10–, C9–, C8–, C6–, C5–, C4–, C2–, C1–, C2'–, C3'–, C4'–, C5'–, and
C6'–H). 13C NMR: d 151.7 (C12a), 147.5 (C11a), 139.3 (C1'), 138.5
(C7), 133.1 (C4'), 132.4 (C5'), 131.5 (C3'), 130.3 (C11), 130.1 (C4b),
129.9 (C2'), 129.5 (C6), 129.4 (C6'), 129.0 (C9), 128.9 (C10), 128.0
(C8), 127.4 (C5), 127.3 (C12b), 124.9 (C13a), 123.5 (C7a), 121.0 (C3),
120.9 (C4), 118.0 (C6a), 117.6 (C2), 116.5 (C1), 110.4 (C4a). MS: m/z
(%) 380/378 (M+, 21/61), 343 (17), 267 (28), 216 (23), 201 (12), 161
(9), 116 (21), 77 (13). Anal. Calc. for C25H15ClN2: C, 79.26; H, 3.99;
N, 7.39. Found: C, 78.98; H, 4.05; N, 7.40%.
13H-indolo[3,2-c]acridine (8a–e), general procedure
A 1-(N-phenylamino)carbazole (7, 1 mmol) was taken up in DMF
(1.8 ml) and POCl3 (4.2 ml) and kept at room temperature for 4 h. The
reaction was monitored by TLC. After completion of the reaction the
mixture was poured into crushed ice and extracted with chloroform.
The organic solution was dried (Na2SO4). Removal of solvent gave
a crude residue which was purified by column chromatography over
silica gel, eluting with chloroform:methanol (98:2), to yield the
corresponding 13H-indolo[3,2-c]acridine (8).
3-Methyl-13H-indolo[3,2-c]acridine (8a): Yellow amorphous solid
(93 mg, 33%), m.p. 147–149°C. IR: νmax 3417, 2930, 2781, 1665,
738 cm–1. UV: λmax (log ε) 225 (4.50), 247 (4.84), 285 (3.85), 296
(4.10), 313 (3.97), 328 (3.93), 338 nm (3.94). 1H NMR: d 8.80 (s, 1H,
C7–H), 8.65 (s, 1H, N13–H), 8.26 (s, 1H, C4–H), 8.08–7.05 (m, 8H,
C11–, C10–, C9–, C8–, C6–, C5–, C2–, C1–H), 2.50 (s, 3H, C3–CH3).
13C NMR: d 162.6 (C12a), 161.5 (C11a), 134.5 (C7), 129.9 (C11), 129.3
(C10), 128.9 (C3), 128.0 (C9), 127.8 (C8), 126.4 (C6), 125.9 (C4b),
125.3 (C7a), 124.7 (C5), 124.4 (C12b), 124.3 (C4), 120.3 (C6a), 119.5
(C13a), 116.4 (C2), 111.1 (C1), 110.9 (C4a) and 29.7 (C3–CH3). MS:
m/z (%) 282 (M+, 65), 271 (23), 267 (17), 225 (19), 211 (28), 197
(21), 181 (12), 157 (21) 143 (18), 130 (19), 115 (15), 77 (12). Anal.
Calc. for C20H14N2: C, 85.08; H, 5.00, N, 9.92. Found: C: 84.98, H:
5.09, N: 9.84%.
1-(N-phenylamino)carbazoles (7a–e), general procedure
To the appropriate 1-oxo-1,2,3,4-tetrahydrocarbazole (1, 5 mmol)
and aniline (5 mmol) in dry o-xylene (20 ml) was added a catalytic
amount of p-toluenesulfonic acid, and the whole was refluxed for
10 h in an oil bath at 160°C. The reaction was monitored by TLC.
After the completion of the reaction the solvent was removed.
The residue was poured into crushed ice, neutralised with dil.
HCl, extracted with ethyl acetate and the extracts dried (Na2SO4).
The crude product was purified by column chromatography
over silica gel using pet.ether: ethyl acetate (98:2) to yield the 1-
(N-phenylamino)carbazole.
6-Methyl-1-(N-phenylamino)carbazole (7a): White crystalline
material (0.6 g, 44%); m.p. 192–194°C. IR: νmax 3388, 3343, 2923,
1
2855, 1586, 1582, 1458, 798 cm–1. H NMR: d 7.83–7.79 (m, 2H,
C2–, C4–H), 7.71 (b s, 1H, N9–H), 7.23–7.12 (m, 6H, C5–, C7–, C8–,
C3'–, C4'–, C5'–H), 6.82–6.75 (m, 1H, C3–H), 6.69–6.64 (d, 2H, C2'–,
C6'–H, J = 7.60 Hz), 5.65 (b s, 1H, C1–NH), 2.45 (s, 3H, C6–CH3).
13C NMR: d, CDCl3 d, 137.5 (C1'), 135.0 (C9a), 129.4 (C4a), 128.9
(C3'), 127.3 (C5'), 125.6 (C6), 124.8 (C1), 122.4 (C8a) 119.8 (C3),
119.6 (C5), 118.9 (C6') 118.5 (C2'), 117.0 (C4'), 115.2 (C7), 112.4 (C2),
110.5 (C8), 106.9 (C4), 106.1 (C5a), and 24.1 (C6–CH3). MS: m/z (%),
M+ 272 (100), 256 (46), 205 (11), 195 (18), 180 (17), 168 (11), 152
(10), 128 (24), 77 (8). Anal. Calc. for C19H16N2: C, 83.79; H, 5.92;
N, 10.28. Found: C, 83.70; H, 5.83; N, 10.21%.
1-Methyl-13H-indolo[3,2-c]acridine (8b): Yellow amorphous solid
(0.127 g, 45%), m.p. 174–176°C. IR: νmax 3276, 2922, 2358, 1672,
746 cm–1. UV: λmax (log ε) 229 (4.68), 254 (4.70) 288 (3.94), 299
1
(4.18), 318 (3.99), 338 (3.78), 349 nm (3.69). H NMR: d 8.79 (s,
1H, C7–H), 8.68 (b s, 1H, N13–H), 8.10–7.00 (m, 9H, C11–, C10–, C9–
, C8–, C6–, C5–, C4–, C3–, C2–H), 2.33 (s, 3H, C1–CH3). 13C NMR: d
161.9 (C12a), 161.5 (C11a), 134.5 (C7), 129.8 (C11), 129.3 (C10), 128.0
(C9), 127.8 (C8), 126.4 (C6), 125.9 (C4b), 125.3 (C7a), 124.4 (C5),
124.3 (C4), 123.3 (C12b), 122.5 (C3), 120.9 (C4a), 120.3 (C6a), 120.1
(C13a), 118.4 (C2), 111.2 (C1), 23.7 (C1–CH3). MS: m/z (%) 282 (M+,
41), 271 (23), 267 (17), 225 (19), 211 (28), 197 (21), 181 (12), 141
(18), 128(9), 115 (15), 77 (7). Anal. Calc. for C20H14N2: C, 85.08; H,
5.00; N, 9.92. Found: C, 85.06; H, 5.03; N, 10.11%.
8-Methyl-1-(N-phenylamino)carbazole (7b): White spongy mass
(0.612 g, 45%); m.p. 161–163°C. IR: νmax 3417, 3365, 3053, 2924,
1
1603, 1582, 1445, 746 cm–1. H NMR: d 8.09–8.05 (d, 1H, C5–H,
J = 7.76), 7.97–7.85 (m, 2H, C2–, C4–H), 7.77 (b s, 1H, N9–H),
7.42–7.32 (m, 5H, C6–, C7–, C3'–, C4'–, C5'–H), 6.90–6.73 (m, 3H,
C3–, C2'–, C6'–H), 5.69 (br s, 1H, C1–NH), 2.45 (s, 3H, C8–CH3).
13C NMR: d 137.1 (C1'), 134.8 (C9a), 129.2 (C4a), 129.1 (C3'), 127.3
(C5'), 126.0 (C6), 125.2 (C1), 121.3 (C8a), 120.1 (C3), 119.1 (C5),
118.2 (C6'), 117.1 (C2'), 116.9 (C4'), 115.9 (C7), 112.9 (C2), 110.9
(C8), 107.1 (C4), 106.7 (C5a), 20.4 (C8–CH3). MS: m/z (%), 272 (M+,
100), 256 (41), 205 (19), 195 (19), 180 (11), 168 (19), 152 (17), 128
(30), 77 (14). Anal. Calc. for C19H16N2: C, 83.79; H, 5.92; N, 10.28.
Found: C, 83.53; H, 5.89; N, 10.21%.
2-Methyl-13H-indolo[3,2-c]acridine (8c): Yellow amorphous
solid (0.113 g, 40%), m.p. 104–105°C. IR: νmax 3422, 2965, 2359,
1667, 743 cm–1. UV: λmax (log ε) 238 (4.64), 250 (4.85), 282 (3.87),
1
296 (4.05), 307 (3.98), 328 (3.59), 339 nm (3.54). H NMR: d 8.73
(s, 1H, C7–H), 8.61 (b s, 1H, N13–H), 8.31 (s, 1H, C4–H), 8.18–6.65
(m, 8H, C11–, C10–, C9–, C8–, C6–, C5–, C3–, C1–H), 2.45 (s, 3H, C2–
CH3). 13C NMR: d 162.0 (C12a), 161.9 (C11a), 133.3 (C7), 130.2 (C11),
129.5 (C10), 127.4 (C9), 127.1 (C8), 126.4(C7a), 126.3 (C6), 125.8
(C4b), 125.4 (C2), 125.1 (C5), 124.1 (C12b), 123.1 (C3), 121.1 (C6a),
120.2 (C4), 120.0 (C13a), 112.1 (C1), 111.2 (C4a), 27.1 (C2–CH3).
MS: m/z (%) 282 (M+, 58), 271 (26), 267 (24), 225 (12), 211 (34),
197 (27), 181 (12), 141 (17), 128 (10), 115 (15), 77 (8). Anal. Calc.
for C20H14N2: C, 85.08; H, 5.00; N, 9.92. Found: C, 85.08; H, 4.98;
N, 9.89%.
7-Methyl-1-(N-phenylamino)carbazole (7c): Dirty white powder
(0.6 g, 44%), m.p. 172–173°C. IR: νmax 3410, 3363, 3046, 2922,
1
1600, 1404, 798 cm–1. H NMR: d 7.98–7.83 (m, 2H, C2–, C4–H),
7.79 (b s, 1H, N9–H), 7.28–7.14 (m, 6H, C5–, C6–, C8–, C3'–, C4'–,
C5'–H), 6.84–6.74 (m, 3H, C3–, C2'–, C6'–H), 5.75 (b s, 1H, C1–NH),
2.51 (s, 3H, C7–CH3). 13C NMR: d 137.6 (C1'), 134.9 (C9a), 129.2
(C3'), 128.9 (C4a), 128.1 (C5'), 124.1 (C1), 123.8 (C7), 122.9 (C8a),
119.8 (C6), 119.5 (C3), 119.2 (C5), 118.3 (C6'), 118.1 (C4'), 117.9
(C2'), 111.9 (C2), 111.5 (C8), 107.2 (C4), 106.5 (C5a), 24.9 (C7–CH3).
MS: m/z (%) 272 (M+, 100), 256 (42), 205 (17), 197 (21), 180 (19),
168 (16), 152 (14), 128 (24), 77 (10). Anal. Calc. for C19H16N2: C,
83.79; H, 5.92; N, 10.28. Found: C, 83.74; H, 5.83; N, 10.24%.
13H-Indolo[3,2-c]acridine (8d): Yellow amorphous solid, (0.105
g, 39%), m.p. 155–156°C. IR: νmax 3413, 2359, 1668, 1492, 746
cm–1. UV, λmax (log ε) 222 (4.43), 246 (4.65), 250 (4.48), 261 (4.32),
1
298 (4.26), 318 (3.99), 325 (3.96), 336 nm (3.96). H NMR: d 8.86
(s, 1H, C7–H), 8.69 (s, 1H, N13–H), 8.38–7.10 (m, 10H, C11–, C10–,
PAPER: 06/4352

JOURNAL OF CHEMICAL RESEARCH 2007 169
C9–, C8–, C6–, C5–, C4–, C3–, C2–, C1–H). 13C NMR: d 162.1 (C12a),
161.1 (C11a), 133.9 (C7), 129.5 (C11), 129.3 (C10), 127.9 (C9), 127.8
(C8), 126.1 (C4b), 125.8 (C6), 125.3 (C7a), 125.1 (C12b), 124.9 (C5),
124.4 (C3), 122.3 (C2), 120.3 (C6a), 119.6 (C13a), 119.4 (C4), 110.8
(C4a), 109.6 (C1). MS: m/z (%) 268 (M+, 60), 267 (17), 225 (12), 211
(21), 197 (32), 141 (12), 128 (9), 115 (15), 77 (7). Anal. Calc. for
C19H12N2: C, 85.05; H, 4.51; N, 10.44. Found: C, 85.01; H, 4.49;
N, 10.45%.
C5–, C4–, C2–, C1–H), 3.73 (s, 3H, N13–CH3) 2.63 (s, 3H, C1–CH3).
Anal. Calc. for C21H16N2: C: 85.10, H: 5.42, N: 9.37. Found:
C: 84.94, H: 5.40, N: 9.29%.
We acknowledge the award of Major Research Project
Grant No.F.No.31-122/2005 from UGC, New Delhi, India.
M.S. thanks UGC, New Delhi for the award of a research
fellowship. Our sincere thanks are due to the Director,
ISO Quality Assurance Cell, IICT, Hyderabad and
The Chairman, NMR Research Centre, IISc, Bangalore,
for providing mass and NMR spectra respectively.
3-Chloro-13H-indolo[3,2-c]acridine (8e): Yellow amorphous solid
(0.127 g, 42%), m.p. 164–167°C. IR: νmax 3415, 2783, 2359, 1668,
1022, 748 cm–1. UV, λmax (log ε) 231 (4.61), 258 (4.72), 290 (3.96),
1
299 (4.18), 320 (4.01), 339 (3.75), 358 nm (3.72). H NMR: d 8.83
(s, 1H, C7–H), 8.73 (s, 1H, N13–H), 8.00–7.04 (m, 9H, C11–, C10–,
C9–, C8–, C6–, C5–, C4–, C2–, C1–H). 13C NMR: d 162.0 (C12a), 159.5
(C11a), 134.5 (C7), 129.3 (C10), 129.1 (C11), 128.6 (C3), 128.0 (C9),
128.1 (C8), 126.5 (C6), 125.8 (C4b), 125.3 (C7a), 124.5 (C12b), 124.4
(C5), 121.6 (C4), 121.1 (C6a), 120.0 (C13a), 111.4 (C2), 110.8 (C4a),
109.5 (C12). MS: m/z (%) 304/302 (M+, 19/58), 267 (21), 256 (13),
195 (21), 180 (12), 168 (13), 152 (19), 128 (16), 77 (8). Anal. Calc.
for C19H11ClN2: C, 75.38; H, 3.66; N, 9.25. Found: C, 75.19; H, 3.69;
N, 9.23%.
Received 11 December 2006; accepted 7 March 2007
Paper 06/4352 doi: 10.3184/030823407X198410
References
1
2
G.R. Humphrey and J.T. Kuethe, Chem. Rev., 2006, 106, 2875.
P. Bhattacharya and D.P. Chakraborty, Progress in the Chemistry of
Organic Natural Products, W. Herz, H. Grisebach, G.W. Kirby and
C. Tamm, eds, Springer Verlag, Wien, 1987, Vol. 52, pp 299-371.
D.P. Chakraborty and S. Roy, Progress in the Chemistry of Organic
Natural Products, W. Herz, H Grisebach, G.W. Kirby and C. Tamm, eds,
Springer Verlag, Wien, 1991, 57, 71.
3
Methylation of indolo[3,2-c]acridines (2 and 8), general procedure
A mixture of the 13H-indolo[3,2-c]acridine (1 mmol) methyl iodide
(2 ml, 0.03 mol) and ignited potassium carbonate (0.55 g) in dry
acetone (10 ml) was refluxed for ca 10 h. The reaction was monitored
by TLC. After completion of the reaction the solvent was removed
and the mixture was poured onto crushed ice and extracted with
chloroform which was then dried (Na2SO4). The crude product after
solvent removal was purified by column chromatography over silica
gel using chloroform:methanol (98:2) to yield the corresponding 13-
methylindolo[3,2-c]acridine (9, 11).
3,13-Dimethyl-7-phenylindolo[3,2-c]acridine (9a): Pale yellow
solid (0.164 g, 44%), m.p. 237–238°C. IR: νmax 2963, 2360, 1651,
1577, 1414, 1261, 1095 cm–1. UV, λmax (log ε) 254 (4.58), 262
(4.11), 267 (3.46), 294 (4.80), 303 (3.67), 318 (3.46), 337 nm (3.97).
1H NMR: d 8.10–7.17 (m, 14H, C11–, C10–, C9–, C8–, C6–, C5–, C4–,
C2–, C1–, C2'–, C3'–C4'–, C5'–, and C6'–H), 4.20 (s, 3H, N13–CH3),
2.66 (s, 3H, C3–CH3). Anal. Calc. for C27H20N2: C: 86.85, H: 5.40,
N: 7.54. Found: C: 86.91, H: 5.34, N: 7.51%.
4
5
6
D.P. Chakraborty, in The Alkaloids, Ed. A. Brossi, Academic Press,
New York, 1993, 44, 257.
H.J. Knolker, in Advances in Nitrogen Heterocycles, Ed. C.J. Moody,
JAI Press, Greenwich (CT), 1986, 1, 273.
R.S. Kapil, in ‘The Alkaloids’, Ed. R.H.F. Manske, Academic Press,
New York, 1971, Vol. 13, 273.
7
8
H.J. Knolker and K.R. Reddy, Chem. Rev., 2002, 102, 4303.
D.J. Hook, J.J. Yacobucci, S. O’Connor, M. Lee, E. Kerns, B. Krishnan,
J. Matson and G. Hesler, J. Antibiot., 1990, 43, 1347.
9
K. Hirata, C. Ito, H. Furukawa, M. Itoigawa, L.M. Cosentino and
K.H. Lee, Bioorg. Med. Chem. Lett., 1999, 9, 119.
10 E. Lescot, G. Muzard, J. Markovits, J. Belleney, B.P. Roques and
J.B. Le Pecq, J. Med. Chem., 1986, 29, 1731 and references cited therein.
11 V.M. Hedin, T. Tabka, L. Poulain, T. Godard, M. Lachevrel, C. Saturino,
J.C. Lancelot, J.Y. Le Talaer and P. Gaudhuchon, Anti-Cancer Drug
Design, 2000, 15, 109.
12 Y.-Z. Hu and Y.-Q. Chen, Synlett., 2005, 1, 42.
13 M. Ishikura, A. Hino, T. Yaginuma, I. Agata and N. Katagiri, Tetrahedron,
2000, 56, 193.
1,13-Dimethyl-7-phenylindolo[3,2-c]acridine
(9b):
Yellow
amorphous solid (0.178 g, 48%), m.p. >300°C. IR: νmax 2910, 2347,
1679, 1549, 1430, 1280, 1089 cm–1. UV, λmax (log ε) 240 (4.47), 250
(4.17), 267 (4.84), 264 (3.66), 280 (4.17), 304 (3.66) 349 (3.76), 340
nm (3.98).1H NMR: d 8.10–7.17 (m, 14H, C11–, C10–, C9–, C8–, C6–,
C5–, C4–, C2–, C1–, C2'–, C3'–C4'–, C5'–, and C6'–H), 4.14 (s, 3H,
N13–H), 2.58 (s, 3H, C1–CH3). Anal. Calc. for C27H20N2: C: 86.85,
H: 5.40, N: 7.54. Found: C: 86.88, H: 5.30, N: 7.56%.
3,13-Dimethylindolo[3,2-c]acridine (11a): Yellow amorphous
solid (0.15 g, 51%), m.p. 291–294°C. IR: νmax 2954, 2352, 1653,
1541, 1410, 1230, 1100 cm–1. UV: λmax (log ε) 224 (4.17), 245
(4.81), 289 (3.67), 318 (3.88), 327 (3.49), 337 (3.94), 341 nm (3.21).
1H NMR: d 8.82 (s, 1H, C7–H), 8.40–7.30 (m, 9H, C11–, C10–, C9–,
C8–, C6–, C5–, C4–, C2–, C1–H), 3.80 (s, 3H, N13–CH3) 2.59 (s, 3H,
C3–CH3). Anal. Calc. for C21H16N2: C: 85.10, H: 5.42, N: 9.37;
Found: C: 85.04, H: 5.46, N: 9.39%.
14 J.M. Petersen, W.R. Bowman, M.R.J. Elsegood, A.J. Fletcher and
P.J. Lovell, J. Org. Chem., 2005, 70, 10615.
15 U. Pindur, Chimia, 1990, 44, 406.
16 W.A. Denny, G.T. Atwell, B.C. Baguley and L.P.G. Wakelin, J. Med.
Chem., 1985, 28, 1568.
17 R.A. Heald and M.F.G. Stevens, Org. Biomol. Chem., 2003, 1, 3377.
18 G.B. Marini-Bottolo and J. Schutz, Helv. Chim. Acta, 1959, 42, 2146.
19 S. Goodwin, A.F. Smith and H.C. Horning, J. Amer. Chem. Soc., 1959,
81, 1903.
20 S. Kondo, M. Katayama and S. Marumo, J. Antibiot., 1986, 39, 727.
21 I.A. Danish and K.J. Rajendra Prasad, J. Chem Res., 2005, 107.
22 A.E. Martin and K.J. Rajendra Prasad, J. Chem Res., 2006, 473.
23 G.H. Kirsch, Curr. Org. Chem., 2001, 5, 507.
24 B.E. Evans, K.E. Rittle, M.G. Bock, R.M. DiPardo, R.M. Friedinger,
W.L. Whitter, G.F. Lundell, D.F. Verber, P.S. Anderson, R.S.L. Chang,
V.J. Lotti, D.H. Cerino, T.B. Chen, P.J. Kling, K.A. Kunkel, J.P. Springer
and J. Hirschfield, J. Med. Chem., 1988, 31, 2235.
25 D. Sowmithran and K.J. Rajendra Prasad, Heterocycles., 1986, 24, 711.
26 K.J. Rajendra Prasad and C.S. Vijayalakshmi, Indian J. Chem., 1994,
33B, 481.
27 R. Balamurali and K.J. Rajendra Prasad, Z. Naturforsch., 1999, 54b,
1618.
1,13-Dimethylindolo[3,2-c]acridine (11b): Yellow amorphous
solid (0.16 g, 53%), m.p. >300°C. IR: νmax 2985, 2367, 1644, 1587,
1421, 1180, 1046 cm–1. UV, λmax (log ε) 229 (4.60), 250 (4.10) 284
1
(3.67), 280 (4.34), 307 (3.84), 324 (3.16), 354 nm (3.89). H NMR:
d 8.88 (s, 1H, C7–H), 8.35–7.43 (m, 9H, C11–, C10–, C9–, C8–, C6–,
PAPER: 06/4352