Synthesis and reactions of pyrido[3,2,1-jk]carbazole-4,6-diones

Article abstract of DOI:10.1002/jhet.600

Pyrido[3,2,1-jk]carbazoles 1, synthesized from carbazoles and alkyl- or arylmalonates, gave regioselective electrophilic substitution reactions at position 5 such as chlorination to 5-chloro derivatives 2, nitration to 5-nitro compounds 3, or hydroxylatio

Full text of DOI:10.1002/jhet.600

September 2011
Synthesis and Reactions of Pyrido[3,2,1-jk]carbazole-4,6-diones
1039
Wolfgang Stadlbauer,* Hoai Van Dang, and Bernd Knobloch
Division of Organic and Bioorganic Chemistry, Department of Chemistry, Karl-Franzens
University of Graz, A-8010 Graz, Austria/Europe
*E-mail: wolfgang.stadlbauer@uni-graz.at
Received May 7, 2010
DOI 10.1002/jhet.600
Published online 13 May 2011 in Wiley Online Library (wileyonlinelibrary.com).
Pyrido[3,2,1-jk]carbazoles 1, synthesized from carbazoles and alkyl- or arylmalonates, gave regiose-
lective electrophilic substitution reactions at position 5 such as chlorination to 5-chloro derivatives 2,
nitration to 5-nitro compounds 3, or hydroxylation to 5-hydroxy derivatives 4. 5-Hydroxy compounds 4
gave on treatment with strong bases ring contraction to 5, 6 or the ring opening product 7. Exchange of
the chloro group in 2 with azide or amines gave the corresponding azides 8 and the 5-amino derivatives
9 and 10. Alkylation of 1 with benzyl chloride or allyl bromide resulted in the formation of 5-C-alky-
lated products 11 together with 4-alkyloxy derivatives 12.
J. Heterocyclic Chem., 48, 1039 (2011).
INTRODUCTION
Formation of by-products by electrophilic substitution at
the two aromatic rings can be avoided because of the
different reactivities of C-5 and aromatic positions.
Electrophilic substitution at position 5 in 4-hydroxy-
pyridocarbazoles 1a–f (from its tautomeric dioxo form)
by chlorine should be easily achieved by reaction with
sulfuryl chloride or elementary chlorine as reagents as
described earlier for 4-hydroxyquinolones [6]. A radical
process can be ruled out because of the mild reaction
conditions. The aspired 5-chloro products 2 were
intended to be used in further reactions because of their
high reactivity (Scheme 1).
Pyrido [3,2,1-jk]carbazol-6-one, which is part of the
heterocyclic skeleton of natural products such as strych-
nos alkaloids [1], contains the biologically interesting
combination of indole and 2-pyridone heterocycles.
Some derivatives have found interest in pharmacological
investigations [2] and in dye chemistry [3]. Recently,
we published the synthesis of 4-hydroxypyrido[3,2,1-
jk]carbazol-6-ones [4], which possess two reactive posi-
tions: the hydroxy group at C-4, which can be substi-
tuted by various nucleophiles, and the CH-acidic proton
at C-5, which is accessible to electrophilic reactions. In
refs. [4] and [5], we published a series of nucleophilic
reactions at position 4; in this contribution, we wish to
report on regioselective electrophilic substitutions at
position 5 to form 5,5-disubstituted pyrido[3,2,1-jk]car-
bazole-4,6-diones.
The chlorination of 1 was performed with sulfuryl
chloride in dioxane solution at 50ꢀC, followed by a
short raise to 90ꢀC to finish the reaction, which gave in
excellent yields of 73–83% 5-chloro-5-substituted-pyri-
docarbazole-4,6-diones 2a–f. Temperatures and reaction
times had to be strictly applied, otherwise unwanted
multiple chlorination products were formed. Infrared
spectral analysis revealed the additional ketone carbonyl
band of C-4 in the region of 1720 cmꢁ1 besides the am-
ide carbonyl band of C-6 at about 1690 cmꢁ1. The aro-
RESULTS AND DISCUSSION
Electrophilic substitution of 5-monosubstituted 4-
hydroxypyridocarbazoles 1 should form regioselectively
5,5-disubstituted pyrido[3,2,1-jk]carbazole-4,6-diones by
reaction at the CH-acidic position of C-5, which results
in the corresponding dioxo structure of the molecule.
1
matic signals in H-NMR showed that no chlorination in
the benzo part of the carbazole nucleus had occurred.
Nitration of 1 (again from its tautomeric dioxo form)
as an established electrophilic reaction should give 5-
C
V
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W. Stadlbauer, H. V. Dang, and B. Knobloch
Vol 48
Scheme 1
temperature, traces of 5-hydroxy-5-methylpyrido[3,2,1-
jk]carbazole-4,6-dione (4a) were present. When the reac-
tion was performed at higher reaction temperature
(60ꢀC), 5-hydroxy-5-methylpyridocarbazoledione 4a was
isolated as the main product (described as method B for
the synthesis of 4a). This can be explained in terms ei-
ther of a direct oxidation of the CH-acidic position 5 by
the oxidative agents present in the reaction mixture,
such as nitrous and nitric acid, or by the subsequent
exchange of the already formed nitro group in 3a
against the hydroxy group to form 4a.
5-Hydroxypyrido[3,2,1-jk]carbazolediones 4 contain
an interesting 2-hydroxy-1,3-diketone structure element
with bioactive properties: 3-hydroxy-3-alkylquinoline-
diones are present in some natural products, e.g., as
inherent compounds of bacteria in Pseudomonas aerugi-
nosa [9] and some derivatives of 2-hydroxy-2-(2-
hydroxyphenyl)indane-1,3-diones have anti-inflamma-
tory activity [10].
The direct displacement of the hydrogen atom at posi-
tion 5 of 1a–e,g,h (from its tautomeric dioxo form) by a
hydroxy group was achieved by oxidation with alkaline
hydrogen peroxide in a buffer solution at pH ¼ 8 or in
acidic media with peroxycarboxylic acids such as perox-
yacetic acid or m-chloroperoxybenzoic acid as reagents
(Scheme 1). The hydroxylated products, 5-hydroxypyri-
docarbazolediones 4a–e,g,h, were obtained in excellent
yield of about 70–90% as yellow crystals. For compari-
son reasons with the natural products [9], the 5-heptyl-
(4g) and 5-nonyl (4h) derivatives were synthesized.
The structure elucidation showed in the infrared spec-
tra a strong, sharp hydroxy band ranging between 3300
and 3500 cmꢁ1 together with the additional ketone and
amide carbonyl band at about 1720 and 1690 cmꢁ1. The
1H-NMR spectra of the 5-CH2 group in the ethyl and
benzyl derivatives 4b and 4d gave splitted signals (4b:
J ¼ 7.4 and J ¼ 13.7 Hz, 4d: J ¼ 13.3 Hz) because of
diastereotopic effects. Mass spectra of hydroxy com-
pounds 4 gave with the APCI (atmospheric pressure
chemical ionization) method mass peaks of M-28. Using
the ESI (electrospray ionization) mass spectral method
for the determination of mass spectra, the spectra of 4
gave the correct masses of the molecule peaks of the
hydroxy compounds. Additional signals could be observed
that were assigned as adducts of 4 with the cations of
sodium and potassium. The formation of such adducts
with alkali metal ions in ESI mass spectra are known and
were investigated recently by Takayama [11].
nitro compounds 3 (Scheme 1), which can be further
used for reduction to amino groups that is planned to be
published in future. The nitration reaction of similar 4-
hydroxyquinolone systems was reported with nitric acid
in boiling acetic acid [7]. However, this reaction
sequence could not be applied for 4-hydroxypyridocar-
bazol-6-one derivatives 1 because a number of by-prod-
ucts were formed by these conditions. To avoid these
difficulties, the nitration reaction was carried out under
milder conditions, using sodium nitrite as catalyst. Start-
ing with 4-hydroxy-5-substituted pyridocarbazol-6-ones
1a–e, dissolved in glacial acetic acid, the reaction with
nitric acid and sodium nitrite led already at room tem-
perature to pure 5-nitro-5-substituted-pyridocarbazole-
4,6-diones 3a–e in good yields of 60–85%. The catalyti-
cal effect of sodium nitrite can be explained by an ini-
tial nitrosation of 1 in position 5 and subsequent oxida-
tion of the nitroso to the desired nitro group [8]. The
infrared spectra showed again the ketone carbonyl band
of C-4 in the region of 1720 cmꢁ1 and the amide car-
bonyl band of C-6 in the region of 1690 cmꢁ1. The
1
presence of all aromatic H-NMR signals of the carba-
zole part proved that no further multinitration had
occurred.
As described above, mass spectra of hydroxy com-
pounds 4 gave the APCI (chemical ionization) method
mass peaks of M-28, which is derived by the elimina-
tion of CO and ring contraction. This matter was already
mentioned in literature [9e]. These findings prompted us
to investigate the possible synthetic application of such
However, another interesting side reaction was
observed, when 4-hydroxypyridocarbazolone 1a was
reacted to the nitro compound 3a using the nitrite/nitric
acid method: in the reaction mixture already at room
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Synthesis and Reactions of Pyrido[3,2,1-jk]carbazole-4,6-diones
1041
Scheme 2
ring contractions. Recently, it was reported that 3-
hydroxy-2,4-quinolinediones in the presence of a base
under nonaqueous conditions form 3-acyloxy-1,3-dihy-
droindol-2-ones via an a-ketol rearrangement [12].
Moreover, it was described that 3-hydroxy-2,4-quinoli-
nediones react with aqueous potassium hydroxide to
produce 2-hydroxy-1,2-dihydroindol-3-ones (2-hydrox-
yindoxyls) and/or isomeric 3-hydroxy-1,3-dihydroindol-
2-ones (dioxindoles) in good yield [13]. Similar ring
contractions were found in 5-hydroxy-5-alkylbarbituric
acids [14].
For our synthetic investigations, we adopted the
method described in ref. [13]. When 5-hydroxy-5-meth-
ylpyridocarbazoledione 4a was vigorously stirred in a
binary mixture of 1.3M aqueous potassium hydroxide
and toluene at room temperature, a ring contraction took
place under formal loss of CO and 4-hydroxy-4-methyl-
pyrrolo[3,2,1-jk]carbazol-5(4H)-one (5a) was formed in
excellent yield (Scheme 2). The structure elucidation
based on mass spectral analysis revealed that the correct
molecular mass with the APCI method was obtained;
the ESI method showed some higher mass fragments
from alkali metal complexes. The infrared spectrum
showed a carbonyl frequency of a 5-ring amide carbonyl
1
group at 1708 cmꢁ1, and in the H-NMR spectra, one
hydroxy signal at 11.91 ppm was visible.
At higher temperatures of about 60–80ꢀC, another
reaction sequence was observed in the ring contraction
of 4a (Scheme 2). In this case, surprisingly, not the car-
bonyl group but the 5-methyl group was cleaved, and
4,4-dihydroxypyrrolo[3,2,1-jk]carbazol-5(4H)-one
(6)
was formed in 55% yield. The structure elucidation
showed two hydroxy signals at 10.23 and 11.87 ppm in
1
the H-NMR spectra; the carbonyl bands in the infrared
spectra at 1672 cmꢁ1 confirm the amide structure. The
mass spectral analysis (APCI method) shows an M-2
peak of the dihydroxy structure of 6; the elemental anal-
ysis is in accordance with this structure. Both products,
5a and 6, involve a ring opening of the six-membered
pyridine part, cleavage of a C-1 ring fragment, and then
a recyclization step to a five-membered pyrrole ring.
The CO elimination to 5a can be explained by hydro-
lytic ring opening and subsequent decarboxylation, fol-
lowing the findings outlined in ref. [13]: one possible
way leads via a base-catalyzed ring contraction to inter-
mediates A and give ketones B by subsequent hydrolysis
of the lactam ring, followed by oxidative decarboxyl-
ation. Rearrangement to C and recyclization is a possi-
ble way to give 4-hydroxypyrrolo[3,2,1-jk]carbazolones
5. The mechanistic aspects of the cleavage of the Me-C
fragment and formation of 6 are not clear until now.
When 5-hydroxypyridocarbazolediones such as 4b
with a 5-ethyl substituent or 4e with a 5-phenyl substitu-
ent were treated with aqueous potassium hydroxide and
toluene at room temperature, no reaction took place. At
higher temperature, the ring-contracted 4-hydroxypyrro-
locarbazolones 5b,c were obtained, with carbonyl fre-
quencies of 1710 or 1675 cmꢁ1 and one OH-signal at
10.46 (5b) or 12.12 ppm (5c; Scheme 2). Mass spectra,
both with APCI and ESI method, confirm the structures
of 5b,c. Ring contraction of 4b and 4e by cleavage of
the ethyl- or phenyl-C fragment to form 4,4-dihydroxy-
pyrrolocarbazolone 6 was not observed.
5-Benzyl-5-hydroxypyridocarbazoledione 4d gave on
treatment with potassium hydroxide at 60–80ꢀC a new
ring-opening product, 1-(9H-carbazol-1-yl)-2-hydroxy-3-
phenylpropan-1-one (7) instead of a ring-contraction
product of type 5 or 6 (Scheme 2). The structure of the
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W. Stadlbauer, H. V. Dang, and B. Knobloch
Vol 48
Scheme 3
purification was necessary; however, it should be
noticed that the thin layer chromatography (TLC) Rf
values of the educts 2 and the products 8 are very simi-
lar and separation could be obtained in most cases only
with HPLC to allow to recognize the end of the reac-
tion. The infrared spectra showed strong bands of the
ketone C-4 frequencies at about 1720 cmꢁ1 and strong
azide bands at about 2120 cmꢁ1. The 5-CH2 group in
the ethyl, butyl, and benzyl derivatives 8b–8d gave
1
again splitted H-NMR signals with J ¼ 7 and J ¼ 13
Hz because of diastereotopic effects.
The exchange of the 5-chloro substituent in 5-chloro-
5-substituted-pyrido[3,2,1-jk]carbazole-4,6-diones
2
against primary or secondary amines as nucleophiles
leads to 5-aminosubstituted pyridocarbazolediones 9 and
10 (Scheme 3). The reaction of a solution of 2a,c,e in
dimethylformamide at 50ꢀC with benzylamine or aniline
gave the amino compounds 9a–f in good yields. In a
similar manner, the secondary aliphatic amines such as
morpholine or piperidine led to compounds 10a–e in
excellent yields. The infrared spectra both of 9 and 10
showed the bands of the ketone C-4 at about 1720 cmꢁ1
and at 1660–1690 cmꢁ1 for the amide at C-6. Again the
5-CH2 group in butyl derivatives 9e,f and 10e gave
splitted 1H-NMR signals with ꢂ7 and ꢂ13 to 14 Hz
because of diastereotopic effects.
The alkylation of 3-alkyl-4-hydroxyquinolones is
known to give 3,3-dialkyl products and 4-enolethers
depending on the variation of the reaction conditions,
because such enolized ‘‘malonylheterocycles’’ can act as
ambident anions: the reaction in aqueous sodium hy-
droxide leads preferable by C-alkylation to 3,3-dialkyl
products, whereas polar aprotic solvents such as dime-
thylformamide favor the formation of 4-enolethers,
which could be rearranged thermically to 3,3-dialkyl
derivatives [15].
ring-opened product is similar to the products obtained
by high pressure–high temperature amination products
of recently reported 4-hydroxypyridocarbazolones 1 [5].
Based on the formation of a phenylogous ketone func-
tion, the carbonyl band in the infrared spectra shows a
low value at 1647 cmꢁ1 1H-NMR spectra show one
,
hydroxy signal at 11.76 ppm, and the mass spectra with
the APCI method show the molecule peak with 100%.
5-Chloropyrido[3,2,1-jk]carbazole-4,6-diones
2 pos-
sess with the 5-chloro substituent a good leaving group
at a sp3 carbon which is easily susceptible for a nucleo-
philic exchange. We introduced in this way nitrogen
substituents such as the azido group or primary and sec-
ondary amines in position 5.
The reaction of 5-butylpyrido[3,2,1-jk]carbazol-6-one
1c with benzylchloride or allylbromide in aqueous so-
dium hydroxide gave in 60–90% yield the corresponding
5-butylpyrido[3,2,1-jk]carbazol-4,6-diones 11a,c, only
with traces of the enolethers 12a,c (Scheme 4), which
could not be obtained in a pure form for characteriza-
The exchange of the 5-chloro substituent in 5-chloro-
pyridocarbazol-6-ones 2a–e against the azide group as
the nucleophile to form 5-azido-5-substituted-pyr-
ido[3,2,1-jk]carbazole-4,6-diones 8a–e was of special in-
terest because similar azidoquinolinediones showed inhi-
bition of human blood platelet aggregation [6d]. The
reaction was carried out with a solution of 2 in dime-
thylformamide with sodium azide as reagent at tempera-
tures of 50ꢀC (Scheme 3). Removal of excess sodium
azide and formed sodium chloride was achieved by
addition of water; this workup effected furthermore the
precipitation of the formed azides 8a–e. The yields of
the azidation reaction were excellent. Usually, no further
1
tion. H-NMR analyses of impure 12a,c (as a mixture
with 11a,c) showed additional OCH2 signals at
5.10 ppm (s, benzyl-OCH2) in 12a and at 4.45 ppm (m,
allyl-OCH2) in 12c besides the benzyl-CH2 signals of
11a at 3.50 ppm and the allyl-CH2 signals of 11c at
2.70–2.90 ppm, similar to ref. [15d,e]. In the same
manner, the 5-benzyl-5-phenyl product 11b was
obtained in 64%. All compounds 11 showed infrared
bands of the dioxo structure: the C-4 ketone band at
about 1700 cmꢁ1 and the C-6 amide band at about
1670 cmꢁ1. Experiments on the thermal rearrangement
of 4-allyloxy-5-butylpyridocarbazolone 12c, which was
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Synthesis and Reactions of Pyrido[3,2,1-jk]carbazole-4,6-diones
1043
Scheme 4
chromatography [16] was carried out on silica gel 60 H (5–40
lm; Merck, Darmstadt, Germany). All reactions were moni-
tored by TLC on 0.2-mm silica gel F 254 plates (Merck,
Darmstadt, Germany) using UV light (254 and 366 nm) for
detection. Analytical HPLC was performed on a Shimadzu LC
20 system equipped with a diode array detector (215 and 254
nm) on a Pathfinder AS reversed phase (4.6150 mm, 5 lm)
column, running an acetonitrile/water gradient (30–100% ace-
tonitrile). Common reagent-grade chemicals are either com-
mercially available and were used without further purification
or prepared by standard literature procedures.
5-Alkyl/Aryl-4-hydroxypyrido[3,2,1-jk]carbazol-6-ones (1a–
h). These compounds were synthesized from carbazole and the
appropriate diethyl alkylmalonates or diethyl phenylmalonate
by thermal cyclocondensation as described in ref. [4].
5-Chloro-5-methyl-4H-pyrido[3,2,1-jk]carbazole-4,6(5H)-dione
(2a). To a solution of 5-methylpyridocarbazolone 1a (2.00 g, 8
mmol) in dioxane (50 mL), sulfuryl chloride (1.0 mL, 12
mmol) was slowly added and the reaction mixture was heated
for 30 min at 50ꢀC, then for 5 min at 90ꢀC. After cooling to
room temperature, the reaction mixture was poured onto
crushed ice/water (200 mL) and the solid filtered and washed
with water. The yield was 1.83 g (81%), yellow needles, mp
145ꢀC (ethanol). IR: 2900–3500 m, 1726 s (4-C¼¼O), 1692 s
obtained impure and in traces only during the synthesis of
11c, showed by TLC tracing of the reaction that on heat-
ing in refluxing dimethylformamide 11c was formed.
1
(6-C¼¼O), 1592 s cmꢁ1. H-NMR (DMSO-d6): d 2.07 (s, 3 H,
CH3), 7.57, 7.65, and 7.70 (3 t, J ¼ 7.5 Hz, 3 ꢃ 1 H, 2-H, 9-
H, 10-H), 8.05 and 8.33 (2 d, J ¼ 7.6 Hz, 2 ꢃ 1 H, 1-H, 11-
H), 8.42 (d, J ¼ 8.2 Hz, 1 H, 3-H), 8.55 (d, J ¼ 7.7 Hz, 1 H,
8-H). Anal Calcd for C16H10ClNO2 (283.72): C, 67.74; H,
3.55; N, 4.94. Found: C, 67.41; H, 3.45; N, 4.80.
CONCLUSIONS
It could be shown that 5-substituted pyrido[3,2,1-
jk]carbazol-6-ones 1 can be electrophilic substituted at
the CH-acidic position C-5 forming 5-chloro-, 5-nitro-,
5-hydroxy-, and 5-alkyl-pyrido[3,2,1-jk]carbazole-4,6-
diones. 5-Hydroxypyrido[3,2,1-jk]carbazole-4,6-diones
gave interesting ring-opening structures. 5-Chloropyr-
ido[3,2,1-jk]carbazole-4,6-diones could subsequently be
used as starting materials for 5-azido- or 5-aminopyr-
ido[3,2,1-jk]carbazole-4,6-diones.
5-Chloro-5-ethyl-4H-pyrido[3,2,1-jk]carbazole-4,6(5H)-dione
(2b). It was obtained from 5-ethylpyridocarbazolone 1b (2.10
g, 8 mmol) using the procedure and workup described for 2a.
The yield was 1.87 g (79%), yellow needles, mp 148ꢀC (etha-
nol). IR: 2900–3500 m, 1723 s (4-C¼¼O), 1695 s (6-C¼¼O),
1603 s cmꢁ1
.
1H-NMR (CDCl3): d ¼ 0.97 (t, J ¼ 7.4 Hz, 3
H, CH3), 2.67 (q, J ¼ 7.3 Hz, 2 H, CH2), 7.52, 7.58, and 7.62
(3 t, J ¼ 7.5 Hz, 3 ꢃ 1 H, 2-H, 9-H, 10-H), 8.07 (d, J ¼ 7.9
Hz, 1 H, 11-H), 8.10 (d, J ¼ 7.9 Hz, 1 H, 1-H), 8.27 (d, J ¼
7.7 Hz, 1 H, 3-H), 8.60 (d, J ¼ 8.1 Hz, 1 H, 8-H). Anal Calcd
for C17H12ClNO2 (297.74): C, 68.58; H, 4.06; N, 4.70. Found:
C, 68.90; H, 4.00; N, 4.61.
EXPERIMENTAL
5-Butyl-5-chloro-4H-pyrido[3,2,1-jk]carbazole-4,6(5H)-dione
(2c). It was obtained from 5-butylpyridocarbazolone 1c (3.00
g, 10.3 mmol) using the procedure and workup described for
2a. The yield was 2.70 g (80%), yellow needles, mp 74ꢀC
(ethanol). IR: 2957–2341 s, 1718 s (4-C¼¼O), 1693 s (6-
General. Melting points were determined using a Stuart
SMP3 melting point apparatus in open capillary tubes. Calori-
metric data were obtained on a Rheometric Scientific DSC-
Plus instrument with the differential scanning calorimetry soft-
ware Orchestrator V6.2.2. The differential scanning calorime-
try plots were recorded between 25–400ꢀC, with a heating rate
of 2–10ꢀC/min, and 1.5–3 mg compound in sealed aluminum
crucibles (11 bar). IR spectra were recorded using a Mattson
Galaxy Series FTIR 7020 instrument with potassium bromide
discs. NMR spectra were recorded on a Bruker AMX 360
C¼¼O), 1604 w cmꢁ1
.
1H-NMR (CDCl3): d 0.89 (t, J ¼ 7.3
Hz, 3 H, CH3), 1.30 and 1.42 (2 q, J ¼ 7.2 Hz, 2 ꢃ 2 H, 2
CH2), 2.67 (t, J ¼ 7.9 Hz, 2 H, 5-CH2), 7.52–7.67 (m, 3 H, 2-
H, 9-H, 10-H), 8.08 and 8.11 (2 d, J ¼ 7.6 Hz, 2 ꢃ 1 H, 1-H,
11-H), 8.28 (d, J ¼ 7.7 Hz, 1 H, 3-H), 8.62 (d, J ¼ 8.1 Hz, 1
H, 8-H). Anal Calcd for C19H16ClNO2 (325.80): C, 70.05; H,
4.95; N, 4.30. Found: C, 70.26; H, 5.09; N, 4.27.
1
instrument (360 MHz H, 90 MHz 13C) or on a Bruker Avance
5-Benzyl-5-chloro-4H-pyrido[3,2,1-jk]carbazole-4,6(5H)-dione
(2d). It was obtained from 5-benzylpyridocarbazolone 1d (3.30
g, 10.2 mmol) using the procedure and workup described for
2a. The yield was 2.70 g (74%), yellow needles, mp 167ꢀC
(ethanol). IR: 2900–3500 m, 1710 s (4-C¼¼O), 1695 m (6-
1
DRX 500 instrument (500 MHz H, 125 MHz 13C). Chemical
shifts are given in ppm (d) from the internal tetramethylsilane
standard. Elemental analyses were performed at the Microana-
lytical Laboratory of the University of Vienna, Austria. Mass
spectra were obtained from an HP 1100 LC/MSD mass spec-
tral instrument (positive or negative APCI ion source, 50–200
V, nitrogen, or AP-ES electrospray method). Dry-column flash
C¼¼O), 1601 s cmꢁ1
.
1H-NMR (DMSO-d6): d 3.79 (s, 2 H,
CH2), 7.08 (s, 5 H, H at Ph), 7.58, 7.63, and 7.68 (3 t, J ¼ 7.7
Hz, 3 ꢃ 1 H, 2-H, 10-H, 9-H), 8.00 and 8.28 (2 d, J ¼ 7.7
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W. Stadlbauer, H. V. Dang, and B. Knobloch
Vol 48
Hz, 2 ꢃ 1 H, 1-H, 11-H), 8.44 (d, J ¼ 8.2 Hz, 1 H, 3-H), 8.50
(d, 7.6 Hz, 1 H, 8-H). Anal Calcd for C22H14ClNO2 (359.82):
C, 73.44; H, 3.92; N, 3.89. Found: C, 73.41; H, 3.87; N, 3.84.
5-Chloro-5-phenyl-4H-pyrido[3,2,1-jk]carbazole-4,6(5H)-dione
(2e). It was obtained from 5-phenylpyridocarbazolone 1e (5.00
g, 16 mmol) using the procedure and workup described for 2a.
The yield was 4.50 g (81%), yellow needles, mp 171ꢀC (etha-
nol). IR: 2900–3500 m, 1710 s (4-C¼¼O), 1695 m (6-C¼¼O),
5-Benzyl-5-nitro-4H-pyrido[3,2,1-jk]carbazole-4,6(5H)-dione
(3d). It was obtained from 5-benzylpyridocarbazolone 1d (1.50
g, 4.6 mmol) using the procedure and workup described for
3a. The yield was 1.00 g (59%), yellow needles, mp 195ꢀC
(methanol/ethyl acetate). IR: 3600–3400 m, 3020–2980 w,
1
1714 s (4-C¼¼O), 1688 s (6-C¼¼O), 1610 w, 1559 s cmꢁ1. H-
NMR (CDCl3): d 4.10 (s, 2 H, CH2), 8.85–6.87 (m, 3 H, H at
Ph), 7.00–7.02 (m, 2 H, H at Ph), 7.43, 7.51, and 7.63 (3 t, J
¼ 7.2 Hz, 3 ꢃ 1 H, 2-H, 9-H, 10-H), 7.91–7.94 (m, 2 H, 1-H,
11-H), 8.07 (d, J ¼ 7.6 Hz, 1 H, 3-H), 8.54 (d, J ¼ 8.2 Hz, 1
H, 8-H). Anal Calcd for C22H14N2O4 (370.37): C, 71.35; H,
3.81; N, 7.56. Found: C, 71.53; H, 3.80; N, 7.60.
1
1601 s cmꢁ1. H-NMR (CDCl3): d 7.36 (t, J ¼ 3.3 Hz, 3 H, H
at Ph), 7.59–7.53 (m, 5 H, 2 H at Ph, 2-H, 9-H, 10-H), 7.62–
7.64 and 8.06–8.09 (2 m, 2 ꢃ 1 H, 1-H, 11-H), 8.25 (d, J ¼
7.6 Hz, 1 H, 3-H), 8.60 (d, J ¼ 8.2 Hz, 1 H, 8-H). Anal Calcd
for C21H12ClNO2 (345.79): C, 72.94; H, 3.50; N, 4.05. Found:
C, 72.71; H, 3.79; N, 4.01.
5-Nitro-5-phenyl-4H-pyrido[3,2,1-jk]carbazole-4,6(5H)-dione
(3e). It was obtained from 5-phenylpyridocarbazolone 1e (3.11
g, 10 mmol) using the procedure and workup described for 3a.
The yield was 2.53 g (71%), yellow needles, mp 175ꢀC (etha-
nol). IR: 3300 w, 2950 w, 1725 s (4-C¼¼O), 1695 s (6-C¼¼O),
5-Chloro-5-hexyl-4H-pyrido[3,2,1-jk]carbazole-4,6(5H)-dione
(2f). It was obtained from 5-hexylpyridocarbazolone 1f (3.19 g,
10.0 mmol) using the procedure and workup described for 2a.
The yield was 2.73 g (77%), yellow needles, mp 65ꢀC (ethanol).
IR: 2955–2345 s, 1715 s (4-C¼¼O), 1695 s (6-C¼¼O), 1605 w
1680 s, 1610 w cmꢁ1 1H-NMR (CDCl3): d 7.00–7.30 (m, 5
.
H, H at Ph), 7.50–7.55 and 7.60–7.85 (2 m, 2 þ 3 H, 9-H, 10-
H, 2-H, 1-H, 11-H), 8.10 (d, J ¼ 7.6 Hz, 1 H, 3-H), 8.50 (d, J
¼ 8.2 Hz, 1 H, 8-H). Anal Calcd for C21H12N2O4 (356.34): C,
70.78; H, 3.39; N, 7.86. Found: C, 71.13; H, 3.71; N, 7.60.
5-Hydroxy-5-methyl-4H-pyrido[3,2,1-jk]carbazole-4,6(5H)-dione
(4a). Method A: A solution of 5-methylpyridocarbazolone 1a
(2.00 g, 8 mmol) was stirred in aqueous sodium hydroxide
(0.25M, 150 mL) until the solution was complete. The solution
was adjusted to pH 8 with aqueous potassium dihydrogenphos-
phate (1M, ꢂ25 mL) and heated to 60ꢀC with intensive stir-
ring. Then hydrogenperoxide (30%, 25 mL) was added and the
reaction mixture was stirred for 6 h at 60ꢀC. A solid precipi-
tated and the reaction mixture was cooled to room tempera-
ture, filtered by suction, and washed with water. The yield was
1.80 g (85%), yellow needles, mp 147ꢀC (ethanol).
cmꢁ1
.
1H-NMR (CDCl3): d 0.88 (t, J ¼ 7.3 Hz, 3 H, CH3),
1.30–1.50 (m, 8 H, 4 CH2), 2.65 (t, J ¼ 7.9 Hz, 2 H, 5-CH2),
7.55–7.65 (m, 3 H, 2-H, 9-H, 10-H), 8.05–8.15 (m, 2 H, 11-H,
1-H), 8.25 (d, J ¼ 7.7 Hz, 1 H, 3-H), 8.65 (d, J ¼ 8.1 Hz, 1 H, 8-
H). Anal Calcd for C21H20ClNO2 (353.85): C, 71.28; H, 5.70;
N, 3.96. Found: C, 70.96; H, 5.49; N, 4.17.
5-Methyl-5-nitro-4H-pyrido[3,2,1-jk]carbazole-4,6(5H)-dione
(3a). To a mixture of 5-methylpyridocarbazolone 1a (3.30 g,
13 mmol) and sodium nitrite (0.50 g, 7.2 mmol) in glacial ace-
tic acid (50 mL) was slowly dropped concentrated nitric acid
(2.5 mL) and stirred for 2 h at 20ꢀC. The reaction mixture was
poured onto crushed ice/water (100 mL), the precipitated solid
filtered and washed with water. The yield was 3.20 g (84%),
yellow crystals, mp 190ꢀC (ethanol). IR: 3600–3400 w, 1721 s
(4-C¼¼O), 1688 s (6-C¼¼O), 1561 s cmꢁ1
.
1H-NMR (CDCl3):
Method B: To a mixture of 5-methylpyridocarbazolone 1a
(2.00 g, 8 mmol) and sodium nitrite (0.50 g, 7.2 mmol) in gla-
cial acetic acid (50 mL) was slowly dropped concentrated ni-
tric acid (2.5 mL) and stirred for 6 h at 60ꢀC. The reaction
mixture was poured onto crushed ice/water (100 mL), the pre-
cipitated solid filtered and washed with water, and recrystal-
lized from ethanol. The yield was 1.27 g (60%), yellow nee-
dles. IR: 3406 s (5-OH), 1711 s (4-C¼¼O), 1681 s (6-C¼¼O),
d 2.20 (s, 3 H, CH3), 7.55–7.67 (m, 3 H, 2-H, 9-H, 10-H),
8.07–8.10 (m, 2 H, 1-H, 11-H), 8.32 (d, J ¼ 7.6 Hz, 1 H, 3-
H), 8.54 (d, J ¼ 8.2 Hz, 1 H, 8-H). Anal Calcd for
C16H10N2O4 (294.27): C, 65.31; H, 3.43; N, 9.52. Found: C,
65.67; H, 3.82; N, 9.83.
5-Ethyl-5-nitro-4H-pyrido[3,2,1-jk]carbazole-4,6(5H)-dione
(3b). It was obtained from 5-ethylpyridocarbazolone 1b (1.50
g, 5.7 mmol) using the procedure and workup described for
3a. The yield was 1.20 g (68%), yellow needles, mp 162ꢀC
(ethanol). IR: 3398 s, 2980 w, 1714 s (4-C¼¼O), 1683 s (6-
1632 w, 1605 m cmꢁ1 1H-NMR (CDCl3): d 1.77 (s, 3 H,
.
CH3), 3.95 (s, 1 H, OH), 7.48–7.62 (m, 3 H, 2-H, 9-H, 10-H),
8.04 (d, J ¼ 7.7 Hz, 2 H, 1-H, 11-H), 8.25 (d, J ¼ 8.5 Hz, 1
H, 3-H), 8.49 (d, J ¼ 8.1 Hz, 1 H, 8-H). Anal Calcd for
C16H11NO3 (265.27): C, 72.45; H, 4.18; N, 5.28. Found: C,
72.78; H, 4.37; N, 5.02.
1
C¼¼O), 1610 w, 1561 s cmꢁ1. H-NMR (CDCl3): d 0.95 (t, J
¼ 7.5 Hz, 3 H, CH3), 2.83 (q, J ¼ 7.5 Hz, 2 H, CH2), 7.55–
7.68 (m, 3 H, 2-H, 9-H, 10-H), 8.06–8.09 (m, 2 H, 1-H, 11-
H), 8.32 (d, J ¼ 7.6 Hz, 1 H, 3-H), 8.57 (d, J ¼ 8.6 Hz, 1 H,
8-H). Anal Calcd for C17H12N2O4 (308.30): C, 66.23; H, 3.92;
N, 9.09. Found: C, 66.47; H, 3.82; N, 8.93.
5-Ethyl-5-hydroxy-4H-pyrido[3,2,1-jk]carbazole-4,6(5H)-dione
(4b). It was obtained from 5-ethylpyridocarbazolone 1b (3.00
g, 11.4 mmol) using the procedure and workup described for
4a (method A). The yield was 2.50 g (79%), yellow needles,
mp 172ꢀC (ethanol). IR: 3393 s (5-OH), 1710 s (4-C¼¼O),
5-Butyl-5-nitro-4H-pyrido[3,2,1-jk]carbazole-4,6(5H)-dione
(3c). It was obtained from 5-butylpyridocarbazolone 1c (1.50
g, 5.2 mmol) using the procedure and workup described for
3a. The yield was 1.00 g (57%), yellow needles, mp 155ꢀC
(methanol/ethyl acetate). IR: 3600–3300 s, 2950–2800 m, 1722
1
1681 s (6-C¼¼O), 1604 s cmꢁ1. H-NMR (CDCl3): d 1.04 (t, J
¼ 7.4 Hz, 3 H, CH3), 2.00 and 2.13 (2 qd, J ¼ 7.4 þ 13.7 Hz,
2 ꢃ 1 H, CH2), 3.92 (s, 1 H, OH), 7.49–7.63 (m, 3 H, 2-H, 9-
H, 10-H), 8.02 and 8.05 (2 d, J ¼ 7.6 Hz, 2 ꢃ 1 H, 1-H, 11-
H), 8.24 (d, J ¼ 7.6 Hz, 1 H, 3-H), 8.50 (d, J ¼ 8.2 Hz, 1 H,
8-H). 13C-NMR: d 7.4 (CH3), 35.0 (CH2), 84.4 (5-C), 116.2,
117.0, 120.8, 124.1, 124.5, 125.1, 125.2, 125.5, 126.9, 128.6,
137.3, 139.7 (12 ArC), 169.3 (6-C), 194.0 (4-C). Anal Calcd
for C17H13NO3 (279.30): C, 73.11; H, 4.69; N, 5.01. Found:
C, 72.78; H, 4.62; N, 4.99.
1
s (4-C¼¼O), 1692 s (6-C¼¼O), 1605 m, 1565 s cmꢁ1. H-NMR
(CDCl3): d ¼ 0.80–0.95 (m, 3 H, CH3), 1.15–1.25 and 1.30–
1.35 (2 m, 4 H, 2 CH2), 2.72–2.77 (m, 2 H, 5-CH2), 7.47–7.68
(m, 3 H, 2-H, 9-H, 10-H), 7.97–8.11 (m, 2 H, 11-H, 1-H),
8.24 (d, J ¼ 7.5 Hz, 1 H, 3-H), 8.51 (d, J ¼ 7.4 Hz, 1 H, 8-
H). Anal Calcd for C19H16N2O4 (336.35): C, 67.85; H, 4.79;
N, 8.33. Found: C, 67.46; H, 4.41; N, 7.95.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

September 2011
Synthesis and Reactions of Pyrido[3,2,1-jk]carbazole-4,6-diones
1045
5-Butyl-5-hydroxy-4H-pyrido[3,2,1-jk]carbazole-4,6(5H)-dione
(4c). Method C: Peroxyacetic acid (32% in acetic acid; 100 mL,
0.48 mol) was added dropwise to a solution of 5-butylpyridocarba-
zolone 1c (29.1 g, 0.1 mol) in sodium hydroxide (0.5M, 960 mL).
The reaction mixture was stirred for 1.5 h at 20ꢀC. The formed pre-
cipitate was separated by suction filtration, dispersed in sodium bi-
carbonate solution (5%, 150 mL), filtered again, and washed with
water until the filtrate was neutral. The crude product was dissolved
in chloroform (200 mL) and extracted with sodium hydroxide
(0.05M, 2 ꢃ 150 mL). The organic layer was dried with sodium sul-
fate and the solvent evaporated under reduced pressure. The yield
was 23.4 g (76%), yellow powder, mp 167ꢀC (ethanol/water). IR:
3480 m (5-OH), 2950 m, 2870 m, 1720 s (4-C¼¼O), 1680 s (6-
C¼¼O), 1605 m, 1595 m cmꢁ1; 1H-NMR (CDCl3): d ¼ 0.80 (t, J ¼
7.0 Hz, 3 H, CH3), 1.05–1.25 (m, 2 H, CH2), 1.30–1.50 (m, 2 H,
CH2), 1.80–2.05 (m, 2 H, 5-CH2), 4.15 (s, 1 H, OH), 7.40–7.65 (m,
3 H, 2-H, 9-H, 10-H) 8.05 (t, J ¼ 7.0 Hz, 2 H, 1-H, 11-H), 8.20 (d,
J ¼ 8.0 Hz, 1 H, 3-H), 8.45 (d, J ¼ 8.0 Hz, 1 H, 8-H). MS [AP-ES,
pos]: m/e (%): 330 ([M þ Na]þ, 100), 308 ([M þ H]þ, 25). Anal
Calcd for C19H17NO3 (307.35): C, 74.25; H, 5.58; N, 4.56. Found:
C, 74.35; H, 5.41; N, 4.49.
5-Hydroxy-5-nonyl-4H-pyrido[3,2,1-jk]carbazole-4,6(5H)-dione
(4h). Method C: To a solution of 5-nonylpyridocarbazolone 1h
(2.00 g, 5.5 mmol) in acetic acid (50 mL) at 110ꢀC, peroxya-
cetic acid (20 mL, 32% in acetic acid) was added. The reac-
tion temperature was lowered to 60ꢀC and the mixture was
stirred for 18 h at this temperature. After cooling to room tem-
perature, the reaction mixture was poured onto crushed ice/
water (200 mL), the precipitate filtered by suction, and washed
with water. The yield was 1.62 g (78%), colorless powder, mp
95ꢀC (methanol/cyclohexane). IR: 3447 s (5-OH), 2918 s,
1
2849 s, 1724 s (4-C¼¼O), 1682 s (6-C¼¼O), 1605 s cmꢁ1. H-
NMR (CDCl3): d 0.85 (t, J ¼ 6.9 Hz, 3 H, CH3), 1.11–1.24
(m, 14 H, 7 CH2), 1.85–1.93 and 1.98–2.07 (2 m, 2 ꢃ 1 H, 5-
CH2), 7.49–7.55 and 7.57–7.63 (2 m, 2 þ 1 H, 10-H, 9-H, 2-
H), 8.01 and 8.05 (2 d, J ¼ 7.7 Hz, 2 ꢃ 1 H, 1-H, 11-H), 8.23
(d, J ¼ 7.7 Hz, 1 H, 3-H), 8.49 (d, J ¼ 8.2 Hz, 1 H, 8-H). MS
[AP-ES, pos]: m/e (%) 416 (22, [M þ K]þ), 400 (100, [M þ
Na]þ), 378 (34, [M þ H]þ), 333 (10). Anal Calcd for
C24H27NO3 (377.49): C, 76.36; H, 7.21; N, 3.71. Found: C,
76.31; H, 7.46; N, 3.54.
4-Hydroxy-4-methylpyrrolo[3,2,1-jk]carbazol-5(4H)-one (5a). A
mixture of 5-hydroxy-5-methylpyridocarbazoledione 4a (0.14
g, 0.52 mmol) and aqueous potassium hydroxide solution
(1.3M, 10 mL) in toluene (15 mL) was stirred at room temper-
ature for 4 h, then the toluene phase was separated and dried
with potassium carbonate (3.0 g), filtered, and the solvent was
removed under reduced pressure. The residue was dissolved in
acetone (1.0 mL), then water (20 mL) was added. The precipi-
tated solid was filtered by suction and washed with water. The
product 5a was separated by dry-column flash chromatography
(elution with toluene/acetone). The yield was 0.10 g (80%),
yellow crystals, mp 101ꢀC (acetone/water). IR: 3414 s (4-OH),
2923 m, 2853 m, 1708 s (5-C¼¼O), 1639 s, 1621 s, 1588 s
5-Benzyl-5-hydroxy-4H-pyrido[3,2,1-jk]carbazole-4,6(5H)-dione
(4d). It was obtained from 5-benzylpyridocarbazolone 1d (3.00
g, 9.2 mmol) using the procedure and workup described for 4a
(method A). The yield was 2.70 g (86%), yellow needles, mp
216ꢀC (ethanol). IR: 3433 s (5-OH), 1730 sh, 1715 s (4-C¼¼O),
1
1684 s (6-C¼¼O), 1605 s cmꢁ1. H-NMR (CDCl3): d 3.37 and
3.34 (2 d, J ¼ 13.3 Hz, 2 ꢃ 1 H, CH2), 3.93 (s, 1 H, OH), 6.99–
7.02 (m, 2 H, H at Ph), 7.10–7.16 (m, 3 H, H at Ph), 7.50–7.56
(m, 2 H, 9-H, 10-H), 7.60–7.64 (m, 1 H, 2-H), 7.98 and 8.03 (2
d, J ¼ 7.7 Hz, 2 ꢃ 1 H, 1-H, 11-H), 8.20 (d, J ¼ 7.7 Hz, 1 H, 3-
H), 8.48 (d, J ¼ 8.2 Hz, 1 H, 8-H). MS [APCI, neg]: m/e (%):
340 ([M ꢁ H]þ, 20), 339 (10), 250 (100). Anal Calcd for
C22H15NO3 (341.37): C, 77.41; H, 4.43; N, 4.10. Found: C,
77.14; H, 4.43; N, 4.04.
cmꢁ1 1H-NMR (DMSO-d6): d 2.59 (s, 3 H, CH3), 7.24–7.33
.
(m, 2 H, 8-H, 9-H), 7.49 (t, J ¼ 8.1 Hz, 1 H, 2-H), 7.79 and
7.99 (d, J ¼ 8.2, 7.7 Hz, 2 ꢃ 1 H, 10-H, 1-H), 8.22 (d, J ¼
7.7 Hz, 1 H, 3-H), 8.56 (d, J ¼ 7.7 Hz, 1 H, 7-H), 11.91 (s, 1
H, OH). MS [API-ES, pos]: m/z (%) ¼ 259 (100, [M þ Na]þ);
MS [APCI, neg]: m/z (%) ¼ 236 (100, [M ꢁ H]þ). Anal Calcd
for C15H11NO2 (237.26): C, 75.94; H, 4.67; N, 5.90. Found:
C, 75.61; H, 4.47; N, 6.21.
5-Hydroxy-5-phenyl-4H-pyrido[3,2,1-jk]carbazole-4,6(5H)-dione
(4e). It was obtained from 5-phenylpyridocarbazolone 1e (3.00
g, 9.6 mmol) using the procedure and workup described for 4a
(method A). The yield was 2.50 g (80%), yellow needles, mp
234ꢀC (ethanol). IR: 3373 s (5-OH), 1718 s (4-C¼¼O), 1681 s
1
(6-C¼¼O), 1602 s, 1593 s cmꢁ1. H-NMR (CDCl3): d 4.45 (s,
4-Ethyl-4-hydroxypyrrolo[3,2,1-jk]carbazol-5(4H)-one (5b). A
mixture of 5-ethyl-5-hydroxypyridocarbazoledione 4b (1.20 g,
4.3 mmol) and aqueous potassium hydroxide (1.3M, 20 mL) in
toluene (60 mL) was stirred at 50ꢀC for 8 h, the toluene phase
was separated and dried with potassium carbonate (3.0 g), then
filtered and the solvent was removed under reduced pressure.
The residue was dissolved in acetone (4 mL) and then water
(80 mL) was added. The precipitated solid was filtered by suc-
tion and washed with water. The product was separated by
dry-column flash chromatography (elution with toluene/ace-
tone). The yield was 0.90 g (83%), yellow crystals, mp 115ꢀC
(methanol). IR: 3500–3300 s, 1710 s (5-C¼¼O), 1636 s, 1619
1 H, OH), 7.24–7.28 (m, 3 H, H at Ph), 7.40–7.43 (m, 2 H, H
at Ph), 7.52–7.58 and 7.61–7.66 (2 m, 2 þ 1 H, 9-H, 10-H, 2-
H), 8.02 and 8.09 (2 d, J ¼ 7.8 Hz, 2 ꢃ 1 H, 1-H, 11-H), 8.27
(d, J ¼ 7.8 Hz, 1 H, 3-H), 8.57 (d, J ¼ 8.2 Hz, 1 H, 8-H). MS
[APCI, neg]: m/e (%): 326 ([M ꢁ H]þ, 28), 300 (10), 298
(100). Anal Calcd for C21H13NO3 (327.34): C, 77.06; H, 4.00;
N, 4.28. Found: C, 76.77; H, 3.83; N, 4.23.
5-Heptyl-5-hydroxy-4H-pyrido[3,2,1-jk]carbazole-4,6(5H)-dione
(4g). It was obtained from 5-heptylpyridocarbazolone 1g (3.30
g, 10 mmol) using the procedure and workup described for 4a
(method A). The yield was 2.30 g (66%), yellow needles, mp
153ꢀC (ethanol). IR: 3373 s (5-OH), 1719 s (4-C¼¼O), 1681 s,
1
1
(6-C¼¼O), 1602 w cmꢁ1. H-NMR (DMSO-d6): d 0.77 (t, J ¼
m, 1589 m, 1573 m cmꢁ1. H-NMR: d 1.27 (t, J ¼ 7.0 Hz, 3
6.5 Hz, 3 H, CH3), 1.08 (m, 6 H, 3 CH2), 1.20–1.25 (m, 4 H,
2 CH2), 1.75–1.90 (m, 2 H, 5-CH2), 6.07 (s, 1 H, OH), 7.52–
7.67 (m, 3 H, 2-H, 9-H, 10-H), 7.93 and 8.30 (2 d, J ¼ 7.7
Hz, 2 ꢃ 1 H, 11-H, 1-H), 8.42 (d, J ¼ 7.9 Hz, 1 H, 3-H), 8.50
(d, J ¼ 7.7 Hz, 1 H, 8-H). MS [AP-ES, pos]: m/e (%): 372
([M þ Na]þ, 100) 350 ([M þ H]þ, 30). Anal Calcd for
C22H23NO3 (349.43): C, 75.62; H, 6.63; N, 4.01. Found: C,
75.64; H, 6.59; N, 4.01.
H, CH3), 3.04 (q, J ¼ 7.4 Hz, 2 H, CH2), 7.31 (t, J ¼ 7.7 Hz,
1 H, 2-H), 7.33–7.36 and 7.52–7.54 (2 m, 2 ꢃ 1 H, 8-H, 9-H),
7.59 and 8.01 (2 d, J ¼ 8.1 and 7.8 Hz, 2 ꢃ 1 H, 10-H, 1-H),
8.13 (d, J ¼ 7.8 Hz, 1 H, 3-H), 8.39 (d, J ¼ 7.6 Hz, 1 H, 7-
H), 10.46 (s, 1 H, OH). 13C-NMR: d ¼ 6.9 (CH3), 32.4 (CH2),
111.5, 114.2, 118.7, 120.5, 120.7, 122.1, 125.3, 126.9, 127.8,
130.0, 139.9, 140.0 (12 ArC of carbazole), 194.2 (4-C), 203.8
(5-C). MS [API-ES, pos]: m/z (%) ¼ 306 (100), 276 (54), 274
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

1046
W. Stadlbauer, H. V. Dang, and B. Knobloch
Vol 48
(90, [M þ Na]þ þ 1). MS [APCI, neg]: m/z (%) ¼ 251 (23),
250 (100, [M ꢁ H]þ), 166 (34). Anal Calcd for C16H13NO2
(251.29): C, 76.48; H, 5.21; N, 5.57. Found: C, 76.87; H,
5.60; N, 5.18.
7.3 Hz, 3 ꢃ 1 H, 2-H, 9-H, 10-H), 8.07 (d, J ¼ 7.7 Hz, 2 H,
1-H, 11-H), 8.26 (d, J ¼ 7.7 Hz, 1 H, 3-H), 8.55 (d, J ¼ 8.3
Hz, 1 H, 8-H). Anal Calcd for C16H10N4O2 (290.28): C, 66.20;
H, 3.47; N, 19.30. Found: C, 66.34; H, 3.39; N, 19.10.
4-Hydroxy-4-phenylpyrrolo[3,2,1-jk]carbazol-5(4H)-one (5c). A
solution of 5-hydroxy-5-phenylpyridocarbazoledione 4e (1.64
g, 5.00 mmol) and aqueous potassium hydroxide (1.3M, 30
mL) in toluene (120 mL) was brought to reaction and worked
up as described for 8b. The yield was 1.20 g (80%), yellow
crystals, mp 158ꢀC (methanol). IR: 3408 s (4-OH), 1675 s (5-
5-Azido-5-ethyl-4H-pyrido[3,2,1-jk]carbazole-4,6(5H)-dione
(8b). It was obtained from 5-chloro-5-ethylpyridocarbazole-
dione 2b (3.04 g, 10.2 mmol) using the procedure and workup
described for 5a. The yield was 2.60 g (84%), yellow needles,
mp 136ꢀC (ethanol). IR: 3500–2900 m, 2126 s (N3), 1722 s
(4-C¼¼O), 1689 s (6-C¼¼O), 1600 s cmꢁ1
.
1H-NMR (CDCl3):
C¼¼O), 1643 s, 1620 m, 1586 s, 1576 s cmꢁ1
.
1H-NMR: d
d 1.02 (t, J ¼ 7.4 Hz, 3 H, CH3), 2.36 (qd, J ¼ 7.0 and 13.0
Hz, 2 H, CH2), 7.54–7.57 and 7.62–7.64 (2 m, 2 þ 1 H, 2-H,
9-H, 10-H), 8.04 and 8.06 (2 d, J ¼ 7.4 Hz, 2 ꢃ 1 H, 1-H, 11-
H), 8.25 (d, J ¼ 7.6 Hz, 1 H, 3-H), 8.55 (d, J ¼ 8.2 Hz, 1 H,
8-H). Anal Calcd for C17H12N4O2 (304.31): C, 67.10; H, 3.97;
N, 18.41. Found: C, 67.20; H, 4.00; N, 18.08.
7.26–7.31 (m, 2 H, H at Ph), 7.50 (t, J ¼ 7.4 Hz, 1 H, 2-H),
7.62–7.70 (m, 3 H, H at Ph), 7.78–7.83 (m, 2 H, 8-H, 9-H),
8.00 (d, J ¼ 7.4 Hz, 2 H, 1-H, 10-H), 8.26 (d, J ¼ 7.7 Hz, 1
H, 3-H), 8.60 (d, J ¼ 7.4 Hz, 1 H, 7-H), 12.12 (s, 1 H, OH).
MS [API-ES, pos]: m/z (%) ¼ 324 (100), 322 (93, [M þ Na]þ
þ 1). MS [APCI, neg]: m/z (%) ¼ 299 (25), 298 (87, [M ꢁ
H]þ), 270 (38), 166 (100). Anal Calcd for C20H13NO2
(299.33): C, 80.25; H, 4.38; N, 4.68. Found: C, 80.64; H,
4.76; N, 4.29.
5-Azido-5-butyl-4H-pyrido[3,2,1-jk]carbazole-4,6(5H)-dione
(8c). It was obtained from 5-butyl-5-chloropyridocarbazole-
dione 2c (3.25 g, 10 mmol) using the procedure and workup
described for 5a. The yield was 3.19 g (96%), yellow powder,
mp 93–96ꢀC (ethanol). DSC: mp 81.2ꢀC onset, 91.1ꢀC peak
max. (5 mcal/mg); decomposition 172.4ꢀC onset, 208.5ꢀC
peak max (ꢁ100 mcal/mg). IR: 3600–3400 s, 2927 w, 2118 s
(N3), 1719 s (4-C¼¼O), 1688 s (6-C¼¼O), 1637 m, 1606 s
4,4-Dihydroxypyrrolo[3,2,1-jk]carbazol-5(4H)-one
(6). A
solution of 5-hydroxy-5-methylpyridocarbazoledione 4a (0.40
g, 1.50 mmol) and aqueous potassium hydroxide solution
(1.3M, 30 mL) in toluene (80 mL) was brought to reaction and
worked up as described for 5b. The yield was 0.20 g (55%),
yellow crystals, mp 138ꢀC (methanol). IR: 3383 s (4-OH),
cmꢁ1
.
1H-NMR (CDCl3): d 0.85 (t, J ¼ 7.0 Hz, 3 H, CH3),
1.30 and 1.40 (2 q, J ¼ 7.0 Hz, 2 ꢃ 2 H, 2 CH2), 2.65 (dt, J
¼ 7.5 and 13.1 Hz, 2 H, 5-CH2), 7.55–7.65 (m, 3 H, 2-H, 9-H,
10-H), 8.05 and 8.10 (2 d, J ¼ 7.5 Hz, 2 ꢃ 1 H, 1-H ,11-H),
8.25 (d, J ¼ 7.5 Hz, 1 H, 3-H), 8.62 (d, J ¼ 8.1 Hz, 1 H, 8-
H). Anal Calcd for C19H16N4O2 (332.36): C, 68.66; H, 4.85;
N, 16.86. Found: C, 68.27; H, 5.05; N, 16.54.
3056 w, 2815 w, 1672 s (5-C¼¼O), 1598 s cmꢁ1
.
1H-NMR
(DMSO-d6): d 7.26, 7.39, and 7.42 (3 t, J ¼ 7.6 Hz, 3 ꢃ 1 H,
2-H, 8-H, 9-H), 7.76 and 8.01 (2 d, J ¼ 7.4 Hz, 2 ꢃ 1 H, 1-H,
10-H), 8.20 (d, J ¼ 7.8 Hz, 1 H, 3-H), 8.50 (d, J ¼ 7.6 Hz, 1
H, 7-H), 10.23 (s, 1 H, OH), 11.87 (s, 1 H, OH). 13C-NMR
(DMSO-d6): d 112.9, 118.8, 120.2, 120.3, 120.7, 121.7, 124.6,
126.8, 127.4, 132.0, 137.3, 141.1 (12 ArH), 193.5 (4-C), 211.8
(5-C). MS [APCI, neg]: m/z (%) ¼ 236 (30, [M ꢁ H]þ ꢁ 2),
194 (100). Anal Calcd for C14H9NO3 (239.23): C, 70.29; H,
3.79; N, 5.85. Found: C, 70.02; H, 3.95; N, 5.93.
5-Azido-5-benzyl-4H-pyrido[3,2,1-jk]carbazole-4,6(5H)-dione
(8d). It was obtained from 5-benzyl-5-chloropyridocarbazole-
dione 2d (3.60 g, 10 mmol) using the procedure and workup
described for 2a. The yield was 2.70 g (74%), yellow needles,
mp 162ꢀC (ethanol). IR: 2600 w, 2116 s (N3), 1721 s (4-
1-(9H-Carbazol-1-yl)-2-hydroxy-3-phenylpropan-1-one (7). A
solution of 5-hydroxy-5-methylpyridocarbazoledione 4d (0.40
g, 1.17 mmol) and potassium hydroxide (1.3M, 30 mL) in tol-
uene (120 mL) was brought to reaction and worked up as
described for 5a. The yield was 0.23 g (62%), yellow crystals,
mp 147ꢀC (acetone/water). IR: 3522 s, 3428 s, 3368 s, 1647
C¼¼O), 1687 s (6-C¼¼O), 1602 s cmꢁ1
.
1H-NMR (CDCl3): d
4.05 and 4.15 (2 d, J ¼ 13.3 Hz, 2 ꢃ 1 H, CH2), 6.92–6.94
(m, 2 H, H at Ph), 7.02–7.08 (m, 3 H, H at Ph), 7.46–7.59 and
7.68 (2 m, 3 H, 2-H, 9-H, 10-H), 7.90 and 8.27 (2 d, J ¼ 7.7
Hz, 1 H, 11-H), 8.35 (d, J ¼ 8.2 Hz, 1 H, 3-H), 8.44 (d, 7.6
Hz, 1 H, 8-H). Anal Calcd for C22H14N4O2 (366.38): C, 72.12;
H, 3.85; N, 15.29. Found: C, 72.10; H, 4.02; N, 14.90.
1
(C¼¼O) s, 1622 s, 1597 s, 1572 s cmꢁ1. H-NMR (DMSO-d6):
d 2.95 and 3.17 (2 qd, J ¼ 7.0 and 13.0 Hz, 2 ꢃ 1 H, CH2),
5.32 (q, J ¼ 7.0 Hz, 1 H, CH), 5.61 (d, J ¼ 7.0 Hz, 1 H, OH),
7.15–7.30 (m, 7 H, 7-H, 6-H, 5 H at Ph), 7.45 (t, J ¼ 7.6 Hz,
1 H, 3-H), 7.77 (d, J ¼ 8.0 Hz, 1 H, 8-H), 8.18 (d, J ¼ 7.7
Hz, 1 H, 5-H), 8.28 (d, J ¼ 7.6 Hz, 1 H, 4-H), 8.45 (d, J ¼
7.5 Hz, 1 H, 2-H), 11.76 (s, 1 H, NH). MS [APCI, pos]: m/z
(%) ¼ 316 (100, [M þ H]þ). MS [APCI, neg]: m/z (%) ¼ 314
(100, [M ꢁ H]þ). Anal Calcd for C21H17NO2 (315.38): C,
79.98; H, 5.43; N, 4.44. Found: C, 79.59; H, 5.82; N, 4.05.
5-Azido-5-methyl-4H-pyrido[3,2,1-jk]carbazole-4,6(5H)-dione
(8a). A mixture of 5-chloro-5-methylpyridocarbazoledione 2a
(3.00 g, 10.5 mmol) and sodium azide (1.00 g, 15.3 mmol) in
dimethylformamide (50 mL) was stirred and heated for 60 min
at 50ꢀC. The reaction mixture was cooled to room temperature
and poured onto crushed ice/water (100 mL), filtered, and
washed with water. The yield was 2.30 g (75%), yellow nee-
dles, mp 155ꢀC (ethanol). IR: 3500–2900 m, 2116 s (N3),
5-Azido-5-phenyl-4H-pyrido[3,2,1-jk]carbazole-4,6(5H)-dione
(8e). It was obtained from 5-chloro-5-phenylpyridocarbazole-
dione 2e (3.45 g, 10 mmol) using the procedure and workup
described for 2a. The yield was 2.39 g (68%), yellow needles,
mp 165–170ꢀC (ethanol). DSC: mp: 167.7ꢀC onset, 173.5ꢀC
peak max. (2 mcal/mg); decomposition: 167.0ꢀC onset,
199.6ꢀC peak max., ꢁ86 mcal/mg. IR: 3500–3300 s, 2117 s
(N3), 1725 s (4-C¼¼O), 1697 s (6-C¼¼O), 1632 s cmꢁ1
.
1H-
NMR (CDCl3): d 7.30–7.50 (m, 5 H, H at Ph), 7.50, 7.55, and
7.60 (3 t, J ¼ 7.5 Hz, 3 ꢃ 1 H, 2-H, 9-H, 10-H), 8.00 and
8.10 (2 d, J ¼ 7.6 Hz, 1 H, 1-H, 11-H), 8.20 (d, J ¼ 7.2 Hz,1
H, 3-H), 8.70 (d, J ¼ 7.9 Hz, 1 H, 8-H). Anal Calcd for
C21H12N4O2 (352.36): C, 71.59; H, 3.43; N, 15.90. Found: C,
71.90; H, 3.72; N, 15.53.
5-Methyl-5-phenylamino-4H-pyrido[3,2,1-jk]carbazole-4,6(5H)-
dione (9a). A solution of 5-chloro-5-methylpyridocarbazole-
dione 2a (2.00 g, 7 mmol) and aniline (5.5 mL, 60 mmol) in
dimethylformamide (20 mL) was heated and stirred for 5 h at
50ꢀC. After cooling to room temperature, the reaction mixture
1711 s (4-C¼¼O), 1684 s (6-C¼¼O), 1600 s cmꢁ1
.
1H-NMR
(CDCl3): d 1.98 (s, 3 H, CH3), 7.55, 7.59 and 7.63 (3 t, J ¼
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

September 2011
Synthesis and Reactions of Pyrido[3,2,1-jk]carbazole-4,6-diones
1047
was poured onto crushed ice/water (100 mL), filtered by suc-
tion, and washed with water. The yield was 1.50 g (63%), yel-
low crystals, mp 230ꢀC (ethanol). IR: 3389 s, 2980 w, 1722 s
4.71 (s, 1 H, NH), 6.38 (d, J ¼ 7.7 Hz, 2 H, H at Ph), 6.70 (t,
J ¼ 7.4 Hz, 1 H, H at Ph), 6.99–7.03 (m, 2 H, H at Ph), 7.52–
7.64 (m, 3 H, 2-H, 9-H, 10-H), 8.10–8.13 (m, 2 H, 1-H, 11-
H), 8.32 (d, J ¼ 7.6 Hz, 1 H, 3-H), 8.61 (d, J ¼ 7.9 Hz, 1 H,
8-H). Anal Calcd for C25H22N2O2 (382.47): C, 78.51; H, 5.80;
N, 7.32. Found: C, 78.71; H, 5.91; N, 7.34.
(4-C¼¼O), 1689 s (6-C¼¼O), 1602 s cmꢁ1
.
1H-NMR (CDCl3):
d 1.87 (s, 3 H, CH3), 3.50 (s, 1 H, NH), 6.37 (d, J ¼ 8.0 Hz,
2 H, H at Ph), 6.72 (t, J ¼ 7.3 Hz, 1 H, H at Ph), 7.05 (t, J ¼
8.0 Hz, 2 H, H at Ph), 7.52–7.64 (m, 3 H, 2-H, 9-H, 10-H),
8.10–8.14 (m, 2 H, 1-H, 11-H), 8.34 (d, J ¼ 7.7 Hz, 1 H, 3-
H), 8.60 (d, J ¼ 8.1 Hz, 1 H, 8-H). Anal Calcd for
C22H16N2O2 (340.39): C, 77.63; H, 4.74; N, 8.23. Found: C,
77.71; H, 4.98; N, 8.27.
5-Methyl-5-benzylamino-4H-pyrido[3,2,1-jk]carbazole-4,6(5H)-
dione (9b). It was obtained from 5-chloro-5-methylpyridocarba-
zoledione 2a (3.00 g, 10.6 mmol) and benzylamine (10 mL,
91 mmol) in dimethylformamide (20 mL) using the procedure
and workup described for 9a. The yield was 3.00 g (80%), yel-
low crystals, mp 159ꢀC (ethanol). IR: 3298 s, 2950–2850 w,
5-Benzylamino-5-butyl-4H-pyrido[3,2,1-jk]carbazole-4,6(5H)-
dione (9f). It was obtained from 5-butyl-5-chloropyridocarbazo-
ledione 2c (3.26 g, 10 mmol) and benzylamine (3.2 mL, 30
mmol) in dimethylformamide (20 mL) after 24 h using the pro-
cedure and workup described for 9a. The yield was 3.09 g
(78%), yellow crystals, mp 154–155ꢀC (methanol). IR: 3445 m,
3380 m, 2800–2970 w, 1710 m (4-C¼¼O), 1660 s (6-C¼¼O),
1595 w cmꢁ1
.
1H-NMR (CDCl3): d 0.90 (t, J ¼ 7 Hz, 3 H,
CH3), 1.20–1.45 (m, 4 H, 2 butyl-CH2), 2.20–2.30 (m, 2 H,
ArCH2), 3.55 (s, 1 H, NH), 4.49–4.51 (m, 2 H, benzyl-CH2),
7.05–7.35 (m, 8 H, 5 H at Ph, 2-H, 9-H, 10-H), 8.10 (d, J ¼ 7.5
Hz, 2H, 1-H, 11-H), 8.30 (d, J ¼ 7.0 Hz, 1 H, 3-H), 8.50 (d, J
¼ 7.0 Hz, 1 H, 8-H). Anal Calcd for C26H24N2O2 (396.49): C,
78.76; H, 6.10; N, 7.07. Found: C, 78.91; H, 5.95; N, 7.35.
5-Methyl-5-morpholin-4-yl-4H-pyrido[3,2,1-jk]carbazole-
4,6(5H)-dione (10a). It was obtained from 5-chloro-5-methyl-
pyridocarbazoledione 2a (1.00 g, 3.5 mmol) and morpholine
(3.0 mL, 35 mmol) in dimethylformamide (20 mL) using the
procedure and workup described for 9a. The yield was 1.02 g
(87%), yellow crystals, mp 165ꢀC (ethanol). IR: 3600–3400 m,
2950–2830 s, 1719 s (4-C¼¼O), 1684 s (6-C¼¼O), 1600 w
1722 s (4-C¼¼O), 1664 s (6-C¼¼O), 1600 w cmꢁ1
.
1H-NMR
(CDCl3): d 1.72 (s, 3 H, CH3), 3.69–3.71 (m, 2 H, CH2),
7.17–7.26 (m, 3 H, H at Ph), 7.41 (d, J ¼ 7.2 Hz, 2 H, H at
Ph), 7.51–7.58 and 7.65–7.67 (2 m, 1 þ 2 H, 2-H, 9-H, 10-H),
8.09 (d, J ¼ 7.7 Hz, 2 H, 1-H, 11-H), 8.27 (d, J ¼ 7.6 Hz, 1
H, 3-H), 8.65 (d, J ¼ 8.2 Hz, 1 H, 8-H). Anal Calcd for
C23H18N2O2 (354.41): C, 77.95; H, 5.12; N, 7.90. Found: C,
77.56; H, 5.30; N, 7.60.
5-Phenyl-5-phenylamino-4H-pyrido[3,2,1-jk]carbazole-4,6(5H)-
dione (9c). It was obtained from 5-chloro-5-phenylpyridocarba-
zoledione 2e (2.00 g, 5.8 mmol) and aniline (5.5 mL, 60
mmol) according to the procedure and workup described for
9a. The yield was 1.94 g (83%), yellow crystals, mp 165ꢀC
(ethanol). IR: 3415 s, 3010 m, 1720 s (4-C¼¼O), 1688 s (6-
cmꢁ1
.
1H-NMR (CDCl3): d 1.72 (s, 3 H, CH3), 2.88 (t, J ¼
4.5 Hz, 4 H, 2 CH2), 3.73 (t, J ¼ 4.5 Hz, 4 H, 2 CH2), 7.50–
7.55 and 7.63–7.65 (2 m, 2 þ 1 H, 2-H, 9-H, 10-H), 8.04 and
8.08 (2 d, J ¼ 7.7 Hz, 2 ꢃ 1 H, 1-H, 11-H), 8.25 (d, J ¼ 7.6
Hz, 1 H, 3-H), 8.64 (d, J ¼ 7.8 Hz, 1 H, 8-H). Anal Calcd for
C20H18N2O3 (334.38): C, 71.84; H, 5.43; N, 8.38. Found: C,
71.63; H, 5.61; N, 8.30.
1
C¼¼O), 1600 s cmꢁ1. H-NMR (CDCl3): d 4.99 (s, 1 H, NH),
6.49 (d, J ¼ 7.7 Hz, 2 H, H at Ph), 6.75 (t, J ¼ 7.3 Hz, 1 H,
H at Ph), 7.10 (t, J ¼ Hz, 2 H, H at Ph), 7.29–7.32 (m, 3 H,
H at Ph), 7.53–7.66 (m, 5 H, 2 H at Ph, 2-H, 9-H, 10-H), 8.11
(t, J ¼ 7.0 Hz, 2 H, 1-H, 11-H), 8.27 (d, J ¼ 7.0 Hz, 1 H, 3-
H), 8.67 (d, J ¼ 8.1 Hz, 1 H, 8-H). Anal Calcd for
C27H18N2O2 (402.46): C, 80.58; H, 4.51; N, 6.96. Found: C,
80.37; H, 4.71; N, 6.97.
5-Methyl-5-piperidin-1-yl-4H-pyrido[3,2,1-jk]carbazole-4,6(5H)-
dione (10b). It was obtained from 5-chloro-5-methylpyridocar-
bazoledione 2a (1.00 g, 3.5 mmol) and piperidine (3.0 mL, 35
mmol) in dimethylformamide (20 mL) using the procedure and
workup described for 9a. The yield was 1.01 g (86%), yellow
crystals, mp 116ꢀC (ethanol). IR: 2940–2820 s, 1704 s (4-
5-Benzylamino-5-phenyl-4H-pyrido[3,2,1-jk]carbazol-4,6(5H)-
dione (9d). It was obtained from 5-chloro-5-phenylpyridocarba-
zoledione 2e (3.00 g, 8.7 mmol) and benzylamine (10.00 mL,
91 mmol) in dimethylformamide (20 mL) according to the pro-
cedure and workup described for 9a. The yield was 3.00 g
(83%), yellow crystals, mp 165ꢀC (ethanol). IR: 3288 s, 3010–
C¼¼O), 1677 s (6-C¼¼O), 1605 m cmꢁ1
.
1H-NMR (CDCl3): d
1.48 (q, J ¼ 5.4 Hz, 2 H, CH2), 1.60 (q, J ¼ 5.4 Hz, 4 H, 2
CH2), 1.69 (s, 3 H, CH3), 2.81 (q, J ¼ 5.3 Hz, 4 H, 2 CH2),
7.47–7.53 and 7.61–7.63 (2 m, 2 þ 1 H, 2-H, 9-H, 10-H), 8.06
and 8.07 (2 d, J ¼ 7.8 Hz, 2 ꢃ 1 H, 1-H, 11-H), 8.21 (d, J ¼
7.4 Hz, 1 H, 3-H), 8.64 (d, J ¼ 8.2 Hz, 1 H, 8-H). Anal Calcd
for C21H20N2O2 (332.41): C, 75.88; H, 6.06; N, 8.43. Found:
C, 75.85; H, 6.19; N, 8.36.
2920 w, 1700 m (4-C¼¼O), 1667 s (6-C¼¼O), 1611 s cmꢁ1
.
1H-NMR (CDCl3): d 3.79 and 3.88 (2 d, J ¼ 13.0 Hz, 2 ꢃ 1
H, CH2), 5.72 (m, 1 H, NH), 7.24–7.27, 7.30–7.34, and 7.51–
7.55 (3 m, 4 þ 2 þ 6 H, 10 H at Ph, 9-H, 10-H), 7.67 (t, J ¼
7.7 Hz, 1 H, 2-H), 8.05 and 8.10 (2 d, J ¼ 7.7 Hz, 1 H, 1-H,
11-H), 8.22 (d, J ¼ 7.6 Hz, 1 H, 3-H), 8.71 (d, J ¼ 8.2 Hz, 1
H, 8-H). Anal Calcd for C28H20N2O2 (416.48): C, 80.75; H,
4.84; N, 6.73. Found: C, 80.36; H, 4.68; N, 6.68.
5-Morpholin-4-yl-5-phenyl-4H-pyrido[3,2,1-jk]carbazol-4,6(5H)-
dione (10c). It was obtained from 5-chloro-5-phenylpyridocar-
bazoledione 2e (2.00 g, 5.8 mmol) and morpholine (5.50 mL,
60 mmol) in dimethylformamide (20 mL) using the procedure
and workup described for 9a. The yield was 1.80 g (78%), yel-
low crystals, mp 230ꢀC (ethanol). IR: 3600–3400 m, 2970–
2830 s, 1715 s (4-C¼¼O), 1681 s (6-C¼¼O), 1605 s, 1596 s
5-Butyl-5-phenylamino-4H-pyrido[3,2,1-jk]carbazole-4,6(5H)-
dione (9e). It was obtained from 5-butyl-5-chloropyridocarba-
zoledione 2c (1.50 g, 4.6 mmol) and aniline (2.00 mL, 22
mmol) in dimethylformamide (20 mL) using the procedure and
workup described for 9a. The yield was 1.30 g (74%), yellow
crystals, mp 201ꢀC (ethanol). IR: 3357 s, 2950–2800 w, 1715
1
cmꢁ1. H-NMR (CDCl3): d 3.01 (m, 4 H, CH2), 3.78 (m, 4 H,
CH2), 7.44–7.67 (m, 8 H, 5 H at Ph, 2-H, 9-H, 10-H), 7.97
and 8.06 (2 d, J ¼ 7.8 Hz, 2 ꢃ 1 H, 1-H, 11-H), 8.18 (d, J ¼
7.8 Hz, 1 H, 3-H), 8.71 (d, J ¼ 7.6 Hz, 1 H, 8-H). Anal Calcd
for C25H20N2O3 (396.45): C, 75.73; H, 5.08; N, 7.07. Found:
C, 75.70; H, 5.19; N, 7.08.
1
s (4-C¼¼O), 1675 s (6-C¼¼O), 1599 s cmꢁ1. H-NMR (CDCl3):
d 0.82 (t, J ¼ 7.2 Hz, 3 H, CH3), 1.19–1.29 and 1.33–1.42 (2
m, 4 H, 2 CH2), 2.18 (dt, J ¼ 7.5 þ 14.3 Hz, 2 H, ArCH2),
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

1048
W. Stadlbauer, H. V. Dang, and B. Knobloch
Vol 48
(401.47): C, 83.77; H, 4.77; N, 3.49. Found: C, 83.99; H,
4.98; N, 3.88.
5-Phenyl-5-piperidin-1-yl-4H-pyrido[3,2,1-jk]carbazol-4,6(5H)-
dione (10d). It was obtained from 5-chloro-5-phenylpyridocar-
bazoledione 2e (3.00 g, 8.7 mmol) and piperidine (10 mL, 91
mmol) in dimethylformamide (20 mL) using the procedure and
workup described for 9a. The yield was 3.02 g (88%), yellow
crystals, mp 165ꢀC (ethanol). IR: 3100 w, 2938 s, 2860–2800
5-Allyl-5-butylpyrido[3,2,1-jk]carbazol-4,6(5H)-dione (11c). 5-
Butyl-4-hydroxypyridocarbazolone 1c (3.11 g, 0.01 mol) and
allylbromide (5.5 mL, 0.064 mol) were brought to reaction
at 40ꢀC and worked up as described for 11a. The yield was
1.95 g (59%), yellowish powder, mp 96–99ꢀC (ethanol/
water). IR: 2980–2750 w, 1700 s, 1665 s, 1630 w, 1600 s.
1H-NMR (CDCl3): d 0.85 (t, J ¼ 7.0 Hz, 3 H, CH3), 1.10–
1.35 (m, 4 H, 2 butyl-CH2), 2.00–2.20 (m, 2 H, butyl-CH2),
2.70–2.90 (m, 2 H, allyl-CH2), 4.95–5.10 (m, 2 H, ¼¼CH2),
5.55–5.80 (m, 1 H, ACH¼¼), 7.30–7.65 (m, 3 H, 2-H, 9-H,
10-H), 7.85–8.10 (m, 3 H, 1-H, 11-H, 3-H), 8.60 (dd, J ¼
7.0 þ 1.5 Hz, 1 H, 8-H). Anal Calcd for C22H21NO2
(331.42) C, 79.73; H, 6.39; N, 4.23. Found: C, 79.46; H,
6.75; N, 3.88.
1
m, 1718 s (4-C¼¼O), 1686 s (6-C¼¼O), 1593 s cmꢁ1. H-NMR
(CDCl3): d 1.53–1.64 (m, 6 H, 3 CH2), 2.74–2.87 (m, 4 H, 2
CH2), 7.26–7.29 (m, 3 H, H at Ph), 7.45–7.54 and 7.62–7.66
(2 m, 2 þ 3 H, 2-H at Ph, 2-H, 9-H, 10-H), 7.98 and 8.07 (2
d, J ¼ 8.3 Hz, 2 ꢃ 1 H, 1-H, 11-H), 8.18 (d, J ¼ 7.6 Hz, 1 H,
3-H), 8.73 (d, J ¼ 8.2 Hz, 1 H, 8-H). Anal Calcd for
C26H22N2O2 (394.48): C, 79.17; H, 5.62; N, 7.10. Found: C,
78.88; H, 5.84; N, 7.10.
5-Butyl-5-morpholin-4-yl-4H-pyrido[3,2,1-jk]carbazole-4,6(5H)-
dione (10e). It was obtained from 5-butyl-5-chloropyridocarba-
zoledione 2c (3.26 g, 0.01 mol) and morpholine (27 mL, 30
mmol) in dimethylformamide (8 mL) after 24 h using the pro-
cedure and workup described for 9a. The yield was 3.19 g
(85%), brown powder, mp 40–45ꢀC. IR: 3600–3400 m, 2950–
REFERENCES AND NOTES
1
2850 s, 1720 s (4-C¼¼O), 1680 s (6-C¼¼O), 1600 s cmꢁ1. H-
[1] (a) Budavari, S., Ed. The Merck Index; Merck & Co Inc:
Rahway, 1996; Vol. 12, p 9020; (b) Smith, G. F. In The Alkaloids;
Manske, R. H. F., Ed.; Academic Press: New York, 1965; Vol. VIII, p
591; (c) Budavari, S., Ed. The Merck Index; Merck & Co Inc: Rah-
way, 1996; Vol. 12, p 1476; (d) Budavari, S., Ed. The Merck Index;
Merck & Co Inc: Rahway, 1996; Vol. 12, p 10170.
NMR (CDCl3): d 0.75 (t, J ¼ 7.0 Hz, 3 H, CH3), 1.00–1.35
(m, 4 H, 2 butyl-CH2), 2.20–2.28 (m, 2 H, ArCH2), 2.80 (t, J
¼ 5.0 Hz, 4 H, 2 morpholine-CH2), 3.65 (t, J ¼ 5.0 Hz, 4 H,
2 morpholine-CH2), 7.45–7.70 (m, 3 H, 2-H, 9-H, 10-H), 8.05
(t, J ¼ 7.0 Hz, 2 H, 1-H, 11-H), 8.25 (d, J ¼ 7.5 Hz, 1 H, 3-
H), 8.65 (d, J ¼ 7 Hz, 1 H, 8-H). Anal Calcd for C23H24N2O3
(376.46): C, 73.38; H, 6.43; N, 7.44. Found: C, 73.76; H,
6.70; N, 7.07.
[2] (a) Ziegler, E.; Litvan, F. (Geigy Chemical Corp.). US Pat.
3,052,678, 1959; Chem Abstr 1963, 58, 3437e; (b) Geigy Chemical
Corp., Brit. Pat. 912,289, 1960; Chem Abstr 1963, 59, 645.
[3] (a) Zirngibl, U. (Sandoz Ltd.). Ger. Offen. DE 2 142 334,
19 720 302, 1972; (b) Zirngibl, U. (Sandoz Ltd.). Ger. Offen. DE 71–
2 142 334—19710824, 1971; Chem Abstr 1972, 77, 36383.
[4] Dang, H. V.; Knobloch, B.; Habib, N. S.; Kappe, T.; Stadl-
bauer W. J Heterocycl Chem 2005, 42, 85.
5-Benzyl-5-butylpyrido[3,2,1-jk]carbazol-4,6(5H)-dione (11a). A
solution of 5-butyl-4-hydroxypyridocarbazolone 1c (10.27 g,
0.035 mol) in aqueous sodium hydroxide (2.92 g, 0.073 mol in
150 mL water) was heated to 80ꢀC. Benzylchloride (9.0 mL,
0.078 mol) was added dropwise under vigorous stirring and
the obtained suspension was stirred for 12 h at 80ꢀC. After
cooling, chloroform (80 mL) was added, the layers were sepa-
rated, and the aqueous layer was extracted with chloroform (2
ꢃ 30 mL). The combined organic layers were washed with
water and dried with sodium sulfate. The solvent was removed
under reduced pressure, the solid product washed with ice-cold
petroleum ether, and dried at room temperature. The yield was
11.68 g (87%), yellowish powder, mp 132–133ꢀC (ethanol);
[5] Dang, H. V.; Stadlbauer, W. J Heterocycl Chem 2006, 43,
65.
[6] (a) Stadlbauer, W.; Laschober, R.; Lutschounig, H.; Schin-
dler, G.; Kappe, T. Monatsh Chem 1992, 123, 617; (b) Ziegler, E.;
Kappe, T. Monatsh Chem 1963, 94, 447; (c) Ziegler, E.; Salvador, R.;
Kappe, T. Monatsh Chem 1962, 93, 1376; (d) Malle, E.; Stadlbauer,
W.; Ostermann, G.; Hofmann, B.; Leis, H. J.; Kostner, G. M. Eur J
Med Chem 1990, 25, 137.
[7] Buckle, D. R.; Cantello, B. C. C.; Smith, H.; Spicer, B. A.
J Med Chem 1975, 18, 726.
IR : 3080–2760 m, 1705 s, 1670 s, 1595 m cmꢁ1 1H-
.
[8] Seidenfaden, W.; Pawellek, D. In Houben-Weyl, Methoden
der Organischen Chemie, 4th ed.; Mu¨ller, E., Ed.; Georg Thieme Verlag:
Stuttgart, 1971; Vol. 10, p 849.
NMR(CDCl3): d 0.80 (t, J ¼ 7.0 Hz, 3 H, CH3), 1.05–1.40
(m, 4 H, 2 butyl-CH2), 2.35 (t, J ¼ 7.1 Hz, 2 H, butyl-CH2),
3.50 (s, 2 H, benzyl-CH2), 6.80–6.95 (m, 3 H, H at Ph), 6.95–
7.15 (m, 2 H, H at Ph), 7.30–7.65 (m, 3 H, 2-H, 9-H, 10-H),
7.85–8.10 (m, 3 H, 1-H, 11-H, 3-H), 8.60 (dd, J ¼ 7.0 þ 1.5
Hz, 1 H, 8-H). Anal Calcd for C26H23NO2 (381.48): C, 81.86;
H, 6.08; N, 3.67. Found: C, 81.90; H, 6.16; N, 3.59.
[9] (a) Budzikiewicz, H.; Schaller, U.; Korth, H.; Pulverer, G.
Monatsh Chem 1979, 110, 947; (b) Kitamura, S.; Hashizume, K.; Iida,
T.; Miyashita, E.; Shirahata, K.; Kase, H. J Antibiot 1986, 39, 1160;
(c) Laschober, R.; Stadlbauer, W. Liebigs Ann Chem 1990, 1083; (d)
Chu, M.; Mierzwa, R.; Xu, L.; He, L.; Terracciano, J.; Patel, M.;
Zhao, W.; Black, T. A.; Chan, T.-M. J Antibiot 2002, 55, 215; (e)
5-Benzyl-5-phenylpyrido[3,2,1-jk]carbazol-4,6(5H)-dione
(11b). 5-Phenyl-4-hydroxypyridocarbazolone
1e
(10.85g,
´ ´
Lepine, F.; Milot, S.; Deziel, E.; He, J.; Rahme, L. G. J Am Soc Mass
0.035 mol) and benzylchloride (9.0 mL, 0.078 mol) were
brought to reaction and worked up as described for 11a.
The yield was 8.98 g (64%), yellow brownish powder, mp
201ꢀC (cyclohexane); lit. mp 201ꢀC [17]. IR: 3040 w, 1705 s,
Spectrom 2004, 15, 862.
[10] (a) Poupelin, J. P.; Saint-Ruf, G.; Perche, J. C.; Lacroix, R.;
Uchida-Ernouf, G.; Narcisse, G.; Hubert, F. Eur J Med Chem 1979,
14, 171; (b) Poupelin, J. P.; Saint-Ruf, G.; Perche, J. C.; Roussey, J.
C.; Laude, B.; Narcisse, G.; Bakri-Logeais, F.; Hubert, F. Eur J Med
Chem 1980, 15, 253; (c) Faber, K.; Steininger, H.; Kappe, T. J Hetero-
cycl Chem 1985, 22, 1081.
1670 s, 1600 m, 1490 m cmꢁ1 1H-NMR (DMSO-d6): d 3.62
.
(s, 2 H, CH2), 6.85–7.25 (m, 10 H, H at Ph), 7.35–7.70 (m, 3
H, 2-H, 9-H, 10-H), 7.90–8.25 (m, 3 H, 1-H, 11-H, 3-H), 8.70
(dd, J ¼ 7.0 þ 1.5 Hz, 1 H, 8-H). MS (EI): m/z (%) ¼ 401
(36, Mþ), 310 (76), 309 (67), 194 (51), 193 (26), 166 (36),
165 (27), 92 (20), 91 (100). Anal Calcd for C28H19NO2
[11] Takayama, M. J Mass Spectrom Soc Jpn 1995, 43, 177.
ˇ
´ ˇ
[12] Klasek, A.; Koristek, K.; Polis, J.; Kosmrlj, J. J. Tetrahe-
dron 2000, 56, 1551.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

September 2011
Synthesis and Reactions of Pyrido[3,2,1-jk]carbazole-4,6-diones
1049
´ ˇ
[13] Kafka, S.; Klasek, A.; Kosmrlj, J. J Org Chem 2001, 66,
[15] (a) Kappe, T.; Ziegler, E. Monatsh Chem 1968, 99, 1943;
(b) Kappe, T.; Sterk, H.; Ziegler, E. Monatsh Chem 1968, 99, 1950;
(c) Kappe, T.; Ziegler, E. Synthesis 1969, 74; (d) Kappe, T.; Fritz, P.
F.; Ziegler, E. Monatsh Chem 1971, 102, 412; (e) Kappe, T., Fritz, P.
F.; Ziegler, E. Chem Ber 1973, 106, 1927.
6394.
¨
[14] (a) Aspelund, H.; Kronlof, J. Acta Acad Aboensis, Math
Phys 1957, 21, 3; (b) Aspelund, H. Acta Acad Aboensis, Math Phys
Ser B 1968, 28, 3; (c) Aspelund, H.; Mandell, L. Acta Acad Aboensis,
Math Phys 1956, 20, 3; (d) Stadlbauer, W.; Kappe, T. Monatsh Chem
1985, 116, 1005.
[16] Harwood, L. M. Aldrichim Acta 1985, 18, 25.
[17] Stadlbauer, W.; Kappe, T. Monatsh Chem 1984, 115, 467.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet