Microwave-assisted multicomponent synthesis of aza-, diaza-, benzo-, and dibenzofluorenedione derivatives

Article abstract of DOI:10.1080/00397910802044249

A microwave procedure was efficiently applied to the synthesis of a series of heteropolycyclic compounds with known or potential biological activities. Antitumor amide 3was obtained in a few minutes and with high yields through a solventless, one-pot cyclization, followed by treatment with the suitable amine. This method was also used to access tetracyclic aza-compounds 5/6, where their selective formation as N,N-syn and N,N-anti regioisomers was investigated under a solventless condition, or by changing the solvent, in the presence of solid supports and a catalytic amount of ecofriendly metal salts. Thermal access to similar polycyclic compounds recently reported under conventional heating by using the preformed pyridinium or isoquinolinium ylides was improved in this instance by microwave irradiation and extended to the synthesis of diaza-esters. In any case, the one-pot, three-component cyclization was more atom-efficient than the N-ylide sequence. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/00397910802044249

Synthetic Communications1, 38: 3003–3016, 2008
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910802044249
Microwave-Assisted Multicomponent Synthesis of
Aza-, Diaza-, Benzo-, and
Dibenzofluorenedione Derivatives
Andrea Defant, Graziano Guella, and Ines Mancini
Laboratory of Bioorganic Chemistry, Department of Physics,
University of Trento, Povo-Trento, Italy
Abstract: A microwave procedure was efficiently applied to the synthesis of a ser-
ies of heteropolycyclic compounds with known or potential biological activities.
Antitumor amide 3 was obtained in a few minutes and with high yields through a
solventless, one-pot cyclization, followed by treatment with the suitable amine. This
method was also used to access tetracyclic aza-compounds 5=6, where their selective
formation as N,N-syn and N,N-anti regioisomers was investigated under a solvent-
less condition, or by changing the solvent, in the presence of solid supports and a
catalytic amount of ecofriendly metal salts. Thermal access to similar polycyclic
compounds recently reported under conventional heating by using the preformed
pyridinium or isoquinolinium ylides was improved in this instance by microwave
irradiation and extended to the synthesis of diaza-esters. In any case, the one-pot,
three-component cyclization was more atom-efficient than the N-ylide sequence.
Keywords: Heterocyclic cyclization, microwave-assisted synthesis, one-pot syn-
thesis, regioselectivity
INTRODUCTION
The unconventional energy source of microwave (MW) irradiation is now
widely used in organic synthesis because of its high efficiency, environ-
mentally friendly nature, and experimental ease of manipulation.[1] The
beneficial effects of MW activation are evident when sensitive reagents
Received October 18, 2007.
Address correspondence to Ines Mancini, Laboratorio di Chimica Bioorganica,
`
Dipartimento di Fisica, Universita di Trento, via Sommarive 14, I-38050
Povo-Trento, Italy. E-mail: mancini@science.unitn.it
3003

3004
A. Defant, G. Guella, and I. Mancini
are involved, products may decompose, or usual methods require forcing
conditions by heating and prolonged reaction times. The MW-assisted
reactions generally lead to higher yields of products and shorter reaction
time than traditional heating methods. Applications to reactions under
solventless conditions[2] in aqueous media and in combination with sup-
ported reagents have been reported.[3] In particular, MW- activated
organic synthesis has been widely employed in modern drug discovery[4]
in connection with a multicomponent approach of the target molecules,
depicted very often by heterocyclic compounds.[5]
Recently, we have reported on novel naphthindolizinedione deriva-
tives whose structures somehow resemble those of known antitumor
agents able to interact with DNA by intercalation. The synthesis involved
a three-component cyclization to give a series of analogs with structural
modifications both in the aromatic system and in the amide chain, among
which compound 3 (Scheme 1) showed the highest and selective cytotoxi-
city.[6] It is noteworthy that ester 2 was only moderately cytotoxic in cul-
tured stomach cancer cells, indicating the decisive role of the amide chain
on the bioactivity. With the aim to investigate the effect of structural
modifications on the naphthindolizinedione skeleton, we have prepared
some indolizino-quinoline-5,12-dione precursors by the cyclization of
compound 4 with ethyl acetoacetate (EAA) and pyridine or picoline[7]
(Scheme 2). The presence of the asymmetric chlorine atoms at the C(6)
and C(7) positions in 4 introduced the possibility of producing two regioi-
somers. The selective formation of the isomers N,N-syn 5 and N,N-anti 6
Scheme 1. Synthesis of aza-benzofluorenedione derivative 2 and the antitumor
amide 3.

Aza-, Diaza-, Benzo-, and Dibenzofluorenedione Derivatives
3005
Scheme 2. Synthesis of regioisomers 5=6 and 7=8 by reaction of 6,7-dichloroqui-
noline-5,8-dione (4) or its metal complex with pyridine or 4-methylpyridine,
respectively.
was solvent- and metal-ion dependent.[7] Based on the comprehensive
mechanism proposed for the formation of 5=6 (which involves attacks
of the C-nucleophile via a Michael addition on the C(6) and C(7) centers
in 4)[7,8] and on the reported advantages of MW irradiation on Michael
additions of various nucleophiles,[9] we have now applied the latter meth-
odology for the synthesis of a series of heteropolycyclic compounds.
Very recently, the synthesis of a series of polycyclic indolizine deriva-
tives including ester 5 by a new reaction sequence involving the use of N-
ylides has been reported.[10] We have extended the MW procedure to this
sequence, covering the investigation of the regioselective production of
diaza-derivatives.
We report here on the results from MW-assisted synthesis of (i)
methyl ester 2 and cytotoxic amide 3, (ii) regioisomers 5=6 both by the
pyridine=EAA[8] and by N-ylide[10] sequences under different experi-
mental conditions (solventless, aqueous medium, presence of catalytic
environmentally friendly metal salts and solid supports), and (iii) related
pentacyclic systems using isoquinoline instead of pyridine.
RESULTS AND DISCUSSION
The one-pot, three-component cyclization giving compound 2 (Scheme 1),
previously achieved under conventional heating,[6] has been here

3006
A. Defant, G. Guella, and I. Mancini
improved by application of MW irradiation of the reagents under
solvent-free conditions. The better results involve a shorter reaction
time, a higher yield to 2, and a lower formation of by-product.[7] In
addition, the procedure offers the chance to carry out the conversion
to the cytotoxic compound 3 by a consecutive MW irradiation of the
reaction mixture added to the amine directly in the same medium wherein
ester 2 was previously prepared. In fact, 2 is first obtained in an
irradiation time of 4 min, followed by the formation of 3 using a further
irradiation time of 10 min. The overall yield of the MW-assisted conver-
sion of 1 ! 3 is 87%, compared with a 73% yield after 7 h of conven-
tional heating.
The MW procedure applied to the synthesis of compounds 5=6 from
4 (Scheme 2) was initially investigated by changing the solvent reaction
(Table 1). The main aim was to improve the reaction conditions and to
study the selectivity in the production of N,N-syn=N,N-anti pair of regioi-
somers, in comparison with the previous conventional method.[7] When
water was used as an ecofriendly solvent, no improvement was achieved,
whereas by using dimethylsulfoxide (DMSO), dimethylformamide
(DMF), and pyridine, we found practically the same isomeric ratio from
conventional heating, but with a higher yield. The neat condition
afforded a better yield, with a regioselectivity similar to the reaction
refluxing in ethanol. The last outcome is also observed in the MW-
assisted reaction of 2 with 4-methylpyridine to afford the regioisomers
7=8 in 80:20 ratio with 85% yield (55% yield of 72:28 products, respect-
ively, under conventional heating[7]).
MW-assisted solvent-free procedure has been reported to find a prac-
tical improvement when the reagents are supported on a MW-inactive
material.[1d] We have first used very common supports such as silica
and alumina and then extended the investigation to celite, bentonite,
molecular sieves, and florisil. Unfortunately, lower values of both yield
and selectivity were observed than in neat condition. In the presence of
florisil, the isomeric ratio was partially inverted (5=6 ¼ 38:62), probably
due to a chelation of the reagent 2 with metal ions present in the compo-
sition of this support (Experimental), in agreement with the catalytic
role played by the metal ions in this reaction investigated under classical
heating.[7] Based on the presence of magnesium ion in florisil composi-
tion (Experimental), our hypothesis was supported by the results obtained
when the reaction was carried out in the presence of magnesium chloride,
furnishing 5=6 in 8:92 ratio, respectively. The regioselectivity was also
investigated under the catalytic presence of other metal salts. If compared
to conventional heating, higher yields were always obtained by MW-
assisted cyclization, although with the same or an even worse regioselec-
tivity, except in the case of ecofriendly magnesium chloride (Table 1).

Aza-, Diaza-, Benzo-, and Dibenzofluorenedione Derivatives
3007
Table 1. Microwave-assisted synthesis of regioisomers 5=6 and comparison with
the results under conventional heating
Microwave Irradiation
Conventional Heatinga
Yield
(%)
Yield
Ratio 5,6 (%) Ratio 5,6
Solvent
Systemb
Metal saltc
Pyridine=Ethyl Acetoacetate Sequenced
EtOH
H2O
DMF
DMSO
Pyridine
CH3CN
t-BuOH
Neat
64:36
50
65:35
73:27
80:20
80:20
67:43
82:18
60:40
56:44
53:47
64:36
48:52
62:38
60:40
38:62
8:92
50
90
94
85
80
88
82
60
58
68
70
60
62
68
62
86
58
69
60
80:20
78:22
80:20
55:45
68
60
38
54
Al2O3
SiO2
Celite
Bentonite
4A-mol sieves
˚
3A-mol sieves
Florisil
˚
MgCl2
FeCl3
Pd (OAc)2
Sc(OTf)3
Sm(OTf)3
25:75
43:57
66:34
21:79
15:85
36
43
39
42
39
42:58
70:30
35:65
40:60
Pyridinium-ylide Sequencee
CH3CN
DMF
t-BuOH
45:55
42:58
45:55
50:50
57:43
78
83
85
75
72
64
48:52
56
CH3CN KF=Al2O3
KF=Al2O3
Neat
CH3CN
MgCl2
62:38
ꢀ
aFor py=EAA sequence: 80 C, 4 h, in EtOH when metal salts were used;[7] for
ꢀ
ylide sequence: in CH3CN, 50 C, 24 h.
bIn the presence of 0.05 g of solid support.
cUsing the dry metal chelate previously obtained by stirring 4 with the metal
salt (0.3 equiv.) in EtOH, 1 h.
d4 (0.01 g, 1 mol. equiv.), EAA (1.3 equiv.), pyridine (6.2 equiv.), 540 W,
ꢀ
4–6 min, 110–140 C.
e4 (0.01 g, 1 mol. equiv.), pyridinium salt 9 (1.1 equiv.), K2CO3 (3.5 equiv.), or
the system otherwise specified, under heating[10] or by irradiation at 230 W,
15 min.

3008
A. Defant, G. Guella, and I. Mancini
Scheme 3. Synthesis of tetracyclic esters 5=6 and 10 by pyridinium N-ylide
sequence.
In addition, the MW-assisted procedure has been found to improve
the formation of 10 via ylide from pyridinium salt 9 (Scheme 3), pre-
viously prepared by the reaction of pyridine with ethyl bromoacetate in
EtOAc.[11] By MW irradiation (230 W, 15 min) of the CH3CN mixture
containing 1 and the in situ generated ylide from 9, a higher yield
(82%) was obtained than that reported after heating 24 h at 50 ꢀC
(58%).[10] When the pyridinium-ylide sequence was applied to the pro-
duction of the isomers 5=6, a very low selectivity resulted with thermal
conditions, as well as with MW irradiation in neat condition, or with dif-
ferent solvents, or when the KF=Al2O3 system was used instead of
K2CO3 as a base (Table 1). These results are in agreement with the
low difference of charge evaluated for the electrophilic C(6) and C(7)
centers of substrate 4 (þ0.141 and þ0.148 respectively by semi-empirical
Zerner’s intermediate neglect of differential overlap [ZINDO] calcula-
tions).[7] A better selectivity resulted from the presence of MgCl2,
although far from the value obtained for the three-component pyridi-
ne=EAA sequence (Table 1). It is noteworthy that a reversed ratio was
obtained by the two sequences. In addition, the formation of N,N-syn
5 as the prevalent product from the pyridinium-ylide sequence in the
presence of metal salt supports the mechanism by Liu et al.[10] for the
reaction of 1. They propose a nucleophilic attack of the ylide on a C-Cl
center in 1, followed by the release of pyridine, which can successively
attack the second C-Cl center. When this sequence is applied to the metal
chelated substrate 4 where C(6) results to be a more electrophilic center
than C(7), the first attack of the ylide is able to give N,N-syn 5 as the
main isomer.
Pentacyclic systems were accessible under similar conditions when
isoquinoline was used instead of pyridine (Scheme 4). Starting from

Aza-, Diaza-, Benzo-, and Dibenzofluorenedione Derivatives
3009
Scheme 4. Synthesis of aza- and diaza-dibenzofluorenedione derivatives 12 and
14=15.
2,3-dichloro-naphtoquinone (1), the compound 12[12] was the only
observed product deriving from the regiospecific closure at the C(1) pos-
ition in the isoquinoline ring, whereas the closure at C(3) position was
expected to afford compound 13 (Scheme 4). The structure of 12 was fully
characterized by high-resolution mass spectrometric measurements and
extensive NMR analysis (Experimental). MW-assisted synthesis of 12
under solvent-free conditions gave a better yield (87%) when compared
to the classical thermal reaction (52%).[12] Moreover, the preparation of
12 performed by direct MW irradiation of the reagent mixture adsorbed
on a thin-layer chromatography (TLC) plate[13] provided a simplified iso-
lation procedure, resulting in an efficient time-saving methodology.
By using compound 4, the isomers N,N-syn 14 and N,N-anti 15
were furnished (Scheme 4). Their structural assignments were based on
the heteronuclear multiple bond correlation (HMBC) correlations
H-C(11)=C(12) (dC 179.50 ppm) for 14 and H-C(8)=C(7) (dC
173.79 ppm) for 15. These assignments are in nice agreement with the
HMBC correlation observed for H-C(11)=C(12) (dC ¼ 174.99 ppm) in
12, according to the structures fully established for similar regioisomers
5 and 6.[7] The same reaction reported by Yanni[14] under thermal con-
ditions gave 14 as a single product, showing a moderate antimicrobial
activity against some bacterial species and the fungus Candida albicans.[14]

3010
A. Defant, G. Guella, and I. Mancini
Table 2. Microwave-assisted synthesis of regioisomers 14=15
Conventional heatinga
Microwave irradiation
Ratio
14,15
Yield
(%)
Ratio
14,15
Yield
(%)
Solvent Systemb
Metal saltc
Isoquinoline=Ethyl Acetoacetate Sequenced
62:38
EtOH
Neat
DMSO
Florisil
35
33
62:38
72:28
50:50
15:85
42:58
80
87
69
60
55
MgCl2
Sc(OTf)3
34:66
Isoquinolinium-ylide Sequencee
38:62
CH3CN
85
a–dAs described in Table 1, with isoquinoline instead of pyridine.
e4 (0.01 g, 1 mol. equiv.), 11 (1.1 equiv.), K2CO3 (3.5 equiv.), 230 W, 15 min.
The N,N-syn structure of 14 was ascribed mainly on mechanistic grounds,
although the rough and poor structural details reported cannot unam-
biguously establish the structure of such a regioisomer. When we per-
formed the reaction under the same thermal conditions and also by
MW irradiation, the two regioisomers 14=15 were obtained (Experi-
mental), in ratio as expected similar to 5=6. Also in this case a remarkable
improvement of the yields was achieved by MW irradiation (80%), if com-
pared to the poor yield (35%) under conventional heating (Table 2).
Although obtained with a lower regioselectivity, the easier chromato-
graphic separation of 14=15 when compared to analog 5=6,[7] allowed us
to obtain each isomer as a pure compound.
The selectivity in the production of the two regioisomers has also
been investigated. The good performance of DMSO as solvent in the
thermal cyclization was confirmed in the MW procedures giving 5=6
(Table 1) and 14=15 (Table 2) with higher values of yield and selectivity
than under the solvent-free conditions. When florisil was used as a solid
support, a worse regioselectivity was achieved, similar to what was
observed for the synthesis of 5=6. As expected, an inversion of a selec-
tivity was achieved in the presence of a catalytic amount of metal salts,
with the best result from magnesium ion chelation (14=15 ¼ 15:85),
although with a moderate yield.
In agreement with the results for the pyridinium-ylide sequence giv-
ing the tetracyclic compounds 5=6, a low selectivity in favor of the N,N-
anti regioisomer was obtained by applying the isoquinolinium-ylide
sequence[10] to the substrate 4 (Table 2).

Aza-, Diaza-, Benzo-, and Dibenzofluorenedione Derivatives
3011
In conclusion, the microwave irradiation has been successfully
applied to the synthesis of a series of heteropolycyclic compounds with
biological activities, including the strongly cytotoxic amide 3. The advan-
tages of this procedure were also observed for an N-ylide sequence
involving the reaction of both pyridinium and isoquinolinium ylides with
compound 1. However, this route, needing the previous formation of the
salt to be used for the in situ formation of N-ylide, failed in comparison
to the three-component sequence in the reaction with 4 when the interest
was focused on the regioselectivity. The successful method of obtaining
compounds 5=6 and 14=15 by the one-pot, three-component sequence
investigated here has a decisive advantage for the rapid access to a library
of related compounds as potential antitumor agents.
EXPERIMENTAL
Materials
Reagents and solvents were used without purification. Solid supports
were alumina (Al2O3), silica (SiO2), bentonite (H2Al2O6Si), florisil
˚
(MgO3Si), celite (SiO2), 3-A molecular sieves (KnNa12-n[(AlO2)12
˚
(SiO2)12] ꢁ xH2O, and 4-A molecular sieves (Na12[(AlO2)12(SiO2)12] ꢁ
xH2O). All evaporations were carried out at room temperature at reduced
pressure. Microwave irradiation was done in TdA Electronics
MG717ADL apparatus working at 2.450 GHz until complete conversion
of the quinone reagent, as checked by thin-layer chromatography (TLC).
The reactions were carried out in a closed vial placed at the center of the
oven cavity, with a beaker containing alumina (250 g) as solid absorber
inside; the temperature was monitored by a Fluke 80T-IR infrared tem-
perature probe. TLC used Merck Kieselgel 60 PF254 and Merck RP-18
F254. Preparative TLC was realized on 20- ꢂ 20-cm Merck Kieselgel 60
F254 0.5-mm plates. High performance liquid chromatography (HPLC)
analysis for compounds 12, 14, and 15 was achieved on 25- ꢂ 1-cm col-
umns packed with Merck-LiChrosorb RP-18 (7 mm) under UV monitor-
ing at k 254 nm and solvent flux 1 ml minꢃ1. Melting points were
measured on a Kofler hot-stage microscope. UV=visible spectra were
taken with a Perkin-Elmer Lambda-3 spectrophotometer and reported
as kmax ( ' ) in nm. FT-IR spectra (nꢃ1 in cmꢃ1) were recorded by Equinox
55 Bruker apparatus, using a film obtained by evaporation of a CH2Cl2
solution. NMR spectra were taken with an Avance 400 Bruker spec-
trometer; 1H at 400 MHz and 13C at 100 MHz in CDCl3, d values in parts
per million (ppm) relative to the solvent residual signals d(H) ¼ 7.25 and
d(C) ¼ 77.00 ppm, where the solvent residual signals are relative to

3012
A. Defant, G. Guella, and I. Mancini
SiMe4(¼0 ppm); J values are in hertz. Multiplicities are from APT experi-
ments. Structural assignments are from 1H, 1H-COSY, heteronuclear sin-
gle quantum correlation (HSQC), and HMBC. Electron-impact (EI) mass
spectra (m=z; rel. %) and HR-EI data were taken with a Kratos-MS80
mass spectrometer with home-built computerized acquisition software.
General Procedure
Ethyl acetoacetate (0.0075 mL, 0.059 mmol) and pyridine (0.022 mL,
0.27 mmol) or isoquinoline (0.032 mL, 0.27 mmol) were added to dichlor-
oquinone 1 or 4 (0.044 mmol) as neat reagent or in the suitable solvent
(0.2 mL) in a closed glass vessel, and the resulting mixture was MW irra-
diated at 540 W for 4–6 min. When the reaction was made in the presence
of a solid support (0.05 g), it and the reagents were mixed as a CH2Cl2
mixture, from which the solvent was evaporated before irradiation. The
treatment of quinone 4 with salts by stirring in EtOH at room temperature
for 1 h furnished the complex, to which EAA and pyridine, 4-picoline, or
isoquinoline were added and evaporated before irradiation. For N-ylide
sequence, a closed vessel containing dichloroquinone 1 or 4 (0.010 g,
0044 mmol), salt 9 (9 mg, 0.048 mmol) or 11 (0.014 g, 0.048 mmol), and
K2CO3 (0.021 g, 0.154 mmol) in the CH3CN or otherwise defined solvent
(0.3 mL) was irradiated at 230 W for 15 min. In each case, the crude reac-
1
tion mixture was directly analyzed by H NMR spectrum for the evalu-
ation of the regioisomeric ratio. The yields reported in Table 1 and
Table 2 were obtained on the products purified by preparative chromato-
graphy (TLC).[7] Their purity was tested to be higher than 99.9% by RP-
18 HPLC analysis with MeOH (tR 10.4, 7.9, and 8.1 min for 12, 14, and 15
respectively). Amide 3 was synthesized from the crude methyl ester 2 by
addition of N,N-dimethylethylenediamine (0.010 mL, 0.09 mmol) and
MW irradiation for 10 min (87% yield from 1). Each reaction was
repeated in triplicate, verifying a good reproducibility of both yield and
regioselectivity (ca 2%). A scale-up to 0.1 g for compounds 5=6 and
14=15 and to 0.5 g for 12 was achieved, giving similar yields.
Data
Methyl-6,11-dioxo-6,11-dihydro-benzo[f]pyrido[1,2-a]indole
12-carboxylate (2)
Orange solid from hexane=ethyl acetate; mp 191 ꢀC [lit.[8] (acetic acid):
190–191 ꢀC]. NMR data were superimposable to the ones reported.[6]
ꢄ
EI-MS m=z (%): 305 (Mþ , 60), 274 (100), 247 (25).

Aza-, Diaza-, Benzo-, and Dibenzofluorenedione Derivatives
3013
6,11-Dioxo-6,11-dihydro-benzo[f]pyrido[1,2-a]indole-(2-
dimethylamino-ethyl)-12-carboxamide (3)
Red solid from chloroform=methanol; mp 142 ꢀC; [lit.[6]: 142–143 ꢀC];
NMR data are in agreement with literature.[6] EI-MS m=z (%): 361
ꢄ
(Mþ , 2), 291 (3), 274 (5), 58 (100).
Ethyl 5,10-dioxo-5,10-dihydro-4,6-diazabenzo[b]fluorene-11-
carboxylate (5)
Orange solid from ethyl acetate. mp 224 ꢀC [lit.[7]: 225–226 ꢀC]. NMR
ꢄ
data are in agreement with literature.[7] EI-MS m=z (%): 320 (Mþ ,
100), 275 (95), 248 (69).
Ethyl 5,10-dioxo-5,10-dihydro-4,9a-diazabenzo[b]fluorene-11-
carboxylate (6)
Orange solid from ethyl acetate. mp 219 ꢀC [lit.[7]: 219–220 ꢀC]. NMR and
EI-MS data are in agreement with literature.[7]
Ethyl 2-methyl-5,10-dioxo-5,10-dihydro-4,6-diazabenzo[b]fluorene-
11 carboxylate (7)
Red powder. NMR data in agreement with literature.[7] EI-MS m=z (%):
ꢄ
334 (Mþ , 18), 262 (45), 83 (30), 43 (100).
Ethyl 2-methyl-5,10-dioxo-5,10-dihydro-4,9a-diazabenzo[b]fluorene-
11-carboxylate (8)
Red powder. NMR data are in agreement with literature.[7] EI-MS
ꢄ
m=z (%): 334 (Mþ , 15), 290 (24), 262 (45), 205 (16), 83 (30), 43
(100).
Ethyl 8,13-dioxo-7a,8,13,13a-tetrahydro-benzo[5,6]indolo[2,1-a]
isoquinoline-14-carboxylate (12)
Yellꢀow solid from petroleum ether (bp 60–90 ꢀC)=chloroform. Mp 240–
241 C (lit.[10] 238–240 ꢀC). UV=vis: kmax (EtOH): 200 (5400), 275
(9960), 295 (3850), 335 (1830), 445 (1240). IR (film): 688 m, 704 m,
1017 s, 1085 s, 1200 m, 1234 s, 1261 m, 1393 w, 1485 m, 1643 w, 1664 s,

3014
A. Defant, G. Guella, and I. Mancini
1720 m. 1H and 13C NMR data are in agreement with the reported
ꢄ
data.[10] EI-MS m=z (%) 369 (Mþ , 10), 324 (9), 297 (11); HR(EI) MS:
369.0992 ꢅ 0.0030 (C23H15NO4, calc. 369.1001).
Ethyl 7,12-dioxo-6b,7,12,12a-tetrahydro-6a,8-diaza-
dibenzo[a,h]fluorene-13-carboxylate (14)
Yellow solid from EtOH. Mp 260–262 ꢀC (lit.[14] >350 ꢀC). UV=vis:
kmax (EtOH): 232 (25500), 271 (40200), 320 (16520), 338 (9700), 465
(8220). IR (film): 702 m, 774 w, 1110 m, 1186 m, 1218 m, 1239 m,
1278w, 1390 w, 1506 m, 1580 w, 1662 s, 1720 m (lit.[14]: 1720, 1660, 1630,
1300–1280). 1H NMR (400 MHz, CDCl3) d 1.51 [t, J ¼ 7.2 Hz,
OCH2CH3]; 4.69 [q, J ¼ 7.2 Hz, OCH2CH3]; 7.36 [d, J ¼ 7.7 Hz, H-
C(5)]; 7.65 [m, H-C(2), H-C(3) and H-C(4)]; 7.83 [m, H-C(10)]; 8.26
[m, H-C(1)]; 8.63 [dd, J ¼ 7.8, 1.7 Hz, H-C(11)]; 9.05 [dd, J ¼ 4.7,
1.7 Hz, H-C(9)]; 9.55 [d, J ¼ 7.5 Hz, H-C(6)]. 13C NMR (100 MHz,
CDCl3) d 14.28 [q, OCH2CH3]; 61.93 [t, OCH2CH3]; 117.98 [d, C(5)];
123.83 [d, C(6)]; 125.00 [d, C(1)]; 126.96, 126.98, 128.99, 129.30 [four
d, C(2), C(3), C(4) and C(10)]; 130.08 [s, C(11a)]; 131.25 [s, C(4a)];
134.77 [d, C(11)]; 149.61 [s, C(7a)]; 153.12 [d, C(9)]; 166.21 (s,
ꢄ
COOEt); 173.43 [s, C(7)]; 178.90 [s, C(12)]. EI-MS m=z (%) 370 (Mþ ,
8), 325 (7), 298 (13); HR(EI) MS: 370.0956 ꢅ 0.0030 (C22H14N2O4, calc.
370.0954).
Ethyl 7,12-dioxo-6b,7,12,12a-tetrahydro-6a,11-diaza-
dibenzo[a,h]fluorene-13-carboxylate (15)
Yellow solid from EtOH. Mp 302–304 ꢀC; UV=vis: kmax (EtOH): 233
(12100), 270 (17900), 305 (8150), 343 (4940), 455 (3100). IR (film):
689 m, 824 w, 962 m, 1110 m, 1184 m, 1210 m, 1220 m, 1487 s, 1508 m,
1
1578 w, 1652 m, 1680 s, 1723 s. H NMR (400 MHz, CDCl3) d 1.53 [t,
J ¼ 7.00 Hz, OCH2CH3]; 4.67 (q, J ¼ 7.0 Hz, OCH2CH3); 7.35 [d,
J ¼ 7.4 Hz, H-C(5)]; 7.67 [m, H-C(2), H-C(3) and H-C(4)]; 7.78 [m, H-
C(9)]; 8.39 [br.d, J ¼ 7.4 Hz, H-C(1)]; 8.59 [br.d, J ¼ 7.4 Hz, H-C(8)];
9.00 [br.d, J ¼ 7.5 Hz, H-C(10)]; 9.44 [d, J ¼ 7.4 Hz, H-C(6)]. 13C
NMR (100 MHz, CDCl3): d 14.07 [q, OCH2CH3]; 62.92 [t, OCH2CH3];
118.00 [d, C(5)]; 124.31 [d, C(6)]; 125.40 [d, C(1)]; 127.50, 128.25,
129.35 and 129.69 [four d, C(2), C(3), C(4) and C(9)]; 130.04 [s,
C(7a)]; 134.80 [d, C(8)]; 149.65 [s, C(11a)]; 153.00 [d, C(10)]; 165.99 (s,
ꢄ
COOEt); 173.79 [s, C(7)]; 179.51 [s, C(12)]. EI-MS m=z (%): 370 (Mþ ,
17), 325 (15), 298 (16); HR(EI) MS: 369.0994 ꢅ 0.0030 (C23H15NO4,
calc. 369.1001).

Aza-, Diaza-, Benzo-, and Dibenzofluorenedione Derivatives
ACKNOWLEDGMENTS
3015
The authors thank A. Sterni, M. Rossi, and D. Avi, University of Trento,
for recording mass, UV=vis, and IR spectra, respectively.
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