Microwave-assisted multicomponent reaction for the synthesis of new and significative bisfunctional compounds containing two furo[3,4-b]quinoline and acridinedione skeletons

Article abstract of DOI:10.1002/jhet.143

(Chemical Equation Presented) In this study, a series of new and significative bisfunctional compounds containing two furo[3,4-b]quinoline and acridinedione skeletons has been synthesized through a rapid one-pot three-component reaction of dialdehydes wit

Full text of DOI:10.1002/jhet.143

742
Microwave-Assisted Multicomponent Reaction for the Synthesis
of New and Significative Bisfunctional Compounds Containing
Two Furo[3,4-b]quinoline and Acridinedione Skeletons
Vol 46
Xing-Han Wang, Wen-Juan Hao, Shu-Jiang Tu,* Xiao-Hong Zhang,
Xu-Dong Cao, Shu Yan, Shan-Shan Wu, Zheng-Guo Han, and Feng Shi
School of Chemistry and Chemical Engineering, Xuzhou Normal University, Xuzhou, Jiangsu
221116, People’s Republic of China
*E-mail: laotu2001@263.net
Received February 28, 2009
DOI 10.1002/jhet.143
Published online 14 July 2009 in Wiley InterScience (www.interscience.wiley.com).
In this study, a series of new and significative bisfunctional compounds containing two furo[3,4-
b]quinoline and acridinedione skeletons has been synthesized through a rapid one-pot three-component
reaction of dialdehydes with N-aryl enaminones and cyclic-1,3-dicarbonyl compounds (tetronic acid and
cyclohexane-1,3-dione) in mixed solvent of glacial acetic acid and N,N-dimethylformamide under
microwave irradiation without catalyst. This method has the advantages of good yield and simple
workup procedure.
J. Heterocyclic Chem., 46, 742 (2009).
INTRODUCTION
such as photoinitiators [6] have been prepared [7]. How-
ever, all these compounds contain only single furoquino-
line skeleton or acridinedione unit. To the best of our
knowledge, the compounds of type C and D including
two furoquinoline skeletons or acridinedione units have
been seldom reported (Fig. 1). With the aim to broaden
the diversity of heterocyclic compound library and in
continuation of our recent interest in the construction of
heterocyclic scaffolds [8], we developed a facile, three-
component reaction between dialdehydes, N-aryl enami-
nones, and cyclic-1,3-dicarbonyl compounds (tetronic
acid and 1,3-cyclohexanedione) under microwave (MW)
heating to afford a series of new polycyclic fused com-
pounds C and D, including two furoquinoline skeletons
or acridinedione units, respectively (Scheme 1).
Podophyllotoxin 1 (Figure 1) is an important lignan
that inhibits microtubule assembly [1]. However,
because attempts to use it for the treatment of human
neoplasia were mostly unsuccessful and complicated by
side effects, extensive structural modifications have been
performed to obtain more potent and less toxic anti-
cancer agents [2]. Among them, 4-aza podophyllotoxin
derivative 2 (Fig. 1) has been reported to be a powerful
DNA topoisomerase inhibitor, working through a mech-
anism of action entirely different from that of the parent,
natural podophyllotoxin [3,4]. This suggests that substi-
tution of the carbon atom at position 4 of podophyllo-
toxin by a nitrogen atom would bring about great
changes in the biological profile. In view of the impor-
tant biological properties of the azapodophyllotoxin, the
modifications on the scaffold of aza-analogs may also
bring significant changes in pharmacological activities.
The furoquinolines A as a kind of azapodophyllotoxin
derivative have been synthesized by the reactions of sin-
gle aldehydes with equivalent of appropriate cyclic-1,3-
dicarbonyl compounds and N-aryl enaminones in our
previous communications [5]. In addition, with a 1,4-di-
hydropyridine (1,4-DHP) parent nucleus, acridine-1,8-
diones B, which showed interesting physical properties
RESULTS AND DISCUSSION
Enaminones and related compounds possessing the
structural unit (NAC¼¼CAZ, Z¼¼COR, CO2R, etc.) are
versatile synthetic intermediates in organic chemistry
that combine the ambient nucleophilicity of enamine
and the electrophilicity of enones [9]. They are fre-
quently applied in the preparation of heterocycles [10].
Our strategy of synthesizing the bisfunctional
C
V
2009 HeteroCorporation

July 2009
Microwave-Assisted Multicomponent Reaction for the Synthesis of New and Significative
Bisfunctional Compounds Containing Two Furo[3,4-b]quinoline and Acridinedione Skeletons
743
Scheme 2
ethylene glycol, glacial acetic acid (HOAc), N,N-dime-
thylformamide (DMF), and mixed solvent of glacial ace-
tic acid and DMF as solvent at 100ꢀC, respectively. All
the reactions were carried out under microwave irradia-
tion (initial power 100 W and maximum power 250 W;
Table 2).
As shown in Table 2, the reactions using the mixed
solvent (VHOAc/VDMF: 2:1) as the solvent resulted in
higher yields and shorter reaction time than those using
ethylene glycol, HOAc, DMF, and other mixed solvent
as solvents. Thus, the mixed solvent (VHOAc/VDMF: 2:1)
was used as the solvent for further optimization of reac-
tion conditions, the same reaction was carried out at
temperatures ranging from 80 to 140ꢀC, with an incre-
ment of 10ꢀC each time. The yield of product 4c was
increased, and the reaction time was shortened when the
temperature was increased from 80 to 120ꢀC. The yield
leveled off when the temperature was further increased
to 130 and 140ꢀC. Therefore, the temperature of 120ꢀC
was chosen for all further microwave-assisted reactions
(Table 3).
Figure 1. The podophyllotoxin derivatives and the unsymmetrical
acridinediones.
compounds, furoquinolines of type C and acridinediones
of type D, was through the reaction of a dialdehyde
with a appropriate cyclic-1,3-dicarbonyl derivative and a
preformed N-aryl enaminones. Representing aromatic
amines with electron-rich group, 4-methylphenylamine
electron-withdrawing group, 4-chlorobenzenamine, and
4-aminophenol, and phenylamine were selected for our
study. The preparation of enaminones 2a–d was com-
monly achieved by refluxing the reaction mixture in an
aromatic solvent, with the removal of the produced
water by azeotropic distillation [11]. We found that
enaminones (2a–d) could be obtained in good to excel-
lent yields by MW heating the mixture of the corre-
sponding amine and 5,5-dimethyl-1,3-cyclohexanedione
in EtOH (95%) at 100ꢀC for 4–6 min (Scheme 2, Table
1) [5].
Under these optimal conditions [the mixed solvent
(VHOAc/VDMF: 2:1, 2.0 mL), 120ꢀC], the reactions of dif-
ferent dialdehydes, various N-aryl enaminones, and te-
tronic acid were performed. Initially, to test the scope of
N-aryl enaminones substrates, dialdehydes and tetronic
acid were used as model substrates (Table 4, entries 1–
6), and the results indicated that N-aryl enaminones
bearing functional groups such as chloro or methyl are
suitable for the reaction. At the same time, we have also
observed delicate electronic effects, that is, N-aryl
enaminones with electron-rich groups (Table 4, entries 3
and 6) reacted rapidly, while electron-withdrawing
groups on the benzene ring (Table 4, entries 1 and 4)
decreased the reactivity, requiring longer reaction times.
Choosing an appropriate solvent is of crucial impor-
tance for the successful microwave-assisted synthesis.
To search for the optimal solvent, the microwave-
assisted reaction of equimolar amount of terephthalalde-
hyde (1a) with 3-(p-tolylamino)-5,5-dimethylcyclohex-2-
enone (2c) and tetronic acid (3a) was examined using
Scheme 1
Table 1
Reaction times and yields for enaminones 2a–2d.
Entry
Product
Time (min)
Yield (%)
m.p. (ꢀC)
1
2
3
4
2a
2b
2c
2d
4
5
5
6
89
91
93
94
207–209
189–190
206–208
249–251
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

744
X.-H. Wang, W.-J. Hao, S.-J. Tu, X.-H. Zhang, X.-D. Cao, S. Yan, S.-S. Wu, Z.-G. Han,
and F. Shi
Vol 46
Table 2
Table 3
Temperature optimization for the synthesis of 4c under MW.
Solvent optimization for the synthesis of 4c under MW.
Entry
Solvent
Time (min)
Yield (%)
Entry
Temp (ꢀC)
Time (min)
Yield (%)
1
2
3
4
5
6
Ethylene glycol
HOAc
DMF
HOAc/DMF (3:1)
HOAc/DMF (2:1)
HOAc/DMF (1:1)
14
14
15
12
12
12
80
81
78
83
85
82
1
2
3
4
5
6
7
80
90
18
16
12
10
8
70
81
85
89
92
90
86
100
110
120
130
140
8
6
To further expand the scope of this method, the
replacement of tetronic acid (3a) with 1,3-cyclohexane-
dione (3b) was examined. To our delight, under the
optimized conditions described earlier, the reactions pro-
ceeded smoothly as well (Table 4, entries 7–11). The
new polycyclic-fused compounds including two acridi-
nedione units were obtained without byproduct.
to synthesize the same product under classical heating
(CH) conditions. The results listed in Table 4 show the
specific activation of this reaction by MW heating.
Simultaneously, the reaction yields were obviously
increased. The difference in yields (MW > CH) may be
a consequence of both thermal effects and specific
effects induced by the microwave field [12,13]. The
reactants in these multicomponent reactions (MCRs)
Additionally, to compare with microwave-assisted
reactions, the same temperature and time were applied
Table 4
The synthesis of compounds 4 at 120°C.
Entry
1
4
1
2
3
Time (min)
14
Yielda (%)
85 (31)
m.p. (ꢀC)
4a
2a
>300
2
3
4
5
6
4b
4c
4d
4e
4f
2b
2c
2a
2b
2c
10
8
89 (44)
92 (40)
82 (32)
86 (29)
88 (35)
>300
>300
>300
>300
>300
16
10
10
7
4g
4h
4i
2a
2c
2d
2c
2d
12
8
84 (51)
92 (46)
87 (41)
85 (38)
90 (45)
>300
>300
>300
>300
>300
8
9
7
10
11
4j
13
10
4k
a Isolated yields under classical heating (CH) conditions.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

July 2009
Microwave-Assisted Multicomponent Reaction for the Synthesis of New and Significative
Bisfunctional Compounds Containing Two Furo[3,4-b]quinoline and Acridinedione Skeletons
745
General procedure for the one-pot synthesis of furo[3,4-
b]quinoline and acridinedione derivative 4 under micro-
wave irradiation conditions. Typically, in a 10-mL EmrysTM
reaction vial, dialdehyde 1 (1 mmol), N-aryl enaminones 2
(1 mmol), tetronic acid or 1,3-cyclohexanedione 3 (1 mmol),
and HOAc/DMF (2:1, 2 mL) were mixed and then capped.
The mixture was irradiated for a given time at 120ꢀC under
microwave irradiation (initial power 100 W and maximum
power 250 W). Upon completion, monitored by TLC, the reac-
tion mixture was filtered to give the crude product, which was
further purified by recrystallization from EtOH (95%) to give
pure furo[3,4-b]quinoline and acridinedione derivative 4.
4-(4-Chlorophenyl)-9-(4-(4-(4-chlorophenyl)-1,3,4,5,6,7,8,9-
octahydro-6,6-dimethyl-1,8-dioxofuro[3,4-b]quinolin-9-yl)-
phenyl)-6,7-dihydro-6,6-dimethylfuro[3,4-b]quinoline-1,8(3H,4H,
5H,9H)-dione (4a). This compound was obtained as pale yel-
low solid (95% ethanol), m.p. > 300ꢀC; IR (potassium bro-
mide, cmꢁ1): 1755 (C¼¼O), 1682 (C¼¼O); 1H NMR: d 7.68–
7.60 (m, 8H, Ar-H), 7.25 (s, 4H, Ar-H), 4.75 (s, 1H, CH), 4.74
(s, 1H, CH), 4.63–4.59 (m, 2H, CH2), 4.56–4.49 (m, 2H,
CH2), 2.23–2.09 (m, 8H, 4CH2), 0.94–0.86 (m, 12H, 4CH3).
Anal. Calcd. for C44H38Cl2N2O6: C, 69.38; H, 5.03; N, 3.68.
Found: C, 71.08; H, 5.07; N, 3.66.
Figure 2. ORTEP diagram of 4f.
contain dipoles and proceed via relatively polar inter-
mediates, which enhance their interactions with MW
and consequently benefit significantly from MW irradia-
tion with respect to more efficient yield and product
purity.
The mechanism of these reactions is similar to those
we have previously reported [5,7], which includes se-
quential condensation, addition, cyclization, and
elimination.
4-Phenyl-6,7-dihydro-9-(4-(1,3,4,5,6,7,8,9-octahydro-6,6-di-
methyl-1,8-dioxo-furo[3,4-b]quinolin-9-yl)phenyl)-6,6-dime-
thylfuro[3,4-b]quinoline-1,8(3H,4H,5H,9H)-dione (4b). This
compound was obtained as pale yellow solid (95% ethanol),
m.p. > 300ꢀC; IR (potassium bromide, cmꢁ1): 1756 (C¼¼O),
In this study, all the products were characterized by
1
melting point, IR, H NMR spectral data, and elemental
analysis. Furthermore, the structure of 4f was estab-
lished by X-ray crystallographic analysis (Fig. 2) [14].
In summary, we have successfully combined the
advantages of microwave technology with multicompo-
nent reactions to facilitate the rapid construction of bis-
furo[3,4-b]quinoline and bisacridinedione skeletons from
readily obtainable and inexpensive materials. Particu-
larly, valuable features of this method included the good
to excellent yields and operational simplicity as well as
increased safety for small-scale high-speed synthesis. In
addition, this series of bisfunctional compounds contain-
ing two furo[3,4-b]quinoline and acridinedione skeletons
may prove new classes of biologically active compounds
for biomedical screening, which is in progress in our
laboratory.
1
1680 (C¼¼O); H NMR: d 7.59–7.54 (m, 10H, Ar-H), 7.26 (s,
4H, Ar-H), 4.77 (s, 1H, CH), 4.75 (s, 1H, CH), 4.62–4.58 (m,
2H, CH2), 4.51–4.45 (m, 2H, CH2), 2.23–2.07 (m, 8H, 4CH2),
0.93–0.85 (m, 12H, 4CH3). Anal. Calcd. for C44H40N2O6: C,
76.28; H, 5.82; N, 4.04. Found: C, 76.41; H, 5.86; N, 4.15.
4-p-Tolyl-6,7-dihydro-9-(4-(1,3,4,5,6,7,8,9-octahydro-6,6-di-
methyl-1,8-dioxo-4-p-tolylfuro[3,4-b]quinolin-9-yl)phenyl)-6,6-
dimethyl-furo[3,4-b]quinoline-1,8(3H,4H,5H,9H)-dione (4c).
This compound was obtained as pale yellow solid (95% etha-
nol), m.p. > 300ꢀC; IR (potassium bromide, cmꢁ1): 1755
(C¼¼O), 1681 (C¼¼O); 1H NMR: d 7.44–7.40 (m, 8H, Ar-H),
7.24 (s, 4H, Ar-H), 4.76 (s, 2H, 2CH), 4.58 (d, 2H, J ¼ 16.0
Hz, CH2), 4.49 (d, 2H, J ¼ 16.0 Hz, CH2), 2.40 (s, 6H,
2CH3), 2.21–2.09 (m, 8H, 4CH2), 0.93 (s, 6H, 2CH3), 0.89 (s,
6H, 2CH3). Anal. Calcd. for C46H44N2O6: C, 76.64; H, 6.15;
N, 3.89. Found: C, 76.69; H, 6.14; N, 3.83. HRMS (ESI): m/z
calcd for: 743.3092 [MþNa]þ, found: 743.3099.
4-(4-Chlorophenyl)-9-(3-(4-(4-chlorophenyl)-1,3,4,5,6,7,8,9-
octahydro-6,6-dimethyl-1,8-dioxofuro[3,4-b]quinolin-9-yl)phenyl)-
6,7-dihydro-6,6-dimethylfuro[3,4-b]quinoline-1,8(3H,4H,5H,9H)-
dione (4d). This compound was obtained as pale yellow solid
(95% ethanol), m.p. > 300ꢀC; IR (potassium bromide, cmꢁ1):
1756 (C¼¼O), 1681 (C¼¼O); 1H NMR: d 7.67 (s, 8H, Ar-H),
7.48 (s, 1H, Ar-H), 7.20–7.17 (m, 1H, Ar-H), 7.07 (d, 2H, J ¼
7.2 Hz, Ar-H), 4.82 (s, 2H, 2CH), 4.68 (d, 2H, J ¼ 16.0 Hz,
CH2), 4.55 (d, 2H, J ¼ 16.0 Hz, CH2), 2.18–2.14 (m, 8H, Ar-
H), 0.94 (s, 6H, 2CH3), 0.85 (s, 6H, 2CH3). Anal. Calcd. for
C44H38Cl2N2O6: C, 69.38; H, 5.03; N, 3.68. Found: C, 69.45;
H, 5.00; N, 3.72.
EXPERIMENTAL
Microwave irradiation was carried out with a microwave
oven EmrysTM Creator from Personal Chemistry, Uppsala,
Sweden. Melting points were determined in the open capilla-
ries and were uncorrected. IR spectra were taken on a FTIR-
Tensor 27 spectrometer in KBr pellets and reported in cmꢁ1
.
1H NMR spectra were measured on a Bruker DPX 400 MHz
spectrometer using TMS as an internal standard and DMSO-d6
as solvent. Elemental analysis was determined by using a Per-
kin-Elmer 240c elemental analysis instrument. HRMS (ESI)
was determined by using micrOTOF-QII HRMS instrument
(BRUKER). X-ray crystallographic analysis was performed
4-Phenyl-6,7-dihydro-9-(3-(1,3,4,5,6,7,8,9-octahydro-6,6-di-
methyl-1,8-dioxo-4-phenylfuro[3,4-b]quinolin-9-yl)phenyl)-6,6-
dimethyl-furo[3,4-b]quinoline-1,8(3H,4H,5H,9H)-dione (4e).
This compound was obtained as pale yellow solid (95%
with
diffractometer.
a
Siemens SMART CCD and
a
Siemens P4
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

746
X.-H. Wang, W.-J. Hao, S.-J. Tu, X.-H. Zhang, X.-D. Cao, S. Yan, S.-S. Wu, Z.-G. Han,
and F. Shi
Vol 46
ethanol), m.p. > 300ꢀC; IR (potassium bromide, cmꢁ1): 1756
(C¼¼O), 1680 (C¼¼O); 1H NMR: d 7.60 (s, 10H, Ar-H), 7.49
(s, 1H, Ar-H), 7.21–7.18 (m, 1H, Ar-H), 7.08 (d, 2H, J ¼ 7.6
Hz, Ar-H), 4.83 (s, 2H, 2CH), 4.67 (d, 2H, J ¼ 16.4 Hz,
CH2), 4.49 (d, 2H, J ¼ 16.4 Hz, CH2), 2.23–2.09 (m, 8H,
4CH2), 0.92 (s, 6H, 2CH3), 0.84 (s, 6H, 2CH3). Anal. Calcd.
for C44H40N2O6: C, 76.28; H, 5.82; N, 4.04. Found: C, 76.34;
H, 5.80; N, 4.08.
4-p-Tolyl-6,7-dihydro-9-(3-(1,3,4,5,6,7,8,9-octahydro-6,6-di-
methyl-1,8-dioxo-4-p-tolylfuro[3,4-b]quinolin-9-yl)phenyl)-6,6-
dimethyl-furo[3,4-b]quinoline-1,8(3H,4H,5H,9H)-dione (4f).
This compound was obtained as pale yellow solid (95% etha-
nol), m.p. > 300ꢀC; IR (potassium bromide, cmꢁ1): 1753
(C¼¼O), 1679 (C¼¼O); 1H NMR: d 7.47–7.39 (m, 9H, Ar-H),
7.21–7.17 (m, 1H, Ar-H), 7.06 (d, 2H, J ¼ 7.2 Hz, Ar-H),
4.81 (s, 2H, 2CH), 4.65 (d, 2H, J ¼ 16.0 Hz, CH2), 4.48 (d,
2H, J ¼ 16.4 Hz, CH2), 2.41 (s, 6H, 2CH3), 2.22–2.08 (m,
8H, 4CH2), 0.92 (s, 6H, 2CH3), 0.83 (s, 6H, 2CH3). Anal.
Calcd. for C46H44N2O6: C, 76.64; H, 6.15; N, 3.89. Found: C,
76.34; H,5.99; N, 4.07. HRMS (ESI): m/z calcd for: 743.3092
[MþNa]þ, found: 743.3090.
2CH3), 2.21–2.14 (m, 8H, 4CH2), 2.09 (s, 2H, CH2), 2.01–
1.94 (m, 4H, 2CH2), 1.85–1.78 (m, 4H, 2CH2), 1.65–1.55 (m,
2H, CH2), 0.88 (s, 6H, 2CH3), 0.70 (s, 6H, 2CH3). Anal.
Calcd. for C50H52N2O4: C, 80.61; H, 7.04; N, 3.76. Found: C,
82.49; H, 7.07; N, 3.77.
10-(4-Hydroxyphenyl)-3,4,6,7-tetrahydro-9-(3-(1,2,3,4,5,6,7,
8,9,10-decahydro-10-(4-hydroxyphenyl)-3,3-dimethyl-1,8-diox-
oacridin-9-yl)phenyl)-3,3-dimethylacridine-1,8(2H,5H,9H,10H)-
dione (4k). This compound was obtained as pale yellow solid
(95% ethanol), m.p. > 300ꢀC; IR (potassium bromide, cmꢁ1):
1634 (C¼¼O); 1H NMR: d 9.94 (s, 2H, 2OH), 7.34–7.23 (m,
5H, Ar-H), 7.10–6.96 (m, 3H, Ar-H), 6.91–6.89 (m, 4H, Ar-
H), 5.09 (s, 2H, 2CH), 2.33–2.14 (m, 10H, 5CH2), 2.05–1.98
(m, 4H, 2CH2), 1.87–1.83 (m, 4H, 2CH2), 1.63–1.61 (m, 2H,
CH2), 0.89 (s, 6H, 2CH3), 0.72 (s, 6H, 2CH3). Anal. Calcd. for
C48H48N2O6: C, 76.98; H, 6.46; N, 3.74. Found: C, 77.03; H,
6.47; N, 3.77.
Acknowledgments. This study was supported by the National
Science Foundation of China (No. 20672090), Six Kinds of Pro-
fessional Elite Foundation of the Jiangsu Province (No. 06-A-
039), the Qing Lan Project (No. 08QLT001), and the Open Foun-
dation of Jiangsu Key Laboratory for Chemistry of Low-Dimen-
sional Materials (No. JSKC07035).
10-(4-Chlorophenyl)-9-(4-(10-(4-chlorophenyl)-1,2,3,4,5,6,7,
8,9,10-decahydro-3,3-dimethyl-1,8-dioxoacridin-9-yl)phenyl)-3,4,
6,7-tetrahydro-3,3-dimethylacridine-1,8(2H,5H,9H,10H)-dione
(4g). This compound was obtained as pale yellow solid (95%
ethanol), m.p. > 300ꢀC; IR (potassium bromide, cmꢁ1): 1639
(C¼¼O); 1H NMR: d 7.68–7.44 (m, 8H, Ar-H), 7.16 (s, 4H,
Ar-H), 5.06–5.01 (m, 2H, 2CH), 2.29–2.09 (m, 10H, 5CH2),
2.04–1.92 (m, 4H, 2CH2), 1.83–1.79 (m, 4H, 2CH2), 1.66–1.61
(m, 2H, CH2), 0.89 (s, 6H, 2CH3), 0.70 (s, 6H, 2CH3). Anal.
Calcd. for C48H46Cl2N2O4: C, 73.37; H, 5.90; N, 3.56. Found:
C, 75.35; H, 6.00; N, 3.53.
10-p-Tolyl-3,4,6,7-tetrahydro-9-(4-(1,2,3,4,5,6,7,8,9,10-deca-
hydro-3,3-dimethyl-1,8-dioxo-10-p-tolylacridin-9-yl)phenyl)-3,3-
dimethyl-acridine-1,8(2H,5H,9H,10H)-dione (4h). This com-
pound was obtained as pale yellow solid (95% ethanol), m.p.
> 300ꢀC; IR (potassium bromide, cmꢁ1): 1634 (C¼¼O); 1H
NMR: d 7.41–7.25 (m, 8H, Ar-H), 7.16 (s, 4H, Ar-H), 5.07–
5.04 (m, 2H, 2CH), 2.42 (s, 6H, 2CH3), 2.29–2.13 (m, 10H,
5CH2), 2.05–1.92 (m, 4H, 2CH2), 1.83–1.78 (m, 4H, 2CH2),
1.64–1.60 (m, 2H, CH2), 0.87 (s, 6H, 2CH3), 0.69 (s, 6H,
2CH3). Anal. Calcd. for C50H52N2O4: C, 80.61; H, 7.04; N,
3.76. Found: C, 80.69; H, 7.06; N, 3.73.
REFERENCES AND NOTES
[1] (a) Van der Eycken, J.; Bosmans, J.-P.; Van Haver, D.;
Vandewalle, M.; Hulkenberg, A.; Veerman, W.; Nieuwenhuizen, R.
Tetrahedron Lett 1989, 30, 3873; (b) Tomioka, K.; Kubota, Y.; Koga,
K. Tetrahedron Lett 1989, 30, 2953; (c) Bosmans, J.-P.; Van der
Eycken, J.; Vandewalle, M.; Hulkenberg, A.; Van Hes, R.; Veerman,
W. Tetrahedron Lett 1989, 30, 3877.
[2] (a) Tomioka, K.; Kubota, Y.; Koga, K. Tetrahedron 1993,
49, 1891; (b) Lienard, P.; Royer, J.; Quirion, J. C.; Husson, H. P. Tet-
rahedron Lett 1991, 32, 2489; (c) Poli, G.; Giambastiani, G. J Org
Chem 2002, 67, 9456.
[3] (a) Hitotsuyanagi, Y.; Fukuyo, M.; Tsuda, K.; Kobayashi,
M.; Ozeki, A.; Itokawa, H.; Takeya, K. Bioorg Med Chem Lett 2000,
10, 315; (b) Marcantoni, E.; Petrini, M.; Profeta, R. Tetrahedron Lett
2004, 45, 2133; (c) Hitosuyanagi, Y.; Kobayashi, M.; Fukuyo, M.;
Takeya, K.; Itokawa, H. Tetrahedron Lett 1997, 38, 8295; (d) Hito-
suyanagi, Y.; Kobayashi, M.; Morita, H.; Itokawa, H.; Takeya, K. Tet-
rahedron Lett 1999, 40, 9107; (e) Tratrat, C.; Renault, S. G.; Husson,
H. P. Org Lett 2002, 4, 3187.
10-(4-Hydroxyphenyl)-3,4,6,7-tetrahydro-9-(4-(1,2,3,4,5,6,7,
8,9,10-decahydro-10-(4-hydroxyphenyl)-3,3-dimethyl-1,8-dioxoa-
cridin-9-yl)phenyl)-3,3-dimethylacridine-1,8(2H,5H,9H,10H)-dione
(4i). This compound was obtained as pale yellow solid (95%
ethanol), m.p. > 300ꢀC; IR (potassium bromide, cmꢁ1): 1635
[4] Tu, S. J.; Zhang, Y.; Jia, R. H. Acta Crystallogr Sect E
2006, 62, o1872.
[5] (a) Tu, S. J.; Zhang, Y.; Jiang, B.; Jia, R. H.; Zhang, J. Y.;
Zhang, J. P.; Ji, S. J. Synthesis 2006, 22, 3874; (b) Tu S. J.; Zhang,
Y.; Jia, R. H.; Jiang, B.; Zhang, J. Y.; Ji, S. J. Tetrahedron Lett 2006,
47, 6521.
1
(C¼¼O); H NMR: d 9.96 (s, 2H, 2OH), 7.26–7.24 (m, 2H, Ar-
H), 7.13–7.10 (m, 6H, Ar-H), 6.92 (s, 4H, Ar-H), 5.03 (s, 2H,
2CH), 2.28–2.12 (m, 10H, 5CH2), 2.03–1.97 (m, 4H, 2CH2),
1.86–1.79 (m, 4H, 2CH2), 1.69–1.60 (m, 2H, CH2), 0.88 (s,
6H, 2CH3), 0.70 (s, 6H, 2CH3). Anal. Calcd. for C48H48N2O6:
C, 76.98; H, 6.46; N, 3.74. Found: C, 77.05; H, 6.43; N, 3.75.
10-p-Tolyl-3,4,6,7-tetrahydro-9-(3-(1,2,3,4,5,6,7,8,9,10-deca-
hydro-3,3-dimethyl-1,8-dioxo-10-p-tolylacridin-9-yl)phenyl)-3,3-
dimethyl-acridine-1,8(2H,5H,9H,10H)-dione (4j). This com-
pound was obtained as pale yellow solid (95% ethanol), m.p.
> 300ꢀC; IR (potassium bromide, cmꢁ1): 1645 (C¼¼O); 1H
NMR: d 7.38–7.34 (m, 9H, Ar-H), 7.11–7.07 (m, 1H, Ar-H),
7.02–6.98 (m, 2H, Ar-H), 5.09 (s, 2H, 2CH), 2.41 (s, 6H,
[6] Timpe, H. J.; Ulrich, S.; Decker, C.; Fouassier, J. P. Macro-
molecules 1993, 26, 4560.
[7] Wang, G. W.; Miao, C. B. Green Chem 2006, 8, 1080.
[8] (a) Tu, S. J.; Jiang, B.; Jia, R. H.; Zhang, J. Y.; Zhang, Y.;
Yao, C. S.; Shi, F. Org Biomol Chem 2006, 4, 3664; (b) Tu, S. J.;
Jiang, B.; Zhang, J. Y.; Jia, R. H.; Zhang, Y.; Yao, C. S. Org Biomol
Chem 2006, 4, 3980; (c) Tu, S. J.; Jiang, B.; Zhang, Y.; Jia, R. H.;
Zhang, J. Y.; Yao, C. S.; Shi, F. Org Biomol Chem 2007, 5, 355; (d)
Tu, S. J.; Li, C. M.; Li, G. G.; Cao, L. J.; Shao, Q. Q.; Zhou, D. X.;
Jiang, B.; Zhou, J. F.; Xia, M. J Combin Chem 2007, 9, 1144.
[9] Greenhill, J. V. Chem Soc Rev 1977, 6, 277.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

July 2009
Microwave-Assisted Multicomponent Reaction for the Synthesis of New and Significative
Bisfunctional Compounds Containing Two Furo[3,4-b]quinoline and Acridinedione Skeletons
747
[10] (a) Andrew, R. J.; Mellor, J. M.; Reid, G. Tetrahedron
[12] (a) Kappe, C. O. Chem Soc Rev 2008, 37, 1127; (b) Dallin-
2000, 56, 7255; (b) Valla, A.; Valla, B.; Cartier, D.; Guillou, R. L.;
Labia, R.; Potier, P. Tetrahedron Lett 2005, 46, 6671.
ger, D.; Kappe, C. O. Chem Rev 2007, 107, 2563.
[13] Razzaq, T.; Kappe, C. O. ChemSusChem 2008, 1, 123.
[14] The single-crystal growth was carried out in ethanol at
room temperature. X-ray crystallographic analysis was performed with
a Siemens SMART CCD and a Semens P4 diffractometer. Crystal data
for 4f: C46H44N2O6, M ¼ 720.83, Triclinic, space group P-1, a ¼
[11] (a) Ostercamp, D. L. J Org Chem 1970, 35, 1632; (b)
Greenhill, J. V. J Chem Soc Perkin Trans 1 1976, 2207; (c) Putkonen,
T.; Tolvanen, A.; Jokela, R.; Caccamese, S.; Parrinello, N. Tetrahedron
2003, 59, 8589; (d) Chen, Y. L.; Mariano, P. S.; Little, G. M.;
O’Brien, D.; Huesmann, P. L. J Org Chem 1981, 46, 4643; (e) Rama-
lingam, K.; Balasubramanian, M.; Baliah, V. Indian J Chem 1972, 10,
62; (f) Azzaro, M.; Geribaldi, S.; Vibeau, B. Synthesis 1981, 880.
3
˚
11.6215(14), b ¼ 13.3902(16), c ¼ 14.7823(19), V ¼ 2171.6(5) A ,
Z ¼ 2, T ¼ 298(2) K, l ¼ 0.073 mmꢁ1, 10,857 reflections measured,
7481 unique reflections, R ¼ 0.0981, Rw ¼ 0.1263.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet