Unexpected and green synthesis of azapodophyllotoxin derivatives via microwave-assisted multicomponent reactions in ammonia water

Article abstract of DOI:10.1080/00397910902964825

An unexpected and green synthesis of azapodophyllotoxin derivatives was realized via microwave-assisted multicomponent reactions of dimedone, tetronic acid, and aromatic aldehydes in ammonia water. This protocol has the advantages of environmental friendl

Full text of DOI:10.1080/00397910902964825

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Unexpected and Green Synthesis of
Azapodophyllotoxin Derivatives via
Microwave-Assisted Multicomponent
Reactions in Ammonia Water
Feng Shi a , Ning Ma a , Yan Zhang b , Ge Zhang a , Bo Jiang a &
Shujiang Tu a
a School of Chemistry and Chemical Engineering, Xuzhou Normal
University, Key Laboratory of Biotechnology for Medicinal Plant,
Xuzhou, Jiangsu, China
b College of Chemistry and Chemical Engineering, Nanjing
University, Nanjing, Jiangsu, China
Version of record first published: 29 Dec 2009.
To cite this article: Feng Shi , Ning Ma , Yan Zhang , Ge Zhang , Bo Jiang & Shujiang Tu (2009):
Unexpected and Green Synthesis of Azapodophyllotoxin Derivatives via Microwave-Assisted
Multicomponent Reactions in Ammonia Water, Synthetic Communications: An International Journal for
Rapid Communication of Synthetic Organic Chemistry, 40:2, 235-241
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Synthetic Communications1, 40: 235–241, 2010
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397910902964825
UNEXPECTED AND GREEN SYNTHESIS OF
AZAPODOPHYLLOTOXIN DERIVATIVES VIA
MICROWAVE-ASSISTED MULTICOMPONENT
REACTIONS IN AMMONIA WATER
Feng Shi,1 Ning Ma,1 Yan Zhang,2 Ge Zhang,1 Bo Jiang,1
and Shujiang Tu1
1School of Chemistry and Chemical Engineering, Xuzhou Normal University,
Key Laboratory of Biotechnology for Medicinal Plant, Xuzhou, Jiangsu, China
2College of Chemistry and Chemical Engineering, Nanjing University,
Nanjing, Jiangsu, China
An unexpected and green synthesis of azapodophyllotoxin derivatives was realized via
microwave-assisted multicomponent reactions of dimedone, tetronic acid, and aromatic
aldehydes in ammonia water. This protocol has the advantages of environmental friendli-
ness, short reaction time, good yields, low cost, and easy operation.
Keywords: Azapodophyllotoxin; green synthesis; microwave irradiation; water
INTRODUCTION
In recent years, microwave-assisted synthesis in water as solvent has been
investigated because it combines the two prominent green chemistry principles of
‘‘safer solvents’’ and ‘‘energy efficiency.’’[1] Besides the general advantages of water
and microwave irradiation (MWI),[2] several important benefits are expected when
combining them together.[3] In addition, multicomponent reactions (MCRs) occupy
an outstanding position in organic and medicinal chemistry by virtue of their intrin-
sic atom economy and selectivity, simple procedures and equipment, time and energy
savings, and environmental friendliness.[4] Thus, it goes without saying that the use
of water as a nontoxic reaction medium, together with the employment of
energy-efficient microwave heating and atom-economical MCRs, must be a syner-
gistic and effective green strategy of synthesis in the sense that the combination
offers greater potential than the three parts in isolation.
Azapodophyllotoxin (Fig. 1) derivatives are well-known anticancer agents[5]
that also have cardiotonic,[6] inotropic,[7] pesticidal,[8] potassium channel opening,[9]
and calcium channel agonistic[10] activities. Moreover, more potent and less toxic
azapodophyllotoxin derivatives with antitumor activities have also been obtained
Received December 22, 2008.
Address correspondence to Shujiang Tu, School of Chemistry and Chemical Engineering,
Xuzhou Normal University, Xuzhou, China. E-mail: laotu2001@263.net
235

236
F. SHI ET AL.
Figure 1. Structure of azapodophyllotoxin.
by extensive structural modifications.[11] However, most modifications were
performed on rings B and C (Fig. 1), and the modifications on ring A were not well
documented.
As a continuation of our efforts on structural modifications of azapodo-
phyllotoxin[12] and synthesis of bioactive heterocyclic compounds with a green
approach,[13] herein we report an unexpected and green synthesis of novel azapodo-
phyllotoxin derivatives 4 instead of the desired products 5 via microwave-assisted,
four-component reactions of dimedone 1, aromatic aldehydes 2, and tetronic acid
3 in ammonia water (Scheme 1).
RESULTS AND DISCUSSION
Initially, the microwave-assisted, four-component reaction of dimedone 1
(1 mmol), aromatic aldehyde 2a (1 mmol), tetronic acid 3 (1 mmol), and excess
ammonia water (1 mL) was employed to prepare the desired compound 5a. Surpris-
ingly, the spectroscopic data indicated this product was not the expected compound
5a but rather another unexpected compound, 4a, which was established on the basis
1
of its spectroscopic data. In the H NMR spectra, the two singlets at d 7.79 and d
6.20 were assigned to the protons of NH and OH group, which were further
comfirmed by D2O exchange. The two doublets with coupling constant of 8.4 Hz
at d 7.24 and d 7.19 were assigned to the protons of p-chlorophenyl group. Another
Scheme 1. The unexpected synthesis of azapodophyllotoxin derivatives.

UNEXPECTED SYNTHESIS OF AZAPODOPHYLLOTOXINS
237
Table 1. Synthesis of 4 in water under MWI
Entry
4
Ar1
Time (min)
Yield (%)
Mp (ꢁC)
1
2
3
4
4a
4b
4c
4d
4-ClC6H4
4-FC6H4
4-BrC6H4
C6H5
5
7
87
85
88
81
265–266
260–261
261–262
268–269
6
10
two singlets at d 4.20 and d 3.20 were assigned to the two tertiary protons. The dime-
done skeleton was confirmed by two multiples in the range of d 2.28–2.39 and d
1.98–2.19, assigned to the protons of two CH2, as well as two singlets at d 1.03
and d 0.94, designated as two methyl groups in dimedone skeleton. Another two
doublets with coupling constant of 8.4 Hz at d 4.15 and d 4.04 were assigned to
the protons of CH2 in the skeleton of tetronic acid. The infrared (IR) spectrum of
compound 5a showed strong absorption at 3302 cmꢀ1 due to the NH group and
broad absorption in the range of 2900–3200 cmꢀ1 due to the OH group. The strong
absorption at 1757 cmꢀ1 was assigned to the C O group and that in the range of
=
1400–1600 cmꢀ1 was designated to the phenyl group. Besides, the structure of this
unexpected compound 4a was also confirmed by high-resolution mass spectrometry
(HRMS), electrospray ionization (ESI).
Then we performed the reaction of dimedone 1 (1 mmol), aromatic aldehyde
2b–d (1 mmol), tetronic acid 3 (1 mmol), and excess ammonia water in the same reac-
tion conditions. Similarly, the unexpected products 4 instead of desired products 5
were afforded. As shown in Table 1, a series of novel azapodophyllotoxin derivatives
4 were successfully synthesized with good yields within a short reaction time via
microwave-assisted MCR in ammonia water.
Scheme 2. The reasonable mechanism of the unexpected reaction.

238
F. SHI ET AL.
Scheme 3. The unexpected synthesis of products 6.
The structures of all these novel compounds were established on the basis of
their spectroscopic data and HRMS.
Although the detailed mechanism of the reaction remains to be fully clarified,
the formation of 4 could be explained by a reaction sequence presented in Scheme 2.
First, the condensation of tetronic acid 3 and aromatic aldehyde 2 gives intermediate
8. Then, the intermediate 8 undergoes Michael addition with enamine 7 (formed
from the condensation of dimedone 1 with ammonia) to give an open-chain inter-
mediate 9, which is subsequently cyclized to afford the final product 4.
However, when the aromatic aldehydes with electron-donating groups such as
alkoxyl group were employed using the same reaction conditions, another unexpec-
ted product, 6, was were afforded (Scheme 3, Table 2), which implied that tetronic
acid did not take part in the reactions at all.
This result indicated that the electronic nature of the substituents on aldehydes
has significant effect on this reaction. However, the reason is still unclear, which
should be investigated in further research.
CONCLUSION
In brief, we have realized an unexpected and green synthesis of novel azapodo-
phyllotoxin derivatives via microwave-assisted MCRs of dimedone, tetronic acid,
and aromatic aldehyde in ammonia water. This protocol has the prominent advan-
tages of environmental friendliness, short reaction time, good yields, low cost, and
easy operation. At the same time, this facile synthesis can not only offer a green syn-
thetic strategy to heterocyclic compounds with biological significance but also enrich
the investigation of microwave-assisted MCRs in water.
EXPERIMENTAL
Microwave irradiation was carried out in a monomodal Emrys Creator from
Personal Chemistry, Uppsala, Sweden. Melting points were determined on an XT5
Table 2. Synthesis of 6 in water under MWI
Entry
6
Ar2
Time (min)
Yield (%)
Mp (ꢁC)
1
2
3
4
6a
6b
6c
6d
4-(CH3)2NC6H4
3,4-(CH3O)2C6H3
3,4-(OCH2O)C6H3
4-CH3OC6H4
6
5
6
8
83
87
84
82
264–266
258–260
323–325
269–271

UNEXPECTED SYNTHESIS OF AZAPODOPHYLLOTOXINS
239
apparatus and are uncorrected. IR spectra were recorded on a Fourier transform
1
(FT)–IR Tensor 27 spectrometer. H NMR spectra were measured on a DPX 400
spectrometer operating at 400 MHz, using dimethyl sulfoxide (DMSO-d6) as solvent
and tetramethylsilane (TMS) as an internal standard. HRMS (ESI) was determined
by MicroTOF-QII HRMS=MS instrument (Bruker).
General Procedure for the Synthesis of Compounds 4 and 6
Under Microwave Irradiation
Typically, in a 10-mL Emrys reaction vial, dimedone 1 (1 mmol), aromatic
aldehyde 2 (1 mmol), tetronic acid 3 (1 mmol), and excess ammonia water (1 mL)
were mixed and then capped. The mixture was irradiated at maximum power of
200 W (initial power 100 W) and 90ꢁC for a given time. The reaction mixture was
cooled to room temperature, poured into water, and filtered to give the crude pro-
duct, which was further purified by recrystallization from ethanol (EtOH) to give
pure product 4 or 6.
Data
9-(4-Chlorophenyl)-3a,4,6,7,9,9a-hexahydro-3a-hydroxy-6,6-dimethylfuro
1
[3,4-b]quinoline-1,8(3H,5H)-dione (4a). H NMR (400 MHz, DMSO-d6) (d, ppm):
7.79 (s, 1H, NH), 7.24 (d, 2H, J ¼ 8.4 Hz, ArH), 7.19 (d, 2H, J ¼ 8.4 Hz, ArH), 6.20
(s, 1H, OH), 4.20 (s, 1H, CH), 4.15 (d, 1H, J ¼ 8.4 Hz, CH2a), 4.04 (d, 1H, J ¼ 8.4 Hz,
CH2b), 3.20 (s, 1H, CH), 2.28–2.39 (m, 2H, CH2), 1.98–2.19 (m, 2H, CH2), 1.03 (s,
3H, CH3), 0.94 (s, 3H, CH3). IR (KBr, n, cmꢀ1): 3302, 3136, 2958, 2929, 2914, 2870,
1757, 1572, 1517, 1474, 1419, 1401, 1371, 1264, 1182, 1125, 1092, 1025, 827, 701, 666.
HRMS (ESI) m=z: calc. for C19H20ClNO4: 362.1154 [M þ H]þ; found: 362.1159
[M þ H]þ.
9-(4-Fluorophenyl)-3a,4,6,7,9,9a-hexahydro-3a-hydroxy-6,6-dimethylfuro
1
[3,4-b]quinoline-1,8(3H,5H)-dione (4b). H NMR (400 MHz, DMSO-d6) (d,
ppm): 7.81 (s, 1H, NH), 7.36 (d, 2H, J ¼ 8.4 Hz, ArH), 7.20 (d, 2H, J ¼ 8.4 Hz,
ArH), 6.23 (s, 1H, OH), 4.20 (s, 1H, CH), 4.17 (d, 1H, J ¼ 8.4 Hz, CH2a), 4.04 (d,
1H, J ¼ 8.4 Hz, CH2b), 3.21 (s, 1H, CH), 2.30–2.41 (m, 2H, CH2), 2.00–2.16 (m,
2H, CH2), 1.03 (s, 3H, CH3), 0.93 (s, 3H, CH3). IR (KBr, n, cmꢀ1): 3303, 3145,
2958, 2930, 2917, 2874, 1759, 1576, 1519, 1420, 1403, 1371, 1265, 1181, 1125,
1073, 1021, 826, 697, 665. HRMS (ESI) m=z: calc. for C19H20FNO4: 346.1450
[M þ H]þ; found: 346.1455 [M þ H]þ.
9-(4-Bromophenyl)-3a,4,6,7,9,9a-hexahydro-3a-hydroxy-6,6-dimethylfuro
1
[3,4-b]quinoline-1,8(3H,5H)-dione (4c). H NMR (400 MHz, DMSO-d6) (d, ppm):
7.79 (s, 1H, NH), 7.40 (d, 2H, J ¼ 8.4 Hz, ArH), 7.19 (d, 2H, J ¼ 8.4 Hz, ArH), 6.20
(s, 1H, OH), 4.18 (s, 1H, CH), 4.15 (d, 1H, J ¼ 8.4 Hz, CH2a), 4.04 (d, 1H, J ¼ 8.4 Hz,
CH2b), 3.20 (s, 1H, CH), 2.31–2.39 (m, 2H, CH2), 1.98–2.05 (m, 2H, CH2), 1.03 (s,
3H, CH3), 0.94 (s, 3H, CH3). IR (KBr, n, cmꢀ1): 3302, 3142, 2959, 2929, 2913, 2869,
1757, 1573, 1518, 1417, 1398, 1371, 1264, 1182, 1124, 1024, 824, 688, 661, 586.
HRMS (ESI) m=z: calc. for C19H20BrNO4: 406.0649 [M þ H]þ; found: 406.0653
[M þ H]þ.

240
F. SHI ET AL.
3a,4,6,7,9,9a-Hexahydro-3a-hydroxy-6,6-dimethyl-9-phenylfuro[3,4-b]
quinoline-1,8(3H,5H)-dione (4d). 1H NMR (400 MHz, DMSO-d6) (d, ppm): 7.74
(s, 1H, NH), 7.09–7.24 (m, 5H, ArH), 6.10 (s, 1H, OH), 4.23 (s, 1H, CH), 4.14 (d,
1H, J ¼ 8.4 Hz, CH2a), 4.03 (d, 1H, J ¼ 8.4 Hz, CH2b), 3.20 (s, 1H, CH), 2.28–2.39
(m, 2H, CH2), 2.00–2.10 (m, 2H, CH2), 1.05 (s, 3H, CH3), 0.95 (s, 3H, CH3). IR
(KBr, n, cmꢀ1): 3294, 3137, 2956, 2928, 2872, 1755, 1574, 1518, 1472, 1402, 1369,
1267, 1185, 1127, 1027, 761, 700, 648, 586. HRMS (ESI) m=z: calc. for
C19H21NO4: 328.1544 [M þ H]þ; found: 328.1549 [M þ H]þ.
9-(4-(Dimethylamino)phenyl)-3,4,6,7-tetrahydro-3,3,6,6-tetramethylacridine-
1,8(2H,5H,9H,10H)-dione (6a). Mp 264–266ꢁC (lit. 264–266ꢁC).[14]
3,4,6,7-Tetrahydro-9-(3,4-dimethoxyphenyl)-3,3,6,6-tetramethylacridine-
1,8(2H,5H,9H,10H)-dione (6b). Mp 258–260ꢁC (lit. 258–260ꢁC).[14]
9-(Benzo[d][1,3]dioxol-5-yl)-3,4,6,7-tetrahydro-3,3,6,6-tetramethylacridine-
1,8(2H,5H,9H,10H)-dione (6c). Mp 323–325ꢁC. (lit. 324–326ꢁC).[14]
3,4,6,7-Tetrahydro-9-(4-methoxyphenyl)-3,3,6,6-tetramethylacridine-
1,8(2H,5H,9H,10H)-dione (6d). Mp 269–271ꢁC. (lit. 269–270ꢁC).[14]
ACKNOWLEDGMENTS
We thank the National Natural Science Foundation of China (Nos. 20672090
and 20810102050), the Key Item of Natural Science Foundation of Xuzhou Normal
University (No. 07XLA04), the Preliminary Item of Xuzhou Normal University on
National Natural Science Foundation of China (No. 08XLY04), the Natural Science
Foundation (09KJB150011) and Qing Lan Project (08QLT001) of Jiangsu
Education Committee, and the Science and Technology Foundation of Xuzhou
(No. XM08C027) for financial support.
REFERENCES
1. (a) Matlack, A. S. Introduction to Green Chemistry; Marcel Dekker Inc.: New York, 2001;
(b) Dallinger, D.; Kappe, C. O. Microwave-assisted synthesis in water as solvent. Chem.
Rev. 2007, 107, 2563–2591.
2. (a) Lindstrom, U. M. Stereoselective organic reactions in water. Chem. Rev. 2002, 102,
2751–2772; (b) Li, C. J. Organic reactions in aqueous media with a focus on carbon–
carbon bond formations: A decade update. Chem. Rev. 2005, 105, 3095–3165; (c) Pirrung,
M. C. Acceleration of organic reactions through aqueous solvent effects. Chem. Eur. J.
2006, 12, 1312–1317; (d) Strauss, C. R. Microwave-assisted reactions in organic
synthesis—Are there any nonthermal microwave effects? Comments. Angew. Chem., Int.
Ed. 2002, 41, 3589–3590; (e) Kappe, C. O. Synthetic methods: Controlled microwave
heating in modern organic synthesis. Angew. Chem., Int. Ed. 2004, 43, 6250–6284.
3. Strauss, C. R.; Trainor, R. W. Developments in microwave-assisted organic chemistry.
Aust. J. Chem. 1995, 48, 1665–1692.
4. (a) Ramon, D. J.; Miguel, Y. Asymmetric multicomponent reactions (AMCRs): The new
frontier. Angew. Chem., Int. Ed. 2005, 44, 1602–1634; (b) Orru, R. V. A.; de Greef, M.
Recent advances in solution-phase multicomponent methodology for the synthesis
of heterocyclic compounds. Synthesis 2003, 1471–1499; (c) Weber, L.; Illgen, K.;

UNEXPECTED SYNTHESIS OF AZAPODOPHYLLOTOXINS
241
Almstetter, M. Discovery of new multicomponent reactions with combinatorial methods.
Synlett 1999, 366–374.
5. (a) Magedov, I. V.; Manpadi, M.; Van Slambrouck, S.; Steelant, W. F. A.; Rozhkova, E.;
Przheval’skii, N. M.; Rogelj, S.; Kornienko, A. Discovery and investigation of antiproli-
ferative and apoptosis-inducing properties of new heterocyclic podophyllotoxin analogues
accessible by a one-step multicomponent synthesis. J. Med. Chem. 2007, 50, 5183–5192;
(b) Hitotsuyanagi, Y.; Fukuyo, M.; Tsuda, K.; Kobayashi, M.; Ozeki, A.; Itokawa, H.;
Takeya, K. 4-Aza-2,3-dehydro-4-deoxypodophyllotoxins: Simple Aza-podophyllotoxin
analogues possessing potent cytotoxicity. Bioorg. Med. Chem. 2000, 10, 315–317.
6. Skrastins, I.; Vitolina, R.; Kastron, V. V.; Dubur, G. Y. Synthesis and cardiotonic activity
of furo[3,4-b]- and difuro[3,4-b:3,4-e]pyridines. Khim.-Farm. Zh. 1995, 29, 31–33.
7. Skrastins, I.; Kastron, V.; Vitolins, R.; Duburs, G.; Stivrina, M. S.; Kaidaka, K. Synthesis and
pharmacological activity of furo-1,4-dihydropyridines. Khim.-Farm. Zh. 1989, 23, 1323–1326.
8. Velten, R.; Adelt, I.; Boehmer, J.; Frackenpohl, J.; Schenke, T.; Loesel, P.; Malsam, O.;
Arnold, C. Preparation of fused quinolines as pesticides. WO Patent 2005097802, 2005;
Chem. Abstr. 2005, 143, 405891.
9. Carroll, W. A.; Agrios, K. A.; Basha, F. Z.; Chen, Y.; Kort, M. E.; Kym, P. R.; Tang, R.;
Turner, S. C.; Yi, L. Preparation of tricyclic heterocycles as potassium channel openers.
WO Patent 2000024741, 2000; Chem. Abstr. 2000, 132, 308329.
10. Patmore, L.; Duncan, G. P.; Clarke, B.; Anderson, A. J.; Greenhouse, R.; Pfister, J. R. RS
30026: A potent and effective calcium channel agonist. Brit. J. Pharmacol. 1990, 99, 687–694.
11. (a) Tomioka, K.; Kubota, Y.; Koga, K. Design, synthesis, and antitumor activity-absolute
configuration relationships of podophyllotoxin aza-analogs. Tetrahedron 1993, 49, 1891–
1900; (b) Lienard, P.; Quirion, J. C.; Husson, H. P. Asymmetric synthesis, XXVIII:
Hydroxylated benzoquinolizidine analogs of podophyllotoxin via the CN(R,S) method.
Tetrahedron 1993, 49, 3995–4006; (c) Madalengoitia, J. S.; Macdonald, T. L. Synthesis of
tetrahydrofurocarbazolones via intramolecular Diels–Alder reactions. Tetrahedron Lett.
1993, 34, 6237–6240; (d) Lehnert, E. K.; Miller, K. E.; Madalengoitia, J. S.; Guzi, T. J.;
Macdonald, T. L. DNA topoisomerase II inhibition by substituted 1,2,3,4-tetrahydro-
carboline derivatives. Bioorg. Med. Chem. Lett. 1994, 4, 2411–2416; (e) Hitotsuyanagi, Y.;
Fukuyo, M.; Tsuda, K.; Kobayashi, M.; Ozeki, A.; Itokawa, H.; Takeya, K. 4-Aza-2,3-
dehydro-4-deoxypodophyllotoxins: Simple Aza-podophyllotoxin analogues possessing
potent cytotoxicity. Bioorg. Med. Chem. Lett. 2000, 10, 315–317; (f) Tratrat, C.; Giorgi-
Renault, S.; Husson, H. P. A multicomponent reaction for the one-pot synthesis of 4-aza-2,
3-didehydropodophyllotoxin and derivatives. Org. Lett. 2002, 4, 3187–3189.
12. (a) Tu, S.; Zhang, Y.; Jia, R.; Jiang, B.; Zhang, J.; Ji, S. A multi-component reaction
for the synthesis of N-substituted furo[3,4-b]quinoline derivatives under microwave
irradiation. Tetrahedron Lett. 2006, 47, 6521–6525; (b) Tu, S.; Zhang, Y.; Zhang, J.; Jiang,
B.; Jia, R.; Zhang, J.; Ji, S. A simple procedure for the synthesis of 4-Aza-podophyllotoxin
derivatives in water under microwave irradiation conditions. Synlett 2006, 17, 2785–2790.
13. (a) Shi, F.; Wang, Q.; Tu, S.; Zhou, J.; Jiang, B.; Li, C.; Zhou, D.; Shao, Q.; Cao, L. A
green and efficient synthesis of furo[3,4-e]pyrazolo[3,4-b]pyridine derivatives in water
under microwave irradiation without catalyst. J. Heterocycl. Chem. 2008, 45, 1103–
1108; (b) Shi, F.; Zhou, D.; Tu, S.; Shao, Q.; Li, C.; Cao, L. An efficient
microwave-assisted synthesis furo[3,4-b][4,7]phenanthroline and indeno[2,1-b][4,7]phenan-
throline derivatives in water. J. Heterocycl. Chem. 2008, 45, 1065–1070; (c) Shi, F.; Zhou,
D.; Li, C.; Shao, Q.; Cao, L.; Tu, S. An efficient and facile microwave-assisted synthesis of
benzo[b][4,7]phenanthroline derivatives in water. J. Heterocycl. Chem. 2008, 45, 405–410.
14. Tu, S.; Lu, Z.; Shi, D.; Yao, C.; Gao, Y.; Guo, C. A convenient synthesis of
9-aryl-3,3,6,6-tetramethyl-1,2,3,4,5,6,7,8,9,10-decahydroacridine-1,8-diones under micro-
wave irradiation without solvent. Synth. Commun. 2002, 32, 2181–2185.