One-Pot, Facile, Highly Efficient, and Green Synthesis of Acridinedione Derivatives Using Vitamin B 1

Article abstract of DOI:10.1080/00397911.2015.1109127

An efficient methodology for the synthesis of acridinedione derivatives 4a-o has been achieved by one-pot, multicomponent condensation of dimedone 1, various amines 2a-d, and substitute aromatic aldehydes 3a-k, in the presence of the easily available, inexpensive, and nontoxic catalyst vitamin B₁(VB₁) as a versatile biodegradable. Synthesis of acridine-type compounds was performed in good yields in water as green solvent. Its high-yield efficiency; clean, ecofriendly, simple workup procedure; and easy purification are regarded as the main advantages of this method besides its green solvent. The synthesized compounds are characterized using spectroscopic analyses (FTIR, ¹H NMR, ¹³C NMR, and high-resolution mass spectrometry) techniques.

Full text of DOI:10.1080/00397911.2015.1109127

Synthetic Communications
An International Journal for Rapid Communication of Synthetic Organic
Chemistry
ISSN: 0039-7911 (Print) 1532-2432 (Online) Journal homepage: http://www.tandfonline.com/loi/lsyc20
One-Pot, Facile, Highly Efficient, and Green
Synthesis of Acridinedione Derivatives Using
Vitamin B1
Ahmet Işık, Burak Aday, Ramazan Ulus & Muharrem Kaya
To cite this article: Ahmet Işık, Burak Aday, Ramazan Ulus & Muharrem Kaya (2015): One-Pot,
Facile, Highly Efficient, and Green Synthesis of Acridinedione Derivatives Using Vitamin B1,
Synthetic Communications, DOI: 10.1080/00397911.2015.1109127
To link to this article: http://dx.doi.org/10.1080/00397911.2015.1109127
View supplementary material
Accepted author version posted online: 30
Oct 2015.
Submit your article to this journal
Article views: 9
View related articles
View Crossmark data
Full Terms & Conditions of access and use can be found at
http://www.tandfonline.com/action/journalInformation?journalCode=lsyc20
Download by: [Monash University Library]
Date: 16 November 2015, At: 02:29

One-Pot, Facile, Highly Efficient, and Green Synthesis of Acridinedione Derivatives
Using Vitamin B1
Ahmet Işık1, Burak Aday1, Ramazan Ulus1, Muharrem Kaya2
1Chemistry Department, Faculty of Arts and Science, Dumlupınar University, Evliya
Çelebi Campus, Kütahya, Turkey, 2Biochemistry Department, Faculty of Arts and
Science, Dumlupınar University, Evliya Çelebi Campus, Kütahya, Turkey
Correspondence to M. Kaya, E-mail: muharrem.kaya@dpu.edu.tr
Abstract
An efficient methodology for the synthesis of acridinedione derivatives 4a-o has been
achieved by one-pot, multi-component condensation of dimedone 1, various amines 2a-d
and substitute aromatic aldehydes 3a-k, in the presence of the easily available,
inexpensive, and nontoxic catalyst vitamin B1 (VB1) as a versatile biodegradable.
Synthesis of acridine-type compounds was performed in high yields in water as green
solvent. Its high-yield efficiency, clean, eco-friendly, simple work-up procedure, and
easy purification are regarded to be the main advantages of this method besides its being
green solvent. The synthesized compounds are characterized using spectroscopic analyses
(IR, 1H-NMR, 13C-NMR and HRMS) techniques.
1

KEYWORDS: Vitamin B1, Acridinedione, Multi-component reaction, One-pot
Synthesis, Cyclization, Green Synthesis
1. INTRODUCTION
Acridinedione derivatives of 1,4-dihydropyridine are compounds having interesting
biological features which are similar to the structure of Nicotinamide Adenine
Dinucleotide (NADH), an important co-enzyme found in cells.[1]
Acridinedione compounds are reported that they can be used as anti-tumor,[2] cytotoxic,[3]
antimicrobial,[4-6] fungicides,[7] anti-multidrug-resistant,[8] β-channel opener in
cardiovascular disease,[9] and as carbonic anhydrase inhibitor for glaucoma treatment[10-12]
and that they are used effectively for the treatment of cancer.[13, 14] Since they indicate
efficiency,[15] these compounds are also used as photo sensitizer in organic dye laser
applications.[16]
The reported synthesis of acridinediones involve Amberlyst-15,[6, 17] Amberlite IR-
120H,[18] CBSA,[19] CTAB,[20] DBSA,[21, 10] FSG-Hf(Npf2)4,[22] Glucose sulfonic acid,[23]
H2SO4,[12] Melamine-formaldehyde resin supported H+,[24] Proline,[25] SiO2-Pr-SO3H,[26]
[TBA]2[W6O19].[27]
Many catalysts used in these synthesis reactions have some disadvantages such as their
reacting in compelling circumstances, being very expensive and difficult to obtain, being
toxic, the abundance of acidic residues, and their synthesis being very difficult. These
2

disadvantages are forcing the researchers for new alternative methods.
Vitamins B, also known as “B Complex” are chemically related micronutrients that work
altogether as a team.
Vitamins B have various functions in the body like helping the cells burn the fat and
glucose needed for the energy, supporting the creation of neurotransmitters like
serotonin, helping the production and repair of DNA, and supporting the intelligence and
memory.[28-30]
Vitamins B1 are very environment friendly substances when compared to other catalysts.
For this reason they are used in many organic reactions as catalysts such as
benzoxanthene,[31, 32] 1H-Benzimidazoles,[33, 34] α-amino phosphonates,[35]
quinoxalines,[36-38] 1,4-dihydropyridines, [39] form-amides,[40] oxazines,[41] and fused
pyridines.[42]
In this study, we wish to report an efficient, green and novel method, for the first time,
for the synthesis of acridinedione derivatives via one-pot MCRs of various aromatic
aldehyde (3a-k), dimedone (1) as cyclic diketones, and various aromatic amines (2a-d) in
highest yields and shortest reaction times by the help of water as clean, eco-friendly,
cheap solvent. Synthesized of all novel molecules have been characterized by IR, 1H-
NMR and 13C-NMR data and high resolution mass spectral analyses, respectively.
3

2. RESULTS AND DISCUSSION
A new, facile, one-pot and efficient method has been designed for the synthesis of
acridinedione compounds. In this method we used cheap and eco-friendly catalyst VB1.
The synthesis of acridinedione compounds were realized in water from dimedone 1,
various amines 2a-d and substitute aromatic aldehydes 3a-k in a single process through
three successive reactions (Aldol condensation, Michael addition and cyclization). These
compounds were prepared by one-pot reaction in high-yield process, and simple work-up
procedure (Scheme 1).
These various substituents subsumed cyano, nitro, halogen (-F, -Cl, -Br), methyl,
methoxy, hydroxyl and isopropyl moieties (Table 1).
The reaction of dimedone (1), benzaldehyde (3f) and 4-chloroaniline (2a) in the presence
of VB1 catalyst in water was selected as the model reaction. Other catalysts we tested are
outlined in Table 2. Whereas as this reaction did not form product in the presence of
catalysts 3-Ethyl-5-(2-hydroxyethyl)-4-methylthiazoliumbromide (5), 3-((4-amino-2-
methylpyrimidin-5-yl)methyl)-5-(2-hydroxyethyl)-4-methylthiazol-3-ium (VB1) was
found to be a good catalyst for this reaction. p-Dodecylbenzenesulfonic acid (6),
Amberliyst-15 (7), and 5-(2-hydroxyethyl)-4-methyl-3-phenylthiazol-3-ium chloride (8)
were much less effective than VB1 catalyst (Scheme 2).
The catalyst plays a crucial role in the success of the reactions in terms of the rate and
yields and these experiments are summarized in Table 3. For example, dimedone (1)
4

reacted with benzaldehyde (3f) and 4-chloroaniline (2a) in the presence of 2% VB1 did
not give the 4f after 48 hours of reaction time. When we increased the amount of the
catalysts to 2%, 5%, 7%, 10%, 13% and 20%, we obtained increased reaction yields as
0%, 45%, 60%, 79%, 79% and 79%, respectively. The use of just 10% VB1 in water at
reflux is enough to support an efficient synthesis.
We also investigated the effects of the solvent through the model reaction catalyzed by
VB1 in various solvents (water, tetrahydrofuran, ethanol, methanol, and ethyl acetate) and
the results are shown in Table 4. It is obvious that water is the best choice as it can be
seen in Table 4.
Whereas the infrared (IR) spectra of all the acridinediones 4a-o aromatic C–H stretching
bands are observed between 3061-3006 cm−1, the aliphatic C–H stretching bands were
observed between 2959-2952 cm−1. Hydroxyl group of 4c and 4o exhibited a peak at
about 3342 cm-1. –CN group of 4a exhibited a peak at 2223 cm-1. Besides, in the IR
spectra of all 4a-o compounds, the carbonyl groups showed sharp peaks in the region
between 1653 and 1632 cm−1.
The 1H-NMR spectra of the compounds 4a-o belonging to protons of the methyl groups
showed singlet peaks in position 3 and 6 between 0.70-0.90 ppm. We observed doublet
peak (6H) at 1.16 ppm and multiple peaks (1H) at 2.80-2.90 ppm for the compound 4b
that directly indicates isopropyl group. The –CH2 group protons of the cyclohexene rings
of the compounds 4a–o showed doublet peaks in the 1.75-2.25 ppm. The compound 4k
5

showed singlet peak that belongs to protons of the methyl group at 2.22 ppm. The
methoxy protons of compound 4l were observed 3.70 ppm. The signals for the –CH
protons were observed at 4.95–5.15 ppm and the signals for the aromatic protons were
observed in the range between 6.61-8.14 ppm. Hydroxyl group proton of compound 4c
and 4o were observed as a broad signal at 9.05 ppm.
The 13C-NMR (APT) spectra of all the compounds 4a-o showed carbonyl carbon peaks
between 195.52-195.63 ppm. The compound 4a displayed a signal for the cyan group
carbon for 109.09 ppm. The signals observed in 13C-NMR (APT) spectra of all the
acridinedione 4a-o molecules are determined to be in line with the recommended
molecule structures.
Also, when their high resolution mass spectra (HRMS) are examined, the observed
molecule ion peaks are in compliance with the recommended structures.
3. CONCLUSION
Easy, effective and practical synthetic method has been developed for the synthesis of
acridinedione cyclization reactions of the various amine, aromatic aldehyde compounds
and dimedone in the presence of environmental friendly, natural, harmless, and highly
efficient VB1 as the catalyst and in water as solvent. With this method, the synthesis of
the acridinediones will be realized as a facile, clean, practical, cheap, eco-friendly. This
method may find a widespread area of usage in synthesis of organic compounds.
6

4. EXPERIMENTAL
4.1. General
The chemicals used in the synthesis of acridinedione derivatives were obtained from
Merck and Aldrich Chemical Company. All chemicals and solvents used for the synthesis
were of spectroscopic reagent grade. Melting points were measured on a Bibby Scientific
Stuart Digital, Advanced, SMP30. Fourier Transform Infrared (FT–IR) spectra were
recorded on a Bruker Optics, ALPHA FT–IR spectrometer. The 1H and 13C NMR spectra
were recorded in a Bruker DPX-300 and were obtained in DMSO-d6 as solvents with
tetramethylsilane as the internal reference. HRMS spectra were detected on an Agilent
Technologies 6530 Accurate-Mass Q-TOF LC/MS at the advanced technology research
centre of Dumlupınar University (ILTEM).
General Procedure For Preparation Of Acridine Derivatives (4a-O)
A mixture of dimedone 1 (2 mmol), benzaldehyde 3f (1 mmol), 4-chloroaniline 2a (1
mmol) and VB1 catalyst (10% mmol) in 10 mL H2O was heated to reflux continuously
for 24 h. The reaction progress was monitored by TLC. The solid product was filtered,
washed with 500 mL water, and recrystallized from ethanol. (72-86%).
4-(10-(4-Chlorophenyl)-3,3,6,6-Tetramethyl-1,8-Dioxo 1,2,3,4,5,6,7,8,9,10-
Decahydroac Ridin-9-Yl)Benzonitrile (4a)
As yellow crystals, (0.388 g, 80 %), mp. 317-319 oC (ethanol); 1H-NMR (300 MHz,
DMSO-d6) δ (ppm): 0.70 (s, 6H, 2x-CH3), 0.90 (s, 6H, 2x-CH3), 1.80 (d, 2H, J= 17.4 Hz,
-CH2), 2.01 (d, 2H, J= 16.0 Hz, -CH2), 2.19 (d, 4H, J= 16.6 Hz, -CH2), 5.10 (s, 1H, -
7

CH), 7.48-7.52 (m, 4H, Ar-H), 7.70 (t, 4H, J= 8.1 Hz, Ar-H); 13C-NMR (75 MHz,
DMSO–d6) δ (ppm): 26.6, 29.6, 32.5, 33.4, 41.4, 49.9, 109.1, 112.6, 119.4, 129.2, 130.5,
132.46, 134.5, 137.6, 151.2, 151.9, 195.53; IR (cm–1): 3056 w (Ar-H), 2959 s (-CH),
2223 s (-CN), 1632 s (C=O), 1605 s (C=C); HRMS (QTOF-ESI): m/z [M+H]+ calcd. for
C30H30ClN2O2: 485.1996; found [M+H]+: 485.2006.
10-(4-Chlorophenyl)-9-(4-Isopropylphenyl)-3,3,6,6-Tetramethyl-3,4,6,7,9,10-Hexa
Hydro Acridine-1,8(2H,5H)-Dione (4b)
1
As yellow crystals, (0.407 g, 81 %), mp. 210 oC (ethanol). H-NMR (300 MHz, DMSO-
d6) δ (ppm): 0.75 (s, 6H, 2x-CH3), 0.90 (s, 6H, 2x-CH3), 1.16 (d, 6H, J= 6.9 Hz, 2x-
CH3), 1.78 (d, 2H, J= 17.4 Hz, -CH2), 2.00 (d, 2H, J= 16.0 Hz, -CH2), 2.16 (d, 2H, J=
4.0 Hz, -CH2), 2.21 (d, 2H, J= 5.5 Hz, -CH2), 2.80-2.90 (m, 1H, -CH), 5.00 (s, 1H, -CH),
7.11 (d, 2H, J= 8,1 Hz, Ar-H), 7.21 (d, 2H, J= 8,1 Hz, Ar-H), 7.40-7.50 (br, 2H, Ar-H),
7.68 (d, 2H, J= 8.8 Hz, Ar-H); 13C-NMR (75 MHz, DMSO–d6) δ (ppm): 24.4, 26.7, 29.7,
31.8, 32.5, 33.4, 41.3, 50.1, 113.7, 126.3, 127.9, 130.6, 134.4, 137.8, 144.1, 146.0, 150.5,
195.6; IR (cm–1): 3052 w (Ar-H), 2959 s ( -CH), 1635 s (C=O), 1574 s (C=C); HRMS
(QTOF-ESI): m/z [M+H]+ calcd. for C32H37ClNO2: 502.2513; found [M+H]+: 502.2527.
10-(4-Chlorophenyl)-9-(4-Hydroxyphenyl)-3,3,6,6-Tetramethyl-3,4,6,7,9,10-Hexa
Hydro Acridine-1,8(2H,5H)-Dione (4c)
1
As yellow crystals, (0.362 g, 76 %), mp. 352 oC (ethanol). H-NMR (300 MHz, DMSO-
d6) δ (ppm): 0.70 (s, 6H, 2x-CH3), 0.90 (s, 6H, 2x-CH3), 1.75 (d, 2H, J= 17,3 Hz, -CH2),
1.99 (d, 2H, J= 16,0 Hz, -CH2), 2.14-2.21 (m, 4H, -CH2), 4.95 (s, 1H, -CH), 6.61 (d, 2H,
8

J= 8.5 Hz, Ar-H), 7.08 (d, 2H, J= 8.5 Hz, Ar-H), 7.35-7.50 (br, 2H, Ar-H), 7.67 (d, 2H,
J= 8.8 Hz, Ar-H), 9.05 (s, 1H, -OH); 13C-NMR (75 MHz, DMSO–d6) δ (ppm): 26.5,
29.8, 31.2, 32.4, 41.3, 50.1, 114.0, 115.1, 128.8, 130.5, 134.3, 137.3, 137.9, 150.2, 155.7,
195.58; IR (cm–1): 3342 br (-OH), 3018 w (Ar-H), 2955 s (-CH), 1634 s (C=O), 1589 s
(C=C); HRMS (QTOF-ESI): m/z [M+H]+ calcd. for C29H31ClNO3: 476.1992; found
[M+H]+: 476.1997.
10-(4-Bromophenyl)-9-(4-Chlorophenyl)-3,3,6,6-Tetramethyl-3,4,6,7,9,10-Hexa
Hydroacridine-1,8(2H,5H)-Dione (4d)
As yellow crystals, (0.437 g, 81 %), mp. 308-310oC (ethanol) 1H-NMR (300 MHz,
DMSO-d6) δ (ppm): 0.70 (s, 6H, 2x-CH3), 0.90 (s, 6H, 2x-CH3), 1.80 (d, 2H, J= 17.3 Hz,
-CH2), 2.01 (d, 2H, J= 16.1 Hz, -CH2), 2.18-2.24 (m, 4H, -CH2), 5.10 (s, 1H, -CH), 7.48
(d, 2H, J= 8.5 Hz, Ar-H), 7.58 (d, 2H, J= 8.7 Hz, Ar-H), 7.66 (d, 2H, J= 8.5 Hz, Ar-H),
8.14 (d, 2H, J= 8.7 Hz, Ar-H) ; 13C-NMR (75 MHz, DMSO–d6) δ (ppm): 26.6, 29.6,
32.5, 33.4, 41.4, 49.9, 112.5, 123.2, 123.8, 129.4, 133.5, 138.0, 146.2, 151.3, 154.0,
195.5; IR (cm–1): 2955 s (-CH), 1632 s (C=O), 1594 s (C=C); HRMS (QTOF-ESI): m/z
[M+H]+ calcd. for C29H30BrClNO2: 538.1160; found [M+H]+: 538.1148.
9-(4-Bromophenyl)-10-(4-Fluorophenyl)-3,3,6,6-Tetramethyl-3,4,6,7,9,10-Hexa
Hydroacridine-1,8(2H,5H)-Dione (4e)
As brown crystals, (0.439 g, 84 %), mp. 292-295 oC (ethanol). 1H-NMR (300 MHz,
DMSO-d6) δ (ppm): 0.70 (s, 6H, 2x-CH3), 0.90 (s, 6H, 2x-CH3), 1.77 (d, 2H, J= 17.4 Hz,
-CH2), 2.00 (d, 2H, J= 16.0 Hz, -CH2), 2.16-2.22 (m, 4H, -CH2), 5.00 (s, 1H, -CH), 7.26
9

(d, 2H, J= 8.4 Hz, Ar-H), 7.42-7.48 (m, 6H, Ar-H); 13C NMR (75 MHz, DMSO–d6) δ
(ppm): 26.6, 29.7, 32.3, 41.4, 50.0, 113.0, 119.2, 130.3, 131.3, 135.1, 146.0, 151.1, 160.7,
164.0, 195.5; IR (cm–1): 3061 w (Ar-H), 2954 s (-CH), 1636 s (C=O), 1577 s (C=C);
HRMS (QTOF-ESI): m/z [M+H]+ calcd. for C29H30BrFNO2: 522.1444; found [M+H]+:
522.1595.
ACKNOWLEDGEMENTS
This research was financed by Dumlupınar University Research Fund (Grant No. 2014-
20).
SUPPLEMENTAL MATERIAL
Supplemental data for this article can be accessed on the publisher’s website.
REFERENCES
Singh, S.; Chhina, S.; Sharma, V. K.; Sachev, S.S. J. Chem Soc. Chem.
Commun. 1982, 8, 453-454.
[1].
[2].
[3].
[4].
Mikata, Y.; Yokoyama, M.; Mogami, K.; Kato, M.; Okura, I.; Chikira, M.;
Yano, S. Inorg. Chim. Acta. 1998, 279, 51-57.
Antonini, I.; Polucci, P.; Kelland, R. L.; Menta, E.; Pescalli, N.; Martelli, S.
J. Med. Chem. 1999, 42, 2535-2541.
Ngadi, L.; Galy, A. M.; Galy, J. P.; Barbe, J.; Cremieux, A.; Sharples, D.
Eur. J. Med. Chem. 1990, 25, 67-70.
[5].
[6].
[7].
Wainwright, M. J. Antimicrob. Chemother. 2001, 47, 1-13.
Kaya, M.; Yıldırır, Y.; Çelik, G. Y. Med. Chem. Res. 2011, 20, 293–299.
Srivastava, A.; Nizamuddin Indian J. Heterocycl. Chem. 2004, 13, 261-264.
10

[8].
Gallo, S.; Atifi, S.; Mahamoud, A.; Santelli-Rouvier, C.; Wolfa’rt, K.;
Molnar, J.; Barbe, J. Eur. J. Med. Chem. 2003, 38, 19-26.
Öcal, B.; Saraç, B.; Şimşek, R.; Yıldırım, S.; Sarıoğlu, Y.; Şafak, C. Eur. J.
Med. Chem. 2002, 37, 519-523.
[9].
[10].
[11].
[12].
[13].
[14].
Kaya, M.; Basar, E.; Çakir, E.; Tunca, E.; Bulbul, M. J. Enzyme Inhib. Med.
Chem. 2012, 27, 509-514.
Ulus, R.; Yeşildağ, İ.; Tanc, M.; Bülbül, M.; Kaya, M.; Supuran, C. T.
Bioorg. Med. Chem. 2013, 21, 5799-5805.
Yeşildağ, İ.; Ulus, R.; Basar, E.; Aslan, M.; Kaya, M.; Bülbül, M. Monatsh.
Chem. 2014, 145, 1027-1034.
Gamage, S. A.; Spicer, J. A.; Atwell, G. J.; Finlay, G. J.; Baguley, B. C.;
Denny, W. A. J. Med. Chem. 1999, 42, 2383-2393.
Pitta, M. G. R.; Souza, E. S.; Barros, F. W. A.; Filho, M. O. M.; Pessoa, O.;
Hernandes, M. Z.; Lima, M. D. C. A. D.; Galdino, S. L.; Pitta, I. D. R. Med. Chem. Res.
2013, 22, 2421–2429.
[15].
Tu, S. J.; Lu, Z.; Shi, D.; Yao, C.; Gao, Y.; Guo, C. Synth. Commun. 2002,
32, 2181-2185.
[16].
Kaya, M.; Yıldırır, Y.; Türker, L. J. Heterocyclic Chem. 2009, 46, 294–297.
Das, B.; Thirupathi, P.; Mahender, I.; Reddy, V. S.; Rao, Y. K. J. Mol.
Catal. A: Chem. 2006, 247, 233-239.
[17].
[18].
Nakhi, A.; Srinivas, P. T. V. A.; Rahman, Md. S.; Kishore, R.; Seerapu, G.
P. K.; Kumar, K. L.; Haldar, D.; Rao, M. V. B.; Pal, M. Bioorg. Med. Chem. 2013, 23,
1828-1833.
11

[19].
Davoodnia, A.; Khojastehnezhad, A.; Tavakoli-Hoseini, N. Bull. Korean
Chem. Soc. 2011, 32, 2243.
[20].
[21].
Xia, J. J.; Zhang, K.H. Molecules 2012, 17, 5339-5345.
Jin, T. S.; Zhang, J. S.; Guo, T. T.; Wang, A. Q.; Li, T. S. Synlett 2004, 12,
1425–1427.
[22].
[23].
Hong, M.; Xiao, G. J. Fluorine Chem. 2012, 144, 7-9.
Wan, Y.; Zhang, X. X.; Wang, C.; Zhao, L. L.; Chen, L. F.; Liu, G. X.;
Huang, S. Y.; Yue, S. N.; Zhang, W. L.; Wu, H. Tetrahedron 2013, 69, 3947-3950.
Rezaei, R.; Khalifeh, R.; Rajabzadeh, M.; Dorosty, L.; Doroodmand, M. M.
Heterocycl. Commun. 2013, 19, 57–63.
[24].
[25].
[26].
[27].
[28].
[29].
[30].
[31].
Venkatesan, K.; Pujari, S. S.; Srinivasan, K. V. Synth. Commun. 2009, 39,
228-241.
Ziarani, G. M.; Badiei, A.; Hassanzadeh, M.; Mousavi, S. Arab. J. of Chem.
2014, 7, 335-339.
Davoodnia, A.; Zare-Bidaki, A.; Behmadi, H. Chin. J. Catal. 2012, 33,
1797-1801.
Abularrage, C. J.; Sidawy, A. N.; White, P. W.; Aidinian, G.; DeZee, K. J.;
Weiswasser, J. M.; Arora, S. Vasc Endovascular Surg 2007, 41, 339.
Christen, W. G.; Glynn, R. J.; Chew, E. Y.; Albert, C. M.; Manson, J. E.
Arch. İntern. Med. 2009, 169, 335-341.
Kuzniarz, M.; Mitchell, P.; Cumming, R. G.; Flood, V. M. Am J
Ophthalmol 2001, 132, 19–26.
Lei, M.; Ma, L.; Hu, L. Synth. Commun. 2011, 41, 3432-3432.
12

[32].
Fatma, S.; Singh, P. K.; Ankit, P.; Shireen; Singh, M.; Singh, J. Tetrahedron
Letters 2013, 54, 6732-6736.
[33].
[34].
[35].
Lei, M.; Ma, L.; Hu, L. Synth. Commun. 2012, 42, 2981-2993.
Chen, F.; Lei, M.; Hu, L. Tetrahedron 2013, 69, 2954-2960.
Mandhale, P. G.; Joshi, R. S.; Nagargoje, D. R.; Gill, C. H. Chin. Chem.
Lett. 2011, 22, 563-566.
[36].
Chen, Y.; Shan, W.; Lei, M.; Hu, L. Tetrahedron 2012, 53, 5923-5925.
Aghapoor, K.; Mohsenzadeh, F.; Talebian, S.; Tehrani, M. J.; Balavari, Y.;
Khanalizadeh, G.; Darahi, H. R. Monatsh. Chem. 2011, 142, 619-624.
Pawar, O. B.; Chavan, F. R.; Suryawanshi, V. S.; Shinde, V. S.; Shinde, N.
D. J. Chem. Sci. 2013, 125, 159-163.
[37].
[38].
[39].
Pradhan, K.; Bhattacharyya, P.; Paul, S.; Das, A. R. Tetrahedron Letters
2012, 53, 5840-5844.
[40].
Lei, M.; Ma, L.; Hu, L. Tetrahedron Letters 2010, 51, 4186-4188.
Dhakane, V. D.; Gholap, S. S.; Deshmukh, U. P.; Chavan, H. V.; Bandgar,
B. P. C. R. Chimie 2014, 17, 431-436.
[41].
[42].
[43].
[44].
[45].
Siddiqui, I. R.; Rai, P.; Rahila; Srivastava, A.; Srivastava, A.; Srivastava, A,
New J. Chem. 2013, 37, 3798-2804.
Tang, Z. Q.; Chen, Y.; Liu, C. C.; Cai, K. Y.; Tu, S. J. J. Heterocyclic
Chem. 2010, 47, 363.
El-Sabbagh, O. I.; Shabaan, M. A.; Kadry, H. H.; Al-Din, E. S. Arch. der
Pharm. 2010, 9, 519-527.
Zhao, L. L.; Teng, D. Acta Crystallogr. Sect. 2008, 64, 1772-1773.
13

[46].
Chen, Y.; Hao, W. J.; Tang, Z. Q.; Jiang, B.; Li, C. M. Acta Crystallogr.
Sect. 2007, 63, 3934.
[47].
[48].
Kidwai, M.; Bhatnagar, D. Tetrahedron Letters 2010, 50, 2700-2703.
Wang, X. S.; Zhang, M. M.; Jiang, H.; Shi, D. Q.; Tu, S. J.; Wei, X. Y.;
Zong, Z. M. Synthesis 2006, 24, 4187-4199.
14

a
Table 1. Synthesis of acridinediones 4a-o in the presence of 10 mmol% VB1
Entry
R
R’
Time (h)
Yieldb
(%)
80
Mp (oC)
Lit. Mp
(oC)
—
4-Cl
4-Cl
4-CN
4-
24
24
317-319
210
4a
4b
81
—
isopropyl
4-OH
4-Cl
4-Cl
4-Br
4-F
24
24
24
24
76
81
84
79
352
—
4c
4d
4e
4f
308-310
292-295
300-302
—
4-Br
—
4-Cl
4-H
(309-
311)[24]
(>300)[43]
(285-
4-Cl
4-Cl
4-NO2
3-NO2
24
24
83
86
315
4g
4h
285-287
286)[44]
(>300)[43]
(>300)[45]
(268-
4-Cl
4-Cl
4-Cl
4-Br
4-F
24
24
24
84
72
74
304-305
280-282
262-265
4i
4j
4k
4-CH3
269)[44]
(269-
4-Cl
4-Br
4-F
4-OCH3
4-H
24
24
82
83
84
255-257
303-305
303-305
4l
270)[46]
(269-
4m
4n
272)[47]
(>300)[48]
4-Cl
24
15

4-OH
4-Br
24
76
316
(>300)[43]
4o
a Reaction conditions: dimedone (2 mmol), benzaldehyde (1 mmol), 4-chloroaniline
(1mmol), catalyst (10 mmol %), solvent (10 mL H2O)
b Experimental yield
16

Table 2. Comparison of the efficiency of the various catalyst used in the synthesis of
acridinedione compound (4f)
Entry
Catalyst
Time/h
24
Yield/%
5
—
60
79
54
72
1
2
3
4
5
6
24
VB1
7
24
24
8
24
17

Table 3. The Optimization of catalyst concentration for preparation of acridinedione
compound (4f) using VB1 as catalyst at reflux in H2O
Entry
1
2
3
4
5
6
2
5
7
10
13
20
Concentration
(%)
—
45
60
79
79
79
Yield (%)
18

Table 4. A comparison of the efficiency of various solvents employed in the synthesis of
the acridinedione compound (4f)
Entry
Solvent
H2O
Time (h)
Yield (%)
24
24
24
24
24
79
40
75
68
53
1
2
3
4
5
THF
Ethanol
Methanol
Ethyl Acetate
19

Scheme 1. The general synthesis scheme implemented for the synthesis of acridinedione
derivatives
20

Scheme 2. The structure of the catalysts tested in the model reaction.
21