Synthesis of 9-Arylhexahydroacridine-1,8-diones Using Phosphate Fertilizers as Heterogeneous Catalysts

Article abstract of DOI:10.1134/S1070428019090185

A new strategy has been proposed for the synthesis of 9-arylhexahydroacridine-1,8-diones by three-component condensation of aromatic aldehydes with 5,5-dimethylcyclohexane-1,3-dione and ammonium acetate in ethanol, using nontoxic, available, and inexpensi

Full text of DOI:10.1134/S1070428019090185

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2019, Vol. 55, No. 9, pp. 1380–1386. © Pleiades Publishing, Ltd., 2019.
Synthesis of 9-Arylhexahydroacridine-1,8-diones
Using Phosphate Fertilizers as Heterogeneous Catalysts
a
a
a
a
a
b
S. Chehab , Y. Merroun , T. Ghailane , R. Ghailane ,* S. Boukhris , M. Akhazzane ,
b
a
A. Kerbal , and A. Souizi
a
Laboratory of Organic, Organometallic, and Theoretical Chemistry, Faculty of Science, Ibn Tofail University,
Kenitra, Morocco
b
Sidi Mohammed Ben Abdellah University, City of Innovation, Fez, Morocco
*
e-mail:ghailane_r@yahoo.fr
Received January 26, 2018; revised June 28, 2019; accepted July 2, 2019
Abstract—A new strategy has been proposed for the synthesis of 9-arylhexahydroacridine-1,8-diones by three-
component condensation of aromatic aldehydes with 5,5-dimethylcyclohexane-1,3-dione and ammonium
acetate in ethanol, using nontoxic, available, and inexpensive phosphate fertilizers [monoammonium phosphate
(
MAP), diammonium phosphate (DAP), and triple super phosphate (TSP)] as heterogeneous catalysts. Notable
advantages of the proposed method include operational simplicity, low cost of the reactants, favorable
environmental profile, good yield, short reaction time, recovery and reuse of the catalyst, and valorization of
Moroccan natural phosphate.
Keywords: heterogeneous catalysts, phosphate fertilizers, MAP, DAP, TSP, 9-arylhexahydroacridine-1,8-
diones.
DOI: 10.1134/S1070428019090185
Recently, the development of clean synthetic pro-
cedures, which enter into the framework of sustainable
chemistry, has become one of the main objectives of
organic synthesis in order to reduce or eliminate the
use of toxic substances that are harmful to the environ-
ment [1]. Undoubtedly, multicomponent reactions are
therefore part of sustainable chemistry and constitute
a novel way of ideal organic synthesis, since complex
structures are rapidly obtained from very simple
substrates involving simple synthetic operations and
environmentally safe processes, such as the use of eco-
friendly solvents and reusable heterogeneous catalysts.
This makes these reactions environmentally benign
show anti-multidrug-resistant [11], antitumor [12], and
fungicidal activity [13], and act as potassium channel
openers in cardiovascular diseases [14] and antimicro-
bial agents [15]. In addition, they are also used as laser
dyes and possess many important photophysical and
electrochemical properties [16].
The importance and usefulness of acridines have
led to the development of numerous methods of their
synthesis. In general, they are synthesized by the three-
component Hantzsch condensation of aldehydes with
β-diketones and ammonium acetate or appropriate
primary amine on heating in organic solvents [17],
under microwave irradiation [18], in ionic liquids
[19–20], or using various catalysts such as FeCl /SiO
[2–3]. Among the three-component reactions, one can
3
2
cite the synthesis of acridine-1,8-diones that form
an important class of heterocyclic compounds due to
their applications in various fields such as biology,
pharmacology, and industry [4]. Structural modifica-
tions of these heterocycles made it possible to develop
products with increased activity and expanded spec-
trum of therapeutic action. Indeed, acridines are active
against malaria [5], cancer [6], and leishmania [7], and
they bind to photo-damaged DNA [8]. They also
exhibit cytotoxicity [9], block potassium channels [10],
[21], In(OTf) [22], cetyl(trimethyl)ammonium
3
bromide (CTAB) [23], CeCl
ammonium hexatungstate [25], nano-Fe
ZnO [27], ceric ammonium nitrate (CAN) [28],
InCl [29], MCM-41-SO H [30], oxalic acid [31],
[MIMPS] 40 [32], TsOH [33], and nanorod
·7H
O [24], tetrabutyl-
3
2
O
4
[26], nano-
3
3
3
-PW12O
3
vanadatesulfuric acid (VSA NRs) [4].
Each of these methods has its own advantages, but
some of them suffer from several disadvantages, such
as the use of costly catalysts, which requires a lot of
1
380

SYNTHESIS OF 9-ARYLHEXAHYDROACRIDINE-1,8-DIONES
1381
Scheme 1.
R
O
O
CHO
DAP, MAP or TSP
EtOH/Reflux
O
O
2
+
+
NH OAc
4
R
Me
Me
Me
Me
Me
Me
N
H
1
2a–2g
3
4a–4g
2 2
R = H (a), Me (b), Me N (c), O N (d), Br (e), MeO (f), Cl (g).
time and money for their preparation, non-reusable
toxic solvents, severe operating condition, low yields,
and long reaction times. Consequently, effective, inex-
pensive, available, nontoxic, and recyclable catalysts
remain needed for the preparation of 9-arylhexahydro-
acridine-1,8-diones with excellent yield in short reac-
tion time under green operating conditions to save cost
and energy while respecting the environment. This
work was aimed at developing a procedure for the
synthesis of 9-arylhexahydroacridine-1,8-diones via
multicomponent reaction between aromatic aldehydes,
dimedone, and ammonium acetate using phosphate
fertilizers, monoammonium phosphate (MAP), diam-
monium phosphate (DAP), and triple super phosphate
reduction of the yield, which may be related to the
insufficiency of the catalyst surface to adsorb the
reagent.
Then, the effect of protic polar (ethanol), aprotic
polar (acetonitrile), and nonpolar solvents (dioxane) on
the yield of 9-arylhexahydroacridine-1,8-diones was
examined. The reaction was also carried out under
solvent-free conditions. The results are summarized in
Table 3. Ethanol gave high yields, and it appeared to
be the most appropriate solvent for this reaction.
Ethanol has a high dipole moment and a relatively high
Yield, %
100
(
TSP) [34–36], as heterogeneous catalysts (Scheme 1).
The efficiency of these catalysts has been demon-
strated by studying different reaction parameters such
as time, solvent nature, and the amount of catalyst.
8
6
4
2
0
0
0
0
0
When the reaction was carried out without a cata-
lyst, no acridine was formed after 60 min. Increase of
the reaction time to 8 h led to the formation of the
desired product in a low yield (40%). In the presence
of a phosphate catalyst, it was possible to obtain the
desired product with an excellent yield (94%) after
only 60 min, which proved the effectiveness of the
three catalysts used (Table 1).
MAP
DAP
TSP
In order to find the optimum conditions, the reac-
tion time was shortened from 60 to 10 min in 10-min
steps. The obtained results are presented in Fig. 1. It is
seen that the yield increases with time reaching (94%)
after 60 min in presence of each catalyst (MAP, DAP,
or TSP). The influence of the amount of the catalyst
was studied by varying it from 0.002 to 0.01 g in a step
of 002 g, other conditions being equal (reaction time
0
20
30
40
50
60
Time, min
Fig. 1. Yields of 9-phenyl-3,3,6,6-tetramethyl-3,4,6,7,9,10-
hexahydroacridine-1,8(2H,5H)-dione (4a) in the reaction of
dimedone (1, 2 mmol) with benzaldehyde (2a, 1 mmol), and
ammonium acetate (1 mmol) in the presence of MAP, DAP,
and TSP (0.01 g) in 3 mL of ethanol (reflux) versus reac-
tion time.
6
0 min; Table 2). The optimal amounts of the catalysts
were 0.01 (8.5 mol %), 0.008 (6.1 mol %), and 0.004 g
1.7 mol %) of MAP, DAP, and TSP, respectively.
Further increase of the catalyst amount led to the
(
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 55 No. 9 2019

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382
CHEHAB et al.
Table 1. Synthesis of 9-phenyl-3,3,6,6-tetramethyl-3,4,6,7,9,10-hexahydroacridine-1,8(2H,5H)-dione (4a) in the presence of
a
MAP, DAP, and TSP
b
Catalyst
Amount of catalyst, g/mol %
Time, min
Yield, g/%
–
0
480
060
060
060
0.139/40
0.328/94
0.328/94
0.328/94
MAP
DAP
TSP
0.01/8.5
0.01/7.6
0.01/4.3
a
Reaction conditions: 2 mmol of dimedone, 1 mmol of ammonium acetate, 1 mmol of benzaldehyde, 0.01 g of MAP, DAP, or TSP,
mL of ethanol, reflux.
Isolated yield.
3
b
Table 2. Synthesis of 9-phenyl-3,3,6,6-tetramethyl-3,4,6,7,9,10-hexahydroacridine-1,8(2H,5H)-dione (4a) in the presence of
a
different amounts of MAP, DAP, and TSP
b
Amount of catalyst, g/mol %
DAP
Yield, g/%
DAP
MAP
TSP
MAP
TSP
0
0
0
0
0
.002/1.7
.004/3.3
.006/5.2
.008/6.9
0.01/8.5
0.002/1.5
0.004/3.1
0.006/4.6
0.008/6.1
00.01/7.6
0.002/0.8
0.004/1.7
0.006/2.6
0.008/3.4
00.01/4.3
0.283/81
0.286/82
0.297/85
0.307/88
0.328/94
0.286/82
0.286/82
0.324/93
0.342/98
0.328/94
0.317/91
0.335/96
0.331/95
0.328/94
0.328/94
a
Reaction conditions: 2 mmol of dimedone, 1 mmol of ammonium acetate, 1 mmol of benzaldehyde, 3 mL of ethanol; reflux, 60 min.
Isolated yield.
b
Table 3. Synthesis of 9-phenyl-3,3,6,6-tetramethyl-3,4,6,7,9,10-hexahydroacridine-1,8(2H,5H)-dione (4a) in different
solvents
b
Yield, g/%
Solvent
MAP
DAP
TSP
EtOH
0.328/94
0.310/89
0.293/84
0.289/83
0.240/69
0.219/63
0.303/87
0.342/98
0.314/90
0.272/78
0.265/76
0.219/63
0.216/62
0.275/79
0.335/96
0.300/86
0.244/70
0.251/72
0.226/65
0.230/66
0.282/81
MeOH
MeCN
THF
Dioxane
Toluene
No solvent
a
Reaction conditions: 2 mmol of dimedone, 1 mmol of ammonium acetate, 1 mmol of benzaldehyde, 0.01 g of MAP, 0.008 g of DAP, and
.004 g of TSP, 3 mL of solvent; reflux, 60 min.
Isolated yield.
0
b
dielectric constant which allow it to separate charges
and thus favor interactions between the active sites of
the reagent, so the products can be easily formed.
Although methanol is a more polar solvent, ethanol
remains the best one. The yields obtained in these two
solvents allowed us to conclude that the polarity is the
main factor; in addition, protic character of the solvent
also plays an important role in proton exchange. The
reaction in nonpolar solvents (dioxane, toluene) gave
the final product in lower yields than in polar solvents.
Thus, the synthesis of 9-arylhexahydroacridine-1,8-di-
one was found to be favored in high-polarity solvents,
more precisely polar protic solvents.
An important factor of the catalytic efficiency is
the ability of the catalyst to be reused several times.
Figure 2 represents the yields after each cycle of the
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 55 No. 9 2019

SYNTHESIS OF 9-ARYLHEXAHYDROACRIDINE-1,8-DIONES
Yield, %
1383
model reaction. It was found that the yields decreased
insignificantly after four cycles; thus the catalysts can
be reused at least four times without appreciable loss
of their activity.
1
00
8
6
0
0
Subsequently, a number of 9-aryl-acridine-1,8-di-
one derivatives 4a–4g with various substituents in the
aryl ring were prepared from the corresponding alde-
hydes, dimedone, and ammonium acetate under the
optimized conditions (Table 4). All compounds 4a–4g
were reported previously, and their melting points
were consistent with published data. In the presence of
MAP as a catalyst, high yields (94, 96, and 97%) were
obtained for aldehydes 2a, 2b, and 2e (R = H, Me, Br),
respectively. The best yields (98, 98, and 95%) were
achieved in the reactions with 2a, 2b, and 2c (R =
MAP
DAP
TSP
40
2
0
0
Cycle 1
Cycle 2
Cycle 3
Cycle 4
Me N), respectively, catalyzed by DAP. The third
2
Fig. 2. Reusability of MAP, DAP, and TSP catalysts in the
model reaction.
catalyst, TSP, ensured the best yields (96 and 92%)
with unsubstituted benzaldehyde (2a) and 4-methyl-
benzaldehyde (2b), respectively. Thus, the catalytic
activity depended on the structures of both catalyst and
initial aldehyde, as well as on the nature of the catalyst
surface. In fact, these parameters are responsible for
the interactions which take place in the catalyst
surface–reagent interface.
attack of the amino group on the carbonyl carbon atom
and removal of water molecule lead to the formation of
acridine-1,8-dione 4. This mechanism is valid for the
three catalysts used.
The catalytic activity of MAP, DAP, and TSP was
compared with the activity of other catalysts used pre-
viously for the same reaction (Table 5). The obtained
data indicate that MAP, DAP, and TSP catalysts give
better yields and shorter reaction times than the other
reported catalysts.
Scheme 2 shows a plausible mechanism for the
formation of 9-arylhexahydroacridine-1,8-diones in the
presence of MAP. The reaction begins with protona-
tion of the carbonyl group in aldehyde 2 by the action
of MAP, followed by condensation with dimedone
molecule to produce intermediate 6 which loses water
molecule to form 7. Next, enaminone 5 formed by the
reaction of dimedone with ammonium acetate adds to
the =CH carbon atom of 7 to give intermediate 8.
Finally, intramolecular cyclization via nucleophilic
To sum up, the use of MAP, DAP, and TSP phos-
phate fertilizers as heterogeneous catalysts provide
a very effective method for the synthesis of 9-aryl-
acridine-1,8-diones with very good yields and in
shorter reaction times. Furthermore, these catalysts
a
Table 4. Synthesis of acridines 4a–4g under the optimized conditions
b
Yield, g/%
melting point, °C
Compound
R
no.
MAP
DAP
TSP
found
reported
4
4
4
4
4
4
4
a
b
c
d
e
f
H
0.328/94
0.348/96
0.337/86
0.347/88
0.414/97
0.307/81
0.329/86
0.342/98
0.356/98
0.372/95
0.351/89
0.325/76
0.235/62
0.147/52
0.335/96
0.334/92
0.349/89
0.309/88
0.325/76
0.273/72
0.276/72
258–260
>260
>260
>260
>260
>260
>260
258–260 [37]
318–320 [24]
280–282 [37]
287–290 [37]
312–315 [24]
269–271 [37]
300–302 [37]
4-Me
4-Me
2
N
4-O
2
N
4-Br
4-MeO
4-Cl
g
a
Reaction conditions: 2 mmol of dimedone, 1 mmol of ammonium acetate, 1 mmol of aldehyde 2a–2g, 0.01 g of MAP, 0.008 g of DAP,
or 0.004 g of TSP, 3 mL of ethanol; reflux, 60 min.
Isolated yield.
b
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1
384
CHEHAB et al.
Scheme 2.
Me
Me
Me
Me
Me
O
O
O
Me
NH OAc
4
O
OH
NH2
1
5
H
O
H
MAP
O
O
O
MAP–
MAP
H
MAP–
H
H
H
OH
OH
Me
Me
Me
Me
O
O
2
6
NH2
Me
O
O
O
O
O
O
Me
H
–
H O
2
–H O
2
Me
Me
Me
Me
Me
Me
Me
Me
Me
O
Me
N
OH NH
H
7
8
4
possess a remarkable recycling capacity. The possi-
bility of using recyclable catalysts under optimum
conditions to synthesize a large number of organic
compounds is the main contribution of this work to
preserving our environment from toxic pollutants.
hexane as eluent. The melting points were measured
on a Kofler hot stage. The H NMR and C NMR
1
13
spectra were recorded in CDCl on a Brucker AV II
3
spectrometer at 300 and 75 MHz, respectively,
General procedure for the synthesis of 9-aryl-
acridine-1,8-diones 4a–4g. A mixture of 0.28 g
EXPERIMENTAL
(
2 mmol) of 5,5-dimethylcyclohexane-1,3-dione,
All chemicals were purchased from Sigma–Aldrich.
The progress of reactions was monitored by TLC on
silica gel F254 plates (Merck) using ethyl acetate–
0.154 g (1 mmol) of ammonium acetate, and 1 mmol
of aromatic aldehyde 2a–2g in 3 ml of ethanol con-
taining MAP, DAP, or TSP as catalyst was heated
Table 5. Synthesis of 9-phenyl-3,3,6,6-tetramethyl-3,4,6,7,9,10-hexahydroacridine-1,8(2H,5H)-dione (4a) in the presence of
phosphate fertilizers and other catalysts
Catalyst
Solvent
EtOH
Temperature, °C
Time, h
Yield, %
Reference
MAP
DAP
TSP
Reflux
Reflux
Reflux
080
1.0
1.0
94
98
96
90
82
87
85
94
95
91
This study
This study
This study
[37]
EtOH
EtOH
1.0
SiO
FSG–Hf(NPf
CMIM][CF COO]
SiO –PrSO
KH PO
2
–I
EtOH
2.5
2
)
4
EtOH–H
2
O
O
Reflux
080
4.0
[38]
[
3
EtOH–H
2
01.33
2.0
[39]
2
3
H
Solvent free
EtOH–H
120
[40]
2
4
2
O
120
5.0
[41]
SSA
H
H
2
2
O
O
070
1.5
[42]
SPNP
Reflux
2.0
[43]
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 55 No. 9 2019

SYNTHESIS OF 9-ARYLHEXAHYDROACRIDINE-1,8-DIONES
1385
under reflux until the reaction was complete (TLC).
The mixture was cooled to room temperature, 5 mL of
chloroform was added, the undissolved catalyst was
filtered off, the filtrate was evaporated, and the residue
was recrystallized from ethanol. Compounds 4a–4g
were characterized on the basis of their melting points
and NMR spectra, which showed a good agreement
with published data [24, 37].
each, CH ), 2.19–2.48 m (8H, CH ), 4.72 s (1H, 9-H),
7.15–7.31 m (4H, Harom). C NMR spectrum, δ , ppm:
C
27.28, 29.28, 31.48, 32.21, 40.83, 50.72, 115.22,
128.61, 129.79, 132.01, 142.75, 162.58, 196.45.
3
2
13
CONFLICT OF INTERESTS
The authors declare the absence of conflict of
interests.
3
,3,6,6-Tetramethyl-9-phenyl-3,4,6,7,9,10-hexa-
1
hydroacridine-1,8(2H,5H)-dione (4a). H NMR spec-
REFERENCES
trum, δ ppm: 0.98 s and 1.09 s (6H each, CH ), 2.14–
3
2
.46 m (8H, CH ), 5.10 s (1H, 9-H), 7.13–7.37 m (5H,
1. Anastas, P.T. and Kirchhoff, M.M., Acc. Chem. Res.,
2
13
2
002, vol. 35, p. 686. doi 10.1021/ar010065m
2. Ramón, D.J. and Yus, M., Angew. Chem., Int. Ed.,
005, vol. 44, p. 1602. doi 10.1002/anie.200460548
. Ganem, B., Acc. Chem. Res., 2009, vol. 42, p. 463. doi
0.1021/ar800214s
Harom), 11.92 s (1H, NH). C NMR spectrum, δ , ppm:
2
1
C
7.20, 29.49, 31.43, 32.76, 46.47, 47.09, 115.60,
25.85, 126.79, 128.08, 138.08,189.40, 195.20.
2
3
3
,3,6,6-Tetramethyl-9-(4-methylphenyl)-
1
3
,4,6,7,9,10-hexahydroacridine-1,8(2H,5H)-dione
1
4. Nasr-Esfahani, M., Montazerozohori, M., and Abdi-
(
4b). H NMR spectrum, δ, ppm: 0.97 s and 1.07 s (6H
zadeh, T., C. R. Chim., 2015, vol. 18, p. 547. doi
each, CH ), 2.13–2.27 m (8H, CH ), 2.22 s (3H,
3
2
1
0.1016/j.crci.2014.07.010
4
8
2
1
′-CH ), 5.31 s (1H, 9-H), 7.00–7.28 m (4H, Harom),
3
5
. Girault, S., Grellier, P., Berecibar, A., Maes, L.,
Mouray, E., Lemière, P., Debreu, MA., Davioud-
Charvet, E., and Sergheraert, C., J. Med. Chem., 2000,
vol. 43, p. 2646. doi 10.1021/jm990946n
1
3
.05 s (1H, NH). C NMR spectrum, δ , ppm: 21.10,
C
7.13, 29.55, 32.60, 33.23, 40.67, 50.94, 113.31,
27.91, 128.70, 135.20, 143.78, 149.19, 195.98.
3
,3,6,6-Tetramethyl-9-(4-nitrophenyl)-
6. Gamage, S.A., Spicer, J.A., Atwell, G.J., Finlay, G.J.,
Baguley, B.C., and Denny, W.A., J. Med. Chem., 1999,
vol. 42, p. 2383. doi 10.1021/jm980687m
3
(
,4,6,7,9,10-hexahydroacridine-1,8(2H,5H)-dione
4d). H NMR spectrum, δ, ppm: 0.97 s and 1.14 s (6H
1
each, CH ), 2.19–2.46 m (8H, CH ), 5.17 s (1H, 9-H),
7. Di Giorgio, C., De Méo, M., Chiron, J., Delmas, F..,
Nikoyan, A., Jean, S., Dumenil, G., Timon-David, P.,
and Galy, J.-P., Bioorg. Med. Chem., 2005, vol. 13,
p. 5560. doi 10.1016/j.bmc.2005.06.045
3
2
6
.51 s (1H, NH), 7.54 d (2H, Harom), 8.10 d (2H, Harom).
1
3
C NMR spectrum, δ , ppm: 27.14, 29.44, 32.72,
C
3
1
4.43, 41.20, 50.57, 112.74, 123.39, 129.04, 148.11,
53.76, 195.19.
8
. Yang, P., Yang, Q., Qian, X., Tong, L., and Li, X.,
J. Photochem. Photobiol., B, 2006, vol. 84, p. 221. doi
9
-(4-Bromophenyl)-3,3,6,6-tetramethyl-
1
0.1016/j.jphotobiol.2006.03.005
3
,4,6,7,9,10-hexahydroacridine-1,8(2H,5H)-dione
9
. Antonini, I., Polucci, P., Kelland, L.R., Menta, E.,
Pescalli, N., and Martelli, S., J. Med. Chem., 1999,
vol. 42, p. 2535. doi 10.1021/jm9805586
1
(
4e). H NMR spectrum, δ, ppm: 0.88 s and 1.01 s (6H
each, CH ), 2.09–2.31 m (8H, CH ), 4.95 s (1H, 9-H),
3
2
1
3
7
.14–7.28 m (4H, Harom), 8.43 s (1H, NH). C NMR
1
0. Gündüz, M.G., Doğan, A.E., Şimşek, R., Erol, K., and
Şafak, C., Med. Chem. Res., 2009, vol. 18, p. 317.
doi 10.1007/s00044-008-9129-9
11. Gallo, S., Atifi, S., Mahamoud, A., Santelli-Rouvier, C.,
Wolfart, K., Molnar, J., and Barbe, J., Eur. J. Med.
Chem., 2003, vol. 3, p. 19. doi 10.1016/S0223-5234(02)
spectrum, δ , ppm: 27.06, 29.53, 32.50, 33.43, 40.56,
C
5
0.77, 112.55, 129.90, 130.15, 145.98, 149.23, 195.55.
-(4-Methoxyphenyl)-3,3,6,6-tetramethyl-
,4,6,7,9,10-hexahydroacridine-1,8(2H,5H)-dione
9
3
1
(
4f). H NMR spectrum, δ, ppm: 0.96 s and 1.07 s (6H
0
1422-8
each, CH ), 2.15–2.48 m (8H, CH ), 3.70 s (3H,
3
2
1
2. Mikata, Y., Yokoyama, M., Mogami, K., Kato, M.,
OCH ), 5.05 s (1H, 9-H), 6.72–6.78 d (2H, Harom),
3
1
3
Okura, I., Chikira, M., and Yano, S., Inorg. Chim. Acta.,
7
.23–7.28 d (2H, Harom), 7.59 s (1H, NH). C NMR
1
0
998, vol. 279, p. 51. doi 10.1016/S0020-1693(98)
0035-8
spectrum, δ , ppm: 27.34, 29, 55, 30.98, 32.78, 40.87,
C
5
1
0.81, 55.11, 113.52, 115.79, 128.96, 129.30, 139.19,
48.49, 162.22, 196.65.
1
1
3. Wainwright, M., J. Antimicrob. Chemother., 2001,
vol. 47, p .1. doi 10.1093/jac/47.1.1
9
-(4-Chlorophenyl)-3,3,6,6-tetramethyl-
4. Berkan, Ö., Saraç, B., Şimşek, R., Yıldırım, Ş.,
Sarıoğlu, Y., and Şafak, C., Eur. J. Med. Chem., 2002,
vol. 37, p. 519. doi 10.1016/S0223-5234(02)01374-0
3
,4,6,7,9,10-hexahydroacridine-1,8(2H,5H)-dione
1
(
4g). H NMR spectrum, δ, ppm: 0.99 s and 1.11 s (6H
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 55 No. 9 2019

1
386
CHEHAB et al.
1
5. Ngadi, L., Galy, A-M., Galy, J-P., Barbe, J.,
Crémieux, A., Chevalier, J., and Sharples, D., Eur J.
Med. Chem., 1990, vol. 25, p. 67. doi 10.1016/0223-
30. Rostamizadeh, S., Amirahmadi, A., Shadjou, N., and
Amani, A.M., J. Heterocycl. Chem., 2012, vol. 49,
p. 111. doi 10.1002/jhet.692
5
234(90)90166-Z
3
3
3
3
1. Sangshetti, J.N., Dharmadhikari, P.P., Chouthe, R.S.,
and Fatema, B., Arab. J. Chem., 2017, vol. 10, p. S10.
doi 10.1016/j.arabjc.2012.06.005
2. Vahdat, S.M., Khaksar, S., Akbari, M., and Baghery, S.,
Arab. J. Chem., 2014, in press. doi 10.1016/
j.arabjc.2014.10.026
3. Maheswari, C.S., Ramesh, R., and Lalitha, A., Res.
Chem. Intermed., 2017, vol. 43, p. 4165. doi 10.1007/
s11164-017-2870-2
4. Bahammou, I., Esaady, A., Boukhris, S., Ghailane, R.,
Habbadi, N., Hassikou, A., and Souizi, A., Mediterr. J.
Chem., 2016, vol. 5, p. 615. doi 10.13171/
mjc56/01607062219-souizi
1
1
1
1
2
2
2
6. Islam, A., Murugan, P., Hwang, K.C., and Cheng, C-H.,
Synth. Met., 2003, vol. 139, p. 347. doi 10.1016/S0379-
6
779(03)00188-7
7. Tong-Shou, J., Rui-Qiao, Z., and Tong-Shuang, L.,
Arkivoc, 2006, vol. 2006, part (xi), p. 176. doi 10.3998/
ark.5550190.0007.b18
8. Tu, S., Gao, Y., Miao, C., Li, T., Zhang, X., Zhu, S.,
Fang, F., and Shi, D., Synth. Commun., 2004, vol. 34,
p. 1289. doi 10.1081/SCC-120030317
9. Venkatesan, K., Pujari, S.S., and Srinivasan, K.V.,
Synth. Commun., 2008, vol. 39, p. 228. doi
1
0.1080/00397910802044306
0. Das, B., Thirupathi, P., Mahender, I., Reddy, V.S., and
Rao, Y.K., J. Mol. Catal. A: Chem., 2006, vol. 247,
p. 233. doi 10.1016/j.molcata.2005.11.048
1. Shaterian, H.R., Hosseinian, A., and Ghashang, M.,
Phosphorus, Sulfur Silicon Relat. Elem., 2008, vol. 183,
p. 3136. doi 10.1080/10426500802066096
2. To, Q.H., Lee, Y-R., Kim, S-H., Bull. Korean. Chem.
Soc., 2012, vol. 33, p. 1170. doi 10.5012/
bkcs.2012.33.4.1170
35. Sibous, S., Boukhris, S., Ghailane, R., Habbadi, N.,
Hassikou, A., and Souizi, A., J. Turk. Chem. Soc., Sect.
Chem., 2017, vol. 4, p. 477. doi 10.18596/jotcsa.286900
36. Sibous, S., Ghailane, T., Houda, S., Ghailane, R.,
Boukhris, S., and Souizi, A., Mediterr. J. Chem., 2017,
vol. 6, p. 53. doi 10.13171/mjc61/01701181035/souizi
37. Ramesh, K.B. and Pasha, M.A., Bioorg. Med. Chem.
Lett., 2014, vol. 24, p. 3907. doi 10.1016/
j.bmcl.2014.06.047
2
2
3. Xia, J-J. and Zhang, K-H., Molecules, 2012, vol. 17,
38. Hong, M. and Xiao, G., J. Fluorine Chem., 2012,
p. 5339. doi 10.3390/molecules17055339
vol. 144, p. 7. doi 10.1016/j.jfluchem.2012.09.006
4. Fan, X., Li, Y., Zhang, X., Qu, G., and Wang, J.,
Heteroatom Chem., 2007, vol. 18, p. 786. doi 10.1002/
hc.20410
39. Patil, D., Chandam, D., Mulik, A., Patil, P., Jagadale, S.,
Kant, R., Gupta, V., and Deshmukh, M., Catal. Lett.,
2014, vol. 144, p. 949. doi 10.1007/s10562-014-1202-z
2
2
2
5. Davoodnia, A., Zare-Bidaki, A., and Behmadi, H., Chin.
J. Catal., 2012, vol. 33, p. 1797. doi 10.1016/S1872-
4
4
4
4
0. Ziarani, G.M., Badiei, A., Hassanzadeh, M., and
Mousavi, S., Arab. J. Chem., 2014, vol. 7, p. 335. doi
10.1016/j.arabjc.2011.01.037
2
067(11)60449-X
6. Ghasemzadeh, M.A., Safaei-Ghomi, J., and Molaei, H.,
C. R. Chim., 2012, vol. 15, p. 969. doi 10.1016/
j.crci.2012.08.010
7. Safaei-Ghomi, J., Ghasemzadeh, M.A., and Zahedi, S.,
J. Mex. Chem. Soc., 2013, vol. 57, p. 01. doi 10.29356/
jmcs.v57i1.228
8. Kidwai, M. and Bhatnagar, D., Tetrahedron Lett., 2010,
vol. 51, p. 2700. doi 10.1016/j.tetlet.2010.03.033
9. Vahdat, S.M. and Baghery, S., Heterocycl. Lett., 2012,
1. Yü, S-J., Wu, S., Zhao, X-M., and Lü, C-W., Res.
Chem. Intermed., 2017, vol. 43, p. 3121. doi 10.1007/
s11164-016-2814-2
2. Mansoor, S.S., Aswin, K., Logaiya, K., and
Sudhan, S.P.N., J. Taibah Univ. Sci., 2014, vol. 8,
p. 265. doi 10.1016/j.jtusci.2014.03.003
2
3. Javid, A., Khojastehnezhad, A., Heravi, M., and
Bamoharram, F.F., Synth. React. Inorg. Met.-Org.,
Nano-Met. Chem., 2012, vol. 42, p. 14. doi
10.1080/15533174.2011.609221
2
vol. 2, p. 43.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 55 No. 9 2019