Magnetically separable recyclable nano-ferrite catalyst for the synthesis of acridinediones and their derivatives under solvent-free conditions

Article abstract of DOI:10.1246/cl.150503

Catalytic activity of nano-ferrite is explored in the synthesis of acridinedione and their derivatives under benign conditions; a greener protocol is reported in terms of excellent yield and recyclability under solvent-free reactions without using any add

Full text of DOI:10.1246/cl.150503

CL-150503
Received: June 15, 2015 | Accepted: July 9, 2015 | Web Released: July 18, 2015
Magnetically Separable Recyclable Nano-ferrite Catalyst for the Synthesis of Acridinediones
and Their Derivatives under Solvent-free Conditions
Palla Mahesh,1,2 Kolakaluri Guruswamy, Bhagavathula Subrahmanya Diwakar, Bhoomireddy Rama Devi,
1
1
2
1
3
4
Yellajyosula Lakshmi Narasimha Murthy, Pratap Kollu, and Sri Venkata Narayan Pammi*
1
Department of Organic Chemistry, Andhra University, Visakhapatnam 530003, India
2
Jawaharlal Technological University, Kukatpally, Hyderabad 500085, India
3
Thin Film Magnetism Group, Cavendish Laboratory, Department of Physics, University of Cambridge, Cambridge CB3 0HE, U. K.
4
Advanced Analytical Laboratory, DST-PURSE Programme, Andhra University, Visakhapatnam 530003, India
(
E-mail: venkat@cnu.ac.kr)
Catalytic activity of nano-ferrite is explored in the synthesis
inexpensive, and non-toxic material, which has been utilized as
a heterogeneous catalyst for various organic reactions. Recently,
because of the unique properties of nanoparticles, synthetic
of acridinedione and their derivatives under benign conditions;
a greener protocol is reported in terms of excellent yield and
recyclability under solvent-free reactions without using any
additive/cocatalyst. Nano-ferrite catalyst is synthesized using
sol­gel process at low temperatures. X-ray diffraction (XRD)
and transmission electron microscopy (TEM) results exhibit
cubic phase of maghemite (γ-Fe2O3) with average particle size
of 18 nm. Furthermore, the catalyst can be easily separated using
an external magnet and reused up to nine cycles without any
significant loss of activity.
1
4­18
chemists have concentrated on nanocatalysts.
Therefore,
synthesis and characterization of catalysts with lower dimen-
sions have become a most interesting topic of research.
Moreover, due to quantum size effects, nanometer-sized particles
may exhibit unique properties for a wide range of applications.
Keeping the above facts in mind and as part of our ongoing
research, herein we report the use of nano-ferrite as hetero-
geneous catalyst for the first time in the synthesis of 9-
aryl-substituted-3,3,6,6-tetramethylhexahydroacridine-1,8-diones.
This method offers advantageous such as short reaction time,
recyclability of the catalyst, and easy work-up procedure.
In this study, we report a simple, efficient, and one-pot
reaction of dimedone, aldehydes, and ammonium acetate using
nano ferrite at 120 °C for the preparation of acridinediones and
their derivatives (Scheme 1). The experimental section for the
synthesis of catalyst and acridinediones and their derivatives has
been provided in supplementary section.
Acridines represent an important class of nitrogen hetero-
cycles with several significant properties such as pigment, dye
properties, photochemical/physical properties, electrochemical
properties, potent anti-malarial, anticancer, and anti-fungal
1
,2
activities, etc.
Natural and synthetic acridines and their
derivatives are effective DNA and RNA-binding compounds
owing to their intercalation abilities as well as being a lipophilic
3
,4
carrier molecule. Synthesis of acridinediones is a continuing
focal point of current research because these moieties are active
pharmaceutical ingredients (APIs) and valuable reactive inter-
XRD patterns (Supporting Information (SI), Figure 1)
confirm the formation of cubic phase maghemite, γ-Fe2O3
(matched with PDF No. 01-089-5892) and the major XRD peak
was obtained at 2ª = 35.9° while the other observed peaks were
at 2ª = 30.5, 43.6, 54.0, 57.5, and 63.2° which suggests strongly
5
mediates for both synthetic and medicinal chemists.
Literature survey reveals that various methods6 have been
reported for preparation of acridinediones and substituted
acridinediones. The reported method for the synthesis of 9-
aryl-3,3,6,6-tetramethylhexahydroacridine-1,8-diones involves
the reaction of two molecules of dimedone (5,5-dimethyl-1,3-
­9
1
9
that γ-phase Fe2O3 is the major phase in this material. The
average grain size of γ-Fe O nanoparticles is calculated using
2
3
the Scherrer formula and was found to be about 18 nm indicating
nanocrystalline nature. The morphology and size of the γ-Fe2O3
nano particles before reaction and after nine runs were analyzed
by transmission electron microscopy (TEM) as shown in SI,
Figures 3a and 3b respectively. The particle size was about 15­
20 nm and their shape was found spheroidal when assessed with
TEM. The presence of some larger particles is attributed to
aggregating or overlapping of smaller particles after nine runs. It
was observed that there is no significant change in morphology
and size of the γ-Fe2O3 nanoparticles after nine runs.
cyclohexadione) with various aromatic aldehydes and ammoni-
um acetate by using different Lewis acid catalysts.1
0­13
However
many of these catalysts undergo disadvantages such as long
reaction time, high catalyst loading, use of solvents, and
deactivation of catalyst on repeated use. Hence there is a need
to develop an environmentally benign protocol for the synthesis
of acridinediones.
Though there are many advantages of homogeneous metal
catalysts there are some difficulties in recovering the catalyst
from the reaction mixture, which severely inhibit their use in
industry and this drawback can be overcome with heterogeneous
nano-ferrite-based catalysts.1
4­17
Recent reports showed that
magnetic nanoparticles are efficient catalysts and they can be
easily separated from the reaction mixture.18 The high surface to
volume ratio of metal oxide nanoparticles is mainly responsible
for their high catalytic performance. Ferrite nanomaterial is
one such reusable catalyst which shows profound catalytic
activity in organic synthesis. Nano-ferrite is a non-hygroscopic,
Scheme 1. Synthesis of 9-aryl-3,3,6,6-tetramethylhexahydroacri-
dine-1,8-diones employing reusable nano-ferrite as catalyst.
1386 | Chem. Lett. 2015, 44, 1386–1388 | doi:10.1246/cl.150503
© 2015 The Chemical Society of Japan

Table 1. Optimization of the catalyst loadinga
Table 3. Synthesis of products 4a­4p by the reaction of aromatic
aldehydes with dimedone and ammonium acetate
a
b
Catalyst
Yield
/%
Time
/min
Product
/
mol %
Time
Yield
Entry
1
Aldehyde
Product
b
Mp/°C
/
min
/%
0
0
96
96
95
94
12 (h)
CHO
4a
6
96
276−278
5
8
6
5
7
2
3
HCHO
4b
4c
7
7
89
93
256−259
271−273
O
O
CHO
1
0
H3CO
OCH3
N
H
15
4
4d
6
91
244−246
OCH3
CHO
OCH3
2
0
Br
5
6
4e
4f
7
8
88
84
253−255
234−238
aCatalyst 0­20 mol %, 5,5-dimethyl-1,3-cyclohexanedione (2 equiv),
benzaldehyde (1 equiv), ammonium acetate (1 equiv), reaction temper-
CHO
OC2H5
b
ature 120 °C. Yields compared to isolated products.
CHO
N
7
8
9
4g
4h
6
8
93
96
166−168
260−264
Table 2. The reaction of arylaldehyde, dimedone, and ammonium
acetate: Effect of solventa
CHO
CHO
N
Amount of
catalyst
Time
Yieldb
/%
CHO
Entry
Solvent
/h
4i
4j
8
8
95
97
258−260
271−273
/
mol %
O
O
1
2
3
4
5
6
7
Acetonitrile
THF
Ethanol
1,4-Dioxane
Methanol
Water
10
10
10
10
10
10
10
2.5
3.0
3.0
4.0
3.0
60
45
72
58
58
40
CHO
10
HO
O
11
12
13
4k
4l
9
7
6
96
97
95
271−273
274−276
227−230
OH
CHO
CHO
4.0
6 (min)
c
F
F
Neat
96, 88
aCatalyst 10 mol %, 5,5-dimethyl-1,3-cyclohexanedione (2 equiv),
benzaldehyde (1 equiv), ammonium acetate (1 equiv), reaction temper-
4m
OH
CHO
Cl
b
ature 120 °C, solvent 15 mL. Yields compared to isolated products.
14
4n
7
97
247−249
c
Yield after 9 cycles.
CHO
CHO
1
1
5
6
4o
4p
7
9
93
89
260−262
236−238
O2N
Fourier transform infrared (FT-IR) studies were performed
to ascertain the metal­oxygen bonding. The FT-IR spectra
of as-synthesized γ-Fe2O3 nanoparticles before reaction (SI,
Figure 3a) and after nine runs (SI, Figure 3b) are shown in SI,
Figure 2. The γ-Fe2O3 shows the absorption in regions of 3742,
CN
CHO
O
O
CHO
1
7
4r
8
7
98
310−312
¹
1
¹1
18
4s
4t
94
72
330−333
249−251
2347, 1124, 550, and 396 cm . The peaks at 540 and 435 cm
S
CHO
correspond to the metal­oxygen vibrational modes. The metal­
oxygen frequencies observed for γ-Fe2O3 nanoparticles were in
accordance with values. There was no significant difference and
no additional peaks were observed of the as prepared catalyst
and after nine runs.
1
9
10
CHO
O
aCatalyst 10 mol %, 5,5-dimethyl-1,3-cyclohexanedione (2 equiv),
aromatic aldehydes (1 equiv), ammonium acetate (1 equiv), reaction
temperature 120 °C. Yields compared to isolated products.
b
Initially, a blank reaction was performed using benzalde-
hyde, dimedone, and ammonium acetate (mole rate 1:2:1) at
reaction with 10 mol % of catalyst (Table 2). Ultimately solvent-
free reactions were preferable in terms of excellent yield in short
reaction times.
120 °C in the absence of nano-ferrite to establish the efficacy of
the catalyst and the results showed that desired product was not
formed even after 12 h of heating. Then focus was diverted to
optimize the amount of catalyst and solvent effect. In order
to evaluate the most appropriate catalyst percentage, a model
reaction using benzaldehyde, ammoniam acetate, and dimedone
Catalyst recovery and reusability have potential advantages
in heterogeneous catalysis for organic reactions and/or trans-
formations in order to employ as industrial applications. The
catalyst was recovered by magnetization after completion of the
reaction, washed with diethyl ether, and the recovered catalyst
was reused for nine cycles. From our investigations, we observe
that nanocatalyst shows excellent to good reactivity with
promising yields even for the next nine cycles in the same
reaction (SI, Table 1).
(mole ratio 1:1:2) was carried out using 0­20 mol % of nano-
ferrite under solvent-free conditions (Table 1).
It was found that 10 mol % of nano-ferrite shows high yield
in short reaction time at 120 °C (Table 1). During our ongoing
studies, effect of solvent was studied for the above model
Chem. Lett. 2015, 44, 1386–1388 | doi:10.1246/cl.150503
© 2015 The Chemical Society of Japan | 1387

number of active sites on the catalyst. This results in good
catalytic activity due to smaller particle size and high surface
area of γ-Fe2O3 catalyst.
In conclusion, a convenient and highly efficient method for
the synthesis of 9-aryl-3,3,6,6-tetramethylhexahydroacridine-
1
,8-diones by condensation reaction of aldehydes with 1,3-
cyclohexanediones by the use of nano-γ-Fe O as an inexpen-
2
3
sive and easily recoverable catalyst has been described. The
attractive features of this synthetic protocol are easy work up
procedure, operational simplicity, and reusability of the catalyst.
Furthermore, products were isolated in good to excellent yields.
The authors are thankful to Defence Research and Develop-
ment Organization (DRDO), New Delhi for providing financial
assistance. The authors are also grateful to the Committee
on strengthening infrastructure for Science & Technology
(
COSIST) Labs, Andhra University for providing spectral data.
Supporting Information is available electronically on J-STAGE.
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1388 | Chem. Lett. 2015, 44, 1386–1388 | doi:10.1246/cl.150503
© 2015 The Chemical Society of Japan