Graphene oxide as highly effective and readily recyclable catalyst using for the one-pot synthesis of 1,8-dioxoacridine derivatives

Article abstract of DOI:10.1166/jnn.2016.12432

Graphene oxide as a highly stable, reusable, isolable, and efficient catalyst has been used for the first time for the synthesis of acridinedione derivatives from dimedone, aromatic aldehydes and various amines with great catalytic performance. One pot synthesis of acridinedione compounds were performed using highly efficient graphene oxide.

Full text of DOI:10.1166/jnn.2016.12432

Article
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Nanoscience and Nanotechnology
Vol. 16, 6498–6504, 2016
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Graphene Oxide as Highly Effective and Readily
Recyclable Catalyst Using for the One-Pot
Synthesis of 1,8-Dioxoacridine Derivatives
Burak Aday1ꢀ†, Handan Pamuk2ꢀ†, Muharrem Kaya2ꢀ∗, and Fatih Sen2ꢀ∗
1Chemistry Department, Faculty of Arts and Science, Dumlupınar University, Evliya Çelebi Campus 43100 Kütahya, Turkey
2Biochemistry Department, Faculty of Arts and Science, Dumlupınar University, Evliya Çelebi Campus 43100 Kütahya, Turkey
Graphene oxide as a highly stable, reusable, isolable, and efficient catalyst has been used for the
first time for the synthesis of acridinedione derivatives from dimedone, aromatic aldehydes and
various amines with great catalytic performance. One pot synthesis of acridinedione compounds
were performed using highly efficient graphene oxide.
Keywords: Graphene Oxide, 1,8-Dioxoacridine, Multi-Component Reaction, One-Pot Synthesis,
Cyclization.
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Copyright: American Scientific Publishers
1. INTRODUCTION
reaction condition, short reaction time, high yield and
recovery.24ꢀ25
In recent years, within the fields of medicinal and organic
synthetic chemistry, there has been an increasing inter-
est in synthetic techniques based on multicomponent reac-
tions (MCR). Especially 1,8-dioxoacridine derivatives have
been synthesized using the MCR system components and
those types of compounds are quite important for syn-
thetic and drug chemistry due to their intensive fluo-
rescence feature.1ꢀ2 Furthermore these compounds have
been also used for anti-tumor,3 cytotoxic,4 anti-microbial,5
fungicides,6 as anti-multidrug-resistant,7 ꢁ-channel opener
in cardiovascular disease,8 carbonic anhydrase inhibitor for
glaucoma treatment.9–13
Graphene oxide (GO) is two-dimensional material of
graphene obtained by the addition of covalently bonded
C–O bond.26 It is worth mentioning that graphene oxide is
often used as a catalyst in batteries, the hydrogen storage,
sensors, super-capacitors, solar cells etc.27–32 but its use as
a catalyst for synthesizing acridinedione derivatives from
different aromatic aldehydes and various amines has not
been reported before. Addressed herein, we report for the
first time graphene oxide as a catalyst for the synthesis of
1,8-dioxoacridine derivatives.
In literature different types of catalysts, for instance
Amberlyst-15,14ꢀ15 Amberlite IR-120H,16 CBSA,17
CTAB,18 DBSA,9ꢀ19 FSG-Hf(Npf2ꢂ4,20 Glucose sulfonic
acid,21 H2SO4,11 Melamine-formaldehyde resin supported
H+,22 Proline23 have been reported for the one-step syn-
thesis of 1,8-dioxoacridine. Since these types of catalysts
have lots of limitations such as difficulty of separating the
catalyst, the cost of the catalysts, and the formation of side
reactions, low efficiency and high reaction temperatures,
there is a scope for discovery of a new catalyst with mild
2. EXPERIMENTAL DETAILS
2.1. Materials and Instrumentation
De-ionized water was filtered by Millipore water purifica-
tion system (18 Mꢃ) analytical grade. All glassware and
Teflon-coated magnetic stir bars were cleaned with aqua
regia, followed by washing with distilled water before dry-
ing in an oven.
The chemicals used in the synthesis of 1,8-dioxoacridine
derivatives were obtained from Merck and Aldrich Chem-
ical Company. All chemicals and solvents used for the
synthesis were of spectroscopic reagent grade.
Melting points were measured on a Bibby Scien-
tific Stuart Digital, Advanced, SMP30. Ultraviolet-Visible
∗Authors to whom correspondence should be addressed.
†These two authors contributed equally to this work.
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J. Nanosci. Nanotechnol. 2016, Vol. 16, No. 6
1533-4880/2016/16/6498/007
doi:10.1166/jnn.2016.12432

Aday et al.
Graphene Oxide as Highly Effective and Readily Recyclable Catalyst Using for the One-Pot Synthesis
(UV-Vis) spectra of the samples were collected on a Perkin-
Elmer LAMBDA 750 spectrophotometer. Fourier Trans-
form Infrared (FT-IR) spectra were recorded on Bruker
2.4.2. 10-(4-chlorophenyl)-3,3,6,6-Tetramethyl-9-(4-
nitrophenyl)-3,4,6,7,9,10 Hexahydroacridine-
1,8(2H,5H)-Dione (4b)
1
ꢀ
As yellow crystals, (0.478 g, 91%), mp. (315–317 C)33
Optics, ALPHA FT-IR spectrometer. The H NMR and
13C NMR spectra were obtained in DMSO-d6 with Bruker
DPX-300 as solvents with tetramethylsilane as the internal
reference. The mass analyses were performed on a Agilent
Technologies 6530 Accurate-Mass Q-TOF LC/HRMS.
1
(ethanol). H-NMR (300 MHz, DMSO-d6) ꢄ (ppm): 0.70
(s, 6H, 2x-CH3), 0.90 (s, 6H, 2x-CH3), 1.80 (d, 2H,
J = 17ꢅ35 Hz, –CH2), 2.01 (d, 2H, J = 16ꢅ13 Hz,
–CH2), 2.18–2.24 (m, 4H, –CH2), 5.10 (s, 1H, –CH),
7.54–7.60 (m, 4H, Ar–H), 7.70 (d, 2H, J = 8ꢅ51 Hz,
Ar–H), 8.14 (d, 2H, J = 8ꢅ68 Hz, Ar–H); 13C-NMR
(75 MHz, DMSO-d6) ꢄ (ppm): 26.57, 29.61, 32.47,
33.35, 41.39, 49.86, 112.51, 119.43, 123.76, 129.43,
134.55, 137.55, 146.16, 151.32, 154.01, 195.53; IR
(cm−1): 3054 w (Ar–H), 2958 w (–CH), 1632 s (C O),
1592 w (C C); HRMS (QTOF-ESI)-: m/z [M + H]+
calcd. For C29H29ClN2NaO4: 527.1714; found [M+Na]+:
527.1729.
2.2. Preparation of Graphene Oxide
Graphene oxide (GO) was synthesized from graphite pow-
der using modified Hummer’s method. In brief, 1 g of
graphite and 0.5 g of sodium nitrate were mixed together
followed by the addition of 23 ml of conc. sulphuric acid
under constant stirring. After 1 h, 3 g of KMnO4 was
added gradually to the above solution while keeping the
ꢀ
temperature less than 20 C to prevent overheating and
explosion. The mixture was stirred at 35 ꢀC for 12 h
and the resulting solution was diluted by adding 500 ml
of water under vigorous stirring. To ensure the comple-
tion of reaction with KMnO4, the suspension was further
treated with 30% H2O2 solution (5 ml). The resulting mix-
ture was washed with HCl and H2O respectively, followed
by filtration and drying, graphene oxide sheets were thus
obtained.
2.4.3. 10-(4-chlorophenyl)-3,3,6,6-Tetramethyl-9-(3-
nitrophenyl)-3,4,6,7,9,10 Hexahydroacridine-
1,8(2H,5H)-dione (4c)
ꢀ
As yellow crystals, (0.464 g, 92%), mp. (285–287 C)34
1
(ethanol). H-NMR (300 MHz, DMSO-d6) ꢄ (ppm): 0.70
(s, 6H, 2x-CH3ꢂ, 0.90 (s, 6H, 2x-CH3), 1.82 (d, 2H, J =
17ꢅ44 Hz, –CH2), 2.02 (d, 2H, J = 16ꢅ04 Hz, –CH2), 2.20
(d, 2H, J = 3.30 Hz, –CH2), 2.25 (d, 2H, J = 4ꢅ95 Hz,
2.3. General Procedure for Preparation of
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–CH2), 5.15 (s, 1H, –CH), 7.51–7.61 (m, 3H, Ar–H), 7.72
1,8-Dioxoacridine DerivativesIP(4:a5–.j8).4U7s.i6n2g On: Sun, 08 May 2016 22:27:16
(d, 2H, J = 8ꢅ79 Hz, Ar–H), 7.78 (d, 1H, J = 7ꢅ87 Hz,
Copyright: American Scientific Publishers
Graphene Oxide as the Catalyst
Ar–H), 7.99–8.03 (m, 1H, Ar–H), 8.12–8.13 (m, 1H,
Ar–H)); 13C-NMR (75 MHz, DMSO-d6) ꢄ (ppm): 26.47,
29.62, 32.52, 32.92, 41.34, 49.84, 112.72, 121.50, 122.56,
130.21, 130.65, 134.58, 134.75, 137.52, 147.88, 148.60,
151.39, 195.63; IR (cm−1): 3049 w (Ar–H), 2956 w (–CH),
1636 s (C O), 1576 s (C C); HRMS (QTOF-ESI): m/z
[M + H]+ calcd. For C29H29ClN2NaO4: 527.1714; found
[M+Na]+: 527.1655.
A mixture of 2 mmol dimedone 1, 1 mmol benzalde-
hyde 2a, 1 mmol 4-bromoaniline 3b and ꢀGraphene oxide
(10 mg) in 3 ml DMF was heated to 100 C continuously
for 90 min. The reaction progress was monitored by TLC.
The solid product was filtered, washed with 500 ml water,
and recrystallized from ethanol (91–94%).
2.4. Characterization of 1,8-Dioxoacridine Derivatives
2.4.1. 10-(4-chlorophenyl)-3,3,6,6-Tetramethyl-9-
Phenyl-3,4,6,7,9,10-Hexahydroacridine-
1,8(2H,5H)-Dione (4a)
2.4.4. 9-(4-bromophenyl)-10-(4-chlorophenyl)-3,3,6,6-
Tetramethyl-3,4,6,7,9,10 Hexahydroacridine-
1,8(2H,5H)-Dione (4d)
ꢀ
As yellow crystals, (0.422 g, 92%), mp. (300–302 C)22
ꢀ
As yellow crystals, (0.504 g, 94%), mp. (304–305 C)33
1
(ethanol). H-NMR (300 MHz, DMSO-d6) ꢄ (ppm): 0.70
1
(ethanol). H-NMR (300 MHz, DMSO-d6) ꢄ (ppm): 0.70
(s, 6H, 2x-CH3), 0.90 (s, 6H, 2x-CH3), 1.78 (d, 2H, J =
17ꢅ43 Hz, –CH2), 2.00 (d, 2H, J = 16ꢅ00 Hz, –CH2),
2.16 (d, 2H, J = 4ꢅ00 Hz, –CH2), 2.22 (d, 2H, J =
5ꢅ44 Hz, –CH2), 5.05 (s, 1H, –CH), 7.07–7.12 (m, 1H,
Ar–H), 7.21–7.32 (m, 4H, Ar–H), 7.48 (d, 2H, J =
5ꢅ44 Hz, 10.58, Ar–H), 7.68 (d, 2H, J = 8ꢅ84 Hz,
Ar–H); 13C-NMR (75 MHz, DMSO-d6) ꢄ (ppm): 26.50,
29.72, 32.33, 32.44, 41.35, 50.03, 113.55, 126.26, 127.97,
128.38, 130.56, 134.37, 137.79, 146.57, 150.58, 195.54;
IR (cm−1): 3026 w (Ar–H), 2954 s (–CH), 1634 s (C O),
1590 s (C C); HRMS (QTOF-ESI): m/z [M+H]+
calcd. For C29H31ClNO2: 460.2043; found [M + H]+:
460.2061.
(s, 6H, 2x-CH3), 0.90 (s, 6H, 2x-CH3), 1.78 (d, 2H, J =
17ꢅ47 Hz, –CH2), 2.01 (d, 2H, J = 16ꢅ05 Hz, –CH2),
2.19 (d, 4H, J = 16ꢅ09 Hz, –CH2), 5.00 (s, 1H, –CH),
7.26 (d, 2H, J = 8ꢅ42 Hz, Ar–H), 7.42–7.50 (m, 4H,
Ar–H), 7.68 (d, 2H, J = 8ꢅ77 Hz, Ar–H); 13C-NMR
(75 MHz, DMSO-d6) ꢄ (ppm): 26.56, 29.66, 32.27,
32.45, 41.35, 49.96, 113.08, 119.25, 130.33, 130.54,
131.26, 134.44, 137.67, 145.96, 150.81, 195.54; IR
(cm−1): 3062 w (Ar–H), 2956 w (–CH), 1635 s (C O),
1576 s (C C); HRMS (QTOF-ESI): m/z [M + H]+
calcd. For C29H30BrClNO2: 538.1148; found [M + H]+:
538.1123.
J. Nanosci. Nanotechnol. 16, 6498–6504, 2016
6499

Graphene Oxide as Highly Effective and Readily Recyclable Catalyst Using for the One-Pot Synthesis
Aday et al.
Figure 1. Synthesis of graphene oxide from graphite.
2.4.5. 10-(4-chlorophenyl)-9-(4-fluorophenyl)-3,3,6,6-
Tetramethyl-3,4,6,7,9,10-Hexahydroacridine-
1,8(2H,5H)-Dione (4e)
Ar–H); 13C NMR (75 MHz, DMSO-d6) ꢄ (ppm): 26.56,
29.73, 31.39, 32.44, 50.07, 55.31, 113.71, 113.83, 128.93,
130.56, 134.34, 137.85, 138.92, 150.28, 157.76, 195.55;
IR (cm−1): 3006 w (Ar–H), 2951 w (–CH), 1638 s (C O),
1577 s (C C); HRMS (QTOF-ESI): m/z [M+H]+ calcd.
For C30H33ClNO3: 490.2149; found [M+H]+: 490.2160.
ꢀ
As yellow crystals, (0.434 g, 91%), mp. (280–282 C)35
1
(ethanol). H-NMR (300 MHz, DMSO-d6) ꢄ (ppm): 0.70
(s, 6H, 2x-CH3), 0.90 (s, 6H, 2x-CH3), 1.78 (d, 2H, J =
17ꢅ43 Hz, –CH2), 2.01 (d, 2H, J = 16ꢅ08 Hz, –CH2),
2.16–2.22 (m, 4H, –CH2), 5.05 (s, 1H, –CH), 7.05 (t, 2H,
J = 8ꢅ84 Hz, Ar–H), 7.29–7.34 (m, 2H, Ar–H), 7.48
(d, 2H, J = 7ꢅ15 Hz, Ar–H), 7.68 (d, 2H, J = 8ꢅ70 Hz,
Ar–H); 13C-NMR (75 MHz, DMSO-d6) ꢄ (ppm): 26.52,
29.68, 31.84, 32.45, 41.35, 49.98, 113.42, 114.86, 129.79,
130.53, 134.42, 137.72, 142.80, 150.64, 159.29, 195.55;
IR (cm−1): 3054 w (Ar–H), 2957 s (–CH), 1637 s (C O),
1576 s (C C); HRMS (QTOF-ESI): m/z [M+H]+ calcd.
For C H ClFNO : 478.1949; found [M+H]+: 478.1956.
2.4.8. 10-(4-bromophenyl)-3,3,6,6-Tetramethyl-9-
Phenyl-3,4,6,7,9,10-Hexahydroacridine-
1,8(2H,5H)-Dione (4h)
ꢀ
As yellow crystals, (0.472 g, 94%), mp. (303–305 C)37
1
(ethanol). H-NMR (300 MHz, DMSO-d6) ꢄ (ppm): 0.70
(s, 6H, 2x-CH3), 0.90 (s, 6H, 2x-CH3), 1.78 (d, 2H,
J = 17ꢅ39 Hz, –CH2), 2.00 (d, 2H, J = 16ꢅ90 Hz,
–CH2), 2.16–2.23 (m, 4H, –CH2), 5.05 (s, 1H, –CH),
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29 30
2
7.07–7.40 (m, 7H, Ar–H), 7.81 (d, 2H, J = 8ꢅ74 Hz,
13
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Ar–H); C-NMR (75 MHz, DMSO-d6) ꢄ (ppm): 26.50,
29.71, 32.32, 32.45, 41.35, 50.03, 113.54, 123.01, 126.27,
127.97, 128.37, 133.54, 138.22, 146.57, 150.51, 195.54;
IR (cm−1): 3028 s (Ar–H), 2954 s (–CH), 1634 s (C O),
1575 s (C C); HRMS (QTOF-ESI): m/z [M+H]+ calcd.
For C29H31BrNO2: 504.1538; found [M+H]+: 504.1529.
Copyright: American Scientific Publishers
2.4.6. 10-(4-chlorophenyl)-3,3,6,6-Tetramethyl-9-(p-
tolyl)-3,4,6,7,9,10-Hexahydroacridine-1,8(2H,5H)-
Dione (4f)
ꢀ
As yellow crystals, (0.435 g, 91%), mp. (262–265 C)34
1
(ethanol). H-NMR (300 MHz, DMSO-d6) ꢄ (ppm): 0.75
(s, 6H, 2x-CH3), 0.80 (s, 6H, 2x-CH3), 1.76 (d, 2H,
J = 17ꢅ29 Hz, –CH2), 1.97–2.22 (m, 9H, –CH2 and
–CH3), 5.00 (s, 1H, –CH), 7.04 (d, 2H, J = 8ꢅ05 Hz,
Ar–H), 7.18 (d, 2H, J = 8ꢅ00 Hz, Ar–H), 7.35–7.55
(m, 2H, Ar–H), 7.68 (d, 2H, J = 8ꢅ82 Hz, Ar–H);
13C NMR (75 MHz, DMSO-d6) ꢄ (ppm): 26.53, 29.15,
31.83, 32.32, 32.43, 41.33, 50.05, 113.69, 127.87, 128.40,
128.96, 134.34, 135.10, 137.83, 143.69, 150.43, 195.54;
IR (cm−1): 3050 w (Ar–H), 2952 w (–CH), 1636 s (C O),
1577 s (C C); HRMS (QTOF-ESI): m/z [M+H]+ calcd.
For C30H33ClNO2: 474.2200; found [M+H]+: 474.2215.
2.4.9. 10-(4-bromophenyl)-3,3,6,6-Tetramethyl-9-(4-
nitrophenyl)-3,4,6,7,9,10-Hexahydroacridine-
1,8(2H,5H)-Dione (4i)
ꢀ
As yellow crystals, (0.510 g, 93%), mp. (310–312 C)
1
(ethanol). H NMR (300 MHz, DMSO-d6ꢂ ꢄ (ppm): 0.70
(s, 6H, 2x-CH3), 0.90 (s, 6H, 2x-CH3), 1.80 (d, 2H, J =
17ꢅ46 Hz, –CH2), 2.00 (d, 2H, J = 15ꢅ93 Hz, –CH2), 2.20
(d, 4H, J = 15ꢅ70 Hz, 2x-CH2), 5.10 (s, 1H, –CH) 7.48
(d, 2H, J = 8ꢅ46 Hz, Ar–H), 7.58 (d, 2H, J = 8ꢅ70 Hz,
2.4.7. 10-(4-chlorophenyl)-9-(4-methoxyphenyl)-3,3,6,6-
Tetramethyl-3,4,6,7,9,10-Hexahydro Acridine-
1,8(2H,5H)-dione (4g)
ꢀ
As yellow crystals, (0.440 g, 91%), mp. (255–257 C)36
1
(ethanol). H-NMR (300 MHz, DMSO-d6) ꢄ (ppm): 0.75
(s, 6H, 2x-CH3), 0.85 (s, 6H, 2x-CH3), 1.76 (d, 2H,
J = 17ꢅ40 Hz, –CH2), 1.97–2.22 (m, 6H, –CH2), 3.70
(s, 1H, –OCH3), 4.95 (s, 1H, –CH), 6.80 (d, 2H, J =
8ꢅ62 Hz, Ar–H), 7.20 (d, 2H, J = 8ꢅ61 Hz, Ar–H),
7.40–7.55 (m, 2H, Ar–H), 7.68 (d, 2H, J = 8ꢅ78 Hz,
Figure 2. FT-IR of graphene oxide.
6500
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Aday et al.
Graphene Oxide as Highly Effective and Readily Recyclable Catalyst Using for the One-Pot Synthesis
Table I. The model study for the one-pot synthesis of 1,8-
dioxoacridines in the presence of various catalysts.
100
80
60
40
20
0
68
72
78
84
94
8
5
6
6
1.5
Figure 3. UV-Vis of graphene oxide.
Time (h)
Yield (%)
Ar–H), 7.83 (d, 2H, J = 8ꢅ40 Hz, Ar–H), 8.14 (d, 2H, J =
8ꢅ61 Hz, Ar–H); 13C-NMR (75 MHz, DMSO-d6ꢂ ꢄ (ppm):
26.57, 29.60, 32.47, 33.35, 41.38, 49.86, 112.50, 123.21,
123.75, 129.42, 132.46, 133.50, 137.98, 146.16, 151.25,
154.00, 195.51; IR (cm−1): 3047 w (Ar–H), 2956 w (C–H),
1631 s (C O), 1575 m (C C); HRMS (QTOF-ESI): m/z
[M + Na]+ calcd. for C29H29BrN2NaO4: 571.1208; found
[M+Na]+: 571.1209.
The prepared GO was characterized by Fourier Trans-
form Infrared (FT–IR) and UV-Vis Spectrophotometer.
FT-IR spectra of graphene oxide (Fig. 2) indicate that
a broad absorption band between 3200–3600 cm−1 cor-
respond to the –OH stretching mode.39 Furthermore, car-
bonyl groups at around 1632 cm−1 and the stretching
vibration of C–O of carboxylic acid and C–OH of alcohol
at around 1155–1032 cm−1 indicate the formation of GO.40
Moreover, UV-Vis spectrum of graphene oxide also
indicates the formation of GO as shown in Figure 3.
The peak at ∼235 nm and shoulder peak at ∼300 nm may
be due to ꢆ–ꢆ∗ transition of the atomic C–C bonds and
n–ꢆ∗ transitions of aromatic C–C bonds, respectively.41
2.4.10. 10-(4-bromophenyl)-9-(4-chlorophenyl)-3,3,6,6-
Tetramethyl-3,4,6,7,9,10Hexahydroacridine-
1,8(2H,5H)-Dione (4j)
ꢀ
As yellow crystals, (0.496 g, 93%), mp. (308–310 C)
1
(ethanol). H NMR (300 MHz, DMSO-d6ꢂ ꢄ (ppm): 0.70
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It is worth mentioning that graphene oxide is often used
(s, 6H, 2x-CH ), 0.90 (s, 6H, 2x-CH ), 1.80 (d, 2H, J =
IP: 5.8.47.62 On: Sun, 08 May 2016 22:27:16
3
3
as a catalyst in lots of reactions but its use as a catalyst
for synthesizing 1,8-dioxoacridine derivatives from aro-
matic aldehydes and various amines has not been reported
before. The synthesis of 1,8-dioxoacridine derivatives were
carried out in a single step containing dimedone (1), aro-
matic aldehydes (2a–g) and various amines (3a, b) by
using GO as a catalyst in DMF solution (Scheme 1).
Besides, the other catalysts such as sulfuric acid,
Amberliyst-15, DBSA, p-TSA have also been tested for
model reaction and compared with GO as shown Table I.
To the best of our knowledge, GO as a catalyst showed
Copyright: American Scientific Publishers
17ꢅ30 Hz, –CH2), 2.01 (d, 2H, J = 16ꢅ07 Hz, –CH2),
2.18–2.24 (m, 4H, –CH2), 5.10 (s, 1H, –CH), 7.48 (d, 2H,
J = 8ꢅ54 Hz, Ar–H), 7.58 (d, 2H, J = 8ꢅ74 Hz, Ar–H),
7.66 (d, 2H, J = 8ꢅ50 Hz, Ar–H), 8.14 (d, 2H, J =
8ꢅ71 Hz, Ar–H); 13C-NMR (75 MHz, DMSO-d6) ꢄ (ppm):
26.56, 29.60, 32.48, 33.35, 41.38, 49.85, 112.50, 123.21,
123.75, 129.43, 133.52, 137.97, 146.16, 151.25, 154.00,
195.52; 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.
3. RESULTS AND DISCUSSION
Table II. A comparison of various solvents employed in the synthesis
GO was synthesized by the modified hummer’s method
(Fig. 1). Briefly, a mixture of sulfuric acid, sodium nitrate,
and potassium permanganate is still widely used with some
modifications.38
of the 1,8-dioxoacridine derivatives.
100
80
77
60
40
20
0
79
80
35
82
R
42
94
46
7
R
H
4
R'
O
O
0.5
12
O
O
2.5
2
Graphene Oxide
DMF, 100ºC
1.5
1.5
+
+
N
NH2
O
3a,b
2a-g
1
R′
4a-j
91–94%
Time (h)
Yield (%)
Scheme 1. Synthesis of 1,8-dioxoacridines in the presence of GO.
J. Nanosci. Nanotechnol. 16, 6498–6504, 2016
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Graphene Oxide as Highly Effective and Readily Recyclable Catalyst Using for the One-Pot Synthesis
Aday et al.
Table III. The optimization of catalyst concentration for the preparation
of acridinedione derivatives using graphene oxide as catalyst in DMF.
Table V. Synthesis of 1,8-dioxoacridines 4a–j in the presence of
10 mg GO.a
Mp. (ꢀC)
Time Yieldb
Entry
R
Rꢁ
(min)
(%)
Found
Reported (ref.)
100
80
60
40
20
0
4a
4b
4c
4d
4e
4f
4g
4h
4i
–H
4-Cl
4-Cl
4-Cl
4-Cl
4-Cl
4-Cl
60
90
120
75
75
75
75
60
75
120
92
91
92
93
91
91
91
94
93
93
300–302 309–311 [22]
315–317 >300 [33]
285–287 285–286 [34]
304–305 >300
280–282 >300
262–265 268–269 [34]
255–257 269–270 [36]
303–305 269–272 [37]
4-NO2
3-NO2
4-Br
4-F
4-CH3
[33]
[35]
1
2
3
4
5
6
7
8
4-OCH3 4-Cl
–H
4-Br
4-Br
4-Br
Amount of catalyst (mg)
Time (h)
Yield (%)
4-NO2
4-Cl
310–312
308–310
–
–
4j
1
0
2
3
5
4
7
5
6
7
8
Notes: aReactions were carried out with dimedone, aromatic benzaldehyde and
various amine, in 2:1:1 molar ratio. bYields refer to isolated pure products.
Amount of catalyst (mg)
3
10
15
20
30
was obtained even after 48 h of stirring at room and/or
lower temperatures. The yield of desired product gradually
increased with increasing temperature from room temper-
the highest yield and lowest reaction time for the synthe-
sis of 1,8-dioxoacridine derivatives compared to the other
catalysts in the literature.
The model reaction was carried out in presence of
various solvents such as methanol, chloroform, water,
ethanol/water, ethanol, DMF and solvent-free media
(Table II). Since the reaction proceeded with the highest
yield in the presence of DMF compared to other solvents,
we have chosen DMF as the solvent for our reaction.
Since the amount of catalyst is another important param-
eter in terms of the reaction efficiency, eight sets of model
reactions have been performed to determine the optimum
catalyst concentration for the best possible yield. The first
set where no catalyst was used led to no formation of
product but while the product yield has been increased
increasing amount of catalyst increase gradually from 3
to 10 mg it has been decreased from 10 to 30 mg possi-
bly due to the protonation of amine groups in the aromatic
ring by the help of carboxylic acid groups of the graphene
oxide (Table III).
ꢀ
ature to 100 C as shown in Table IV.
As a summary, the highest efficiency on the model reac-
ꢀ
tion was observed at 100 C by using 10 mg of GO in
DMF. All reactions have been performed under these opti-
mum conditions as shown in Table V.
A
plausible mechanism for the synthesis 1,8-
dioxoacridine derivatives in the presence of graphene
oxide is shown in Scheme 2. Firstly, the GO bind with
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oxygen of carbonyl group, hence it increases the carbonyl
Copyright: American Scientific Publishers
activity which in turn makes alpha hydrogen very acidic
thereby facilitating the enolization and nucleophilic attack
to the aromatic aldehydes leading to the formation of kno-
evenagel product. Then the knoevenagel product reacted
in Michael fashion with another molecule of C–H active
molecule and furnished intermediate. Then aniline deriva-
tives induced cyclization offered the desired produced.
All the products have been characterized by FT-IR,
NMR, and HRMS analyzes. The infrared (FT-IR) spectra
After optimization of the solvent and catalyst amount
for the model reaction, we have tried to find optimum
temperature and it was observed that no desired product
Table IV. The optimization of temperature for preparation of 1,8-
dioxoacridine derivatives using graphene oxide as catalyst in DMF.
200
150
100
50
0
1
2
3
4
5
6
7
Time (h)
Yield (%)
Temperature (ºC)
1
2
3
4
5
6
7
Scheme 2. Recommended mechanism pathway for the graphene oxide
catalyzed synthesis of 1,8-dioxoacridine derivatives.
Time (h)
48
48
24
1.5
1.5
1.5
1.5
6502
J. Nanosci. Nanotechnol. 16, 6498–6504, 2016

Aday et al.
Graphene Oxide as Highly Effective and Readily Recyclable Catalyst Using for the One-Pot Synthesis
Table VI. Recyclable performance of GO in the model reaction.
short reaction times, would be a rather attractive synthetic
method in the future.
95
90
94
85
92
90
Acknowledgments: This research was financed by
Dumlupınar University Research Fund (Grant Nos. 2014-
62 and 2014-05) as well as by the Dumlupınar University
ILTEM research laboratory.
80
75
70
87
84
80
1
2
3
4
5
6
Yield (%)
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Received: 6 September 2015. Accepted: 28 September 2015.
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Copyright: American Scientific Publishers
6504
J. Nanosci. Nanotechnol. 16, 6498–6504, 2016