Synthesis of benzo[h]quinolone and benzo[c]acridinone derivatives by Fe3O4@PS-Arginine[HSO4] as an efficient magnetic nanocatalyst

Article abstract of DOI:10.1002/jhet.4125

Fe₃O₄ magnetic nanoparticles were synthesized and functionalized by propylsilan and after that arginine. The synthesized Fe₃O₄@PS-Arginine magnetic nanoparticles were modified to obtain Fe₃O₄

Full text of DOI:10.1002/jhet.4125

Synthesis of benzo[h]quinolone and benzo[c]acridinone derivatives by
Fe3O4@PS-Arginine[HSO4] as an efficient magnetic nanocatalyst
Maryam Kargar Karkhah, Hassan Kefayati , Shahab Shariati
Department of Chemistry, Rasht Branch, Islamic Azad University, Rasht, Iran
Abstract
Fe3O4 magnetic nanoparticles were synthesized and functionalized by propylsilan and after
that arginine. The synthesized Fe3O4@PS-Arginine magnetic nanoparticles were modified to
obtain Fe3O4@PS-Arg[HSO4]. These nanoparticles were used as environmental friendly solid
acid magnetic nanocatalyst for the synthesis of 2-amino-4-arylbenzo[h]quinoline-3-
carbonitrile and 10,10-dimethyl-7-aryl-9,10,11,12-tetrahydrobenzo[c]acridin-8(7H)-one
derivatives via the one-pot reaction of α-naphthilamine and aromatic aldehydes with
malononitrile or dimedone. Simple operation, high reaction yields, reusability of catalyst for
several times, short reaction time and easy separation from reaction mixture are the key
advantages of using this catalyst.
Keywords: Arginine, Benzo[h]quinoline, Benzo[c]acridine, α-naphthylamine, Fe3O4
magnetic nanoparticles
H Tel.: +98 1333480215, Fax: +98 1333480233, P. O. Box: 41335-3516; E-mail: kefayati@iaurasht.ac.ir,
haskefayati@gmail.com (H. Kefayati)
JHJGHGHJNJN
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1. Introduction
Quinoline scaffold has a special importance in the natural and synthetic organic compounds.1
Quinoline derivatives are an important class of heterocycles due to their wide range of
biological and pharmacological potentialities2 such as anticancer,3 antibacterial,4
antiprotozoal, antiproliferative,5 antitumor,6 anti-inflammatory,7 antifungal, antioxidant,
antihypertensive,8 antimalarial9, antitubercular10, anti-HIV agents11. Also, acridine derivatives
have been known since the 19th century where they were first used as pigments and dyes.12
Wide ranges of acridines were tested for anti-malarial activities and among them the
introduction of benzo analogue is one of the types of nuclei variation that has received a
considerable attention.13
Various methods have been reported for the synthesis of the quinoline derivatives such as
Skraup and modified Skraup methods,14,15 domino reaction via sodium hydroxide catalyst,16
microwave assisted solvent free reaction,17 microwave assisted Friedländer synthesis,18 use of
homogeneous and heterogeneous catalyst,19,20 cobalt ferrite nanoparticle catalyst in water,21
microwave and reflux assisted,22 cooperative anomeric based oxidation mechanism,23 reflux
assisted as potential DNA-intercalating antitumor agents24, etc. In 2007, Shujiang et al.
reported the synthesis of 2-amino-4-arylbenzo[h]quinoline-3-carbonitrile derivatives without
using of catalyst but the reaction time was too long (5-8 h).25 Therefore, introducing of new
and convenient methods to synthesize quinoline derivatives can be helpful.
In recent years, magnetic nanoparticles (MNPs), especially, Fe3O4 have attracted
considerable attention due to strong adsorption ability, super para magnetism, reusability and
simple separation.26,27 Also, application of Fe3O4 MNPs in technical, biological and medical
fields are intensively studied.28-30 Furthermore, Fe3O4 nanoparticles have emerged as robust
and high surface area heterogeneous catalyst.31-34 Various strategies have successfully
demonstrated the applications of Fe3O4 nanoparticle-immobilized or supported catalysts.35
In our recently studies, we designed highly efficient magnetic nanocatalysts for the synthesis
of heterocyclic compounds by functionalizing Fe3O4 MNPs with amino acids.36-40 One of
these nanocatalysts is Fe3O4@Propylsilan-Argenine (Fe3O4@PS-Arg), which was firstly
synthesized by us as a chiral catalyst and used for the enantioselective synthesis of chromene
derivatives.40 In this study, we wish to investigate the efficacy of Fe3O4@PS-Arg[HSO4] as a
novel catalyst for the synthesis of some acridine and novel quinoline derivatives. Successful
2
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synthesis of two important families of heterocycles (quinoline and acridin) with a high yield
and in a minimum of reaction time shows that, this catalyst can be effectively used for the
synthesis of other heterocyclic families.
2.
Experimental
2.1. General
All chemical materials and solvents were purchased from Merck (Darmstadt, Germany).
Melting points were measured using an Electro Thermal IA 9100 melting point apparatus
(UK). Fourier transform infrared (FT-IR) spectra were obtained in the range of 400-4000 cm-
1
using pressed potassium bromide (KBr) pellets with a Shimadzu FT-IR 8600
1
13
spectrophotometer (Japan). H and C NMR spectra were recorded on a Bruker DRX-250
MHz instrument (Karlsruhe, Germany) using DMSO solvent and TMS as internal reference.
2.2. Preparation of Fe3O4@PS-Arg[HSO4] MNPs
Fe3O4 and Fe3O4@PS-Arg MNPs were synthesized according to our previous reports.40,41
Fe3O4@PS-Arg[HSO4] MNPs were prepared by stirring of Fe3O4@PS-Arg (1 g) and 30 mL
H2SO4 (0.05 M) at room temperature for 24 h. The obtained solid catalyst was filtered and
washed (3 × 10 mL) with water and dried at 110 °C for 24 h.
2.3. General method for the synthesis of 2-amino-4-arylbenzo[h]quinoline-3-carbonitrile
(5a-e) and 10,10-dimethyl-7-aryl-9,10,11,12-tetrahydrobenzo[c]acridin-8(7H)-one (6a-e)
A mixture of α-naphthilamine (1 mmol), malononitrile or dimedone (1 mmol), aromatic
aldehyde derivatives (1 mmol) and Fe3O4@PS-Arg[HSO4] MNPs (0.07 g) in 5 mL ethanol
was refluxed. After completion of the reaction (monitored by TLC), 5 mL ethanol was added
and the precipitate was dissolved at the hot ethanol. The magnetic nanocatalyst was separated
with a magnet (1.4 T) and the solution was filtered. The crude (5a-f) and (5a-e) products
were obtained by cooling the solution at room temperature and recrystallizing from ethanol to
afford the pure compounds.
2.4. Spectral data of the products
2-Amino-4-(4-nitrophenyl)benzo[h]quinoline-3-carbonitrile (5a):
Yield 95%, mp: 246-248 °C (Reported mp: 247-248 °C [25]), IR (KBr) (vmax/cm-1): 3484,
3359, 2224, 1614, 1562, 1515, 1485, 1344; 1H NMR (250 MHZ, DMSO-d6) δH (ppm): 7.03
3
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(d, J =9.0 Hz, 1H), 7.30 (br s, 2H, NH2), 7.53 (d, J =9.0 Hz, 1H), 7.65-7.90 (m, 5H), 8.45 (d,
J = 8.5 Hz, 2H), 9.01 (d, J =7.5 Hz, 1H); 13C NMR (62 MHz, DMSO-d6) δc (ppm): 93.0,
116.3, 116.7, 122.8, 124.1, 124.3, 125.4, 127.2, 128.3, 129.5, 130.1, 131.4, 135.0, 142.2,
148.5, 153.5, 157.0.
2-Amino-4-(3-nitrophenyl)benzo[h]quinoline-3-carbonitrile (5b):
Yield 93%, mp: 281-283 °C (Reported mp: 280-283 °C [25]), IR (KBr) (vmax/cm-1): 3489,
3371, 2218, 1616, 1560, 1523, 1451, 1347; 1H NMR (250 MHZ, DMSO-d6) δH (ppm): 7.08
(d, J = 8.75 Hz , 1H), 7.29 (br s, 2H, NH2), 7.49 (d, J = 8.75 Hz , 1H), 7.67-7.98 (m, 5H),
8.40-8.45 (m, 2H) 9.01-9.02 (m, 1H); 13C NMR (62 Hz, DMSO-d6) δc (ppm): 93.5, 116.5,
116.9, 122.9, 124.1, 124.7, 125.4, 127.1, 128.2, 129.5, 130.0, 131.0, 135.0, 136.4, 137.1,
148.3, 148.5, 153.1, 157.1.
2-Amino-4-(4-chlorophenyl)benzo[h]quinoline-3-carbonitrile (5c):
Yield 95%, mp: 233-235 °C (Reported mp: 236-239 °C [25]), IR (KBr) (vmax/cm-1): 3486,
3373, 2219, 1626, 1547, 1550, 1485, 1291; 1H NMR (250 MHZ, DMSO-d6) δH (ppm): 7.10
(d, J = 9 Hz, 1H), 7.20 (br s, 2H, NH2), 7.48-7.55 (m, 2H), 7.66-7.69 (m, 3H), 7.85-7.92 (m,
2H), 8.49 (s, 1H), 8.99-9.02 (m, 1H); 13C NMR (62 Hz, DMSO-d6) δc (ppm): 93.4, 116.6,
117.0, 123.0, 123.9, 125.4, 127.0, 128.2, 129.3, 129.9, 130.1, 130.5, 131.6, 132.6, 134.3,
135.0, 139.5, 154.4, 157.1, 160.5.
2-Amino-4-(4-bromophenyl)benzo[h]quinoline-3-carbonitrile (5d):
Yield 93%, mp: 244-246 °C (Reported mp: 244-246 °C [25]), IR (KBr) (vmax/cm-1): 3486,
1
3374, 2218, 1626, 1549, 1573, 1483, 1290; H NMR (250 MHZ, DMSO-d6) δH (ppm): 7.08-
7.47 (m, 5H), 7.67-7.81 (m, 5H), 9.00-9.01 (m, 2H); 13C NMR (62 Hz, DMSO-d6) δc (ppm):
93.3, 116.6, 116.9, 123.0, 123.4, 124.0, 125.4, 127.1, 128.2, 129.5, 129.9, 131.8, 132.2,
134.7, 135.0, 148.4, 154.4, 157.1.
2-Amino-4-(3-bromophenyl)benzo[h]quinoline-3-carbonitrile (5e):
Yield 88%, mp: 231-232 °C, IR (KBr) (vmax/cm-1): 3506, 3381, 2216, 1645, 1589, 1487,
1
1407, 1234; H NMR (250 MHZ, DMSO-d6) δH (ppm): 7.09 (d, J = 8.7 Hz, 1H), 7.22 (br s,
2H, NH2), 7.53-7.89 (m, 7H), 8.49 (d, 1H), 8.98-9.01 (d, J = 6.5 Hz, 1H); 13C NMR (62 Hz,
DMSO-d6) δc (ppm): 93.5, 115.9, 116.4, 121.8, 122.4, 123.0, 124.0, 125.4, 126.5, 127.7,
128.9, 129.4, 130.8, 131.5, 132.1, 132.7, 134.4, 137.2, 153.4, 156.5.
4
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10,10-Dimethyl-7-(4-chlorophenyl)-9,10,11,12-tetrahydrobenzo[c]acridin-8(7H)-one
(6a):
Yield 96%, mp: 265-267 °C (Reported mp: 268-270 °C [34]), IR (KBr) (vmax/cm-1): 3333,
3005, 2960, 1604, 1568, 1488, 1372, 1262; 1H NMR (250 MHZ, DMSO-d6) δH (ppm): 0.93 (s,
3H, CH3), 1.03 (s, 3H, CH3), 2.11 (dd, J = 15.75 Hz, J = 13.25 Hz, 2H, H-11), 2.65 (dd, J =
16.5 Hz, J = 17.25 Hz, 2H, H-9), 4.97 (s, 1H), 6.01 (s, 1H), 6.82-7.70 (m, 8H), 8.43 (d, J =
7.2, 1H), 9.28 (s, 1H, NH); 13C NMR (62 Hz, DMSO-d6) δc (ppm): 27.3, 28.3, 29.6, 32.0,
32.5, 50.6, 106.9, 115.7, 119.3, 122.2, 122.9, 124.8, 125.6, 127.9, 128.4, 129.6, 130.3, 131.1,
134.6, 143.2, 147.2, 152.7, 193.9.
10,10-Dimethyl-7-(2-chlorophenyl)-9,10,11,12-tetrahydrobenzo[c]acridin-8(7H)-one
(6b):
Yield 90%, mp: 267-268 °C (Reported mp: 266-268 °C [34]), IR (KBr) (vmax/cm-1):
3300,2962, 2923, 1586, 1515, 1499, 1390, 1264; 1H NMR (250 MHZ, DMSO-d6) δH (ppm):
1.00 (s, 3H, CH3), 1.06 (s, 3H, CH3), 2.10 (dd, J =16.0 Hz, J = 16.25 Hz, 2H, H-11), 2.69
(dd, J = 17.25 Hz, J = 17.0 Hz, 2H, H-9), 5.70 (s, 1H), 7.05-7.78 (m, 9H), 8.44 (d, J = 8 Hz,
1H), 9.24 (s, 1H, NH).
10,10-Dimethyl-7-(3-nitrophenyl)-9,10,11,12-tetrahydrobenzo[c]acridin-8(7H)-one (6c):
Yield 93%, mp: 270-272 °C (Reported mp: 271-273 °C [34]), IR (KBr) (vmax/cm-1): 3314,
2870, 1613, 1564, 1523, 1485, 1344.
10,10-Dimethyl-7-(2,4-dichlorophenyl)-9,10,11,12-tetrahydrobenzo[c]acridin-8(7H)-one
(6d):
Yield 93%, mp: 283-284°C (Reported mp: 285-287 °C [34]), IR (KBr) (vmax/cm-1): 3333,
3060, 2874, 1586, 1495, 1467, 1368, 1260.
10,10-Dimethyl-7-phenyl-9,10,11,12-tetrahydrobenzo[c]acridin-8(7H)-one (6e):
Yield 95%, mp: 259-261°C (Reported mp: 261-263 °C [34]), IR (KBr) (vmax/cm-1): 3305,
2961, 2890, 1598, 1566, 1490, 1303, 1259.
10,10-Dimethyl-7-(4-methoxyphenyl)-9,10,11,12-tetrahydrobenzo[c]acridin-8(7H)-one
(6f):
Yield 90%, mp: 260-262 °C (Reported mp: 259-261 °C [34]), IR (KBr) (vmax/cm-1): 3324,
2990, 2975, 1610, 1574, 1487, 1372, 1256.
5
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3.
Results and discussion
At first, Fe3O4 MNPs were synthesized and functionalized by tri-methoxysilylpropyl chloride
and arginine to give Fe3O4@PS-Arg. After reaction with H2SO4 (0.05 M) at room
temperature (for 24 h) Fe3O4@PS-Arg[HSO4] MNPs were obtained (Scheme 1). The
structure of these nanoparticles was confirmed by FT-IR spectroscopy (Figure 1a-c).40
Scheme 1. The reaction sequence for the synthesis of Fe3O4@PS-Arg[HSO4] MNPs
6
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Figure 1. FT-IR spectra of (a) Fe3O4, (b) Fe3O4@PS-Arg, and (c) Fe3O4@PS-Arg[HSO4]
We studied synthesis of 2-amino-4-(4-nitrophenyl)benzo[h]quinoline-3-carbonitrile (5a) by
the reaction of α-naphthilamine (1 mmol), malononitrile (1 mmol) and 4-nitrobenzaldehyde
(1 mmol) as a model reaction in absence and presence of Fe3O4@PS-Arg as catalyst (Scheme
2). As the results are shown in Table 1, no product was obtained, even with prolonged
reaction times (60 min) and with increasing reaction temperature to 110 ◦C (Table 1, entry 1-
3).
Scheme 2. Synthesis of 2-amino-4-(4-nitrophenyl)benzo[h]quinoline-3-carbonitrile
7
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Table 1. Effect of various amounts of catalyst and different solvents in the synthesis of 2-amino-4-(4-
nitrophenyl)benzo[h]quinoline-3-carbonitrile (5a)
Entry
Catalyst
Amount of
catalyst
Solvent
Condition
Time
[min]
60
Yield
[%]
-
1
2
3
4
5
Free
-
EtOH
EtOH
DMF
EtOH
EtOH
Reflux
Reflux
110 ◦C
Reflux
Reflux
Fe3O4@PS-Arg
0.05 (g)
0.05(g)
0.05 (g)
0.07 (g)
60
60
15
5
-
Fe3O4@PS-Arg
-
Fe3O4@PS-Arg[HSO4]
Fe3O4@PS-Arg[HSO4]
87
95
6
7
Fe3O4@PS-Arg[HSO4]
Fe3O4@PS-Arg[HSO4]
Fe3O4@PS-Arg[HSO4]
Fe3O4@PS-Arg[HSO4]
CH3COOH
0.1 (g)
0.07 (g)
EtOH
CH2Cl2
DMF
Reflux
Reflux
100 ◦C
Reflux
Reflux
Reflux
Reflux
5
95
72
85
83
52
59
67
45
8
0.07 (g)
15
9
0.07 (g)
CH3CN
EtOH
25
10
11
12
10 (mol %)
10 (mol %)
10 (mol %)
300
120
200
H2SO4
EtOH
P-TSA
EtOH
Reaction conditions: α-Naphthilamine (1 mmol), malononitrile or dimedone (1 mmol), 4-nitrobenzaldehyde (1
mmol)
Since, the Fe3O4@PS-Arg is a basic catalyst, it seems that by modifying it to Fe3O4@PS-
Arg[HSO4], the desired product can be formed. Therefore, we modified Fe3O4@PS-Arg by
H2SO4 (Scheme 1). The appearance of the signals at 1038 cm-1 (attributed to the vibration of
-
sulfoxide group of HSO4 ) and broad band at 2700-3400 cm-1 (attributed to the OH vibration
of COOH) indicate the successfully synthesis of Fe3O4@PS-Arg[HSO4] MNPs (Figure 1c).
The amount of acid loaded on the magnetic nanoparticles was evaluated by acid-base titration
in the presence of phenolphthalein indicator. The result showed that, the surface of 1 g of the
magnetic nanocatalyst was loaded by 562 mg acid. Also, we investigated 0.1 and 0.05 M
concentration of H2SO4 to obtain ionic liquid loaded MNPs. The experiments showed that by
using of 0.1 M H2SO4, dissolution of MNPs was occurred. With decreasing the H2SO4
concentration to 0.05 M, the ionic liquid was formed without any considerable loss in the
Fe3O4 core. Therefore, in further experiments 0.05 M of H2SO4 was utilized.
The size and morphology of Fe3O4@PS-Arg[HSO4] were studied by SEM and TEM. As
shown in Figure 2, the TEM and SEM images show that Fe3O4@PS-Arg[HSO4] MNPs were
spherical with uniform size (70-90 nm).
8
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Figure 2. The TEM (a) and SEM (b) images of Fe3O4@PS-Arg[HSO4]
The thermal behavior of Fe3O4@PS-Arg[HSO4] was investigated by thermogravimetric
analysis (TGA). As shown in Figure 3, the weight loss of 5% below 100 °C was related to the
loss of adsorbed water molecules. TGA results showed other weight decreasing from 100 to
700 °C due to the decomposition of the organic groups (about 12%). Thus, the TGA curve
confirmed the successful functionalization of magnetic nanoparticles.
TG(%)
120
100
80
60
40
20
0
0
200
400
600
800
1000
Temperature (oC)
Figure 3. TGA thermogram of Fe3O4@PS-Arg[HSO4]
The magnetic properties of the Fe3O4 and Fe3O4@PS-Arg[HSO4] MNPs were measured
using vibrating sample magnetometer (VSM) and the curves are shown in Figure 4. The
9
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saturation magnetization of Fe3O4 at 25 °C was 78 emu g-1 while for the Fe3O4@PS-Arg
[HSO4] MNPs was 25 emu g-1. These values show the super-paramagnetic property of the
synthesized MNPs that are sufficient for magnetic separation with a magnet. The decrease in
the saturation magnetization of coated Fe3O4 was related to the existence of coating on the
surface of Fe3O4 core.
Figure 4. Magnetic hysteresis curves of the (a) Fe3O4; (b) Fe3O4@PS-Arg[HSO4] MNPs
Evaluating of the surface area of Fe3O4@PS-Arg[HSO4] MNPs was carried out using BET
(Brunauer-Emmett-Teller) plot (R2 = 0.9999). From this method, as, BET (specific BET surface
area) = 35.709 m2 g-1, Vm (BET monolayer capacity) = 8.2042 cm3 (STP) g-1, C
(exponentially related to the energy of monolayer adsorption) = 49.305, total pore volume
(p/p0=0.990) = 0.2431 cm3 g-1 and mean pore diameter = 27.231 nm were obtained. Also, the
specific surface area was calculated by Langmuir isotherm as as,Lang = 36.368 m2 g-1, Vm =
8.3556 cm3 (STP) g-1.
10
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Figure 5. (a) The pore size distribution curve (insert) (b) nitrogen adsorption-desorption
isotherms measured at 77 K, of the synthesized Fe3O4@PS-Arg[HSO4] MNPs
Figure 5 (a, b) shows the nitrogen adsorption-desorption isotherm of the synthesized
Fe3O4@PS-Arg[HSO4] MNPs. The hysteresis loop obtained from the nitrogen sorption
isotherm (Figure 5. b) matched with H3 type of IUPAC classification (1985) showing non-
rigid aggregates of plate-like particles [42, 43]. Using the BJH plot (Figure 5 a), the pore size
distribution of the MNPs was calculated by the desorption branches of the isotherm using the
BJH (Barrett-Joyner-Halenda) formula as Vp (the mean volume of the pores) = 0.2445 cm3 g-
1, ap (surface of pores) =42.092 m2 g-1 and rp, peak (Area) = 6.95 nm.
The model reaction was studied in the presence of Fe3O4@PS-Arg[HSO4] MNPs (0.05 g) as a
solid acid magnetic nanocatalyst and the product 5a was obtained with good yield (87%) at
15 min (Table 1, entry 4), surprisingly. In continuation, the reaction was studied by various
amounts of catalyst and different solvents in the presence of Fe3O4@PS-Arg[HSO4] (Table 1,
entry 4-9). The results showed 0.07 g of catalyst gave the best yield of product (95%) at the
least time (5 min). Further, it was found that EtOH was the favorable solvent for the reaction
(Table 1, entry 4). Also, we studied the reaction in the presence of other homogenous acidic
catalysts such as CH3COOH, H2SO4, P-TSA (Table 1, entry 10-12) and the results were
11
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compared with Fe3O4@PS-Arg[HSO4]. As expected, Fe3O4@PS-Arg[HSO4] is more efficient
than other catalysts. Probably, this may be due to the high surface area of the catalyst. Also,
because of the presence of ammonium, guanidinium and hydrogen sulfate groups, the effect
of catalyst increases, synergistically.
After determination of optimum conditions, the efficiency of Fe3O4@PS-Arg[HSO4]
MNPs as catalyst for the synthesis of quinolone or acridine derivatives was evaluated by
reaction of aromatic aldehyde derivatives and α-naphthilamine with malononitrile or
dimedone (Scheme 3). In all studied cases, Fe3O4@PS-Arg[HSO4] MNPs gave the
corresponding products 5a-e and 6a-f with excellent yield in short time (Table 2).
Scheme 3. Synthesis of 2-amino-4-arylbenzo[h]quinoline-3-carbonitrile and 10,10-dimethyl-
7-aryl- 9,10,11,12-tetrahydrobenzo[c]acridin-8(7H)-one
Table 2. Synthesis of 2-amino-4-arylbenzo[h]quinoline-3-carbonitrile (5a-e) and 10,10-dimethyl-7-
aryl-9,10,11,12-tetrahydrobenzo[c]acridin-8(7H)-one (6a-f)
Products
Structures
Time (min) Yield (%)
Mp (◦C)
Mp [lit]
95
5
246-248
247-248[25]
5a
12
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93
95
281-283
233-235
280-283[25]
236-239[25]
5b
5c
10
5
5
93
88
244-246
231-232
244-246[25]
5d
5e
15
-
96
265-267
268-270[44]
6a
5
5
267-268
270-272
266-268[44]
90
93
6b
6c
10
271-273[44]
13
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93
95
6d
6e
10
283-284
259-261
285-287[44]
5
261-263[44]
259-261[44]
90
6f
10
260-262
-
Reaction conditions: α-Naphthilamine (1 mmol), aromatic aldehyde (1 mmol) , Fe3O4@PS-Arg[HSO4 ] (0.07 g),
malononitrile or dimedone (1 mmol), and ethanol (5 mL), reflux
A comparison was made between the efficiency of Fe3O4@PS-Arg[HSO4] MNPs and some
other catalysts for the synthesis of quinoline and acridine derivatives in previous literature
(Table 3), which showed that the efficiency of Fe3O4@PS-Arg[HSO4] is better.
Table 3. The comparison between Fe3O4@PS-Arg[HSO4] and some other catalysts for synthesis of 5a
and 6a
Structures
Catalyst
Condition
Time Yield
(%)
Fe3O4@PS-Arg[HSO4]
Reflux in EtOH
5 min
95
14
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Reflux in EtOH
Reflux in EtOH
8 h
95[25]
-
Fe3O4@PS-Arg[HSO4]
5 min
96
-
Ultrasonic in EtOH
Reflux in EtOH
1 h
1 h
90[44]
L-Proline
97[45]
SuSA
Reflux in EtOH
1.5 h
95[46]
A probable mechanism for this reaction is shown in scheme 4. It seems, the electrophilic
character of aldehyde is enhanced by Fe3O4@PS-Arg[HSO4] MNPs as catalyst. Condensation
of malononitrile or dimedone with aldehyde affords products V and VII via a Knoevenagel
reaction. Subsequently, products V or VII react with α-naphthilamine by a Michael addition
to afford intermediate VIII or IX. Then, intramolecular cyclization of VIII or IX gave the
desired product 5 or 6.
15
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Scheme 4. Probable mechanism for the synthesis of 2-amino-4-arylbenzo[h]quinoline-3-carbonitrile
(5a-e) and 10,10-dimethyl-7-aryl-9,10,11,12-tetrahydrobenzo[c] acridin-8(7H)-one (6a-f)
The reusability of Fe3O4@PS-Arg[HSO4] MNPs was confirmed on the model reaction
(Figure 6). Finally, the catalyst was separated from the reaction mixture by a magnet and
washed with ethanol and then dried at 100 °C. The separated catalyst was reused for the
16
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synthesis of 5a for five times. After five successive runs, recycled Fe3O4@PS-Arg[HSO4]
MNPs showed no noticeable loss of efficiency with regard to the reaction time and yield.
100
95
95
90
85
80
75
70
91
87
85
81
5
1
2
3
4
Figure 6. Reusability of catalyst for synthesis of 5a
4. Conclusion
In summary, Fe3O4@PS-Arg[HSO4] MNPs efficiently catalyzed the one‐pot synthesis of
10,10-dimethyl-7-aryl-9,10,11,12-tetrahydrobenzo[c]acridin-8(7H)-one and 2-amino-4-
arylbenzo [h]quinoline-3-carbonitrile. This catalyst can be easily separated from the reaction
mixture and reused up to five times without any significant reduction in its activity or the
reaction yield. Simple operation, clean reaction procedure and reusability of the catalyst,
make it attractive for the large range heterocyclic synthesis.
Acknowledgment
Financial support by Rasht Branch, Islamic Azad University is gratefully acknowledged.
Supporting information
Supporting information associated with this article can be found, in the online version,
at…
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Graphical Abstract
Synthesis of benzo[h]quinolone and benzo[c]acridinone derivatives by
Fe3O4@PS-Arginine[HSO4] as an efficient magnetic nanocatalyst
Maryam Kargar Karkhah, Hassan Kefayati , Shahab Shariati
Department of Chemistry, Rasht Branch, Islamic Azad University, Rasht, Iran
Corresponding author. Tel.: +98 1333480215, Fax: +98 1333480233, P. O. Box: 41335-3516;
E-mail: kefayati@iaurasht.ac.ir, haskefayati@gmail.com (H. Kefayati)
22
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