Novel nano-titania embedded on graphite (nano-TiO2@Cg) as an efficient, eco-friendly, and recyclable catalyst for one-pot, solvent-free synthesis of 4-aryl-3,4-dihydroquinolin-2(1H)-ones, 3-methyl-4-aryl/alkyl-2,4,5,7-tetrahydropyrazolo[3,4-b]pyridin-6-ones, and coumarin-3-carboxylic esters

Article abstract of DOI:10.1007/s11164-018-3560-4

Abstract: A novel acid catalyst has been synthesized by commercial anatase phase nano-TiO₂ and graphite (nano-TiO₂@C_g) via a simple procedure and characterized by Fourier transform infrared spectroscopy, energy-dispersive X-ray spectroscopy, thermogravimetric analysis, field emission scanning electron microscopy, and potentiometric titration techniques. It has been utilized as a convenient nano-catalyst to accelerate the one-pot, solvent-free, three-component reaction of Meldrum’s acid, aromatic amines (5-methylpyrazol-3-amine), and various aromatic aldehydes to form 4-aryl-3,4-dihydroquinolin-2-(1H)-ones and 3-methyl-4-aryl/alkyl-2,4,5,7-tetrahydropyrazolo[3,4-b]pyridin-6-ones, respectively. The catalytic activity has also examined for the preparation of coumarin-3-carboxylic esters from Meldrum’s acid, salicylaldehydes, and alcohols successfully. Low catalyst loading, clean process without utilizing any hazardous solvent, easy workup procedure, reusability and recyclability of the nano-catalyst within four runs without activity loss, high yields of the products, in addition with utilizing a vast range of substrates are some highlighted points of the reported protocols. Graphical abstract: [Figure not available: see fulltext.]

Full text of DOI:10.1007/s11164-018-3560-4

Research on Chemical Intermediates
https://doi.org/10.1007/s11164-018-3560-4(0123456789(). -, vo Vl
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Novel nano-titania embedded on graphite (nano-TiO2@Cg)
as an efficient, eco-friendly, and recyclable catalyst for one-
pot, solvent-free synthesis of 4-aryl-3,4-dihydroquinolin-
2(1H)-ones, 3-methyl-4-aryl/alkyl-2,4,5,7-
tetrahydropyrazolo[3,4-b]pyridin-6-ones, and coumarin-3-
carboxylic esters
Kobra Nikoofar1 Fatemeh Molaei Yielzoleh1
•
Received: 24 June 2018 / Accepted: 10 August 2018
Ó Springer Nature B.V. 2018
Abstract
A novel acid catalyst has been synthesized by commercial anatase phase nano-TiO2
and graphite (nano-TiO2@Cg) via a simple procedure and characterized by Fourier
transform infrared spectroscopy, energy-dispersive X-ray spectroscopy, thermo-
gravimetric analysis, field emission scanning electron microscopy, and potentio-
metric titration techniques. It has been utilized as a convenient nano-catalyst to
accelerate the one-pot, solvent-free, three-component reaction of Meldrum’s acid,
aromatic amines (5-methylpyrazol-3-amine), and various aromatic aldehydes to
form 4-aryl-3,4-dihydroquinolin-2-(1H)-ones and 3-methyl-4-aryl/alkyl-2,4,5,7-tet-
rahydropyrazolo[3,4-b]pyridin-6-ones, respectively. The catalytic activity has also
examined for the preparation of coumarin-3-carboxylic esters from Meldrum’s acid,
salicylaldehydes, and alcohols successfully. Low catalyst loading, clean process
without utilizing any hazardous solvent, easy workup procedure, reusability and
recyclability of the nano-catalyst within four runs without activity loss, high yields
of the products, in addition with utilizing a vast range of substrates are some
highlighted points of the reported protocols.
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s11164-
018-3560-4) contains supplementary material, which is available to authorized users.
Extended author information available on the last page of the article
123

K. Nikoofar, F. Molaei Yielzoleh
Graphical abstract
Keywords Meldrum’s acid Á 4-Aryl-3,4-dihydroquinolin-2-(1H)-one Á 3-Methyl-4-
aryl/alkyl-2,4,5,7-tetrahydropyrazolo[3,4-b]pyridin-6-one Á Nano-TiO2@Cg Á
Coumarin-3-carboxylic esters Á Solvent-free conditions Á Multi-component
reaction
Introduction
Titanium dioxide or titania (TiO2) as
a white eco-friendly (LD50 oral
rat [ 10,000 mg kg-1) pigment has widely been applied in the manufacture of
paint, surface coatings on paper, and as a filler in rubber and plastics [1]. This nano-
metal oxide, has been confirmed to be a widely used dual-functionality reagent/
123

Novel nano-titania embedded on graphite (nano-TiO2@Cg) as…
catalyst due to its high activity, non-toxicity, easy availability, reusability, strong
oxidizing power, and long-term stability. Examples of its industrial application
include its antibacterial effect on Escherichia coli strain [2], catalyst support for
proton-exchange membrane fuel cells [3], catalyst for rhodamine B degradation [4],
and photosensitization effect of nano-TiO2 thin film on dye-sensitized solar cells
(DSSCs) [5]. The titanium nano-sized oxide showed catalytic activity in some
organic transformations such as Hantzsch ester and polyhydroquinoline derivative
synthesis [6], preparation of quinoxalines [7], Knoevenagel–Michael cycloconden-
sation reaction [8], and bis(indolyl)methane synthesis [9].
Graphite is a natural source of carbon with uniform hybridization and long-range
order [10] that has been built from hexagonal planes of carbon atoms.
Geim et al. mechanically demonstrated that the energy level between single
sheets from the p-stacked layers of graphite are about 5.9 kJ mol-1 which is related
to the cohesive Van der Waals forces [11]. It is a highly ordered and crystalline
material composed of aromatic sheets with a constant interlayer spacing of
0.335 nm [12].
Over the past few years, graphite has been considered to be an effective,
alternative, and promising Lewis acid catalyst and has received much attention
because of its low price, sustainability, ready availability, lack of toxicity, easy
handling, and environmentally friendly properties [13].
It has been used as catalyst and mixed catalyst-support for different kinds of
transformations such as preparation of 1,5-benzodiazepines [14], synthesis of
amidoalkyl naphthols [15], solvent-free oxidation of dec-1-ene [16], four-
component preparation of highly functionalized pyrroles [17], Meerwein arylation
of pyrroles, multi-component click preparation of 1,2,3-triazoles [12], and Michael
addition of indoles to nitroolefins [18].
Hetero compounds containing 4-aryl-3,4-dihydroquinolin-2-one motifs possess
promising biological activities and pharmaceutical properties, and function as
cancer chemoprotectives [19], atypical antipsychotics [20], and antidepressants
[21]. Some these classes of adducts are key building blocks for the synthesis of
marine alkaloid acridine units [22]. 4-Aryl-3,4-dihydroquinolin-2(1H)-one scaffolds
have been prepared through various strategies such as an internal Friedel–Crafts
alkylation of N-cinnamoylanilines in the presence of trifluoroacetic acid (TFA) [23],
an aldol reaction [24], Ru-catalyzed 6-endo-trig cyclization of N-[2-(1-phenylvi-
nyl)phenyl]formamide [25], Schmidt rearrangement [26], and other routes [27].
Pyrazolopyridone derivatives are another form of Meldrum’s acid-based
heterocycles which demonstrate many biological and medicinal activities, such as
a noncovalent DprE1 inhibitor with potent anti-mycobacterial activity [28], anti-
cancer properties [29], and anti-bacterial activities against ATPase subunit of DNA
gyrase B [30]. Commonly, they have been prepared via three-component reaction of
an aldehyde, Meldrum’s acid, and 3-methyl-1H-pyrazol-5-amine using glycol
(PEG)-400 [31], sonic waves [32], and Fe?3-K10 montmorillonite [33].
Coumarin-3-carboxylic esters, which have been prepared using simple and
cheaply available salicylaldehydes, Meldrum’s acid, and alcohols in the presence of
FeCl3 [34], are some of Meldrum’s acid-based heterocycles which function as a
selective monoamine oxidase inhibitory [35] and are also used in chemotherapeutic
123

K. Nikoofar, F. Molaei Yielzoleh
studies
on
schistosomiasis
[36].
Some
substituted
coumarin-3-
carboxylatosilver(I) complexes also showed in vitro antibacterial and antifungal
activities [37].
The solid-state reaction (or solvent-free reaction) possesses several advantages
such as reduced pollution, low costs, simplicity in process and handling, and
elimination of harmful organic solvents, which account for a great proportion of the
waste materials [38]. These aspects make this protocol especially important from
economic and ecological viewpoints.
Experimental
Materials and measurements
All chemicals were purchased from Merck, Aldrich, and Alfa Aesar and were used
without further purification. Commercial nano-titania (anatase phase, average
particle size of 25–30 nm, and 0.24 g/cm3) has been purchased from Nanosany
Corporation. FT-IR spectra were recorded from a KBr disk using an Bruker Tensor
27 FT-IR instrument. Melting points were determined on an Electrothermal 9200
analyzer and are uncorrected. Proton nuclear magnetic resonance (1H NMR) spectra
were recorded with a Bruker DRX (400 MHz) machine in DMSO-d6 solvent.
Elemental analyses were determined using a Thermo-Finnigan Flash EA 1112
Series. Mass spectroscopy was obtained using a GC-Mass 5973 network mass
selective detector, GC 6690 Agilent device. The scanning electron microscope
(FESEM, VEGA\\TESCAN-LMU) used to characterize the nano-structures.
Thermogravimetric analysis were conducted using a Netzsch TGA 209 F1
apparatus. The potentiometric study was been using an Orion 620 pH meter.
Ultrasonication was performed in a Wise clean bath with power of 90 W. Progress
of the reaction was monitored by thin layer chromatography (TLC) technique using
commercially available silica gel sheets. Preparative layer chromatography (PLC)
was carried out on 20 9 20-cm2 plates, coated with a 1-mm-thick layer of Merck
silica gel PF254, prepared by applying the silica as slurry and drying in air.
Preparation of nano-TiO2@Cg
In order to activate the graphite surface, a mixture of graphite powder (5 g) and
concentrated nitric acid (3 mL) in 20 mL of absolute ethanol was stirred for 5 h at
room temperature. The solution was centrifuged and decanted followed with drying
in an oven at 70 °C for 2 h. Then, nano-TiO2 (1 g in 50 mL absolute ethanol) added
to dried solid and sonicated for 30 min, followed by stirring at 70 °C within 5 h.
After cooling, the suspension was centrifuged and rinsed with more absolute ethanol
(10 mL). The resultant solid was again dried in a 60 °C oven for 3 h. The obtained
black powder is nano-TiO2@Cg that containing 20% (w/w) nano-titanium on the
surface of graphite which has been characterized via FT-IR, EDX, TGA/DTG,
FESEM), and potentiometric titration techniques.
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Novel nano-titania embedded on graphite (nano-TiO2@Cg) as…
General procedure for synthesis of 4-aryl-3,4-dihydroquinolin-2(1H)-ones
and 3-methyl-4-aryl/alkyl-2,4,5,7-tetrahydropyrazolo[3,4-b]pyridin-6-ones
A mixture of Meldrum’s acid 1 (1 mmol), amines 2a–d or 5-methylpyrazol-3-amine
2e (1 mmol), and aldehydes 3a–g (1 mmol) in the presence of nano-TiO2@Cg
powder (0.004 g) was magnetically stirred under solvent-free conditions at 90 °C
for the desired reaction time monitored by TLC (n–hexane/ethylacetate eluent, 2:1
for 4-aryl-3,4-dihydroquinolin-2(1H)-ones and 1: 1 for 3-methyl-4-aryl/alkyl-
2,4,5,7-tetrahydropyrazolo[3,4-b]pyridin-6-ones). After completion of the reaction,
methanol (10 mL) was added and the catalyst separated through filtration.
Purification of the products was gained by plate chromatography of the mixture
to give the corresponding solid products 4a–n.
4-(3-Nitrophenyl)-3,4-dihydroquinolin-2(1H)-one (4g)
Viscous liquid. IR (KBr, cm-1): 3240 (NH), 2924, 2854, 1711 (CO), 1622, 1475,
767 (N–H). 1H NMR (400 MHz, DMSO-d6): 9.37 (brs, 1H, NH), 8.52–7.82 (m, 5H,
Ar), 7.77–7.71 (m, 3H, Ar), 7.70–7.69 (m, 2H, Ar), 4.18 (t, J = 10.2 Hz, 1H, CH),
2.54–2.25 (m, 2H, CH2). m/z 318 [M?], 193 [M?]-C6H5NO2, 185 [M?]-C6H5, -
NH2COCH3, 148 [naphthylamine]?, 127 [naphthyl]?, 74 [C2H5CONH2]?. Anal.
calcd. for C19H14N2O3: C, 71.69; H, 4.43; N, 8.80%; found: C, 71.41; H, 4.22; N,
8.42%
1,4-{3-Methyl-6-oxo-4,5,6,7-tetrahydro-1H-pyrazol[3,4-b]pyridine-4-yl)}benzene (4n)
Melting point (Mp) 217–220 °C. IR (KBr, cm-1): 3174 (NH), 2961, 1650 (CO),
1365, 734 (N–H), 486. 1H NMR (400 MHz, DMSO-d6): 11.75 (brs, 1H, NH), 10.11
(brs, 1H, NH), 7.30–7.29 (m, 1H, Ar), 6.19–6.17 (m, 1H, Ar), 3.50–3.47 (m, 1H,
CH), 3.15 (s, 3H, CH3), 2.42–2.18 (m, 2H, CH2). m/z 376 [M?], 329 [M?]-NH2CO,
265 [M?]-2C2H5, -2N2, 225 [M?]-C7H7NO3, 198 [M?]-C7H7NO3, -2Me, 109
[methylpyrazolyl]?. Anal. calcd. for C20H20N6O2: C, 63.82; H, 5.35; N, 22.32%;
found: C, 63.43; H, 5.12; N, 22.11%
General procedure for synthesis of coumarin-3-carboxylic esters
A mixture of Meldrum’s acid 1 (1.2 mmol), alcohols 5a–c (1 mmol), salicylalde-
hydes 6a–f (1 mmol), and nano-TiO2@Cg (0.04 g) was stirred under solvent-free
conditions at 100 °C. After completion of the reaction, the nano-catalyst was
separated by addition of methanol and filtration; the pure adducts 7a–k were
obtained by pale chromatography (n-hexane/ethylacetate eluent, 2:1).
8-Methoxy-2-oxo-2H-chromene-3-carboxylate (7h)
Mp 220–223 °C. IR (KBr, cm-1): 2956, 2855, 1749 (CO), 1474, 1417, 1272, 1102.
1H NMR (400 MHz, DMSO-d6): 8.65 (s, 1H, CH), 7.45–7.28 (m, 3H, Ar), 3.61 (s,
3H, CH3), 3.15 (s, 3H, CH3). m/z 234 [M?], 203 [M?]-OMe, 188 [M?]-OMe, -Me,
123

K. Nikoofar, F. Molaei Yielzoleh
159 [M?]-C6H5, 120 [methoxytolyl]?, 120 [anisolyl]?. Anal. calcd. for C12H10O5:
C, 61.54; H, 4.30%; found: C, 61.28; H, 4.22%
3-Oxo-2H-bnzo[f]chromene-2-carboxylate (7i)
Viscous liquid. IR (KBr, cm-1): 2930, 1739 (CO), 1601, 1434, 1334, 1276, 1161.
1H NMR (400 MHz, DMSO-d6): 8.58 (d, J = 10.5 Hz, 1H, Ar), 8.29 (d,
J = 10.41 Hz, 1H, Ar), 8.03 (s, 1H, CH), 7.91–7.87 (m, 2H, Ar), 7.64–7.57 (m,
2H, Ar), 3.61 (s, 3H, CH3). m/z 254 [M?], 236 [M?]-Me, 223 [M?]-OMe, 210
[M?]-CO2, -Me, 139 [naphthyl]?, 84 [methylacrylyl]?. Anal. calcd. for C15H10O4:
C, 70.86; H, 10.08%; found: C, 70.48; H, 10.02%
Results and discussion
Characterization of the catalyst
The FT-IR spectrum of nano-TiO2@Cg is presented in Fig. 1. As can be seen, the
stretching of C–H bonds of the graphite at 2922 cm-1 and 2853 cm-1 in addition to
the Ti–O–Ti peak at 706 cm-1 with a shoulder at 522 cm-1 [39] confirmed
successful embedding of nano-titania on the graphite surface. The broad band at
3647–3440 cm-1 belongs to the hydroxyl groups of adsorbed water on the nano-
structure surface.
The TGA/DTG diagram is shown in Fig. 2. According to the results, the
endothermic main weight loss of 83.3% took placed in one step which started
at 580 °C and ended at 670 °C. The main weight lost displayed at
265–380 °C occurred in a single endothermic step. The degradation in one
step confirmed that the synthesized nano-structure is a single system, not a
binary system.
The FESEM pattern of the synthesized catalyst is shown in Fig. 3, revealing the
product consists of nano-spheres with the average diameter of 35–50 nm. It also
demonstrates the morphology of the commercial nano-titania (average size of
25–30 nm) was not changed during the process.
EDAX results of nano-TiO2@Cg in Fig. 4 indicate that the catalyst is only made
up of carbon, titanium, and oxygen. No impurity related to nitric acid usage during
the activation of graphite has been observed.
The total acidity of the nano-catalyst was measured by potentiometric titration
with N-hexylamine as a strong base. Its adsorption could be expected on the
nano-structure sites related to its total solid acidity of nano-TiO2@Cg. The
potentiometric titration curves obtained for graphite, nano-titania, and the
supported catalyst are shown in Fig. 5. This technique evaluated the total number
of acid sites (meq N-hexylamine/g catalyst) and their strength (E) on the catalyst
surface. According to the scales illustrated in the correlation diagram at the
bottom of Fig. 5, graphite and nano-titania (with E values of -190 mV and
-148 mV, respectively) are classified as very weak acids. The nano-catalyst
showed an E of -10 mV which make it an acid with weak acidity power. The
123

Novel nano-titania embedded on graphite (nano-TiO2@Cg) as…
Fig. 1 FT-IR spectrum for nano-TiO2@Cg
Fig. 2 TGA/DTG diagram of nano-TiO2@Cg
data affirmed that supporting nano-titania on the graphite surface increased it
total acid sites. It is observed that the strength of acid sites of nano-TiO2@Cg is
stronger than each of its solid constituents [40].
123

K. Nikoofar, F. Molaei Yielzoleh
Fig. 3 FESEM image of nano-TiO2@Cg
Fig. 4 EDAX diagram of nano-TiO2@Cg
Investigation the catalytic activity
In the next step, the catalytic activity of nano-TiO2@Cg was examined in the
preparation of 4-aryl-3,4-dihydroquinolin-2(1H)-ones. In order to optimize the
reaction conditions, the reaction of Meldrum’s acid 1, aniline 2a, and
4-chlorobenzaldehyde 3b, in a 1:1:1 molar ratio, was considered as a model
reaction to determine the effect of various parameters. According to Table 1, the
model reaction proceeded in the presence of different solvents as well as solvent-
free situations. The best results obtained were in the absence of solvent. The results
123

Novel nano-titania embedded on graphite (nano-TiO2@Cg) as…
Fig. 5 Investigation of acidic strength of nano-TiO2@Cg via potentiometric titration curves
(entries 3–5) affirmed that the best temperature is 70 °C and elevating up to 90 °C
didn’t affect the progress of the reaction. Examination of the catalyst amount
revealed that 0.004 g is the best amount (Table 1, entries 6–8). In addition, in order
to affirm the strengthened catalytic activity of the synthesized nano-structure in
comparison with the pure nano-titania or graphite, the model reaction has also been
performed with each of them separately (entries 9 and 10). As can be seen,
embedding nano-TiO2 on the graphite surface increased it catalytic efficacy (entries
5, 9, and 10). The reaction without catalyst didn’t produce any by-products and the
substrate stayed intact (entry 11). All the entries of Table 1 have been examined in a
one-pot and one-step mode.
Based on optimized conditions, the reaction of Meldrum’s acid (1), aniline
derivatives (2a–e), and benzaldehydes (3a–d) proceeded in the presence of nano-
TiO2@Cg (0.004 g) at 90 °C under solvent-free conditions. The results are
summarized in Table 2.
According to the observed data in Table 2, aniline 2a and its electron-donating as
well as electron-withdrawing substituents reacted with Meldrum’s acid 1 and
123

K. Nikoofar, F. Molaei Yielzoleh
Table 1 Summary of the reaction conditions in the synthesis of 4-(4-chlorophenyl)-3,4-dihydroquinolin-
2(1H)-one 4b
Cl
H
O
NH2
O
O
O
O
N
H
4b
O
Cl
3b
1
2a
Entry
Conditions
Nano-TiO2@Cg amount (g)/solvent (5 mL)/temperature (°C)
Time (h)
Yielda (%)
1
0.004/H2O/reflux
0.004/EtOH/reflux
0.004/–/rt
3
5
2
4
45
–
3
4.5
4.5
4
4
0.004/–/70
52
90
65
57
67
53
12
–
5
0.004/–/90
6
0.004/–/100
0.002/–/90
3
7
4
8
0.008/–/90
4
9
0.004b/–/90
0.004c/–/90
–/–/90
4
10
11
4
4
aIsolated yields
bThe utilized catalyst was pure nano-TiO2
cThe utilized catalyst was graphite
different benzaldehyde derivatives 3a–c to obtain the corresponding products
successfully (entries 1–6). 1-Naphthylamine 2e, as a dense candidate of aromatic
amine, performed the same transformations well (entry 7). Utilizing 5-methylpyr-
azol-3-amine 2f, as a potent pharmaceutically heteroaromatic amine with different
benzaldehydes, also yielded 3-methyl-4-aryl/alkyl-2,4,5,7-tetrahydropyrazolo[3,4-
b]pyridin-6-ones 4h–l very well (entries 8–12). This condensation has also
performed well with butyraldehyde as an aliphatic model (entry 13). No significant
substituent effect relationship has been observed in the case of electron-donating
and electron-withdrawing benzaldehydes or amines.
The condensation of 1, 2f, and terephthaldehyde 3g, as a bifunctional aromatic
aldehyde, obtained the corresponding product 4n in good yield (entry 14). This
observation affirmed the interesting regiospecific condensation in both aldehydic
moieties without obtaining any byproduct of the one-moiety condensation reaction.
All the products were isolated and characterized by their Mp and spectroscopic data
(FT-IR, 1H NMR, and mass spectroscopy) in comparison with their authentic
samples.
In the second part of the research, the catalytic activity of the newly prepared
nano-catalyst was examined in the preparation of coumarin-3-carboxylic acid ester
123

Novel nano-titania embedded on graphite (nano-TiO2@Cg) as…
Table 2 Synthesis of 4-aryl-3,4-dihydroquinolin-2(1H)-one and 3-methyl-4-aryl/alkyl-2,4,5,7-tetra-
hydropyrazolo[3,4-b]pyridin-6-ones in the presence of nano-TiO2@Cg under solvent-free conditions at
90 °Ca
Entry
Amine
Aldehyde
Product
Time (h) Yield (%)
Mp (°C)
192-194
[41]
1
4a
4b
4
4
57
90
3a
2a
2a
213-215
[41]
2
3
3b
3a
188-189
[41]
4c
4d
4e
4
75
57
96
2b
200-201
[42]
4
5
3b
4.5
2.5
2c
2c
149-151
[42]
3c
3a
147-149
[41]
6
7
8
4f
4g
4h
4.5
5.5
5
73
91
63
2d
Viscous
New
3d
3a
2e
2f
303-305
[43]
123

K. Nikoofar, F. Molaei Yielzoleh
Table 2 continued
>300
9
2f
3b
4i
5
94
[43]
>300
10
11
2f
2f
3c
4j
5
3
72
[43]
266-268
3d
4k
93
[43]
>300
12
13
2f
2f
4l
3.5
5
98
[43]
3e
3f
258-260
4m
92
[43]
217-220
14b
2f
4n
5
97
New
3g
aAmine (1 mmol), aldehyde (1 mmol), Meldrum’s acid (1 mmol), nano-TiO2@Cg (0.004 g)
b1: 2f: 3g molar ratio of 2:1:2 in the presence of nano-TiO2@Cg (0.008 g)
via the one-pot, three-component condensation of Meldrum acid 1, alcohols 5a–c,
and salicylaldehydes 6a–f in the presence of 0.04 g of the nano-TiO2@Cg at 100 °C
under solvent-free conditions. It is interesting to mention that this class of
compounds has been studied very rarely (Table 3).
According to the obtained results, methanol and ethanol condensed with different
benzaldehydes successfully (entries 1–8). 2-Hydroxy-1-naphatldehyde, as a bicyclic
sterically hindered candidate, performed the reaction well (entry 9). Benzyl alcohol,
123

Novel nano-titania embedded on graphite (nano-TiO2@Cg) as…
a
Table 3 Synthesis of coumarin-3-carboxylic acid esters in the presence of nano-TiO2@Cg
Entry
1
Alcohol
Salicylaldehyde
Product
Time (h) Yield (%)
Mp (°C)
90–91
[33]
3
73, 71, 69b
5a
6a
6b
7a
7b
7c
192–193
[33]
2
3
5a
5a
5
6
82
81
175–177
[33]
6c
6a
118–120
[33]
4
5
6
6
86
74
5b
5b
7d
7e
7f
222–224
[33]
6b
6c
184–185
[33]
6
7
5b
5b
6
6
71
87
226–228
[33]
6d
6e
7g
7h
220–223
New
8
9
5b
5b
5
5
82
74
Viscose
New
6f
7i
88–91
[44]
10
11
6a
5
5
97
74
5c
5c
7j
236–237
[33]
6b
7k
aMeldrum’s acid (1 mmol), salicylaldehydes (1 mmol), alcohols (1 mmol) and nano-TiO2@Cg (0.04 g)
in the absence of solvent at 100 °C
bYields of 3 runs
123

K. Nikoofar, F. Molaei Yielzoleh
as another selection, produced the desired coumarin carboxylic ester analogues in
good yield (entries 10–11).
Finally, the reusability and recovery of the synthesized nano-catalyst was also
examined in the preparation of 7a. After completion of the reaction, methanol
(10 mL) was added to reaction mixture and the catalyst was filtered and washed
with further methanol (2 9 5 mL). With evaporation of the solvent followed by air
drying, the solid residue was utilized for another run. The results in Table 3 (entry
1) showed the catalyst could be recovered and reused simply at least for three runs
without activity loss.
Conclusions
In conclusion, we have explored a simple, efficient, and eco-friendly protocol for
the synthesis of 4-aryl-3,4-dihydroquinol-2-(1H)-ones and 3-methyl-4-aryl/alkyl-
2,4,5,7-tetrahydropyrazolo[3,4-b]pyridin-6-ones via a one-pot, three-component
reaction employing nano-TiO2@Cg as a novel, nontoxic, and efficient catalyst. The
newly synthesized nano-powder also promoted preparation of coumarin-3-
carboxylic acid esters successfully. The procedure offers several advantages,
including mild and neutral conditions, good yields of the products, elimination of
solvent, operational simplicity, minimum environmental impact, and easy workup.
Acknowledgements The authors thank Alzahra University for financial support of this research.
References
1. D. Astruc, F. Lu, J.R. Aranzaes, Angew. Chem. Int. Ed. 44, 7852 (2005)
2. R. Ahmad, M. Sardar, Int. J. Innov. Res. 2, 3569 (2013)
3. N. Rajalakshmi, N. Lakshmi, K.S. Dhathathreyan, Int. J. Hydrog. Energy 33, 7521 (2008)
4. F. Sayilkan, M. Asilturk, S. Sener, S. Erdemoglu, M. Erdemoglu, H. Sayilkan, Turk. J. Chem. 31, 219
(2007)
5. R.K. Saini, D. Singh, S. Bhagwan, V. Nishal, I. Singh, J. Nanoelectron. Optoelectron. 11, 715 (2016)
6. M. Tajbakhsh, E. Alaee, H. Alinezhad, M. Khanian, F. Jahani, S. Khaksar, P. Rezaee, M. Tajbakhsh,
Chin. J. Catal. 33, 151 (2012)
7. B.B.F. Mirjalili, A. Akbari, Chin. Chem. Lett. 22, 753 (2011)
8. A. Khazaei, A.R. Moosavi-zare, Z. Mohamadi, V. Khakhizadeh, J. Afshar, J. Chin. Chem. Soc. 63,
165 (2016)
9. M. Rahimizadeh, Z. Bakhtiarpoor, H. Eshghi, M. Pordel, G. Rajabzadeh, Monatsh. Chem. 140, 1465
(2009)
10. F.C. Cowlard, J.C. Lewis, J. Mater. Sci. 2, 507 (1967)
11. R. Zacharia, H. Ulbricht, T. Hertel, Phys. Rev. B Condens. Matter Mater. Phys. 69, 155406 (2004)
12. M. d’Halluin, Th Mabit, N. Fairley, V. Fernnandez, M.B. Gawwande, E. Le Grognec, F. Felpin,
Carbon 93, 974 (2015)
13. A. Schaetz, M. Zeltner, W.J. Stark, ACS Catal. 2, 1267 (2012)
14. R. Jamatia, A. Gupta, B. Dam, M. Saha, A. Kumar Pal, Green Chem. 19, 1576 (2017)
15. ZhK Lei, X. Li, X. Lu, H. Huang, ChJ Liu, Molecules 18, 1653 (2013)
16. U.N. Gupta, H. Alshammari, N.F. Dummer, R.L. Jenkins, D. Bethell, G.J. Hutchings, Catal. Sci.
Technol. 5, 1307 (2015)
17. K.N. Naeesh, G.M. Raghavendra, C.N. Revanna, T.A. Jenifer Vijay, K.S. Rangappa, K. Mantelingu,
Synth. Commun. 44, 1103 (2014)
18. S.B. Parsekar, S. Naik, M.M. Naik, S.G. Tilve, Monatsh. Chem. 146, 691 (2015)
123

Novel nano-titania embedded on graphite (nano-TiO2@Cg) as…
19. S. Luqman, A. Meena, P. Singh, T.P. Jondratyuk, L.E. Marler, J.M. Pezzuto, A.S. Negi, Chem. Biol.
Drug Des. 80, 616 (2012)
20. J.M. Singer, B.M. Barr, L.L. Coughenour, T.F. Gregory, M.A. Walters, Bioorg. Med. Chem. Lett. 15,
4560 (2005)
21. J. Krapcho, J. Schwartz, E.R. Squibb, US Patent 3994900
22. T. Ozturk, A. McKillop, Can. J. Chem. 78, 1158 (2000)
23. K. Li, L.N. Foresee, J.A. Tunge, J. Org. Chem. 70, 2881 (2005)
24. J. Wang, R.P. Discordia, G.A. Crispino, J. Li, J.A. Grosso, R. Polniaszek, V.C. Truc, Tetrahedron
Lett. 44, 4271 (2003)
25. B. Li, Y. Park, S. Chang, J. Am. Chem. Soc. 136, 1125 (2014)
26. E.F.M. Stephenson, J. Chem. Soc. 1956, 2557 (1956)
27. I. Mieri¸na, M. Jure, A. Stikute, Chem. Heterocycl. Compd. 52, 509 (2016)
28. G.H. Elgemeie, M.A. Abu-Zaied, S.A. Loutfy, Tetrahedron 73, 5853 (2017)
29. J. Feng, N. Haynes, J.C. Hermann, K. Kim, J. Liu, N.R. Scott, L. Yi, M.E. Zak, G. Zhao, US Patent
(2013) US20130345215 A1
30. J.B. Cross, J. Zhang, Q. Yang, M.F. Mesleh, J.A.C. Romero, B. Wang, D. Bevan, K.M. Poutsiaka, F.
Epie, T. Moy, A. Daniel, J. Shotwell, B. Chamberlain, N. Carter, J. Barker, M.D. Ryan, ChA Metcalf,
J. Silverman, K. Nguyen, B. Lippa, R.E. Dolle, A.C.S. Med, Chem. Lett. 7, 374 (2016)
31. X. Zhong, G. Dou, D. Wang, Molecules 18, 13139 (2013)
32. A. Azimi Roshan, M. Mamaghani, N.O. Mahmoodi, F. Shirini, Chin. Chem. Lett. 23, 399 (2012)
33. M. Mamaghani, F. Shirini, N.O. Mahmoodi, A. Azimi-Roshan, H. Hashemlou, J. Mol. Struct. 5, 169
(2013)
34. X. He, Y. Shang, Y. Zhou, Zh Yu, G. Han, W. Jin, J. Chen, Tetrahedron 71, 863 (2015)
35. F. Chimenti, D. Secci, A. Bolasco, P. Chimenti, A. Granese, O. Befani, P. Turini, S. Alcaro, F.
Ortuso, Bioorg. Med. Chem. Lett. 14, 3697 (2004)
36. Y.L. Zhang, B.Z. Chen, K.Q. Zheng, M.L. Xu, L.Z. Zhang, X.H. Lei, Yao Xue Xue Bao 17, 17
(1982)
37. B.S. Creaven, D.A. Egan, K. Kavanagh, M. McCann, A. Noble, B. Thati, M. Walsh, Inorg. Chim.
Acta 359, 3976 (2006)
38. K. Tanaka, F. Toda, Chem. Rev. 100, 1025 (2000)
39. X. Zhang, F. Zhang, K.-Y. Chan, Appl. Catal. A 284, 193 (2005)
40. R. Cid, G. Pecci, Appl. Catal. 14, 15 (1985)
41. D. Azarifar, D. Sheikh, Synth. Commun. 43, 2517 (2013)
42. I. Mieri¸na, A. Stikute, M. Jure, Chem. Heterocycl. Compd. 50, 1137 (2014)
43. H. Veisi, A. Maleki, S. Jahangard, Tetrahedron Lett. 56, 1882 (2015)
ˇ
44. M. Sova, A. Perdih, M. Kotnik, K. Kristan, T.L. Rizner, T. Solmajer, S. Gobec, Bioorg. Med. Chem.
14, 7404 (2006)
Affiliations
Kobra Nikoofar1 Fatemeh Molaei Yielzoleh1
•
&
Kobra Nikoofar
kobranikoofar@yahoo.com; k.nikoofar@alzahra.ac.ir
1
Department of Chemistry, Faculty of Physics and Chemistry, Alzahra University,
Vanak, Tehran 1993893973, Iran
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