Titania nanomaterials: Efficient and recyclable heterogeneous catalysts for the solvent-free synthesis of poly-substituted quinolines via Friedlander hetero-annulation

Article abstract of DOI:10.1039/c3ra46128a

The present communication describes the use of titania (TiO₂) nanomaterials of different sizes (16 nm, 35 nm, 70 nm, 200 nm, and 1000 nm) as heterogeneous catalysts for the preparation of a series of medicinally significant poly-substituted qui

Full text of DOI:10.1039/c3ra46128a

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Titania nanomaterials: efficient and recyclable
heterogeneous catalysts for the solvent-free
synthesis of poly-substituted quinolines via
Friedlander hetero-annulation†
Cite this: RSC Adv., 2014, 4, 6638
a
a
b
Prabal Bandyopadhyay,ab G. K. Prasad, Manisha Sathe, Pratibha Sharma,
*
b
a
*
Ashok Kumar and M. P. Kaushik
The present communication describes the use of titania (TiO2) nanomaterials of different sizes (16 nm,
35 nm, 70 nm, 200 nm, and 1000 nm) as heterogeneous catalysts for the preparation of a series of
medicinally significant poly-substituted quinoline derivatives via Friedlander hetero-annulation. These
TiO2 nanomaterials exhibited remarkable catalytic activity with a high substrate to catalyst molar ratio
(20 : 1) to achieve the synthetic targets in excellent yields ranging from 81–94%. The effect of catalyst
particle size on the yield of the quinolines was also investigated. Yields of product were found to
decrease when the TiO2 particle size increased from 16 nm to 1000 nm. GC-MS data indicated that TiO2
nanoparticles having 16 nm and 35 nm size of anatase phase provided better yields of the target
compound, followed by particles of 70 nm in size, whereas 200 nm and 1000 nm size of anatase phase
did not show the formation of the product under the same reaction conditions. The use of catalyst in
solvent-free reaction conditions and its reusability up to five-cycles with similar catalytic response are
the unique features of this heterogeneous catalysis. Furthermore, greater selectivity, cost-efficiency,
clean reaction profiles, simple work-up procedure and high yield are the noteworthy features of this
eco-friendly green protocol.
Received 25th October 2013
Accepted 18th December 2013
DOI: 10.1039/c3ra46128a
www.rsc.org/advances
assembly into a variety of nano-structures and meso-structures
with enhanced electronic and photonic functions.7 Moreover,
1. Introduction
quinolines have been employed in the study of bioorganic and
bioorgano-metallic processes.8
The quinoline ring system is an important constituent of
pharmacologically active synthetic compounds as this core
structure has been found to be associated with a wide spectrum
of biological properties1 such as DNA binding capability,2 anti-
tumor activities3 and acting as a DNA-intercalating carrier.4 Also
quinolines and their derivatives constitute the integral part of
various drugs such as anti-malarial, anti-bacterial, anti-asth-
matic, anti-hypertensive, anti-inammatory, and anti-platelet
activity drugs and as tyrokinase PDGF-RTK inhibiting agents.5
Some currently available effective anti-malarial agents such as
quinine, chloroquine, meoquine, and primaquine contain a
quinoline core moiety.6 In addition to medicinal applications,
quinoline derivatives are found to undergo hierarchical self-
Considering the signicant applications in the elds of
medicinal, bioorganic, industrial and synthetic organic chem-
istry, there has been tremendous interest in developing efficient
methods for the synthesis of quinolines. Many methods have
been reported in the literature for the construction of quinoline
building blocks, which include the classical Skraup, Doebner–
von Miller, Friedlander, Ptzinger, Conrad–Limpach and
Combes methods.9 Amongst them, the Friedlander annula-
tion10 is one of the most simple and straightforward approaches
for the synthesis of polysubstituted quinolines. The Friedlander
quinoline synthesis consists of the reaction between aromatic
ortho-amino ketones or aldehydes and a second carbonyl
compound containing a reactive a-methylene functionality.
Uncatalyzed Friedlander synthesis requires more drastic reac-
aDefence Research & Development Establishment, Jhansi Road, Gwalior 474 002, M.P.,
India. E-mail: mpkaushik@rediffmail.com; Fax: +91-751-2343972; Tel: +91-751-
2340042
tion conditions, with temperatures in the range 150–220 C.11
ꢀ
The reaction can be promoted by acid or base catalysis or by
heating. However, under thermal or base catalyzed conditions,
2-aminobenzophenone fails to react with simple ketones such
as cyclohexanone, deoxybenzoin and b-keto esters. In general,
better yields of quinolines could be achieved under acid
bSchool of Chemical Sciences, Devi Ahilya University, Takshashila Campus, Khandwa
Road, Indore 452 001, M.P., India. E-mail: drpratibhasharma@yahoo.com; Fax: +91-
731-2470352; Tel: +91-731-2460208
† Electronic supplementary Information (ESI) available: General experimental
information, spectral characterization data and copies of ESI-MS and GC-MS
spectra of the products. See DOI: 10.1039/c3ra46128a
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catalysis conditions.12 In many cases acid catalyzed Friedlander
condensations have been found to be more effective than
those by bases, especially when one of the reactants is a 2-
aminoarylketone.13
Acid catalysts such as hydrochloric acid, sulfuric acid,
p-toluenesulfonic acid and polyphosphoric acids have been
widely employed for this conversion.11a,14 In addition, modied
methods employing phosphoric acid, diphosgene, AuCl3, NaF,
ZnCl2, FeCl3, CuCl2, Sc(OTf)3, silver phosphotungstate,
NaAuCl4$2H2O, CeCl3$7H2O, Nd(NO3)3$6H2O, I2, sulfamic acid,
and ionic liquids have been reported for the synthesis of
quinolines.15 More recently, Y(OTf)3 has been employed for this
conversion.15f However, most of the synthetic protocols reported
so far suffer from several bottlenecks, such as the requirement
of drastic reaction conditions (strong acids, high temperatures),
prolonged reaction time, use of toxic and expensive reagents,
use of hazardous solvents, formation of by-products which
resulted in poor yields of the desired product and use of
hazardous and oen expensive acid and base catalysts. More-
over, the synthesis of these heterocycles has been carried out in
polar aprotic solvents such as acetonitrile, THF, DMF and
DMSO leading to complex isolation and tedious work-up
procedures. These processes also generate waste-containing
solvent and catalyst, which have to be recovered, treated, and
disposed off. Furthermore, the main disadvantage of almost all
existing methods is that the catalysts are destroyed during the
reaction work-up procedure and cannot be recovered or reused.
As a consequence, search for new methods/reagents/catalysts to
overcome these limitations are still an important experimental
challenge to synthetic organic chemists. In the light of these
shortcomings, in this paper we wish to propose a simple and
Scheme
1
Synthesis of polyfunctionalized quinolines using TiO2
nanomaterials via Friedlander hetero-annulation.
larger surface area to volume ratio and increased number of
surface defect sites.20
Particle size also plays a crucial role in the dynamics of
electron/hole recombination processes and it inuences
catalytic properties. In addition to these, TiO2 is more stable,
abundant, non toxic, and economical. For this purpose, we have
synthesized TiO2 materials of nanosize by a modied sol–gel
method and characterized them by XRD, TEM, N2 BET, and FT-
IR techniques. In continuation of our work on new synthetic
strategies,19,21,22 herein, we report the size dependant applica-
tion of TiO2 nanomaterials of different sizes (16 nm, 35 nm,
70 nm, 200 nm, and 1000 nm) as reusable heterogeneous
catalysts for the synthesis of polysubstituted quinoline deriva-
tives 3a–n (Scheme 1) via Friedlander hetero-annulation under
solvent-free conditions. Subsequently, we have studied the
effect of particle size of TiO2 on the yields of quinoline deriva-
tives by GC-MS (see ESI†).
¨
efficient quinoline synthesis consisting of a Friedlander annu-
lation strategy with TiO2 as a reusable heterogeneous acid
catalyst.
Furthermore, the toxic and volatile nature of many organic
solvents used in organic synthesis has posed a serious threat to
the environment. Consequently, methods that successfully
2. Results and discussions
2.1. Characterization of the TiO2 particles
minimize their use are currently the subject of considerable TEM was used to determine the crystallite sizes of TiO2 particles
attention for synthetic chemists.16,17 Moreover, it is important to synthesized by modied sol–gel method followed by hydro-
note that the combination of heterogeneous catalysis with the thermal treatment. Temperature for hydrothermal treatment
use of solvent-free conditions represent a suitable way toward was kept at 100 ꢀC, and 180 ꢀC for 24 h for 16 nm and 35 nm size
the so-called ideal synthesis. Recent advances in nanotech- of anatase phase, respectively. TEM imageꢀ of TiO2 particles
nology have led to an increasing demand for multifunctional obtained by hydrothermal treatment at 100 C shows the crys-
materials. Highly ordered materials function as excellent cata- tallites with ꢁ16 nm size (Fig. 1), whereas, the image of TiO2
ꢀ
lysts owing to their high surface area and surface functional- particles obtained by hydrothermal treatment at 180 C shows
ities. Thus, the synthesis of ordered nanomaterials has crystallites 35 nm in size. Particle sizes of purchased samples
attracted a great deal of research interest in the last few years.18 were found to be 70, 200, and 1000 nm by SEM analysis (Fig. 2).
The advantages of nanocatalyst and solvent-free reaction
TEM and SEM data also indicated that both the synthesized
conditions can provide better compromise to achieve as well as the purchased TiO2 particles were spherical in shape.
a
parameters of green protocol for the synthesis of quinoline They also show randomly oriented aggregates of spherical
derivatives. Recently we explored successfully the use of meso- nanoparticles whose sizes range from 16 nm to 1000 nm.
porous mixed metal oxide nanocrystals for the synthesis of Enlargement of crystallite size from 16 nm to 35 nm with
pharmacologically signicant 1,2-disubstituted benzimidazoles increased hydrothermal temperature can be ascribed to crys-
and 2-substituted benzothiazoles.19
tallization of large particles due to increased rate of nucleation
The physical and chemical properties of TiO2 materials and growth at increased temperatures. Moreover, titania crys-
depend on their particle size. Smaller sized particles are tals were found to be self assembled in random manner to form
expected to exhibit better chemical reactivity because of the aggregates with porous structure. Porous aggregates composed
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of self-assembled nanoparticles probably formed due to the
structural similarity of the TiO2 nanoparticles as well as the
charges that were present on their surface.
These defects probably formed during the nucleation and
growth of the nanoparticles. XRD data of synthesized and
purchased titania particles depicted peaks at 2q values 25.2ꢀ,
37.8ꢀ, 48.0ꢀ, 53.8ꢀ, and 62.7ꢀ. These peaks can be attributed to
the presence of (1 0 1), (0 0 4), (2 0 0), (1 0 6), and (2 1 5) indices.
This XRD (Fig. 3.) pattern illustrates 2q values and relative
intensities of peaks that match with JCPDS data of the anatase
phase of TiO2. The data also illustrated peak broadening in
XRD pattern indicating the formation of crystallites with very
small size.
Surface area to volume ratio plays a signicant role in the
catalytic activity of a material along with surface defects present
on TiO2 particles. On decreasing particle size, surface area to
volume ratio increases gradually, thereby enhancing the cata-
lytic activity. In order to understand how the values of surface
area change, titania particles of various sizes were characterized
by nitrogen adsorption measurements. Nitrogen adsorption
Fig. 1 TEM image of TiO2 nanocrystals (16 nm).
Fig. 2 SEM images of TiO2 particles of size (a) 1000 nm, (b) 200 nm, (c) 70 nm, (d) 35 nm.
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Fig. 3 XRD pattern of TiO2 particles of different sizes (1000 nm,
200 nm, 70 nm, 35 nm, and 16 nm).
Fig. 5 Pore size distribution data of titania particles of various sizes.
The values of surface area and pore volume obtained from
nitrogen adsorption data are given in Table 1. Of all these,
titania particles having 16 nm size exhibited high values of
surface area 186 m2 gÀ1. All the materials exhibited meso
porosity and values of pore volume were observed to be in the
range of 0.03 to 0.29 mL gÀ1. The pore size distribution data is
depicted in Fig. 5.
TiO2 particles seemed to aggregate in order to satisfy steric
and electrical charge imbalances and formed mesopores. In
addition to this, average pore diameter decreased from 13.7 nm
to 5.0 nm when the size of the material was reduced from
1000 nm to 16 nm. This observation can be ascribed to the fact
that when bigger sized particles aggregated, voids of relatively
larger size were found to be formed, whereas on reduction of
size, materials with smaller sized voids were observed to be
formed on aggregation and this is well illustrated in Table 1.
Besides surface area to volume ratio, surface hydroxyl
groups, surface defects, oxygen vacancies in TiO2 nanoparticles
Fig. 4 Nitrogen adsorption isotherms of titania particles of various
sizes.
data indicated type IV isotherm (Fig. 4) with hysteresis typical of
mesoporous materials having pore maxima centred at 5.0 in
case of particles of sizes 16 nm.
Table 1 BET Surface area, cumulative pore volume and pore diameter
values for TiO2 particles of various sizes
Crystallite BET surface
Cumulative pore Pore diameter
Sl. No. size (nm) area (m2 gÀ1
)
volume (mL gÀ1
)
(nm)
1.
2.
3.
4.
5.
1000 nm
200 nm
70 nm
35 nm
16 nm
16.5
14.8
31
75
186
0.03
0.02
0.08
0.27
0.29
13.7
12.0
11.0
10.2
5.0
Fig. 6 FT-IR spectrum of titania particles of 16 nm size.
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Table
3
Recyclability of the TiO2 nanocatalyst (16 nm) for the
are expected to play major role in providing reactive sites for
the preparation of poly-functionalized quinolines via Fried-
lander hetero-annulation. A broad FT-IR signal centred at
ꢁ3300 cmÀ1 indicated the presence of hydroxyl groups in
titania nanoparticles of 16 nm size (Fig. 6). Collectively, surface
hydroxyl groups, oxygen vacancies, Lewis acid sites, and other
defects in TiO2 nanoparticles play major role in the preparation
of polyfunctionalized quinolines via Friedlander hetero-
annulation.
Hence keeping these facts in mind, herein, we were inter-
ested in achieving the Friedlander quinoline synthesis using
TiO2 nanomaterials as the catalytic support under solvent free
conditions. Our investigation started with an optimization
study for the reaction between 2-aminoacetophenone 1 and
synthesis of ethyl 2,4-dimethylquinoline-3-carboxylate (3a)a
Entry
Cycle
Yieldb (%)
1
2
3
4
5
Cycle 1
Cycle 2
Cycle 3
Cycle 4
Cycle 5
92
90
89
88
86
a
Reaction condition: The mixture of 2-aminoacetophenone (1 mmol),
ethyl acetoacetate (1.25 mmol), TiO2 nanomaterials (5 mol%) was
heated at 80 ꢀC for 12 min. b Yields aer consecutive cycles.
Considering the optimized reaction conditions in hand, the
ethyl acetoacetate 2a in the presence of a catalytic amount of scope of the protocol was further explored for the reaction of a
TiO2 (Table 2), which established that the best conditions variety of substituted acyclic and cyclic ketones/diketones/
ꢀ
involved 5 mol% of TiO2 at 80 C to afford the corresponding b-keto esters (containing active methylene groups) (Table 3).
ethyl 2,4-dimetyl quinoline-3-carboxylate (3a) (Table 4, entry 1) The desired coupling followed by intramolecular cyclization
in 92% yield without any side products (Fig. 7). This two was obtained with acyclic b-keto esters (entries 1–5, Table 4) in
component coupling reaction proceeded efficiently at reux 81–94% yield. Likewise, using this protocol, acyclic diketone
temperature with high selectivity under solvent-free reaction and 2-aminoacetophenone underwent coupling followed by
condition. GC-MS data indicated that TiO2 nanoparticles having intramolecular ring closure to give the corresponding 1-(2,4-
16 nm and 35 nm size of anatase phase provided better yields of dimethylquinolin-3-yl)ethanone (entry 6, Table 4) in 89% yield.
the target compound, followed by particles of 70 nm in size, Furthermore, cyclic ketones such as cyclopentanone, cyclohex-
whereas 200 nm and 1000 nm size of anatase phase did not anone, 2-methylcyclohexanone (entries 7–9, Table 4) also
show the formation of the product under the same reaction afforded the desired products with 85–88% yield.
conditions (see GC-MS spectra in the ESI†).
Additionally, the reaction was also successful with cyclic
diketones, such as cyclohexane-1,3-dione, 2-methylcyclohexane-
1,3-dione (entries 10 and 11, Table 4), under the same reaction
condition with 84–87% yield. Our effort to produce alkyl
9-methyl-2,3-dihydro-1H-cyclopenta/cyclohexa[b]quinoline-3-
carboxylate derivative, from cyclic b-keto esters (entries 12–14,
Table 4) was also successful with 78–90% yield. In all these cases
the target products, i.e., quinoline derivatives 3a–f and fused
polycyclic quinolines 3g–n were obtained in high regiose-
lectivity and good to excellent yields under mild and solvent-free
conditions with simple work-up. It is evident from the MS data
of crude products (see ESI†) that all reactions were clean and no
self-condensation products were formed which are normally
observed under basic conditions. Both ketones and b-keto
esters afforded excellent yields of products in a short reaction
time. The optimized reaction condition shows that using 5 mol
% of TiO2 nanomaterials under solvent free conditions gave the
best results in terms of yields and reaction time. During the
reaction work-up we found that the TiO2 nanomaterials remain
as solid material, insoluble in ethylacetate. However, the
product and unreacted starting material are soluble in ethyl-
acetate. Thus, the TiO2 acts as an acidic solid support and its
hydrogen bonding interactions are sufficient to augment the
catalyzed reaction. Also, in case of the reaction of ethyl ace-
toacetate we have checked the recyclability of such TiO2 nano-
materials for ve times. It gives the reaction with same
efficiency (only slight decrease from 92% to 86%) as that of
fresh TiO2 nanomaterials.
2.2. Reusability of the catalyst
At the end of the reaction, the catalyst was ltered-off, from the
crude reaction mixture, washed with mixture of hot ethanol and
water, dried and activated at 300 ꢀC for 2 h, and reused as such
for subsequent experiments (up to ve cycles) under similar
reaction conditions. It was noticed that yields of the product
remained comparable in these experiments (Table 3), and
thereby showing the recyclability and reusability of the catalyst
without any signicant loss in catalytic activity. The recyclability
of the catalyst was veried on the reaction of 2-amino-
acetophenone and ethyl acetoacetate (Table 3) to afford quin-
olines in 92 to 86% yields over ve cycles.
Table 2 Effect of catalyst concentration for the synthesis of ethyl
2,4 dimethylquinoline-3-carboxylate (3a) using TiO2 nanomaterials
(16 nm)a
Catalyst conc.
(mol%)
Reaction
Entry
timeb (min)
Yieldc (%)
1
2
3
4
5
1
2.5
5
10
20
12
12
12
12
12
55
69
92
90
84
a
Reaction condition: The mixture of 2-aminoacetophenone (1 mmol),
ethyl acetoacetate (1.25 mmol), with different concentration of catalyst
Higher amounts of the TiO2 nanomaterials did not improve
the yields. However, in the absence of TiO2 nanomaterials, the
reaction did not proceed even aer long reaction times (10–24 h).
b
was heated at 80 ꢀC. All the reactions were monitored by TLC and
GC-MS. c Isolated yield.
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Table 4 Synthesis of quinoline and polycyclic quinolines (3a–n)a using
TiO2 nanomaterials (16 nm)
Entry Ketone (2)
Product (3)
Timeb (min) Yieldc (%)
1
12
27
92
94
Fig. 7 GC-MS spectrum of the product (3a) using TiO2 nanoparticles
as the catalyst.
2
3
All the compounds were well characterized by 1H-NMR,
13C-NMR, and ESI-MS spectral analyses (see ESI†). These results
show that TiO2 nanomaterials being easily available and
cheaper can act as good acid catalyst under solvent free reaction
conditions. The efficient and successful utilization of TiO2
nanomaterials in such type of fundamental transformations
suggests that its utility can be further extended to the various
transformations. When we carried out the same reaction in
solution using various solvents like acetonitrile, ethanol,
dichloromethane we get poor results. Hence it may be possible
that under solvent free conditions TiO2 nanomaterials can
provide an efficient H-bonding interaction forces to catalyze the
reaction. The possible mechanistic path for the synthesis of
polyfunctionalized quinolines using TiO2 nanoparticles via
Friedlander hetero-annulation is given in Fig. 8. The TiO2
nanoparticles used contain surface hydroxyl groups, oxygen
vacancies, Lewis acid sites (Ti4+), and other defects which play a
major role in providing reactive sites for the preparation of
polysubstituted quinolines. The Lewis acid sites and surface
hydroxyl groups in TiO2 react with carbonyl oxygen of ketone/
b-keto ester 2 through the formation of surface bound hydrogen
bonded species, which undergo intramolecular cyclization to
produce the target heterocycles.
34
87
4
5
6
45
22
35
83
81
89
7
8
9
21
27
14
88
85
85
3. Experimental
3.1. Materials
10
11
10
25
87
84
TiO2 of different sizes 1000 nm, 200 nm, 70 nm, 35 nm, and
16 nm of pure anatase form were used in this study. Among
them, TiO2 particles having 16 and 35 nm sizes were prepared in
our laboratory by a modied sol–gel method. TiO2 of pure
anatase phase having 1000 nm, 200 nm, 70 nm sizes were
purchased from Alfa-Aesar, UK. Titanium tetrachloride was
purchased from Acros Organics, UK. Ethanol and acetone were
obtained from E. Merck India Ltd. 2-Aminoacetophenone and
various aromatic and aliphatic ketones were purchased from
Sigma Aldrich, India. Chemicals purchased from Across, Sigma-
Aldrich and Merck (India) were used without further
purication.
12
13
12
37
90
84
14
20
78
3.2. Catalyst preparation
TiO2 particles of 16 and 35 nm in size were prepared in our
laboratory by a modied sol–gel method as follows: 50 g of TiCl4
was slowly added to 500 mL of ethanol at 0 C in an ice-water
bath. During the mixing process, a large quantity of yellowish
a
Reaction condition: 2-aminoacetophenone (1 mmol), ethyl acetoacetate
ꢀ
b
(1.25 mmol), TiO2 nanomaterials (5 mol%). All the reactions
monitored by TLC and GC-MS. c Isolated yield.
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Fig. 8 Proposed mechanism for the synthesis of polyfunctionalized quinolines using TiO2 nanomaterials.
gas, presumably EtCl and HCl, was released as a consequence of reaction progress was monitored by TLC. Aer the completion
the predominant alcoholysis of TiCl4 for 12 h with ethanol and a of reaction, it was cooled to room temperature and extracted
partial hydrolysis of TiCl4 with the residual water. Aer stirring with ethyl acetate. The catalyst was separated out by ltration
at ambient conditions for 2 h, a transparent yellowish sol was from the crude reaction mixture. The product was then extrac-
formed which was then placed in an oven and baked at 87 ꢀC for ted with ethyl acetate. Organic layer was separated, dried over
3 days, producing an off-white powder. The powder obtained anhydrous sodium sulfate and concentrated under reduced
was calcined at 600 ꢀC for 2 h to give titania crystallites of pressure. The crude product was then puried by column
relatively larger size.23
chromatography over silica gel using hexanes/EtOAc (9 : 1, v/v)
as the eluting solvent system, yielding the pure products. In
some cases the product was viscous while the solid products
were primarily identied by comparison of their melting point
with the reported value. Further the products were conrmed by
spectral analysis.
3.3. Catalyst characterization techniques
Powder X-ray diffraction (XRD) patterns of the prepared
samples along with commercial ones were obtained by X Pert
Pro Diffractometer, Panalytical, Netherlands, using Cu Ka
radiation. Transmission electron microscopy (TEM) measure-
ments were done on a Tecnai FEI transmission electron
microscope. Samples were suspended in 30 mL acetone, and
then suspension was sonicated for 30 min. Aer that, the
suspension was placed on carbon coated copper grids of 3 mm
diameter and dried at room temperature prior to the analysis.
Scanning electron microscopy (SEM) measurements were done
on a FEI instrument. N2 BET measurements were performed on
ASAP 2020, Micrometrics, USA. FT-IR measurements were
recorded as KBr pellets on a Bruker Tensor 27 spectrometer.
4. Conclusion
In conclusion, a simple, efficient and environmentally benign
method has been developed using TiO2 nanomaterials as
heterogeneous nanocatalyst for the synthesis of quinoline and
polycyclic quinolines via Friedlander hetero-annulation of
2-aminoacetophenone with a-methylene ketones under solvent-
free reaction conditions. It was revealed that with the decrease
of particle size from 1000 nm to 16 nm, there was a gradual
increase in the yield of the quinoline derivatives. This one-pot,
titania nanomaterial catalyzed synthetic method is an unprec-
edented, inexpensive and rapid alternative for the generation of
3.4. Catalytic activity: synthesis of quinoline derivatives
To a mixture of 2-aminoacetophenone (1 mmol) and enolisable structurally diversied polyfunctionalized quinolines. The
ketone (1.25 mmol), catalytic amount (5 mol%) of TiO2 nano- combination of titania nanocatalyst in solvent-free reaction
materials (16 nm) was added at room temperature under stir- conditions under heterogeneous catalysis conditions was
ring. The reaction mixture was heated on oil bath at 80 ꢀC. The instrumental in reducing the reaction times and increasing
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yields. The environmental compatibility and excellent reus-
ability of the catalyst and operational simplicity and high yields
are among the other added advantages that make this approach
an attractive alternative for the synthesis of target heterocycles.
Chem., 2002, 67, 9449; (c) H. Skraup, Chem. Ber., 1880, 13,
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¨
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of the reactions by simple ltration and washing; (3) target
products are obtained in excellent yields under mild reaction
conditions; and (4) the reactions are carried out under solvent
free conditions with economic benets.
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Acknowledgements
We are thankful to Defence Research & Development Organi-
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