Au-doped TiO2 nanoparticles for selective photocatalytic synthesis of quinaldines from anilines in ethanol

Article abstract of DOI:10.1016/j.tetlet.2010.07.071

A convenient eco-friendly photocatalytic synthesis of quinaldines has been developed by a simple one-pot reaction of anilines in ethanol solution with Au-loaded TiO₂ under UV irradiation. Upon irradiation in the presence of Au-TiO₂, aniline and oxidation products derived from ethanol undergo condensation-cyclization to afford quinaldines.

Full text of DOI:10.1016/j.tetlet.2010.07.071

Tetrahedron Letters 51 (2010) 4911–4914
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Au-doped TiO2 nanoparticles for selective photocatalytic synthesis
of quinaldines from anilines in ethanol
*
K. Selvam, M. Swaminathan
Department of Chemistry, Annamalai University, Annamalainagar 608 002, India
a r t i c l e i n f o
a b s t r a c t
Article history:
A convenient eco-friendly photocatalytic synthesis of quinaldines has been developed by a simple one-
pot reaction of anilines in ethanol solution with Au-loaded TiO2 under UV irradiation. Upon irradiation
in the presence of Au-TiO2, aniline and oxidation products derived from ethanol undergo condensa-
tion–cyclization to afford quinaldines.
Received 29 May 2010
Revised 7 July 2010
Accepted 14 July 2010
Available online 17 July 2010
Ó 2010 Elsevier Ltd. All rights reserved.
Keywords:
Aniline
Au-TiO2
Photocatalysis
Quinaldine
Selectivity
Organic transformations for the synthesis of fine chemicals
through semiconductor photocatalysis have become an important
area of research for the last two decades.1,2 The fact that some
chemical reactions occur only in photocatalytic systems is particu-
larly significant for this application.3–6 However, in spite of several
semiconductor-mediated reactions, examples of combined redox
reactions are rather limited in the literature.7–9 For multi-step syn-
thesis, an illuminated semiconductor does offer a unique feature:
an intermediate generated at one reactive site (oxidatively or
reductively) can be the substrate at another reactive site. The inte-
grated use of both the reactive sites can complete a sophisticated
multi-step synthesis in ‘one-pot’.
Quinoline and its derivatives have been the subject of much re-
search due to their importance in various applications and their
widespread biochemical significance. A large variety of quinoline
derivatives have been used as antimalarial, anti-inflammatory,
antiasthmatic, antibacterial, antihypertensive, and tyrokinase
PDGF-RTK inhibiting agents.10–13 In view of these properties, great
efforts have been made to develop new and efficient synthetic
routes to quinoline derivatives in both synthetic organic and
medicinal chemistry. Many of these routes have limitations,
including long reaction time and harsh reaction conditions with
hazardous reagents.
tetrahydroquinolines have been carried out. A number of photocat-
alysts such as TiO2, TiO2 with a co-catalyst (p-toluenesulfonic acid),
and others have been used.14–16 However, the selective formation of
quinaldine derivatives from anilines has not been reported. From
the point of view of selective conversion of fine chemicals, particular
attention is devoted to the possibility of converting anilines to the
corresponding quinaldines with good chemo- and regio-selectivity.
Our laboratory has been engaged mainly with the development of
modified semiconductor photocatalysts for environmental remedi-
ation and organic synthesis.17–19 Thus in the present study, we
examined photocatalytic conversion of aniline and its derivatives
with absolute ethanol using TiO2 or Au-TiO2 as photocatalysts. To
our knowledge this Letter describes the first synthesis of quinal-
dines from anilines under mild conditions using UV light. Nanome-
ter-sized Au particles on TiO2, (Au/TiO2) were prepared by sol–gel
method,20 and characterized by AFM, TEM, X-ray diffraction
(XRD), and diffuse reflectance spectroscopy (DRS) techniques (see
Supplementary data, Figs. S1–S4).
The catalytic activity of Au-TiO2 for the synthesis of quinaldine
2 was investigated for the reaction of aniline 1 with ethanol.21 The
concentrations of 1 and the product, quinaldine 2, in EtOH solution
upon photoirradiation (365 nm) were measured over times (Fig. 1).
With pure TiO2 ( Fig. 1a), 6 h photoirradiation was required to
achieve >99% consumption of 1, affording 2 in only circa 50% and
2,3-dimethylindole (15%) in addition to small amounts of other
reduction products (5%). The structure of each product was
confirmed by GC/MS (see Supplementary data). The percentage
yield was determined by comparison with the retention times
of authentic samples and by co-injection with the authentic
Apart from thermal synthetic routes to quinolines, very few
studies on photocatalytic cyclization of nitrobenzene and its
derivatives to yield the corresponding substituted quinolines and
* Corresponding author. Tel.: +91 4144 225072; fax: +91 4144 238145.
E-mail address: chemres50@gmail.com (M. Swaminathan).
0040-4039/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2010.07.071

4912
K. Selvam, M. Swaminathan / Tetrahedron Letters 51 (2010) 4911–4914
Table 2
Effect of water content on photocatalytic properties
Run
Conditions
Neat ethanol
Ethanol–H2O (99/1)
Ethanol–H2O (98/2)
Ethanol–H2O (96/4)
Yield of quinaldine (%)
75
30
17
5
Conversion (%)
1
90
99
99
85
2
3
4
All reactions were performed with a 25 mM alcoholic solution of a reactant 50 mg
of Au-TiO2 suspension, I = 1.381 Â 10À3 einstein LÀ1 sÀ1, irradiation time = 4 h.
indicates that Au-TiO2 promotes rapid and selective quinaldine
production.
The higher conversion of aniline with Au-TiO2 (Fig. 1b) is due to
the trapping of electrons by Au on the excited TiO2. This enhances
the charge separation between electron and hole.22 This hole accel-
erates the oxidation of the alcohol to aldehyde, thus facilitating the
rapid condensation between 1 and the aldehyde. The trapped
electrons by the gold particles are consumed efficiently by the
reduction of H+ formed during the oxidation of the alcohol.23 Con-
trolled experiments demonstrated that aniline did not undergo any
reaction in the absence of TiO2 or without irradiation. The progress
of the reaction was monitored by TLC and yields reported were
estimated on the basis of GC. GC–MS chromatograms recorded at
different reaction times of the photocatalytic conversion of aniline
in ethanol are presented in Supplementary data (Fig. S5).
This process is tolerant for the synthesis of various substituted
quinaldines. Photoirradiation of alcohol solutions that contained
various anilines and the Au-TiO2 catalyst successfully afforded
the corresponding quinaldines (Table 1). In the case of p-toludine,
the main product was 2,6-dimethylquinoline. m-Toludine and o-
toludine produced 2,7-dimethylquinoline (80%) and 2,8-dimethyl-
quinoline (68%), respectively. Irradiation of 3,5-dimethylaniline
and 2,5-dimethylaniline led to the formation of 2,5,7-trimethyl-
quinoline and 3,5,7-trimethylquinoline. When p-anisidine was
used, 6-methoxyquinaldine was formed in slightly higher yield.
In the case of 4-chloro- and 4-fluoroanilines, the yield of quinal-
dines was very low. This is attributable to photoinduced dehalo-
genation. Dehalogenated anilines have been identified in GC–MS
analysis. It is interesting to observe that p-phenatidine has a con-
version efficiency of 94% in the presence of irradiated Au-TiO2. This
is in contrast to the combined redox reaction of m-nitroanisole to
tetrahydroquinoline, where the reaction proceeds rather slowly
due to the presence of OCH3 compared to those having alkyl sub-
stituent under the same reaction conditions.14
Figure 1. Time-dependent change in the concentrations of substrate and products
during photoirradiation of aniline in neat EtOH with (a) TiO2 and (b) Au-TiO2
catalyst. Reaction conditions: 25 mM of aniline in ethanol, TiO2 = 50 mg.
compounds. The main product identified was quinaldine. In con-
trast, Au (1%)-TiO2 promoted the rapid and selective production
of 2 by achieving 99% consumption of 1 with only 4 h irradiation
to afford 2 in 75% yield and 2,3-dimethylindole (10%) (Fig. 1b). This
Table 1
Photocatalytic synthesis of various substituted quinaldines
Run
1
Conditionsa
Aniline
Products yield (%)
Byproduct (%)
5
Conversion
90
Quinaldine (75)
2,3-Dimethylindole (10)
2
3
4
4
5
6
7
8
9
o-Toludine
m-Toludine
p-Toludine
o-Anisidine
m-Anisidine
p-Anisidine
3,5-Dimethylaniline
2,5-Dimethylaniline
3,5-Dimethoxylaniline
p-Phenatidine
p-Chloroaniline
p-Fluoroaniline
2,8-Dimethylquinoline (68)
2,7-Dimethylquinoline (80)
2,6-Dimethylquinoline (70)
5-Methoxy-2-methylquinoline (78)
7-Methoxy-2-methylquinoline (84)
6-Methoxy-2-methylquinoline (80)
2,5,7-Trimethylquinoline (76)
3,5,7-Trimethylquinoline (77)
5,7-Dimethoxy-2-methylquinoline (74)
6-Ethoxyquinaldine (88)
16
14
12
5
7
5
3
6
7
6
84
94
82
83
91
85
79
83
81
94
87
84
10
11
12
6-Chloro-2-methylquinoline (14)
6-Fluoro-2-methylquinoline (8)
73
76
All reactions were performed with a 25 mM alcoholic solution of a reactant, 50 mg of Au-TiO2 suspension, I = 1.381 Â 10À3 einstein LÀ1 sÀ1
,
irradiation time = 4 h.
a
Remaining unreacted amine.

K. Selvam, M. Swaminathan / Tetrahedron Letters 51 (2010) 4911–4914
4913
Scheme 1. Schematic overview over the possible reaction pathways.
Other photocatalytic experiments have been carried out sus-
pending Au-TiO2 (50 mg) in different mixtures of EtOH–H2O con-
More evidence for the reaction pathway B is the formation of
tetrahydroquinoline, which was also detected by GC–MS (see Sup-
plementary data). 2-Methyl-1,2,3,4-tetrahydroquinolin-4-yl(phe-
nyl)amine (I) can be formed via cycloaddition of the imine (III)
to its enamine tautomer. Subsequent elimination of an aniline mol-
ecule yields the dihydroquinoline (II) as the intermediate. These
results are in a good agreement with results published by Forrest
et al. who demonstrated the viability of a mechanism for the ther-
mal synthesis of 2-methylquinoline from aniline and acetaldehyde
taining aniline (25 mM). Table
2 shows that the yield of
quinaldine after 4 h irradiation decreases from 75% to about 10%
with the increase in the amount of water. In water the photogener-
ated OH radicals can attack aniline in a non-selective manner. There
is also the possibility that water favors the hydration of the accu-
mulated aldehyde leading to the corresponding acid,24 which can
be further oxidized to CO2 and H2O. The decrease in yield may also
be due to the reaction of imine intermediates with water.
Scheme 1 provides a tentative overview of plausible reaction
mechanisms leading to the cyclization products identified by GC–
MS. The initial step in the reaction which is necessary for all the
reactions is the photocatalytic oxidation of the alcohol to aldehyde
by valance band holes on Au-TiO2. The photocatalytic formation of
aldehyde from alcohol was well established.25
in the liquid phase that does not involve the formation of an
a,b-
unsaturated aldehyde.27
This new photochemical activity of Au-TiO2 is of general inter-
est in the field of photocatalysis. Further studies are in progress to
establish the possible employment of solar active semiconductor
catalysts for the exploitation of solar light and also to apply this
reaction for heterocyclic amines with different alcohols.
Pathways A and B (Scheme 1) suggest the formation of an imine
(Schiff base) via the reaction between the aniline and acetalde-
hyde, whereas pathway C requires the intermediate formation of
crotonaldehyde, the product of an aldol condensation of two acet-
aldehyde units. In fact, the condensation reaction to form imines is
catalyzed in acidic conditions provided by the Au-TiO2 surface. The
acidic sites could be titanol groups, TiÁ Á ÁOH; generated during the
oxidation of alcohols.26 Note that crotonaldehyde was not detected
by GC–MS under our experimental conditions. We believe that
crotonaldehyde is produced in low concentration and consumed
readily. In fact, when crotonaldehyde was made to react with
N-ethylideneaniline thermally, the reaction was completed within
4 h.
Acknowledgment
One of the authors, K.S. is thankful to CSIR, New Delhi, for the
award of Senior Research Fellowship.
Supplementary data
Supplementary data (GC–MS chromatograms recorded at differ-
ent reaction times of the photocatalytic conversion of aniline in
ethanol and characterization of Au-TiO2 by X-ray diffraction
(XRD), atomic force microscopy (AFM), transmission electron
microscope (TEM), and diffuse reflectance spectroscopy (DRS))

4914
K. Selvam, M. Swaminathan / Tetrahedron Letters 51 (2010) 4911–4914
20. Au(x)-TiO2 samples, containing different gold loadings [x (wt %) = Au/
(TiO2 + Au)100; x = 0.05, 0.1, 0.2, 0.5, 1.0] were prepared by a conventional
photodeposition method, in which photoirradiation of an aqueous solution
home made TiO2 with HAuCl4Á4H2O afforded gray powder of the Au-TiO2
catalyst.
associated with this article can be found, in the online version, at
doi:10.1016/j.tetlet.2010.07.071.
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365 nm medium-pressure mercury lamp (Sankyo Denki, Japan; intensity
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