Covalently immobilized indium(III) composite (In/SiO2) as highly efficient reusable catalyst for A3-coupling of aldehydes, alkynes and amines under solvent-free conditions

Article abstract of DOI:10.1016/j.molcata.2015.01.021

We describe the synthesis and application of a silica-xerogel-supported indium(III) composite (In/SiO₂). Using X-ray photoelectron spectroscopy, by the first time it was possible to identify that the indium is bonded to the silica through coval

Full text of DOI:10.1016/j.molcata.2015.01.021

Accepted Manuscript
Title: Covalently Immobilized Indium (III) Composite
(
In/SiO ) as Highly Efficient Reusable Catalyst for
2
3
A -Coupling of Aldehydes, Alkynes and Amines under
Solvent-Free Conditions
Author: Tiago Lima da Silva Raon ´ı Scheibler Rambo Daniel
da Silveira Rampon C a´ tia Schwartz Radatz Edilson Valmir
Benvenutti Dennis Russowsky Paulo Henrique Schneider
PII:
S1381-1169(15)00036-9
DOI:
Reference:
http://dx.doi.org/doi:10.1016/j.molcata.2015.01.021
MOLCAA 9404
To appear in:
Journal of Molecular Catalysis A: Chemical
Received date:
Revised date:
Accepted date:
7-11-2014
14-1-2015
22-1-2015
´
Please cite this article as: Tiago Lima da Silva, Raoni Scheibler Rambo, Daniel
da Silveira Rampon, C a´ tia Schwartz Radatz, Edilson Valmir Benvenutti, Dennis
Russowsky, PauloHenriqueSchneider, CovalentlyImmobilizedIndium(III)Composite
(In/SiO2) as Highly Efficient Reusable Catalyst for A3-Coupling of Aldehydes,
Alkynes and Amines under Solvent-Free Conditions, Journal of Molecular Catalysis
A: Chemical http://dx.doi.org/10.1016/j.molcata.2015.01.021
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3
Covalently Immobilized Indium (III) Composite (In/SiO ) as Highly Efficient Reusable Catalyst for A -Coupling of
2
Aldehydes, Alkynes and Amines under Solvent-Free Conditions
a
a
a
b
Tiago Lima da Silva, Raoní Scheibler Rambo, Daniel da Silveira Rampon, Cátia Schwartz Radatz, Edilson Valmir
a
a
*a
Benvenutti, Dennis Russowsky, and Paulo Henrique Schneider
a
Institute of Chemistry, Federal University of Rio Grande do Sul (UFRGS), P.O. Box 15003, 91501-970, Porto Alegre-RS,
Brazil
Instituto de Química e Geociências, Universidade Federal de Pelotas (UFPel), P.O. Box 354, 96010-900, Pelotas-RS,
b
Brazil
*
Corresponding author. +55 51 3308 9636. E-mail address: paulos@iq.ufrgs.br (P. H. Schneider).
Highlights
Synthesis and complete characterization of a supported indium composite (In/SiO2)
Identification that the indium is bonded to silica through covalent In–O–Si bonds.
3
Synthesis of propargylamines through an A -coupling reaction promoted by In/SiO .
2
Microwave assisted reactions
The supported In composite could be reused for four times without losing efficiency
Graphical abstractIndium-Silicon linked: A recyclable well characterized hybrid catalyst has been
3
applied in A -coupling solvent free reaction under conventional and microwave heating to afford
propargylamines in high yields.
Abstract
We describe the synthesis and application of a silica-xerogel-supported indium (III) composite (In/SiO ). Using X-ray
2
photoelectron spectroscopy, by the first time it was possible to identify that the indium is bonded to the silica through
covalent In–O–Si bonds. The N adsorption/desorption isotherms revealed that the In/SiO composite presents pores with
2
2
diameters between 1 and 4 nm, which allows it to be used as a heterogeneous catalyst. Thus, this composite was used as
3
catalyst in an A -coupling reaction with several aldehydes, amines and acetylenes, leading to the formation of
propargylamines in good-to-excellent yields in solvent-free conditions, using both conventional heating and microwave
irradiation (MW). The recyclability was evaluated under both conditions and no considerable reduction in the yields was
observed after four cycles.
Keywords: Indium, supported catalyst, silica xerogel, multicomponent reaction, propargylamines.
1. Introduction
In recent years, In (III) salts have received increased attention as novel, green, Lewis acidic, water-tolerant
catalysts for organic synthesis, showing high chemo-, regio- and stereoselectivity. Compared to conventional
Lewis acids, In (III) salts have the advantages of stability, recyclability, operational simplicity and strong tolerance
to oxygen- and nitrogen-containing compounds [1]. As homogeneous catalysts, In (III) salts have been widely
used and investigated in cycloaddition [2], Friedel-Crafts [3], Mannich [4] and allylation reactions [5]; however,
only a few examples of supported indium salts have been reported in the previous publications as heterogeneous
catalysts [6].
The search for methodologies that are environmentally benign, practical and economical has become a target
in the chemical community. In this sense, transition-metal-catalyzed multicomponent reactions have received
great endeavors in the last decade and have been shown to be a powerful synthetic tool, as they allow the
formation of several bonds including new C–C bonds in an one-pot procedure, leading to highly functionalized
structures from simple molecules [7].
Propargylamines have attracted much attention from organic chemists, as they are present in the structure of
many natural products and potent drug molecules such as β-lactams, oxotremorine analogues, conformationally
restricted peptides, isosteres, allylamines and oxazoles [8]. Also, the potential biological activity of
propargylamines represents their major purpose against cellular apoptosis. The (R)-N-propargyl-1-aminoindane
(
Rasagiline, 1, Fig. 1), the most potent in preventing cell death [9], and deprenyl (Selegiline, 2, Fig. 1), used as an
effective adjuvant to L-DOPA in the treatment of Parkinson’s disease [10], are representative examples.

These compounds are versatile nitrogen-containing synthetic building blocks, largely applied in the synthesis of
important compounds such as β-lactams, pyrroles, imidazoles and oxazolidin-2-ones [11]. Despite their
importance, there are relatively few reliable methods for their synthesis, which usually explore the relatively high
acidity of the terminal acetylenic C–H bond to form alkynyl–metal reagents by reacting them with strong bases
[
11,12]. Nevertheless, these methodologies show some disadvantages, such as the requirement for
stoichiometric ratios, high moisture sensitivity and strictly controlled reaction conditions.
In recent years, enormous progress has been achieved on C–H bond activation in terminal alkynes [13]. In this
3
way, the synthesis of propargylamines using A -coupling can be promoted by several transition-metal catalysts,
such as gold [14], silver [15], copper [16], indium [17], and others [18], also including different metal nanoparticles
[
19]. The reaction proceeds through the direct addition to carbon–nitrogen double bonds (preformed imines) or
using one-pot multicomponent reactions. An interesting approach was recently described by Zhang and co-
workers [20] developing a highly effective and efficient methodology using InCl3 as a catalyst for the
multicomponent reaction through C–H activation, leading to aromatic and aliphatic propargylamines with almost
quantitative yields.
With regards to these homogeneous systems, in most cases, they involve expensive transition metals or non-
environmentally friendly compounds, which are often lost at the end of the reaction. In order to achieve the
required recyclability of catalysts, several heterogeneous systems have been developed and successfully applied
3
in catalyzed A -coupling reactions [21,22,23]. Among them, silica is often employed, owing to its high surface
area, good accessibility as well as its high chemical, mechanical and thermal stability [24].
Surprisingly, as far as we observed, there are few reports on the use of metal-supported catalysts for the
synthesis of propargylamines [21a-b,22b,23c-d]. It is important to note that only one example using an In (III)-
supported catalyst in a one-pot multicomponent reaction has been reported [25].
3
In this work, silica-xerogel-supported indium (III) salt catalyst (In/SiO ) was applied in the one-pot A -coupling
2
under solvent-free conditions. An important feature of this xerogel is that the catalyst is not just embedded in the
silica, but it is also covalently immobilized to the support. To the best of our knowledge, this is the first report of
the use of wide characterized indium chemically bonded to silica as a catalyst for propargylamines.
2. Experimental
2.1. Materials and methods
Aldehydes, amines, acetylenes, tetraethylorthosilicate (TEOS), InCl and other solvents were purchase from
3
1
Sigma Aldrich and used without further purification. Carbon and hydrogen nuclear magnetic resonance ( H-NMR
and C-NMR, respectively) spectra were recorded on 300 MHz Varian Inova 300 and Varian VNMRs 300
13
spectrometers. Chemical shifts (δ) are expressed in ppm downfield from tetramethylsilane as an internal standard
in spectra obtained using CDCl . Coupling constants are reported in Hz. Microwave-assisted reactions (MW)
3
were performed on a focused microwave reactor (CEM) at indicated temperatures, using an irradiation power of
50 W and a pressure of 100 psi. XPS (X-Ray Photoelectron Spectroscopy) was performed in an Omicron-
SPHERA station using AlKα radiation (1486.6 eV). The anode was operated at 225 W (15 kV, 15 mA). Survey
spectra were recorded with 50 eV pass energy. The In 3d region was recorded with a higher resolution (pass
energy of 10 eV). The detection angle of the photoelectrons, with respect to the sample surface (take-off angle),
was fixed at 53° for all measurements. The C 1s signal from adventitious carbon at 285 eV was used as an
internal energy reference. All spectra were fitted assuming a Shirley background. Lines were fitted by 70%
Gaussian + 30% Lorentzian functions, with set values of full-width at half maximum for each line. EDS was
performed for the In/SiO composite, which was dispersed on a double-faced conducting tape on an aluminium
2
support and coated with a thin film of carbon, using Baltec SCD 050 Sputter-Coater apparatus. The images were
obtained using SEM (scanning electron microscopy) on a Jeol microscope (model JSM 5800), connected to a
secondary electron detector and an X-ray energy-dispersive spectrometer. The EDS (energy-dispersive X-ray
spectroscopy) elemental analysis was obtained using seven measurements from different images, with
magnifications from 4000 to 15000×. The N adsorption/desorption isotherms of the In/SiO composite and pure
2
2
SiO were determined at the liquid-nitrogen boiling point, using Tristar II Krypton 3020 Micromeritics equipment.
2
The materials were previously degassed at 120°C under vacuum for 10 h. The specific surface areas were
determined by the BET (Brunauer–Emmett–Teller) multipoint technique [26] and the pore size distribution curves
were obtained by using the BJH (Barrett–Joyner–Halenda) and DFT (Density Functional Theory) methods [27].
2.2. Synthesis of In/SiO2
The synthesis of the In/SiO composite was adapted from procedures previously reported for other composites
2
[
25]. InCl (1.43 g) was added to a mixture containing ethanol (5 mL), water (2 mL) and concentrated HCl (3
3
drops). The mixture was magnetic stirred until complete dissolution. Then, TEOS (5 mL) was added and the
mixture was stirred for an additional 15 min. It was then stored for 5 days under ambient conditions, covered,
without sealing, for gelation and solvent evaporation. The resulting solid was comminuted and heated for 24 h at

120ºC. Afterwards, the solid was extensively washed with ethyl alcohol and water, and finally heat-treated for an
additional 24 h at 100ºC. A reference sample of pure SiO , without addition of InCl , was simultaneously
2
3
synthesized in the same way.
.3. General experimental procedure for the synthesis of propargylamines
In a 10mL round-bottomed flask equipped with a magnetic stirring bar, aldehyde (1.1 mmol), amine (1.2 mmol),
2
alkyne (1.3 mmol) and 10 mol% In/SiO (0.050 g) were added. The mixture was stirred for 12h at 70°C. After that,
2
ethyl acetate (10–20 mL) was added and the organic solution was separated from the In/SiO composite by
2
filtration. The solvent was evaporated under reduced pressure and the residue was purified by column
chromatography over silica gel, eluting with hexanes/ethyl acetate (90/10) mixture, yielding the products. All
products are known compounds and spectral data obtained are in agreement with previous reports.
2.4. General experimental procedure for the synthesis of propargylamines under MW irradiation
In a 10mL glass vial equipped with a magnetic stirring bar and containing the appropriate aldehyde (1.1 mmol),
amine (1.2 mmol) and alkyne (1.3 mmol), 10 mol% In/SiO (0.050 g) was added and the vial was tightly sealed
2
with an aluminum/Teflon crimp top. The mixture was then irradiated in a focused MW reactor (CEM) at 70ºC,
using an irradiation power of 50 W and a pressure of 100 psi. After stirring for 10 min, ethyl acetate (10 mL) was
added and the organic solution was separated from the In/SiO composite by filtration. The solvent was
2
evaporated under reduced pressure and the residue was purified by column chromatography over silica gel,
eluting with hexane/ethyl acetate (90/10) mixture, yielding the products.
3. Results and Discussion
The In/SiO composite material was synthesized using the sol-gel method. The amount of indium present in the
2
In/SiO composite was estimated using EDS elemental analysis, which was performed using seven different SEM
2
images. The average result was 1.0 ± 0.05 mmol of indium per gram of composite. The In/SiO composite was
2
submitted to XPS analysis. The In 3d and O 1s peaks are shown in Fig. 2, and the binding energy values are
3+
presented in Table 1, along with some already reported values for the In ion, as well as chloride and oxide
3+
species. It can be observed that the In 3d5/2 and 3d3/2 peaks for In in the In/SiO composite, appear close to the
2
reported InCl values, but are slightly shifted towards oxide species.
3
3+
This result suggests that the In ions are link with unsaturated oxygen and chloride forming O–In–Cl (x = 1 or
x
2
), as already reported for the In/TiO composite, which is synthesized by the same way [28]. Additionally, the O
2
1s spectrum shows two components, one at 533.4 eV in a major proportion that is compatible with the oxygen of
SiO , and a second minor peak that appears at 531.6 eV. This minor peak presents an intermediate value
2
between the reported SiO and In O values (Table 1). It is important to point out that the position of the O 1s
2
2
3
peak is related to the electronegativity of the element bonded to the oxygen. Silicon presents a higher Pauling
electronegativity than indium (1.90 for silicon and 1.78 for indium). This difference is enough to result in higher 1s
binding energy for oxygen on silica (ca. 533 eV) in comparison with In O (ca. 530 eV). Therefore, the
2
3
intermediate value of the minor peak (531.6 eV), observed in the present work (Table 1 and Fig. 2), provides
evidence that there is a fraction of oxygen atoms that are bonded to silicon and indium simultaneously,
compatible with the Si–O–In–Cl structure. This hypothesis has already been proposed in previous report for
x
silica–hafnia materials, where the Si–O–Hf bond was detected in a similar way [29].
Textural analysis of the In/SiO composite and pure SiO is presented in Fig. 4. The N isotherms (Fig. 4a) are
2
2
2
of type I for microporous materials, as expected for materials gelified in the presence of HCl as a catalyst [36].
The BET specific surface areas were 424 ± 15 and 493 ± 20 m² g-1 for In/SiO and SiO , respectively. From the
2
2
BJH analysis (Fig. 4b), it can be seen that In/SiO composite shows small difference in the mesopore size
2
distribution, compared with pure silica. The In/SiO composite presents a fraction of mesopores with a diameter
2
between 2 and 4 nm, whereas pure SiO should be predominantly microporous, having a pore diameter lower
2
than 2 nm. The appearance of mesoporosity in In/SiO is more evident from DFT analysis, presented in Fig. 4c,
2
where it is clearly possible to observe that the In/SiO composite presents pores with diameters in the 1–4 nm
2
range. These results indicate that the presence of the InCl during the gelation process produces small textural
3
changes in relation to pure silica. Therefore, the high surface area and pore size distribution of the In/SiO2
composite render it a promising material to be applied as a catalyst.
Taking into account the textural properties of the In/SiO composite, its ability as a heterogeneous Lewis acid
2
3
catalyst in promoting organic reactions was evaluated. As a test reaction, an A -coupling reaction between an

aldehyde, an alkyne and an amine was chosen. The products of this type of reaction are propargylamines, which
are synthetically versatile, key intermediates for the preparation of many nitrogen-containing biologically active
compounds. For initial studies, we selected the reaction of benzaldehyde (1a), pyrrolidine (2a) and
phenylacetylene (3) (Table 2).
As shown in Table 2, the influence of temperature, catalyst loading and reaction time were analyzed. In the first
experiment, benzaldehyde (1.1 mmol), pyrrolidine (1.2 mmol), phenylacetylene (1.3 mmol) and the In/SiO2
composite (10 mol%) were mixed together under solvent-free and atmospheric conditions at room temperature,
and after 12 h, no product was observed (Table 2, entry 1). Despite our initial misfortune, we decided to perform
the same reaction using higher temperatures. When the reaction was carried out at 50°C, the product was
obtained in 20% yield (Table 2, entry 2), and by changing the temperature to 70°C, the reaction proceeded
smoothly and generated the desired product propargylamine 4a in 94% yield (Table 2, entry 3). Higher reaction
temperatures also influence the product yields (entries 4 and 5), were a remarkable reduction on yield was
observed. Additionally, by thin-layer chromatography (TLC), we detected that longer reaction times and higher
temperatures led to the formation of a complex mixture of by-products.
Finally, the impact of the In/SiO catalyst loading on the reaction efficiency was investigated (Table 2, entries 7–
2
1
1). By decreasing the amount of the heterogeneous catalyst from 10 mol% to 5, 2.5 or 1 mol%, the reaction did
not go to completion (Table 2, entry 3 and entries 7–9), and no product was formed in the absence of catalyst
Table 2, entry 11), showing that this parameter had an effective influence on the reaction course. Other indium
(
salt, InBr , was also used to produce a composite material and was also employed in this reaction, affording the
3
desired product with a slight decrease on the reaction yield, when compared with the InCl analogous (Table 2,
3
entries 3 and 10).
After reaction conditions optimization, several aldehydes, amines and phenylacetylene were investigated to
check the versatility of the protocol; the results are summarized in Table 3. In general, all reactions proceeded
smoothly with good yields. When different aromatic aldehydes were used, it was observed that the products were
obtained in satisfactory yields, even when electron-withdrawing or electron-donating groups were attached to the
aromatic moiety (Table 3, entries 1–3). Gratifyingly, alkyl derivatives are also suitable for the reaction, furnishing
the desired products in good yields from valeraldehyde and butyraldehyde (Table 3, entries 6 and 7).
By changing the secondary amine to piperidine or morpholine, a significant decrease in the reaction yield was
observed and the desired products were obtained in 62 and 60% yield, respectively (Table 3, entries 4 and
5).These results are in accordance with the reduced amounts of reactive amines, owing to the stereoelectronic
effects, thus making the nucleophilic attack of the nitrogen atom of the amine more difficult in forming the
intermediate imine. Once again, less nucleophilic piperidine leads to lower yield when aliphatic aldehydes were
employed.
In recent years, it has been shown that organic reactions can be influenced by microwave irradiation (MW) [37].
In all these cases, the authors disclose that the use of MW irradiation can considerably decrease the reaction
time, usually along with an increase in the product yields [1,38]. In this way, in order to develop an efficient
protocol in terms of energy economy, we performed these multicomponent reactions under focused MW
irradiation. Thus, the mixture of benzaldehyde (1a), pyrrolidine (2a) and phenylacetylene (3) was irradiated at
different temperatures and times, using the In/SiO composite as catalyst (Table 4).As shown in Table 4, the
2
reactions performed at 70°C and 10 minutes under microwave irradiation(50 W) furnished the propargylamine 4a
o
in 97% yield (Table 4, entry 1). By decreasing the temperature to 50 C, lower yields were achieved (Table 4,
entries 1 and 3). Besides, higher temperatures provided a slight lower reaction yield (Table 4, entry 2). In another
set of experiments, we investigated the influence of the amount of catalyst employed. As observed under
conventional heating conditions, the reaction yield drops by reducing the catalyst loading from 10 mol% to 7 or 5
mol% (Table 4, entries 4 and 5). A decrease in the product yield was also observed with lower reaction times
from 10 to 6 min (Table 4, entries 6 and 7).
In order to check the versatility of the protocol, the activity of the In/SiO heterogeneous catalyst was then
2
evaluated in a set of experiments under microwave irradiation, as summarized in Table 5. In general, all reactions
proceeded smoothly with good yields. A structurally diverse range of aryl aldehydes with electron-withdrawing or
electron-donating groups, as well as aliphatic ones, were successfully employed in this reaction. Regarding the
amines, the same behavior was observed in this protocol compared to the conventional heating method. The
results depicted in Table 5 show that microwave irradiation is better than conventional heating (Table 3 and Table
5), furnishing the corresponding products in comparable yields and in very short reaction times.
An important feature of supported catalysts is the possibility of recycling, which makes them an excellent
choice, considering economic and environmental aspects. Thus, in an extension of this work, we verified the
possibility of reuse the In/SiO catalyst in a model reaction (Fig. 3). To our delight the catalytic system was
2
successfully recycled four times without significant decrease in chemical yields. These results are in accordance
with the proposed structure, discussed above, where the indium species are covalently bonded to the silica
matrix.

3
Based on previous InCl -catalyzed one-pot A -coupling [17a], a plausible mechanism for the formation of the
3
product using In/SiO composite is depicted in Scheme 1: the supported catalyst could first react with the terminal
2
alkyne to form a stable In (III) alkynyl complex through a C–H bond activation on the In/SiO composite surface.
2
On the other hand, formation of the iminium ions from aldehydes and secondary amines could be accelerated in
the presence of Lewis acid and HCl released in reaction medium. The resulting indium acetylide intermediate can
subsequently react with the iminium salt generated in situ to give the corresponding propargylamine and
regenerate the In (III) species.
Conclusions
To summarize, we used the sol-gel method to synthesize an In/SiO composite. The In(III) ion is bonded to the
2
silica matrix surface, forming a Si–O–In–Cl structure (x = 1 or 2). To the best of knowledge, this is the first report
x
of the use of a wide characterized indium composite, which is chemically bonded to silica, as a catalyst for the
synthesis of propargylamines. The In/SiO composite shows a specific surface area and porosity that allows their
2
3
application as heterogeneous catalysts in one-pot multicomponent A -coupling reactions under solvent-free
conditions with both conventional and microwave heating.
The new catalyst afforded the products with good-to-excellent yields even when different aldehydes and amines
were used. Another important feature is that high recyclability was achieved under microwave irradiation: after
four recycles, without decreasing the reactions yields. Thus, our work describes an efficient and recyclable
3
heterogeneous catalyst based on a silica–indium xerogel, as well as its applications in multicomponent A -
coupling reactions, in order to improve the synthesis of propargylic amines, taking into account green-chemistry
statements.
Acknowledgements
The authors are gratefull to Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Fundação de Amparo
a Pesquisa do Estado do Rio Grande do Sul (FAPERGS) and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
(
CAPES) for financial support and the fellowship awards. They also thank the Centro de Microscopia Eletrônica (UFRGS)
for EDS analysis.
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37
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Figures And Tables:
Fig. 1. Propargylamines with biological activities.
Fig. 2.XPS spectra of the In/SiO composite; In 3d (left) and O 1s (right).
2
Fig. 3.Recyclability of the In/SiO catalytic system under microwave irradiation.
2
Fig. 4. Textural analysis of In/SiO composite: a) N adsorption/desorption isotherms, b) BJH pore size
2
2
distribution, and c) DFT pore size distribution.
Scheme 1. Plausible mechanism for catalytic synthesis of propargylamines using In/SiO composite.
2
Table 1 XPS analysis of In/SiO composite.
2
H Binding
energy (eV)
Compound
InCl3
Head 5
In
d5/2
In 3d3/2
O 1s
3
446.0 453.5
[30]
4
45.9
[31]
This
work
[32]
[33]
446.1 453.8
In O
445.1 452.2
2
3
4
4
44.8
44.7
530.5 [34]

5
30.1 [35]
SiO2
532.8 [35]
5
32.6 [28]
This
In/SiO2
445.8 453.4
531.6
work
This
5
33.4
work
a
Table 2 Optimization of the reaction conditions using In/SiO composite.
2
b
c
Entry Time Temperature Catalyst
Yield
(
h)
(°C)
r.t.
50
70
80
90
70
70
70
70
70
70
(mol%)
10
10
10
10
10
10
5
2.5
1
10
-
(%)
nd
20
94
82
62
46
88
85
85
82
nd
1
2
3
4
5
6
7
8
9
1
1
12
12
12
12
12
18
12
12
12
12
12
d
0
1
a
All reactions were carried out with benzaldehyde (1.1 mmol); pyrrolidine (1.2 mmol) and
phenylacetylene (1.3 mmol) under solvent-free and atmospheric conditions. Mol% of catalyst refers to
In.
b
Catalyst: In/SiO composite.
Isolated yields.
2
c
d
InBr was used to synthesise the In/SiO composite.
3
2
3
a
Table 3 A -coupling reaction using In/SiO composite as the catalyst.
2
b
Entry Aldehyde Amine Product
Yield
%)
(
O
N
1
94
H
1a
1a
O
N
N
H
2
3
82
1
b
1a
4
b
O
N
N
H
1a
Br
86
1
c
Br
4c

O
N
N
H
4
5
6
62
60
76
1
a
1b
4
d
O
O
N
N
H
1a
1b
4e
O
N
N
H
1
d
1
a
4f
O
N
7
8
N
H
76
58
1
e
1
a
4
g
O
N
N
H
1e
1b
4h
a
All reactions were performed with aldehyde (1.1 mmol), amine (1.2 mmol) and acetylene (1.3 mmol)
under solvent-free and atmospheric conditions. Mol% of catalyst refers to In.
b
Isolated yields.
[
a]
Table 4 Optimization of the reaction conditions under MW irradiation.
N
O
In/SiO
2
+
+
Ph
H
N
H
Ph
Solvent-free
Microwave (50W)
1a
2a
3
4a
b
Entry Temperature In/SiO2
Time
(min.)
10
10
10
10
10
8
6
Yield
(%)
97
93
69
71
58
72
60
(°C)
(mol%)
1
2
3
4
5
6
7
70
90
50
70
70
70
70
10
10
10
7
5
10
10
a
All reactions were carried out with benzaldehyde (1.1 mmol); pyrrolidine (1.2 mmol) and
phenylacetylene (1.3 mmol) under solvent-free conditions, MW irradiation and atmospheric pressure.
Mol% of catalyst refers to In.
b
Isolated yields.
3
a
Table 5 A -coupling reaction catalyzed by In/SiO composite under MW irradiation.
2

R
R
N
O
In/SiO2 (10 mol%)
Solvent-free, 70 °C
R
R
+
+
Ph
H
N
H
R'
R'
a-e
10 min. MW
1
2a-c
3
4a-h
b
Entry Aldehyde Amine Product
Yield
)
(%
O
N
N
H
1
2
94
82
1
a
1
a
4
a
O
N
H
N
1
a
1b
4b
O
N
N
H
3
Br
86
1c
1a
Br
4c
O
N
N
H
4
5
62
60
1
a
1
b
4
d
O
N
O
N
H
1a
1
b
4e
O
N
N
H
1
d
6
7
8
9
76
76
58
71
1
a
4
f
O
N
N
H
1e
1
a
4
g
O
N
N
H
1
b
1
e
4h
O
N
N
H
O
O
4i
1
f
1a
a
Reactions were performed with aldehyde (1.1 mmol), amine (1.2 mmol) and acetylene (1.3 mmol)
under solvent-free conditions, microwave irradiation and atmospheric pressure. Mol% of catalyst refers
to In.

b
Isolated yields.

fx1 .

fx10 .

fx11 .

fx12 .

fx13 .

fx14 .

fx15 .

fx16 .

fx17 .

fx18 .

fx19 .

fx2 .

fx20 .

fx21 .

fx22 .

fx23 .