Stable mesoporous Fe/TiO2 nanoparticles: A recoverable catalyst for solvent-free synthesis of propargylamine via C[sbnd]H activation

Article abstract of DOI:10.1016/j.apcata.2014.09.044

Fe-doped mesoporous metal oxides (Fe/MO₂, M = Si and Ti) were synthesized with particle size in the range of 10–15 nm via modified sol–gel method. The Fe modified SiO₂ and TiO₂ have proved to be very efficient catalysts in three-component coupling of aldehydes, alkynes and amines for the solvent-free synthesis of proargylamines. Among the two Fe-doped metal oxide catalysts, Fe/TiO₂ gives 94% propargylamine yield at 245 W microwave power for few minutes under solvent free condition and found to be a better catalyst. With a Fe/TiO₂ heterogeneous catalyst and in the absence of solvent, the proposed process for propargylamine synthesis is green and environmentally benign protocol.

Full text of DOI:10.1016/j.apcata.2014.09.044

Accepted Manuscript
Title: Stable mesoporous Fe/TiO2 nanoparticles: A
recoverable catalyst for solvent-free synthesis of
propargylamine via C-H activation
Author: Deepali A. Kotadia Saurabh S. Soni
PII:
S0926-860X(14)00595-X
DOI:
Reference:
http://dx.doi.org/doi:10.1016/j.apcata.2014.09.044
APCATA 15025
To appear in:
Applied Catalysis A: General
Received date:
Revised date:
Accepted date:
18-6-2014
23-9-2014
25-9-2014
Please cite this article as: D.A. Kotadia, S.S. Soni, Stable mesoporous
Fe/TiO2 nanoparticles: A recoverable catalyst for solvent-free synthesis of
propargylamine via C-H activation, Applied Catalysis A, General (2014),
http://dx.doi.org/10.1016/j.apcata.2014.09.044
This is a PDF file of an unedited manuscript that has been accepted for publication.
As a service to our customers we are providing this early version of the manuscript.
The manuscript will undergo copyediting, typesetting, and review of the resulting proof
before it is published in its final form. Please note that during the production process
errors may be discovered which could affect the content, and all legal disclaimers that
apply to the journal pertain.

1
2
3
Stable mesoporous Fe/TiO2 nanoparticles: A recoverable catalyst for solvent-
free synthesis of propargylamine via C-H activation
4
5
6
Deepali A. Kotadia, Saurabh S. Soni*
7
8
Department of Chemistry, Sardar Patel University, Vallabh Vidyanagar 388120, Gujarat, INDIA
9
10
11
12
13
14
15
16
17
* Author to whom all correspondence should be address (email: soni_b21@yahoo.co.in)
Telephone: +91-2692-226857-Ext.216
18
19
20
1
Page 1 of 34

21
22
Abstract
23
24
25
26
27
28
29
30
Fe-doped mesoporous metal oxides (Fe/MO2, M = Si and Ti) were synthesized with particle size
in the range of 10-15 nm via modified sol-gel method. The Fe modified SiO2 and TiO2 have
proved to be very efficient catalysts in three-component coupling of aldehyde, alkynes and
amines for the solvent-free synthesis of proargylamines. Among the two Fe-doped metal oxide
catalysts, Fe/TiO2 gives 94 % propargylamine yield at 245W microwave power for few minutes
under solvent free condition and found to be a better catalyst. With a Fe/TiO2 heterogeneous
catalyst and in the absence of solvent, the proposed process for propargylamine synthesis is
green and environmentally benign protocol.
31
32
33
34
35
36
37
38
Keywords : Doped-metal oxide, Mesoporous material, Fe-catalysed reaction, Aldehyde-Amine-
Alkyne reaction, Propargylamine synthesis
39
2
Page 2 of 34

40
1. Introduction
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
61
62
Multicomponent reactions are of prime importance due to their ability to construct desired
molecules from easily available raw materials in a one-pot operation with high atom economy
and multiple-bond forming efficiency. Especially attractive are multicomponent reactions which
allow the formation of several bonds including C-C bond in single-step procedure [1-3]. The
three component coupling of an Aldehyde, an Alkyne and an Amine, commonly called as A3-
coupling to give propargylamine as product is a multicomponent reaction that has received much
attention in recent years [4]. Propargylamines are versatile intermediates for the preparation of
various nitrogen-containing compounds and are key components of biologically active
pharmaceuticals and natural products [5-7]. In the past few years various transition metal
catalysts have been employed in the synthesis of propargylamine from A3-coupling, which
includes Cu [8-11], Au [12-15], Ag [16-19], Ir [20], Ni [21], Zr [22], Re [23], Fe [24-26], Hg2Cl2
[27], In [28], Co [29], Zn [30,31] and Cu/RuII bimetallic systems [32]. These transition metals
can be used both as homogeneous and heterogeneous catalysts. Use of these metals as
homogeneous catalyst for A3-coupling reaction suffers from major drawbacks like loss of
precious as well as hazardous metal catalyst like Au, Ag, Ir or Zr which are not recyclable and
they are difficult to separate from reaction mixture. Alternative to homogeneous catalysts,
various heterogeneous catalysts like Au, Ag and Cu in ILs, supported Au, Ag, Cu were
successfully used as catalyst for A3-coupling with recyclability and reusability of these catalysts
[8-19]. However, many catalysts were derived from heavy or rare metals and their toxicity and
prohibitive prices constitute severe drawbacks for large-scale applications. In contrast, iron is
one of the most abundant metal on earth, and consequently one of the most inexpensive and
environmentally friendly one with special reactivity [33]. These features make it valuable and
3
Page 3 of 34

63
64
65
66
67
68
69
70
71
72
73
74
75
76
77
78
79
80
81
82
83
84
85
advantageous in synthetic processes and catalysis. Many iron catalyzed reactions such as (in
general) addition, substitution, cross-coupling, cycloaddition, hydrogenation and reduction
reactions have been described in the past few years [34-36]. Among these, cross-coupling
(aromatic carbon-carbon bond coupling) reactions have recently emerged as exceedingly
important methodologies for the preparation of complex organic molecules. Fe catalyzed carbon-
carbon bond, carbon-heteroatom bond and heteroatom-heteroatom bond-forming reactions have
been described recently. The propargylamine synthesis from aldehyde, amine and alkyne
coupling has been previously synthesized using Fe metal as catalyst for C-H activation [24-26].
The various Fe metal employed were in salt form viz., FeCl3, FeCl2, etc. Although the use of
homogeneous Fe catalyst has shown their potential activity, their loss at the end of the reaction
decreased their utility, at least for industrial purposes. In case of heterogeneous catalyst, there is
possibility of metal leaching during the reaction, which creates problem of recovery with its
consequence comparable to the interference like homogeneous catalysts. Stability of catalyst
should be a must during any chemical reaction which can be achieved by many ways, among
which metal doping is of particular interest.
From the past few years, transition metal doped mesoporous materials by the sol-gel process is a
widely accepted method for the preparations of doped nanomaterials [37-42]. These mesoporous
materials are increasingly being employed in a number of industrially important areas which
include catalysis, adsorption processes, membrane separation and many more. Nanoparticles are
defined as having 1-50 nm diameters, a size range where metals can show size dependent
properties. The smaller the clusters of atoms, the higher are the percentage of atoms on the
surface rendering nanoparticles very interesting in catalysis [1,42]. For synthesis of such
materials, the nature and local environment of the catalyst strongly depends on the synthetic
4
Page 4 of 34

86
87
route, which dramatically influences the catalytic performance. The deliberate incorporation of
transition metals in a porous support (Silica, Titania) can therefore be the crucial step for the
final catalytic properties and/or possible applications. The heterogenization of transition metal on
solid support such as silica, titania, aluminia, brings the classic advantages of heterogeneous
catalysis like stability to high temperature, easy removal from the reaction medium, and the
bottom-up approach for nanoparticles synthesis. Fe-doped oxides (SiO2, TiO2, CeO2) have been
previously reported for various applications such as photocatalysis, oxidation reactions and as
semiconductors [37-43]. The incorporation of iron species into a mesostructured matrix can be
achieved in several ways e.g. sol-gel method [37-42], hydrothermal [47], chemical synthesis [48]
and plasma pyrolysis [49, 50]. The most common method is the post synthesis impregnation of
the preformed porous material with an inorganic precursor like Fe(NO3)3 or FeCl3 [51,52].
Another method is the direct synthesis in which silica and transition metal (Fe) oxide precursors
are mixed in solution and condensed by sol-gel processing to form a mixed metal oxide network.
Recently, Nasralla et. al.[37] reported thermally stable Fe-doped TiO2 nanopowder by sol-gel
method. They showed that, 5% (molar ratio) Fe-doped TiO2 nanoparticles were able to change
the electronic and optical properties of the materials. The proposed method has advantage to
control the concentration of dopant in the metal oxide matrix.
88
89
90
91
92
93
94
95
96
97
98
99
100
101
102
103
104
105
106
107
108
The above protocols suffer from one or two drawbacks like large agglomeration of inorganic
precursors outside the mesopore, or precipitation of iron oxide before the sol-gel process starts.
The above stated drawbacks has been overcome by Supplit and group [53] where the iron species
were incorporated into a thin film silica matrix by one-pot synthesis route, where, in the first step
metal alkoxides were covalently bonded to a non-ionic polyethylene oxide (PEO) based
surfactant by reaction with terminal hydroxyl group of surfactants, which was further used to
5
Page 5 of 34

109
110
111
112
113
114
115
prepare films and powders by Evaporation induced self assembly (EISA) [54-59]. These various
applications and previous work done in our laboratory on transition metal-doped nanoparticles
[41,42] prompted us to present our independent results by synthesizing Fe on titania and silica,
where FeCl3 (the Fe salt precursor) is covalently bonded to P123 (PEO20-PPO70-PEO20) block-
copolymer by replacing terminal hydroxyl hydrogen by Fe. This modified surfactant is then used
to prepare powders by sol-gel process. The synthesized Fe/TiO2 and Fe/SiO2 were screened for
their catalytic activity for A3-coupling reaction under microwave irradiation.
116
2. Materials and Methods
117
118
119
120
121
122
123
124
125
126
127
128
129
130
The block co-polymer surfactant Pluronic® P123 (Polyethylene oxide-polypropylene oxide-
Polyethylene oxide (PEO20-PPO70-PEO20), MW-5750 g/mol), Titanium isopropoxide (Ti(iPrO)4),
Tetraethoxysilane (TEOS), FeCl3, and the coupling starting substrates were purchased from
Sigma-Aldrich, India. HCl and Ethanol used were of analytical grade laboratory reagent. The
synthesized Fe-doped nanoparticles were characterized for their structure and texture by X-Ray
Diffraction (XRD), Brunauer, Emmett and Teller (BET) surface area, Transmission Electron
Microscopy (TEM), Scanning Electron Microscopy (SEM), Energy Dispersive Spectroscopy
(EDS) and Dynamic Light Scattering (DLS) techniques. The XRD measurements were
performed on a Rigaku D/max 2500 X-ray Diffractometer. Diffraction patterns were recorded
with Cu Kα radiation (40kV, 30mA) over a 2θ range of 3-80˚C at a scan rate of 2˚/min. BET
surface area, average pore volume, and average pore diameter were measured by physisorption
of N2. The isotherms were elaborated according to the BET method for surface area calculation,
and pore size distribution curves derived from the desorption branches for the porous materials
with BJH (Barrett-Joyner-Halenda) methods on Micromeritics Gemini 2375 Surface area
6
Page 6 of 34

131
132
133
134
135
136
137
138
139
140
141
142
143
144
145
analyzer. The TEM measurements were conducted by using a Philips Tecnai 20 (Holland)
transmission electron microscope at an acceleration voltage of 200kV with a W emitter and
LaB6 electron source. A single drop of the sample was deposited on a carbon-coated copper grid
and dried at room temperature under atmospheric pressure. The SEM observations were carried
out using JSM-7600F Field Emission Gun-Scanning Electron Microscopes (FEG-SEM) at an
acceleration voltage of 0.1 to 30 kV. The DLS measurements were carried out on Malvern
instrument, Zetasizer ZS-90 (for nanosizer) Particle size analyzer. Microwave (model no: CATA
R I, Catalyst System, India) used was with specific features like 10 power level stages (100%) up
to 700 W, IR temperature Sensor, magnetic stirrer and MW flask (quartz) with reflux condenser.
All the coupling reactions were performed in oven-dried glassware under an inert atmosphere of
dry N2. Reactions were monitored by thin layer chromatography using 0.25 mm E. Merck silica
gel coated glass plates (60F- 254) with UV light to visualize the course of reaction. The coupling
products were analyzed by 1H and 13C NMR (400 MHz Bruker Scientific, Switzerland) and GC-
MS (GC-Mass Spectrometer, Perkin Elmer, Auto system XL, GC+) spectroscopic techniques. IR
measurements were carried out by FTIR (ABB Inc., Canada).
146
147
2.1 Synthesis of mesoporous materials
2.1.1 Synthesis Fe-P123 mixture
148
149
150
151
152
Sodium metal (40 - 45 mmol) was dissolved on reflux in 25 ml toluene and to it P123-toluene
solution was added and refluxed for 4h for formation of Na-salt of P123. To this warm solution
an equivalent amount of dry FeCl3 was added and the mixture was subjected to reflux for two
more hours. It was then left for NaCl precipitation overnight. The solution was removed by
syringe and the sediment extracted twice with 20 ml portions of toluene on reflux. The solution
7
Page 7 of 34

153
154
fractions were joined and evaporated to dryness in vacuo, leaving an orange-brown waxy solid
named Fe-P123 surfactant mixture.
155
2.1.2 Fe-doped Titania
156
157
158
159
160
161
162
163
164
165
Mesoporous doped titania were synthesized (by method earlier reported by our group) [48,49]
from titanium tetraisopropoxide (35 mmol) to which HCl (37 %) (63 mmol) is added with
constant stirring at 0˚C and after completion of addition continued to stir for 30min at room
temperature. A second solution prepared by dissolving the Fe-P123 surfactant mixture in ethanol
under acidic conditions was then added to the former one. The resultant was kept for ageing for
one day under humid atmosphere (RH ~60%) and then under atmospheric conditions for self-
evaporation of solvent which was then oven dried. The crude sticky material was calcined at
450˚C for 30min at a heating rate of 2˚C/min to obtain a fine Fe/TiO2 powder which was further
characterized using XRD, BET, TEM, SEM, EDS, IR and DLS measurements. The FTIR
spectrum of Fe/TiO2 is given in supporting information (Fig. S1).
166
2.1.3 Fe-doped Silica
167
168
169
170
171
172
173
Mesoporous doped silica were synthesized using a prehydrolyzed solution containing TEOS (42
mmol), ethanol (5 g) and HCl (37 %) (0.055 M) which was stirred for an hour. A second solution
prepared by dissolving the Fe-P123 surfactant mixture in ethanol under acidic conditions, was
then added to the former one. The resultant was kept for ageing for one day under humid
atmosphere and then under atmospheric conditions for self evaporation of solvent which was
then oven dried, grounded to form fine yellow colored powder. The final doped silica was rinsed
in ethanol for 2 h at 80 ˚C to remove surfactant and then dried at 80 ˚C giving fine free flowing
8
Page 8 of 34

174
175
176
powder. The synthesized Fe/SiO2 was then characterized using XRD, BET, TEM, SEM, EDS
and DLS measurements. The FTIR spectrum of Fe/SiO2 is given in supporting information (Fig.
S2).
177
2.2 General procedure for the synthesis of Propargylamine
178
179
180
181
182
183
184
185
186
187
Phenyl acetylene (1.2 mmol), Aldehyde (1.0 mmol), Alkyne (1.1 mmol) and Fe/TiO2 (50 mg)
were taken in a two-necked microwave flask equipped with reflux condenser and a magnetic
stirring bar. The mixture was irradiated at 245 W microwave power under stirring for 20 min.
After the completion of reaction, the resultant is taken up in diethyl ether and filtered using a
sintered glass-funnel to remove catalyst. The etheric content was further washed with water and
separated. The combined organic phases were dried with Na2SO4, filtered, concentrated and
purified using chromatographic techniques when and where needed to give the corresponding
propargylamine in excellent yields. The residue (Fe/TiO2) was washed with diethyl ether and
acetone to ensure removal of any organic substrate from the surface of the catalyst. Catalyst was
then vacuum dried in oven characterized by TEM measurements and reused in next run.
188
189
3. Results and Discussion
3.1 Characterization of Fe-doped MO2 nanoparticles
190
191
192
193
194
For the synthesis of Fe-doped material, initially Fe was bonded to polymeric P123 by modifying
method reported earlier [53]. In the present case (Scheme 1) sodium salt of poly(ethylene oxide)-
poly(propylene oxide)-polyethylene oxide) [(PEO)20-(PPO)70-(PEO)20] block co-polymer was
prepared where the terminal hydrogen of hydroxyl groups were replaced by Na, to which Fe salt
was added leading to formation of Fe-P123 system with NaCl precipitation. These Fe metal
9
Page 9 of 34

195
196
197
198
199
200
201
202
203
204
205
206
207
208
209
210
211
212
213
214
modified surfactants were added to a respective pre-hydrolyzed silica and titania solution giving
brown sols. These prepared sols were kept for ageing and then for self evaporation of solvent to
generate uniform porosity and fine structure formation. The powder obtained in case of silica
was rinsed with ethanol to remove polymeric surfactant and resultant obtained was yellowish
free flowing Fe-doped silica powder. While for titania, a sticky material was obtained, which
was then subjected to calcination at 450 ˚C giving a light yellow colored Fe-doped titania
powder. These synthesized materials were characterized for their structural and morphological
studies. The XRD patterns for Fe/TiO2 and Fe/SiO2 prepared using sol-gel process were
measured. XRD pattern of Fe-TiO2 powder (Figure S3, please see supporting information) shows
that Fe/TiO2 is crystalline material in anatase phase. There was no diffraction peak of rutile and
no ferum compound was found. This shows that the presence of transition metal Fe neither
influence the transformation of anatase to rutile (unlike work done by Ganesh et al. [46]), nor
creates new crystal phases. No characteristic peaks of Fe metal or its oxide can be detected as is
doped in titania in a small quantity and it was not enough to be detected. The full width at half
maximum height of the peak at 23.3˚ 2θ was 0.010031˚(radian). Scherrer’s equation was used to
estimate the crystalline domain size and the estimated crystalline domain size for Fe/TiO2 was
found to be 14.8 nm. The XRD analysis of Fe/SiO2 (Figure S4, please see supporting
information) showed two broad diffraction peaks around 2θ values of 11.8 and 22.3 due to
amorphous silica and no particular reflection of Fe were found in XRD. Also, the broad peaks
are characteristics of small particles with crystallite diameter lower than 15 nm.
215
216
217
The Nitrogen adsorption-desorption isotherms and size distribution plots of Fe/TiO2 and Fe/SiO2
are depicted in Figure 1, which shows a type-IV isotherm with a large hysteresis indicating a 3D
intersection network of porous structure according to IUPAC explanation and capillary
10
Page 10 of 34

218
219
220
221
222
223
224
225
226
condensation of N2 is occurring during the adsorption process. For Fe/TiO2, the specific surface
area calculated according to the BET equation was 64.17 m2/g and the total pore volume was
0.031 cm3/g which corresponds to an average pore diameter (4V/A by BET) of 5.4 nm. The pore
size distribution derived from the isotherm data using BJH model was quite broad with a
maximum at 5.48 nm. On the other hand for Fe/SiO2, the pore size distribution based on the
adsorption branch of the isotherm is relatively broad with an average pore diameter of 3.6 nm.
The narrow pore size distribution indicates good homogeneity of the pores. The BET surface
area and pore volume of the material are about of 236 m2/g and 0.041 cm3/g respectively. The
BJH pore size distribution was found to be 4.3nm which is quite close to average pore diameter.
227
228
229
230
231
232
233
234
235
The morphologies of synthesized materials were examined using TEM, SEM, EDS and DLS
measurements. The TEM image of Fe/TiO2 (Figure S5(a)) shows clear spherical and non-
homogeneous structures having diameter in range from 7-14nm which is consistent with the
result obtained from XRD analysis while Fe/SiO2 exhibits a disordered sponge like pore
structure (Figure S5(b)). Figure 2 represents the SEM micrographs for the doped materials. The
nanoparticles obtained from Fe/TiO2 are of regular shapes and are quite smooth. Clear
nanostructures can be seen having grain size of ~10 nm which are in agreement with the result
obtained from TEM measurements. The SEM results of Fe/SiO2 shows porous structure of silica
matrix.
236
237
238
239
To gain information whether the nanoparticles contains the doped Fe metal atoms, EDS analysis
was carried out and typical EDS spectrum is shown in Figure 3. In both cases, signal of Fe
particles is accompanied by Ti and Si, which confirms that Fe metal particles are selectively
deposited on the titania and silica particles for Fe/TiO2 and Fe/SiO2 respectively. The results
11
Page 11 of 34

240
241
shows 1.00 wt% and 3.03 wt% of Fe content have been embedded in Fe/TiO2 and Fe/SiO2
respectively.
242
243
244
245
246
247
248
249
250
251
252
In order to correlate the morphology of nanoparticles, we have characterized the Fe/TiO2 and
Fe/SiO2 in aqueous solution by DLS measurements. Figure 4 depicts the particle size distribution
of synthesized materials which shows that the mean diameter of Fe/TiO2 nanoparticles is ~10-15
nm having a spherical shape, while Fe/SiO2 shows the nanoparticles polydispersed in shape with
two different sizes, one in the range of 10 nm might be for Fe nanoparticles and the other
between 17-20 nm belongs to silica. The slightly larger particle size might be due to the
agglomeration of silica particle because of amorphous nature which affects the catalytical
activity. The mean diameter, ~ 15 nm for Fe/TiO2 is in agreement with size obtained by XRD,
TEM and SEM measurements. The above measurements show that Fe/TiO2 and Fe/SiO2 NPs
have porosity and large surface area therefore can be good candidate as catalyst for numerous
reactions.
253
3.2 Catalytic activity of Fe-doped MO2
254
255
256
257
258
259
260
261
The sol-gel process is of particular interest for designing catalytically active materials with
specific properties and/or with improved performances compared to those of classical catalysts.
It allows preparation of catalytically active materials which can be directly cast on supports at
the sol stage. So, the synthesized Fe/TiO2 and Fe/SiO2 mesoporous materials were tested as
catalyst for the Aldehyde-Alkyne-Amine coupling reactions. To search for the optimal doped
catalyst, screening of Fe/TiO2 and Fe/SiO2 along with the reaction conditions were carried out.
We selected first the simplest A3-coupling reaction with a commonly used Amine-Piperidine, a
reactive Aldehyde-Formaldehyde and Phenylacetylene as Alkyne precursor in a ratio of 1 : 1.1 :
12
Page 12 of 34

262
263
264
265
266
267
268
269
270
271
272
273
274
275
276
277
278
279
280
281
282
283
284
1.2 (Table 1). The reaction was irradiated in solvent free condition at 210 W microwave power
(Temperature reached = 54 ˚C) for 15min using Fe/SiO2 and Fe/TiO2 catalyst, the desired
propargylamine was isolated in 58 % and 60 % yield respectively (Entry 1 and 2, Table 1). In an
attempt to increase the yield of propargylamine, we carried out the reaction using various organic
solvents. Indeed, yields were quite similar in polar, slightly polar and non-polar solvents (Entry
3-10, Table 1) at MW power of 210 W. At a little higher MW power of 245 W, the reaction
proceeds well specially when tetrahyrofuran, THF (temperature reached = 62 ˚C) was used as
solvent (Entry 11 and 12, Table 1). When the reaction was carried out under solvent free
conditions, the reaction was far more efficient being almost quantitative under such conditions
when Fe/TiO2 was used as catalyst. To avoid the use of volatile solvents and to reduce the
environmental pollution, the three component coupling reactions were performed under solvent-
free conditions in presence of Fe/TiO2 (Temperature reached = 60 ˚C). Use of heterogeneous
solid supports led to higher efficiencies for A3-coupling reaction. Fe/TiO2 was found to be a
better catalyst than Fe/SiO2, though the Fe content is higher in doped SiO2 material. The better
catalytic activity of Fe/TiO2 might be because of the crystalline phase (anatase) of titania with
porous framework, due to which the accessibility of active site Fe becomes much more easier
compared to amorphous doped silica. Moreover, due to the process of calcinations followed for
Fe/TiO2, there is very strong metal-support interactions compared to Fe/SiO2 catalyst. This
shows that the Fe content does not play a major role in enhancing the reaction efficiency and
propargylamine yield, but the type of solid support does. During the course of our further
optimization of the conditions, when using 50 mg of catalyst the reaction goes effectively, but
with lesser yields but when 100 mg of Fe/TiO2 was used, the reactions were generally completed
in 20 min when performed at 245 W MW power under solvent less condition giving very good
13
Page 13 of 34

285
286
product yields. Increasing catalyst amount above this leads to no such improvements in
propargylamine yield.
287
288
289
290
291
292
293
294
295
296
297
298
299
300
301
302
The scope of the reaction was evaluated for different combinations of aldehydes and amines with
phenyl acetylene applying the optimal conditions using Fe/TiO2. As depicted in Table 2, the
reaction works very well for a wide range of substrates with very good to excellent yields. In
general, both aromatic and aliphatic aldehydes underwent the addition reaction smoothly.
However, the reaction was found strongly influenced by the nature of aldehyde. As can be seen
from the results, aliphatic aldehydes were found to be more reactive than the aromatic aldehydes.
A variety of aromatic aldehydes possessing electron withdrawing and electron donating groups
were examined for A3-coupling reaction and both the functionalities afforded the corresponding
Propargylamines in good to excellent yields. In order to study the scope of amine substrates, a
combination of Formaldehyde/Phenyl acetylene/Amines was chosen and various amines were
examined. Piperidine and Morpholine gave the corresponding Propargylamine in excellent
isolated yields. While for aldehydes, the smaller is the aldehydes higher is the product yield
obtained. With respect to the secondary amines, cyclic amines reacted efficiently under standard
conditions, whereas acyclic amines, such as Dibenzylamines and Diphenylamines (Entry 3, 4,
Table 2) generated the corresponding products in moderate to good yields. The 1H-NMR spectra
of selected products are given in Figure S7.
303
304
305
306
Solid catalysts for C-C coupling reactions have been primarily developed as a means to separate
the reaction products from the catalyst, potentially facilitating decreased process cost due to
reduced catalyst loss and simplified product purification. It is only rare that highly active
heterogeneous systems are accompanied by serious mechanistic studies about the real nature of
14
Page 14 of 34

307
308
309
310
311
312
313
314
315
316
317
318
319
catalysis. Keeping the concept in mind a tentative mechanism for the A3-coupling is shown in
Scheme 2 which involves C–H activation of the alkyne by the transition metal catalyst. The
metal acetylide formation, a common step for Sonogashira and A3-coupling, is still poorly
understood. Generally weak bases presented in the reaction media (starting amine, final
propargylamine.) are unable to deprotonate the terminal alkyne directly. The transition metals are
well known to form π complexes with terminal alkynes, thereby increasing the acidity of the C–
H bond, thus here Fe/TiO2 plays a major role in enhancing the reaction efficiency by activating
the C–H bond. The Fe/TiO2 catalyst reacts with the alkyne to form an alkynyl Fe complex. The
microwave irradiation speeds up the formation of the alkynyl Fe complex and A3 –coupling
reaction [10]. The A3 –coupling using a primary amine is thought to commence with the in situ
formation of an imine and subsequently attack by alkynyl Fe and undergo intramolecular transfer
of the alkyne moiety to the imine (please see product B in Scheme 2). Decomplexation produces
the free propargylamine, (product C in Scheme 2) and regenerates the Fe/TiO2 catalyst.
320
321
322
323
324
325
326
327
In order to determine whether the reaction proceeded in a homogeneous or heterogeneous
fashion, hot filtration test was performed for A3-coupling reaction of Formaldehyde, Piperidine
and Phenyl acetylene. Rapid separation of Fe/TiO2 catalyst from the reaction mass after a
reaction time of 5 min under MW conditions was carried out and the hot reaction mass was
allowed to react further under similar conditions. We found that no further progress in reaction
was observed as no propargylamine formation was observed (GC-MS). This shows no evidence
of Iron leaching into the products which was also confirmed by ICP test, which in turn provides
evidence of TiO2 acting as a good scaffold for Fe catalyst precursors.
15
Page 15 of 34

328
329
330
331
332
333
334
335
The catalytic stability of Fe/TiO2 was studied by separating and recycling the catalyst.
Recyclability of the catalyst was tested for the reaction of Formaldehyde, Piperidine and Phenyl
acetylene under solvent-free conditions. After carrying out the reaction, the catalyst was
separated by simple filtration, washed with acetone, dried and used for the next run. We
observed that the catalytic activity of Fe/TiO2 was restored within the limits of the experimental
errors for five successive runs as presented in Table 3. The recycled Fe/TiO2 catalyst was further
characterized by TEM which shows no major change in its morphology (Figure S6, Supporting
information).
336
4. Conclusions
337
338
339
340
341
342
343
344
In conclusion, Fe-doped Titania (Fe/TiO2) and Silica (Fe/SiO2) mesoporous materials were
synthesized by sol-gel process and characterized using XRD, BET, TEM, SEM, EDS and DLS
measurements. The particle size in the range of 10-15 nm was observed from the measurements.
The synthesized Fe/TiO2 and Fe/SiO2 were used and screened for the Aldehyde-Alkyne-Amine
coupling reaction. Among the two, Fe/TiO2 was proved to be an effective catalyst for A3-
coupling reaction under solvent-free condition and microwave irradiation. The absence of
solvent, low reaction time under microwaves and heterogeneous recyclable catalyst imply a very
low energetic cost and very low environmental impact, thus resulting in green process.
345
Acknowledgments
346
347
Authors are thankful to SICART, Vallabh Vidyanagar for TEM and GC-MS analysis, and SAIF,
IIT Bombay for SEM-EDS analysis. Authors are also very thankful to Mr. Sahaj and Dr. U. H.
16
Page 16 of 34

348
349
Patel, Department of Physics for XRD measurements. One of the author DAK is highly thankful
to UGC-Delhi for providing financial assistance in terms of meritorious fellowship.
350
351
352
353
354
355
356
357
358
359
360
361
362
363
364
365
366
367
368
369
370
371
372
17
Page 17 of 34

373
374
375
376
References
1. M. Moreno-Manas, R. Pleixats, Acc. Chem. Res. 36 (2003) 638.
2. Y. Gu, Green Chem. 14 (2012) 2091.
377
378
3. N. Isambert, M. M. S. Duque, J. -C. Plaquevent, Y. Genisson, J. Rodriguez, T. Constantieux,
Chem. Soc. Rev. 40 (2011) 1347.
379
4. C. Wei, L. Zhang, C. J. Li, Synlett (2004) 1472.
380
381
5. M. A. Huffman, N. Yasuda, A. E. DeCamp, E. J. J Grabowski, J. Org. Chem. 60 (1995)
1590.
382
6. D. Enders, U. Reinhold, Tetrahedron: Asymmetry 8 (1997) 1895.
383
384
7. G. S. Kauffman, G. D. Harris, R. L. Dorow, B. R. P. Stone, R. L. Parsons Jr., J. A. Pesti, N.
A. Magnus, J. M. Fortunak, P. N. Confalone, W. A. Nugent, Org. Lett. 2 (2000) 3119.
385
386
387
388
389
390
391
392
393
394
8. S. Nakamura, M. Ohara, Y. Nakamura, N. Shibata, T. Toru, Chem. Eur. J. 16 (2010) 2360.
9. M. K. Patil, M. Keller, B. M. Reddy, P. Pale, J. Sommer, Eur. J. Org. Chem. (2008) 4440.
10. J. B. Bariwal, D. S. Ermolat’ev, E. V. Van der Eycken, Chem. Eur. J 16 (2010) 3281.
11. A. Fodor, A. Kiss, N. Debreczeni, Z. Hell, I. Gresits, Org. Biomol. Chem. 8 (2010) 4575.
12. X. Zhang, A. Corma, Angew. Chem. Int. Ed. 47 (2008) 4358.
13. M. Kidwai, V. Bansal, A. Kumar, S. Mozumdar, Green Chem. 9 (2007) 742.
14. V. K. -Y. Lo, Y. Liu, M. -K. Wong, C. -M. Che, Org. Lett. 8 (2006) 1529.
15. C. Wei, C. -J. Li, J. Am. Chem. Soc. 125 (2003) 9584.
16. C. Wei, Z. Li, C. -J. Li, Org. Lett. 5 (2003) 4473.
17. Z. Li, C. Wei, L. Chen, R. S. Varma, C. –J. Li, Tetrahedron Lett. 45 (2004) 2443.
395
396
18. K. M. Reddy, N. S. Babu, I. Suryanarayana, P. S. Sai Prasad, N. Lingaiah, Tetrahedron Lett.
47 (2006) 7563.
397
398
399
19. P. Li, L. Wang, Y. Zhang, M. Wang, Tetrahedron Lett. 49 (2008) 6650.
20. S. Sakaguchi, T. Mizuta, M. Furuwan, T. Kubo, Y. Ishii, Chem. Commun. (2004) 1638.
21. S. Samai, G. C. Nandi, M. S. Singh, Tetrahedron Lett. 51 (2010) 5555.
18
Page 18 of 34

400
401
402
403
22. L. C. Akullian, M. L. Snapper, A. H. Hoveyda, Angew. Chem. Int. Ed. 42 (2003) 4244.
23. Y. Kuninobu, Y. Inoue, K. Takai, Chem. Lett. 35 (2006) 1376.
24. W. –W. Chen, R. V. Nguyen, C. –J. Li, Tetrahedron Lett. 50 (2009) 2895.
25. P. Li, Y. Zhang, L. Wang, Chem. -Eur. J. 15 (2009) 2045.
404
405
26. T. Zeng, W. –W. Chen, C. M. Cirtiu, A. Moores, G. Song, C. –J. Li, Green Chem. 12 (2010)
570.
406
407
408
409
410
411
27. L. Pin-Hua, W. Lei, Chin. J. Chem. 23 (2005) 1076.
28. Y. Zhang, P. Li, M. Wang, L. Wang, J. Org. Chem. 74 (2009) 4364.
29. W. –W. Chen, H. –P. Bi, C. –J. Li, Synlett (2010) 475.
30. E. Ramu, R. Varala, N. Sreelatha, S. R. Adapa, Tetrahedron Lett. 48 (2007) 7184.
31. C. Mukhopadhyay, S. Rana, Catal. Commun. 11 (2009) 285.
32. B. Roy, R. Raj, B. Mukhopadhyay, Tetrahedron Lett. 50 (2009) 5838.
412
413
33. F. A. Cotton and G. Wilkinson, Inorganic Chemistry, 4th edn, Verlag Chemie: Weinheim,
1982.
414
415
416
34. C. Bolm, J. Legros, J. L. Paih, L. Zani, Chem. Rev. 104 (2004) 6217.
35. B. D. Shrey, A. Furstner, Acc. Chem. Res. 41 (2008) 1500.
36. A. Correa, O. G. Mancheno, C. Bolm, Chem. Soc. Rev. 37 (2008) 1108.
417
418
37. N. Nasralla, M. Yeganesh, Y. Astuti, S. Piticharoenphun, N. Shantahmasebi, A. Kompany,
M. Karimipour, B. G. Mendis, N. R. J. Poolton, L. Siller, Sientia Irania F 20 (2013) 1018.
419
420
38. C. H. Deng, S. D. Brooks, G. Vidaurre, D. C. O. Thornton, Aerosol Sci. & Technol. 48
(2014) 193.
421
422
39. C. Liu, J. Li, J. Qi, J. Wang, R. Luo, J. Shen, X. Sun, W. Han, L. Wang, ACS Appl. Mater.
Interfaces 6 (2014) 13167.
423
424
425
426
40. O. Mero, M. –T. Sougrati, J. –C. Jumas, S. Margel, Langmuir 30 (2014) 9850.
41. D. A. Kotadia, U. H. Patel, S. Gandhi, S. S. Soni, RSC Adv. 4 (2014) 32826.
42. S. S. Soni, D. A. Kotadia, Catal. Sci. Technol. 4 (2014) 510.
43. J. Yu, Q. Xiang, M. Zhou, Appl. Catal. B. Environ. 90 (2009) 595.
19
Page 19 of 34

427
428
44. S. Yu, H. J. Yun, D. M. Lee, J. Yi, J. Mater. Chem. 22 (2012) 12629.
45. Z. Zhang, D. Han, S. Wei, Y. Zhang, J. Catal. 276 (2010) 16.
429
430
46. I. Ganesh, P. P. Kumar, A. K. Gupta, P. S. C. Sekhar, K. Radha, G. Padmanabham, G.
Sundararajan, Proc. Appl. Ceramics 6 (2012) 21.
431
47. J. Zhu, W. Zheng, B. He, J. Zhang, M. Anpo, J. Mol. Cat. A 216 (2004) 35.
432
433
48. C. Y. Wang, C. Bottcer, D. W. Bahnemann, J. K. Dohrmann, J. Mater. Chem. 13 (2003)
2329.
434
435
49. R. Alexandrescn, I. Morjan, M. Scarisoreanu, R. Birjega, E. Popovici, I. Soare, L. Gavrila-
Fluorescu, I. Voicu, I. Sandu, E. Vasile, E. Figgemeier, Thin Solid Films 24 (2007) 8438.
436
437
50. X. Zhang, M. Zhou, L. Lei, Catal. Commun. 7 (2006) 427.
51. Y. Sun, S. Walspurger, J. –P. Tessonnier, B. Louis, J. Sommer, Appl. Catal. A 300 (2006) 1.
438
439
52. T. Tsoncheva, J. Rosenholm, C. V. Teixeira, M. Dimitrov, M. Linden, C. Minchev,
Microporous Mesoporous Mater. 89 (2006) 209.
440
441
53. R. Supplit, N. Husing, H. Bertagnolli, M. Bauer, V. Kessler, G. A. Seisenbaeva, S.
Bernstorff, S. Gross, J. Mater. Chem. 16 (2006) 4443.
442
443
444
445
446
54. C. J. Brinker, Y. Lu, A. Sellinger, H. Fan, Adv. Mater. 11 (1999) 579.
55. S. S. Soni, M. J. Henderson, J. –F. Bardeau, A. Gibaud, Adv. Mater. 20 (2008) 1493.
56. S. S. Soni, G. S. Dave, M. J. Henderson, A. Gibaud, Thin Solid Films 531 (2013) 559.
57. M. J. Aliaga, D. J. Ramon, M. Yus, Org. & Biomol. Chem. 8 (2010) 43.
447
448
449
450
451
20
Page 20 of 34

452
453
454
455
456
457
458
459
460
461
462
463
464
465
466
467
468
Caption to Schemes :
Scheme 1 Schematic representation for synthesis of Fe-doped TiO2 and SiO2
Scheme 2 Catalytic cycle of A3-coupling reactions catalyzed by Fe/TiO2 catalysts
21
Page 21 of 34

469
470
Fe-TiO2 and SiO2
Mesoporous material
471
472
473
474
475
476
477
478
Scheme 1
22
Page 22 of 34

479
480
481
Fe
TiO2
R1
H
NHR3
R2
R1
(C)
Microwave
R3
Fe/TiO2
N
R1
Fe/TiO2
(A)
R3
R1
R3NH2
N
R2
(B)
+
R2CHO
R2
H
482
483
484
485
486
487
488
489
Scheme 2
23
Page 23 of 34

490
491
Caption to Figures
492 Figure 1 N2 adsorption–desorption isotherms of (a) Fe/TiO2 and (b) Fe/SiO2 along with
493
494
495
496
497
corresponding pore size distribution derived from adsorption isotherm (inset)
Figure 2 The SEM images of synthesized (a) Fe/TiO2 and (b) Fe/SiO2 nanoparticles
Figure 3 The typical(aE)DS pattern of (a) Fe/Ti(Ob) and (b) Fe/SiO2 nanoparticles
2
Figure 4 Particles size analysis (DLS) of (a) Fe/TiO2 and (b) Fe/SiO2 nanoparticles
498
499
500
501
502
503
504
505
506
507
508
24
Page 24 of 34

60
50
40
30
20
10
0.010
0.008
0.006
0.004
0.002
20
40
60
80 100 120 140 160
Pore diameter, (A)
(a)
0.0
0.2
0.4
0.6
0.8
1.0
Relative Pressure (P/P0)
509
0.025
0.020
0.015
0.010
0.005
0.000
50
40
30
20
10
0
0
10
20
30
40
50
60
Pore diameter, (A)
(b)
0.0
0.2
0.4
0.6
0.8
1.0
Relative Pressure (P/P0)
510
511
Figure 1
512
513
25
Page 25 of 34

514
515
516
517
518
(a)
(b)
519
520
Figure 2
521
522
523
524
525
526
26
Page 26 of 34

527
528
529
(a)
(b)
530
531
Figure 3
532
533
534
535
536
537
538
539
27
Page 27 of 34

540
541
542
543
544
100
90
80
70
60
50
40
30
20
10
0
60
50
40
30
20
10
0
(a)
(b)
5
10
15
20 25 30 35 40
5
10
15
20 25 30 35 40
Size (d.nm)
Size (d.nm)
545
546
Figure 4
547
548
549
550
551
552
28
Page 28 of 34

553
Tables
554
555
556
557
558
559
560
561
562
563
564
565
566
567
568
569
570
571
572
573
574
575
576
Table 1 Test experiments for optimization of A3-Coupling reactiona
Table 2 The A3-coupling reactions of various aldehydes and amines with phenyl acetylenea
a
Table 3 Recyclability study of Fe/TiO2
29
Page 29 of 34