Organic synthesis via magnetic attraction: Benign and sustainable protocols using magnetic nanoferrites

Article abstract of DOI:10.1039/c2gc36455g

Magnetic nano-catalysts have been prepared using simple modification of iron ferrites. The nm size range of these particles facilitates the catalysis process, as an increased surface area is available for the reaction; the easy separation of the catalysts by an external magnet and their recovery and reuse are additional beneficial attributes. Glutathione bearing nano-ferrites have been used as organocatalysts for the Paal-Knorr reaction and homocoupling of boronic acids. Nanoferrites, post-synthetically modified by ligands, were used to immobilize nanometals (Cu, Pd, Ru, etc.) which enabled the development of efficient, sustainable and green procedures for azide-alkynes-cycloaddition (AAC) reactions, C-S coupling, O-allylation of phenol, Heck-type reactions and hydration of nitriles.

Full text of DOI:10.1039/c2gc36455g

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Organic synthesis via magnetic attraction: benign and
sustainable protocols using magnetic nanoferrites†
Cite this: Green Chem., 2013, 15, 398
R. B. Nasir Baig and Rajender S. Varma*
Magnetic nano-catalysts have been prepared using simple modification of iron ferrites. The nm size
range of these particles facilitates the catalysis process, as an increased surface area is available for the
reaction; the easy separation of the catalysts by an external magnet and their recovery and reuse are
additional beneficial attributes. Glutathione bearing nano-ferrites have been used as organocatalysts for
the Paal–Knorr reaction and homocoupling of boronic acids. Nanoferrites, post-synthetically modified by
ligands, were used to immobilize nanometals (Cu, Pd, Ru, etc.) which enabled the development of
efficient, sustainable and green procedures for azide–alkynes-cycloaddition (AAC) reactions, C–S coupling,
O-allylation of phenol, Heck-type reactions and hydration of nitriles.
Received 13th September 2012,
Accepted 12th November 2012
DOI: 10.1039/c2gc36455g
www.rsc.org/greenchem
high-surface-area heterogeneous catalyst support.3 They offer
an added advantage of being magnetically separable, thereby
1. Introduction
In homogeneous catalysis, the chemo-, regio-, and enantio- eliminating the requirement of catalyst filtration after com-
selectivity of the catalyst is better but the difficulty of catalyst pletion of the reaction. Engaged in the development of greener
separation from the final product creates economic and and sustainable pathways for organic transformations,4,5 nano-
environmental barriers. To overcome these drawbacks, che- materials,6 and nano-catalysis,7 herein, a simple and efficient
mists and engineers have investigated a wide range of strat- synthesis of nano-ferrite-supported, magnetically recyclable,
egies; the use of heterogeneous catalyst systems appears to be and inexpensive catalysts and their applications in organic syn-
the best logical solution.1 The vast majority of the novel hetero- thesis are reported.
genized catalysts are based on silica supports, due to the
fact that organic groups can be robustly anchored to the silica
surface to provide catalytic centers.2 The common structural
1.1. Magnetic nano-catalysts (MNC)
feature of these materials is the anchoring of the catalytic mole-
cule (dopant) in the pores of silica, a phenomenon that
imparts unique chemical and physical properties to the result-
ing hybrid silica. A vast majority of the industrial, hetero-
geneous catalysts are high-surface area solids onto which an
active component is dispersed or attached. Although attempts
have been made to make all active sites on solid supports
accessible for the reaction only, sites on the surface are avail-
able for catalysis, which decreases the overall reactivity of the
catalyst system. To address this issue, the emerging area of
nano-catalysis can ideally provide the solution as most of the
catalyst surface is available for the reaction. Among them func-
tionalized magnetic nanoparticles are very good alternatives to
conventional materials as a robust, readily available, and a
The applications of magnetic nano-catalysts are increasing
steadily in the field of catalysis as they are designed at the
nano-level, especially for heterogeneous catalysis. MNC can
assist researchers in the design of catalysts with good activity,
stability, selectivity and reusability by virtue of isolation using
an external magnet; most heterogeneous systems require a fil-
tration or a centrifugation step or a tedious workup of the final
reaction mixture to recover the catalyst. These active magnetic
nanocatalytic systems possess several advantages over conven-
tional catalyst systems:
•
Magnetic nanocatalysts are small in size and have an
enormous surface area to volume ratio.
Since the available surface area of the active component
•
of the catalyst is large, the contact between the reactant mole-
cules and the catalyst is enhanced to a great extent which
facilitates the heterogeneous catalytic system; reaction rates
closer to its homogeneous counterpart can be achieved.
Sustainable Technology Division, National Risk Management Research Laboratory,
U.S. Environmental Protection Agency, 26 West M.L.K. Dr., MS 443, Cincinnati,
•
Easy control over size, shape, and morphology makes it
OH 45268, USA. E-mail: varma.rajender@epa.gov; Fax: +1 513-569-7677;
possible to rationally design the materials that are specifi-
cally needed for a particular catalytic application; tuning the
properties of metals is easily possible when working at the
Tel: +1 513-487-2701
†Presented, in part, at the 244th ACS National Meeting Philadelphia, Aug 19–23,
2012.
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nanoscale, which would be impossible with their macroscopic patterns and relative intensities of all the peaks matched well
counterparts. with those of magnetite (JCPDS card no. 00-002-1035). No
Magnetic nature allows them to be separated using exter- other oxide or hydroxide phase was observed; the broad XRD
•
nal magnet thus facilitating recyclability and reusability.
peaks clearly indicate the nanocrystalline nature of the
material. Transmission electron microscopy (TEM) analysis
2. Results and discussion
2.1 Design and synthesis of a magnetic nanoferrite-
supported glutathione catalyst
Organocatalysis has been extensively explored during the past
decade but much remains to be accomplished, especially in
the context of developing truly sustainable protocols. In view
of our ongoing program in the development of greener and
sustainable processes for organic synthesis and nano-
catalysis,4–7 an approach is envisioned: (a) a magnetic nano-
particle supported organocatalyst, (b) a totally benign aqueous
protocol which does not involve the use of organic solvents,
even in the work-up step, and (c) the use of glutathione as an
organocatalyst.
The first step in the development of this concept was the
selection of amino acids for the functionalization of magnetic
nanoparticles. It was decided to explore the completely benign
tripeptide glutathione, an essential component of plants and
human cell systems, as an organocatalyst. An additional
benefit of using glutathione is the presence of the highly reac-
tive thiol group in the middle of the molecule, which can be
used for anchoring to the nano-ferrite surfaces, keeping active
sites free for catalysis. To the best of our knowledge, neither
ubiquitous glutathione nor a magnetic nanoparticle-supported
organocatalyst has been exploited previously for any organo-
catalytic reactions, despite the potential activity of such a system.
The nano-organocatalyst (nano-FGT) was prepared in excellent
yield using a post-functionalization method (Scheme 1).7a
The crystalline structures of nano-FGT were determined
Fig. 1 (a) Powder XRD pattern and (b) TEM image of nano-FGT. (c) FTIR spectra
by powder X-ray diffraction (XRD) (Fig. 1(a)); the diffraction for glutathione; (d) FTIR spectra for the nano-FGT catalyst.
Scheme 1 Synthesis of nanoparticle-supported glutathione (nano-FGT).
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(Fig. 1(b)) of the organocatalyst showed uniform-sized particles optimized for the Paal–Knorr reaction using benzylamine as a
with spherical morphology with an average size range of substrate and using nano-FGT under MW irradiation con-
10–12 nm. Anchoring of glutathione on the surface of mag- ditions (Table 1).
netic nanoparticles was confirmed by FT-IR spectroscopy
(Fig. 1c and 1d).
MW-assisted chemistry was used due to the efficiency of the
interaction of microwaves with the polar nano-catalyst as they
allow rapid heating of the reaction mixture to required temp-
eratures with precise control.4,5,16 The reaction was first con-
ducted using nano-FGT in toluene as a reaction medium at
120 °C; a poor conversion was observed. Increasing the reac-
tion temperature to 140 °C provided no significant increase in
conversion. Interestingly, when the reaction was carried out in
a mixture of toluene and water, good conversion was achieved.
Encouraged from this result, the reaction was carried out in
pure water; 92% conversion was achieved in 20 min at 140 °C
under MW irradiation. No product formation was observed
when the reaction was tested with non-functionalized ferrites,
which clearly confirms that supported glutathione is the cata-
lytic species. Using these optimized reaction conditions, the
scope of this catalyst was then investigated for the Paal–Knorr
reaction of a variety of amines (Fig. 2).
2.2 MW-assisted Paal–Knorr reaction using magnetic nano-
FGT catalyst
The Paal–Knorr reaction in which amines are converted to
pyrrole in one step has gained great interest in the synthetic
organic chemistry, as these heterocycles are intermediates for
various pharmaceutical drugs.8 A range of clean protocols have
been developed.9–14 However, most of the above methods
involve the use of excess amounts of catalysts, toxic organic
solvents, and tedious workup and cannot be considered as real
green protocols. Hence, this glutathione-coated magnetic
nanomaterial was explored as
a nano-organocatalyst for
Paal–Knorr reactions (Scheme 2).15 Reaction conditions were
The nano-FGT displayed high catalytic activity for Paal–
Knorr reactions. A variety of amines reacted efficiently with tet-
rahydro-2,5-dimethoxyfuran to afford the desired pyrrole
derivatives in good yields (Fig. 2). The rates were barely influ-
enced by the aliphatic or aromatic nature of the amines,
showing the high activity of the catalyst. Chiral (S)-α-methyl-
benzylamine and (R)-α-methylbenzylamine yielded the corre-
sponding pyrroles without racemization. A heterocyclic and
aliphatic amine also underwent the Paal–Knorr reaction to the
corresponding pyrrole in good yield. This protocol is also suit-
able for acid hydrazide.
Scheme 2 Nano-FGT promoted Paal–Knorr reactions.
Table 1 Optimization of reaction conditions
S.N.
Solvent
Temp. (°C)
Time (min)
Conversiona
1
2
3
4
5
6
Toluene
Toluene
Toluene + water
Water
Water
Water
120
140
140
120
140
140
30
30
30
30
20
30
>5%
>5%
80%
70%
92%
95%
2.3 Homocoupling of arylboronic acids
Symmetrical biaryl motifs are present in a wide range of
natural products, which have interesting properties. A number
a Reaction conditions: 1 mmol of benzyl amine, 25 mg of nano-FGT.
Fig. 2 Synthesis of pyrroles using a magnetic nano-FGT catalyst.
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Scheme 3 Nano-FGT catalysed homocoupling of aryl boronic acids.
Fig. 3 Synthesis of biaryls using nano-FGT as a catalyst.
of organic protocols including the Suzuki and Sonogashira the phase separation of the desired product from the aqueous
cross coupling reactions as well as their homocoupling alterna- media occurred in most cases, thus facilitating the isolation of
tives can synthesize this important family of compounds. Both the crude product by simple decantation rather than tedious
types of reactions have generally been reported to be catalyzed extraction processes. Consequently, the use of volatile organic
with a variety of supported transition metals or transition solvents is reduced during product workup. In a few cases, the
metal complexes and oxidants under basic conditions in a solid product precipitated out; the product could then be iso-
range of solvents.17 The nano-FGT catalyst was tested for the lated by simple filtration.
homocoupling of aryl boronic acid (Scheme 3).18 Interestingly
To evaluate lifetime and level of reusability of the catalyst,
the catalyst works well with a wide range of substrates in the experiments were conducted using the recycled nano-FGT
aqueous media under microwave conditions (Fig. 3) and catalyst for the Paal–Knorr reaction of benzylamine. After the
reused several times without losing its activity. The reaction completion of the first reaction, the product layer was removed
works well under neutral conditions; however, a few drops of by decantation and the catalyst was recovered magnetically,
0.1 N NaOH was added in order to facilitate the solubility of washed with water and methanol, and dried. A new reaction
aryl boronic acid in water.
was then conducted with fresh reactants under similar con-
ditions. It was found that the developed catalyst could be used
at least 5 times without any change in activity. Alternatively,
the reaction could be carried out by simply removing the
product layer and adding fresh benzylamine and tetrahydro-
2,5-dimethoxyfuran, and similar results were obtained.
2.4 Recovery and reuse of nano-FGT catalyst
Separation of the catalyst and isolation of products are the
main operations in aqueous organocatalysis.19 Catalyst recov-
ery is often performed by filtration that reduces efficiency and
extractive isolation of products requires large amounts of
organic solvents. In the case of the Paal–Knorr reaction,
because of the super-paramagnetic nature of the material,
2.5 Design and synthesis of magnetic bimetallic nano-
FGT-Cu catalyst
within a few seconds after stirring was stopped, the reaction The first step in the accomplishment of this goal was the syn-
mixture turned clear and the catalyst was deposited on the thesis and functionalization of magnetic nanoparticles. The
magnetic bar which was easily removed using an external catalyst was prepared by sonicating nano-ferrites with gluta-
magnet. It was observed that after completion of the reactions, thione (Scheme 4) in water for 2 h followed by the addition of
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Scheme 4 Synthesis of nano-ferrite supported glutathione-copper (nano-FGT-Cu(0)) catalyst.
CuCl2 at a basic pH. Cu nanoparticles on the glutathione func- XRD (Fig. 4b) indicating that the Cu species is highly dispersed
tionalized nano-ferrites, nano-Fe3O4-glutathione (nano-FGT-Cu), on ferrites. The weight percentage of copper in nano-FGT-Cu
were separated using an external magnet, washed with water fol- was found to be 1.57% by inductively coupled plasma-atomic
lowed by methanol, and dried under vacuum at 60 °C for 8 h. emission spectroscopy (ICP-AES) analysis.
The catalyst was characterized by X-ray diffraction (XRD)
2.6 Triazole synthesis using nano-FGT-Cu copper catalyst
(Fig. 4b) and transmission electron microscopy (TEM) (Fig. 4a),
which confirms the formation of single-phase Fe3O4 nanoparti-
cles with spherical morphology and a size range of 10–25 nm.
FT-IR confirms the anchoring of glutathione on ferrite surfaces.
The signals pertaining to the copper metal were not detected by
The 1,2,3-triazole family has shown interesting biological prop-
erties, such as anti-allergic,20 anti-bacterial,21 and anti-HIV
activity.22 Additionally, 1,2,3-triazoles are found in fungicides,
herbicides, and dyes.23 The recently discovered copper(I)
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Fig. 4 (a) TEM of nano-FGT-Cu, (b) XRD of nano-FGT-Cu.
Scheme 5 Screening of magnetic catalysts for cycloaddition of benzyl azide and phenyl acetylene.
catalysis of this transformation,24 which accelerates the reac-
Table 2 Screening of catalystsa
tion up to 107 times, has placed it in a class of its own and has
enabled many novel applications. To further improve the
utility and user-friendliness of this process, a practical multi-
component variant was developed. Initially, experiments were
performed to optimize the reaction conditions for cyclo-
addition of benzyl azide and phenylacetylene in aqueous
media. First, the reaction was conducted using nano-Fe3O4
and nano-Fe3O4-glutathione (nano-FGT) in water under micro-
wave (MW) irradiation at 120 °C, which furnished 1,4 and 1,5
cyclic adducts in 20% yield and in 1 : 1 ratio (Scheme 5,
Table 2). In order to develop a magnetically recoverable catalyst
Entry
Catalyst
Time
Yield
Selectivity
1
2
3
4
Fe3O4
10 min
10 min
10 min
10 min
20
20%
80
1 : 1
1 : 1
3 : 1
Fe3O4-glut
Fe3O4-Cu
Nano-FGT-Cu
99%
100 : 0
a Reaction conditions: 1.2 mmol of benzyl azide, 1.0 mmol of alkyne,
100 mg of nano-FGT-Cu catalyst. MW, 120 °C, power 100 Watt.
reaction mixture to required temperatures.26,27 The expeditious
for regio-selective cycloaddition of alkynes and azides, the reaction was completed within 8 min to give very high yields of
the corresponding 1,2,4 triazoles.28a In the case of a highly
electron withdrawing group present in the alkynes (entry 3,
reaction of iron oxide with Cu(0) at its surface,25 i.e. using the
nano-Fe3O4-Cu bimetallic catalyst, was performed. Though the
rate of the reaction improved and 80% conversion was Table 3), the rate of the reaction was found to be relatively slow
and required 12 min for completion whereas in all of the other
cases (entries 1, 2, 4–6, Table 3) the reaction was completed
observed (10 min, MW, 120 °C, H2O), the selectivity of the reac-
tion was poor (3 : 1). To develop a highly active magnetically
recoverable catalyst, the nano-FGT-Cu catalyst was then pre- within 8 min. Encouraged by the preliminary results, further
studies were undertaken to make the reaction greener and
more sustainable. It was decided to perform this reaction in
pared by immobilizing Cu(0) on the nano-FGT surface
(see Scheme 4) with a particle size of 10–25 nm, and tested for
the cycloaddition of benzyl azide and phenyl acetylene. A very one-pot via in situ azide generation followed by cycloaddition
using a magnetically separable nano-FGT-Cu catalyst. At the
starting point of the exploration, alkyl halides, aromatic
selective formation of the 1,4 adduct in quantitative yield was
observed (Scheme 5, Table 2). After identifying the active nano-
magnetic catalyst, its role as a catalyst was then explored for alkynes, and sodium azide were suspended in water, together
with the nano-FGT-Cu catalyst (Scheme 6), in a 10 mL sealed
glass tube. After 10–15 min of irradiation and subsequent
the Huisgen [3 + 2]-cycloaddition. Initially, the reactions of
benzyl azide with a variety of alkynes under MW in water were
examined (120 °C, MW, H2O). MW-assisted chemistry was cooling to room temperature, the catalyst was separated mag-
netically. The triazole product often solidified from the
mixture upon completion of the reaction and could be isolated
used due to the efficiency of the interaction of microwaves
with the polar nano-catalyst as they allow rapid heating of the
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Table 3 Reaction of benzyl azide with alkyne catalyzed by a magnetic nano-FGT-Cu catalyst
Entry
1
Alkyl halide
Alkyne
Times
8 min
Product
Yielda
99%
2
3
4
5
6
8 min
12 min
8 min
8 min
8 min
97%
86%
98%
94%
95%
a Reaction conditions: 1.2 mmol of benzyl azide, 1.0 mmol of alkyne, 100 mg of nano-FGT-Cu catalyst. MW, 120 °C, power 100 Watt.
by simple filtration and purified by crystallization or by using with NaN3 (1.5 mmol) were treated in water, irradiated in an
a short column (Table 4). To check the regio-selectivity of the MW oven for 4 min at 120 °C followed by the addition of
multicomponent reaction, the products formed from the reac- 2-amino phenylacetylene (1.0 mmol) and further subjected to
tion of benzyl bromide and phenyl acetylene were compared MW irradiation for another 8 min. The reaction proceeded very
(Table 4, entry 1) with an authentic sample.
cleanly and furnished the corresponding triazole in 87% yield
It was established that the triazole was formed in a comple- (Table 4, entry 12). To further demonstrate the general applica-
tely regio-selective manner, with no contamination by the 1,5- bility and versatility of the nano-FGT-Cu catalyst, the mixture
regioisomer. In almost all cases, the reactions proceeded of benzyl bromide, sodium azide, and aliphatic alkynes and
smoothly to completion within 10 min, and the products were catalyst (Table 5) were irradiated in water. In all of the cases
isolated in excellent yields and high purity (Table 4). The 4- (Table 5, entries 1–3), the reactions proceeded smoothly at
bromo butene (Table 4, entry 13) was found to be less reactive 120 °C and required 12 min to afford the desired triazoles. In
among other halides. However, the reaction was completed the case of ethyl propionate (Table 5, entry 4), the reaction
(as analyzed by TLC) within 15 min. In the case of alkynes, the gave a mixture of products. To minimize the formation of by-
reactions were over in 10 min except for the reaction of p-nitro products the reaction temperature was reduced to 80 °C, which
phenylacetylene (Table 4, entry 6) which required 15 min. The led to an increase in the reaction time to 20 min (Table 5, entry
presence of various functional groups (CHO, NO2, halides, 4) and furnished the corresponding triazole in 85% yield. Con-
OMe, etc.) or a hetero ring in either of the substrates did not currently, Li et al. reported a magnetic copper–iron nanoparticle
affect the product formation in the one-pot treatment of alkyl for the azide–alkyne cycloaddition reaction in water.28b
halides, alkynes, and sodium azide with a catalyst except for
2.7 Recovery and reusability of nano-FGT-Cu catalyst
the reaction of 2-amino phenylacetylene (Table 4, entry 12),
which gave the complex mixture of products. It is believed that
the free amine may react with benzyl bromide along with
sodium azide, which leads to the formation of multiple pro-
ducts. In order to synthesize the corresponding triazole with a
free amine group, some changes were made in the sequence of
addition of the reactants. First, benzyl bromide (1.2 mmol)
The lifetime of the catalyst and its level of reusability are very
significant factors. To determine recyclability of nano-FGT-Cu,
a set of experiments was performed for the cycloaddition of
benzyl azide and phenylacetylene using the recycled nano-
FGT-Cu catalyst. After the completion of the first reaction, the
catalyst was recovered magnetically, washed with methanol,
Scheme 6 Synthesis of triazoles via a one-pot multi-component reaction.
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Table 4 Synthesis of triazoles via a one-pot multicomponent reaction catalyzed by a magnetic nano-FGT-Cu catalyst
Entry
1
Alkyl halide
Alkyne
Times
Product
Yielda
94%
10 min
2
3
4
5
6
7
8
10 min
10 min
10 min
10 min
15 min
10 min
10 min
94%
92%
88%
86%
80%
90%
87%
9
10 min
10 min
89%
92%
10
11
12
10 min
10 min
89%
87%b
13
15 min
91%
a Reaction conditions: 1.2 mmol of alkyl halides, 1.5 mmol of NaN3, 1.0 mmol of alkyne, 100 mg of nano-FGT-Cu catalyst. MW, 120 °C, power 100
Watt. b (i) Reaction conditions: 1.2 mmol of benzyl bromide, 1.5 mmol of NaN3, MW, 4 min, 120 °C, power 100 Watt. (ii) 1.0 mmol of alkyne,
100 mg of nano-FGT-Cu catalyst. MW, 8 min, 120 °C, power 100 Watt.
and dried at 60 °C for 30 min. A new reaction was then per- synthesis of many molecules that are of biological and
formed with fresh reactants, under the same conditions. The material interest.29 Organosulfur compounds are used in
nano-ferrite-supported Cu catalyst could be reused at least diverse fields with various applications, such as treatment of
three times without any change in activity (Table 6).28
diabetes, cancer, inflammation, Alzheimer’s disease, and
HIV.30–32 Traditionally, couplings were achieved under drastic
conditions, such as high reaction temperatures with the use of
toxic and high boiling polar solvents like quinoline, HMPA
and N,N-dimethylacetamide (DMF). Organosulfur chemistry
has been a beneficiary of the progress in transition metal cata-
lysis but C–S cross-coupling reactions are underexplored as
compared to C–N or C–O bond formation due to the deactiva-
tion of the metal catalyst by organosulfur compounds.33
3. Application of nano-FeDOPACu in
organic synthesis
3.1 Coupling of aryl halides with thiols
The carbon–sulfur cross-coupling reaction plays a significant
role in organic synthesis and constitutes a key step in the
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Table 5 Synthesis of triazoles using aliphatic alkynes catalyzed by nano-FGT-Cu
Entry
1
Alkyl halide
Alkyne
Times
Product
Yielda
92%
12 min
2
3
4
12 min
12 min
20 min
84%
89%
85%b
a Reaction conditions: 1.2 mmol of benzyl bromide, 1.5 mmol of NaN3, 1.0 mmol of alkyne, 100 mg of nano-FGT-Cu catalyst. MW, 120 °C, power
100 Watt. b Reaction conditions: 1.2 mmol of benzyl bromide, 1.5 mmol of NaN3, 1.0 mmol of alkyne, 100 mg of nano-FGT-Cu catalyst. MW,
20 min, 80 °C, power 100 Watt.
Table 6 Recycling of the catalyst
environment for the reaction. Isopropanol appeared to be the
logical choice. The reaction in a THF–iPrOH (1 : 1) mixture at
reflux temperature for 24 h showed a significant improvement
but did not proceed to completion. To reduce the reaction
time, the reaction was conducted under microwave (MW)
irradiation conditions at 120 °C for 25 min, which afforded the
corresponding coupled product in quantitative yield (Table 8,
entry 14). The cross-coupling of a wide variety of commercially
available aryl iodides and aryl bromides with thiophenols
occurred neatly; the corresponding diaryl sulfides were
obtained in good to excellent yields (Table 9). Electron with-
drawing and donating substituents on aryl halides did not
show a significant effect on the yield or the reaction time.
Interestingly, as in the case of thiophenols, para-chlorothio-
phenol did not undergo self-coupling and gave the desired
cross-coupled products (Table 9, entries 2, 4, 7, 9 and 11). The
reaction of 4-nitrothiophenol, however, proceeded sluggishly
and required 45 min for completion (Table 9, entry 5). Interest-
ingly, unlike other copper catalytic systems,39,40 it was selective
towards C–S bond formation and ineffective for C–O, C–N, and
C–C bond coupling and cycloaddition reactions.
No. of cycles
Yield
1
2
3
99%
97%
98%
Palladium catalyzed C–S cross-coupling reactions, using Pd
(PPh3)4 as a catalyst,34 require an additional ligand along with
precious Pd and an inert atmosphere.35 On the other hand, Co
and Ni catalysts are associated with toxicity.36,37 Thus, the
development of alternative, inexpensive, ligand-free, air and
moisture insensitive, and recyclable catalysts for this useful
reaction is highly desirable in the context of environmental
and industrial concerns.
Initially, the experiments were performed to identify
the appropriate catalyst for the coupling of thiophenols
(1.2 equiv.) with 4-bromonitrobenzene (1.0 equiv.). First, the
reaction was explored using nano-α-Fe3O4 and nano-α-Fe3O4-
dopamine (nano-FeDOPA) in DMF at reflux temperature using
Cs2CO3 as a base, but no product formation occurred. The cat-
alyst was modified using CuCl2 with a particle size of
10–25 nm, termed nano-α-Fe3O4-dopamine copper (nano-
FeDOPACu) (Scheme 7).38 The coupling of thiophenols with
1-bromo-4-nitrobenzene using this catalyst afforded a selective
formation of corresponding sulfides in 70% yield (Table 7).
In the context of optimization of solvent and base, the reac-
tion did not proceed in water and in traditional solvents such
as DMF, THF and CH3CN gave coupled products in moderate
yield (Table 8). The use of K2CO3 or Cs2CO3 did not signifi-
cantly affect the outcome of the reaction. The observation that
rapid formation of the corresponding disulfide takes place,
which precluded the availability of free thiol for coupling after
a certain reaction time, prompted the search for a reductive
3.2 Recovery and reusability of nano-FeDOPACu catalyst
For practical applications of heterogeneous systems, the life-
time of the catalyst and its level of reusability are significant
factors. To clarify this issue, the reaction of 1-bromo-4-
nitrobenzene with thiophenol using the recycled nano-FeDO-
PACu catalyst was examined. After completion of the first reac-
tion, the catalyst was recovered magnetically, washed with
methanol, and dried at 60 °C for 30 min. A new reaction was
then performed with fresh reactants, under the same
conditions. The nano-ferrite supported Cu catalyst could be
reused at least three times without any change in activity
(Table 10). Metal leaching, as measured by ICP-AES analysis of
the catalyst before and after the three reactions, showed Cu
concentration to be 0.82% before the reaction and 0.81% after
the reaction. The TEM image of the catalyst taken after the
third cycle of the reaction does not show a significant change
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Scheme 7 Synthesis of a nano-Fe3O4-DOPA-Cu (nano-FeDOPACu) catalyst.
Table 7 C–S coupling of 1-bromo-4-nitro-benzene: screening of the catalyst
4. Application of nano-FeDOPAPd in
organic synthesis
4.1 O-Allylation of phenols
Allyl ethers are important starting materials for a wide range of
organic reactions, including the 1,3-hydrogen shift, [3,3]-sigma-
tropic rearrangement, and polymerization reactions,41 in
addition to being a popular protecting group for alcohols.42
The traditional method for the synthesis of allyl ethers is the
Williamson-type ether synthesis, which involves the use of
Entry
Catalyst
Times
Yield
1
2
3
Fe3O4
Nano-FeDOPA
Nano-FeDOPACu
24 h
24 h
24 h
0%
0%
70%
in the morphology and the size of the catalyst nanoparticles strongly basic metal alkoxide anions and highly active allyl
(10–25 nm), which indicates the retention of the catalytic halides or their equivalents.43 Comparatively, the addition of
activity after recycling.44 No Cu metal was detected in the reac- oxygen nucleophiles to η3-allyl metal complexes of various
tion solvent after completion of the reaction, which confirms transition metals44–47 provides an attractive mild alternative
the fact that dopamine provides enough binding sites on the approach for their synthesis using much less reactive allyl alco-
surface of Fe3O4 nanoparticles and serves as a pseudo-ligand hols, allyl esters, or allyl carbonates. However, most of the
by coordinating with Cu. This strategy minimizes deterio- existing methods for transition metal catalyzed O-allylation via
ration, prevents metal leaching, and enables efficient catalyst η3-allyl metal intermediates are accomplished using a non-
recycling.
recyclable homogeneous catalyst in various toxic solvents.44–47
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In continuation of this work, nano-FeDOPAPd was explored for
the aqueous O-allylation of phenols. A wide range of phenols
undergo unprecedented allylic substitution reactions with
various allylic acetates in air under refluxing aqueous media con-
ditions within 3–10 h whilst in the presence of the nano-FeDO-
PAPd catalyst; a mild base, sodium bicarbonate, is adequate to
produce the allyl ethers (Scheme 8, Table 11) in good yields.48
Table 8 Optimization of reaction conditions
Entry
Solvent
Base
Temp
Times
Yielda
1
2
3
4
5
6
7
8
H2O
H2O
H2O
DMF
DMF
THF
THF
CH3CN
CH3CN
THF : iPrOH
THF : iPrOH
iPrOH
iPrOH
iPrOH
NaOH
K2CO3
Cs2CO3
K2CO3
Cs2CO3
K2CO3
Cs2CO3
K2CO3
Cs2CO3
K2CO3
Cs2CO3
Cs2CO3
K2CO3
K2CO3
100 °C
100 °C
100 °C
153 °C
153 °C
65 °C
65 °C
82 °C
82 °C
Reflux
Reflux
82 °C
82 °C
120 °C
24 h
24 h
24 h
24 h
24 h
24 h
24 h
24 h
24 h
24 h
24 h
24 h
24 h
25 min
—
—
—
70%
70%
65%
66%
63%
65%
77%
76%
79%
81%
98%b
Table 10 Recycling of the catalyst
9
10
11
12
13
14
No. of cycles
Yield
a Reaction conditions: 1.2 mmol of thiophenol, 1.0 mmol of aryl
halide, 100 mg of nano-FeDOPACu catalyst. b Reaction conditions:
1.2 mmol of thiophenol, 1.0 mmol of aryl halide, 100 mg of nano-
FeDOPACu catalyst. MW, 120 °C, power 100 Watt.
1
2
3
98%
97%
97%
Table 9 Synthesis of diaryl sulfide
Entry
1
Substrate
Thiophenols
Product
Times
Yielda
98%
25 min
2
3
4
5
6
25 min
25 min
25 min
45 min
25 min
95%
95%
63%
85%
92%
7
25 min
94%
8
25 min
25 min
25 min
91%
89%
98%
9
10
11
12
25 min
30 min
96%
88%
a Reaction conditions: 1.2 mmol of thiophenol, 1.0 mmol of aryl halide, 100 mg of nano-FeDOPACu catalyst. MW, 120 °C, power 100 Watt.
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4.2 Heck-type arylation
The diaryliodonium salts are a class of hypervalent iodine
reagents. They are trivalent iodine compounds with two
carbon ligands. These salts are stable towards heat and
oxygen, nontoxic, and non-explosive. The application of diary-
liodonium salts in organic synthetic chemistry is ever
Scheme 8 O-Allylation of phenols with allylic acetates.
Table 11 O-Allylation of phenols with allylic acetatesa
Entry
1
Phenols
Allylic acetates
Time (h)
6
Products
Yieldb
80%
2
5
85%
3
4
5
5
87%
83%
90%c
5
10
6
7
9
79%
85%
10
8
9
3
8
75%
87%
10
11
12
13
8
8
8
8
75%
73%
76%
81%
a A mixture of phenol (1 mmol), allylic acetates (1 mmol), sodium bicarbonate (2 mmol) and Pd catalyst (50 mg, 4.8 mol%) in water (2.5 mL) was
heated to reflux in air. b Yields refer to those of column purified isolated products. c The reaction mixture in DMF (2 mL) was heated at 90 °C.
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Table 12 Heck type arylation of alkenes using diaryliodonium salts catalyzed by nano-FeDOPAPd
Entry
Ar
R
Product yielda
1
2
3
4
5
6
7
8
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
4-MeC6H4
3-NO2C6H4
3-NO2C6H4
3-NO2C6H4
2,4,6-(Me)3C6H2
4-t-BuC6H4
4-OMeC6H4
COCH3
CH2OAc
CO2nBu
C6H5
C6H5CH2
CH2OH
CH2OAc
CH2OAc
COOMe
CO2nBu
COCH3
CH2OAc
CH2OAc
90%
88%
85%
78%
69%
45%
82%
80%
75%
81%
72%
82%
84%
9
10
11
12
13
a Reaction conditions: 1.1 mmol of alkene, 1 mmol of diaryliodonium salt, and 50 mg (4.8 mol%) of [nano-FeDOPAPd] catalyst with aq. PEG-400
(1 : 1, v/v) subjected to ultrasonication (1 to5 min).
Table 13 Recyling of the catalyst
conditions. The nano-ferrite supported Pd catalyst could be
reused at least six times (Table 13) without any change in
activity. Metal leaching, as measured by ICP-AES analysis of
the catalyst before and after the three reactions, showed Pd
concentration to be 7.91% before the reaction and 7.85% after
the reaction. No Pd metal was detected in the reaction solvent
after completion of the reaction, which confirms the fact
No. of cycles
Catalyst
Yield
that dopamine provides enough binding sites on the surface
of Fe3O4 nanoparticles and serves as a pseudo-ligand by
coordinating with Pd. This strategy minimizes deteriora-
tion, prevents metal leaching, and enables efficient catalyst
recycling.
1
2
3
4
5
6
Fe3O4-DOPAPd
Fe3O4
Fe3O4
Fe3O4
Fe3O4
85%
84%
85%
83%
82%
82%
Fe3O4
5. Application of magnetically separable
ruthenium catalyst in organic synthesis
increasing.49–57 Recently, the iodonium salts have been
employed in the Heck-type coupling, however, with limited
substrate scope and yields.57 We extended our ongoing studies
on nano-FeDOPAPd as a catalyst for the Heck reaction using
diaryliodonium salts. The Heck coupling of diaryliodonium
salts with variety of alkenes (activated and non-activated)
proceeded expeditiously (1–5 min) in aqueous PEG-400(1 : 1)
without using any base under ultrasonication conditions
(Table 12).58
Amides, an important class of compounds in the chemical
and pharmaceutical industries, have been prepared by the
hydration of nitriles, catalyzed by strong acids and bases. This
strategy produced several by-products including carboxylic
acids. Because of the use of strong reagents/catalysts and
harsh conditions, sensitive functional groups on nitrile mol-
ecules could not be kept intact, consequently decreasing the
selectivity of the reaction protocol. Several heterogeneous cata-
lyst systems were developed to overcome the drawbacks of the
homogeneous processes. However, the turnover numbers of
4.3 Recovery and reusability of nano-FeDOPAPd catalyst
For practical applications, the lifetime and the stability of the these protocols were still small and the reusability of the cata-
catalyst are very important. To clarify this issue, the reaction of lyst was a challenge. A recently developed hydration method in
p-cresol with cinnamyl acetate using a recycled nano-FeDO- pure water was a good attempt in terms of reaction conditions
PAPd catalyst was examined. After completion of the first reac- and product yields.59 It required expensive ruthenium com-
tion, the catalyst was recovered magnetically, washed with plexes as catalysts and needed traditional work-up using toxic
methanol, and dried at 60 °C for 30 min. A new reaction organic solvents for isolation of the product. A greener and
was then performed with fresh reactants, under the same sustainable method for hydration of nitriles was successfully
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Fig. 5 Synthesis of a magnetically separable nano-Ru(OH)x catalyst.
Table 14 Optimization of reaction conditionsa
Entry Catalyst
Temperaturec Timeb Conversion
1
2
3
4
5
Nano[Fe3O4]
Nano[Fe3O4]
Nano[Fe3O4]-[Ru(OH)x] 100
Nano[Fe3O4]-[Ru(OH)x] 130
Nano[Fe3O4]-[Ru(OH)x] 130
100
130
30
30
20
20
30
0%
0%
30%
65%
85%
Scheme 9 Nanoferrite–[Ru(OH)x]-catalyzed hydration of nitriles.
developed by using a magnetic ruthenium hydroxide nano- a Reactions were carried out with 1 mmol of benzonitrile, 100 mg of
nanocatalyst, in water under MW irradiation. b Reaction temperature.
catalyst under aqueous MW conditions.60 Nano-Ru(OH)x was
c Reaction time.
prepared in two steps: (1) magnetic nanoparticles were functio-
nalized by post-synthetic functionalization via sonication of
nano-ferrites with dopamine in an aqueous medium and (2)
ruthenium (Ru) chloride was added followed by hydrolysis
using sodium hydroxide solution (Fig. 5). This ruthenium
hydroxide coated nanomaterial was then explored as a hetero-
geneous catalyst for hydration of nitriles in an aqueous
Initially, experiments were performed to optimize the
reaction conditions for hydration of benzonitrile as a sub-
strate, in an aqueous medium (Table 14). The reaction was
conducted using nanoferrites; hydration did not proceed at
100 °C or at 130 °C even after 30 min of MW exposure
(Table 14, entries 1 and 2). Nanoferrite–[Ru(OH)x] was then
medium as
a benign solvent under microwave (MW)
irradiation conditions (Scheme 9).
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Table 15 Hydration of nitriles using nanoferrite–[Ru(OH)x]a
(Table 14, entry 4), which was further increased to 85% by
extending the reaction time by another 10 min (Table 14,
entry 5).
Entry
1
Substrate
Product
Yieldb
85%
Using the above optimized conditions, the scope of the
nanoferrite–[Ru(OH)x] catalyst was then explored for hydration
of a variety of nitriles (Table 15). Nanoferrite–[Ru(OH)x] has
shown high catalytic activity for hydration of activated, inacti-
vated, and heterocyclic nitriles in pure water. A variety of benzo-
nitrile derivatives (Table 15, entries 1 and 10) as well as
aliphatic nitriles (Table 15, entries 11 and 12) were smoothly
hydrated to the corresponding amides in excellent yield. The
rates were barely influenced by the electronic effects of the
substituents on the aromatic ring of benzonitriles. Interest-
ingly, the hydration of m- and p-nitro benzonitriles (Table 15,
entries 5 and 6) as well as 3- and 4-cyanopyridine (Table 15,
entries 7 and 8) proceeded with a similar rate, without any
difference in reactivity, which shows negligible influence of
substituent’s position on the reaction rate. However, hydration
of isonicotinonitrile N-oxide does not yield the corresponding
isonicotinoamide N-oxide, instead isonicotinoamide was
obtained (Table 15, entry 9). Hydration of the benzo[1,3-d]-
dioxole-5-carbonitrile proceeded only at the cyano group to
afford the corresponding amide, while keeping the dioxole
ring intact (Table 15, entry 10).
Although this catalyst works well, it suffers from the
requirement of an elaborate and tedious procedure for their
synthesis that involves three steps: (i) synthesis of nanoferrite,
(ii) postsynthetic modification via anchoring of ligands which
may be toxic and, (iii) immobilization of the ruthenium metal.
To overcome this drawback and to avoid the use of toxic
ligands and reagents, a one-step procedure was developed for
the synthesis of magnetic silica supported ruthenium as a
magnetically retrievable catalyst (Scheme 10).61 The scope of
the magnetic silica supported ruthenium catalyst Nano-
Fe@SiO2Ru was then demonstrated for the hydration of a
variety of nitriles.61 The catalyst displayed high activity for
hydration of activated, inactivated, aliphatic, and heterocyclic
nitriles in pure water. It also displayed high activity for a
2
3
4
88%
84%
61%c
5
88%
6
85%
88%
85%
75%
80%
7
8
9
10
11
12
13
14
86%
76%
82%
85%
a Reactions were carried out with
1 mmol of nitrile, 100 mg
nanocatalyst at 130 °C for 30 min, in water under MW irradiation.
b Isolated yield. c Reaction time 45 min.
tested as a catalyst at 100 °C for 20 min under MW
irradiation where the low conversion of nitrile to amide
(30%) was observed (Table 14, entry 3). However, when the
reaction temperature was increased to 130 °C, the reaction
proceeded expeditiously with 65% conversion within 20 min
Scheme 10 One-pot synthesis of a nano-Fe@SiO2Ru catalyst.
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variety of benzonitrile derivatives as well as aliphatic nitriles 7.4 Synthesis of nano-FGT-Cu catalyst
that were smoothly hydrated to the corresponding amides in
excellent yield.
Glutathione-functionalized nano-Fe3O4 (1 g) was dispersed in
a water–methanol mixture (1 : 1). CuCl2·2H2O (100 mg) sol-
ution in water was added to the reaction mixture. Hydrazine
monohydrate solution in water was added dropwise to bring
the pH of this mixture to 9, followed by the addition of 0.1 g of
NaBH4. The reaction mixture was then stirred for 24 h at room
6. Conclusion
In conclusion, varieties of magnetic nano-ferrites modified temperature. The product was allowed to settle, washed several
with various ligands have been synthesized. Glutathione times with water and acetone, and dried under vacuum at
bearing nano-ferrites have been used as organocatalysts for 60 °C for 2 h. Catalyst characterization by X-ray diffraction
the Paal–Knorr reaction and homocoupling of boronic acids. (XRD) (Fig. 4b) and transmission electron microscopy (TEM)
A variety of other nanoferrites, post-synthetically modified by (Fig. 4a) confirms the anchoring of Cu nanoparticles on ferrite
ligands, were used to immobilize nanometals (Cu, Pd, Ru, etc.) surfaces. The weight percentage of Cu in the catalyst was
which enabled the development of efficient, sustainable and found to be 1.57% by ICP-AES analysis.
green procedures for azide–alkynes-cycloaddition (AAC) reac-
7.5 Synthesis of nano-ferrite-dopamine-metal (Cu and Pd)
catalyst
tions, C–S coupling, O-allylation of phenol, Heck-type reactions
and hydration of nitriles. Because of their reduced size, in
the nm range, most of the catalyst surface is now avail-
able for the reaction. An additional salient feature is that
the catalyst can be easily separated, recycled and reused
several times using an external magnet without any loss in
activity.
Amine-functionalized nano-Fe3O4 (1 g) was dispersed in water
and metal salt solution in water was added to the mixture.
Hydrazine monohydrate solution in water was added dropwise
to bring the pH of this mixture to 9 followed by the addition of
0.1 g of NaBH4. The reaction mixture was then stirred for 24 h
at room temperature. The product was allowed to settle,
washed several times with water and acetone, and dried under
vacuum at 60 °C for 2 h. The weight percentage of metals (Cu
and Pd) in the catalyst was determined using ICP-AES analysis.
7. Experimental section
7.1 Synthesis of magnetic nano-ferrites
7.6 Synthesis of nanoferrite-[Ru(OH)x] catalyst
FeSO4·7H2O (13.9 g) and Fe2(SO4)3 (20 g) were dissolved in
500 mL water in a 1000 mL beaker. Ammonium hydroxide
(25%) was added slowly to adjust the pH of the solution to 10.
The reaction mixture was then continually stirred for 1 h at
60 °C. The precipitated nanoparticles were separated magneti-
cally, washed with water until the pH reached 7, and then
dried under vacuum at 60 °C for 2 h. Ferrite was characterized
by X-ray diffraction (XRD) and transmission electron
microscopy (TEM). This magnetic nano-ferrite (Fe3O4) was
then used for further chemical modification.
Amine-functionalized nano-[Fe3O4] (2 g) was dispersed in
water. A RuCl3 solution in water (60 mL, 8.3 × 10−3 M) was
then added to it and stirred for 20 min. An aqueous solution
of sodium hydroxide (1 m) was added dropwise to bring the
pH of this mixture to 13. The resulting slurry was stirred for
36 h at room temperature. The product was separated magneti-
cally, washed several times with water and methanol, and
dried under vacuum at 50 °C for 2 h. The weight percentage of
Ru in the catalyst was found to be 3.22% by ICP-AES analysis.
7.7 Synthesis of magnetic silica supported ruthenium
hydroxide nanoparticles
7.2 Surface modification of nano-ferrites with glutathione
Nano-Fe3O4 (0.5 g) was dispersed in water (15 mL) and metha-
nol (5 mL) and sonicated for 15 min. Glutathione (reduced
form) (0.2 g) dissolved in water (5 mL) was added to this sol-
ution and again sonicated for 2 h. The glutathione-functiona-
lized nanomaterial (nano-organocatalyst) was then isolated by
centrifugation, washed with water and methanol, and dried
under vacuum at 50–60 °C.
FeSO4·7H2O (2.78 g) and Fe2(SO4)3 (4.0 g) were dissolved in
200 mL water in a 500 mL beaker. Ammonium hydroxide
(25%) was added slowly to adjust the pH of the solution to 10.
The reaction mixture was then continually stirred for 1 h at
50 °C. The reaction mixture was cooled down to room tempera-
ture. To this solution, tetraethyl orthosilicate (TEOS, 10 mL)
was added and vigorous stirring was continued for 18 h under
ambient conditions. To this solution, RuCl3 (600 mg) was
added; the pH of the solution was adjusted to ∼10 using
7.3 Surface modification of nano-ferrites with dopamine
Nano-[Fe3O4] (2 g) was dispersed in 25 mL water by sonication ammonium hydroxide solution (25%) and stirring continued
for 30 min. Dopamine hydrochloride (2 g) dissolved in 5 mL of for another 24 h. Magnetic silica supported Ru-hydroxide
water was added to this solution and again sonicated for 2 h. nanoparticles were separated using an external magnet,
The amine-functionalized nanomaterial was then precipitated washed with water, followed by acetone, and dried under
using acetone, isolated by using an external magnet, and dried vacuum at 50 °C for 8 hours. The catalyst was characterized by
under vacuum at 50 °C for 2 h.
X-ray diffraction (XRD) and transmission electron microscopy
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(TEM). The weight percentage of Ru was found to be 3.96% 120 °C (temperature monitored by a built-in infrared sensor),
and Si 6.85% by inductively coupled plasma-atomic emission 100 Watts, and 10–60 psi for 25–45 min. After completion of
spectroscopy (ICP-AES) analysis.
the reaction, the catalyst was easily removed from the reaction
mixture using an external magnet. After separation of the cata-
lyst, the solid product was filtered off or extracted with ethyl
7.8 Paal–Knorr reaction of amines using nano-FGT
The amines (1 mmol), tetrahydro-2,5-dimethoxyfuran acetate and purified by column chromatography.
(1.1 mmol), and nano-FGT (25 mg) were placed in a 10 mL
crimp sealed thick-walled glass tube equipped with a pressure
sensor and a magnetic stirrer. Water (2 mL) was added and the
reaction mixture was thoroughly mixed. The reaction tube was
7.12 O-Allylation of phenols by allylic acetates using nano-
FeDOPAPd catalyst
then placed inside the cavity of a CEM Discover focused MW
A mixture of phenol (1 mmol), allylic acetate (1 mmol),
synthesis system, operated at 140 °C (temperature monitored
NaHCO3 (2 mmol), and Pd catalyst (50 mg, 4.8 mol%) was
added to 2.5 mL of water. The aqueous reaction mixture was
heated to reflux for the required time as indicated in Table 9.
by a built-in infrared sensor) with a power of 50–250 W, and a
pressure of 50–180 psi for 20 min. After completion of the reac-
tion, the phase separation of the desired product from the
The progress of the reaction was monitored by TLC. Standard
aqueous medium occurred, facilitating the isolation of the
work-up with ethyl acetate followed by simple column chrom-
crude product by simple decantation, which was further puri-
atography provided the pure product.
fied by simply passing through a short silica column.
7.9 Synthesis of triazole from benzyl azide and alkyne
Benzyl azide (1.2 mmol), alkyne (1.0 mmol), and nano-FGT-Cu 7.13 Heck-type arylation using nano-FeDOPAPd catalyst
catalyst (100 mg) were placed in a crimp-sealed thick-walled
The diaryliodonium salt (1 mmol), alkene (1.1 mmol), and
glass tube equipped with a pressure sensor and a magnetic
50 mg (4.8 mol%) of nano-FeDOPAPd catalyst with aqueous
stirrer. Water (4 mL) was added to the reaction mixture. The
PEG-400 (1 : 1, v/v, 3 mL) are subjected to ultrasonication
(1–5 min) (cycle: 20 s pulse and 10 s pause) in a high intensity
sonicator. Upon completion of the reaction, as indicated by
reaction tube was placed inside the cavity of a CEM Discover
focused microwave synthesis system, operated at 120 °C (temp-
erature monitored by a built-in infrared sensor), 100 Watts,
TLC, the catalyst is separated using an external magnet. The
and 10–60 psi for 8–12 min. After completion of the reaction,
reaction mixture is diluted with water and the crude product is
extracted using ethyl acetate. The organic layer is dried over
the catalyst was easily removed from the reaction mixture
using an external magnet. After separation of the catalyst, the
anhydrous Na2SO4 and purified by passing through a silica gel
solid product was filtered off or extracted with ethyl acetate
column. The recovered magnetic catalyst was washed with
acetone, dried under vacuum, and reused for the next batch of
and recrystallized.
the reaction. All the synthesized compounds have been
reported in the literature and characterized by comparing their
spectral data.
7.10 Synthesis of triazoles via in situ generation of alkyl
azides
Alkyl halides (1.2 mmol), NaN3 (1.5 mmol), alkyne (1.0 mmol),
and nano-FGT-Cu catalyst (100 mg) were placed in a crimp-
sealed thick-walled glass tube equipped with a pressure sensor
and a magnetic stirrer. 4 mL of water was added to the reaction
7.14 Hydration of nitriles using nanoferrite-[Ru(OH)x]
catalyst
mixture. The reaction tube was placed inside the cavity of a
CEM Discover focused microwave synthesis system, operated at 1 mmol of nitrile and 100 mg of nanoferrite-[Ru(OH)x]
120 °C (temperature monitored by a built-in infrared sensor), (0.003 mole% of Ru) catalyst were placed in a crimp-sealed
100 Watts, and 10–60 psi for 10–20 min. After completion of thick-walled glass tube equipped with a pressure sensor and a
the reaction, the catalyst was easily removed from the reaction magnetic stirrer. 5 mL of water was then added to the reaction
mixture using an external magnet. After separation of the mixture. The reaction tube was placed inside the cavity of a
catalyst, the solid product was filtered off or extracted CEM Discover focused microwave synthesis system, operated at
with ethyl acetate and recrystallized or purified by column 130 °C (temperature monitored by a built-in infrared sensor)
chromatography.
with a power of 50 to 140 Watt and a pressure of 10–60 psi for
30 min (Table 14, entry 5). After completion of the reaction,
the reaction mixture turned clear and the catalyst was depos-
7.11 Synthesis of diaryl sulfides
Aryl halide (1.0 mmol), thiophenol (1.2 mmol), and nano- ited on the magnetic bar within 30–45 s, which was easily
FeDOPACu catalyst (100 mg) were placed in a crimp-sealed removed from the reaction mixture using an external magnet.
thick-walled glass tube equipped with a pressure sensor and a After separation of the catalyst, the clear liquid was cooled
magnetic stirrer. Isopropanol (5 mL) was added to the reaction slowly resulting in analytically pure crystals of benzamides,
mixture. The reaction tube was placed inside the cavity of a which can be isolated from the water medium by simple
CEM Discover focused microwave synthesis system, operated at decantation/filtration.
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12 B. Wang, Y. Gu, C. Luo, T. Yang, L. Yang and J. Suo, Tetra-
hedron Lett., 2004, 45, 3417.
Acknowledgements
Nasir Baig was supported by the Postgraduate Research 13 G. Minetto, L. F. Raveglia and M. Taddei, Org. Lett., 2004, 6,
Program at the National Risk Management Research Labora- 389.
tory administered by the Oak Ridge Institute for Science and 14 Z. H. Zhang, J. J. Li and T. S. Li, Ultrason. Sonochem., 2008,
Education through an interagency agreement between the U.S. 15, 673.
Department of Energy and the U.S. Environmental Protection 15 (a) V. Polshettiwar, B. Baruwati and R. S. Varma, Chem.
Agency. We thank Dr Douglas Young for reading the manu-
script and providing valuable comments.
Commun., 2009, 1837; (b) V. Polshettiwar and R. S. Varma,
Tetrahedron, 2010, 66, 1091.
16 R. B. Nasir Baig and R. S. Varma, Chem. Soc. Rev., 2012, 41,
1559.
17 J. Tsuji, Palladium Reagents and Catalysts, WileyVCH,
Chichester, UK, 2nd edn, 2004.
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