Selective reduction of ketones using water as a hydrogen source under high hydrostatic pressure

Article abstract of DOI:10.1039/c2ob25941a

A selective reduction of a broad variety of ketones is described. The method is based on the combination of a Ni-Al alloy and high hydrostatic pressure (HHP, 2.8 kbar) in an aqueous medium. The reaction of the Ni-Al alloy with water provides in situ hydrogen generation and the high pressure ensures that the H₂ formed remains in the solution, thus the CO reduction readily occurs. The application of the HHP resulted in selective formation of the desired products and the common problem of non-selective overhydrogenation could be avoided. In most cases the reductions resulted in high yields and excellent selectivities without the use of any base.

Full text of DOI:10.1039/c2ob25941a

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PAPER
Selective reduction of ketones using water as a hydrogen source under high
hydrostatic pressure
a
b
a
a
a
Anna Tomin, Alexander Lazarev, Matthew P. Bere, Hana Redjeb and Béla Török*
Received 16th May 2012, Accepted 17th July 2012
DOI: 10.1039/c2ob25941a
A selective reduction of a broad variety of ketones is described. The method is based on the combination
of a Ni–Al alloy and high hydrostatic pressure (HHP, 2.8 kbar) in an aqueous medium. The reaction of the
Ni–Al alloy with water provides in situ hydrogen generation and the high pressure ensures that the H2
formed remains in the solution, thus the CvO reduction readily occurs. The application of the HHP
resulted in selective formation of the desired products and the common problem of non-selective
overhydrogenation could be avoided. In most cases the reductions resulted in high yields and excellent
selectivities without the use of any base.
generated more interest, a recent paper analyses this reaction
from a green chemistry point of view.
Introduction
11
The reduction of carbonyl compounds is a fundamental trans-
formation in synthetic organic chemistry. New applications for
these reactions are constantly being developed. The use of safe
and convenient reagents and solvents is the focus of recent
developments to address the ever growing concern of safety and
Based on the literature there are several areas of chemical syn-
thesis where HHP did and could prove to be beneficial.
One such system is when one or more of the reactants are in
the gaseous phase at the temperature of the reaction, while the
others are dissolved in solution. In such systems the lack of
effective mass transfer from the gas to the solution could be a
serious limitation. The application of high pressure increases the
solubility of an otherwise hardly soluble gas in a liquid medium.
Hydrogenation is probably one of the leading examples for this
problem, as hydrogen is generally not well soluble in organic
solvents.
1
2
sustainability to minimize or, preferably, eliminate waste.
Activation of chemical reactions by high hydrostatic pressure
(HHP) in combination with the thermal effect or catalysts pro-
3
vides an opportunity for the synthesis of a series of compounds.
The method was used for the production of hydroxy amides
from lactones and amines at 9 kbar and at 30–65 °C by Otani
4
et al. In recent years HHP-assisted chemistry has evolved to a
Hydrogenation of aryl ketones was successfully performed
over a wide range of catalysts under mild conditions leading to
novel technology that fosters the development of environmen-
tally benign processes for organic synthesis. To underline this
statement several examples can be enumerated, such as sulfam
12
the corresponding alcohols. For example, hydrogenation over
platinum, rhodium and ruthenium was rapid and quantitative at
13
production by the intramolecular Diels–Alder reaction under
room temperature and atmospheric pressure. RANEY® nickel
5
14
1
3 kbar. HHP-assisted chemistry was used to induce the asym-
has also been used, giving excellent yields. Supported nickel
catalysts required high temperatures (100–150 °C) and high
pressures (100–165 atm) and also gave almost quantitative
metric hetero-Diels–Alder reaction of oxindoles and isatins by
Hiyoshizo et al. The Diels–Alder cycloaddition of low reactiv-
ity alkoxybenzylideneacetone derivatives with methyl-1,3-buta-
dienes at 8–11 kbar has been accomplished as well.
Transformation of lactams into ω-aminocarboxamides was also
achieved in CH CN under 10 kbar pressure. The stability and
oligomerization of amino acids were investigated at 180–400 °C
and 10–50 kbar. Nitrogen containing heterocycles were syn-
6
15
yields.
7
Hydrogenation of carbonyl groups occurs readily over most
catalysts. However, care must be exercised in preventing side
reactions of multifunctional substrates. The most common side
reactions are dehydration or hydrogenolysis of the resulting
hydroxyl compounds and overhydrogenation of the products to
8
3
9
1
6
thesized in water using the aza-Michael reaction under high
pressure conditions.
the corresponding cyclohexane and alkane derivatives.
10
1
7
The hyperbaric aza-Michael reaction
With the rise of the concept of Green Chemistry, extended
efforts have been made toward the use of water as a possible
18
solvent or reagent. In the field of reductions water was used as
a solvent in the hydrogenation of CvN double bonds catalyzed
by cyclodextrin-stabilized Pd nanoparticles. Tashiro et al. pio-
a
University of Massachusetts Boston, 100 Morrissey Blvd., Boston, MA,
USA. E-mail: bela.torok@umb.edu; Fax: (+1)-617-287-6030;
Tel: (+1)-617-287-6159
19
b
Pressure BioSciences Inc., 14 Norfolk Avenue, South Easton, MA, USA
neered the reduction of aryl ketones to the corresponding
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alcohols or alkane derivatives in water using various metal–Al
thus overcoming the common mass transfer limitations of regular
hydrogenations.
Typically, 25–80 °C and 1.3–2.8 kbar was used for the selec-
tive reduction of ketones to secondary alcohols. The only
remaining workup that was required is a filtration and an extrac-
tion followed by solvent evaporation.
2
0
alloys (Ni–Al, Co–Al, Cu–Al and Fe–Al). While the reduction
of acetophenones using a Ni–Al alloy in water under microwave
irradiation proceeded to give the corresponding alkylbenzenes in
good yields, the selectivity towards alcohols remained an un-
resolved issue due to the high reactivity of the alloy at elevated
21
temperatures.
Using the above described general procedure 3-nitroacetophe-
none, 4-fluoroacetophenone, 4-chloroacetophenone, 3-methyl-
acetophenone, 4-methylacetophenone, 2,4-dimethylacetophenone,
4-fluorobenzophenone and 3-nitroacetophenone were selected as
model substrates to investigate the effect of experimental vari-
ables on the outcome of the reaction. For comparison, all reac-
tions were performed at 40 °C with stirring at atmospheric
pressure and under 2.8 kbar (Table 1). In addition, sonication
and microwave irradiation, as alternative activation methods,
were tested as well. In all cases the reaction vessel containing a
mixture of a ketone (0.24 mmol, 1 equiv.), Ni–Al alloy
(2.7 mmol, 11 equiv.) and water (2 mL) was stirred at a given
temperature and time (Table 1). After the sample was filtered and
extracted with dichloromethane, the organic layer was concen-
trated in vacuo and analyzed.
Ni–Al alloy in a dilute alkaline aqueous solution at 90 °C has
been shown to be a powerful reducing agent, which is highly
effective in the reduction of phenol, naphthalenes, biphenyls,
acenaphthene and benzophenones to the corresponding hydro-
22
carbon derivatives, in the absence of any organic solvents.
However, the high reactivity usually results in complete hydro-
genation and/or the formation of multi-component product
mixtures.
Further pursuing our interest in developing new synthetic
23
methodologies, we explored the HHP-assisted chemical syn-
thesis in hydrogenation systems where the hydrogen is generated
in situ. Herein we describe the application of HHP in the selec-
tive reduction of ketones in water using a nickel–aluminium
alloy.
The room-temperature process is a mild reduction system;
however, in several cases it gave low yield or selectivity, or no
product at all (4-F-benzophenone). The other activation methods
gave mixed results and no consistent picture could be drawn
regarding their application. Sonication appeared to significantly
activate the reduction for several starting materials (4-Cl-, 3-Me-
Results and discussion
In order to alleviate the above-mentioned selectivity problems,
we decided to apply high hydrostatic pressure to achieve more
effective control over the reaction. The major advantage of the
high pressure is that it would keep the in situ formed hydrogen
in the reaction mixture. Higher hydrogen concentration in the
solution would ensure that the reaction could be carried out
under moderate conditions, hence resulting in improved
selectivity.
First, the reduction of a broad variety of acyclic, cyclic and
aryl ketones was performed with a Ni–Al alloy in water under
high hydrostatic pressure. To achieve this goal we employed a
Pressure Biosciences Barocycler HUB440 bench-top high
pressure generator (Pressure Biosciences, Inc.), which is capable
of generating and controlling hydrostatic pressure from 0.03 to
or 3-NO -acetophenone) that reacted rapidly resulting in 100%
2
conversion and 67–90% alcohol selectivities in a relatively short
period of time (entries 7, 11, 27, Table 1). Other substrates,
however, gave only 33–48% yield under the same conditions.
The beneficial effect of ultrasounds could be at least in part
explained by the well-known surface cleaning effect of ultrasonic
24
waves. Since the in situ generation of hydrogen is a very
important part of the reaction mechanism, the clean, oxide-free
aluminum surface is crucial. The removal of the surface Al O3
2
layer shortens the induction period and results in rapid reaction
rates. It, however, must be noted that the sonochemical reactions
showed significant experimental errors. Depending on the place-
ment (horizontal location and depth) of the reaction vessels in
the ultrasonic bath the yields greatly varied. We found in other
experiments that the sonochemical pretreatment of the RANEY
alloy is useful, however, carrying out the reaction fully under
ultrasonic irradiation is not recommended. Microwave-assisted
4
kbar. Depending on the sample volume up to 48 samples can be
tested at the same time under identical reaction conditions in this
apparatus. In the method employed, the mixture of the ketone,
Ni–Al alloy and water was placed in a 150 μL MicroTube, the
tube inserted into the cartridge and then the cartridge was placed
in the high pressure chamber. A computer-controlled instrument
maintained the reaction chamber under pressure at the desired
temperature. While the instrument is capable of sophisticated
dynamic pressure control over time, in this study we opted for
the constant pressure option for simplicity.
In order to examine the scope and potential of this method we
explored the selective reduction of various common ketones
under high hydrostatic pressure in combination with heating.
During the reaction, water and the aluminum content of the alloy
reacted, providing the hydrogen for the reductions while the
remaining Ni formed an effective high surface area RANEY®-
25
reactions occurred rapidly but provided poor selectivities for
the alcohols compared to the other methods due to the high
activity.
The application of HHP commonly resulted in controllable
conditions. The reactions could be stopped at the alcohol stage
since neither alkane nor alkene derivatives could be isolated as
alternative products. Therefore, HPP is providing better yield
and selectivity with most but not every substrate studied. It pro-
vided well reproducible conditions and consistent results. Thus it
has been chosen as the activation method of choice for sub-
sequent experiments.
For further evaluation of the characteristics of the HHP-
assisted reactions, four different ketone : alloy molar ratios were
tested with 3-nitroacetophenone (Fig. 1). Initially, 0.024 mmol
of ketone and 0.12 mmol/0.27 mmol/0.54 mmol or 0.70 mmol
2
0,21
Ni type hydrogenation catalyst.
Thus, this approach can be
considered a heterogeneous catalytic hydrogenation with in situ
generated hydrogen. The use of the high hydrostatic pressure
ensured that the produced hydrogen remained in the solution,
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Table 1 Reduction of aryl ketones with stoichiometric amounts of a Ni–Al alloy in water under various conditions
a
Yield (%)
d
d
Entry
Substrate
Pressure (kbar)
Energy source
Time (h)
Temperature (°C)
C
(%)
S (%)
1
2
3
4
5
6
7
8
9
4-Fluoroacetophenone
—
2.8
—
—
—
2.8
—
—
—
2.8
—
—
—
2.8
—
—
—
2.8
—
—
—
2.8
—
—
—
2.8
—
—
—
—
24
24
2
40
40
25
80
40
40
25
80
40
40
25
80
40
40
25
80
40
40
25
80
40
40
25
80
40
40
25
80
24
23
0
28
82
25
96
100
0
0
95
100
Sonication
MW irradiation
—
—
Sonication
MW irradiation
—
—
Sonication
MW irradiation
—
—
Sonication
MW irradiation
—
2
4-Chloroacetophenone
3-Methylacetophenone
4-Methylacetophenone
2,4-Methylacetophenone
4-Fluorobenzophenone
16
16
2
2
8
8
2
2
8
8
2
2
7
7
2
2
6
6
2
2
8
8
2
2
b
100
24
100
100
100
60
100
100
47
100
97
100
48
0
0
64
90
58
b
76
67
98
33
80
95
100
0
97
94
100
0
1
0
1
1
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
—
Sonication
MW irradiation
—
0
—
80
84.4
25
69
96
84
49
Sonication
MW irradiation
—
—
Sonication
MW irradiation
33
52
63
100
100
100
c
3-Nitroacetophenone
a
b
c
d
GC yields. Alcohol was identified as 1-phenylethanol. Alcohol was identified as 1-(3-aminophenyl)ethanol in each case. C – conversion;
S – selectivity.
of the Ni–Al alloy in water were tested at 40 °C and 2.8 kbar.
During the reaction 3-nitroacetophenone was converted to
benzophenones, cyclic and aliphatic ketones. The method was
successfully applied for the reduction of these ketones, although
the reaction conditions had to be slightly optimized according to
the substrate. The results of these experiments are summarized in
Table 2.
Ethyl acetoacetate, a simple β-ketoester, was chosen as a
model for the reduction of an aliphatic ketone. The experiment
required slightly elevated temperature (80 °C) and gave ethyl
3-hydroxybutanoate with practically quantitative yield (entry 1,
Table 2). Following this encouraging result cycloalkanones were
investigated to extend the variety of substrates. Similar results
were observed and complete conversion of the starting material
resulted in the corresponding alcohol with 100% selectivity,
1
-(3-aminophenyl)ethanol as the main product. Although the com-
pound contained an NO group that is also known to be highly
2
susceptible to reduction, only a small amount of 3-ethylaniline
and 3-vinylaniline was determined as byproducts. The observed
results, namely the yield of 1-(3-aminophenyl)ethanol, show an
optimum as a function of increasing molar Ni–Al alloy/substrate
ratio. At a 1 : 11 ketone : Ni–Al alloy molar ratio the complete
consumption of the starting material was observed, providing the
alcohol with 92% selectivity.
Initial experiments were performed to determine temperature,
pressure and reaction times required to complete the transform-
ation selectively. The first series of experiments demonstrated
that reaction time depends on the structure and substituents of
the ketones. The best conditions were found at 40 °C, 11 molar
equivalent of alloy and a pressure of 2.8 kbar.
mostly within
6 h at 80 °C (entries 2–5, Table 2)
with one example at 50 °C (entry 4, Table 2). A significant
advantage of this reduction system is that it tolerates the presence
of N and S atoms in the substrates. Cyclohexene derivatives con-
taining nitrogen or sulfur atoms in the ring readily underwent
reduction with high selectivity without poisoning the Ni–Al
alloy or the in situ formed RANEY® type Ni catalyst (Table 2,
entries 6–7).
These results indicated that the high pressure method is a valu-
able selective reduction system. As a next step, we intended to
map the scope of this procedure and selected a broad range of
commercially available ketones, including acetophenones,
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Table 2 Reduction of acyclic, cyclic and aryl ketones to their
corresponding secondary alcohols with a Ni–Al alloy in water under
high hydrostatic pressure (2.8 kbar)
a
Yield (%)
d
d
Entry
Substrate
Time (h)
Temp. (°C)
C (%)
S (%)
1
2
6
80
80
100
100
100
100
16
3
4
6
80
50
100
100
100
100
8.5
5
6
7
6
6
6
80
80
80
100
100
100
100
100
100
8
9
8
40
40
50
100
100
25.5
95
94
99
7
1
0
16
11
24
40
23
100
b
1
2
16
16
45
45
92.4
100
54
b
Fig. 1 Effect of the ketone : Ni–Al alloy molar ratio on the selective
reduction of 3-nitroacetophenone with the Ni–Al alloy in water under
high hydrostatic pressure (2.8 kbar): (A) formation of 1-(3-aminophe-
nyl)ethanol; (B) formation of 3-ethylaniline; (C) formation of 3-vinyl-
aniline (Note: Fig. 1B and C has different scales for better illustration).
13
14
48
16
8.5
8
30
50
40
64
84
c
1
5
6
45.3
100
98
1
96
Under the same mild conditions a variety of substituted aryl
methyl ketones were hydrogenated, as shown in Table 2. Substi-
tution of the aromatic ring with methyl groups, such as
4
-methyl- and 2,4-dimethylacetophenones, led to the expected
alcohols with 100% yield and 95% or 94% selectivity (entries
–9, Table 2). Substrates bearing electron withdrawing halogen
a
b
c
GC yields. Alcohol was identified as 1-phenylethanol. Alcohol was
d
identified as 1,2-diphenylethanol. C – conversion; S – selectivity.
8
substituents at the para position appeared to be more challenging
and provided only moderate yields (23–25%, entries 10, 11,
Table 2).
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Next, increasing the bulkiness of the substituents, 4-fluoroben-
zophenone and 2-bromo-2-phenylacetophenone were reduced.
They afforded the corresponding alcohols in 84% and 95%
selectivity, however, the conversion decreased to 64% and 45%
Experimental
General information
All carbonyl compounds were purchased from Aldrich and were
used without further purification. The Ni–Al alloy used as a
reducing agent was also an Aldrich product. Solvents used in
synthesis were of a minimum purity of 99.5% and were pur-
chased from ThermoFisher Scientific. The mass spectrometric
identification of the products has been carried out by an Agilent
(entries 14, 15, Table 2), respectively. 4-Fluorobenzophenone
produced the expected alcohol in good yield, while undesired
further reduction to diphenylmethane (4%) or cyclohexylphenyl-
methane (<1%) was minimal.
Reduction of 3-nitroacetophenone was also completed. It
yielded the corresponding aminoalcohol (entry 16, Table 2). In
the case of nitro substituents, the first reduction step was always
the transformation of nitro- to amino-group followed by the
reduction of the carbonyl group.
6
850 gas chromatograph-5973 mass spectrometer system (70 eV
electron impact ionization) using a 30 m long DB-5 type column
J&W Scientific).
(
The application of the alloy for hydrogenation of several halo-
genated substrates resulted in an undesired partial to full dechlor-
ination or debromination. For example, full conversion of
α-bromo-p-chloroacetophenone resulted in 1-phenylethanol as a
major product with 48% yield (entry 13, Table 2) along with
p-chloroacetophenone (40.6%) and vinylbenzene (less than 1%).
While the carbonyl reduction was highly selective for 2-bromo-
General procedure for the high hydrostatic pressure-assisted
reduction of carbonyl compounds with the Ni–Al alloy in water
The reactions were carried out with a Pressure BioSciences Baro-
cycler HUB440 bench-top high pressure generator using static
pressure levels between 1.3 and 2.8 kbar in a 55 mL insulated
jacketed pressure vessel. The ketone (0.024 mmol), Ni–Al alloy
1
,2-diphenylethanone (entry 15, Table 2) and no overhydro-
(0.27 mmol) and water (110 μL) were added into 150 μL fluoro-
genated products were observed the debromination resulted in
the formation of 1,2-diphenylethanol.
Based on the above data, the HHP-assisted selective reduction
of ketones represents a broadly applicable approach for the
reduction of carbonyl compounds.
polymer MicroTubes (also from Pressure BioSciences) which
were placed in a stainless steel cartridge and the barocycler was
set to the desired temperature and pressure. After the predeter-
mined time the reaction was quenched by removing the cartridge
from the barocycler. The samples were filtered, the filtrate
The major advantages of this approach are as follows:
extracted with CH Cl and were directly analyzed by GC-MS.
(i) The reaction is highly selective for the reduction of the car-
2
2
Further remaining workup was evaporation of the solvent.
bonyl group. The problems, such as overhydrogenation or mul-
tiple product formation, commonly associated with the use of the
Ni–Al alloy can be largely avoided.
Acknowledgements
(
ii) The reaction is carried out in water, the most benign,
readily available and inexpensive solvent.
iii) The solvent also serves as an economic source of hydro-
The authors acknowledge financial support by the University of
Massachusetts Boston; A. T. is thankful to the Rosztoczy Foun-
dation for their financial support.
(
gen, thus no extra hydride or hydrogen addition is required. This
is achieved without the use of any strong base.
(
iv) The use of the in situ formed RANEY® Ni type hetero-
geneous catalyst allows easy product separation.
v) The only byproduct or waste that forms during the reac-
References
(
1
M. B. Smith and J. March, March’s Advanced Organic Chemistry, Wiley,
tions is a small amount of alumina supported Ni catalyst (Ni/
Al O ) that could be recycled and used as a heterogeneous
Hoboken, NJ, 6th edn, 2007.
2 Handbook of Green Chemistry and Technology, ed. J. Clark and D. Mac-
quarrie, Blackwell Publishing, 2002; K. Mikami, Green Reaction Media
in Organic Synthesis, Blackwell, Oxford, 2005 D. Chaturvedi and
N. C. Barua (ed.), Organic Synthesis using Green Reaction Media. Curr.
Org. Synth., 2012, 9, 1, and papers published in this special issue.
2
3
hydrogenation catalyst.
3
High Pressure Chemistry, ed. H. Kelm, D. Reidel Publishing Co.,
Dodrech/Boston/London, 1978.
Conclusions
4
K. Matsumoto, S. Hashimoto, T. Uchida, T. Okamoto and S. Otani, Bull.
Chem. Soc. Jpn., 1989, 62, 3138.
In conclusion, a novel method for the selective reduction of
various ketones has been described. The HHP-assisted trans-
formations of acyclic, cyclic and aryl ketones to their corres-
ponding alcohols have been conducted successfully providing a
selective method for this reaction. In all of the processes the
reactions were performed safely and the products were obtained
in good to excellent yields and selectivities. The major advan-
tage of this method is that the common byproducts of overhydro-
genation can be completely avoided. The process, with its highly
effective and selective design, provides an alternative for the
selective reduction of carbonyl compounds and based on our
preliminary experience it can be extended to the selective
reductions of other functional groups.
5 V. O. Rogachev and P. Metz, Nat. Protocols, 2006, 1, 3076.
6
M. Kaori, Y. Tomoyuki, M. Jacques, N. Keiji, I. Yoshiyasu and
K. Hiyoshizo, Synlett, 2011, 2080.
B. Ballerini, L. Minuti and O. J. Piermatti, J. Org. Chem., 2010, 75,
7
4
251.
8 H. Kotsuki, M. Iwasaki and H. Nishizawa, Tetrahedron Lett., 1992, 33,
945.
4
9
T. Otake, T. Taniguchi, Y. Furukawa, F. Kawamura, H. Nakazawa and
T. Kakegawa, Astrobiology, 2011, 11, 799.
10 U. Imam, N. Keiji, I. Yoshiyasu and K. Hiyoshizo, Synlett, 2008, 1402.
11 A. Y. Rulev, H. Kotsuki and J. Maddaluno, Green Chem., 2012, 14, 503–
508.
12 G. V. Smith and F. Notheisz, Heterogeneous Catalysis in Organic Chem-
istry, Academic Press, London, 1999.
13 A. Kulkarni and B. Török, Curr. Org. Synth., 2011, 8, 187.
Org. Biomol. Chem., 2012, 10, 7321–7326 | 7325
This journal is © The Royal Society of Chemistry 2012

View Article Online
1
4 M. Guisnet, J. Barbier, J. Barrault, C. Bouchoule, D. Duprez, G. Perot
and C. Montassier, Heterogeneous Catalysis and Fine Chemicals
III, Stud. Surf. Sci. Catal., Elsevier, 1993, vol. 78; Synthetic
Methods of Organic Chemistry, ed. G. Tozer-Hotchkiss, Karger,
W.-H. Zhou and B. Török, Org. Lett., 2011, 13, 5124; A. Daştan,
A. Kulkarni and B. Török, Green Chem., 2012, 14, 17.
24 T. J. Mason and J. P. Lorimer, Sonochemistry, Ellis Horwood, Chichester,
1988; Synthetic Organic Sonochemistry, ed. J. L. Luche, Plenum Press,
New York, 1998; K. S. Suslick, in Handbook of Heterogeneous Catalysis,
ed. G. Ertl, H. Knözinger and J. Weitkamp, Wiley-VCH, Weinheim,
1997, vol. 3, p. 1350; B. Török, K. Balázsik, K. Felföldi and M. Bartók,
Ultrason. Sonochem., 2001, 8, 191–200; R. S. Varma, Green Chem. Lett.
Rev., 2007, 1, 37–45.
25 A. Loupy, Microwaves in Organic Synthesis, Wiley-VCH, Weinheim,
2002; C. O. Kappe, Angew. Chem., Int. Ed., 2004, 43, 6250–6284;
C. O. Kappe and A. Stadler, Microwaves in Organic and Medicinal
Chemistry, Wiley-VCH, Weinheim, 2005; J. P. Tierney and P. Lidström,
Microwave-Assisted Organic Synthesis, Blackwell, Oxford, 2005;
C. O. Kappe, D. Dallinger and S. S. Murphree, Practical Microwave
Synthesis for Organic Chemists-Strategies, Instruments, and Protocols,
Wiley-VCH, Weinheim, 2008; C. O. Kappe, Chem. Soc. Rev., 2008, 37,
1127–1139; W. Santagada, F. Frecentese, E. Perisutti, F. Fiorino,
B. Severino and G. Caliendo, Mini-Rev. Med. Chem., 2009, 9, 340–358;
C. O. Kappe and D. Dalinger, Mol. Diversity, 2009, 13, 71–193; Micro-
wave Heating as a Tool for Sustainable Chemistry, ed. N. Leadbeater,
CRC Press, Boca Raton, FL, 2010.
2
008, vol. 72.
1
1
1
5 R. L. Augustine, Heterogeneous Catalysis for the Synthetic Chemist,
Marcel Dekker Inc, New York, 1995.
6 B. Török, Á. Molnár, K. Borszéky, E. Tóth-Kádár and I. Bakonyi, Stud.
Surf. Sci. Catal., 1993, 78, 179.
7 P. T. Anastas and J. C. Warner, Green Chemistry: Theory and Practice,
Oxford University Press, 1998.
1
1
8 C.-J. Li, Acc. Chem. Res., 2010, 43, 581.
9 S. C. Mhadgut, K. Palaniappan, M. Thimmaiah, S. A. Hackney, B. Török
and J. Liu, Chem. Commun., 2005, 3207.
2
2
2
2
0 K. Ishimoto, Y. Mitoma, S. Nagashima, H. Tashiro, G. K. S. Prakash,
G. A. Olah and M. Tashiro, Chem. Commun., 2003, 514.
1 A. Miyazawa, M. Tashiro, G. K. S. Prakash and G. A. Olah, Bull. Chem.
Soc. Jpn., 2006, 79, 791.
2 G.-B. Liu, H.-Y. Zhao, J.-D. Zhu, H.-J. He, H.-J. Yang, T. Thiemann,
H. Tashiro and M. Tashiro, Synth. Commun., 2008, 38, 1651.
3 A. Kulkarni and B. Török, Green Chem., 2010, 12, 875; S. Bag,
S. Dasgupta and B. Török, Curr.Org. Synth., 2011, 8, 237; A. Kulkarni,
7326 | Org. Biomol. Chem., 2012, 10, 7321–7326
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