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Ohmic heating as a new ecient process for organic

synthesis in water
Joana Pinto,a Vera L. M. Silva,*a Ana M. G. Silva,b Artur M. S. Silva,*a Jos C. S. Costa,c
Lus M. N. B. F. Santos,*c Roger Enes,a Jos A. S. Cavaleiro,a
Antnio A. M. O. S. Vicented and Jos A. C. Teixeirad
A new and ecient process for organic synthesis in aqueous media based on a direct ohmic heating

Received 11th September 2012,

Accepted 24th January 2013

reactor is described. Four representative organic transformations, a DielsAlder cycloaddition, a nucleophilic substitution, an N-alkylation and a Suzuki cross-coupling reaction, were performed using this
process. The results, when compared with those obtained under conventional external heating (oil bath)

DOI: 10.1039/c3gc36881e

and microwave heating, showed that ohmic reactor allows faster and more uniform heating and an
induced increase of dynamics/mobility of charged species leading in several cases to higher reaction

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yields and shorter reaction times.

Introduction
Green chemistry has obtained the status of a major scientific
discipline while trying to solve environmental problems
caused by chemical and pharmaceutical industries, related to
the use of toxic chemicals and high energy consumption.1
Therefore, synthetic chemists are challenged to consider more
environmentally benign and sustainable methods for the generation of the desired target molecules. In fact, one of the challenges of the current chemical industry is reducing the use of
toxic organic solvents.2 In this context, the chemical transformations in aqueous media arouse great interest since water
is a non-toxic, non-flammable solvent and readily available at
low cost.
Water has a high thermal capacity, making the exothermic
processes safer and more selective, especially when they are
performed on a large scale. In the late 1980s and early 1990s,
work by Grieco, Breslow and Engberts highlighted how the

a
Department of Chemistry & QOPNA Campus Universitrio de Santiago, University of
Aveiro, 3810-193 Aveiro, Portugal. E-mail: artur.silva@ua.pt, verasilva@ua.pt;
Fax: +351234370084; Tel: +351234370714
b
REQUIMTE, Department of Chemistry and Biochemistry, Faculty of Sciences,
University of Porto, 4169-007 Porto, Portugal
c
Centro de Investigao em Qumica, Departamento de Qumica e Bioqumica,
Faculdade de Cincias da Universidade do Porto, Rua Campo Alegre 687,
4169-007 Porto, Portugal. E-mail: lbsantos@fc.up.pt; Fax: +351220402569;
Tel: +351220402536
d
IBB-Institute for Biotechnology and Bioengineering, Centre of Biological
Engineering, Universidade do Minho, Campus de Gualtar, P-4710-057 Braga,
Portugal
Electronic supplementary information
(ESI)
available. See DOI:
10.1039/c3gc36881e

970 | Green Chem., 2013, 15, 970975

unique properties of water, as expressed in strong hydrogen

bonding interactions and hydrophobic interactions, enhance
the rate and selectivity of organic transformations performed
below the boiling point of water.3 Later on, Katritzky and
Siskin emphasized that the solvent properties of water at hightemperatures are similar to those of polar organic solvents at
room temperature, thus favouring ionic versus thermal free
radical solution phase reactions with organic compounds.4
Under these conditions, water can have one or more roles: as
catalyst, reactant, and solvent. The roles of water in a wide
variety of organic reactions at high-temperature and supercritical water (from 200 C to 600 C) were reviewed by Parsons,5
An et al.,6 Simoneit,7 Savage8 and Kus.9
Water near its critical point can participate in hydrogenbonding interactions, which can allow formation of alternate
lower-energy transition states or stabilize existing transition
states, and it can dissociate to form H+ and OH, which can
accelerate acid- and base-catalyzed reactions.
The growing list of examples in which reactions performed
in water are not only faster but also more selective (either
chemo-, regio- or enantioselective) highlights the importance
of performing reactions in water.10
The idea of performing reactions using on water conditions was proposed by Sharpless et al., who described several
examples of successful reactions performed with substantial
rate acceleration when insoluble reactants are stirred in
aqueous emulsions or suspensions without the addition of
any organic cosolvent.11 For highly insoluble reactants involving two-phase systems, the on-water eect involves transphase interactions of water with transition states and reactants. This on water phenomenon is being widely explored
and was recently reviewed by Fokin12 and Coyne.13

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Green Chemistry
In addition, microwave-assisted organic synthesis in water
is also being also widely explored.14 Concerning eciency, the
use of controlled microwave heating under sealed-vessel conditions has been shown to dramatically reduce reaction times
and increase product yields when compared to the conventional synthetic methods.14c,d However, there are some important
limitations of this method that remain unsolved. One of them
is related to the energy eciency of microwave ovens, and
some studies have shown that, in the case of reflux using an
open vessel system in small scale, microwave radiation consumes significantly more energy than the techniques of conventional heating (mantle or oil bath). This is due in large part
to the low eciency of the magnetron in converting electrical
into microwave energy (on the order of 5060%).15 These
studies also showed that energy consumption with microwave
radiation depends on the nature of the solvent, more precisely
the dipole moment (which aects the characteristics of radiation absorption by the reaction mixture), its boiling point and
scale of operations laboratory-scale (500200 mmol of
reagents in a volume of 400300 mL).15 Microwave heating for
the large industrial scale is very problematic because the penetration depth of microwave radiation in absorbing media is
limited, and the issue of security would also increase problems.16 Until now scaling was performed only on laboratory
scale, on the order of a few grams to hundreds of grams, or in
flow reactors, for a few kilograms.17 The technology involved in
the design of microwave apparatus makes high investment
cost a disadvantage. Sometimes the measures of pressure and
temperature are very troublesome. This makes comparison
with the classical reaction conditions dicult and leads to
speculation about the existence of non-thermal eects or
also called microwave eects on chemical reactions.16,18
Ohmic heating can be an alternative heating process for
organic transformations, with potential advantages in terms of
performance compared to microwave-assisted synthesis. This
is an advanced thermal processing method where the reaction
mixture or the medium, which serves as an electrical resistor,
is heated by passing electricity through it. The heating occurs
in the form of internal energy transformation (from electric to
thermal) within the reaction mixture. Therefore, ohmic
heating can be seen as an internal thermal energy generation
technology, and not only as a thermal energy transfer,
meaning that it does not depend on the heat transfer to the
medium.19a,b Thus, electrical energy is dissipated into heat
with high eciency, which results in a high speed heating rate
of 100 C min1, allowing rapid and uniform heating (temperature homogeneity). The fluctuation of the applied electric
field in the reactor will increase the directional dynamics of
charged species and dipole orientation in solution.19be
This heating process depends on the electrical impedance,
more precisely the AC resistance of the medium and the
applied voltage. On the other hand, the applied voltage
depends on the input power from the amplifier, which also
depends on the AC resistance of the medium. As the distance
between electrodes is fixed (23 mm), the field strength applied
will vary from experiment to experiment. In common with

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microwave heating, electrical energy is transformed into heat
due to ion movement and friction. However, unlike microwave
heating, the depth of penetration is virtually unlimited and
the extent of heating is governed only by the spatial uniformity
of electrical conductivity throughout the reaction medium and
its residence time in the ohmic reactor.19 Thus, the scaling of
direct ohmic heating for the pilot scale or even the industrial
scale should not present the limitations and diculties found
in microwave radiation.
Although there are already many applications of ohmic
heating in the food industry,19 to our knowledge the application of this process in chemical synthesis, particularly in
organic synthesis in aqueous media, has not been reported so
far.
The key goal of this project is to explore a new heating
process based on an ohmic heating reactor for organic synthesis, using water as the solvent and as conducting media.
In ohmic heating, the electrical energy provided to the
reactor is ideally used only for heat generation, electrochemical reactions, which are chemical reactions at electrode
solution interfaces induced by electrical potential and current,
are undesirable. These reactions can be avoided or eectively
inhibited by choosing an appropriate electrode material,20a
through pulsed ohmic heating approaches20b or using high frequency alternating current.20c In our case, we used a sinusoidal AC-voltage of high frequency (25 kHz) that decreases the
time interval of electrical polarization minimizing the occurrence of side oxidationreduction reactions. The use of high
frequency leads to minimization of the system polarizability
leading to a higher electrical eciency since it reduces the
capacitive component. Since a standard system is not commercially available, a new prototype ohmic heating reactor was
designed, optimized and tested previously (PT no 105908,
2011-09-27).21 A schematic representation of the ohmic
heating reactor apparatus is presented in Fig. 1.
The power control of the ohmic heating reactor is adjusted
manually and is done based on the amplitude of the signal
generator as well as through gain of the power amplifier. The
definition of the dissipated power is also dependent on the
overall reactor impedance which can be tuned using dierent
sizes of electrodes, or by changing the concentration of
charged species in solution. This ohmic reactor is especially
suitable for synthesis in aqueous media, where the reaction
medium is electrically conductive as in the case of aqueous
solutions of acids, bases or salts. Its application to nonconducting media can be achieved by adding a small amount
of a strong electrolyte such as NaCl, since it does not interfere
with the chemical reaction. This reactor has also magnetic stirring to increase the homogeneity of the solution, even when
there is some reagent dispersion or precipitation.
In order to explore the benefits of this process, four
dierent types of aqueous organic transformations, a Diels
Alder cycloaddition, a nucleophilic substitution, an N-alkylation and a Suzuki cross-coupling reaction, were carried
out in the ohmic heating reactor under refluxing water. We
chose these reactions because they are all well-known,

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Table 1 DielsAlder cycloaddition of 9-hydroxymethylanthracene 1 with

N-methylmaleimide 2 under conventional (oil bath), microwave (MW) and
ohmic heating (H)

Entry

Heating method

Scale (mmol)

Timea (min)

Yieldb (%)

1
2
3

Oil bath
MW
Hc

0.47
0.47
0.47

15
2
2

57
53
80

a
Time that the reaction mixture is kept at 100 C (fixed hold time in
the case of MW heating). b Yield of pure adduct after filtration. c NaCl
(30 mg) was added as electrolyte (see the Experimental section).

Due to the wide application of this reaction, the DielsAlder

cycloaddition of 9-hydroxymethylanthracene 1 with N-methylmaleimide 2 was chosen as the first model reaction to be conducted under the three heating processes (conventional,
microwave and ohmic heating). The results are summarized in
Table 1. Gratifyingly, we found that the expected cycloadduct 3
was obtained in the highest yield using ohmic heating (80%)
in only 2 minutes of reaction. The reaction time was the same
as that used under microwave heating, which gave relatively
lower yield (53%).
Nucleophilic substitution of 2,4-dinitrofluorobenzene with
glycine
Fig. 1

Schematic representation of the ohmic heating reactor apparatus.

straightforward and have well elucidated mechanisms. These

reactions were also performed in both conventional (oil bath)
and microwave heating under similar reaction conditions in
order to compare the performance of these three processes. It
is expected that a significant reduction of reaction time and an
increase in energetic eciency of the chemical transformations
can be achieved by using this novel ohmic heating process.

Results and discussion

DielsAlder cycloaddition of 9-hydroxymethylanthracene with
N-methylmaleimide
The DielsAlder reaction is the most widely employed synthetic
reaction in organic synthesis for the construction of six-membered rings. In 1980, Rideout and Breslow reported that both
rate enhancement and excellent selectivity could be achieved
by certain DielsAlder reactions when they were performed in
diluted aqueous solutions.22 In the meantime, other Diels
Alder reactions were successfully performed in water, allowing
in some cases higher yields and higher selectivity.23

972 | Green Chem., 2013, 15, 970975

Aryl halides have low reactivity toward nucleophilic reagents

like OH, OR, NH3 and CN, therefore this type of reaction
usually requires several hours at room temperature to give a
satisfactory yield.24 In an attempt to develop a more ecient
heating process and compare it with the other two heating
methods commonly used, 2,4-dinitrofluorobenzene 4 was left
to react with glycine 5 in refluxing water.25
The results presented in Table 2 show that there are no significant dierences between the three methods, ohmic heating
gives similar results of yield and reaction time compared to
the other heating methods. This reaction can be visually monitored in conventional and ohmic heating once product 6 precipitates in the reaction medium as a yellow solid. The closed
cavity of the microwave used does not allow this visual
monitoring.
N-Alkylation of amines: reaction of benzyl chloride with
piperidine
CN bond formation is one of the most important transformations in organic synthesis and amines are widely used as
intermediates to prepare solvents, fine chemicals, agrochemicals, pharmaceuticals and catalysts for polymerization.26
However the reaction between alkyl halides and amines, in the

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Table 2 Nucleophilic substitution reaction of 2,4-dinitrouorobenzene 4 with

glycine 5 under conventional (oil bath), microwave (MW) and ohmic heating
(H)

Entry

Heating method

Scale (mmol)

Timea (min)

Yieldb (%)

1
2
3
4

Oil bath
MW
MW
H

3.7
3.7
3.7
3.7

5
0.58c
1
1

92
86
91
95

Time that the reaction mixture is kept at 100 C (fixed hold time in
the case of MW heating). b Yield of pure product after filtration.
c
0.58 min was performed to compare with the literature.

presence of a base, requires long reaction times and aords

low yields of the desired products.27 Therefore, in order to ascertain the comparative eectiveness of the two most common
heating methods and ohmic heating, the reaction between alkyl
halides and amines was carried out in the presence of aqueous
NaOH solution using the three heating methods.26
The comparative results are shown in Table 3. These results
show that ohmic heating is more eective in terms of reaction
time compared to conventional heating but aords a lower
yield when compared to microwave heating. However both
methods (microwave and ohmic heating) are more eective in
terms of reaction time and yield than conventional heating.
Suzuki cross-coupling reaction of phenylboronic acid with
1-(4-bromophenyl)ethanone
The Suzuki reaction is one of the most used reactions for selective establishment of CC bonds, in particular for the formation of biaryls that are products found in a wide range of
herbicides, pharmaceuticals and natural products, as well as
in conducting polymers and liquid crystalline materials.28
The results for the Suzuki coupling reaction are shown in
Table 4. Using the same reaction time in the three
Table 3 N-Alkylation of amines: reaction of benzyl chloride 7 with piperidine 8
under conventional (oil bath), microwave (MW) and ohmic heating (H)

Entry

Heating method

Scale (mmol)

Timea (min)

Yieldb (%)

1
2
3

Oil bath
MW
H

11.4
11.4
11.4

720
10
10

55
79
68

a
Time that the reaction mixture is kept at 100 C (fixed hold time in
the case of MW heating). b Yield of pure product after purification by
column chromatography.

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Table 4 Suzuki cross-coupling reaction of 1-(4-bromophenyl)ethanone 10

with phenylboronic acid 11 under conventional (oil bath), microwave (MW) and
ohmic heating (H)

Entry

Heating method

Scale (mmol)

Timea (min)

Yieldb (%)

1
2
3

Oil bath
MW
H

10
10
10

10
10
10

54
51
61

a
Time that the reaction mixture is kept at 100 C (fixed hold time in
the case of MW heating). b Yield of pure product after crystallization.

experiments, we found that the yield of 12 was slightly better

under ohmic heating.
Considering our results, we observed that in two cases
(DielsAlder cycloaddition and Suzuki cross-coupling reaction)
the yields obtained under ohmic heating were significantly
higher than those obtained under conventional and microwave
heating. In the nucleophilic substitution reaction, the yields
were very good and the reactions occurred in a few minutes
using all three heating methods. Regarding the N-alkylation of
amines, a significant reduction of reaction time was achieved
using both microwave and ohmic heating. Regarding the
ohmic heating, the induced higher dynamics of charged
species in solution is probably related to the increasing speed
of the studied reactions.
Except for the N-alkylation of amines, in all the other reactions the products precipitated in the reaction medium and
were easily isolated after filtration without the use of organic
solvents. Treatment of resulting water may lead to additional
costs that are not considered in this work.
Concerning safety aspects, the reactor vessel is an open
system, where there is no chance to have overpressure, and the
reactor itself is installed in a hood. Regarding the thermal
security there is an independent temperature protection
system, that was attained by using a programmable alarm/
temperature reader with an alarm system (K3MA-L, temperature meter from Omron), to avoid reactor overheating. An electrical protection circuit avoids an electrical short circuit, which
includes an emergency button that acts on the contactors and
shuts o the power input from the AC amplifier to the reactor
and the reactor support is connected to the ground.

Experimental
Methods
Preparative thin-layer chromatography was carried out with
Merck silica gel (60 DGF254) and column chromatography
with Merck silica gel 60 (70230 mesh). NMR spectra were

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recorded on a Bruker Avance 300 spectrometer (300.13 MHz
for 1H and 75.47 MHz for 13C), with CDCl3 used as the solvent
if not stated otherwise. The internal standard was TMS (see
ESI). Microwave-assisted reactions were carried out in a CEM
Discovery Labmate circular single-mode cavity instrument
(300 W max magnetron power output) from CEM Corporation.
Reactions were carried out in an open-vessel using a 50 mL
round-bottom flask filled with the reaction mixture and
equipped with a condensator. For experiments carried out in
an oil bath ( paran) under reflux conditions, a 50 mL roundbottom flask was used and it was immersed into the bath
before the heating started. For experiments carried out under
ohmic heating, the 50 mL reactor was filled with the reaction
mixture, closed and the mixture was heated to reflux. For
25 mL of the reaction mixture the length of electrodes
immersed in the reaction mixture is 20 mm. For all paran
oil-bath, microwave and ohmic heating experiments, a
medium magnetic stirring speed was used.
General procedure for the DielsAlder cycloaddition of
9-(hydroxymethyl)anthracene with N-methylmaleimide
A mixture of 9-(hydroxymethyl)anthracene 1 (0.032 g,
0.156 mmol) and N-methylmaleimide 2 (0.052 g, 0.468 mmol,
3 equiv.) in 25 mL of water was refluxed using the methods
and conditions summarized in Table 1. After cooling to room
temperature, the mixture was allowed to stay in ice for
34 hours to enable complete crystallization of the cycloadduct. The solid was filtered, washed with iced water and
dried under vacuum. Product 3 was obtained pure (1H and 13C
NMR provided in ESI) with the yields described in Table 1.
General procedure for the nucleophilic substitution reaction
of 2,4-dinitrofluorobenzene with glycine
2,4-Dinitrofluorobenzene 4 (0.50 mL, 3.76 mmol) was added to
a mixture of glycine 5 (0.282 g, 3.74 mmol) and sodium bicarbonate (0.630 g, 7.50 mmol, 2 equiv.) in 25 mL of water and
the mixture was refluxed using the methods and conditions
summarized in Table 2. The desired product precipitated after
the addition of a few drops of HCl (2 N) to the reaction
mixture. The yellow N-arylated amino acid 6 was collected via
filtration under vacuum and washed with water (2 12 mL) to
give the pure compound 6 (1H and 13C NMR provided in ESI)
with the yields described in Table 2.
General procedure for N-alkylation of amines: reaction of
benzyl chloride with piperidine
A mixture of benzyl chloride 7 (1.31 mL, 11.4 mmol), piperidine 8 (1.12 mL, 11.4 mmol) and sodium hydroxide (0.20 g,
5 mmol) in 25 mL of water was refluxed using the methods
and conditions summarized in Table 3. After completion of
the reaction (monitored by TLC), the product was extracted
with ethyl acetate (3 25 mL) and purified by column chromatography using hexaneethyl acetate (4 : 1) as the eluent.
Product 9 was obtained pure (1H and 13C NMR provided in
ESI) with the yields described in Table 3.

974 | Green Chem., 2013, 15, 970975

Green Chemistry
General procedure for the Suzuki cross-coupling reaction of
1-(4-bromophenyl)ethanone with phenylboronic acid
A mixture of (4-bromophenyl)ethanone 10 (1.990 g, 10 mmol),
phenylboronic acid 11 (1.586 g, 13 mmol), sodium carbonate
(0.403 g, 3.8 mmol), tetrabutylammonium bromide (TBAB)
(0.322 g, 1 mmol) and palladium(II) acetate (8.98 mg, 3.97
102 mmol) in 25 mL of water was refluxed using the methods
and conditions summarized in Table 4. Product 12 was
obtained pure (1H and 13C NMR provided in ESI) after crystallization with 2-propanol with the yields described in Table 4.

Conclusions
The high performance and eciency of ohmic heating in
several chemical transformations has been described. From
the results obtained for four model organic transformations
comparing the three heating methods (classical heating,
microwave radiation and ohmic heating), the following conclusions can be drawn: ohmic heating can be used for organic
transformations in aqueous media. This process gives similar
results to microwave radiation or in some cases even better,
this is clearly seen for the DielsAlder reaction, and is much
more ecient than classical heating. The main advantages are
(i) simplicity of design, (ii) cost of the reactor, (iii) its easy
maintenance and handling, (iv) the low heat capacity and (v)
low thermal inertia of the ohmic heating process. Besides, its
high eciency, the possibility of fast and uniform heating, as
well as the possibility of visual monitoring and addition of
reagents during the reaction, which in most microwave closed
cavities is not possible, make the use of this process a highly
advantageous and versatile option for organic synthesis
especially in water. Moreover, in the ohmic heating process the
energy transfer depends on the electrical impedance of the
medium and the applied voltage. The ohmic heating process
has huge potential to increase the reactivity eciency, has
clear economic advantages and is environmentally
sustainable.
To better illustrate the scope of this heating method other
examples of organic reactions are being studied and will be
reported in the near future, as well as the scaling up of the
reactor.

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