Activation and deactivation of a chemical transformation by an electromagnetic field: Evidence for specific microwave effects in the formation of grignard reagents

Article abstract of DOI:10.1002/anie.201100856

It's field density, not temperature! Modifying the electric field strength in a microwave experiment can completely change the outcome of a reaction. Whereas a low field strength in Grignard reagent formation from Mg metal and aryl halide leads to acceleration of the initiation step, using a high field strength at the same temperature suppresses Mg insertion, favoring solvent decomposition and passivation of the Mg metal (see scheme). Copyright

Full text of DOI:10.1002/anie.201100856

Communications
DOI: 10.1002/anie.201100856
Microwave Chemistry
Activation and Deactivation of a Chemical Transformation by an
Electromagnetic Field: Evidence for Specific Microwave Effects in the
Formation of Grignard Reagents**
Bernhard Gutmann, Alexander M. Schwan, Benedikt Reichart, Christian Gspan,
Ferdinand Hofer, and C. Oliver Kappe*
Despite the large body of published work in the field of
Our investigations in this area were inspired by a recent
report by Hulshof and co-workers on the microwave-assisted
insertion of Mg metal into carbon–halogen bonds (Grignard
[1–3]
microwave-assisted organic synthesis (MAOS),
there is
still considerable controversy on the exact reasons why
microwave irradiation is able to enhance or otherwise
[9]
reagent formation). The authors demonstrated that for
certain substrates (e.g. 2-halothiophenes) the formation of the
corresponding organomagnesium reagents could be signifi-
cantly accelerated by applying microwave irradiation at
constant power utilizing a multimode instrument. The experi-
ments were performed at approximately 658C under open
vessel reflux conditions using dry THF as solvent in an Ar
atmosphere. The interaction between the microwave field and
the Mg turnings produced clearly visible electrostatic dis-
charge phenomena between the Mg particles (arcing), causing
a distortion of the Mg surface resulting in smaller and thus
more reactive spherical Mg particles, as evidenced by scan-
ning electron microscopy (SEM), and possibly also to a
[
4]
influence chemical processes. Of particular importance in
this context is the question of whether the electromagnetic
field—the electric or magnetic field component—can interact
with specific substrates in a reaction mixture to generate
effects that are not correlated with a macroscopic change in
temperature (i.e. “specific” or “nonthermal” microwave
[
4,5]
effects).
Although these types of microwave effects have
been frequently postulated when the outcome of a chemical
transformation performed under microwave conditions was
different from the conventionally heated counterpart at the
[4]
same monitored reaction temperature, recent investigations
suggest that in the majority of these cases experimental
artifacts connected to erroneous temperature measurements
are responsible for the observed phenomena, rather than
removal of the passivating MgO/Mg(OH) layer present on
2
[
9]
the non-activated Mg turnings.
[
6–8]
genuine electromagnetic field effects.
To further enhance these remarkable acceleration effects
we decided to reevaluate the formation of Grignard reagents
using single-mode microwave reactors, which generally pro-
vide substantially higher field densities than multimode
Herein we present a unique chemical transformation that
under 2.45 GHz microwave irradiation is dramatically influ-
enced by the electromagnetic field, and not by temperature.
At the same macroscopically determined reaction temper-
ature, this organometallic process can be either accelerated
[
2]
instruments. As a suitable model substrate 2-chloropyridine
(1) was selected as we anticipated that this comparatively
nonreactive heteroarene chloride would allow the detection
of any rate enhancements comparing conventional and
microwave heating techniques in a reliable and reproducible
manner (Scheme 1). The following general reaction condi-
(
relative to the conventionally heated control experiment) in
a low-density microwave field or suppressed by applying a
high-density field. We also demonstrate that as a result of this
exceptional dependence on electric field strength, the same
chemical reaction when performed in different microwave
instruments can lead to entirely different results.
[
*] B. Gutmann, A. M. Schwan, B. Reichart, Prof. Dr. C. O. Kappe
Christian Doppler Laboratory for Microwave Chemistry (CDLMC)
and Institute of Chemistry, Karl-Franzens-University Graz
Heinrichstrasse 28, 8010 Graz (Austria)
Scheme 1. Model transformation for the investigation of microwave
effects.
Fax: (+43)0316-380-9840
E-mail: oliver.kappe@uni-graz.at
Homepage: http://www.maos.net
tions were chosen: Mg turnings (220 mg, ca. 9 mmol, average
particle size 2–3 mm, see Figure S1a in the Supporting
Information), anhydrous THF (3.0 mL), and 2-chloropyridine
C. Gspan, Prof. Dr. F. Hofer
Institute for Electron Microscopy and Fine Structure Research
Graz University of Technology
(1) (226 mg, 2.0 mmol) were placed in a 10 mL pyrex round-
bottom flask fitted with a reflux condenser and a magnetic stir
bar under an atmosphere of Ar.
Initial reference experiments were performed using con-
ventional heating in a preheated oil bath. As the formation of
Grignard reagents by direct insertion of Mg metal into
carbon–halogen bonds is notoriously difficult to control and
Steyrergasse 17, 8010 Graz (Austria)
[
**] This work was supported by a grant from the Christian Doppler
Research Society (CDG). We thank D. I. Heimo Kotzian for
performing electromagnetic field simulations.
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.201100856.
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[
10]
to reproduce, all sets of experiments described herein were
performed at least five times to ensure statistical relevance.
Not entirely unexpectedly, the obtained conversion data for
the formation of Grignard reagent 2 using conventional
heating (THF reflux, 658C) showed significant variability;
initiation started between 25 and 45 min (Figure S2a in the
Supporting Information). In a subsequent set of experiments
the exact same transformation was performed in a single-
mode microwave reactor (CEM Discover) in open-vessel
[
2]
mode. Similar to the results reported by Hulshof and co-
workers, a significant rate acceleration of the initiation step
was observed (5–15 min) using either 200 W or 300 W of
constant microwave power (these experiments are discussed
in detail in the Supporting Information; see Figures S2–S4).
In some respects, these accelerations are related to the
activation of Mg metal and the initiation of the formation of
[
10]
Grignard reagents under sonochemical conditions.
In an attempt to further enhance this transformation and
to probe the influence of a higher electric field strength on the
initiation step, we subsequently performed experiments in a
single-mode microwave reactor with 850 W installed max-
imum magnetron output power (Anton Paar Monowave
Figure 1. Temperature (T) and power (P) profiles for the microwave-
assisted conversion of 2-chloropyridine (1) to Grignard reagent 2
[8]
3
00). Apart from the higher nominal magnetron power, the
(Scheme 1) in temperature-control mode. Monowave 300 reactor, 658C
specific design of the single-mode cavity in this instrument
generates a significantly higher electric field strength and thus
set temperature, internal fiber-optic temperature control, simultaneous
cooling, magnetic stirring (600 rpm). Data are shown using “as-fast-
as-possible” (a), and “ramp” modes (b). For clarity, only the first
[11]
power density than other single-mode microwave reactors.
5
min of the experiment is shown. A simulation of the corresponding
Since this instrument only allows sealed vessel microwave
processing in cylindrical tubes, temperature controlled runs at
electric field strength and volume power distribution at 16 and 240 W
microwave power is shown in Figures S5 and S6 in the Supporting
Information.
6
58C monitored by an internal fiber-optic probe were carried
out to mimic the open vessel experiments executed at
constant power and reflux conditions described above. The
Grignard reagent formation (Scheme 1) was initially per-
formed by applying a set temperature of 658C using the
standard “as-fast-as-possible” heating option on the Mono-
reaction temperature only gradually to the target value of
658C, the applied magnetron power was drastically reduced
and never rises above 16 W (Figure 1b). Under these
conditions, the occurrence of electrostatic discharges is
minimized, as clearly seen by the built-in camera, and for
all runs full conversion of the 2-chloropyridine starting
material (1) was observed within 60 min.
Evidently, both the acceleration and retardation of the
Grignard reagent formation from 2-chloropyridine (1) and
Mg metal is somehow connected to arcing phenomena
resulting from exposure of electrically conductive Mg turn-
ings to a microwave field. Remarkably, using comparatively
low electric field strengths the reaction is accelerated, while
applying high electric field strength conditions the same
transformation experiencing an identical 658C macroscopic
bulk temperature is almost completely retarded. Since we
hypothesized that both phenomena are associated to an
activation/deactivation effect of the Mg surface, the electro-
static discharges occurring between Mg turnings in THF were
studied in more detail. For this purpose, the microwave
irradiation experiments described above were repeated in the
absence of the 2-chloropyridine substrate (1); Mg turnings
with THF alone were irradiated in various microwave instru-
ments.
[8]
wave 300. This heating algorithm attempts to reach the set
temperature as rapidly as possible (ca. 30 s) and thus com-
paratively high initial microwave power levels are applied.
Violent electrostatic discharges were observed by using a
built-in camera, in particular during the initial 25 s heating
phase of the experiment in which nominal magnetron output
power levels of up to 150 W were reached. The arcing was
particularly intense when the reaction vial was concurrently
cooled with compressed air during microwave irradiation.
This so-called “simultaneous cooling” technique allows
higher levels of microwave power to be administered to the
reaction mixture, thereby potentially enhancing any effects
[12]
that are dependent on the electric field strength. In our
case, when using simultaneous cooling a maximum power
level of 240 W was observed (Figure 1a), leading to very
intense arcing during the initial phase of the experiment.
To our surprise, monitoring of the reaction mixture by
HPLC–UV revealed that under these high power density
conditions virtually no conversion was observed. Even after
6
0 min of irradiation at 658C in all of the six attempts the
reaction mixture consisted mainly of unreacted 2-chloropy-
ridine starting material (1), and only very small amounts of
pyridine quenching product (0–5%) were detected.
In contrast, when a heating ramp of 2 min was pro-
grammed on the Monowave 300 instrument, which rises the
Arcing phenomena in metal–solvent systems under micro-
wave irradiation have been studied in detail by Whittaker and
Mingos and are critically dependent on many factors includ-
ing, for example, metal particle size and morphology, solvent
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Communications
ionization energy and dielectric loss tangent, and the applied
had undergone significant changes and that the originally
shiny Mg surface was now covered with dark material,
presumably resulting from THF decomposition (see below).
To establish if the extreme arcing phenomena seen in the
Monowave 300 instrument could also be reproduced in a
different single-mode microwave reactor of similar design,
the same set of Mg/THF irradiation experiments was repeated
in a Biotage Initiator 2.5 instrument, which provides 400 W of
maximum magnetron output power. Remarkably, under
comparable conditions (300 W constant power, 20 s, 658C
maximum temperature), no arcing was experienced at all and
the Mg turnings recovered after microwave irradiation were
therefore very similar in appearance to untreated samples
(Figure 2c). Even applying 400 W of constant magnetron
power for 2 min (reaching 2008C) did not lead to any visible
changes on the Mg particles or to the formation of carbona-
ceous material as a result of arcing.
To obtain preparative amounts of the carbonaceous
material described above for analytical purposes, an experi-
ment involving several heating and cooling cycles in the
Monowave 300 reactor was designed, which allowed higher
power levels to be administered for prolonged time periods.
Intense arcing during irradiation was maintained over a
period of 4 ꢀ 50 s by performing four heating/cooling cycles at
a set temperature of 1208C (see Figure S8). Extreme arcing
was clearly audible and visible on the built-in camera
[13]
electric field strength.
With the CEM Discover system
under open vessel THF reflux conditions as described above,
light arcing between individual Mg turnings could be
observed at an applied constant magnetron power of 200 W.
After 5 min of irradiation at 658C applying constant 200 W
magnetron power, slight discoloration and the formation of
small amounts of a fine dispersion of gray particles/powder
was observed, not unlike the results described by Hulshof and
co-workers using a multimode microwave system (see Fig-
[
2]
[9]
ure S7a).
To perform valid comparative studies of arcing results
achieved in individual single-mode microwave reactors,
experiments under sealed vessel conditions were subse-
quently carried out in the Discover system. A stirred Mg/
THF mixture exposed to 300 W of constant microwave power
in a 10 mL sealed pyrex vial reached a temperature of 658C,
corresponding to the boiling point of THF, within 17 s. After
this comparatively short irradiation period, the Mg turnings
appeared essentially unchanged (Figure 2a). Only by extend-
(Figure 3) and led to around 30 mg of black amorphous
material, which could easily be separated by sedimentation
techniques from the heavier Mg particles.
Figure 3. Real-time images of electrostatic discharge (arcing) between
stirred Mg turnings in THF in a high field density microwave reactor
(
Monowave 300). Clearly visible is the stir bar at the bottom of the
Figure 2. Effect of constant power microwave irradiation (300 W) on
stirred Mg turnings in THF (maximum temperature 658C) using three
single-mode microwave reactors with different field strengths: a) CEM
Discover; b) Anton Paar Monowave 300; c) Biotage Initiator EXP 2.5.
See main text for discussion.
vial.
The remaining THF solution and a toluene extract of the
carbonaceous material was analyzed by GC–(EI)MS analysis,
which revealed the presence of trace amounts of a range of
(poly)aromatic hydrocarbons, including, for example, naph-
ing the irradiation time to 20 min in a temperature controlled
run (658C) were small amounts of a dispersion of gray
particles/powder formed as a result of mild arcing, similar to
the results obtained under open-vessel conditions (Fig-
ure S7b).
thalene, pyrene, fluoranthene, and 4-H-cyclopenta-
[def]phenantrene (Figure S9). Because of the apparent sol-
vent disintegration in these experiments, the pressure in the
sealed microwave vial increased to around 17 bar, presumably
as a result of low molecular weight solvent decomposition
products (Figure S8).
Careful analysis of the irradiated Mg turnings themselves
(and of somewhat smaller Mg particles formed during the
arcing process) by scanning electron microscopy (SEM) in
combination with energy-dispersive x-ray spectrometry
(EDXS) confirmed our assumption that the Mg turnings,
while clearly showing the impact of violent electrostatic
discharges, were covered with a layer of the carbonaceous
material formed during solvent decomposition (Figures S10
In stark contrast, using the Monowave 300 for the same
constant power sealed vessel experiment applying 300 W
nominal magnetron output power for just 8 s (maximum
reached temperature again 658C) produced violent electrical
arcing, which was accompanied by the formation of substan-
tial amounts of carbonaceous material resulting from the
[
13,14]
decomposition of THF solvent (Figure 2b).
Visual
inspection of the Mg turnings after microwave irradiation
clearly revealed that the morphology of the Mg metal surface
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and S11 in the Supporting Information). Examination of the
fine black carbonaceous powder by X-ray diffraction (XRD)
analysis revealed the occurrence of small Mg metal particles
in addition to finely distributed MgO nanoparticles (Fig-
ure S12 in the Supporting Information). TEM investigations
produces a passivating layer of graphitized core/shell MgO/
carbon nanoparticles covering the Mg metal, effectively
preventing access of the organohalogen reagent to the Mg
metal surface and thus shutting down the formation of the
organomagnesium (Grignard) reagent. Both pathways are
probably best categorized as examples of “specific” micro-
wave effects as the macroscopic reaction temperature in both
cases relative to the conventionally heated experiment is the
same (Figure S15), and clearly both the activation and
deactivation seen under microwave irradiation cannot be
duplicated by conventional conductive heat-transfer meth-
(
Figure 4) demonstrated that the MgO nanoparticles had
diameters ranging from 2 to 20 nm (black particles in
[5,16]
ods.
Of general importance to the field of microwave
chemistry, the data presented herein for the first time provide
clear evidence that the exact same reaction when carried out
in different commercially available microwave instruments
can lead to entirely different results, even at the same
macroscopically determined reaction temperature.
Received: February 2, 2011
Published online: June 7, 2011
Figure 4. Transmission electron microscopy (TEM) investigation of the
fine black carbonaceous powder formed by high field density micro-
wave irradiation of Mg turnings. a) Dark MgO particles are embedded
in carbon; b) high resolution TEM image showing a MgO cube with
the [100] lattice fringes which is covered by partly graphitized carbon
Keywords: electromagnetic fields · Grignard reaction ·
.
microwave chemistry · nanoparticles
(
for further characterization data, see Figures S12–S14 in the Support-
ing Information).
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(
Figure S13). These findings were confirmed by an electron
diffraction investigation (Figure S14). Apparently, microwave
arcing under these extreme conditions will produce a plasma
[
[13]
environment with temperatures > 11008C, leading in the
particular case discussed herein to the carbonization of the
THF solvent and to the formation of MgO nanoparticles, the
oxygen presumably being derived from the THF molecule.
The results presented herein demonstrate for the first time
that the outcome of a chemical reaction can be influenced
both in a positive (activation) or negative (deactivation) way
by electric field strength using microwave irradiation. For the
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[
[
[9]
(
“activation”). In contrast, exposure of the same reaction
mixture to high field density conditions results in more
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integration of the THF solvent into carbonaceous material
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